Omsk State Medical University

Idursulfase and idursulfase beta currently used for enzyme replacement therapy of mucopolysaccharidosis type II (MPS II) do not cross the blood-brain barrier (BBB), which significantly limits the treatment of neurocognitive impairment in patients. Verenafusp alfa (Clotilia®, GENERIUM JSC) contains a recombinant modified iduronate-2-sulfatase enzyme covalently linked to the Fab fragment of a monoclonal antibody against the human insulin receptor, which crosses the BBB. Objective: The aim of this multicenter, open-label, multicohort phase II–III study was to evaluate the safety, pharmacokinetics, pharmacodynamics (PD), efficacy, and optimal dose selection of verenafusp alfa in different age groups of patients. Materials and methods: The interim analysis included data from 18 patients under 18 years of age in 6 age cohorts. Cohort enrollment was performed sequentially with decreasing patient age, first for the 2 mg/kg dose (Group 1) in cohorts 2, 3, 5, and then for the 3 mg/kg dose (Group 2) in cohorts 4, 6, 7. The study included 52 weekly infusions of verenafusp alfa. The PD criterion was the level of glycosaminoglycans (GAGs) in urine, blood, and cerebrospinal fluid (CSF). Efficacy parameters included assessment of somatic manifestations and neurocognitive functions; safety parameters included assessment of adverse events (AEs) and the dynamics of anti-drug antibody (ADA) formation. Results: The increase in verenafusp alfa concentration in CSF was more pronounced in Group 2 (3 mg/kg) – 252.5 [221.4; 351.54] pg/mL, as well as in the group of children under 6 years of age – 302.02 [244.72; 388.83] pg/mL. The decrease in heparan sulfate (HS) levels in CSF at week 52 was more pronounced in Group 2 (3 mg/kg) – 49% (p=0.084), and also in the group of patients under 6 years of age – 53% (p=0.027). Urinary and blood GAG levels remained stable, taking into account prior idursulfase therapy in 94% of patients. An 18% increase in the 6-minute walk test distance was observed in the overall group of patients under 18 years of age (p=0.020), accompanied by a statistically significant increase in range of motion in the shoulder, knee, and left hip joints. Liver and spleen volumes remained stable. Stabilization and/or improvement of neurocognitive function parameters were observed in patients with MPS II. The AEs observed in 50% of patients were non-serious, classified as infusion reactions of mild or moderate severity, with a predictable and manageable spectrum and frequency. ADA formation against the drug was observed in 40% of patients. Conclusion: Weekly intravenous administration of verenafusp alfa for one year achieved control of urinary GAG levels, stabilization and/or improvement of neurocognitive functions, and reduction of somatic manifestations of MPS II in previously treated patients with idursulfase drugs aged 2 to 16 years. After one year of therapy, an increase in verenafusp alfa concentration and a decrease in HS levels in CSF were observed, confirming its ability to cross the BBB and prevent neurodegenerative changes in the CNS.

The relevance of studying the incidence of acute poisoning, toxic exposure, and their consequences in the population is determined by the need for emergency hospitalization in specialized toxicology departments, the high risk of adverse outcomes in individuals of working age, significant socioeconomic losses, and the widespread and constantly changing composition of toxicants, including medications, pesticides, household chemicals, and synthetic drugs. Aim: to assess the dynamics of hospitalized morbidity in the city of Omsk due to acute poisoning, toxic exposure, and their consequences. Materials and methods: A retrospective, observational, descriptive, and evaluative study was conducted in Omsk from 2016 to 2025. Data from hospital discharge records (Form № . 066/u‑02) and emergency notifications of acute chemical poisoning cases (Form № 58–1/u) were used. Statistical data processing utilized traditional methods for calculating extensive and intensive indicators, the mean error of the indicator (m), and the significance of differences was assessed using Student’s t-test. Results. From 2016 to 2025, the incidence of hospitalized cases due to acute poisoning and toxic exposure in Omsk decreased by 2,7 times. There was a 2,3-fold decrease in the incidence of poisoning from ethanol and its surrogates, a 1,9-fold decrease from medications, a 3.0-fold decrease from narcotics and psychoactive substances, a 2,6-fold decrease from corrosive poisons, a 4,4- fold decrease from toxic gases, a 3,1-fold decrease from industrial poisons, and an 8,6-fold decrease from uncategorized poisons. However, there was an 11.1% increase in the incidence rate due to toxic effects from substances, primarily non-medical ones. Conclusions. During the study period, the profile of hospitalized patients with toxicological problems in Omsk changed, characterized by a significant decrease in hospitalizations for acute poisoning and toxic effects, while the number of hospitalizations due to toxic effects increased. Monitoring and assessing hospitalized morbidity rates allows for the study of regional toxicological characteristics for decision-making in the area of chemical safety.

A family with joint hypermobility syndrome (JHS) and hyperelastic skin is presented. Clinically, the proband was diagnosed in childhood with Ehlers–Danlos syndrome, but the diagnosis was not genetically confirmed. In young adulthood, the proband developed disabling kidney disease requiring renal replacement therapy (RRT) and subsequently kidney transplantation. The proband’s daughter was found to have renal pathology in the neonatal period on urinalysis, which progressed rapidly during adolescence. Careful examination of the daughter’s lifestyle revealed that at the age of 10 she became involved in jumping fitness (trampoline exercise) and did not follow a rational diet or nutritional regimen. Correction of these issues—adjustment of physical activity and nutrition, along with nephroprotective therapy with perindopril—led to encouraging results after two months of follow-up: disappearance of proteinuria and a sharp decrease in microhematuria. This clinical observation of a family with connective tissue dysplasia and an unidentified genetic defect, despite whole-genome sequencing of the proband, demonstrates the possibilities of epigenetic influence with positive outcomes through personalized recommendations for the proband’s offspring.

Highlights Multifocal atherosclerosis is characterized by the involvement of two or more vascular bed. The high prevalence of multifocal atherosclerosis is associated with a poorer prognosis. A clinical and anamnestic analysis of patients with multifocal atherosclerosis was conducted, along with a comprehensive assessment of treatment adherence. The obtained results demonstrate predominant comorbidity and low treatment adherence among patients with multifocal atherosclerosis, which calls for new approaches to the prevention of cardiovascular events in this patient cohort. Aim. To evaluate the clinical and anamnestic characteristics and treatment adherence of patients with multifocal atherosclerosis who had experienced a cardiovascular event. Methods. The study included 200 patients, including 54 (27%) women and 146 (73%) men aged 75 years or younger. All patients had experienced a cardiovascular event and had multifocal atherosclerosis documented by instrumental examination methods. Results. The age of patients included in the study was 65.0 [43.0; 74.0] years. Patients included in the study were characterized by high systolic and diastolic blood pressure. Most men were overweight, with a similar increase in waist circumference in both sexes (p = 0.626). The primary clinical diagnosis in all patients was coronary artery disease. The presence of multifocal atherosclerosis in patients was confirmed by the presence of coronary atherosclerosis in 100% of patients, as well as by involvement of individual vascular beds. A very low proportion of respondents –12% were characterized as sufficiently adherent. Conclusion . Patients with multifocal atherosclerosis are characterized by high comorbidity and low adherence to treatment, which directly affects the effectiveness of ongoing therapeutic and preventive measures.

Acute respiratory viral infection (ARVI) is one of the causes of global morbidity. Arterial hypertension (AH) is the most common chronic non-infectious disorder, which may be accompanied by ARVI occurence. The aim of the study is to investigate the clinical features of ARVI of various etiologies (COVID-19, influenza, and unspecified) in patients with arterial hypertension. The retrospective, comparative study included 535 patients divided into three groups: ARVI of unspecified etiology (group 1), 249 persons; COVID-19 (group 2), 250 patients; influenza (group 3), 36 cases. Each of the three groups included two subgroups: A, only ARVI (unspecified, COVID-19, influenza); B, ARVI (unspecified, COVID-19, influenza) accomplished by AH conditioin. Statistical data processing was carried out using STATISTICA 10.0 software packages. The manifestations of intoxication and catarrhal syndrome occurred in patients of subgroups 1A and 1B, their severity was different. In respondents with ARVI and AH (subgroup 1B), the course of ARVI differs in the following parameters: runny nose (χ2 = 4.3; p = 0.040), sore throat (χ2 = 4.3; p = 0.037), fever to febrile levels (χ = 24.5; p = 0.000). The clinical picture in patients with COVID-19 + hypertension differed from patients with COVID-19 without hypertension in that more patients had anosmia (χ2 = 3.84; p = 0.050), headaches (χ2 = 3.84; p = 0.050), myalgia (χ2 = 4.38; p = 0.036), sleep disorders (χ2 = 4.11; p = 0.043), cough (χ2 = 4.18; p = 0.041), prolonged febrile fever (U = 2.01; p = 0.044) (χ2 = 5.74; p = 0.017). Patients with influenza and AH were more likely to report nasal congestion (χ2 = 9.93; p = 0.002), cough (χ2 = 4.11; p = 0.043), and fever (χ2 = 11.25; p = 0.000), which lasted up to 8.5 days (U = 2.59; p = 0.023). For all patients, regardless of the genesis of ARVI in the presence of AH, febrile fever was more common and longer. The manifestations of intoxication and catarrhal syndrome in patients with influenza + AH are distinguished by the complaints of nasal congestion, cough and sleep disorders. In normotensive patients with COVID-19, loss of smell, headache, myalgia, sleep disorders were more common. Knowledge of the clinical features of the course of ARVI of various etiologies in patients with AH will allow for timely therapy correction of both ARVI and AH at the early stages.