Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

An effective day case treatment combination for refractory neuropathic mixed incontinence

OBJECTIVE: Women with drug refractory neurogenic mixed incontinence (NMI) have limited minimally invasive treatment options and require reconstructive surgery. We examined efficacy of a combination of day case intradetrusor (ID) botulinum toxin (BTX-A) bladder injections and transobturator (TOT) or tension free vaginal tape (TVT). MATERIALS AND METHODS: Eleven women who are pharmacotherapy intolerant or who have drug refractory NMI were treated. Two opted for open surgery and the remaining 9 received 1000 units of Dysport diluted in 30 mL saline cystoscopically at 30 ID sites followed by TOT in 6 or TVT in 3 as a day case combination treatment. Patient demographics, pre and post treatment videocystometrogram (VCMG), pad test and International Committee on Incontinence Questionnaire (ICIQ) scores were recorded. At 6 weeks (repeat ICIQ, pad test and patient satisfaction), at 3 and 12 months (VCMG) and 'current' (ICIQ and patient satisfaction) was recorded. RESULTS: The mean age was 56.7 years (range 41 to 78) with a mean follow up of 19.1 months (range 7 to 33). All women were continent at 3 and 12 months. Quality of life (ICIQ scores) improved at 6 weeks (p > 0.001) and remained stable up to the last follow up (p > 0.001). Eight women have stopped using pads. At 3 months, there was significant improvement in MDP (p > 0.014) and MCC (p = 0.002). Anticholinergics were discontinued in 7 with global high satisfaction with the treatment BTX-A injections were repeated in 4 (mean 13.5 months). CONCLUSION: Anticholinergic refractory women with NMI can be effectively treated as a day case with combination of ID BTX-A injections and TVT or TOT

Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array

Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (