Aprepitant boasted a protective effect against olanzapine-induced metabolic syndrome and its subsequent hepatic, renal, and ovarian dysfunction; Role of IGF1/p-AKT/FOXO1 and NFκB/IL-1ß/TNF-α signaling pathways in female Wistar albino rats.

Olanzapine-induced metabolic syndrome (MS) is a primary risk factor for insulin resistance, hepatorenal damage, and polycystic ovarian syndrome. The objective of the current study was to assess the protective effects of aprepitant (AP) against MS caused by olanzapine and the associated ovarian, renal, and liver dysfunction via modulation of IGF1/p-AKT/FOXO1 and NFκB/IL-1ß/TNF-α signaling pathways. AP mitigated all biochemical and histopathological abnormalities induced by olanzapine and resulted in a significant reduction of serum HOMA-IR, lipid profile parameters, and a substantial decrease in hepatic, renal, and ovarian MDA, IL-6, IL-1ß, TNF-α, NFκB, and caspase 3. Serum AST, ALT, urea, creatinine, FSH, LH, and testosterone also decreased significantly by AP administration. The FOXO 1 signaling pathway was downregulated in the AP-treated group, while GSH, SOD, and HDL cholesterol levels were elevated.

A Case Series of Persistent SARS-CoV-2 Infection in Immunocompromised Pediatric Patients.

Diagnosis and management of SARS-CoV-2 infection in immunocompromised patients are extremely challenging. These patients can have atypical clinical courses, and there is a paucity of data regarding clinical features, diagnostic findings, and the safety and efficacy of available therapeutic agents used to treat COVID-19 in these patients. In this case series, we report atypical COVID-19 presentations in 4 immunocompromised pediatric patients who were admitted with acute respiratory failure after an initial diagnosis of COVID-19 a few weeks earlier. All patients included in this cohort showed persistent worsening respiratory symptoms for several weeks before hospital presentation. While they manifested common COVID-19 sequelae, they also had rare COVID-19-related pathognomonic and radiographic features developed along their hospital course. Multiple therapeutic agents were used in their COVID-19 management, including corticosteroids, remdesivir, and monoclonal antibodies. All three patients who have received concurrent therapy with remdesivir, hydrocortisone, and monoclonal antibodies survived, and only one patient died as a direct complication of COVID-19 ARDS with secondary pulmonary mucormycosis. Our outcomes suggest the potential benefit of remdesivir use in combination with hydrocortisone and monoclonal antibodies in the management of severe COVID-19 ARDS in this group, as well as the importance of close surveillance and early administration of broad empirical antimicrobial and antifungal coverage if clinically indicated in this high-risk population.