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Objective Approximately one-third of sepsis patients experience poor outcomes including chronic critical illness (CCI, intensive care unit (ICU) stay > 14 days) or early death (in-hospital death within 14 days). We sought to characterize lipoprotein predictive ability for poor outcomes and contribution to sepsis heterogeneity. Design Prospective cohort study with independent replication cohort. Setting Emergency department and surgical ICU at two hospitals. Patients Sepsis patients presenting within 24 h. Methods Measures included cholesterol levels (total cholesterol, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C]), triglycerides, paraoxonase-1 (PON-1), and apolipoprotein A-I (Apo A-I) in the first 24 h. Inflammatory and endothelial markers, and sequential organ failure assessment (SOFA) scores were also measured. LASSO selection assessed predictive ability for outcomes. Unsupervised clustering was used to investigate the contribution of lipid variation to sepsis heterogeneity. Measurements and main results 172 patients were enrolled. Most (~ 67%, 114/172) rapidly recovered, while ~ 23% (41/172) developed CCI, and ~ 10% (17/172) had early death. ApoA-I, LDL-C, mechanical ventilation, vasopressor use, and Charlson Comorbidity Score were significant predictors of CCI/early death in LASSO models. Unsupervised clustering yielded two discernible phenotypes. The Hypolipoprotein phenotype was characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1), higher SOFA scores, and worse clinical outcomes (45% rapid recovery, 40% CCI, 16% early death; 28-day mortality, 21%). The Normolipoprotein cluster patients had higher cholesterol levels, less endothelial dysfunction, lower SOFA scores and better outcomes (79% rapid recovery, 15% CCI, 6% early death; 28-day mortality, 15%). Phenotypes were validated in an independent replication cohort (N = 86) with greater sepsis severity, which similarly demonstrated lower HDL-C, ApoA-I, and higher ICAM-1 in the Hypolipoprotein cluster and worse outcomes (46% rapid recovery, 23% CCI, 31% early death; 28-day mortality, 42%). Normolipoprotein patients in the replication cohort had better outcomes (55% rapid recovery, 32% CCI, 13% early death; 28-day mortality, 28%) Top features for cluster discrimination were HDL-C, ApoA-I, total SOFA score, total cholesterol level, and ICAM-1. Conclusions Lipoproteins predicted poor sepsis outcomes. A Hypolipoprotein sepsis phenotype was identified and characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1) and organ failure, and worse clinical outcomes.

ObjectiveThe specialty of emergency medicine and recognition of the need for emergency care continue to grow globally. The specialty and emergency care systems vary according to context. This study characterizes the specialty of emergency medicine around the world, trends according to region and income level, and challenges for the specialty. MethodsWe distributed a 56‐question electronic survey to all members of the American College of Emergency Physicians International Ambassador Program between March 2019 and January 2020. The Ambassador Program leadership designed the survey covering specialty recognition, workforce, system components, and emergency medicine training. We analyzed results by country and in aggregate using SAS software (SAS Institute Inc). We tested the associations between World Bank income group and number of emergency medicine residency‐trained physicians (RTPs) and emergency medicine specialty recognition using non‐parametric Fisher's exact testing. We performed inductive coding of qualitative data for themes. ResultsSixty‐three out of 78 countries’ teams (80%) responded to the survey. Response countries represented roughly 67% of the world's population and included countries in all World Bank income groups. Fifty‐four countries (86%) recognized emergency medicine as a specialty. Ten (16%) had no emergency medicine residency programs, and 19 (30%) had only one. Eight (11%) reported having no emergency medicine RTPs and 30 (48%) had <100. Fifty‐seven (90%) had an emergency medical services (EMS) system, and 52 (83%) had an emergency access number. Higher country income was associated with a higher number of emergency medicine RTPs per capita ( P = 0.02). Only 6 countries (8%) had >5 emergency medicine RTPs per 100,000 population, all high income. All 5 low‐income countries in the sample had <2 emergency medicine RTPs per 100,000 population. Challenges in emergency medicine development included lack of resources (38%), burnout and poor working conditions (31%), and low salaries (23%). ConclusionsMost surveyed countries recognized emergency medicine as a specialty. However, numbers of emergency medicine RTPs were small, particularly in lower income countries. Most surveyed countries reported an EMS system and emergency access number. Lack of resources, burnout, and poor pay were major threats to emergency medicine growth.

The specialty of emergency medicine (EM) is in varying stages of development around the world. Members of the American College of Emergency Physicians (ACEP) international ambassador program were surveyed to document the growth and current state of emergency medicine around the world. This was a descriptive, cross-sectional survey with 66 items covering EM specialty development, training, and working conditions. Data were collected digitally from January to September 2023. We performed a descriptive statistical analysis and analyzed categorical data using chi-squared and Fisher’s exact test. Responses were obtained from 69/77 countries with ACEP ambassadors (90%). EM was a recognized specialty in 63/69 (91%) responding countries. Fifty-nine responding countries (86%) have a national EM society. A total of 113,254 EM residency-trained physicians (EMRTPs) were reported working in 77,563 emergency departments, caring for a total population of 6.05 billion. Sixty countries (87%) report EM residencies, totaling 1790 programs; 1 in 3 respondents have only 1 EM training program. Countries with higher income levels had more EMRTPs per capita; of those with at least 1 EMRTP per 100,000 population, 27 were upper-middle or high income, whereas only 1 was lower-middle or low income. The field of EM continues to gain traction globally, and the number of countries recognizing EM as a specialty is increasing. Most countries surveyed recognized EM as a specialty and many more EMRTPs were reported compared with 2019. The number of EM residency programs and EMRTPs in practice continues to grow. The 2023 ACEP ambassador reports highlight growth, expansion in EM training, and specialty professionalization around the world.

Metabolic derangements in sepsis influence phosphate levels, which may predict mortality outcomes. We investigated the association between initial phosphate levels and 28-day mortality in patients with sepsis. We conducted a retrospective analysis of patients with sepsis. Initial (first 24 hours) phosphate levels were divided into phosphate quartile groups for comparisons. We used repeated-measures mixed-models to assess differences in 28-day mortality across the phosphate groups, adjusting for other predictors identified by the Least Absolute Shrinkage and Selection Operator variable selection technique. A total of 1,855 patients were included with 13% overall 28-day mortality (n=237). The highest phosphate quartile (>4.0 milligrams per deciliter [mg/dL]) had a higher mortality rate (28%) than the three lower quartiles (P<0.001). After adjustment (age, organ failure, vasopressor administration, liver disease), the highest initial phosphate was associated with increased odds of 28-day mortality. Patients in the highest phosphate quartile had 2.4 times higher odds of death than the lowest (≤2.6 mg/dL) quartile (P<0.01), 2.6 times higher than the second (2.6-3.2 mg/dL) quartile (P<0.01), and 2.0 times higher than the third (3.2-4.0 mg/dL) quartile (P=0.04). Septic patients with the highest phosphate levels had increased odds of mortality. Hyperphosphatemia may be an early indicator of disease severity and risk of adverse outcomes from sepsis.

Virtual communities of practice (VCoPs) facilitate distance learning and mentorship by engaging members around shared knowledge and experiences related to a central interest. The American College of Emergency Physicians and Emergency Medicine Residents’ Association's Global Emergency Medicine Student Leadership Program (GEM‐SLP) provides a valuable model for building a VCoP for GEM and other niche areas of interest. This VCoP facilitates opportunities for experts and mentees affiliated with these national organizations to convene regularly despite barriers attributed to physical distance. The GEM‐SLP VCoP is built around multiple forms of mentorship, monthly mentee‐driven didactics, academic projects, and continued engagement of program graduates in VCoP leadership. GEM‐SLP fosters relationships through (1) themed mentoring calls (career paths, work/life balance, etc); (2) functional mentorship through didactics and academic projects; and (3) near‐peer mentoring, provided by mentors near the mentees’ stage of education and experience. Monthly mentee‐driven didactics focus on introducing essential GEM principles while (1) critically analyzing literature based on a journal article; (2) building a core knowledge base from a foundational textbook; (3) applying knowledge and research to a project proposal; and (4) gaining exposure to training and career opportunities via mentor career presentations. Group academic projects provide a true GEM apprenticeship as mentees and mentors work collaboratively. GEM‐SLP mentees found the VCoP beneficial in building fundamental GEM skills and knowledge and forming relationships with mentors and like‐minded peers. GEM‐SLP provides a framework for developing mentorship programs and VCoPs in emergency medicine, especially when niche interests or geographic distance necessitate a virtual format.

RationaleSepsis is a life-threatening, dysregulated response to infection. Lipid biomarkers including cholesterol are dynamically regulated during sepsis and predict short-term outcomes. In this study, we investigated the predictive ability of lipid biomarkers for physical function and long-term mortality after sepsis.MethodsProspective cohort study of sepsis patients admitted to a surgical intensive-care unit (ICU) within 24 h of sepsis bundle initiation. Samples were obtained at enrollment for lipid biomarkers. Multivariate regression models determined independent risk factors predictive of poor performance status (Zubrod score of 3/4/5) or survival at 1-year follow-up.Measurements and main resultsThe study included 104 patients with surgical sepsis. Enrollment total cholesterol and high-density lipoprotein (HDL-C) levels were lower, and myeloperoxidase (MPO) levels were higher for patients with poor performance status at 1 year. A similar trend was seen in comparisons based on 1-year mortality, with HDL-C and ApoA-I levels being lower and MPO levels being higher in non-survivors. However, multivariable logistic regression only identified baseline Zubrod and initial SOFA score as significant independent predictors of poor performance status at 1 year. Multivariable Cox regression modeling for 1-year survival identified high Charlson comorbidity score, low ApoA-I levels, and longer vasopressor duration as predictors of mortality over 1-year post-sepsis.ConclusionsIn this surgical sepsis study, lipoproteins were not found to predict poor performance status at 1 year. ApoA-I levels, Charlson comorbidity scores, and duration of vasopressor use predicted 1 year survival. These data implicate cholesterol and lipoproteins as contributors to the underlying pathobiology of sepsis.

OBJECTIVES/GOALS: Septic shock is a lethal condition. Research suggests that overall sepsis mortality varies by race, but less is known about demographic differences in septic shock mortality. Our objectives were to describe the septic shock population using a large, state-wide data repository and identify demographic predictors of septic shock mortality. METHODS/STUDY POPULATION: This was a retrospective review of patients with septic shock in the One Florida Data Trust from 2012-2018. Patients were classified as having septic shock if they received vasopressors and had either 1) an ICD-9 or 10 code for septic shock or 2) an ICD-9 or 10 code for infection and an ICD-9 or 10 code for organ dysfunction. Demographic data and place of residence prior to admission was collected. The primary outcome was 90 day mortality. T-test and chi-square tests were used to test association of individual predictors and mortality. Multiple logistic regression was used to identify predictors of mortality after adjustment for other variables. Level of significance was set at 0.05. SAS v9.4 (Cary, NC) was used for analyses. RESULTS/ANTICIPATED RESULTS: There were 11,790 patients with septic shock. The mean(SD) age was 61(16) years. With regard to race/ethnicity 66% identified as white, 27% as black, 3.7% as Hispanic, and 3.5% as other races (non-white, non-black, non-Hispanic). Most came from home (57%). Overall, 39% died. Mortality varied by race (p<0.01): white 39%, black 39%, Hispanic 31%, other races 51%. In the logistic regression model, age, race, and residence were significant predictors of mortality, after adjustment for other variables. Each additional year of age had a 2.7% increased odds of mortality (OR 1.03; 95% CI 1.02-1.03; p<0.01). Compared to white patients, odds of death were 1.6 times higher for other races (95% CI 1.3-2.0; p <0.01) and non-significantly higher for black patients (OR 1.1; 95% CI 1.0-1.2; p = 0.05). Compared to those from home, odds of death were highest for those from a skilled nursing facility (OR 1.5; p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Patients who identified as other races had increased mortality from septic shock compared to white patients after adjusting for other variables. Septic shock mortality also increased with age and varied by residence. Further analyses are needed to examine racial disparities and control for comorbidities, severity of illness, and aspects of resuscitation. CONFLICT OF INTEREST DESCRIPTION: The authors report no conflicts of interest, except for Dr. Fernandez, who reports personal payment from Physio-Control, Inc. for speaker fees.

ABSTRACT IMPACT: Identifying racial disparities in septic shock mortality, a common and lethal condition, can inform future research and policy efforts aimed at understanding the drivers these disparities and addressing the underlying factors in order to reduce disparities and improve health. OBJECTIVES/GOALS: Septic shock is a major public health problem with significant mortality. Existing data indicate racial disparities in sepsis incidence, but evidence is limited on differences in septic shock outcomes. Our objective was to determine the association between race and septic shock mortality in a statewide cohort while controlling for clinical factors. METHODS/STUDY POPULATION: This was a retrospective analysis of septic shock patients in the One Florida Data Trust between 2012-18. Data was collected regarding age, sex, race, insurance status, and selected comorbid conditions [liver disease, hypertension, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), end-stage renal disease (ESRD), and human immunodeficiency virus infection (HIV)]. To account for severity of illness, we assigned Sequential Organ Failure Assessment scores for components based on laboratory values (labSOFA), and collected data on mechanical ventilation use and initial lactate. The primary outcome was 90-day mortality. The Least Absolute Shrinkage and Selection Operator (LASSO) method was used for variable selection for the multivariable regression model. RESULTS/ANTICIPATED RESULTS: There were 13,932 septic shock patients with a mean (SD) age of 61(16) years. Of these, 68% identified as white, 28% as black, 2.1% as Hispanic, and 2.0% as other races. 90-day mortality was 32% (n=4,437) and 59% required mechanical ventilation. Significant independent predictors of mortality in the regression model were age (OR 1.04; p<0.01), black race (1.72; p<0.01), lactate (1.10; p<0.01), mechanical ventilation (3.62; p<0.01), labSOFA (1.18; p<0.01), history of liver disease (1.75; p<0.01), hypertension (0.70; p<0.01), COPD (0.87; p<0.01), CHF (1.18; p<0.01), HIV (1.30; p=0.05), and the interaction between age and black race. Black patients had 1.72 times the odds of mortality compared to white patients. For every one-year decrease in age, black patients had a 1% increased odds of mortality (OR 1.01; p < 0.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: Black patients have increased odds of dying from septic shock compared to white patients after controlling for age, selected comorbid conditions, and markers of illness severity. Future work is needed to move beyond demonstrating septic shock disparities and towards understanding the underlying factors.

Extant REIT research largely overlooks operating leases as an alternative source of financing. In this study, we hand-collect lease information of 334 unique REITs over the period of 1993 to 2018, and we document that an increasing number of REITs have been including operating leases in their capital structure to finance income-generating investment properties. We examine the determinants of the operating lease decision and find that REITs which adopt operating leases tend to be larger and have more growth opportunities as measured by Tobin’s Q. But they also have higher leverage, report lower funds from operations, and higher risk. We further find that operating lease intensity for REITs is negatively affected by credit ratings, but not by growth opportunities. Lastly, we examine the market effect related to operating lease decision and find that REITs with operating leases are associated with lower shareholder returns. Overall, our findings imply that operating leases are employed as an alternative financing source by REITs that are highly levered and cannot rely much on their internal funding. As a result, the market does not view the use of operating leases in the REIT sector favorably.

REITs hold relatively little cash and access capital markets often due to their favorable dividend tax status. The transparent nature of REITs, in theory, implies low information asymmetry. However, we present evidence that this phenomenon is temporal. We find that information asymmetry is relatively low when REITs access the capital markets, when compared to non-accessing periods, based on bid-ask spreads for a large number of REITs. Further, we find that REIT size and turnover affect bid-ask spreads, but the pattern of lower bid-ask spreads surrounding capital market access does manifest itself when we investigate subsamples, dependent on size and turnover. Our findings are consistent with the idea that REITs increase their disclosure when they access the capital markets, which in turn lowers information asymmetry.