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Background Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with coronavirus disease 2019 (COVID-19) pneumonia, but the optimal dose is unknown. Methods Patients hospitalized for moderate to severe COVID-19 pneumonia were randomized 1:1 to receive standard of care treatment and 1–2 doses of intravenous tocilizumab 4 mg/kg or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble interleukin 6 receptor (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60. The secondary end point was safety. Key exploratory efficacy end points included clinical status, time to discharge, mortality rate, and incidence of mechanical ventilation. Results Of 100 patients randomized, 49 received tocilizumab 4 mg/kg and 48 received 8 mg/kg. In pharmacokinetic and sIL-6R assessments, dose-dependent differences were seen in patients who received 1 or 2 doses of 4 or 8 mg/kg. Serum concentrations of IL-6, ferritin, and CRP and safety outcomes were comparable between groups. Through day 60, serious adverse events were reported in 30.6% and 25.0% of patients in the 4- and 8-mg/kg groups, respectively. Eight patients (16.3%) in the 4-mg/kg group and 6 (12.5%) in the 8-mg/kg group died. Exploratory time-to-event outcomes favored 8 mg/kg within the first 2 weeks. Conclusions In patients with moderate to severe COVID-19 pneumonia who received tocilizumab 4 or 8 mg/kg, pharmacokinetic and sIL-6R assessments showed expected dose-dependent effects; pharmacodynamic assessments and safety were comparable, with no new safety signals. Further study is required before a lower dose of tocilizumab can be recommended in patients with COVID-19 pneumonia. Clinical Trials Registration NCT04363736. [ABSTRACT FROM AUTHOR]

Objective: Currently, there are no objective metrics included in the intensive care unit (ICU) discharge decision making process. In this study, we evaluate Rothman Index(RI) data for a possible metric as part of a quality improvement project. Our objectives were to determine whether RI could predict adverse events occurring within 72 hours of ICU discharge decision, the optimal clinical cutoff value for this metric, and to determine whether there is a relation between the RI warning alert 24 hours prior to discharge and adverse events postdischarge. Design: Retrospective observational study. Setting: Single center tertiary hospital. Patients: Adult medical ICU patients discharged from the ICU between January 20, 2015 and March 14, 2015. Interventions: None. Measurements and Main Results: A total of 194 patients were studied with mean age of 62.74 (18.37) years. Data collection included RI at the time of decision-making for ICU discharge and the presence of any warning signals in the previous 24 hours. A 72-hour follow-up chart review recorded any adverse events, including readmission to a higher level of care, discontinuation of discharge due to clinical status change, emergency department visit if discharged home, rapid response activation, or cardiopulmonary arrest postdischarge. Adverse events after ICU discharge were observed in 31 (16%) patients with 9 events being ICU readmission (4.6%). Based on an age-adjusted multivariate model, a higher RI was associated with lower odds of an adverse event (odds ratio [OR] = 0.969, P =.006, confidence interval [CI]: 0.9487-0.9911). An RI value ≥ 50 was associated with 72% lower odds of an adverse event (OR = 0.2887, 95% CI = 0.1278-0.6517 and P =.003) compared to RI < 50. This RI cutoff value was associated with the largest decrease in odds of events. As expected, patients with a very high-risk warning alert had a higher proportion of adverse events compared to patients who did not. (31.75% vs 12.65%, P = <.02). Conclusions: Patients who have an RI < 50 or a very high-risk warning alert have a higher risk of adverse events postdischarge from the ICU. Rothman Index may be a useful metric for ICU discharge decision-making. [ABSTRACT FROM AUTHOR]

Background: We present data on a cohort of patients diagnosed with sepsis over a 10‐year period comparing outcomes in solid organ transplant (SOT) and non–solid organ transplant (non–SOT) recipients. Methods: This is a retrospective single‐center study of patients with diagnosis of sepsis from 1/1/06 to 6/30/16. Cases and controls were matched by year of sepsis diagnosis with propensity score matching. Conditional logistic regression and repeated measurement models were performed for binary outcomes. Trends over time for in‐hospital mortality were determined using the Cochran‐Armitage test. A gamma‐distributed model was performed on the continuous variables. Results: Overall, there were 18 632 admission encounters with a discharge diagnosis of sepsis in 14 780 unique patients. Of those admissions, 1689 were SOT recipients. After 1:1 matching by year, there were three thousand three hundred and forty patients (1670 cases; 1670 controls) diagnosed with sepsis. There was a decreasing trend for in‐hospital mortality for sepsis over time in SOT patients and non–SOT patients (P <.05) due to early sepsis recognition and improved standard of care. Despite higher comorbidities in the SOT group, conditional logistic regression showed that in‐hospital mortality for sepsis in SOT patients was similar compared with non–SOT patients (odds ratio [OR] =1.14 [95% confidence interval {CI}, 0.95‐1.37], P =.161). However, heart and lung SOT subgroups had higher odds of dying compared with the non–SOT group (OR = 1.83 [95% CI, 1.30‐2.57], P <.001 and OR = 1.77 [95% CI, 1.34‐2.34], P <.001). On average, SOT patients had 2 days longer hospital length of stay compared with non–SOT admissions (17.00 ± 19.54 vs 15.23 ± 17.07, P <.05). Additionally, SOT patients had higher odds of hospital readmission within 30 days (OR = 1.25 [95% CI, 1.06‐1.51], P =.020), and higher odds for DIC compared with non–SOT patients (OR = 1.76 [95% CI, 1.10‐2.86], P =.021). Conclusion: Sepsis in solid organ transplants and non–solid organ transplant patients have similar mortality; however, the subset of heart and lung transplant recipients with sepsis has a higher rate of mortality compared with the non–solid organ transplant recipients. SOT with sepsis as a group has a higher hospital readmission rate compared with non–transplant sepsis patients. [ABSTRACT FROM AUTHOR]

Summary: Neurological manifestations of coronavirus disease 2019 most commonly present in severe cases and range from mild complications, such as headache and dizziness, to severe complications, such as encephalopathy and acute cerebrovascular disease. Seizures, however, are an underreported neurological manifestation of this disease. We present three critically ill coronavirus disease 2019 patients with EEG monitoring who developed new-onset seizures and encephalopathy up to three-and-a-half weeks after symptom onset. There are several speculated etiologies for the development of new-onset seizures; however, the pathogenic mechanism remains unknown. Testing of coronavirus disease 2019 in the cerebrospinal fluid in addition to extensive research on neurological manifestations is warranted., Competing Interests: D. Gotur receives funding from Cyclomedica, Gilead, Biopharma, and Cellkenos. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)