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№4, 2022. Неврология

Pages 11-14. Влияние мелоксикама на показатели коагулограммы у пациентов с болью в спине, перенесших COVID-19. Путилина М.В., Шабалина Н.И., Гришин Д.В., Курушина О.В.

Summary:

Meloxicam effect on coagulogram parameters in patients with back pain after COVID-19

M.V. Putilina1, N.I. Shabalina2, D.V. Grishin3, O.V. Kurushina4


1Pirogov Russian National Research Medical University, Moscow

2Central Clinical Hospital RZD-Medicine, Moscow

3City Clinical Hospital No. 15, Moscow

4Volgograd State Medical University, Volgograd


Background: musculoskeletal symptoms commonly develop or worsen in patients who had COVID-19. The occurrence of musculoskeletal pain after infection can probably be explained by the direct primary viral attack to the muscles and peripheral nerves, and secondary hypoxia, which enhances the processes of hypercoagulation and inflammation, as well as microcirculatory disorders with the microthrombosis development.

Aim: to study the meloxicam effect on coagulogram parameters in patients with back pain after COVID-19.

Patients and Methods: a retrospective study included 50 patients aged 35 to 50 years with a diagnosis of dorsopathy (lower back pain), who had suffered COVID-19 within 40 to 90 days before inclusion in the study. Pain syndrome therapy included the prescription of meloxicam, a solution for intramuscular administration of 10 mg/mL (intramuscularly, 1.5 ml once a day for 10 days). All patients were examined during the first visit (Visit 1) and 14 days after therapy (Visit 2). At each visit, the following indicators were assessed: neurological status and the pain severity on a visual analog scale (VAS). Laboratory tests were performed a day after Visits 1 and 2: complete blood count with platelet count, levels of inflammatory markers and coagulogram indicators.

Results: 10 days after therapy with meloxicam, a statistically significant reduction of pain syndrome according to VAS (p<0.001) was registered. During the treatment, there was a significant decrease in the ESR and C-reactive protein levels, normalization of platelet levels, as well as there was no effect on activated partial thromboplastin time (APTT), thromboplastin time (TT), prothrombin time in a statistically significant decrease in the D-dimer level (p<0.006). There were no adverse events during the meloxicam use.

Conclusion: meloxicam had no effect on coagulogram parameters in patients with back pain after COVID-19.

Keywords: meloxicam, COVID-19, dorsopathy, back pain, inflammatory markers, coagulogram, musculoskeletal symptoms.

For citation: Putilina M.V., Shabalina N.I., Grishin D.V., Kurushina O.V. Meloxicam effect on coagulogram parameters in patients with back pain after COVID-19. RMJ. 2022;4:11–14.




Pages 15-19. Когнитивные и астенические расстройства после COVID-19. Захаров В.В., Громова Д.О., Эдильгиреева Л.А., Садуллаева Т.А.

Summary:

Cognitive and asthenic disorders after COVID-19

V.V. Zakharov, D.O. Gromova, L.A. Edilgireeva, T.A. Sadullayeva

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

A new coronavirus infection commonly entails persistent neurological complications, among the most common of which are cognitive and asthenic symptoms. The article provides data on the occurrence and clinical patterns of cognitive and asthenic symptoms after COVID-19, their association with the infectious disease severity, clinical significance and impact on everyday life. The article also discusses the pathogenesis of cognitive, asthenic and other neurological COVID-19 complications, including the following: direct invasion of the cerebral substance by the SARS-CoV-2; immune and metabolic disorders; occurrence of cerebrovascular diseases as a result of COVID-19-induced endotheliitis; cerebral hypoxia; social isolation due to restrictive measures; decompensation of concomitant diseases. Adding that, there are highlighted issues of prevention and treatment of COVID-19-induced neurological complications, including cerebrovascular diseases. The effect of antiplatelet therapy (prescribed to the patients with cardiovascular diseases for the prevention of recurrent ischemic events) on the COVID-19 course and complications is analyzed. The article describes a clinical case of persistent and significant cognitive impairment in a young woman who suffered a relatively mild COVID-19.

Keywords: COVID-19, SARS-CoV-2, new coronavirus infection, post-covid syndrome, endotheliitis, cognitive impairment, asthenia, cerebrovascular diseases.

For citation: Zakharov V.V., Gromova D.O., Edilgireeva L.A., Sadullayeva T.A. Cognitive and asthenic disorders after COVID-19. RMJ. 2022;4:15–19.



Pages 2-6. Особенности клинического течения болезни Паркинсона при отложении железа в базальных ганглиях. Буряк А.Б., Труфанов А.Г.

Summary:

Parkinson’s disease patterns in neurodegeneration with brain iron accumulation

A.B. Buryak1,2, A.G. Trufanov2


1S.M. Kirov Military Medical Academy of the Ministry of Defense of Russia, St. Petersburg

2I.I. Mechnikov North-Western State Medical University, St. Petersburg

Aim: to evaluate the association of iron deposition in the structures of the extrapyramidal system with the clinical picture patterns in patients with various stages of Parkinson’s disease (PD).

Patients and Methods: the study included 92 patients with PD (42 patients with stage II according to the Hoehn and Yahr scale, and 50 patients with stage III according to the Hoehn and Yahr scale). All patients underwent comprehensive clinical and neuropsychological testing according to the following scales: Unified Parkinson’s Disease Rating Scale (UPDRS), Freezing of Gait Questionnaire (FOGQ), Gait and Balance Scale (GABS), Frontal Assessment Battery (FAB), Mini-Mental State Examination (MMSE), Beck’s Depression Inventory. Also, all patients underwent magnetic resonance imaging (MRI) of the head using the Magnetom Trio A Tim 3.0 Tesla magnetic resonance tomograph with a susceptibility weighted imaging (SWI). ROI: substantia nigra (SN), nucleus ruber (NR), putamen, pale globe (PG), head of the caudate nucleus (CN), dentate body (DB). During SWI, the signal strength from each studied area was manually measured.

Results: statistically significant differences were found in the UPDRS and its sections, FOGQ, GABS, MMSE and FAB, between patients with stage II and III PD according to the Hoehn and Yahr scale. Statistically significant differences in signal strength indicators from the right and left SNs, right and left putamens, left PG, right and left CNs were revealed among the studied groups. Correlation analysis results showed that iron deposition in the structures of the extrapyramidal system with the UPDRS and its sections results predominated in patients with stage II according to the Hoehn and Yahr scale; in patients with stage III — with the UPDRS III, FOGQ, GABS, MMSE, FAB and Beck’s Depression Inventory.

Conclusion: a gradual increase in the brain iron accumulation in the PD progression was revealed. Multiple associations of iron deposition in the structures of the extrapyramidal system with various patterns of the clinical picture were revealed in patients with both stages II and III according to the Hoehn and Yahr scale. The combined use of complex clinical and neuropsychological examination with MRI of the head in SWI mode allows to assess the role of iron in the PD pathogenesis, identify biomarkers of disease progression and the development of its motor and non-motor manifestations.

Keywords: Parkinson’s disease, iron deposition, ferroptosis, basal ganglia, susceptibility weighted imaging, magnetic resonance imaging.

For citation: Buryak A.B., Trufanov A.G. Parkinson’s disease patterns in neurodegeneration with brain iron accumulation. RMJ. 2022;4:2–6.



Pages 20-25. Применение селективных ингибиторов циклооксигеназы-2 у пациентов с поясничной болью — фокус на безопасность.  Камчатнов П.Р., Ханмурзаева С.Б., Чугунов А.В. , Ханмурзаева Н.Б., Агабекова Э.С.

Summary:

Selective cyclooxygenase-2 inhibitors in patients with low back pain: focus on safety

P.R. Kamchatnov1, S.B. Khanmurzayeva2, A.V. Chugunov1, N.B. Khanmurzayeva2, E.S. Agabekova3

1Pirogov Russian National Research Medical University, Moscow 

2Dagestan State Medical University, Makhachkala

3City Clinical Hospital, Makhachkala

Low back pain (LBP) is a widespread musculoskeletal pain syndrome associated with a decrease in the life quality of patients and significant treatment expenses. Osteoarthritis (OA) of the lumbar facet joints can be considered as one of the important causes of LBP development. Commonly, a variety of pathogenetic mechanisms and clinical manifestations of LBP complicate the drug selection. The article analyzes information concerning the possibility of using a selective cyclooxygenase type 2 (sCOX-2) inhibitor, etoricoxib, for the treatment of patients with LBP. The article also presents the randomized clinical trial results concerning the efficacy and safety of its use in patients with LBP. The possibility of using this drug in patients (requiring a certain treatment duration, in particular, in LBP, which has developed in the setting of the facet joint OA) is extremely important, since it is necessary not only to relieve acute pain syndrome but also to inhibit the inflammatory process. In some cases, long-term treatment is required in OA, since an excessively short treatment course may not provide sufficient antiinflammatory effect, representing one of the reasons for the early onset of subsequent exacerbation.

Keywords: low back pain, osteoarthritis, nonsteroidal anti-inflammatory drugs, cyclooxygenase inhibitors, etoricoxib, tolerability.


For citation: Kamchatnov P.R., Khanmurzayeva S.B., Chugunov A.V. et al. Selective cyclooxygenase-2 inhibitors in patients with low back pain: focus on safety. RMJ. 2022;4:20–25.




Pages 26-32. Доказательная эффективность и безопасность применения комбинации витаминов группы В(тиамина, пиридоксина и цианокобаламина) в сочетании с диклофенаком натрия для лечения острой боли в спине. Рачин А.П., Шаров М.Н., Рачин С.А., Прокофьева Ю.С., Филиппова О.В.

Summary:

Evidence-based efficacy and safety of vitamin B complex (thiamine, pyridoxine and cyanocobalamin) in combination with diclofenac sodium for the treatment of acute back pain

A.P. Rachin1,2, M.N. Sharov3, S.A. Rachin2,4, Yu.S. Prokofieva5, O.V. Filippova6


1National Medical Research Center of Rehabilitation and Balneology, Moscow

2National association of experts in comorbid neurology, Moscow

3A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow

4I.P. Pavlov First St. Petersburg State Medical University, St. Petersburg

5Research Center of Neurology, Moscow

6I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

Nowadays, back pain is considered a common problem, for the treatment of which non-pharmacological and pharmacological methods are used (with the inclusion of NSAIDs). However, at present, there is no ideal treatment method. The article discusses the possibilities of using adjuvant agents that can reduce the dose of NSAIDs or the treatment duration. The analgesic effect of thiamine, pyridoxine and cyanocobalamin in therapeutic doses, including in combination with NSAIDs, has been studied. The article also considers results of a systematic review and meta-analysis in the studies on the efficacy of diclofenac in combination with vitamin B versus diclofenac as monotherapy for the treatment of low back pain. It was shown that the most significant effect of combination therapy was a reduction in the treatment duration and a decrease in the pain intensity. The results of the pharmacoeconomical analysis concerning the use of the combined analgesic, Neurodiclovit, vers us available alternatives are also presented. An analysis of vitamin drug offers shows that an attempt to replace Neurodiclovit with a combination of diclofenac with vitamin B leads to problems with the choice of drugs and dosages, without providing significant economic benefits. In turn, a change in the doses of drugs may be accompanied by a change in the treatment efficacy and safety.

Keywords: thiamine, pyridoxine, cyanocobalamin, diclofenac, back pain, combined analgesic, pharmacoeconomical analysis.

For citation: Rachin A.P., Sharov M.N., Rachin S.A. et al. Evidence-based efficacy and safety of vitamin B complex (thiamine, pyridoxine and cyanocobalamin) in combination with diclofenac sodium for the treatment of acute back pain. RMJ. 2022;4:26–32.

Pages 33-37. Когнитивные нарушения у больных, перенесших COVID-19. Камчатнов П.Р., Черемин Р.А., Скипетрова Л.А., Абусуева Б.А., Пышкина Л.И., Ханмурзаева С.А.

Summary:

Cognitive disorders in patients after COVID-19

P.R. Kamchatnov1, R.A. Cheremin2, L.A. Skipetrova2, B.A. Abusueva3, L.I. Pyshkina1, S.A. Khanmurzayeva3

1Pirogov Russian National Research Medical University, Moscow

2Center for Speech Disorders and Neurorehabilitation, Moscow

3Dagestan State Medical University, Makhachkala

Nowadays, doctors of all specialties in Russia and worldwide are dealing not only with a new coronavirus infection but also with the COVID-19 comorbidities, the so-called post-covid syndrome (PCS). PCS manifestations are diverse and characterized by symptoms from various body systems, and neurological disorders are particularly important: cognitive disorders, asthenic, vegetative, and anxiety disorders, leading to a decrease in the patients’ life quality and a slowdown in the recovery rate. The most significant neurological disorders are observed in patients over 50 years with initially concomitant cardiovascular pathology. The wide prevalence of PCS, its significant impact on the patients’ life requires the search for adequate therapeutic methods. Of undoubted interest is the use of peptide preparations with neuroprotective and neuropreparative effects. The authors present their data f rom the first experience of using the domestic drug, Cellex (pig brain polypeptides), to treat patients with small vessel disease and PCS with cognitive disorder. Therapy positive effect was noted as a decrease in the severity of cognitive disorder, anxiety and asthenic syndromes. Adding that, there was a good tolerability and the absence of severe side effects.

Keywords: COVID-19, post-covid syndrome, cognitive impairment, asthenic syndrome, small vessel disease, chronic cerebral ischemia, treatment.

For citation: Kamchatnov P.R., Cheremin R.A., Skipetrova L.A. et al. Cognitive disorders in patients after COVID-19. RMJ. 2022;4:33–37.



Pages 38-43. Особенности терапии нейропатии лицевого нерва (паралич Белла) при коморбидных состояниях. Алексеевич Г.В., Алексеевич Г.Ю., Исаева Н.В.

Summary:

Characteristics of facial neuropathy (Bell’s palsy) therapy in comorbid conditions

G.V. Alekseyevich1, G.Yu. Alekseyevich2,3, N.V. Isaeva2,3


1"Arnica" Family Clinic LLC, Krasnoyarsk

2Krasnoyarsk Regional Clinical Hospital, Krasnoyarsk

3Krasnoyarsk State Medical University named after Prof. Voino-Yasenetsky, Krasnoyarsk

The prevalence of facial neuropathy (FN) (Bell’s palsy, facial nerve palsy) ranges from 20 to 30 people per 100 thousand populations, and among mononeuropathies it ranks 2nd in incidence. In 75% of cases, FN is idiopathic. In 25%, FN is due to secondary causes. In some cases, FN is a component of Ramsay Hunt syndrome (multiple neuropathy of cranial nerves during ophthalmic zoster). The review examines modern approaches to the diagnosis and treatment of FN from the standpoint of evidence-based medicine. The authors draw attention on the fact that with an obvious picture of FN, it is necessary to conduct a thorough examination of the patient, since prosoparesis can be only one of the another life-threatening disease manifestations. In all cases of the idiopathic FN, hormonal therapy with the corticosteroid group should be prescribed. If a viral infection is suspected, antiviral drugs such as acyclovir should be added. The prescription of non-drug methods such as reflexology, physiotherapy, facial gymnastics did not show their benefit in the recovery rate, however, they did not cause deterioration in the condition. The efficacy of including anticholinesterase drugs, B vitamins, and electrotherapy in the therapy course is questionable. The use of these treatment methods can contribute to the development of complications.

Keywords: facial neuropathy, Bell’s palsy, facial nerve palsy, lagophthalmos, facial nerve, prosoparesis, complications.

For citation: Alekseyevich G.V., Alekseyevich G.Yu., Isaeva N.V. Characteristics of facial neuropathy (Bell’s palsy) therapy in comorbid conditions. RMJ. 2022;4:38–43.



Pages 44-50. Тромбэктомия при инсульте головного мозга. Авдеева В.Е., Котов А.С.

Summary:

Thrombectomy in stroke

1M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow

2A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow

Cerebrovascular accident (CVA) or stroke is the leading underlying condition of neurological disorder and ranks 4th among the causes of adult mortality. Thus, timely reperfusion therapy is an important method of effective care for patients with stroke. The administration of endovascular techniques in the treatment of patients with acute ischemic stroke in the form of mechanical thrombectomy and selective thrombolysis has opened a new era in modern neurology. The article describes two clinical cases with the successful use of mechanical thrombectomy in female patients older than 70 years with ischemic stroke. In both patients, mechanical thrombectomy using second-generation stent retrievers and aspiration techniques was performed urgently, within 6 hours from the onset of ischemic stroke due to the presence of contraindications to systemic thrombolysis. CT and MRI perfusions performed at the examination stage made it possible to clearly visualize the penumbra, which is larger than the infarct area. In both cases, the result of timely intervention was a regression of neurological symptoms, which confirms the efficacy of this treatment method and the feasability of its use in elderly and senile patients.

Keywords: cerebrovascular accident, st roke, atrial fibrillation, thromboextraction, thrombectomy, stent retriever, systemic thrombolytic therapy, penumbra.

For citation: Avdeeva V.E., Kotov A.S. Thrombectomy in stroke. RMJ. 2022;4:44–50.

Pages 51-54. Возможности повышения эффективности нейропротективной терапии у пациентов с острыми и хроническими цереброваскулярными заболеваниями, когнитивными нарушениями и астеническим синдромом различной этиологии: резолюция совета экспертов.

Summary:

Possibilities of improving the efficacy of neuroprotective therapy in patients with acute and chronic cerebrovascular diseases, cognitive disorders and asthenic syndrome of various etiologies: Expert Committee resolution

On March 26, 2022, an Expert Committee was held in Moscow on the possibilities of improving the efficacy of neuroprotective therapy in patients with acute and chronic cerebrovascular diseases, cognitive disorders and asthenic syndrome of various etiologies. Much attention of experts was paid to the therapeutic possibilities of Brainmax®, which is an innovative national drug in the form of a fixed combination of two molecules: ethylmethylhydroxypyridine succinate and meldonium.

For citation: Danilov An.B., Danilov Al.B. Possibilities of improving the efficacy of neuroprotective therapy in patients with acute and chronic cerebrovascular diseases, cognitive disorders and asthenic syndrome of various etiologies: Expert Committee resolution. RMJ. 2022;4:51–54.




Pages 7-10. Резорбция грыжи межпозвонкового диска. Феномен транзиторного увеличения размера. Ткачев А.М., Епифанов А.В., Акарачкова Е.С., Смирнова А.В., Илюшин А.В., Гордеева И.Е.

Summary:

Resorption of herniated intervertebral disc. Phenomenon of transient increase in size

A.M. Tkachev1,2, A.V. Epifanov2, E.S. Akarachkova3, A.V. Smirnova4, A.V. Ilyushin1, I.E. Gordeeva1,5

1Tkachev Clinic, Volgograd

2Tkachev Epifanov Clinic, Moscow

3International Society "Stress under Control", Moscow

4Medical Institute named after Berezin Sergey, St. Petersburg

5Volgograd State Medical University, Volgograd

Background: conservative treatment of herniated intervertebral discs (HID) is commonly accompanied by a decrease in their size, which is called HID resorption. Currently, it has been revealed that a transient size increase can accompany the process of HID resorption. However, there is no data on this phenomenon frequency and its role in the resorption process.

Aim: to determine the frequency of pseudoprogression or transient size increase of HID and to determine its role in the process of HID resorption.

Patients and Methods: the study included 327 patients aged 43.2±9.4 years with herniated lumbar and cervical disc who underwent conservative physical therapy. Patients had a decrease in HID size by over 50%. All patients underwent from 3 to 9 MRI scans, depending on the rate of HID resorption. The follow-up period ranged from 1.5 to 18 months.

Results: in 285 (87.1%) patients, there was a transient size increase of the hernia tissue, which was accompanied by a signal amplification on T2-weighted pulse sequences in the period from 2 to 5 months (3.4±0.9 months) in 266 (81.3%) cases, after which a subsequent decrease in the HID size occurred. In 233 (71.2%) cases, there was an increase in the signal from HID. In 195 (59.6%) patients, partial restoration of the intervertebral disc height was noted. An improvement in vertebral column statics accompanied HID resorption in 85 (25.9%) patients.

Conclusion: a transient size increase of HID is a pseudoprogression phenomenon observed  during HID resorption. It can be a positive prognostic marker and should be considered as a presumable predictor of the HID resorption onset.

Keywords: herniated intervertebral disc, resorption, pseudoprogression, phenomenon of transient size increase.

For citation: Tkachev A.M., Epifanov A.V., Akarachkova E.S. et al. Resorption of herniated intervertebral disc. Phenomenon of transient increase in size. RMJ. 2022;4:7–10.



№3, 2022. Клинические рекомендации и алгоритмы для практикующих врачей

Pages 13-19. На приеме пациент с функциональным билиарным расстройством. Особенности терапевтической коррекции. Пахомова И.Г.

Summary:

A patient with functional biliary disorder. Specificity of therapeutic management

I.G. Pakhomova


V.A. Almazov National Medical Research Center, St. Petersburg


In recent years, the dramatic growth of functional gastrointestinal disorders (including biliary tract disorders) has been reported. Numerous factors (e.g., unhealthy diet, obesity, psychogenic factors, etc.) account for this phenomenon. In addition, diagnostic armamentarium has significantly improved. Functional biliary disorders include gallbladder and sphincter of Oddi dysfunction. This paper describes diagnostic approaches and management in a woman with functional gallbladder disorder. A complex algorithm involving changes in diet, lifestyle, and psychology is of crucial importance. Antispasmodics are among first-line medications. They target cystic duct sphincter in gallbladder dysfunction and sphincter of Oddi in its dysfunction. Therefore, medications with a selective effect on the biliary tract should be prescribed to achieve the maximum effect and minimize adverse reactions of functional biliary disorder treatment. Hymecromone, which provides a selective antispasmodic effect on the sphincter of Oddi and cystic duct, is considered one of these agents.

Keywords: functional biliary disorder, gallbladder dyskinesia, biliary pain, antispasmodics, hymecromone.

For citation: Pakhomova I.G. A patient with functional biliary disorder. Specificity of therapeutic management. RMJ. 2022;3:13–19.

Pages 20-23. Современное понимание функции и дисфункции эндотелия сосудов. Обзор литературы. Юпатов Е.Ю., Курманбаев Т.Е., Тимошкова Ю.Л.

Summary:

Understanding endothelial function and dysfunction: state-of-the-art (a review)

E.Yu. Yupatov1, T.E. Kurmanbaev2, Yu.L. Timoshkova2


1Kazan State Medical Academy — Branch of the Russian Medical Academy of Continuous Professional Education, Kazan

2S.M. Kirov Military Medical Academy, St. Petersburg


Tissue metabolism, which directly depends on blood flow velocity, is crucial for the normal functioning of human and animal organisms. Endothelial cells have an essential role in tissue respiration and metabolism. These cells are characterized by unique reparative activity extensively involved in angiogenesis throughout life. Various endothelial cells have metabolic properties that determine their functions during angiogenesis when stimulated with growth factors. Hypoxia is one of the principal stimulators of angiogenesis, thereby having a vital role in the pathogenesis of atherosclerosis and malignancies. Susceptibility to damaging factors accounts for endothelial dysfunction with increased vascular permeability, cytokine and adhesion molecule synthesis, generation of pro-thrombotic environment, and cell dedifferentiation. The result is organ dysfunction. Endothelial dysfunction is the critical element of many disorders, e.g., preeclampsia, atherosclerosis, and COVID-19 complications. This paper reviews current data on endothelial metabolism, involvement in angiogenesis, and the role of endothelial dysfunction in the COVID-19 pathogenesis.

Keywords: endothelium, angiogenesis, endothelial dysfunction, hypoxia, glycolysis, COVID-19.

For citation: Yupatov E.Yu., Kurmanbaev T.E., Timoshkova Yu.L. Understanding endothelial function and dysfunction: state-of-the-art (a review). RMJ. 2022;3:20–23.

Pages 24-27. Мифы и реальность терапии статинами: ответы на самые актуальные вопросы. Сергиенко И.В.

Summary:

Myths and reality of statin therapy: answers to most pressing issues

I.V. Sergienko


National Medical Research Center of Cardiology, Moscow


Today, cardiovascular diseases (CVD) are the leading cause of mortality and disability worldwide. According to the WHO, mortality from CVD was 17.9 million (32% of all deaths worldwide) in 2019. According to the international and Russian guidelines, statins are the mainstay of medical treatment in high-risk patients and patients with established atherosclerotic CVD. Statins have numerous beneficial effects. However, in Russia and elsewhere, adherence to lipid-lowering therapy is low. These drugs receive unfounded criticism from the media and even some practitioners. The arguments against statin therapy include potential side effects. Since the efficacy and safety of these medications are clear, while the information on adverse effects is not mostly consistent with facts, we provide a scientific analysis of the efficacy and safety of lipid-lowering therapy, in particular, an original member of this class of drugs, atorvastatin.

Keywords: statins, cardiovascular diseases, hyperlipidemia, statin-associated muscle symptoms, cognitive disorders, safety.

For citation: Sergienko I.V. Myths and reality of statin therapy: answers to most pressing issues. RMJ. 2022;3:24–27.

Pages 28-33. Анализ влияния длительной нормализации гликемического контроля на течение субклинической диабетической периферической нейропатии у пациентов с сахарным диабетом 2 типа. Фокина А.С., Зилов А.В., Строков И.А., Демура Т.А., Сурнина З.В., Фадеев В.В.

Summary:

Analysis of the effect of long-term glycemic control on the course of subclinical diabetic neuropathy in type 2 diabetes

A.S. Fokina1, A.V. Zilov1, I.A. Strokov1, T.A. Demura1, Z.V. Surnina2, V.V. Fadeev1

1I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

2Scientific Research Institute of Eye Diseases, Moscow

Background: distal symmetrical polyneuropathy (DSP) is the most common neurological complication of diabetes from the peripheral nervous system. DSP is a significant social medical issue due to a significant reduction in the duration and quality of life of patients with diabetes.

Aim: to assess the possibility of reversing the impairment of peripheral nerve fibers identified by up-to-date diagnostic techniques in patients with type 2 diabetes (T2D) and subclinical DSP in the setting of long-term (over 5 months) improvement of glycemic control.

Patients and Methods: electrophysiological, morphological, and morphometric parameters of peripheral nerve fibers in patients with T2D and subclinical DSP (n=40) were compared at baseline and after 5 months in the setting of the reduction and maintenance of target glycemia (HbA1c≤6.5%). Subclinical DSP was established by electroneuromyography. Punch crus skin b iopsy and immunohistochemistry of nerve fiber density (PGP 9.5 staining) were performed to assess thin nerve fibers and vascular supply of skin. Confocal laser scanning microscopy using the authors’ algorithm of data processing was performed to assess thin nerve fibers of the cornea.

Results: in patients with T2D and subclinical DSP, reduction and maintenance of target glycemia (HbA1c≤6.5%) over a 5-month period increased the sural sensory nerve action potential (р=0.010), significantly improved of skin flap morphology (p=0.025), increased the density of intradermal nerve fibers by 1.5 times (p=0.004) and the number of intradermal vessels per unit area (p=0.007), and decreased thin corneal nerve tortuosity (p≤0.05).

Conclusion: in T2D, a complex evaluation of the peripheral nervous system is needed in the early stages to detect subclinical DSP and avoid further complications. The improvement and maintenance glycemic control over a 5-month period resulted in reliable positive ch anges in small and, more importantly, large nerve fibers.

Keywords: type 2 diabetes, glycemic control, diabetic neuropathy, electroneuromyography, skin biopsy, confocal laser scanning microscopy.

For citation: Fokina A.S., Zilov A.V., Strokov I.A. et al. Analysis of the effect of long-term glycemic control on the course of subclinical diabetic neuropathy in type 2 diabetes. RMJ. 2022;3:28–33.

Pages 34-39. Возможности флувоксамина в терапии COVID-19 и постковидного синдрома. Петров В.А., Максимов М.Л., Звегинцева А.А.

Summary:

Fluvoxamine capabilities in the therapy of COVID-19 and post-COVID syndrome

V.A. Petrov1, M.L. Maximov2–4, A.A. Zvegintseva3

1A. Tsyb Medical Radiological Research Centre — Branch of the National Medical Research Radiological Centre, Obninsk

2Russian Medical Academy of Continuous Professional Education, Moscow

3Kazan State Medical Academy — Branch of the Russian Medical Academy of Continuous Professional Education, Kazan

4Pirogov Russian National Research Medical University, Moscow

Amid a decrease in the COVID-19 incidence, the severity of its course and mortality, and the patient management with post-COVID syndrome remains relevant. Currently, the post-COVID symptoms include fatigue, pain (myalgia and arthralgia), reduced physical strength and endurance, performance capability, life quality, and daily activity. Common mental manifestations are anxiety disorders, depression, emotional stress, the development mechanism of which may be different: direct viral neurotropic effect, cytokine imbalance. The pharmacotherapy of post-COVID syndrome may include anti-inflammatory drugs, painkillers, psychopharmaceuticals, neurocytoprotectors, antiplatelet agents and anticoagulants, vitamins. Fluvoxamine, according to various trials, can be used not only during the early rehabilitation, providing a direct psychotropic effect but also as an antiviral drug for the treatment and prevention of severe COVID-19 course, which also has an anti-inflammatory, antiplatelet and immunomodulatory effect. The article determines the criteria that the patient must meet to start fluvoxamine therapy.

Keywords: new coronavirus infection, COVID-19, prevention, treatment, post-COVID syndrome, antidepressant, antiplatelet, anti-inflammatory effect, fluvoxamine, rehabilitation, pharmacotherapy, psychotropic effect.

For citation: Petrov V.A., Maximov M.L., Zvegintseva A.A. Fluvoxamine capabilities in the therapy of COVID-19 and post-COVID syndrome. RMJ. 2022;3:34–39.

Pages 4-8. Результаты исследования по оценке клинической эффективности специализированных продуктов для диетического лечебного питания больных фенилкетонурией детей, взрослых и беременных женщин линейки «Нонфеник®». Семенова Н.А., Шестопалова Е.А., Байдакова Г.В., Жукова Т.П., Ратникова С.Ю., Зайцева Е.С., Нургалиева Л.Р., Куцев С.И.

Summary:

Clinical efficacy of "Nonphenic", a line of specialty foods for nutritional care in children, adults, and pregnant women with phenylketonuria: study results

N.A. Semenova1, E.A. Shestopalova1, G.V. Baydakova1, T.P. Zhukova2, S.Yu. Ratnikova2, E.S. Zaytseva2, L.R. Nurgalieva3, S.I. Kutsev1


1Research Center for Medical Genetics, Moscow, Russian Federation

2V.N. Gorodkov Ivanovo Research Institute for Maternity and Childhood, Ivanovo, Russian Federation

3Republican Medical Genetic Center, Ufa, Russian Federation


Background: phenylketonuria (PKU) was the first hereditary metabolic disease for which high diet efficacy preventing its symptoms was demonstrated. A low-protein diet and specialty foods lacking phenylalanine should be prescribed as early as possible to control plasma PKU levels. PKU treatment is challenging due to low adherence to the diet. New specialty foods were introduced to improve the quality of medical care for PKU.

Aim: to assess the efficacy of specialty foods for nutritional care in children, adults, and pregnant women with PKU.

Patients and Methods: open-label, multicenter, prospective approbation was performed in outpatient facilities. The study included 60 patients. Nine patients received "Nonphenic®-13˝ designed for children under one year. Six patients received "Nonphenic®-20˝ designed for children aged 1–3 years. Nineteen patients received "Nonphenic®-40˝ designed for children aged 3–7 years. Eighteen patients received "Nonphenic®-70˝ designed for children over seven years. Eight patients received "Nonphenic®-75˝ designed for children over seven years, adults, and pregnant women. The treatment duration was 30±2 days. Clinical efficacy and safety were evaluated according to the Good Clinical Practice principles and based on clinical and laboratory findings.

Results: mean PKU levels reduced (significantly in patients who received "Nonphenic®-70˝ and "Nonphenic®-75˝) and were within safe ranges. Tyrosine levels were similar at the first and second visits and were within normal ranges. Parents and physicians were completely satisfied with the study products. Moreover, parents reported rapid adaptation to the novel food. No serious adverse events related to the study product which required treatment cancellation were reported during clinical approbation.

Conclusions: this study has demonstrated the clinical efficacy and safety of specialty foods for nutritional care in children, adults, and pregnant women with PKU.

Keywords: phenylketonuria, specialty foods for nutritional care, phenylalanine, diet therapy.

For citation: Semenova N.A., Shestopalova E.A., Baydakova G.V. et al. Clinical efficacy of ˝Nonphenic˝, a line of specialty foods for nutritional care in children, adults, and pregnant women with phenylketonuria: study results. RMJ. 2022;3:4–8.

Pages 40-42. Терапия остеоартрита у пациентов с недифференцированной дисплазией соединительной ткани. Клестер Е.Б., Плинокосова Л.А.

Summary:

Therapy for osteoarthritis in undifferentiated connective tissue dysplasia

E.B. Klester, L.A. Plinokosova

Altay State Medical University, Barnaul

Aim: to assess the efficacy and tolerability of AMBENE® Bio for knee osteoarthritis secondary to undifferentiated connective tissue dysplasia.

Patients and Methods: this study enrolled 150 women with established gonarthrosis (Kellgren–Lawrence grade 1–2) secondary to undifferentiated connective tissue dysplasia (median age 45.7 years, median disease duration 3.2 years) who received NSAIDs and AMBENE® Bio. Monthly monitoring included physical examination, assessment using visual analogue scale (VAS) and self-assessment (WOMAC) over a 12-month period.

Results: after one month of treatment, pain severity at rest and movement-evoked pain severity measured by VAS decreased in 73.33% and 62% of women, respectively. The WOMAC score reduced from 27.57±6.35 to 6.12±1.35 (p<0.01). Six months after completion the first treatment course, pain severity increased, i.e., overall WOMAC score significantly increased to 17.32±2.12 (p<0.01). Repeated treatment course with AMBENE® Bio reduced pain severity at rest and movement-evoked pain severity measured by VAS reduced in 88% and 74% of women. Overall WOMAC score reduced to 4.12±1.01 (p<0.01). Six months after re-treatment course with AMBENE® Bio, pain at rest and movement-evoked pain reappeared only in 15.33% and 30% of women, respectively (measured by VAS). Overall WOMAC score was 8.14±1.78 (p<0,01).

Conclusion: AMBENE® Bio reduces pain severity and need for NSAIDs. Re-treatment courses improve symptoms and prolong remission.

Keywords: undifferentiated connective tissue dysplasia, osteoarthritis, gonarthrosis, chondroprotectors, visual analogue scale, WOMAC, osteoarthritis treatment, non-steroidal anti-inflammatory drugs.

For citation: Klester E.B., Plinokosova L.A. Therapy for osteoarthritis in undifferentiated connective tissue dysplasia. RMJ. 2022;3:40–42.

Pages 43-50. Остеоартроз фасеточных и реберно-поперечных суставов позвоночника как причина хронической боли в грудном отделе позвоночника. Яковлева Е.В., Баринов А.Н.

Summary:

Osteoarthrosis of facet and costotransverse joints is the cause of chronic thoracic back pain

E.V. Yakovleva1, A.N. Barinov2

1I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

2JSC Group of companies Medsi, Moscow


Osteoarthrosis (or osteoarthritis) is one of the most common causes of reduced working capacity and quality of life. Disorders of facet and costotransverse joints is considered to be one of the leading causes of chronic thoracic and thoracic back pain. The authors describe their experience with diagnosing and treating chronic thoracic back pain in 52 patients aged 30–68 years. Facet and costotransverse joint syndrome as the leading cause of thoracic back pain was identified in 12 patients (23.07%). Patients were informed of a favorable prognosis, received recommendations on physical activity, and were prescribed non-steroidal anti-inflammatory drugs and myorelaxants. Within a month, the clinically significant analgesic effect of this therapy was achieved in 13 patients (25%). Thirty-nine patients (75%) proceeded to treatment using interventional techniques. This study has demonstrated that the interdisciplinary approach is most effective to manage chronic thoracic back pain.

Keywords: osteoarthrosis, osteoarthritis, facet syndrome, musculoskeletal pain, myofascial pain syndrome, interventional therapy, cognitive behavioral treatment, rehabilitation, etoricoxib.

Pages 51-54. Постинсультная артропатия: опыт применения хондропротективной терапии. Антипенко Е.А., Седышев Д.В., Сорокина А.А.

Summary:

Post-stroke arthropathy: therapy experience using chondroprotective agents

E.A. Antipenko1, D.V. Sedyshev2, A.A. Sorokina2

1Volga Research Medical University, Nizhny Novgorod

2Nizhni Novgorod Regional Clinical Hospital named after N.A.Semashko, Nizhny Novgorod

Aim: to evaluate the efficacy of AMBENE®BIO use as part of complex rehabilitation of painful shoulder joint in post-stroke arthropathy.

Patients and Methods: 52 patients with painful arthropathy of the shoulder joint were included in the follow-up in the early period of ischemic stroke. All patients received a complex of rehabilitation actions conducted by a multidisciplinary rehabilitation team, including positioning, kinesiotherapy, physiotherapy, and occupational therapy. Adding that, they underwent basic therapy aimed at secondary prevention of stroke. Nonsteroidal anti-inflammatory drugs could not be used at this rehabilitation stage due to the contraindications. The main group (n=30) additionally received AMBENE®BIO intramuscularly 10 times a day. The following parameters in the main group and the comparison group were evaluated: severity of pain syndrome by using a visual analog scale (VAS), the movement amplitude in the shoulder joint, and the achievement of rehabilitation goals on days 7, 14, and 21 of follow-up.

Results: statistically significant expansion of the passive range of motion in the shoulder joint was observed in both groups starting from day 7 of follow-up concerning shoulder abduction, and starting from day 14 concerning shoulder flexion and extension. However, the increase in positive tendency was more definite in the main group. The expansion of the passive range of motion in the shoulder joint led to an increase in the rehabilitation potential of patients. Thus, it allowed to achieve the specified rehabilitation goals related to the patient self-care.

Conclusion: the inclusion of AMBENE®BIO in the rehabilitation complex in post-stroke arthropathy of the shoulder joint helps to reduce pain, expand the passive range of motion and increase the rehabilitation efficacy in this patient cohort.

Keywords: post-stroke arthropathy, painful shoulder syndrome, therapy with chondroprotective agents, post-stroke rehabilitation.

For citation: Antipenko E.A., Sedyshev D.V., Sorokina A.A. Post-stroke arthropathy: therapy experience using chondroprotective agents. RMJ. 2022;3:51–54.



Pages 55-57. Социально-эпидемиологические особенности чесотки у геронтологических больных. Тлиш М.М., Кузнецова Т.Г., Наатыж Ж.Ю., Ерохина Е.В.

Summary:

Social epidemiological pattern of scabies in gerontological patients

M.M. Tlish, T.G. Kuznetsova, Zh.Yu. Naatyzh, E.V. Erokhina


Kuban State Medical University, Krasnodar

Improving the quality and accessibility of preventive and rehabilitation care for elderly and senile patients is one of the primary goals of today’s healthcare. Limited self-care and mobility, multiple comorbidities, and social-economic volatility are relevant medical social factors predisposing to parasitic skin diseases in these age groups. In addition, age-related reduction in epidermal barrier reparation, immune dysfunction, and neurodegenerative disorders account for an atypical and severe course of infectious dermatoses, particularly in other somatic diseases. As a result, somatic comorbidities and dermatoses aggravate each other. This paper describes a scabies nidus in gerontological patients, addresses the epidemiological investigation results, and discusses significant aspects of scabies dissemination and course in these patients. Since scabies is currently a high-prevalent condition, the analysis of epidemiological locus and the areas of improving medical social care in elderly and senile patients are relevant for dermatology, gerontology, and related disciplines

Keywords: scabies, epidemiological focus, gerontological patients, interdisciplinary approach, medical social care, health care quality.

For citation: Tlish M.M., Kuznetsova T.G., Naatyzh Zh.Yu., Erokhina E.V. Social epidemiological pattern of scabies in gerontological patients. RMJ. 2022;3:55–58.



Pages 59-63. Киндлер-синдром — редкая форма врожденного буллезного эпидермолиза. Гаджимурадова К.М., Жукова О.В., Гаджимурадов М.Н., Алиева С.Н.

Summary:

Kindler syndrome: a rare type of inherited epidermolysis bullosa

K.M. Gadzhimuradova1, O.V. Zhukova2, M.N. Gadzhimuradov1, S.N. Aliyeva3

1Dagestan State Medical University, Makhachkala

2Moscow Research and Practical Center for Dermatovenereology and Cosmetology, Moscow

3Republican Dermatovenerologic Dispensary, Makhachkala

Kindler syndrome (KS) is a rare autosomal recessive inherited genodermatosis, which manifests as bullae on the skin and mucous membranes from birth. Pathognomonic symptom consists of a combination of photosensitivity, poikiloderma and skin atrophy with structural gum weakness. Diagnosis of KS is based on clinical data and a detailed family history. The article presents a clinical case of an 11-year-old male patient with KS, who suffers from the bullous elements in the oral area and nail deformities from infancy. Among the disease manifestations there are carious teeth, malocclusion, ankyloglossia, atrophic glossitis, skin photosensitivity, visual deterioration, dyspnea. Adding that, the patient family history and presented disease manifestations attracts attention. His father, uncle and grandmother suffer from inherited nail pathology — onychogryphosis, and his mother — severe skin photo sensitivity. It can be assumed that recessive carriage of this gene may manifest as onychogryphosis, as well as cutaneous itching in response to sun exposure. The patient management with KS provides for symptomatic treatment, the creation of a safe environment and regular follow-up by a dermatologist and related specialists.

Keywords: inherited epidermolysis bullosa, Kindler syndrome, family history, poikiloderma, recessive gene.

For citation: Gadzhimuradova K.M., Zhukova O.V., Gadzhimuradov M.N., Aliyeva S.N. Kindler syndrome: a rare type of inherited epidermolysis bullosa. RMJ. 2022;3:59–63.

Pages 64-69. Медицинские и правовые аспекты соблюдения клинических рекомендаций Минздрава России в амбулаторно-поликлинической практике (интервью с экспертами).

Pages 9-12. Стеатогепатоз и стеатогепатит у детей с ожирением: терапевтические подходы. Звягин А.А., Фатеева Н.Ю., Чубаров Т.В., Жданова О.А.

Summary:

Steatohepatosis and steatohepatitis in overweight children: therapeutic methods

A.A. Zvyagin, N.Yu. Fateeva, T.V. Chubarov, O.A. Zhdanova


Voronezh State Medical University named after N.N. Burdenko, Voronezh


The article presents data on the treatment of non-alcoholic fatty liver disease (NAFLD), commonly presented in overweight children (up to 77%). This pathology is based on the lipid accumulation in hepatocytes and the cell death in the liver with progressive inflammation, apoptosis and fibrosis. NAFLD includes several forms: steatosis, steatohepatitis, fibrosis. Steatosis and steatohepatitis are reversible stages in complex therapy. Since these pathological conditions in most cases are associated with overweight or obesity, the treatment of children with this pathology includes both non-drug methods (lifestyle modification, diet therapy, physical activity) and the use of different pharmacological drugs, biologically active substances with antioxidant effects (omega-3, omega-6 fatty acids, α-tocopherol, docosahexagenoic acid, choline, astaxanthin). The best known drugs for non-alcoholic steatohepatosis and steatohepatitis are preparations with ursodeoxycholic acid (UDCA). These preparations can become a promising group to treat various NAFLD forms because of their hepatoprotective, choleretic, cholelitholytic, hypocholesterolemic effect in combination with diet therapy and physical activity.

Keywords: steatohepatosis, steatohepatitis, non-alcoholic fatty liver disease, children, ursodeoxycholic acid, treatment, children.

For citation: Zvyagin A.A., Fateeva N.Yu., Chubarov T.V., Zhdanova O.A. Steatohepatosis and steatohepatitis in overweight children: therapeutic methods. RMJ. 2022;3:–12.



№1, 2022. Эндокринология

Pages 15-19. Структурные и функциональные особенности изменения миокарда в патогенезе диабетической кардиомиопатии при сахарном диабете 1 типа. Гольдшмид А.Е., Балакшина Н.А., Еремина Ю.С., Полубояринова И.В., Фадеев В.В.

Summary:

Structural and functional patterns of myocardial changes in the pathogenesis of diabetic cardiomyopathy in type 1 diabetes mellitus

A.E. Goldshmid, N.A. Balakshina, Yu.S. Eremina, I.V. Poluboyarinova, V.V. Fadeev


I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow


Cardiovascular diseases (CVD) are the main cause of fatal outcome in patients with type 1 diabetes mellitus (DM). The definition of diabetic cardiomyopathy includes structural and functional changes in the myocardium (in diabetes without manifestations of coronary heart disease (CHD) or hypertension), due to which it is difficult to isolate the diabetic cardiomyopathy. DM causes endothelial dysfunction and early atherosclerosis. At the same time, hyperglycemia does not affect the left ventricular ejection fraction, and the presence of hypertrophy is an optional sign for ventricular dysfunction. It is unclear whether diabetes affects myocardial function without late complications. DM leads to a decrease in myocardial glucose uptake and glucose oxidation. Due to this, it results in cardiovascular performance reduction, energy generation and loss of "metabolic fl exibility". Insulin resistance in DM is one of the pathogenesis links and may be an important therapeutic target. In patients with DM, the increased risk of CVD development is underestimated. There are also no tools for stratification and prevention of CVD.

Keywords: diabetes mellitus, cardiovascular diseases, ventricular dysfunction, diabetic cardiomyopathy, hyperglycemia, endothelial dysfunction, atherosclerosis.

For citation: Goldshmid A.E., Balakshina N.A., Eremina Yu.S. et al. Structural and functional patterns of myocardial changes in the pathogenesis of diabetic cardiomyopathy in type 1 diabetes mellitus. RMJ. 2022;1:15–19.



Pages 2-2. Слово редактора. Зилов А.В.

Pages 20-25. Преимущества ингибирования натрий-глюкозного котранспортера 1 типа в повседневной клинической практике. Малолеткина Е.С., Фадеев В.В.

Summary:

Benefits in inhibition of sodium-glucose cotransporter-1 in clinical practice

E.S. Maloletkina, V.V. Fadeev


I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a relatively new class of drugs used for the treatment of type 2 diabetes mellitus (DM2). Using SGLT-2 inhibitors in clinical practice is of interest not only to endocrinologists but also to doctors of related specialties. The article presents a review of studies on the efficacy and safety of a drug from the SGLT-2 inhibitors group — canagliflozin. Canagliflozin has an additional double insulin-independent mechanism of action relative to other representatives of SGLT-2 inhibitors class. It is associated with the inhibition of not only SGLT-2 in the kidneys but also SGLT-1 in the intestine and kidneys, which can contribute to better control of glycemia level, including postprandial glucose. In clinical studies, canagliflozin has proven its efficacy in reducing the risk of adverse cardiovascular events, as we ll as the risks associated with heart failure in patients with DM2. The presented nephroprotective properties of canagliflozin formed the basis of a registered indication to reduce the risk of renal and cardiovascular outcomes in patients with DM2 and diabetic nephropathy. The favorable safety and tolerability profile of the drug allows its widespread use in patients with DM2.

Keywords: sodium-glucose cotransporter-2 inhibitors, diabetes mellitus, nephropathy, nephroprotection, cardiovascular events, heart failure.

For citation: Maloletkina E.S., Fadeev V.V. Benefits in inhibition of sodium-glucose cotransporter-1 in clinical practice. RMJ. 2022;1:20–25.



Pages 26-30. Опухоли щитовидной железы, микроэлементы, ожирение и инсулинорезистентность: есть ли взаимосвязь?. Квиткова Л.В., Халимова А.С.

Summary:

Is there any correlation between thyroid cancer, microelements, obesity, and insulin resistance?

L.V. Kvitkova, A.S. Khalimova

Kemerovo State Medical University, Kemerovo

In recent years, the prevalence of thyroid nodules has been growing. The role of external factors provoking thyroid carcinogenesis (e.g., exposure of carcinogens and mutagens, oxidative stress, etc.) is established. The role of the abnormalities of microelement content in the human body, obesity, high insulin concentrations, and insulin resistance in inducing oncogenic signal pathways in thyroid cells is currently studied. This paper reviews the role of microelement imbalance, imbalanced nutrition, obesity, and insulin resistance in the development of thyroid cancer. Intake of food supplements containing microelements and elimination of microelement imbalance are assumed to prevent thyroid cancer, given their crucial role in thyroid carcinogenesis. However, these issues are to be clarified. The authors discuss the favorable effect of metformin on thyroid functions in patients with insulin resistance and hypothyroidism since metformin is known to protect from cancer by inhibiting proliferation and carcinogenesis and regulating cellular aging and apoptosis. Metformin provides both direct and indirect anticancer effects. Further studies on these medications are needed to clarify their therapeutic and preventive role in thyroid carcinogenesis.

Keywords: carcinogenesis, obesity, insulin resistance, abnormal microelement content, metformin.

For citation: Kvitkova L.V., Khalimova A.S. Is there any correlation between thyroid cancer, microelements, obesity, and insulin resistance? RMJ. 2022;1:26–30.



Pages 3-8. Клиническая значимость патогистологического исследования при остеомиелите костей стопы у пациентов с диабетической остеоартропатией. Бурлева Е.П., Бабушкина Ю.В., Зайцева Л.Н.

Summary:

Clinical relevance of histopathology in foot osteomyelitis in diabetic osteoarthropathy

E.P. Burleva1, Yu.V. Babushkina2, L.N. Zaytseva1


1Ural State Medical University, Yekaterinburg

2Sverdlovsk Regional Clinical Hospital No. 1, Yekaterinburg

Aim: to assess the clinical relevance of osteomyelitis histopathology in diabetic osteoarthropathy.

Patients and Methods: clinical data of 17 patients with osteomyelitis in diabetic osteoarthropathy and histological samples collected during surgical resection were studied. At baseline, all patients were divided into three groups. Group 1 included 12 patients with acute osteomyelitis or its flare-up. Group 2 included 2 patients with quiescent chronic osteomyelitis. Group 3 included 3 patients with diabetic osteoarthropathy and soft tissue infection. Middle and posterior portions of the foot were predominantly affected (n=16). Standard histopathology with H&E stain and van Gieson’s stain was performed. Semi-quantitative assessment of samples using the Histopathological Osteomyelitis Evaluation Score (HOES), its sensitivity, specificity, the positive and negative prognostic value was determined. Clinical diagnoses and morphological reports were compared.

Results: two groups of conditions were isolated based on histopathology, i.e., osteomyelitis in diabetic osteoarthropathy (n=14: chronic osteomyelitis, n=13, and acute osteomyelitis, n=1) and diabetic osteoarthropathy without osteomyelitis (n=3). A description of these processes was provided. Articular cartilage lesions (e.g., dystrophy, thinning, and cracks) were diabetic osteoarthropathy hallmarks. Osteonecrosis, bone remodeling, and fibrosis were typical for diabetic osteoarthropathy and osteomyelitis. Cellular infiltration with lymphocytes and polymorphonuclear leukocytes (characteristic of infections) was also seen at the inflammatory phase of diabetic osteoarthropathy. Significant neutrophil infiltration of the bone marrow was a relevant morphological criterion of acute osteomyelitis in diabetic osteoarthropathy (n=1). Meanwhile, no relevant criteria for chronic (even active) osteomyelitis were identified. HOES sensitivity was 68.4%, specificity 20%, positive prognostic value 64.7%, and negative prognostic value 11.8%.

Conclusion: given similar histopathology (particularly in chronic osteomyelitis), the histopathological report cannot be considered a single criterion to verify osteomyelitis in diabetic osteoarthropathy. Both histopathology and HOES should be used to assess retrospectively non-invasive diagnostic tools for diabetic osteoarthropathy and osteomy elitis in diabetic osteoarthropathy.

Keywords: diabetic osteoarthropathy, osteomyelitis, histopathology, morphological diagnosis, Histopathological Osteomyelitis Evaluation Score.

For citation: Burleva E.P., Babushkina Yu.V., Zaytseva L.N. Clinical relevance of histopathology in foot osteomyelitis in diabetic osteoarthropathy. RMJ. 2022;1:3–8.

Pages 31-35. Методы оценки злокачественного потенциала узлов щитовидной железы. Соломадин Ю.С., Сыч Ю.П., Фадеев В.В.

Summary:

Methods for assessing the malignant potential of thyroid nodes

Yu.S. Solomadin, Yu.P. Sych, V.V. Fadeev


I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

Thyroid cancer (TC) ranks first in prevalence among malignant neoplasms of the endocrine glands. It accounts for 0.5% in the total structure of oncological diseases and up to 5% among head and neck cancers. The main task of the specialist in identifying the thyroid node is to assess the prognosis of tumor mass using ultrasound, radionuclide and molecular genetic diagnostics. The combination of ultrasound, cytological and radiological characteristics of the node makes up its phenotypic image. Ultrasound is the method of choice in the diagnosis of thyroid nodes, which allows to determine the indications for a fine needle aspiration (FNA). According to the FNA results, the article gives a cytological conclusion in accordance with the Bethesda classification: the thyroid node is assigned to one of 6 categories. At the same time, the most difficult to assess the ris k of malignancy are Bethesda III and IV categories (follicular tumors). The risk of follicular tumor malignancy varies from 6% to 30%, which requires diagnostic hemithyroidectomy with histology of the biopsy specimen or the use of molecular genetic research methods (mutations in RAS/MAPK, BRAFV600E, TERT, and microRNA expression). MIBI scintigraphy (methoxyisobutylisonitrile, labeled with 99mTc-pertechnetate) is a promising test for the exclusion of malignancy in follicular tumors. This review is devoted to the methods concerning preoperative assessment of the malignancy of thyroid follicular tumors.

Keywords: thyroid, nodular goiter, TIRADS classification, scintigraphy, 99mTc-MIBI, review.

For citation: Solomadin Yu.S., Sych Yu.P., Fadeev V.V. Methods for assessing the malignant potential of thyroid nodes. RMJ. 2022;1:31–35.



Pages 36-40. Гипофосфатазия: семейный случай редкого заболевания. Романенко Е.С.

Summary:

Hypophosphatasia: a family rare disease

E.S. Romanenko

South Ural State Medical University, Chelyabinsk

Hypophosphatasia (HPP) is a rare hereditary disease characterized by a very diverse clinical manifestations, which hinders a timely diagnosis. The article presents a description of a family HPP — two brothers of the same family had the disease manifested in childhood. The first clinical symptoms began to appear in the first year of life. Clinical manifestations were typical for HPP: rickets-like lower limb deformities, muscle weakness, poor exercise tolerance, early tooth loss. The symptoms of the disease were observed from various organs and systems, which significantly affected the physical health and patients quality of life. Despite the typical clinical manifestations, the diagnosis of HPP was established in the older brother at the age of 6 years. Difficulties in the diagnosis led to a delayed prescription of therapy. It is possible to suspect HPP on the basis of a combination of disease clinical signs and chara cteristic changes according to X-ray examination. For differential diagnosis, it is necessary to determine the activity of alkaline phosphatase. The diagnosis is confirmed by the detection of a mutation in the ALPL gene based on the results of a molecular genetics. Early diagnosis of HPP is essential for the timely prescription of enzyme replacement therapy with asphotase alpha.

Keywords: hypophosphatasia, alkaline phosphatase, ALPL gene, stridor, enzyme replacement therapy, asphotase alpha.

For citation: Romanenko E.S. Hypophosphatasia: a family rare disease. RMJ. 2022;1:36–40.

Pages 41-45. Возможность влияния на многофакторность развития гликемии при сахарном диабете 2 типа комбинированным сахароснижающим препаратом. Зилов А.В., Фокина А.С., Фадеев В.В.

Summary:

Combined hypoglycemic agent impact on the multifactorial development of glycemia in type 2 diabetes mellitus

A.V. Zilov, A.S. Fokina, V.V. Fadeev


I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

The review discusses the issues concerning pancreatic islet cell dysfunction, the interaction of α-, β- and Δ-cells, the role of drugs that potentiate the incretin effect and their ability to affect the insulin resistance. Alogliptin, a typical representative of the DPP-4 inhibitors, increases the sensitivity of β-cells to the stimulating effect of food, elevating insulin secretion and inhibiting glucagon secretion. Pioglitazone is currently the main agonist of PPAR γ receptors. Its activity is aimed at increasing insulin sensitivity of muscles, liver, and adipose tissue. In recent years, both drugs have been well studied in the treatment of type 2 diabetes mellitus (DM2) in cardiovascular safety trials, as well as in non-alcoholic fatty liver disease and other conditions. The combination of these drugs significantly reduced HbA1c and fasting glycemia levels versus monotherapy in various groups of patients under the following terms: previously not receiving hypoglycemic drugs, previously receiving metformin, previously receiving a combination of metformin + pioglitazone. The presence of a finished dosage form of alogliptin + pioglitazone is convenient for patients, as it increases compliance with the treatment. This is one of the therapy options if there is intolerance or contraindications to metformin, or the next-line therapy if the use of metformin is ineffective in patients with DM2.

Keywords: alogliptin, pioglitazone, incretin effect, co mbination therapy, finished dosage form, insulin resistance.

For citation: Zilov A.V., Fokina A.S., Fadeev V.V. Combined hypoglycemic agent impact on the multifactorial development of glycemia in type 2 diabetes mellitus. RMJ. 2022;1:41–45.



Pages 9-14. Применение биосимиляров инсулиновых аналогов аспарт и лизпро в помпе. Саверская Е.Н., Елтышева Т.Э., Карпов Д.С., Коробкина М.П., Заикин П.Г.

Summary:

Biosimilars of aspart and lispro analogues in the insulin pump

E.N. Saverskaya1, T.E. Eltysheva2, D.S. Karpov2, M.P. Korobkina2, P.G. Zaikin2


1Moscow State University of Food Production, Moscow

2Pharm-Holding CJSC, St. Petersburg

Background: insulin biosimilars hold a firm place in the treatment of patients with diabetes mellitus who need insulin therapy. The requirements for conducting trial confirming the biosimilar bioequivalence at the preclinical and clinical stages are regulated, which improves the biosimilar quality. Of particular interest is the use of biosimilar insulin analogues in the insulin pump.

Aim: to assess the stability of the produced substances (insulin biosimilars) according to the following indicators: quantitative determination, impurity content, pH level, as well as the dosing accuracy, and the tendency to catheter occlusion when used in insulin pumps.

Patients and Methods: aspart (RinFast®) and lispro (RinLis®) biosimilars were studied using the following pumps: MiniMedTM 640G, MiniMed Paradigm REAL-Time (with continuous glucose monitoring) and Accu-Chek® Combo. Studies on the dosing accuracy and the tendency to catheter occlusion were conducted using gravimetric analysis for 72 hours. Quantitative content analysis of insulin, related impurities and those exceeding the molecular weight of lispro was conducted with liquid chromatography for 72 hours at five points.

Results: the study demonstrated the stability of the substances produced by such indicators as quantitative determination, impurity content and pH level. The dosing accuracy of the used insulin pumps with both drugs corresponded to the initial dosing accuracy stated by the manufacturer. During the test, there was no occlusion signal, i.e. there was no tendency to catheter occlusion for 72 hours, which is equal to the recommended interval for infusion line replacement.

Conclusion: the stability of substances proven in these studies allows the use of RinFast® and RinLis® in insulin pumps.

Keywords: biosimilars, lispro, aspart, pump, occlusion, flash monitoring, insulin therapy.

For citation: Saverskaya E.N., Eltysheva T.E., Karpov D.S. et al. Biosimilars of aspart and lispro analogues in the insulin pump. RMJ. 2022;1:9–14.





№2, 2022. Болезни дыхательных путей. Оториноларингология

Pages 11-15. Патогенетически значимые факторы риска прогрессирования впервые выявленного инфильтративного туберкулеза легких. Басиева О.З., Джагаева З.К., Кобесов Н.В., Малиев Б.М.

Summary:

Pathogenically important risk factors for the progression of newly diagnosed infiltrative pulmonary tuberculosis

O.Z. Basieva, Z.K. Dzhagaeva, N.V. Kobesov, B.M. Maliev

North Ossetia State Medical Academy, Vladikavkaz

Aim: to evaluate the role of certain pathogenic factors (i.e., endogenous intoxication, lipid peroxidation, and immune imbalance) in the progression of tuberculosis and the potential tools to manage them.

Patients and Methods: this prospective cohort study included 60 patients aged 25–60 years with newly diagnosed infiltrative pulmonary tuberculosis (TB). All participants were divided into two groups (30 patients each). Comparison group patients (18 women [60%], mean age 47.2±3.6 years) received standard anti-TB treatment. Study group patients (16 women [53.3%], mean age 44.7±3.25 years) additionally received Imunofan® (arginil-α-aspartil-lysil-valil-tyrosil-arginine), an immunoregulatory peptide (two series of 10–15 injections, 50 mg IM). Changes in clinical presentations, radiological findings, CBC parameters, indicators of intoxication, lipid peroxidation, antioxidant system, and immune functions were evaluated. Examinations were performed one and three months after starting treatment.

Results: infiltrative pulmonary TB is associated with significant alterations in homeostasis, e.g., endogenous intoxication, activation of lipid peroxidation and phospholipase, inhibition of antioxidant activity, and immune imbalance. These are important factors of TB progression. In patients with limited lung damage, the intensity of these predictors was minimal compared to patients with advanced disease associated with more severe and persistent impairments. The efficacy of standard anti-TB treatment was inadequate (less significant improvement in lab tests and lung tissue infiltration) .

Conclusions: immunoregulatory peptide as a part of complex treatment of newly diag-nosed infiltrative pulmonary TB at early stages provides a focused and relatively fast effect on pathogenically important alterations of homeostasis. Imunofan® improves infection course and helps eliminate the pathogen.

Keywords: tuberculosis, endotoxicosis, lipid peroxidation, phospholipase, antioxidant system, immunity.

For citation: Basieva O.Z., Dzhagaeva Z.K., Kobesov N.V., Maliev B.M. Pathogenically important risk factors for the progression of newly diagnosed infiltrative pulmonary tuberculosis. RMJ. 2022;2:11–15.

Pages 16-20. Эффект применения экстрамелкодисперсной комбинации беклометазон/формотерол на ранней стадии формирования модели ХОБЛ. Титова О.Н., Кузубова Н.А., Лебедева Е.С., Преображенская Т.Н.

Summary:

The effect of using an extrafine combination of beclomethasone/formoterol at an early stage of COPD model formation

O.N. Titova1, N.A. Kuzubova1, E.S. Lebedeva1, Т.N. Preobrazhenskaya2

1I.P. Pavlov First Saint-Petersburg State Medical University, St. Petersburg

2S.M. Kirov Military Medical Academy, St. Petersburg

Aim: to evaluate the effect of an extrafine combination of the glucocorticosteroid beclomethasone and the long-acting β2-adrenomimetic formoterol at an early formation stage of an experimental model of chronic obstructive pulmonary disease (COPD).

Patients and Methods: a COPD model was reproduced in rats using inhaled nitrogen dioxide 60-day exposure. Starting from the 16th day of exposure, the experimental group received daily inhalations of beclomethasone/formoterol, while the control group received a placebo. At the end of the 60-day exposure, the cellular composition and cytokine profile of bronchoalveolar lavage (BAL), the content of secretory IgA (SIgA) and surfactant proteins B and D (SP-B and SP-D) were determined. Histology of the lungs was performed.

Results: neutrophils, lymphocytes and proinflammatory mediators count significantly increased in the BAL of the control group. Pulmonary epithelium damage (areas of desquamation, dystrophy and atrophy, squamous metaplasia, goblet cell hyperplasia, the inverted ratio of the number of ciliated and g oblet cells, signs of pulmonary emphysema) was accompanied by a deterioration in its functional activity (SIgA, SP-B, SP-D). In the experimental group, the cellular and cytokine composition of BAL did not differ from the intact values. In the bronchial epithelium, there were no areas of exfoliated epithelial cells, denuded basement membrane, areas of dystrophy, atrophy, and squamous metaplasia. The ratio of ciliated and goblet cells corresponded to the norm (5:2). There were no signs of airway wall remodeling and emphysema. Secretory IgA and surfactant protein B and D count in BAL did not significantly differ from the values of the intact group.

Conclusion: the use of an extrafine combination of beclomethasone/formoterol (at the stage of initial structural damage to the respiratory tract caused by nitrogen dioxide poisoning) allowed to prevent excessive damage to the bronchoalveolar epithelium, significantly reduce the neutrophilic inflammation activity, preserve the immune func tion of the bronchial epithelium and prevent the morphofunctional picture formation of the COPD model (characteristic of animals that did not receive the treatment).

Keywords: COPD, beclomethasone/formoterol, extrafine combination, neutrophil, inflammation, small airway dysfunction, proinflammatory cytokines, surfactant proteins.

For citation: Titova O.N., Kuzubova N.A., Lebedeva E.S., Preobrazhenskaya Т.N. The effect of using an extrafine combination of  beclomethasone/formoterol at an early stage of COPD model formation. RMJ. 2022;2:16–20.

Pages 2-5. Заболеваемость бронхиальной астмой детей в Московской области: эпидемиологическая характеристика. Бокова Т.А., Карташова Д.А., Троицкая Е.В.

Summary:

The incidence of asthma in children of the Moscow region: epidemiological characteristics

T.A. Bokova1,2, D.A. Kartashova1, E.V. Troitskaya1

1M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow

2Pirogov Russian National Research Medical University, Moscow

Aim: to study the prevalence of asthma (A) in children of the Moscow region and the distribution peculiarities of incidence indicators depending on the age, gender and area of residence.

Patients and Methods: a descriptive epidemiological study was performed using data from the annual report forms of Federal Statistical Monitoring No. 12 «Information on the number of diseases registered in patients living in the service area of a medical institution» concerning the child population (including 0 to 17 years) for 2020.

Results: diagnosis of A (J45.0–45.9) registered in 17,757 children, which was 1.2% of the total child population in the region. Boys — 67%, girls — 33%. The total incidence of A was 116.5 per 10,000 children in the Moscow region. The average age of children with A was 11.6±3.86 years. The age at the time of diagnosis was 9.6±4.06 years. Atopic asthma (J45.0) (80.2%) was registered more commonly, while unspecified (J45.9) (17.4%), mixed (J45.8) (2.1%) and non-allergic (J45.1) (0.3%) were less common. The highest incidence rates of A per 10,000 children were registered in the following cities: Dubna (161.5), Zhukovsky (145.4), Shchelkovo (135.2) and Klin (133.0); the smallest — in Naro-Fominsk (37.0), Solnechnogorsk (31.7) and Chekhov (31.8). Atopic A was registered more commonly (62–99%) in all regions. The highest percentage of unspecified A was in the following cities: Khimki (35.9%), Naro-Fominsk (27.7%), Domodedovo (26.9%), Pushkino (24.8%), Orekhovo-Zuyevo (21.0%); the smallest — in Zhukovsky (0.4%), Dubna (0.5%). The mixed and non-allergic forms of A were registered less commonly and not in all regions.

Conclusions: the indicators concerning the general incidence of A are characterized by heterogeneity and a significant spread, which, along with differences in the diagnosis frequency of various disease forms, can be explained both by the environmental characteristics of the area of residence and a possible problem of hypo- or overdiagnosis, which requires further study and clarification.

Keywords: bronchial asthma, children, incidence, prevalence, environmentally caused diseases, differential diagnosis.

For citation: Bokova T.A., Kartashova D.A., Troitskaya E.V. The incidence of asthma in children of the Moscow region: epidemiological characteristics. RMJ. 2022;2:2–5.

Pages 21-24. Длительная кислородотерапия в лечении пациентов с дыхательной недостаточностью, обусловленной врожденным кифосколиозом. Кузубова Н.А., Титова О.Н., Склярова Д.Б., Александров А.Л.

Summary:

Long-term oxygen therapy in the treatment of patients with respiratory failure due to congenital kyphoscoliosis

N.A. Kuzubova, O.N. Titova, D.B. Sklyarova, A.L. Alexandrov

I.P. Pavlov First St. Petersburg State Medical University, St. Petersburg

Background: chest wall distortion in kyphoscoliosis leads to severe restrictive disorders, alveolar hypoventilation and pulmonary gas exchange abnormalities. The role of long-term oxygen therapy (LTOT) in kyphoscoliosis has not been sufficiently studied.

Aim: to determine the effect of LTOT on the clinical course, pulmonary gas exchange parameters and hemodynamics in patients with congenital kyphoscoliosis complicated by chronic respiratory failure (CRF).

Patients and Methods: 30 patients with congenital kyphoscoliosis and CRF (mean age 55.62±6.9 years) were examined. The patients were divided into 2 groups: group 1 — 20 patients with hypoxemia (partial pressure of oxygen in arterial blood (PaO2): 57.68±7.24 mm Hg) and hypercapnia (partial pressure of carbon dioxide in arterial blood (PaCO2): 52.8±of 6.96 mm Hg) treated with LTOT for 16 h per day at a flow rate of 3 L/min; group 2 — 10 patients with hypoxemia (PaO2: 55.92±6.67 mm Hg) and hypercapnia (PaCO2: 51.2±7.21 mm Hg) who did not receive LTOT. Echocardiography, spirometry, arterial blood gas test were performed at intervals of 1 year. The number of hospitalizations during the year was estimated.

Results: initially, patients from both groups had significant restrictive disorders in the lungs, hypertrophy and right heart dilatation, an increase of pulmonary artery systolic pressure (PASP) to 46.35±7.64 mm Hg, right ventricular diastolic dysfunction. LTOT helped to reduce the dyspnea severity, improve gas exchange: PaO2 was 72.68±7.24 mm Hg (p<0.05), PaCO2 — 40.8±5.25 mm Hg (p<0.05). In group 1, there was a decrease of PASP — 39.15±5.33 mm Hg (versus baseline, р<0.05), a decrease in the size and improvement in the right ventricular diastolic dysfunction (versus group 2 indicators, p<0.05). The number of hospitalizations during LTOT has significantly decreased.

Conclusion: LTOT use in patients with kyphoscoliosis and CRF helps to reduce the dyspnea severity, reduce the hospitalizations number, improve pulmonary gas exchange and cardiopulmonary hemodynamics.

Keywords: kyphoscoliosis, hypoxemia, long-term oxygen therapy, pulmonary hypertension, diastolic dysfunction, right ventricle.

For citation: Kuzubova N.A., Titova O.N., Sklyarova D.B., Alexandrov A.L. Long-term oxygen therapy in the treatment of patients with respiratory failure due to congenital kyphoscoliosis. RMJ. 2022;2:21–24.

Pages 25-30. Возможности применения топической антибактериальной терапии в оториноларингологической практике. Владимирова Т.Ю., Волов Н.В.

Summary:

The topical antibiotic therapy in ENT practice

T.Yu. Vladimirova1, N.V. Volov2

1Samara State Medical University, Samara 

2«Outpatient centre No.1», Samara

Aim: to evaluate the clinical efficacy of framycetin solution for intranasal use in the complex therapy of acute bacterial rhinosinusitis (moderate severity).

Patients and Methods: a prospective randomized controlled study included 80 patients (mean age 33.13±8.5 years) with acute bacterial rhinosinusitis. The study participants were randomly assigned to two groups of 40 people: main and control. Patients in both groups received standard therapy in accordance with current clinical guidelines. In the main group, in addition, topical antibacterial therapy with framycetin in the dosage form of a nasal spray 1.25% was prescribed. The effectiveness of the therapy was assessed on the basis of anterior rhinoscopy data (the severity of mucosal edema and the presence of discharge on a 10-point visual analogue scale, VAS), the results of the SNOT-22 questionnaire, and a 10-point VAS for determining the severity of the condition. The examination was carried out at the primary outp atient appointment with an otorhinolaryngologist and again after 5 and 10 days.

Results: during the study in both groups, a stable positive trend of complaints and clinical status was demonstrated, which persisted throughout the entire follow-up period. According to the results of the study, on the 5th day of therapy, the frequency of complaints, which were marked as the main ones by the majority of patients, in the main group was lower than in the control group, more than 2 times, and the severity of almost all the main symptoms in this group was 3 times less than in the control group. The complete absence of complaints after treatment in the main group was noted by 15% of the examined, in the control group — by 10%. At the same time, only in the control group remained 5% of patients who assessed their condition as severe. According to the data of anterior rhinoscopy, upon re-examination on the 5th day, the swelling of the nasal mucosa in the main group corresponded to 5.20 10.45 points versus 8.0±0.65 points in the control group, the presence of discharge – 7.10±0.45 points and 7,4±0,5 points, respectively, on the 10th day – 3.6±0.3 points and 4,7±0,52 points, 2.8±0.3 points and 3,6±0,6 points, respectively.

Conclusion: a drug based on framycetin spray has a positive effect on the dynamics of the course of acute bacterial rhinosinusitis, improves overall well-being by restoring nasal breathing, which indicates the expediency of its use in the complex therapy of acute bacterial rhinosinusitis.

Keywords: rhinosinusitis, difficulty in nasal breathing, topical therapy, framycetin, spray, quality of life.

For citation: Vladimirova T.Yu., Volov N.V. The topical antibiotic therapy in ENT practice. RMJ. 2022;2:25–30.



Pages 31-35. Симптоматическое лечение заложенности носа: повышение эффективности и безопасности топической терапии. Богомильский М.Р., Радциг Е.Ю., Пивнева Н.Д.

Summary:

Symptomatic treatment of nasal congestion: improving the efficacy and safety of topical therapy

M.R. Bogomilsky 1, E.Yu. Radtsig1, N.D. Pivneva2

1Pirogov Russian National Research Medical University, Moscow

2Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Moscow

Background: nasal congestion is one of the most common complaints in pediatric practice. To reduce the severity of the adverse events (nose burning sensation, dry nasal mucosa, etc.) after the use of topical decongestants (TDs) in acute rhinitis, it is proposed to additionally use products with regenerating, protective and moisturizing effects.

Aim: to evaluate the treatment efficacy and tolerability during uncomplicated acute rhinosinusitis with a combination of xylometazoline and a complex preparation based on hyaluronic acid, vitamin E and lemon essential oil (Olyfrin).

Patients and Methods: a prospective single-center continuous non-randomized comparative study included patients aged 3 to 18 years with symptoms of acute infectious rhinitis, who were randomly divided into 2 groups. In group 1, patients received TDs: nasal spray with xylometazoline and a complex preparation based on hyaluronic acid, vitamin E and lemon essential oil (in the form of a nasal spray); in group 2 — only xylometazoline TD. The duration of TD use for therapeutic purposes was 7 days. Group 1 continued to use the complex preparation from day 8 to day 30. The following actions were performed in each of the groups: complaints evaluation, a routine ENT examination on the day of inclusion in the study, on the 7th and 30th day from the treatment initiation, including recording the results (evaluated on a 10-point VAS scale) in the patient’s chart.

Results: on the 7th day from the treatment initiation, patients of both groups noted an improvement in their condition. However, only in group 1, the dry nasal mucosa, nasal crusting, and especially bloody boogers in the nasal cavity were statistically significantl y (p<0.05) less (in terms of detection frequency and severity) than in the group 2. Recurrent episodes of rhinitis from the 7th to the 30th day of treatment in the group 1 were recorded in 14 (35%) patients, in group 2 — 37 (93%) (p<0,001).

Conclusions: the use of preparations with protective, regenerating and antioxidant effect on the nasal mucosa in the treatment of acute rhinitis can significantly reduce the adverse evetns after TDs use and shorten the recovery period of the epithelium and nasal mucosa after the inflammatory process.

Keywords: acute rhinitis, decongestants, xylometazoline hyaluronic acid, tocopherol, dry nasal mucosa, relapse.

For citation: Bogomilsky M.R., Radtsig E.Yu., Pivneva N.D. Symptomatic treatment of nasal congestion: improving the efficacy and safety of topical therapy. RMJ. 2022;2:31–35.

Pages 36-40. Современные аспекты протезирования просвета гортани и трахеи после реконструктивных операций.  Кирасирова Е.А., Олтаржевская Н.Д., Хлыстова Т.С., Усова М.И., Лафуткина Н.В., Мамедов Р.Ф., Резаков Р.А., Кулабухов Е.В., Тютина С.И., Егорова Е.А.

Summary:

Modern aspects of larynx and trachea prosthesis after reconstructive surgery

E.A. Kirasirova1,2, N.D. Oltarzhevskaya3, T.S. Khlystova3, M.I. Usova1, N.V. Lafutkina1, R.F. Mamedov1, R.A. Rezakov1, E.V. Kulabukhov2, S.I. Tyutina1, E.A. Egorova1

1Clinical Research Institute of Otorhinolaryngology named after L.I. Sverzhevsky, Moscow

2Pirogov Russian National Research Medical University, Moscow

3Coletex LLC, Moscow

Background: one of the significant stages concerning patient management after reconstructive surgeries of larynx and trachea is the formed airway lumen prosthesis.

Aim: to evaluate the efficacy of the developed sodium alginate hydrogel for the larynx and trachea prosthesis in the treatment of patients with chronic cicatricial stenosis of the larynx and trachea and bilateral laryngeal paralysis.

Patients and Methods: in 2018–2021, 51 patients were examined and treated in the Department of Reconstructive Surgery of Hollow Neck Organs. 30 patients of the main group had the laryngeal and tracheal lumen prosthesis in the intra- and postoperative period using the developed hydrogel tampon. 21 patients of the control group had an elastic or Merocel tampon inserted into the laryngeal-tracheal lumen according to the standard procedure. The article pre sents conducted endoscopic and cytological studies to evaluate the larynx and tracheal prosthesis results with proposed tampon.

Results: according to endoscopy in the main group, there were no inflammatory phenomena after tampon removal and the beginning of epithelialization in the mucous membrane of the larynx and trachea was already established 7 days after surgery. The cytology of inflammatory touch smears was noted up to 5 days. Starting from 6 to 7 days, an inflammatory-regenerative cytogram was noted. According to the results of further follow-up, there was no restenosis of the laryngeal and tracheal lumen. Adding that, implanted allogeneic structures were not rejected. The long-term results of surgical treatment were satisfactory: there were no complications in the postoperative period, repeated surgeries were not required. In the control group, inflammatory phenomena of the postoperative area were observed for 7–12 days after tampon removal. Epithelization of the wounded area began 8 days after surgery. The cytogram with inflammatory activity persisted for 5–10 days after tampon removal from the laryngeal and tracheal lumen. There were complications in 5 patients developed from 2 weeks to 2 months, 4 of them required repeated surgical interventions.

Conclusion: the obtained preliminary data indicated the prospects of intra- and postoperative use of a sodium alginate h ydrogel tampon for prosthesis of the laryngeal and tracheal lumen.

Keywords: larynx, trachea, cicatrical stenosis, prosthesis, reconstructive surgery, sodium alginate.

For citation: Kirasirova E.A., Oltarzhevskaya N.D., Khlystova T.S. et al. Modern aspects of larynx and trachea prosthesis after reconstructive surgery. RMJ. 2022;2:36–40.



Pages 41-45. Выбор оптимального инструмента для хирургических вмешательств в полости носа. Карпищенко С.А., Рябова М.А., Улупов М.Ю., Шумилова Н.А., Тихомирова Е.К., Портнов Г.В.

Summary:

Choosing an optimal medical equipment for surgical interventions in the nasal cavity

S.A. Karpishchenko, M.A. Ryabova, M.Yu. Ulupov, N.A. Shumilova, E.K. Tikhomirova, G.V. Portnov


Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg

Modern rhinosurgery is characterized by the widespread introduction of minimally invasive endonasal endoscopic techniques using the latest technological solutions. Surgical manipulations in the nasal cavity must meet strict criteria of efficiency and safety. The development of native endoscopic, laser and electrical equipment has made it possible to conduct operations both in inpatient and outpatient conditions, which increases the requirements for comfort and painlessness of intervention. The possibility concerning simultaneous use of endoscopic techniques allows better visualization of the surgical site and reduces the risks of postoperative complications. It is no coincidence that various surgical methods in the nasal cavity (using laser and electronic radio-wave equipment) have become widespread. In this article, the most effective and safe surgical treatment methods for nasal cavity diseases  conducted with the help of laser and electrocautery are considered (the benefits of their use are also indicated). The author presents his experience of using laser and electrosurgical medical equipment in the treatment of chronic rhinitis, nasal synechiae, recurrent nosebleeds, vascular tumors of the nasal cavity. The importance of the correct exposure mode selection and strict compliance with the procedure regulations were emphasized, which reduces the risk of intra- and postoperative complications.

Keywords: rhinosurgery, laser, 0.97µm, 1.56 µm, 1.94 µm, electrocoagulation, electrocauter, monopolar, bipolar.

For citation: Karpishchenko S.A., Ryabova M.A., Ulupov M.Yu. et al. Choosing an optimal medical equipment for surgical interventions in the nasal cavity. RMJ. 2022;2:41–45.

Pages 46-49. Синдром назальной обструкции после перенесенной новой коронавирусной инфекции, вызванной штаммом «омикрон»(клиническое наблюдение). Кириченко И.М., Попадюк В.И., Козлова Н.С.

Summary:

Nasal obstruction after coronavirus infection caused by the omicron strain (clinical case)

I.M. Kirichenko1,2, Popadyuk V.I.1, N.S. Kozlova2


1Peoples’ Friendship University of Russia, Moscow

2ON CLINIC Arbat LLC, Moscow

The pandemic of the new coronavirus disease 2019 (COVID-19) preserves for over two years. During this period, according to the WHO statistics, over 260 million confirmed cases of COVID-19 have been registered, including more than five million deaths caused by COVID-19. The new SARS-CoV-2 Omicron virus is the most rapidly spreading variant that occurs in adults with SARS symptoms. Symptoms of ENT organ lesion, such as rhinorrhea, nasal obstruction, tickling sensation and sore throat, commonly come to the fore. In some cases, there can be an exacerbation of chronic ENT diseases, such as tonsillitis, sinusitis, otitis media. The transport function of the nasal mucosa and paranasal sinuses is disrupted. The combination of topical mucolytic therapy and light decongestants can improve drainage function and prevent the development of congested inflammation in the sinus, leading to nasal breathing improvement. The authors present their clinical case concerning exacerbation of chronic sinusitis after COVID-19 in a male patient with allergic rhinitis and structural changes in the nasal cavity.

Keywords: ARVI, COVID-19, omicron strain, mucolytic therapy, decongestant, sinusitis.

For citation: Kirichenko I.M., Popadyuk V.I., Kozlova N.S. Nasal obstruction after coronavirus infection caused by the omicron strain (clinical case). RMJ. 2022;2:46–49.

Pages 50-54. Местная терапия острого тонзиллофарингита. Карпищенко С.А., Колесникова О.М.

Summary:

Topical therapy of acute tonsillopharyngitis

S.A. Karpischenko, O.M. Kolesnikova

Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg

Sore throat and acute tonsillopharyngitis account for more than 2% and 5% of the causes of all outpatient seeking for primary care in adults and children, respectively. Bacterial infection can occur primarily or secondarily, as a result of the pathogenic microflora overlay during viral infection or by increasing the opportunistic microflora growth, in the ENT organs. Topical therapy is one of the key stages in the treatment of acute tonsillopharyngitis. The clinical recommendations recommend topical therapy in the form of rinses, orodispersible tablets and sprays. Topical therapy can be combined, including a stage of gargarism, which allows to mechanically wash off pathogens, formed plaque with pathogen accumulation and food particles (infection source of the already inflamed pharyngeal mucosa. When choosing antimicrobials for topical therapy, preference should be given to those with a low-resistance potential, as well as with a favorable safety profile. The authors cite a clinical case of a female patient with acute tonsillopharyngitis. The prescription of a topical antimicrobial agent (nitrofural) allowed to quickly alleviate the disease symptoms and prevent the use of a systemic antibacterial drug.

Keywords: acute tonsillopharyngitis, tonsillitis, antibiotic resistance, antibiotic therapy, nitrofural, clinical recommendations.

For citation: Karpischenko S.A., Kolesnikova O.M. Topical therapy of acute tonsillopharyngitis. RMJ. 2022;2:50–54.

Pages 6-10. Особенности течения внебольничной пневмонии, ассоциированной с SARS-CoV-2, у детей. Белых Н.А., Аникеева Н.А., Панферухина А.Ю., Фокичева Н.Н., Шилина С.А., Фалетров М.В., Федосеева Н.Ю., Майборода В.В., Горячев В.В., Соловьева О.А.

Summary:

Patterns of the community-acquired pneumonia course associated with SARS-CoV-2 in children

N.A. Belykh1, N.A. Anikeeva1, A.Yu. Panferukhina1, N.N. Fokicheva2, S.A. Shilina2

M.V. Faletrov2, N.Yu. Fedoseeva2, V.V. Mayboroda1, V.V. Goryachev2, O.A. Solovyova1

1Ryazan State Medical University, Ryazan

2City Clinical Hospital No. 11, Ryazan


Aim: to study the clinical and laboratory patterns of community-acquired pneumonia course associated with SARS-CoV-2 in children.

Patients and Methods: a study included 55 children (30 boys, 25 girls) hospitalized in City Clinical Hospital No. 11 (Ryazan) from April 2020 to March 2021 with an established diagnosis: COVID-19, community-acquired pneumonia.

Results: among the examined patients, there was a predominance of children over 12 years (61.8%). 32 (58.2%) patients had an intrafamilial transmission with laboratory-confirmed cases of COVID-19 in relatives. 17 (30.9%) patients had various comorbidities, mainly obesity, diseases of the cardiovascular and central nervous system. The main clinical manifestations in patients who underwent the follow-up were intoxication, respiratory tract lesions and gastrointestinal symptoms. In 63.6% of cases, lung damage corresponded to mild severity (CT-1). IgM antibodies to Mycoplasma pneumoniae were detected in 15 (27.3%) patients, and pathogens of different species (among which pneumococci were the dominant pathogens) were sown by bacteriologic culture technique when analyzing a throat swab in 29 (52.7%) children. At the same time, mixed mycoplasma pneumonia infection was registered in 6 (10.9%) cases. A direct correlation was revealed between the stage of lung dama ge and C-reactive protein level (r=0.31, p=0.019), ALT (r=0.30, p=0.05) and lactate dehydrogenase (r=0.27, p=0.05), as well as the presence of concomitant diseases (r=0.41, p=0.002). There was a positive trend in the condition of all patients during the ongoing therapy.

Conclusion: in SARS-CoV-2-associated pneumonia, concomitant respiratory infection of mycoplasma, pneumococcal and mixed (Mycoplasma pneumoniae) etiology was most commonly detected (16.4, 12.7 and 10.9%, respectively). A statistically significant positive correlation was found between the stage of lung damage and the presence of concomitant diseases, as well as a deviation from the norm of several laboratory parameters. In timely treatment, most patients had a favorable disease outcome.

Keywords: children, community-acquired pneumonia, new coronavirus infection, comorbid pathology, viral pneumonia, Mycoplasma pneumoniae, pneumococcal pneumonia.



№10, 2021. Клинические рекомендации и алгоритмы для практикующих врачей

Pages 11-20. Рандомизированное открытое многоцентровое сравнительное исследование терапевтической эффективности, безопасности и переносимости комплексного растительного препарата BNO 1030 при лечении легких форм COVID-19. Попович В., Кошел И., Хаман Ю., Лещак В., Малофийчук О., Капустина Н., Шевага И., Шевага О., Куницка Т.

Summary:

A randomized, open-label, multicentre, comparative study of therapeutic efficacy, safety, and tolerability of complex herbal drug BNO 1030 in the treatment of mild forms of COVID-19

V. Popovych1, I. Koshel2, Y. Haman3, V. Leschak3, O. Malofiichuk4, N. Kapustina4, I. Shevaga5, O. Shevaga5 , T. Kunytska1

1 Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine

2Institute of Postgraduate Education, National Medical University, Ivano-Frankivsk, Ukraine

3Uzhgorod National University, Uzhhorod, Ukraine

4Regional Clinical Hospital of Gerbachevsky, Ivano-Frankivsk, Ukraine

5Kamianets-Podilsky City Hospital, Kamianets-Podilsky, Ukraine

Background: COVID-19 is a high burden for medicine and society as still no specific therapy exists. Most patients depend on symptomatic treatment, comparable to that in common respiratory infection e.g. Many cases of COVID-19 show mild forms without need of hospitalization.

Aim: analyze the efficacy, safety, and tolerability of the herbal medicinal product BNO 1030 in mild cases of COVID-19 to offer an additional symptomatic relive.

Patients and Methods: the study was designed as an open label randomized, prospective, multicentred clinical trial. Out of 133 screened outpatients aged 18 to 70 with mild COVID-19 symptoms 120 patients were randomised (1:1) in 2 parallel groups. The main group received BNO 1030 (Tonsilgon® N) in addition to symptomatic therapy (acetaminophen or ibuprofen). The control group got a symptomatic therapy only. The patients with laboratory proven COVID-19 were included for the final analyses: 47 — in the main group and 46 — in the control one. The evaluation criteria were dynamics of the symptoms: hyperthermia, myalgia, nasal congestion, nasal discharge, coughing, anosmia, rhinolalia, sore throat, duration of the use of antipyretics (clinically significant fever). These symptoms were assessed during the physician’s visit on a 4-point scale and self- assessed via ten-point visual analogue scale (VAS) daily in a patient’s diary. The primary endpoint was the decrease of the average score compared to the baseline defined as "therapeutic benefit" from the usage of BNO 1030.

Results: in the comparison of both groups over the treatment time, the main group (n=47) showed a greater decrease in the severity of symptoms, assessed by the doctor on a 4-point scale on V2 (4th day) and V3 (14th day) compared to those on V1, as well as a reduction of the antipyretics intake duration (p<0.05). Significant differences of the main group were obtained, too, based on the results of symptoms self-assessment by the patient. The "therapeutic benefit" from the use of BNO 1030 was 3 days. There is an increase in the number of recovered patients from 73.9–96.6 %, and a decrease in the number of hospitalized patients from 8.6–4.4 % in the main group, as compared to the data of the control group (p<0.05). All patients tolerated the herbal medicine well. 

Conclusions: BNO 1030 offers a safe and effective treatment benefit in patients with mild forms of diagnosed COVID-19 aged 18–70 in addition to symptomatic treatment with acetaminophen or NSAIDs. COVID-19 positive patients treated with Tonsilgon® N showed an earlier relive of symptoms when being treated with BNO 1030.

Keywords: Phytotherapy, BNO 1030, Tonsilgon, mild COVID-19, coronavirus infection.

For citation: Popovych V., Koshel I., Haman Y. et al. A randomized, open-label, multicentre, comparative study of therapeutic efficacy, safety, and tolerability of complex herbal drug BNO 1030 in the treatment of mild forms of COVID-19. RMJ. 2021;10:11–20.

Pages 21-26. Респираторные инфекции сочетанной этиологии — особенности клинической картины, подходы к терапии. Николаева С.В., Каннер Е.В., Каннер И.Д., Лапкин Н.М., Горелов А.В.

Summary:

Respiratory co-infections: clinical presentations, treatment approaches

S.V. Nikolaeva1, E.V. Kanner1, I.D. Kanner2, N.M, Lapkin3, A.V. Gorelov1,4

1Central Research Institute of Epidemiology of the Russian Federal Service 

for Supervision of Consumer Rights Protection and Human Well-Being, Moscow

2Lomonosov Moscow State University, Moscow

3Yaroslavl State Medical University, Yaroslavl

4I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

Acute respiratory infections (ARIs) are still an important issue. They rank fifth among infectious and parasitic diseases. In Russia, ARIs are included in diseases with the highest economic relevance. Currently, co-infection is of particular importance. This paper addresses hypotheses that explain the role of dysbiosis (associated with the increased count of pathobionts) in the development of inflammation and reduction in epithelial integrity favoring viral invasion into upper airway mucosa. Three scenarios of the interaction of respiratory pathogens between each other (i.e., synergy, antagonism, or indifference), which account for predominant clinical presentations and disease course in co-infection, are described. The paper also discusses some clinical features of flu and SARS-CoV-2-infection and highlights symptoms typical for both disorders, allowing for differential diagnosis. Challenges in treating viral infections of the respiratory tract are accounted for by unreasonably freq uent use of systemic antibiotics that result in poor prognosis, increased risk of adverse reactions, and a growing number of antibiotic-resistant microbial strains. Finally, the use of medications stimulating the production of interferons, the critical element of antiviral defense, is substantiated.

Keywords: respiratory infections, co-infections, pathobionts, flu, SARS-CoV-2, therapy.

For citation: Nikolaeva S.V., Kanner E.V., Kanner I.D. et al. Respiratory co-infections: clinical presentations, treatment approaches. RMJ. 2021;10:21–26.



Pages 27-30. Ингибиторы протонной помпы — в фокусе полиморбидный пациент. Казюлин А.Н., Шиндина Т.С., Щербенков И.М., Архипова C.C.

Summary:

Proton pomp inhibitors: focus on a multimorbid patient

A.N. Kazyulin1, T.S. Shindina2, I.M. Shcherbenkov3, C.C. Arkhipova4

1A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow

2Polyclinics No. 5, Moscow

3Multidisciplinary Clinics "Center of Endosurgery and Lithotripsy", Moscow

4LLC "Universal", Moscow

This paper discusses the selection of a proton pump inhibitor (PPI) in multimorbid patients. In these patients, polypharmacy associated with high risks of cumulative adverse effects of drug interactions comes to the fore. The authors describe a woman with gastroesophageal reflux disease (GERD) and comorbid cardiovascular disease, metabolic syndrome, and diabetes. The diagnostic algorithm in the lack of therapeutic effect of PPIs is addressed. Polymorphism of genes encoding CYP2C19 and CYP3A4 isoenzymes is considered the cause of refractory GERD. Most likely, this woman belongs to so-called rapid metabolizers. Ineffective treatment is accounted for because metabolites of a prescribed PPI have shown no pharmacological activity. The authors uncover the mechanism of action of rabeprazole given cytochrome P450 gene polymorphisms, thereby preventing hydrochloric acid secretion effectively and making drug effects predictable. Clinical studies on drug interactions in multimorbid patients rec eiving rabeprazole are addressed. Rabeprazole is an effective and safe treatment modality in patients with GERD and comorbidities.

Keywords: rabeprazol, drug interactions, gastroesophageal reflux disease, polypharmacy, multimorbid patient, proton pomp inhibitors.

For citation: Kazyulin A.N., Shindina T.S., Shcherbenkov I.M., Arkhipova C.C. Proton pomp inhibitors: focus on a multimorbid patient. RMJ. 2021;10:27–30.



Pages 3-10. Вакцинотерапия вируса простого герпеса: от прошлого до настоящего — где мы? Обзор литературы. Мелехина Е.В., Солдатова Е.Ю., Музыка А.Д., Понежева Ж.Б.

Summary:

Vaccination of herpes simplex virus: past to present — where are we? Literature review

E.V. Melekhina, E.Yu. Soldatova, A.D. Musica, Zh.B. Ponezheva

Central Research Institute of Epidemiology of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow

The recurrent course of herpes simplex virus type 1 and 2 is an urgent medical and social problem. Nowadays, there are not many direct antiviral drugs in the arsenal of doctors that have proven efficacy against herpes viruses. Treatment of patients with recurrent herpes viruses is difficult due to the pathogenesis peculiarities and the ability of immune evasion. The use of etiotropic therapy can lead to resistance occurrence. In the current situation, the use of specific vaccines is an important issue in the treatment and prevention of recurrent herpes viruses. The literature review is devoted to herpes vaccine therapy with the given detailed description of various vaccine types. Information about the vaccination efficacy in the recurrent course of the herpes virus is contradictory. Thus, the efficacy of some vaccines shown in preclinical studies has not been confirmed in clinical trials. Also, clinical efficacy has been demonstrated for other vaccines. Promising directions in the treatment of herpesvirus infections are the development of improved therapy regimens using vaccines, recombinant interferons, and probiotics, which allow to quickly prepare the patient for the vaccine therapy onset, as well as to lengthen the period of subsequent remission.

Keywords: herpes simplex virus, herpesvirus infection, vaccination, vaccine therapy, genital herpes, labial herpes, ocular herpes.

For citation: Melekhina E.V., Soldatova E.Yu., Musica A.D., Ponezheva Zh.B. Vaccination of herpes simplex virus: past to present — where are we? Literature review. RMJ. 2021;10:3–10.



Pages 31-35. Случай распространенного эозинофильного поражения желудочно-кишечного тракта. Кузьмина А.В., Новожилов Н.В., Требушенков А.Ю., Буланов Д.В., Жамбеев А.А., Жиляев Е.В.

Summary:

Сase of common eosinophilic infiltrates of the gastrointestinal tract

A.V. Kuzmina1, N.V. Novozhilov1, A.Yu. Trebushenkov1, D.V. Bulanov1, A.A. Zhambeev1, E.V. Zhilyaev1-3

1European Medical Center, Moscow

2Pirogov Russian National Research Medical University, Moscow

3Russian Medical Academy of Continuous Professional Education, Moscow

Eosinophilic gastrointestinal disorders are a group of diseases characterized by dense eosinophilic tissue infiltration of various organs in the gastrointestinal tract, leading to morphological and functional disorders, such as eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis and eosinophilic colitis. The article presents a clinical case of a 17-year-old male patient with a common eosinophilic disease involving the esophagus, stomach, small and large intestines. The disease was manifested by nausea, vomiting, diarrhea and significant eosinophilia. The diagnosis was confirmed by laboratory and morphological data. The disease course was complicated by cervical lymphadenitis with phlebitis and jugular vein thrombosis, which regressed during antibacterial and anticoagulant therapy. Disease regression was achieved during treatment with ketotifen and medium doses of glucocorticoid. Based on the literature data, the authors discussed modern approaches to the diagnosis and treatment of eosinophilic diseases. The peculiarity of the case was the uncommon process spreading from the gastroesophageal junction to the cecum,  as well as an uncommon complication in the form of left-sided supraclavicular lymphadenitis occurrence, complicated by subclavian vein thrombosis and internal jugular vein thrombosis.

Keywords: eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enterocolitis, lymphadenitis.

For citation: Kuzmina A.V., Novozhilov N.V., Trebushenkov A.Yu. et al. Сase of common eosinophilic infiltrates of the gastrointestinal tract. RMJ. 2021;10:31–35.



Pages 36-40. Актуальные вопросы выбора базисной терапии остеоартрита. Елисеева Л.Н., Бочарникова М.И., Бледнова А.Ю., Жихарева О.А.

Summary:

Topical issues concerning the choice of basic therapy for osteoarthritis

L.N. Eliseeva, M.I. Bocharnikova, A.Yu. Blednova, O.A. Zhikhareva

Kuban State Medical University, Krasnodar

Aim: to retrospectively evaluate the efficacy and safety of diacerein in the treatment of patients with osteoarthritis.

Patients and Methods: the study involved 28 patients with gonarthrosis and 25 with grade 3–4 coxarthrosis included in the waiting list for total endoprosthesis replacement with an expected surgical intervention period of more than 3–4 months. Diacerein was prescribed at a dose of 50 mg once a day for the first 3–4 weeks, followed by an increase up to 50 mg 2 times a day. Analgesic efficacy was evaluated using a 100 mm visual analog scale (VAS). Safety was assessed by the presence of side effects (including from the gastrointestinal tract) and changes in laboratory parameters.

Results: the average age of patients with coxarthrosis was 62.2±3.4 years, patients with gonarthrosis — 60±4.6 years. The intensity of the pain syndrome, estimated by VAS in the initial state, was 68.3±11.3 mm in patients with coxarthrosis and 70.6±8.8 mm in patients with gonarthrosis. During therapy, the pain severity decreased to 56.0±10.2 and 42.1±9.3 mm, respectively. At the same time, the need for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) decreased from 92.0 to 64.0 % in patients with coxarthrosis and 92.86 to 85.71 % in patients with gonarthrosis. No side effects of diacerein were detected during the pre- and postoperative follow-up. When assessing glycemic and creatinine control with glomerular filtration rate, no changes were found during therapy.

Conclusion: the inclusion of diacerein in complex therapy makes it possible to refuse NSAIDs intake or significantly reduce their dosages while maintaining analgesic and anti-inflammatory effects. The absence of significant side effects and adverse events ensures the safety of diacerein in patients with osteoarthritis and comorbid conditions.

Keywords: osteoarthritis, comorbidity, diabetes me llitus, diacerein, SYSADOA, chondroprotectors.

For citation: Eliseeva L.N., Bocharnikova M.I., Blednova A.Yu., Zhikhareva O.A. Topical issues concerning the choice of basic therapy for osteoarthritis. RMJ. 2021;10:36–40.



Pages 42-43. COVID-19 и постковидный синдром: как сохранить и восстановить здоровье?.

Pages 44-48. Перипартальная кардиомиопатия: патогенез, клиника, диагностика, лечение, прогноз. Веселовская Н.Г., Чумакова Г.А., Николаева М.Г., Горбачева Н.С., Отт А.В.

Summary:

Peripartum cardiomyopathy: pathogenesis, presentations, diagnosis, treatment, and prognosis

N.G. Veselovskaya1,2, G.A. Chumakova1,2, M.G. Nikolaeva2,3, Gorbacheva2, A.V. Ott2

1Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo

2Altay State Medical University, Barnaul

3Altay Branch of the National Medical Research Center of Hematology, Barnaul

Peripartum cardiomyopathy (PPCM) is a myocardial disorder with left ventricular (LV) systolic dysfunction and clinical signs of heart failure that presents in late pregnancy through the first months after delivery in previously healthy women. An irreversible myocardial lesion with persistent LV failure and high-grade abnormal heart rhythm result in unfavorable outcomes in young women. Therefore, timely diagnosis and treatment for PPCM (that provides recovery in most cases) are essential.

In recent years, oxidative stress as a factor potentiating PPCM development has been studied. The pathogenic relevance of a 16-kDa N-terminal prolactin fragment that provides a toxic effect on myocardium and cardiomyocyte apoptosis is established. In addition, the placenta produces antiangiogenic factors during pregnancy, e.g., sol uble vascular endothelial growth factor receptor (sFlt-1). Its high concentrations provoke LV dysfunction during pregnancy. Some trials demonstrate the efficacy of pathogenic therapy with bromocriptine to improve myocardial contractility and disease outcome.

However, more studies on PPCM prevalence in various ethnic groups and regions, etiology, risk factors, optimal therapy (including bromocriptine), long-term outcomes, and treatment duration after LV functional recovery.

Keywords: peripartum cardiomyopathy, oxidative stress, heart failure, left ventricular dysfunction, cardiomyocytes, bromocriptine, pregnancy, prolactin, apoptosis.

For citation: Veselovskaya N.G., Chumakova G.A., Nikolaeva M.G. et al. Peripartum cardiomyopathy: pathogenesis, presentations, diagnosis, treatment, and prognosis. RMJ. 2021;10:44–48.



Pages 50-55. Диабетическая невропатия — междисциплинарная проблема в клинической практике. Екушева Е.В.

Summary:

Diabetic neuropathy: interdisciplinary problem in clinical practice

E.V. Ekusheva1,2

1Academy of Postgraduate Education of the Federal Scientific and Clinical Center of the Federal Medical Biological Agency of Russian Federation, Moscow

2Belgorod State University, Belgorod

Diabetic neuropathy is one of the most significant and common complications of diabetes mellitus (DM), leading to impairment, severe maladaptation, early disability and death. Diabetic neuropathy is a complex of polymorphic clinical and subclinical syndromes characterized by diffuse or focal lesion of the fibers in the peripheral and/or autonomous nervous system (as a result of metabolic, vascular and other disorders associated with DM) and has characteristic manifestations and course. The article discusses the clinical signs and variants of diabetic neuropathy course, and the issues of diagnosis and therapy of patients with this disease. To date, the only drug with proven efficacy for pathogenetic therapy of diabetic neuropathy is thioctic acid (α-lipoic acid), which serves as a powerful endogenous antioxidant and cofactor of the most important mitochondrial enzyme complexes involved in the oxidative metabolism processes. The article presents the review of studies, the results of which indicate the efficacy of thioctic acid, and also describes own clinical experience of thioctic acid use in patients with diabetic neuropathy. The importance of early diagnosis of diabetic neuropathy and timely complex therapy, including thioctic acid preparations, is emphasized, as it will significantly affect the severity and further progression of the pathological process in patient with DM.

Keywords: diabetes mellitus, diabetic neuropathy, diabetic polyneuropathy, neuropathic pain, α-lipoic acid, thioctic acid.

For citation: Ekusheva E.V. Diabetic neuropathy: interdisciplinary problem in clinical practice. RMJ. 2021;10:50–55.

Pages 57-62. Применение методов редактирования генома и генной терапии в лечении заболеваний человека. Птицина С.Н.

Summary:

Genome editing and gene therapy methods in the treatment of human diseases

S.N. Ptitsina

All-Russian Institute of Scientific and Technical Information of the Russian Academy of Sciences, Moscow

This review is devoted to one of the urgent problems of modern biomedicine — gene therapy of hereditary human diseases using new genetic technologies (genome editing systems, ZFN and TALEN nucleases, CRISPR-Cas9). The information from the databases of All-Russian Institute of Scientific and Technical Information of the Russian Academy of Sciences, SCOPUS, PubMed for 2015–2020 is analyzed. It is concerned both the general issues description of the new biotechnologies and disease models development, the use of various vectors, delivery systems, genetic engineering methods, and the successful application of the above technologies in the treatment of specific diseases. The article presents examples of modeling and therapy of neuromuscular, oncological, immunological, hematological and neurodegenerative human diseases. It also discusses the ethical issues that inevitably arise when editing the human genome. The results of the publication analysis from databases (All-Russian Institute of Scientific and Technical Information of the Russian Academy of Sciences, SCOPUS, PubMed for 2015–2020) provide an opportunity to generate new scientific and information products on the problems of medical genetics. It is expected that the data obtained will be useful to both geneticists and clinicians.

Keywords: hereditary diseases, biomedicine, genetics, gene therapy, methods, genome editing, CRISPR-Cas9 system, biotechnologies, databases.

For citation: Ptitsina S.N. Genome editing and gene therapy methods in the treatment of human diseases. RMJ. 2021;10:57–62.



Pages 63-68. Перспективы применения низкоинтенсивного лазерного излучения в иммунологии. Миславский О.В., Алексеев Ю.В., Федоскова Т.Г., Смирнов В.В., Иванов А.В., Маштакова С.Р.

Summary:

Prospects for the use of low-level laser radiation in immunology

O.V. Mislavsky1, Yu.V. Alekseev2, T.G. Fedoskova1, V.V. Smirnov1, A.V. Ivanov3, S.R. Mashtakova1,4

1National Research Center Institute of Immunology of the Russian Federal Medical Biological Agency, Moscow

2Skobelkin State Scientific Center of Laser Medicine of the Federal Medical and Biological Agency, Moscow

3N.N. Blokhin National Medical Research Center of Oncology, Moscow

4Laboratory of the Center of Immunology and Reproduction, Moscow

The article presents modern concepts concerning biological action mechanisms of low-level laser radiation, as well as experimental animal models and modern cell culture studies showing the efficacy of using devices (with power from 30 mW to 250–400 mW) for low-level laser therapy. The article also gives examples of effective clinical use of this therapy type, which affects the immune system of animals and humans.

To reduce allergic inflammation (based on the considered modelled cases on animals), it can be considered to study sources with a wavelength of 660 nm, whereas to reduce inflammatory activity — with a wavelength of 810, 830 and 904 nm. Sources with a wavelength of 1264 to 1270 nm are promising for further study of their therapeutic effects on an allergic patient.

Keywords: low-level laser therapy, laser biomodulation, primary radiation acceptors, light-oxygen effect.

For citation: Mislavsky O.V., Alekseev Yu.V., Fedoskova T.G. et al. Prospects for the use of low-level laser radiation in immunology. RMJ. 2021;10:63–68.





№9, 2021. Кардиология

Pages 1-5. Недостаточный ответ тромбоцитов на применение ацетилсалициловой кислоты и клопидогрела при ишемической болезни сердца после коронарной реваскуляризации. Является ли резистентность к антитромбоцитарным препаратам обратимой?. Мальцева А.Н., Гринштейн Ю.И.

Summary:

Lack of platelet response to the use of acetylsalicylic acid and clopidogrel in coronary heart disease after coronary revascularization. Is resistance to antiplatelet drugs reversible?

A.N. Maltseva1,2, Yu.I. Grinshtein1


1Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk

2I.S. Berzon Krasnoyarsk Interregional City Hospital No. 20, Krasnoyarsk


Cardiovascular pathology has occupied leading positions in the structure of morbidity and mortality for many decades. At the present stage of cardiology development, increasingly greater attention is paid to primary and secondary prevention. As part of therapy aimed at preventing the occurrence of both primary and recurrent cardiovascular events, the key place is occupied by antiplatelet drugs. However, despite modern therapy, the possibility of coronary revascularization remains the risk of adverse cardiovascular events. There are various causes of recurrent thrombosis, myocardial infarction, strokes, etc. One of the reasons is resistance to antiplatelet drugs, in particular, to acetylsalicylic acid and clopidogrel. In order to prevent this phenomenon, it is necessary to understand the mechanisms of its development and the factors contributing to its occurrence. This  article discusses clinical, molecular and cellular, metabolic, genetic and other patterns that may be the cause of this phenomenon in patients with coronary heart disease, including after coronary revascularization. The data on the causes of resistance reversibility and the expected predictors, used to predict and prevent the occurrence of cardiovascular accidents are presented.

Keywords: resistance, acetylsalicylic acid, clopidogrel, coronary revascularization, platelets, coronary artery disease, coronary artery bypass graft.

For citation: Maltseva A.N., Grinshtein Yu.I. Lack of platelet response to the use of acetylsalicylic acid and clopidogrel in coronary heart disease after coronary revascularization. Is resistance to antiplatelet drugs reversible? RMJ. 2021;9:1–5.



Pages 12-16. Основные подходы к профилактике поражения слизистой желудочно-кишечного тракта у кардиологических больных. Минушкина Л.О.

Summary:

Key preventive approaches to gastrointestinal mucosal injury in cardiological patients

L.O. Minushkina

Central State Medical Academy, Moscow

This paper reviews the aspects of the safety of antithrombotic therapy in cardiological patients. The most common antithrombotic agent used in cardiology is acetylsalicylic acid (ASA). Gastrointestinal (GI) mucosal injury and GI bleedings are relatively common in these individuals. Primary tools to prevent complications, i.e., gastric acid secretion inhibitors and coated ASA, are described. According to current guidelines, proton pump inhibitors (PPIs) are the primary tools to prevent GI tract injury and GI bleedings. In general, PPIs are effective in preventing upper GI tract damage. Therefore, their long-term use is required in cardiological diseases. ASA containing antacid (buffered ASA which dissolves in the stomach) and enteric-coated ASA (which dissolves and is absorbed in the intestinal alkaline environment, thereby affecting drug bioavailability) are prescribed to protect GI mucosa. Pharmacokinetics and pharmacodynamics of  buffered and coated formulations are discussed.

Keywords: acetylsalicylic acid, gastrointestinal bleeding, gastrointestinal mucosa, dyspepsia, antithrombotic therapy, buffered formulations.

For citation: Minushkina L.O. Key preventive approaches to gastrointestinal mucosal injury in cardiological patients. RMJ. 2021;
9:12–16.

Pages 17-21. Лечение отечного синдрома у больных хронической сердечной недостаточностью: успехи есть, но проблемы остаются. Дроботя Н.В., Калтыкова В.В., Пироженко А.А.

Summary:

Edema syndrome treatment in patients with chronic heart failure: obtained successes vs. remained problems 

N.V. Drobotya, V.V. Kaltykova, A.A. Pirozhenko

Rostov State Medical University, Rostov-on-Don

Chronic heart failure (CHF) remains one of the most acute problems of modern therapy and cardiology. Despite the successes achieved in the CHF treatment, the rate of patients with a low ejection fraction, and, as a consequence, with decompensation, remains quite high. In the foreground, they have the edema syndrome problem, which exacerbates cardio-hemodynamic disorders, dramatically reduces exercise tolerance and life quality. The main group of drugs used for edema syndrome treatment is diuretics. In recent years, preference is given to loop diuretics, which include the main representatives of this class — furosemide and torasemide. The study results on the comparison of their effects (TORIC, DUEL–CHF, etc.) demonstrated distinct torasemide advantages, which can not only reduce the CHF clinical manifestations but also positively affect the prognosis. The problem in the edema syndrome treatment remains an adequate dosage of the drug, which should ensure the achieve ment and maintenance of euvolemia condition of the patient. It is suggested that the dosage presence of torasemide 20 mg could contribute not only to improving its diuretic efficacy, but also CHF patient’s compliance.

Keywords: chronic heart failure, edema syndrome, euvolemia condition, loop diuretics, torasemide, Trigrim.

For citation: Drobotya N.V., Kaltykova V.V., Pirozhenko A.A. Edema syndrome treatment in patients with chronic heart failure: obtained successes vs. remained problems. RMJ. 2021;9:17–21.



Pages 22-26. Эффективная антигипертензивная терапия: на что врачу необходимо обратить внимание?. Смирнова М.Д., Небиеридзе Д.В.

Summary:

Effective blood pressure-lowering therapy: what to consider?

M.D. Smirnova1, D.V. Nebieridze2

1National Medical Research Center of Cardiology, Moscow

2National Medical Research Center of Therapy and Preventive Medicine, Moscow

Treatment for arterial hypertension (AH) implies a reduction of blood pressure and organ protection since organ involvement (e.g., left ventricular hypertrophy, microalbuminuria, etc.) significantly increases the risk of cardiovascular events. Damage of target organs is relatively common in AH, even at early stages. Numerous randomized clinical trials have demonstrated that monotherapy effectively reduces BP only in a few patients, while most patients require a combination of at least two medications to control BP. This review paper discusses the selection of optimal hypotensive drug combinations. Clinical trials demonstrate the advantages of combining an angiotensin-converting enzyme inhibitor (ramipril) and calcium channel blocker (amlodipine), particularly a fixed-dose combinati on of ramipril and amlodipine, in routine practice in various patient groups. This combination provides pleiotropic effects. The role of depression and anxiety as significant independent risk factors of cardiovascular events is discussed. The importance of smoking cessation, body weight control, and physical activity is highlighted.

Keywords: ramipril, amlodipine, fixed-dose combination, blood pressure-lowering treatment, organ protection.

For citation: Smirnova M.D., Nebieridze D.V. Effective blood pressure-lowering therapy: what to consider? RMJ. 2021;9:22–26.

Pages 26-30. Сравнительная оценка влияния небиволола и метопролола на метаболические показатели и вазомоторную функцию эндотелия у больных эссенциальной артериальной гипертензией. Семенкин А.А., Живилова Л.А., Назаров А.Г., Притыкина Т.В., Друк И.В., Логинова Е.Н.

Summary:

Nebivolol versus metoprolol: comparative evaluation of their effect on metabolic parameters and endothelial vasomotor function in patients with essential hypertension

A.A. Semenkin, L.A. Zhivilova, A.G. Nazarov, T.V. Pritykina, I.V. Druk, E.N. Loginova

Omsk State Medical University, Omsk

Aim: to compare the vascular and metabolic effects of monotherapy with metoprolol tartrate and nebivolol hydrochloride in the treatment of  patients with uncomplicated essential hypertension. 

Patients and Methods: the study included 50 patients treated with metoprolol (n=25) or nebivolol (n=25) for 3 months. The following parameters were monitored at baseline and at the end of the study: body mass index (BMI), waist circumference (WC), lipid spectrum, blood glucose, blood pressure (BP), endothelium-dependent (EDV) and endothelium-independent (EIDV) vasodilation of the brachial artery, determined by high-resolution ultrasound.

Results: the study protocol was completed by 19 patients from the metoprolol group and 18 patients from the nebivolol group. In both groups, a similar degree of reduction in BP and heart rate was achieved. The following vascular parameters significantly differ between groups with significant improvement of EDV and EIDV on nebivolol (p<0,05 for both parameters), tendency to decrease of EDV and significant decrease of EIDV (p<0,05) on metoprolol. Significant differences were also revealed in the BMI trend (no changes in the nebivolol group versus significant increase in the metoprolol group, p<0.05), WC (decreasing tendency in the nebivolol group and a significant increase in the metoprolol group, p<0,05), HDL cholesterol (a significant increase in the nebivolol group and a significant decrease in the metoprolol group, p<0.01) and blood glucose (a significant decrease in the nebivolol group and a significant increase in the metoprolol group, p<0,001). In th e combined group (n=37) during therapy, significant negative correlations were revealed between changes in EDV and WC, total cholesterol, LDL cholesterol and blood glucose.

Conclusion: thus, two selective beta-blockers, (metoprolol and nebivolol) have the opposite effect on metabolic and vascular parameters: negative effect — metoprolol, and positive effect — nebivolol, which can potentially cause a diverse prognosis of patients with hypertension during long-term therapy. There is an association between the endothelial and metabolic effects of the studied drugs. 

Keywords: essential hypertension, metoprolol, nebivolol, endothelial vasomotor function, metabolic disorders.

For citation: Semenkin A.A., Zhivilova L.A., Nazarov A.G. et al. Nebivolol versus metoprolol: comparative evaluation of their effect on metabolic parameters and endothelial vasomotor function in patients with essential hypertension. RMJ. 2021;9:26–30.



Pages 31-34. Роль тревожных расстройств у пациентов с сердечно-сосудистой патологией, перенесших COVID-19. Филиппов Е.В.

Summary:

Role of anxiety disorders in patients with cardiovascular pathology who experienced COVID-19

E.V. Filippov

Ryazan State Medical University, Ryazan

Circulatory system diseases (CSD) are one of the most common causes of fatal outcomes in the Russian Federation. The article presents a study overview that examined the association between anxiety and adverse outcomes (AO) (including cardiovascular outcomes and all-cause mortality) in patients. In a recent large meta-analysis, it was found that there may be an association of anxiety with various AO (cardiovascular mortality, stroke, heart failure). The author considers the pathogenetic mechanisms of AO in patients with anxiety, which are based on two components: biological and behavioral. The biological component depends on the severity of anxiety and depression. Besides, it is a trigger for the development of «new» negative emotions and chronic stress. The article also discusses the anxiety role in patients who experienced COVID-19, as well as autonomic disorders associated with the post-covid syndrome. The author present s his clinical case concerning the development of post-covid syndrome, accompanied by increased anxiety and vegetative symptoms, and describes its therapy in a patient who suffered from long-term arterial hypertension.

Keywords: anxiety, circulatory system diseases, postural orthostatic tachycardia syndrome, sinus tachycardia, COVID-19, mortality.

For citation: Filippov E.V. Role of anxiety disorders in patients with cardiovascular pathology who experienced COVID-19. RMJ. 2021;9:31–34.

Pages 36-38. Кардиомиопатия Такоцубо: клинический случай. Азизова Д.Д., Алдабергенова А.М., Жумабай К.Т., Канафина Г.Б., Тургамбаева Ж.Р.

Summary:

Takotsubo cardiomyopathy: a clinical case

D.D. Azizova, A.M. Aldabergenova, K.T. Zhumabai, G.B. Kanafina, Zh.R. Turgambayeva  

Astana Medical University, Nur-Sultan, Kazakhstan

Takotsubo cardiomyopathy belongs to the group of heterogeneous diseases. It is a primary acquired stress-induced syndrome resulting from dysfunction of myocardial mid- and apical segments in the setting of resting global left ventricular contractility or hyperkinesis of the basal segments. This cardiomyopathy occurs in 1–2% of all patients with acute coronary syndrome signs, mainly in postmenopausal women without significant atherosclerotic coronary artery lesions. Clinical manifestations are similar to the myocardial infarction symptoms, and therefore, diagnosis establishment is somewhat complicated. Medical treatment commonly includes standard therapy used for myocardial infarction and heart failure since Takotsubo cardiomyopathy is complicated by the occurrence of heart failure in almost half of cases. Therapy duration is 1 to 4 weeks, during which the contractile function of the heart restores in most cases. The prognosis is commonly favorable. The article presents a clinical case of a female patient with Takotsubo cardiomyopathy. This is the first recorded case on the territory of Kazakhstan. The clinical picture, stages of diagnosis and complications in diagnosis establishment are described.

Keywords: Takotsubo cardiomyopathy, apical segmental dysfunction, transient apical hypokinesis, apical ballooning syndrome, stress-induced cardiomyopathy.

For citation: Azizova D.D., Aldabergenova A.M., Zhumabai K.Т. et al. Takotsubo cardiomyopathy: a clinical case. RMJ. 2021;9:36–38.

Pages 39-40. STADA и ведущие эксперты обсудили возможности использования антиагрегантовво время и после заболевания COVID-19.

Pages 6-10. Оригинальные и воспроизведенные лекарственные средства: действительно ли они сопоставимы? Акцент на моксонидин. Переверзев А.П.

Summary:

Original and reproduced medicinal products: are they comparable? Emphasis on moxonidine

A.P. Pereverzev

Russian Medical Academy of Continuous Professional Education, Moscow

Nowadays, life expectancy worldwide is growing and, according to the World Health Organization, the number of people over 60 will double by 2050. With increasing life expectancy, the number of patients with arterial hypertension increases, which leads to the need for antihypertensive drugs with moxonidine.

A medicinal product (MP) with a new active substance, which is the 1st registered and approved in clinical practice based on the preclinical and clinical study results confirming its quality, efficacy and safety, is called an original MP. After the expiration of the patent protection period, any pharmaceutical companies receive the right to manufacture and sell MPs equivalent to the original in terms of the qualitative and quantitative composition of active substances, as well as an equivalent dosage form (reproduced MPs, generics). To register the MP data, it is sufficient to conduct bioequivalence studies, i.e. confirmation of pharmacokinetic parameters comparable to the original MP in the same dosages and administration method. The article considers the differences between the original and reproduced MPs due to the difference in the composition of the excipients, using the example of moxonidine, and presents the potential mechanisms underlying them.

Keywords: bioequivalence, safety, excipients, reproduced medicinal products, moxonidine.

For citation: Pereverzev A.P. Original and reproduced medicinal products: are they comparable? Emphasis on moxonidine. RMJ. 2021;9:6–10.





№8, 2021. Урология. Хирургия

Pages 11-13. Опыт трансплантации донорской почки пациентам с терминальной стадией хронической почечной недостаточности. Дунаевская С.С., Косик А.А., Карташков Е.В.

Summary:

Experience of donor kidney transplantation in patients with end-stage chronic renal disease

S.S. Dunaevskaya1,2, A.A. Kosik1,2, E.V. Kartashkov2

1Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk

2Federal Siberian Research Clinical Center of the Federal Medical and Biological Agency, Krasnoyarsk

Kidney transplantation, which provides a high life quality to patients with end-stage chronic renal disease, is recognized worldwide as one of the main achievements of modern medicine. The article presents our experience concerning the surgical treatment of 44 patients who underwent orthotopic renal transplantation for various indications from 2018 to 2020. Kidney transplantation from a deceased donor was performed in 39 (88.6%) patients, from a living donor — in 5 (11.4%) patients. There were the following indications for kidney transplantation: end-stage renal disease in the outcome of chronic glomerulonephritis — 28 (64%) patients, polycystic kidney disease — 9 (20%) patients, diabetic nephropathy — 4 (9%) patients, chronic pyelonephritis — 3 (7%) patients. Besides, the article presents an example of successful multistage treatment of a patient with  autosomal dominant polycystic kidney disease who underwent nephrectomy after kidney transplantation. The right-sided native nephrectomy was performed as planned, while the acute pyelonephritis served as an indication for the left-sided native nephrectomy. During the surgical exploration, attention was drawn to the large kidney size, which occupied the entire left half of the abdominal cavity.

Keywords: chronic renal disease, transplantation, donor kidney, autosomal dominant polycystic kidney disease, native kidney, acute pyelonephritis.

For citation: Dunaevskaya S.S., Kosik A.A., Kartashkov E.V. Experience of donor kidney transplantation in patients with end-stage chronic renal disease. RMJ. 2021;8:11–13.



Pages 14-24. Возможности КТ-исследований в диагностике нарушений венозной гемодинамики. Шайдаков Е.В., Санников А.Б., Емельяненко В.М., Рачков М.А., Крюкова Л.Н., Баранова А.Е.

Summary:

Possibilities of CT study in diagnostics of hemodynamic disorders

E.V. Shaidakov1, A.B. Sannikov2,3, V.M. Emelianenko3, M.A. Rachkov2, L.N. Kryukova2, A.E. Baranova2

1N.P. Bekhtereva Institute of the Human Brain of the Russian Academy of Sciences, St. Petersburg

2Clinic of Innovative Diagnostics "Medica", Vladimir

3Pirogov Russian National Research Medical University, Moscow

Due to the possibility of solving a large number of technical problems, the method of computed tomography (CT) venography is widely used nowadays. However, it has not yet received clinical recognition in the diagnosis of chronic venous diseases. This article analyzes the results of studying the CT venography use, describing the methods of indirect and direct contrast CT venography. It also shows the possibilities of using contrast CT venography in the diagnosis of deep vein thrombosis and discusses the opportunities concerning the combined use of CT venography and CT angiopulmonography in the diagnosis of pulmonary embolism. Contrast-enhanced CT venography can become an indispensable tool in studying the patterns of the topographic and anatomical structure of the venous bed. Using the example of their research, the authors demonstrate the possibilities of direct CT venography of the lower extremities. The  need for more accurate topical diagnostics with 3D imaging of the lower extremity and pelvic venous system with CT venography is due to the growing interest of vascular and interventional surgeons in testing and more active administration of endovascular correction of venous blood flow in phlebological practice. The use of magnetic resonance imaging (MRI) and CT imaging will help to clarify the data of clinical anatomy, as well as to look differently at some of the main path-dependent hemodynamic links in the development of cardiovascular diseases in patients with venous diseases.

Keywords: computed tomography, computed tomography venography, magnetic resonance imaging, magnetic resonance venography, chronic venous diseases.

For citation: Shaidakov E.V., Sannikov A.B., Emelianenko V.M. et al. Possibilities of CT study in diagnostics of hemodynamic disorders. RMJ. 2021;8:14–24.



Pages 25-28. Применение цианобактерий рода Arthrospira в ранозаживлении. Праздников Э.Н., Евсюкова З.А.

Summary:

The use of cyanobacteria of the genus Arthrospira in the wound healing

E.N. Prazdnikov, Z.A. Evsyukova

A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow

The skin is the only external barrier to protect the body from harmful environmental effects, which makes it extremely vulnerable to various types of damage. In case of skin integrity violation, there is an urgent need for an effective healing method. However, despite the availability of a wide range of healing agents and significant achievements in the field of regenerative medicine, the problem of wound healing is still of concern to many specialists from various fields of medicine. It is because the result of the wound process is commonly the formation of an esthetically unacceptable scar or cicatricial deformity, which negatively affects the life quality of the patient. Among the variety of external agents used in different wound process phases, the extract of cyanobacterium spirulina (the unique cellular composition used at all stages of cutaneous wound healing, which is the subject of nume rous studies and developments) attracted attention. Also, the relative availability of cyanobacteria spirulina (compared with the high-tech process of artificial regenerants synthesis) makes it the subject of scientific research. This article presents some studies on the use of spirulina in wound healing.

Keywords: wound healing, regenerants, spirulina, cyanobacteria, wound process, antioxidants, regenerative process.

For citation: Prazdnikov E.N., Evsyukova Z.A. The use of cyanobacteria of the genus Arthrospira in the wound healing. RMJ. 2021;8:25–28.

Pages 29-32. Бактериальные биопленки в ортопедии: проблема и возможные перспективы профилактики. Гордина Е.М., Божкова С.А.

Summary:

Bacterial biofilms in orthopedics: the problem and possible prospects for prevention

E.M. Gordina, S.A. Bozhkova

Vreden National Medical Research Center of Traumatology and Orthopedics, St. Petersburg

This review presents modern views on the formation of a chronic orthopedic infection associated with the biofilm formation of bacteria. The stages of biofilm formation, the phenotypes of bacterial cells existing in them, as well as their role in the pathogenesis of implant-associated infection are briefly considered. The biofilm state allows pathogens to be resistant to antibiotic treatment and to the effects of immune system factors due to structural and metabolic heterogeneity because of simultaneous coexistence of microbial cells in various states, combined with active synthesis of the intercellular matrix. Currently, there are several directions in the prevention of microbial adhesion and maturation of films on orthopedic implants. For preventive and therapeutic purposes in traumatology and orthopedics, in addition to systemic and local antibacterial drugs, materials can be used to create implants with certain physical and chemical properties of surfaces. The main action targets of anti-biofilm agents are given This review shows the results of the clinical use of silver and iodine for the prevention and treatment of infectious complications during orthopedic operations. It is concluded that, despite all the optimistic results, most of the applied methods are still to be studied and difficult to scale up to industry standards, which requires further research.

Keywords: biofilms, biofilm formation, periprosthetic joint infection, implant-associated infection, implants.

For citation: Gordina E.M., Bozhkova S.A. Bacterial biofilms in orthopedics: the problem and possible prospects for prevention.
RMJ. 2021;8:29–32.



Pages 3-6. Эффективность индивидуального подбора дозы силденафила в форме спрея у мужчин с эректильной дисфункцией. Кузьменко А.В., Кузьменко В.В., Гяургиев Т.А.

Summary:

The efficacy of drug dosage adjustment of spray sildenafil in men with erectile dysfunction

A.V. Kuzmenko, V.V. Kuzmenko, T.A. Gyaurgiev

N.N. Burdenko Voronezh State Medical University, Voronezh

Background: phosphodiesterase-5 inhibitors are the main drugs for the treatment of erectile dysfunction (ED). Over the past few years, new dosage forms of these drugs have appeared on the pharmaceutical market, which potentially predominate over the conservative tablet form.

Aim: to evaluate the efficacy and safety of drug dosage adjustment of oral spray sildenafil in men with ED.

Patients and Methods: a prospective study included 60 patients aged 19 to 50 years with ED. At visit 1, all patients completed the International Index of Erectile Function (IIEF-5) questionnaire to assess the severity of ED, as well as the Hamilton Rating Scale for Depression (HRSD) to  identify psychoemotional disorders. All patients were prescribed oral spray sildenafil at an initial dose of 50 mg (4 taps) on-demand, but at least once a week. Therapy assessment was conducted at visits 2, 3 and 4 after 4, 8 and 16 weeks, respectively. It included an analysis of the average score trend according to the IIEF questionnaire, an assessment of the overall sexual satisfaction of patients and the control of adverse events.

Results: the majority (n=32) were men with moderate ED. Psychoemotional disorders corresponded to mild (n=17) and moderate (n=43)  severity. Therapy at the initial dosage was effective in 42 (70%) of 60 patients, but in 5 cases it was accompanied by the occurrence of mild and moderate adverse events that required a reduction in the drug dosage. In 18 (30%) patients, the desired effect after drug intake at an initial dosage of 50 mg was not achieved. Thus they had to individually increase the dosage. Due to the ability to flexible adjustment of drug dosage in increments of 12.5 mg (1 tap), 3 patients (5%) stopped at a dose of 37.5 mg, 4 (6.7%) — at a dose of 62.5 mg, 5 (8.3%) — at a dose of 87.5 mg, i.e. 12 patients (20%) took doses that are not available during sildenafil intake in tablet form. According to the results of the psychoemotional state assessment of patients, 7 (11.7%) of them retained signs of mild psychoemotional disorders, the remaining 53 (88.3%) men had no changes in their psychoemotional state.

Conclusion: the study results demonstrated the efficacy and safety of sildenafil use in the form of a spray to correct ED. The possibility of flexible adjustment of the drug dosage helps to increase therapy compliance and reduce the number of adverse events.

Keywords: erectile dysfunction, sildenafil, phosphodiesterase-5 inhibitors, spray.

For citation: Kuzmenko A.V., Kuzmenko V.V., Gyaurgiev T.A. The efficacy of drug dosage adjustment of spray sildenafil in men with erectile dysfunction. RMJ. 2021;8:3–6.

Pages 33-36. Протокол профилактики и консервативного лечения персистирующих отеков после ринопластики. Евсюкова З.А., Глушко А.В.

Summary:

Protocol of prevention and conservative treatment of persistent edema after rhinoplasty

Z.A. Evsyukova1, A.V. Glushko2,3

1A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow

2I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

3Institute of Plastic Surgery and Cosmetology, Moscow

Due to the high popularity and relative availability of surgical methods concerning appearance enhancement, rhinoplasty consistently occupies a leading position among all types of plastic surgery, remaining difficult to use in both technical and recovery terms. Commonly, edema after even gentle closed rhinoplasty with the use of modern surgical methods, including piezotome, persist not less than a year, provoking the fibrous tissue formation, which makes the patient and the surgeon decide on the need for repeated intervention. With the increase in the number of repeated interventions on the nasal tissues, the following question arises: how to avoid certain complications and ensure a predictable surgery result. Based on the 3-year experience of working with such patients, we have developed a proto col for the treatment of postoperative edema, which we actively use both on patients after primary rhinoplasty and after repeated surgeries. This protocol allows not only to stop edema, but also to prevent fibrous changes. It helps to avoid repeated surgical interventions and increase patient satisfaction with the surgery result.

Keywords: rhinoplasty recovery, rhinoplasty, treatment of surgical complications, postoperative edema, soft tissue edema, neodymium laser.

For citation: Evsyukova Z.A., Glushko A.V. Protocol of prevention and conservative treatment of persistent edema after rhinoplasty. RMJ. 2021;8:33–36.



Pages 38-40. Лечение обширных инфицированных ран после реваскуляризации нижних конечностей. Фокин А.А., Макаров А.В.

Summary:

Treatment of extensive infected wounds after lower extremity revascularization

A.A. Fokin1,2, A.V. Makarov1,2

1South Ural State Medical University, Chelyabinsk

2Chelyabinsk Regional Clinical Hospital, Chelyabinsk

Among the peripheral artery diseases, the most catastrophic course is characterized by chronic limb-threatening ischemia (CLTI). Successful reconstruction of the main blood flow in patients with CLTI is not a guarantee of a positive treatment result in general. The presence and prevalence of necrosis and the presence of wound infection are the factors determining the possibility of limb preservation. Prolonged hospital stays, the likelihood of getting the hospital flora resistant to many antibiotics, reduced tissue regeneration and numerous interventions are the factors that worsen wound healing in this category of patients. The addition of antibiotic-resistant flora is a significant risk factor for limb loss. The authors present their own experience of patient management with peripheral arterial disease of the lo wer extremities and ulcerative and necrotizing foot lesions. Patients underwent lower limb revascularization, necrectomy, and negative pressure wound therapy. The authors noted the positive effect of silver sulfadiazine use in wound therapy. The balanced patient management, combining active surgical treatment with topical effect on wound healing, allows preventing amputation.

Keywords: peripheral artery diseases, chronic limb-threatening ischemia, antibiotic resistance, revascularization, necrectomy, negative pressure wound therapy, silver sulfadiazine.

For citation: Fokin A.A., Makarov A.V. Treatment of extensive infected wounds after lower extremity revascularization. RMJ. 2021;8:38–40.



Pages 7-10. Эпидемиология мочекаменной болезни и результаты пилотного исследования использования фиброкаликолитотрипсии. Зубков И.В., Битеев В.Х., Коротаев П.Н., Головизнин Ю.В., Ивина Я.А., Шевченко А.А.

Summary:

Epidemiology of urolithiasis and pilot study results concerning the use of extracorporeal shock wave lithotripsy

I.V. Zubkov1, V.Kh. Biteev1, P.N. Korotaev2, Yu.V. Goloviznin2, Ya.A. Ivina2, A.A. Shevchenko1

1Kirov State Medical University, Kirov

2Clinical Hospital «Russian Railways-Medicine of the city of Kirov», Kirov

Urolithiasis is a chronic systemic disease resulting from metabolic disorders and/or the influence of environmental factors, which is manifested by the stone formation in the upper urinary tract. Urolithiasis has a high tendency to relapse, despite the significant development of therapy technologies. There is also the possibility of a substantial increase in the risks of morbidity and disability in professional groups, for instance, in the group of railway workers. Given the peculiarities and severity of labor in railway transport, the detection of kidney stones in workers directly related to the train movement (engine drivers, assistant engine drivers, etc.) is the basis for their suspension from work. The authors presented their own experience of evaluating the efficacy and safety of extracorpor eal shock wave lithotripsy in the treatment of patients (railway workers diagnosed with urolithiasis). A total of 26 patients of both sexes aged 30 to 62 years were treated (mean age — 41 years). The most common were lesions of the upper calyx (34.6%) and single calculi (60–66.7%) with an average size of 4 mm. The surgery duration averaged 50 minutes, and the number of hospital bed days averaged 5. The patients share who had intraoperative and postoperative complications was 7.7% and 11.5%, respectively. Open clinical study results concerning the use of extracorporeal shock wave lithotripsy in the treatment of patients diagnosed with urolithiasis demonstrated a low level of complications and sufficient method efficacy.

Keywords: nephrolithiasis, urolithiasis, intraoperative complications, postoperative complications, extracorporeal shock wave lithotripsy, lithotripsy.

For citation: Zubkov I.V., Biteev V.Kh., Korotaev P.N. et al. Epidemiology of urolithiasis and pilot study results concerning the use of extracorporeal shock wave lithotripsy. RMJ. 2021;8:7–10.



№7, 2021. Ревматология

Pages 13-16. Активность болезни и коморбидные заболевания у больных системной красной волчанкой — что изменилось за два десятилетия?. Гайдукова И.З., Мазуров В.И., Инамова О.В., Фонтуренко А.Ю., Алиев Д.Б., Лейнеман Я.А., Корнилова Е.А., Шаповалов А.А., Нагирняк И.М.

Summary:

Disease activity and comorbidities in patients with systemic lupus erythematosus — what has changed in two decades?

I.Z. Gaydukova1,2, V.I. Mazurov1,2, O.V. Inamova1,2, A.Yu. Fonturenko1,2, D.B. Aliyev2, Ya.A. Leineman1, E.A. Kornilova1, A.A. Shapovalov3, I.M. Nagirnyak3

1I.I. Mechnikov North-Western State Medical University, St. Petersburg

2St. Petersburg Clinical Rheumatology Hospital No. 25, St. Petersburg

3TechLab LLC, St. Petersburg

Background: systemic lupus erythematosus (SLE) is a disease which medical and social significance is determined by a decrease in the life quality of patients and high mortality (due to the direct damaging disease action on the patient’s body), as well as an increase in the comorbidities incidence. It is currently unknown whether the introduction of new approaches to the SLE diagnosis and treatment of patients can significantly change the disease activity and the comorbidities incidence in this population.

Aim: to conduct a comparative analysis of disease activity and comorbidities structure in the patient cohort with SLE diagnosed from 2000 to 2009 and 2010 to 2019.

Patients and Methods: demographic, clinical, laboratory data and comorbid conditions of patients with SLE observed in the St. Petersburg Clinical Rheumatology Hospital No. 25 (whose diagnosis was verified in the periods from 01.01.2000 to 31.12.2009 («history» cohort) and from 01.01.2010 to 31.12.2019 («current» cohort)) were studied.

Results: despite the differences in approaches to the diagnosis, follow-up and treatment of patients with SLE, it was found that the main demographic, clinical, laboratory indicators, as well as the structure of comorbid conditions in both cohorts were comparable. The number of patients who have not achieved low disease activity or remission remained high (44.4% and 47.1% of patients in the «history» and «current» cohorts, respectively, had SLEDAI-2K > 4), as well as patients with changes in the vital organs functions and comorbidity. Non-steroidal remission was extremely rare, 76% of patients continued to take prednisolone in doses exceeding 7.5 mg/day.

Conclusion: the change in the patient management with SLE for two consecutive decades did not lead to a significant change in the disease activity indicators. The incidence of comorbidities in the indicated periods also did not undergo significant changes: the incidence of cardiovascular diseases and risk factors for their development still remains high. The results obtained indicate the need to search for new approaches to SLE treatment that can reduce glucocorticoids use while maintaining minimal disease activity.

Keywords: systemic lupus erythematosus, activity, comorbidities, treatment, glucocorticoids.

For citation: Gaydukova I.Z., Mazurov V.I., Inamova O.V. et al. Disease activity and comorbidities in patients with systemic lupus erythematosus — what has changed in two decades? RMJ. 2021;7:13–16.

Pages 18-23. Анемия и ремоделирование миокарда левого желудочка у пациентов с аксиальными спондилоартритами — существует ли взаимосвязь?. Сафарова К.Н., Махина В.И., Ребров А.П.

Summary:

Anemia and left ventricular remodeling in patients with axial spondyloarthritis — is there any association?

K.N. Safarova1, V.I. Makhina2, A.P. Rebrov1

1Saratov State Medical University named after V.I. Razumovsky, Saratov

2Regional Clinical Hospital, Saratov

Aim: to evaluate the possible association between anemia occurrence and left ventricular (LV) remodelling in patients with axial spondyloarthritis (axSpA).

Patients and Methods: 92 patients with axSpA were examined: 65 (70.6%) men; age — 37 [31; 45] y.o.; axSpA duration — 16 [9; 21] years. BASDAI and ASDAS-CRP indices were calculated, as well as hemogram, erythrocyte sedimentation rate (ESR), ferrokinetic parameters, C-reactive protein (CRP) level were studied. All patients underwent transthoracic echocardiography (EchoCG). The following 4 groups of patients were formed depending on the anemia and/or hypertension presence: group 1 — patients without anemia and hypertension (n=25), group 2 — patients with anemia without hypertension (n=34), group 3 — patients with hypertension without anemia (n=22), group 4 — patients with anemia and hypertension (n=11). 

Results: the proportion of patients with normal LV g eometry according to EchoCG data tended to decrease in groups 3 and 4 versus groups 1 and 2 (50 and 46% vs. 80 and 73%, respectively; p=0.056). The incidence of various types of LV remodeling in groups: LV concentric remodelling — 12% of patients of group 1, 12% of group 2, 27% of group 3 and 18% of group 4; concentric LV hypertrophy — 4% of patients of group 1, 6% of group 2, 5% of group 3, in patients of group 4, this type of LV remodeling was absent; eccentric LV hypertrophy — 4% of patients of group 1, 9 % of group 2, 18% of group 3 and 36% of group 4 (p=0.165 for all).

Conclusion: the study did not show statistically significant differences in the incidence of LV remodeling in patients with axSpA, depending on the presence of anemia. However, the highest incidence of eccentric LV hypertrophy was recorded in patients with hypertension and anemia. The incidence of LV remodeling naturally increased in patients with a longer course of axSpA, which was characterized by the accumulation of traditional cardiovascular risk factors (primarily hypertension, obesity and dyslipidemia). In this regard, the fundamental strategy for modifying the risk of cardiovascular pathology occurrence and progression in patients with axSpA should be considered the inhibition of the systemic inflammation activity and the control of traditional cardiovascular risk factors.

Keywords: anemia, inflammation, axial spondyloarthritis, left ventricular remodeling, left ventricular hypertrophy.

For citation: Safarova K.N., Makhina V.I., Rebrov A.P. Anemia and left ventricular remodeling in patients with axial spondyloarthritis — is there any association? RMJ. 2021;7:18–23.

Pages 24-30. Влияние бессимптомной гиперурикемии на коморбидные заболевания и возможности ее коррекции. Мазуров В.И., Башкинов Р.А., Гайдукова И.З., Фонтуренко А.Ю.

Summary:

The effect of asymptomatic hyperuricemia on comorbidities and the possibility of its correction

V.I. Mazurov1,2, R.A. Bashkinov1,2, I.Z. Gaidukova1,2, A.Yu. Fonturenko1,2

1I.I. Mechnikov North-Western State Medical University, St. Petersburg

2Clinical Rheumatology Hospital No. 25, St. Petersburg

Uric acid (UA) is the end product of purine metabolism. An increase in its serum level is defined as hyperuricemia (HU). In the absence of gouty arthritis signs, HU is considered asymptomatic. In recent decades, there has been a worldwide tendency to increase the prevalence of HU, which, as it turned out, has a wide range of effects on the progression of a large variety of pathologies with a therapeutic profile. Experimental and clinical studies have proven a high association of HU with various comorbidities. There are direct pathogenetic associations concerning elevated UA level with the occurrence and progression of cardiovascular pathology, damage to the musculoskeletal system, kidney disease and metabolic syndrome, which indicates that asymptomatic HU (aHU) is becoming a general therapeutic problem. That is why the conditions for the initiation of urate-lowering therapy (UST) in aHU are presented in the regulatory doc uments of the Russian Medical Society for Arterial Hypertension (RMSAH), IDEA and many other medical communities. At the same time, the viewpoints of specialists of various profiles remain ambiguous regarding the prescription of oral therapy in aHU, which raises the question concerning the expediency of preparing an interdisciplinary consensus on the patient management with aHU and comorbidities.

Keywords: uric acid, asymptomatic hyperuricemia, comorbidities, urate-lowering therapy.

For citation: Mazurov V.I., Bashkinov R.A., Gaidukova I.Z., Fonturenko A.Yu. The effect of asymptomatic hyperuricemia on comorbidities and the possibility of its correction. RMJ. 2021;7:24–30.

Pages 3-6. Клинико-лабораторные маркеры ревматической кахексии при ревматоидном артрите. Папичев Е.В., Заводовский Б.В., Сивордова Л.Е., Ахвердян Ю.Р., Полякова Ю.В.

Summary:

Clinical and laboratory markers of rheumatoid cachexia in rheumatoid arthritis

E.V. Papichev, B.V. Zavodovskii, L.E. Sivordova, Yu.R. Akhverdyan, Yu.V. Polyakova

Research Institute of Clinical and Experimental Rheumatology named after A.B. Zborovsky, Volgograd

Aim: to study the prevalence and clinical and laboratory characteristics of rheumatoid cachexia (RC) in patients with rheumatoid arthritis (RA), as well as to identify indicators, the determination of which can improve the RC detection.

Patients and Methods: 110 patients with RA were included in the retrospective study. All patients underwent a standard clinical and laboratory examination. Besides, laboratory methods were used to determine the highly sensitive C-reactive protein level, antibodies to cyclic citrullinated peptides (AB-CCP), bone metabolism indicators (CTX-I, P1NP, 25(OH)D), Urine CartiLaps / creatinine index. Using dual-energy x-ray absorptiometry (DEXA) with the Total Body program, the body composition was determined. RC was diagnosed when there was a decrease in the body mass index (BMI) of fat-free tissues below the 10th percentile and an increase in the BMI of adipose tissues above the 25th percentile.

Results: the study included subjects of working age (median 53.7 y.o.), mainly women with long-term disease duration (85.5% of patients had the advanced or late clinical stage of RA). The clinical profile of patients was dominated by rheumatoid factor (RF) positivity and AB-CCP, moderate disease activity, the presence of erosive arthritis, moderate limitation of physical activity. RC was diagnosed in 25 patients.

Statistically significant risk factors for the RC development is the RA duration and the presence of RF. The long disease duration increases the risk of developing this condition by 5.8%. Among RF-negative patients, RC was almost 10 times less common (OR 0.11, p=0.032). RA duration with the maximum total value of sensitivity and specificity for RC was 9.5 years (60% sensitivity and 38% specificity). In the group of patients with RC (n=20), the median cumulative dose of glucocorticoids (GC) was statistically higher than in the group without RC (n=68): 8,5 [6,2–17,5] g and 5.8 [3.6–13.7] g, respectively (Z=-1.98, p=0.047). Among the patients who continued receiving GC during the study, 16 were patients with RC with a median daily dose of GC of 5 [4–8] mg, and 61 — without RC, at a dose of GC of 8 [5–10] mg (Z=2.58, p=0.01).

Conclusion: it is advisable to determine the body composition in patients with an established diagnose of RA more than 10 years ago to detect RC. Alertness to this condition should be higher in the RF-positive form of arthritis and prolonged use of GC.

Keywords: rheumatoid arthritis, rheumatoid cachexia, rheumatoid factor, glucocorticoids.

For citation: Papichev E.V., Zavodovskii B.V., Sivordova L.E. et al. Clinical and laboratory markers of rheumatoid cachexia in rheumatoid arthritis. RMJ. 2021;7:3–6.



Pages 32-38. Штрихи к «портрету» пациента с болевым синдромом. Разные подходы к терапии в зависимости от локализации боли и возраста больного. Шавловская О.А.

Summary:

Outlines of the patient profile with pain syndrome. Different approaches to therapy depending on the pain localization and the age of the patient

O.A. Shavlovskaya


International University of Rehabilitation Medicine, Moscow, Russian Federation

More than 90% of people are prone to pain syndromes. 15% to 25% of the adult population suffers from chronic pain. The prevalence of chronic pain in the elderly group can reach 86%. The article is aimed at the help of the doctor in choosing treatment tactics, focusing on the patient profile with a pain syndrome (considering the pain syndrome localization and the patient’s age). Neck pain (cervicalgia) in the setting of degenerative changes in the cervical vertebrae is observed in 25% of adults under 40 years, in 50% — after 40 years, in 85% — at the age of 60 years. Cervicalgia is commonly observed in women aged 40 years. The front-line therapy is nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with a muscle relaxant and various therapeutic exercises, as well as chondroitin sulfate (CS) preparations. As a rule, patients with low back pain (LBP) with or without muscular tonic syndrome are people over the age of 50, mainly women. Equally combinations of drugs are used to relieve pain: NSAIDs + muscle relaxant; NSAIDs + CS injections; less common, oral glucosamine sulfate (GS) monotherapy. Therapy of elderly people with pain syndrome should consider the patient’s age characteristics with comorbid somatic diseases, osteoarthritis (OA), involutional ch anges (sarcopenia), locomotive syndrome. Considering the latest recommendations of European and American researchers, the effect on pain in the elderly can be achieved by using CS and GS, which have proven anti-inflammatory activity and structural modifications.

Keywords: low back pain, osteoarthritis, nonsteroidal anti-inflammatory drugs, SYSADOA, chondroitin sulfate, Chondroguard, glucosamine sulfate, Sustaguard Artro.

For citation: Shavlovskaya O.A. Outlines of the patient profile with pain syndrome. Different approaches to therapy depending on the pain localization and the age of the patient. RMJ. 2021;7:32–38.



Pages 39-39. Парентеральный хондроитина сульфат включен в клинические рекомендации «Коксартроз» (2021) и «Гонартроз» (2021), (пресс-релиз).

Pages 40-43. Есть ли преимущества у комбинированных анальгезирующих средств по сравнению с монотерапией?. Дыдыкина И.С., Арутюнова Е.В., Коваленко П.С.

Summary:

Are there any benefits of combined analgesics compared to monotherapy?

I.S. Dydykina1, E.V. Arutyunova2, P.S. Kovalenko1

1Research Institute of Rheumatology named after V.A. Nasonova, Moscow

2Lomonosov Moscow State University, Moscow

Nowadays, it is known that inadequate pain management leads to a decrease in the life quality of patients, an extension of the recovery period and an increase in mortality. Thus, the rational choice and safe use of medicines in the treatment of pain and inflammation is one of the main tasks of a practicing physician. This article discusses the possibility of using a combination of paracetamol and diclofenac in the treatment of pain of various origins. The results of randomized controlled trials are presented, in which the efficacy and safety of this combination were studied in patients with musculoskeletal diseases, as well as after surgery, toothache, etc. Different mechanisms of action and administration localizations of paracetamol and diclofenac allow using a lower dose of drugs while maintaining or increasing their therapeutic effect. This approach is a promising strategy for maximizing the benefit-risk ratio in the pharmacother apy of pain, especially in comorbid and elderly patients. Various mechanisms of action and administration localizations of paracetamol and NSAIDs, in particular diclofenac, allow considering this combination appropriate and justified.

Keywords: pain, paracetamol, diclofenac, NSAIDs, comorbidity, pharmacotherapy of pain, combined analgesics.

For citation: Dydykina I.S., Arutyunova E.V., Kovalenko P.S. Are there any benefits of combined analgesics compared to monotherapy? RMJ. 2021;7:40–43.

Pages 44-49. Этанерцепт и его биоаналог в лечении ревматоидного артрита: эффективность и безопасность. Чичасова Н.В., Лила А.М.

Summary:

Etanercept and its biosimilar in the treatment of rheumatoid arthritis: efficacy and safety

N.V. Chichasova1,2, A.M. Lila1,2

1Research Institute of Rheumatology named after V.A. Nasonova, Moscow

2Russian Medical Academy of Continuous Professional Education, Moscow

Nowadays, the main goal of rheumatoid arthritis treatment is to achieve remission, whereas the alternative goal is to achieve low disease activity for six months in every patient. The article presents data on the efficacy and safety of the original drug — etanercept — and its biosimilar Erelzi®, registered in the Russian Federation. The data on the immunogenicity of genetically engineered biological drugs (GEBD) with an emphasis on the tumor necrosis factor-α (TNF-α) inhibitors are presented. The article indicates the benefits of etanercept over other TNF-α inhibitors associated with its low immunogenicity. Predictors of an increase in the odds ratio for achieving remission with etanercept treatment and the possibility of maintaining remission with a halving of etanercept dose were presented. As for etanercept biosimilar, data on the comparability of pharmacokinetics with the original drug were presented, as well as the results of a multicenter randomized double-blind 48-week study that showed comparability of efficacy and safety compared with the original etanercept. The data on the preservation of treatment efficacy and safety when switching from the original etanercept to this biosimilar were also presented. The introduction of GEBD biosimilars into clinical practice makes it possible to reduce the treatment cost (covering more patients) and increase the availability of optimal therapy for patients with rheumatic diseases. 

Keywords: etanercept, efficacy, safety, immunogenicity, biosimilar, rheumatoid arthritis.

For citation: Chichasova N.V., Lila A.M. Etanercept and its biosimilar in the treatment of rheumatoid arthritis: efficacy and safety. RMJ. 2021;7:44–49.

Pages 50-54. Оптимальная уратснижающая терапия у пациентов с подагрой — современная трактовка проблемы. Цурко В.В., Громова М.А.

Summary:

Optimal urate-lowering therapy in patients with gout — modern version of the problem

V.V. Tsurko1,2, M.A. Gromova1

1Pirogov Russian National Research Medical University, Moscow

2Russian Medical Academy of Continuous Professional Education, Moscow

Gout is the most common type of inflammatory arthritis caused by the deposition of monosodium urate crystals in the joints and surrounding tissues in the setting of hyperuricemia, characterized by painful acute pain leading to disability. The goal of long-term therapy is to reduce the level of serum uric acid (SUA), which helps to dissolve crystals and eliminate tophi, reduce the frequency of gout exacerbations and prevent progressive joint damage and comorbid pathology development. Despite the availability of national and international recommendations and the effective medications for gout treatment that have already been developed and applied in clinical practice, therapy results are commonly unsatisfactory. The reason for these drawbacks is commonly multifactorial, including the doc tor-patient interaction. Poor adherence to urate-lowering therapy (ULT) is a common and significant factor in adverse outcomes for patients. The article examines gaps in the gout treatment, discusses patient management, including treatment tactics for concomitant diseases, with the mandatory achievement of the SUA target level to improve adherence to oral therapy, which ultimately provides a controlled disease course and a favorable prognosis.

Keywords: gout, hyperuricemia, clinical recommendations, urate-lowering therapy, goal achievement, commitment.

For citation: Tsurko V.V., Gromova M.A. Optimal urate-lowering therapy in patients with gout — modern version of the problem. RMJ. 2021;7:50–54.

Pages 56-60. Лечение синдрома Фелти: современные подходы. Спицина С.С., Зборовская И.А., Трофименко А.С., Мозговая Е.Э., Бедина С.А., Мамус М.А.

Summary:

Treatment of Felty syndrome: modern approaches

S.S. Spitsina1, 2, I.A. Zborovskaya1, A.S. Trofimenko1, E.E. Mozgovaya1, S.A. Bedina1, M.A. Mamus1

1Research Institute of Clinical and Experimental Rheumatology named after A.B. Zborovsky, Volgograd

2Volgograd State Medical University, Volgograd

Felty syndrome is a rare (less than 1%) type of seropositive rheumatoid arthritis, in which neutropenia and splenomegaly occur. Clinical manifestations of Felty syndrome also include severe destructive joint damage, rheumatoid nodules, lymphadenopathy, hepatopathy, vasculitis, lower-extremity ulcers, skin pigmentation, etc. The causes of neutropenia are considered to be both a decrease in the granulopoiesis intensity and an increase in the peripheral destruction of granulocytes. Recurrent bacterial infections commonly develop due to severe neutropenia. This can cause an increase in the patients’ mortality, which requires special diagnostic caution due to the similarity of Felty syndrome manifestations with adverse events in the treatment of rheumatoid arthritis. Based on the up-to-date data, the treatment tactics of Felty syndrome has a number of features. Neutropenia ca n be effectively corrected with the help of some disease-modifying anti-rheumatic drugs, primarily methotrexate. Among genetically engineered biological drugs, encouraging results were achieved with the use of rituximab; for cases of severe neutropenia with recurrent infection, there is an experience in using granulocyte colony-stimulating factor. Splenectomy should be considered as a last measure in patients with Felty syndrome who do not respond to conservative treatment methods.

Keywords: rheumatoid arthritis, Felty syndrome, basic anti-inflammatory therapy, methotrexate, genetically engineered biological therapy, tumor necrosis factor α inhibitors, rituximab, granulocyte colony-stimulating factor, splenectomy.

For citation: Spitsina S.S., Zborovskaya I.A., Trofimenko A.S. et al. Treatment of Felty syndrome: modern approaches. RMJ. 2021;7:56–60.



Pages 62-65. Фенилбутазон: место неселективных НПВП в современной врачебной практике. Свинцицкая И.С., Волков К.Ю., Бологов С.Г.

Summary:

Phenylbutazone: non-selective NSAIDs in modern medical practice

I.S. Svintsitskaya, K.Yu. Volkov, S.G. Bologov

S.M. Kirov Military Medical Academy, St. Petersburg

Despite the long history of the use of non-steroidal anti-inflammatory drugs (NSAIDs) in clinical practice, research continues concerning the comparative evaluation of the efficacy and safety of various NSAIDs classes, taking into account their selectivity with respect to the effect on cyclooxygenase. The article is devoted to one of the most well-known and studied drugs — phenylbutazone. The review reflects some historical aspects of phenylbutazone use, it’s pharmacokinetic and pharmacodynamic patterns that cause a prolonged effect. The review also indicates the main adverse events and methods of their control. The expediency of using parenteral forms of NSAIDs (in particular phenylbutazone) in patients with acute pain, providing rapid onset of analgesic effect, is substantiated. It is noted that a balanced approach to phenylbutazone use can minimize the risk of severe toxic responses (primarily from the b one marrow), significantly limiting the drug use by specialists, including in outpatient practice. The article presents the study results confirming the efficacy and safety of phenylbutazone use in injectable form for the relief of acute pain syndrome associated with degenerative-dystrophic and rheumatic diseases of the musculoskeletal system.

Keywords: phenylbutazone, non-steroidal anti-inflammatory drugs, efficacy, safety, acute pain.

For citation: Svintsitskaya I.S., Volkov K.Yu., Bologov S.G. Phenylbutazone: non-selective NSAIDs in modern medical practice. RMJ. 2021;7:62–65.



Pages 66-69. Необычный лихорадочный синдром как специфическая форма протекания генерализованной энтеровирусной инфекции на фоне анти-B-клеточной терапии. Кузьмина А.В., Логинов А.В., Жамбеев А.А., Глазунов П.А., Жиляев Е.В.

Summary:

Uncommon fever as a specific form of generalized enterovirus infection during anti-B-cell therapy

A.V. Kuzmina1, A.V. Loginov1, A.A. Zhambeyev1, P.A. Glazunov1, E.V. Zhilyaev1–

1European Medical Center, Moscow

2Pirogov Russian National Research Medical University, Moscow

3Russian Medical Academy of Continuous Professional Education, Moscow

The advanced use of targeted immunosuppressive antitumor drugs is accompanied by an increase in the risk of rare opportunistic infections and in the incidence of unusual course of common infections. The article presents a clinical case of a severe enterovirus infection course with a specific clinical picture in a 38-year-old female patient suffering from B-cell lymphoma and receiving obinutuzumab. The methods of differential diagnosis used to detect enterovirus infection, as well as the ongoing treatment using human immunoglobulin, are described. The safety issues concerning the use of monoclonal antibodies directed against B-lymphocytes are also discussed. The clinical case presented in the article is of interest to doctors of various specialties, since it demonstrates the uncommon cause of fever of unknown origin, polymyositis and uncommon edematous syndrome, the possible m echanisms of which are also discussed by the authors. The description of the clinical case may be especially useful for doctors who follow-up patients during treatment with anti-B-cell drugs. The high significance of enterovirus infection in such patients is due to an unfavorable prognosis in the absence of specific treatment. Thus, timely diagnosis is crucial.

Keywords: B-cell lymphoma, obinutuzumab, enterovirus infection, differential diagnosis, edema, human immunoglobulin, monoclonal antibodies.

For citation: Kuzmina A.V., Loginov A.V., Zhambeyev A.A. et al. Uncommon fever as a specific form of generalized enterovirus infection during anti-B-cell therapy. RMJ. 2021;7:66–69.

Pages 7-12. Влияние пневмококковой вакцинации на риск развития инфекционных осложнений у пациентов с ревматоидным артритом, получающих лечение таргетными противовоспалительными препаратами (данные Московского Единого Регистра Артритов (МЕРА)). Жиляев Е.В., Лукина Г.В., Муртазалиева Д.А., Кольцова Е.Н., Шмидт Е.И., Лыткина К.А., Шмитько А.В., Благовидов Д.А., Костинов М.П.

Summary:

The effect of pneumococcal vaccination on the risk of infectious complications in patients with rheumatoid arthritis treated with targeted anti-inflammatory drugs (data from the Moscow Unified Arthritis Registry (MUAR))

E.V. Zhilyaev1,2,3, G.V. Lukina4,5, D.A. Murtazalieva4, E.N. Koltsova4, E.I. Shmidt6, K.A. Lytkina7, A.V. Shmit’ko8, D.A. Blagovidov8, M.P. Kostinov8,9

1CJSC European Medical Center, Moscow

2Russian Medical Academy of Continuous Professional Education, Moscow

3Pirogov Russian National Research Medical University, Moscow

4Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow

5Research Institute of Rheumatology named after V.A. Nasonova, Moscow

6City Clinical Hospital No. 1 named after N.I. Pirogov, Moscow

7City Clinical Hospital No. 4, Moscow

8І.І. Mechnikov Research Institute of Vaccines and Sera, Moscow

9I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

Background: pneumococcal vaccines — 23-valent pneumococcal polysaccharide vaccine (PPV23) and 13-valent pneumococcal conjugate vaccine (PCV13) are recommended for use in most patients with rheumatic diseases. However, data confirming the clinical efficacy of such vaccination is limited.

Aim: to evaluate the effect of vaccination with pneumococcal vaccines (PPV23 and PCV13) in patients with rheumatoid arthritis (RA) receiving genetically engineered biological drugs (GEBDs) and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) on the risk of developing infectious adverse events of various categories in real clinical practice.

Patients and methods: data analysis of the Moscow Unified Arthritis Registry (MUAR) for 2018–2020 was conducted. The patients with RA over 18 y.o. receiving GEBD or tsDMARDs were included. All infectious, respiratory infectious and serious infectious events were studied for the same period in vaccinated and unvaccinated patients.

Results: 832 patients were included in the analysis, of which 40 were vaccinated with PCV13, 35 — with PPV23. The follow-up was 319±198 days. A total of 237 infectious events were recorded, of which 201 were respiratory and 21 — serious. Acute respiratory infections prevailed among the events (70.0% of all infectious and 82.6% of respiratory infectious events). Survival curve comparison (log-rank test), as well as a comparison of the Cox proportional hazard regression, including adjusted for the most important risk factors for infectious events (age and smoking), revealed a significant reduction in the risk of any infectious events (p=0.012 and p=0.015, respectively) in patients immunized with PCV13, compared with unvaccinated. These patients also showed a statistically significant reduction in the risk of respiratory infections (p=0.009 and p=0.014, respectively). No significant effect of PPV23 vaccine on the risk of these events has been established. There w as no significant effect of any of the vaccines on the serious infectious event probability.

Conclusion: in this study, the clinical efficacy of PCV13 was demonstrated for the first time in patients with RA receiving therapy with tsDMARDs. The effect was achieved mainly by reducing the incidence of acute respiratory infections.

Keywords: rheumatoid arthritis, pneumococcal vaccine, pneumonia, targeted synthetic disease-modifying anti-rheumatic drugs, confounders, smoking, age.

For citation: Zhilyaev E.V., Lukina G.V., Murtazalieva D.A. et al. The effect of pneumococcal vaccination on the risk of infectious complications in patients with rheumatoid arthritis treated with targeted anti-inflammatory drugs (data from the Moscow Unified Arthritis Registry (MUAR)). RMJ. 2021;7:7–12.

Pages 70-73. Спондилоартриты: трудности диагностики и возможности современных методов высокотехнологичной помощи. Вахлевский В.В., Свинцицкая И.С., Тыренко В.В.

Summary:

Spondyloarthritis: diagnostic challenges and possibilities of modern methods of high-tech medical care

V.V. Vakhlevsky, I.S. Svinitskaya, V.V. Tyrenko

S.M. Kirov Military Medical Academy, St. Petersburg

In the diagnosis of rheumatic diseases, detailed complaints, medical history, laboratory and instrumental research methods are crucial. The correctness of the treatment tactics and patient management depends on the timely diagnosis, which ensures retardation in the disease progression and allows achieving effective disease control in dynamics. The article describes a clinical case of lately diagnosed ankylosing spondylitis (AS) in a 34-year-old young patient with severe coxitis. The disease onset started with the pain occurrence in the left hip joint (HJ). For two years, the patient was under follow-up with a diagnosis of reactive arthritis of unspecified etiology with systemic manifestations. Despite the ongoing therapy (prednisolone, sulfasalazine), the articular syndrome progression was noted. After an additional examination, the diagnosis of high-activity AS (ASDASCRP — 3.03, BASDAI — 3.6), with non-axial (bilateral coxitis) manifestations, HLA-B27-positive was established criterion-wise. Complication: stage III bilateral coxarthrosis with a predominant lesion of the left HJ with severe pain syndrome. To achieve a rapid effect and reduce the disease progression, a TNF-α inhibitor was prescribed. As a result of treatment, disease low activity was achieved, which made it possible to successfully perform total left HJ replacement.

Keywords: ankylosing spondylitis, coxitis, coxarthrosis, hip replacement, genetically engineered biological therapy, TNF-α inhibitor, prednisolone.

For citation: Vakhlevsky V.V., Svinitskaya I.S., Tyrenko V.V. Spondyloarthritis: diagnostic challenges and possibilities of modern methods of high-tech medical care. RMJ. 2021;7:70–73.

Pages 74-78. Два взгляда на проблему остеоартрита и остеохондроза: сравнение подходов к терапии (пострелиз).

Summary:

Two views on the problem of osteoarthritis and osteochondrosis: comparison of approaches to the therapy (post-release)

On November 8–10, 2021, the Xll Congress «Manage Pain» was held. The congress objectives were the following: to spread advanced knowledge on the problem of pain, improve the interaction between doctors of various specialties and international experience exchange in organizing care and therapy for patients suffering from various pain syndromes. The event was organized with the participation of the following organizations: World Institute of Pain (WIP), European Pain Federation (EFIC), Association for Interventional Pain Management (AIPM), Russian Headache Research Society (RHRS), etc.

The audience of the event included leading specialists in the field of neurology and psychiatry, therapists, doctors of family medicine, psychologists, anesthesiologists, surgeons, nutritionists, urologists, gastroenterologists, endocrinologists, gynecologists and doctors of other specialties whose professional activities were related to the study, diagnosis and treatment of pain syndromes.

On November 8, 2021, within the framework of the Congress, Promomed company held an interactive session dedicated to the therapy of patients with osteoarthritis and osteochondrosis. The symposium was co-chaired by Andrey B. Danilov (Doctor of Sciences (Medicine), Professor of the Department of Nervous Diseases of the I.M. Sechenov First Moscow State Medical University), and Alexander M. Lila (Doctor of Sciences (Medicine), Professor, Director of the V.A. Nasonova Research Institute of Rheumatology). The session featured presentations on the topics: «Individual approach to the treatment of patients with osteoarthritis», «Osteochondrosis: a new look at an old problem», «Clinical study results on the efficacy and safety of AMBENE®Bio (COLIBRI)».

For citation: Danilov A.B., Lila A.M., Feklistov A.Yu. Two views on the problem of osteoarthritis and osteochondrosis: comparison of approaches to the therapy (post-release). RMJ. 2021;7:74–78.



№6, 2021. Клинические рекомендации и алгоритмы для практикующих врачей. Гастроэнтерология

Pages 101-104. Интегральные гематологические индексы как маркер развития пострезекционной печеночной недостаточности. Дунаевская С.С., Сачивко К.В., Косик А.А., Бережная М.А., Наркевич А.Н.

Summary:

Integral hematological indices as a marker of the postresection liver failure

S.S. Dunaevskaya, K.V. Sachivko, A.A. Kosik, M.A. Berezhnaya, A.N. Narkevich

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk

Background: acute liver failure is the most dangerous complication after liver resection, characterized by acute, rapidly developing a hepatic injury.

Aim: to determine the patterns of changes in the integral hematological indices (IHI), to assess their diagnostic value in patients with the development of postresection liver failure (PLF). 

Patients and Methods: the study included 54 patients, among them 32 (59%) women (the average age of patients was 59.5 [49.7; 66] years), who underwent segmental resection or hemihepatectomy for malignant and benign liver tumors. The patients were divided into two groups: group 1 (n=44) — consisted of patients who had not been diagnosed with PLF in the postoperative period, group 2 (n=10) — the postoperative period was complicated by the development of hepatic failure. In all patients at admission, as well as on the 3rd day after surgery, the indicators of the complete blood count with the calculation of the WBC count were studied, and the values of the leukocyte indices of cellular reactivity were determined.

Results: IHI comparative analysis in patients with different postoperative period revealed statistically significant differences in most of the base indicators. It was found that the leukocyte intoxication index by J.J. Kalf-Kalif, modified leukocyte intoxication index of B.A. Reis, modified leukocyte intoxication index of V.K. Ostrovsky and hematological intoxication index in the postoperative period in the group of patients with the liver failure significantly (p=0.005, p=0.041, p=0.041, p=0.001, respectively) differed from the indicators of patients without liver failure. An increase in these indices can serve as an early diagnostic criterion for PLF development.

Conclusion: the method of calculating IHI is a simple and cheap diagnostic method that can be used only with the results of the leukocyte formula. The determination of diagnostically significant indices in dynamics can be used as a prognostic and screening method for detecting PLF.

Keywords: liver failure, liver resection, diagnosis, screening, integral hematological indices, leukocyte index.

For citation: Dunaevskaya S.S., Sachivko K.V., Kosik A.A. et al. Integral hematological indices as a marker of the postresection liver failure. RMJ. 2021;6:101–104 (in Russ.).

Pages 14-17. С-реактивный белок в оценке пациентов с респираторными симптомами до и в период пандемии COVID-19. Андреева Е.А.

Summary:

C-reactive protein in the assessment of patients with respiratory symptoms before and during the COVID-19 pandemic

E.A. Andreeva

Northern State Medical University, Arkhangelsk

The article is devoted to the role of C-reactive protein (CRP) in the diagnosis of respiratory diseases and patient management with respiratory symptoms. The article presents the clinical recommendations of the Russian professional communities, including CRP level determination in various respiratory diseases. CRP role as an indicator of bacterial infection, as well as critical levels and changes in the CRP concentration in the disease dynamics, are considered. The article also discusses point-of-care testing of CRP role as a «here and now» strategy that allows deciding on the prescription of antibacterial therapy at the time and place where medical care is provided. This approach minimizes unnecessary antibiotic therapy, especially in primary health care settings. The significance of CRP determining during the COVID-19 pandemic as an inflammatory marker in new coronavirus infection is consi dered. Indications for determining the CRP concentration in patients with COVID-19, proposed by international and Russian recommendations, including the current version of the Temporary Methodological Guidelines «Prevention, diagnosis and treatment of new coronavirus disease (COVID-19)», are presented. The article discusses the need to determine the CRP concentration to plan the patient management with respiratory infections in the near future, taking into account the current COVID-19 pandemic.

Keywords: C-reactive protein, point-of-care testing, respiratory infections, clinical recommendations, COVID-19, pneumonia, inflammatory markers, antibacterial therapy.

For citation: Andreeva E.A. C-reactive protein in the assessment of patients with respiratory symptoms before and during the COVID-19 pandemic. RMJ. 2021;6:14–17 (in Russ.).

Pages 18-22. Пациент с ГЭРБ после перенесенной новой коронавирусной инфекции. Рациональная фармакотерапия на клиническом примере. Пахомова И.Г.

Summary:

Patient with GERD after a new coronavirus infection. Rational pharmacotherapy in clinical case

I.G. Pakhomova

V.A. Almazov National Medical Research Center, Saint-Petersburg

In 2020, the global health system is facing a new coronavirus infection caused by SARS-CoV-2. Among many publications devoted to the features of the infection clinical manifestations and its treatment, there are works on the gastrointestinal (GI) manifestations of COVID-19. Information about post-COVID-19 manifestations from the GIT is rather scarce. At the same time, doctors are faced in clinical practice with a considerable proportion of patients with COVID-19 GI manifestations and adverse events on some drugs prescribed to the patients with SARS-CoV-2. Such patient management may present some difficulties since there are no available recommendations for their management. Gastroesophageal reflux disease (GERD) is one of the most common pathologies of the GIT. To date, possible links in the pathogenesis of GERD have been studied and described. Proton pump inhibitors (PPIs), prokinetics, esophagoprotec tion, etc. are effective in GERD treatment. It will be rational to combine them. However, among PPIs, rabeprazole has a dual mechanism of action: antisecretory and cytoprotective, which makes it possible to achieve a rapid and effective clinical and endoscopic response to therapy. This review provides information on the patient management with GERD after COVID-19 in the clinical case.

Keywords: gastroesophageal reflux disease, GERD, COVID-19, proton pump inhibitors, rabeprazole.

For citation: Pakhomova I.G. Patient with GERD after a new coronavirus infection. Rational pharmacotherapy in clinical case. RMJ. 2021;6:18–22 (in Russ.).

Pages 23-26. Роль неинвазивной вентиляции легких в комплексной терапии больных хронической обструктивной болезнью легких с гиперкапнической дыхательной недостаточностью. Кузубова Н.А., Титова О.Н., Склярова Д.Б.

Summary:

The role of non-invasive ventilation in the complex therapy of patients with chronic obstructive pulmonary disease with hypercapnic
respiratory failure

N.A. Kuzubova1, O.N. Titova1, D.B. Sklyarova2

1Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg

2Vvedenskaya City Clinical Hospital, Saint-Petersburg

Background: hypercapnia development in patients with chronic obstructive pulmonary disease (COPD) with chronic respiratory failure leads to a decrease in the efficacy of long-term oxygen therapy (LTOT), an increase in the number of exacerbations and an increased risk of fatal outcome.

Aim: to determine the role of non-invasive lung ventilation (NVL) in the complex respiratory therapy of COPD complicated by chronic hypercapnic respiratory failure (HRF).

Patients and Methods: a prospective study included 30 patients with severe COPD (group D) with chronic HRF during disease remission. There were 2 groups: group 1 (n=14) — patients with COPD and HRF (partial pressure of carbon dioxide (PaСО2) of 54.7±7.2 mm Hg), receiving NIV and LTOT; group 2 (n=16) — patients with COPD and HRF (PaСО2 52,8±o6.96 mm Hg) who received only LTOT. Group 1 was prescribed with BiLevel NIV 3 hours a day on the daily basis and LTOT 16 hours a day, flow rate — 3 L/min. Group 2 received only LTOT in a similar mode. The mMRC (Modified Medical Research Council) Dyspnea Scale, exercise tolerance test (6-minute walk test), blood oxygen saturation, blood gas composition, the main pulmonary function parameters, and pulmonary artery systolic pressure (PASP) were evaluated. The studies were conducted three times: initially, after 2 weeks and after 12 months of therapy.

Results: during NIV and LTOT, there was a decrease in dyspnea severity in group 1 (p<0.05), an increase in exercise tolerance, a significant decrease in PaCO2 (54.7±7.2 to 43.14±4.86 mm Hg, p<0.05) and an increase in PaO2. NIV use throughout the year contributed to a decrease in the number of hospitalizations associated with severe COPD exacerbation (from 3.0±1.37 to 1.2±0.5, p<0,05).

Conclusion: NIV use in patients with COPD and HRF during LTOT contributed not only to improving the parameters of gas exchange, improving the clinical condition but also to reducing the number of exacerbations that require hospitalization. In patients receiving LTOT, it is necessary to monitor the gas exchange indicators for the timely detection of HRF and NIV prescription.

Keywords: chronic obstructive pulmonary disease, hypercapnia, hypoxemia, respiratory failure, long-term oxygen therapy, non-invasive ventilation.

For citation: Kuzubova N.A., Titova O.N., Sklyarova D.B. The role of non-invasive ventilation in the complex therapy of patients with chronic obstructive pulmonary disease with hypercapnic respiratory failure. RMJ. 2021;6:23–26 (in Russ.).

Pages 27-32. Опыт применения препарата инозин пранобекс у детей с рецидивирующими респираторными инфекциями. Мелехина Е.В., Музыка А.Д., Понежева Ж.Б., Горелов А.В.

Summary:

Inosine pranobex experience in children with recurrent respiratory infections

E.V. Melekhina, A.D. Muzyka, Zh.B. Ponezheva, A.V. Gorelov

Central Research Institute of Epidemiology of the Russian Federal Service for Supervision 

of Consumer Rights Protection and Human Well-Being, Moscow

Aim: to evaluate the efficacy of various treatment regimens using inosine pranobex in children with monthly infections of the respiratory tract in the setting of herpesvirus infections (hvi) reactivation, including combined forms.

Patients and Methods: 91 children aged 3 to 17 years with monthly respiratory infections were examined on an outpatient basis during the previous 3 months of follow-up and laboratory-confirmed active forms of HVI, including concomitant forms in 41% of cases. Of these, 12 children were treated with inosine pranobex, 29 — inosine pranobex + recombinant interferon (IFN), 24 children — inosine pranobex + meglumine acridone acetate. The comparison group consisted of 26 children who underwent topical therapy of inflammatory changes in the oropharynx with herbal medicines. In total, befo re the therapy initiation, infection reactivation caused by human herpes virus 6A/B was determined in 85.8% of children, Epstein-Barr virus — 35.6%, cytomegalovirus infection — 7.5%, herpes simplex virus — 1–16%. Therapy clinical effect was evaluated 3 months after the end of therapy by the presence or absence of respiratory infection cases.

Results: in patients receiving inosine pranobex + meglumine acridonacetate, there was the most statistically significant decrease (p=0.016, according to the Student’s t-test) in the severity of the inflammatory changes in the posterior pharyngeal wall after therapy. In the group of patients receiving inosine pranobex + recombinant IFN, the most significant decrease in regional lymphadenopathy (p=0.036, according to the Mann–Whitney U-test) and hepatomegaly was determined during therapy (p=0.003, according to the Student’s t-test). The largest number of patients with a complete clinical effect over the next 3 months was demonstrated in the group receiving inosine pranobex and recombinant IFN. After the end of therapy, laboratory markers of HVI rea ctivation were manifested in 47% of children, while the rate of concomitant infections decreased from 41% to 8%. The complete clinical effect after the end of the study was recorded in 86% of patients treated with inosine pranobex + recombinant IFN, in 75% of patients in the inosine pranobex monotherapy group, and 63% of patients treated with inosine pranobex + meglumine acridonacetate. In the comparison group, acute respiratory infections were absent only in 8% of cases. The differences between the groups receiving therapy and the comparison group were statistically significant.

Conclusion: inosine pranobex has clinical and virological efficacy in the treatment of recurrent respiratory infections in children associated with HVI reactivation, including concomitant forms.

Keywords: children, recurrent respiratory infections, concomitant infections, herpesvirus infections.

For citation: Melekhina E.V., Muzyka A.D., Ponezheva Zh.B., Gorelov A.V. Inosine pranobex experience in children with recurrent respiratory infections. RMJ. 2021;6:27–32 (in Russ.).

Pages 33-39. Фармакорезистентная эпилепсия. Клиническая лекция. Котов А.С., Фирсов К.В., Санду Е.А.

Summary:

Pharmacoresistant epilepsy. Clinical lecture

A.S. Kotov, K.V. Firsov, E.A. Sandu


M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow

The article analyzes the definition of the concept pharmacoresistant epilepsy (PRE). The social significance of this disease is noted. The article also gives a detailed description of various types of PRE (genetic traits, morphological substrates, clinical phenomena, some typical biomarkers). Further study prospects of these predictors for the early detection of persons with PRE, as well as the main diagnostic methods in patients with pharmacoresistant epilepsy, including non-invasive and minimally invasive procedures of pre-surgical diagnosis are described. The main surgical treatment methods (resective and functional) are given, the method and types of invasive and non-invasive brain stimulation are considered. There are the main types of therapeutic diets in patients with PRE, such as the classic ketogenic diet, medium-chain triglyceride ketogenic diet, the modified Atkins diet, low glycemic diet. Adding that, the article gives the basic principles of pharmacological therapy for PRE. It is particularly noted that in pharmacoresistance, it is necessary to take into account not only the impossibility of achieving a sustained remission of seizures but also the presence of significant adverse events that, even in achieved remission, can force the patient to refuse to take an antiepileptic drug.

Keywords: epilepsy, pharmacoresistance, predictors, diagnosis, treatment, electrical stimulation.

For citation: Kotov A.S., Firsov K.V., Sandu E.A. Pharmacoresistant epilepsy. Clinical lecture. RMJ. 2021;6:33–39 (in Russ.).



Pages 4-5. Вакцинация беременных против COVID-19: оперативная информация. Заплатников А.Л., Гирина А.А.

Summary:

COVID-19 vaccination of pregnant women: current information

A.L. Zaplatnikov1, A.A. Girina2


1Russian Medical Academy of Continuous Professional Education, Moscow

2Khanty-Mansiysk State Medical Academy, Khanty-Mansiysk


Pregnant women are at risk for severe COVID-19, preterm birth, and other adverse outcomes during pregnancy. Preliminary data indicate that COVID-19 vaccination during pregnancy protects from the severe course of COVID-19 and is not accompanied by an adverse effect on pregnancy and the fetus. However, conclusions about the safety and efficacy of pregnant women immunization against COVID-19 will be possible only after receiving all the results of ongoing studies.

Keywords: pandemic, COVID-19, new coronavirus infection, pregnant women, vaccination.

For citation: Zaplatnikov A.L., Girina A.A. COVID-19 vaccination of pregnant women: current information. RMJ. 2021;6:4–5 (in Russ.).



Pages 40-47. Разработка инновационной программы для профилактики суставного болевого синдрома у пациентов с высокими рисками его возникновения в амбулаторной практике. Страхов М.А., Шишкин А.А., Бондаренко В.А., Загородний Н.В., Егиазарян К.А., Ахпашев А.А., Гаев Т.Г., Шевалеева Н.В., Левков В.Ю.

Summary:

An innovative program for the prevention of joint pain in high-risk patients in outpatient practice

M.A. Strakhov1-3, A.A. Shishkin2, V.A. Bondarenko2, N.V. Zagorodniy1,4, K.A. Egiazaryan2, A.A. Akhpashev3,4, T.G. Gaev3, N.V. Shavaleeva3, V.Yu. Levkov2

 

1N.N. Priorov National Medical Research Center for Trauma & Orthopedics, Moscow

2Pirogov Russian National Research Medical University, Moscow

3Federal Scientific & Clinical Center of the Federal Medical Biological Agency, Moscow

4Russian University of Peoples’ Friendship, Moscow

 

This paper addresses the authors’ materials on the development of the evidence-based preventive algorithm for joint pain in high-risk patients. This algorithm provides a differentiated management approach and involves consistent use of non-pharmacological (therapeutic and preventive exercises) and pharmacological treatments depending on pain severity. A set of exercises is shaped depending on the patient’s age and physical performance and efficacy of exercises according to evidence-based medicine. After expert analysis of the type of gymnastics, only exercises improving motion amplitude, muscle strength, and coordination were selected. Moreover, a combination of gymnastics exercises can serve as both physical therapy and therapeutic and preventive instrument. Pharmacotherapy, the next step to manage joint pain, includes various non-steroidal anti-inflammatory drugs. The novelty of this project is the discussion of pain prevention in the light of evidence-based therapeutic and preventive gymnastics exercises and their integration into current international guidelines on pain management.

Keywords: pain, joint pain, therapeutic and preventive program, pain prevention, evidence-based medicine, nimesulide.

For citation: Strakhov M.A., Shishkin A.A., Bondarenko V.A. et al. An innovative program for the prevention of joint pain in high-risk patients in outpatient practice. RMJ. 2021;6:Р 40-47 (in Russ.).


Pages 48-52. Проблемы безопасности лечения пациентов с дорсалгией. Камчатнов П.Р., Чугунов А.В., Ашалмагомедова З.А., Шемшединова А.М.

Summary:

Safety issues in the treatment of patients with dorsalgia

P.R. Kamchatnov1, A.V. Chugunov1, Z.A. Ashalmagomedova2, A.M. Shemshedinova2

1Pirogov Russian National Research Medical University, Moscow

2Dagestan State Medical University, Makhachkala

Patient management with dorsalgia requires not only timely and reliable pain relief and rehabilitation measures but also compliance with the treatment safety. Unfortunately, the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of such patients is associated with a certain risk of adverse events. The review examines the main complications during NSAIDs use from the gastrointestinal tract, cardiovascular and hepatobiliary system, etc., assesses the risks of adverse events in patients with comorbid pathology, analyzes their occurrence causes and ways to overcome them. When choosing a drug for the treatment of patients with an existing disease of these organs, you should choose those with minimal risk of complications and use short courses of treatment. The article provides information on flurbiprofen, which has a number of benefits that allow this drug to be widely used in the treatment of patients with dorsalgia.

Keywords: dorsalgia, pain syndrome, nonsteroidal anti-inflammatory drugs, treatment, adverse events.

For citation: Kamchatnov P.R., Chugunov A.V., Ashalmagomedova Z.A., Shemshedinova A.M. Safety issues in the treatment of patients with dorsalgia. RMJ. 2021;6:48–52 (in Russ.).



Pages 5-8. Региональные аспекты вакцинопрофилактики в условиях пандемии новой коронавирусной инфекции COVID-19. Дмитриев А.В., Федина Н.В., Гудков Р.А., Петрова В.И., Заплатников А.Л.

Summary:

Regional aspects of vaccination in the era of the COVID-19 pandemics

А.V. Dmitriev1, N.V. Fedina1, R.A. Gudkov1, V.I. Petrova1, А.L. Zaplatnikov2

1Ryazan State Medical University, Ryazan

2Russian Medical Academy of Continuous Professional Education, Moscow

Aim: to assess the coverage of children aged 0–18 years with vaccination in 2018–2020 in the Ryazan region and to perform a comparative analysis of monthly immunization plan as a part of the national calendar of prophylactic immunization of children aged 0–18 years in the first year of the COVID-19 pandemic.

Patients and Methods: monthly and annual formulations No. 6 “Data on children and adults vaccinated against infections” (from December 31, 2018, to December 31, 2020) as well as monthly and annual formulations No. 5 “Data on preventive vaccinations” (from January to December 2020) in the Ryazan region were analyzed. Anonymous in-person voluntary questioning of 60 out-patient pediatricians on the novel coronavirus infection was performed.

Results: the coverage with vaccination in the Ryazan region in 2018–2020 is a rather high being at least 95%. In the second quarter of 2020, a significant reduction in the coverage with all calendar prophylactic vaccinations was reported being in line with the recommendations on the temporary suspension of vaccination in April-May 2020. The removal of limitations of immunization in May 2020 provided a gradual increase in the coverage of children of the Ryazan region with vaccination and the recovery to standard ratios in June 2020.

Conclusion: the COVID-19 pandemics in 2020 compromised vaccination plans in April-May as a result of limitations and quarantine. However, the vaccination plan was fully implemented by the end of 2020. This can be accounted for by vaccine runner-up measures realized in the summer and autumn of 2020.

Keywords: pandemics, COVID-19, immunization, vaccination, national calendar of prophylactic immunization, immunization plan.

For citation: Dmitriev А.V., Fedina N.V., Gudkov R.A. et al. Regional aspects of vaccination in the era of the COVID-19 pandemics. RMJ. 2021;6:5–8 (in Russ.).

Pages 53-55. Ассоциация вируса герпеса человека 6 типа с синдромом хронической тазовой боли: клиническое наблюдение. Ковалык В.П., Юрлов К.И., Гомберг М.А., Шувалов А.Н., Малиновская В.В., Кущ А.А.

Summary:

Association of human herpesvirus 6 with chronic pelvic pain syndrome: a clinical case

V.P. Kovalyk1, K.I. Yurlov2, M.A. Gomberg3, A.N. Shuvalov2, V.V. Malinovskaya2, A.A. Kusch2


1Federal Research and Clinical Center of the Federal Medical Biological Agency, Moscow

2National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya, Moscow

3Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology, Moscow

In chronic prostatitis/chronic pelvic pain syndrome IIIA (CP/CPPS) there is an increased WBC count in the prostate gland secret, but the standard diagnostic search for microbial agents is commonly unsuccessful. During the introduction of molecular genetics into clinical practice, the number of studies on the role of viral agents in this disease began to increase. Human herpesvirus 6 (HHV-6) has a tropism to nerve cells, and therefore, their role in neurodegenerative diseases and pain syndromes is being studied. The uniqueness of this virus is the possibility of its embedding in the chromosome telomere and its congenital transmission. The article presents a clinical case of HHV-6 detection in urogenital samples in the presence of CP/CPPS in clinically significant titers. HHV-6 was the only probable etiological agent of this disease. The conducted antiviral therapy using a combination of a nucleoside analog (Valacyclovir) (1000 mg per day for 90 days and interferon α-2b drug with antioxidants in rectal suppositories of 3 million IU 2 times a day for 10 days, then 3 times a week for 3 weeks) showed a good clinical and virological effect.

Keywords: chronic prostatitis, chronic pelvic pain, herpesvirus 6, antiviral therapy.

For citation: Kovalyk V.P., Yurlov K.I., Gomberg M.A. et al. Association of human herpesvirus 6 with chronic pelvic pain syndrome: a clinical case. RMJ. 2021;6:53–55 (in Russ.).

Pages 56-62. Влияние бессимптомной гиперурикемии на течение коморбидной патологии у пациентов с остеоартритом и возможности ее коррекции. Мазуров В.И., Гайдукова И.З., Башкинов Р.А., Фонтуренко А.Ю., Петрова М.С., Инамова О.В.

Summary:

Asymptomatic hyperuricemia impact on the comorbid pathology course in patients with osteoarthritis and the possibility of its correction

V.I. Mazurov1,2, I.Z. Gaidukova1,2, R.A. Bashkinov1,2, A.Yu. Fonturenko1,2, M.S. Petrova1,2, O.V. Inamova1,2

1I.I. Mechnikov North-Western State Medical University, Saint-Petersburg

2Clinical Rheumatology Hospital No. 25, Saint-Petersburg

Background: hyperuricemia is diagnosed when the level of serum uric acid (SUA) exceeds 360 µmol/L in women and 420 µmol/L in men. The importance of hyperuricemia in the development of comorbid conditions (in the absence of gouty arthritis), as well as the need for the use of urate-lowering therapy (ULT) in asymptomatic hyperuricemia (AHU), are the subject of discussion among specialists of the medical community.

Aim: to study the incidence and treatment patterns of comorbid conditions in patients with osteoarthritis and AHU.

Patients and Methods: data of patients with OA and AHU were analyzed on the basis of Saint-Petersburg City Registry of Patients with Gout and AHU data. Gender and age of patients, laboratory parameters, the presence of comorbid conditions and the drug therapy received were analyzed.

Results: the analysis included data of 400 patients with AHU. It was found that in AHU, the incidence of arterial hypertension, angina pectoris, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, chronic heart failure, transient  ischemic attacks, cerebrovascular diseases, obesity, type 2 diabetes mellitus, peptic ulcer disease, chronic pyelonephritis and chronic kidney disease significantly (p<0.05) exceeds the population indicator. Only 36.75% of patients received allopurinol as the ULT. Improvement of the SUA level during treatment was achieved in 20.4% of patients. The main reasons for not achieving the SUA target levels were the prescription of deliberately low doses of the drug and the lack of their titration according to the SUA level during treatment.

Conclusion: AHU is a condition associated with metabolic syndrome, kidney disease, and cardiovascular disease. ULT, during which allopurinol (Milurit®, EGIS) is commonly used as a registered drug for the «hyperuricemia» indication, may be one of the promising options for solving problems associated with AHU. It should be noted that the ULT prescription may not be sufficient without dose titration of the drug according to the SUA level and the absence of non-drug correction of cardiovascular risk factors.

Keywords: uric acid, asymptomatic hyperuricemia, comorbid conditions, urate-lowering therapy, allopurinol.

For citation: Mazurov V.I., Gaidukova I.Z., Bashkinov R.A. et al. Asymptomatic hyperuricemia impact on the comorbid pathology course in patients with osteoarthritis and the possibility of its correction. RMJ. 2021;6:56–62 (in Russ.).

Pages 63-66. Эффективность и безопасность использования фенилбутазона для внутримышечного введения при остеоартрите коленного сустава. Нестеренко В.А., Каратеев А.Е., Зеленов В.А., Зоткин Е.Г.

Summary:

Efficacy and safety of phenylbutazone use intramuscularly in knee osteoarthritis

V.A. Nesterenko, A.E. Karateev, V.A. Zelenov, E.G. Zotkin


Research Institute of Rheumatology named after V.A. Nasonova, Moscow

Background: osteoarthritis (OA) is the most common disease among joint diseases. In OA, there is developing chronic pain that decreases the life quality of patients, leading to significant limitations in daily activities and disability. One of the leading treatment methods is the use of non-steroidal anti-inflammatory drugs (NSAIDs).

Aim: to evaluate the efficacy and safety of phenylbutazone intramuscular injections in knee OA.

Patients and Methods: 30 patients participated in the prospective study, including 21 (70%) women (the median age of all patients was 48 [35; 62] years) with a confirmed diagnosis of OA according to X-ray examination data and the presence of active synovitis according to ultrasound results. All patients received intramuscular injections of AMBENIUM® parenteral 2 ml with an interval of 7 days. The efficacy criteria were the pain dynamics during movement (according to the 100 mm VAS) and functional status (according to the HAQ-DI and KOOS questionnaires), and the dynamics of ultrasound inflammatory indicators in the knee joint. The treatment results were assessed during 5 consecutive visits: before the start of the course, after the 2nd and 3rd administration (after 7±2 and 14±2 days), after 28±2 and 56±2 days after the start of the study.

Results: during treatment, there was a significant improvement in all indicators of pain and knee joint function. The average pain severity according to VAS at baseline and by the end of the follow-up was 40 [30; 60] and 20 [0; 30] mm (p=0.000008), respectively; the average values of the KOOS indicator were 59.6 [32.5; 73.6] and 72.7 [54.9; 87.4] points (p=0.009469), for HAQ-DI — 1.1 [0.88; 1.75] and 1.0 [0.84; 1.3] points (p=0.07). As a result of the treatment, the excess amount of fluid was preserved only in 30% of patients. There was a significant (p<0.05) decrease in the thickness of the synovial membrane and the amount of fluid in the bursa. No serious adverse events were observed.

Conclusion: injection therapy with AMBENIUM® parenteral is an effective method of relieving pain in knee OA and is associated with a low risk of adverse events.

Keywords: osteoarthritis, knee joint, synovitis, pain, nonsteroidal anti-inflammatory drugs, phenylbutazone, parenteral administration.

For citation: Nesterenko V.A., Karateev A.E., Zelenov V.A., Zotkin E.G. Efficacy and safety of phenylbutazone use intramuscularly in knee osteoarthritis. RMJ. 2021;6:63–66 (in Russ.).



Pages 68-74. Место и роль парентеральной формы хондроитина сульфата в терапии остеоартрита: мультидисциплинарный Консенсус. Лила  А.М., Ткачева О.Н., Наумов  А.В., Алексеева Л.И., Кочиш А.Ю., Котовская Ю.В., Рачин А.П., Сарвилина И.В.

Summary:

Place and role of the parenteral form of chondroitin sulfate in the treatment of osteoarthritis: multidisciplinary Consensus

A.M. Lila1,2, O.N. Tkacheva3, A.V. Naumov3, L.I. Alekseeva1, A.Yu. Kochish4, Yu.V. Kotovskaya3, A.P. Rachin5, I.V. Sarvilina6

1Research Institute of Rheumatology named after V.A. Nasonova, Moscow 

2Russian Medical Academy of Continuous Professional Education, Moscow

3Pirogov Russian National Research Medical University, Moscow

4Russian Scientific Research Institute of Traumatology and Orthopedics named after R.R. Vreden, Saint-Petersburg

5National Medical Research Center of Rehabilitation and Balneology, Moscow

6Medical Center «Novomedicina» LLC, Rostov-on-Don

The article presents the first Consensus on the place and role of the parenteral form of chondroitin sulfate (CS) in the treatment of osteoarthritis (OA). An increase in the medical and social burden of OA was noted worldwide. The evidence base analysis on the efficacy and safety of its use was carried out in patients with comorbid pathologies and secondary OA of large joints. The clinical sections of the consensus discuss the place of the CS parenteral form in modern clinical recommendations for the patient management with OA, as well as the possibilities of using CS at the stages of providing traumatological and rehabilitative medical care to patients with OA, and the role of CS in the treatment of OA. It has been shown that the CS parenteral form for intramuscular and intra-articular administration (Chondroguard®) has a number of pharmaceutical and clinical benefits, and, therefore, can be recommended for initial use in exacerbations of chronic joint and back pain in OA, including in comorbid patients. It is recommended to include CS for intra-articular and intramuscular administration in the treatment regimen for secondary OA of large joints (post-traumatic and dysplastic OA) at the stages of providing traumatological and rehabilitative medical care.

Keywords: osteoarthritis, comorbidity, chondroitin sulfate, Chondroguard, asthenia, standardization, pharmaceutical substance, pharmaceutical analysis.

For citation: Lila A.M., Tkacheva O.N., Naumov A.V. et al. Place and role of the parenteral form of chondroitin sulfate in the treatment of osteoarthritis: multidisciplinary Consensus. RMJ. 2021;6:68–74 (in Russ.).

Pages 75-80. Кардиоваскулярная безопасность нестероидных противовоспалительных препаратов. Чичасова Н.В., Лила А.М.

Summary:

Cardiovascular safety of nonsteroidal anti-inflammatory drugs

N.V. Chichasova1,2, A.M. Lila1,2


1Research Institute of Rheumatology named after V.A. Nasonova, Moscow

2Russian Medical Academy of Continuous Professional Education, Moscow

The article is devoted to the problem of the safety of nonsteroidal anti-inflammatory drugs (NSAIDs) with an emphasis on their adverse events (AEs) in relation to the cardiovascular system. The association of these AEs to the mechanism of action of NSAIDs was discussed. It was indicated that for the AEs prevention, it is necessary to assess the risk factors for the development of complications associated with NSAIDs use. Factors of high and moderate cardiovascular risk were identified. The article discusses the interpretation complexity of the changes in the cardiovascular system due to the high incidence of comorbid conditions in the pathology of the musculoskeletal system, as well as the involvement of chronic inflammation in the genesis of atherosclerosis and, as a result, cardiovascular pathology development (or aggravation of the course). Data on the increase in the risk  of cardiovascular complications with dose increment of selective and non-selective NSAIDs were presented. It was noted that only very high doses of selective cyclooxygenase 2 (COX-2) inhibitors could be considered potentially dangerous in long-term continuous administration in groups with the risk of developing cardiovascular complications. The article also presents the data of a large-scale cohort study comparing cardiovascular risk during selective COX-2 inhibitors intake, according to which meloxicam has some superiority. The high safety of meloxicam was confirmed by the data of meta-analyses and systematic reviews, which showed that meloxicam did not worsen the course of arterial hypertension and coronary heart disease, did not aggravate edema, did not increase the incidence of myocardial infarction or thrombotic events. Meloxicam intake is associated with a slight increase in the combined risk of cardiovascular complications (risk ratio — 1.14, 95% confidence interval 1.04 d01.25), mainly its vascular component, without increasing myocardial and renal risk. It was noted that the simultaneous administration of meloxicam and acetylsalicylic acid to healthy volunteers did not affect the disaggregation effect of the latter.

Keywords: nonsteroidal anti-inflammatory drugs, NSAIDs, meloxicam, rofecoxib, celecoxib, non-selective NSAIDs, cardiovascular safety, risk, prevention.

For citation: Chichasova N.V., Lila A.M. Cardiovascular safety of nonsteroidal anti-inflammatory drugs. RMJ. 2021;6:75–80 (in Russ.).



Pages 81-87. Холестатические заболевания печени: алгоритмы диагностики и лечения. Полунина Т.Е.

Summary:

Cholestatic liver diseases: diagnostic and treatment algorithms

T.E. Polunina


A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow


Over the past decade, significant progress has been made in understanding the molecular basis of bilification and the cholestasis pathophysiology. The article presents the goals of cholestasis therapy, which help to understand existing treatment methods and contribute to the development of new drugs for cholestatic liver diseases (CLD). This article also briefly summarizes the current concepts of bilification and cholestasis occurrence. Treatment of CLD is illustrated by the example of the most common chronic cholestatic liver disease — primary biliary cholangitis.

Keywords: bile, cholestasis, cholestatic liver diseases, primary biliary cholangitis, ursodeoxycholic acid.

For citation: Polunina T.E. Cholestatic liver diseases: diagnostic and treatment algorithms. RMJ. 2021;6:81–87 (in Russ.).

Pages 87-92. Гетеротопия слизистой оболочки желудка в проксимальном отделе пищевода: исторический ракурс и современный взгляд. Долгушина А.И., Хихлова А.О., Олевская Е.Р., Науменко О.В.

Summary:

Heterotopic gastric mucosa in the proximal esophagus: historical aspect and modern view

A.I. Dolgushina1, A.O. Khikhlova1,2, E.R. Olevskaya1,2, O.V. Naumenko2

1South Ural State Medical University, Chelyabinsk

2Chelyabinsk Regional Clinical Hospital, Chelyabinsk

According to the autopsy data, heterotopic gastric mucosa in the proximal esophagus (or inlet patch), which is an area of ectopic mucosa (characteristic of the stomach), is diagnosed more commonly than it is visualized endoscopically, and also is accompanied by clinical symptoms. The article is devoted to the etiology and pathogenesis of the inlet patch, as well as to the analysis concerning the prevalence of pathology and clinical manifestations. The article also presents modern clinical and pathological classification, which includes five individual groups based on the clinical, endoscopic and histological characteristics of the inlet patch. The literature data on the association of inlet patch in the upper esophagus with functional disorders of the gastrointestinal tract (GIT), Barrett’s esophagus, as well as its neoplastic transformation are considered. Special attention is paid to the diagnosis of the inlet patch based on a targeted examination of the cervical esophagus using modern endoscopic equipment. The article presents the principles of drug therapy and endoscopic tr eatment of symptomatic patients with the inlet patch. The review demonstrates the importance of clinicians’ awareness of this pathology and a multidisciplinary approach to patient management.

Keywords: heterotopia, gastric mucosa, upper third of the esophagus, inlet patch, esophagogastroduodenoscopy, radiofrequency ablation.

For citation: Dolgushina A.I., Khikhlova A.O., Olevskaya E.R., Naumenko O.V. Heterotopic gastric mucosa in the proximal esophagus: historical aspect and modern view. RMJ. 2021;6:87–92 (in Russ.).

Pages 9-13. Пандемия новой коронавирусной инфекции в Кабардино-Балкарской Республике. Опыт региона. Шогенова М.С., Хутуева С.Х., Тлупова И.Б., Аккиева М.А., Шогенова Л.С.

Summary:

The pandemic of a new coronavirus infection in the Kabardino-Balkarian Republic. Regional experience

M.S. Shogenova1,2, S.Kh. Khutueva1, I.B. Tlupova1, M.A. Akkieva1, L.S. Shogenova2


1Center of Allergology of the Ministry of Health of the KBR, Nalchik

2Kabardino-Balkarian State University named after H.M. Berbekov, Nalchik

Aim: to analyze various clinical indicators in patients with a new coronavirus infection and determine the main disease markers.

Patients and Methods: 55 case histories of patients diagnosed with new coronavirus infection (COVID-19) were analyzed. There were 5 groups: group 1 — mild course; group 2 —moderate course with lung damage up to 25% (according to CT); group 3 — moderate course with lung damage 25–50% (according to CT); group 4 — severe course; group 5 — extremely severe course. The examination included clinical and biochemical studies, coagulogram, determination of SARS-CoV-2 RNA by polymerase chain reaction (PCR), as well as IgM and IgG antibodies to the SARS-CoV-2 betacoronavirus nucleocapsid protein by enzyme immunoassay.

Results: it was found that in the COVID-19 clinical picture, the manifestations of gastroenterocolitis (13 patients, 23.6%) and cutaneous eruption (3 patients, 5.5%), along with intoxication syndrome, were significant. In patients depending on the severity of detected eritropeniya (3,51±0,1×1012/L in group 5), leukopenia (2,93±0,1×109/L in group 5) and elevated ESR (46,14±2.0 mm/h in group 5), which has significant differences versus the groups 3 and 4. Acute-phase proteins — C-reactive protein (CRP), D-dimer, ferritin — had statistically significant differences (p<0.01) and increased in groups depending on the COVID-19 course, for instance, CRP increased more than 15 times. A direct correlation was established (r=0.68, p<0.01) between CRP level and COVID-19 course. A direct correlation was recorded between an increase in the level of CRP, interleukin-6 (IL-6) and COVID-19 course (r=0.56, p<0.05), which suggests that CRP and IL-6 are markers of COVID-19 severity.

Conclusion: thus, the study identified clinical COVID-19 masks —intestinal (23.6% of patients) and cutaneous (5.5% of patients). At the disease onset before the pneumonia occurrence, the PCR diagnosis of COVID-19 is more informative, which confirms the presence of 100% positive results of a PCR smear on SARS-CoV-2 RNA in group 1 and 100% negative results of a PCR smear on SARS-CoV-2 RNA in group 5.

Keywords: new coronavirus infection, COVID-19, D-dimer, ferritin, saturation, lung damage rate, clinical masks.

For citation: Shogenova M.S., Khutueva S.Kh., Tlupova I.B. et al. The pandemic of a new coronavirus infection in the Kabardino-Balkarian Republic. Regional experience. RMJ. 2021;6:9–13 (in Russ.).



Pages 93-95. Потенциальная роль кишечной микробиоты в формировании болезни Альцгеймера. Бикбавова Г.Р., Лопата С.И., Кидалов М.Б., Ахмедов В.А.

Summary:

Potential role of the gut microbiota in the development of Alzheimer’s disease

G.R. Bikbavova, S.I. Lopata, M.B. Kidalov, V.A. Akhmedov

Omsk State Medical University, Omsk

Over the past 10 years, leading experts in the study of Alzheimer’s disease (AD) pathogenesis have suggested that immune-mediated systemic inflammatory responses may play a leading role in AD development. We have summarized the literature data on the potential impact of gut microbiota disorders on AD development. Publications from GoogleSchoolar and PubMed resources were used in this study. It is known that some gut microflora representatives produce gamma-aminobutyric acid (GABA), which has a neuroprotective function and can inhibit immune-inflammatory responses, as well as participate in the proliferation of neuronal precursor cells. The gut microbiota participates in the synthesis of serotonin, which plays a crucial role in the processes of learning, memory formation, and higher cognitive functions that are affected in AD. A low amount of intestinal Lactobacillus and Bifidobacterium reduces the amount of GABA and serotonin in the intestine and central nervous system, which can mediate the launch of a systemic inflammatory response cascade and impaired higher cognitive functions. Lactobacillus among the metabolic products produces 3- (3’-hydroxyphenyl) —propionic acid and 3-hydroxybenzoic acid, which can inhibit the assembly of β-amyloid from the protein precursor. Therefore, the maintenance of Lactobacillus physiological function can play a key role in AD prevention.

Keywords: Alzheimer’s disease, amyloid cascade, gut microbiota, microbiome, dysbiotic processes, antibiotic therapy, systemic inflammatory response syndrome.

For citation: Bikbavova G.R., Lopata S.I., Kidalov M.B., Akhmedov V.A. Potential role of the gut microbiota in the development of Alzheimer’s disease. RMJ. 2021;6:93–95 (in Russ.).

Pages 96-100. Дефицит и недостаточность витамина D, факторы риска и его коррекция у людей пожилого возраста. Сафонова Ю.А., Торопцова Н.В.

Summary:

Vitamin D deficiency and insufficiency, risk factors and its correction in the elderly patients

Yu.A. Safonova1,2, N.V. Toroptsova2

1I.I. Mechnikov North-Western State Medical University, Saint-Petersburg

2Research Institute of Rheumatology named after V.A. Nasonova, Moscow

Aim: to study the vitamin D level in elderly and senile patients, to identify factors that contribute to its decrease and to evaluate the efficacy of the replacement therapy.

Patients and Methods: a prospective cohort study conducted from 2016 to 2018 included 506 people aged 65 years and older (354 women and 152 men), whose median age was 74 [68; 78] years, who did not take vitamin D preparations 6 months before the start of the study. Patients were divided into three age groups: group 1 – 243 patients aged 65–74 years (48.0%), group 2 – 223 patients aged 75–84 years (44.1%), and group 3–40 patients aged 85 years and older (7.9%). All those included in the study underwent an anthropometric measurement and calculation of the body mass index (BMI). The level of physical activity was determined by the International Physical Activity Questionnaires (IPAQ). The content of 25-hydroxy vitamin D (25(ОН)D) was determined by immunochemiluminescence analysis. The study was conducted during a period of low insolation from September to May. The therapy efficacy was evaluated after 3 and 12 months among 202 patients who completed the study.

Results: deficiency and insufficiency of 25(ОН)D was detected in 86.4% of patients over 65 years of age. The risk of vitamin D deficiency increased with increasing age and reached 77.5% of people aged 85 years and older (p<0.01), and was also higher in persons with insufficient BMI (relative risk (RR) =1.39; 95% CI: 1.24–1.55; p<0.0001), in obese people (RR=1.23; 95% CI: 1.06–1.42; p=0.0057) and low physical activity (RR=1.37; 95% CI: 1.12–1.68; p=0.0021). All patients with hypovitaminosis D underwent its correction using cholecalciferol, which allowed to achieve an adequate level of 25(ОН)D in 91.3% of cases and maintain it for 12 months in 90.6% of patients with a maintaining dose of vitamin D.

Conclusion: a high incidence of hypovitaminosis D was revealed among the elderly and senile patients; its adequate correction allowed not only to normalize but also to maintain its optimal level.

Keywords: vitamin D deficiency, hypovitaminosis D, elderly age, correction of vitamin D level, cholecalciferol.

For citation: Safonova Yu.A., Toroptsova N.V. Vitamin D deficiency and insufficiency, risk factors and its correction in the elderly patients. RMJ. 2021;6:96–100 (in Russ.).





№5, 2021. Неврология

Pages 11-16. Оценка эффективности комплексного физиотерапевтического лечебного подхода, направленного на стимуляцию процесса резорбции грыж межпозвонковых дисков поясничного отдела позвоночника. Ткачев А.М., Епифанов А.В., Акарачкова Е.С., Смирнова А.В., Илюшин А.В., Гордеева И.Е.

Summary:

Efficacy of complex physiotherapeutic approach to stimulate the resorption of lumbar disc herniation

A.M. Tkachev1,2,3, A.V. Epifanov3, E.S. Akarachkova4, A.V. Smirnova1, A.V. Ilyushin3, I.E. Gordeeva5

1Sergey Berezin Medical Institution, St. Petersburg

2Tkachev’s Clinic, Volgograd

3Tkachev’s and Epifanov’s Clinic, Moscow

4International Society “Stress under Control”, Moscow

5Volgograd State Medical University, VolgogradAim: to assess the efficacy of treatment approaches aimed at stimulating the resorption of lumbar disc herniation (LDH) in the acute stage of LDH, Volgograd

Patients and Methods: 101 patients (50 women and 51 men) with acute leg pain (≥ 6 points by VAS scale) resulting from LDH were enrolled. Initial LDH size and its changes were measured by MRI. All patients received gabapentin (300–2400 mg daily, dose adjustment after 3 and 8 weeks. At baseline, all patients underwent 12 consecutive daily acupuncture and laser therapy (MLS M6, Beka, Russian Federation). 12 weeks after finishing physiotherapy, all patients underwent re-MRI. Further management strategy was based on MRI results and clinical presentation, i.e., to proceed to treatment (persistent pain or no pain but persistent LDH) or to stop treatment (the lack of pain and reduced LDH sizes). Patients who proceeded to treatment were prescribed with repeated complex physiotherapy. This protocol was followed until pain relief and LDH resorption.

Results: after the first, second, and third courses of physiotherapy, 26 patients (25.7%), 47 patients (46.5%), and 22 patients (21.8%), respectively, stopped the treatment. 6 patients (5.9%) required the fourth course of physiotherapy. The rate and level of LDH resorption were directly proportional to LDH size at baseline. The mean LDH resorption period was 4.4 months. In the first 12 weeks, mean gabapentin dose to relieve leg pain was 1320±50 mg daily. Patients who proceeded to treatment required, on average, 489±30 mg daily.

Conclusions: acute LDH treatment using complex physiotherapy (acupuncture and MLS laser therapy) plus gabapentin that maintains natural inflammation is an effective and safe strategy that reduces the size of LDH.

Keywords: disc herniation, spontaneous resorption, inflammation, gabapentin, acupuncture.

For citation: Tkachev A.M., Epifanov A.V., Akarachkova E.S. et al. Efficacy of complex physiotherapeutic approach to stimulate the resorption of lumbar disc herniation. RMJ. 2021;5:11–16.

Pages 17-22. Роль комплексного препарата витаминов группы В, уридина и холина в терапии хронического болевого синдрома у пациентов с падениями. Наумов  А.В., Мороз В.И., Маневич Т.М.

Summary:

Complex medication containing B vitamins, uridine, and choline for chronic pain management in patients who fall

A.V. Naumov, V.I. Moroz, T.M. Manevich

Russian Research Clinical Center for Gerontology, Pirogov Russian National Research Medical University, Moscow

Background: chronic pain in elderly patients is associated with the increased rate of falls. Drug effects on the functional status and autonomy are the key issue of pain management in elderly patients.

Aim: to assess the efficacy of a complex medication containing B vitamins, uridine, and choline for chronic pain management in patients who fall.

Patients and Methods: this study included 60 patients with chronic pain and falls. These patients were divided into two groups (30 patients each). Study group patients received complex treatment including standard therapies for chronic pain (i.e., gabapentin, cholecalciferol, diclofenac, and omeprazole) and B vitamins in combination with uridine and choline (one dragee daily). Control group patients received standard therapies for chronic pain only. After two months, pain severity measured by VAS and WOMAC sca les, physical functioning, the severity of neuropathic pain component, and the risk of falls were evaluated.

Results: pain reduction, as demonstrated by VAS and WOMAC scores was more significant in the study group compared to the controls. Moreover, the treatment resulted in more significant reduction of time for five rises from the chair and timed up and go test. More significant changes, as demonstrated by increased score of the Short Physical Performance Battery were also seen in the study group. Complex treatment for musculoskeletal pain resulted in a significant reduction in the risk of falling.

Conclusions: a medication containing B vitamins, uridine, and choline as a component of the complex treatment for musculoskeletal pain reduces pain severity, clinical manifestations of neuropathic pain, and the risk of falling in patients over 60 with chronic pain.

Keywords: chronic pain, musculoskeletal pain, falls, neuropathic pain, thermoesthesia.

For citation: Naumov A.V., Moroz V.I., Manevich T.M. Complex medication containing B vitamins, uridine, and choline for chronic pain management in patients who fall. RMJ. 2021;5:17–22.

Pages 2-5. Влияние цитиколина на когнитивные функции у пациентов, перенесших COVID-19. Зуева И.Б., Ким Ю.В., Суслова М.Ю.

Summary:

Citicoline effect on cognitive function in COVID-19 patients

I.B. Zueva1, Yu.V. Kim2, M.Yu. Suslova1

1Saint Petersburg Medico-Social Institute, Saint Petersburg

2Pavlov First Saint Petersburg State Medical University, Saint Petersburg


Background: there is growing evidence that coronaviruses can affect not only the lungs but also other organs and systems, in particular, the central nervous system. However, little is currently known about the coronavirus infection long-term effects on the brain and its consequences in terms of cognitive functioning.

Aim: to study the effect of citicoline therapy on the cognitive functions and emotional status of patients who experienced COVID-19.

Patients and methods: 48 subjects were included in the study. The main group consisted of patients who experienced COVID-19 (n=24, mean age 43.72±5.21 years), the control group — healthy subjects (n=24, mean age 44.18±5.32 years). Patients of the main group were randomized into two subgroups of 12 patients: subgroup A r eceived citicoline orally at a dose of 1000 mg/day (100 mg in 1 ml), subgroup B did not receive treatment. The study duration was 14 days. Neuropsychological test was performed initially and after the end of the study.

Results: the majority of patients who experienced COVID-19 reported the following: persistent fatigue — 24 (100%), poor sleep — 20 (83.3%), palpitations — 20 (83.3%), memory loss — 18 (75%). The main group of patients showed a decrease in the short-term memory index (6.45±1.14 and 8.97±1.51 points, p<0.05), the MMSE test result (27.26±2.10 and 29.81±2.93 points, p<0.05), encryption test (40.37±9.64 and 48.91 ± 9.86 seconds, p<0.05), and increase in the anxiety level (9.34±0,45 and 4.12±0.21 points, p<0.05) versus the control group. In the subgroup A, during citicoline therapy, there was an improvement in memory index (6.48±1.15 and 8.32±1.49 points, p<0.05; 6.53±1.18 and 7.34±1.25 points, respectively, p>0.05), general cognitive functions (27.51±2.13 and 28.89±2.41 points, p<0.05; 27.62±2.29 and 27.95±2.36 points, respectively, p>0.05), encryption test results (40.34±9.61 and 46.72±9.83 seconds, p <0.05; 41.56±9.62 and 42.28±9.75 seconds, respectively, p>0.05), improved sleeping (19.38±0.61 and 21.64±0.74 points, p<0.05; 19.20±0.58 and 19.82±0.63 points, respectively, p>0.05), a decrease in the anxiety level (9.27±0.47 and 7.14±0.31 points, p<0.05; 9,35±0.46 and 8.81±0.44 points, respectively, p>0.05) versus the subgroup B.

Conclusion: there was an improvement in cognitive functions in general, a decrease in anxiety level and normalization of sleep during citicoline treatment of patients who have suffered from COVID-19.

Keywords: cognitive disorders, memory, attention, anxiety, COVID-19, citicoline.

For citation: Zueva I.B., Kim Yu.V., Suslova M.Yu. Citicoline effect on cognitive function in COVID-19 patients. RMJ. 2021;5:2–6.



Pages 24-29. Особенности ведения пациентов с нейродегенеративными заболеваниями в условиях пандемии COVID-19. Пилипович А.А.

Summary:

Characteristics of patient management with neurodegenerative diseases during COVID-19 pandemic

A.A. Pilipovich

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

There is no evidence that neurodegenerative diseases, including Parkinson’s disease (PD), worsen the COVID-19 outcome. However, in the advanced PD stages, the risk of respiratory decompensation increases due to the motor and vegetative disorders. Patients with cognitive decline during pandemic have an increased risk of infection, as well as an increase in the severity of the underlying disease due to stress. The review presents patient management tactics in dementia and the doctor’s response to this behavior, as well as some additional methods that can help patients cope with stress. High-tech treatment methods that are used in the advanced PD stage do not have contraindications for coronavirus infection. Their use is recommended to continue even in the intensive care unit to ensure constant antiparkinsonian support, to avoid motor and non-motor complications in the akin etic crisis. An important task is to provide all patients with neurodegenerative diseases with conditions for communication with medical personnel, which can be achieved through telemedicine technologies that are actively developing in the context of a pandemic.

Keywords: neurodegenerative diseases, Parkinson’s disease, Alzheimer’s disease, dementia, COVID-19, SARS-CoV-2, amantadine.

For citation: Pilipovich A.A. Characteristics of patient management with neurodegenerative diseases during COVID-19 pandemic. RMJ. 2021;5:24–29.

Pages 30-34. Поражение периферической нервной системы при коронавирусной инфекции COVID-19. Камчатнов П.Р., Евзельман М.А., Чугунов А.В.

Summary:

Peripheral nervous system disorders in COVID-19 

P.R. Kamchatnov1, M.A. Evzelman2, A.V. Chugunov1

1Pirogov Russian National Research Medical University, Moscow 2Orel State University named after I.S. Turgenev, Orel

The high incidence of a new coronavirus infection (COVID-19), the variety of organs and body systems involved in the pathological process in this disease, and commonly severe course with disabling consequences have caused deep interest in this problem. A common lesion of the peripheral nervous system (PNS) was found in patients with COVID-19, which allowed to suggest the neurotropic nature of the SARS-CoV-2. The article presents information about PNS lesions in COVID-19 and discusses possible mechanisms of their development. Among others, it is suggested that immune disorders play a key role in the initiation and subsequent progression of changes in the PNS. Article provides information on the possible role of B vitamins metabolic disorders in the pathogenesis of PNS lesions in COVID-19 (including through the impact on various parts of the immune system) and on the association of vitamin B deficiency with a more severe disease course. The possibilities of these disorders’ correlation are discussed.

Keywords: COVID-19, neuropathy, Guillain-Barre syndrome, anosmia, dysgeusia, thiamine, pyridoxine, cyanocobalamin, treatment.

For citation: Kamchatnov P.R., Evzelman M.A., Chugunov A.V. Peripheral nervous system disorders in COVID-19. RMJ. 2021;5:30–34.







Pages 35-41. Аффективные нарушения у пациентов с церебральной микроангиопатией в период пандемии COVID-19. Воробьева О.В.

Summary:

Affective disorders in patients with cerebral microangiopathy during the COVID-19 pandemic

O.V. Vorobieva

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

The most common and least studied type of cerebrovascular pathology is cerebral microangiopathy (CMA). Patients with vascular risk factors (hypertension, diabetes, obesity, etc.) are more vulnerable to the SARS-CoV-2 virus since the concomitant endothelial dysfunction and antioxidant protection break-down increase the probability of infection and contribute to a more severe disease course. COVID-19 outcomes, in particular, are affected by the cerebral perfusion level. Thus, slowing the progression of cerebrovascular pathology is one of the most important protective measures. At the same time, even a mild COVID-19 course can worsen cerebral perfusion and exacerbate affective and cognitive symptoms. In patients with a silent form of CMA, SARS-CoV-2 infection may contribute to the clinical manifestation of symptoms. The article describes the etiopathogenetic CMA aspects and the affective disorders associated with CMA. It also notes the problems faced by patients with such disorders in the context of the COVID-19 pandemic. Methods for the complex therapy of affective disorders in patients with CMA during the COVID-19 pandemic are considered.

Keywords: cerebral m icroangiopathy, affective disorders, cognitive disorders, endothelial dysfunction, COVID-19.

For citation: Vorobieva O.V. Affective disorders in patients with cerebral microangiopathy during the COVID-19 pandemic. RMJ. 2021;5:35–41.

Pages 42-44. Транзиторная ишемическая атака: агрессивная лечебная стратегия. Широков Е.А.

Summary:

Transient ischemic attack: an aggressive treatment strategy

E.A. Shirokov

Branch of the S.M. Kirov Military Medical Academy, Moscow, Russian Federation

In recent decades, vascular catastrophes (stroke and myocardial infarction) are the leading causes of early death and permanent disability. The prevention of vascular catastrophes by modifying the classical cardiovascular risk factors is the key measure to address this issue. Transient ischemic attacks (TIAs) increase the risk of all vascular events. Diagnosing TIAs, clarifying the causes and mechanisms of the decompensation of cerebral blood circulation, and reasonable targeted treatment prevent severe complications in patients with high cardiovascular risk being a considerable preventive resource. This paper discusses the evolution of approaches that consider TIAs as a risk factor for vascular events in high-risk patients and the use of neuroimaging techniques that determine management strategy. The authors analyze the efficacy and safety of aggressive treatment approach implying the prescription of dual antithrombotic, antihypertensive, lipid-lowering therapies. The differences in the approaches to prescribe treatment according to the guidelines of the world leading cardiological societies are highlighted.

Keywords: transient ischemic attack, stroke, dual antiplatelet therapy, antihypertensive therapy, lipid-lowering therapy, statins, antiplatelet drugs.

For citation: Shirokov E.A. Transient ischemic attack: an aggressive treatment strategy. RMJ. 2021;5:42–44.



Pages 45-49. Хроническая ишемия мозга: взгляд из ХХI века. Захаров В.В., Слепцова К.Б., Мартынова О.О.

Summary:

Chronic cerebral ischemia: a view from the ХХI century

V.V. Zakharov, K.B. Sleptsova, O.O. Martynova

First Moscow State Medical University named after I.M. Sechenov (Sechenov University), Moscow

The article is devoted to one of the most common forms of chronic cerebral circulatory disorders — chronic cerebral ischemia (CCI), the risk factors of which are various diseases with small-caliber vascular lesions (microangiopathy): arterial hypertension, diabetes mellitus, cerebral amyloid angiopathy, less common — genetic vasculopathy, vasculitis, etc. The article also considers the main pathogenetic mechanisms of chronic progressive vascular cerebral damage: recurrent brain infarctions without stroke, microhemorrhages, focal and diffuse changes in the white matter (leukoareosis). The questions concerning the earliest and most common clinical manifestations of CCI — cognitive disorders, the peculiarity of which is the inability to concentrate, problems with control and visuospatial functions with relative memory preservation, are covered in detail. In addition to controlling the risk factors, treatment of patients with CII involves the prescription of pathogenetically based treatment aimed at the main mechanisms of brain damage and/or activation of the neurorestoration processes. The article presents the experience of using the neuroprotective and neurotrophic drug, Cellex®, in cerebral vascular diseases, and considers its effect on the severity of cognitive disorders.

Keywords: chronic cerebral ischemia, silent strokes, leukoareosis, microhemorrhages, vascular cognitive disorders, neuroprotection.

For citation: Zakharov V.V., Sleptsova K.B., Martynova O.O. Chronic cerebral ischemia: a view from the ХХI century. RMJ.
2021;5:45–
49.

Pages 50-54. Применение комбинированных лекарственных препаратов для лечения пациентов с острой дорсалгией. Чугунов А.В., Камчатнов П.Р.

Summary:

The use of combined drugs for the treatment of patients with acute dorsalgia

A.V. Chugunov, P.R. Kamchatnov

Pirogov Russian National Research Medical University, Moscow

Musculoskeletal pain syndromes, in particular dorsalgia, are a common cause of seeking medical care. Timely relief of acute dorsalgia reduces the risk of adverse events and prevents the formation of chronic pain syndrome. The review, based on data from randomized trials, meta-analyses, and systematic reviews, discusses the efficacy and safety of the most widely used NSAIDs and paracetamol for acute pain relief. Special emphasis is placed on adverse events, including those from the cardiovascular system, gastrointestinal tract, liver, the risk of which depends on the prescribed dose and regimen duration. The possibility and expediency of their combined use (including as part of a combined drug containing low doses of paracetamol and diclofenac, which complement each other’s effects) are separately considered. The results concerning the prescription of this combination, which demonstrated the tr eatment efficacy and safety, are presented.

Keywords: musculoskeletal pain, dorsalgia, treatment, diclofenac, panoxen, adverse events, tolerability, treatment.

For citation: Chugunov A.V., Kamchatnov P.R. The use of combined drugs for the treatment of patients with acute dorsalgia. RMJ. 2021;5:50–54.



Pages 55-58. Миастения гравис у ребенка (клиническое наблюдение). Вороширина К.А., Гранкин Е.В.

Summary:

Myasthenia gravis in children (clinical case)

K.A. Voroshirina, E.V. Grankin

Regional Children’s Clinical Hospital, Orenburg

Myasthenia gravis is an autoimmune disease accompanied by a neuromuscular transmission disorder. The clinical picture in this disease is represented by a transient or increasing weakness of the skeletal (striated) muscles of the face, trunk and limbs. The article describes a clinical case of a 13-year-old male patient with a generalized rapidly progressive form of myasthenia gravis. Presumably, in the setting of an acute respiratory infection, the patient developed generalized weakness, bulbar disorders with the flaccid tetraplegia development, respiratory arrest with a transfer to an artificial lung ventilation (ALV). A diagnostic search was conducted concerning inflammatory, infectious and neoplastic lesions of the spinal cord and brain, and other diseases characterized by the neuromuscular transmission disorder. According to the MRI results of the cervical spine, examination of the cerebrospinal fluid, electron euromyography, determination of acetylcholine receptor antibodies, no pathology was found. Treatment with the use of specific immunotherapy with high doses of human IgG, as well as cholinesterase inhibitors, provided positive dynamics in the form of spontaneous breathing restoration, regression of bulbar disorders, and an increase in the movement volume of the extremities. Neurological symptoms completely regressed during regular use of cholinesterase inhibitors. Since myasthenia gravis is characterized by clinical polymorphism of symptoms and the absence of specific changes according to the study results, the doctor needs to know the characteristics of the disease clinical course. It will timely allow to establish the correct diagnosis and prescribe effective treatment.

Keywords: myasthenia gravis, generalized weakness, bulbar disorders, acetylcholine receptor antibodies, cholinesterase inhibitors, immunosuppressive therapy.

For citation: Voroshirina K.A., Grankin E.V. Myasthenia gravis in children (clinical case). RMJ. 2021;5:55–58.

Pages 60-64. Синдром Гийена — Барре и COVID-19: клинические наблюдения. Бондарь С.А., Маслянский А.Л., Смирнова А.Ю., Новожилова М.А., Симаков К.В., Янишевский С.Н., Конради А.О.

Summary:

Guillain-Barré syndrome and COVID-19: clinical cases

S.A. Bondar, A.L. Maslyansky, A.Yu. Smirnova, M.A. Novozhilova, K.V. Simakov, S.N. Yanishevskiy, A.O. Konradi

V.A. Almazov National Medical Research Center, Saint Petersburg

Since the outbreak of the new coronavirus infection (COVID-19), which subsequently increased to the pandemic scale, the number of reports concerning disease neurological manifestations has increased. One of the rare among them is Guillain-Barré syndrome (GBS). It is necessary to accumulate data to determine the patterns of the SARS-CoV-2-induced GBS clinical course and clarify its pathogenesis, which is probably autoimmune. The article presents two clinical cases concerning the GBS development during typical COVID-19 manifestations in 58-year-old men. The interval from the COVID-19 onset to the GBS manifestation was 5 and 13 days, respectively. In described cases, GBS was more severe than GBS development during COVID-19: both patients required invasive ventilation, both developed sepsis and acute kidney injury, which led to the fatal outcome of one of them. Antibodies to gangliosides were detected in only one patient, but they could not be detected. The patterns of the manifestations, GBS diagnosis and treatment in the presented patients should contribute to additional research, including providing greater clarity in the disease pathogenesis.

Keywords: COVID-19, SARS-CoV-2, Gu illain-Barré syndrome, intravenous immunoglobulin, plasmapheresis, antibodies to gangliosides.

For citation: Bondar S.A., Maslyansky A.L., Smirnova A.Yu. et al. Guillain-Barré syndrome and COVID-19: clinical cases. RMJ. 2021;5:60–64.

Pages 7-10. Траектория когнитивных функций у пациентов пожилого и старческого возраста: результат участия в программе тренировок по скандинавской ходьбе и терапии витамином D. Зуева И.Б., Мальцева Е.В., Суслова М.Ю., Ким Ю.В.

Summary:

Trajectories of cognitive function in elderly and senile patients: the result of participation in the Nordic walking program and vitamin D therapy

I.B. Zueva1, E.V. Maltseva2, M.Yu. Suslova2, Yu.V. Kim3

1Saint-Petersburg Medico-Social Institute, Saint Petersburg

2LLC Care Home "Nevskaya Dubrovka", Leningrad region, Dubrovka town

3Pavlov First Saint Petersburg State Medical University, Saint Petersburg

Background: cognitive function and life quality decrease with age. In this regard, various programs are being developed that contribute to the preservation of cognitive functions. Moderately intensive physical activity with vitamin D is particularly promising, as levels of vitamin D decline in the elderly and senile age.

Aim: to study the impact of the Nordic walking (NW) program and vitamin D therapy (DeTriFerol, LLC "Grotex", Russia) on cognitive functions in patients of elderly and senile age.

Patients and Methods: 40 subjects were included in a randomized controlled open-label study. They were divided randomly into 2 groups of 20 patients. In group 1 (mean age of patients 78.32±5.41 years), patients underwent NW program and vitamin D therapy (DeTriFerol) at a dose of 4000 IU/day; in group 2, patients (mean age 79.25±5.38 years) received only vitamin D therapy at the same dosage. The duration of the program was 16 weeks. In all patients, vitamin D levels were determined and neuropsychological testing was performed initially and after the program was completed.

Results: there was a correlation between vitamin D level, response rate, attention (r=0.42, p<0.01), memory, information storage and reproduction (r=0.38, p<0.01). The association between the result of the MMSE test and vitamin D level was revealed (r=0.37, p<0.01). By the end of the follow-up period, groups 1 and 2 showed improvements in short-term memory (3.47±1.15 and 5.39±1.43; 3.58±1.18 and 4.35±1.28 points, respectively, p<0.05), MMSE test results (24.68±2.45 and 26.25±2.72; 24.71±2.31 and 25.37±2.52 points, respectively, p<0.05), and encryption (34.84±8.93 and 38.92±9.04; 34.51±8.67 and 36.17±9.01 seconds, respectively, p<0.05). In both groups, there was an improvement in sleep parameters and a decrease in the level of depression.

Conclusion: it was found that vitamin D level correlates with cognitive functions in general, as well as with indicators of attention and memory. Conducting the NW program during vitamin D therapy provides a more significant improvement in cognitive functions versus vitamin D monotherapy in elderly and senile patients.

Keywords: cognitive functions, depression, anxiety, Nordic walking, vitamin D, DeTriFerol.

For citation: Zueva I.B., Maltseva E.V., Suslova M.Yu., Kim Yu.V. Trajectories of cognitive function in elderly and senile patients: the result of participation in the Nordic walking program and vitamin D therapy. RMJ. 2021;5:7–10.



№4, 2021. Клинические рекомендации и алгоритмы для практикующих врачей

Pages 10-16. Современные взгляды на роль кишечной микробиоты в формировании патологии кишечника. Гаус О.В., Беляков Д.Г.

Summary:

Modern views on the gut microbiota role in intestinal pathology

O.V. Gaus, D.G. Belyakov

Omsk State Medical University, Omsk

Association between the gut microbiota and human health is generally recognized. The emergence of molecular and genetic diagnostic methods has made it possible to make revolutionary discoveries in the field of studying the gastrointestinal tract microbiome. The article describes the characteristics of gastrointestinal tract colonization, depending on the type of delivery and feeding features. The article also shows the diet role in the formation of the quantitative and qualitative composition of the gut microbiota. Current information on the microbiota role in the pathogenesis of functional and organic intestinal diseases (irritable bowel syndrome, inflammatory bowel diseases, colorectal cancer) is presented. Special attention is paid to the gut microbiota impact on the risk of development and the nature of the COVID-19 course, which is currently under the close attention of researchers worldwide. It is noted that dysbiotic changes with an increase in the relative number of co nditionally pathogenic bacteria and pathobionts (during a decrease in the useful representatives proportion of the commensal microbiota) persisted even after complete recovery of patients. Modern methods concerning correcting the gut microbiota composition with an emphasis on the use of prebiotics are also presented.

Keywords: gut microbiota, microbiome, irritable bowel syndrome, Crohn’s disease, ulcerative colitis, colorectal cancer, COVID-19, prebiotic, dietary fibers, OptiFibre.

For citation: Gaus O.V., Belyakov D.G. Modern views on the gut microbiota role in intestinal pathology. RMJ. 2021;4:10–16.




Pages 17-21. Исследование параметров иммунной системы при профилактике острых респираторных вирусных инфекций препаратом с противовирусной и иммунотропной активностью у здоровых добровольцев. Головачева Е.Г., Афанасьева О.И., Попова В.В., Краснов А.А., Левина А.В., Апрятина В.А., Петленко С.В.

Summary:

Study concerning immune system parameters in the prevention of acute respiratory viral infections using a drug with antiviral and immunotropic activity in healthy subjects

E.G. Golovacheva1, O.I. Afanasieva1, V.V. Popova2, A.A. Krasnov3, A.V. Levina4, V.A. Apryatina4, S.V. Petlenko5

1Smorodintsev Research Institute of Influenza, Saint Petersburg

2LLC MedFort, Saint Petersburg

3S.M. Kirov Military Medical Academy, Saint Petersburg

4JSC MBSPC CYTOMED, Saint Petersburg

5 S.N. Golikova Scientific and Clinical Center of Toxicology of the Federal Medical Biological Agency of Russian Federation, Saint Petersburg

Aim: to study the safety and immunotropic efficacy concerning long-term administration of various dosage forms (powder and syrup) of Cytovir®-3 with antiviral and immunotropic activity during non-specific immunoprophylaxis.

Patients and Methods: 40 subjects (average age 25.9±3.6 years) were examined who received the drug at a dose of 12 ml 3 times a day for 14 days. During screening, on the 7th and 17th days of the study, the following immunological parameters were evaluated: induced oxidative activity of granulocytes and monocytes in the blood; total interferon (IFN) titer count in the serum; production of virus-induced IFN-α and-β; serum IgA count; secretory IgA count in saliva; phagocytic and oxidative activity of granulocytes and monocytes of peripheral blood.

Results: a statistically significant increase in the number of subjects with high titers of virus-induced IFN-α and-β (1/160 and 1/320) was revealed during the drug administration. There was a significant increase in the median of stimulated oxidative activity of neutrophilic granulocytes: from 275 c.u. (at screening) up to 945.5 c.u. e. (by the 17th day; Cytovir®-3 powder) and from 282 c.u. up to 453 c.u. (Cytovir®-3, syrup).

Conclusions: Cytovir®-3 in two dosage forms within the declared indications for use (prevention and treatment of influenza and ARVI), has a positive effect on a number of parameters of innate immunological reactivity of the body. Long-term drug administration with a high safety profile allows for increasing the body’s immune resistance to infectious agents, especially during the epidemic period.

Keywords: nonspecific immunoprophylaxis, innate immunity, secretory IgA, granulocyte oxidative activity, virus-induced interferon-α and-β, phagocytosis.

For citation: Golovacheva E.G., Afanasieva O.I., Popova V.V. et al. Study concerning immune system parameters in the prevention of acute respiratory viral infections using a drug with antiviral and immunotropic activity in healthy subjects. RMJ. 2021;4:17–21.



Pages 22-25. Клинико-лабораторная характеристика COVID-19. Маннанова И.В., Семенов В.Т., Понежева Ж.Б., Макашова В.В., Гришаева А.А., Мелехина Е.В., Плоскирева А.А., Николаева С.В., Малеев В.В.

Summary:

Clinical and laboratory characteristics of COVID-19

I.V. Mannanova1, V.T. Semenov2, Zh.B. Ponezheva1, V.V. Makashova1, A.A. Grishaeva1, E.V. Melekhina1, A.A. Ploskireva1, S.V. Nikolaeva1, V.V. Maleev1

1Central Research Institute of Epidemiology of the Federal Service on Customers’ Rights Protection and Human Well-being Surveillance, Moscow

2Center for Restorative Medicine and Rehabilitation “Berozovaya Roscha”, Medical Unit of the Ministry of Internal Affairs of the Russian Federation, Moscow

Aim: to identify clinical and laboratory patterns of COVID-19 in hospitalized patients with mild and moderate severity.

Patients and Methods: the study included 227 patients with COVID-19 aged 18 to 93 years (average age of men — 48.0±2.8 years (158 (69.6%), women — 69 (30.4%)). In 151 patients (66.5%), the presence of SARS-Cov-2 virus was confirmed by polymerase chain reaction (PCR), and in 76 people (33.5%), the diagnosis was clinically and epidemiologically established in the presence of a negative PCR result. The examination of patients was conducted according to the temporary recommendations «Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)».

Results: the disease clinical picture in most patients was characterized by the presence of bilateral viral pneumonia (in 185 patients (81.5%)), whereas in 37 patients (16.3%), the disease proceeded without lung damage in the ARVI form with involvement of the upper respiratory tract. Among patients with pneumonia, mild severity was recorded in 52 (80%) patients, and moderate — in 133 (20%) patients. Men in comparison to women were more likely to have symptoms of intoxication (50.6% vs. 28.2%) and dyspnea (28.2% vs. 10.1%). 73% of patients had different degrees of respiratory failure (RF), quarter of patients (26%) had no signs of RF. According to CT data, at the time of hospitalization, lung tissue damage of varying degrees was observed in 88% of patients. Dynamics of most patients showed a decrease in the lung damage degree, however, in 30% of cases there was no lung damage regression at the end of the hospitalization period.

Conclusion: the new coronavirus infection caused by SARS-Cov-2 is a systemic disease with multiple organ damage and requires further careful study of clinical and immunological patterns.

Keywords: coronavirus, COVID-19, SARS-Cov-2, pneumonia, respiratory failure, computed tomography.

For citation: Mannanova I.V., Semenov V.T., Ponezheva Zh.B. et al. Clinical and laboratory characteristics of COVID-19. RMJ. 2021;4:22–25.







Pages 26-30. Помогая пациенту, защити себя! Что нужно знать каждому педиатру (пострелиз). Габай П.Г., Радциг Е.Ю., Духанин А.С.

Summary:

Protect yourself when helping the patient! What every pediatrician needs to know? (post-release)

P.G. Gabai1, E.Yu. Radtsig2, A.S. Dukhanin2

1Federal Research and Clinical Center of the Federal Medical Biological Agency, Moscow

2Pirogov Russian National Research Medical University, Moscow

From March 5 to 7, 2021, Moscow hosted the XXIII Congress of Pediatricians of Russia with international participation "Actual Problems of Pediatrics" with the I Conference on Social Pediatrics. As part of the congress, the symposium "Protect yourself when helping the patient! What every pediatrician needs to know?" was held. P.G. Gabay (lawyer, senior lecturer of the Department of Public Health Organization, Academy of Postgraduate Education, Federal Research and Clinical Center of the Federal Medical Biological Agency) in his report discussed the legal aspects of the doctor’s work, including the problem of prescribing off-label medicinal products and the problem of obtaining informed voluntary consent. Professor E. Yu. Radtsig reviewed current evidence-based methods to the treatment of ENT diseases in children. Professor A.S. Dukhanin presented a report on the comparison of the original and reproduced framycetin-based products.

Keywords: off-label, topical antibiotic, framycetin, rhinopharyngitis, adenoiditis, sinusitis, original product, generic, otitis, rifamycin.

For citation: Gabai P.G., Radtsig E.Yu., Dukhanin A.S. Protect yourself when helping the patient! What every pediatrician needs to know? (post-release). RMJ. 2021;4:26–30.

Pages 31-34. Дефицит лизосомной кислой липазы — орфанное заболевание в практике педиатра. Бокова Т.А., Чибрина Е.В.

Summary:

Lysosomal acid lipase deficiency — orphan disease in the practice of pediatricians

T.A. Bokova1,2, E.V. Chibrina3

1M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow

2Pirogov Russian National Research Medical University, Moscow

3Children’s Clinical Multidisciplinary Center of the Moscow Region, Mytishchi

This article presents a family clinical case of a rare lysosomal storage disease in autosomal recessive manner – lysosomal acid lipase deficiency (LALD). LALD is caused by mutations in the lysosomal acid lipase A (LIPA) gene encoding lysosomal acid lipase (LCL), an enzyme responsible for the hydrolysis of cholesterol esters and triglycerides that are delivered to lysosomes. As a result of a decrease or complete absence of LCL activity, cholesterol esters and triglycerides are not hydrolyzed and accumulate in the lysosomes of the body’s cells, including macrophages, endothelial cells, and hepatocytes. This can lead to accelerated development of atherosclerosis, liver failure, and untimely death. LALD has an extremely variable clinical picture and can occur without the presence of obvious clinical signs until the patient goes to the doctor with another pathology or as part of a routine medical examination. For instance, in our patients, the disease was  suspected upon admitting to the hospital with a diagnosis of acute obstructive bronchitis, when elevated liver enzymes, dyslipidemia and hepatomegaly were detected in both cases. Since LALD can be fatal even in patients with a long-term stable condition, it is important to identify patients with disease at an early stage and treat them appropriately with enzyme replacement therapy. LALD should be suspected in patients with dyslipidemia (low level of high-density lipoprotein cholesterol and high level of low-density lipoprotein cholesterol) in combination with elevated liver enzymes or hepatomegaly.

Keywords: lysosomal acid lipase deficiency, lysosomal acid lipase, orphan disease, storage disease, Wolman disease, cholesterol ester storage disease.

For citation: Bokova T.A., Chibrina E.V. Lysosomal acid lipase deficiency — orphan disease in the practice of pediatricians. RMJ. 2021;4:31–34.

Pages 35-39. Проблемы диагностики и лечения ботулизма у детей: клиническое наблюдение. Сабинина Т.С., Новиков Д.В., Федоров П.В., Багаев В.Г., Мелехина Е.В.

Summary:

Problems of diagnosis and treatment of botulism in children: clinical case

T.S. Sabinina1, D.V. Novikov1, P.V. Fedorov1, V.G. Bagaev2, E.V. Melekhina3

1Khimki Regional Hospital, Khimki

2Russian Medical Academy of Continuous Professional Education, Moscow

3Central Research Institute of Epidemiology of The Federal Service on Customers’ Rights Protection and Human Well-being Surveillance, Moscow

Botulism remains an urgent problem in the XXI century. Although the number of cases registered in the Russian Federation has decreased in recent years, practising physicians of various specialities continue to face this problem. It is known that the botulism outcome depends on the early diagnosis of disease and the immediate administration of serum. However, the amount of botulinum toxin in the patient’s body is a factor in determining the disease severity. The article presents the patient management of a 9-year-old patient with severe botulism in the intensive care unit, with a favourable outcome. The article also describes the clinical picture dynamics, the characteristics of pharmacological therapy and the tactics of decision-making about the need for an ALV. The difficulties concerning establishing a diagnosis at the disease onset and the importance of a careful analysis of the anamnestic data are noted. Special attention is paid to the importance of physical and psychological rehabilitation. It is concluded that intensive therapy of botulism should be comprehensive and conducted in hospitals that have experience of long-term ALV in children.

Keywords: botulism, children, treatment, intensive care, artificial lung ventilation.

For citation: Sabinina T.S., Novikov D.V., Fedorov P.V. et al. Problems of diagnosis and treatment of botulism in children: clinical case. RMJ. 2021;4:35–39.

Pages 4-9. Изучение гепатопротективной активности терпенсодержащего препарата на модели алкогольного повреждения печени. Выштакалюк А.Б., Парфенов А.А., Маганова Ф.И., Лацерус Л.А.

Summary:

Study of the hepatoprotective activity concerning the terpene-based product on a model of alcohol-related liver disease

A.B. Vyshtakalyuk1, A.A. Parfenov1, F.I. Maganova2, L.A. Latserus2


1A.E. Arbuzov Institute of Organic and Physical Chemistry, Subdivision of Kazan Scientific Center of the Russian Academy of Sciences, Kazan

2LLC "Initium-Pharm", Moscow


Aim: to study the possibility of using a terpene-based product as a hepatoprotector.

Patients and Methods: the experiment was conducted on 48 Wistar rats (male, average weight 323.5±6.5 g, age 2.5–3.0 months) divided into 8 groups of 6 animals. A model of ethanol-induced liver pathology was taken with long-term administration of 40% ethanol at a dose of 7 mL/kg for 4 weeks to study the hepatoprotective characteristics of the terpene-based dietary supplement, CardioOrganic® Omega-3. Starting from the 3rd week of the ethanol administration initiation, the animals were injected with the test substances (CardioOrganic® Omega-3, flaxseed oil in various concentrations, product based on milk thistle extract) per os, continuing to administer ethanol. Then, at the end of the ethanol administration, test substances were administered for another 3 days. At the end of administration of all substances, the animals were euthanized, and the liver and blood were taken for analysis. The general health condition was examined: dynamics of the animal body weight and biochemical parameters of the blood were evaluated, the mass coefficient and pathomorphological changes in the liver were determined.

Results: the terpene-containing product, CardioOrganic® Omega-3, as the product based on the milk thistle extract, contributed to: normalization (increase) of the ALT and GGT levels, sharply reduced versus the normal value as a result of alcohol exposure due to impaired functional activity of hepatocytes; a shift towards the norm (increase) of the De Ritis ratio; a decrease in the level of LDH and alkaline phosphatase; normalization of the ratio concerning direct and indirect bilirubin (increase in direct bilirubin and decrease in indirect bilirubin); normalization (lowering) of the total protein level and albumin and globulins ratio (increase in the albumin concentration and decrease in the globulins concentration). Besides, there was an improvement in the structural and morphological organization of the liver under the effect of the studied substances. There was a decrease in the signs of hydropic and granular dystrophy, hepatocyte necrosis, and fibrotic changes.

Conclusion: terpene-based product, CardioOrganic® Omega-3, exhibits hepatoprotective characteristics on the model of alcoholic liver disease in rats, which allows us to consider terpene-based compounds as promising hepatoprotectors.

Keywords: terpenoids, terpene-based drugs, hepatoprotector, alcohol-related liver disease, experiment.

For citation: Vyshtakalyuk A.B., Parfenov A.A., Maganova F.I., Latserus L.A. Study of the hepatoprotective activity concerning the terpene-based product on a model of alcohol-related liver disease. RMJ. 2021;4:4–9.

Pages 40-44. Растительный препарат на основе гексанового экстракта Serenoa repens у пациентов с симптомами нижних мочевыводящих путей. Кривобородов Г.Г., Тур Е.И.

Summary:

Herbal medicinal product based on the hexane extract of Serenoa repens in patients with lower urinary tract symptoms

G.G. Krivoborodov1, E.I. Tur2

1Pirogov Russian National Research Medical University, Moscow

2Santa Maria alle Scotte Hospital, Siena

Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are a widespread problem among elderly and senile men. Herbal medicinal products are an effective and safe treatment option for this disease. Among them, Serenoa repens hexane extract — Permixon, has the broadest evidence base of clinical efficacy. This literature review highlights the main research works on the study of Permixon use in patients with LUTS due to BPH, indicating the equal efficacy of Serenoa repens hexane extract and classic drugs used in the treatment of this disease — α-adrenoblockers and 5α-reductase inhibitors with a better safety profile of Permixon. The article presents modern studies that indicate the successful Permixon use both as monotherapy and in combination with drugs of other groups used in the treatment of LUTS. Despite the successful use of Serenoa repens extract, not all the data about it are so unambiguous. Nevertheless, it is concluded that for
a certain number of patients with LUTS, Permixon can serve as a means of monotherapy and represent itself as the first-line drug.

Keywords: lower urinary tract symptoms, herbal medicine, benign prostatic hyperplasia, Serenoa repens extract, tamsulosin, 5α-reductase inhibitors, α-adrenoblockers.

For citation: Krivoborodov G.G., Tur E.I. Herbal medicinal product based on the hexane extract of Serenoa repens in patients with lower urinary tract symptoms. RMJ. 2021;4:40–44.

Pages 44-47. Хроническая тазовая боль при аденомиозе. Методы лечения. Эседова А.Э., Меджидова А.М.

Summary:

Chronic pelvic pain with adenomyosis. Treatment methods

A.E. Esedova, A.M. Medzhidova

Dagestan State Medical University, Makhachkala

Background: the urgency of the problem concerning adenomyosis is caused not only by the severity of disease clinical manifestations but also by the diagnosis complexity at the onset stage, long-term and progressive course, persistent chronic pelvic pain, which reduces the life quality.

Aim: to increase the treatment efficacy of adenomyosis in patients with chronic pelvic pain syndrome.

Patients and Methods: a prospective comparative study was conducted with 150 female patients of reproductive age (from 24 to 38 years). 120 of them, who were treated, had primary or secondary infertility and adenomyosis, and complained of pain during periods of different severity. 30 healthy women planning pregnancy were under the follow-up (control group). Group 1 (n=60) underwent surgical treatment of adenomyosis, of which 30 women were followed up after surgery, and 30 received dienogest at a dose of 2 mg for 6 months. Group 2 (n=60) did not undergo surgery, 30 of them were under the follow-up, and the rest received dienogest at a dose of 2 mg for 6 months. The pain severity was assessed using a visual analog scale (VAS), as the size of the uterus and the uterine artery resistance index.

Results: during dienogest intake, the most significant reduction in the pain severity was achieved: 1.5 times after 3 months and almost 3 times after 6 months (p<0.05). A statistically significant (p<0.05) decrease in the uterine artery resistance index was observed only in the subgroups of patients receiving dienogest. Besides, it was found that hormonal treatment caused a decrease in the uterus size, which correlated with a  decrease in pain during periods.

Conclusion: treatment with dienogest at a dose of 2 mg may be the treatment of choice in patients with adenomyosis accompanied by severe pain syndrome.

Keywords: adenomyosis, chronic pelvic pain syndrome, dyspareunia, dienogest, dopplerometry.

For citation: Esedova A.E., Medzhidova A.M. Chronic pelvic pain with adenomyosis. Treatment methods. RMJ. 2021;4:44–47.

Pages 49-52. Работа в ночную смену и гипераммониемия у врачей. Плотникова Е.Ю., Воросова О.А., Баранова Е.Н., Карягина М.С., Краснов К.А., Синьков М.А.

Summary:

Night shift and hyperammonemia in doctors

E.Yu. Plotnikova1, O.A. Vorosova2, E.N. Baranova1,2, M.S. Karyagina2, K.A. Krasnov1,2, M.A. Sinkov3

1Kemerovo State Medical University, Kemerovo

2Kemerovo Clinical Emergency Hospital, Kemerovo

3Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo

Background: chronic circadian rhythm sleep disorder is associated with a variety of health risks, including sleep and gastrointestinal disorders, and cardiovascular diseases. Besides, lack of sleep and sleep disorders increase the incidence of dementia. Pathophysiological mechanisms of non-cirrhotic hyperammonemic encephalopathy are multifactorial and poorly understood.

Aim: to assess the degree of asthenia and cognitive impairment, ammonia level, and study the L-ornithine-L-aspartate (LOLA) effect in hyperammonemia in duty medical officers of the city emergency hospital.

Patients and Methods: 31 doctors of therapeutic and surgical profile aged from 22 to 45 years were under the follow-up. All doctors worked in the day shift and had 8–12-night shifts per month. Subjects in the clinical follow-up were examined for ammonia level before and after duty. After, they were asked to complete the Number Connecting Test and Subjective Scale of Asthenia. Eight doctors with the highest levels of ammonia during the next duty took 3 LOLA sachets. After the duty, these subjects were again examined the ammonia level in their blood and offered to complete tests in dynamics.

Results: initially, almost all doctors (n=31) had an increased level of ammonia in capillary blood to an average of 107.19±43.72 μg/dL and increased after the duty to an average of 133.81±69.60 μg/dL (p=0.047). Asthenia severity increased from 37.48±12.81 points to 47.16±15.33 points (p=0.0015). During LOLA intake (n=8), the ammonia level decreased from 181.00±57.7 µg/dL to 129.37±61.1 µg/dL (p=0.0000924). A slight increase in the asthenia severity was statistically insignificant (p=0.026).

Conclusion: we recommend that those medical officers who have increased working hours, night shift, fatigue and asthenia, should monitor the level of ammonia. Thus, if it increases, it shall be reduced to normal value with medication.

Keywords: night shift, asthenia, circadian rhythm disorder, dementia, hyperammonemia, L-ornithine-L-aspartate.

For citation: Plotnikova E.Yu., Vorosova O.A., Baranova E.N. et al. Night shift and hyperammonemia in doctors. RMJ. 2021;4:49–52.



Pages 54-58. Диагностический триумвират боли: от понимания — к действию. Баринов А.Н., Плужникова М.Н.

Summary:

Diagnostic triumvirate of pain: from understanding to action

A.N. Barinov1, M.N. Pluzhnikova2

1I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

2Institute of Higher Nervous Activity and Neurophysiology of RAS, Moscow

The article presents a new diagnostic concept of pain, assumming three basic types of pain syndromes: nociceptive, neuropathic and nociplastic. Medical risk factors of chronic pain are described. The article also covers in detail the questions concerning one of the most striking manifestations of social communication disorders in any pain syndromes — the pain catastrophizing. The modern approach to the treatment of pain syndromes implies the earliest possible prescription of drugs, regardless of their development etiological origin. Treatment patterns of each of the above pain types, involving the use of different drug groups aimed at different mechanisms of nociception and antinociception, are presented. Special attention is paid to individual methods of non-drug therapy, which can be used for any pain type. The article describes modern methods of short-term psychological interventions that  can improve the treatment efficacy: hypnotherapy and cognitive behavioral therapy. Understanding the pain syndrome type and the leading mechanisms of pain development in a particular patient allows to recommend individual therapy aimed at eliminating not only the symptoms, but also the underlying cause of the disease.

Keywords: nociceptive pain, neuropathic pain, nociplastic pain, catastrophizing, short-term psychological interventions, cognitive behavioral therapy, paracetamol, tramadol.

For citation: Barinov A.N., Pluzhnikova M.N. Diagnostic triumvirate of pain: from understanding to action. RMJ. 2021;4:54–58.

Pages 59-62. Случай успешного лечения мукормикоза околоносовых пазух перед аллогенной трансплантацией гемопоэтических стволовых клеток. Долгов О.И., Попова М.О., Карпищенко  С.А., Пинегина О.Н., Роднева Ю.А., Рогачева Ю.А., Маркова И.В., Залялов Ю.Р., Бондаренко С.Н., Афанасьев Б.В.

Summary:

Сase of successful treatment of mucormycosis of the paranasal sinuses before allogeneic hematopoietic stem cell transplantation

O.I. Dolgov1, M.O. Popova1, S.A. Karpishchenko1,2, O.N. Pinegina1, Yu.A. Rodneva1, Yu.A. Rogacheva1, I.V. Маркова1, Yu.R. Zalyalov1

S.N. Bondarenko1, B.V. Afanasiev1

1Pavlov First Saint-Petersburg State Medical University, Saint Petersburg

2Saint Petersburg Research Institute of Ear, Throat, Nose and Speech, Saint Petersburg

Hematopoietic stem cell transplantation (HSCT) is a modern method of treating hematological diseases. HSCT is accompanied by certain risks due to the cytostatic therapy side effects, agranulocytosis period, and impaired cellular and humoral immunity. The development of infectious complications during anticancer therapy prior to transplantation calls into question not only the achievement of the underlying disease remission, but also the possibility of subsequent HSCT.

The article describes a case of successful combined treatment of mucormycosis of the paranasal sinuses in a female patient with acute myeloid leukemia occurred during anticancer therapy, which was performed in order to achieve the underlying disease remission before allogeneic HSCT from unrelated donors. The article also considers disease clinical manifestations, tendency of the paranasal sinuses’ lesions, combination therapy and surgical intervention in conditions of cytostatic pancytopenia. X-ray and endoscopic images of nasal cavity mucormycosis lesions, as well as the results of microscopic examinatio n are presented. The authors conclude that with timely diagnosis, early drug therapy, appropriate preparation and surgical treatment, it is possible to achieve a favorable outcome in the treatment of rapidly progressive life-threatening complication — mucormycosis of the paranasal sinuses in the setting of cytostatic pancytopenia.

Keywords: mucormycosis, acute leukemia, antitumor chemotherapy, hematopoietic stem cell transplantation, endoscopic rhinosurgery, sinusitis.

For citation: Dolgov O.I., Popova M.O., Karpishchenko S.A. et al. Сase of successful treatment of mucormycosis of the paranasal sinuses before allogeneic hematopoietic stem cell transplantation. RMJ. 2021;4:59–62.

Pages 63-66. Актуальные вопросы использования осельтамивира при гриппе. Фесенко О.В.

Summary:

Topical issues concerning oseltamivir use in influenza

O.V. Fesenko

Russian Medical Academy of Continuous Professional Education, Moscow

The rapid spread of COVID-19 and the increasing number of severe cases have diverted medical attention from the problem of influenza and other acute respiratory viral infections. Influenza causes annual epidemics and periodic pandemics with high morbidity rate, due to the high population susceptibility to this infection. Every flu outbreak has serious health, social, and economic consequences. The most significant of the influenza virus group is the influenza A virus. In recent decades, a negative trend in the epidemic process is the increasing incidence of influenza B outbreaks. Since the late 1970s, intensive research has been conducted on the development of etiotropic drugs for influenza therapy. Representatives of the neuraminidase inhibitors class are considered by the WHO as effective treatments for influenza A and B. In recent years, the gold standard of etiotropic therapy and prevention is oseltamivir. The drug has a systemic effect, prevents the release of viral particles. Drug efficacy and safety for the treatment and prevention of influenza are confirmed by a large number of studies combined in several meta-analyses. The article deals with the issues of influenza epidemiology and characteristics of the current course, and analyzes the study results evaluating oseltamivir efficacy and safety.

Keywords: ARVI, influenza, influenza virus, neuraminidase, prevention, epidemic.

For citation: Fesenko O.V. Topical issues concerning oseltamivir use in influenza. RMJ. 2021;4:63–66.



Pages 68-73. Фармакогенетическое управление эффективностью и безопасностью ингибиторов протонных помп. Карева Е.Н.

Summary:

Pharmacogenetic management concerning efficacy and safety of proton-pump inhibitors

E.N. Kareva1,2


1I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

2Pirogov Russian National Research Medical University, Moscow


Proton-pump inhibitors (PPIs) are used to treat acid-related diseases. Despite the recognized PPIs efficacy and safety, some patients do not have an adequate response or develop adverse events related to treatment. The variability of patients’ response to medicinal products may be associated with different mechanisms, but commonly this is due to the variability of metabolic enzymes genotype (rapid and poor metabolizers), which affects the effective drug concentration in the blood. One of the main PPI metabolism enzymes is CYP2C19. Large epidemiological studies confirm the association between the PPIs concentration and CYP2C19 gene polymorphism, resulting in variations of efficacy and safety. The article presents data on the pharmacokinetics and pharmacodynamics of currently available PPIs with an assessment of cytochrome isoforms in their metabolism and the potential role of CYP2C19 genetic variation in the therapeutic PPIs efficacy. The article also shows current recommendations for dosage modification of omeprazole, lansoprazole, pantoprazole, and dexlansoprazole depending on the patient’s metabolic phenotype. There is no need in rabeprazole dosage modification due to the peculiarities of its metabolism. Genotype-based dosage promises to improve therapeutic outcomes and minimize adverse events.

Keywords: gene polymorphism, personalized medicine, omeprazole, lansoprazole, pantoprazole, rabeprazole, metabolizers, CYP2C19.

For citation: Kareva E.N. Pharmacogenetic management concerning efficacy and safety of proton-pump inhibitors. RMJ. 2021;4:68–73.




Pages 74-77. Эффективность, безопасность и приверженность лечению внутривенными бисфосфонатами при постменопаузальном остеопорозе. Беляева И.Б.

Summary:

Efficacy, safety, and adherence to intravenous bisphosphonate treatment in postmenopausal osteoporosis

I.B. Belyaeva

I.I. Mechnikov North-Western State Medical University, Saint Petersburg

Postmenopausal osteoporosis is one of the most common clinical types of osteoporosis. The article presents the main stages of the osteoporosis pathogenesis, directly related to the formation of estrogen deficiency and bone remodeling disorder. Particular attention is paid to the efficacy and safety of bisphosphonates (BP) administration, which are the first-line drugs in the treatment of this pathology. The article also presents the ability of BP to inhibit pathological bone resorption and stimulate bone formation and highlights the data of international placebo-controlled and Russian follow-up studies, which indicate the high efficacy of ibandronic acid (IA). It was noted that the use of IA with intravenous administration of 3 mg once every 3 months leads to the restoration of bone metabolism, an increase in bone mineral density (BMD) and strength, and reduces the risk of vertebral and extravertebral fractures in high-risk patients. Analysis of the results concerning the dynamic follow-up of patients receiving IA indicates its aftereffect during the 12 months after the end of treatment for the preservation of the spine BMD. The benefit of ibandronate intravenous administration route is the possibility for patients with gastrointestinal pathology (esophageal ulcers, esophagitis), as well as a reduction in the frequency of use (once every 3 months), which increases adherence to therapy.

Keywords: postmenopausal osteoporosis, bisphosphonates, ibandronic acid, compliance, cardiovascul ar risk.

For citation: Belyaeva I.B. Efficacy, safety, and adherence to intravenous bisphosphonate treatment in postmenopausal osteoporosis. RMJ. 2021;4:74–77.



Pages 78-80. Повышение эффективности терапии хронических дерматозов. Русак Ю.Э., Горшкова А.В., Ефанова Е.Н.

Summary:

Improving the treatment efficacy of chronic dermatoses

Yu.E. Rusak, A.V. Gorshkova, E.N. Efanova

Surgut State University, Surgut

Aim: to increase the treatment efficacy of chronic dermatoses by including meldonium in complex therapy.

Patients and Methods: a prospective study was conducted, which included 40 patients: 24 of them women with atopic dermatitis (n=14), eczema (n=14) and psoriasis (n=12). The median age was 51.3 years. Concomitant pathology was observed in 20 patients, while the other
20 patients had a comorbid condition. Depending on the indicated treatment, the patients were divided into 2 groups of 20 subjects. Group 1 with comorbid diseases received standard treatment using antihistamines, external glucocorticosteroids for 4 weeks. Group 2 with concomitant pathology received similar treatment according to the standard regimen with meldonium addition at a dose of 500 mg/day for 4 weeks. The incidence of relapses, the duration of remission periods, the area of cutaneous lesions, and the values of the SpO2 index were evaluated. The patients were followed up for 12 months.

Results: initially, all patients were characterized by the predominance of parasympathetic nervous system regulation, which was manifested by severe itching, insomnia and decreased work ability. Treatment result with the inclusion of meldonium was a decrease in the cutaneous lesions area during the next exacerbation, an increase in the duration of the relapse-free period, a reduction in the exacerbation period
to 14 days, and an increase in blood oxygen saturation level (p<0.05) versus patients who received only standard therapy.

Conclusion: meldonium inclusion in the complex therapy of chronic dermatoses in the setting of comorbid and concomitant pathology increases the therapy efficacy, improves sleep and increases work ability.

Keywords: chronic dermatoses, atopic dermatitis, eczema, psoriasis, patients, meldonium, comorbid condition.

For citation: Rusak Yu.E., Gorshkova A.V., Efanova E.N. Improving the treatment efficacy of chronic dermatoses. RMJ. 2021;4:78–80.



№3, 2021. Болезни дыхательных путей. Оториноларингология

Pages 13-18. N-ацетилцистеин в комплексном лечении COVID-ассоциированной пневмонии. Авдеев С.Н., Гайнитдинова В.В., Мержоева З.М., Берикханов З.Г., Медведева И.В., Горбачева T.Л.

Summary:

N-acetylcysteine in the complex treatment of COVID-19 pneumonia

S.N. Avdeev1,2, V.V. Gainitdinova1, Z.M. Merzhoeva1, Z.G.-M. Berikhanov1, I.V. Medvedeva1, T.L. Gorbacheva1

1Sechenov University, Moscow

2Research Institute of Pulmonology of the Russian Federal Medical Biological Agency, Moscow

Background: the available data on the treatment results of a new coronavirus infection (COVID-19) using all medicinal products do not allow for making a firm conclusion about their efficacy or inefficacy. Therefore, their use is permissible by decision of the medical commission in accordance in the prescribed manner, if the potential benefit to the patient exceeds the risk of their use. Drug choice for COVID-19 treatment regimens is based on data on efficacy and safety, their mechanism of action, and potential interactions. Pharmacological activity of N-acetylcysteine (NAC) and its potential effect in inhibition the progression of COVID-19 make it a promising therapeutic agent in COVID-19.

Aim: to evaluate the efficacy of NAC in the comprehensive treatment of a moderate COVID-19 pneumonia.

Patients and Methods: the study included adult patients (n=46) with moderate COVID-19 pneumonia, grade 2 CT. The age of the patients was 57 (51; 71) years, BMI — 30 (27.1; 32.3) kg/m2, disease duration before hospitalization — 7 (6; 8) days, temperature at the time of hospitalization — 37.5 (37.1; 37.8) °C. Two study groups were randomly formed. The first group (n=22) received standard COVID-19 treatment. Patients of the second group (n=24) additionally received NAC 1200–1500 mg/day intravenously. NAC was prescribed simultaneously during the initiation of standard therapy.

Results: this study showed that the inclusion of NAC in the comprehensive treatment of moderate COVID-19 pneumonia led to a statistically significant increase in the oxygen saturation, oxygenation index, difference in delta increase of the oxygenation index, higher rate of decline in the volume of lung damage and inter-group difference in delta decline. There was also a statistically significantly more intense rate of a decrease in C-reactive protein levels than in the standard treatment group and a reduction of hospitalization duration in the group receiving NAC.

Conclusion: study results indicated the efficacy of NAC inclusion in the comprehensive treatment of moderate COVID-19 pneumonia.

Keywords: COVID-19 pneumonia, oxygenation index, lung damage volume, hospitalization duration, treatment, N-acetylcysteine.

For citation: Avdeev S.N., Gainitdinova V.V., Merzhoeva Z.M. et al. N-acetylcysteine in the complex treatment of COVID-19 pneumonia. RMJ. 2021;3:13–18.

Pages 19-23. Нетяжелая внебольничная пневмония. Зайцев А.А.

Summary:

Non-severe community-acquired pneumonia

A.A. Zaitsev

Main Military Clinical Hospital named after N.N. Burdenko, Moscow

According to the World Health Organization (WHO), pneumonia and influenza firmly hold the 3rd place in the list of the main reasons of fatal outcomes worldwide achieving more than 3 million deaths annually. Adding that, a new coronavirus infection (COVID-19) was also the cause of the death of 2.5 million people in a year. Both in pneumonia and COVID-19, the mortality rate among elderly patients, especially patients with comorbidities (for example, patients with COPD, diabetes mellitus, chronic heart failure, malignant neoplasms, etc.) significantly exceeded the mortality rate among young and middle-aged patients without concomitant diseases. This article presents current issues concerning diagnosis and treatment of community-acquired pneumonia from the standpoint of national recommendations. The most important sections relate to the issues of lung damage in the framework of influenza and coronavirus infection, as well as the possibilities of disease diagnosing and the role of biomarkers related to inflammation. A significant place is given to the choice of empirical antimicrobial therapy for non-severe community-acquired pneumonia. The problem of increase in the number of strains resistant to antibiotics was also discussed. The inappropriate use of antibiotics, such as macrolides, beta-lactam antibiotics, and quinolones, is a well-known predisposing factor for the formation of resistance to them, especially in pneumococci.

Keywords: community-acquired pneumonia, antimicrobial therapy, antibiotics, clinical recommendations, resistance, pneumococcus.

For citation: Zaitsev A.A. Non-severe community-acquired pneumonia. RMJ. 2021;3:19–23.

Pages 24-26. Современные тенденции в эпидемиологии туберкулеза и ВИЧ-инфекции в мире и в Российской Федерации. Афанасьев Е.И., Русских О.Е.

Summary:

Modern trends in the epidemiology of tuberculosis and HIV infection worldwide and in the Russian Federation

E.I. Afanasiev1, O.E. Russkikh1,2

1Izhevsk State Medical University, Izhevsk

2Republican Clinical Tuberculosis Hospital of the Ministry of Health of the Udmurt Republic, Izhevsk

The article provides a brief overview of the modern trends in the epidemiology of tuberculosis and HIV infection in the Russian Federation and worldwide, indicating the complex impact of this combined pathology. The main epidemiological tuberculosis indicators over the past 10 years have downward trend: tuberculosis incidence in the Russian Federation from 2009 to 2019 decreased by 50.1%, prevalence decreased by 53.3%, mortality rate decreased to 70.9% (up to 5.2 per 100 000 population, among which 18% of cases was associated with the AIDS development). Whereas, HIV infection retains its position: about 40 million people are infected worldwide (20.1% of whom did not know their HIV status), more than 1 million cases were registered in the Russian Federation at the beginning of 2019. In 2018, tuberculosis incidence among patients with HIV infection in Russia was 1764.3 per 100 000 HIV-infected patients, which is 58.6 times more than the average in the Russian Federation in patients without HIV infection. Thus, in recent years, there has been an increase in the number of patients with combined pathology of HIV infection and tuberculosis in the Russian Federation.

Keywords: tuberculosis, HIV infection, HIV-associated tuberculosis, incidence, mortality, prevalence, epidemiology, infectious disease.

For citation: Afanasiev E.I., Russkikh O.E. Modern trends in the epidemiology of tuberculosis and HIV infection worldwide and in the Russian Federation. RMJ. 2021;3:24–26.

Pages 27-30. Профилактика и лечение гриппа у взрослых. Игнатова Г.Л., Антонов В.Н.

Summary:

Prevention and treatment of influenza in adults

G.L. Ignatova, V.N. Antonov


South Ural State Medical University, Chelyabinsk


Annual seasonal influenza epidemics of varying severity led to significant morbidity and mortality worldwide. According to the World Health Organization, up to 646 thousand patients die from seasonal influenza every year worldwide. People get sick with the flu at any age, however, there are populations at increased risk.

This article is devoted to topical issues concerning diagnosis, treatment and prevention of influenza. The following data on risk factors for adverse outcomes and complications are presented: adults aged >65 years, pregnant women, people with certain chronic diseases, residents of nursing homes and other long-term care facilities, overweight patients, unvaccinated patients. The data on the vaccination efficacy at different age periods, as well as the recommended vaccines composition for the 2020/2021 season, are shown. In the treatment section, the main priority is given to the use of antiviral evidence-based drugs. The efficacy of domestic antiviral drug, Influcein, as well as its regimens, are considered.

Keywords: seasonal influenza, epidemic, influenza complications, antiviral drugs, vaccination.

For citation: Ignatova G.L., Antonov V.N. Prevention and treatment of influenza in adults. RMJ. 2021;3:27–30.



Pages 3-7. Патологическая анатомия поражения сосудов при гриппе и вирусно-бактериальной пневмонии. Двораковская И.В., Титова О.Н., Ариэль Б.М., Платонова И.С., Волчков В.А., Кузубова Н.А.

Summary:

Pathological anatomy of vascular lesions in influenza and viral-bacterial pneumonia

I.V. Dvorakovskaya1, O.N. Titova1, B.M. Ariel2, I.S. Platonova1, V.A. Volchkov3, N.A. Kuzubova1

1Research Institute of Pulmonology of the I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg

2St. Petersburg Research Institute of Phthisiopulmonology, Saint Petersburg

3St. Petersburg State University, Saint Petersburg

Aim: to evaluate the structural changes of vessels in influenza and viral-bacterial pneumonia, and their role in thanatogenesis.

Patients and Methods: 387 autopsy reports were analyzed in St. Petersburg hospitals in 2016, and clinical diagnoses were compared with anatomicopathological or forensic diagnoses to determine the underlying disease and its complications. Most of the deceased (64.3% of the total number) were male patients. Microscopic examination of lung preparations and other organs stained with hematoxylin and eosin, as well as immunohistochemistry of influenza A virus nucleoproteins expression in alveolocytes and macrophages were performed.

Results: presenile age plays a key role in thanatogenesis, since the maximum mortality was observed in the age group of 60–79 years (42.2%), while the minimum mortality — in the group of 20–39 years (11.9%). The main cause of fatal outcome was severe pneumonia, the exact etiology of which was not established, since bacterioscopic and bacteriological studies were not conducted. Microscopic examination revealed hemorrhagic and necrotic and deep fibrinous-ulcerative lesions of the tracheal and bronchial mucosa, as well as exudative necrotic processes in the pulmonary parenchyma, peribronchitis and acute destructive bronchiectasis. These were combined with dystrophic and necrobiotic changes in the vascular wall, its permeability disorder, hyperemia, stasis, thrombosis and hemorrhages characteristic of vasculitis. The severity degree of morphological manifestations concerning vascular pathology (as essential patterns of influenza and combined influenza bacterial infection) varied significantly depending on the disease duration and the severity of secondary bacterial infection.

Conclusions: the combination of inflammatory changes in the lungs with circulatory disorders in influenza and viral-bacterial pneumonia creates a detailed picture of the black lung. Bacterial flora activation by the type of autoinfection in the setting of depressed immunity in influenza, along with severe inflammation to vessels and pulmonary parenchyma, plays a leading role in thanatogenesis.

Keywords: influenza, pneumonia, autoinfection, bronchitis, alveolitis, vasculitis, circulatory disorders, underlying disease, complication, thanatogenesis.

For citation: Dvorakovskaya I.V., Titova O.N., Ariel B.M. et al. Pathological anatomy of vascular lesions in influenza and viral-bacterial pneumonia. RMJ. 2021;3:3–7.



Pages 30-33. Оценка слухового поведения ребенка раннего возраста (LittlEARS) после кохлеарной имплантации при глухоте различной этиологии. Кузовков В.Е., Сугарова С.Б., Лиленко А.С., Каляпин Д.Д., Луппов Д.С.

Summary:

LittlEARS behavioral assessment of hearing after cochlear implantation in infants and toddlers with deafness of various etiologies

V.E. Kuzovkov1, S.B. Sugarova2, A.S. Lilenko2, D.D. Kalyapin2, D.S. Luppov2

1S.M. Kirov Military Medical Academy, Saint Petersburg

2Saint Petersburg Research Institute of Ear, Throat, Nose and Speech, Saint Petersburg

Background: since 2018, Saint-Petersburg Research Institute of Ear, Throat, Nose and Speech has been conducting a study on the etiological spectrum of congenital deafness in candidates for cochlear implantation. One of the important criteria for evaluating the results of cochlear implantation is to identify the level of auditory and speech development of the child after receiving the first auditory experience.

Aim: to evaluate the results of auditory and speech development of infants and toddlers after cochlear implantation, taking into account the etiological profile of congenital deafness via Little Ears Auditory Questionnaire (LittlEARS) concerning behavioral assessment of hearing in infants and toddlers.

Patients and Methods: 100 children were examined who made up  3 study groups and 5 dropout patients: group I consisted of patients with non-syndromic genetic hearing loss (44 patients), group II — patients with syndromic hearing loss (14 patients), group III — patients with congenital cytomegalovirus infection (37 patients). LittlEARS was conducted twofold: 7 days after the initial fitting of the cochlear implant and 6 months later.

Results: during the first survey in group I, the average result was 7.07±0.37 points, in group II — 7.35±0.67 points, in group III — 7.03±0.54 points, the differences were not statistically significant (p=0.72). The total score was formed mainly due to responses to non-speech signals; the differences between the groups were not statistically significant (p=0.56). According to the second survey, the average result in group I was 17.77±0.71 points, in group II — 16.93±1.13 points, in group III — 13.78±1.21 points, the difference in results was statistically significant (p=0.011). The differences between the groups were due to the statistical difference in the number of points standing for speech signals (p=0.036).

Conclusion: at the first stage of the study, there were no significant differences in indicators of patients with various etiology of deafness. After 6 months, group III showed lower test scores versus children with genetic hearing disorders due to a lower increase in the average number of responses to speech stimuli, while maintaining the same ratio of responses to non-speech stimuli.

Keywords: cochlear implantation, aural rehabilitation, congenital deafness, genetic hearing loss, cytomegalovirus infection.

For citation: Kuzovkov V.E., Sugarova S.B., Lilenko A.S. et al. LittlEARS behavioral assessment of hearing after cochlear implantation in infants and toddlers with deafness of various etiologies. RMJ. 2021;3:30–33.



Pages 34-38. Современные подходы к диагностике и лечению острого риносинусита. Кириченко И.М., Козлова Н.С.

Summary:

Modern methods to the diagnosis and treatment of acute rhinosinusitis

I.M. Kirichenko1,2, N.S. Kozlova2

1Peoples’ Friendship University of Russia, Moscow

2ON CLINIC Arbat LLC, Moscow

Acute rhinosinusitis is quiet a common disease in most countries, which generally occurs in the setting of viral infections. In acute viral infection of the nasal cavity and paranasal sinuses, the ciliated epithelium loses its cilia and its ability to purify and protect. As a result, mucous membrane gets swelling and inflammation. Discharge congestion is an appropriate growing medium for bacteria, which leads to the occurrence of acute bacterial rhinosinusitis (ABRS). Prescribing antibiotics for mild to moderate ABRS is not justified and contributes to increased antibiotic resistance. The use of topical medication that reduces mucosal swelling and improve the outflow of inflammatory secretions from the nasal sinuses, helps to relieve the symptoms of inflammation and improve the patients’ condition. Sinuforte based on cyclamen europaeum extract causes reflex hypersecretion in the mucous membrane. Mucus secretion is improved due to the direct osmotic actio n of the drug components, as well as due to the stimulation of hypersecretion, in combination with decongestant effect, thereby facilitating nasal breathing and secretion evacuation from the sinuses. Studies conducted in Russia and abroad on the use of Sinuforte in acute rhinosinusitis have shown that the drug contributes to the symptoms’ resolution, reduces the time of disease progression and the need for antibiotics or increases their effect.

Keywords: mucosa, paranasal sinuses, acute rhinosinusitis, mucociliary clearance, antibiotic resistance.

For citation: Kirichenko I.M., Kozlova N.S. Modern methods to the diagnosis and treatment of acute rhinosinusitis. RMJ. 2021;3:34–38.



Pages 40-42. Местная терапия верхнечелюстных пазух после эндоназального удаления включений костной плотности. Карпищенко С.А., Болознева Е.В., Карпищенко Е.С.

Summary:

Topical therapy of the maxillary sinuses after endonasal removal of bone density inclusions

S.A. Karpishchenko1,2, E.V. Bolozneva1, E.S. Karpishchenko1

1Pavlov First Saint Petersburg State Medical University, Saint Petersburg

2Saint Petersburg Research Institute of Ear, Throat, Nose and Speech, Saint Petersburg

The maxillary sinus is a pyramidal cavity in the maxilla that has various functions. In the sinus cavity, the pathological bone masses and human-induced ones are possible as a result of the sinus augmentation surgery. Alveolar ridge augmentation is performed in patients with a lack of bone height for the dental implant placement. As the surgery result, the maxillary sinus volume decreases, which does not affect the subjective and objective respiratory assessment of a patient. Osteoma is a benign tumor of bone tissue. The incidence of maxillary sinus osteomas among all paranasal sinus osteomas is only 2%. Commonly, osteomas do not manifest clinical symptoms, but are a random finding during radiation detection methods, such as cone-beam computed tomography, multi-section computed tomography, teleroentgenography, orthopantomography.

A clinical case of maxillary sinus osteoma surgica l removal by endoscopic transnasal approach under the navigation system control is shown. The mass is represented by a mixed osteoma. In the postoperative period, irrigation of the nasal cavity with saline solutions and treatment with a drug containing propylene glycol, dexpanthenol, hydroxyethylcellulose and octenidine dihydrochloride were used to prevent infectious and inflammatory complications.

Keywords: maxillary sinus, osteoma, bone grafting, sinus augmentation surgery, endoscopic surgery.

For citation: Karpishchenko S.A., Bolozneva E.V., Karpishchenko E.S. Topical therapy of the maxillary sinuses after endonasal removal of bone density inclusions. RMJ. 2021;3:40–42.

Pages 43-47. Алгоритм хирургического лечения пациента с тяжелой формой тотального полипозного полисинусита. Болознева Е.В., Карпищенко С.А., Павлов В.Е.

Summary:

Surgical treatment algorithm of a patient with severe form of total rhinosinusitis with nasal polyps

E.V. Bolozneva1, S.A. Karpishchenko1,2, V.E. Pavlov1

1Pavlov First Saint Petersburg State Medical University, Saint Petersburg

2Saint Petersburg Research Institute of Ear, Throat, Nose and Speech, Saint Petersburg

Chronic pathology of the nose and paranasal sinuses is quite common, its proportion among all diseases increases every year. Chronic rhinosinusitis with nasal polyps and without polyps depends on the stage of the pathological process, the patient’s condition severity, and the damage to adjacent anatomical formations. Surgical treatment is recommended in cases of a widespread polyposis process (total or subtotal obstruction of the nasal cavity, filling two or more paranasal sinuses with polyps, blocking with a single polyp of the following areas: natural ostium, choana, nasal passage). A modern method of surgical treatment concerning paranasal sinus pathology is functional endoscopic sinus surgery. The article presents a clinical case of the compilation and application of the surgical treatment algorithm for a patient with total destructive rhinosinusitis with polyps. The severity of the patient’s condition was due to the presence of concomitant diseases: hypertension, grade 2 obesity, chronic bronchitis, chronic obstructive pulmonary disease. A correctly formulated algorithm of pre-examination in the preoperative period made it possible to identify changes in the paranasal sinuses and tracheobronchial tree signifi cant for surgical intervention and anesthetic support. Intraoperative monitoring was carried out using endoscopic techniques and electromagnetic navigation system, which allowed the patient to provide an adequate amount of surgery and prevent the possible risks of severe fatal bleeding.

Keywords: chronic rhinosinusitis with nasal polyps, destructive rhinosinusitis with polyps, endoscopic endonasal rhinosurgery, electromagnetic navigation system, endotracheal anesthesia.

For citation: Bolozneva E.V., Karpishchenko S.A., Pavlov V.E. Surgical treatment algorithm of a patient with severe form of total rhinosinusitis with nasal polyps. RMJ. 2021;3:43–47.



Pages 8-12. Алгоритм диагностики гастроэзофагеальной рефлюксной болезни при бронхиальной астме. Титова О.Н., Кузубова Н.А., Ковалева Л.Ф., Склярова Д.Б., Филиппов Д.И., Смирнов А.А.

Summary:

Algorithm for the diagnosis of gastroesophageal reflux disease in bronchial asthma

O.N. Titova1, N.A. Kuzubova1, L.F. Kovaleva1, D.B. Sklyarova2, D.I. Filippov3, A.A. Smirnov3

1Research Institute of Pulmonology of the I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg

2Vvedenskaya City Clinical Hospital, Saint Petersburg

3Research Institute for Surgery and Emergency Medicine of the I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg

Aim: to develop an algorithm for the diagnosis of gastroesophageal reflux disease (GERD) in bronchial asthma (BA).

Patients and Methods: the study included 32 patients with a moderate to severely controlled and partially controlled BA course, observed at the Research Institute of Pulmonology of the I.P. Pavlov First Saint Petersburg State Medical University. All the patients received controller therapy according to the Federal Clinical Guidelines for the diagnosis and treatment of BA. The examination included the use of АСТ (Asthma Control Test), spirometry with a bronchodilator test, fibroesophagogastroduodenoscopy, consultation with a gastroenterologist, daily esophageal impedance pH monitoring, and Numerical Rating Scale for pain intensity.

Results: at the time of the examination, partial control over the BA symptoms was observed in 7 patients, the ACT score was 22.3±1.1 points. In this group of patients, the following association of respiratory manifestations was revealed — complaints concerning the respiratory organs (coughing, a feeling of "wheezing", non-productive habit cough, sternal pain, respiratory distress) in a horizontal position and the presence of GERD. The nature of reflux was determined, which was necessary for a differentiated approach to the prescription of anti-reflux therapy: acid reflux was detected in 1 patient, weakly acidic — in 2, mixed acid-base and severe reflux — in 3. Successful anti-reflux therapy allowed to reduce and completely eliminate the use of additional inhalations "on demand" of formoterol/budesonide by the end of 4 weeks.

Conclusion: the lack of possible BA control during the optimal controller therapy in some cases may be due to the presence of concomitant GERD. Timely diagnosis of GERD and its pharmacological correction contributes to achieving optimal BA control, reducing the doses of inhaled glucocorticosteroids and long-acting β2-agonists, as well as preventing the progression and possible complications of GERD.

Keywords: bronchial asthma, gastroesophageal reflux disease, reflux, respiratory symptoms, spirometry, daily esophageal impedance pH monitoring.

For citation: Titova O.N., Kuzubova N.A., Kovaleva L.F. et al. Algorithm for the diagnosis of gastroesophageal reflux disease in bronchial asthma. RMJ. 2021;3:8–12.



№2, 2021. Эндокринология

Pages 10-12. Косвенные способы оценки инсулинорезистентности при метаболическом синдроме. Мадянов И.В.

Summary:

Indirect methods for assessing insulin resistance in metabolic syndrome

I.V. Madyanov

Chuvash State University named after I.N. Ulyanov, Cheboksary

Chuvash Republic Postgraduate Doctors’ Training Institute, Cheboksary

Aim: to study the possibility of using calculated indices based on the results of determining routine clinical laboratory parameters for assessing insulin resistance (IR) in metabolic syndrome (MS).

Patients and Methods: the study included 77 subjects with MS who met the criteria of the International Diabetes Federation (2005). The following parameters were measured in all subjects: height, body weight, waist circumference, and fasting blood levels of insulin, glucose, triglycerides (TG), and high-density lipoprotein cholesterol (HDL–C). On the basis of the studied parameters, the insulin-based and non-insulin-based IR indices were determined using generally accepted formulas. Insulin-based indices included the following: HOMA-IR, Caro, QUICKI; non-insulin-based included: TG/HDL–C, visceral obesity, lipid accumulation, triglyceride-glucose (TyG) and metabolic indices. Association between these indices was estimated using the Spearman’s rank correlation coefficient (rs).

Results: it was shown that all calculated non-insulin-based indices significantly weakly and moderately correlated with H OMA-IR index. 4 out of 5 of these indices (excluding the TyG index) were significantly associated with QUICKI index. However, none of the non-insulin-based indices showed a statistically significant association with Caro index. Non-insulin-based indices were paired with HOMA-IR index approximately equally (the range of rs fluctuations was 0.25–0.34). Based on the ratio of TG to HDL–C, the simplest by definition and calculation IR index had a moderate correlation coefficient with HOMA-IR index equal to 0.33 (p=0.005).

Conclusion: non-insulin-based IR indices calculated on the basis of routine clinical laboratory parameters cannot be fully used to assess IR in MS during the work of general practitioner. It is necessary to continue the search for other (more accurate) non-insulin-based methods for diagnosing IR in subjects with MS.

Keywords: metabolic syndrome, insulin resistance, IR indices, HOMA-IR, TG/HDL–C index.

For citation: Madyanov I.V. Indirect methods for assessing insulin resistance in metabolic syndrome. RMJ. 2021;2:10–12.

Pages 13-17. Различия в накоплении висцеральной и эпикардиальной жировой ткани у больных с ишемической болезнью сердца и без нее. Миклишанская С.В., Саидова М.А., Орловский А.А., Сычев А.В., Карлова Н.А., Мазур Н.А.

Summary:

Differences in the accumulation of visceral and epicardial adipose tissues in patients with and without coronary heart disease

S.V. Miklishanskaya1, M.A. Saidova1,2, A.A. Orlovskiy2, A.V. Sychev2, N.A. Karlova1, N.A. Mazur1

1Russian Medical Academy of Continuous Professional Education, Moscow

2Institute of Clinical Cardiology named after A.L. Myasnikov, Division of the National Medical Research Center of Cardiology, Moscow

Aim: to evaluate epicardial adipose tissue (EAT) thickness and the content of visceral adipose tissue (VAT), as well as their association with metabolic disorders in overweight and obese patients with coronary heart disease (CHD) versus patients without CHD.

Patients and Methods: 152 patients (66 women and 86 men) were examined. The height was measured using a metal stadiometer Rm-1 «Diakoms» (Russia). The measurement of weight, body mass index (BMI), percentage of total adipose tissue and VAT was carried out using Omron BF-508 body composition monitor (Japan). EAT thickness was estimated using a 2D-EchoCG.

Results: 93 patients with the leading pathology had CHD, 59 patients had no CHD, there were other cardiovascular diseases (hypertension, abnormal heart rhythm). When comparing groups with and without CHD, statistically significantly higher values of VAT and, respectively, EAT were found in patients with CHD on the basis of comparable BMI. VAT percentage was 14 [11; 18] % and 13 [10; 14.5] % in patients with and without CHD, respectively (p=0.025). EAT thickness was 7 [6; 9] mm and 6 [5; 8] mm in patients with and without CHD, respectively (p=0.017). Patients with CHD had significantly higher glucose levels (p=0.023) and lower HDL cholesterol levels (p<0.0001) versus patients without CHD. There were no statistically significant differences in triglyceride levels between the groups (p=0.107).

Conclusion: on the basis of comparable BMI level, the values of VAT and EAT were significantly higher in the group with CHD versus the group without CHD, which can be considered  as one of the reasons for the disease development. The higher content of VAT was combined with higher values of glucose and low values of HDL cholesterol in the group with CHD versus the group without CHD.

Keywords: bioelectrical impedance analysis, visceral adipose tissue, epicardial adipose tissue, coronary heart disease, hypertension.

For citation: Miklishanskaya S.V., Saidova M.A., Orlovskiy A.A. et al. Differences in the accumulation of visceral and epicardial adipose tissues in patients with and without coronary heart disease. RMJ. 2021;2:13–17.

Pages 18-25. Синдром повышенной креатинфосфокиназы плазмы как диагностическая дилемма. Евдокимова Н.Е., Цыганкова О.В., Латынцева Л.Д.

Summary:

Evaluation of plasma creatine phosphokinase as a diagnostic dilemma

N.E. Evdokimova1, O.V. Tsygankova1,2, L.D. Latyntseva1

1Institute of Internal and Preventive Medicine, the branch of the Federal Research Center "Institute of Cytology and Genetics of the Siberian Department of the Russian Academy of Sciences", Novosibirsk

2Novosibirsk State Medical University, Novosibirsk

The article analyzes the literature data and current recommendations of international expert communities on conditions accompanied by an increased level of total creatine phosphokinase (CPK) and its isoforms in plasma. Attention is paid not only to the most common causes (such as acute myocardial infarction, acute stroke, dermatomyositis/polymyositis, hypothyroidism, paraneoplastic syndrome) but also to other less common pathological conditions (intake of a number of medications, hypoparathyroidism, neuromuscular diseases, obstructive sleep apnea syndrome, etc.), that a doctor of any specialty may encounter. Besides, there are reference points given for the interpretation of the plasma CPK level and its isoforms, depending on laboratory methods of determination, racial and gender-age characteristics, and physical development of the patient. The possible causes of unreliable results in the CPK dete rmination are associated with the presence of type 1 and 2 macrocomplexes, as well as CPK-BB in the blood serum, the identification of which is possible during electrophoresis. Their detection can be a reflection of autoimmune and tumor processes. Adding that, the review presents an algorithm of actions for doctors in case of suspected statin-associated muscle symptoms and asymptomatic hyperCKemia based on the clinical recommendations.

Keywords: creatine phosphokinase, CPK, acute myocardial infarction, statin-associated muscle symptoms, muscular dystrophy, hypothyroidism, idiopathic inflammatory myopathies, paraneoplastic syndrome.

For citation: Evdokimova N.E., Tsygankova O.V., Latyntseva L.D. Evaluation of plasma creatine phosphokinase as a diagnostic dilemma. RMJ. 2021;2:18–25.

Pages 26-30. Ожирение и инсулинорезистентность: механизмы развития и пути коррекции. Барсуков И.А., Демина А.А.

Summary:

Obesity and insulin resistance: pathogenesis and ways of correction

I.A. Barsukov, A.A. Demina

M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow

Obesity is currently one of the major healthcare problems. Pathologies associated with obesity (insulin resistance, type 2 diabetes mellitus and cardiovascular diseases) have a significant impact not only on the patient but also on the healthcare system and society as a whole. Insulin resistance is the main pathogenetic mechanism for the development of type 2 diabetes mellitus and many other diseases that significantly affect society. Thus, it is extremely important to understand this condition pathogenesis. The article describes the primary risk factors and mechanisms for the development of insulin resistance: molecular mechanisms, inflammation, endoplasmic reticulum stress, mitochondrial dysfunction. The article also considers the main therapeutic principles concerning correction of this condition, including new drug classes. The accumulation of clinical experience and further research data will help to determine a more precise place of the new drug class in the treatment algorithms for carbohydrate metab olism disorders.

Keywords: diabetes mellitus, obesity, insulin resistance, molecular mechanisms, endoplasmic reticulum stress, mitochondrial dysfunction.

For citation: Barsukov I.A., Demina A.A. Obesity and insulin resistance: pathogenesis and ways of correction. RMJ. 2021;2:26–30.



Pages 3-8. Определение уровня кортизола в слюне, собранной в позднее вечернее время, в скрининге эндогенного гиперкортицизма. Тимкина Н.В., Цой У.А., Курицына Н.В., Литвиненко Е.В., Васильева Е.Ю., Гринева Е.Н.

Summary:

Late-night salivary cortisol as a screening of endogenous hypercortisolism

N.V. Timkina, U.A. Tsoy, N.V. Kuritsyna, E.V. Litvinenko, E.Yu. Vasileva, E.N. Grineva

V.A. Almazov National Medical Research Center, Saint Petersburg

Aim: to analyze the results concerning evaluation of late-night salivary cortisol (LNSC), performed by electrochemiluminescence (ECL) assay in patients with different body weight for the screening of Cushing’s syndrome, and to determine the optimal cut-off value of LNSC for detection of endogenous hypercortisolism (EHC).

Patients and Methods: the study included 100 patients with evaluated LNSC for the purpose of primary diagnosis of EHC. The reference value was 6.7 nmol/L. At least one test for the diagnosis of EHC was used to confirm the study results. The statistical analysis was performed using the IBM SPSS Statistics v. 23 package. LNCS threshold value was determined using receiver-operator characteristic (ROC) analysis, where EHC presence was selected as the dependent variable.

Results: among 100 patients, the diagnosis of EHC was established in 28 cases. The patients’ body m ass index did not differ: in patients with EHC, the median was 31 [27; 37], and in patients without EHC — 29.4 [26; 33], p=0.475. According to the ROC analysis for the diagnosis of EHC, the optimal LNCS cut-off value with a sensitivity of 93% and a specificity of 87% was 6.6 nmol/L. The area under the curve (AUC) was 0.944, р<0.001. The sensitivity/specificity for the values of 6.7 nmol/L and 6.85 nmol/L was 89.3% / 88% and 89% / 88%, respectively. The sensitivity for 9.4 nmol/L was 71%, whereas the specificity was 91.7%.

Conclusion: according to our data during ECL, the optimal cut-off value for LNSC was 6.6 nmol/L in the EHC screening. The threshold values, 6.7 nmol/L and 6.85 nmol/L, were not significantly inferior in sensitivity and specificity, and can also be used in the diagnosis of EHC.

Keywords: electrochemiluminescence assay, salivary cortisol, endogenous hypercortisolism, Cushing’s syndrome, sensitivity, specificity.

For citation: Timkina N.V., Tsoy U.A., Kuritsyna N.V. et al. Late-night salivary cortisol as a screening of endogenous hypercortisolism. RMJ. 2021;2:3–8.



Pages 31-36. Роль ингибиторов дипептидилпептидазы-4 в управлении сахарным диабетом 2 типа. Демидова Т.Ю., Скуридина Д.В.

Summary:

The role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes mellitus

T.Yu. Demidova, D.V. Skuridina


Pirogov Russian National Research Medical University, Moscow


Type 2 diabetes mellitus (DM2) is currently one of the major healthcare problems. Every year, the increasing morbidity rate, the development of late disabling complications from the cardiovascular and nervous systems, kidneys, and eyes significantly reduce the life expectancy and life quality of the population. They also put a huge burden on the healthcare system of all countries worldwide. As it is known, DM2 is a multifactorial disease. At present, a number of pharmacological agents have been developed affecting most of the pathogenetic factors for DM2 development, which increase the concentration of insulin in the blood (direct administration of insulin or its production stimulation), improve insulin sensitivity, delay the passage and absorption of carbohydrates from GIT, increase the excretion of glucose by the kidneys. Dipeptidyl peptidase-4 (DPP-4) inhibitors class or gliptins refers to agents with incretin activity. By inhibiting the DPP-4 enzyme in the patient’s blood, drugs of this class increase the biological activity of hormones — incretins (such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide), which increase insulin secretion and reduce glucagon production in response to food intake. Thus, by activating the incretin response, DPP-4 inhibitors affect one of the main DM2 pathogenetic links. This review examines the currently available data on the efficacy and safety of DPP-4 inhibitors in DM2 treatment and presents a new domestic drug of this class — Evogliptin.

Keywords: type 2 diabetes mellitus, glycated hemoglobin, glucagon-like peptide-1, glucose-dependent insulin secretion, dipeptidyl peptidase-4, dipeptidyl peptidase-4 inhibitors, incretins, antidiabetic medications.

Pages 37-41. Метформин: время расширять показания?. Вербовой А.Ф., Вербовая Н.И., Ломонова Т.В., Долгих Ю.А.

Summary:

Metformin: is it time to expand the indications?

A.F. Verbovoy, N.I. Verbovaya, T.V. Lomonova, Yu.A. Dolgikh

Samara State Medical University, Samara

Metformin is known as an antidiabetic drug since the middle of the last century. It is widely used in clinical practice concerning the treatment of carbohydrate metabolism disorders. The effect of this drug is due to its impact on insulin resistance, which is a key link in the type 2 diabetes mellitus pathogenesis. However, in the last two decades, there have begun to appear researches demonstrating its effect on many body systems. The article presents data concerning the possible expansion of indications for metformin prescription. Metformin has been shown to have a positive effect in Huntington’s disease and Alzheimer’s disease, and to improve cognitive function in stroke patients. The anti-inflammatory effect of this drug, its ability to protect blood vessels from inflammation and oxidative stress are described. Metformin also has a beneficial impact in cardiovascular pathology, has an anti-a therogenic mechanism of action, and reduces the risks of micro- and macrovascular complications of type 2 diabetes mellitus. Separately, metformin efficacy in various types of cancer should be noted. The article shows its ability to block the progression of various tumors. The question concerning the metformin impact on the aging process is discussed.

Keywords: metformin, biguanides, type 2 diabetes mellitus, Huntington’s disease, Alzheimer’s disease, inflammation, oxidative stress, cardiovascular system, microvascular complications, oncology, aging.

For citation: Verbovoy A.F., Verbovaya N.I., Lomonova T.V., Dolgikh Yu.A. Metformin: is it time to expand the indications? RMJ. 2021;2:37–41.

Pages 42-48. Гипофосфатазия. Обзор клинических случаев, опубликованных в РФ. Гуркина Е.Ю., Воинова В.Ю., Кузенкова Л.М., Соснина И.Б., Витебская А.В., Костик М.М., Шатохина Н.С., Черняк И.Ю., Храмова Е.Б., Романенко Е.С., Вяткина А.С., Абрукова А.В.

Summary:

Hypophosphatasia. Review of clinical cases published in the Russian Federation

E.Yu. Gurkina1, V.Yu. Voinova2, L.M. Kuzenkova3, I.B. Sosnina4, A.V. Vitebskaya5, M.M. Kostik6, N.S. Shatokhina7I.Yu. Chernyak7, E.B. Khramova8, E.S. Romanenko9, A.S. Vyatkina10, A.V. Abrukova11

1V.A. Almazov National Medical Research Center, Saint Petersburg

2Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Moscow

3National Medical Research Center for Children’s Health, Moscow

4Children’s Consultative and Diagnostic Center, Saint Petersburg

5Clinical Institute of Child Health named after N.F. Filatov of the First Moscow State Medical University named after I.M. Sechenov (Sechenov University), Moscow

6Saint-Petersburg State Pediatric Medical University, Saint Petersburg

7Children’s Regional Clinical Hospital, Krasnodar

8Tumen State Medical University, Tumen

9South Ural State Medical University, Chelyabinsk

10Children’s Regional Clinical Hospital, Perm

11Presidential Perinatal Center, Cheboksary

Hypophosphatasia (HPP) is a rare polymorphic disease that has different clinical manifestations depending on the age during disease onset and its severity. A wide range of symptoms affects various organs and systems, such as the musculoskeletal system (bones, muscles, joints), respiratory system, nervous system and kidneys, which can have a significant impact on the patient’s physical health and life quality. The prevalence of severe HPP in the European population is known, however, it is difficult to assess the prevalence of milder HPP forms due to the significant heterogeneity of clinical manifestations and the lower frequency of diagnosis. The review provides a modern view concerning HPP etiology and pathogenesis, as well as discusses diagnostic criteria and treatment options. Data from published clinical cases of HPP are also presented. Thus, as of 2020, Russian medical literature described 16  cases of children with the diagnosis of hypophosphatasia. The analysis of clinical cases published in Russian medical scientific journals has shown recommendation expediency to assess the level of tissue-specific alkaline phosphatase in the presence of any bone pathology with rickets-like manifestations in the patient.

Keywords: hypophosphatasia, HPP, tissue-specific alkaline phosphatase, TNSALP, ALPL gene, asfotase alfa, rickets-like diseases.

For citation: Gurkina E.Yu., Voinova V.Yu., Kuzenkova L.M. et al. Hypophosphatasia. Review of clinical cases published in the Russian Federation. RMJ. 2021;2:42–48.





№1, 2021. Кардиология. Ангиология

Pages 10-16. Особенности терапии ишемической болезни сердца у пациентов с туберкулезом и хронической обструктивной болезнью легких. Викторова И.А., Багишева Н.В., Моисеева М.В., Мордык А.В., Ароян А.Р., Филипенко Г.В., Самсонов К.Ю., Стативка Е.А.

Summary:

Treatment for ischemic heart disease in patients with tuberculosis and chronic obstructive pulmonary disease

I.A. Viktorova1, N.V. Bagisheva1, M.V. Moiseeva1, A.V. Mordyk1, A.R. Aroyan1, G.V. Filipenko2, K.Yu. Samsonov2, E.A. Stativka3


1Omsk State Medical University, Omsk

2Clinical Anti-tuberculosis Dispensary, Omsk

3City Polyclinics No. 4, Omsk

Aim: to optimize the treatment for ischemic heart disease (IHD) in patients with pulmonary tuberculosis (PL) and chronic obstructive pulmonary disease (COPD).

Patients and Methods: this prospective comparative study included 68 patients with PL, COPD, and IHD aged 40–70 years (mean age 65.35±9.9 years). All patients were subdivided into four groups based on antianginal therapy. Group 1 patients received bisoprolol and amlodipine (B+A), group 2 patients received bisoprolol and Nitrosorbide (B+N), group 3 patients received bisoprolol and trimetazidine (B+T), and group 4 patients received verapamil and trimetazidine (V+T). All medications were titrated to achieve clinical effect and/or adverse effects. Clinical data, arterial oxygen saturation, and 24-hour Holter monitoring records were evaluated.

Results: the improvement after antianginal therapy was reported in all four groups, i.e., the reduction in weekly intake of nitroglycerin, an increase in the distance until retrosternal pain occurs, the improvement of arterial oxygen saturation, reduction in heart rate, and improvement of ST segment depression (by 24-hour Holter monitoring). The best effect was achieved when using V+T or B+T (if bisoprolol was well-tolerated). Six out of 51 patients (11.7%) who received bisoprolol were switched to V+T due to the increase of cough and dyspnea. In this group, antianginal parameters after treatment were similar to those of group B+T, while treatment tolerability was better. Adequate therapy for IHD in patients with PL and COPD contributed to the increase in the efficacy of anti-tuberculosis treatment and the reduction in time to a negative swab as the first step of curing for tuberculosis.

Conclusions: verapamil and trimetazidine are the most rational and effective modalities in terms of safety and antianginal effect.

Keywords: coronary heart disease, stable angina, chronic obstructive pulmonary disease, pulmonary tuberculosis, comorbidity.

For citation: Viktorova I.A., Bagisheva N.V., Moiseeva M.V. et al. Treatment for ischemic heart disease in patients with tuberculosis and chronic obstructive pulmonary disease. RMJ. 2021;1:10–16.

Pages 17-24. Индивидуальный подход к лечению пациентов с АГ и коморбидной патологией: роль блокаторов кальциевых каналов. Карпов Ю.А.

Summary:

Personalized treatment approach to hypertension in comorbid patients: calcium channel blockers

Yu.A. Karpov 

National Medical Research Center of Cardiology, Moscow


Blood pressure (BP) monitoring is the major tool to manage hypertension, one of the important and independent cardiovascular risk factors. According to current clinical guidelines, five classes of first-line antihypertensives (including calcium channel blockers/CCB) are recommended to control or maintain target BP. A rational combination of antihypertensives is much more effective in terms of BP lowering than increasing the dose of one drug. Meanwhile, monotherapy for hypertension is recommended in some patients (e.g., in patients with low-risk stage 1 hypertension and systolic BP < 150 mm Hg, high-risk patients with high-normal BP, frail or older patients). This paper reviews clinical studies on the efficacy and safety of CCB for hypertension. In most controlled studies demonstrating CCB efficacy in terms of prognosis, dihydropyridines (mainly amlodipine) were prescribed. The safety of CCB in comorbid patients is discussed.

Keywords: hypertension, comorbidity, amlodipine, calcium channel blockers, clinical g uidelines, dihydropyridines.

For citation: Karpov Yu.A. Personalized treatment approach to hypertension in comorbid patients: calcium channel blockers. RMJ. 2021;1:17–24.

Pages 25-28. Статины — длительность приема и снижение сердечно-сосудистого риска. Сергиенко И.В., Прус Ю.А.

Summary:

Statins: treatment duration and cardiovascular risk reduction 

I.V. Sergienko, Yu.A. Prus

National Medical Research Center of Cardiology, Moscow


Hyperlipidemia is one of the leading risk factors of cardiovascular diseases. According to European and Russian clinical guidelines, statins are the first-line therapies for hyperlipidemia. These agents have demonstrated their efficacy to reduce cardiovascular morbidity and mortality. Adequate lipid-lowering treatment inhibits the progression of atherosclerosis and, therefore, prevents cardiovascular disorders and disability and reduces the rate of re-hospitalizations for myocardial revascularization. However, treatment success largely depends on adherence. Atorvastatin is one of the most effective, well-studied, most prescribed, and most sold drugs of this class. This paper reviews clinical studies on the efficacy of atorvastatin. Many large-scale clinical trials (GREACE, TNT, MIRACL, AVERT etc.) have demonstrated the efficacy of original atorvastatin for the primary and secondary prevention of cardiovasc ular diseases. The use of atorvastatin in comorbid patients with diabetes, hypertension, chronic kidney disease, and stroke is addressed. The authors also discuss the studies on atorvastatin safety. Ample evidence suggests that original atorvastatin is safe and well tolerated at doses of 10–80 mg.

Keywords: statins, hyperlipidemia, cardiovascular diseases, cardiovascular risk.

For citation: Sergienko I.V., Prus Yu.A. Statins: treatment duration and cardiovascular risk reduction. RMJ. 2021;1:25–28.

Pages 29-33. Дигиталисная интоксикация: диагностика, лечебная тактика и профилактика. Дядык А.И., Куглер Т.Е., Здиховская И.И., Ракитская И.В.

Summary:

Digitalis intoxication: diagnosis, management strategy, and prevention

A.I. Dyadyk , T.E. Kugler, I.I. Zdikhovskaya, I.V. Rakitskaya


M. Gorkiy Donetsk National Medical University, Donetsk, DPR


Current guidelines recommend prescribing cardiac glycosides with caution. However, considering their pharmacological properties and narrow therapeutic index, the rate of incorrect use of cardiac glycosides in clinical practice is still high. Digitalis toxicity develops at various serum concentrations of digoxin (generally, at concentrations > 2.0 ng/ml). Preventive strategies for digitalis toxicity should be based on both serum digoxin concentrations and its risk factors. Optimal doses of cardiac glycosides should be selected based on patient’s age, comorbidities, renal functions, and drug interactions. A wide spectrum of cardiac and non-cardiac manifestations of digitalis toxicity significantly hampers its diagnosis. The most common symptoms are irregular heartbeat and conduction abnormalities, nausea, vomiting, weakness, dizziness, headache, psychic disorders, and vision loss. The management strategy for digitalis toxicity is based on the severity of clinical signs. Severe life-threatening arrhythmias are a reason to prescribe anti-digoxin antibodies (Fab-fragments), which are, unfortunately, not readily available in Russian clinical practice.

Keywords: cardiac glycosides, digoxin, adverse effects, digitalis toxicity, arrhythmia, Fab-fragments.

For citation: Dyadyk A.I., Kugler T.E., Zdikhovskaya I.I., Rakitskaya I.V. et al. Digitalis intoxication: diagnosis, management strategy, and prevention. RMJ. 2021;1:29–33.



Pages 34-42. МР-флебография в диагностике гемодинамических нарушений у пациентов с хроническими заболеваниями вен нижних конечностей. Шайдаков Е.В., Санников А.Б., Емельяненко В.М., Крюкова Л.Н., Баранова А.Е., Рачков М.А.

Summary:

MRI venography in the diagnosis of hemodynamic disorders in patients with chronic venous diseases of the lower extremities

E.V. Shaidakov1, A.B. Sannikov2,3, V.M. Emelianenko3, L.N. Kryuchkova2, A.E. Baranova2, M.A. Rachkov2

1N.P. Bechtereva Institute of the Human Brain of the Russian Academy of Sciences, Saint Petersburg

2Clinic of Innovative Diagnostics "Medica", Vladimir

3Pirogov Russian National Research Medical University, Moscow

The article presents the analysis concerning studies of venous circulation pathology in the inferior vena cava system using magnetic resonance imaging (MRI). Special attention is paid to the attempts to use this method in the diagnosis of chronic venous diseases (CVD) of the lower limbs with magnetic resonance venography (MRV). The gradual introduction of MRV methods in the diagnosis of deep vein thrombosis (DVT) of the lower limbs and venous thromboembolism (VTE) has been shown. Methods of non-contrast-enhanced MRV based on the effect of blood flow are divided into two groups: methods based on the amplitude of Time-of-Flight (TOF) and methods based on Phase Contrast (PC). The techniques of conducting non-contrast-enhanced MRV, which has again received intensive development in recent years, are described in detail. One of these methods was direct visualization of a blood clot using  fast pulse sequences: bSSFP, BBTI, DANTE. The latest studies on this method of diagnosing DVT of the lower limbs were published in 2019, and they showed the high diagnostic value of the method. Specificity and sensitivity are shown for all commonly used MRV methods. Conducting MRV in patients with CVD is a promising diagnostic task in phlebology.

Keywords: magnetic resonance imaging, magnetic resonance venography, computed tomography, CT venography, chronic venous diseases, deep vein thrombosis of the lower limbs, varicosity.

For citation: Shaidakov E.V., Sannikov A.B., Emelianenko V.M. et al. MRI venography in the diagnosis of hemodynamic disorders in patients with chronic venous diseases of the lower extremities. RMJ. 2021;1:34–42.



Pages 43-48. Методы снижения частоты контраст-индуцированного острого почечного повреждения после чрескожных коронарных вмешательств. Хильчук А.А., Абугов С.А., Щербак С.Г., Гладышев Д.В.

Summary:

Methods to reduce the rate of contrast-induced acute kidney injury after percutaneous coronary interventions

A.A. Khil’chuk1–3, S.A. Abugov2, S.G. Shcherbak3, D.V. Gladyshev1,3

1City Hospital No. 40, Saint Petersburg, Sestroretsk

2B.V. Petrovsky Russian Research Center of Surgery, Moscow

3Saint Petersburg State University, Saint Petersburg

Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic injury of kidney parenchyma occurring after the administration of iodinated radiocontrast agent (RCA). The number of patients who receive high-technology cardiologic care increases annually, the consumption of RCA also increases. The result is a higher rate of CI-AKI after coronary angiography and percutaneous coronary interventions. CI-AKI increases the rate and number of cardiovascular complications, the length of in-hospital stay, and the need in renal replacement therapy and is also associated with a 5-fold increase in the hospital mortality rate. CI-AKI is more common in patients with chronic kidney disease. Preventive and treatment strategies for CI-AKI involve minimization of RCA via the reduction of its volume or the use of specific equipment (e.g., intravascular ultrasound or optical coherence tomography). Various additional  measures to reduce the risk of CI-AKI can be applied as well, i.e., radial approach, ischemic preconditioning, hemodynamic support in high-risk patients. The authors review the methods for CI-AKI prevention and analyze technical aspects to improve the quality of medical care in patients with high risk of CI-AKI after percutaneous coronary interventions.

Keywords: kidney injury, radiocontrast agents, prevention of kidney injury, percutaneous coronary intervention, coronary angiography.

For citation: Khil’chuk A.A., Abugov S.A., Shcherbak S.G., Gladyshev D.V. Methods to reduce the rate of contrast-induced acute kidney injury after percutaneous coronary interventions. RMJ. 2021;1:43–48.

Pages 5-9. Оценка гемодинамических параметров у больных, госпитализированных с декомпенсацией хронической сердечной недостаточности. Пырикова Н.В., Осипова И.В., Мозгунов Н.А.

Summary:

Hemodynamic parameters in patients admitted for decompensated chronic heart failure

N.V. Pyrikova1, I.V. Osipova1, N.A. Mozgunov2


1Altai State Medical University, Barnaul

2City Clinical Hospital No. 11, Barnaul

Aim: to assess hemodynamic parameters with respect to gender in patients with decompensated congestive heart failure (CHF).

Patients and Methods: this point-prevalence retrospective study included 297 case records of patients who were consistently admitted for decompensated CHF from July 2018 to July 2019.

Results: 92.3% of patients were diagnosed with hypertension, 58.6% with atrial fibrillation (AF), 33.7% with prior myocardial infarction, 31.6% with type 2 diabetes, 21.5% with angina pectoris, and 64.6% with kidney diseases (stage 3 or more advanced). More women than men (by 17.2%) were admitted, women were older than men by 5.3 years. 9.4% of patients were diagnosed with CHF class II, 70.4% with CHF class III, and 20.2% with CHF class IV. At admission, more than half of patients (52.8%) were diagnosed with hypertension stage I or more advanced (30.2% were diagnosed with hypertension stage III). In 81.6% patients with AF, heart rate was 110 rpm or more. Among patients with sinus rhythm, 29.3% have tachycardia. Left ventricular hypertrophy was diagnosed in 57.9%, preserved ejection fraction (EF) in 46.1%, mid-range EF in 33.3%, and reduced EF in 20.6%. At admission, optimal-to-high normal blood pressure (BP) was observed more commonly in men than in women (by 1 2.0%). Meanwhile, more women than men (by 11.5%) achieved target BP. At admission, more men with AF than women (by 14.5%) had tachycardia, while more women with AF than men (by 10.5%) had normal
heart rate.

Conclusions: our findings can be applied for planning of medical care for decompensated CHF to optimize the treatment for this condition.

Keywords: congestive heart failure, left ventricular ejection fraction, hemodynamics, blood pressure, atherosclerosis, atrial fibrillation.

For citation: Pyrikova N.V., Osipova I.V., Mozgunov N.A. Hemodynamic parameters in patients admitted for decompensated chronic heart failure. RMJ. 2021;1:5–9.



№13, 2020. Урология. Хирургия

Pages 10-12. Особенности лечения пациентов с мужским фактором бесплодия в условиях пандемии COVID-19. Кузьменко А.В., Кузьменко В.В., Гяургиев Т.А.

Summary:

Treatment characteristics of patients with male factor infertility in COVID-19

A.V. Kuzmenko, V.V. Kuzmenko, T.A. Gyaurgiev


Voronezh State Medical University named after N.N. Burdenko, Voronezh


Over the past 20 years, the male factor infertillity in marriage has increased from 30% to 50%. The causes of this condition can be various diseases and pathological processes, including those caused by viral infections, in particular SARS-CoV-2. The article discusses possible mechanisms of SARS-CoV-2 effect on the male reproductive system, including damage to testicular tissues due to the SARS-CoV-2 penetration into the cell by attaching the S protein to the angiotensin-converting enzyme-2, which may be present in testicular tissue cells. Besides, not only the virus itself, but also the therapy can negatively affect male reproductive function. The article justifies the use of antioxidants in the setting of a systemic inflammatory process accompanied by fever, which can increase oxidative stress and have a gonadotoxic effect. The study results confirming the efficacy of one of the most studied antioxidant complexes — AndroDoz® — are presented. It significantly improves the semen quality and can be recommended for male infertility due to oxidative stress.

Keywords: COVID-19, SARS-CoV-2, male infertility, blood-testis barrier, oxidative stress, antioxidants.

For citation: Kuzmenko A.V., Kuzmenko V.V., Gyaurgiev T.A. Treatment characteristics of patients with male factor infertility in COVID-19. RMJ. 2020;13:10–12.

Pages 14-18. Опыт лечения гиперактивного мочевого пузыря: клинические наблюдения. Салюков Р.В., Салюкова Ю.Р., Фролова М.В.

Summary:

Treatment experience of overactive bladder: clinical cases

R.V. Salyukov1,2, Yu.R. Salyukova3, M.V. Frolova4

1RUDN University, Moscow

2Rehabilitation Center for Disabled People «Preodolenie», Moscow

3Russian Scientific Center of Roentgenoradiology, Moscow

4Lomonosov Moscow State University, Moscow

Overactive bladder (OAB) is a common syndrome accompanied by a number of lower urinary tract symptoms. The first line of medical therapy for OAB is medicines belonging to the group of m-cholinolytics. Medicines of this group are not safe, as they can penetrate the blood-brain barrier and affect cognitive functions, which is especially important in light of the fact that OAB is more common in elderly patients. Fesoterodine is the only drug from m-cholinolytics group that is classified as class B according to the FORTA classification for safety and efficacy. The article presents descriptions of several clinical cases with OAB that differ in the etiology and course, comorbid background, gender and age of patients. In all cases it was possible to achieve a stable positive effect with fesoterodine. Fesoterodine can be used in patients with dysuric disorders after transurethral resection of the prostate, benign prostatic hyperplasia, in the inefficacy of another cholinolytic, and in idiopathic and neurogenic OAB. Autonomic dysreflexia may be a new promising indication for fesoterodine use, but this statement requires further research.

Keywords: fesoterodine, overactive bladder, benign prostatic hyperplasia, neurogenic lower urinary tract dysfunction, autonomic dysreflexia.

For citation: Salyukov R.V., Salyukova Yu.R., Frolova M.V. Treatment experience of overactive bladder: clinical cases. RMJ. 2020;13:14–18.




Pages 2-5. Персонализированная комплексная терапия больных с доброкачественной гиперплазией предстательной железы в сочетании с хроническим простатитом. Баранников И.И., Кузьменко А.В., Кузьменко В.В., Гяургиев Т.А.

Summary:

Individual complex therapy of patients with benign prostatic hyperplasia in combination with chronic prostatitis

I.I. Barannikov, A.V. Kuzmenko, V.V. Kuzmenko, T.A. Gyaurgiev

Voronezh State Medical University named after N.N. Burdenko, Voronezh

Aim: to evaluate the efficacy of complex treatment of patients with benign prostatic hyperplasia (BPH) in combination with chronic prostatitis (CP), taking into account individual patient chronobiological characteristics.

Patients and Methods: 60 patients with BPH and category II CP were examined. Patients were randomly divided into two groups of 30 people. In the comparison group (CG), patients received standard therapy (tamsulosin 0.4 mg once a day, levofloxacin 500 mg once a day) for 28 days. Patients of the main group (MG) received standard therapy in combination with physiatrics with SMART-PROST device in the chronorhythm acrophase. Micturition frequency, the number of night urinations, the average score on the I-PSS, QoL, NIH-CPSI scales, the maximum urinary flow rate, prostate volume and residual urine volume, and bacterioscopic and bacteriological examination of expressed prostatic secretions were evaluated. After the end of the therapy course, all patients underwent transurethral resection of the prostate and bacteriological examination of resected prostate tissue fragments. Complications incidence was evaluated over the next 6 months.

Results: statistically more significant positive trend (p<0.05) was registered for all indicators in the MG after 4 weeks. Bacteriological examination of expressed prostate secretions  revealed the following: bacteria were initially detected in all 60 (100%) patients, after 2 weeks — in 11 (36.7%) in the CG and in 10 (33.3%) in the MG, after 4 weeks — in no cases. In resected prostate fragments, the microorganism’s growth was detected in 5 (16.7%) patients in CG and in 1 (3.3%) in MG. During 6 months of follow-up, acute urinary retention was detected in 2 (6.7%) patients, leukocyturia — in 18 (60%), hematuria — in 5 (16.7%), bacteriuria — in 14 (46.7%), and in MG — in 1 (3,3%), 10 (33,3%), 2 (6,7%) and 7 (23.3%) patients, respectively.

Conclusion: complex therapy of patients with BPH and CP, taking into account their individual chronobiological characteristics, can improve the results of conservative and surgical treatment.

Keywords: chronic bacterial prostatitis, benign prostatic hyperplasia, transurethral resection of the prostate, chronotherapy, acrophase, chronorhythm, physiotherapy, SMART-PROST device.

For citation: Barannikov I.I., Kuzmenko A.V., Kuzmenko V.V., Gyaurgiev T.A. Individual complex therapy of patients with benign prostatic hyperplasia in combination with chronic prostatitis. RMJ. 2020;13:2–5.

Pages 20-22. Клинические эффекты и механизм действия препаратов в урологии: все ли мы знаем? (Пост-релиз).

Summary:

Clinical effects and mechanism of action concerning drugs in urology: do we know everything? (post-release)

On November 28, 2020, in Moscow, a breakout session was held on lower urinary tract symptoms, chronic prostatitis, and chronic pelvic pain syndrome in men within the framework of the XX Congress of the Russian Society of Urology. Among the speakers was Professor L.G. Spivak, who presented a report on the topic: “Clinical effects and mechanism of action concerning drugs in urology: do we know everything?»

One of the questions was devoted to the treatment methods of patients with dysuria and the possibilities of symptomatic therapy. The cytomedins role in the functioning of various organs and tissues was considered in relation to the problem of benign prostatic hyperplasia and chronic prostatitis. The place of organotherapy drugs in the treatment of these pathological conditions was determined.

Keywords: dysuria, chronic prostatitis, benign prostatic hyperplasia, neurohumoral regulation, cytokines, peptides.

For citation: Clinical effects and mechanism of action concerning drugs in urology: do we know everything? (post-release). RMJ. 2020;13:20–22.



Pages 24-27. Анализ эффективности вариантов локального использования гомеопатического препарата при дорсопатиях. Агасаров Л.Г.

Summary:

Analysis of the options effectiveness for topical use of homeopathic preparation in dorsopathies

L.G. Agasarov

Sechenov University, Moscow

Professional Reflexology Association, Moscow

National Medical Research Center of Rehabilitation and Balneology, Moscow

Aim: to evaluate the effectiveness of two options for the original administration of Zeel® T in dorsopathies.

Patients and Methods: 90 patients with acute lumbosacral dorsopathy underwent the follow-up. The examination program included neurological, psychological and electrophysiological (thermo- and rheography) analysis. Patients were divided into 3 groups, in which Zeel® T was prescribed along with conventional therapy. In the comparison group, the drug was administered intramuscularly, while in the two main groups — topically by pharmacopuncture (injections in the area of acupuncture points) or phonophoresis, respectively.

Results: the study noted the therapeutic validity of topical drug administration, including a distinct analgesic effect. Differences within the main groups concerned thermographic characteristics, with the predominance of pharmacopuncture in distal hypothermia reduction. Changes in rheogram indices were comparable. According to the catamnesis, the incidence of dorsopathy exacerbations did not exceed 27% outside of reliable intergroup differences. However, only in the main groups the increase in neurological symptoms was minor.

Conclusion: the established effectiveness of pharmacopuncture and phonophoresis can be explained by the combination of reflex and drug effects provided by these methods. At the same time, the known differences in the achieved effects, as well as the execution peculiarities, determine the choice of a specific method. Based on the above, we can recommend the use of different administration methods of Zeel® T depending on the existing conditions and therapy goals.

Keywords: dorsopathies, complex drugs, pharmacopuncture, phonophoresis, thermography, rheovasography.

For citation: Agasarov L.G. Analysis of the options effectiveness for topical use of homeopathic preparation in dorsopathies. RMJ. 2020;13:24–27.



Pages 28-32. Комплексное лечение постиммобилизационной тугоподвижности голеностопного сустава. Ершов В.Е., Кривова А.В., Захаров В.П.

Summary:

Complex treatment of ankle stiffness after immobilization

V.E. Ershov, A.V. Krivova, V.P. Zakharov

Tver State Medical University, Tver

Aim: to study the effect of bionic cross-linked hyaluronic acid on the rehabilitation of patients with ankle fractures and clinical manifestations of ankle stiffness after immobilization.

Patients and Methods: the study included 52 patients (mean age 43.9±13.1 years) with ankle fractures of varying degrees after immobilization, who did not undergo surgery. The average immobilization period of the ankle joint was 32.9±5.9 days. The follow-up was carried out for 21 days after the external fixation of the ankle fracture. Main group (n=23) received Flexotron® CROSS single dose into the ankle joint on the 1st day after immobilization. Control group (n=29) underwent a conventional rehabilitation course without intra-articular administration of hyaluronic acid derivatives.

Results: in the main group, the achievement of the optimal range of motions in the ankle joint (80% of the healthy joint motion range) was observed on average 5.9 days earlier than in the control group (p<0.05), which allowed patients to weight-bear on an injured body part. Improvement in segment function was accompanied by the pain reduction. VAS indicators on the 3rd day of follow-up in the main group were on average 1.9 points lower than in the control group (p<0.05). The achieved analgesic effect and the range of motions in the ankle joint in the main group were persisted throughout the entire follow-up period. No analgesics were taken by the main group, while in the control group, 7 (24%) patients took painkillers "on demand".

Conclusion: the follow-up results indicated a high efficiency of using the bionic cross-linked hyaluronic acid preparation in the complex treatment of contractures after immobilization.

Keywords: ankle fracture, hyaluronic acid, joint contracture, stiffness after immobilization.

For citation: Ershov V.E., Krivova A.V., Zakharov V.P. Complex treatment of ankle stiffness after immobilization. RMJ. 2020;13:28–32.



Pages 33-44. Возможности МРТ-исследований в визуализации сосудистого русла нижних конечностей. Шайдаков Е.В., Санников А.Б., Емельяненко В.М., Крюкова Л.Н., Баранова А.Е., Рачков М.А.

Summary:

Possibilities of MRI studies in visualization of the vascular bed of the lower extremities

E.V. Shaidakov1, A.B. Sannikov2,3, V.M. Emeliyanenko3, L.N. Kryukova2, A.E. Baranova2, M.A. Rachkov2

1N.P. Bekhtereva Institute of the Human Brain of the Russian Academy of Sciences, Saint-Petersburg

2Clinic of Innovative Diagnostics "Medica", Vladimir

3Pirogov Russian National Research Medical University, Moscow

This literature review analyzes the research data on the methodology of magnetic resonance imaging (MRI) in relation to the vascular system and the choice of optimal scan modes. Given that this material is designed primarily for vascular surgeons and phlebologists, the authors briefly describe the essence of the physical phenomena underlying the receipt of MRI images, without which it is not possible to conduct a careful analysis of the benefits and drawbacks of MR-аngiography (MRA) and the search for the optimal scan mode for MR-venography.

When describing the non-contrast and contrast MRA methods, attention is paid to the conservative methods of image processing in 2D mode using pulse sequences: spin-echo, multi-echo, turbo spin-echo, Fast Advanced Spin Echo (FASE), Gradient Echo and Inversion Recovery. Besides, emphasis is placed on the most modern solutions, including: multiplantar reformatting, maximum intensity projection, subvolume maximum intensity, surface rendering, volume rendering and virtual intraluminal endoscopy. In relation to all current methods of conducting MRA, specificity and informativeness are shown with a detailed analysis of benefits and drawbacks. The nuances of understanding the obtained angiographic image in T1 and T2 weighted images and the phenomena of "bright blood" and "dark blood" are shown.

Given that in the Russian literature there is almost no data concerning the MRI possibilities in the diagnosis of hemodynamic disorders in patients with vascular pathology, it seems that this material is relevant and will cause some interest from various specialists.

Of particular interest is the potential use of non-contrast and contrast MRA methods in the study of venous pathology of the lower extremities and pelvis, especially with regard to timely and accurate diagnosis of deep venous thrombosis and venous thromboembolism, which occupy a special position in the structure of patients with chronic venous disorders of the lower extremities.

Keywords: magnetic resonance imaging, magnetic resonance angiography, magnetic resonance venography, computed tomography, computed tomography venography, chronic venous diseases, diagnostics, deep vein thrombosis of the lower extremities, varicosity.

For citation: Shaidakov E.V., Sannikov A.B., Emeliyanenko V.M. et al. Possibilities of MRI studies in visualization of the vascular bed of the lower extremities. RMJ. 2020;13:33–44.

Pages 45-47. Хирургическое лечение пациентки с гигантской нейрофибромой промежности. Быстров С.А., Шестаков Е.В., Безбородов А.И., Лисин О.Е., Арустамян А.В., Семеная Е.В., Полетаева С.В., Каторкин С.Е.

Summary:

Surgical treatment of a patient with giant perineal neurofibroma

S.A. Bystrov, E.V. Shestakov, A.I. Bezborodov, O.E. Lisin, A.V. Arustamyan, E.V. Semenaya, S.V. Poletaeva, S.E. Katorkin

Samara State Medical University, Samara

The article describes the successful surgical treatment of a patient with neurofibromatosis type I and giant perineal neurofibroma, which hinder movements and interfere with hygiene procedures. The 60x30 cm tumor spread to the right gluteal and perianal areas, the right labia majora area, and the posterior surface of the right thigh, significantly deteriorating the patient’s life quality. The choice of surgical treatment tactics was determined by the huge tumor size. Intraoperatively, special attention was paid to perianal and perineal areas, where local flaps grafting was used to hide the defect. When removing abnormal tissues, it was necessary to avoid damage to the sphincter muscle fibers and thereby prevent the development of fecal incontinence. Blood components (fresh frozen plasma, red blood cell suspension) were transfused intraoperatively. Blood loss was 300 ml. In the early postoperative period (2 months  after the operation), a satisfactory condition of post-operative scars and a significant improvement in the life quality were noted. Healing by primary intention. Anal sphincter function is not impaired. The patient performs hygiene procedures without any difficulties.

Keywords: von Recklinghausen’s disease, peripheral neurofibromatosis, phacomatosis, myxoid neurofibroma, surgical treatment.

For citation: Bystrov S.A., Shestakov E.V., Bezborodov A.I. et al. Surgical treatment of a patient with giant perineal neurofibroma. RMJ. 2020;13:45–47.

Pages 6-9. Диагностика и лечение пациентов с инфертильностью, развившейся на фоне хронического простатита. Шевырин А.А.

Summary:

Diagnosis and treatment of patients with infertility that developed in the setting of chronic prostatitis

A.A. Shevyrin

Ivanovo State Medical Academy, Ivanovo

Background: male infertility is a clinical manifestation of many different pathological conditions. It is known that physical and chemical changes in the prostate gland that occur during inflammation lead to changes in the semen quality.

Aim: to evaluate the semen quality, the microbiology of sperm and prostatic secretions in patients with infertility and chronic prostatitis, as well as to compare the efficacy of various treatment regimens for this pathology.

Patients and Methods: the study included 50 men of fertility age from 18 to 36 years, suffering from infertility and having various manifestations of pathospermia that occurred in the setting of chronic prostatitis. In group I (n=25), patients received Actifert-Andro dietary supplement in addition to standard treatment for chronic prostatitis according to the standard regimen, in group II (n=25) — only standard drug therapy. The examination was perfor med using general, clinical, laboratory and ultrasound methods in accordance with generally accepted standards.

Results: after three months of treatment in group I, general indices of the semen condition (viscosity, colliquation time, color, admixtures), as well as its morphology and viability were normal almost in all patients. In 6 cases, there was unexpressed sperm agglutination and mild asthenozoospermia, there was no aggregation and MAR-test was negative. In group II, the presence of mucus in the ejaculate, a change in ejaculate pH, an increase in the semen viscosity and in its colliquation time were determined after the therapy course. Adding that, asthenozoospermia was more significant, in some cases — oligo-asthenoteratozoospermia, there were also cases of agglutination and semen aggregation, the MAR-test was weakly positive.

Conclusion: Actifert-Andro addition to the complex therapy of male infertility, developed in the setting of chronic prostatitis, can influe nce different spermatogenesis disorder links, which is especially important given polygenic nature of this disease.

Keywords: male infertility, chronic prostatitis, pathospermia, complex therapy, semen analysis, prostatic fluid.

For citation: Shevyrin A.A. Diagnosis and treatment of patients with infertility that developed in the setting of chronic prostatitis. RMJ. 2020;13:6–9.





№12, 2020. Клинические рекомендации и алгоритмы для практикующих врачей

Pages 14-16. Сложности дифференциальной диагностики сахарного диабета 2 типа в клинической практике. Ушанова Ф.О., Измайлова М.Я., Плахотняя В.М.

Summary:

Challenges in the differential diagnosis of type 2 diabetes in clinical practice

F.O. Ushanova, M.Ya. Izmailova, V.M. Plakhotnyaya

Pirogov Russian National Research Medical University, Moscow

This article addresses the differential diagnostic aspects of type 2 diabetes (T2D) in a younger patient. Diabetes is a group of metabolic conditions with a common feature, chronic hyperglycemia. T2D is a complex multietiological heterogeneous disease requiring personalized treatment approach. Meanwhile, the clinical portrait of a T2D patient has long ago gone beyond the conventional views of type 2 diabetes. Gradual and slow progression of clinical manifestations in younger patients requires differential diagnosis between type 1 diabetes (T1D), T2D, maturity-onset diabetes of the young (MODY), and latent autoimmune diabetes mellitus in adults (LADA). In these cases, the diagnosis should not rely on patient’s age and phenotypic features only. Patients with atypical manifestations of diabetes require modern diagnostic tests (i.e., immunochemistry and molecular genetic testing) which, h owever, are not always available in routine clinical practice. Nevertheless, glucose-lowering therapy should be promptly prescribed irrespective of the etiology of hyperglycemia since it is well-known that early adequate glycemic control reduces the risk of micro- and macrovascular complications.

Keywords: type 2 diabetes, type 1 diabetes, diagnosis, metformin, safety, efficacy.

For citation: Ushanova F.O., Izmailova M.Ya., Plakhotnyaya V.M. Challenges in the differential diagnosis of type 2 diabetes in clinical practice. RMJ. 2020;12:14–16.



Pages 17-22. Нарушения кишечного микробиоценоза: актуальные аспекты терминологии, клиники, профилактики. Голошубина В.В., Трухан Д.И., Багишева Н.В.

Summary:

Intestinal microbiocenosis disorder: current aspects of terminology, clinical picture and prevention

V.V. Goloshubina, D.I. Trukhan, N.V. Bagisheva

Omsk State Medical University, Omsk

Bacterial flora in the gastrointestinal tract (GI) has a topical and systemic effect not only on the digestive organs but also on the entire body. Numerous studies have proved the pathogenetic association of the intestinal biocenosis state not only with GI diseases but also with pathological processes of other body organs and systems. At the same time, quantitative and qualitative changes in the normal intestinal microflora commonly occur as a result of various adverse events in humans and the development of various pathological conditions. In this review, the current aspects of terminology and clinical picture of intestinal microbiocenosis disorders are considered. Probiotics, prebiotics and synbiotics occupy an important place in the combination therapy of intestinal microbiocenosis disorders and clinical manifestations, associated with them. The review examines the main mechanisms of probiotic-host interaction, probiotics possibl e effects, and the requirements for them. Probiotics, prebiotics and synbiotics are used as the first-line treatment in the prevention of intestinal microbiocenosis disorders and associated possible metabolic shifts.

Keywords: intestinal microbiocenosis, dysbiosis, dysbacteriosis, clinical picture, prevention, probiotic, prebiotic, synbiotic, Bifidobacterium lactis, inulin, cholecalciferol.

For citation: Goloshubina V.V., Trukhan D.I., Bagisheva N.V. Intestinal microbiocenosis disorder: current aspects of terminology, clinical picture and prevention. RMJ. 2020;12:17–22.

Pages 24-29. Роль пищевых волокон в коррекции нарушений микробиоты и поддержании иммунитета. Ардатская М.Д.

Summary:

Role of dietary fiber in correcting microbiota disorders and maintaining immunity

M.D. Ardatskaya

Central State Medical Academy of the Administrative Department of the President of the Russian Federation, Moscow

The article discusses the association between the microbiota and the functioning of individual organs, systems and the entire macroorganism. This interaction is realized at the level of low-molecular-weight metabolites of the intestinal microbiota that can activate, inhibit, modify the processes, functions, and reactions of various organs and systems of the human body. Violation of their qualitative or quantitative ratio is the occurrence and progression factor of many gastrointestinal, metabolic, cardiovascular, hematological, neuropsychiatric, autoimmune and other diseases. The presented volume of reliable clinical data indicates that the prebiotics use, in particular dietary fiber (DF), for the correction of intestinal microbiota disorders is a promising method in the treatment and prevention of various diseases. In turn, partially hydrolyzed guar (cyam opsis) DF (registered in the Russian Federation under the trade name OptiFiber) due to their effects (such as regulating the intestine, reducing abdominal pain, reducing flatus and bloating, increasing the resident intestinal microflora amount and its metabolic activity) helps restore and maintain intestinal eubiosis, normalize the consistency and frequency of stool, relieve symptoms of irritable bowel syndrome, and increase immunity to influenza. At the same time, OptiFiber does not have significant side effects and can be administered for a long-term period in order to supplement the nutrition with the necessary amount of DF.

Keywords: microbiota, short-chain fatty acids (SCFAs), intestinal microbiocenosis, dietary fiber, cyamopsis, immunity, influenza.

For citation: Ardatskaya M.D. Role of dietary fiber in correcting microbiota disorders and maintaining immunity. RMJ. 2020;12:24–29.

Pages 30-34. Выбор НПВП для лечения острой и хронической боли у пациентов с ревматоидным артритом на амбулаторно-поликлиническом этапе. Василюк В.Б., Фарапонова М.В., Сыраева Г.И.

Summary:

Selection of NSAIDs for the treatment of acute and chronic pain in patients with rheumatoid arthritis at the outpatient stage

V.B. Vasilyuk1,2, M.V. Faraponova1, G.I. Syraeva1,3

1Research Center EcoSafety LLC, Saint-Petersburg

2North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg

3Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg

Background: one of the most common manifestations of rheumatoid arthritis (RA) is pain syndrome, which significantly worsens the life quality of patients. The standard of medical care for RA involves the oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs).

Aim: comparative evaluation of analgesic effect AMBENIUM® parenteral (study drug, SD) and diclofenac sodium (reference drug, RD) in patients with acute low back pain.

Patients and Methods: an open-label comparative randomized study on the efficacy and safety of AMBENIUM® parenteral versus diclofenac sodium in relieving acute low back pain included 164 patients aged 18 to 72 years with pain intensity of more than 80 points on the visual analog scale (VAS).

Results: therapy with AMBENIUM® parenteral SD was no less effective than therapy with diclofenac sodium for relieving acute low back pain. In the group of patients who received the SD, the pain intensity index on the VAS scale 2 hours after drug administration was statistically significantly low (p=0.003) than in the group receiving RD, while the analgesic effect during SD administration occurred statistically significantly earlier (p=0.013). When evaluating the pain dynamics using the McGill Pain Questionnaire, the efficacy of AMBENIUM® parenteral has been shown starting from the 4th hour after administration, which indicated that SD was no less effective than RD in terms of pain dynamics (p<0.05).

Conclusion: based on the study results, AMBENIUM® parenteral was found to be sufficiently effective in patients with acute low back pain. The SD profile, as well as its risk-benefit ratio, were characterized as «favorable» versus other oral NSAIDs, in particular, with diclofenac sodium.

Keywords: rheumatoid arthritis, pain syndrome, low back pain, nonsteroidal anti-inflammatory drugs, parenteral, AMINIUM® parenteral.

For citation: Vasilyuk V.B., Faraponova M.V., Syraeva G.I. Selection of NSAIDs for the treatment of acute and chronic pain in patients with rheumatoid arthritis at the outpatient stage. RMJ. 2020;12:30–34.

Pages 36-48. Лекарственно-индуцированный дефицит электролитов. Часть 2. Лекарственно-индуцированная гипомагниемия. Остроумова О.Д., Кочетков А.И., Клепикова М.В.

Summary:

Drug-induced electrolyte disorder. Part 2. Drug-induced hypomagnesemia

O.D. Ostroumova1,2, A.I. Kochetkov1, M.V. Klepikova1

1Russian Medical Academy of Continuous Professional Education, Moscow

2Sechenov University, Moscow

Drug-induced hypomagnesemia is caused by a wide range of medications, including those widely used in clinical practice (diuretics, proton pump inhibitors, insulin preparations, aminoglycosides, antineoplastic drugs, drugs used in cardiology (digoxin) and pulmonology (beta-agonists, theophylline, glucocorticosteroids). The prevalence of drug-induced hypomagnesemia is not generally known, but can reach 90% among certain classes of medications. A special feature of magnesium is its small percent in the blood serum composition (only 0.3% of the total amount in the human body), while the largest percent is found in the intracellular compartment. This commonly makes it difficult for early diagnosis of hypomagnesemia, which increases the risk of dangerous clinical signs concerning magnesium deficiency occurrence. Diagnosis of this condition is based on the detection of low magnesium levels in the blood. Methods have also been developed for determining the intracellular and interstitial magnesium content in red blood cells, white blood cells, platelets, macrophages, muscle tissue, hair, nails, and teeth. Due to the frequent combination of hypomagnesemia (including drug-induced) with potassium deficiency, the rational treatment tactics for such patients is to simultaneously fill the lack of these cations. High efficiency and safety profile in hypomagnesemia treatment was  proved by the use of combined preparation of potassium and magnesium asparaginate, which allows for combined correction of electrolyte disorders in magnesium deficiency, and, according to the viewpoint of Russian experts, it is also the first-line drug in this clinical picture.

Keywords: hypomagnesemia, drug-induced hypomagnesemia, hypokalemia, adverse events, potassium and magnesium asparaginate.

For citation: Ostroumova O.D., Kochetkov A.I., Klepikova M.V. Drug-induced electrolyte disorder. Part 2. Drug-induced hypomagnesemia. RMJ. 2020;12:–48.

Pages 4-8. Клиническая и патофизиологическая роль липопротеина (а) в развитии атеросклероз-ассоциированных заболеваний. Цыганкова О.В., Бондарева К.И., Латынцева Л.Д., Старичкова А.А.

Summary:

Clinical and pathophysiological role of lipoprotein (a) in the development of diseases associated with atherosclerosis

O.V. Tsygankova1,2, K.I. Bondareva2, L.D. Latyntseva2, A.A. Starichkova3


1Novosibirsk State Medical University, Novosibirsk

2Institute of Internal and Preventive Medicine, the branch of the Federal Research Center "Institute of Cytology and Genetics of the Siberian Department of the Russian Academy of Sciences", Novosibirsk

3Federal Research Center of Fundamental and Translational Medicine, Novosibirsk

The article analyzes the literature data and clinical recommendations reflecting the role of lipoprotein (a) (Lp(a)) as a pro-atherogenic factor. The article shows the prevalence of a marked increase in this indicator. It also highlights the level of cardiovascular risk in such patients, which is comparable to that in hereditary heterozygous familial hypercholesterolemia. A review of available and developed medicines affecting Lp(a) was conducted. Along with this, we present our own clinical case of a female patient with a Lp(a) level of 440.25 nmol/l (with reference values up to 50 nmol/l) who experienced a transient ischemic attack at the age of 45 years in the setting of previously underdiagnosed arterial hypertension. Subsequently, the patient had preventable arterial hypertension, took combined antihypertensive therapy and rosuvastatin 10–20  mg/day on a regular basis with the target values achievement of low-density lipoprotein cholesterol. Despite this, at the age of 54, she experienced the onset of angina pectoris, and at the age of 56, magnetic resonance imaging of the brain in connection with cervicalgia revealed signs of an ischemic stroke of unknown duration in the right hemisphere. It shows the adverse contribution of Lp(a) high level to the pathogenesis of diseases associated with atherosclerosis.

Keywords: lipoprotein (a), dyslipidemia, diseases associated with atherosclerosis, high cardiovascular risk.

For citation: Tsygankova O.V., Bondareva K.I., Latyntseva L.D., Starichkova A.A. Clinical and pathophysiological role of lipoprotein (a) in the development of diseases associated with atherosclerosis. RMJ. 2020;12:4–8.

Pages 50-55. Исследование токсических и аллергенных свойств мелиттина, полученного из отечественного пчелиного яда. Федоскова Т.Г., Мартынов А.И., Пампура А.Н., Миславский О.В., Шабанов Д.В., Маштакова С.Р., Головкина Е.Д.

Summary:

Study of the toxic and allergenic properties of melittin obtained from honey bee venom

T.G. Fedoskova1, A.I. Martynov1, A.N. Pampura2, O.V. Mislavsky1, D.V. Shabanov1, S.R. Mashtakova1, E.D. Golovkina1

1State Research Center "Institute of Immunology" of the Federal Medical and Biological Agency, Moscow

2Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Moscow

Aim: to study the toxic and allergenic activity of melittin, the main component of bee venom, which makes up 35–50% of the venom total dry weight, using various diagnostic methods.

Patients and Methods: we used melittin from the bee venom of the company Sigma (USA) and melittin obtained from domestic raw bee venom (RBV). The toxic and allergenic activity of the studied peptide was studied on the model of various laboratory animals with different degrees of sensitivity. Specific IgE level was studied by the method of enzyme Immunoassay. The method of active cutaneous anaphylaxis was applied in order to study the melittin sensitizing properties.

Results: it was shown that the toxic effect of domestic melittin from RBV was not inferior to the foreign melittin. Laboratory animal model most sensitive to the melittin  toxic properties was found. The coincidence of the dose-dependent effect for acute toxicity was noted. The allergenic properties of the studied peptide were studied when administrating the least toxic doses of melittin (0.1 LD50).

Conclusion: the presence of pronounced toxic properties and weak allergenic properties of melittin indicate that it is not advisable to use melittin as part of antihistamines.

Keywords: insect sting allergy, honey bee, Apis mellifera, bee venom, melittin, toxic properties, allergenic properties.

For citation: Fedoskova T.G., Martynov A.I., Pampura A.N. et al. Study of the toxic and allergenic properties of melittin obtained from honey bee venom. RMJ. 2020;12:50–55.

Pages 56-60. Современные лечебно-диагностические инструменты оценки назальной функции и нарушений обоняния у пациентов с аллергическим ринитом. Алгоритм комплексной терапии. Чурюкина Э.В., Уханова О.П.

Summary:

Modern medical and diagnostic tools for assessing nasal function and olfactory disorders in patients with allergic rhinitis. Complex therapy algorithm

E.V. Churyukina1, O.P. Ukhanova2,3

1Rostov State Medical University, Rostov-on-Don

2Stavropol State Medical University, Stavropol

3Stavropol Regional Clinical Hospital, Stavropol

Additional diagnostic tests have become important not only in otorhinolaryngology, neurology, psychiatry, but also in allergology. This article is devoted to the evaluation of olfactory function in patients with nasal obstruction and severe allergic rhinitis. A comprehensive application of three available tools for assessing olfactory dysfunction and nasal congestion in patients was described for the first time in the routine practice of an allergist-immunologist before and after therapy of allergic rhinitis. These tools include: portable PNIF (Peak Nasal Inspiratory Flow measurement) meter, UPSIT (University of Pennsylvania Smell Identification Test — «Qualitative smell evaluation analysis» test), combined decongestant with second generation antihistamine (Frinosol). Accurate evaluation of olfactory functi on disorders among our patients is very important before and after conservative, disease modifying and surgical treatment methods. Combined use of the PNIF, UPSIT and Frinosol results, in addition to detecting quantitative evaluation concerning olfactory disorders, demonstrates the impact of nasal obstruction assessment procedures on clinical results, as well as the objective achievement in nasal respiratory function improvement during therapy.

Keywords: allergic rhinitis, nasal obstruction, anosmia, olfactory assessment, UPSIT, Peak Nasal Inspiratory Flow.

For citation: Churyukina E.V., Ukhanova O.P. Modern medical and diagnostic tools for assessing nasal function and olfactory disorders in patients with allergic rhinitis. Complex therapy algorithm. RMJ. 2020;12:56–60.

Pages 61-64. Корь у взрослых в период эпидемического неблагополучия. Ретроспективное исследование. Харченко Г.А., Кимирилова О.Г.

Summary:

Measles in adults during epidemic ill-being: retrospective study

G.A. Kharchenko, O.G. Kimirilova

Astrakhan State Medical University, Astrakhan

Background: тeasles is an anthroponous airborne infection with a high susceptibility in all age groups of the population. For 6 months of 2019, 3251 cases of measles were registered in 64 regions of Russia, which indicated a tense epidemic situation of measles.

Aim: to establish the clinical and epidemiological patterns of measles in adults in Astrakhan region (AR) during epidemic ill-being.

Patients and Methods: epidemiological data, main symptoms and incidence depending on the period and severity of the disease were analyzed in a retrospective study (this study included 382 patients with measles (aged 18 to 60 years) for the period from January 2013 to July 2019).

Results: it was found that 64 of 382 patients (17%) were not vaccinated against measles, 85 of 382 (22%) had no vaccination history, and 8 of 382 (2%) refused vaccination. Measles in adults of all age groups (vaccinated and unvaccinated) occurred typically with a predominance of moderate degree in 85% of patients. Koplik’s spots were detected in 32%, stage manifestation of maculopapular rash — in 100%, and pigmentation — in 81% of patients. Mild course of measles was observed in 208 (54%) patients. The causes of moderate course were bronchitis (in 64 patients (16%)) and pneumonia (in 12 patients (3%)). Exacerbation of concomitant somatic diseases was recorded in 98 (25%) patients. Preliminary diagnoses in 236 patients during the subclinical period of measles were the following: acute respiratory viral infection (ARVI) — in 78 (33%), measles — in 158 (67%); during the rash period (146 patients) — measles in 124 (85%), rubella — in 5 (3.4%), ARVI, toxic and allergic reaction — in 15 (10.3%), infectious mononucleosis — in 2 (1.3%) patients.

Conclusions: the populat ion with measles aged 18 to 29 years dominates in AR. The share of seronegative individuals in the indicator groups of AR population in 2013–2018 was from 15.7% to 23.8%. Registration of measles in adults (vaccinated and revaccinated) might be associated with a decrease in post-vaccination immunity. All this indicates the need for additional revaccination against measles.

Keywords: measles, adults, epidemiology, incidence, clinical picture, vaccination.

For citation: Kharchenko G.A., Kimirilova O.G. Measles in adults during epidemic ill-being: retrospective study. RMJ. 2020;12:61–64.

Pages 66-70. Эволюция острых респираторных вирусных инфекций сочетанной этиологии у детей. Николаева С.В., Хлыповка Ю.Н., Музыка А.Д., Усенко Д.В., Шабалина С.В., Медкова А.Ю., Горелов А.В., Понежева Ж.Б.

Summary:

Evolution of acute respiratory viral coinfections in children

S.V. Nikolaeva1, Yu.N. Khlypovka1,2, A.D. Muzyka1, D.V. Usenko1, S.V. Shabalina1, A.Yu. Medkova2, A.V. Gorelov1,3, Zh.B. Ponezheva1

1Central Research Institute of Epidemiology of the Russian Federal Service for Supervision 

 of Consumer Rights Protection and Human Well-Being, Moscow

2Central Clinical Hospital and Polyclinic, Moscow

3I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

Aim: to analyze the changes in the etiology and clinical presentations of coexisted acute respiratory viral infections (ARVIs) in children over a 17-year period.

Patients and Methods: the comparative retrospective analysis of the etiology, population, and clinical presentations of ARVIs in children admitted to Moscow hospitals in 2002–2003 (group 1, n=130) and 2018–2019 (group 2, n=133) was performed. At admission, ARVI etiology was identified by polymerase chain reaction (oral or nasal smears and/or discharge, sputum) and enzyme immunoassay (antibodies to herpesvirus type 1, 2, and 6, cytomegalovirus, Epstein–Barr virus, Chlamydia, and Mycoplasma).

Results: children younger than 6 years predominated in both groups (84.7% and 88%, respectively, p>0.05). No gender differences were reported. In 2018–2019, the children were infected more evenly across the year, without clear seasonality. The increase in the percentage of the identified etiology of ARVIs (from 61.3% in 2002–2003 to 76.3% in 2018–2019) and the portion of ARVI coinfections (from 12.1% in 2002–2003 to 17.3% in 2018–2019) in children admitted to hospitals was revealed. Meanwhile, the percentage of children younger than 1 year reduced but the percentage of children aged 3–6 years visiting preschool facilities increased. Over the last years, the etiology of ARVI coinfections has changed from respiratory syncytial virus (53% of ARVI coinfections in 2002–2003) to rhinovirus (34.8% of ARVI coinfections in 2018–2019). The clinical presentations of ARVIs were characterized by acute onset, high temperature, and catarrhal syndrome. Temperature reaction tended to be more severe but of less duration in 2018–2019. The percentage of pneumonias reduced in 2018–2019 compared to 2002–2003. The result was less often prescription of antibacterial therapy in all groups of children. Additionally, reduced severity and duration of abnormal breath sounds revealed by auscultation was seen in 2018–2019.

Conclusions: our findings allow for a rational planning of preventive and/or therapeutic measures considering age-related characteristics of children, season, and the clinical features of ARVI coinfections.

Keywords: children, viral infections, ARVI, coinfections, prevention.

For citation: Nikolaeva S.V., Khlypovka Yu.N., Muzyka A.D. et al. Evolution of acute respiratory viral coinfections in children. RMJ. 2020;12:66–70.



Pages 72-76. Микробиом влагалищного биотопа: от нормы до патологии. Летяева О.И.

Summary:

Microbiome of the vaginal biotope: from norm to pathology

O.I. Letyaieva

South Ural State Medical University, Chelyabinsk

The literature review presents data on the modern view concerning the state of colonization resistance of the female reproductive system, etiology, sexually transmitted infections pathogenesis, and urogenital infections. The review also considers the role of Lactobacillus flora as the main protection factor of the genital tract from pathogens invasion. Potential risks of pathological processes development in the case of functional inferiority of lactobacilli were indicated. The role of microbial associations was discussed from the perspective of modern microbiology. Data on the significance of microbial associations of Chlamydia trachomatis spp. with anaerobic microorganisms in the initiation of inflammatory and neoplastic processes were presented. The issues of co-infections amongst genital mycoplasmas and Trichomonas vaginalis were considered. Modern views about biofilms formed by Gardnerella vaginalis were also reflected. New data on fungi participation of the Candida genus in maintaining the pathological process in the female reproductive system, especially the interaction of fungi with the vaginal epithelium were shown. The review also highlights the issues of immunological protection during infection with obligate and opportunistic microorganisms. According to current research data and current clinical recommendations, the possibility of combined drug (metronidazole and miconazole) rational use for topical treatment of mixed infections in women was shown.

Keywords: genital tract, microbial associations, Chlamydia trachomatis, Trichomonas vaginalis, urogenital infections, Gardnerella vaginalis, Candida, biofilm, miconazole, metronidazole.

For citation: Letyaieva O.I. Microbiome of the vaginal biotope: from norm to pathology. RMJ. 2020;12:72–76.

Pages 77-79. Роль микроРНК при злокачественных новообразованиях органов брюшной полости с явлениями перитонеального канцероматоза. Ганцев К.Ш., Кзыргалин Ш.Р., Ишмуратова К.Р.

Summary:

The role of miRNA in abdominal cancer with peritoneal carcinomatosis

K.Sh. Gantsev, Sh.R. Kzyrgalin, K.R. Ishmuratova

Bashkir State Medical University, Ufa

Late diagnosis of peritoneal carcinomatosis in abdominal cancer verified by noninvasive and invasive imaging techniques (i.e., positron emission tomography, computed tomography, magnetic resonance imaging, laparoscopy, laparotomy etc.) accounts for low survival of these patients. Low efficacy of early diagnostic tests and a lack of a common approach to treatment choice demonstrate that the mechanisms of the development and progression of abdominal cancer with peritoneal carcinomatosis are to be investigated.

Research of cancer molecular mechanisms is of particular importance over the last decade. Numerous studies support the involvement of microRNA (miRNA) in cancer development and progression. This article reviews current conception of miRNA role in the development of gastric and colorectal cancer and associated peritoneal carcinomatosis. The role of miRNA in cancer pathogenesis is described. Our findings demonstrate the impo rtance of studying molecular genetic hallmarks of tumor growth and potential use of miRNA as a diagnostic marker and predicting factor in abdominal cancer with peritoneal carcinomatosis.

Keywords: abdominal cancer, gastric cancer, colorectal cancer, peritoneal carcinomatosis, miRNA, diagnostic markers.

For citation: Gantsev K.Sh., Kzyrgalin Sh.R., Ishmuratova K.R. The role of miRNA in abdominal cancer with peritoneal carcinomatosis. RMJ. 2020;12:77–79.

Pages 9-13. Влияние генетических особенностей на максимальное потребление кислорода и систолическую функцию левого желудочка в норме и в реабилитационном периоде после острого инфаркта миокарда. Головенкин С.Е., Никулина С.Ю., Максимов В.Н., Орлова Ю.В., Пелипецкая Е.Ю.

Summary:

Genetic characteristics effect on maximum oxygen consumption and left ventricular systolic function in normal condition and rehabilitation period after acute myocardial infarction

S.E. Golovenkin1, S.Yu. Nikulina1, V.N. Maximov2, Yu.V. Orlova1, E.Yu. Pelipetskaya1

1Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk

2Institute of Internal and Preventive Medicine, the branch of the Federal Research Center «Institute of Cytology and Genetics of the Siberian Department of the Russian Academy of Sciences», Novosibirsk

Myocardial infarction (MI) is the most dangerous manifestation of coronary heart disease, commonly leading to fatal outcome. Competently conducted rehabilitation measures can reduce cardiovascular mortality by a quarter and increase patient recovery by 1.5 times. The modern patient rehabilitation system includes appropriate measures immediately after the patient is admitted to the intensive care unit and their continuation at the outpatient stage throughout the year. At the same time, rehabilitation measures sometimes give different efficacy with the same severity of MI and concomitant pathology. This suggests the patients’ genetic characteristics influence on rehabilitation measures effect. The efficacy of rehabilitation measures largely depends on the maximum oxygen consumption and restoration of left ventricular systolic function. The article discusses the study results concerning patients’ genetic characteristics and an increase in ma ximum oxygen consumption during physical training, and association between the patients’ genetic characteristics and left ventricle systolic function in cardiovascular disease. The revealed polymorphisms associated with maximum oxygen consumption and systolic function restoration can be the subject of study in patients undergoing rehabilitation after MI. These study results will make it possible to individualize the rehabilitation process, which will increase the effectiveness of the ongoing rehabilitation measures and will have a positive effect on the disease prognosis.

Keywords: myocardial infarction, genetics, rehabilitation, maximum oxygen consumption, adaptation to physical activity, restoration of left ventricular systolic function, single-nucleotide polymorphism, allele.

For citation: Golovenkin S.E., Nikulina S.Yu., Maximov V.N. et al. Genetic characteristics effect on maximum oxygen consumption and left ventricular systolic function in normal condition and rehabilitation period after acute myocardial infarction. RMJ. 2020;12:9–13.



№11, 2020. Клинические рекомендации и алгоритмы для практикующих врачей

Pages 14-18. Оксигенотерапия при сердечно-сосудистых заболеваниях и инфекции COVID-19. Ухолкина Г.Б.

Summary:

Oxygen therapy for cardiovascular diseases and COVID-19 infection

G.B. Ukholkina1,2

1City Clinical Hospital named after S.S. Yudin of the Moscow Health Department, Moscow

2Multidisciplinary Medical Center of the Central Bank of the Russian Federation, Moscow


The article discusses the pathophysiology of hypoxia, the mechanisms of its elimination with oxygen therapy, and the toxic effects of oxygen. It also highlights modern recommendations and algorithms for application in cardiovascular diseases, including in combination with bronchopulmonary pathology. Given the data of evidence-based medicine, controversial and unclear aspects of oxygen therapy and the possibility of negative consequences if used incorrectly are discussed. The world experience of using oxygen therapy for the new COVID-19, including additional methods for improving the oxygenation (prone position), is discussed, and the author also shares his personal experience in treating comorbid patients with COVID-19. The modern methods of inhalation oxygen therapy and indications for their use, including non-invasive ventilation, high-flow nasal oxygenation (a promising, but no t widely used technique in our country), various types of oxygen therapy with masks, devices for home oxygen therapy are described.

Keywords: oxygen therapy, hypoxemia, oxygen, blood oxygen saturation, saturation, acute respiratory distress syndrome, new coronavirus infection, COVID-19, inhalations, oxygen masks.

For citation: Ukholkina G.B. Oxygen therapy for cardiovascular diseases and COVID-19 infection. RMJ. 2020;11:14–18.



Pages 20-28. Лекарственно-индуцированный дефицит электролитов. Часть 1. Лекарственно-индуцированная гипокалиемия. Остроумова О.Д., Переверзев А.П., Клепикова М.В.

Summary:

Drug-induced electrolyte imbalance. Part 1. Drug-induced hypokalemia

O.D. Ostroumova, A.P. Pereversev, M.V. Klepikova

Russian Medical Academy of Continuous Professional Education, Moscow


The incidence of severe drug-induced hypokalemia in medical institutions is about 4.32–4.64 per 10,000 visits per year. Drug-induced hypokalemia is caused by many medications: diuretics, adrenoceptor agonists, drugs used for chemotherapy of malignant neoplasms, glucocorticosteroids, antibacterial drugs, etc. Polypragmasia, long-term use of certain medications and their use in high doses are also associated with an increased risk of drug-induced hypokalemia. Its clinical manifestations correspond to those of hypokalemia in general and include depression, paresthesia, lower limb muscle cramps, convulsions, hyporeflexia, muscle weakness, decreased myocardial contractile function, various heart rhythm disorders, nausea, vomiting, intestinal paresis, intestinal obstruction, muscle necrosis, etc. The most accurate and reliable method for diagnosing hypokalemia is to determine the potassium level in the blood serum. Potassium deficiency is also characterized by ECG changes. When the potassium level in the blood serum of 2.5–3.9 mmol/L, oral potassium supplementation is required during which the patient can be treated on an outpatient basis. When the potassium concentration in the blood serum <2.5 mmol/L, in-patient care is required — infusion therapy with subsequent switch to oral potassium su pplementation. The article presents the benefits of potassium and magnesium asparaginate in the treatment of hypokalemia, including drug-induced.

Keywords: adverse events, hypokalemia, drug-induced hypokalemia, potassium, potassium and magnesium asparaginate.

For citation: Ostroumova O.D., Pereversev A.P., Klepikova M.V. Drug-induced electrolyte imbalance. Part 1. Drug-induced hypokalemia.
RMJ. 2020;11:20–29.



Pages 30-34. Инсулинотерапия при сахарном диабете 2 типа у пациентов с морбидным ожирением: факторы эффективной компенсации нарушений углеводного обмена. Амосова М.В., Гурова О.Ю., Глинкина И.В., Малолеткина Е.С., Фадеев В.В.

Summary:

Insulin therapy for type 2 diabetes mellitus in patients with morbid obesity: factors for effective compensation of carbohydrate metabolism indicators

M.V. Amosova, O.Yu. Gurova, I.V. Glinkina, E.S. Maloletkina, V.V. Fadeev

Sechenov University, Moscow

Aim: to study the factors that determine the efficacy of insulin therapy in patients with type 2 diabetes mellitus (DM2) and morbid obesity (MO).

Patients and Methods: the study included 141 patients with DM2 and MO. 61 patients received GLP-1 receptor agonists in combination with basal insulin and Metformin (group 1), 40 patients received basal insulin in combination with sulfonylurea drug and metformin (group 2), and 40 patients received basal-bolus insulin therapy with metformin (group 3). Initially and after 24 weeks, all patients underwent clinical and laboratory examinations, as well as assessment of their cognitive status, eating behavior, life quality by questionnaires, and sleep quality by polysomnography.

Results: cognitive impairment was detected in 56.1% of patients with DM2 and MO. The presence and severity of cognitive decline significantly affected the effectiveness of hypoglycemic therapy: HbA1c dynamics after 24 weeks of therapy (95% confidence interval) in patients without cognitive impairment -1.1% (-0.9; -2.2), with pre-dementia states -0.6% (-0.5; -1.3), with dementia -0.6% (-0.2; -1.4) (p<0.001). 84.4% of patients were diagnosed with eating disorders, represented in 67% of cases by a combination of emotiogenic, external and restrictive types. During GLP-1 receptor agonists therapy, there was a tendency to improve the life quality, initially reduced in all patients. Obstructive sleep apnea was detected n 86.9% of patients, with a severe degree of this disorder — in 61.5% of patients.

Conclusion: it is advisable to assess the cognitive status, eating behavior, and sleep quality to choose hypoglycemic therapy individually for patients with DM2 and MO. The high prevalence of cognitive impairment among patients with DM2 and MO determines the priority of prescribing the simplest insulin therapy regimens.

Keywords: diabetes mellitus, morbid obesity, in sulin therapy, GLP-1 receptor agonists, cognitive impairment, obstructive sleep apnea, eating disorders, life quality.

For citation: Amosova M.V., Gurova O.Yu., Glinkina I.V. et al. Insulin therapy for type 2 diabetes mellitus in patients with morbid obesity: factors for effective compensation of carbohydrate metabolism indicators. RMJ. 2020;11:30–34.

Pages 35-38. Опыт лечения лекарственного поражения печени. Тарасова Л.В., Арямкина О.Л., Волкова Т.В.

Summary:

Experience in treating drug-induced liver injury

L.V. Tarasova1,2, O.L. Aryamkina1,3, T.V. Volkova1,3


1Surgut State University, Surgut

2Chuvash State University named after I.N. Ulyanov, Cheboksary

3Surgut Regional Clinical Hospital, Surgut


Drug-induced liver injury (DILI) is one of the main adverse events of pharmacotherapy. New medicines appearance on the pharmaceutical market, the increase in the number of DILI caused by herbal preparations and dietary supplements, as well as the market expansion for immunobiological preparations, make medicines as the most important etiological factors of liver injury. The choice of tactics for the patient management with DILI is determined by the course and severity of the disease, the characteristics of the use of potentially hepatotoxic preparation, and the individual characteristics of the patient. There are common links in the DILI pathogenesis, including hypoxia, de-energization (deficit of ATP production), damage to hepatocyte membranes and inhibition of antioxidant protection. Therefore, pathogenetic pharmacotherapy and prevention of liver injury are based on preparations with a mechanism of acti on aimed at eliminating one or more links in the pathogenesis. One of these preparations is Remaxol, which includes antihypoxants and antioxidants of metabolic type: natural metabolites, substrates and cofactors involved in energy metabolism. The article presents the result of using Remaxol in a patient with drug-induced hepatotoxicity. The use of Remaxol made it possible to achieve clinical and biochemical remission, preventing the development of severe liver injury, and helped to preserve the recommended therapy duration of the underlying disease.

Keywords: drug-induced liver injury, hepatotoxicity, adverse events of pharmacotherapy, antioxidant, antihypoxant.

For citation: Tarasova L.V., Aryamkina O.L., Volkova T.V. Experience in treating drug-induced liver injury. RMJ. 2020;11:35–38.



Pages 39-42. Влияние интерлейкина-17 на патогенез и риски развития сердечно-сосудистых заболеваний при спондилоартритах. Василенко Е.А., Мазуров В.И., Гайдукова И.З., Дадалова А.М., Королев М.А., Гайдукова Е.К.

Summary:

Interleukin-17 effect on the pathogenesis and risks of cardiovascular diseases in spondylarthritis

E.A. Vasilenko1, V.I. Mazurov1, I.Z. Gaidukova1, A.M. Dadalova1, M.A. Korolev2, E.K. Gaidukova3


1North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg

2Research Institute of Clinical and Experimental Lymphology (NIIKEL), the branch of the Federal Research Center "Institute of Cytology and Genetics of the Siberian Department of the Russian Academy of Sciences", Novosibirsk

3Clinical Rheumatology Hospital No. 25, Saint-Petersburg


Background: the critical value of the IL-17 for the pathogenesis of spondyloarthritis (SpA) led to the emergence of new genetic engineering biological drugs that inhibit IL-17. At the same time, it is possible that IL-17 may have a certain value in modifying the risk of cardiovascular diseases in SpA.

Aim: to study the association of cardiovascular risks in patients with axial spondylitis (axial SpA) and genetic polymorphism responsible for IL-17 synthesis, assessed by various scales: Systematic COronary Risk Evaluation (SCORE), QRESEARCH Cardiovascular Risk Algorithm (QRISK3), Reynolds Risk Score (RRS).

Patients and Methods: 48 patients aged 25 to 69 years (74.6% men) were examined with confirmed axial SpA who met the ASAS (2009) criteria, including those with extra-skeletal lesions (psoriasis). Cardiovascular risks were assessed using the QRISK3, SCORE, and RRS scales. Genetic typing was performed according to IL17A-197 AG, IL17-F7 His/Arg, IL17F-11139 CG, and the concentration of highly sensitive C-reactive protein (hs-CRP) was determined.

Results: factor analysis revealed correlations between the risk of significant cardiovascular events, CRP level, and the carrier of various IL-17A and IL-17F alleles. The highest capacity and direct association with an increased risk of fatal cardiovascular outcomes was achieved in individuals homozygous for the AA IL-17A allele and heterozygous for the CG IL-17F allele. An inverse relationship was found in the presence of homozygous for the GG IL-17A and CC IL-17F alleles. In the course of the study, data were obtained on the presence of a direct association between an increase in cardiovascular risk and the CRP level.

Conclusion: increased cardiovascular risk in axial SpA may be associated with genetically determined altered secretion of IL-17 subtypes, which in the future may determine the validity of IL-17 blockade use in patients with axial SpA with a high cardiovascular risk.

Keywords: cardiovascular risk, axial spondyloarthritis, psoriatic arthritis, prevention of cardiovascular diseases, SCORE, QRISK, Reynolds Risk Score, interleukin-17.

For citation: Vasilenko E.A., Mazurov V.I., Gaidukova I.Z. et al. Interleukin-17 effect on the pathogenesis and risks of cardiovascular diseases in spondylarthritis. RMJ. 2020;11:39–42.



Pages 4-8. Особенности течения и факторы неблагоприятного прогноза коронавирусной инфекции COVID-19 у пациентов с иммуновоспалительными заболеваниями. Мазуров В.И., Гайдукова И.З., Бакулин И.Г., Инамова О.В., Фонтуренко А.Ю., Самигуллина Р.Р., Крылова А.И., Гайдукова Е.К.

Summary:

Patterns of COVID-19 infection course and factors of adverse prognosis in patients with immune-mediated inflammatory disease


V.I. Mazurov1,2, I.Z. Gaidukova1,2, I.G. Mazurov1, O.V. Inamova1,2, A.Yu. Fonturenko1, R.R. Samigullina1, A.I. Krylova2, E.K. Gaidukova2


1North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg

2Clinical Rheumatological Hospital No. 25, Saint-Petersburg


Background: the new COVID-19 infection is a poorly studied problem of modern medicine and rheumatology.

Aim: to study the patterns of COVID-19 infection course in patients with immune-mediated inflammatory rheumatic diseases (RD) on the basis of clinical practice data.

Patients and Methods: the analysis of data concerning patients with confirmed immune-mediated inflammatory RD and COVID-19 infection (n=31: 9 men and 22 women) was conducted. Enrollment period: 15.03.2020–15.06.2020.

Results: severe COVID-19 was observed in 38.7% of patients with RD: 49% of them were hospitalized and 16% of patients died. All the deceased patients had pneumonia with 75–100% lung damage, alveolar-capillary block syndrome, acute respiratory distress syndrome and severe respiratory failure. 4 out of 5 deceased patients had macrophage activation syndrome (MAS), whereas, two of them h ad MAS in combination with sepsis. The adverse prognosis of COVID-19 was influenced not so much by the current RD activity as by pre-existing organ damage (end-stage renal disease, chronic heart failure, etc.). All the deceased patients were female. Most of the deceased patients had a pathology of obesity, hypertension, chronic kidney disease, and a history of thrombotic events. The presence of obesity of any degree more than three times increased the risk of an adverse prognosis with COVID-19 in patients with RD.

Conclusion: immune-mediated inflammatory RD are associated with an increase in mortality from total or subtotal COVID-associated pneumonia in combination with MAS and sepsis in the setting of pre-existing internal organ damage (a significant decline of kidney function, chronic heart failure, etc.) and with the presence of obesity and diabetes.

Keywords: immune-mediated inflammatory diseases, rheumatic diseases, new coronavirus infection, COVID-19, coronavirus , pneumonia, adverse prognosis.

For citation: Mazurov V.I., Gaidukova I.Z., Mazurov I.G. et al. Patterns of COVID-19 infection course and factors of adverse prognosis in patients with immune-mediated inflammatory disease. RMJ. 2020;11:4–8.

Pages 43-48. Магнитно-резонансная томография как дополнительный инструмент выбора терапии при лечении остеоартрита. Гайдукова И.З., Мазуров В.И., Инамова О.В.

Summary:

Magnetic resonance imaging as an additional tool for treatment tactics for osteoarthritis

I.Z. Gaidukova1,2, V.I. Mazurov1,2, O.V. Inamova1,2

1North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg

2Clinical Rheumatology Hospital No. 25, Saint-Petersburg

Aim: to establish the association between the intensity of pain in knee osteoarthritis (OA) and inflammatory changes in the knee detected by MRI with an assessment of changes in dynamics during treatment with NSAIDs.

Patients and Methods: in 46 patients with knee OA (n=46) and pain not less than 4.0 (according to NRS), pain intensity and WOMAC index were measured at baseline and 3 months after NSAIDs treatment (±10 days). MRI of the knee was performed in T1 STIR sequence. During MRI, the following patterns were assessed: the presence of subchondral bone marrow edema (SBME), the number and size of its foci, and the presence of synovitis / tenosynovitis. MRI was repeated after 3 months ± 10 days in patients with inflammatory changes.

Results: initially, signs of inflammatory changes in the knee joints were observed in the majority of patients (72%) with knee OA and joint pain not less than 4.0 poi nts. 39 patients completed the study. 3 months after treatment with NSAIDs, there was a positive trend in all parameters of the WOMAC index — the total index decreased from 64.4±15.4 to 24.12±11.1 points (n=39, p<0.05). According to the results of repeated MRI, the number of patients with SBME significantly reduced, while the number of patients with synovitis and tenosynovitis decreased slightly. The reduction degree in the total WOMAC index and joint pain was greater in patients who initially had signs of subchondral bone inflammation, compared with patients who did not have SBME before the treatment (p<0.05 for all comparisons).

Conclusions: patients with knee OA and severe pain had inflammatory changes in the subchondral bone in 72% of cases according to MRI; synovitis occurred in 91.3% of cases. The presence of inflammatory foci (but not synovitis) in the subchondral bone was associated with an increase in pain in the knee joint and a good response to NSAIDs, the  effect of which was manifested both clinically (pain reduction) and visually (disappearance or decrease of osteitis in the subchondral bone).

Keywords: osteoarthritis, low-grade inflammation, joint pain, MRI-detected inflammation, non-steroidal anti-inflammatory drugs, NSAIDs.

For citation: Gaidukova I.Z., Mazurov V.I., Inamova O.V. Magnetic resonance imaging as an additional tool for treatment tactics for osteoarthritis. RMJ. 2020;11:43–48.



Pages 49-53. Влияние секукинумаба на развитие дисфункции миокарда у пациентов с анкилозирующим спондилитом. Фейсханова Л.И., Лапшина С.А.

Summary:

Secukinumab effect on the myocardial dysfunction development in patients with ankylosing spondylitis

L.I. Feiskhanova, S.A. Lapshina


Kazan State Medical University, Kazan


Background: in ankylosing spondylitis (AS), early subclinical changes in the myocardium mostly remain undiagnosed. The impact of genetic engineering biological therapy (GEBT) on these changes is also unclear.

Aim: to establish the association between the secukinumab intake and changes in systolic and diastolic functions of myocardium in patients with AS.

Patients and Methods: 69 patients with confirmed AS were examined: the first group included 33 patients (average age 38.8±4.74, 63.6% of men) who received the interleukin 17 (IL-17) inhibitor — secukinumab, the second group — 36 patients who did not receive GEBT (average age 42.5±11 years, 66.7% of men). The control group included 40 healthy subjects, comparable in gender and age. Patients underwent tissue doppler echocardiography, transthoracic echocardiogram, and determination of matrix metalloproteinase-9 (MMP-9) level in blood serum. Statistical processing  of results was performed using STATISTICA 10.0 software.

Results: there was significantly (p<0.01) higher left ventricular mass index and ejection fraction in patients with AS compared to the control group, although they were generally within normal range. Moreover, the indicators were the highest among patients who did not receive GEBT, diastolic dysfunction was diagnosed only in this group (in 38.9%). In the setting of the secukinumab therapy, there was an increase in the systolic function of the myocardium. Analysis of the MMP-9 level in the blood serum of patients with AS showed significant (p<0.001) differences with the control group. In the group of patients receiving secukinumab, the elevation of MMP-9 level was associated with a deterioration of right ventricular systolic function and left ventricular diastolic function.

Conclusion: AS is characterized by a high frequency of subclinical cardiovascular disease. Inhibition of IL-17 can reduce diastolic dysfunction, which is confirmed by an improvement in myocardial contrac tility during secukinumab therapy.

Keywords: ankylosing spondylitis, spondylarthritis, diastolic dysfunction, myocardial contractility, secukinumab, interleukin 17 inhibitor, matrix metalloproteinase, tissue doppler echocardiography.

For citation: Feiskhanova L.I., Lapshina S.A. Secukinumab effect on the myocardial dysfunction development in patients with ankylosing spondylitis. RMJ. 2020;11:49–53.

Pages 54-58. Сердечно-сосудистая безопасность повторных назначений эторикоксиба при подагрическом артрите. Гайдукова И.З., Мазуров В.И., Фонтуренко А.Ю., Башкинов Р.А., Петрова М.С., Инамова О.В., Шаповалов А.А., Нагирняк И.М.

Summary:

Cardiovascular safety profile of repeated etoricoxib courses in gout

I.Z. Gaidukova1,2, V.I. Mazurov1,2, A.Yu. Fonturenko1,2, R.A. Bashkinov1,2, M.S. Petrova1,2, O.V. Inamova1,2, A.A. Shapovalov3, I.M. Nagirnyak3


1North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg

2Clinical Rheumatological Hospital No. 25, Saint-Petersburg

3TechLAB LLC, Saint-Petersburg


Background: non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat gout attacks in short courses. Repeated courses of NSAIDs are prescribed for chronic or recurrent gout, which leads to an increase in the total dose and duration of course, changing the safety profile of treatment.

Aim: to study the incidence of myocardial infarction (MI), arterial hypertension (AH), and chronic kidney disease (CKD) in patients with chronic or recurrent gout with repeated courses of etoricoxib (EC).

Patients and Methods: an analysis of the features of EC use in patients with gout was performed based on the data of the Saint Petersburg city register of gout and asymptomatic hyperuricemia from 2000 to 2019, formed on the basis of the GALENOS cloud electronic data storage system (Techlab LLC).

Results: the register included data of 1,725 patien ts with gout, of whom 315 people took EC and 118 had repeated courses (average age 57.1±7.9 years; 43 women). Age-and gender-matched patients with gout who received other NSAIDs in repeated courses (n=60) made up the control group. The follow-up period averaged 4.85±3.36 (1–17) years. The average duration of EC treatment was 24.9±15.2 (8–87) days, and other NSAIDs-37.1±9.8 (21–74) days (p<0.0001). The NSAID intake index (Dugados Functional Index) for EC was equal to 6.8%, for other NSAIDs — 10.2% (p<0.05). The average dosage of EC was 92.3±16.8 (60–120) mg/day. During follow-up, 7 (3.9%) patients were diagnosed with AH, 45 (25.3%) with CKD, and 2 (1.7%) patients had MI. The occurrence of cardiovascular diseases was more commonly detected in patients who alternated EC with other NSAIDs, versus patients who received EC or other NSAIDs without switching, and versus population indicators (p<0.05 for all comparisons).

Conclusion: the use of repeated EC courses of for the treatment of chronic or recurrent gout is not associated with an increase in the risk of MI, hypertension, or CKD, provided that EC is not switched to other NSAIDs, since in this case the shortest duration of administration and the total dose of NSAIDs are achieved.

Keywords: gout, chronic inflammation, cardiovascu lar safety profile, non-steroidal anti-inflammatory drugs, coxibs.

For citation: Gaidukova I.Z., Mazurov V.I., Fonturenko A.Yu. et al. Cardiovascular safety profile of repeated etoricoxib courses in gout. RMJ. 2020;11:54–58.



Pages 59-63. Особенности иммунного ответа у больных внебольничной пневмонией с сочетанной сердечно-сосудистой патологией. Титова О.Н., Кузубова Н.А., Александров А.Л., Перлей В.Е., Тихонова К.А.

Summary:

Immune response characteristics in patients with community-acquired pneumonia and comorbid cardiovascular pathology

O.N. Titova1, N.A. Kuzubova1, A.L. Alexandrov1, V.E. Perley1, K.A. Tikhonova2


1National Research Institute of Pulmonology of the Pavlov First Saint Petersburg State Medical University, Saint-Petersburg

2Vvedenskaya City Clinical Hospital, Saint-Petersburg

Aim: to identify the characteristics of the immune status in patients with community-acquired pneumonia (CAP) and comorbid cardiovascular pathology (CCP), and its effect on the clinical course, cardiopulmonary hemodynamics and disease prognosis.

Patients and Methods: 58 patients, were examined and divided into two groups. The first group included 43 patients with CAP (74%) who had clinically significant CCP (average age 62±10 years). The second group consisted of 15 patients with CAP (26%) without concomitant diseases, (average age 56±15 years).

Results: a lower hemoglobin level was determined in group 1 (117.04±6.05 g/l), lower values of serum IL-8 and IL-6 — 2 and 2.3 times, respectively, while the average IL-17 values were almost more than two times higher than in group 2. The presence of direct, strong, reliable associations between the increased value of IL-17 and the content of neutrophils and young forms of WBC (r=0.85, and r=0.91, respectively, p<0.05) was established. In group 1, there was a direct medium-strong association, between the level of serum IL-17 and the time to reach the maximum ejection rate in the right ventricular outflow tract (r=0.61, p<0.05), as well as a direct strong association with the diameter of the inferior vena cava (r=0.86, p<0.05).

Conclusion: the revealed correlation between IL-17, myeloperoxidase and echocardiographic parameters in these patients indicated that the increasing level of pro-inflammatory cytokine was not only due to the development of the inflammatory process but also to the presence of concomitant CCP . The dynamics of the serum IL-17 level in patients with CAP can serve as a prognostic criterion for the severity of the pathological process and the functional state of the cardiopulmonary circulation.

Keywords: community-acquired pneumonia, comorbid cardiovascular pathology, proinflammatory cytokines, interleukin, myeloperoxidase, cardiopulmonary hemodynamics.

For citation: Titova O.N., Kuzubova N.A., Alexandrov A.L. et al. Immune response characteristics in patients with community-acquired pneumonia and comorbid cardiovascular pathology. RMJ. 2020;11:59–63.



Pages 64-68. Клинико-лабораторные аспекты аллергии на укусы комарами у детей Московского региона. Рыбникова Е.А., Образцов И.В., Продеус А.П., Федоскова Т.Г.

Summary:

Clinical and laboratory aspects of mosquito bite allergy in children of the Moscow region

E.A. Rybnikova1,2, I.V. Obraztsov1, A.P. Prodeus1, T.G. Fedoskova2,3

1Children’s City Clinical Hospital No. 9 named after G.N. Speransky, Moscow

2Pirogov Russian National Research Medical University, Moscow,

3State Research Center “Institute of Immunology» of the Federal Medical and Biological Agency, Moscow

Aim: to provide clinical and laboratory characteristics for pediatric patients with mosquito bite allergy on the example of the population in Moscow, to determine the proportion of mosquito bite allergy in the general structure of allergic pathology in children and to determine the aggravating risk factors of its occurrence.

Patients and Methods: 1587 patients under 18 y.o. were examined. The presence of hypersensitivity manifestations, their clinical patterns, and allergy diagnostics data were evaluated based on the study in vitro. The first part of the study involved 705 children with a confirmed atopic diagnosis including a history of mosquito bite allergy (247 children in the main group) or without it (426 children in control group 1). In the second part of the study, the main group was compared with the control group 2, which consisted of 14 children without allergic pathology and atopic predisposition (conditionally healthy), who had a history of allergic symptoms to mosquito bites.

Results: children with confirmed allergic pathology had complaints about the occurrence of hyperergic reactions of varying severity to mosquito bites in 35% of cases. Children of preschool (66.7%) and junior school (16.7%) ages predominated. In 88.7% of them there were the manifestations of topical reactions. In 11.3% of cases, there was the development of mild to moderate systemic reactions. No severe systemic reactions were observed. Patients of the main group with insect-bite allergy  suffered from skin manifestations in the form of atopic dermatitis (22.7% and 13.3%, p<0.05) and recurrent urticaria (3.2% and 1.4%, p<0.05) more often than patients of control group 1. There was a correlation (Pearson correlation coefficient: η=0.71, p<0.05) between the incidence of allergic symptoms to mosquito bites and the presence of allergic dermatosis. 2.7% of children in the main group had cross-sensitization with fish and/or seafood allergens. In 3.6% of cases, the development of IgE-mediated allergy was noted.

Conclusion: aggravating factors for the development of mosquito bite allergy are the following: preschool age (4–7 years), the presence of allergic dermatoses, the presence of allergies to fish and/or seafood. It is necessary to further study the mechanisms of insect —bite allergy and search for new diagnostic tools.

Keywords: insect-bite allergy, children, mosquitoes, Skeeter syndrome, domestic allergy, food allergy, prevalence, cross-reactivity.

For citation: Rybnikova E.A., Obraztsov I.V., Prodeus A.P., Fedoskova T.G. Clinical and laboratory aspects of mosquito bite allergy in children of the Moscow region. RMJ. 2020;11:64–68.



Pages 69-74. Острый и рецидивирующий цистит. Что нам известно?. Ходырева Л.А., Зайцев А.В., Берников А.Н., Куприянов Ю.А., Строганов Р.В., Арефьева О.А.

Summary:

Acute and recurrent cystitis. What do we know?

L.A. Khodyreva1,2, A.V. Zaitsev1, A.N. Bernikov1, Yu.A. Kupriyanov1,2, R.V. Stroganov3, O.A. Arefieva2,3

1A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow

2Research Institute for Healthcare and Medical Management of Moscow Healthcare Department, Moscow

3City Clinical Hospital named after S.I. Spasokukotsky, Moscow

The growing antibiotic resistance of urinary tract infection pathogens is an urgent problem worldwide. Rational use of antibacterial drugs and alternative non-antibacterial prevention of lower urinary tract infections are aimed at solving this problem. The article presents current data on the etiology, pathogenesis, diagnosis, treatment, and prevention of acute uncomplicated and recurrent lower urinary tract infection. The article also shows the results of clinical studies on the use of proanthocyanidins, D-mannose and vitamin D3 in the complex treatment and prevention of acute infectious and inflammatory process in the urinary bladder. According to the scientific literature, the mechanism of action of alternative drugs and their efficacy in reducing the frequency of relapses is demonstrated.

Keywords: urinary tract infection, urinary bladder, recurrent infection, postcoital prevention, proanthocyanidins, D-mannose, vitamin D3.

For citation: Khodyreva L.A., Zaitsev A.V., Bernikov A.N. et al. Acute and recurrent cystitis. What do we know? RMJ. 2020;11:69–74.

Pages 75-78. Бактериальный вагиноз. Возможные пути решения проблемы. Ильина И.Ю., Доброхотова Ю.Э.

Summary:

Bacterial vaginosis. Possible solutions to the problem

I.Yu. Ilina, Yu.E. Dobrokhotova

Pirogov Russian National Research Medical University, Moscow

The article is devoted to the problem of bacterial vaginosis (BV) which is the main cause of vaginal dysbiosis in women of the reproductive period. The article highlights the features of diagnosis and treatment. Due to the fact that in BV one has to deal with polymicrobial associations, the sheer fact of detecting opportunistic microflora is not informative in the diagnosis of vaginal infections. The ratio of lactobacilli and opportunistic microorganisms is of fundamental importance. Despite the existing treatment algorithms presented in the clinical guidelines and confirmed by many studies, there are still many unresolved issues. This is due to the variety of microorganisms, leading to the BV development, and difficulties in treatment. Special attention is paid to the possibility of using a combined drug for intravaginal administration containing metronidazole 100 mg and miconazole nitrate 100 mg (Ginocaps)  in outpatient gynecological practice. This combined drug is recommended for BV treatment in combination with metronidazole intake. Besides, this drug can be recommended for the treatment of co-infection and in the presence of pathological vaginal discharge in women, especially of a recurrent nature, as well as in the absence of diagnostics to determine the pathogen, since it is effective against anaerobes and yeast-like fungi of the Candida genus.

Keywords: bacterial vaginosis, pathological vaginal discharge, Amsel’s criteria, Nugent’s criteria, metronidazole, miconazole.

For citation: Ilina I.Yu., Dobrokhotova Yu.E. Bacterial vaginosis. Possible solutions to the problem. RMJ. 2020;11:76–78.



Pages 79-80. Разработка методики количественного определения дубильных веществ в корнях ревеня лекарственного. Семенюта К.Н., Куркин  В.А., Шмыгарева А.А., Саньков А.Н.

Summary:

Development of assay methods for tannins content in Rheum officinale B.

K.N. Semenyuta, V.A. Kurkin, A.A. Shmygareva, A.N. Sankov

Orenburg State Medical University, Orenburg

Rheum officinale B. is a medicinal plant widely used in the traditional medicine of the European Union, United Kingdom, Japan and China and is promising for use in national pharmacy. Rheum officinale B. and Rheum palmatum L. are closely related plant species that contain two dominant groups of biologically active substances — anthracene derivatives and tannins. The aim of the study was to determine the optimal conditions for extracting tannins from the Rheum officinale B. and develop an assay technique. The study objects were the roots of Rheum officinale B. Electronic spectra were measured using Unico 2800 UV spectrophotometer. Solutions UV spectra of water extracts from raw materials were studied. Catechin was used as a reference standard, which had a maximum absorption at a wavelength of 282±2 nm. Optimal conditions for extracting tannins from the Rheum officinale B.: extraction  solvent — water; raw material/extraction solvent ratio — 1:50; extraction time — 15 minutes in a boiling water bath. Assay method for tannins content in Rheum officinale B. by spectrophotometry on the basis of catechin at the analytical wavelength of 282±2 nm has been developed. The content of tannins in the Rheum officinale B. was 25.35%.

Keywords: Rheum palmatum L., Rheum officinale B., roots, tannins, catechin, standardization, spectrophotometry.

For citation: Semenyuta K.N., Kurkin V.A., Shmygareva A.A., Sankov A.N. Development of assay methods for tannins content in Rheum officinale B. RMJ. 2020;11:78–80.

Pages 9-13. Особенности течения пневмоний, вызванных SARS-CoV-2, у госпитализированных пациентов: опыт Санкт-Петербурга. Титова О.Н., Волчков В.А., Кузубова Н.А., Козырев А.Г., Черменский А.Г., Волчкова Е.В.

Summary:

Patterns of the pneumonia course caused by SARS-CoV-2 on inpatient basis: clinical experience in St. Petersburg

O.N. Titova1, V.A. Volchkov2, N.A. Kuzubova1, A.G. Kozyrev1, A.G. Chermenskii1, E.V. Volchkova3

1Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg

2Saint-Petersburg State University, Saint Petersburg

3Saint-Petersburg State Pediatric Medical University, Saint Petersburg

Background: one of the typical manifestations of a new coronavirus infection (COVID-19) is pneumonia.

Aim: to evaluate the patterns of pneumonia course in patients with COVID-19 and analyze the results of treatment depending on its type.

Patients and Methods: the medical documents of hospitalized patients with pneumonia caused by SARS-CoV-2 (n=229) were studied. Three groups were formed: I group (n=86) — patients who were discharged with clinical improvement and were not observed in the intensive care unit (ICU); II group (n=55) — patients who were discharged but were in the ICU during treatment; III group (n=88) — cases with a fatal outcome.

Results: patients from group III were older compared to groups I and II (p<0.001), and suffered from at least one concomitant pathology, mainly cardiological or neuropsychiatric. Groups II and III compared to group I were characterized by a more pronounced decrease in oxygen saturation on the day of hospitalization (p<0.001), as well as by the increase in the neutrophil-lymphocyte ratio in peripheral blood (p<0.001), the rate of erythrocyte sedimentation (p=0.045 for I/II and p=0.019 for I/III) and C-reactive protein concentration (p<0.001). Subgroups that received or did not receive umifenovir significantly differed in relation to the need for artificial lung ventilation (ALV) (p=0.013) and the number of cases with fatal outcome (p=0.002). This was more the case for patients who needed treatment in ICU. The use of lopinavir/ritonavir in the subgroup of patients who required ALV was associated with a decrease in the number of fatal outcomes, p=0.044.

 Conclusions: the probability of a fatal outcome in patients with pneumonia caused by SARS-CoV-2 increased with ageing and underlying cardiological and neuropsychiatric pathology. Predictors of severe pneumonia were significant laboratory signs on the day of hospitalization. The downward trend towards mortality in the subgroups of patients with severe COVID-19 prescribed with lopinavir/ritonavir and umifenovir requires further study.

Keywords: COVID-19, SARS-CoV-2, pneumonia, severe course, oxygen saturation, neutrophil-lymphocyte ratio, erythrocyte sedimentation rate, C-reactive protein, lopinavir, ritonavir, umifenovir.

For citation: Titova O.N., Volchkov V.A., Kuzubova N.A. et al. Patterns of the pneumonia course caused by SARS-CoV-2 on inpatient basis: clinical experience in St. Petersburg. RMJ. 2020;11:9–13.



№10, 2020. Кардиология

Pages 12-16. Плейотропные эффекты азилсартана медоксомила у больных артериальной гипертензией и хронической обструктивной болезнью легких. Григорьева Н.Ю., Королёва М.Е., Конторщикова К.Н., Соловьева Д.В.

Summary:

Pleiotropic effects of azilsartan medoxomil in patients with arterial hypertension and chronic obstructive pulmonary disease

N.Yu. Grigorieva, M.E. Koroleva, K.N. Kontorschikova, D.V. Solovieva

Volga Research Medical University, Nizhny Novgorod

Aim: to compare the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on endothelial function and lipid peroxidation (LP) in patients with arterial hypertension (AH) in combination with chronic obstructive pulmonary disease (COPD).

Patients and Methods: patients were divided into 2 groups (n=30 each). In the first group, patients received ARBs II (azilsartan medoxomil) at a dose of 40 mg/day, in the second group — ACE (fosinopril) at a dose of 20 mg/day. Ambulatory blood pressure monitoring was performed in all patients before and after 1 and 6 months from the start of treatment, as well as the mean pulmonary artery pressure (mPAP), endothelial function, and COPD indicators were studied.

Results: аfter 6 months of the study, all patients in group 1 managed to achieve the target blood pressure (BP) without increasing the dose of the drug. In group 2, BP was also normalized in all patients, but 5 patients had to increase the fosinopril dose to 40 mg/day. After 6 months, all patients had a statistically significant decrease in mPAP vs. the baseline (p<0.001); it was more significant in group 1 (p=0.01). After 6 months, endothelium-dependent vasodilation (EDV) in group 1 improved and amounted to 9.4±2.1% (p<0.001 vs. the baseline). In group 2, EDV significantly increased to 8.5±2.3 (p<0.001) by the end of treatment. The degree of differences in EVD between the azilsartan medoxomil and fosinopril groups was 3,7,5%. In group 1, there was more significant normalization of COPD products, as well as NO2 and NO3 indicators.

Conclusion: there was more significant improvement in COPD indicators, endothelial function, as well as a decrease in mPAP in patients with AH and COPD after 6 months of treatment with azilsartan medoxomil vs. fosinopril treatment, which suggests a more pronounced performance of pleiotropic effects of ARBs in this patient cohort.

Keywords: arterial hypertension, chronic obstructive pulmonary disease, endothelial dysfunction, lipid peroxidation, azilsartan medoxomil.

For citation: Grigorieva N.Yu., Koroleva M.E., Kontorschikova K.N., Solovieva D.V. Pleiotropic effects of azilsartan medoxomil in patients with arterial hypertension and chronic obstructive pulmonary disease. RMJ. 2020;10:12–16.

Pages 17-19. Роль матриксной металлопротеиназы 9 в ремоделировании миокарда левого желудочка. Шумаков Д.В., Зыбин Д.И., Попов М.А.

Summary:

Matrix metalloproteinase 9 in the left ventricular remodeling

D.V. Shumakov, D.I. Zybin, M.A. Popov

Moscow Regional Clinical Research Institute named after M.F. Vladimirsky, Moscow

Nowadays, chronic heart failure after myocardial infarction (MI) develops approximately in one of four patients and has a high five-year mortality rate (more than 50%), despite modern conservative treatment regimens. That is why understanding the mechanisms of heart failure is extremely relevant. Matrix metalloproteinases are key enzymes involved in left ventricular remodeling. At the same time, an issue concerning the effect of metalloproteinases on the basal cardiomyocyte membranes remains incompletely resolved. It is the basal membranes that are the link between the extracellular matrix and cardiomyocytes, participating in the transmission of the force of contractions during systole. One of the most well-studied is matrix metalloproteinase 9 (MMP-9). A more comprehensive study of MMP-9, especially in relation to the type IV collagen destruction in the basal cardiomyocyte membranes, may  help to optimize the chronic heart failure treatment tactics after MI and to improve the prognosis for difficult-to-treat patients. This review is devoted to the study of the MMP-9 effect on left ventricular remodeling.

Keywords: matrix metalloproteinases, heart failure, type IV collagen, left ventricular remodeling, myocardial infarction.

For citation: Shumakov D.V., Zybin D.I., Popov M.A. Matrix metalloproteinase 9 in the left ventricular remodeling. RMJ. 2020;10:17–19.

Pages 2-7. Возможности применения никорандила у полиморбидных пациентов со стабильной стенокардией напряжения при неэффективности пролонгированных нитратов и противопоказаниях к реваскуляризации. Некрасов А.А., Тимощенко Е.С., Валикулова Ф.Ю., Ярославцева М.А., Новиков М.Ю., Некрасова Т.А., Дурыгина Е.М.

Summary:

Possibilities of using nicorandil in patients with multimorbidity and preserved angina of effort in the inefficacy of long-acting nitrates and contraindications to revascularization

A.A. Nekrasov1, E.S. Timoshenko2, F.Yu. Valikulova1, M.A. Yaroslavtseva2, M.Yu. Novikov2, T.A. Nekrasova1, E.M. Durygina1

1Volga Research Medical University, Nizhny Novgorod

2City Clinical Hospital No. 5, Nizhny Novgorod

Aim: to study the possibilities of using nicorandil in patients with multimorbidity with preserved functional class II–III angina of effort in the inefficacy of long-acting nitrates and contraindications to revascularization.

Patients and Methods: an open prospective study was conducted, which included 40 patients (average age 72.7±9.14 years) who had 3 or more severe chronic diseases (cardiovascular, oncological, etc.) with confirmed inefficacy of long-acting nitrates (a combination of complaints concerning chest pain at least 2 times a week with ischemic changes in the myocardium according to 24-Hour ECG Monitoring). The follow-up was performed during conventional therapy, including long-acting nitrates (7–10 days) after replacing them with nicorandil (Kordinik®, PIQ-PHARMA LLC, the Russian Federation) 10 mg 2 times a day (7–10 days) and after increasing its dose to 20 mg 2 times a day (4 weeks). Each patient kept a daily diary, where they recorded angina attacks, short-acting nitrates regimen, and adverse events. They were examined twice (at the beginning and end of the study) using the 24-Hour ECG Monitoring.

Results: during nicorandil therapy, there was a decrease in the number of angina attacks from 7.8±6.53 to 3.4±3.09 (p<0.0001) and the need for short-acting nitrates from 4.5±4.35 to 1.4±2.34 nitroglycerin tablets (p<0.0001). According to 24-Hour ECG Monitoring data, there was a decrease in the daily average number of myocardial ischemia episodes from 14.8±6.23 to 2.8±2.34 (p=0.0004) and their duration from 64.1±34.32 to 9.1±9.74 min (p=0.0003), in the absence of significant adverse events.

Conclusion: nicorandil is an effective and safe drug in patients with multimorbidity and preserved angina of effort with tolerance to long-acting nitrates and contraindications to revascularization. Nicorandil can be considered as the second-line drug for angina of effort in this patient cohort.

Keywords: nicorandil, angina of effort, patient with multimorbidity, nitrate inefficacy, revascularization.

For citation: Nekrasov A.A., Timoshenko E.S., Valikulova F.Yu. et al. Possibilities of using nicorandil in patients with multimorbidity and preserved angina of effort in the inefficacy of long-acting nitrates and contraindications to revascularization. RMJ. 2020;10:2–7.

Pages 20-24. Розувастатин как доступное средство для эффективной профилактики сердечно-сосудистых заболеваний. Колмакова Т.Е., Алексеева И.А., Ежов М.В.

Summary:

Rosuvastatin as an affordable medicine for effective prevention of cardiovascular diseases

T.E. Kolmakova, I.A. Alexeeva, M.V. Ezhov

National Medical Research Center of Cardiology, Moscow

According to the latest ESC (European Society of Cardiology) Guidelines on dyslipidemia management for the prevention of cardiovascular diseases, low-density lipoprotein (LDL) cholesterol is the only causative risk factor for the development of atherosclerosis complications. In everyday clinical practice, the target level of LDL cholesterol is rarely achieved, which is especially important for high-risk patients of cardiovascular complications. In comparison with other statins, rosuvastatin is already most effective in initial doses and has a better safety profile. Lower all-cause mortality has been shown in patients receiving rosuvastatin versus those treated with other statins. Besides, the significant effect of rosuvastatin was observed in patients with metabolic syndrome, type 2 diabetes mellitus; reduction in the risk of cardiovascular complications in patients with arterial hypertension was also noted. Thera py with rosuvastatin has shown the reduction of complications risk in patients without cardiovascular diseases but with a moderate risk of their occurrence.

Keywords: dyslipidemia, low-density lipoprotein cholesterol, rosuvastatin, efficacy, safety, generics.

For citation: Kolmakova T.E., Alexeeva I.A., Ezhov M.V. Rosuvastatin as an affordable medicine for effective prevention of cardiovascular diseases. RMJ. 2020;10:20–24.



Pages 25-28. Поздние осложнения чрескожных коронарных вмешательств. Шумаков Д.В., Шехян Г.Г., Зыбин Д.И., Ялымов А.А., Степина Е.В., Попов М.А.

Summary:

Late complications of percutaneous coronary interventions

D.V. Shumakov, G.G. Shekhyan, D.I. Zybin, A.A. Yalymov, E.V. Stepina, M.A. Popov

Moscow Regional Clinical Research Institute named after M.F. Vladimirsky, Moscow

According to the World Health Organization, cardiovascular diseases occupy first place in the world as the causes of fatal outcomes. At present, percutaneous coronary intervention (PCI) is the standard treatment regimen of patients with atherosclerotic lesions of the coronary arteries. The introduction of second-drug-eluting stents (SDES) into clinical practice has increased the efficacy and safety of PCI by reducing the severity of inflammatory changes, as well as increasing the rate of regeneration and endothelization of the artery at the stent implantation site. However, the technique and technology of intervention itself prevent the complete regeneration of vascular structure and function and are associated with the risk of late stent dysfunction. Patients who have undergone PCI with SDES implantation remain at risk of late stenting complications (stent thrombosis, restenosis, neoa therosclerosis and bleeding), which are described in this review. Neoatherosclerosis plays an important role in the pathogenesis of acute coronary syndrome after stenting, as well as the recurrence of clinical symptoms after PCI. Advanced cardiac imaging and long-term dual antiplatelet therapy may be of fundamental importance for further understanding and treatment of this pathological process.

Keywords: coronary heart disease, percutaneous coronary intervention, drug-eluting stents, restenosis, stent thrombosis, bleeding.

For citation: Shumakov D.V., Shekhyan G.G., Zybin D.I. et al. Late complications of percutaneous coronary interventions. RMJ. 2020;10:25–28.



Pages 29-34. Замедление прогрессирования мультифокального атеросклероза у больной с первичной гиперхолестеринемией на фоне длительной (16 лет) гиполипидемической терапии. Сусеков А.В., Лугинова З.Г., Горнякова Н.Б., Балахонова Т.В.

Summary:

Retarding progression of multifocal atherosclerosis in a patient with primary hypercholesterolemia in the setting of long-term hypolipidemic therapy (for 16 years)

A.V. Susekov1, Z.G. Luginova2, N.B. Gornyakova3, T.V. Balakhonova4

1Russian Medical Academy of Continuous Professional Education, Moscow

2Republic Hospital No. 1 of the National Medical Center, Yakutsk

3National Medical Research Center of Cardiology, Moscow

4Sechenov University, Moscow

Increasing the level of apoB-containing lipoproteins in blood plasma is the most important modifiable risk factor for atherosclerosis and its complications. Primary hypercholesterolemia is characterized by an increase in low-density lipoprotein cholesterol (LDL-C) > 4.9 mmol/l and requires intensive statin treatment and/or combined lipid-lowering therapy in accordance with current guidelines. The article presents a clinical case of a 73-year-old female patient with primary polygenic hypercholesterolemia, coronary heart disease (CHD), carotid, coronary and peripheral artery atherosclerosis, who has received such treatment for the last 16 years. During this period, the level of LDL-C fluctuated in the range of 1.39–4.26 mmol/l; the treatment was well tolerated at the maximum intensity of therapy with original rosuvastatin and ezetimibe. Dynamic monitoring data by transcranial doppler ultrasound of car otid and peripheral arteries allowed to state the atherosclerosis stabilization. During the follow-up, it was possible to control the CHD course, as evidenced by clinical data and the results of treadmill tests series. Within 16 years of follow-up, planned stenting surgery was performed due to critical stenosis in the common carotid artery. There were no serious complications (heart attack, stroke, acute coronary syndrome).

Keywords: primary hypercholesterolemia, long-term follow-up, rosuvastatin, ezetimibe, atherosclerosis, stabilization.

For citation: Susekov A.V., Luginova Z.G., Gornyakova N.B., Balakhonova T.V. Retarding progression of multifocal atherosclerosis in a patient with primary hypercholesterolemia in the setting of long-term hypolipidemic therapy (for 16 years). RMJ. 2020;10:29–34.



Pages 35-39. Инфаркт миокарда у молодого мужчины со специфическими факторами риска ишемической болезни сердца, длительно занимавшегося бодибилдингом. Мартынов А.Ю., Диане М.Л., Байрамов С.

Summary:

Myocardial infarction in a young male patient with specific risk factors for coronary heart disease who was a bodybuilder for a long time

A.Yu. Martynov, M.L. Diane, S. Bayramov

Peoples’ Friendship University of Russia, Moscow

Most researchers of myocardial infarction note its gradual “rejuvenation”. The article presents a clinical case of a young male patient (28 y.o.), who was a bodybuilder for a long time and was admitted to the hospital with the acute myocardial infarction confirmed by electrocardiography data. Coronary angiography revealed an occlusion of the left anterior descending artery with thrombus formation in the proximal segment, which required repeated thromboextraction, angioplasty, and the installation of a drug-eluting stent. The case specificity was that the patient had only one classic risk factor for coronary heart disease — chronic stress. The Reeder’s test score was 1.71 (high level of psychoemotional stress). At the same time, there were specific modifiable risk factors for myocardial infarction — abuse of energy drinks for 8 years (up to 1.5 liters per day) and long-term use of anabolic steroids (methandrostenolone and testosterone tablets intramuscularly). The role of severe infection (which patient has suffered shortly before) that provoked activation of systemic inflammation factors and prothrombotic activity, as well as the violation of the training regime, was considered among the possible causes of myocardial infarction.

Keywords: myocardial infarction, young age, risk factor, bodybuilding, energy drinks, anabolic steroids, coronary angiography, acute ventricular aneurysm.

For citation: Martynov A.Yu., Diane M.L., Bayramov S. Myocardial infarction in a young male patient with specific risk factors for coronary heart disease who was a bodybuilder for a long time. RMJ. 2020;10:35–39.



Pages 7-11. Прогностическое значение лабораторных и структурно-функциональных аспектов ремоделирования сердечно-сосудистой системы у больных с хронической сердечной недостаточностью ишемического генеза. Алиева А.М., Алмазова И.И., Резник Е.В., Никитин И.Г.

Summary:

Prognostic value of laboratory parameters and structural and functional aspects of cardiac remodeling in patients with chronic heart failure of ischemic origin

A.M. Alieva1, I.I. Almazova2, E.V. Reznik1, I.G. Nikitin1

1Pirogov Russian National Research Medical University, Moscow

2Russian Medical Academy of Continuous Professional Education, Moscow

Aim: to determine the prognostic value of laboratory parameters and structural and functional aspects of cardiac remodeling in patients with chronic heart failure (CHF).

Patients and Methods: the study included 218 patients with coronary heart disease (CHD) and CHF (the average age of patients was 54.4±8.9 years). Upon admission to the hospital, a clinical examination was performed. After discharge, the follow-up of the patients was conducted every 6 months in the first 2 years, and then once a year for 5 years. The end point was considered to be cardiac death.

Results: 124 patients were available for the follow-up. Given 3 cases of sudden cardiovascular death, the cause of death in 25 patients was progressive heart failure (HF), including 22 who died from the acute decompensated heart failure. Three patients died from acute HF that developed in the early postoperative period after coronar y artery bypass grafting. Patients with cardiac death were older and had a longer CHD course. Among the dead patients, there were significantly more with severe HF, arterial hypertension of grade 2 or more, and postinfarction cardiosclerosis. The following risk factors significantly affected five-year survival: age 65; left ventricular ejection fraction (LVEF) — 45.5%; left ventricular end-systolic volume index (LV ESVI) — 81%; left atrial size — 4.45 cm; the number of sites with impaired contractility — 5; stenosis of the proximal third of the anterior interventricular branch — 72.5%, C-reactive protein (CRP) — 6.5 mg/l. The following biochemical parameters regarding cardiac death: creatinine levels ≥ 98.65 mmol/l; brain natriuretic peptide precursor (proBNP) ≥ 420.2 fmol/ml; CRP ≥ 6.5 mg/l; LDL cholesterol ≥ 4.33 mmol/l. The most effective regression analysis model included LVEF of 45.5% and serum CRP of 6.5 mg/l. LVEF of 45.5% had a sensitivity of 89 .7% and a specificity of 90.4%.

Conclusion: proBNP, CRP and LVEF showed a high prognostic significance regarding cardiac death.

Keywords: chronic heart failure, echocardiography, ejection fraction, brain natriuretic peptide precursor.

For citation: Alieva A.M., Almazova I.I., Reznik E.V., Nikitin I.G. Prognostic value of laboratory parameters and structural and functional aspects of cardiac remodeling in patients with chronic heart failure of ischemic origin. RMJ. 2020;10:7–11.



№9, 2020. Клинические рекомендации и алгоритмы для практикующих врачей

Pages 13-17. Взаимодействие антиэпилептических препаратов и противовирусных средств для лечения COVID-19: нужна ли коррекция противоэпилептической терапии?. Холин A.A., Заваденко Н.Н., Холина Е.A., Заваденко А.Н., Нестеровский Ю.Е.

Summary:

Drug-drug interaction of anti-epileptic drugs and antiviral agents for the treatment of COVID-19: is it necessary to correct antiepileptic therapy?

A.A. Kholin, N.N. Zavadenko, E.A. Kholina, A.N. Zavadenko, Yu.E. Nesterovskii


Pirogov Russian National Research Medical University, Moscow


Epilepsy is one of the most common neurological diseases observed in almost every 100th person; a new coronavirus infection (COVID-19) pandemic can not pass by this patient cohort. In conditions of infection, patients with epilepsy should continue the selected antiepileptic therapy. The authors analyze the world experience of evaluating the drug-drug interaction between various antiepileptic drugs (AEDs) and antiviral and antiparasitic agents used to treat infections caused by SARS-CoV-2 pathogen and recommendations for their compatibility. In this review, the summary table shows the interactions of most AEDs used with such drugs as atazanavir, darunavir/cobicistat, lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, nitazoxanide, ribavarin, tocilizumab and oseltamivir. Of the broad-spectrum AEDs, levetiracetam therapy alone is the safest for the patient with epilepsy if there is a  need to treat a severe viral infection, such as COVID-19. It is not advisable to use a combination of vigabatrin with glucocorticoids due to the risk of SUDEP (Sudden Unexpected Death in Epilepsy). Such AEDs as vigabatrin, gabapentin, retigabine and pregabalin are also without adverse interactions with antiviral agents, but the range of their use is significantly limited.

Keywords: epilepsy, anti-epileptic drugs (AEDs), antiviral drugs, COVID-19.

For citation: Kholin A.A., Zavadenko N.N., Kholina E.A. et al. Drug-drug interaction of anti-epileptic drugs and antiviral agents for the treatment of COVID-19: is it necessary to correct antiepileptic therapy? RMJ. 2020;9:13–17.



Pages 18-22. «Коронавирусный синдром»: профилактика психотравмы, вызванной COVID-19. Соловьева Н.В., Макарова Е.В., Кичук И.В.

Summary:

“Сoronavirus syndromе”: prevention of phsychotrauma caused by COVID-19

N.V. Solovieva1, E.V. Makarova1,2, I.V. Kichuk3


1Personilized Psychiatry JSC, Moscow

2National Medical Research Center of Rehabilitation and Resort Medicine, Moscow

3Pirogov Russian National Research Medical University, Moscow


COVID-19 (COronaVIrus Disease 2019) is a new viral infection characterized by rapid spread, high mortality rate, significant social and economic consequences that destroy the usual way of life. Coronavirus syndrome is a mental disorder presenting itself a response to the COVID-19 pandemic. Presumably, the coronavirus syndrome will affect up to 10% of the population involved in the pandemic, mainly people who have been exposed to a combination of psychosocial and biological factors of stress vulnerability. The article discusses predisposing factors and clinical manifestations of coronavirus syndrome. The risk groups of developing coronavirus syndrome are medical workers who provide care to patients with COVID-19; patients who have suffered a severe disease form, lost relatives and friends, as well as those who have suffered extensive financial losses and lost their jobs. The authors consider treatment methods for coronavirus syndrome: psychotherapy (cognitive behavioural therapy with narrative and exposure methods) and pharmacotherapy, which should be aimed at relieving anxiety, restoring sleep, treating depression and other mental disorders. The a uthors also emphasize that timely psychotherapy and pharmacotherapy of the coronavirus syndrome is very important since it is assumed that this syndrome will reduce the work productivity of the population at a time when it will be extremely necessary for economic recovery.

Keywords: COVID-19, post-traumatic stress disorder, psychotherapy, pharmacotherapy, fabomotizol, anxiolytic.

For citation: Solovieva N.V., Makarova E.V., Kichuk I.V. “Coronavirus syndromе”: prevention of phsychotrauma caused by COVID-19. RMJ. 2020;9:18–22.

Pages 2-6. Коронавирусная болезнь COVID-19: неиспользованные возможности терапии. Громов А.А., Кручинина М.В., Рабко А.В.

Summary:

Coronavirus disease CIVID-19 - unused therapy opportunities

A.A. Gromov 1,2, M.V. Kruchinina 1, A.V. Rabko 1,2

Research Institute of Therapy and Preventive Medicine - a branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk

LLC Center for the prevention of thrombosis, Novosibirsk

High mortality and the enormous socio-economic consequences of the COVID-19 virus epidemic require the immediate development of effective treatment methods. The main complication of coronovirus infection, leading to the development of a fatal outcome, is pneumonia, respiratory and multiple organ failure, which develop in some patients with COVID-19 infection.

An analysis of the clinical, laboratory and pathoanatomical picture of the SARS-CoV-2 virus lesion according to the literature suggests that there are disturbances in the microcirculation and oxygen transportation, erythrocyte hemolysis, intraalveolar fibrinogenesis and microthrombogenesis in the pathogenesis of patients, which fits into the picture of chronic hemolytic microtrombovascular syndrome of second and second intravascular coagulation (chronic DIC).

The prevention of these processes, preventive and early therapy, the combined use of anticoagulants, antiplatelet agents of the erythrocyte series, membrane-stabilizing drugs and, possibly, mild thrombolytic drugs for outpatient use, according to the authors, can prevent the development of life-threatening complications and reduce mortality of patients COVID-19.

Early prophylactic therapy with anticoagulants, antiplatelet agents and membrane-stabilizing drugs, an early treatment regimen for pneumonia with outpatient thrombolytic drugs and anticoagulants are proposed. To prevent hemorrhagic complications, two schemes for identifying risk groups for hemorrhagic complications and the use of thrombolytic therapy in these patients in lower doses have been proposed.

Keywords: SARS-CoV-2, COVID-19, microthrombosis, microcirculatory disorders, anticoagulant therapy, antiplatelet agents, red blood cells

For citation: Gromov A.A., Kruchinina M.V., Rabko A.V. COVID-19: therapy possibilities in reserve. RMJ. 2020;9:2–6.




Pages 24-30. Применение препарата Тималин® при заболеваниях органов дыхания. Перспективы использования при COVID-19. Хавинсон В.Х., Кузник Б.И., Стуров В.Г., Гладкий П.А.

Summary:

Thymalin use for respiratory diseases. Application potential in COVID-19

V.Kh. Khavison1,2, B.I. Kuznik3, V.G. Sturov4, P.A. Gladkii4


1St. Petersburg Institute of Bioregulation and Gerontology, Saint-Petersburg 

2Pavlov Institute of Physiology of the Russian Academy of Sciences, Saint-Petersburg

3Chita State Medical Academy, Chita

4Novosibirsk State University, Novosibirsk


Thymalin® (thymus extract) is aimed at correction of cellular and humoral immunity and hemostasis system. This medication has a significant antioxidant effect, stimulates phagocytosis, regeneration processes and improves cellular metabolism processes. During experiment, it prevents the atherosclerosis development in animals on an atherogenic diet. This medication is a geroprotector that can increase animal life expectancy when administered systematically. The use of this drug in respiratory diseases (acute pneumonia, chronic obstructive bronchitis, a combination of obstructive chronic bronchitis with chronic pneumonia, lung abscess, bronchial asthma, and etc.) is accompanied by immunogram normalization, a decrease of the pro-inflammatory cytokines level, which should prevent the cytokine storm syndromes. At the same time, the state of the hemostatic system and inflammatory acute-phase proteins is normalized. When using Thymalin®, the frequency of complications, the process transition to a chronic form and the period of inpatient stay decreased. Great clinical results in respiratory diseases were obtained when Thymalin® was co-administered with heparin. We consider it promising to study Thymalin® efficacy and safety in the treatment of patients with COVID-19.

Keywords: thymus extract, Thymalin, heparin, immunity, hemostasis, inflammatory acute-phase proteins, pneumonia, respiratory distress syndrome, COVID-19.

For citation: Khavison V.Kh., Kuznik B.I., Sturov V.G., Gladkii P.A. Thymalin use for respiratory diseases. Application potential in COVID-19. RMJ. 2020;9:24–30.



Pages 32-38. О перспективах использования витамина D и других микронутриентов в профилактике и терапии COVID-19. Громова О.А., Торшин И.Ю., Малявская С.И., Лапочкина Н.П.

Summary:

About the prospects of using vitamin D and other micronutrients in the prevention and therapy of COVID-19

O.A. Gromova1,2, I.Yu. Torshin1,2, S.I. Malyavskaia3, N.P. Lapochkina4


1Computer Science and Control of the Russian Academy of Sciences, Moscow

2Lomonosov Moscow State University, Moscow

3Northern State Medical University, Arkhangelsk

4Ivanovo State Medical Academy, Ivanovo 

Vitamin D deficiency, which occurs in 80% of Russians, is associated with impaired functioning of the innate and acquired immunity and an increased risk of viral and bacterial diseases. In the setting of vitamin D deficiency, chronic inflammation develops in a patient of any age, which significantly reduces the body’s resistance to bacterial and viral diseases. Innate antiviral immune bolstering is the most important direction of the new COVID-19 prevention among the general population. Given the biological role of vitamin D in maintaining antiviral immunity and the significant prevalence of vitamin D deficiency, its compensation is a necessary component for the prevention of new COVID-19. This review presents the systematic analysis results of the texts of 20,600 publications on coronavirus infections, conducted by artificial intelligence methods based on the topological theory of recognition. There  are two main directions for improving the efficacy of COVID-19 therapy and prevention: reducing the effects of the so-called cytokine storm syndrome and compensating of the patient’s chronic comorbid pathologies. Vitamin D is essential for maintaining the levels and activity of interferon-dependent proteins involved in antiviral defense, reducing the effects of the cytokine storm syndrome and compensating of comorbid pathologies.

Keywords: COVID-19, RNA viruses, micronutrients, vitamin D, SARS-CoV-2, cytokine storm syndrome, immunity, prevention.

For citation: Gromova O.A., Torshin I.Yu., Malyavskaia S.I., Lapochkina N.P. About the prospects of using vitamin D and other micronutrients in the prevention and therapy of COVID-19. RMJ. 2020;9:32–38.

Pages 39-44. Липосомальный лактоферрин как потенциальное средство профилактики и лечения COVID-19. Санмигель Г.С., Кочергина Ю., Альборс А., Диаз Е., Ороваль М., Уэсо Г., Серрано Х.М.

Summary:

Liposomal Lactoferrin as Potential Preventative and Cure for COVID-19

Gabriel Serrano Sanmiguel1, I. Kochergina1, A. Albors2, E. Diaz3, M. Oroval3, G. Hueso3, J.M. Serrano3


1Dr. Serrano Dermatology Clinic, Valencia, Spain

2Medical Department of Sesderma Laboratories, Valencia, Spain

3Research Department of Sesderma Laboratories, Valencia, Spain

Aim: this study is aimed at evaluating the efficacy of bovine liposomal lactoferrin (LLF) for the treatment of COVID-19 on outpatient basis.

Patients and Methods: a prospective observational study was performed in 75 patients with typical symptoms of COVID-19 who tested positive to IgM/IgG rapid test. Patients were isolated and treated at home using remote systems, reviewed twice a day for 10 days, and followed up to 1 month. A liposomal bovine lactoferrin (LLF) nutritional syrup food supplement (32 mg of LF / 10 ml plus 12 mg of vitamin C) was administered orally in 4 to 6 doses per day for 10 days. In addition, a zinc solution was administered at the dose of 10 mg / 10 ml twice or three times a day. A control group of 12 patients who took only LLF was included. All family members in contact with patients (256 persons) were also treated with half of this dose.

Results: the most frequent symptoms in our patients were a very heavy sensation of tiredness or weakness (95%), alteration in the perception of smelling and taste (88%), cough (83%) and muscular pain (67%). Oral treatment with LLF and LLF + zinc solution allowed for significant improvement in 100% of patients within the first 4–5 days. Same treatment at lower dose prevented the disease in healthy persons directly related with the affected patients.

Conclusion: LF possess antiviral, immunomodulatory and anti-inflammatory effects which might be important for the treatment of COVID-19 infection. The authors concluded that there is a potential use of LLF for the prevention and treatment of COVID-19.

Keywords: COVID-19, liposomal bovine lactoferrin, viral infection, respiratory tract infection, prevention.

For citation: Serrano G., Kochergina I., Albors A. et al. Liposomal Lactoferrin as Potential Preventative and Cure for COVID-19. RMJ. 2020;9:39–44 (translation into Russian).

Pages 46-50. Новые возможности выбора ингаляционного устройства для пациентов с бронхиальной астмой и хронической обструктивной болезнью легких. Архипов В.В.

Summary:

New options for choosing an inhalation device for patients with asthma and chronic obstructive pulmonary disease

V.V. Arkhipov


Russian Medical Academy of Continuous Professional Education, Moscow


The variety of drug delivery for the treatment of asthma and chronic obstructive pulmonary disease (COPD) allows using the differentiated approach when choosing an inhaler for each patient. The review considers various types of inhalers and the characteristics of their use in clinical practice. Dry-powder inhalers are a good alternative for patients who are unable to accurately synchronize the activation of a pressurized metered dose inhaler (pMDI), however, most dry-powder inhalers require a relatively high-volume flow rate on inhalation, commonly at least 60 L/min. In clinical practice, it is not possible to measure the inspiratory flow rate in each patient. However, it is possible to distinguish the types of patients who commonly have insufficient inspiration flow rate. Thus, the efficacy of dry-powder inhalers decreases in children aged 6 to 11 years and elderly patients wit h COPD and asthma. In these patient cohorts, it may be more preferable to use Symbicort® Rapihaler — pMDI that contains the same active components as the widely used Symbicort® Turbuhaler®.

Keywords: chronic obstructive pulmonary disease, bronchial asthma, Symbicort, Turbuhaler, Rapihaler, dry-powder inhaler, pressurized metered dose inhaler.

For citation: Arkhipov V.V. New options for choosing an inhalation device for patients with asthma and chronic obstructive pulmonary disease. RMJ. 2020;9:46–50.

Pages 51-58. Ревматоидный артрит: роль врача общей практики в улучшении исходов заболевания. Чичасова Н.В., Лила  А.М., Верткин  А.Л.

Summary:

Rheumatoid arthritis: the role of a general practitioner in improving disease outcomes

N.V. Chichasova1,2, A.M. Lila1,2, A.L. Vertkin3

1Research Institute of Rheumatology named after V.A. Nasonova, Moscow

2Russian Medical Academy of Continuous Professional Education, Moscow

3A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow

The article discusses the role of a primary care physician (therapist) in improving the immediate and long-term outcomes of rheumatoid arthritis (RA). 2010 Rheumatoid Arthritis Classification Criteria, created for early diagnosis of the disease are presented in this aticle. These classification criteria describe the RA pathogenetic stages from the phase of autoimmune disorders induction to the clinical stage. According to the National Guidelines on the RA stages diagnosis for general practitioners, there are simplified criteria for early RA diagnosis, in the presence of which the patient should immediately be referred to a rheumatologist. The RA onset variants and recommendations for the necessary laboratory and instrumental examination of a patient with detected arthritis are also given.  The European League Against Rheumatism presents the arthralgia definition suspected of developing RA, which directs the general practitioners to identify RA in patients at a very early (preclinical) stage. It also brings up the principles of RA therapy, the place of symptomatic and baseline therapy and the need for early prescription of adequate therapy to improve the diseases outcomes. At present, the possibilities of methotrexate as an anchor drug in the RA treatment are being discussed: the conditions necessary to achieve the maximum and long-term methotrexate effect by using the subcutaneous form of the drug and the role of the general practitioner in conducting controlled treatment of patients with RA. Recommendations for the prevention and treatment of adverse reactions during the methotrexate use, for screening during planning the prescription of genetically engineered biological drugs and Janus kinase inhibitors are presented. The article also discusses the infeasibility  concerning the unjustified discontinuation of baseline treatment.

Keywords: rheumatoid arthritis, diagnostics, treatment tactics, methotrexate, efficacy, safety.

For citation: Chichasova N.V., Lila A.M., Vertkin A.L. Rheumatoid arthritis: the role of a general practitioner in improving disease outcomes. RMJ. 2020;9:51–58.



Pages 59-64. Терапия железодефицитной анемии в гериатрической практике. Кропова О.Е., Шиндина Т.С., Максимов  М.Л., Галявич  А.С., Александрова Е.Б.

Summary:

Therapy of iron-deficiency anemia in geriatric practice

O.E. Kropova1, T.S. Shindina1, M.L. Maximov2,3, A.S. Galyavich4, E.B. Alexandrova1

1Outpatient Clinic No. 5, Moscow

2Kazan State Medical University, the branch of the Russian Medical Academy of Continuous Professional Education, Kazan

3Pirogov Russian National Research Medical University, Moscow

4Kazan State Medical University, Kazan 

The review examines the causes, pathogenesis, as well as issues of diagnosis and correction of iron-deficiency anemia (IDA) in gerontological practice. IDA may have the pluricausal origin in patients of elderly and senile age. Systemic hypoxia caused by anemia worsens the course of concomitant diseases and affects life expectancy. Anemia is an independent factor of adverse prognosis in patients with chronic heart failure (CHF), while up to 70% of anemia cases in patients with CHF are iron-deficient. When diagnosing IDA, it is necessary to focus on the hemoglobin concentration, state indicators of red blood cells and iron metabolism in the body. The article describes methods to the IDA treatment in elderly and senile patients, taking into account the pharmacokinetics and pharmacodynamics of bivalent and trivalent iron medications for oral and parenteral administration. It is necessary to give preference to medications based on the trivalent iron(III)-hydroxide polymalt ose complex for enteral administration to minimize the frequency of adverse reactions. If there is no response to therapy with oral medications, it is indicated to use modern non-dextran intravenous iron medications in case of rapid correlation of IDA or iron deficiency before surgery.

Keywords: iron metabolism, iron-deficiency anemia, bivalent iron, trivalent iron, gerontology, anemia treatment, rational pharmacotherapy, polypragmasia, chronic heart failure, pharmacotherapy safety.

For citation: Kropova O.E., Shindina T.S., Maximov M.L. et al. Therapy of iron-deficiency anemia in geriatric practice. RMJ. 2020;9:59–64.



Pages 65-70. Современные подходы к лечению острых и хронических болей у пациентов с заболеваниями опорно-двигательного аппарата: фокус на безопасность фармакотерапии. Чичасова Н.В., Лила А.М.

Summary:

Modern methods to the treatment of acute and chronic pain in patients with musculoskeletal disorders: the focus on the pharmacotherapy safety

N.V. Chichasova1,2, A.M. Lila1,2

1Research Institute of Rheumatology named after V.A. Nasonova, Moscow

2Russian Medical Academy of Continuous Professional Education, Moscow

All disorders of the musculoskeletal system are characterized by the development of chronic pain syndrome. The most common cause is the presence of chronic inflammation of the synovial membrane. The first-line means for the treatment of chronic joint pathology are commonly non-steroidal anti-inflammatory drugs (NSAIDs). They are also used to relieve acute pain. Nimesulide is the only NSAID belonging to the class of arylsulfonamides. This review discusses the possibility of using nimesulide in the treatment of chronic and acute pain in patients with musculoskeletal disorders. The authors analyze the results of foreign and national randomized and open comparative studies on the efficacy and safety of nimesulide in acute and chronic pain in patients with musculoskeletal disorders. Based on the presented data, the researchers conclude that nimesulide has a pronounced anti-inflam matory and analgesic effect with the high rate of its action, and good tolerability, including in patients with NSAID gastropathy, metabolic syndrome and hypertension. The use of nimesulide in the dosage form of gel for external use allows to reach a greater effect when combined with the tablet form. It does not worsen the therapy tolerability, which is especially important for comorbid patients.

Keywords: musculoskeletal disorders, nimesulide, Nise, pharmacodynamics, efficacy, tolerance, comorbidity.

For citation: Chichasova N.V., Lila A.M. Modern methods to the treatment of acute and chronic pain in patients with musculoskeletal disorders: the focus on the pharmacotherapy safety. RMJ. 2020;9:65–70.

Pages 7-12. Острые инфекционные заболевания у детей: превентивные меры и патогенетическая терапия (симпозиум в рамках VI конгресса Евро-Азиатского общества по инфекционным болезням).

Pages 71-76. Фармакотерапия, проверенная временем: от механизмов к клинической эффективности. Максимов М.Л., Малыхина А.И., Шикалева А.А.

Summary:

Time-proved pharmacotherapy: from mechanisms to clinical efficacy

M.L. Maximov1, A.I. Malykhina2, A.A. Shikaleva1

1Kazan State Medical University, the branch of the Russian Medical Academy of Continuous Professional Education, Kazan

2Center of Endosurgery and Lithotripsy (CELT) JSC, Moscow

This review article, based on the significant number of sources, describes the full range of pharmacological effects, the mechanism and aspects of the clinical use of the original national Dimephosphon® (INN: dimethyloxobuthylphosphonilmethylate). Vasoactive and antihypoxic, neuroprotective and cerebroprotective, as well as antioxidant effects of this drug are considered. The article also notes the ability of this non-anticholinesterase organophosphorus compound to normalize cerebrovascular reactivity, reduce vascular tone, improve arterial elasticity, normalize regional blood flow and oxygen-dependent energy metabolism in the structures of the central nervous system. Adding that, this drug can optimize intracellular metabolism of the brain, prevent the reaction of lipid peroxidation and implement the antiacidotic effect by virtue of the intensification of the renal and pulmonary regulation mechanisms of the acid-base state body condition (as one of the most important and strictly stabilized parameters of homeostasis). Dimephosphon® increases organ blood flow and tissue metabolism, and also leads to a decrease in the content of lactic and pyruvic acids in brain tissues. At present, there is a large clinical use of dimethyloxobuthylphosphonilmethylate in acute disorders of cerebral blood flow, postoperative and posttraumatic cerebral disorders, Meniere’s disease and autonomic dysfunction, as well as in cerebrospinal injury.

Keywords: dimephosphone, neuroprotector, cerebroprotector, antioxidant, antihypoxant, vasoprotector, blood flow, vascular tone, metabolism, acid-base condition.

For citation: Maximov M.L., Malykhina A.I., Shikaleva A.A. Time-proved pharmacotherapy: from mechanisms to clinical efficacy. RMJ. 2020;9:71–76.

Pages 77-80. Разработка состава, методики получения и стандартизация лекарственного растительного препарата «Марены красильной сироп». Рыбалко М.В., Куркин  В.А., Шмыгарева А.А., Саньков А.Н.

Summary:

Rubia tinctorum L. syrup — composition development, techniques and standardization of medicinal plant preparation

M.V. Rybalko, V.A. Kurkin, A.A. Shmygareva, A.N. Sankov


Orenburg State Medical University, Orenburg

The aim of the study was to develop composition, techniques and standardization of medicinal plant preparation – Rubia tinctorum L. syrup. The study objects were rhizomes and roots of Rubia tinctorum L. Electronic spectra were measured using Unico 2800 UV spectrophotometer and Vilitek VBS ultrasonic bath. The study compared four extraction methods: maceration, percolation, repercolation, and fractional maceration using ultrasound. The method of fractional maceration with ultrasound proved to be the most effective extraction method for Rubia tinctorum L. raw materials.  For syrup preparation, a spissum extract of Rubia tinctorum L. was used. It was obtained by evaporation of water extraction and sugar syrup (made according to the compendial procedure). The following composition of Rubia tinctorum L. syrup has been developed: spissum extract of Rubia tinctorum L. — 3.5 g; 96.6% alcoh ol — 7.0 g; sugar syrup — 32.25 g. The result of the study was the development of methods for the assay of the anthracene derivatives content on the basis of ruberitrinic acid in the Rubia tinctorum L. spissum extract and syrup by spectrophotometry. The content of anthracene derivatives in the spissum extract of Rubia tinctorum L. was 8.7%±0.002 %, in the syrup — 0.75±0.002 %. During the study, the authors selected a method aimed at obtaining an extract for the manufacturing of Rubia tinctorum L. syrup by fractional maceration with ultrasound. The composition of Rubia tinctorum L. syrup was justified and methods for assay of anthracene derivatives content in the Rubia tinctorum L. spissum extract and syrup on the basis of ruberitrinic acid using spectrophotometry were developed. 

Keywords: Rubia tinctorum L., Rubia tinctorum L., rhizomes and roots, anthracene derivatives, ruberitrinic acid, spectrophotometry, spissum extract, syrup.

For citation: Rybalko M.V., Kurkin V.A., Shmygareva A.A., Sankov A.N. Rubia tinctorum L. syrup — composition development, techniques and standardization of medicinal plant preparation. RMJ. 2020;9:77–80.





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