Balkan Medical Journal最新文献

Familial Mediterranean Fever (FMF) is the first described and most prevalent monogenic autoinflammatory periodic fever syndrome worldwide. The disease is caused by pathogenic variants in the MEFV (Mediterranean fever) gene, which lead to dysregulated innate immune responses and a persistent hyperinflammatory state. Despite extensive genetic characterization, the molecular mechanisms linking MEFV mutations to aberrant inflammation remain incompletely understood. Moreover, substantial clinical heterogeneity-manifested as incomplete penetrance, variable expressivity, and modulation by additional autoinflammatory genes-indicates that FMF pathogenesis extends beyond classical Mendelian inheritance. Emerging evidence suggests that epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA regulation, may contribute to phenotypic variability, disease severity, and therapeutic response; however, available data are limited and occasionally conflicting. This review provides a comprehensive and up-to-date overview of the genetic, molecular, and epigenetic factors implicated in FMF, highlights unresolved controversies, and proposes future research priorities aimed at elucidating disease mechanisms and improving clinical management.

Background: Childhood interstitial lung diseases (chILD) and immunodeficiencies are rare, heterogeneous, and clinically challenging disorders.

Aims: This study aimed to evaluate the clinical and radiological characteristics of immunodeficiency-related chILD using data from the Türkiye chILD Registry (chILD-TR).

Study design: We conducted a retrospective cohort study using data collected from the chILD-TR in 2023.

Methods: Patients registered with the B3 code, according to the chILD-European classification, from 18 participating centers were included. Patients were classified into primary immunodeficiency (PID) and secondary immunodeficiency (SID) groups. Demographic, clinical, and radiological variables were compared between the two groups.

Results: Among 667 patients registered in the chILD-TR, 114 (17%) had immunodeficiency-related chILD, including 53 (47%) females. The median current age was 156 months (range: 23-357), the age at symptom onset was 60 months (range: 0-215), and the age at chILD diagnosis was 85 months (range: 2-217). PID was identified in 77 patients (67.6%) and SID in 37 patients (32.4%). The PID group had significantly lower median current age, age at first symptom, and age at chILD diagnosis compared with the SID group (p < 0.05). No significant differences were observed in growth z-scores between the groups (p > 0.05). A history of hematopoietic stem cell transplantation (HSCT) and a diagnosis of bronchiolitis obliterans (BO) were more frequent in the SID group (p < 0.05). The most common computed tomography findings were ground-glass opacities in PID and mosaic perfusion in SID. During follow-up, 14 patients (12.3%) died.

Conclusion: Immunodeficiency-associated chILD encompasses a heterogeneous spectrum of disorders and is associated with increased mortality. Distinct clinical and radiological patterns were observed between PID and SID. These findings underscore the importance of early detection, individualized diagnostic strategies, and ongoing follow-up to improve outcomes in this high-risk population. Recognition of post-infectious BO and following HSCT is critical for timely intervention.

Background: The fetal liver is perfused by the umbilical vein (UV) and the main portal vein (MPV), both of which are crucial for nutrient delivery. The configuration of the umbilicoportal anastomosis may influence MPV blood flow and potentially affect fetal liver perfusion in fetuses with fetal growth restriction (FGR).

Aims: To evaluate absolute and normalized UV and MPV blood flows in fetuses with normal growth and FGR, and to investigate the effect of umbilicoportal anastomosis type on MPV flow.

Study design: This prospective case-control study included 108 appropriate-for-gestational-age (AGA) fetuses and 43 FGR fetuses between 18 and 37 weeks of gestation, evaluated over nine months.

Methods: Ultrasound was used to measure UV and MPV diameters, while Doppler ultrasound assessed time-averaged maximum velocities. Flow volumes were calculated as time-averaged maximum velocity volume and normalized to estimated fetal weight (TAMXVVN) and abdominal circumference. Anastomoses were categorized as T-, X-, or H-shaped. Z-scores were derived from AGA nomograms.

Results: Compared with AGA fetuses, FGR fetuses exhibited significantly smaller UV diameters, lower absolute UV flow, UV-TAMXVVN, and UVTAMXVV/ AC (p < 0.05), but higher MPV-TAMXVVN (p < 0.05), suggesting compensatory redistribution. Both UV and MPV flows showed strong correlations with gestational age (r > 0.7, p < 0.001). UV-TAMXVVN Z-scores decreased with gestation, whereas MPV-TAMXVVN Z-scores increased until 32 weeks before plateauing. Blood flow parameters did not differ significantly across anastomosis types in either group.

Conclusion: FGR fetuses demonstrate reduced UV perfusion with compensatory increases in MPV flow. The type of umbilicoportal anastomosis does not significantly affect MPV blood flow.