Metabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function.

Preservation quality of donor hearts is a key determinant of transplant success. Preservation duration beyond 4 hours is associated with primary graft dysfunction (PGD). Given transport time constraints, geographical limitations exist for donor-recipient matching, leading to donor heart underutilization. Here, we showed that metabolic reprogramming through up-regulation of the enzyme immune response gene 1 (IRG1) and its product itaconate improved heart function after prolonged preservation. Irg1 transcript induction was achieved by adding the histone deacetylase (HDAC) inhibitor valproic acid (VPA) to a histidine-tryptophan-ketoglutarate solution used for donor heart preservation. VPA increased acetylated H3K27 occupancy at the IRG1 enhancer and IRG1 transcript expression in human donor hearts. IRG1 converts aconitate to itaconate, which has both anti-inflammatory and antioxidant properties. Accordingly, our studies showed that Irg1 transcript up-regulation by VPA treatment increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in mice, which was accompanied by increased antioxidant protein expression [hemeoxygenase 1 (HO1) and superoxide dismutase 1 (SOD1)]. Deletion of Irg1 in mice (Irg1-/-) negated the antioxidant and cardioprotective effects of VPA. Consistent with itaconate's ability to inhibit succinate dehydrogenase, VPA treatment of human hearts increased itaconate availability and reduced succinate accumulation during preservation. VPA similarly increased IRG1 expression in pig donor hearts and improved its function in an ex vivo cardiac perfusion system both at the clinical 4-hour preservation threshold and at 10 hours. These results suggest that augmentation of cardioprotective immune-metabolomic pathways may be a promising therapeutic strategy for improving donor heart function in transplantation.

Assessing the Impact of COVID-19 on the 2021 Orthopaedic Surgery Match Outcomes.

The purpose of this study was to assess the influence of the COVID-19 pandemic on the 2021 orthopaedic surgery residency match outcomes. Because in-person away rotations and interviews were canceled during the 2020 to 2021 application cycle, we hypothesized that applicants would match at their home program at a higher rate in 2021 than in previous years. Methods: We queried allopathic orthopaedic surgery residency websites and social media accounts for names of residents and medical school information for cohorts matching from 2017 through 2021. To assess availability of and participation in virtual away rotations, we administered a survey to Accreditation Council for Graduate Medical Education-accredited allopathic orthopaedic surgery residency programs. The primary outcome was the annual proportion of applicants matching at the program affiliated with their medical school ("home program"). Subgroup analyses were stratified by Doximity reputation ranking and availability of a virtual away rotation. Results: We identified 2,632 residents who matched between 2017 and 2020 and 698 residents who matched in 2021. Overall home program match rate and likelihood of home matching were higher in 2021 compared with 2017 to 2020 (28% vs. 20%; odds ratio [OR] = 1.51, 95% confidence interval [CI] 1.24-1.82, p < 0.001). The increase in the home match rate at programs ranked in the top 30 (27% vs. 20%, p = 0.034) was similar to the increase at programs ranked outside the top 30 (28% vs. 20%, p < 0.001). Of the 66 (48%) programs that responded to the survey, 16 (24%) offered a virtual away rotation. Programs with a higher Doximity ranking were more likely than lower-ranked programs to offer a virtual away rotation (OR = 6.75, 95% CI 1.95-23.4, p = 0.003). Home match rates did not differ significantly between programs that offered a virtual away rotation and those that did not (26% vs. 32%, p = 0.271). Conclusions: A higher proportion of orthopaedic surgery residency applicants matched at their home program in 2021 compared with previous years. Limitations on in-person activities due to the COVID-19 pandemic may have contributed to this rise. Level of Evidence: N/A.

The 50 Most Cited Articles in Knee Medial Collateral Ligament Injury Research.

Background: Medial collateral ligament (MCL) injury is a common orthopaedic knee injury with a plethora of published articles regarding evaluation, treatment, and outcome. Purpose: To perform a comprehensive bibliometric analysis of the 50 most cited articles in MCL research. Study Design: Cross-sectional study. Methods: We performed a keyword search of the Institute for Scientific Information's Web of Knowledge database for the identification of articles published before September 2021 encompassing the MCL. The conducted search yielded 9534 articles. The results were then filtered using predetermined guidelines and criteria, and the 50 most cited articles were selected for analysis. Extracted data included title, authors, citation count, year of publication, topic, journal, article type, country of origin, and level of evidence. Results: The selected 50 articles ranged from 1976 to 2013. The largest proportion was classified as having level 4 evidence (n = 12; 24%). The majority of the articles were published in the decade from 2000 to 2009 (n = 17; 34%), followed by 1990 to 1999 (n = 16; 32%). The mean raw citation score per article was 133 (range, 74-422). The most popular topic discussed was surgical technique and outcome (n = 14; 28%), followed by anatomy and biomechanics (n = 13; 26%). Conclusion: This study provides a comprehensive and objective measure of the most cited articles on MCL research. Knowledge of the characteristics of these most influential articles improves the understanding of MCL injury and can guide discussion for future research.