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Although five-alpha reductase inhibitor (5-ARI) is one of standard treatment for benign prostatic hyperplasia (BPH) or alopecia, potential complications after 5-ARI have been issues recently. This study aimed to investigate the risk of depression after taking 5-ARI and to quantify the risk using meta-analysis. Materials and Methods: Materials and Methods: A total of 209,940 patients including 207,798 in 5-ARI treatment groups and 110,118 in control groups from five studies were included for final analysis. Inclusion criteria for finial analysis incudes clinical outcomes regarding depression risk in BPH or alopecia patients. Overall hazard ratio (HR) and odds ratio (OR) for depression were analyzed. Moderator analysis and sensitivity analysis were performed to determine whether HR or OR could be affected by any variables, including number of patients, age, study type, and control type. Results: Results: The pooled overall HRs for the 5-ARI medication was 1.23 (95% confidence interval [CI], 0.99-1.54) in a random effects model. The pooled overall ORs for the 5-ARI medication was 1.19 (95% CI, 0.95-1.49) in random effects model. The subgroup analysis showed that non-cohort studies had higher values of HR and OR than cohort studies. Moderator analysis using meta-regression showed that there were no variables that affect the significant difference in HR and OR outcomes. However, in sensitivity analysis, HR was significantly increased by age (p=0.040). Conclusions: Conclusions: Overall risk of depression after 5-ARI was significantly not high, however its clinical importance needs validation by further studies. These quantitative results could provide useful information for both clinicians and patients.

Objective Residual regurgitation is common after congenital surgery for right ventricular outflow tract malformation. It is accepted as there is no competent valve solution in a growing child. We investigated a new surgical technique of trileaflet semilunar valve reconstruction possessing the potential of remaining sufficient and allow for some growth with the child. In this proof-of-concept study, our aim was to evaluate if it is achievable as a functional pulmonary valve reconstruction in vitro. Methods Explanted pulmonary trunks from porcine hearts were evaluated in a pulsatile flow-loop model. First, the native pulmonary trunk was investigated, after which the native leaflets were explanted. Then, trileaflet semilunar valve reconstruction was performed and investigated. All valves were initially investigated at a flow output of 4 L/min and subsequently at 7 L/min. The characterization was based on hydrodynamic pressure and echocardiographic measurements. Results Eight pulmonary trunks were evaluated. All valves are competent on colour Doppler. There is no difference in mean pulmonary systolic artery pressure gradient at 4 L/min (P = 0.32) and at 7 L/min (P = 0.20). Coaptation length is increased in the neo-valve at 4 L/min (P < 0.001, P < 0.001, P = 0.008) and at 7 L/min (P < 0.001, P = 0.006, P = 0.006). A windmill shape is observed in all neo-valves. Conclusions Trileaflet semilunar valve reconstruction is sufficient and not-stenotic. It resulted in an increased coaptation length and a windmill shape, which is speculated to decrease with growth of the patient, yet remain sufficient as a transitional procedure until a long-term solution is feasible. Further in vivo investigations are warranted.

Background: Cancer genomes are shaped by DNA damage and repair. DNA Repair deficiencies in cancers may result in characteristic mutational patterns, as exemplified by deficiency of BRCA1/2 and efficacy prediction for PARP-inhibitors. We systematically evaluated the ability to identify and predict mono- or biallelic deficiencies of 736 DDR genes from associations with genome-wide mutational patterns, including structural variants, across 6,065 whole-genome sequenced cancers. Results: We assembled 535 cancer-specific patient cohorts with shared deficiency of a DNA damage response gene. We trained and evaluated a predictive model for each cohort, and shortlisted 24 gene deficiencies that could be predicted with high accuracy from mutational patterns. These included expected gene deficiency models for BRCA1/2, MSH3/6, TP53, and CDK12. CDK12 is associated with tandem-duplications, and we demonstrate that this association can predict gene deficiency with high accuracy (AUROC=0.97) in prostate cancers. Our novel associations include deficiencies of ATRX, IDH1, HERC2, CDKN2A, PTEN, and SMARCA4. We found that loss of ATRX or IDH1, which are often co-mutated, were associated with the same mutational phenotype in central nervous system cancers; HERC2 loss was associated with an increased number of short deletions in skin cancers and significantly co-occurring with TP53 loss; and PTEN loss was associated with decreased levels of structural rearrangements in cancers of the uterus and the central nervous system. Conclusion: Our systematic, generic approach yielded a catalogue of predictive models, which may provide targets for research and development of treatment, and potentially help guide therapy.

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