Search

Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assays effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Ushers syndrome, Lebers congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

Medical deep neural networks (DNNs) trained upon coarse image inputs are inherently insensible to fine-grained anatomic features. To enhance DNN perception on delicate microvascular structures, we proposed using a straightforward angiographic mobile-dense hybrid network (AMDenseNet) in tandem with a flexible input split, suppression, and swap perturbation (InSSS-P) framework to perform explainable diagnostics for microvascular diseases. Mechanistically, InSSS-P and AMDenseNet conjointly (1) decompose complex anatomy inputs into LEGO-like blocks, then (2) distill plexus-wise vascular block significance from the rearranged anatomy input-output samplings. To validate the robustness of the proposed model, we trained AMDenseNet to detect blind-threatening retina exudative age-related macular degeneration (exAMD) from the micrometer-scaled optic coherence tomographic angiography (OCTA), wherein our AMDenseNet annotated triple-specific (plexus, branch, and exudate activity) neovascular (NV) features at a diagnostic precision that is comparable to the gold standard dye-based angiography. Interestingly, when we applied plexus-wise InSSS-P to the AMDenseNet predictions, the permutate results demonstrated that input perturbation at deep capillary plexus (DCP) layer abrogated model-awared exAMD features and resulted in false-negative exAMD impressions. On the contrary, choroid capillary (CC) input perturbations contributed to false-positive exAMD characterization. Notably, the AMDenseNet triple-specific NV annotation functionality was disrupted by either DCP or CC input perturbations, indicating the significance of DCP and CC in the task of exAMD characterization. In sum, this study employed anatomy decomposition approaches to distill plexus-wise microvascular significance and highlighted the analytic potential of leveraging an anatomy-sensible model to discover novel disease biomarkers. [ABSTRACT FROM AUTHOR]

Background: Sjögren's Syndrome (SS), mainly affecting women in their midlife, is characterized by persistent inflammation in glands producing tears and saliva, often leading to significant complications. This study investigates the differences in autonomic system functioning between individuals with SS and healthy controls. Methods: From April 2019 to December 2022, 329 diagnosed primary SS (pSS) patients and 30 healthy controls were enrolled at Taipei Veterans General Hospital, Taipei, Taiwan. The study assessed autonomic nervous system functioning using various HRV metrics. Participants were divided based on age and AECG criteria, including salivary gland biopsy and autoantibody status. Results: Significant differences in Heart Rate Variability (HRV) were observed between pSS patients and healthy controls. The total power index was notably lower in pSS patients (4.98 ± 1.29) than in controls (5.54 ± 1.21, p =.022). Additionally, Vagal (VAG) activity was significantly reduced in the pSS group (4.95 ± 1.33) compared to the healthy control group (5.47 ± 1.19, p =.041). Age‐stratified analysis highlighted that the ≤50 years pSS group had a higher heart rate (77.74 ± 10.42) compared to the >50 years group (73.86 ± 10.35, p =.005). This group also showed a higher total power index (5.78 ± 1.30) versus the >50 years group (4.68 ± 1.19, p <.001), and significantly lower VAG activity (4.70 ± 1.26, p =.007) compared to healthy controls. Furthermore, the Standard Deviation of Normal‐to‐Normal Intervals (SDNN) was greater in the ≤50 years SS group (44.45 ± 37.12) than in the >50 years group (33.51 ± 26.18, p =.007). In pSS patients, those positive for both salivary gland biopsy and autoantibodies demonstrated a lower Total Power (4.25 ± 1.32) and R‐wave validity (93.50 ± 4.79, p <.05) than other groups, suggesting more severe autonomic imbalance. The R‐R interval variation (RRIV) was also significantly higher in this dual‐positive group (696.10 ± 975.41, p <.05). Additionally, the ESSPRI for dryness was markedly higher in the dual‐positive group (8.10 ± 1.45, p <.05), indicating more severe symptoms. These findings reveal significant variations in autonomic function in SS patients, especially in those with dual‐positive biopsy and autoantibody status. Conclusion: This study demonstrates significant autonomic dysfunction in pSS patients compared to healthy controls, particularly in those positive for both salivary gland biopsy and autoantibodies. The age‐stratified analysis further emphasizes the impact of aging on autonomic system functioning in pSS, suggesting a need for age‐specific management approaches in pSS patient care. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with end stage renal disease have a high all-cause and cardiovascular mortality. Secondary hyperparathyroidism and vitamin D deficiency are considered part of the mechanism for the excess mortality observed. We aimed to evaluate the relationship between vitamin D use and all-cause mortality. Methods In this retrospective cohort study, we included all incident patients who started hemodialysis in Taiwan between 2001 and 2009. Patients were followed from landmark time, i.e., the 360th day from hemodialysis initiation, through the end of 2010 or death. We evaluated the association between activated vitamin D use or not before landmark time and all-cause mortality using conditional landmark analysis with Cox regression. We used group-based trajectory model to categorize high-dose versus average-dose users to evaluate dose-response relationships. Results During the median follow-up of 1019 days from landmark time, vitamin D users had a lower crude mortality rate than non-users (8.98 versus 12.93 per 100 person-years). Compared with non-users, vitamin D users was associated with a lower risk of death in multivariate Cox model (HR 0.91 [95% CI, 0.87–0.95]) and after propensity score matching (HR 0.94 [95% CI, 0.90–0.98]). High-dose vitamin D users had a lower risk of death than conventional-dose users, HR 0.75 [95% CI, 0.63–0.89]. The association of vitamin D treatment with reduced mortality did not alter when we re-defined landmark time as the 180th day or repeated analyses in patients who underwent hemodialysis in the hospital setting. Conclusions Our findings supported the survival benefits of activated vitamin D among incident hemodialysis patients.

Background and study aims Endoscopic mucosal resection (EMR) is a standard method for removing sessile colorectal polyps ≥ 10 mm. Recently, underwater EMR (UEMR) has been introduced as a potential alternative. However, the effectiveness and safety of UEMR compared with conventional EMR is un clear. Patients and methods In this 1:1 propensity score (PS) matched retrospective cohort study, we compared the en bloc resection rates, procedure time, intraprocedural and delayed bleeding rates, and incidence of muscle layer injury. We also performed subgroup analyses by sizes of polyps (