Association of Body Mass Index with Multiple Organ Failure in Hospitalized Patients with COVID-19: A Multicenter Retrospective Cohort Study.

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m2 (compared to the BMI < 25 kg/m2 reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m2 increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P = .01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction.

Factors Associated with Severity of Acute Kidney Injury and Adverse Outcomes in Critically Ill Patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a well-recognized complication of coronavirus disease 2019 (COVID-19). The short and long-term outcomes of patients who develop AKI have not been well characterized. METHODS: In this multicenter retrospective cohort study, we describe the clinical characteristics and outcomes of critically ill adults with severe COVID-19 and AKI. Patient-level variables were extracted from the electronic medical record. Using nadir-to-peak serum creatinine, AKI was defined using the KDIGO definition. Multivariable logistic regression analyses examined factors associated with development of moderate-to-severe (stage 2-3) AKI, severe (stage-3) AKI, and the composite of renal replacement therapy (RRT) or in-hospital death. RESULTS: Among 459 critically ill adults with COVID-19, 371 (80.1%) developed AKI, with 179 (37.9%) developing stage-3 AKI. Male gender, black and Asian/Native American race, lower baseline estimated glomerular filtration rate (eGFR), higher body mass index (BMI), and higher Acute Physiology and Chronic Health Evaluation (APACHE) IV score were more prevalent among patients with severe AKI, as were systemic markers of inflammation. On multivariable analysis, male gender, black and Asian/Native American race, higher APACHE IV score, lower baseline eGFR, and higher BMI (mainly the highest BMI stratum ≥35 kg/m2) were independently associated with higher stages of AKI severity. Male gender, lower baseline eGFR, and higher APACHE IV score were also independently associated with the composite of RRT or in-hospital death. Moderate-to-severe AKI and severe AKI were independently associated with in-hospital death, and there was a significant interaction between BMI and moderate-to-severe AKI for the outcome of in-hospital death. Among 83 (18.1%) patients who required RRT, 27 (32.5%) survived, and 12 (44.4%) remained dialysis-dependent at discharge. At 3 and 6 months, 5 (41.7%) and 4 (33.3%) remained dialysis-dependent, respectively. CONCLUSIONS: AKI is common in critically ill adults with COVID-19. Several patient-level risk factors are associated with higher stages of AKI severity. BMI might be an effect modifier of AKI severity for in-hospital death. Among AKI survivors, there is a high rate of short- and long-term dialysis dependence.

MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID-19 severe respiratory failure (MUST COVID): A retrospective cohort study.

Background: Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure. Methods: A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO2/FiO2 ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis. Results: tPA was associated with significant PaO2/FiO2 improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term p < 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term p = 0.00). D-dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO2/FiO2 ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration. Conclusions: These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population.

Rescue therapy for severe COVID-19-associated acute respiratory distress syndrome with tissue plasminogen activator: A case series.

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented stresses on modern medical systems, overwhelming the resource infrastructure in numerous countries while presenting a unique series of pathophysiologic clinical findings. Thrombotic coagulopathy is common in critically ill patients suffering from COVID-19, with associated high rates of respiratory failure requiring prolonged periods of mechanical ventilation. Here, we report a case series of five patients suffering from profound, medically refractory COVID-19-associated respiratory failure who were treated with fibrinolytic therapy using tissue plasminogen activator (tPA; alteplase). All five patients appeared to have an improved respiratory status following tPA administration: one patient had an initial marked improvement that partially regressed after several hours, one patient had transient improvements that were not sustained, and three patients had sustained clinical improvements following tPA administration. LEVEL OF EVIDENCE: Therapeutic, Level V.

Oxacillin-induced leukocytoclastic vasculitis.

Leukocytoclastic vasculitis (LCV) refers to a histopathological pattern of neutrophil predominant inflammatory process of small vessels associated with fibrinoid necrosis. Cutaneous LCV usually presents as symmetrically distributed palpable purpuric nodules of the lower extremities with or without systemic involvement. Although 50% of LCV cases are idiopathic, it can be secondary to identifiable causes such as malignancy, autoimmune conditions, infections, and medications. Medications have been implicated in up to 25% of cases; sulfonamides, NSAIDs, and beta-lactams have the most frequent association. We herein present a 32-year-old female who developed palpable purpura over hands and lower limbs 12 days after exposure to oxacillin administered for infective endocarditis. Punch biopsy from the skin lesions confirmed the diagnosis of LCV. Given the temporal relationship between oxacillin administration and development of skin findings, the diagnosis of oxacillin-associated LCV was suspected. Discontinuation of drug resulted in resolution of the lesions confirming the diagnosis. To our knowledge, this is the second case of oxacillin-induced cutaneous LCV described in literature.

A 46-Year-Old Woman With Dyspnea From an Inhalational Exposure, Triggering Thyroid Storm and Subsequent Multi-Organ System Failure.

BACKGROUND: Thyroid storm is a rare, life-threatening condition which arises in patients with thyrotoxicosis, with an annual incidence of 2 patients per 1,000,000 and a mortality rate of 11%. CASE: We present the case of a 46-year-old-female with a medical history of controlled mild intermittent asthma, who presented with a severe asthma exacerbation, that triggered thyroid storm after exposure to polyurethane fumes. CONCLUSION: This patient represents, to the best of our knowledge, the first patient in whom the stress related to a severe asthma attack triggered the development of thyroid storm. She also is the first patient with no indication of cardiac dysfunction who developed fatal cardiac arrest after initiation of b-blockade for treatment of thyroid storm.

Cell death and autophagy in tuberculosis.

Mycobacterium tuberculosis has succeeded in infecting one-third of the human race though inhibition or evasion of innate and adaptive immunity. The pathogen is a facultative intracellular parasite that uses the niche provided by mononuclear phagocytes for its advantage. Complex interactions determine whether the bacillus will or will not be delivered to acidified lysosomes, whether the host phagocyte will survive infection or die, and whether the timing and mode of cell death works to the advantage of the host or the pathogen. Here we discuss cell death and autophagy in TB. These fundamental processes of cell biology feature in all aspects of TB pathogenesis and may be exploited to the treatment or prevention of TB disease.