Vol 94, No 8 (2022)

Cover Page

Full Issue

Editorial

Prospects for personalized Helicobacter pylori eradication therapy. Pro et contra

Simanenkov V.I., Alekseenko S.A.

Abstract

The article is devoted to debatable aspects of Helicobacter pylori eradication therapy. The eradication cancer-preventive effects are considered. A negative comorbidity between H. pylori infection and such diseases as gastroesophageal reflux disease, inflammatory bowel disease and bronchial asthma has been described. The perspectives of populational, individualized and personalized strategies for H. pylori eradication therapy assessment are given. Recommendations for individualized H. pylori eradication strategy implementation in practical healthcare are proposed.

Terapevticheskii arkhiv. 2022;94(8):935-939
pages 935-939 views

GUIDELINES

Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians

Simanenkov V.I., Maev I.V., Tkacheva O.N., Alekseenko S.A., Andreev D., Bakulina N.V., Bakulin I.G., Bordin D.S., Vlasov T.D., Vorobyeva N.M., Grinevich V.B., Gubonina I.V., Drobizhev M.Y., Efremov N.S., Karateev A.E., Kotovskaya Y.V., Kravchuk I., Krivoborodov G.G., Kulchavenya E.V., Lila A.M., Maevskaya M.V., Nekrasova A.S., Poluektova E.A., Popkova T.V., Sablin O.A., Solovyeva O.I., Suvorov A.N., Tarasova G.N., Trukhan D.I., Fedotova A.V.

Abstract

This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС).

In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts. Twenty-eight Practical Guidelines for Physicians statements were adopted by the Expert Council using the "delphic" method. Such main groups of epithelial protective drugs as proton pump inhibitors, bismuth drugs and probiotics are discussed in these Guidelines from the positions of evidence-based medicine. The clinical and pharmacological characteristics of such a universal epithelial protector as rebamipide, acting at the preepithelial, epithelial and subepithelial levels, throughout gastrointestinal tract, are presented in detail.

Terapevticheskii arkhiv. 2022;94(8):940-956
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Original articles

The study of microcirculation and tissue metabolism as early diagnostic criteria for the risk of diabetic foot development

Mkrtumyan A.M., Zvenigorodskaya L.A., Shinkin M.V.

Abstract

Aim. To assess the state of the microvasculature, tissue metabolism and its reserve capabilities for the purpose of early intervention for the prevention of diabetic foot syndrome.

Materials and methods. Thirty patients were examined. The patients were divided into three groups depending on the hypoglycemic therapy (metformin, empagliflozin, dapagliflozin). The comparison group consisted of 12 volunteers who did not have carbohydrate metabolism disorders.

Results. It was found: the HbA1c indicator significantly decreased in all three groups; significant dynamics in the state of the microvasculature was not observed in any of the three groups; in all groups, there was an improvement in tissue metabolism, however, in this case, no significant dynamics were observed in any of the 3 groups, which indicates the need for provocative tests.

Conclusion. For this purpose, the authors recommend the method of combined use of laser Doppler flowmetry and laser fluorescence spectroscopy. This technique allows diagnosing the state of the microvasculature and tissue metabolism and its reserve capabilities, using thermal and cold tests.

Terapevticheskii arkhiv. 2022;94(8):957-962
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Composition of oropharyngeal microbiota in patients with COVID-19 of different pneumonia severity

Starikova E.V., Galeeva J.S., Andreev D.N., Sokolov P.S., Fedorov D.E., Manolov A.I., Pavlenko A.V., Klimina K.M., Veselovsky V.A., Zaborovsky A.V., Evdokimov V.V., Andreev N.G., Devkota M.K., Fomenko A.K., Khar'kovskii V.A., Asadulin P.O., Kucher S.A., Cheremushkina A.S., Yanushevich O.O., Maev I.V., Krikheli N.I., Levchenko O.V., Ilina E.N., Govorun V.M.

Abstract

Aim. To identify features of the taxonomic composition of the oropharyngeal microbiota of COVID-19 patients with different disease severity.

Materials and methods. The study group included 156 patients hospitalized with confirmed diagnosis of COVID-19 in the clinical medical center of Yevdokimov Moscow State University of Medicine and Dentistry between April and June 2021. There were 77 patients with mild pneumonia according to CT (CT1) and 79 patients with moderate to severe pneumonia (CT2 and CT3). Oropharyngeal swabs were taken when the patient was admitted to the hospital. Total DNA was isolated from the samples, then V3–V4 regions of the 16s rRNA gene were amplified, followed by sequencing using Illumina HiSeq 2500 platform. DADA2 algorithm was used to obtain amplicon sequence variants (ASV).

Results. When comparing the microbial composition of the oropharynx of the patients with different forms of pneumonia, we have identified ASVs associated with the development of both mild and severe pneumonia outside hospital treatment. Based on the results obtained, ASVs associated with a lower degree of lung damage belong predominantly to the class of Gram-negative Firmicutes (Negativicutes), to various classes of Proteobacteria, as well as to the order Fusobacteria. In turn, ASVs associated with a greater degree of lung damage belong predominantly to Gram-positive classes of Firmicutes – Bacilli and Clostridia. While being hospitalized, patients with severe pneumonia demonstrated negative disease dynamics during treatment significantly more often.

Conclusion. We have observed differences in the taxonomic composition of the oropharyngeal microbiota in patients with different forms of pneumonia developed outside hospital treatment against COVID-19. Such differences might be due to the presumed barrier function of the oropharyngeal microbiota, which reduces the risk of virus titer increase.

Terapevticheskii arkhiv. 2022;94(8):963-972
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Modification of dietary patterns in patients with non-alcoholic steatohepatitis

Sasunova A.N., Goncharov A.A., Morozov S.V., Isakov V.A.

Abstract

Aim. To assess efficacy of dietary patterns’ modification with the use of specialized food in patients with non-alcoholic steatohepatitis (NASH).

Materials and methods. We developed new specialized food (SPP2) based on literature data on the role of dietary patterns in pathogenesis of NASH. It contained ω-3 PUFAs, soluble dietary fiber, phospholipids, α-lipoic acid, coenzyme Q10, L-carnitine, complex of vitamins. Patients with NASH (per EASL guidelines), were invited to participate in the study and were randomly assigned to receive either isocaloric diet (ICD) alone (based on the results of indirect calorimetry – Cosmed, Italy) or isocaloric diet with specialized food (2 portions of SPP2 a day), for 14 days. Repeated examinations of body composition with phase angle analysis (InBody, Republic of Korea) and blood chemistry were performed at baseline (BL) and after 14 days (EOT). The patients were advised to follow usual physical activity during the study. Non-parametric statistics was used to compare BL and EOT characteristics in the groups.

Results. The groups did not differ by age, proportion of females, and baseline characteristics of body composition. Adherence to the diet was 87.5% in the ICD group and 88.2% in the ICD+SPP group (p=0.65). Compliance with the use of SPP was 100%. In the ICD+SPP group significant reduction of body weight was achieved (117.5±30.1 kg initially, vs 114.9±28.8 kg at EOT; p=0.007), whereas in the ICD group it was not statistically significant (106.7±22.1 kg at BL vs 104.0±16.8 kg at EOT, respectively; p=0.07). In contrast to the ICD group, in those who received ICD+SPP significant decrease in cholesterol (5.3±1.3 mmol/L at BL vs 4.6±1.3 mmol/L at EOT; p=0.003), LDL (3.7±1.0 mmol/L vs 3.3±1.0 mmol/L, respectively; p=0.009), alkaline phosphatase (132.6±99.1 vs 112.0±87.0 U/L; p=0.04), GGT (54.5±33.2 vs 37.5±19.7 U/L; p=0.04), insulin resistance index (6.1±3.2 vs 3.2±1.5, respectively; p=0.04) was detected.

Conclusion. Modification of dietary patterns with the use of a specialized food in combination with low-calorie diet allows achieving significant reduction of weight and improve lipid and carbohydrate metabolism, reduce severity of cholestasis in patients with NASH.

Terapevticheskii arkhiv. 2022;94(8):973-978
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Comparative evaluation of the effectiveness of narlaprevir in the composition of interferon and interferon-free treatment regimens for patients with chronic hepatitis C

Grushko I.P., Romanova E.B., Tverdokhlebova T.I., Gapon M.N., Vodyanitskaya S.Y.

Abstract

Aim. Our aim was to give a comparative assessment of the effectiveness of using narlaprevir in combination with pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) and interferon-free mode in patients with chronic hepatitis C (CHC).

Materials and methods. The prospective cohort study included 187 patients infected with genotype 1b of hepatitis C virus. Of these, 107 (the 1st group of patients) received narlaprevir – 200 mg once a day, ritonavir – 100 mg once a day, Peg-IFN-alpha-2a – 180 mkg subcutaneously once a week and ribavirin at a dose depending on body weight (1000–1200 mg per day) for 12 weeks, and then the standart "dual" therapy (Peg-IFN-alpha-2a + ribavirin) was continued until 24 weeks. Patients of the 2nd group (n=80) received antiviral therapy in an interferon-free mode. They received narlaprevir – 200 mg once daily, ritonavir – 100 mg once daily, and daclatasvir – 60 mg once daily for 12 weeks.

Results. With the use of an interferon-containing treatment regimen, a sustained virological response was achieved in 92.4% of previousle untreated patients with CH and in 66.7% patients with "unsuccessful" experience of the previous course of treatment. In 5.6% of cases, there was an early termination of treatment due to the development of adverse events. 80 (100%) patients completed the course of treatment with narlaprevir in the interferon-free mode. Sustained virological response was reached by 75 (90%) patients.

Conclusion. Real clinical practice indicates that the use of narlaprevir in the non-interferon mode is not inferior in efficiency to the interferon-containing treatment regimen and demonstrates a more favorable safety profile.

Terapevticheskii arkhiv. 2022;94(8):979-984
pages 979-984 views

Esophagoprotective therapy in patients with erosive esophagitis

Bakulina N.V., Tikhonov S.V., Topalova Y.G., Ilchishina T.A., Vasiliev R.V.

Abstract

Aim. To evaluate the advantages of using combined therapy of proton-pump inhibitors (PPIs) and esophagoprotector in comparison with basic therapy of PPIs for 4 weeks based on the results of changes in the endoscopic picture.To compare the effectiveness of 4-week PPI therapy and 4-week combination therapy with PPI and esophagoprotector Alfasoxx (sodium hyaluronate, chondroitin sulfate, poloxomer 407) in patients with erosive esophagitis (EE) of any degree according to the Los Angeles Endoscopic Classification.

Materials and methods. 81 patients with EE A–C according to the Los Angeles endoscopic classification (1994) was enrolled in the study on the basis of the clinic of Peter the Great, Mechnikov North-Western State Medical University. By computer randomization, patients were divided into the control group – 40 patients (pantoprazole 40 mg 1 time per day) and the intervention group – 41 patients (pantoprazole 40 mg 1 time per day + Alfasoxx 1 sachet qid). The therapy was carried out for 4 weeks. In all patients before and after therapy, the frequency and severity of the main symptoms of gastroesophageal reflux disease (GERD) were assessed, esophagogastroduodenoscopy was performed.

Results. The advantage of combination therapy over standard PPI monotherapy in patients with EE was revealed. According to the results of the control endoscopy, healing of erosions of the esophageal mucosa was observed in 39 out of 41 (95.1%) patients in the intervention group and 32 out of 39 (82.1%) in the control group. The proportion of patients who showed an improvement in the endoscopic picture before and after treatment for 4 weeks by at least 1 level according to the Los Angeles classification was significantly higher in the comparison group – 41 patients (100%), while in the control group 33 patients (85%); p<0.009. After treatment, the combination therapy group had a lower incidence (p<0.01) and severity of heartburn (p<0.01). The same results are demonstrated by combination therapy regarding the symptom – belching of air: in the study group after treatment, this symptom occurred less frequently (p=0.014), its severity was significantly less than in the control group (p<0.01). There was a statistically significant decrease in the need for on-demand antacid therapy in the study group.

Conclusion. In this study involving 81 patients with erosive GERD, the benefits of combination therapy were demonstrated. The addition of Alfasoxx medical device to PPI therapy increases the clinical and endoscopic efficacy of therapy. This positive effect is associated with the esophagoprotective properties of the drug, based on unique pharmacodynamic characteristics. Combination therapy for GERD is preferred in patients with EE. Studies have shown the expediency of using Alfasoxx in case of insufficient effectiveness of classical acid-suppressive therapy for GERD.

Terapevticheskii arkhiv. 2022;94(8):985-991
pages 985-991 views

Clinical notes

Masks hiding mitochondrial neurogastrointestinal encephalomyopathy. Case report

Maev I.V., Kolmakova E.V., Bardakov S.N., Deev R.V., Krivolapov Y.A., Kotkas I.E., Manushina E.A., Kurbatov S.A., Tsygankova P.G., Emelin A.M., Bakulina N.V.

Abstract

The first documented case of mitochondrial neurogastrointestinal encephalomyopathy was described in 1962 by R. Luft. The variety and am-biguity of the clinical manifestations of the disease complicate its early diagnosis and treatment. The first clinical manifestations of the disease are associated with the pathology of the gastrointestinal tract. Low alertness and insufficient awareness of doctors delays the timely diagnosis of mitochondrial neurogastrointestinal encephalomyopathy. The aim of the work is to increase the alertness and awareness of narrow specialties about the possibility of differential diagnosis of an extremely rare detected disease on the base of our clinical observation.

Terapevticheskii arkhiv. 2022;94(8):992-998
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Reviews

Role of interleukin-1 in human diseases: pharmacotherapy prospects: A review

Nasonov E.L.

Abstract

According to current concepts, human immunoinflammatory diseases (IIDs), depending on the prevailing mechanisms of immunopathogenesis, are divided into two main categories: autoimmune and autoinflammatory. At the same time, both autoimmune and autoinflammatory mechanisms are involved in the pathogenesis of most IIDs, and the complex interaction of these mechanisms is reflected in the polymorphism of clinical presentation, course variants, outcomes and therapy efficacy. It is suggested that in IIDs, overproduction of cytokines of the interleukin (IL)-1 family, which is one of the key regulators of innate immunity, determines the "crossing" between autoinflammation and autoimmunity mechanisms. Currently, anakinra, a recombinant non-glycosylated analog of the IL-1 receptor antagonist that blocks both IL-1b and IL-1a signaling, and canakinumab, a monoclonal antibody to IL-1b, are used in clinical practice to inhibit the pathological effects of IL-1. Analysis of the treatment outcomes with these drugs suggests that IL-1 inhibition should be considered a promising direction of pharmacotherapy of systemic autoinflammatory diseases and critical conditions associated with hyperinflammation in children and adults.

Terapevticheskii arkhiv. 2022;94(8):999-1005
pages 999-1005 views

Rationale for choosing an antibiotic for the treatment of cystitis: recommendations of clinical pharmacologists: A review

Yakovlev S.V., Suvorova M.P.

Abstract

In recent years, the harmonization of domestic and foreign clinical recommendations for the treatment of cystitis has been achieved. Nitrofurans and fosfomycin trometamol are recommended as first line therapy antibiotics, and oral 3rd generation of cephalosporins are recommended as alternative antibiotics; fluoroquinolones are excluded from the recommended medications due to an unfavorable safety profile. The main rationale for inclusion of antibiotics in the recommendations as a first line therapy of cystitis is the level of resistance of uropathogens to antibiotics, primarily Escherichia coli. Stable low level of resistance of E. coli in Russia was noted to nitrofurans and fosfomycin (<5%), higher to cephalosporins. Among nitrofurans, furazidine is characterized by higher activity against E. coli compared to nitrofurantoin. The potassium salt of furazidine in dosage form with magnesium carbonate is preferred, since it is characterized by higher bioavailability and provides a therapeutic level of concentrations in urine above the MIC during the entire dosing period. Due to the global increase in the resistance of uropathogens observed in recent years, experts have begun to pay more and more attention to the ecological safety of antimicrobial therapy in order to minimize the risk of concomitant (collateral) damage, contributing to the selection of multi-drug resistant strains of microorganisms. In the latest WHO document of 2021, experts divided antibiotics into three groups (ACCESS, WATCH, RESERVE) according to the priority of choice. The ACCESS group of drugs for the treatment of cystitis includes nitrofurantoin and furazidine as agents with minimal collateral effect, while fosfomycin trometamol and cephalosporins are listed in the WATCH group. Thus, from the standpoint of ecological safety, WHO experts recommend prescribing nitrofurans in the treatment of cystitis in the first line of therapy.

Terapevticheskii arkhiv. 2022;94(8):1006-1013
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Hyaluronic acid in the treatment of osteoarthritis of various localization: A review

Filatova Y.S., Soloviev I.N.

Abstract

The article discusses the treatment of osteoarthritis (OA), the prevalence of which is high, and according to some forecasts it will increase by 50% in the next 20 years. The authors emphasize the high comorbidity among patients suffering from OA and high cardiovascular and gastrointestinal risks with frequent use of NSAIDs, the volume of consumption of which is constantly increasing. Discussing recommendations for the treatment of patients with OA, the article focuses on the use of hyaluronic acid (HA) preparations in the treatment of OA. The mechanisms of anti-inflammatory and chondroprotective actions of HA in the joint, its effect on cartilage and synovial membrane are discussed. Attention is drawn to the fact that, despite more than 30 years of experience in the effective use of HA preparations in the treatment of OA, this procedure is still a subject of controversy among international professional communities. The article presents data from meta-analyses and systematic reviews confirming the effectiveness of the use of intra-articular management of HA preparations in OA of various localization (knee joints, hip joints, hand joints). In conclusion, the recommendations of the technical expert group established at the International Symposium on Intra-Articular Treatment are given to determine the criteria for the successful administration of HA in OA of various localizations, as well as predictors of success and non-success of therapy with HA drugs. The experts identified indications, contraindications for intra-articular administration of HA preparations, as well as conditions associated with an increased risk of therapy failure. In conclusion, the authors draw conclusions about the importance of using HA preparations for intra-articular administration for the treatment of OA, starting from the early stages, following the recommendations of experts.

Terapevticheskii arkhiv. 2022;94(8):1014-1019
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Modern extemporaneous formulations in the geriatric care management: current opportunities and future challenges. A review

Korol L.A., Egorova S.N., Kudlay D.A., Krasnyuk I.I., Sologova S.S., Korol V.A., Smolyarchuk E.A., Sadkovskii I.A., Mandrik M.A.

Abstract

Age-associated disorders, including cognitive functions, that often occur in geriatric patients, necessitate the use of novel approaches to provide appropriate medical care, pharmacoprophylaxis and pharmacotherapy among them. At the same time, an important objective of the national healthcare system is not only stimulating of pharmaceutical companies and pharmacies to expand the range of medicines intended for elderly patients, but also increasing availability of medicinal products, including the integration of extemporaneous formulations into clinical practice. Presented review considers several features of the regulation of the use of extemporaneous formulations in the treatment of geriatric patients. Examples of prescriptions that are used in Russian medical practice and are of the greatest interest in the treatment of elderly patients are also presented.

Terapevticheskii arkhiv. 2022;94(8):1020-1027
pages 1020-1027 views

Consensuns

Experience of anticipatory therapy with IL-6 receptor inhibitors and perspectives for its use in the evolution of COVID-19

Chulanov V.P., Bakirov B.A., Vezikova N.N., Gorodin V.N., Zhuravleva M.V., Zagrebneva A.I., Ivanov I.G., Lomakin N.V., Lukina G.V., Moysova D.L., Mutovina Z.I.

Abstract

The Advisory Board chaired by the chief specialist in infectious diseases of the Ministry of Health of Russian Federation, Professor V.P. Chulanov was held on June 18, 2022 in Saint Petersburg.

Aim. The main purpose of the Board was following discussion:

  1. the analysis of the real-world data of levilimab as an anticipatory therapy for COVID-19 in hospitalized patients;
  2. the review of the experience and perspectives of levilimab as an anticipatory anti-inflammatory option for outpatient patients who meet defined clinical and laboratory criteria.

Results. The analyzed data on clinical efficacy and safety formed the basis of recommendations proposed by experts for the use of levilimab in the inpatient and outpatient medical care for COVID-19.

Terapevticheskii arkhiv. 2022;94(8):1028-1035
pages 1028-1035 views

History of medicine

Fabulus of the concert for the 100th anniversary of Yevdokimov Moscow State University of Medicine and Dentistry

Pashkov K.A.

Abstract

On the basis of critical analysis of sources the author reveals the role of doctors in opera productions, ballet and art in general. Looking through opera librettos and director's productions the author makes conclusions about characteristic human health problems, treatment methods used and the social status of doctors. About 10 percent of the four hundred opera and ballet productions performed today include doctor characters. These characters differ significantly from each other, depending on the time of creation of the work or the era reflected in the plot.

Terapevticheskii arkhiv. 2022;94(8):1036-1041
pages 1036-1041 views


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