The PVR-TIPS may be considered for patients with obliterative PVT who are otherwise appropriate candidates for LT. The high rate of MPV patency post-TIPS placement suggests flow reestablishment as the dominant mechanism of thrombus resolution.

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.

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.

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 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 x Potential effect x Safeguard; range 1-least risk to 1000-most risk). Results The FMECA 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 highest 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 (RPN 448). Conclusions 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.