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Abstract Objective: To synthesize the methodologies of studies that evaluate the impacts of heat exposure on morbidity and mortality. Methods: Embase, MEDLINE, Web of Science, and Scopus were searched from date of inception until 1 March 2023 for English language literature on heat exposure and health outcomes. Records were collated, deduplicated and screened, and full texts were reviewed for inclusion and data abstraction. Eligibility for inclusion was determined as any article with climate‐related heat exposure and an associated morbidity/mortality outcome. Results: Of 13,136 records initially identified, 237 articles were selected for analysis. The scope of research represented 43 countries, with most studies conducted in China (62), the USA (44), and Australia (16). Across all studies, there were 141 unique climate data sources, no standard threshold for extreme heat, and 200 unique health outcome data sources. The distributed lag non‐linear model (DLNM) was the most common analytic method (48.1% of studies) and had high usage rates in China (68.9%) and the USA (31.8%); Australia frequently used conditional logistic regression (50%). Conditional logistic regression was most prevalent in case‐control studies (5 of 8 studies, 62.5%) and in case‐crossover studies (29 of 70, 41.4%). DLNMs were most common in time series studies (64 of 111, 57.7%) and ecological studies (13 of 20, 65.0%). Conclusions: This review underscores the heterogeneity of methods in heat impact studies across diverse settings and provides a resource for future researchers. Underrepresentation of certain countries, health outcomes, and limited data access were identified as potential barriers.

Femoral atherosclerotic plaques are less inflammatory than carotid plaques histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 patients undergoing femoral (n = 23) or carotid (n = 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n = 13), flow cytometry (n = 24), and IHC (n = 12). Comparative scRNA-Seq of CD45+-selected leukocytes from femoral (n = 9; 35,265 cells) and carotid (n = 4; 30,655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell–like macrophages and monocytes comprised higher proportions of myeloid cells in carotid plaques, whereas noninflammatory foam cell–like macrophages and LYVE1-overexpressing macrophages comprised higher proportions of myeloid cells in femoral plaque (P < 0.001 for all). A significant comparative excess of CCR2+ macrophages in carotid versus plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively antiinflammatory profile in femoral plaque, whereas cytotoxic CD8+ T cells were more prevalent in carotid plaque. In conclusion, human femoral plaques exhibit distinct macrophage phenotypic and transcriptional profiles as well as diminished CD8+ T cell populations compared with human carotid plaques

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

OBJECTIVES:. Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN:. Multicenter cohort study. SETTING:. ICUs at 68 hospitals across the United States. PATIENTS:. A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity

Background: Social vulnerability is an important determinant of cardiovascular health. Prior investigations have shown strong associations of social determinants of health with cardiovascular risk factors, imaging findings, and clinical events. However, limited data exist regarding the potential role of social vulnerability and related physiologic stressors on tissue-level pathology.Methods: We analyzed clinical data and linked autopsy reports from 853 decedent individuals who underwent autopsy from 4/6/2002 to 4/1/2021 at a large urban medical center. The mean age at death was 62.9 (SD = 15.6) and 49% of decedent individuals were men. The primary exposure was census-tract level composite social vulnerability index based on the Centers for Disease Control and Prevention Social Vulnerability Index (SVI). Individuals were geocoded to census tracts and assigned SVI accordingly. Four myocardial tissue-level outcomes from autopsy were recorded as present or absent: any coronary atherosclerosis, severe/obstructive coronary atherosclerosis, myocardial fibrosis, and/or myopericardial inflammation. Multivariable-adjusted logistic regression models were constructed with SVI as the primary exposure and covariates including age, sex, race, body mass index (BMI), diabetes, and hypertension. Additional analyses were performed stratified by clinical diagnoses of heart failure (HF) and coronary artery disease (CAD).Results: In the overall cohort, SVI was not associated with outcomes on cardiac pathology in multivariable-adjusted models. However, in stratified multivariable-adjusted analyses, higher SVI (higher social vulnerability) was associated with a higher odds of myocardial fibrosis among individuals without clinical diagnoses of HF.Conclusions: Higher indices of social vulnerability are associated with a higher odds of myocardial fibrosis at autopsy among individuals without known clinical diagnoses of HF. Potential pathophysiological mechanisms and implications for prevention/treatment of myocardial dysfunction require further study.