BackgroundMore than 500,000 hospitalized patients survive severe sepsis annually in the USA. Recent epidemiological evidence, however, demonstrated that these survivors have significant morbidity and mortality, with 3-year fatality rates higher than 70%. To investigate the mechanisms underlying persistent functional impairment in sepsis survivors, here we developed a model to study severe sepsis survivors following cecal ligation and puncture (CLP).MethodsSepsis was induced in mice by CLP and survivors were followed for twelve weeks. Spleen and blood were collected and analyzed at different time points post-sepsis.ResultsWe observed that sepsis survivors developed significant splenomegaly. Analysis of the splenic cellular compartments revealed a major expansion of the inflammatory CD11b+ Ly-6CHigh pool. Serum high-mobility group box 1 (HMGB1) levels in the sepsis surviving mice were significantly elevated for 4-6 weeks after post-sepsis, and administration of an anti-HMGB1 monoclonal antibody significantly attenuated splenomegaly as well as splenocyte priming. Administration of recombinant HMGB1 to naive mice induced similar splenomegaly, leukocytosis and splenocyte priming as observed in sepsis survivors. Interestingly analysis of circulating HMGB1 from sepsis survivors by mass spectroscopy demonstrated a stepwise increase of reduced form of HMGB1 (with known chemo-attractant properties) during the first 3 weeks, followed by disulphide form (with known inflammatory properties) 4-8 weeks after CLP.DiscussionOur results indicate that prolonged elevation of HMGB1 is a necessary and sufficient mediator of splenomegaly and splenocyte expansion, as well as splenocyte inflammatory priming in murine severe sepsis survivors.

Obesity is a major risk factor for insulin resistance, type 2 diabetes mellitus and cardiovascular disease. The pathophysiology of obesity is associated with chronic low-grade inflammation. Adipose tissue in obesity is significantly infiltrated by macrophages that secrete cytokines. The mechanisms of interaction between macrophages and adipocytes, leading to macrophage activation and increased cytokine release, remain to be elucidated. We reasoned that an adipocyte-derived factor might stimulate activation of macrophages. We have identified pigment epithelium-derived factor (PEDF) as a mediator of inflammation that is secreted by adipocytes and mediates macrophage activation. Recombinant PEDF activates macrophages to release tumor necrosis factor (TNF) and interleukin-1 (IL-1). The PEDF receptor adipose triglyceride lipase (ATGL) is required for PEDF-mediated macrophage activation. Selective inhibition of ATGL on macrophages attenuates PEDF-induced TNF production, and PEDF enhances the phosphorylation of p38 and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases. PEDF administration to rats results in increased serum TNF levels, and insulin resistance. Together, these findings suggest that PEDF secreted by adipocytes contributes to the onset and maintenance of chronic inflammation in obesity, and may be a therapeutic target in ameliorating insulin resistance.

Objective: As the Coronavirus Disease 2019 pandemic continues, appropriate management of thoracic complications from Coronavirus Disease 2019 needs to be determined. Our objective is to evaluate which complications occurring in patients with Coronavirus Disease 2019 require thoracic surgery and to report the early outcomes.Methods: This study is a single-institution retrospective case series at New York University Langone Health Manhattan campus evaluating patients with confirmed Coronavirus Disease 2019 infection who were hospitalized and required thoracic surgery from March 13 to July 18, 2020.Results: From March 13 to August 8, 2020, 1954 patients were admitted to New York University Langone Health for Coronavirus Disease 2019. Of these patients, 13 (0.7%) required thoracic surgery. Two patients (15%) required surgery for complicated pneumothoraces, 5 patients (38%) underwent pneumatocele resection, 1 patient (8%) had an empyema requiring decortication, and 5 patients (38%) developed a hemothorax that required surgery. Three patients (23%) died after surgery, 9 patients (69%) were discharged, and 1 patient (8%) remains in the hospital. No healthcare providers were positive for Coronavirus Disease 2019 after the surgeries.Conclusions: Given the 77% survival, with a majority of patients already discharged from the hospital, thoracic surgery is feasible for the small percent of patients hospitalized with Coronavirus Disease 2019 who underwent surgery for complex pneumothorax, pneumatocele, empyema, or hemothorax. Our experience also supports the safety of surgical intervention for healthcare providers who operate on patients with Coronavirus Disease 2019.

Objective The purpose of this study was to compare operative strategies and patient outcomes in acute type A aortic dissection (ATAAD) repairs before and after the implementation of a multi-disciplinary aortic surgery team. Methods Between May 2005 and July 2014, 101 patients underwent ATAAD repair at our institution. A dedicated multidisciplinary aortic surgery team (experienced aortic surgeon, perfusionists, cardiac anesthesiologists, nurses, and radiologists) was formed in 2010. We retrospectively compared ATAAD repair outcomes in patients before (2005–2009, N = 39) and after (2010–2014, N = 62) implementation of our program. Expected operative mortality was calculated using the International Registry of Acute Aortic Dissection preoperative predictive model. Results This study demonstrated a significant reduction in operative mortality after implementation of the aortic surgery program (30.8% vs. 9.7%; P = 0.014). There was also an increase in the complexity of surgical technique and perfusion strategies with fewer postoperative complications related to respiratory (P < 0.0001) and renal failure (P = 0.034). Baseline demographics were similar, and there was no statistically significant difference in International Registry of Acute Aortic Dissection predictive variables between the 2 groups. However, there was a 3.5-fold reduction in the observed-to-expected (O/E) operative mortality ratio. There was a 50% increase in volume with a significant number of patients being admitted directly to our aortic center for ATAAD repair, thus avoiding delay in operation related to transfers from a secondary hospital. Conclusions Patient outcomes are improved when the surgical treatment of ATAAD is managed by a high-volume multidisciplinary aortic surgery team.

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