Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial.

STUDY OBJECTIVE: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. METHODS: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. RESULTS: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). CONCLUSION: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.

Acai Berry (Euterpe sp.) Extracts Are Neuroprotective against L-Glutamate-Induced Toxicity by Limiting Mitochondrial Dysfunction and Cellular Redox Stress.

Aberrant accumulation of the neurotransmitter L-glutamate (L-Glu) has been implicated as a mechanism of neurodegeneration, and the release of L-Glu after stroke onset leads to a toxicity cascade that results in neuronal death. The acai berry (Euterpe oleracea) is a potential dietary nutraceutical. The aim of this research was to investigate the neuroprotective effects of acai berry aqueous and ethanolic extracts to reduce the neurotoxicity to neuronal cells triggered by L-Glu application. L-Glu and acai berry effects on cell viability were quantified using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and effects on cellular bioenergetics were assessed via quantitation of the levels of cellular ATP, mitochondrial membrane potential (MMP), and production of reactive oxygen species (ROS) in neuroblastoma cells. Cell viability was also evaluated in human cortical neuronal progenitor cell culture after L-Glu or/and acai berry application. In isolated cells, activated currents using patch-clamping were employed to determine whether L-Glu neurotoxicity was mediated by ionotropic L-Glu-receptors (iGluRs). L-Glu caused a significant reduction in cell viability, ATP, and MMP levels and increased ROS production. The co-application of both acai berry extracts with L-Glu provided neuroprotection against L-Glu with sustained cell viability, decreased LDH production, restored ATP and MMP levels, and reduced ROS levels. Whole-cell patch-clamp recordings showed that L-Glu toxicity is not mediated by the activation of iGluRs in neuroblastoma cells. Fractionation and analysis of acai berry extracts with liquid chromatography-mass spectrometry identified several phytochemical antioxidants that may have provided neuroprotective effects. In summary, the acai berry contains nutraceuticals with antioxidant activity that may be a beneficial dietary component to limit pathological deficits triggered by excessive L-Glu accumulations.

Oliguria on the Day of Intubation Is Associated With Mortality in Patients With Acute Respiratory Distress Syndrome.

To investigate the relationship between oliguric acute kidney injury (AKI) and mortality in patients with acute respiratory distress syndrome (ARDS). DESIGN: Retrospective cohort study. SETTING: This investigation took place at a single-center, tertiary referral multidisciplinary comprehensive healthcare hospital in metropolitan Detroit, Michigan. PATIENTS: Adult patients 18 years old or older hospitalized in the ICU and diagnosed with ARDS on mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred eight patients were included in the final analysis. Risk factors associated with mortality included advanced age (p < 0.001), increased body mass index (p = 0.008), and a history of chronic kidney disease (p = 0.023). Presence of AKI by day 1 of intubation, with elevated creatinine (p = 0.003) and oliguria (p < 0.001), was significantly associated with mortality. On multivariate analysis, advanced age (relative risk [RR], 1.02), urine output on the day of intubation (RR, 0.388), bicarbonate level (RR, 0.948), and Sequential Organ Failure Assessment severity score (RR, 1.09) were independently associated with mortality. A receiver operating characteristic curve identified a threshold urine output on the day of intubation of 0.7 mL/kg/hr (area under the curve, 0.75; p < 0.001) as most closely associated with inpatient mortality (i.e., urine output < 0.7 mL/kg/hr is associated with mortality). CONCLUSIONS: For patients with ARDS, oliguria on the day of intubation was independently associated with increased mortality. Urine output of less than 0.7 mL/kg/hr predicted 80% of inpatient deaths. These findings herald an augmented understanding of the role of urine output in medical decision-making and prognostication.

Risk Factors Associated With Hospitalization and Death in COVID-19 Breakthrough Infections.

Background: Characterizations of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections are limited. We aim to characterize breakthrough infections and identify risk factors associated with outcomes. Methods: This was a retrospective case series of consecutive fully vaccinated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a multicenter academic center in Southeast Michigan, between December 30, 2020, and September 15, 2021. Results: A total of 982 patients were identified; the mean age was 57.9 years, 565 (59%) were female, 774 (79%) were White, and 255 (26%) were health care workers (HCWs). The median number of comorbidities was 2; 225 (23%) were immunocompromised. BNT162b2 was administered to 737 (75%) individuals. The mean time to SARS-CoV-2 detection was 135 days. The majority were asymptomatic or exhibited mild to moderate disease, 154 (16%) required hospitalization, 127 (13%) had severe-critical illness, and 19 (2%) died. Age (odds ratio [OR], 1.14; 95% CI, 1.04-1.07; P < .001), cardiovascular disease (OR, 3.02; 95% CI, 1.55-5.89; P = .001), and immunocompromised status (OR, 2.57; 95% CI, 1.70-3.90; P < .001) were independent risk factors for hospitalization. Additionally, age (OR, 1.06; 95% CI, 1.02-1.11; P = .006) was significantly associated with mortality. HCWs (OR, 0.15; 95% CI, 0.05-0.50; P = .002) were less likely to be hospitalized, and prior receipt of BNT162b2 was associated with lower odds of hospitalization (OR, 0.436; 95% CI, 0.303-0.626; P < .001) and/or death (OR, 0.360; 95% CI, 0.145-0.898; P = .029). Conclusions: COVID-19 vaccines remain effective at attenuating disease severity. However, patients with breakthrough infections necessitating hospitalization may benefit from early treatment modalities and COVID-19-mitigating strategies, especially in areas with substantial or high transmission rates.

Low- Versus High-Dose Methylprednisolone in Adult Patients With Coronavirus Disease 2019: Less Is More.

BACKGROUND: Corticosteroids use in severe coronavirus disease 2019 (COVID-19) improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC). METHODS: This was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on November 17, 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (September 1 to November 15, 2020) were compared to the LDC group (November 30, 2020 to January 20, 2021). High-dose corticosteroids was defined as 80 mg of methylprednisolone daily in 2 divided doses, and LDC was defined as 32-40 mg of methylprednisolone daily in 2 divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events. RESULTS: Four-hundred seventy patients were included: 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, P = .712). This finding remained intact when controlling for additional variables (odds ratio, 0.947; confidence interval, 0.515-1.742; P = .861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (P < .001). No differences were noted in any of the other secondary outcomes. CONCLUSIONS: Low-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.

Progression to Critical Illness and Death in Patients With Breakthrough Hospitalizations.

Background: Characterization of disease progression and outcomes after coronavirus disease 2019 (COVID-19)-related hospitalization in vaccinated compared with unvaccinated individuals is limited. Methods: This was a retrospective case-control study of symptomatic vaccinated (cases) and unvaccinated (controls) participants hospitalized for COVID-19 between December 30, 2020, and September 30, 2021, in Southeast Michigan. Hospitalized adult patients with lab-confirmed COVID-19 were identified through daily census report. Breakthrough infection was defined as detection of severe acute respiratory syndrome coronavirus 2 ≥14 days after completion of the primary vaccination series. The association between prior vaccination and critical COVID-19 illness (composite of intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], 28-day mortality) was examined. Results: Two hundred ten (39%) fully vaccinated and 325 (61%) unvaccinated patients were evaluated. Compared with controls, cases were older, had more comorbidities (4 [3-7] vs 2 [1-4]; P < .001), and were more likely to be immunocompromised. Cases had less severe symptoms compared with controls (2 [1-2] vs 2 [2-3]; P < .001) and were less likely to progress to critical COVID-19 illness (33.3% vs 45.5%; P < .001); 28-day mortality was significantly lower in cases (11.0% vs 24.9%; P < .001). Symptom severity (odds ratio [OR], 2.59; 95% CI, 1.61-4.16; P < .001) and modified Sequential Organ Failure Assessment score on presentation (OR, 1.74; 95% CI, 1.48-2.06; P < .001) were independently associated with development of critical COVID-19 illness. Prior vaccination (OR, 0.528; 95% CI, 0.307-0.910; P = .020) was protective. Conclusions: COVID-19-vaccinated patients were less likely to develop critical COVID-19 illness and more likely to survive. Disease severity at presentation was a predictor of adverse outcomes regardless of vaccination status.