[Use of a combination of the virus-neutralizing monoclonal antibodies casirivimab and imdevimab for mild to moderate COVID-19 in patients at high risk of progression: Results of the non-interventional observational study].

AIM: To evaluate the efficacy and safety of a combination of virus-neutralizing monoclonal antibodies - MAB (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with risk factors in real word settings. MATERIALS AND METHODS: A non-interventional non-comparative observational study with primary prospective data collection included 108 patients with mild to moderate COVID-19 (mean age 61 years), who had risk factors for developing severe disease. All patients (n=108) were treated with a combination of MAB casirivimab and imdevimab intravenous single infusion 1200 mg (600 mg of each component). The efficacy and safety of MAB were assessed at 7, 14, and 28 days after infusion. RESULTS: Efficacy. Indications for hospitalization by day 7 from the moment of MAB administration were in 0.9% (n=1), by day 14 - in 1.9% (n=2), by day 28 - in 0.9% of patients; to stay in the intensive care units by the 7th day - in 4.6% (n=5), by the 14th day - in 0.9% (n=1), by the 28th day - in 0.9% (n=1) patients. During 28 days of follow up, the need for mechanical ventilation and extracorporeal membrane oxygenation was registered in 2/108 (1.8%) patients. There were no deaths directly related to COVID-19 in the assessed cohort of patients. Safety. By the 28th day of the follow up, no adverse effects due to MAB therapy were registered. CONCLUSION: An analysis of the results of a non-interventional observational study summarized in this article showed the high efficacy and safety of virus-neutralizing MAB combination (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with of risk factors for severe COVID-19 in real word settings.

[Efficacy of dupilumab in real practice in the treatment of severe forms of asthma and atopic dermatitis (comparative retrospective study)].

BACKGROUND: Dupilumab, a fully human monoclonal antibody directed against the common α-subunit of interleukin (IL)-4 receptors and blocking signaling from both IL-4 and IL-13, may be recommended for the treatment of moderate to severe atopic dermatitis (AD) and bronchial asthma (BA). AIM: To perform a comparative assessment of the effectiveness of maintenance therapy with dupilumab in patients with severe BA as the main indication for genetically engineered biological drugs and in patients with severe asthma with concomitant severe AD as the indication for targeted therapy. MATERIALS AND METHODS: A 6-month retrospective comparative study was performed at the specialized reference center for allergology and immunology. The study included 115 adult patients of both sexes treated with dupilumab for uncontrolled severe asthma as the main indication for targeted therapy (BA group; n=65) or for a combination of severe uncontrolled asthma and severe AD (BAAD; n=50). Dupilumab was administered subcutaneously for 6 months. The first dose was 600 mg once and then 300 mg Q2W. Evaluation of the effectiveness of dupilumab therapy at 6 months of treatment in both groups included achieving asthma control (ACT, ACQ5), improving pulmonary function test, reducing the risk of exacerbations and the need for systemic glucocorticosteroids (SGCS), improving quality of life (AQLQ), change of biomarkers (FeNO, eosinophil count) and the course of comorbid diseases, including improvement in the AD (SCORAD, EASI) and rhinosinusitis polyposa (SNOT-22). RESULTS AND CONCLUSION: During dupilumab therapy, in a significant proportion of patients, regardless of the presence or absence of other T2-associated diseases (e.g., AD or rhinosinusitis polyposa), an improvement in asthma was demonstrated as early as in the first 6 months of treatment with dupilumab in all recommended domains for assessing the response to targeted therapy: improving asthma control and respiratory function, reducing the frequency of moderate and severe exacerbations associated with the use of SGCS and/or hospitalization, a positive effect on the quality of life and the comorbid diseases, as well as a cumulative reduction in the need for SGCS.

Condition of the Right Heart in Patients With COVID-19­Associated Pneumonia: Follow-Up During Hospitalization.

Aim      Dynamic assessment of the right heart in patients with COVID-19-associated pneumonia of different severity during regression of the systemic inflammatory response (SIR).Material an methods    This single-center prospective study included 46 patients with the novel coronavirus infection COVID-19 and viral pneumonia according to chest multispiral computed tomography (CT). Laboratory and echocardiographic examinations of patients were performed.Results Based on the results of evaluation with the Clinical Condition Scale (CCS-COVID), patients were divided into two groups: group A, patients with a score from 6 to 9 and group B, patients with a score from 10 to 14. The study results of both groups were evaluated twice: on day 10±2.5 from the onset of symptoms (groups A10 and B10, respectively) and again on day 17±1.8 (groups A17 and B17, respectively). Patients of group B10 had more pronounced SIR (C-reactive protein, 111.38±52.5 mg / l) and a larger volume of ground-glass opacity (38.3±9.6 %). At the first stage, higher values of right ventricular global longitudinal strain (RV GLS) were detected in group B10 compared to group A10 (23.2±4.8 % vs. 19.9±3.5 %, р=0.048). During the regression of SIR intensity and the positive dynamics of CT, lower values of Е / А were observed in group B17 (1.0 [0.98; 1.2]) vs. group А17 (1.4 [1.18; 1.5, p=0.015), and е' / a' in group B17 (0.66 [0.58; 0.85]) vs. 0.95 [0.79; 1.12] in group B17 (p=0.010). Е / А and е' / a' ratios were correlated with total lactate dehydrogenase fraction (r= -0.452 and p=0.006; r= -0.334 and p=0.050, respectively).Conclusion      In patients with severe COVID-19-associated pneumonia during regression of SIR intensity, changes in the parameters that reflected RV diastolic dysfunction were observed.

[Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies].

BACKGROUND: Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. AIM: To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. MATERIALS AND METHODS: Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. RESULTS: In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). CONCLUSION: The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

[Levilimab and baricitinib prescribing experience in outpatient COVID-19 patients' treatment].

AIM: To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19. MATERIALS AND METHODS: A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia. RESULTS: According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 36.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 36.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression. CONCLUSION: The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.

[Efficacy and safety of regdanvimab in patients with mild/moderate COVID-19 and high risk of progression of the disease: a retrospective study in a short-term stay unit].

BACKGROUND: The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease. AIM: To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit. MATERIALS AND METHODS: Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. INCLUSION CRITERIA: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). EXCLUSION CRITERIA: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR. STATISTICS: Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the KaplanMeier method. The significance level was determined at p0.05. RESULTS: A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study. CONCLUSION: In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.

Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study.

BACKGROUND: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. METHODS: The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. RESULTS: Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6-14.6%]) vs 13.0% (95% CI [7.5-18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31-1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11-1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8-16 mg dexamethasone). CONCLUSIONS: Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date.

[Criteria for the optimal use of interleukin-6 receptor blockers in patients with COVID-19].

AIM: To determine the criteria for the optimal use of IL-6 receptor blockers in patients with COVID-19 community-acquired pneumonia based on predictors of adverse outcomes. MATERIALS AND METHODS: The single-center, non-randomized prospective study included 190 patients with community-acquired pneumonia caused by coronavirus 2 between the beginning of March and the end of May 2020. Of these, 89 patients received tocilizumab and 101 patients received sarilumab. The study inclusion criterion for the patient was indications for initiating therapy with one of the inhibitors of IL-6 receptors (anti-IL-6R) according to the Interim guidelines (versions 4 and 5). The exclusion criterion was the need to re-prescribe genetically engineered biological therapy (GEBT). The severity of the patient's condition was assessed according to the early warning score (NEWS2), the volume of lung tissue lesions was assessed according to computed tomography (CT). Laboratory monitoring included counting the absolute (abs) number of lymphocytes, serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), D-dimer, lactate dehydrogenase, fibrinogen. Statistical data processing was conducted by nonparametric methods using the IBM SPSS Statistics V-22 software. RESULTS: The phenotype of a patient with a negative outcome prognosis was described: a male patient over 50 years of age with aggravated premorbid background (with cardiovascular diseases, obesity and/or chronic renal disease), lung lesion CT 34, saturation less than 93% upon inhalation of atmospheric air, persisting for 2448 hours after GEBT. According to the blood test, lymphopenia was below 1000 U/L and CRP levels were above 50 mg/L. The laboratory parameters and clinical picture of the patient progressively worsened after 911 days of illness, regardless of the use of Anti-IL-6R. The features of patients monitoring when administering IL-6 receptor blockers have been determined. CONCLUSION: IL-6 receptor blockers should be administered to patients hospitalized with severe COVID-19 before the development of hyperinflammatory reactions. The optimal "therapeutic window" is 78 days of illness.

N-Terminal Fragment of Brain-Type Natriuretic Peptide (NT-proBNP) as a Prognostic Marker in Patients with Newly Diagnosed Multiple Myeloma Complicated by Dialysis-Dependent Renal Failure.

Prognostic value of N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) was analyzed in patients with multiple myeloma complicated by dialysisdependent renal failure. The prospective study included 20 patients with newly diagnosed multiple myeloma. The concentrations of NT-proBNP were measured before antimyeloma chemotherapy. The median age of the patients was 67 (63-76) years. The median glomerular filtration rate was 4 (4, 5) ml/min/1.73 m2. For overall survival, the area under ROC curve was 0.75 and the cut-off point was 7000 pg/ml. At median follow-up of 17.3 months, the overall survival was 76.6±14.8 and 27.3±13.4% (p=0.02) for cases with NT-proBNP levels below and above the cut-off point, respectively. There were no cases of death due to cardiovascular causes. We concluded that the increase in serum concentration of NT-proBNP>7400 pg/ml is associated with the severity of kidney damage and the risk of non-cardiac mortality.

[Awareness of the Risk Factors for Cardiovascular Disease in Different Types of Hospitalized Medical Patients].

OBJECTIVE: to study medical awareness of cardiovascular risk factors (FR) in hospitalized patients of the cardiac and internal medicine units (CU and IMU). MATERIALS AND METHODS: A total of 100 patients from CU (n=50) and IMU (n=50) of a Moscow city hospital were included into the survey. The patients were interviewed during the I-II days of hospital stay. A special questionnaire was developed including socio-demographic and clinical indicators, open questions on the knowledge of traditional cardiovascular RFs and their target values. RESULTS: Patients of both units did not differ in gender and age. The survey revealed an extremely low awareness of major cardiovascular RFs of patients in both units: practically none of them indicated as RFs for cardiovascular disease elevated cholesterol (0 and 2 %, respectively, p>0.05) and blood pressure (0 % and 2 %, respectively, p>0.05). The majority of patients in both units (74 and 68 %, respectively, p>0.05) reported only 1-2 RFs. Patients in both units often believed that stress is the main cardiovascular RF (66 % and 50 %, respectively, p>0.05). CONCLUSION: The survey revealed a low awareness of cardiovascular RFs in different types of medical patients at time of hospital admission.

[Bilateral nephrectomy in patients with end-stage renal failure and chronic active pyelonephritis].

This study analyzed the results of bilateral nephrectomy in 14 patients with end-stage renal disease (ESRD) and chronic active pyelonephritis. Seven patients had urosepsis, and 10 patients had a purulent form of pyelonephritis, which was one-sided in 7 of them. In the early postoperative period, on average, after 9.3 days, 9 patients died. Statistically significant risk factors for death were: chronic hemodialysis, long-term antibiotic therapy, and existing sepsis. Intraoperative complications and postoperative morbidity were not significantly associated with death. The study results imply the need of differentiated approach to bilateral nephrectomy in patients with ESRD and risk factors for fatal outcome. It must be performed on the strong indications since the intervention does not lead to eradication of sepsis. It is advisable to perform "preventive, sanation" bilateral nephrectomy in the "cold period" in patients at risk for developing urosepsis.

[The first national experience of laparoscopic removal of the transplanted kidney].

As a rule, the excision of a non-functioning renal graft in late (over 12 months) post-transplant period is performed using Fedorov subcapsular technique. This is because the kidney is embedded in scar tissue due to immune response to the allograft. This surgical approach is associated with the two major complications: bleeding during surgery or early postoperative hematoma and infection of hematoma confined in the remaining kidney capsule. To reduce blood loss and the risk of inflammatory complications, we, for the first time, carried out laparoscopic transplantectomy in a 42 year old female patient using the extracapsular technique. The operative time was 245 min, intraoperative blood loss - 350 ml. The patient was discharged to outpatient treatment on the 10th day. For the first time, such a surgery was successfully performed in 2010 in Turkey; in 2014 robotic transplantectomy was reported in the United States. No data on laparoscopic transplantectomy was found in the available national sources.

[Effect of cytokines and stromal cells of adipose tissue on integration of a two-component composite net imlant into biological tissues].

Morphological changes in biological tissues, surrounding the composite net-like implant, owing large pores "Ultrapro", and also its combination with adipose transplant, fibrin, enriched with thrombocytes, were studied in experiment on 36 adult male rats of a Wistar line. While application of such construction the processes of creation and organization of connective tissue, neoangiogenesis as well as development of a new adipose tissue are improved. As a consequence of increase of concentration of highly active biological substances and regenerative cytokines in combination of the net implant with adipose transplant, containing multipotent stem cells, proliferative activity of all cellular elements, surrounding the net implant, is raising, what predispose its optimal integration into surrounding tissues.

[Clinical epidemiology of multiple sclerosis in Moscow. Сlinical demo-graphic characteristics in population of one region of Moscow]. / Klinicheskaia épidemiologiia rasseiannogo skleroza v Moskve. Sovremennye kliniko-demograficheskie osobennosti na primere populiatsii odnogo iz okrugov goroda.

The changes in clinical features of multiple sclerosis (MS) are noted worldwide which can be explained by diagnosis improvement and DMT implementation. Epidemiological studies of 2008-2012 in the North-West Administrative District of Moscow noted the higher proportion of women among patients of MS (M:F=1:2.61), longer duration of the disease (mean 14.3±10.6 years, maximum - 53 years) and life expectancy of patients (44.3±12.7 years, the maximum age - 77 years). The percentage of patients with secondary progressive course of MS increased (35%). In addition, MS onset before 16 years old was diagnosed more often (5.66% of cases) and late onset MS was identified in 4.04% of the cases. Up to 45.9% of MS patients have moderate and expressed disability (group 1 and 2 disability).

[Clinical epidemiology of multiple sclerosis in Moscow. Descriptive epidemiology in population of one region of Moscow].

The epidemiological study of multiple sclerosis (MS) has been done in the population (927 400 people) of the North-Western Administrative District (SZAO) of Moscow for the period of 2008-2012. In average for the 5 years the prevalence of MS was amounted to 53.38 cases per 100 000 population, incidence was 2.16 cases per 100 000 population and the mortality rate was 0.23 cases per 100 000 population. Thus, the population of SZAO belongs to high-incidence area. An increase in the prevalence of MS as well as a reduction of incidence and mortality were observed during a comparative analysis with the epidemiological indicators of MS in Moscow in the period of 1991-1996. Such dynamics of epidemiological indicators is due to the accumulation of patients in population that, in the first place, is related with the quality improvement of diagnostic and therapeutic-rehabilitative measures which increased the frequency of early diagnosis and patient's life expectancy together with the implementation of disease-modifying therapy (DMT) and modern methods of symptomatic treatment.

[The severe course of hyperparathyroidism in the elderly: Clinical cases].

Primary hyperparathyroidism (PHPT) is a disease of the endocrine system caused by excessive secretion of parathyroid hormone (PTH) and is characterized by a pronounced violation of calcium and phosphorus metabolism. More recently, in Russia, PHPT was detected extremely rarely and often hid under the mask of recurrent urolithiasis, generalized osteoporosis and other pathologies. As a result, patients did not receive adequate treatment, which in a certain percentage of cases led to the development of serious complications.The clinical cases of severe PHPT in postmenopausal women are presented in this article.