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PurposeTo develop nomograms that predict the detection of clinically significant prostate cancer (csPCa, defined as ≥GG2 [Grade Group 2]) at diagnostic biopsy based on multiparametric prostate MRI (mpMRI), serum biomarkers, and patient clinicodemographic features.Materials and methodsNomograms were developed from a cohort of biopsy-naïve men presenting to our 11-hospital system with prostate specific antigen (PSA) of 2–20 ng/mL who underwent pre-biopsy mpMRI from March 2018-June 2021 (n = 1494). The outcomes were the presence of csPCa and high-grade prostate cancer (defined as ≥GG3 prostate cancer). Using significant variables on multivariable logistic regression, individual nomograms were developed for men with total PSA, % free PSA, or prostate health index (PHI) when available. The nomograms were both internally validated and evaluated in an independent cohort of 366 men presenting to our hospital system from July 2021-February 2022.Results1031 of 1494 men (69%) underwent biopsy after initial evaluation with mpMRI, 493 (47.8%) of whom were found to have ≥GG2 PCa, and 271 (26.3%) were found to have ≥GG3 PCa. Age, race, highest PIRADS score, prostate health index when available, % free PSA when available, and PSA density were significant predictors of ≥GG2 and ≥GG3 PCa on multivariable analysis and were used for nomogram generation. Accuracy of nomograms in both the training cohort and independent cohort were high, with areas under the curves (AUC) of ≥0.885 in the training cohort and ≥0.896 in the independent validation cohort. In our independent validation cohort, our model for ≥GG2 prostate cancer with PHI saved 39.1% of biopsies (143/366) while only missing 0.8% of csPCa (1/124) with a biopsy threshold of 20% probability of csPCa.ConclusionsHere we developed nomograms combining serum testing and mpMRI to help clinicians risk stratify patients with elevated PSA of 2–20 ng/mL who are being considered for biopsy. Our nomograms are available at https://rossnm1.shinyapps.io/MynMRIskCalculator/ to aid with biopsy decisions.

Background COVID‐19 measures such as masking, social distancing, and staying indoors may mitigate chronic rhinosinusitis (CRS) symptoms. We evaluate whether these measures correlated with improved symptoms in patients with CRS. Methods This retrospective study compared SNOT‐22 survey data from the Northwestern CRS Registry at the time of enrollment and at years 1–5 of follow‐up. The final sample consisted of 1826 SNOT‐22 surveys for 598 patients. April 10, 2020 to December 31, 2021 was considered \"during the pandemic\" and prior to March 11, 2020 was considered \"pre‐pandemic.\" Wilcoxon test was used to compare SNOT22 at enrollment pre‐pandemic versus during pandemic. Separate linear mixed models were performed to estimate SNOT22 at 1 to 5 years after enrollment pre‐pandemic versus during pandemic. Results Subjects enrolled during the pandemic had worse SNOT22 scores than those enrolled pre‐pandemic (53 vs. 42, p = .0024). Total SNOT‐22 scores were improved during the pandemic than before the pandemic at 1 year follow‐up (18.17 vs. 12.22, p = .001). This effect persists when evaluating the nasal (7.33 vs. 5.13, p = .003), sleep (2.63 vs. 1.39, p = .008), function (1.40 vs. 0.72, p = .015), and emotion (0.77 vs. 0.17, p < .001) domains individually. There was no statistically significant difference in total SNOT‐22 score at Years 2–5 of follow‐up. Conclusions Patients with CRS experience a greater reduction in symptom severity in their first year of treatment during the pandemic than before the pandemic, plausibly from measures such as masking and staying indoors. Level of Evidence 4

Social media (SoMe) offers great potential to expand access to health information, but a significant proportion of users consume its content instead of consulting a physician. We sought to quantify the volume and characterize the accuracy of men’s health-related content on TikTok and Instagram. We searched TikTok and Instagram for the terms: testosterone, erectile dysfunction, male infertility, semen retention, Peyronie’s disease, and vasectomy. The top 10 hashtags for each term were used to estimate the total impressions for each term on each platform, and posts were then characterized by creator type, content type, and accuracy (1 to 5 scale). TikTok had 2,312,407,100 impressions and Instagram had 3,107,300 posts across all topics. Semen retention had the most impressions on TikTok (1,216,074,000) and posts on Instagram (1,077,000). Physicians created only a small portion of total TikTok and Instagram posts (10.3% and 12.9%, respectively). Across all topics, the accuracy of content was poor (2.6 ± 1.7), however, physician posts were more accurate than non-physician posts (mean 4.2 ± 1.2 vs 2.3 ± 1.6, p  < 0.001, respectively). Men’s health content is popular on TikTok and Instagram but is not accurate. We recommend that physicians actively engage in SoMe to address misinformation.

We sought to characterize the prevalence of sexual dysfunction and barriers to treatment among male physicians. Between June and December 2022, male physicians were invited to complete a questionnaire regarding sexual function. Surveys were disseminated electronically via social media and professional medical societies using Qualtrics (Provo, UT). In totla, 235 responses were included in the final analysis. The mean age of respondents was 36.3 ± 7.4 years (range 23–72). 27 (11.5%) reported having seen a doctor for sexual health. Of these 27, 40.7% saw a physician for erectile dysfunction, 29.6% for low libido, 22.2% for premature ejaculation, 7.4% for delayed ejaculation, and 33.3% for other concerns. An additional 29 (12.3%) considered establishing care for sexual issues but didn’t, mostly due to being too busy. 46 (19.6%) respondents reported having taken medication to improve erectile function. Therefore, in a cohort of young male physicians, 23.8% had seen or considered seeing a doctor for sexual health concerns, and nearly 1 in 5 had taken medication for erectile dysfunction. Male physicians appear to be at higher risk for sexual dysfunction than the general population and face significant and unique barriers in access to care for sexual dysfunction.

The COVID-19 pandemic has had a profound global impact on governments, health care systems, economies, and populations around the world. Within the East Asia and Pacific region, some countries have mitigated the spread of the novel coronavirus effectively and largely avoided severe negative consequences, while others still struggle with containment. As the second wave reaches East Asia and the Pacific, it becomes more evident that additional SARS-CoV-2 surveillance is needed to track recent shifts, rates of increase, and persistence associated with the pandemic. The goal of this study is to provide advanced surveillance metrics for COVID-19 transmission that account for speed, acceleration, jerk, persistence, and weekly shifts, to better understand country risk for explosive growth and those countries who are managing the pandemic successfully. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed. We provide novel indicators to measure disease transmission. Using a longitudinal trend analysis study design, we extracted 330 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in East Asia and the Pacific as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. The standard surveillance metrics for Indonesia, the Philippines, and Myanmar were concerning as they had the largest new caseloads at 4301, 2588, and 1387, respectively. When looking at the acceleration of new COVID-19 infections, we found that French Polynesia, Malaysia, and the Philippines had rates at 3.17, 0.22, and 0.06 per 100,000. These three countries also ranked highest in terms of jerk at 15.45, 0.10, and 0.04, respectively. Two of the most populous countries in East Asia and the Pacific, Indonesia and the Philippines, have alarming surveillance metrics. These two countries rank highest in new infections in the region. The highest rates of speed, acceleration, and positive upwards jerk belong to French Polynesia, Malaysia, and the Philippines, and may result in explosive growth. While all countries in East Asia and the Pacific need to be cautious about reopening their countries since outbreaks are likely to occur in the second wave of COVID-19, the country of greatest concern is the Philippines. Based on standard and enhanced surveillance, the Philippines has not gained control of the COVID-19 epidemic, which is particularly troubling because the country ranks 4th in population in the region. Without extreme and rigid social distancing, quarantines, hygiene, and masking to reverse trends, the Philippines will remain on the global top 5 list of worst COVID-19 outbreaks resulting in high morbidity and mortality. The second wave will only exacerbate existing conditions and increase COVID-19 transmissions.

Introduction Low testosterone (T) is linked with frailty, which predicts poor postoperative recovery across many surgical procedures. Therefore, low T may impact perioperative outcomes for surgical patients. We sought to characterize the association between low T, frailty, and perioperative outcomes in patients undergoing transurethral resection of the prostate (TURP) and laser photovaporization of the prostate (PVP). Materials and methods We retrospectively reviewed men across our integrated healthcare system who underwent TURP or PVP with a recorded T level within one year prior to their procedure date. Low T was defined as a serum T <300 ng/dL. We compared clinical characteristics, lab values, and frailty, determined by the Hospital Frailty Risk Score (HFRS), of patients with low vs. normal T. Univariable and multivariable analyses were used to assess the association between low T and hospital readmission at 30, 90, and 180 days postoperatively. Results Among 175 patients who underwent either TURP or PVP, 86 (49.1%) had low T, and 89 (50.9%) had normal T. Patients with low T were older (68.7 ± 9.3 vs. 64.8 ± 11.8 years old, p = 0.016) and had longer postoperative length of stay (4.2 ± 10.5 vs. 1.4 ± 0.9 days, p = 0.03). Patients with low T had a significantly higher rate of readmission within 180 days (28% vs. 13%, p = 0.02). Low T was not independently associated with frailty. On univariable logistic regression, preoperative T was associated with readmission at 90 and 180 days. On multivariable regression, low preoperative T was no longer associated with 90-day readmission. Conclusions Almost half of the men undergoing transurethral surgery in our cohort had low T. Low T was independently associated with a higher risk of 180-day readmission on multivariable analysis. These findings indicate a possible prognostic role for low T screening in men undergoing transurethral prostatic surgery. Further studies are needed to determine whether preoperative treatment of low T can impact perioperative outcomes.

The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges’ g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

Studies of DNA methylation (DNAm) in solid human tissues are relatively scarce; tissue-specific characterization of DNAm is needed to understand its role in gene regulation and its relevance to complex traits. We generated array-based DNAm profiles for 987 human samples from the Genotype-Tissue Expression (GTEx) project, representing 9 tissue types and 424 subjects. We characterized methylome and transcriptome correlations (eQTMs), genetic regulation in cis (mQTLs and eQTLs) across tissues and e/mQTLs links to complex traits. We identified mQTLs for 286,152 CpG sites, many of which (>5%) show tissue specificity, and mQTL colocalizations with 2,254 distinct GWAS hits across 83 traits. For 91% of these loci, a candidate gene link was identified by integration of functional maps, including eQTMs, and/or eQTL colocalization, but only 33% of loci involved an eQTL and mQTL present in the same tissue type. With this DNAm-focused integrative analysis, we contribute to the understanding of molecular regulatory mechanisms in human tissues and their impact on complex traits. As part of the enhanced GTEx (eGTEx) project, 987 human samples from 9 tissue types and 424 donors are assayed using DNA methylation microarrays. Colocalization of GWAS variants, eQTLs and mQTLs shows diverse links between genetic variation, molecular phenotypes and complex traits.

Inherited genetic variation affects local gene expression and DNA methylation in humans. Most expression quantitative trait loci ( cis -eQTLs) occur at the same genomic location as a methylation QTL ( cis -meQTL), suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, here we use co-localization methods to identify eQTL-meQTL pairs likely to share a causal variant. We use partial correlation and mediation analyses to identify >400 of these pairs showing evidence of a causal relationship between expression and methylation (i.e., shared mechanism) with many additional pairs we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite associations with expression and methylation, although many SNPs affect multiple CpGs in opposite directions. This work demonstrates the pervasiveness of co-regulated expression and methylation in the human genome. Applying this approach to other types of molecular QTLs can enhance our understanding of regulatory mechanisms. Most expression QTLs (eQTLs) co-occur with a DNA methylation QTL (meQTL), suggesting a common causal variant. Here the authors analyse DNA and RNA from blood and identify eQTL-meQTL pairs likely to share a causal variant, finding that expression and methylation are often genetically co-regulated.

The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.