Atopic dermatitis is a heterogeneous disease with diverse immunological endotypes. Modern methods of high-resolution molecular analysis (RNA sequencing, spatial transcriptomics, multiomix approaches) have allowed to identify various endotypes of the disease: Th2/ILC2-associated (ILC2 — type 2 innate lymphoid cells, Th — T helpers); Th22-associated; Th17/Th1 mixed; late onset endotype (with low IgE levels); ILC2- dominant endotype; minimally inflammatory endotype. This review provides a detailed analysis of the pathogenesis mechanisms of each endotype, including unique cytokine profiles (IL-4/IL-13/IL-31, IL-22, IL-17/interferon gamma; IL — interleukin), the main cell- mediated mechanisms (resident Th2 cells, ILC2, cytotoxic CD8+ Th22 cells) and their direct effect on the epidermal barrier and neuroimmune interactions. The main focus of the review is justification of the targeted biological therapy (inhibitors of IL-4/IL-13, IL-13, IL-31, JAK-STAT) choice based on the dominant pathway. The strategies for stratifying patients using serum biomarkers (TARC/CCL17, IL-22, IL-17) and the transcriptomic skin profile are considered. Endotype-based therapy personalization may represent a novel approach for management of patients with severe atopic dermatitis and resistance to conventional treatments, which allows to overcome the torpidity to the standard therapy.
Literature data from open sources (eLibrary, Scopus, Web of Science, PubMed) were analyzed and summarized with no limitations on search depth. The search was conducted using the following keywords: dorsopathy, inflammation, disc extrusion, disc herniation, discogenic radiculopathy, dorsopathy, disc inflammation. Analysis of the obtained data suggests the formation of a new perspective on the problem of inflammation in the area of discogenic radiculopathy through the segregation of certain findings into isolated “paradoxes” or “vicious circles” of the described problem, thereby expanding the epistemological horizons of the pathogenesis of dorsopathies. Aseptic inflammation in the intervertebral disc area is a multiphase process that includes preclinical biomechanical imbalance, the onset of dorsopathy, and the phase of extrusion formation and resolution. The development of inflammation is associated with the contact spread of immune and neuroinflammatory reactions to neural structures, along with simultaneous activation of reparative mechanisms. The proposed approach makes it possible to substantiate preventive and therapeutic strategies aimed at accelerating the resolution of the pathological process.
Background: Evidence-based practice (EBP) is central to high-quality healthcare, yet its implementation in the Middle East remains insufficiently characterized across professions. This study assessed EBP implementation, attitudes, and competencies among healthcare professionals in multiple Middle Eastern countries. Methods: We conducted a multi-center cross-sectional analytical study using the Evidence-Based Practice Questionnaire (EBPQ). Licensed healthcare professionals with at least one year of clinical experience were recruited using stratified convenience sampling. Data were collected electronically via KoBoToolbox from 3 November 2025 to 9 December 2025. EBPQ subscales (practice, attitude, skills/knowledge) were scored on a 7-point Likert scale. Scores were categorized into low, moderate, and high based on scale midpoints. Descriptive statistics and inferential analyses (chi-square with Monte Carlo simulation, Spearman’s rank correlation) were performed; p < 0.05 was considered significant. Results: A total of 518 participants were included. Mean (SD) scores were 2.88 (1.46) for practice, 3.67 (1.16) for attitude, and 4.10 (1.47) for skills/knowledge. Most participants had low practice (75.5%) and low overall EBP competency (53.1%). Age was significantly associated with practice (Spearman ρ = 0.207, p < 0.0005), while gender, profession, and country were not significantly associated (p = 0.214, 0.598, and 0.067, respectively). Conclusions : EBP practice among healthcare professionals in the Middle East was low despite modestly positive attitudes and moderate self-reported skills. Educational and organizational strategies are needed to bridge the evidence-to-practice gap across the region.
Background . Generalized forms of meningococcal disease caused by Neisseria meningitidis are characterized by rapid course and high mortality. The pathogen serogroup distribution varies between regions and changes over time, which determines the need for vaccines covering currently relevant serogroups A, C, W and Y. Licensed quadrivalent conjugate vaccines differ both in polysaccharide content and in carrier protein, which properties are considered among the factors shaping the T-dependent immune response. Objective. The aim of the study is to evaluate immunogenicity, reactogenicity, and safety of meningococcal conjugate vaccine MenACWY-CRM197 compared with previously licensed MenACWY-DT vaccine in healthy people aged 3–55 years. Methods. Multicenter, randomized, comparative, single-blind, parallel-group, phase III trial was conducted in 16 clinical centers among Russian Federation. All study participants were allocated 1:1 across three sequential age groups (I — 18–55 years, II — 11–17 years, III — 3–10 years). The transition between groups was performed after positive conclusion on vaccine safety according to interim safety data by independent data monitoring committee. Both vaccines were administered intramuscularly once at dosage of 0.5 ml. The primary endpoint was the proportion of participants achieving seroconversion based on serum bactericidal antibody (SBA) titers against meningococcal serogroups A, C, Y, and W at Visit 3 (Day 29 ± 1); non-inferiority was considered demonstrated if the lower bound of the 95% confidence interval (CI) for the difference in proportions exceeded –10%. Secondary endpoints (seroprotection at SBA titer > 1:4, geometric mean titers (GMT), reverse cumulative titer distribution curves) and safety outcomes were analyzed without adjustment for comparisons multiplicity; corresponding p-values are descriptive. Results . A total of 240 participants were randomized (120 per group); the per-protocol population comprised 239 participants. Seroconversion by Visit 3 was achieved in at least 98.33% of participants for each of the four meningococcal serogroups in both groups; and it was achieved in all participants for serogroups C and W. The lower bounds of the 95% CI for the proportions difference for meningococcal serogroup A (0.83%; 95% CI –3.82…5.72) and serogroup Y (–0.007%; 95% CI –4.51…4.47) exceeded the non-inferiority margin confirming the study hypothesis for the primary endpoint. SBA titers increased significantly from Visit 1 to Visit 3 for all serogroups in both groups (p < 0.001). No differences in GMT between groups were revealed for meningococcal serogroups A, W, and Y; while the post-vaccination GMT in the investigational vaccine group was higher (306.7 vs 222.9; p = 0.017) for serogroup C. The studied vaccine demonstrated favorable safety profile. At least one adverse event (AE) was reported in 53.33% of participants in the investigational vaccine group and in 56.67% of the reference group (p = 0.604). No differences between groups were revealed in the distribution of AE by severity, causal relationship, or outcomes in the pooled population. The distribution of AE by severity differed (ratio of mild AE 86.46% vs 73.68% in the comparison group; p = 0.033) in the analysis by age stratum, among adolescents aged 11–17 years in the MenACWY-CRM197 vaccine group; in children aged 3–10 years, systemic reactions were reported in 20.0% and 40.0% of participants, respectively (p = 0.051). No serious AE related to vaccination and no fatal outcomes were reported. Conclusion. In terms of seroconversion frequency against all four meningococcal serogroups, the MenACWY-CRM197 vaccine was non-inferior to the reference vaccine. Safety and reactogenicity profiles in the pooled population were comparable. The superior result of the investigational vaccine for secondary endpoints (GMT against meningococcal serogroup C) and the results of reactogenicity analysis by age stratum were obtained without controlling for type I error probability and require further study in specifically designed trials. The obtained data confirms the immunogenicity and acceptable tolerability of the MenACWY-CRM197 vaccine in individuals aged from 3 to 55 years. The study results allow us to consider using this vaccine for meningococcal infection prevention in children, adolescents, and adults as part of mass vaccination. Trial registration : protocol GNG-DE-III-24, version 1.0, August 15, 2024; clinical trial authorization by the Ministry of Health of Russian Federation No.532, November 07, 2024.
