SUMMARY Bcl-2 can be converted into a pro-apoptotic molecule by nuclear receptor Nur77. However, the development of Bcl-2 converters as anti-cancer therapeutics has not been explored. Here we report the identification of a Nur77-derived Bcl-2 converting peptide with 9 amino acids (NuBCP-9) and its enantiomer, which induce apoptosis of cancer cells in vitro and in animals. The apoptotic effect of NuBCPs and their activation of Bax are not inhibited but rather potentiated by Bcl-2. NuBCP-9 enantiomers bind to the Bcl-2 loop, which shares the characteristics of structurally adaptable regions with many cancer-associated and signaling proteins. NuBCP-9s act as molecular switches to dislodge the Bcl-2 BH4 domain, exposing its BH3 domain, which in turn blocks the activity of anti-apoptotic Bcl-XL.

Rationale: No direct comparisons of clinical features, laboratory values, and outcomes between critically ill patients with coronavirus disease (COVID-19) and patients with influenza in the United States have been reported. Objectives: To evaluate the risk of mortality comparing critically ill patients with COVID-19 with patients with seasonal influenza. Methods: We retrospectively identified patients admitted to the intensive care units (ICUs) at two academic medical centers with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza A or B infections between January 1, 2019, and April 15, 2020. The clinical data were obtained by medical record review. All patients except one had follow-up to hospital discharge or death. We used relative risk regression adjusting for age, sex, number of comorbidities, and maximum sequential organ failure scores on Day 1 in the ICU to determine the risk of hospital mortality and organ dysfunction in patients with COVID-19 compared with patients with influenza. Results: We identified 65 critically ill patients with COVID-19 and 74 patients with influenza. The mean (±standard deviation) age in each group was 60.4 ± 15.7 and 56.8 ± 17.6 years, respectively. Patients with COVID-19 were more likely to be male, have a higher body mass index, and have higher rates of chronic kidney disease and diabetes. Of the patients with COVID-19, 37% identified as Hispanic, whereas 10% of the patients with influenza identified as Hispanic. A similar proportion of patients had fevers (∼40%) and lymphopenia (∼80%) on hospital presentation. The rates of acute kidney injury and shock requiring vasopressors were similar between the groups. Although the need for invasive mechanical ventilation was also similar in both groups, patients with COVID-19 had slower improvements in oxygenation, longer durations of mechanical ventilation, and lower rates of extubation than patients with influenza. The hospital mortality was 40% in patients with COVID-19 and 19% in patients with influenza (adjusted relative risk, 2.13; 95% confidence interval, 1.24–3.63; P = 0.006). Conclusions: The need for invasive mechanical ventilation was common in patients in the ICU for COVID-19 and influenza. Compared with those with influenza, patients in the ICU with COVID-19 had worse respiratory outcomes, including longer duration of mechanical ventilation. In addition, patients with COVID-19 were at greater risk for in-hospital mortality, independent of age, sex, comorbidities, and ICU severity of illness.

Objective The decision to admit a patient to the intensive care unit (ICU) is complex, reflecting patient factors and available resources. Previous work has shown that ICU census does not impact mortality of patients admitted to the ICU. However, the effect of ICU bed availability on patients outside the ICU is unknown. We sought to determine the association between ICU bed availability, ICU readmissions, and ward cardiac arrests. Design In this observational study using data collected between 2009 and 2011, rates of ICU readmission and ward cardiac arrest were determined per 12-hour shift. The relationship between these rates and the number of available ICU beds at the start of each shift (accounting for census and nursing capacity), were investigated. Grouped logistic regression was used to adjust for potential confounders. Setting Five specialized adult ICUs comprising 63 adult ICU beds in an academic medical center. Patients Any patient admitted to a non-ICU inpatient unit was counted in the ward census and considered at risk for ward cardiac arrest. Patients discharged from an ICU were considered at risk for ICU readmission. Measurements and Main Results Data were available for 2086 of 2190 shifts. The odds of ICU readmission increased with each decrease in the overall number of available ICU beds (OR=1.06 [95% CI, 1.00–1.12], p=0.03), with a similar but not statistically significant association demonstrated in ward cardiac arrest rate (OR= 1.06 [95% CI, 0.98–1.14], p=0.16). In subgroup analysis, the odds of ward cardiac arrest increased with each decrease in the number of medical ICU beds available (OR= 1.26 [95% CI, 1.06–1.49], p=0.01). Conclusions Reduced ICU bed availability is associated with increased rates of ICU readmission and ward cardiac arrest. This suggests that systemic factors are associated with patient outcomes and flexible critical care resources may be needed when demand is high.