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Background Organ transplant is the preferred treatment for end-stage organ disease, yet the majority of patients with end-stage organ disease are never placed on the transplant waiting list. Limited access to the transplant waiting list combined with the scarcity of the organ pool result in over 100,000 deaths annually in the United States. Patients face unique barriers to referral and acceptance for organ transplant based on social determinants of health, and patients from disenfranchised groups suffer from disproportionately lower rates of transplantation. Our objective was to review the literature describing disparities in access to organ transplantation based on social determinants of health to integrate the existing knowledge and guide future research. Methods We conducted a scoping review of the literature reporting disparities in access to heart, lung, liver, pancreas and kidney transplantation based on social determinants of health (race, income, education, geography, insurance status, health literacy and engagement). Included studies were categorized based on steps along the transplant care continuum: referral for transplant, transplant evaluation and selection, living donor identification/evaluation, and waitlist outcomes. Results Our search generated 16,643 studies, of which 227 were included in our final review. Of these, 34 focused on disparities in referral for transplantation among patients with chronic organ disease, 82 on transplant selection processes, 50 on living donors, and 61 on waitlist management. In total, 15 studies involved the thoracic organs (heart, lung), 209 involved the abdominal organs (kidney, liver, pancreas), and three involved multiple organs. Racial and ethnic minorities, women, and patients in lower socioeconomic status groups were less likely to be referred, evaluated, and added to the waiting list for organ transplant. The quality of the data describing these disparities across the transplant literature was variable and overwhelmingly focused on kidney transplant. Conclusions This review contextualizes the quality of the data, identifies seminal work by organ, and reports gaps in the literature where future research on disparities in organ transplantation should focus. Future work should investigate the association of social determinants of health with access to the organ transplant waiting list, with a focus on prospective analyses that assess interventions to improve health equity.

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score &gt, 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0&ndash, 10%, 11&ndash, 20%, &gt, 20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0&ndash, 10% GS (58.0%), 11&ndash, 20% GS (13.5%), &gt, 20% GS (19.7%), 8.8% were not biopsied. The rate of kidney discard was 48.5%, 33.6% in 0&ndash, 10% GS, 68.9% in 11&ndash, 20% GS, and 77.4% in &gt, 20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0&ndash, 10% GS, 70.9% for &gt, 10% GS, and 74.8% for the no biopsy group. Among kidneys with &gt, 10% GS, there was no significant difference in death-censored graft survival between 11&ndash, 20% GS and &gt, 20% GS. Recipients with &gt, 10% GS had an increased risk of graft failure (HR = 1.27, p &lt, 0.001), compared with 0&ndash, 10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and &gt, 10% GS. Conclusion: In &gt, 85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS &gt, 10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

Background The goal of this study was to assess systems and processes involved in the operating room (OR) to intensive care unit (ICU) handoff in an attempt to understand the criticality of specific steps of the handoff. Methods We performed a failure modes, effects, and criticality analysis (FMECA) of the OR to ICU handoff of deceased donor liver transplant recipients using in-person observations and descriptions of the handoff process from a multidisciplinary group of clinicians. For each step in the process, failures were identified along with frequency of occurrence, causes, potential effects and safeguards. A Risk Priority Number (RPN) was calculated for each failure (frequency × potential effect × safeguard; range 1-least risk to 1,000-most risk). Results Using FMECA, we identified 37 individual steps in the OR to ICU handoff process. In total, 81 process failures were identified, 22 of which were determined to be critical and 36 of which relied on weak safeguards such as informal human verification. Process failures with the greatest risk of harm were lack of preliminary OR to ICU communication (RPN 504), team member absence during handoff communication (RPN 480), and transport equipment malfunction (Risk Priority Number 448). Conclusion Based on the analysis, recommendations were made to reduce potential for patient harm during OR to ICU handoffs. These included automated transfer of OR data to ICU clinicians, enhanced ICU team member notification processes and revision of the postoperative order sets. The FMECA revealed steps in the OR to ICU handoff that are high risk for patient harm and are currently being targeted for process improvement.

Laparoscopic approaches to complex hepatobiliary cases are becoming more commonplace. As the practice of living donor liver transplants (LDLT) has evolved into an accepted alternative for certain patients as a source of donor organs, the application of laparoscopic techniques to these operations has also been introduced with an interest in improving donor outcomes and potential appeal of the donor procedure. The scope of laparoscopy ranges from the laparoscopically assisted left or right hepatic lobectomy (“hybrid”) approach, to pure laparoscopic left lateral segments. Recently, robotic and purely laparoscopic approaches to right and left lobes have been reported by advanced minimally invasive surgeons with extensive experience in robotic and laparoscopic liver resection. Safety remains paramount to the performance of LDLT, and laparoscopic techniques must always be considered in light of optimal donor safety.

Inflammatory bowel diseases such as ulcerative colitis represent serious health burdens, both because of the tissue-damaging disease itself, and because of an elevated risk of colon cancer. The increased expression of many members of the matrix metalloproteinase (MMP) family of enzymes that occurs in colitis, has long been associated with the destructive nature of the disease. Recent findings in cancer and other MMP-associated diseases, however, led us to question whether MMPs are indeed detrimental in the setting of colitis. Here, we focus on a single MMP family member, MMP10, and assess its role in a murine model of colonic tissue damage induced by dextran sulphate sodium (DSS) treatment. Using mice genetically deficient for MMP10, we find that absence of this enzyme leads to significantly worse disease scores and failure to resolve inflammation even after extended recovery periods. We show that MMP10 is produced predominantly by infiltrating myeloid cells in both murine and human colitis. Through bone marrow transplant experiments, we confirm that bone marrow-derived MMP10 contributes to colitis severity. Mice lacking MMP10 have a significantly higher propensity for development of dysplastic lesions in the colon after two rounds of DSS exposure. Thus, we conclude that MMP10 is required for resolution of DSS-induced colonic damage, and in its absence, chronic inflammation and ultimately dysplasia occurs.

This meta-analysis was conducted with the aims to summarize all available evidence on (1) prevalence of pre-existing atrial fibrillation (AF) and/or incidence of AF following kidney transplantation; (2) the outcomes of kidney transplant recipients with AF; and (3) the trends of estimated incidence of AF following kidney transplantation over time. A literature search was conducted utilizing MEDLINE, EMBASE, and the Cochrane Database from inception through March 2018. We included studies that reported (1) prevalence of pre-existing AF or incidence of AF following kidney transplantation or (2) outcomes of kidney transplant recipients with AF. Effect estimates from the individual study were extracted and combined utilizing random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018086192). Eight cohort studies with 137,709 kidney transplant recipients were enrolled. Overall, the pooled estimated prevalence of pre-existing AF in patients undergoing kidney transplantation was 7.0% (95% CI: 5.6–8.8%) and pooled estimated incidence of AF following kidney transplantation was 4.9% (95% CI: 1.7–13.0%). Meta-regression analyses were performed and showed no significant correlations between year of study and either prevalence of pre-existing AF (p = 0.93) or post-operative AF after kidney transplantation (p = 0.16). The pooled odds ratios (OR) of mortality among kidney transplant recipients with AF was 1.86 (3 studies; 95% CI: 1.03–3.35). In addition, AF is also associated with death-censored allograft loss (2 studies; OR: 1.55, 95% CI: 1.02–2.35) and stroke (3 studies; OR: 2.54, 95% CI: 1.11–5.78) among kidney transplant recipients. Despite advances in medicine, incidence of AF following kidney transplant does not seem to decrease over time. In addition, there is a significant association of AF with increased mortality, allograft loss, and stroke after kidney transplantation.

Inflammatory mediators are of considerable interest as potential therapeutic targets in various cancers. Here we investigate whether interleukin (IL)-4 receptor alpha (IL4Ralpha), a component of the receptor complex for the T helper 2 cytokines IL4 and IL13, plays a role in colonic tumorigenesis. IL4Ralpha protein expression was seen in tumor cells of 28/48 human colon adenocarcinomas on a tissue microarray. In human and murine colon tumor cell lines analyzed in vitro, all of which expressed IL4Ralpha, treatment with exogenous ligand resulted in dose-dependent increases in proliferation. IL4 decreased apoptosis only in HCT116 cells. An orthotopic allograft model was used to determine in vivo effects of tumor cell-specific IL4Ra ablation. MC38 murine tumor cells with the IL4Ra gene knocked down showed reduced proliferation but no difference in apoptosis compared with controls after implantation in ceca of syngeneic mice. Mice null for IL4Ra and wild-type controls were treated with azoxymethane and dextran sulfate sodium to induce tumor formation. Mice with global deletion of IL4Ra had significantly fewer and smaller tumors. Reduced tumorigenicity correlated with decreased proliferation and increased apoptosis. Systemic blockade of IL4Ralpha-IL4 interactions with a chimeric soluble receptor protein gave similar results in the cecal implant model. Thus, IL4Ralpha, a component of the IL4R and IL13R, contributes to tumor formation in a mouse model of colitis-associated cancer. Proliferation appears to be directly mediated via IL4Ralpha on the epithelial tumor cells. Survival may be an indirect response mediated via other host cells. Our results support therapeutic targeting of IL4Ralpha in colon cancer.

Background/aim: The anterior and posterior vagal trunks supply the each side of the gastric mucosa separately, and the denervation of either side does not impair the functional capacity of the other, leaving gastric acid output and circulating gastrin levels unchanged. In this study, we investigated the importance of the neural innervation and the brain-gut axis in cancer initiation by performing vagotomy in hypergastrinemic transgenic (INS-GAS) mice with a phenotype of spontaneous gastric cancer. Methods: Age/sex matched wild-type (WT) and INS-GAS mice were killed at 1, 2, 4, 6, 8, 10 and 12 months of age (at least 10 mice/ group) for histological examination of gastric cancer. INS-GAS mice at 6 months of age were randomized into 4 groups of surgery: unilateral anterior truncal vagotomy (29 mice), bilateral truncal vagotomy with pyloroplasty (24), pyloroplasty (27), and sham operation (25). Both the anterior and posterior sides of the stomachs were removed at 6 months postoperatively (i.e., 12 months of age) for pathological and immunohistochemical analyses. Results: Gastric cancer was found neither in WT mice regardless of age nor in INS-GAS mice that were

Ulcerative colitis is the most common inflammatory bowel disease, and is associated with increased risk of colon cancer. Understanding the mechanisms by which carcinogenesis occurs in the setting of colitis could lead to both prevention strategies and improved therapies. Matrix metalloproteinase-10 (MMP10), a member of the matrix metalloproteinase family of proteolytic enzymes, is expressed at healing edges of colonic ulcers. Although MMPs are usually considered as destructive players in inflammatory disease, we considered the possibility that MMP10 had a beneficial role in ulcerative colitis. We used dextran sulfate sodium (DSS) treatment in MMP10-null and corresponding control wild-type mice to investigate the consequences of MMP10 deletion on colitis development and recovery. Groups of mice were exposed to DSS for 7-day periods and sacrificed at different timepoints following the cessation of the DSS. Strikingly, MMP10-null mice were more severely affected by the treatment as determined by gross observations such as weight loss and colon length. Histological analysis at the various timepoints indicated that wild-type mice showed almost complete recovery from DSS within 14 days after DSS treatment. In contrast, MMP10-null mice still showed clear signs of damage with persistent inflammatory foci and non-healing ulcers. In situ hybridization indicated MMP10 expression predominantly in inflammatory cells, although some fibroblasts were also positive. Colonic epithelium was negative for MMP10. Bone marrow transplant experiments indicated that wild-type bone marrow partially rescued the MMP10-null phenotype. Measurement of cytokines by ELISA in colonic lavage fluid from MMP10-null and wild-type mice showed that IL-1α was significantly increased in the absence of MMP10. Levels of other cytokines such as TNFα, IL6, IL17 and G-CSF were not different. Multiple exposures to DSS results in conversion of an acute colitis to a chronic inflammatory disease. With only 2 DSS exposures, MMP10-null mice manifested a chronic condition which failed to resolve even after 3 months. Similarly-treated wild-type mice, however, appeared normal at this timepoint. Examination of the colonic tissue from the DSS double exposure showed a significant increase in the number of dysplastic foci present in the MMP10-null mice. Thus, expression of MMP10 appears necessary for resolution of colitis, and in its absence, the development of chronic colitis results in tumor development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1351.