The use of synthetic mesh remains an appropriate solution for most ventral hernia repairs. Laparoscopic ventral hernia repair has created a niche for both expanded polytetrafluoroethylene and composite mesh, as they are suited to intraperitoneal placement. Preliminary studies have demonstrated that the newer biologic prosthetics are reasonable options for hernia repair in contaminated fields and for large abdominal wall defects; however, more studies need to be done before advocating the use of these biologics in other settings.

Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high mobility group box 1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE sufficient (wildtype) or deficient (RAGE−/−) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardio-pulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia and decreased compliance, all of which were attenuated in RAGE −/− mice. Neutralizing systemic HMGB1, induced by TBI, reversed hypoxia and improved lung compliance. Compared to wildtype donors, lungs from RAGE−/− TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung pre-transplantation and predicted impaired oxygenation post-transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway prior to transplant may improve recipient outcomes following lung transplantation.

The epithelial complement inhibitory proteins (CIPs) cluster of differentiation 46 and 55 (CD46 and CD55) regulate circulating immune complex-mediated complement activation in idiopathic pulmonary fibrosis (IPF). Our previous studies demonstrated that IL-17A mediates epithelial injury via transforming growth factor ␤1 (TGF-␤1) and down-regulates CIPs. In the current study, we examined the mechanistic role of TGF-␤1 in complement activationmediated airway epithelial injury in IPF pathogenesis. We observed lower epithelial CIP expression in IPF lungs compared to normal lungs, associated with elevated levels of complement component 3a and 5a (C3a and C5a), locally and systemically. In normal primary human small airway epithelial cells ( Idiopathic pulmonary fibrosis (IPF) is a disease of high mortality for which lung transplantation is considered the only definitive therapy. Its pathogenesis remains largely unknown (1), but emerging concepts point to repeated injury to bronchiole-like epithelial cells and hyperplastic type II alveolar epithelial cells lining areas of honeycomb fibrosis (1, 2). These injured epithelial cells produce key profibrotic factors, including transforming growth factor ␤ (TGF-␤), which is implicated in epithelial injury (3-5) and epithelial-tomesenchymal transition (EMT; refs. 6, 7).The complement system is an integral arm of innate and adaptive immunity. Early studies demonstrated evidence of circulating immune complexes (8) and complement activation (9) in patients with IPF. In experimental models of IPF, antifibrotic effects due to deletion of complete downstream complement factors (10), specifically complement component 5 (C5; ref. 11), were reported. C3a and C5a are implicated in autoimmune diseases (12), chronic lung transplant rejection (13), experimental allergic asthma (14), and Abbreviations: ATII, alveolar type II; C3a, complement component 3a; C3aR, complement component 3a receptor; C5a, complement component 5a; C5aR, complement component 5a receptor; CD46, cluster of differentiation 46; CD55, cluster of differentiation 55; CIP, complement inhibitory protein; E-CAD, E-cadherin; EMT, epithelial-mesenchymal transition; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IL-17A, interleukin-17A; IPF, idiopathic pulmonary fibrosis; p38MAPK, mitogen-activated protein kinase; PARP, poly(ADP-ribose) polymerase; PCR, polymerase chain reaction; RNAi, RNA interference; SABM, small airway basal medium; SAEC, small airway epithelial cell; siRNA, small interference RNA; SMAD7, mothers against decapentaplegic homolog 7; TGF-␤1, transforming growth factor ␤, isoform 1 4223 0892-6638/14/0028-4223 © FASEB wnloaded from www.fasebj.org by (158

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Obliterative bronchiolitis (OB) post lung transplantation involves IL-17 regulated autoimmunity to type V collagen and alloimmunity, which could be enhanced by complement activation. However, the specific role of complement activation in lung allograft pathology, IL-17 production, and OB are unknown. The current study examines the role of complement activation in OB. Complement regulatory protein (CRP) (CD55, CD46, Crry/CD46) expression was down regulated in human and murine OB; and C3a, a marker of complement activation, was up regulated locally. IL-17 differentially suppressed Crry expression in airway epithelial cells in vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and decreased local C3a production. Exogenous C3a enhanced IL-17 production from alloantigen or autoantigen (type V collagen) reactive lymphocytes. Systemically neutralizing C5 abrogated the development of OB, reduced acute rejection severity, lowered systemic and local levels of C3a and C5a, recovered CRP expression, and diminished systemic IL-17 and IL-6 levels. These data indicated that OB induction is in part complement dependent due to IL-17 mediated down regulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed forward loop that may enhance CRP down regulation, suggesting that complement blockade could be a therapeutic strategy for OB.

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Background. Extracorporeal membrane oxygenation (ECMO) artificially supports respiratory and cardiac function when conventional techniques fail. ECMO has been described as a treatment modality for acute pulmonary and cardiac failure following orthotopic liver transplantation (OLT). Here, we present a series of adult OLT recipients placed on ECMO after transplantation for both respiratory and cardiac indications and review the literature on the role of ECMO in the setting of OLT. Methods. For the patient series, we cross-referenced all patients who underwent OLT at our institution between 2007 and 2018 with the ECMO database of our institution and described these cases. For the literature review, we identified cases and series that described the use of ECMO after liver transplantation in adult recipients. Results. A total of 1792 patients underwent OLT. Eight patients were placed on ECMO (0.4%), 5 men and 3 women aged 28 to 68 years (4 venovenous and 4 venoarterial). Three of (38%) 8 patients survived to discharge and are alive today. In the literature, we identified 3 series and 12 case reports of ECMO following OLT, with the majority of the literature derived from the Asian OLT experience. Conclusions. ECMO following liver transplantation should be considered as a viable rescue strategy in patients with severe cardiopulmonary failure. ECMO is particularly effective if the cause of cardiopulmonary failure is recognized promptly and is thought to be transient. This is the largest series in the United States and demonstrates a 38% survival rate, which is comparable to other reports in the literature from Asia.

The fact that BFB-CBT resulted in larger improvements in pain coping skills, and was well accepted by the patients, underlines the importance and feasibility of psychological treatments in the clinical management of TMD.