Background:Insomnia characterised by difficulties in falling asleep and maintaining sleep, and early awaking, is a prevalent worldwide sleep disorder. While previous studies have suggested an association between insomnia and adverse glycaemic control, the evidence remains inconclusive. Therefore, this meta-analysis aims to explore this association. Methods:Insomnia was assessed based on defined criteria, including related symptoms such as poor sleep quality and low sleep efficiency. Glycaemic control was evaluated using indicators such as fasting plasma glucose, haemoglobin A1c, and the presence of diabetes. A literature search was performed in PubMed, Web of Science, and Scopus. The quality of the included studied was assessed using The Newcastle-Ottawa Scale. Effect sizes, including odds ratio, relative risk, mean difference, and standard mean difference, were chosen based on data type. Forest plots visually displayed pooled effect sizes and corresponding 95% confidence intervals, while the I2 test calculated heterogeneity. Meta-regression and subgroup analysis explored potential sources of heterogeneity. Leave-one-out sensitivity analysis assessed result robustness, and Begg's and Egger's tests evaluated publication bias. Results:Ninety-one articles, comprising 84 are cross-sectional studies, (five are case-control studies, and two are cohort studies) with 2 217 521 participants, were included. Ten separate meta-analyses were conducted based on variable type (binary/continuous), study design (cross-sectional, case-control, or cohort), and measurement of exposures/outcomes. All meta-analyses indicated a positive association between insomnia (related symptoms) and adverse glycaemic control. However, three meta-analyses showed significant heterogeneity, and three lacked robustness. No publication bias was detected across any of the analyses. Conclusions:Insomnia is likely associated with adverse glycaemic control. As the included studies are observational, future research should prioritise diverse methodologies and robust study designs to further explore this complex relationship. Keywords:insomnia, insomnia related symptoms, glycaemic control, systematic review, meta-analysis. Registration:PROSPERO CRD42024491688.

PURPOSE:High consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited. METHODS:Fruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case-control studies. Unconditional logistic regression was used to estimate study-specific odds ratio's (ORs) with 95% confidence intervals (CIs) and combined using a random-effects model for intakes of total fruits, total vegetables, and subgroups of fruits and vegetables. RESULTS:A total of 11 case-control studies were included, comprising 5637 BC cases and 10,504 controls. Overall, participants with the highest intakes versus the lowest intakes of fruits in total (OR 0.79; 95% CI 0.68-0.91), citrus fruits (OR 0.81; 95% CI 0.65-0.98), pome fruits (OR 0.76; 95% CI 0.65-0.87), and tropical fruits (OR 0.84; 95% CI 0.73-0.94) reduced the BC risk. Greater consumption of vegetables in total, and specifically shoot vegetables, was associated with decreased BC risk (OR 0.82; 95% CI 0.68-0.96 and OR 0.87; 95% CI 0.78-0.96, respectively). Substantial heterogeneity was observed for the associations between citrus fruits and total vegetables and BC risk. CONCLUSION:This comprehensive study provides compelling evidence that the consumption of fruits overall, citrus fruits, pome fruits and tropical fruits reduce the BC risk. Besides, evidence was found for an inverse association between total vegetables and shoot vegetables intake.

Abstract V-domain Ig Suppressor of T-cell Activation (VISTA), a promising immuno-oncology target, is primarily expressed by immunosuppressive myeloid cells that infiltrate solid tumors. VISTA may contribute to resistance to anti-PD-(L)1 and anti-CTLA-4 therapies and correlates with a poor prognosis. KVA12123 is a human IgG1 monoclonal antibody that specifically binds to VISTA at neutral and acidic pHs. It was designed to improve pharmacokinetic (PK) characteristics as well as reduce the risk of cytokine release syndrome (CRS). KVA12123 exhibited strong anti-tumor activity alone and in combination with anti-PD1 in preclinical studies. It demonstrated an excellent safety profile in non-human primates. The VISTA-101 clinical trial is a first-in-human, Phase 1/2, multicenter, open-label, safety, PK and pharmacodynamic (PD) evaluation of KVA12123, both as monotherapy and in combination with pembrolizumab, in adult patients with advanced solid tumors (NCT05708950). METHODS: The phase 1 of VISTA-101 is an accelerated Bayesian Optimal Interval Design consisting of two arms: Part A) KVA12123 monotherapy dose escalation from 3 mg to 1000 mg including 6 cohorts and Part B) KVA12123 dose escalation from 30 mg to 1000 mg in combination with 400 mg fixed dosing of pembrolizumab including 4 cohorts. The primary objectives are safety, tolerability and to define a recommended phase 2 dose. Safety, PK and receptor occupancy data were considered during dose escalation. VISTA-101 is also assessing PD and predictive biomarkers of response. Patient tumor response is evaluated by iRECIST. RESULTS: Forty-two patients have been enrolled in the dose escalation monotherapy arm of the study. KVA12123 was administered at doses ranging from 3 to 1000 mg every 2 weeks over a 6-week cycle. KVA12123 was well tolerated at all dose levels and no DLTs were observed. The most frequently observed adverse events were grade 1 or 2 transient infusion-related reactions. No evidence of CRS-associated cytokines were detected. PK analysis demonstrated greater than dose-proportional exposure consistent with target-mediated metabolism. A VISTA receptor occupancy assay demonstrated full target engagement at doses of 30 mg and above. PD analysis indicated a dose-dependent induction of pro-inflammatory myeloid derived cytokines and chemokines involved in immune cell activation and recruitment to the tumor microenvironment including CCL2, CCL3, CCL4 and CXCL10. Increases in nonclassical monocytes, NK cells, CD4+ and CD8+ T cells were also demonstrated, consistent with observations made in preclinical models and indicative of VISTA target engagement. Patient tumor response evaluations in the monotherapy arm will be reported. The study continues to evaluate KVA12123 both as a monotherapy and in combination with pembrolizumab to define the recommended phase 2 dose. Citation Format: Evan Y. Yu, Jason Henry, Manish R. Patel, Paul Swiecicki, Ida Micaily, Benjamin Garmezy, Kalyan Banda, Vinny Hayreh, Kurt Lustig, Yulia Ovechkina, Shawn P. Iadonato, Thierry Guillaudeux, Lee Rosen. Interim results of the ongoing phase 1-2 clinical trial of KVA12123, an engineered IgG1 targeting VISTA, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT068.

A meta-analysis published in 2018 indicated a significant association between the dietary inflammatory index (DII) and risk of urologic cancers (UC). The number of included studies was limited, and more research has been published on this topic since then. The current study aimed to find a more precise estimate of the association between dietary inflammatory potential and risk of UC by updating the previous meta-analysis. The PubMed and Embase databases were searched between January 2015 and April 2023 to identify eligible articles. Combined relative risk (RR) and 95% confidence intervals (CI) were calculated by random-effects model to assess the association between dietary inflammatory potential and risk of UC by comparison of the highest versus the lowest category of the DII/empirical dietary inflammatory pattern (EDIP) or by using the continuous DII/EDIP score. The analysis, including 23 studies with 557,576 subjects, showed different results for UC. There was a significant association for prostate cancer among case-control studies (RR = 1.75, 95% CI: 1.34-2.28), whereas among cohort studies a null association was found (RR = 1.02, 95% CI: 0.96-1.08). For bladder cancer, a nonsignificant association was observed in both case-control (RR = 1.59, 95% CI: 0.95-2.64) and cohort studies (RR = 1.03, 95% CI: 0.86-1.24). Pooled RR from 3 case-control studies displayed a statistically significant association between the DII and risk of kidney cancer (RR = 1.27, 95% CI: 1.03-1.56). Although DII was positively associated with all types of UC, no association was found for EDIP. The present meta-analysis confirmed that an inflammatory diet has a direct effect on the development of prostate cancer and kidney cancer. Large-scale studies are needed to demonstrate the association between dietary inflammatory potential and risk of UC and provide effective nutritional advice for UC prevention. PROTOCOL REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023391204).

BACKGROUND:Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways.METHODS:We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed.RESULTS:The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly.CONCLUSION:In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC.HighlightsThe current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention.The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiotaOur results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.

Abstract Background The incidence of acute pancreatitis (AP) is increasing over years, which brings enormous economy and health burden. However, the aetiologies of AP and underlying mechanisms are still unclear. Here, we performed a two‐sample Mendelian randomization (MR) analysis to investigate the associations between all reported possible risk factors and AP using publicly available genome‐wide association study summary statistics. Methods A series of quality control steps were taken in our analysis to select eligible instrumental single nucleotide polymorphisms which were strongly associated with exposures. To make the conclusions more robust and reliable, we utilized several analytical methods (inverse‐variance weighting, MR‐PRESSO method, weighted median, MR‐Egger regression) that are based on different assumptions of two‐sample MR analysis. The MR‐Egger intercept test, radial regression and leave‐one‐out sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on each exposure. A two‐step MR method was applied to explore mediators in significant associations. Results Genetic predisposition to cholelithiasis (effect estimate: 17.30, 95% CI: 12.25–22.36, p = 1.95 E‐11), body mass index (0.32, 95% CI: 0.13–0.51, p < 0.001), body fat percentage (0.57, 95% CI: 0.31–0.83, p = 1.31 E‐05), trunk fat percentage (0.36, 95% CI: 0.14–0.59, p < 0.005), ever smoked (1.61, 95% CI: 0.45–2.77, p = 0.007), and limbs fat percentage (0.55, 95% CI: 0.41–0.69, p < 0.001) were associated with an increased risk of AP. In addition, whole‐body fat‐free mass (−0.32, 95% CI: −0.55 to −0.10, p = 0.004) was associated with a decrease risk of AP. Conclusion Genetic predisposition to cholelithiasis, obesity and smoking could be causally associated with an increased risk of AP, and whole body fat‐free mass could be associated with a decreased risk of AP.

Background & aims:Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus, thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk. Methods:Individual dietary data were pooled from ten cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose-response relationships (Model 1) were examined using a nonparametric test for trend. Results:In total, 1994 cases and 518,002 non-cases were included in the analyses. The present study showed no significant associations between individual nutrient intake and BC risk. A significant decreased BC risk was observed for high vitamin D intake with moderate calcium and low phosphorus intake (Model 2: HRhigh vitD, mod Ca, low P: 0.77, 95% CI: 0.59-1.0 0). No significant dose-response analyses were observed. Conclusion:The present study showed a decreased BC risk for high dietary vitamin D intake in combination with low calcium intake and moderate phosphorus intake. The study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns. & COPY; 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background Although conventional prediction models for surgical patients often ignore intraoperative time-series data, deep learning approaches are well-suited to incorporate time-varying and non-linear data with complex interactions. Blood lactate concentration is one important clinical marker that can reflect the adequacy of systemic perfusion during cardiac surgery. During cardiac surgery and cardiopulmonary bypass, minute-level data is available on key parameters that affect perfusion. The goal of this study was to use machine learning and deep learning approaches to predict maximum blood lactate concentrations after cardiac surgery. We hypothesized that models using minute-level intraoperative data as inputs would have the best predictive performance. Methods Adults who underwent cardiac surgery with cardiopulmonary bypass were eligible. The primary outcome was maximum lactate concentration within 24 h postoperatively. We considered three classes of predictive models, using the performance metric of mean absolute error across testing folds: (1) static models using baseline preoperative variables, (2) augmentation of the static models with intraoperative statistics, and (3) a dynamic approach that integrates preoperative variables with intraoperative time series data. Results 2,187 patients were included. For three models that only used baseline characteristics (linear regression, random forest, artificial neural network) to predict maximum postoperative lactate concentration, the prediction error ranged from a median of 2.52 mmol/L (IQR 2.46, 2.56) to 2.58 mmol/L (IQR 2.54, 2.60). The inclusion of intraoperative summary statistics (including intraoperative lactate concentration) improved model performance, with the prediction error ranging from a median of 2.09 mmol/L (IQR 2.04, 2.14) to 2.12 mmol/L (IQR 2.06, 2.16). For two modelling approaches (recurrent neural network, transformer) that can utilize intraoperative time-series data, the lowest prediction error was obtained with a range of median 1.96 mmol/L (IQR 1.87, 2.05) to 1.97 mmol/L (IQR 1.92, 2.05). Intraoperative lactate concentration was the most important predictive feature based on Shapley additive values. Anemia and weight were also important predictors, but there was heterogeneity in the importance of other features. Conclusion Postoperative lactate concentrations can be predicted using baseline and intraoperative data with moderate accuracy. These results reflect the value of intraoperative data in the prediction of clinically relevant outcomes to guide perioperative management.

Developing dye-based isothermal nucleic acid amplification (INAA) at low temperatures such as 37 °C remains a technical challenge. Here, we describe a nested phosphorothioated (PS) hybrid primer-mediated isothermal amplification (NPSA) assay which only utilizes EvaGreen (a DNA-binding dye) to achieve specific and dye-based subattomolar nucleic acid detection at 37 °C. The success of low-temperature NPSA essentially depends on employing Bacillus smithii DNA polymerase, a strand-displacing DNA polymerase with wide range of activation temperature. However, the NPSA's high efficiency entails nested PS-modified hybrid primers and the additives of urea and T4 Gene 32 Protein. To address the inhibition of urea on reverse transcription (RT), one-tube two-stage recombinase-aided RT-NPSA (rRT-NPSA) is established. By targeting human Kirsten rat sarcoma viral (KRAS) oncogene, NPSA (rRT-NPSA) stably detects 0.2 aM of KRAS gene (mRNA) within 90 (60) min. In addition, rRT-NPSA possesses subattomolar sensitivity to detect human ribosomal protein L13 mRNA. The NPSA/rRT-NPSA assays are also validated to obtain consistent results with PCR/RT-PCR methods on qualitatively detecting DNA/mRNA targets extracted from cultured cells and clinical samples. As a dye-based, low-temperature INAA method, NPSA inherently facilitates the development of miniaturized diagnostic biosensors.

Identification of protein quantitative trait loci (pQTL) helps understand the underlying mechanisms of diseases and discover promising targets for pharmacological intervention. For most important class of drug targets, genetic evidence needs to be generalizable to diverse populations. Given that the majority of the previous studies were conducted in European ancestry populations, little is known about the protein-associated genetic variants in East Asians. Based on data-independent acquisition mass spectrometry technique, we conduct genome-wide association analyses for 304 unique proteins in 2,958 Han Chinese participants. We identify 195 genetic variant-protein associations. Colocalization and Mendelian randomization analyses highlight 60 gene-protein-phenotype associations, 45 of which (75%) have not been prioritized in Europeans previously. Further cross-ancestry analyses uncover key proteins that contributed to the differences in the obesity-induced diabetes and coronary artery disease susceptibility. These findings provide novel druggable proteins as well as a unique resource for the trans-ancestry evaluation of protein-targeted drug discovery.

Although GWASs have been conducted to investigate genetic variation of bladder tumorigenesis, little is known about genetic interactions that may influence bladder cancer (BC) risk. By leveraging large-scale participants from UK Biobank, we established a discovery database with 4000 Caucasian participants (2000 cases vs 2000 non-cases), a database with 1648 Caucasian participants (824 cases vs 824 non-cases) and 856 non-Caucasian participants (428 cases vs 428 non-cases) as validation. We then performed a genome-wide SNP-SNP interaction investigation related to BC risk based a machine learning approach (ie, GenEpi). Moreover, we used the selected interactions to build a BC screening model with an integrated interaction-empowered polygenic risk score (iPRS) based on Cox proportional hazard model. With Bonferroni correction, we identified 10 statistically significant pairs of SNPs, which located in 17 chromosomes. Of these, four SNP-SNP interactions were found to be positively associated with BC risk among Caucasian participants (ORs 1.57-2.03), while six SNP-SNP interactions showed negatively associated with BC risk (ORs 0.54-0.65). Only four of the SNP-SNP interactions were consistently identified in non-Caucasian participants located in ST7L-ADSS2, FHIT-CHDH, LARP4B-LHPP and RBFOX3-MPRIP. In addition, the iPRS showed a HR of 1.81 (95% CI: 1.46-2.09) compared the highest tertile to the lowest tertile, with an enhanced AUC (0.91; 95% CI:0.85-0.97) than PRS (AUC: 0.86; 95% CI:0.76-0.95; P-DeLong test = 2.2 x 10(-4)). In summary, this study identified several important SNP-SNP interactions for BC risk, and developed an iPRS model for BC screening, which may help to identify the people at high-risk state of BC before early manifestation.

Atezolizumab is an anti-PD-L1 antibody that was approved for patients with mUC following platinum-containing regimens. IL-7 (CYT107) is a homeostatic cytokine that supports the proliferation and persistence of T cells. We hypothesized that addition of CYT107 would improve responses to PD-L1 inhibition by atezo. We performed a randomized trial (NCT03513952) in mUC comparing the combination of CYT107 and atezo to atezo alone. Patients with mUC who had progressive disease after platinum-containing chemotherapy were screened. Key eligibility criteria included ECOG PS 0-2, measurable disease (by RECIST 1.1), and no prior checkpoint inhibitor or cytokine immunotherapy. A safety run-in using the combination of CYT107 and atezo was performed, followed by randomization 1:1 to atezo 1200 mg IV q3wks +/- CYT107 10 ug/kg IM qwk X 4. The primary endpoint was objective response rate (ORR), with secondary endpoints including clinical benefit rate, PFS, DOR, OS, and safety. Detailed immune response analysis and exploratory correlative analyses are in progress. A total of 47 patients were enrolled. Patient demographics between arms were well-balanced. ORR was 26.3% for the combination vs 23.8% for atezo alone (p=0.43). There were no significant differences in clinical benefit rate, PFS, DOR, or OS. No dose limiting toxicities were seen in the safety run-in cohort (n=7). 76.9% (20/26) of patients on the CYT107 arm received all four doses. The combination of CYT107 and atezo was well tolerated compared to the atezo arm, with overall grade 3-4 adverse events (AEs) occurring in 46.2% (12/26) and 63.2% (12/19), respectively. Immune-mediated AEs of any grade occurred in 50% (13/26) vs 68.4% (13/19), respectively. 6.3% vs 17.6% of patients on the combination vs monotherapy arm discontinued therapy due to toxicity. This is the first randomized trial of atezolizumab +/- IL-7 (CYT107) in mUC. During the trial, the FDA approval for atezo in mUC was withdrawn, which limited enrollment. However, our results show that the addition of CYT107 to atezo is safe/tolerable, although there was no improvement in clinical outcomes compared to atezo monotherapy.

You have accessJournal of UrologyCME1 May 2022PD53-09 ANTIBODY DRUG CONJUGATES AND VARIANT HISTOLOGY MUSCLE-INVASIVE BLADDER CANCER: ARE THE TARGETS PRESENT IN PRIMARY AND/OR METASTATIC TUMORS? Fady Ghali, Martine Roudier, Funda Vakar-Lopez, Jose Garcia, Yan Wang, Gavin Ha, Petros Grivas, John Lee, Evan Yu, Bruce Montgomery, Andrew Hsieh, Jonathan Wright, and Hung-Ming Lam Fady GhaliFady Ghali More articles by this author , Martine RoudierMartine Roudier More articles by this author , Funda Vakar-LopezFunda Vakar-Lopez More articles by this author , Jose GarciaJose Garcia More articles by this author , Yan WangYan Wang More articles by this author , Gavin HaGavin Ha More articles by this author , Petros GrivasPetros Grivas More articles by this author , John LeeJohn Lee More articles by this author , Evan YuEvan Yu More articles by this author , Bruce MontgomeryBruce Montgomery More articles by this author , Andrew HsiehAndrew Hsieh More articles by this author , Jonathan WrightJonathan Wright More articles by this author , and Hung-Ming LamHung-Ming Lam More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002630.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nectin-4 and Trop-2 are cell surface targets of novel humanized monoclonal antibody-drug conjugates, Enfortumab-vedotin (EV) and Sacituzumab govitecan (SG), respectively. These agents are FDA-approved for locally advanced/metastatic urothelial cancer (UC), however their wider role in the treatment of variant histology bladder cancer (BC) is unknown. We describe the expression level and sub-cellular localization of Nectin-4 and TROP-2 via immunostaining in histologic variants of BC within primary and matched metastatic samples. METHODS: Immunohistochemistry for Nectin-4 and TROP-2 was performed (using Abcam 192033 and 214488 respectively) on matched primary and metastatic tumor samples from patients with metastatic BC collected via rapid autopsy. Staining was scored by intensity (0-3) and multiplied by % of positive cells resulting in a range of 0-300 H-score. Membranous and cytoplasmic staining were separately evaluated for each sample. RESULTS: A total of 68 samples from 20 patients were collected and analyzed, of which 27 were urothelial carcinoma (UC), 17 plasmacytoid (PUC), 19 Squamous cell carcinoma (SCC), and 5 neuroendocrine (NE); 11 samples were collected from primary tumor sites, 20 from lymph node (LN) and 37 from various metastatic sites; 17 of 20 patients (85%) had received systemic chemotherapy and 35% had received immunotherapy. No patient had received EV or SG. Table 1 demonstrates mean membranous and cytoplasmic H-score levels as well as % positive rates for Nectin-4 and TROP-2. Nectin-4 localized primarily in the cytoplasm rather than the membrane in PUC and SCC for LN and metastatic sites, while primary tumors demonstrated relatively even Nectin-4 distribution between membrane and cytoplasm. TROP-2 was expressed at equivalent levels in both membrane and cytoplasm for both PUC and SCC, and the high expression was conserved from primary to metastases. CONCLUSIONS: Nectin-4 and TROP-2 are highly expressed in UC and variant histology BC, both at primary and metastatic sites, but not in NE histology. Whether differences in membranous vs cytoplasmic localization affects response to EV or SG is unknown. The implications of these findings on treatment response for variant histology BC warrant further study in clinical trials, which we are launching. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e913 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fady Ghali More articles by this author Martine Roudier More articles by this author Funda Vakar-Lopez More articles by this author Jose Garcia More articles by this author Yan Wang More articles by this author Gavin Ha More articles by this author Petros Grivas More articles by this author John Lee More articles by this author Evan Yu More articles by this author Bruce Montgomery More articles by this author Andrew Hsieh More articles by this author Jonathan Wright More articles by this author Hung-Ming Lam More articles by this author Expand All Advertisement PDF downloadLoading ...

Background: This review aims to investigate the association of sex with the risk of multiple COVID-19 health outcomes, ranging from infection to death. Methods: Pubmed and Embase were searched through September 2020. We considered studies reporting sex and coronavirus disease 2019 (COVID-19) outcomes. Qualitative and quantitative data were extracted using standardised electronic data extraction forms with the assessment of Newcastle Ottawa Scale for risk of bias. Pooled trends in infection, hospitalization, severity, intensive care unit (ICU) admission and death rate were calculated separately for men and women and subsequently random-effects meta-analyses on relative risks (RR) for sex was performed. Results: Of 10,160 titles, 229 studies comprising 10,417,452 patients were included in the analyses. Methodological quality of the included studies was high (6.9 out of 9). Men had a higher risk for infection with COVID-19 than women (RR = 1.14, 95%CI: 1.07 to 1.21). When infected, they also had a higher risk for hospitalization (RR = 1.33, 95%CI: 1.27 to 1.41), higher risk for severe COVID-19 (RR = 1.22, 95%CI: 1.17 to 1.27), higher need for Intensive Care (RR = 1.41, 95%CI: 1.28 to 1.55), and higher risk of death (RR = 1.35, 95%CI: 1.28 to 1.43). Within the period studied, the RR for infection and severity increased for men compared to women, while the RR for mortality decreased for men compared to women. Conclusions: Meta-analyses on 229 studies comprising over 10 million patients showed that men have a higher risk for COVID-19 infection, hospitalization, disease severity, ICU admission and death. The relative risks of infection, disease severity and death for men versus women showed temporal trends with lower relative risks for infection and severity of disease and higher relative risk for death at the beginning of the pandemic compared to the end of our inclusion period. PROSPERO registration: CRD42020180085 (20/04/2020)

The effects of fat intake from different dietary sources on bladder cancer (BC) risk remains unidentified. Therefore, the present study aimed to investigate the association between fat intakes and BC risk by merging world data on this topic. Data from 11 cohort studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) study, provided sufficient information on fat intake for a total of 2731 BC cases and 544 452 noncases, which yielded 5 400 168 person-years of follow-up. Hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox-regression models stratified on cohort. Analyses were adjusted for total energy intake in kilocalories, gender, smoking status (model-1) and additionally for sugar and sugar products, beers, wine, dressing and plant-based and fruits intakes (model-2). Among women, an inverse association was observed between mono-unsaturated fatty acids (MUFAs) and BC risk (HR comparing the highest with the lowest tertile: 0.73, 95% CI: 0.58-0.93, P-trend = .01). Overall, this preventative effect of MUFAs on BC risk was only observed for the nonmuscle invasive bladder cancer (NMIBC) subtype (HR: 0.69, 95% CI: 0.53-0.91, P-trend = .004). Among men, a higher intake of total cholesterol was associated with an increased BC risk (HR: 1.37, 95% CI: 1.16-1.61, P-trend = .01). No other significant associations were observed. This large prospective study adds new insights into the role of fat and oils in BC carcinogenesis, showing an inverse association between consumption of MUFAs and the development of BC among women and a direct association between higher intakes of dietary cholesterol and BC risk among men.