Vol 93, No 8 (2021)

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Pharmacotherapy of inflammatory bowel diseases: efficacy performance and safety management

Bakulin I.G., Skalinskaya M.I., Maev I.V., Skazyvaeva E.V., Zhuravleva M.S., Gaikovaya L.B., Bakulina N.V., Ermakov A.I., Alekseenko E.S., Ivanova K.N., Solovev M.V.


Treatment of inflammatory bowel diseases – IBD (Crohn’s disease, ulcerative colitis) is aimed at achieving clinical, endoscopic and histological remission, minimizing surgical complications, and ensuring a normal quality of life. However, the use of medical treatment is potentially associated with various adverse events, among which infectious complications, malignant neoplasms, as well as myelotoxicity, hepatotoxicity, skin lesions and others. The risk of side effects depends on the type of drug therapy (5-aminosalicylates, thiopurines, biologicals, etc.), the duration of treatment, the presence of extra-intestinal manifestations, etc. The article provides an overview of data on both the effectiveness and frequency of various side effects of the main classes of drugs in IBD, presents methods of investigation which can predict the effectiveness and development of side effects, the implementation of which can be considered as a variant of personalized therapy in IBD.

Terapevticheskii arkhiv. 2021;93(8):841-852
pages 841-852 views

Original articles

Prevalence and prognostic value of gastroenterological manifestations of COVID-19: data from the Russian University Clinic

Ianushevich O.O., Maev I.V., Krikheli N.I., Levchenko O.V., Rogova I.V., Zaborovskii A.V., Andreev D.N., Kebina A.L., Bordin D.S., Bakulin I.G., Bakulina N.V., Andreev N.G., Asadulin P.O., Bagdasarian A.S., Devkota M.K., Evarnitskaia N.R., Krikunova O.V., Kucher S.A., Sokolov F.S., Fomenko A.K., Khar'kovskii V.A., Sharina I.A.


Aim. Assessment of the prevalence and prognostic value of gastroenterological manifestations in patients with COVID-19.

Materials and methods. A single-center retrospective cohort study was carried out. Only cases with laboratory confirmed detection of SARS-CoV-2 virus RNA using polymerase chain reaction in oro-/nasopharyngeal smear samples were subject to analysis. Patients with documented (according to anamnestic data and/or according to examination data during hospitalization) organic pathology of the gastrointestinal tract (GIT) and/or hepatobiliary system, malignant neoplasms of any localization, as well as pregnant patients were excluded from the general register of retrospective data. The final cohort was divided into two groups depending on the presence of gastrointestinal symptoms: COVID-19 with gastrointestinal symptoms (cases) and COVID-19 without gastrointestinal symptoms (control).

Results. The final sample consisted of 3764 patients, including 2108 (56%) women and 1656 (44%) men. The average age of the subjects included in the analysis was 58.0 years (95% confidence interval – CI 48.6–63.0). In the study cohort, gastroenterological manifestations (alone or in combination) were recorded in 885 (23.51%) patients. Calculation of the odds ratio (OR) of unfavorable and lethal outcomes between the analyzed groups showed that the presence of gastroenterological symptoms significantly increases the chances of lethal outcome in a cohort of elderly and senile patients (OR 1.6817, 95% CI 1.0335–2.7364; p=0.0364), determines a higher risk of hospitalization or transfer to the intensive care unit (OR 1.2959, 95% CI 1.0547–1.5922; p=0.0136), development of acute respiratory distress syndrome (OR 1.5952, 95% CI 1.3164–1.9329; p<0.0001), as well as the need for mechanical ventilation (OR 1.2849, 95% CI 1.077–1.5329; p=0.0054).

Conclusion. The present study has demonstrated that gastroenterological symptoms are detected in about one in four patients infected with the SARS-CoV-2 virus and multiply the risk of adverse and life-threatening complications of COVID-19.

Terapevticheskii arkhiv. 2021;93(8):853-861
pages 853-861 views

Clinical and pharmacological approaches to the choice of a drug for a tension-type headache relief

Shikh E.V., Khaytovich E.D., Perkov A.V.


The article goes to describe clinical and pharmacological approaches to choosing a drug with an optimal efficacy/safety profile, providing the necessary analgesic effect in tension-type headache. TRPV1 brain receptors are considered the main action point of the mediator.

Aim. The purpose of this study is a comparative analysis of the pharmacodynamic and pharmacokinetic parameters of ibuprofen and paracetamol as a part of fixed dose combination and as monotherapy in tension – type headaches.

Materials and methods. Comparative dissolution kinetics test; Comparative analysis of pharmacokinetic parameters using the PubMed/MEDLINE database.

Results. The median Tmax of ibuprofen as a part of a fixed-dose combination and as a monotherapy is 75 minutes. The median Tmax of paracetamol is 30 min when taken in a fixed dose combination and 40 min as a monotherapy. In patients who received the fixed dose combination, the concentration of ibuprofen in the blood plasma after 10 minutes – 6.64 μg/ml-1; after 20 minutes – 16.81 μg/ml-1, while when taken in the same dose in as a monotherapy, respectively, 0.58 and 9.00 μg/ml-1. The mean plasma concentrations of paracetamol after 10 and 20 minutes in patients receiving the fixed combination were 5.43 and 14.54 μg/ml-1, respectively, compared with 0.33 and 9.19 μg/ml-1 for paracetamol as monotherapy. dissolution kinetics test of the Paracytolgin: after 5 minutes, 20% of paracetamol passed into the solution in a system with a pH of 1.2; in a system with a pH of 4.5 – 36.4%; in a system with a pH of 6.8 – 33.5%; after 10 minutes, respectively 68.5, 98.0 and 89.6%. After 15 minutes, almost complete dissolution was noted in all systems: 98.5, 98.8 and 100.5%, respectively.

Discussion. The combination of ibuprofen and paracetamol makes it possible to enhance the analgesic effect as a result of additive action by the help of central mechanisms. The fixed dose combination of ibuprofen and paracetamol significantly increases the rate of absorption of paracetamol, which has potential therapeutic benefits in terms of a faster analgesia’s onset.

Conclusion. The fixed dose combination of ibuprofen and paracetamol provides faster and long-term anaesthesia with a comparatively lower dosage of each analgesic.

Terapevticheskii arkhiv. 2021;93(8):862-868
pages 862-868 views

Osteosarcopenia in chronic pancreatitis

Kozlova I.V., Bykova A.P.


Aim. To determine clinical features and some mechanisms of osteosarcopenia development in patients with chronic pancreatitis (CP).

Materials and methods. A case–control study was conducted on the basis of the Saratov State Clinical Hospital 5 in 2015–2018 of patients with CP. In a study of 161 patients with CP included, the control group – 30 healthy individuals. Patients were divided into groups according to the etiology of CP: 79 – with toxic-metabolic CP, 82 – with biliary CP. To determine the risks of low-energy fractures, 154 patients were tested with the “Fracture risk assessment tool” (FRAX). Along with the standard examination, 30 patients with CP dual-energy X-ray absorptiometry was performed. To assess the state of skeletal muscles, body mass index was determined, hand-held dynamometry was performed, and a set of Short Physical Performance Battery (SPPB) tests was used. Along with the assessment of traditional risk factors for osteosarcopenia – gender, age, state of reproductive function in women, body mass index, functional state of the pancreas (pancreas) – the quantitative content of interleukins (IL)-2, 6, 8 in in colonic biopsies was analyzed by enzyme-linked immunosorbent assay (ELISA).

Results. Bone disorders, according to densitometry, was detected in 70.0% of patients with CP, in 13.3% of the control group. Presarcopenia was detected in 62 (38.5%) patients with CP, sarcopenia – in 34 (21.1%), in the control group presarcopenia and sarcopenia were not detected. Sarcopenia was statistically significantly more common in toxic-metabolic CP than in biliary CP (÷2=11.6; p<0.001). Correlations of the lumbar spine T-score and IL-6 (r=-0.29; p=0.03), IL-8 (r=-0.29; p=0.04) were revealed. Correlations between sarcopenia and the concentration of cytokines in the in the colon mucosa in CP were determined (IL-2: r=0.44; p<0.001; IL-6: r=0.48; p<0.001; IL-8: r=0.42; p<0.001).

Conclusion. The development of osteopenia and sarcopenia syndromes in CP is interrelated and associated with both traditional risk factors and an increased concentration of cytokines in the in the colon mucosa.

Terapevticheskii arkhiv. 2021;93(8):869-875
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Risk factors for pancreatitis and pancreatic cancer

Grigor’eva I.N., Efimova O.V.


Aim. To identify and compare the frequency of alcohol consumption, tobacco smoking, levels of main macronutrients, vitamins and mineral elements consumption in patients with acute (AP) and chronic pancreatitis (CP) and pancreatic cancer (PC).

Materials and methods. At the observational clinical cross-sectional uncontrolled case-study 65 patients with AP or CP (group 1) and 45 patients with PC (group 2) were examined. A survey of patients was carried out: questionnaire on tobacco smoking, a frequency questionnaire on alcohol consumption, a questionnaire for assessing the frequency of food consumption.

Results. The frequency of smoking (33.8, 20.0%; p>0.05), alcohol consumption ≥1 times/week during the last year (21.5, 15.6%; p>0.05) did not differ significantly between the two groups. The highest consumption rates of total, vegetable, animal protein, total carbohydrates, refined sugar, animal fat, cholesterol, MUFA, dietary fiber, vitamins (â-carotene, vitamin B1, B2, C, PP), mineral elements (iron, potassium, calcium, magnesium, sodium, phosphorus) and the daily energy content of the diet were determined in PC than in the AP and CP group. Among patients of group 1, deficient intake of fat-soluble vitamin A (93.3, 54.8%; p=0.009) and vitamin E (80.0, 48.4%; p=0.041) was more common in the subgroup of patients with excretory pancreatic insufficiency than without it, and the chance of having hypercholesterolemia was associated with a deficient intake of vitamin E [Ex(B)=3.3, 95% CI 1.5–9.3; p=0.027].

Conclusion. There were no differences in the frequency of smoking and alcohol consumption between patients with AP and CP and PC. The highest indices of the main macronutrients, daily energy content of the diet, micronutrients (except for vitamins A, E) were found in PC than in the group of patients with AP and CP. Among patients with AP and CP with excretory pancreatic insufficiency, a lower intake of fat-soluble vitamins was noted and associations of hypercholesterolemia with deficient intake of vitamin E were obtained.

Terapevticheskii arkhiv. 2021;93(8):875-882
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Diagnostic significance of clinical and laboratory indices in predicting non-alcoholic fatty liver disease during screening studies

Nosov A.E., Zenina M.T., Gorbushina O.Y., Baidina A.S., Vlasova E.M., Alekseev V.B.


Aim. To study the significance of clinical and laboratory non-invasive indexes along with the insulin resistance index when carrying out diagnostic assessment of non-alcoholic fatty liver disease (NAFLD) during screening examinations.

Materials and methods. The study involved 348 employees working at oil-production enterprises. An ultrasound scanning of the liver was carried out to assess the criteria of NAFLD. The following indexes were calculated: fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation products (LAP), and homeostasis model assessment of insulin resistance (HOMA1-IR). The prognostic significance of these indexes in relation to the probability of NAFLD diagnosis based on ultrasound data was studied using single-factor and multi-factor logistic regression models followed by ROC-analysis.

Results. The FLI, HSI, and HOMA1-IR indexes in single-factor logistic regression models showed a high statistical significance when carrying out diagnostic assessment the NAFLD with good model calibration capability. The percentage of correct binary classification regards the presence/absence of NAFLD amounted to 82.4% for FLI, 79.7% for HSI, and 72.7% for HOMA1-IR (p<0.001). According to the ROC-analysis, the area under the curve (AUC) by the NAFLD diagnostic assessment was 0.917 (95% CI 0.889–0.945); 0.880 (95% CI 0.846–0.915) and 0.849 (95% CI 0.764–0.934), respectively. The multi-factor logistic regression model with the inclusion of FLI and HOMA1-IR 72.7% enabled us to achieve the correct binary classification in terms of NAFLD in 84.2% of cases. When it comes to the ROC-analysis, considering the probabilities predicted in the multi-factor logistic model as the test variable and NAFLD in ultrasound examination as the state variable, it was possible to set the value of AUC 0.933 (95% CI 0.882–0.985).

Conclusion. The studied clinical and laboratory indexes (FLI, HSI, HOMA1-IR) have a high diagnostic significance regarding NAFLD diagnosed using ultrasonographic criteria. The application of the proposed two-factor logistics model makes it possible to predict the presence of NAFLD when examining a large number of patients, without involving additional ultrasound diagnostics specialists in order to use medical resources rationally.

Terapevticheskii arkhiv. 2021;93(8):883-889
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Diagnostics and treatment of non-alcoholic fatty liver disease with concomitant asthenic syndrome

Pavlov A.I., Ivolgin A.F., Katenko S.V., Eremin M.N., Molodova A.I., Levchenko O.B., Karakozov A.G.


Aim. Analysis of the effectiveness of therapy for non-alcoholic fatty liver disease (NAFLD) with severe asthenic syndrome.

Materials and methods. In the period from 2017 to 2019, on the basis of the gastroenterology center of the Vishnevsky 3-rd Central Military Clinical Hospital, 247 patients with NAFLD, including those at the stage of steatohepatitis, and severe asthenic syndrome were examined and treated. The main group included 124 patients, the control group – 123 patients. All patients underwent complex laboratory and instrumental diagnostics and neuropsychological research using the subjective asthenia assessment scale (MFI-20). In both groups, domestic drugs were included in the therapy regimen: from the 1st to the 10th day, Heptrong solution 3 ml intramuscularly in the morning; from the 1st to the 60th day – UDCA 250 mg orally, 3 capsules at bedtime, Omega-3 forte 1000 mg, 2 capsules in the morning with meals. In group I patients received additionally – from the 1st to the 10th day intravenous drip Cytoflavin 10 ml + 0.9% NaCl solution 200 ml; pentoxifylline solution 5 ml + 0.9% NaCl solution 200 ml. Then, from the 11th to the 60th day, Cytoflavin inside, 2 tablets 2 times a day. Pentoxifylline inside 400 mg 1 tablet 3 times a day. All patients underwent neuropsychological examination using the subjective asthenia rating scale (MFI-20).

Results. The effectiveness of treatment in patients of both groups was assessed by clinical, laboratory data and neuropsychological studies. In the main group, a significant reduction in asthenic syndrome was achieved against the background of diagnosed NAFLD compared with the control group.

Conclusion. The early inclusion of patients with NAFLD and severe asthenic syndrome in the treatment regimen, in addition to the basic therapy of Cytoflavin, achieved a significantly high therapeutic effect in the form of normalization of the main clinical, laboratory and instrumental parameters, as well as a significant reduction in the manifestations of asthenia.

Terapevticheskii arkhiv. 2021;93(8):890-896
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Efficacy of trimebutine in the treatment of functional gastrointestinal disorders: an observational multicenter study

Andreev D.N., Maev I.V.


Aim. Evaluation of the practice of using trimebutine (tablets, 300 mg, extended release), for the treatment of patients with functional gastrointestinal disorders (FGID) in primary health care.

Materials and methods. A prospective observational multicenter non-interventional study was carried out, which included patients of both sexes aged 18 to 60 years with a verified diagnosis of functional gastrointestinal disorders (functional dyspepsia, irritable bowel syndrome, biliary tract dysfunction, sphincter of Oddi dysfunction, postcholecystectomy syndrome). Trimebutine was prescribed in accordance with the instructions for medical use: orally, 300 mg twice per day for 28 days. The severity of simptoms was evaluated by five-point rating scale.

Results. The study included 4433 patients, the per protocol sample consisted of 3831 people. The proportion of patients with a significant decrease in the severity of abdominal pain after treatment was 74.73% (95% confidence interval – CI 73.32–76.11). At the and of the study a statistically significant decrease in the severity of FGID` simptoms was observed: epigastric pain/burning (mean score at the 1st visit was 1.21 [95% CI 1.18–1.25], at the 2nd visit – 0.22 [95% CI 0.2–0.23]; p<0.001), abdominal pain (1st visit – 2.01 [95% CI 1.98–2.04), 2nd visit – 0.33 [95% CI 0.31–0.35]; p<0.001), biliary pain (1st visit – 1.22 [95% CI 1.18–1.26], 2nd visit – 0.2 [95% CI 0.19–0.22]; p<0.001), postprandial fullness and early satiation (1st visit – 1.29 [95% CI 1.25–1.32], 2nd visit – 0.21 [95% CI 0.19–0.22]; p<0.001), severity of heartburn (1st visit – 0.92 [95% CI 0.88–0.95], 2nd visit – 0.18 [95% CI 0.17–0.20]; p<0.001), belching (1st visit – 1.13 [95% CI 1.09–1.16], 2nd visit – 0.22 [95% CI 0.21–0.24]; p<0.001), as well as abdominal distention (1st visit – 1.99 (95% CI 1, 96, 2.03), 2nd visit – 0.43 [95% CI 0.41–0.45]; p<0.001).

Conclusion. The present prospective observational multicenter non-interventional study has demonstrated that trimebutine is an effective approach to treating FGID.

Terapevticheskii arkhiv. 2021;93(8):897-903
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The use of drug based on technologically processed antibodies to endocannabinoid receptor type 1 in the treatment of obesity in adults: results of a multicenter double blind placebo controlled randomized clinical trial

Demidova T.Y., Krasil’nikova E.I., Vorob’ev S.V., Morugova T.V., Adasheva T.V.


Aim. To evaluate the clinical efficacy and safety of Dietressa at a dose of 6 tablets per day for 24 weeks in the treatment of patients with Class 1 obesity. To compare the clinical efficacy of two treatment regimens (1 tablet 6 times per day and 2 tablets 3 times per day) for 24 weeks in the treatment of patients with Class 1 obesity.

Materials and methods. A clinical trial included 493 patients with Class 1 obesity from 18 to 65 years. The proportion of patients who lose greater than or equal to 5 percent of baseline body weight, an average decrease of body weight, a change in waist circumference, dynamics of the quality of life, and the safety of the therapy were assessed.

Results. A weight decrease was established among patients without regard to the studied regimens of Dietressa (in a daily dose of 6 tablets with a six- or three-time intake). The goals were achieved by 49% [53%] of patients in the first treatment regimen (statistically significant compared to placebo therapy: p=0.04) [р=0.018]), 48% (51%) in the second (p=0.004 [р=0.0004]) and 48% [52%] of patients in the combined Dietressa group (p=0.0007 [р<0.0001]). The average absolute weight loss was -4.4±4.2 [-4.8±4.2] kg in the Dietressa-1 group (p=0.0001 [р<0.0001]) and -4.4±4.4 [-4.7±4.4] kg in the Dietressa-2 group (p<0.0001) [р<0.0001]). Against the background of the conducted therapy mental component was improved on week 4 (p<0.0001) and 24 (p=0.006) as well as parameter of physical health on week 4 (p=0,003) and 12 (p=0,006). Waist circumference significantly decreased every 4 weeks in patients receiving Dietressa (p<0.0001 for three comparisons between weeks). A 6-month course of Dietressa therapy demonstrated a favorable safety profile. The frequency of adverse events had no significant differences between Dietressa and Placebo groups.

Conclusion. The monotherapy with Dietressa is safe, and it leads to at least 5 percent reduction in body weight during 24 weeks of therapy in patients with Class 1 obesity.

Terapevticheskii arkhiv. 2021;93(8):904-915
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A prospective randomized comparative study of the efficacy and safety of a two-week bismuth-based quadrotherapy of Helicobacter pylori infection with the inclusion of the probiotic containing Bifidobacterium longum BB-46 and Enterococcus faecium ENCfa-68

Yakovenko E.P., Strokova T.V., Iakovenko A.V., Ivanov A.N., Soluyanova I.P., Vasilyev N.N.


Aim. To study the efficacy and safety of a two-week bismuth-based quadruple of Helicobacter pylori (Hp) infection with the inclusion of a probiotic Bifiform.

Materials and methods. An open prospective comparative randomized study included 68 Hp-positive patients: 22 with a confirmed diagnosis of peptic ulcer disease, 46 with chronic gastritis, gastroduodenitis and erosions in the pylorobulbar zone. The diagnosis and Hp infection were verified by the results of endoscopic and morphological studies, as well as using the 13C-urease breath test and determination of the Hp antigen in the feces. Depending on the therapy, the patients were randomized into 2 groups: the main group was taken 2 times a day for 14 days omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg + bismuth tripotassium dicitrate 240 mg + Bifiform 2 capsules 2 times a day; control – similar therapy was carried out, but without the inclusion of Bifiform. Repeated testing for Нр was carried out one month after the termination of the course of treatment.

Results. When using bismuth-containing quadruple, a high frequency of Hp eradication was noted, which in the ITT analysis was 86.1 and 68.8% (p>0.05) and in the PP analysis it was 93.9 and 95.7% (p>0.05) in patients of the main and control groups, respectively. Side effects of drug therapy were detected in 16.7 and 43.8% (p<0.05), which was the reason for the early termination of therapy as a result of their development in 5.6 and 28% (p<0.05) in patients of the main and control groups, respectively. The inclusion of the probiotic Bifiform in the eradication triple therapy of Hp infection reduced the frequency of detection of colonic dysbiosis from 27.8 to 3.6% and had a positive effect on the indices of local immunity (increased content of plasma cells in the inflammatory infiltrate and a stable level of secretory immunoglobulin A in coprofiltrate).

Conclusion. A prospective, comparative, randomized study has shown that when using a two-week bismuth-based quadruple the eradication rate exceeds 90%. The inclusion of Bifiform in the eradication scheme dramatically reduces the frequency of adverse events and increases patient compliance, and also maintains the protective factors of the gastrointestinal mucosa at a higher level.

Terapevticheskii arkhiv. 2021;93(8):916-922
pages 916-922 views

Gastroenterological symptoms in COVID-19 patients with mild severity of the disease: opportunities to optimize antidiarrheal therapy

Ardatskaya M.D., Butorova L.I., Kalashnikova M.A., Nugaeva N.R., Ovchinnikov Y.V., Oynotkinova O.S., Pavlov A.I., Plavnik R.G., Sayutina E.V., Topchiy T.В., Trunova S.N.


Background. The novel coronavirus infection COVID-19 can be manifested by damage to the organs of the gastrointestinal tract (GIT). Damage to the gastrointestinal tract by the SARS-CoV-2 virus leads to a violation of the microbial-tissue complex of the mucous membrane of the digestive tract. A common gastroenterological manifestation of COVID-19 is diarrhea.

Aim. Study of the clinical features of gastroenterological disorders and the possibility of optimizing the treatment of diarrheal syndrome in patients with COVID-19 with a mild form of viral infection.

Materials and methods. The observation group consisted of 230 patients with mild COVID-19: K-group (n=115) – with respiratory symptoms, I group (n=115) – with gastrointestinal manifestations in combination and without signs of respiratory damage. In order to compare the effectiveness of treatment of diarrheal syndrome, patients of group I are randomized into 2 subgroups: Ia (n=58) – prebiotic treatment (Zacofalk®) and Ib (n=57) – enterosorbents.

Results. The development of gastrointestinal symptoms with SARS-CoV-2 infection is significantly more often noted in comorbid patients (67%). Gastrointestinal symptoms were dominated by diarrhea (93.9%) and flatulence (76.5%), in 1/3 of patients they were the first manifestos of infection. It was established that in 98.4% of patients of group I (against 42.6% of the K-group) signs of infectious intoxication were detected. In patients with gastrointestinal lesions, an elongation of the febrile period by 9±1.5 days was noted, a later (6 days) verification of the viral etiology of the disease. It was found that in patients of group I, the regression of clinical symptoms, the duration of viral disease, the dynamics of antibody formation, the prognosis for the development of IBS-like disorders in the post-infectious period depended on the treatment. In patients taking (Zacofalk®), these indicators were significantly better.

Conclusion. In mild cases, to reduce the severity of viral intestinal damage, for effective relief of intestinal symptoms, to reduce the risk of IBS-like symptoms, it is advisable to prescribe (Zacofalk®) in an initial dose of 3 tablets per day.

Terapevticheskii arkhiv. 2021;93(8):923-931
pages 923-931 views

Clinical notes

A medicinal liver injury with an immunomodulatory drug of natural origin. Case report

Reznik E.V., Yudin D.V., Gudilova Y.Y., Baikova I.E., Karmanova S.E., Nikitin I.G.


As practice shows, there are many alternative drugs that cause drug damage to the liver. A case of medicinal damage to the liver with an immunomodulatory herbal preparation Immunostimulating collection, which included St. John's wort, Elecampane, Kopeichnik, Echinacea, Licorice, Rosehip, is presented. A 39-year-old patient came to the clinic with complaints of yellowing of the skin, whites of the eyes, heaviness in the epigastrium after eating, lightening of feces, dark urine, sour taste in the mouth, bloating, pruritus, decreased appetite, pronounced general weakness, drowsiness 10 days after you start taking herbal immunostimulant. The diagnosis of drug damage to the liver was made taking into account the history and laboratory parameters, since the patient had negative markers of viral hepatitis and increasing of biochemical blood tests: alanine transferase up to 2800 U/l (norm up to 32 U/L), aspartate transferase up to 1776 U/l (norm up to 31 U/l), total bilirubin up to 577 U/l (norm up to 21 U/l), direct bilirubin up to 116 U/l (norm up to 4.3 U/l), alkaline phosphatase up to 112 U/l (norm up to 98 U/l). After the withdrawal of the immunomodulator and the appointment of therapy, including diet, enzyme replacement therapy, drugs clinical and laboratory manifestations of liver drug damage completely disappeared. This confirms the leading role of the immunoactive drug, which the patient took in the toxic effect on the liver.

Terapevticheskii arkhiv. 2021;93(8):932-935
pages 932-935 views

Chronic intestinal pseudoobstruction: difficulties in diagnosis and treatment. Case report

Khatkov I.E., Tsvirkun V.V., Parfenov A.I., Akhmadullina O.V., Krums L.M., Subbotin V.V., Bykova S.V., Kuzmina T.N., Novikova E.V., Shishin K.V., Khomeriki S.G., Degterev D.A., Lashchenkova Z.P.


The article presents a clinical case of a 23-year-old patient with an extremely severe congenital form of chronic intestinal pseudoobstruction coupled with a neuromyopathy,colon malrotation, malabsorption, bacterial overgrowth syndrome, cholelithiasis and gastrostasis, which excluded bowel transplantation. Long-term treatment in the intensive care unit with combined, mainly parenteral nutrition for 6 months, using antibiotics, prokinetics, intestinal decompression allowed to achieve partial stabilization of the patient’s condition and transfer to home treatment with the continuation of adequate complex therapy.

Terapevticheskii arkhiv. 2021;93(8):936-942
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Celiac crisis in patients with celiac disease. Case report

Babanova A.V., Krums L.M., Bykova S.V., Parfenov A.I., Dudina G.A., Sabelnikova E.A., Khomeriki S.G., Lesko K.A., Dbar S.R.


Celiac crisis (CC) is a rare life-threatening course of celiac disease, observed mainly in children. In adults, CK can be the first manifestation of the disease and, very rarely, a relapse that occurs in patients who do not follow the gluten-free diet (AGD). Triggers can be stress, surgery, childbirth, etc. A clinical observation of CC developed in a 49-year-old patient with previously established latent celiac disease with subtotal villous atrophy, stage Marsh III C is presented. The patient did not comply with AHD. After severe angina, she developed anorexia, diarrhea, emaciation, coagulopathy, bilateral pulmonary embolism, infarction pneumonia, and enterogenic sepsis. As a result of intensive therapy with prednisolone, Fraxiparine, antibiotics, fresh frozen plasma and strict adherence to hypertension, remission of the disease was achieved.

Terapevticheskii arkhiv. 2021;93(8):943-948
pages 943-948 views


Roles of active forms of vitamin D in supporting innate immune systems and in reducing excess inflammation in COVID-19

Gromova O.A., Torshin I.I., Chuchalin A.G., Kozhevnikova E.N., Malyavskaya S.I.


A reduced supply of micronutrient vitamin D leads to a more severe course of coronavirus infection (COVID-19). Vitamin D deficiency is combined with a decrease in innate antiviral immunity and excess of inflammation. Vitamin D supplementation stimulates the synthesis of antibacterial peptides and is important for weakening the cytokine storm, reducing excessive acute and chronic inflammation, and also for compensating for chronic comorbid pathologies. Active forms of vitamin D (alfacalcidol, etc.) are of particular importance for compensating for vitamin D deficiency in elderly patients, endocrine-immune dysfunction, sarcopenia, chronic renal failure (in which the metabolism of vitamin D in the kidneys is disturbed).

Terapevticheskii arkhiv. 2021;93(8):948-953
pages 948-953 views

Obesity as a risk factor for diseases of the digestive system

Andreev D.N., Kucheryavyy Y.A.


Currently, the global prevalence of obesity among the world’s adult population is about 650 million people, which makes it possible to consider this chronic metabolic disease as a non-infectious pandemic of the 21st century. It has been proven that obesity is associated with several gastroenterological diseases, while the mechanisms of these associations are extremely heterogeneous and multifactorial. Hypertrophy and hyperplasia of adipocytes in obesity lead to a change in the profile of adipokine production (a decrease in adiponectin, an increase in leptin), an increase in the production of pro-inflammatory cytokines (interleukin-1, 6, 8, tumor necrosis factor á), C-reactive protein, free fatty acids, as well as active forms of oxygen (superoxide radicals, H2O2). All the above induces the development of chronic slowly progressive inflammation, oxidative stress, and insulin resistance. In addition, peptides secreted by adipocytes (adiponectin, leptin, nesfatin-1 and apelin) can modulate gastrointestinal motility, acting both centrally and peripherally. The qualitative and quantitative changes in the intestinal microbiota observed in obese patients (increased Firmicutes and decreased Bacteroidetes) lead to a decrease in the production of short-chain fatty acids and an increase in the intestinal permeability due to disruption of intercellular tight junctions, which leads to increased translocation of bacteria and endotoxins into the systemic circulation. Numerous studies have demonstrated the association of obesity with diseases of the esophagus (gastroesophageal reflux disease, Barrett’s esophagus, esophageal adenocarcinoma, esophageal motility disorders), stomach (functional dyspepsia, stomach cancer), gallbladder (cholelithiasis, gallbladder cancer), pancreas (acute pancreatitis, pancreatic cancer), liver (non-alcoholic fatty liver disease, hepatocellular carcinoma), intestine (diverticular disease, irritable bowel syndrome, colorectal cancer).

Terapevticheskii arkhiv. 2021;93(8):954-962
pages 954-962 views

Liver cirrosis and complication risk management

Bakulin I.G., Oganezova I.A., Skalinskaya M.I., Skazyvaeva E.V.


Liver cirrhosis (LC) takes the main place in the structure of the pathology of the digestive system in terms of the frequency of mortality, as well as in the development of fatal and poorly controlled complications, which requires the search for effective methods for preventing the progression of the disease and the development of complications. The article provides updated information on the role of the intestinal microbiota, as well as endotoxemia and increased intestinal permeability syndromes in the pathophysiology of LC and its complications. The results of recent meta-analyses of the impact of dysbiotic disorders on the prognosis of the LC and the options for their correction are presented. Understanding of the significance of involvement of gut microbiota in the pathogenesis of LC has become one of the “levers of management” of the risks of complications of LC. In this case, the “liver–gut” axis can be considered to be the leading link to the formation of most of the main complications of LC.

Terapevticheskii arkhiv. 2021;93(8):963-968
pages 963-968 views

The role of visceral hypersensitivity in the pathogenesis of irritable bowel syndrome

Makarova A.A., Ruchkina I.N., Parfenov A.I., Indeykina L.K., Romashkina N.V.


This research includes visceral sensitivity and its mechanisms involved in the development of irritable bowel syndrome. Visceral hypersensitivity occupies the key place. The research has the description of etiological factors that form visceral hypersensitivity and also visceral sensitivity instrumental research methods, based on the use of the balloon dilation. The research also has the schemes of drug therapy for irritable bowel syndrome meanwhile the special attention is paid to the possible use of the sorbed probiotics and psychopharmacological drugs.

Terapevticheskii arkhiv. 2021;93(8):969-974
pages 969-974 views

Is histological remission of ulcerative colitis achievable?

Knyazev O.V., Kagramanova A.V., Khomeriki S.G., Parfenov A.I.


Current conception of deep remission in patients with ulcerative colitis (UC) consists of clinical remission, endoscopic mucosal healing and normalization of laboratory markers. Histological remission should not be used as a primary end point for therapeutic efficacy, but instead should be considered as a marker of deep remission. The main goal of UC treatment should be focused on endoscopic healing of colon mucosa, decrease of inflammation activity, prolonged remission, absence of disease recurrence, and also histologic remission. Nevertheless, the term histologic remission has not yet been fully validated and no histologic indexes have been standardized. We need single unified definition for remission, based on multicentral studies analysis. One of important challenge is restoration of normal colon mucosal and results of multiple studies showed contradictory tests for assessing histologic remission, thus remaining an issue for further discussion.

Terapevticheskii arkhiv. 2021;93(8):975-981
pages 975-981 views

Rational treatment of patients with functional dyspepsia

Kazakov A.S., Zyryanov S.K., Ushkalova E.A., Nasretdinova E.K.


Functional dyspepsia is one of the most common functional disorders of the gastrointestinal tract, which resulted from impaired motor skills, visceral hypersensitivity, increased mucosal permeability, disorders of the autonomic nervous system, etc. There is no specific therapy for this disease, which often leads to the irrational use of various groups of drugs. Drug therapy is recommended only during periods of symptoms. The main options of pharmacotherapy include the use of proton pump inhibitors, phytotherapeutic drugs, eradication therapy of Helicobacter pylori. Against the background of possible motor disorders, prokinetics are also one of the possible treatment options, but cisapride has long been withdrawn from sale due to cardiotoxicity, the use of domperidone and metoclopramide is limited due to side effects, especially with long-term therapy, so currently the only prokinetic that can be used in everyday clinical practice is itopride. In refractory cases, tricyclic antidepressants and psychotherapeutic approaches are another effective treatment option.

Terapevticheskii arkhiv. 2021;93(8):982-985
pages 982-985 views

Combine therapy as a modern approach to treatment of allergic rhinitis

Emelyanov A.V.


Allergic rhinitis (AR) is one the most common allergic diseases affecting from 10 to 40% of the population in different countries, including Russia. AR is a risk factor of bronchial asthma, other upper airway disease and may decrease patient quality of life, their productivity, increase probability of occupational traumatism, depression and anxiety. AR also presents a substantial economic burden. The rationale to use fixed dose combination of intranasal steroids and topical H1 antihistamines includes suboptimal control of symptoms by monotherapy, its complementary pharmacologic activity and the results of clinical trials. This review focused on fixed dose combination of intranasal mometasone furoate and olopataine. Double blind placebo-controlled and open clinical trials have confirmed that this combination decreased severity of nasal and ocular symptoms of seasonal and perennial AR, improved patient quality of life and had a good tolerability. Its efficacy was higher than those of monotherapy. Fast onset of action and sustainable effect on symptoms (during 1 yr) may improve adherence patients to the treatment and control of symptoms of AR.

Terapevticheskii arkhiv. 2021;93(8):986-990
pages 986-990 views

Conference proceedings

Breathing freely is possible! How to help patients with bronchial asthma and polyposis rhinosinusitis?


On June 23–25, under the auspices of the Year of Science and Technology in Russia, the 17th International Interdisciplinary Congress of Allergology and Rhinosinusitis was held in Moscow. The 17th International Interdisciplinary Congress of Allergology and Immunology, where the results of current research, approaches to therapy and prevention of diseases based on modern clinical guidelines were presented. The event included a symposium "Breathe freely – it is possible! How to help patients with bronchial asthma and polyposis rhinosinusitis?" with the participation of leading Russian specialists.

Terapevticheskii arkhiv. 2021;93(8):991-998
pages 991-998 views

History of medicine

Methodical abdominal palpation: the history of the development of the method

Banzelyuk E.N., Borodulin V.I., Pashkov K.A., Topolyanskiy A.V.


Despite the development of instrumental and laboratory methods, objective examination of a patient is an important diagnostic doctor’s tool, especially at the first contact with the patient and in outpatient practice. The physician Frantz Glénard (1848–1920) [France] and russian professors Vasily P. Obraztsov (1851–1920) and Theodor Georg (Fyodor) Hausmann (1868–1944) developed methodical abdominal palpation, which entered clinical practice a little more than a hundred years ago. Their brief biographies and scientific achievements are review, and the contribution of each of them to the creation of the abdomen’s palpation is discussed in the article. For the first time, some aspects of F.O. Hausmann’s biography from archival sources are present and clarify.

Terapevticheskii arkhiv. 2021;93(8):999-1002
pages 999-1002 views

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