Bidirectional associations between sensorineural hearing loss and depression and anxiety: a meta-analysis.

Background: Recently, the prevalence of sensorineural hearing loss (SNL) has been increasing, and several studies have suggested that depression, anxiety, and SNL may be associated with each other, however, individual findings still have discrepancies. To the best of our knowledge, no scholars have systematically elucidated the bidirectional associations between SNL, depression, and anxiety disorders from the perspective of meta-analysis. In this study, we aimed to systematically evaluate the bidirectional associations between SHL and depressive and anxiety symptoms, and to provide evidence-based medical evidence for reducing SNL, depression, and anxiety disorders. Methods: We performed systematic review based on priori protocol that was registered with PROSPERO (No. CRD42022365963). Systematic search of PubMed, Embase, and Web of Science databases identified articles published as of June 1, 2023, on the relationship between SNL and depression and anxiety. Meta-analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CIs) for the outcome metrics, and the results were combined to assess bivariate associations between the disorders with fixed or random effects. Sensitivity and subgroup analyzes were conducted to analyze sources of heterogeneity, and Egger's and Begg's tests combined with funnel plots were applied to assess publication bias. Results: Summary analysis of the results of 20 studies covering 675,291 individuals showed that the bidirectional association between SNL and depression and anxiety disorders. The incidence (OR = 0.17, 95% CI: 0.09-0.28) and risk (OR = 1.43, 95% CI: 1.32-1.55) of depression and morbidity were higher in SNL patients than the general population. Elevated prevalence (OR = 0.46, 95% CI: 0.28-0.65) and risk (OR = 1.30, 95% CI: 1.11-1.48) of SNL were also observed in depressed patients. The prevalence of anxiety disorders among SNL patients was about 40% (OR = 0.40, 95% CI: 0.24%-0.57), which was associated with higher risk (OR = 1.83, 95% CI: 1.42-2.24) of development than the general population. Incidence of SNL in patients with anxiety disorders was approximately 31% (OR = 0.31, 95% CI: 0.29-0.33). Additionally, subgroup analyzes showed that the bidirectional associations between SNL, depression, and anxiety disorders was influenced by age, region, and mode of diagnosis of the disorders (SNL, depression, anxiety). Conclusion: There are bidirectional associations between SNL and depression and anxiety disorders, which was influenced by age and region and the method the disorders (SNL, depression, anxiety) were diagnosed.

Genomic profiling in amyloid light-chain amyloidosis reveals mutation profiles associated with overall survival.

Background: Amyloid light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibres derived from immunoglobulin that can lead to irreversible organ damage. Information about genomic profiles of AL amyloidosis is lacking.Methods: In this study, we adopted a two-step strategy to investigate the mutational profile of AL amyloidosis bone marrow plasma cells (PCs) and their clinical implications. In step one, whole-exome sequencing was performed in bone marrow PCs and paired with normal tissue from 10 AL amyloidosis patients, by which we identified 10 significantly mutated genes (SMGs). In step two, we constituted a targeted gene sequencing (TGS) panel covering the frequently mutated genes identified in step one, genes reported in prior AL amyloidosis studies, and known cancer driver mutations. Then, we analysed an expanded cohort of AL amyloidosis patients (N = 48) with this panel comprising 98 genes.Results: Four recurrent mutations were identified by TGS and verified by Sanger sequencing: ASB15 (c. 844 C > T), ASCC3 (c. 1595 A > G), HIST1H1E (c. 311 C > T) and KRAS (c. 35 G > A), among which the first three mutations were associated with inferior overall survival (OS). Additionally, we found that the number of mutations identified by the TGS panel of 98 genes could be a prognostic predictor for OS.Conclusions: In summary, we revealed genomic profiling in AL amyloidosis and found mutation profiles associated with OS.

Differences between low and high grade fetal adenocarcinoma of the lung: a clinicopathological and molecular study.

BACKGROUND: Fetal adenocarcinoma of the lung (FLAC) is a rare entity of lung cancer. It is classified into low-grade fetal adenocarcinoma (L-FLAC) and high-grade fetal adenocarcinoma (H-FLAC). We aim to report the clinicopathological and molecular features of FLAC in Chinese patients. METHODS: FLACs were screened from a consecutive lung adenocarcinoma series comprising 920 cases. The clinicopathological features L-FLAC and H-FLAC were retrospectively reviewed via immunohistochemical study and mutation analysis. RESULTS: Three L-FLAC and five H-FLAC cases were identified. L-FLAC mainly occurred in young patients and was predominantly in stage I upon diagnosis and conferred favorable outcomes. L-FLAC tumors were characterized by the glycogen-rich columnar cells lining the complex glandular structures, with low nuclear atypia, morule formation, and mainly nuclear- and cytoplasmic-localized ß-catenin expression. In contrast, H-FLAC predominantly occurred in elderly men with a history of smoking. The stage of H-FLAC was often advanced at presentation and had a poor prognosis. H-FLAC tumors exhibited more prominent atypia of the nucleus, the absence of morule formation, and largely membrane-localized ß-catenin. All 5 H-FLACs were immunohistochemically characterized by overexpression of the p53 protein; the L-FLAC tumors were negative for p53. Two cases of H-FLAC were positive for AFP. No Her-2 or ALK-D5F3 overexpression was observed in any of the tumors. EGFR L858R point mutation was identified in one of the H-FLAC cases. EGFR T790M mutation was detected in one of the L-FLAC cases. No mutations in KRAS, PIK3CA or BRAF were detected. CONCLUSIONS: L-FLAC and H-FLAC exhibited distinctive clinicopathological, immunophenotypic and molecular features with potential prognostic value.

Circulating free DNA in the era of precision oncology: Pre- and post-analytical concerns.

Cancer treatment has entered the era of precision medicine, where knowledge of a patient's genetic profile is used to facilitate early diagnosis, drug selection, prognosis, prediction of drug responsiveness, the onset of secondary resistance, and relapse. Circulating free DNA (cfDNA) has emerged as an ideal source of genetic information for cancer patients, and numerous studies have explored its validity in various clinical applications. However, clinical implementation of cfDNA-based tests has been slow. In this review, we addressed some of the pre- and post-analytical issues regarding cfDNA tests. First, we summarized the characteristics of cfDNA and reviewed the methods used to identify tumor-derived cfDNA from the pool of total cfDNA. Second, we described the procedures used to extract cfDNA, which have a great impact on representativeness and yield. Finally, we discussed our thoughts on the validation of cfDNA-based tests and the reporting of test results amid drastic limitations.