The cellular and mechanistic bases underlying endothelial regeneration of adult large vessels have proven challenging to study. Using a reproducible in vivo aortic endothelial injury model, we characterized cellular dynamics underlying the regenerative process through a combination of multi-color lineage tracing, parabiosis, and single-cell transcriptomics. We found that regeneration is a biphasic process driven by distinct populations arising from differentiated endothelial cells. The majority of cells immediately adjacent to the injury site re-enter the cell cycle during the initial damage response, with a second phase driven by a highly proliferative subpopulation. Endothelial regeneration requires activation of stress response genes including Atf3, and aged aortas compromised in their reparative capacity express less Atf3. Deletion of Atf3 reduced endothelial proliferation and compromised the regeneration. These findings provide important insights into cellular dynamics and mechanisms that drive responses to large vessel injury.

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Background Locally advanced pancreatic tumors may require vascular reconstruction for complete resection. However, pancreatoduodenectomy with vascular resection (PDVR) remains a subject of debate due to increased complications. Methods Patients were identified using the ACS NSQIP Participant User Data Files from 2014 to 2019. Results The 30-day mortality rate was 2.7%; major complications occurred in 32.2%. There is an increasing trend of PDVR in patients requiring pancreatectomy. There were no significant differences in mortality between PDVR with vein, artery, or venous and arterial resections. High BMI and postoperative biliary stent were risk factors for early complications. High BMI and COPD increased risk of early mortality. Chemotherapy and chemoradiotherapy were negative predictors for early morbidities and mortality, respectively. Conclusion This study identifies the predictors of early morbidity and mortality in PDVR. The results of this study may assist decision making in perioperative management to optimize overall survival and guide additional research.

bilirubin. Cirrhotic patients had a lower platelet count (184 vs 252; p ¼ 0.028). Operative times were shorter with smaller tumors (3.3 vs 5.6 cm; p<0.001) and fewer lobar resections (7% vs 26%; p<0.001) resulting in smaller margins (0.857 vs 1.037 cm; p ¼ 0.028) but equivalent local recurrence rate (1.1% vs 2.2%;p ¼ 0.548). Cirrhotic resections required increased resources including ICU and overall length of stay. CONCLUSION: Minimally invasive cirrhotic resection appears to be technically feasible and safe in tertiary centers but should be performed in the appropriate patient population. However, the long-term sequeala of smaller margins will need to be evaluated in long-term oncologic studies. This study should serve as a starting point to a larger and longer cohort or propensity study to support this procedure in this complex area of hepatobiliary surgery.