Browsing by Author "Sharma, Gaurav"

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    Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections
    (Wolters Kluwer, 2021) Smith, Michael J.; Boutzoukas, Angelique; Autmizguine, Julie; Hudak, Mark L.; Zinkhan, Erin; Bloom, Barry T.; Heresi, Gloria; Lavery, Adrian P.; Courtney, Sherry E.; Sokol, Gregory M.; Cotten, C. Michael; Bliss, Joseph M.; Mendley, Susan; Bendel, Catherine; Dammann, Christiane E. L.; Weitkamp, Jörn-Hendrik; Saxonhouse, Matthew A.; Mundakel, Gratias T.; Debski, Julie; Sharma, Gaurav; Erinjeri, Jinson; Gao, Jamie; Benjamin, Daniel K., Jr.; Hornik, Christoph P.; Smith, P. Brian; Cohen-Wolkowiez, Michael; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee; Pediatrics, School of Medicine
    Background: In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population. Methods: Infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3) at doses stratified by postmenstrual age. Due to slow enrollment, a protocol amendment allowed eligible infants already receiving study regimens to enroll without randomization. The primary outcome was mortality within 30 days of study drug completion. Secondary outcomes included adverse events, outcomes of special interest, and therapeutic success (absence of death, negative cultures, and clinical cure score >4) 30 days after study drug completion. Results: One hundred eighty infants [128 randomized (R), 52 nonrandomized (NR)] were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 [95% confidence interval (CI): 1.39-12.13], 4.53 (95% CI: 1.21-15.50), and 4.07 (95% CI: 1.22-12.70) for groups 1, 2, and 3, respectively. Conclusions: Each of the antibiotic regimens are safe in premature infants with cIAI.
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    The Ex Vivo Human Translaminar Autonomous System to Study Spaceflight Associated Neuro-ocular Syndrome Pathogenesis
    (Nature, 2022-10) Peng, Michael; Curry, Stacy M.; Liu, Yang; Lohawala, Husain; Sharma, Gaurav; Sharma, Tasneem P.; Ophthalmology, School of Medicine
    Spaceflight-Associated Neuro-ocular Syndrome (SANS) is a significant unexplained adverse reaction to long-duration spaceflight. We employ an ex vivo translaminar autonomous system (TAS) to recreate a human ocular ground-based spaceflight analogue model to study SANS pathogenesis. To recapitulate the human SANS conditions, human ocular posterior segments are cultured in the TAS model for 14 days. Translaminar pressure differentials are generated by simulating various flow rates within intracranial pressure (ICP) and intraocular (IOP) chambers to maintain hydrostatic pressures of ICP: IOP (12:16, 15:16, 12:21, 21:16 mmHg). In addition, optic nerves are mechanically kinked by 6- and 10-degree tilt inserts for the ICP: IOP;15:16 mmHg pressure paradigm. The TAS model successfully maintains various pressure differentials for all experimental groups over 14 days. Post culture, we determine inflammatory and extracellular component expression changes within posterior segments. To further characterize the SANS pathogenesis, axonal transport capacity, optic nerve degeneration and retinal functional are measured. Identifiable pathogenic alterations are observed in posterior segments by morphologic, apoptotic, and inflammatory changes including transport and functional deficits under various simulated SANS conditions. Here we report our TAS model provides a unique preclinical application system to mimic SANS pathology and a viable therapeutic testing device for countermeasures.