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1.
J Am Coll Surg ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832690

RESUMO

BACKGROUND: Traumatic hemothorax (HTX) is often managed with tube thoracostomy (TT); however, TT carries a high complication rate. In 2017, a guideline was implemented at our Level I trauma center to observe traumatic HTX ≤300mL in hemodynamically stable patients. We hypothesized that this guideline would decrease TT placement without increasing observation failure rates. METHODS: This was a single-center retrospective review of all adult patients admitted with a HTX on computed tomography (CT) before (2015-2016) and after (2018-2019) the guideline implementation. Exclusion criteria were TT placement prior to CT scan, absence of CT scan, death within 5 days of admission, and a concurrent pneumothorax (PTX) >20mm. HTX volume was calculated using CT scan images and Mergo's formula: V=d 2xL (V: volume; d: depth; L: length). The primary outcome was observation failure, defined as the need for TT, video-assisted thoracoscopic surgery, thoracotomy after repeat imaging or worsening of symptoms and pulmonary morbidity. RESULTS: A total of 357 patients met inclusion criteria, of whom 210 were admitted after guideline implementation. There were no significant differences in baseline demographics, comorbidities, or injury characteristics across both cohorts. The post-implementation cohort had a significant increase in observation rate (75% vs 59%) and a decrease in TT placement (42% vs 57%). Moreover, the post-implementation group had a statistically significant shorter hospital (6 vs 8 days) and ICU (2 vs 3 days) LOS. No significant differences in observation failure, pulmonary complications, 30-day readmission, or 30-day mortality were observed across both cohorts. CONCLUSION: The implementation of the 300mL guideline led to a decrease in TT placement without increasing observation failure or complication rates. LEVEL OF EVIDENCE: Level III, Therapeutic/Care Management.

2.
Mol Ther Methods Clin Dev ; 32(2): 101258, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38779336

RESUMO

Genetic manipulation of animal models is a fundamental research tool in biology and medicine but is challenging in large animals. In rodents, models can be readily developed by knocking out genes in embryonic stem cells or by knocking down genes through in vivo delivery of nucleic acids. Swine are a preferred animal model for studying the cardiovascular and immune systems, but there are limited strategies for genetic manipulation. Lipid nanoparticles (LNPs) efficiently deliver small interfering RNA (siRNA) to knock down circulating proteins, but swine are sensitive to LNP-induced complement activation-related pseudoallergy (CARPA). We hypothesized that appropriately administering optimized siRNA-LNPs could knock down circulating levels of plasminogen, a blood protein synthesized in the liver. siRNA-LNPs against plasminogen (siPLG) reduced plasma plasminogen protein and hepatic plasminogen mRNA levels to below 5% of baseline values. Functional assays showed that reducing plasminogen levels modulated systemic blood coagulation. Clinical signs of CARPA were not observed, and occasional mild and transient hepatotoxicity was present in siPLG-treated animals at 5 h post-infusion, which returned to baseline by 7 days. These findings advance siRNA-LNPs in swine models, enabling genetic engineering of blood and hepatic proteins, which can likely expand to proteins in other tissues in the future.

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