Empiric use of anticoagulation in hospitalized patients with COVID-19: a propensity score-matched study of risks and benefits.

BACKGROUND: Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients. METHODS: We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts. RESULTS: The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345-0.657, p < 0.001) with longer median survival (14 days vs 8 days, p < 0.001), but these associations were not observed in the overall cohort (p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p < 0.001). Furthermore, patients with a HAS-BLED score of ≥2 had a higher risk of mortality (HR 1.482, 95% CI 1.110-1.980, p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114-3.729, p = 0.016). CONCLUSION: Empiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.

Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. METHODS: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. RESULTS: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 (P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PaO2: FiO2) were significantly improved during days 4-7 (P < 0.05 for all). CONCLUSIONS: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated. Replicating results and scaling the intervention are important, but prone positioning may represent an additional therapeutic option in patients with ARDS due to COVID-19.

Non-islet cell tumor hypoglycemia as an initial presentation of hepatocellular carcinoma coupled with end-stage liver cirrhosis: A case report and review of literature.

BACKGROUND: Non-islet cell tumor hypoglycemia (NICTH) is a rare cause of persistent hypoglycemia seen in patients with hepatocellular carcinoma (HCC). It is likely to be underdiagnosed especially in the patients with poor hepatic function and malnutrition. Herein, we report a rare case of NICTH as the initial presentation of HCC in a patient with chronic hypoglycemia due to end-stage liver cirrhosis. CASE SUMMARY: A 62-year-old male with chronic fasting hypoglycemia secondary to end-stage hepatitis C-related cirrhosis, presented with altered mental status and dizziness. He was found to have severe hypoglycemia refractory to glucose supplements. Imaging studies and biopsy discovered well differentiated HCC without metastasis. Further evaluation showed low insulin, C-peptide and beta-hydroxybutyrate along with a high insulin-like growth factor-2/insulin-like growth factor ratio, consistent with the diagnosis of NICTH. As patient was not a candidate for surgical resection or chemotherapy, he was started on prednisolone with some improvements in the glucose homeostasis, but soon decompensated after a superimposed hospital acquired pneumonia. CONCLUSION: NICTH can occur as the sole initial presentation of HCC and is often difficult to correct without tumor removal. Clinicians should maintain high clinical suspicion for early recognition of paraneoplastic NICTH in patients at risk for HCC, even those with chronic fasting hypoglycemia in the setting of severe hepatic failure and malnutrition.

Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome due to COVID-19: A Cohort Study and Analysis of Physiology.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. METHODS: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. RESULTS: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 ( P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (P a O 2 :FiO 2 ) were significantly improved during days 4-7 ( P < 0.05 for all). CONCLUSIONS: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every eight patients treated. Replicating results and scaling the intervention are important, but prone positioning may represented an additional therapeutic option in patients with ARDS due to COVID-19.