ImportanceObesity and metabolic syndrome are highly prevalent among the US population and are associated with the dysregulation of sex hormones. An increase in obesity and metabolic syndrome may also be associated with exposure to phthalates. The association of exposure to phthalate metabolites with sex hormones and metabolic health has been understudied in the female population.ObjectiveTo evaluate the association between exposure to common phthalate metabolites with total testosterone (TT) levels, sex hormone–binding globulin (SHBG) levels, obesity, and metabolic syndrome among women.Design, Setting, and ParticipantsThis cross-sectional study used data collected from the National Health and Nutrition Examination Survey during 2013 to 2016. Female participants aged 15 years or older with urinary profiles containing common phthalate metabolites were included in this study. Statistical analyses were performed from March 15, 2021, to April 30, 2022.ExposuresUrinary concentrations of phthalate metabolites were classified into tertiles, and the lowest tertile was used as a reference category. The concentrations of phthalate metabolites and their composite scores based on clustering were also used in the analysis.Main Outcomes and MeasuresSerum concentrations of TT and SHBG were dichotomized into high TT levels (>46 ng/dL [to convert to nanomoles per liter, multiply by 0.0347] for age <50 years and >32 ng/dL for age ≥50 years) and low SHBG levels (<2.85 μg/mL [to convert to nanomoles per liter, multiply by 10.53]) as established for the female population. Obesity was defined as a body mass index of 30 or more (calculated as weight in kilograms divided by height in meters squared), and metabolic syndrome was defined using the National Cholesterol Education Program criteria. The serum concentrations of TT and SHBG were also included in the validation analyses. Modified Poisson models were used to estimate the adjusted relative risk (RR) with 95% CIs for the associations.ResultsAmong the 2004 women included in this study, the mean (SD) age was 46.6 (18.5) years (14.7% Hispanic participants, 62.7% non-Hispanic White participants, and 13.2% non-Hispanic Black participants; 17.4% of participants were born outside the US [weighted percentages]; 230 (11.8%) had high TT levels, 210 (10.4%) had low SHBG levels, 825 (39.8%) had obesity, and 965 (45.5%) had metabolic syndrome (weighted percentages). Of the 13 phthalate metabolites, 8 had the highest tertile level greater than 6.2 ng/mL (range, 0.5-75.2 ng/mL). High levels of exposure to mono(2-ethyl-5-carboxypentyl) phthalate (RR, 1.84 [95% CI, 1.33-2.54]), mono(2-ethyl-5-oxohexyl) phthalate (RR, 1.77 [95% CI, 1.21-2.59]), mono(2-ethyl-5-hydroxyhexyl) phthalate (RR, 1.94 [95% CI, 1.34-2.81]), and monobenzyl phthalate (RR, 1.75 [95% CI, 1.21-2.54]) were associated with low SHBG levels but not with high TT levels. High levels of exposure to some of these metabolites were also associated with obesity and metabolic syndrome. Most associations were specific to premenopausal or postmenopausal women.Conclusions and RelevanceIn this cross-sectional study, exposure to certain phthalate metabolites could be associated with low SHBG levels, obesity, and metabolic syndrome depending on menopausal status.

Sepsis is characterized by a dysregulated host immune response to infection, leading to organ dysfunction and a high risk of death. The cecal ligation and puncture (CLP) mouse model is commonly used to study sepsis, but animal mortality rates vary between different studies. Technical factors and animal characteristics may affect this model in unanticipated ways, and if unaccounted for, may lead to serious biases in study findings. We sought to evaluate whether mouse sex, age, weight, surgeon, season of experiments, and timing of antibiotic administration influenced mortality in the CLP model. Methods: We created a comprehensive dataset of C57BL/6J mice that had undergone CLP surgery within our lab during years 2015-2020 from published and unpublished studies. The primary outcome was defined as the time from sepsis induction to death or termination of study (14 days). The Log rank test and Cox regression models were used to analyze the dataset. The study included 119 mice, of which 43% were female, with an average age of 12.6 weeks, an average weight of 25.3 g. 38 (32%) of the animals died. Results: In the unadjusted analyses, experiments performed in the summer and higher weight predicted a higher risk of mortality. In the stratified Cox model by sex, summer season (adjusted hazard ratio [aHR]=5.61, p=0.004) and delayed antibiotic administration (aHR=1.46, p=0.029) were associated with mortality in males, whereas higher weight (aHR=1.52, p=0.005) significantly affected mortality in females. In addition, delayed antibiotic administration (HR=1.42, p=0.025) was associated with mortality in the nonsummer seasons, but not in the summer season. Discussion: In conclusion, some factors specific to sex and season have a significant influence on sepsis mortality in the CLP model. Consideration of these factors along with appropriate group matching or adjusted analysis is critical to minimize variability beyond the experimental conditions within a study.

Objectives This study examines whether patient outcomes were affected when the hemoglobin (Hb) transfusion threshold was lowered by 1 g/dL during COVID-19–related blood shortages. Methods Outcomes of lowered Hb thresholds (from <7 to <6 g/dL) were defined by 14-month intervals in 2 patient groups (prepandemic [January 2019-February 2020] and pandemic [April 2020-May 2021]). We evaluated patient admissions, pretransfusion (if transfused) or nadir admission (if not transfused) Hb levels between 5.0 and 8.0 g/dL, and total red blood cell (RBC) transfusions during admission (if transfused). Baseline variables and outcomes were selected from electronic health records. Primary COVID-19–related admissions were excluded. Regression analysis was conducted to determine outcomes. Results Those in the prepandemic group (1976) and pandemic group (1547) were transfused. Fewer RBCs (2186, vs 3337) were used in the prepandemic group than in the pandemic group, respectively. Those in the prepandemic group had significantly higher rates of hypertension and diabetes as well as more smokers. Significant differences were observed when comparing the number of procedures and incidence of sepsis between the patient groups. Similar patterns were observed for the not transfused and transfused subgroups. Conclusions Patient outcomes were not affected after implementing lower Hb pretransfusion thresholds. Although confounding factors were mitigated, some may have been associated with procedures or sepsis. Proactive patient blood management strategies during COVID-19–related blood shortages may include adopting lower Hb thresholds.

The prevalence of concomitant deep vein thrombosis (DVT) and its impact on 30-day outcomes in Hispanic patients with acute pulmonary embolism (PE) is unknown. We retrospectively studied a cohort of Hispanic patients admitted for acute PE to determine the relationship of concomitant DVT to clot burden on chest computer tomography (CT), right heart strain, and 30-day mortality. We identified 391 patients admitted with acute PE; 168 (42.9%) had concomitant DVTs on admission; 39 patients (9.9%) died during the 30-day follow-up: 12 patients without concomitant DVT and 27 with concomitant DVT, respectively ( p < .001). The presence of a proximal DVT independently predicted 30-day mortality even after adjusting for age, gender and admission PE severity index scores (PESI) (hazard ratio [HR] 2.0; 95% confidence interval [CI]: 1.4-3.0, p = .001). Proximal DVTs remained a significant predictor of 30-day mortality in patients with low and intermediate PESI scores (HR 2.5; 95% CI: 1.1-6.0, p = .035). The prevalence of concomitant DVT in Hispanic patients presenting with acute DVT is relatively lower than other ethnic groups. However, a proximal location of a DVT is of significant prognostic relevance. Hispanic patients with acute PE should routinely undergo compression doppler ultrasonography (CDUS) of the lower extremities.