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Desai CS, Gruessner AC, Khan KM, Fishbein TM, Jie T, Rodriguez Rilo HL, Gruessner RWG. Isolated intestinal transplants vs. liver-intestinal transplants in adult patients in the United States: 22 yr of OPTN data. Abstract: We examined the outcomes of adult intestinal transplants (ITx); isolated ITx vs. liver-intestinal transplants (L-ITx) were compared using the UNOS database (1987-2009). Of 759 ITx transplants in 687 patients, 463 (61%) were isolated and 296 (39%) were L-ITx. Patient survival for primary isolated ITx at one, three, and five yr was 84%, 66.7%, and 54.2%; and primary L-ITx was, 67%, 53.3%, and 46% (p = 0.0005). Primary isolated ITx graft survival at one, three, and five yr was 80.7%, 57.6%, 42.8%; primary L-ITx was 64.1%, 51%, 44.1% (p = 0.0003 at one, three yr, Wilcoxon test). For retransplants (n = 72), patient and graft survival for isolated ITx (n = 41) at five yr was 40% in era 1 (1987-2000) and 16% in era 2 (p = 0.47); for retransplanted L-ITx (n = 31), it improved from 14% to 64% in era 2 (p = 0.01). Cox regression: creatinine >1.3 mg/dL and pre-transplant hospitalization were negative predictors for outcome of both; bilirubin >1.3 mg/dL was a negative predictor for isolated ITx and donor age >40 yr for L-ITx. Isolated ITx should be considered prior to liver disease for adults with intestinal failure; L-ITx is preferable for retransplantation. [ABSTRACT FROM AUTHOR]

Standard therapy for advanced ovarian cancer (OC) consists of radical debulking cytoreductive surgery followed by adjuvant chemotherapy. An important risk factor for OC is genetic predisposition, with BRCA1 or BRCA2 mutations accounting for the majority of hereditary OC. Mutation in BRCA ultimately causes accumulation of genetic alterations because of the failure of cells to arrest and repair DNA damage or to undergo apoptosis, resulting in tumorigenesis. Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as a promising approach for managing BRCA-associated cancers, especially high-grade OC and breast cancers. They lead to synthetic lethality in BRCA-mutated cells by stalling the replication forks in homologous recombination-deficient (HR) cells. Four PARP inhibitors (olaparib, niraparib, rucaparib, and talazoparib) are currently approved by the Food and Drug Administration for OC, breast, and pancreatic cancer indications and are being evaluated for other BRCA-associated cancers. Despite their clinical efficacy, cancer cells generally develop resistance to them through several mechanisms. Understanding these mechanisms is crucial for developing strategies to counter resistance and identify the basic mechanisms of DNA damage response. This review focuses on the mechanism of action of PARP inhibitors, understanding various causes of resistance, and building strategies to overcome PARP inhibitor resistance., Competing Interests: None

Background: We sought to evaluate potential disparities in kidney transplant rates in a single state in the United States. We studied the potential to mitigate disparities with a specialized clinic using it as a model presentation., Methods: Based on data from the United States Renal Data System and Organ Procurement and Transplantation Network, we estimated the yearly end-stage renal disease and waitlist addition, stratified by race/ethnicity from 2000 to 2018. Institution rates were analyzed similarly, and the implementation of a focused Latino clinic was evaluated., Results: The number of patients added to the national transplant waitlist has increased by 40% in non-Latino whites and by 160% in Latinos from 2000 to 2017. Comparing the period from 2000 to 2004 to 2015 to 2018 in North Carolina, the waitlist increased for Latino patients by 482% and non-Latino whites by 23%. One year after a designated Latino transplant clinic at our institution, there was a 125% increase in the number of Latino referrals for kidney transplant evaluation, a 142% increase in the number of waitlisted Latino patients, and an increase in kidney transplants of 145%., Conclusion: With the increasing number of patients in the Latino community who are diagnosed with end-stage renal disease, there is a direct benefit for a culturally competent program that addresses access to transplants., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Marijuana is legalized for either medical or recreational use in over half of the states in the United States and in Canada, but many transplant centers will not list patients who are using marijuana. However, the effect of marijuana on transplant outcomes remains unclear. Thus, we performed a retrospective analysis of all adult (≥18 years old) liver transplant patients treated at our center between 2007 and 2017. Patients were grouped according to their marijuana use and tobacco smoking status. We also evaluated tobacco smoking status for the comparative evaluation. Posttransplant morbidity, mortality, and graft survival were evaluated. In total, 316 patients were included: 171 (54%) patients were tobacco smokers (70 current; 101 former), 81 (26%) patients were marijuana smokers (13 current; 68 former), and 64 (20#x0025;) patients were both marijuana and tobacco smokers. A total of 136 (43%) reported never smoking marijuana or tobacco. After adjustment, current tobacco users were over 3 times as likely to die within 5 years compared with never users (hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.63-6.46; P < 0.001), but no difference was seen between current/former and never marijuana users (HR, 0.52; 95% CI, 0.26-1.04; P = 0.06). No significant differences in inpatient respiratory complications, reintubation, or >24-hour intubation was seen. Overall, pretransplant marijuana use, past or current, does not appear to impact liver transplant outcomes, though tobacco smoking remains detrimental., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Defining clinically relevant biomarkers for early stage hepatocellular carcinoma (HCC) in a high-risk population of cirrhotic patients has potentially far-reaching implications for disease management and patient health. Changes in glycan levels have been associated with the onset of numerous diseases including cancer. In the present study, we used liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS) to analyze N-glycans in sera from 183 participants recruited in Egypt and the U.S. and identified candidate biomarkers that distinguish HCC cases from cirrhotic controls. N-Glycans were released from serum proteins and permethylated prior to the LC-ESI-MS analysis. Through two complementary LC-ESI-MS quantitation approaches, global profiling and targeted quantitation, we identified 11 N-glycans with statistically significant differences between HCC cases and cirrhotic controls. These glycans can further be categorized into four structurally related clusters, matching closely with the implications of important glycosyltransferases in cancer progression and metastasis. The results of this study illustrate the power of the integrative approach combining complementary LC-ESI-MS based quantitation approaches to investigate changes in N-glycan levels between HCC cases and patients with liver cirrhosis.

The production, sale, and consumption of multiple vitamins is a multibillion-dollar industry. Most Americans take some form of supplement ostensibly for prevention of cardiovascular disease. It has been claimed that vitamin A retards atherogenesis. Vitamin C is an antioxidant and is thought to possibly decrease free radical-induced endothelial injury, which can lead to atherosclerotic plaque formation. Vitamin E has been extensively studied for its possible effects on platelet function as well as inhibition of foam-cell formation. Low levels of vitamin D have been thought to negatively impact myocardial structure and increase the risk for cardiovascular events. Increased intake of vitamin B6, B12, and folate has been associated with reduction of homocysteine levels; elevated homocysteine blood levels have been associated with the occurrence of stroke, heart attack, and cardiovascular death. The purpose of this study was to review the currently available literature for vitamin supplementation with respect to prevention of cardiovascular disease. Unfortunately, the current evidence suggests no benefit exists with vitamin supplementation in the general US population. Further research is needed to evaluate whether there are specific populations that might benefit from vitamin supplementation., (© 2014 Wiley Periodicals, Inc.)

Background: We evaluated the outcomes of intestinal retransplantation in children and adults in the United States., Methods: The United Network for Organ Sharing data were analyzed from October 1987 to August 2009., Results: In adult isolated intestinal transplant (ITx) retransplants (n=41), patient survival was 80.1%, 47.4%, and 28.5% at 1, 3, and 5 years, which was worse than primary isolated ITx (P=0.005). For liver ITx (L-ITx) retransplants (n=31), patient survival was 63.1%, 56.1%, and 46.8% and was not significantly different than primary L-ITx. In pediatric isolated ITx retransplants (n=28), patient survival at 1, 3, and 5 years was 80.7%, 74%, and 57.5%; graft survival was 76.4%, 56.6%, and 44%. In L-ITx retransplants (n=49), patient survival was 42%, 42%, and 42%; graft survival was 39%, 39%, and 39%. Patient and graft survival in adult L-ITx retransplants were better in era 2 (January 2001-August 2009) than era 1 (October 1987-December 2000) (P=0.01). Among pediatric L-ITx retransplants, outcomes were worst in children younger than 2 years (n=12). In regression analysis, prior hospitalization was a negative predictor for all the groups of patients (relative risk, 5.4)., Conclusion: Patient and graft survival in adult isolated ITx are less favorable after a retransplant compared with a primary transplant. Patient and graft survival are also poor in pediatric L-ITx after a retransplant, especially for children younger than 2 years of age. L-ITx retransplant results improved significantly in era 2 in adult recipients.