Genome-wide analyses identify 21 infertility loci and over 400 reproductive hormone loci across the allele frequency spectrum.

Genome-wide association studies (GWASs) may help inform treatments for infertility, whose causes remain unknown in many cases. Here we present GWAS meta-analyses across six cohorts for male and female infertility in up to 41,200 cases and 687,005 controls. We identified 21 genetic risk loci for infertility (P≤5E-08), of which 12 have not been reported for any reproductive condition. We found positive genetic correlations between endometriosis and all-cause female infertility (rg=0.585, P=8.98E-14), and between polycystic ovary syndrome and anovulatory infertility (rg=0.403, P=2.16E-03). The evolutionary persistence of female infertility-risk alleles in EBAG9 may be explained by recent directional selection. We additionally identified up to 269 genetic loci associated with follicle-stimulating hormone (FSH), luteinising hormone, oestradiol, and testosterone through sex-specific GWAS meta-analyses (N=6,095-246,862). While hormone-associated variants near FSHB and ARL14EP colocalised with signals for anovulatory infertility, we found no rg between female infertility and reproductive hormones (P>0.05). Exome sequencing analyses in the UK Biobank (N=197,340) revealed that women carrying testosterone-lowering rare variants in GPC2 were at higher risk of infertility (OR=2.63, P=1.25E-03). Taken together, our results suggest that while individual genes associated with hormone regulation may be relevant for fertility, there is limited genetic evidence for correlation between reproductive hormones and infertility at the population level. We provide the first comprehensive view of the genetic architecture of infertility across multiple diagnostic criteria in men and women, and characterise its relationship to other health conditions.

Clinical evolution and mortality of critically ill patients with SARS-CoV-2 pneumonia treated with remdesivir in an adult intensive care unit of Paraguay.

BACKGROUND: The health crisis due to Covid-19 led to the search for therapeutics that could improve the evolution of the disease. Remdesivir, an antiviral that interferes with viral replication, was one of the first to be used for the treatment of this pathology. OBJECTIVE: To determine clinical course and mortality of patients with severe SARS-CoV-2 pneumonia treated with remdesivir, in comparison of those who didn't receive the medication. PATIENTS AND METHODS: Retrospective cohort study, with medical records review of COVID-19 patients, between August 2020 and August 2021. The subjects were divided into two groups, those who received remdesivir before or after admission to intensive care and those who didn't. The primary outcome variable was mortality in intensive care. RESULTS: Of 214 subjects included, 109 (50,9%) received remdesivir. The median of days for the drug administration was 8 (2-20), IQR: 3. The bivariate analysis prove that the use of remdesivir was related with lower risk of develop Acute Respiratory Distress Syndrome (ARDS) (p = 0,019; OR: 0,521) and lower requirement of mechanical ventilation (p = 0,006; OR:0,450). Additionally, patients treated with remdesivir develop less kidney injury (p = 0,009; OR: 0,441). There was a total of 82 deaths, 29 (26,6%) in the remdesivir group and 53 (50,5%) in the control group [p < 0,001; OR: 0,356 (0,201-0,630)]. All the risk factors associated with mortality in the bivariate analysis were entered into the multivariate analysis by logistic regression, the use of remdesivir remained associated as an independent protective factor to mortality (p = 0.034; OR: 0.429). CONCLUSION: Critically ill patients with SARS-CoV-2 pneumonia treated with remdesivir had a lower risk of death and need for mechanical ventilation and develop less ARDS as compared to the control group. No differences were found in the presentation of adverse effects.

Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

Academic Rank and Productivity Among United States Cardiothoracic Surgeons.

BACKGROUND: Despite a significant growth of women trainees in cardiothoracic surgery recently, women remain a minority of cardiothoracic surgeons and hold a minority of leadership positions. This study evaluates differences in cardiothoracic surgeon subspecialty choices, academic rank, and academic productivity between men and women. METHODS: The Accreditation Council for Graduate Medical Education database was used to identify 78 cardiothoracic surgery academic programs in the United States, including integrated, 4+3, and traditional fellowships, as of June 2020. A total of 1179 faculty members were identified within these programs, 585 adult cardiac surgeons (50%), 386 thoracic surgeons (33%), and 168 congenital surgeons (14%), and other, 40 (3%). Data were collected using institutional websites, ctsnet.org, doximity.com, linkedin.com, and Scopus. RESULTS: Of the 1179 surgeons, only 9.6% were women. Overall, women composed 6.7% of adult cardiac, 15% of thoracic, and 7.7% of congenital surgeons. Among subspecialties, women represent 4.5% (17 of 376) of full professors and 5% (11 of 195) of division chiefs in cardiothoracic surgery in the United States, have shorter career durations, and lower h-indices compared with men. However, women had similar m-indices, which factors in career length, compared with men in adult cardiac (0.63 vs 0.73), thoracic (0.77 vs 0.90), and congenital (0.67 vs 0.78) surgeons. CONCLUSIONS: Career duration, including cumulative research productivity, appears to be the most important factors predicting full professor rank, potentially contributing to persistent sex-based disparities in academic cardiothoracic surgery.