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Background: Airway Pressure Release Ventilation (APRV) is a pressure controlled intermittent mandatory mode of ventilation characterized by prolonged inspiratory time and high mean airway pressure. Several studies have demonstrated that APRV can improve oxygenation and lung recruitment in patients with Acute Respiratory Distress Syndrome (ARDS). Although most patients with COVID-19 meet the Berlin criteria for ARDS, hypoxic respiratory failure due to COVID-19 may differ from traditional ARDS as patients often present with severe, refractory hypoxemia and significant variation in respiratory system compliance. To date, no studies investigating APRV in this patient population have been published. The aim of this study was to evaluate the effectiveness of APRV as a rescue mode of ventilation in critically ill patients diagnosed with COVID-19 and refractory hypoxemia. Methods: We conducted a retrospective analysis of patients admitted with COVID-19 requiring invasive mechanical ventilation who were treated with a trial of APRV for refractory hypoxemia. PaO2/FIO2 (P/F ratio), ventilatory ratio and ventilation outputs before and during APRV were compared. Results: APRV significantly improved the P/F ratio and decreased FIO2 requirements. PaCO2 and ventilatory ratio were also improved. There was an increase in tidal volume per predicted body weight during APRV and a decrease in total minute ventilation. On multivariate analysis, higher inspiratory to expiratory ratio (I: E) and airway pressure were associated with greater improvement in P/F ratio. Conclusions: APRV may improve oxygenation, alveolar ventilation and CO2 clearance in patients with COVID-19 and refractory hypoxemia. These effects are more pronounced with higher airway pressure and inspiratory time.

Hepatic lipase (HL) and lipoprotein lipase (LPL) activities (HLA, LPLA) modify lipoproteins and facilitate their binding to hepatic receptors. Apolipoprotein E (APOE) physically interacts with the lipases, and the three common haplotypes of the APOE gene (ε2, ε3, and ε4) yield protein isoforms (E2, E3, and E4, respectively) that are functionally different. Lipase activities themselves differ by sex and exercise training status. The interaction of APOE genotype, exercise training, and sex effects on lipase activities has not been studied. We measured postheparin plasma lipase activities in normolipidemic men and women with the three most common APOE genotypes, which are the haplotype combinations ε2/ε3 (n = 53 ), ε3/ε3 (n = 62), and ε4/ε3 (n = 52), enrolled in 6 mo of aerobic exercise training. These haplotype combinations comprise an estimated 11.6, 62.3, and 21.3% of the population, respectively. Baseline HLA was 35% lower in women than in men (P < 0.0001). In men but not women, HLA was higher in ε2/ε3 group compared with ε4/ε3 (P = 0.01) and ε3/ε3 (P = 0.05). Neither sex nor APOE genotype affected baseline LPLA. Training decreased HLA by 5.2% (P = 0.018) with no APOE effect. The apparent increase in LPLA following exercise was significant and APOE dependent only when corrected for baseline insulin (P < 0.05). Exercise decreased LPLA by 0.8 μmol free fatty acid (FFA)·ml⁻¹·h⁻¹ (-6%) in ε3/ε3 compared with the combined increases of 6.6% in ε2/ε3 and 12% in ε4/ε3 (P = 0.018 vs. ε3/ε3). However, these differences were statistically significant only after correcting for baseline insulin. We conclude that common APOE genotypes interact with 1) sex to modulate HLA regardless of training status, with ε2/ε3 men demonstrating higher HLA than ε3/ε3 or ε4/ε3 men, and 2) aerobic training to modulate LPLA, regardless of sex, with ε3/ε3 subjects showing a significant decrease compared with an increase in ε2/ε3 and ε3/ε4 after controlling for baseline insulin.

INTRODUCTION: Ecthyma gangrenosum (EG) is a necrotizing vasculitis, commonly observed in immunocompromised patients with Pseudomonas aeruginosa bacteremia. Rarely, it can be seen with other bacterial, fungal, and viral infections. We report a rare etiology of EG in an immunocompetent patient caused by methicillin-sensitive Staphylococcus aureus (MSSA). CASE PRESENTATION:A 62-year-old man with hypertension presented to the emergency department for pain and swelling of the right lower extremity after a crush injury one week prior. Initial vital signs were remarkable for a blood pressure of 84/43 mmHg and a pulse rate of 134 beats per minute. Examination revealed a gangrenous right great toe and well-circumscribed purpuric papules with a violaceous border and central pallor on the patient's skin most prominent over the legs and lower abdomen. Laboratory findings were significant for leukocytosis and lactic acidosis. Intravenous fluids were initiated, blood cultures were collected, and he was started on vancomycin and cefepime. He rapidly progressed to septic shock requiring vasopressors and was admitted to the intensive care unit. The patient underwent amputation of the right great and punch biopsies of the skin lesions. Despite aggressive critical care management, he continued to deteriorate and developed acute hypoxemic respiratory failure and acute kidney injury requiring renal replacement therapy. Blood, wound, and urine cultures grew MSSA. Skin biopsy results revealed necrobiosis and suppurative dermatitis with gram-positive cocci in clusters, consistent with EG due to MSSA bacteremia. Antibiotic coverage was narrowed to nafcillin, however, he continued to deteriorate with progressive multiorgan failure. He was ultimately transitioned to comfort measures and died peacefully in the presence of family.DISCUSSION: To the best of our knowledge, there are only two reported cases of EG secondary to MSSA infection (1,2). One of a healthy 15-month-old girl who developed EG, and toxin-mediated systemic findings and the second of a 54-year-old female with metastatic gastric adenocarcinoma and recent chemotherapy. This is the first reported case of an immunocompetent adult patient with MSSA EG. Reported predisposing risk factors for EG include immunodeficiency, recent chemotherapy, burns, malnutrition, and tuberculosis infection. The literature describes two different forms of EG, bacteremic and non-bacteremic. Mortality rates in patients with EG due to bacteremia are significantly higher compared to patients without bacteremia (3).CONCLUSIONS: This case is unique as our patient had a rare presentation of EG due to MSSA bacteremia with none of the previously described predisposing risk factors.