Sex-Related Differences in the Phenotype and Course of Inflammatory Bowel Disease: SEXEII Study of ENEIDA.

BACKGROUND & AIMS: The impact of patient sex on the presentation of inflammatory bowel disease (IBD) has been poorly evaluated. Our aims were to assess potential disparities in IBD phenotype and progression between sexes. METHODS: We performed an observational multicenter study that included patients with Crohn's disease (CD) or ulcerative colitis from the Spanish Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales registry. Data extraction was conducted in July 2021. RESULTS: A total of 51,595 patients with IBD were included, 52% were males and 25,947 had CD. The median follow-up period after diagnosis was 9 years in males and 10 years in females. In CD, female sex was an independent risk factor for medium disease onset (age, 17-40 y) (relative risk ratio, 1.45; 95% CI, 1.31-1.62), later disease onset (age, >40 y) (relative risk ratio, 1.55; 95% CI, 1.38-1.73), exclusive colonic involvement (odds ratio, 1.24; 95% CI, 1.14-1.34), inflammatory behavior (odds ratio, 1.14; 95% CI, 1.07-1.21), and extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.38-1.59). However, female sex was a protective factor for upper gastrointestinal involvement (odds ratio, 0.84; 95% CI, 0.79-0.90), penetrating behavior (odds ratio, 0.76; 95% CI, 0.70-0.82), perianal disease (odds ratio, 0.77; 95% CI, 0.71-0.82), and complications (odds ratio, 0.73; 95% CI, 0.66-0.80). In ulcerative colitis, female sex was an independent risk factor for extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.26-1.61). However, female sex was an independent protective factor for disease onset from age 40 onward (relative risk ratio, 0.76; 95% CI, 0.66-0.87), left-sided colonic involvement (relative risk ratio, 0.72; 95% CI, 0.67-0.78), extensive colonic involvement (relative risk ratio, 0.59; 95% CI, 0.55-0.64), and abdominal surgery (odds ratio, 0.78; 95% CI, 0.69-0.88). CONCLUSIONS: There is sexual dimorphism in IBD. The patient's sex should be taken into account in the clinical management of the disease.

Sex bias in prediction and diagnosis of cardiac surgery associated acute kidney injury.

BACKGROUND: Female sex has been recognized as a risk factor for cardiac surgery associated acute kidney injury (CS-AKI). The current study sought to evaluate whether female sex is a risk factor for CS-AKI, or modifies the association of peri-operative change in serum creatinine with CS-AKI. METHODS: Observational study of adult patients undergoing cardiac surgery between 2000 and 2019 in a single U.S. center. The main variable of interest was registered patient sex, identified from electronic medical records. The main outcome was CS-AKI within 2 weeks of surgery. RESULTS: Of 58526 patients, 19353 (33%) were female; 12934 (22%) incurred AKI based on ≥ 0.3 mg/dL or ≥ 50% rise in serum creatinine (any AKI), 3320 (5.7%) had moderate to severe AKI, and 1018 (1.7%) required dialysis within 2 weeks of surgery. Female sex was associated with higher risk for AKI in models that were based on preoperative serum creatinine (OR, 1.35; 95% CI, 1.29-1.42), and lower risk with the use of estimated glomerular filtration, (OR, 0.90; 95% CI, 0.86-0.95). The risk for moderate to severe CS-AKI for a given immediate peri-operative change in serum creatinine was higher in female compared to male patients (p < .0001 and p < .0001 for non-linearity), and the association was modified by pre-operative kidney function (p < .0001 for interaction). CONCLUSIONS: The association of patient sex with CS-AKI and its direction was dependent on the operational definition of pre-operative kidney function, and differential outcome misclassification due to AKI defined by absolute change in serum creatinine.

Bystander cardiopulmonary resuscitation differences by sex - The role of arrest recognition.

PURPOSE: To assess whether bystander cardiopulmonary resuscitation (CPR) differed by patient sex among bystander-witnessed out-of-hospital cardiac arrests (OHCA). METHODS: This study is a retrospective analysis of paramedic-attended OHCA in New South Wales (NSW) between January 2017 to December 2019 (restricted to bystander-witnessed cases). Exclusions included OHCA in aged care, medical facilities, with advance care directives, from non-medical causes. Multivariate logistic regression examined the association of patient sex with bystander CPR. Secondary outcomes were OHCA recognition, bystander AED application, initial shockable rhythm, and survival outcomes. RESULTS: Of 4,491cases, females were less likely to receive bystander CPR in private residential (Adjusted Odds ratio [AOR]: 0.82, 95%CI: 0.70-0.95) and public locations (AOR: 0.58, 95%CI:0.39-0.88). OHCA recognition during the emergency call was lower for females arresting in public locations (84.6% vs 91.6%, p = 0.002) and this partially explained the association of sex with bystander CPR (∼44%). This difference in recognition was not observed in private residential locations (p = 0.2). Bystander AED use was lower for females (4.8% vs 9.6%, p < 0.001); however, after adjustment for location and other covariates, this relationship was no longer significant (AOR: 0.83, 95%CI: 0.60-1.12). Females were less likely to be in an initial shockable rhythm (AOR: 0.52, 95%CI: 0.44-0.61), but more likely to survive the event (AOR: 1.34, 95%CI: 1.15-1.56). There was no sex difference in survival to hospital discharge (AOR: 0.96, 95%CI: 0.77-1.19). CONCLUSION: OHCA recognition and bystander CPR differ by patient sex in NSW. Research is needed to understand why this difference occurs and to raise public awareness of this issue.

Longitudinal alterations in the urinary virome of kidney transplant recipients are influenced by BK viremia and patient sex.

Little is known about the urinary virome and how it interacts with the host, particularly in renal transplant diseases. Using metagenomic sequencing, we characterized the urinary virome of 23 kidney transplant recipients longitudinally (11 BKV+ patients and 12 BKV- patients). We applied linear mixed effects models, PERMANOVA, k-means clustering, and MaAsLin2 algorithms to determine virome signatures associated with post-transplant time, BK viremia status, and patient sex. We found that the richness and alpha diversity of urinary virome were significantly different in renal transplant recipients with BKV+ over time in comparison to BKV- (richness P = 0.012, alpha P < 0.0001). Female BKV- patients had significantly higher virome richness than males (P = 0.0063). Virome beta diversity was significantly different between patients by BKV status (P < 0.001). Additionally, we identified underlying interactions between patient sex and BKV status, in terms of virome beta diversity (P = 0.008). BK polyomavirus infections were primarily of subtypes IA, IB1, and IB2. The non-BK dominant samples clustered into six urinary virome community states. BKV- samples had more anelloviruses than BKV+ samples though this difference was not statistically significant. Lastly, we identified specific viruses, associated with BKV+ and time in our samples. Our results indicate that dynamic alterations in the urinary virome over the post-transplant period in kidney transplant recipients can be shaped by BK viremia and patient sex. These findings advance our fundamental understanding of the urinary virome and support a new line of investigation in renal disease and transplantation. IMPORTANCE: The urinary microbiome is increasingly implicated in renal health and disease. While most research focuses on bacteria communities of the microbiome, factors that influence the urinary virome are not understood. Here, we investigated the urinary virome of 23 adult kidney transplant recipients longitudinally over 14 weeks post-transplant. We show that alterations in the urinary virome are associated with kidney transplant recipients with BK polyomavirus viremia that can lead to BK nephropathy and allograft rejection. By modeling the temporal dynamics post-transplant, we delineated specific profiles of the urinary virome associated with patient sex and urinary community states. These findings reveal fundamental aspects of the urinary virome that can be leveraged to better manage kidney diseases.

Sex Bias in Prediction and Diagnosis of Cardiac Surgery Associated Acute Kidney Injury.

Background: Female sex has been recognized as a risk factor for cardiac surgery associated acute kidney injury (CS-AKI). The current study sought to evaluate whether female sex is a risk factor for CS-AKI, or modifies the association of peri-operative change in serum creatinine with CS-AKI. Methods: Observational study of adult patients undergoing cardiac surgery between 2000 and 2019 in a single U.S. center. The main variable of interest was registered patient sex, identified from electronic medical records. The main outcome was CS-AKI within 2 weeks of surgery. Results: Of 58526 patients, 19353 (33%) were female; 12934 (22%) incurred AKI based on ≥ 0.3 mg/dL or ≥ 50% rise in serum creatinine (any AKI), 3320 (5.7%) had moderate to severe AKI, and 1018 (1.7%) required dialysis within 2 weeks of surgery. Female sex was associated with higher risk for AKI in models that were based on preoperative serum creatinine (OR, 1.35; 95% CI, 1.29-1.42), and lower risk with the use of estimated glomerular filtration, (OR, 0.90; 95% CI, 0.86-0.95). The risk for moderate to severe CS-AKI for a given immediate peri-operative change in serum creatinine was higher in female compared to male patients (p < .0001 and p < .0001 for non-linearity), and the association was modified by pre-operative kidney function (p < .0001 for interaction). Conclusions: The association of patient sex with CS-AKI and its direction was dependent on the operational definition of pre-operative kidney function, and differential outcome misclassification due to AKI defined by absolute change in serum creatinine.

Sex difference in the association between type of bystander CPR and clinical outcomes in patients with out of hospital cardiac arrest.

Background: A recent study suggested that women with out-of-hospital cardiac arrest have a smaller survival benefit with bystander cardiopulmonary resuscitation than men. We evaluated whether this weaker association between bystander cardiopulmonary resuscitation and survival in women is related to dispatcher-assisted vs unassisted bystander cardiopulmonary resuscitation. Methods: In a national registry in the Republic of Korea, we identified adult patients with out-of-hospital cardiac arrest during 2013-2018. The main exposure was type of bystander cardiopulmonary resuscitation (categorized as none, dispatcher-assisted, and unassisted). The primary outcome was favourable neurological survival. Multivariable logistic regression evaluated for an interaction between sex and type of bystander cardiopulmonary resuscitation. Results: Of 93,245 patients with out-of-hospital cardiac arrest, there were 31,578 (33.9%) women and 61,667 (66.1%) men. Overall, both types of bystander cardiopulmonary resuscitation were associated with favourable neurological survival (unassisted: adjusted OR, 1.81 [95% CI: 1.66-1.98]; dispatcher-assisted: adjusted OR, 1.44 [95% CI: 1.33-1.56]). When unassisted cardiopulmonary resuscitation was administered, the association between bystander cardiopulmonary resuscitation and favourable neurological survival was similar between women and men: adjusted ORs of 1.59 (95% CI: 1.30-1.95) in women and 1.88 (95% CI: 1.71-2.08) in men; interaction p = 0.65). In contrast, when dispatcher-assisted cardiopulmonary resuscitation was administered, the association differed by sex: adjusted ORs of 1.08 (95% CI: 0.90-1.92) in women and 1.55 (95% CI: 1.42-1.69) in men; interaction p < 0.0002). Conclusions: Dispatcher-assisted cardiopulmonary resuscitation was associated with favourable neurological survival in men but not in women whereas unassisted bystander cardiopulmonary resuscitation was associated with favourable neurological survival in women and men.

Sex-Related Differences Include Stage, Histology, and Survival in Urethral Cancer Patients.

PURPOSE: To test the effect of sex on histologic subtype, stage at presentation, treatment, and cancer-specific mortality (CSM) in urethral cancer. PATIENTS AND METHODS: We identified urethral cancer patients within the Surveillance, Epidemiology, and End Results (SEER) registry (2004-2016). After matching for tumor and patient characteristics, cumulative incidence plots and multivariable competing risks regression models, adjusted for other-cause mortality, tested CSM according to sex. RESULTS: Of 1645 eligible urethral cancer patients, 1073 (65%) were male. Urothelial histologic subtype was most frequent in male (59%) but not female (27%) subjects. Adenocarcinoma, squamous cell carcinoma, and other histologies were more frequent in female patients. Most male subjects harbored T1N0M0 (32%) stage disease, whereas most female subjects harbored T3-4N0M0 (29%) stage disease. In urothelial and adenocarcinoma histologic subtypes, African American female subjects were most prevalent (31 and 78%) versus whites (16 and 52%) versus Hispanics (27 and 74%). In T1N0M0 stage, single-mode surgical treatment was more frequent in male than female patients (respectively, 73% vs 59%). In T3-4 and/or N1-2 stage disease, multimodal therapy was more frequent in female than male (42% vs 37%) patients. In nonmetastatic urethral cancer (T1-4N0-2M0), after propensity score matching for stage, race, treatment, and age, cumulative incidence plots showed 5-year CSM of 36% and 25% in female and male patients, respectively, and after further multivariable adjustment resulted in 1.3-fold higher CSM in female as opposed to male patients (P = .07). CONCLUSION: Female patients with urethral cancer present with higher disease stage. Despite higher rates of multimodal therapy, and despite matching for stage disadvantage, female subjects with urethral cancer exhibited higher CSM.

Monocytes Do Not Contribute to Sex Differences Seen in the Pharmacokinetics of Pegylated Liposomal Doxorubicin.

Pegylated liposomal doxorubicin (PLD) is widely utilised in cancer chemotherapy, but exhibits large inter-individual pharmacokinetic variability and sex differences in plasma clearance. Population pharmacokinetic modelling has suggested PLD plasma clearance correlates with peripheral monocyte counts, while sex hormones are known to affect endocytosis and phagocytosis in mononuclear cells. This study investigated whether sex hormones affect the uptake of PLD by human monocytes and macrophages in vitro. 17ß-estradiol, but not testosterone, inhibited the uptake of PLD in a concentration dependent manner in undifferentiated (but not differentiated) THP-1 cells, and primary monocytes obtained from women, but not men. Effects of estradiol were only evident at very high concentrations seen during pregnancy. No differences were observed in monocyte count or monocyte subtypes between males and females. These data show that monocytes do not contribute to sex differences seen in PLD clearance in humans of reproductive age.

To eat or not to eat? Indicators for reduced food intake in 91,245 patients hospitalized on nutritionDays 2006-2014 in 56 countries worldwide: a descriptive analysis.

BACKGROUND: Inadequate nutrition during hospitalization is strongly associated with poor patient outcome, but ensuring adequate food intake is not a priority in clinical routine worldwide. This lack of priority results in inadequate and unbalanced food intake in patients and huge amounts of wasted food. OBJECTIVES: We evaluate the main factors that are associated with reduced meal intake in hospitalized patients and the differences between geographical regions. DESIGN: We conducted a descriptive analysis of data from 9 consecutive, annual, and cross-sectional nutritionDay samples (2006-2014) in a total of 91,245 adult patients in 6668 wards in 2584 hospitals in 56 countries. A general estimation equation methodology was used to develop a model for meal intake, and P-value thresholding was used for model selection. RESULTS: The proportion of patients who ate a full meal varied widely (24.7-61.5%) across world regions. The factors that were most strongly associated with reduced food intake on nutritionDay were reduced intake during the previous week (OR: 0.20; 95% CI: 0.17, 0.22), confinement to bed (OR: 0.49; 95% CI: 0.44, 0.55), female sex (OR: 0.53; 95% CI: 0.5, 0.56), younger age (OR: 0.74; 95% CI: 0.64, 0.85) and older age (OR: 0.80; 95% CI: 0.74; 0.88), and low body mass index (OR: 0.84; 95% CI: 0.79, 0.90). The pattern of associated factors was homogenous across world regions. CONCLUSIONS: A set of factors that are associated with full meal intake was identified and is applicable to patients hospitalized in any region of the world. Thus, the likelihood for reduced food intake is easily estimated through access to patient characteristics, independent of world regions, and enables the easy personalization of food provision. This trial was registered at clinicaltrials.gov as NCT02820246.

The effect of patient sex on survival in patients undergoing isolated coronary artery bypass surgery receiving a radial artery.

OBJECTIVES: To determine whether patient sex makes a difference to in-hospital mortality and survival in patients undergoing isolated coronary artery bypass graft surgery (CABG) receiving a radial artery graft. METHODS: Analysis of consecutive patients on a validated prospective cardiac surgery database was performed for patients undergoing isolated CABG. Uni- and multivariate analyses were performed for in-hospital mortality and long-term survival. A propensity analysis was also performed. RESULTS: Overall mortality was 2.1% (n = 284) for all cases, n = 13 369. Median follow-up was 7.0 (interquartile range 4.1-10.1) years. Of the cases 28.2% of males (n = 384) and 29.7% of females (n = 764) had a radial artery utilized. Univariate analysis demonstrated that in-hospital mortality was significantly lower in male patients, P < 0.001, and radial artery use was associated with increased survival in males, P < 0.0001, but not in females, P = 0.82. In male patients, multivariate analysis failed to identify the radial artery as a risk factor for in-hospital death. The radial artery was identified as a significant prognostic factor, associated with improved long-term survival (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.69-0.88, P = 0.0001). Propensity analysis confirmed this finding (HR 0.76, 95% CI 0.67-0.86, P < 0.0001). In female patients, multivariate analysis failed to identify the radial artery as a significant factor determining in-hospital mortality or long-term survival. Propensity analysis confirmed these findings. CONCLUSION: Males derive a significant survival advantage if they receive a radial artery graft when undergoing isolated CABG. The radial artery makes no difference to long-term survival in female patients. Radial artery use does not affect in-hospital mortality regardless of patient sex.