Open Controlled Study Research Articles

Presence of Cryptosporidium spp and other enteroparasites with pathogenic potential in hemodialysis patients: an open controlled study.

The World Health Organization (WHO) points out that infection by enteroparasites can affect ~3.5 billion people around the world. Hemodialysis (HD) patients may be more susceptible to infections by opportunistic pathogens due to impaired immune function. We evaluated enteroparasite infection in a sample of HD-patients from two dialysis centers and in a control group. Fecal samples were processed using the Hoffmann-Pons-Janner, Ritchie, Willis, and Rugai techniques. Patients with kidney failure from two dialysis centers undergoing HD for more than 3 months were included. The control group consisted of relatives of the patients without overt CKD. The TaqMan PCR and multiplex real-time PCR were carried out for detection of Cryptosporidium spp. and C. parvum and to differentiate the Entamoeba (E.) histolytica/E. dispar complex, respectively. A total of 97 HD patients and 42 controls were enrolled in the study. Fifty (51.5%) fecal samples from the HD group were positive for enteroparasites, as were 26 (61.9%) from the control group (P = 0.260). S. stercoralis was the single helminth detected and was only present in HD-patients. Coproscopy detected seven positive samples for the E. histolytica/E. dispar complex, three from HD patients and four from controls: by PCR, all samples were positive for the non-pathogenic E. dispar. Safranin-stained fecal smear slides were all negative for Cryptosporidium spp. However, by PCR, amplification for Crypstosporidium spp. was seen in six samples, all from the HD patients. Two of the species were classified as C. hominis by PCR-RFLP. Enteroparasite infection as detected by traditional techniques were not more prevalent in HD patients, but S. stercoralis was only found in these patients. It is noteworthy that Cryptosporidium spp. infection, also affecting only HD patients, could only be detected by molecular biology techniques.

The feasibility of allergen-specific immunotherapy for bronchial asthma in children with polysensitization

Relevance. There is a shortage of studies that would evaluate the effectiveness of allergen immunotherapy (AIT) in children with bronchial asthma (BA) and polysensitization.The aim of the study: to evaluate AIT effectiveness with house dust mite (HDM) allergens in the treatment of BA in children polysensitized to perennial allergens, based on the dynamics of the symptoms and medications score.Materials and methods. The open prospective controlled study included 36 children aged 9,6 [6,9; 12,3] years (from 6 years 1 months to 14 years 3 months) with moderate atopic asthma (21 children (58%) and mild asthma (15 children (42%) and polysensitization to household allergens. Each patient was observed in the study for 4 years: 1 year of preliminary observation and 3 years of sublingual AIT with D. pteronyssinus and D. farinae (Staloral, Stallergenes Greer, France). For each year of observation, asthma symptoms and medications used were assessed, and the combined Score was calculated. To confirm sensitization, a prick test was performed using a standard method with allergens: house dust, D. pteronyssinus, D. farinae, cat, dog, horse, pillow feather (Biomed, Russia).Results. Over 2 years of AIT, the decrease in the symptom and medication Score was 46,9%, and at the end of 3rd year of therapy, 59,8% (р = 0,0001 from baseline). A decrease in the combined Score exceeding 34.9% compared to baseline was noted in all patients in the study.Conclusion. Sublingual AIT with HDM allergens is highly effective in the treatment of asthma in children with domestic polysensitization, in terms of reducing symptoms of the disease, the need for pharmacotherapy and the combined Score of symptoms and medications. A significant positive effect was registered already from the first year of AIT and continues to increase over subsequent years of therapy.

Characteristics of the molecular sensitization profiles in patients with birch pollen allergy and cross-reactive food allergy to PR-10 proteins

BACKGROUND: Birch pollen allergy is widespread and is the main allergic disease in Russia. Cross-reactive food allergy, often found in patients with birch pollen allergy, is an underestimated problem that complicates the course of pollinosis and requires further study to improve the quality of diagnosis and personalized recommendations for such patients. AIM: To study the features of the molecular sensitization profile of adult patients with birch pollen allergy and cross-reactive food allergy to PR-10 proteins. MATERIALS AND METHODS: Twenty-five adult patients with confirmed birch pollen allergy, with or without cross-reactive food allergy, were included in an open single-center interventional prospective controlled nonrandomized study. Specific IgE to 112 allergens was determined by multiplex analysis using ImmunoCAP ISAC (ThermoFisher, Sweden). Patients with cross-reactive food allergy completed a validated questionnaire on cross-reactive food allergy symptoms and causative allergens. The primary endpoint of the study was the assessment of the sensitization profile to Bet v 1 and PR-10 proteins (Mal d 1, Ara h 8, Cor a 1.0101, Cor a 1.0401, Act d 8, Api g 1, Pru p 1, and Gly m 4) and the clinical characteristics of the sensitized patients. The secondary endpoint was the comparison of patients with and without cross-reactive food allergy and the evaluation of how sensitization to Bet v 1 and PR-10 homologs can affect clinical manifestations of cross-reactive food allergy in patients. RESULTS: The study included 25 patients aged 18–55 years, from which two comparable groups were formed: group 1 consisted of 13 patients with cross-reactive food allergy symptoms and group 2 (without cross-reactive food allergy) consisted of 12 patients who had never experienced cross-reactive food allergy symptoms. Analysis of the sensitization profile to PR-10 allergens revealed similar patterns in both groups; however, sIgE concentrations to all allergens were significantly higher in group 1. A strong correlation was found between the number of triggering products and total IgE level with PR-10 proteins (r=0.81; p=0.001). The severity of cross-reactive food allergy symptoms correlated with the total level of IgE to PR-10 proteins (r=0.97; p 0.0001). The cutoff level for total sIgE to food PR-10 proteins, equal to 70 ISU-E, allowed us to distinguish patients with only oral allergic syndrome from those with systemic manifestations of cross-reactive food allergy. CONCLUSION: The results of the study are applicable in clinical practice and have prognostic value in determining the severity of cross-reactive food allergy.

Nutritional counselling in adults promoting adherence to the Mediterranean diet as adjuvant in the treatment of major depressive disorder (INDEPT): a randomized open controlled trial study protocol

BackgroundMajor Depressive Disorder (MDD) is a leading cause of disability worldwide. Approximately one-third of patients with MDD do not respond to treatment, and often exhibit elevated inflammation biomarkers, which are associated with worse prognosis. Previous research has linked healthier dietary patterns, such as the Mediterranean Diet (MedDiet), with a lower risk of MDD and symptoms of depression, potentially due to their anti-inflammatory properties. The aim of this study is to evaluate the effectiveness of a nutritional counselling intervention promoting MedDiet to alleviate symptoms of depression in adults recently diagnosed with MDD and presenting with elevated inflammation biomarkers.MethodsThis study is a randomized controlled trial (RCT) that will recruit adults from outpatient clinics, between the ages of 18 and 70 years who have been diagnosed with MDD and are currently receiving treatment with the first prescribed antidepressant, and who exhibit elevated inflammation biomarkers (interleukin-6 and/or C-reactive protein). The control group will receive treatment-as-usual (TAU) only. The primary outcome of the study will be the change in symptoms of depression, as measured by the Beck Depression Inventory 2 (BDI-II), after 12 weeks of intervention. Data analysis will follow an intention-to-treat approach. Secondary outcomes will include changes in inflammation biomarkers, quality of life, adherence to the MedDiet, and cost-effectiveness of nutritional counselling. All outcomes will be assessed at baseline, after the 12-week intervention, and at 6- and 12-months post-baseline.DiscussionThis study will be the first RCT to evaluate the effect of a nutritional intervention with anti-inflammatory properties, as an adjuvant in the treatment of MDD, in individuals diagnosed with MDD and elevated inflammation biomarkers. The results of this study may contribute to the development of more effective and personalized interventions for MDD patients with elevated inflammation biomarkers.

INDICATORS OF ANGIOGENESIS IN PREGNANT WOMEN WITH ARTERIAL HYPERTENSION

The role of the factors of angiogenesis and hormones of pregnancy in pregnant women with hypertension has been studied inadequately and their interaction in such patients is not fully elucidated at present time. Aim. To detect peculiarities of angiogenesis factors and placental hormones in pregnant women with arterial hypertension I and II grades in comparison with results of healthy pregnant women. Materials and methods. Conducting a prospective study of 88 pregnant women, which included: analysis of clinical and anamnestic characteristics and study of the peculiarities of pregnancy in women with chronic hypertension in the first trimester of pregnancy (11-12 weeks). The open prospective controlled study involved 61 pregnant women with chronic arterial hypertension (CAH) 1-2 degree, who were included in the first - the main group. The second control group included 27 healthy pregnant women with physiological pregnancies. Among the angiogenesis indices, the placental growth factor (PlGF), as a pro-angiogenic factor and placental soluble fms-like tyrosine kinase (sFlt-1) was determined as an anti-angiogenic factor, sFlt-1/PlGF ratio was also estimated. Statistical analysis was done by using «STATISTICA® for Windows 6.0» (Stat Soft Inc., № AXXR712D833214FAN5). Results. In the first trimester of pregnancy (11-12 weeks of gestation) in women with CAH is determined by a shift in the balance between pro- and antiangiogenic factors, manifested by statistically significant (p˂0.05) increase in sFlt-1 levels (1700, 9 pg / ml) and a decrease in PlGF levels in3.7 times (9.1 pg / ml) and, accordingly, an increase in the levels of the coefficient K in 5.3 times (sFlt-1 / PlGF) (184.5). The mean values of estradiol, progesterone and chorionic gonadotropin levels in pregnant women with CAH did not differ statistically significantly from those of the control group (p˃0.05). These changes indicate the presence of angiogenesis disorders in pregnant women with chronic hypertension, starting from the first trimester of gestation. Conclusions. Pregnant women with CAH in І trimester have disturbances in balance between pro-angiogenic and anti-angiogenic factors with prevalence of sFlt-1 and reducing of PlGF in serum plasma. Due to such disbalance in pregnant women with CAH of 1 and 2 grade changed cooperation between angiogenesis factors and hormones from direct to inverse. It may lead to development of placental insufficiency in future. That’s why treatment/prophylaxis of it should be administered to pregnant women with CAH in 1 trimester.

Bacterial ligands in the rehabilitation of healthcare workers after COVID-19

Immune defense mechanisms in survivors of the COronaVIrus Disease-19 (COVID-19) and development of their rehabilitation during the pandemic both portray a great scientific and practical interest.The aim of the study was to explore effect of Immunovac-VP-4® (I-VP-4), a vaccine based on bacterial ligands, on the clinical and airway mucosal immunity parameters, along with systemic immune response in a group of medical workers in post-COVID period and in persons who did not develop the disease.Methods. 82 healthcare workers aged from 18 to 65 years were included in a prospective open controlled study. The participants were divided into 4 groups: groups 1 (n = 20) and 2 (n = 27) included those with a history of COVID-19, and groups 3 (n = 18) and 4 (n = 17) included those who did not have the disease. Volunteers in groups 1 and 3 received I-VP-4. Samples of oral fluid, induced sputum, nasopharyngeal and oropharyngeal mucosa scrapings, and venous blood were examined. The levels of total secretory immunoglobulin class A (sIgA) and immunoglobulin G (IgG) were determined by enzyme immunoassay. The phagocytic index (PI) of leukocytes was assessed by flow cytometry.Results. The group of patients who did not have COVID-19 and received IVP-4 (Group 3) showed a tendency to a smaller number of COVID-19 cases, as well as some reduction in days of incapacity for work due to the acute respiratory infections (ARI). The vaccine improved airway mucosal immunity parameters and innate immune response. sIgA increased in the induced sputum (p < 0.005) and unchanged in the oropharyngeal mucosa samples in Group 1. The PI of macrophages in oral fluid doubled (p < 0.05) in this group. At the same time, those parameters decreased in Group 2. In non-infected vaccinated patients (Group 3), a significant increase of PI of blood monocytes was found on the day 90 of the study (p < 0.05). Also, a four-fold increase of PI of macrophages in oral fluid in comparison with Group 4 (p < 0.05) was noted.Conclusion. I-VP-4 improved airway mucosal immunity mechanisms and the systemic immune response. The vaccine can be recommended for rehabilitation programs for COVID-19 survivors and for prevention of ARIs.

Effects of physical rehabilitation on exercise tolerance in post-COVID patients: results of an open controlled trial

The issue of physical rehabilitation of post-COVID patients stays relevant up to this day. Most publications discuss inpatient rehabilitation and only few publications describe outpatient physical rehabilitation of such patients.The aim. Our study was performed to investigate efficacy of outpatient physical rehabilitation of post-COVID patients with lung injury.Methods. This was a prospective non-randomized open controlled study. All patients with COVID-19-associated lung injury were referred to supervised outpatient rehabilitation program. We analyzed 6-minute walk test (6-MWT) results, evaluation of dyspnea using Borg scale and assessment of oxygen saturation (SpO2) using pulse oxymeter before and after walking.Results. The rehabilitation group included 24 patients and the control group included 6 patients. The baseline and demographic findings did not differ significantly between the groups. The 6-minute distance (6-MWD) (р = 0.000018), heat rate at rest (р = 0.017) and after walking (р = 0.017), dyspnea after walking (р = 0.017), oxygen saturation at rest (р = 0.030) and after walking (р = 0.0021) improved significantly in the rehabilitation group and did not change significantly in the control group. At the end of the study, 6-MWD increased by 63.2 ± 36.3 m in the rehabilitation group compared to 14.0 ± 28.8 m in the control group (р = 0,01) and exertional dyspnea score increased by 0 (0 – 1) compared to 1 (1 – 2) in the control group (p = 0.033).Conclusion. Supervised outpatient physical rehabilitation in outpatient settings can accelerate physical recovery in post-COVID patients with lung injury.

The effects of drinking bicarbonate-rich mineral water in calcium oxalate stone formers: an open label prospective randomized controlled study in an Asian cohort.

To examine the effects of drinking bicarbonate-rich mineral water in patients with calcium oxalate stones. This was an open label prospective randomized controlled study comparing the effects of a bicarbonate-rich mineral water versus plain water on urine biochemistry in patients with calcium oxalate stones. The mineral water group were instructed to consume 1.25L of mineral water per day at meal times, and supplemented by plain water. Their total intake was up to 3L/day. Control group consumed only plain water up to 3L/day. 24h urine analyses were performed at baseline, 1, 4, 8 and 12weeks after starting protocol. 58 patients were recruited for the study. 51 patients were included in the final analysis. Baseline data were comparable between the two groups. Over the course of 12weeks, compared to patients drinking plain water, those drinking mineral water had higher overall urinary volume (difference = 644.0ml/24h, 95% CI = (206.7, 1081.3)), higher overall urinary magnesium (difference = 1.894mmol/24h, 95% CI = (1.006, 2.782)), and pH (difference = 0.477, 95% CI = (0.149, 0.804)). However, there was no difference in urinary oxalate and Tiselius index. Mineral water group had net increase of urinary citrate (at each study point compared to baseline) which was sustained until week 12, whereas plain water group showed no significant change. Drinking bicarbonate-rich mineral water in calcium oxalate stone formers increased stone inhibitors such as magnesium, citrate and moderate degree of urinary alkalinization compared to patients drinking plain water, but it did not alter Tiselius index or urinary oxalate after 12weeks.

Indicators of angiogenesis and hormonal profile in pregnant women with chronic hypertension in the first trimester

The role of angiogenesis factors and hormonal profile in pregnant women with arterial hypertension has not been detailed studied, and their interaction in such patients has not been determined at present time.The objective: to determine the features of angiogenesis factors and hormonal profile in pregnant women with arterial hypertension of the 1and 2 grade. Materials and methods. A prospective study was conducted in 88 pregnant women, which included: analysis of clinical and anamnestic characteristics and the study of pregnancy characteristics in women with chronic arterial hypertension (CAH) in the I trimester of pregnancy (11–12 weeks). The open prospective controlled study involved 61 pregnant women with CAH of the 1 and 2 stages which consisted the main group. The control group included 27 healthy pregnant women with physiological pregnancy. Concentrations of human chorionic gonadotropin (hCG), progesterone (PG), estradiol (E) and markers of angiogenesis – placental growth factor (PlGF) as a proangiogenic factor and soluble fms-like tyrosine kinase (sFlt-1) as an antiangiogenic factor were determined in the blood serum of all patients, sFlt-1/PGF ratio was also estimated (K). Statistical analysis was performed using «STATISTICA® for Windows 13.0».Results. In the I trimester of pregnancy in women with CAH, a shift in the balance between pro- and anti-angiogenic factors is determined, which is manifested by a statistically significant (p<0.05) increase sFlt-1 level (1700.9 pg/ml) and a decrease PlGF level in 3.7 times (9.1 pg/ml) and, accordingly, an increase K coefficient (sFlt-1/PlGF) by 5.3 times (184.5). The mean concentrations of E, PG and hCG in pregnant women of the main group did not differ statistically significantly from those in the control group. However, according to the results of the correlation analysis, PlGF and PG indicators have feedback in pregnant women with CAH (r=-0.29; p<0.05). When calculating the correlation of PlGF and hormones, it was found that in pregnant women with CAH there is their growth according to the control group, namely the indicator hCG correlates with PlGF (51.8 units vs. 14.8 units) 3.5 times, E correlates with PlGF (309.7 units vs. 70.0 units) 4.4 times and PG correlates with PlGF (4.8 units vs. 1.0 units) 4.8 times (p<0.001 for all indicators). These changes indicate the presence of angiogenesis disorders in pregnant women with chronic hypertension, starting from the I trimester of gestation.Conclusions. Pregnant women with CAH in the I trimester have disturbances in balance between pro-angiogenic and anti-angiogenic factors with prevalence of sFlt-1 and decrease of PlGF in blood serum. Because of such imbalance in pregnant women with CAH of the 1 and 2 grade, the interaction of angiogenesis factors and hormones changed from direct to inverse. It may lead to the development of placental dysfunction in the future, so treatment and prevention should be provided for the pregnant women with CAH in the I trimester.

The abdominal-transhiatal surgical approach versus the thoracoabdominal surgical approach in Siewert type II adenocarcinoma of the esophagogastric junction: protocol for a multicenter prospective, open, parallel, and randomized controlled trial

BackgroundTo date, Siewert type II adenocarcinoma of the esophagogastric junction (ST-II AEG) can be removed radically utilizing either the abdominal-transhiatal (TH) or the right thoracoabdominal (RTA) approaches. Because of a paucity of high-quality direct evidence, the appropriate surgical approach for ST-II AEG remains debatable. In the present, only several retrospective studies are available, representing ambiguous results. Thus, prospective randomized clinical trials are demanded to compare the survival, oncological outcomes, safety and efficiency and life quality between the TH and RTA approach in patients with resectable AEG of Siewert type II.MethodsA prospective, multicenter, open, randomized, and parallel controlled study named S2AEG will be conducted. Three hundred and twelve patients who match the inclusion criteria but not the exclusion criteria will be participating in the trial and randomly divided into the TH (156) and RTA (156) cohorts. The primary efficacy endpoint is the 3-year disease-free survival (DFS) following the operation. The rate of R0-resection, the number and site of lymph nodes infiltrated and dissected, postoperative complications, hospital days and life quality are the second endpoints.DiscussionThis study is the first prospectively randomized controlled trial aiming to compare the surgical outcomes between TH and RTA approaches in patients with resectable ST-II AEG. It is hypothesized that patients in the TH cohort would harvest equivalent oncological results and survival while maintaining acceptable life quality when compared to patients in the RTA cohort. Our findings will provide high-level clinical evidence for clinical decision-making on the appropriate surgical approach for patients with ST-II AEG. Embarked in November 2019, this research will be completed 3 years after the final participant’s enrolment date.Trial registrationClinical Trial.gov ID: NCT04910789 May 29, 2021. Name: S2AEG.

Тривожно-когнітивні розлади у пацієнтів з метаболічним синдромом: клініко-нейровізуалізаційна діагностика, лікування

Мета дослідження: вивчити когнітивний, психоемоційний стан та нейровізуалізаційні показники головного мозку в пацієнтів середнього віку з хронічними формами цереброваскулярних захворювань на фоні метаболічного синдрому; вивчити клінічну ефективність, безпечність, вплив на когнітивні показники, тривогу вітчизняного препарату Вітаксон® у пацієнтів з хронічними формами цереброваскулярних захворювань на фоні метаболічного синдрому. Матеріали і методи. У відкритому контрольованому дослідженні взяли участь 60 пацієнтів віком від 42 до 61 року (Ме = 52 [Q1 = 54; Q3 = 60]) з метаболічним синдромом. Пацієнтам основної групи (n = 30) до базисної терапії додавався препарат Вітаксон®. У контрольній групі (n = 30) пацієнти отримували лише базисну терапію. Критерієм включення в дослідження була наявність тривожно-когнітивних розладів у пацієнтів з дисциркуляторною енцефалопатією І–ІІ ст. на фоні метаболічного синдрому. Проводили клініко-лабораторне обстеження та нейропсихологічне тестування за шкалами: МоСА; Спілбергера; Бека; таблицями Шульте. За допомогою методу волюметрії на МРТ-сканері Toshiba Vantage Titan 1,5 оцінено стан головного мозку в 41 пацієнта. Проводили кореляційний аналіз показників об’єму кори й білої речовини скроневої й лобної часток та когнітивно-тривожних порушень в пацієнтів з метаболічним синдромом та без нього. Результати. Після 24-денного курсу лікування відбулось покращення когнітивних функцій за шкалою МоСА в обох групах (в основній групі — на 1,5 бали; у контрольній — на 0,5 балів), у групі, у якій пацієнти приймали Вітаксон®, відмінності були вірогідними (р < 0,05). Показники реактивної тривожності за шкалою Спілбергера покращились в основній групі (42,4 ± 3,4 бала до лікування та 24,6 ± 2,8 бала на 24-ту добу), у контрольній відповідні показники суттєво не відрізнялись (41,2 ± 3,2 бала та 39,1 ± 2,1 бала відповідно). Аналіз результатів тестування за таблицями Шульте показав вірогідне зменшення показників виконання завдань після лікування в групі, що приймала Вітаксон® (р < 0,05). Показники депресії за шкалою HADS після лікування покращились в обох групах, але ступеня статистичної вірогідності не було досягнуто. Аналіз волюметричних досліджень показав погіршення когнітивних функцій за шкалою МоСА при зменшенні об’єму кори в лобній і скроневій частках. Визначався кореляційний зв’язок між показниками об’єму кори лобної і скроневої часток і результатами когнітивних функцій за шкалою МоСА. Індекс кореляції r = 0,49 для показників скроневої частки та r = 0,43 — для лобних часток. Модулі коефіцієнтів кореляції були середньої сили. Висновки. У пацієнтів з МС визначалось зменшення об’ємів сірої речовини в скроневих і лобних частках, що корелювало з когнітивним дефіцитом за шкалою МоСА. Ці дані свідчать більшою мірою про змішаний характер когнітивних порушень — судинно-дегенеративний. Проведення волюметричного дослідження в поєднанні з нейропсихологічним дозволяє на стадії помірних когнітивних порушень прогнозувати подальший розвиток захворювання. Наявність позитивного нейротропного ефекту на когнітивно-тривожні прояви та відсутність значимих побічних явищ у препарату Вітаксон® дозволяють рекомендувати його для лікування хронічних форм цереброваскулярних захворювань у пацієнтів з метаболічним синдромом.

КЛИНИЧЕСКИЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ИНФЕКЦИИ COVID-19 У ГОСПИТАЛИЗИРОВАННЫХ ДЕТЕЙ РАЗЛИЧНОГО ВОЗРАСТА

Despite the global prevalence of Coronavirus disease 2019 (COVID-19) and the study of the disease around the world, there are many questions about the clinical course, diagnosis and prevention of new infection. There is even less research on the course of COVID-19 infection in children than in adults. The variability of symptoms in children, their frequency, severity, and prognostic value are not well understood. In order to analyze the nature of the course of COVID-19 in children of different ages, a single-center prospective open continuous controlled study was carried out, which included patients under the age of 18 years, hospitalized for one month (May 2020) with COVID-19 infection at the Urals Scientific and Research Institute for Maternal and Child Care of the Ministry of Healthcare of Russian Federation (Yekaterinburg, Sverdlovsk Oblast, Russia). The study was approved by the local ethics committee. Materials and methods of research: on the basis of the Ural Scientific Research Institute for Maternal and Child Care, 107 children 0–17 years old with mild and moderate forms of COVID-19 infection were examined. More than 70% of admitted patients are infants and preschool children. Results and discussions: the intrafamilial focus became the main source of infection. The most frequent clinical manifestations on admission were cough, pyrexia, catarrhal symptoms; on the 5–6th day, the appearance of gastrointestinal syndrome in the form of diarrhea, nausea, vomiting was noted more often in children under 3 years of age. The asymptomatic course of COVID-19 infection was observed more often in schoolchildren (up to 67% of adolescents 13–17 years old). In patients under 1 year of age, asymptomatic course was noted much less frequently (37.5%). In children under 3 years of age, pneumonia was more often confirmed (up to 33%) and gastrointestinal syndrome in the form of diarrhea, nausea, vomiting (up to 50% of patients under 1 year of age). According to laboratory data, in children under 3 years old, a decrease in erythrocytes, hemoglobin, hematocrit was more often observed, and in schoolchildren and adolescents (7–17 years old) – a decrease in leukocyte counts, lymphopenia. Conclusion: In the analysis of the course of COVID-19 infection in children of different ages, a hypothesis about two variants of clinical manifestations has been put forward. In the first variant, pneumonia with COVID-19 was characterized by persistent, poorly controlled fever, severe symptoms of intoxication, impaired microcirculation, changes in the electrocardiogram, more pronounced changes in indicators of general and biochemical blood tests. In the second variant, pneumonia was tolerated by children more easily, was characterized by less pronounced symptoms of intoxication, inhibited by hyperthermia, but patients had positive PCR tests for SARS-CoV-2 longer. Our study did not establish the relationship between the pneumonia variant and the age and gender of the patients, but there may be a need for further research.

УРОВЕНЬ ГЛИАДОМОРФИНОВ И КАЗОМОРФИНОВ У ДЕТЕЙ С РАССТРОЙСТВАМИ АУТИСТИЧЕСКОГО СПЕКТРА

High frequency of detection of various disorders of the gastrointestinal tract in patients with autism spectrum disorders (ASD) formed the basis of the first attempts to prescribe diet therapy. Despite the fact that diets are not officially included in the complex of therapeutic measures for ASD, the use of gluten-free (GFD) and casein-free diets (CFD) is widespread practice. The aim of the study was to assess the level of gliadomorphins (GM) and casomorphins (CM) in the blood of children with ASD, depending on the eating style and in comparison with healthy peers. Materials and methods of research: a prospective continuous open controlled study with the participation of 230 children aged 3–15 years. The first group included 36 patients with ASD who had been observing GFD for more than 6 months; in addition, 18 children were also on CFD. Boys in the group ware 23 (64%), girls – 13 (36%). The second group included 49 children with ASD who had no dietary restrictions. Boys – 35 (71%), girls – 14 (29%). The third (control) group consisted of 145 apparently healthy children: boys – 83 (57.3%), girls – 62 (42.7%). Determination of CM and GM levels was performed on a Multiskan Go analyzer (Thermo Fisher Scientific, Finland) by enzyme-linked immunosorbent assay using Human Gliadomorphin ELISA Kit and Human Casomorphin ELISA Kit (Hycult Biotech, Netherlands). Results: more boys than girls were included in all study groups; no statistically significant differences in gender distribution were found (p=0.2). The median age values in the 1st group was 6.5 [4.0; 8.0] (3; 15) years, in the 2nd – 6.0 [4.0; 7.0] (3; 15) years, in the 3rd – 8.0 [6.0; 11.0] (3; 15) years, the differences are statistically significant (p=0.0001). The content of GM in the blood serum of children with ASD, adhering to GFD, is statistically significantly lower by 2.6 times compared with children not adhering to diet therapy – 0.61 [0.41; 0.80] (0.12; 6.42) and 1.6 [0.70; 2.38] (0.18; 4.03) ng/ml (p<0.001) and does not differ statistically significantly from the level in the control group – 0.41 ng/ml [0.31; 0.72] (0.14; 4.18) ng/ml (p>0.005). The content of CM in the blood serum of children with ASD, adhering to CFD and GFD, is also 1.25 times lower than in children not adhering to diet therapy 1.85 [1.04; 2.07] (0.16; 3.83) and 2.34 [2.11; 2.72] (0.93; 3.29) pg/ml (p<0.001) and 1.3 times lower than the level of the control group – 2.45 [2.13; 2.89] (1.22; 26.88) pg/ml (p<0.001). Conclusion: the results obtained confirm the theory/possibility of exorphin intoxication of ASD development, which may be pathogenetically significant for some patients with ASD, which must be taken into account when implementing an individual approach to prescribing GFD, CFD.

МИКРОБИОЛОГИЧЕСКАЯ ХАРАКТЕРИСТИКА ПАТОГЕННОЙ ФЛОРЫ У ДЕТЕЙ С ОСТРЫМ И ХРОНИЧЕСКИМ ПИЕЛОНЕФРИТОМ

The study of dynamically changing antibiotic sensitivity of uropathogenic strains in children with pyelonephritis is of great scientific and practical interest, since the course and outcome of the disease and the success of cure depend on it. Objective of the study: to study the microbial landscape of urine and antimicrobial sensitivity of pathogens in children with acute (AP) and exacerbation of chronic pyelonephritis (CP) for timely correction of empirical antibacterial (AB) therapy. Materials and methods of research: a prospective open non-randomized controlled singlecenter study to study the microbial landscape of urine and antimicrobial sensitivity of pathogens in children with AP and CP was conducted at the Speransky Children's City Clinical Hospital No. 9. Inclusion criteria: compliance with the diagnostic criteria for the onset of AP and CP, age from 1 to 14 years, the possibility of assessing the microbiological spectrum of urine before starting AB therapy, determination in urine cultures of strains producing extended spectrum betalactamases (ESBL) and/or carbapenemases (CP-CRE). Results: 552 results of urine bacteriological tests were analyzed. Bacteriuria was detected in 68,3% (n=376) patients, of which 161 (42,8%) were diagnosed with AP, 215 (57,2%) with CP. The structure of pathogens was dominated by gram-negative flora (53,8–70,8%), among which enterobacteria prevailed (79,5%), the dominant microorganism was E. coli (48%). Gram-positive microflora was represented by Enterococcus faecalis (35%). Among enterobacteriaceae, there was a statistically significant increase (p<0,05) in the number of ESBL and/or CP producers, as well as their associations, from 8,8% in 2016 to 25% in 2019–2020 with a peak increase of up to 31% in 2018. A study of resistograms noted that E. coli retains high levels of sensitivity to amoxicillin/clavulanate, however, since 2019, a high frequency of ceftriaxone-resistant strains has been recorded, and in 2020, the detection rate of resistant strains has increased to cefotaxime of E. coli strains. The highest and most stable activity against E. coli ESBL was shown by meropenem and ertapenem. There is a tendency towards a decrease in the sensitivity of Kl. pneumoniae to amoxicillin/clavuanate, fosfomycin and amikacin. The emergence in 2020 of strains of Enterococcus faecalis resistant to amoxicillin/clavuanate and a tendency to a decrease in sensitivity to gentamicin while maintaining a high sensitivity to amikacin were recorded. Conclusion: the results obtained indicate the importance of monitoring the AB-sensitivity of uropathogenic strains in order to increase the effectiveness of empiric therapy and reduce the prescription of inactive antibacterial drugs in children with AP and CP.

Fixed combination of ramipril and indapamide in patients with hypertension and non-alcoholic fatty liver disease: focus on the large arteries

Objective.To assess the effect of antihypertensive therapy with ramipril and indapamide on the elasticity of the vascular wall of the large arteries in relation to insulin resistance and chronic low-intensity inflammation in patients with hypertension (HTN) and non-alcoholic fatty liver disease (NAFLD).Design and methods.An open prospective controlled study was conducted: 30 patients with HTN stage I–II in combination with NAFLD (Fatty Liver Index (FLI) > 60) at the age of 45–65 years were included. Washout period was scheduled 5–7 days before the baseline examination, followed by the prescription of one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg), depending on the required dosage (Konsilar-D 24 VERTEX AO, Russia) and were given recommendations on lifestyle changes and weight loss. A clinical examination was carried out, indicators of daily blood pressure (BP) monitoring and central aortic pressure (CAP), pulse wave velocity (PWV), lipid and carbohydrate metabolism, chronic low-intensity inflammation and the severity of insulin resistance before and after treatment were analyzed.Results.After 24-week therapy with a fixed combination of ramipril and indapamide at an average dosage of 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively, 100% of patients with HTN and NAFLD achieved target BP levels. According to 24-hour BP monitoring data, a significant decrease in systolic BP (SBP) and diastolic BP (DBP) was observed, both in the daytime (Δ12 mm Hg, р = 0,0001; Δ5,5 mm Hg, р = 0,0019, respectively), and at night (Δ13,5 mm Hg, р = 0,0006; Δ5,5 mm Hg, р = 0,0054, respectively). In addition, there was a significant decrease in CAP in the daytime (SBPao p = 0,0011, DBPao p = 0,0022) and night hours (SBPao p = 0,0015, DBPao p = 0,00124), and a statistically significant decrease in augmentation index (day p = 0,0460, night p = 0,0182). When evaluating clinical data and bioimpedance measurements, a decrease in waist circumference (p = 0,0000), hip circumference (p = 0,0001), the proportion of subcutaneous (p = 0,0134) and visceral (p = 0,0019) fat was found, which may indicate a decrease in the severity of visceral obesity. Also, during treatment, there is a decrease in the severity of insulin resistance (and the concentration of tumor necrosis factor alpha (TNF-α) (p < 0,0001) and CRP (p = 0,0002) in blood plasma. Finally, fixed combination of ramipril and indapamide led to a significant decrease in vascular stiffness (p = 0,0166) and a decrease in the proportion of patients with PWV paradoxical test (p = 0,0320). Correlation analysis showed that increased stiffness of the large arteries in patients with HTN and NAFLD is closely related to insulin resistance and lipid metabolism. At the same time, after 24-week therapy by a fixed combination of ramipril and indapamide, a decrease in the vascular stiffness in patients with HTN and NAFLD significantly correlated with the TNF-α concentration.Conclusions.A 24-week therapy by the fixed combination of ramipril and indapamide iin patients with HTN and NAFLD is associated with the persistent decrease in BP and CAP, both during the day and at night. There was a decrease in the vascular rigidity in muscular arteries. The treatment and recommendations for changing the lifestyle are associated with the decrease in the severity of abdominal obesity and insulin resistance, as well as the decrease in the severity of low-intensity systemic inflammation in patients with HTN and NAFLD, and a significant correlation was established between a decrease in TNF-α and an increase in the vascular elasticity of muscle and elastic type arteries.

Therapeutic efficacy and safety of Unani formulation in patients of Fasaad-e-tashahhum-e-dam (dyslipidemia): a randomized open standard controlled clinical study

Background: Hyperlipidemia which is interchangeably used with the term dyslipidemia essentially refers to the condition of abnormality of lipid levels measured in the blood typically due to the disorder of lipoprotein metabolism. The objective of this study was to determine the therapeutic effect and safety of newly formulated drug on patients with Fasaad-e-Tashahhum-e-Dam (dyslipidemia) and compare it with the effect of Unani formulation and rosavastatin.Methods: The present study was open randomized controlled clinical study. The study subjects were divided in two groups, one group was given test drug (test group) and another group was given control drug (control group). All the patients who qualified the inclusion criteria were randomly placed in either test or control group.Results: In the present study we observed that both the groups were comparable with respect to age, sex lifestyle, family history and mizaj. We found that both Unani formulated drug and standard drug rosavastatin significantly improves the lipid parameters after the treatment with a p value of (<0.001*).Conclusions: We concluded that the overall effect of the proposed Unani formulated drug was found quite fascinating in the treatment of dyslipidemia. Apart from drug safety, visible improvements were evident in objective parameters like cholesterol, triglyceride and LDL, VLD. However, the present study did not revealed that Unani drug is superior to standard drug instead both the treatments are equally effective on the improvement of lipid profile parameters.

ОПТИМИЗАЦИЯ ПРОТИВОВИРУСНОЙ ТЕРАПИИ НОВОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИИ COVID-19 У ДЕТЕЙ

The aim of the research is to study of the efficacy and safety of VIFERON® drug, rectal suppositories (interferon α-2b) 1,000,000 IU and 3,000,000 IU, and VIFERON®, gel for external and local use (interferon α-2b) 36,000 IU/g , in the complex therapy of a сoronavirus disease 2019 (COVID-19) in children. Materials and methods of research: as part of the open multicenter prospective controlled non-randomized study, 140 patients aged 1 to 17 years with the сoronavirus disease 2019 (COVID-19) were examined, and hospitalized in the infectious diseases hospital (Krasnoyarsk interdistrict clinical hospital № 1) in Krasnoyarsk from 20.04.20 to 1.08.20. Depending on the conducted antiviral therapy, the observed patients were divided into 2 groups: the main (70 people) and control (70 people). Starting from the moment of hospitalization, the main group of patients in the complex therapy received the preparation of interferon (IFN) α-2b with antioxidants (vit E and C), rectal suppositories, and IFNα-2b, gel for external and local use, according to the proposed schemes depending on age; patients of the control group were prescribed Umifenovir (Arbidol®) in age-specific dosages. The criteria of effectiveness of the therapy were the period of treatment of the main clinical symptoms of the disease (cough, nasal congestion, runny nose, sore throat, conjunctivitis, taste and smell impairment, abdominal pain, diarrhea, etc.), elimination of viral antigen in samples from the nasopharynx and feces, product dynamics of IgM and IgG antibodies to SARS-CoV-2 in the blood serum. Results: the clinical efficacy and safety of high dose polytherapy of IFNα-2b with antioxidants, rectal suppositories in combination with IFNα-2b with antioxidants, gel for external and local use in the therapy of COVID-19 in children were confirmed. Since the appointment of therapy in patients of the main group, in comparison with the control group, the time for relief of the main clinical symptoms of COVID-19 has been statistically significantly reduced: nasal congestion – from 7 to 3 days (p=0,0001), sore throat – from 7 to 3 days (p=0,0001), hyperemia in the oropharynx – from 10 to 5 days (p=0,0001), mild cough – from 7 to 5 days (p=0,05), catarrhal conjunctivitis – from 5 to 3 days (p=0,012), smell disorders – from 10 to 4 days (p=0,001) and taste – from 10 to 4 days (p=0,001). The period of complete relief of all clinical symptoms according to the «total score» was statistically significantly reduced from 9 days in the control group to 5 days in the main group (p=0,05). The elimination time of SARS-CoV-2 from the nasopharynx was also statistically significantly reduced by 5 days in the main group of patients (p=0,05). In patients receiving increased doses of IFNα-2b with antioxidants, intestinal sanitation occurred 2,5 times more frequent, statistically significant increase in the level of IgG antibodies to SARS-CoV-2 was detected in comparison with patients of the control group (p=0,05). No adverse events were recorded in the observed patients of both groups. Conclusion: the proven efficacy and safety of combined antiviral therapy with IFNα-2b with antioxidants, rectal suppositories in combination with IFNα-2b with antioxidants, gel for external and local use, are the basis for its widespread implementation into pediatric practice for the treatment of patients with сoronavirus disease 2019 COVID-19.

НЕИНВАЗИВНЫЕ МАРКЕРЫ ФИБРОГЕНЕЗА У ДЕТЕЙ С ОСТРЫМ И ХРОНИЧЕСКИМ ВТОРИЧНЫМ ПИЕЛОНЕФРИТОМ

Objective of the study: to study the clinical significance of the determination of angiotensin 2 (Ang II) and transforming growth factor β1 (TGF-β1) in urine of children with acute and chronic secondary pyelonephritis (PN) for increasing the efficiency of diagnosis of the disease. Materials and methods of research: a prospective open non-randomized controlled longitudinal single-center study was carried out in the Speransky City Children’s Hospital № 9 from January 10, 2015 to June 2020 to study the sensitivity and specificity of the tests under study. 60 children from 1 to 15 years old with acute and chronic secondary PN were examined. Children were divided into 2 groups: 1st – 30 patients with the onset of acute PN, 2nd – 30 patients with recurrent chronic secondary PN. The control group consisted of 20 apparently healthy children. In the 1st group of patients, girls predominated (24 children, 80%), the median age was 7 [3; 9] years, the median duration of followup is 41 [8; 45] months from the onset of the disease. In the 2nd group girls also predominated – 23 (77%), the median age – 8 [5; 11] years, the median duration of the disease at the time of inclusion in the study was 5 [3; 9] years. Most children were diagnosed with vesicoureteral reflux (VUR): grade I–II – in 18 (60%) and grade II–III – in 7 (23%). Incomplete renal doubling was detected in 4 (14%) patients, complete – in one (3%). The control group mainly consisted of girls – 16 (80%), the median age – 5,5 [3,25; 8,75] years. All patients underwent a study of general clinical and biochemical blood test, general analysis of urine, determination in a single morning portion of urine by enzyme immunoassay method according to ELISA TGF-β1 and Ang II. To standardize the level of TGF-β1 and Ang II in the urine, the level of creatinine in each portion of urine was determined and the results were converted to 1 mg of creatinine. Instrumental examination included ultrasound of the kidneys and bladder before and after micturition. Static nephroscintigraphy was performed 6 months after the onset of the disease or recurrence of chronic secondary PN. Results: it was found that at the onset of acute PN and with relapses of chronic secondary PN, there was an increased urinary excretion of TGF-β1 (p=0,002) and Ang II (p=0,002) when compared with the control group. It was shown that the level of increase in these markers depended on the form of PN. There were statistically significant differences in the urinary excretion of TGF-β1 and Ang II in children with acute PN and exacerbation of chronic secondary PN prior to the initiation of antibiotic therapy (p=0,001 and p=0,001, respectively). Urinary levels of Ang II and TGF-β1 in patients with exacerbation of chronic secondary PN in the first days of the microbial-inflammatory process in the renal parenchyma were by an order of magnitude higher than those in children with the onset of acute PN. A high degree of correlation was revealed between the level of uAng II/Cr and uTGF-β1/Cr (r=0,75, p=0,0001 and r=0,89, p=0,0001, respectively) in the 1st and 2nd groups of children (r=0,86, p=0,0001 and r=0,75, p=0,001, respectively) in the acute phase of the disease before antibiotic therapy with the data obtained during static nephroscintigraphy in the period of remission of the disease. Conclusion: the results indicate the importance of studying the urinary excretion of Ang II/Cr and TGF-β1/Cr as additional diagnostic markers for the identification of patients with a relapse current of PN, as well as to predict the degree of development of sclerotic processes in the renal tissue in children with different forms of PN.

ELECTRO-PHOTONIC EMISSION ANALYSIS IN FUNCTIONALLY HEALTH RESPONDENTS AND PATIENTS WITH NON-COMMUNICABLE DISEASES

The aim: Of this publication is to evaluate the results of EPEA in functionally healthy respondents and patients with NCDs to deepen fundamental knowledge of Systemic Medicine, increase the effectiveness of measures to prevent and treat NCDs by improving their diagnosis and prevention through the introduction of modern science-intensive technologies. Materials and methods: 114 respondents were included in an open non-randomized controlled study. 66 сcomorbid patients (71% - men; median age - 61(43; 80) years) with verified Ischemic Heart Disease: functional class II-III angina pectoris were included in the Main Group. 78 functionally healthy young people (23% - men; median age - 23(20; 30) years) who did not play sports regularly were a Control Group. EPEA was made on a digital software hardware device Bio-Well 2.0 (Bio-Well 2.0, Russia-USA). Results: Significant differences in AEFE indicators in functionally healthy individuals and patients with NCDs were established. Qualitative indicators of AEFE (indicators of area, intensity, energy of emission) were significantly higher in functionally healthy individuals compared to patients with NCDs. Geometric indicators of AEFE (indicators of length of contours and radii of luminescence) were significantly higher in patients with NCDs than in healthy individuals, which confirmed the visually uneven and more complex contour of luminescence of the fingers in them. Conclusions: AEFE parameters have significant differences in functionally healthy individuals and patients with NCDs. AEFE is a fundamentally new promising approach to assessing the level of activity of metabolic processes at the tissue level in living biological systems, including in the normal human body and in patients with NCDs.

Comparison of Image-Guided Iodine-125 Seed Interstitial Brachytherapy and Local Chemotherapy Perfusion in Treatment of Advanced Pancreatic Cancer

Objective To compare the efficacy and safety of iodine-125 seed interstitial brachytherapy and local chemotherapy perfusion in treatment of advanced pancreatic cancer. Methods The present open prospective randomized control study included a total of 165 cases of advanced pancreatic cancer patients who were admitted in our hospital during December 2016 to April 2019. All patients were randomized into two groups with 84 cases in iodine-125 group and 81 cases in chemotherapy perfusion group. Basic clinical characteristics and demographic data were collected. The main outcome was the tumor efficiency. The pain condition was measured by visual analogue scale (VAS) and the Karnofsky score was also measured at different time points, before the treatment, 1 d, 7 d, 14 d, 1 mon, 2 mon and 3 mon after treatment. Serum levels of CEA, CA19-9 and CA50 were measured by immunochemiluminescence. The overall survival was analyzed by K-M curve. Results The ratio of partial remission patients was significantly higher, and the ratio of stable disease (SD)+progressive disease patients was also remarkably lower in iodine-125 group than the chemotherapy perfusion group. The mean VAS scores decreased markedly after treatment and were significantly lower and the mean Karnofsky scores were remarkably higher in iodine-125 group than the chemotherapy perfusion group. The levels of CA19-9 and CA50 were remarkably lower in iodine-125 group, however no significant difference was found for CEA. The survival analysis by K-M curve showed the iodine-125 patients had longer overall survival time than the chemotherapy perfusion group. No infection, pancreatic fistula, biliary fistula, intestinal fistula, gastrointestinal obstruction or radiation enteritis was found in both groups. Conclusion Iodine-125 seed interstitial brachytherapy could achieve better efficacy with no increased side complications than chemotherapy perfusion in advanced pancreatic cancer.