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Mesenteric ischemia and reperfusion (I/R) injury can ensue from a variety of vascular diseases and represents a major cause of morbidity and mortality in intensive care units. It causes an inflammatory response associated with local gut dysfunction and remote organ injury. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of metabolic homeostasis. The catalytic α1 subunit is highly expressed in the intestine and vascular system. In loss-of-function studies, we investigated the biological role of AMPKα1 in affecting the gastrointestinal barrier function. Male knock-out (KO) mice with a systemic deficiency of AMPKα1 and wild-type (WT) mice were subjected to a 30 min occlusion of the superior mesenteric artery. Four hours after reperfusion, AMPKα1 KO mice exhibited exaggerated histological gut injury and impairment of intestinal permeability associated with marked tissue lipid peroxidation and a lower apical expression of the junction proteins occludin and E-cadherin when compared to WT mice. Lung injury with neutrophil sequestration was higher in AMPKα1 KO mice than WT mice and paralleled with higher plasma levels of syndecan-1, a biomarker of endothelial injury. Thus, the data demonstrate that AMPKα1 is an important requisite for epithelial and endothelial integrity and has a protective role in remote organ injury after acute ischemic events.

COVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. To expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients, including matched analysis of the whole-blood transcriptome, plasma proteomics with two complementary platforms, cytokine profiling, plasma and red blood cell metabolomics, deep immune cell phenotyping by mass cytometry, and clinical data annotation. We refer to this multidimensional dataset as the COVIDome. We then created the COVIDome Explorer, an online researcher portal where the data can be analyzed and visualized in real time. We illustrate herein the use of the COVIDome dataset through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19, revealing associations between CRP levels and damage-associated molecular patterns, depletion of protective serpins, and mitochondrial metabolism dysregulation. We expect that the COVIDome Explorer will rapidly accelerate data sharing, hypothesis testing, and discoveries worldwide., Competing Interests: Declaration of interests J.M.E. serves in the COVID Development Advisory Board for Elly Lilly and has provided consulting services to Gilead Sciences Inc. J.M.E. also serves on the Cell Reports Advisory Board. The remaining authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Salvage and delayed esophagectomy after chemoradiation therapy (CRT) have been associated with increased morbidity and mortality, but recent series have shown similar outcomes compared to timely esophagectomy. We aim to evaluate outcomes for delayed and salvage esophagectomy for esophageal adenocarcinoma utilizing a large national database., Methods: The National Cancer Database for 2004 to 2014 was queried for patients with clinical stage II or III esophageal adenocarcinoma who underwent preoperative CRT and esophagectomy. Patients who underwent surgery <90 days after CRT were defined as the timely esophagectomy group (n = 7822), and those who underwent surgery ≥90 days after CRT were defined as the delayed esophagectomy group (n = 667)., Results: A total of 8489 patients met our inclusion criteria. The median post-CRT interval was 49 days (range, 40-61 days) for the timely esophagectomy group and 109 days (range, 97-132 days) for the delayed esophagectomy group. The delayed group was more likely to be of black race (2.3% vs 1.2%; P < .01) and more likely to have Medicare (47.9% vs 39.8%; P < .001). There were no significant between-group differences in chemotherapy regimens (P = .17), radiation dose (P = .18), or surgical approach (P = .48). The delayed esophagectomy group had higher rates of pathological complete response (22.2% vs 18.6%; P = .043) and 90-day postoperative mortality (10.4% vs 7.8%; P < .01). On multivariate analysis, delayed esophagectomy was not independently associated with decreased overall survival., Conclusions: In this large retrospective database study, despite increased perioperative mortality, delayed and salvage esophagectomy for adenocarcinoma appear to have similar long-term survival as timely esophagectomy. Delayed and salvage esophagectomy may be offered to patients who do not receive timely esophagectomy after CRT., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Pediatric sepsis is a leading cause of morbidity and mortality in children. One of the most common and devastating morbidities is sepsis-related acute kidney injury (AKI). AKI was traditionally thought to be related to low perfusion and acute tubular necrosis. However, little acute tubular necrosis can be found following septic AKI, and little is known about the mechanism of septic AKI. Olfactomedin-4 (OLFM4) is a secreted glycoprotein that marks a subset of neutrophils. Increased expression of OLFM4 in the blood is associated with worse outcomes in sepsis. Here, we investigated a pediatric model of murine sepsis using murine pups to investigate the mechanisms of OLFM4 in sepsis. When sepsis was induced in murine pups, survival was significantly increased in OLFM4-null pups. Immunohistochemistry at 24 h after the induction of sepsis demonstrated increased expression of OLFM4 in the kidney, which was localized to the loop of Henle. Renal cell apoptosis and plasma creatinine were significantly increased in wild-type versus OLFM4-null pups. Finally, bone marrow transplant suggested that increased OLFM4 in the kidney reflects local production rather than filtered from the plasma. These results demonstrate renal expression of OLFM4 for the first time and suggest that a kidney-specific mechanism may contribute to survival differences in OLFM4-null animals.

Background: Enhanced recovery protocols are associated with improved recovery. However, data on outcomes following the implementation of an enhanced recovery protocol in colorectal cancer are limited. We set out to study the postoperative outcomes, opioid use patterns, and cost impact for patients undergoing colon or rectal resection for cancer., Methods: A retrospective review of all elective colorectal cancer resections from January 2015 to June 2018 at a single institution was performed. Patient demographics, operative details, and postoperative outcomes were collected. Colon and rectal patients were studied separately, with comparison of patients before and after the implementation of an enhanced recovery protocol., Results: One hundred ninety-two patients underwent elective colorectal resection for cancer. In January 2016, an enhanced recovery protocol was implemented for all elective resections - 71 patients (33 colon and 38 rectal) underwent surgery before implementation and 121 patients (56 colon and 65 rectal) underwent surgery after implementation of the enhanced recovery protocol. There were no differences with regard to age, gender, or body mass index before or after implementation (all P > .05). For both colon and rectal cancer patients, the enhanced recovery protocol reduced time to regular diet (both P < .05) and length of stay (colon: 3 vs 4 days; rectal: 4 vs 6 days; both P < .01). Enhanced recovery protocol patients also consumed fewer total narcotics (colon: 44 vs 184 morphine milligram equivalents, P < .01; rectal: 121 vs 393 morphine milligram equivalents, P < .01)., Conclusions: Enhanced recovery protocol use reduced length of stay and narcotic use with similar total costs and no difference in 30-day complications for both colon and rectal cancer resections., (© 2019 Published by Elsevier Inc.)