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BACKGROUND: Portable ex vivo lung perfusion during lung transplantation is a resource-intensive technology. In light of its increasing use, we evaluated the cost-effectiveness of ex vivo lung perfusion at a low-volume lung transplant center in the USA. METHODS: Patients listed for lung transplantation (2015-2021) in the United Network for Organ Sharing database were included. Quality-of-life was approximated by Karnofsky Performance Status scores 1-year post-transplant. Total transplantation encounter and 1-year follow-up costs accrued by our academic center for patients listed from 2018 to 2021 were obtained. Cost-effectiveness was calculated by evaluating the number of patients attaining various Karnofsky scores relative to cost. RESULTS: Of the 13 930 adult patients who underwent lung transplant in the United Network for Organ Sharing database, 13 477 (96.7%) used static cold storage and 453 (3.3%) used ex vivo lung perfusion, compared to 30/58 (51.7%) and 28/58 (48.3%), respectively, at our center. Compared to static cold storage, median total costs at 1 year were higher for ex vivo lung perfusion ($918 000 vs. $516 000; p = 0.007) along with the cost of living 1 year with a Karnofsky functional status of 100 after transplant ($1 290 000 vs. $841 000). In simulated scenarios, each Karnofsky-adjusted life year gained by ex vivo lung perfusion was 1.00-1.72 times more expensive. CONCLUSIONS: Portable ex vivo lung perfusion is not currently cost-effective at a low-volume transplant centers in the USA, being 1.53 times more expensive per Karnofsky-adjusted life year. Improving donor lung and/or recipient biology during ex vivo lung perfusion may improve its utility for routine transplantation.
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Previous systematic reviews evaluating piezoelectric osteotomy are of critically low quality. We conducted a high-quality systematic review and meta-analysis to evaluate outcomes for piezoelectric versus conventional osteotomy. Methods: The study protocol was published a priori (PROSPERO: CRD42021287877). MEDLINE, Embase, Web of Science, and CENTRAL were searched for studies comparing piezoelectric versus conventional osteotomes and reporting at least one outcome of interest (clinical or patient-reported outcomes, PROs). Methodological quality and risk of bias were assessed using GRADE and Cochrane's RoB-2/ROBINS-I tools, respectively. Random effects models were applied. Results: Of 347 articles, 10 studies (nine randomized controlled trials; one prospective cohort study) including 554 patients were included. Piezoelectric osteotomy was associated with significantly reduced edema [standardized mean difference (SMD), -0.67; 95% confidence interval (CI), -1.03 to -0.30; P < 0.0004], ecchymosis (SMD, -0.93; 95% CI, -1.13 to -0.73; P < 0.00001), and pain (SMD, -1.48; 95% CI, -2.07 to -0.88; P < 0.00001) compared with standard osteotomy. Odds of mucosal injury were significantly lower following piezoelectric osteotomy (odds ratio, 0.06; 95% CI, 0.01 to 0.52; P = 0.01). There was no difference in duration of osteotomy (SMD, 3.15; 95% CI, -1.82 to 8.12; P = 0.22) or total procedure duration (SMD, 0.46; 95% CI, -0.43 to 1.36; P = 0.31). One study reported PROs, favoring piezoelectric osteotomy. Conclusion: This systematic review and meta-analysis provides support (albeit weak, due to low-quality evidence) for piezoelectric over conventional osteotomy, for reducing morbidity in the early postoperative period. High-quality level I data reporting PROs will optimize shared decision-making/informed consent.
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SARS-CoV-2 enters host cells through its viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells. Here, we show that functionalized nanoparticles, termed "Nanotraps," completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells. The liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and phagocytosis-specific phosphatidylserines. The Nanotraps effectively captured SARS-CoV-2 and completely blocked SARS-CoV-2 infection to ACE2-expressing human cell lines and primary lung cells; the phosphatidylserine triggered subsequent phagocytosis of the virus-bound, biodegradable Nanotraps by macrophages, leading to the clearance of pseudotyped and authentic virus in vitro. Furthermore, the Nanotraps demonstrated an excellent biosafety profile in vitro and in vivo. Finally, the Nanotraps inhibited pseudotyped SARS-CoV-2 infection in live human lungs in an ex vivo lung perfusion system. In summary, Nanotraps represent a new nanomedicine for the inhibition of SARS-CoV-2 infection.
