Background With standard miniature swine donors, survivals of only 3 days have been achieved in primate liver-transplant recipients. The recent production of alpha1,3-galactosyl transferase knockout (GalT-KO) miniature swine has made it possible to evaluate xenotransplantation of pig organs in clinically relevant pig-to-non-human primate models in the absence of the effects of natural anti-Gal antibodies. We are reporting our results using GalT-KO liver grafts. Methods We performed GalT-KO liver transplants in baboons using an immunosuppressive regimen previously used by our group in xeno heart and kidney transplantation. Post-operative liver function was assessed by laboratory function tests, coagulation parameters and histology. Results In two hepatectomized recipients of GalT-KO grafts, post-transplant liver function returned rapidly to normal. Over the first few days, the synthetic products of the donor swine graft appeared to replace those of the baboon. The first recipient survived for 6 days and showed no histopathological evidence of rejection at the time of death from uncontrolled bleeding, probably caused by transfusion-refractory thrombocytopenia. Amicar treatment of the second and third recipients led to maintenance of platelet counts of over 40 000 per μl throughout their 9- and 8-day survivals, which represents the longest reported survival of pig-to-primate liver transplants to date. Both of the last two animals nevertheless succumbed to bleeding and enterococcal infection, without evidence of rejection. Conclusions These observations suggest that thrombocytopenia after liver xenotransplantation may be overcome by Amicar therapy. The coagulopathy and sepsis that nevertheless occurred suggest that additional causes of coagulation disturbance must be addressed, along with better prevention of infection, to achieve long-term survival.

Background The shortage in donor livers has led to increased use of allografts derived from donation after cardiac death (DCD). The compromised viability in these livers leads to inferior post-transplantation allograft function and survival compared with donation after brain death (DBD) donor grafts. In this study, we reconditioned DCD livers using an optimized normothermic machine perfusion system. Methods Livers from 12 Yorkshire pigs (20–30 kg) were subjected to either 0 min (WI-0 group, n = 6) or 60 min (WI-60 group, n = 6) of warm ischemia and 2 h of cold storage in UW solution, followed by 4 h of oxygenated sanguineous normothermic machine perfusion. Liver viability and metabolic function were analyzed hourly. Results Warm ischemic livers showed elevated transaminase levels and reduced ATP concentration. After the start of machine perfusion, transaminase levels stabilized and there was recovery of tissue ATP, coinciding with an increase in bile production. These parameters reached comparable levels to the control group after 1 h of machine perfusion. Histology and gross morphology confirmed recovery of the ischemic allografts. Conclusion Our data demonstrate that metabolic and functional parameters of livers with extended warm ischemic time (60 min) can be significantly improved using normothermic machine perfusion. We hereby compound the existing body of evidence that machine perfusion is a viable solution for reconditioning marginal organs.

PURPOSE: 1) To pilot a health disparities curriculum for incoming first year medical students and evaluate changes in knowledge. 2) To help students become aware of personal biases regarding racial and ethnic minorities. 3) To inspire students to commit to serving indigent populations.METHODS: First year students participated in a 5-day elective course held before orientation week. The course used the curricular goals that had been developed by the Society of General Internal Medicine Health Disparities Task Force. Thirty-two faculty members from multiple institutions and different disciplinary backgrounds taught the course. Teaching modalities included didactic lectures, small group discussions, off-site expeditions to local free clinics, community hospitals and clinics, and student-led poster session workshops. The course was evaluated by pre-post surveys.RESULTS: Sixty-four students (60% of matriculating class) participated. Survey response rates were 97-100%. Students' factual knowledge (76 to 89%, p<.0009) about health disparities and abilities to address disparities issues improved after the course. This curriculum received the highest rating of any course at the medical school (overall mean 4.9, 1 = poor, 5 = excellent).CONCLUSIONS: This innovative course provided students an opportunity for learning and exploration of a comprehensive curriculum on health disparities at a critical formative time.

Background. Structural valve degeneration (SVD) is a major flaw of bioprostheses. An apparent increase in the SVD rate has been observed among patients who received the Trifecta bioprosthesis (Abbott Vascular, Santa Clara, CA).Methods. This study retrospectively reviewed 1058 consecutive patients who underwent aortic valve placement with a stented bioprosthesis between January 2011 and December 2015. Patients were grouped into a Trifecta group (508 [48.0%] patients with Trifecta bioprostheses) and a non-Trifecta group (550 [52.0%] patients with other bioprostheses).Results. Patients in the Trifecta group were older (69.7 years vs 64.6 years; P [ .001), were more likely female (40.4% vs 28.0%; P [ .001), more often had aortic stenosis (85.1% vs 77.1%; P [ .001), and received smaller valves (23.0 mm vs 25.0 mm; P < .001) than patients in the non-Trifecta group. SVD occurred in 28 patients (Trifecta, n [ 22; n [ 6) within 7 years. Aortic regurgitation or mixed stenosis/

The identity of Na+/H+ exchanger (NHE) isoforms in the human small intestine and colon and their role in vectorial Na+ absorption are not known. The present studies were undertaken to examine the regional and vertical axis distribution of NHE-1, NHE-2, and NHE-3 mRNA in the human intestine. Ribonuclease protection assays were used to quantitate the levels of mRNA of these isoforms in various regions of the human intestine. In situ hybridization technique was used to localize NHE-2 and NHE-3 mRNA in the colon. The NHE-1 isoform message was present uniformly throughout the length of the human intestine. In contrast, mRNA levels for human NHE-2 and NHE-3 isoforms demonstrated significant regional differences. The NHE-3 abundance was found in decreasing order: ileum > jejunum > proximal colon = distal colon. The NHE-2 message level in the distal colon was significantly higher than in the proximal colon but was evenly distributed in the small intestine. In addition, NHE-2 mRNA was present in surface epithelial cells as well as in cells of the crypt region, suggesting the presence of NHE-2 message throughout the vertical axis of the colonic crypts. In contrast, NHE-3 mRNA was localized to surface colonocytes in the proximal colon. On the basis of this tissue-specific localization of NHE-2 and NHE-3 mRNA, it can be speculated that the relative contribution of NHE-2 and NHE-3 isoforms in Na+ absorption in the human intestine may be region specific, and these putative apical isoforms may be differentially regulated.

American ginseng is a commonly used herbal medicine in the United States. When ginseng is taken orally, its active components, ginsenosides, are reportedly biotransformed by intestinal microbiota. Previous pharmacokinetic evaluations of ginseng in humans have focused on its parent constituents. However, the metabolites, especially those transformed by intestinal microbiota, have not been carefully studied. We used an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) method to determine 15 ginsenosides and/or metabolites and their bioavailability in humans. Six healthy human subjects received a single oral dose of 10 g of American ginseng root powder, after which samples of their blood were collected at 0, 2, 4, 7, 9 and 12 h for measurement of ginsenoside/metabolite levels in plasma. Ginsenosides Rb1, Rd, Rg2 and compound K (C-K) were detected in human plasma samples at different time points. The Rb1 concentration peak was 19.90 ± 5.43 ng/ml at 4 h. C-K was detected from 7 h to 12 h with 7.32 ± 1.35 ng/ml at 12 h. Since the last time point was at 12 h, C-K peak level was not observed. The areas under the concentration curves (AUC) from 0 to 12 h were 155.0 ± 19.5 ng•h/ml for Rb1 and 26.4 ± 6.4 ng•h/ml for C-K, respectively. The gradual decrease of Rb1 levels and the delayed increase in levels of C-K observed in human subjects supported previous reports that enteric microbiota played a key role in transforming Rb1 to C-K.

Purpose There is little evidence regarding which factors and strategies are associated with high proportions of underrepresented minority (URM) faculty in academic medicine. The authors conducted a national study of U.S. academic medicine departments to better understand the challenges, successful strategies, and predictive factors for enhancing racial and ethnic diversity among faculty (i.e., physicians with an academic position or rank). Method This was a mixed-methods study using quantitative and qualitative methods. The authors conducted a cross-sectional study of eligible departments of medicine in 125 accredited U.S. medical schools, dichotomized into low-URM (bottom 50%) versus high-URM rank (top 50%). They used t tests and chi-squared tests to compare departments by geographic region, academic school rank, city type, and composite measures of “diversity best practices.” The authors also conducted semistructured in-depth interviews with a subsample from the highest-and lowest-quartile medical schools in terms of URM rank. Results Eighty-two medical schools responded (66%). Geographic region and academic rank were statistically associated with URM rank, but not city type or composite measures of diversity best practices. Key themes emerged from interviews regarding successful strategies for URM faculty recruitment and retention including institutional leadership, the use of human capital and social relationships and strategic deployment of institutional resources. Conclusions Departments of medicine with high proportions of URM faculty employ a number of successful strategies and programs for recruitment and retention. More research is warranted to identify new successful strategies and to determine the impact of specific strategies on establishing and maintaining workforce diversity.

Our data indicate that massive hemorrhage in the setting of liver xenotransplantation might be avoided by supplementation with primate clotting components. However, coagulation competent hepatic xenograft recipients may be predisposed to graft loss related to small vessel thrombosis and ischemic necrosis.