Murmansk Regional Clinical Hospital

In everyday neurological practice, B-cell-depleting therapies are playing an increasingly important role in the treatment of active forms of multiple sclerosis (MS). Among the most well-studied agents are monoclonal antibodies (mAbs) targeting the CD20 receptor on lymphocytes: ocrelizumab (a humanized mAb) and ofatumumab (a fully human mAb), which bind to different extracellular epitopes of the CD20 receptor. In relapsing forms of MS, the pharmacological characteristics of these agents often necessitate switching from the better-known intravenous drug ocrelizumab to the subcutaneous agent ofatumumab.This review, illustrated through clinical case examples, discusses the primary reasons for such a switch-both objective (such as insufficient efficacy or intolerance) and subjective. Among the latter, an increasingly relevant factor is the phenomenon of "treatment fatigue" associated with regular intravenous infusions, particularly when therapy has been ongoing for a long period. This fatigue may manifest as feelings of exhaustion or low mood, which negatively impact adherence and, consequently, treatment efficacy.

This article brings together the opinions of leading experts in the field of cardiac arrhythmia interventional treatment using multipolar mapping. The advantages and applicability of the PENTARAY® NAV eco mapping catheter are discussed in detail.

Background. In an era of breakthroughs in cancer immunotherapy, CheckMate 067 studies declared the combination of PD-1 and CTLA-4 inhibitors a new standard of care for patients with metastatic melanoma (MM). A significant limitation of the widespread use of the combination of ipilimumab and nivolumab in routine clinical practice is the high risk of severe immune-mediated adverse events. Prolgolimab and nurulimab are a combination of fixed doses of original monoclonal antibodies (manufactured by JSC "BIOCAD," Russia) to the PD-1 receptor (prolgolimab) and the CTLA-4 receptor (nurulimab) (3:1 ratio). This paper presents the results of an international, multicenter, double-blind, placebo-controlled, comparative, randomized, phase II OBERTON clinical study to investigate the efficacy and safety of nurulimab + prolgolimab combination therapy with continued prolgolimab therapy compared to prolgolimab alone as first-line therapy in patients with unresectable melanoma (uRM) or MM (NCT03913923). Materials and methods. The study included patients with uRM or MM who were not previously treated for metastatic disease. The patients were randomized into two groups (1:1). Patients in group 1 were treated with a nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) combination at a dose of 0.2 mL/kg (equivalent to 1 mg/kg of nurulimab and 3 mg/kg of prolgolimab) once every 3 weeks during the first 4 blinded infusions. Patients in group 2 received prolgolimab monotherapy at a dose of 3 mg/kg once every 3 weeks during the first 4 blinded infusions. Starting from infusion 5, patients in both groups received open prolgolimab 1 mg/kg once every 2 weeks. The primary endpoint of the study was progression-free survival (PFS). The study is registered on ClinicalTrials.gov under the number NCT05732805 and is currently ongoing, but recruitment of new patients has been completed. Results. One hundred seventeen patients were randomized and received at least one dose of the study therapy. At a median follow-up of 16.79 months, the median PFS was 12.2 (4.9; not achieved) months in the nurulimab + prolgolimab group and 2.8 (1.5; 4.7) months in the prolgolimab monotherapy group (95% confidence interval 0.36-0.90, hazard ratio 0.57). PFS at 24 months was 41% in the nurulimab + prolgolimab group and 25.4% in the prolgolimab monotherapy group. In both groups, the therapy was well tolerated. Grade 3-4 immune-mediated adverse events were reported in 15.5% of patients who received nurulimab + prolgolimab, compared with 1.7% of those who received prolgolimab alone. The most frequent grade 3-4 treatment-related adverse events in both treatment groups were increased alanine aminotransferase and aspartate aminotransferase and asthenia. Overall, the safety profile was favorable, as expected for the class of immune checkpoint inhibitors, anti-CTLA-4, and anti-PD-1 monoclonal antibodies. Discussion. The results demonstrate a favorable safety profile in both the nurulimab + prolgolimab combination and prolgolimab monotherapy groups as the first-line treatment for uRM or MM. The assessment of the primary endpoint, PFS, showed the benefit of combination immunotherapy followed by switching to prolgolimab compared to prolgolimab alone. Conclusion. Combination immunotherapy with the CTLA-4 inhibitor nurulimab and the PD-1 inhibitor prolgolimab, available as a combination of solutions of two drugs in a single vial, with a further switch to monotherapy with prolgolimab, can fill an important niche in the treatment of patients with uRM or MM. Confirmation of the obtained data on the efficacy and safety of the combined regimen of nurulimab + prolgolimab in comparison with PD-1 inhibitor monotherapy is expected from the ongoing phase III BCD-217-2 OCTAVA study (NCT05732805).

Background. Suppurative septic postpartum complications occupy a leading position in the structure of causes of maternal mortality. Information about the characteristics of pathogenic microflora in various forms of complications and analysis of its resistance to antibacterial drugs determine the choice of rational therapy for this pathology.Objectives — to characterize the isolated pathogenic microflora in obstetric patients with suppurative septic postpartum complications.Methods. A retrospective cohort study was conducted at the Department of Obstetrics and Gynecology No. 2 of the Omsk State Medical University and the Department of Gynecology of the Omsk Regional Clinical Hospital. The study included 123 cesarean section patients treated from January 2013 to December 2022 who were divided into three groups: Group A — uncomplicated course of postpartum endometritis, n = 55; Group B — complicated forms of postpartum endometritis, n = 48: B1 — local complications (suture failure following cesarean section; parametritis) n = 29; B2 — pelvic peritonitis, n = 19; Group C — septic complications following critical obstetric conditions, n = 20. The pathogenic microflora of uterine and abdominal cavities was examined; the extent of contamination with a pathogen and sensitivity to antibacterial drugs were determined. The isolated microorganisms were identified using a MicroTax bacteriological analyzer (Austria), Vitek2 Compact (France) and routine methods; a disk diffusion method was employed to determine the sensitivity of microorganisms to antibacterial drugs. Calculations were performed using licensed Microsoft Office Excel 2013 and Statistica 10 programs (StatSoft Inc., USA). Nonparametric nominal data were compared using Pearson’s chi-squared test with p-value determination.Results. The pathogenic microflora was dominated by S. epidermidis, E. faecalis, E. coli, and E. faecium. In 2018–2022, a statistically significant decrease was observed in the isolation rate of S. epidermidis (p = 0.016), E. faecalis (p < 0.001), and E. faecium (p = 0.05). The highest resistance was exhibited by bacteria to the following antibiotics: S. epidermidis — cephalosporins (30.16%); E. faecalis — fluoroquinolones (33.33%); E. coli — cephalosporins (65.91%) and β-lactamase-resistant penicillins (40.91%); E. faecium — aminopenicillins (64.10%) and fluoroquinolones (50.0%); А. baumannii — fluoroquinolones, cephalosporins, carbapenems (100%), and aminoglycosides (84.2%). A contamination assessment revealed a high titer of isolated microorganisms in 60.53% of cases. We found a statistically significantly higher isolation rate of S. еpidermidis (p < 0.001), E. faecium (p = 0.01), and A. baumannii (p = 0.02) in the setting of pelvic peritonitis as compared to uncomplicated endometritis. In the case of suppurative septic complications due to critical obstetric conditions, the isolation rate was higher for S. еpidermidis (p <0.001), E. coli (p = 0.04), E. faecium (p = 0.005), A. baumannii (р<0.001), and K. рneumoniae (p = 0.04).Conclusion. The antibiotic resistance of pathogenic microorganisms calls for the development of new organ system support technologies and the use of methods capable of sorbing microorganisms and their toxins in the area of inflammation.

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Introduction. In recent years, there has been an increase in the prevalence and incidence diabetes type 1. The high-quality glycemic control is critical in reducing the risk of developing and progression of vascular complications and adverse outcomes of diabetes. Self-monitoring blood glucose (SMBG) and professional continuous glucose monitoring (PCGM) provide the data set which must be interpreted using multiple indicators of glycemic control. A number of researchers have demonstrated the relationship between the time in range (TIR) and the risk of developing both micro- and macrovascular complications of diabetes. Considering the insufficient amount of data on TIR differences depending on the glucose level assessment method and the significant potential of using this indicator for the stratification of the risk of both micro- and macrovascular complications of diabetes, the study of TIR differences based on the data of PCGM and SMBG is relevant at present.Aims. To estimate the time range according to professional continuous glucose monitoring and self-monitoring of blood glucose levels in the patients with diabetes type 1 among the adult population to improve the control of the disease course.Materials and methods. An interventional open-label multicenter study in the patients with diabetes type 1 was conducted. The patients with diabetes type 1 aged 18 and older, with the disease duration of more than 1 year receiving the therapy with analog insulin was enrolled into the study. The calculation of the indicators of the time spent in the ranges of glycemia was carried out on the basis of the data of PCGM and SMBG.Results and discussion. We examined 218 patients who met the inclusion criteria and did not have exclusion criteria. The presented differences in the indicators of time in ranges indicate the comparability of the SMBG and PCGM methods.Conclusions. When assessing the indicators of time in the ranges of glycemia obtained on the basis of the data of PCGM and SMBG, clear correlations and linear dependence were demonstrated, which indicates the comparability of these parameters regardless of the measurement method.

To study the long-term functional results of surgical treatment of patients with acquired cholesteatoma, their dependence on the age of patients, the type of cholesteatoma and the type of surgery. The article presents the results of a dynamic comparison of the functional results of surgical treatment of 332 adults and 104 children with various forms of acquired middle ear cholesteatoma who underwent both closed and open surgical procedures. There were no statistically significant differences in hearing function into two age's groups depending on the type of cholesteatoma acquired. Average air conduction in adult patients for all types of cholesteatoma were ranked within 34.55-44.19 dB, air-bone gaps - 24.14-31.12 dB; in children - 33.72-39.16 dB and 27.33-34.95 dB, respectively. The exception was a group of adult patients with secondary cholesteatoma of the pars tensa. In the postoperative period, in patients of both age groups with all types of cholesteatoma, an improvement in the average values of air conduction by 18-20 dB and a decrease in the average values of the air-bone thresholds by 17-21 dB were noted. Analysis of the results of open surgical interventions showed a somewhat worse functional efficiency on 5-9 dB for air conduction average and 18-20 dB for air-bone gaps, both for adults and children. The stability of the achieved level of auditory function at all stages of postoperative observation was also noted. Surgical treatment of children and adult with all types of acquired cholesteatoma can improve hearing function and achieve stable results when using closed or open types of operations.

We examined 150 patients with osteoarthritis of hip joints. The stage of development of arthrosis is II–III (according to Kellgren-Lawrence). Statistical processing was carried out, and the risk factors at the population level were revealed, which provide the emergence of coxarthrosis and affect the patient’s circulation.