Balkan Medical Journal最新文献

Background: Hyperuricemia and gout are common metabolic disorders that show substantial disparities in prevalence and management across different socioeconomic status.

Aims: To investigate the association between social determinants of health (SDOH) and mortality risk in adults with hyperuricemia and/or gout, to assess whether the interaction between SDOH and gout/hyperuricemia status influences mortality risk.

Study design: A retrospective cohort study.

Methods: We analyzed 6,560 United States (US) adults (mean age 58 years, 60.02% men) with hyperuricemia and/or gout from the 1999-2018 National Health and Nutrition Examination Survey. The primary study outcomes were all-cause and cardiovascular mortality. A control group of 6,560 adults without hyperuricemia or gout was measured using propensity-score matching based on age, sex, and race. SDOH was measured using a composite score (range 0-8) created from eight socioeconomic indicators: education, employment, food security, family income-to-poverty ratio, marital status, health insurance coverage, insurance type, and home ownership.

Results: Over a median follow-up of 101 months, 1,335 (14.76%) deaths occurred among participants with hyperuricemia and/or gout, including 496 (5.33%) cardiovascular deaths. Relative to adults with hyperuricemia and/or gout who had an SDOH score of 7-8, the hazard ratios (95% confidence intervals) for those with SDOH scores of 5-6, 3-4, and ≤ 2 were 1.48 (1.21-1.81), 1.85 (1.49-2.28), and 2.38 (1.82-3.11), respectively, for all-cause mortality, and 1.62 (1.16-2.25), 1.65 (1.18-2.31), and 2.10 (1.24-3.54), respectively, for cardiovascular mortality. Restricted cubic spline analyses demonstrated an inverse relationship between SDOH and both mortality outcomes. Subgroup analysis indicated that the association between SDOH and mortality risk was stronger among participants younger than 60 years. Interaction analyses showed that hyperuricemia/gout status did not significantly modify the association between SDOH and mortality.

Conclusion: Cumulative social disadvantage, indicated by a lower SDOH score, independently predicted higher mortality risk in US adults with hyperuricemia and/or gout, with the most pronounced effects observed in individuals under 60 years. Notably, the unfavorable cardiovascular effects associated with SDOH appeared more evident in adults without hyperuricemia or gout than in those with these conditions.

Background: Aberrations in cadherin-related 23 (CDH23) account for a significant proportion of familial autosomal recessive non-syndromic hearing loss (DFNB12), a common subtype of hereditary hearing loss worldwide.

Aims: This study aimed to elucidate the molecular basis and pathogenic mechanism of DFNB12 in an affected girl from a nine-member pedigree.

Study design: Family-based genetic study with pedigree analysis.

Methods: Clinical whole-exome sequencing combined with pedigree analysis was used to identify disease-causing mutations. The potential functional consequences of these mutations were investigated using structural bioinformatic approaches, including homology modeling, molecular dynamics simulations, and other relevant tools.

Results: The proband carried compound heterozygous variants: a known pathogenic maternal variant (c.6049G > A) and a paternal haplotype comprising two linked variants (c.3262G > A and c.6911G > A), each individually classified as benign. Pedigree segregation analysis demonstrated that the paternal haplotype acts as a single pathogenic allele.

Conclusion: Two individually benign variants can combine to form a novel pathogenic haplotype (c.3262A-c.6911A). This mechanism may be under-recognized in routine variant interpretation pipelines. Our findings underscore the importance of evaluating the combined effects of linked benign variants to ensure accurate genetic counseling.

Background: Accurate identification of medulloblastoma molecular subgroups is essential, particularly in settings lacking advanced genomic tools. Conventional markers, such as β-catenin, present significant challenges in reliably detecting the WNT-activated subgroup (WNT-AG).

Aims: To evaluate the utility of lymphoid enhancer-binding factor 1 (LEF1), Cyclin D1, and receptor tyrosine kinase-like orphan receptor 2 (ROR2) as immunohistochemical (IHC) markers for molecular subgroup classification and to assess their prognostic significance.

Study design: Retrospective cohort study.

Methods: IHC analysis was performed using LEF1, Cyclin D1, and ROR2. Two distinct LEF1 staining patterns were identified: nuclear (nLEF1) and punctate (pLEF1). A subset of 29 cases, selected based on predefined criteria, underwent EPIC array Methylation analysis. Findings were correlated with recurrence and survival outcomes.

Results: Among the 94 cases, 12.8% were WNT-AG, 54.3% were sonic hedgehog-activated subgroup (SHH-AG), and 33.0% were Groups 3 and 4 (G3/4). nLEF1 demonstrated higher specificity and sensitivity for WNT-AG than β-catenin, identifying it as a more reliable diagnostic marker. High pLEF1 expression was strongly associated with SHH-AG. Cyclin D1 positivity was predominantly observed in WNT-AG. While ROR2 did not identify WNT-AG effectively, its absence in Group 3 cases was notable. Prognostic analysis revealed that LEF1 expression patterns correlated with favorable survival outcomes: total LEF1 (tLEF1) and nLEF1 were associated with improved overall survival, whereas pLEF1 and tLEF1 were linked to better progression-free survival.

Conclusion: Nuclear LEF1 (nLEF1) is at least as effective as β-Catenin in identifying WNT-AG and may serve as a superior diagnostic marker. Cyclin D1 can be used as a complementary marker in WNT-AG detection. ROR2 negativity may indicate G3 tumors, though further studies are warranted to confirm its prognostic value.