Key Points Question What is the risk of developing cardiomyopathy among patients with the acute phase of Chagas infection or the indeterminate chronic form of Chagas disease? Findings In this systematic review and meta-analysis of 32 studies of patients with Chagas disease, the pooled estimated annual rate of cardiomyopathy was 4.6% among patients with acute Chagas infection and 1.9% among patients with indeterminate chronic Chagas disease. Meaning The findings indicate that asymptomatic individuals with indeterminate chronic Chagas disease without cardiac injury and individuals with acute Chagas infection may have a significant risk of developing chronic cardiomyopathy.

Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3 g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24 h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24 h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased basal Crf mRNA in the central nucleus of the amygdala, but no additional effects of stress or caffeine consumption were observed in other brain regions. Together these findings suggest that adolescent caffeine consumption may increase vulnerability to psychiatric disorders including anxiety-related disorders, and this vulnerability may result from dysregulation of the neuroendocrine stress response system.

Background Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids reduced mortality in a cohort of HIV-negative PJP patients. Methods We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995-2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify mortality predictors. Results Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), or solid organ transplantation (10.7%). HIV-negative patients had higher rates and duration of mechanical ventilation and ICU stay. Survival was significantly increased in HIV-negative patients receiving adjuvant corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (p=0.034). In an adjusted multivariable model, no adjuvant corticosteroids use was associated with higher mortality (OR 13.5, 95% CI: 1.1-158.5, p= 0.039) regardless of HIV status. Conclusions We found substantial mortality among HIV-negative patients with PJP and adjuvant corticosteroid use was associated with decreased mortality. Response to corticosteroids is best established in HIV infected patients, but emerging reports suggest a similar beneficial response in PJP patients without HIV infection. Further prospective studies may establish a more definitive role of corticosteroid addition among HIV-negative patients with PJP.

Background: Diabetes mellitus is an established risk factor for bacterial infections, but its role in cryptococcosis is unclear. The study aimed to determine whether uncontrolled diabetes (HbA1c >7%) was an independent risk factor for mortality in cryptococcosis. Methods: A retrospective case–control study partially matched by age and gender was performed in patients tested for Cryptococcus infection at the University of Colorado Hospital from 2000 to 2019. A multivariable logistic regression model was used to identify mortality predictors. Cox proportional hazard model was used for survival analysis. Results: We identified 96 cases of cryptococcosis and 125 controls. Among cases, cryptococcal meningitis (49.0%) and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis with uncontrolled diabetes had a higher mortality at 10 weeks (50% versus 7%, p = 0.006) and 1 year (66.7% versus 13.8%, p = 0.005) compared to pulmonary cases with controlled or no diabetes. Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10 weeks [hazard ratio 8.4, confidence interval (CI): 1.4–50.8, p = 0.02] and 1 year (hazard ratio 7.0, CI: 1.7–28.4, p = 0.007) among pulmonary cryptococcosis cases. Multivariable analysis showed a significantly increased odds of 10 weeks [odds ratio (OR) = 4.3, CI: 1.1–16.5, p = 0.035] and 1 year (OR = 5.0, CI: 1.4–18.3, p = 0.014) mortality for uncontrolled diabetes among pulmonary cryptococcosis cases. After adjustment for gender, age, and case/control, for every 1% increase in HbA1c levels, the odds of pulmonary cryptococcosis mortality at 1 year increased by 11% (OR = 1.6, CI 95%: 1.1–2.3, p = 0.006). Conclusion: Uncontrolled diabetes is associated with worse outcomes in pulmonary cryptococcosis, including a 4-fold and 6-fold increased odds of death at 10 weeks and 1 year, respectively. Glucose control interventions should be explored to improve clinical outcomes in patients with pulmonary cryptococcosis.

Background: Yellow fever (YF) virus has the potential to cause fatal outcomes among at-risk individuals visiting endemic areas. Vaccinating travelers who are at risk is necessary to prevent virus-related life-threatening complications. We lack data on the clinical features of persons seeking YF vaccination. We aim to describe the characteristics of a cohort of persons receiving the YF vaccine before travel. Methods: A retrospective analysis of 964 travelers receiving the YF vaccine (Stamaril®) from Oct 2016 to Jul 2019 was performed at the University of Colorado Hospital, U.S. Percentages, means, and standard deviations were calculated. A multivariate logistic regression model was built to evaluate the association between receiving YF vaccination less than 10 days before departure and visiting friends and relatives (VFR). Results: The average age of the subjects was 39 ± 18 years with a range of nine months to 83 years. Persons who were 60 years of age and older represented 17%. Women consisted of 52%, and most of the travelers were Caucasians (64%). Travelers reported traveling to Africa (57%) or South America (40%). The primary destinations for travelers overall were Kenya (19%), Uganda (11%), and Tanzania (11%) in Africa; and Peru (14%) and Brazil (13%) in South America. The most common reasons for travel included leisure (44%), VFR (18%), and mission trips (10%). Comorbidities included a history of hematologic disorders (4%), HIV infection (2%), and diabetes mellitus (3%). The average duration between vaccine administration and travel was 43 days. Those VFR were two times more likely to receive the YF vaccination <10 days before departure. Conclusions: Identifying the type of travel, itinerary, and underlying medical conditions allows providers to administer the YF vaccine to travelers safely. There is a need to identify strategies to improve the timing of YF vaccination among VFR travelers.

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Background Yellow fever (YF) vaccine has the potential to cause viscerotropic and neurotropic disease in at-risk individuals. Screening patients is necessary to prevent vaccine-related life-threatening complications. We lack data on the clinical features of patients seeking YF vaccination. We aim to describe the characteristics of a cohort of patients receiving the YF vaccine before travel. Methods A retrospective analysis of 964 patients receiving the YF vaccine (Stamaril®) from Oct 2016 to Jul 2019 was performed at the University of Colorado Hospital in the United States. Percentages, means, and standard deviations were calculated. A multivariate logistic regression model was built to evaluate the association between receiving YF vaccination less than 10 days before departure and visiting friends and relatives (VFR). Results The average age of patients was 39 ± 18 years with a range of 9 months to 83 years. Patients who were 60 years of age and older represented 17%. Women consisted of 52%, and most of the patients were Caucasians (64%). Patients reported traveling to Africa (57%) or South America (40%). The primary destination for patients overall was Kenya (19%), Uganda (11%), and Tanzania (11%) in Africa; and Peru (14%) and Brazil (13%) in South America. The most common reasons for travel included leisure (44%), VFR (18%), and mission trips (10%). Comorbidities included a history of hematologic disorders (4%), HIV infection (2%), and diabetes mellitus (3%). The average duration between vaccine administration and travel was 43 days. Those visiting friends and relatives were 2 times more likely to receive the YF vaccination less than 10 days before departure. Table 1. A cohort of patients receiving the Yellow Fever vaccine at the University of Colorado Hospital. Figure 1. Heat map of destinations among patients receiving the YF vaccine. Figure 2. Reasons for travel among patients receiving the YF vaccine (n=964). Conclusion Identifying the type of travel, itinerary, and underlying medical conditions allows providers to administer the YF vaccine to travelers safely. There is a need to identify strategies to improve the timing of YF vaccination among travelers visiting friends and relatives. Disclosures All Authors: No reported disclosures

BackgroundDiabetes mellitus is an established risk factor for bacterial infections, but its role in Cryptococcosis is unclear. The study aimed to determine whether uncontrolled diabetes (HbA1c >7%) was an independent risk factor for mortality in cryptococcosis.MethodsA retrospective case-control study partially matched by age and gender was performed in patients tested for Cryptococcus infection at the University of Colorado Hospital from 2000-2019. A multivariable logistic regression model was used to identify mortality predictors. Cox proportional hazard model was used for survival analysis.ResultsWe identified 96 cases of Cryptococcosis and 125 controls. Among cases, cryptococcal meningitis (49.0%) and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis had a higher mortality at 10 weeks (50% vs 7%, p=0.006) and one year (66.7% vs 13.8%, p=0.005). Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10-weeks (hazard ratio 8.4, CI: 1.4-50.8, p=0.02), and 1-year (hazard ratio 7.0, CI: 1.7-28.4, p=0.007) among pulmonary cryptococcosis cases. Multivariable analysis showed a significantly increased odds of 10-weeks (OR=4.3, CI: 1.1-16.5, p=0.035) and one-year (OR=5.9, CI: 2.2-15.8, p=0.014) mortality for uncontrolled diabetes among pulmonary cryptococcosis cases. After adjustment for gender, age, and case/control, for every 1% increase in HbA1c levels, the odds of pulmonary cryptococcosis mortality at one-year increased by 11% (OR = 1.6, CI 95%: 1.1-2.3, p= 0.006).ConclusionUncontrolled diabetes is associated with worse outcomes in pulmonary cryptococcosis, including a 4-fold and 6-fold increased odds of death at 10-weeks and 1-year, respectively. Glucose control interventions should be explored to improve clinical outcomes in patients with pulmonary cryptococcosis.