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At the beginning of the SARS Co V2 (COVID-19) pandemic, women worldwide represented the majority of health care workers. As part of the fight against the pandemic, women health care workers became a part of the significant frontline response. This led to unique challenges that affected women physicians as well as the women patients they were taking care of. The American College of Cardiology Women in Cardiology International Working Group set up a webinar to discuss the challenges being faced by women physicians and women patients in various parts of the world and look towards finding possible solutions for these issues in a webinar themed ?WIC Global Perspectives: COVID-19.?

Abstract Objectives Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients. Methods We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization. Results Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96–1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00–1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19. Conclusions Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.

Abstract Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low‐density lipoprotein [LDL] and high‐density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels ( P < 5 × 10 −8 ) were identified as instrumental variables, and assessed using genome‐wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non‐endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non‐endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non‐endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non‐endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

Abstract Importance:SARS-CoV-2 virus gains access and infects target cells via angiotensin converting enzyme 2 (ACE2) receptor. Because angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) could increase the expression of ACE2, there are growing concerns that their use could increase the risk of SARS-CoV-2 infection. Cardiac societies have called for epidemiological research about this emerging controversy. Objective:We sought to systematically review the literature and perform a meta-analysis about prior use of ACEI/ARBs and risk of SARS-CoV-2 infection.Data source:We searched multiple data sources including PubMed , ClinicalTrial.org , and medrxiv.org from November 2019 through May 16, 2020. Study selection:Any study that reported on the adjusted association of prior use of ACEIs / ARBs and risk of acquiring SARS-CoV-2 infection was eligible. Two authors independently reviewed eligible studies and extracted data into a prespecified data collection form. Data synthesis:An inverse variance meta-analytic approach was used to pool adjusted odds ratios using a random effect model meta-analysis. I2 test was used to assess in-between studies heterogeneity. The Newcastle–Ottawa quality assessment scale (NOS) was used to assess the quality of included studies. Main outcome and Measures:The association between the prior use of ACEIs or ARBs and risk of SARS-CoV-2 infection was assessed using pooled OR and 95% confidence interval. Results:Six case control studies that enrolled a total of 5657 patients (2536 patients in ACEIs arm and 3121 patients in ARBs arm ) and 721,859 controls were included in our meta-analysis. Two of the included studies were from the USA, one from Italy, one from China, one from Spain, and one from South Korea. All included studies scored high based on NOS scale. Prior use of ACEIs was not significantly associated with an increased risk of SARS-CoV-2 infection, OR 0.93, CI (0.85,1.02), I2=20%. Similarly, prior use of ARBs was not significantly associated with an increased risk of SARS-CoV-2 infection, OR 0.86, CI (0.67,1.10), I2=93%. Sensitivity analysis was performed by removing a study that could have been affected by residual confounding; OR for ARB 1.04, CI (0.96,1.12), I2=32%.Conclusion:Findings from this systematic review and meta-analysis suggest that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19. Our results are in support of the recent recommendations of cardiac societies and provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs due to fear of COVID-19.

Background: Prostate cancer (PrC) is the second-most frequent cancer in men, its incidence is emerging globally and is the fifth leading cause of death worldwide. While diagnosis and prognosis of PrC have been studied well, the associated therapeutic biomarkers have not yet been investigated comprehensively. This systematic review and meta-analysis aim to evaluate the theragnostic effects of microRNA expressions on chemoresistance in prostate cancer and to analyse the utility of miRNAs as clinical theragnostic biomarkers. Methods: A systematic literature search for studies reporting miRNA expressions and their role in chemoresistance in PrC published until 2018 was collected from bibliographic databases. The evaluation of data was performed as per PRISMA guidelines for systematic review and meta-analysis. Meta-analysis was performed using a random-effects model using Comprehensive Meta-Analysis (CMA) software. Heterogeneity between studies was analysed using Cochran’s Q test, I2 and the Tau statistic. Quality assessment of the studies was performed using the Newcastle–Ottawa Scale (NOS) for the methodological assessment of cohort studies. Publication bias was assessed using Egger’s bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill methods. Findings: Out of 2909 studies retrieved, 79 studies were shortlisted and reviewed. A total of 17 studies met our eligibility criteria, from which 779 PrC patients and 17 chemotherapy drugs were examined, including docetaxel and paclitaxel. The majority of the drug regulatory genes reported were involved in cell survival, angiogenesis and cell proliferation pathways. We studied 42 miRNAs across all studies, out of which two miRNAs were found to be influencing chemosensitivity, while 21 were involved in chemoresistance. However, the remaining 19 miRNAs did not appear to have any theragnostic effects. Besides, the prognostic impact of the miRNAs was evaluated and had a pooled HR value of 1.960 with 95% CI (1.377–2.791). Interpretation: The observation of the current study depicts the significance of miRNA expression as a theragnostic biomarker in medical oncology. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in PrC. Hence, the current systematic review and meta-analysis provide insight on the use of miRNA as PrC biomarkers, which can be harnessed as molecular candidates for therapeutic targeting.

AbstractBackgroundBody mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.MethodsTo improve statistical power and interpretation for gene‐environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype‐Tissue Expression Project for all genes with heritability ≥1%. We used a mixed‐effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI‐CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2.ResultsAmong 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10−5), PSMC5 (P = 4.51 × 10−4) and CD33 (P = 2.71 × 10−4) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10−5) and SCN1B (P = 2.76 × 10−4) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10−5).ConclusionsAggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

PAX1deficiency causes a syndromic form of SCID by altering differentiation of thymic epithelial cells and other pharyngeal pouch tissues.

ABSTRACTBackground:Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC.Methods:We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam‐Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c‐statistic.Results:Model fit was good at 1 year (c‐statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam‐Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam‐Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over‐weighting of AST in these patients accounted for the observed versus predicted survival discrepancy.Conclusions:All 3 models offered good short‐term discrimination of outcomes but only fair long‐term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric‐specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.

Background: Latissimus dorsi myocutaneous flap (LDMF) with tissue expander provides excellent results in breast reconstruction. Acellular dermal matrix (ADM) has been used in expander-based reconstruction (EBR) with good results. This study assesses how ADM compares to LDMF in EBR. Methods: The cohorts comprised 124 patients (218 breasts) who had EBR using ADM between 2006 and 2012, and 242 patients (266 breasts) who had EBR using LDMF between 1994 and 2012. Postoperative complications, reoperations, Breast-Q scores, and objectively assessed aesthetic outcomes were compared. Results: Median age was 55 years for both ADM (range 23–84) and LDMF (range 26–88) groups. No statistically significant differences were noted between the groups in the rates of major postoperative complications (P > 0.3). Forty-nine of the 218 (22.5%) in the ADM group and 67 of 266 (25.2%) in the LDMF group had a total of 63 and 84 reoperations, respectively (P = 0.52), with no significant differences in the reoperations rate (P > 0.3). No significant differences were observed in the Breast-Q scores. Some categorical differences were noted in the aesthetic outcomes; however, the difference between the overall outcomes was not significant (P = 0.54). Conclusion: Our study revealed no statistically significant differences in the complications or reoperation rates, patient satisfaction, or overall aesthetic outcomes when comparing the use of ADM to LDMF in EBR. In conclusion, this study supports the hypothesis that ADM performs as well as LDMF in EBR.