Clinical Characteristics and Predictors of Mortality in Minority Patients Hospitalized with COVID-19 Infection.

OBJECTIVES: To identify the early mortality predictors in minority patients hospitalized with coronavirus disease 2019 (COVID-19). DESIGN: Demographics, presenting characteristics, admission laboratory data, ICU admission, and mortality data were collected from 200 consecutively hospitalized patients with COVID-19. RESULTS: The mean (SD) age was 58.9 (15.1) years, 121(60.5%) were men, 143 (71.5%) were African Americans, and 33 (16.5%) were Latino. Common presenting symptoms were cough 130 (65.0%), shortness of breath 129 (64.5%), and fever 121 (60.5%). One or more comorbid illness occurred in 171 (85.5%) and common comorbidities were hypertension (130 (65.2%)), diabetes (100 (50.0%)) and chronic kidney disease (60 (30.0%)). Of the 200 patients, 71 (35.5%) were treated in the ICU, 47 (24.2%) received mechanical ventilation, 45 (22.5%) died, and 155(77.5%) patients discharged home alive. The non-survivors were significantly older and had elevated markers of inflammation, coagulation, and acute organ damage on presentation. Age ≥ 65 years (odds ratio (OR), 3.78; 95% CI, 1.74-8.22; P = .001), lactate dehydrogenase level > 400 IU/L (OR, 9.1; 95% CI, 2.97-28.1; p < 0.001), C-reactive protein > 20 mg/dl (OR, 5.56; 95%CI, 1.84-16.8; p < 0.001), ferritin > 2000 ng/ml (OR, 5.42; 95%CI, 1.63-17.9; p = 0.006), creatinine kinase > 1000 iu/l (OR, 3.57; 95% CI, 1.23 10.3; p = 0.019), procalcitonin > 2.5 ng/ml (OR, 4.21; 95% CI, 1.47-12.0; p = 0.007), D-dimer level > 3.0 µg/ml (OR,10.9; 95% CI, 3.33-36.2; p = < 0.001), creatinine > 2 mg/dl (OR, 4.5; 95% CI, 1.29-15.8; P = 0.018) at admission were associated independently with increases risk of in-hospital mortality. CONCLUSION: Patients of advanced age that present with elevated biomarkers of inflammation, coagulation, and end-organ damage were at higher risk of mortality.

Geographic Variation in Racial Disparities in Mortality From Influenza and Pneumonia in the United States in the Pre-Coronavirus Disease 2019 Era.

BACKGROUND: In 2018, influenza and pneumonia was the eighth leading cause of death in the United States. Since 1950, non-Hispanic blacks (NHBs) have experienced higher rates of mortality than non-Hispanic whites (NHWs). Previous studies have revealed geographic variation in mortality rates by race. The identification of areas with the greatest disparity in influenza and pneumonia mortality may assist policymakers in the allocation of resources, including for the coronavirus disease 2019 pandemic. RESEARCH QUESTION: Does geographic variation in racial disparity in influenza and pneumonia mortality exist? STUDY DESIGN AND METHODS: The Centers for Disease Control and Prevention database for Multiple Cause of Death between 1999 and 2018 for NHB and NHW decedents ≥ 25 years of age with a Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems code for influenza (J09-J11) and pneumonia (J12-J18) was used. Age-adjusted mortality rates (AAMRs) with 95% CIs were computed by race for Health & Human Services (HHS) regions and urbanization in NHBs and NHWs. RESULTS: In 1999 through 2018, there were 540,476 deaths among NHBs and NHWs 25 to 84 years of age. AAMRs were higher in NHBs than NHWs in each age group and in seven of 10 HHS regions. The greatest disparity was in HHS regions 2 (New York and New Jersey) and 9 (Arizona, California, Hawaii, and Nevada). In HHS region 2, NHBs (24.6; 95% CI, 24.1-25.1) were more likely to die than NHWs (15.7; 95% CI, 15.6-15.9). Similarly, in region 9, NHBs (23.2; 95% CI, 22.7-23.8) had higher mortality than NHWs (16.1; 95% CI, 15.9-16.2). Within these regions, disparities were greatest in the core of major metropolitan areas. A very high AAMR in NHBs was noted in large, central metropolitan areas of region 2: 28.2 (95% CI, 27.6-28.9). INTERPRETATION: In 1999 through 2018, the NHB-NHW disparity in AAMRs from influenza and pneumonia was greatest in central metropolitan areas of HHS regions 2 and 9.

Review: Hemodynamic Characteristics and Outcomes of Sickle Cell Disease Associated Pulmonary Hypertension.

Pulmonary hypertension (PH) is a leading cause of morbidity and early mortality in adults with sickle cell disease (SCD). However, the prevalence, hemodynamic profile and prognosis of SCD-PH remain controversial and need frequent updates. Pulmonary hypertension determined by right heart catheterization (RHC) occurs in 6% to 10% of adults with SCD. Hemodynamically, SCD-PH may be pre-capillary or post-capillary in nature. The exact etiology is unknown and often multifactorial; hence a thorough diagnostic evaluation following established PH guidelines is essential to determine disease prevalence, etiology and outcomes. Data on the efficacy and safety of pulmonary arterial hypertension (PAH) therapy are limited in SCD; clinical trials in these patients are urgently needed. This review provides an overview of RHC-determined hemodynamic characteristics, current management modality and outcomes; we also highlight recent advances and unmet research needs in SCD-PH.

Obesity and Pulmonary Function in African Americans.

BACKGROUND: Obesity prevalence in United States (US) adults exceeds 30% with highest prevalence being among blacks. Obesity is known to have significant effects on respiratory function and obese patients commonly report respiratory complaints requiring pulmonary function tests (PFTs). However, there is no large study showing the relationship between body mass index (BMI) and PFTs in healthy African Americans (AA). OBJECTIVE: To determine the effect of BMI on PFTs in AA patients who did not have evidence of underlying diseases of the respiratory system. METHODS: We reviewed PFTs of 339 individuals sent for lung function testing who had normal spirometry and lung diffusion capacity for carbon monoxide (DLCO) with wide range of BMI. RESULTS: Functional residual capacity (FRC) and expiratory reserve volume (ERV) decreased exponentially with increasing BMI, such that morbid obesity resulted in patients breathing near their residual volume (RV). However, the effects on the extremes of lung volumes, at total lung capacity (TLC) and residual volume (RV) were modest. There was a significant linear inverse relationship between BMI and DLCO, but the group means values remained within the normal ranges even for morbidly obese patients. CONCLUSIONS: We showed that BMI has significant effects on lung function in AA adults and the greatest effects were on FRC and ERV, which occurred at BMI values < 30 kg/m2. These physiological effects of weight gain should be considered when interpreting PFTs and their effects on respiratory symptoms even in the absence of disease and may also exaggerate existing lung diseases.

HSP90 inhibition by 17-DMAG reduces inflammation in J774 macrophages through suppression of Akt and nuclear factor-κB pathways.

OBJECTIVE: This study was designed to determine whether inhibition of heat shock protein 90 (HSP90) reduces pro-inflammatory mediator production by decreasing the nuclear factor (NF)-κB and Akt signaling pathways in immune-stimulated macrophages. METHODS: J774A.1 murine macrophages were treated with the HSP90 inhibitor 17-DMAG (0.01, 0.1 or 1 µM) prior to immune stimulation with lipopolysaccharide and interferon-γ. Expression of Akt, inhibitor of κB kinase (IKK), and heat shock proteins were measured in whole cell lysates by Western blotting. Phosphorylated Akt and inhibitor of κB (IκB) were measured in whole cell lysates by ELISA. Cell supernatants were analyzed for interleukin (IL)-6, tumor necrosis factor (TNF)-α and nitric oxide (NO). Translocation of NF-κB and heat shock factor (HSF)-1 was assessed by immunofluorescence. RESULTS: Treating cells with 17-DMAG reduced expression of Akt and IKK in immune-stimulated cells. 17-DMAG reduced nuclear translocation of NF-κB and reduced immune-stimulated production of IL-6, TNF-α and NO, but did not decrease inducible nitric oxide synthase expression. CONCLUSIONS: Our studies show that the immune-mediated NF-κB inflammatory cascade is blocked by the HSP90 inhibitor 17-DMAG. Due to the broad interaction of HSP90 with many pro-inflammatory kinase cascades, inhibition of HSP90 may provide a novel approach to reducing chronic inflammation.