A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients With COVID-19.

OBJECTIVES: This study retrospectively compares the effectiveness of methylprednisolone to dexamethasone in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) requiring intensive care. DESIGN: This is an institutional review board approved cohort study in patients with COVID-19 requiring intensive care unit (ICU) admission. Patients admitted and requiring oxygen supplementation were treated with no steroids, methylprednisolone, or dexamethasone. SETTING: This study takes place in the ICU's at a large, tertiary, public teaching hospital serving a primarily low-income community in urban Los Angeles. PATIENTS: All eligible patients admitted to the ICU for COVID-19 respiratory failure from March 1 to July 31, 2020 were included in this study. INTERVENTIONS: A total of 262 patients were grouped as receiving usual care (n = 75), methylprednisolone dosed at least at 1mg/kg/day for ≥ 3 days (n = 104), or dexamethasone dosed at least at 6 mg for ≥7 days (n = 83). MEASUREMENTS AND MAIN RESULTS: All-cause mortality within 50 days of initial corticosteroid treatment as compared to usual care was calculated. The mortality effect was then stratified based on levels of respiratory support received by the patient. In this cohort of 262 patients with severe COVID-19, all-cause mortalities in the usual care, methylprednisolone, and dexamethasone groups were 41.3%, 16.4% and 26.5% at 50 days (P < 0.01) respectively. In patients requiring mechanical ventilation, mortality was 42% lower in the methylprednisolone group than in the dexamethasone group (hazard ratio 0.48, 95% CI: 0.235-0.956, P = 0.0385). CONCLUSIONS: In COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone can lead to a further decreased mortality as compared to dexamethasone.

Systemic and cell intrinsic roles of Gqalpha signaling in the regulation of innate immunity, oxidative stress, and longevity in Caenorhabditis elegans.

Signal transduction pathways that regulate longevity, immunity, and stress resistance can profoundly affect organismal survival. We show that a signaling module formed by the G protein alpha subunit, Gqalpha, and one of its downstream signal transducer phospholipase C beta (PLCbeta) can differentially affect these processes. Loss of Gqalpha and PLCbeta functions result in increased sensitivity to pathogens and oxidative stress but confer life span extension. Gqalpha and PLCbeta modulate life span and immunity noncell autonomously by affecting the activity of insulin/IGF1 signaling (IIS). In addition, Gqalpha and PLCbeta function cell autonomously within the intestine to affect the activity of the p38 MAPK pathway, an important component of Caenorhabditis elegans immune and oxidative stress response. p38 MAPK activity in the intestine is regulated by diacylglycerol levels, a product of PLCbeta's hydrolytic activity. We provide genetic evidence that life span is largely determined by IIS, whereas p38 MAPK signaling is the primary regulator of oxidative stress in PLCbeta mutants. Pathogen sensitivity of Gqalpha and PLCbeta mutants is a summation of the beneficial effects of decreased IIS through reduced neuronal secretion and the detrimental effects of reduced activity of intestinal p38 MAPK. We propose a model whereby Gqalpha signaling differentially regulates pathogen sensitivity, oxidative stress, and longevity through cell autonomous and noncell autonomous effects on p38 MAPK and insulin/IGF1 signaling, respectively.

Klebsiella brain abscess in an immunocompetent patient: a case report.

BACKGROUND: Klebsiella pneumoniae brain abscesses are a rare entity and typically present in immunocompromised patients. We present a case of an overall healthy patient who developed a Klebsiella pneumoniae brain abscess in the absence of liver pathology. CASE PRESENTATION: A 46-year-old Vietnamese man with past medical history significant for hypertension presented to the hospital with acute on chronic worsening of altered mental status, personality changes, and gait dysfunction. Initial vitals revealed temperature of 37.1 °C, heart rate 87 beats/minute, blood pressure 150/87 mmHg, respiratory rate 18/minute, and oxygen saturation 99% on room air. Physical exam was notable for altered mental status, Glasgow Coma Scale (GCS) score of 14, and right lower facial droop. Cardiopulmonary exam was within normal limits. Head computed tomography (CT) showed a left frontotemporal mass, with subsequent brain magnetic resonance imaging (MRI) revealing a ring-enhancing lesion concerning for a brain abscess. The abscess was urgently drained; however, there was intraoperative spillage into the ventricles. Intraoperative cultures grew Klebsiella pneumoniae, and the patient was maintained on appropriate antibiotics. He developed worsening mental status, septic shock, and cerebral edema requiring decompressive left hemicraniectomy. Computed tomography of the abdomen and pelvis revealed no hepatic lesions. The patient did not improve, and the family elected for comfort measures. CONCLUSION: High mortality is associated with Klebsiella pneumoniae (as opposed to Klebsiella oxytoca) brain abscesses, especially in the setting of intraventricular spread. This case illustrates the need for early detection, and an aggressive medical and surgical treatment approach is required for a potential favorable outcome.