Background The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. Methods In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT04351152 , and is completed. Findings Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41–137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79–89) participants in the lenzilumab group and in 190 (78%; 72–83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. Interpretation Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with CO...

BackgroundObstructive sleep apnea (OSA) is frequently seen with atrial fibrillation (AF) and is associated with increased cardiovascular morbidity, including hypertension, congestive heart failure, ischemic heart disease, and stroke. However, the impact of OSA on in-hospital outcomes of patients with AF is unclear. MethodologyAll patients aged ≥18 admitted primarily for AF between January 2016 and December 2017 were identified in the National Inpatient Sample database. They were then categorized into those with OSA and those without OSA. The primary outcome was in-hospital mortality. Unadjusted and adjusted analysis was performed on appropriate variables of interest. ResultsOf 156,521 primary AF hospitalizations, 15% of the patients had OSA. Baseline characteristics revealed no race disparity between the two groups. However, compared to those without OSA, the OSA group was younger and had a significantly higher proportion of males, obesity, heart failure, hypertension, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia. Long-term anticoagulation and inpatient cardioversion were also higher in the OSA group. Following propensity matching, inpatient mortality was similar between the two groups [0.54% in OSA vs. 0.51% in non-OSA; adjusted odds ratio = 1.06 (95% confidence interval = 0.82-1.35)]. Similarly, OSA was not significantly associated with acute kidney injury, cardiac arrest, gastrointestinal bleed, acute stroke, or length of stay. However, the OSA group was less anemic and required fewer in-hospital blood transfusions. ConclusionsAlthough OSA is highly prevalent in AF patients, inpatient mortality and cardiovascular outcomes such as cardiac arrest, stroke, or major bleeding were similar in AF patients with or without concomitant OSA with no significant differences in length of stay.

Background: Heart failure (HF) remains one of the leading causes of death in the United States. While many large-scale studies show a positive relationship between cardiovascular mortality and body mass index (BMI), several studies have also observed lower mortality rates among obese HF patients. Therefore, we sought to assess the impact of BMI on in-hospital outcomes in patients admitted with HF.Methods: Patients hospitalized with congestive heart failure (CHF) diagnosis between 2005 and 2014 were identified from the US National Inpatient Sample database using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and procedural codes. The sample was divided into three groups based on their BMI. In-hospital outcomes were assessed in different groups and sub-groups.Results: We identified 8,674,190 patients admitted with a primary diagnosis of HF, out of which 1.8% had BMI between 30 and 39.9 kg/m 2 and 3.7% had BMI >40 kg/m 2 . In-hospital mortality was reported in 5.6% of patients with BMI <30 kg/m 2 , compared to 2.3% in those with BMI 30-39.9 kg/m 2 and 3.1% in the group with BMI >40 kg/m 2 . After adjusting for various confounders, in-hospital mortality was lower in those with BMI 30-39.9 kg/m 2 than those with BMI <30 kg/m 2 (OR 0.56; CI 0.51-0.62). Similarly, in-hospital mortality was lower in those with BMI >40 kg/m 2 than those with BMI <30 (OR 0.87; CI 0.81-0.92). Conclusion:Even though this study supports the findings of previous smaller studies illustrating the existence of the "obesity paradox" in HF hospitalizations, the pathogenesis behind this paradoxical effect is still unclear.

BackgroundSubstance use is widely prevalent among young adults and is associated with increased cardiovascular morbidity and mortality such as sudden cardiac arrest, acute coronary syndrome, arrhythmias, and cardiomyopathy. However, they are limited studies analyzing the impact of substance use disorder on inhospital outcomes among young patients with cardiovascular events. MethodsAll patients aged 18-39 years admitted primarily for major cardiovascular events including acute myocardial infarction (AMI), arrhythmia, cardiac arrest, acute ischemic stroke, and venous thromboembolic events in 2019 were identified in the National Inpatient Sample database. They were then categorized into those with and without concomitant substance use disorder (SUD). The primary outcome was in-hospital mortality. Unadjusted and adjusted analysis was performed on appropriate variables of interest. ResultsOf 57,985 hospitalizations with cardiac events, 12,115 (20%) of young adults had concomitant SUD. SUD was significantly associated with cardiac arrest (OR 3.3; CI 2.4-4.4), atrial fibrillation (OR 1.5; CI 1.3-1.7), AMI (OR 1.3; CI 1.2-1.6), heart failure (OR 2.6; CI 2.4-3.0) (all p<0.05) despite a lower prevalence of traditional cardiovascular risk factors than non-users. Logistic regression showed acute kidney injury (aOR 1.5; CI 1.3-1.8; p<0.001) and inpatient mortality (aOR 1.6; CI 1.2-2.2; p<0.001) were also significantly higher in young patients presenting with cardiac events and concomitant SUD. There was no difference in the length of stay or incidence of gastrointestinal bleed between the two groups. ConclusionIn young patients presenting with a cardiovascular event, concurrent substance use disorder was associated with increased in-hospital mortality despite significantly lower comorbidities.

IntroductionEnterococcus faecium is a commensal organism commonly colonizing the human gastrointestinal tract. Although it is generally a non-virulent organism, E. faecium can cause significant morbidity and mortality due to its inherent and acquired resistances to commonly used antimicrobials. Patients who are immunosuppressed are particularly vulnerable.Case presentationA 65–75-year-old patient with a history of an orthotopic liver transplant for hepatitis C infection and diabetes was re-admitted to the hospital with abdominal pain and fever. The patient had several recent admissions related to the presentation reported here, which included treatment with a prolonged course of broad-spectrum antibiotics. The patient was found to have a recurrent liver abscess and blood cultures grew vancomycin-resistant E. faecium, non-susceptible to all tested agents: ampicillin, penicillin, vancomycin, daptomycin and linezolid. The patient was started initially on chloramphenicol intravenously while awaiting additional susceptibility testing, which ultimately revealed chloramphenicol non-susceptibility. Tigecycline was started but the patient ultimately decided to pursue hospice care.ConclusionMulti-drug-resistant organisms are increasingly being recognized and are associated with poorer outcomes, particularly in immunosuppressed patients. We describe a particularly resistant organism and discuss potential therapeutic options.