Global knockout of ROMK potassium channel worsens cardiac ischemia-reperfusion injury but cardiomyocyte-specific knockout does not: Implications for the identity of mitoKATP.

The renal-outer-medullary­potassium (ROMK) channel, mutated in Bartter's syndrome, regulates ion exchange in kidney, but its extra-renal functions remain unknown. Additionally, ROMK was postulated to be the pore-forming subunit of the mitochondrial ATP-sensitive K+ channel (mitoKATP), a mediator of cardioprotection. Using global and cardiomyocyte-specific knockout mice (ROMK-GKO and ROMK-CKO respectively), we characterize the effects of ROMK knockout on mitochondrial ion handling, the response to pharmacological KATP channel modulators, and ischemia/reperfusion (I/R) injury. Mitochondria from ROMK-GKO hearts exhibited a lower threshold for Ca2+-triggered permeability transition pore (mPTP) opening but normal matrix volume changes during oxidative phosphorylation. Isolated perfused ROMK-GKO hearts exhibited impaired functional recovery and increased infarct size when I/R was preceded by an ischemic preconditioning (IPC) protocol. Because ROMK-GKO mice exhibited severe renal defects and cardiac remodeling, we further characterized ROMK-CKO hearts to avoid confounding systemic effects. Mitochondria from ROMK-CKO hearts had unchanged matrix volume responses during oxidative phosphorylation and still swelled upon addition of a mitoKATP opener, but exhibited a lower threshold for mPTP opening, similar to GKO mitochondria. Nevertheless, I/R induced damage was not exacerbated in ROMK-CKO hearts, either ex vivo or in vivo. Lastly, we examined the response of ROMK-CKO hearts to ex vivo I/R injury with or without IPC and found that IPC still protected these hearts, suggesting that cardiomyocyte ROMK does not participate significantly in the cardioprotective pathway elicited by IPC. Collectively, our findings from these novel strains of mice suggest that cardiomyocyte ROMK is not a central mediator of mitoKATP function, although it can affect mPTP activation threshold.

The Impact of the COVID-19 Pandemic on Geographic Placement of Applicants to General Surgery Residency Programs.

OBJECTIVE: COVID-19 greatly influenced medical education and the residency match. As new guidelines were established to promote safety, travel was restricted, visiting rotations discontinued, and residency interviews turned virtual. The purpose of this study is to assess the geographic trends in distribution of successfully matched General Surgery applicants prior to and after the implementation of pandemic guidelines, and what we can learn from them as we move forward. DESIGN: This was a retrospective review of 129 Accreditation Council for Graduate Medical Education (ACGME) accredited, academic General Surgery Residency Programs across 46 states and the District of Columbia. Categorically matched residents' medical schools (i.e., home institutions), medical school states, and medical school regions as defined per the Association of American Medical Colleges (AAMC), were compared to the same geographic datapoints as their residency program. Preliminary residents were excluded. Residents in the 2018, 2019, and 2020 cycles were sub-categorized into the "pre-COVID" group and residents in the 2021 and 2022 applications cycles were sub-categorized into the "post-COVID" group. The percentages of residents who matched at their home institution, in-state, and in-region were examined. SETTING: Multiple ACGME-accredited, university-affiliated General Surgery Residency Programs across the United States of America. PARTICIPANTS: A total of 4033 categorical General Surgery residents were included. RESULTS: Of 4033 categorical residents who matched between 2018 and 2022, 56.1% (n = 2,263) were in the pre-COVID group and 43.9% (n = 1770) were in the post-COVID group. In the pre-COVID group 14.4% (n = 325) of residents remained in-home (IH), 24.4% (n = 553) in-state (IS), and 37.0% (n = 837) in- region (IR), compared to 18.8% IH (n = 333), 27.8% IS (n = 492), and 39.9% IR (n = 706) in the post-COVID group, respectively. Significant increases for IH and IS resident matching at 4.5% and 3.4%, respectively, were noted in the post-COVID period (p < 0.05). CONCLUSION: The COVID-19 pandemic, and the ensuing changes adopted to promote safety, significantly impacted medical student opportunities and the General Surgery residency application process. General Surgery match data over the last 5 years reveals a statistically significant increase in the percentage of applicants matching at in-home and in-state institutions after the pandemic.