Smoking and lower urinary tract symptoms in Reduction by Dutasteride of Prostate Cancer Events Trial.

BACKGROUND: Benign prostatic hyperplasia is common in older men, with many developing lower urinary tract symptoms (LUTS) that impair quality of life. Smoking has many well-established adverse effects, but its effects on benign prostatic hypertrophy (BPH) and associated LUTS are unclear. We sought to determine if smoking is a risk factor for the incidence of LUTS in asymptomatic men and for the progression of LUTS in symptomatic men. METHODS: We performed a post-hoc analysis of Reduction by Dutasteride of Prostate Cancer Events in 3060 "asymptomatic" men with baseline International Prostate Symptom Score (IPSS) < 8 and in 2198 symptomatic men with baseline IPSS ≥ 8 not taking 5α-reductase inhibitors or α-blockers. We used multivariable Cox regression models to assess associations between smoking status at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first report of medical or surgical treatment for BPH, or sustained clinically significant LUTS (two reports of IPSS > 14). Among symptomatic men, LUTS progression was defined as IPSS increase of ≥4 points from baseline, surgical intervention for BPH, or starting a new BPH drug. RESULTS: Of 3060 asymptomatic men, 15% (n = 467) were current, 40% (n = 1231) former, and 45% (n = 1362) never-smokers. Of 2198 symptomatic men, 14% (n = 320) were current, 39% (n = 850) former, and 47% (n = 1028) never-smokers. In asymptomatic men, compared with never-smokers, current and former smoking at baseline were not associated with LUTS incidence (adjusted hazard ratio [adj-HR] = 1.08; 95% confidence interval [95% CI]: 0.78-1.48 and adj-HR = 1.01; 95% CI: 0.80-1.30). In symptomatic men, compared with never-smokers, current and former smoking at baseline were not associated with the progression of LUTS (adj-HR = 1.11; 95% CI: 0.92-1.33 and adj-HR = 1.03; 95% CI: 0.90-1.18). CONCLUSIONS: In REDUCE, smoking status was not associated with either incident LUTS in asymptomatic men or progression of LUTS in symptomatic men.

Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy.

Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8+ T cell axis in both blood and inflamed joints. CX3CR1hi CD8+ T cells in blood and CXCR3hi CD8+ T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1hi CD8+ T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.

Statin Use and Lower Urinary Tract Symptoms Incidence and Progression in Reduction by Dutasteride of Prostate Cancer Events (REDUCE) Trial.

PURPOSE: Benign prostatic hyperplasia (BPH) is a common disease often manifested by lower urinary tract symptoms (LUTS). We previously found statins were associated with modest attenuations in prostate growth over time in REDUCE. We tested whether statins were associated with LUTS incidence in asymptomatic men and LUTS progression in symptomatic men. MATERIALS AND METHODS: We performed a post-hoc analysis of REDUCE in 3,060 "asymptomatic" men with baseline International Prostate Symptom Score (IPSS) <8 and in 2,198 symptomatic men with baseline IPSS ≥8 not taking α-blockers or 5α-reductase inhibitors. We used multivariable Cox regression models to assess associations between statin use at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first reported medical or surgical treatment for BPH or sustained clinically significant LUTS (2 reports of IPSS >14). Among symptomatic men, LUTS progression was defined as IPSS increase ≥4 points from baseline, any surgical procedure for BPH, or initiation of a BPH drug. RESULTS: Among asymptomatic and symptomatic men, 550 (18%) and 392 (18%) used statins at baseline, respectively. On multivariable analysis, statin use was not associated with LUTS incidence (HR 1.05; 95% CI 0.78-1.41, p=0.74) in asymptomatic men, or with LUTS progression (HR 1.13; 95% CI 0.96-1.33, p=0.15) in symptomatic men. Similar results were seen in the dutasteride and placebo arms when stratified by treatment assignment. CONCLUSIONS: In REDUCE, statin use was not associated with either incident LUTS in asymptomatic men or LUTS progression in symptomatic men. These data do not support a role for statins in LUTS prevention or management.

Deoxyfluorination of Carboxylic Acids with KF and Highly Electron-Deficient Fluoroarenes.

A deoxyfluorination reaction of carboxylic acids using potassium fluoride (KF) and highly electron-deficient fluoroarenes is reported here, giving acyl fluorides in moderate to excellent yield (57-92% based on NMR integration and 34-95% for isolated examples).

Analysis of Medical Data Using Community Detection on Inferred Networks.

Performing network-based analysis on medical and biological data makes a wide variety of machine learning tools available. Clustering, which can be used for classification, presents opportunities for identifying hard-to-reach groups for the development of customized health interventions. Due to a desire to convert abundant DNA gene co-expression data into networks, many graph inference methods have been developed. Likewise there are many clustering and classification tools. This paper presents a comparison of techniques for graph inference and clustering, using different numbers of features, in order to select the best tuple of graph inference method, clustering method, and number of features according to a particular phenotype. An extensive machine learning based analysis of the REGARDS dataset is conducted, evaluating the CoNet and K-Nearest Neighbors (KNN) network inference methods, along with the Louvain, Leiden and NBR-Clust clustering techniques. Results from analysis involving five internal cluster evaluation indices show the traditional KNN inference method and NBR-Clust and Louvain clustering produce the most promising clusters with medical phenotype data. It is also shown that visualization can aid in interpreting the clusters, and that the clusters produced can identify meaningful groups indicating customized interventions.

Investigation of round goby viral haemorrhagic septicaemia outbreak in New York.

Eleven viral haemorrhagic septicaemia virus (VHSV) genotype IVb isolates were sequenced, and their genetic variation explored to determine the source of a VHS outbreak on the eastern shore of Cayuga Lake. An active fish kill of round gobies (Neogobius melanostomus, Pallas) was intensively sampled at King Ferry, NY and nearby Long Point State Park in May 2017. Gross lesions observed on 67 moribund round gobies and two rock bass (Ambloplites rupestris, Rafinesque) included moderately haemorrhagic internal organs and erythematous areas on the head, flank, and fins. RT-qPCR tests for VHSV were positive for all 69 fish. Viral isolation on epithelioma papulosum cyprinid cells showed cytopathic effect characteristic of VHSV for six round goby samples from King Ferry. The complete nucleotide sequence of the VHSV IVb genomes of five Cayuga Lake round goby isolates were derived on an Illumina platform along with 2017 VHSV IVb isolates from round gobies collected from the following: Lake Erie near Dunkirk, NY; the St. Lawrence River near Clayton and Cape Vincent, NY; and Lake St. Lawrence near Massena, NY. The phylogenetic tree created from these aligned sequences and four other complete VHSV IVb genomes shows Cayuga Lake isolates are closely related to the Lake Erie isolates.

Predictors of spontaneous ureteral stone passage in the presence of an indwelling ureteral stent.

Patients presenting acutely with obstructing stones often have a ureteral stent placed as a temporizing solution. Ureteroscopy is then commonly performed in a staged fashion, but occasionally the stone is found to have passed. We aimed to identify the frequency and predictors of ureteral stone passage with a stent in place. Records were reviewed to identify patients who had a stent placed for a single ureteral stone. Subsequent ureteroscopy or CT scan was used to ascertain stone passage. Effect of age, gender, BMI, stone diameter, alpha blocker use, urinary tract infection, hydronephrosis, and stent duration on stone passage was assessed. Inclusion and exclusion criteria were met in 209 patients. Mean maximum stone diameter was 6.5 ± 2.5 mm. Passage rates for stones < 3 mm, 3-4.9 mm, 5-6.9 mm, and ≥ 7 mm were 50%, 13%, 10%, and 0%, respectively. The overall rate of passage was 8%. Stone passage was associated with smaller maximum stone diameter, more distal stone location, and longer duration of stent before ureteroscopy/CT on univariate analysis (p < 0.01). Stone diameter and stent duration remained significantly associated on multivariable analysis (p = 0.001 and p = 0.05, respectively). Our findings suggest ureteral stone passage with a concurrent ureteral stent is not a rare event as it occurred in 14% of stones less then 7 mm in maximum diameter. Stone size and duration of stent before ureteroscopy or CT were found to be independent predictors of passage. Select patients with small ureteral stones who have been stented should be considered for a trial of urine straining or repeat imaging before subsequent ureteroscopy.

Racial Variation in the Outcome of Subsequent Prostate Biopsies in Men With an Initial Diagnosis of Atypical Small Acinar Proliferation.

BACKGROUND: African American (AA) men are known to have more aggressive prostate cancer (PCa) compared with Caucasian American men. We sought to determine predictors of subsequent detection and risk stratification of PCa in a racially diverse group of men with atypical small acinar proliferation (ASAP) on initial prostate biopsy. MATERIALS AND METHODS: A retrospective analysis was conducted on data from men with ASAP on initial prostate biopsy who subsequently received confirmatory biopsies between September 2000 and July 2015. Biopsies with more than 3 years between initial and confirmatory biopsies were excluded. Race, age, body mass index, transrectal ultrasound volume, serum prostate-specific antigen (PSA), PSA velocity, PSA density, and elapsed time between biopsies were assessed for predictive value in subsequent PCa diagnosis after an initial finding of ASAP. RESULTS: Of 106 men analyzed, 75 (71%) were AA and 31 (29%) were non-AA. Baseline variables revealed AA men had higher PSA levels, PSA velocity, and PSA density (all P < .05). PCa was diagnosed in subsequent biopsy in 42 (40%) patients without significant racial variation; 30 (40%) AA versus 12 (39%) non-AA. Of the 42 PCa patients, 25 (24%) met Epstein criteria for significant disease without racial variation; 18 (24%) AA versus 7 (23%) non-AA. Only 10 (9%) patients had any component of Gleason 4; 7 (9%) AA versus 3 (10%) non-AA. In multivariate analysis, increasing age, PSA level, and PSA density were significant predictors of PCa. CONCLUSION: AA men diagnosed with ASAP on initial prostate biopsy do not have increased risk of PCa on confirmatory biopsy compared with non-AA men.