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

Incidence of and Risk Factors for Recurrent Urinary Tract Infections in Renal Transplant Recipients

Background: Recurrent urinary tract infections (rUTIs) are common after renal transplantation (RTx), and the impact on graft and patient survival remains controversial. Objective: In this study, we investigate the incidence and risk factors for rUTIs in a cohort of RTx recipients and evaluate the effect on graft and patient survival. Design, setting, and participants: A retrospective cohort of adult patients who underwent RTx at Rigshospitalet, Denmark, between 2014 and 2021 was evaluated in this study. Outcome measurements and statistical analysis: Risk factors for rUTIs were explored with a multivariable cause-specific Cox proportional hazard analysis. The Kaplan-Meier estimate was used to assess overall survival. Results and limitations: A total of 571 RTx recipients were included. The median age was 52 yr (interquartile range: 42–62 yr). Of the cases, 62% were deceased donor RTx. A total of 103 recipients experienced rUTIs. We found increasing age (hazard ratio [HR]: 1.02 per year increase, 95% confidence interval [95% CI]: 1.00–1.04, p = 0.02), female gender (HR: 2.1, 95% CI: 1.4–3.3, p < 0.001), history of lower urinary tract symptoms (HR: 2.3, 95% CI: 1.4–3.5, p = 0.001), and a UTI within 30 d of surgery (HR: 3.5, 95% CI: 2.1–5.9, p < 0.001) were associated with rUTIs. No influence of rUTIs on overall or graft survival was observed. Conclusions: One in six patients experience rUTIs after RTx. Pre- and postoperative variables affect the risk of rUTIs, but none are easily modifiable. In this cohort, rUTIs did not affect the graft function or survival. The etiology of rUTIs remains poorly understood, and there is a continuous need to study how rUTIs can be reduced and treated optimally. Patient summary: In this study, we looked at the risk factors for recurrent urinary tract infections in patients after kidney transplantation. We conclude that 21.5% of patients experience recurrent urinary tract infections 5 years after kidney transplantation. Multiple risk factors were found and should be taken into consideration by clinicians

Surgical Complications Following Renal Transplantation in a Large Institutional Cohort

Background. Successful renal transplantation (RTx) relies on immunosuppression and an optimal surgical course with few surgical complications. Studies reporting the postoperative complications after RTx are heterogeneous and often lack systematic reporting of complications. This study aims to describe and identify postoperative short-term and long-term complications after RTx in a large institutional cohort and identify risk factors for a complicated surgical course. Methods. The study is a retrospective single-center cohort of 571 recipients who underwent living or deceased donor open RTx between 2014 and 2021. Data were collected on background information and perioperative and postoperative data. Complications were defined as short-term (30 d) after transplantation and graded according to the Clavien-Dindo classification. Multivariable logistic regression was performed to evaluate risk factors for serious short-term complications and multivariable time-dependent Cox regression to evaluate risk factors for long-term complications. Results. A total of 351 patients received a graft from a deceased donor, and 144 of these grafts were on perfusion machine before transplantation. One or more short-term complications occurred in 345 (60%) patients. Previous RTx was associated with short-term Clavien-Dindo >2 complications in recipients (odds ratio = 2.08; 95% confidence interval [CI], 1.18-3.69; P = 0.01). Being underweight (body mass index 2 and vascular complications. Increasing blood loss per 100 mL was associated with increased odds of short-term Clavien-Dindo >2 (odds ratio = 1.11; 95% CI, 1.01-1.21; P = 0.032). No associations were found for long-term complications after RTx. The 5-y cumulative incidence of graft loss was 12.6% (95% CI, 8.9-16.3). Conclusions. Short-term complications are common after RTx, and risk factors for severe short-term complications include previous RTx, increasing age, and low body mass index. No risk factors were identified for severe long-term complications. Further studies should explore whether new surgical techniques can reduce surgical complications in RTx

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