Transcatheter edge-to-edge repair (TEER) is approved for patients with symptomatic severe mitral regurgitation (MR) who are deemed inoperable or at high surgical risk with life expectancy of more than 1 year, but has also been used off-label in patients with hypertrophic obstructive cardiomyopathy (HOCM) for symptomatic relief who are not candidates for septal reduction therapy. An 83-year-old woman with decompensated heart failure was found to have HOCM with systolic anterior motion of the mitral valve and a large P2 flail segment with ruptured cords. TEER was performed resulting in mild MR and resolution of the prior left ventricular outflow tract gradient.
View Article and Find Full Text PDFNormothermic machine perfusion (NMP) facilitates utilization of marginal liver allografts. It remains unknown whether clinical benefits offset additional costs in the real-world setting. We performed a comparison of outcomes and hospitalization costs for donor livers preserved by NMP versus static cold storage (SCS) at a high-volume center.
View Article and Find Full Text PDFToxicokinetic (TK) assays and in vitro-in vivo extrapolation (IVIVE) models are New Approach Methods (NAMs) used to translate in vitro points of departure to exposure estimates required to reach equivalent blood concentrations. Per- and polyfluoroalkyl substances (PFAS) are a large chemical class with wide-ranging industrial applications for which only limited toxicity data are available for human health evaluation. To address the lack of TK data, a pooled primary human hepatocyte suspension model was used with targeted liquid chromatography-mass spectrometry to investigate substrate depletion for 54 PFAS.
View Article and Find Full Text PDFDrug-induced kidney injury (DIKI) is of significant concern, both during drug development and in clinical practice. We report a patient-centric approach for clinical implementation of the FDA-qualified kidney safety biomarker panel, highlighting Phase 1 and 2 trials for candidate therapeutics in Pfizer's portfolio (PFE-1 and PFE-2, respectively) that induced kidney tubular injury in rat toxicity studies. Clusterin (CLU), cystatin-C (CysC), kidney injury molecule-1 (KIM-1), N-acetyl-beta-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin (OPN) were measured in urine samples from (i) Phase 1 healthy volunteers (HVs; n = 12) dosed with PFE-1, (ii) Phase 2 rheumatoid arthritis (RA) patients (n = 266) dosed with PFE-2, (iii) lupus patients on standard-of-care therapies (n = 121), and (iv) healthy volunteers (n = 60).
View Article and Find Full Text PDFAir pollution is known to be one of the major risk factors for premature morbidity and mortality globally, which are preventable. Therefore, the public is informed about air pollution through the Air Quality Index (AQI). The AQI represents integrated data of selected pollutants and produces a combined overall index for specific locations and time.
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