ICU outcomes and survival in patients with severe COVID-19 in the largest health care system in central Florida.

BACKGROUND: Observational studies have consistently described poor clinical outcomes and increased ICU mortality in patients with severe coronavirus disease 2019 (COVID-19) who require mechanical ventilation (MV). Our study describes the clinical characteristics and outcomes of patients with severe COVID-19 admitted to ICU in the largest health care system in the state of Florida, United States. METHODS: Retrospective cohort study of patients admitted to ICU due to severe COVID-19 in AdventHealth health system in Orlando, Florida from March 11th until May 18th, 2020. Patients were characterized based on demographics, baseline comorbidities, severity of illness, medical management including experimental therapies, laboratory markers and ventilator parameters. Major clinical outcomes analyzed at the end of the study period were: hospital and ICU length of stay, MV-related mortality and overall hospital mortality of ICU patients. RESULTS: Out of total of 1283 patients with COVID-19, 131 (10.2%) met criteria for ICU admission (median age: 61 years [interquartile range (IQR), 49.5-71.5]; 35.1% female). Common comorbidities were hypertension (84; 64.1%), and diabetes (54; 41.2%). Of the 131 ICU patients, 109 (83.2%) required MV and 9 (6.9%) received ECMO. Lower positive end expiratory pressure (PEEP) were observed in survivors [9.2 (7.7-10.4)] vs non-survivors [10 (9.1-12.9] p = 0.004]. Compared to non-survivors, survivors had a longer MV length of stay (LOS) [14 (IQR 8-22) vs 8.5 (IQR 5-10.8) p< 0.001], Hospital LOS [21 (IQR 13-31) vs 10 (7-1) p< 0.001] and ICU LOS [14 (IQR 7-24) vs 9.5 (IQR 6-11), p < 0.001]. The overall hospital mortality and MV-related mortality were 19.8% and 23.8% respectively. After exclusion of hospitalized patients, the hospital and MV-related mortality rates were 21.6% and 26.5% respectively. CONCLUSIONS: Our study demonstrates an important improvement in mortality of patients with severe COVID-19 who required ICU admission and MV in comparison to previous observational reports and emphasizes the importance of standard of care measures in the management of COVID-19.

Chest computed tomography findings in HIV-infected individuals in the era of antiretroviral therapy.

BACKGROUND: Chest radiographic abnormalities were common in HIV-infected individuals in the pre-combination antiretroviral therapy era, but findings may differ now due to a changing spectrum of pulmonary complications. METHODS: Cross-sectional study of radiographic abnormalities in an HIV-infected outpatient population during the antiretroviral therapy era. Demographics, chest computed tomography, and pulmonary function tests were obtained in HIV-infected volunteers without acute respiratory illness from the University of Pittsburgh HIV/AIDS clinic. Overall prevalence of radiographic abnormalities and potential risk factors for having any abnormality, nodules, or emphysema were evaluated using univariate and multivariable analyses. RESULTS: A majority of the 121 participants (55.4%) had a radiographic abnormality with the most common being emphysema (26.4%), nodules (17.4%), and bronchiectasis (10.7%). In multivariate models, age (odds ratio [OR] per year  = 1.07, 95% confidence interval [CI] 1.04-1.14, p<0.001), pneumonia history (OR  = 3.60, 95% CI  = 1.27-10.20, p = 0.016), and having ever smoked (OR  = 3.66, p = 0.013, 95% CI  = 1.31-10.12) were significant predictors of having any radiographic abnormality. Use of antiretroviral therapy, CD4 cell count, and HIV viral load were not associated with presence of abnormalities. Individuals with radiographic emphysema were more likely to have airway obstruction on pulmonary function tests. Only 85.8% participants with nodules had follow-up imaging resulting in 52.4% having stable nodules, 23.8% resolution of their nodules, 4.8% development of a new nodule, and 4.8% primary lung cancer. CONCLUSIONS: Radiographic abnormalities remain common in HIV-infected individuals with emphysema, nodules, and bronchiectasis being the most common. Age, smoking, and pneumonia were associated with radiographic abnormalities, but HIV-associated factors did not seem to predict risk.

Targeted therapies in small-cell lung cancer.

Small-cell lung cancer is an aggressive form of lung cancer that, overall, remains the most common cause of cancer death in the US. Some advances have been made in the treatment of small-cell lung cancer using cytotoxic chemotherapeutic agents but no truly targeted therapies are available as of yet. At present, research is focused on finding therapies that can target the specific molecular mechanisms responsible for the survival, growth and metastasis of the tumor thereby improving responses to chemotherapy and minimizing toxicity. Several new agents, such as angiogenesis inhibitors and regulators of apoptosis, have reached clinical testing and multiple others are in preclinical trials. Some of these will be discussed in this review.

GM-CSF receptor expression and signaling is decreased in lungs of ethanol-fed rats.

Alcohol abuse dramatically increases the risk of acute lung injury. In an experimental rat model of ethanol-mediated susceptibility to lung injury, recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF) restored alveolar epithelial barrier function both in vitro and in vivo, even during acute endotoxemia. These findings suggested that the alveolar epithelium, which secretes GM-CSF into the airway where it is required for alveolar macrophage maturation, likewise responds to GM-CSF priming in a receptor-mediated manner. In this study we determined that both the GM-CSF receptor alpha- and beta-subunits (GM-CSFRalpha and GM-CSFRbeta) are expressed throughout the rat airway epithelium and that this expression was significantly decreased in the alveolar epithelium following chronic ethanol ingestion (6 wk). In parallel, PU.1, the master transcription factor for GM-CSF signaling in hematopoietic cells, is also expressed in alveolar epithelial cells, and ethanol ingestion likewise decreased PU.1 protein expression and nuclear binding in the alveolar epithelium. Finally, GM-CSF signaling as reflected by PU.1 expression and nuclear binding was restored with recombinant GM-CSF treatment in vitro. We conclude that chronic ethanol ingestion decreases GM-CSF receptor expression and signaling in the lung epithelium. Consequently, we speculate that dampening of GM-CSF stimulation of the alveolar epithelium is responsible at least in part for the diverse functional defects that characterize the alcoholic lung and could be a therapeutic target in acute lung injury.

Cytokine imbalance in acute coronary syndrome.

The excessive mortality of coronary heart disease is attributed primarily to rupture and thrombotic transformation of the atherosclerotic plaque. Inflammation plays a critical role in plaque destabilization and vulnerability. Inflammation is not confined to the culprit segment but is convincingly widespread in the coronary and remote vascular beds. Systemic inflammatory, thrombotic and hemodynamic factors are relevant to the pathological and clinical outcome. In addition to their fundamental role in thrombosis, there is ample evidence that platelets contribute significantly to promoting plaque inflammation. A new paradigm of unbalanced cytokine-mediated inflammation is emerging, providing diagnostic and therapeutic opportunity for intervention. Amplifying intrinsic anti-inflammatory mechanisms constitutes attractive avenues for future investigation.