Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expanded and antigen-driven endomysial T cells, the disease is resistant to immunotherapies. Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months. We designed a proof-of-principle study to examine if one series of Alemtuzumab infusions in sIBM patients depletes not only peripheral blood lymphocytes but also endomysial T cells and alters the natural course of the disease. Thirteen sIBM patients with established 12-month natural history data received 0.3 mg/kg/day Alemtuzumab for 4 days. The study was powered to capture ≥10% increase strength 6 months after treatment. The primary end-point was disease stabilization compared to natural history, assessed by bi-monthly Quantitative Muscle Strength Testing and Medical Research Council strength measurements. Lymphocytes and T cell subsets were monitored concurrently in the blood and the repeated muscle biopsies. Alterations in the mRNA expression of inflammatory, stressor and degeneration-associated molecules were examined in the repeated biopsies. During a 12-month observation period, the patients’ total strength had declined by a mean of 14.9% based on Quantitative Muscle Strength Testing. Six months after therapy, the overall decline was only 1.9% (P < 0.002), corresponding to a 13% differential gain. Among those patients, four improved by a mean of 10% and six reported improved performance of daily activities. The benefit was more evident by the Medical Research Council scales, which demonstrated a decline in the total scores by 13.8% during the observation period but an improvement by 11.4% (P < 0.001) after 6 months, reaching the level of strength recorded 12 months earlier. Depletion of peripheral blood lymphocytes, including the naive and memory CD8+ cells, was noted 2 weeks after treatment and persisted up to 6 months. The effector CD45RA+CD62L­ cells, however, started to increase 2 months after therapy and peaked by the 4th month. Repeated muscle biopsies showed reduction of CD3 lymphocytes by a mean of 50% (P < 0.008), most prominent in the improved patients, and reduced mRNA expression of stressor molecules Fas, Mip-1a and αB-crystallin; the mRNA of desmin, a regeneration-associated molecule, increased. This proof-of-principle study provides insights into the pathogenesis of inclusion-body myositis and concludes that in sIBM one series of Alemtuzumab infusions can slow down disease progression up to 6 months, improve the strength of some patients, and reduce endomysial inflammation and stressor molecules. These encouraging results, the first in sIBM, warrant a future study with repeated infusions (Clinical Trials. Gov NCT00079768).

| INTRODUC TI ONOnce a therapy for neonates with severe respiratory and cardiac impairment, extracorporeal membrane oxygenation (ECMO) is being utilized with greater frequency in the critically ill adult population. 1-4 ECMO has shown encouraging results as a rescue therapy that serves as a replacement for pulmonary and/or cardiovascular function while the heart and lungs recover from a catastrophic insult in the postoperative period. At our center, ECMO has been utilized with increasing frequency in the critically ill adult population. 5 Prior to transplantation, patients with liver failure often have multiple organ system impairment. Coagulopathy, portal hypertension, and an impaired immune system are chief among the maladies associated with acute and chronic liver disease. 6-8 In the perioperative period, the added stress of a rigorous surgery and subsequent liver engraftment may lead to further physiological derangements that predispose patients to cardiopulmonary failure. 9,10 These can lead to intrinsic lung conditions, such as ARDS or to cardiopulmonary failure from right heart impairment and pulmonary thrombosis. Prior to the utilization of adult ECMO, these conditions carried a high mortality rate. 11 The use of veno-venous (VV) ECMO has been Abstract Background: Postoperative severe cardiopulmonary failure carries a high rate of mortality. Extracorporeal membrane oxygenation (ECMO) can be used as a salvage therapy when conventional therapies fail. Methods: We retrospectively reviewed our experience with ECMO support in the early postoperative period after liver transplant between September 2011 and May 2016.Results: Out of 537 liver transplants performed at our institution, seven patients required ECMO support with a median age of 52 and a median MELD score of 28.Veno-venous ECMO was used in four patients with severe respiratory failure while the rest required veno-arterial ECMO for circulatory failure. The median time from transplant to cannulation was 3 days with a median duration of ECMO support of 7 days. All patients except one were successfully decannulated. The median hospital length of stay was 58 days with an in-hospital mortality of 28.6%. Conclusion:Extracorporeal membrane oxygenation can be considered a viable rescue therapy in the setting of severe postoperative cardiopulmonary failure.Extracorporeal membrane oxygenation therapy was successful in saving patients who were otherwise unsalvageable. K E Y W O R D Scardiopulmonary failure, ECMO, liver failure

IntroductionDeep vein thrombosis (DVT) and pulmonary embolism (PE) are surgical complications estimated to occur in 5% to 10% of patients. There are limited data regarding DVT/PE in the early postoperative period in liver transplant patients. The aim of this study is to determine risk factors that influence the incidence of DVT/PE and the effectiveness of prophylaxis.MethodsWe reviewed the records of 999 patients who underwent initial liver transplant between January 2000 and June 2012 at Henry Ford Hospital. In 2011, a standardized prophylactic regimen using subcutaneous (SQ) heparin was initiated. All patients that developed either upper/lower extremity DVT or PE within the first 30 days of transplant formed the cohort of this study.ResultsOn multivariate analysis, only peripherally inserted central catheter (PICC) placement and SQ heparin were associated with DVT/PE. In patients receiving heparin, 3 (1.0%) had DVT/PE versus 25 (3.5%) who did not receive heparin (P = 0.03). Sixteen (6.9%) patients that had a PICC developed DVT/PE compared with 12 (1.6%) patients without a PICC (P < 0.001). In the heparin group, DVT/PE with PICC was reduced to 3 (3.0%) versus 13 (9.9%) in those with a PICC and did not receive heparin (P = 0.03). Mean time from transplant to DVT/PE diagnosis was 12.3 days. Length of hospitalization was significantly longer in patients who developed DVT/PE (18.5 vs 10.0 days, P < 0.001).ConclusionsIn this study, we demonstrated that PICC placement significantly increases the likelihood of DVT/PE in liver transplant recipients. Prophylactic SQ heparin effectively reduced DVT/PE events in this patient population.