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Purpose: Residual neuromuscular blockade can impair postoperative respiratory mechanics, promoting hypoxemia and pulmonary complications. Sugammadex, with its unique mechanism of action, may offer a more effective reversal of neuromuscular blockade and respiratory function than neostigmine. We sought to test the primary hypothesis that children undergoing noncardiac surgery exhibit better initial recovery oxygenation when administered sugammadex than those administered neostigmine.

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Uncovering the impact of COVID-19-mediated bidirectional dysregulation of cytochrome P450 3A4 on systemic and pulmonary drug concentrations using physiologically based pharmacokinetic modeling.

Drug Metab Dispos

January 2025

Current affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Current affiliation: OneDrug Inc., Toronto, Ontario, Canada; Program in Translational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Centre for Applied Pharmacokinetic Research, School of Health Sciences, University of Manchester, Manchester, United Kingdom. Electronic address:

Several clinical studies have shown that COVID-19 increases the systemic concentration of drugs in hospitalized patients with COVID-19. However, it is unclear how COVID-19-mediated bidirectional dysregulation of hepatic and pulmonary cytochrome P450 (CYP) 3A4 affects drug concentrations, especially in the lung tissue, which is most affected by the disease. Herein, physiologically based pharmacokinetic modeling was used to demonstrate the differences in systemic and pulmonary concentrations of 4 respiratory infectious disease drugs when CYP3A4 is concurrently downregulated in the liver and upregulated in the lung based on existing clinical data on COVID-19-CYP3A4 interactions at varying severity levels including outpatients, non-intensive care unit (ICU), and ICU patients.

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Objective: To compare the effectiveness and safety of tofacitinib (TOF) calcineurin inhibitor (CNI) as initial immunosuppressive regimen for anti-melanoma differentiation-associated gene 5-positive dermatomyositis with interstitial lung disease (MDA5+DM-ILD).

Methods: Adult Chinese patients with newly-diagnosed MDA5+DM-ILD (ILD course<3 months) from five tertiary referral centres between April 2014 and January 2023 were included for this retrospective cohort study. The primary effectiveness endpoint was lung transplantation-free survival within 1 year.

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Background: The results of pulmonary vein isolation are limited by arrhythmia recurrence, which is most often due to a failure to effectuate a durable contiguous circumferential transmural lesion around the pulmonary vein (PV) ostia. We postulated that enhancing the index ablation line through use of multiple cryoballoon diameters would be superior to standard ablation with bonus freeze.

Methods: We enrolled 226 consecutive patients referred for cryoballoon-based PV isolation (PVI).

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Background: Multiple primary malignancies (MPM) are a rare scenario, particularly in patients with hepatocellular carcinoma (HCC). Research addressing MPM patients with HCC is limited. Therefore, we conducted a retrospective study to explore the clinical features and outcomes of MPM patients involving HCC.

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