Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization

There is an urgent need for therapeutic interventions for desensitization and antibody-mediated rejection (AMR) in sensitized patients with preformed or de novo donor-specific HLA antibodies (DSA). The risk of AMR and allograft loss in sensitized patients is increased due to preformed DSA detected at time of transplant or the reactivation of HLA memory after transplantation, causing acute and chronic AMR. Alternatively, de novo DSA that develops post-transplant due to inadequate immunosuppression and again may lead to acute and chronic AMR or even allograft loss. Circulating antibody, the final product of the humoral immune response, has been the primary target of desensitization and AMR treatment. However, in many cases these protocols fail to achieve efficient removal of all DSA and long-term outcomes of patients with persistent DSA are far worse when compared to non-sensitized patients. We believe that targeting multiple components of humoral immunity will lead to improved outcomes for such patients. In this review, we will briefly discuss conventional desensitization methods targeting antibody or B cell removal and then present a mechanistically designed desensitization regimen targeting plasma cells and the humoral response

Psychosocial Assessment of Candidates for Transplantation (PACT) Score Identifies High Risk Patients in Pediatric Renal Transplantation

Background: Currently, there is no standardized approach for determining psychosocial readiness in pediatric transplantation. We examined the utility of the Psychosocial Assessment of Candidates for Transplantation (PACT) to identify pediatric kidney transplant recipients at risk for adverse clinical outcomes.Methods: Kidney transplant patients <21-years-old transplanted at Duke University Medical Center between 2005 and 2015 underwent psychosocial assessment by a social worker with either PACT or unstructured interview, which were used to determine transplant candidacy. PACT assessed candidates on a scale of 0 (poor candidate) to 4 (excellent candidate) in areas of social support, psychological health, lifestyle factors, and understanding. Demographics and clinical outcomes were analyzed by presence or absence of PACT and further characterized by high (≥3) and low (≤2) scores.Results: Of 54 pediatric patients, 25 (46.3%) patients underwent pre-transplant evaluation utilizing PACT, while 29 (53.7%) were not evaluated with PACT. Patients assessed with PACT had a significantly lower percentage of acute rejection (16.0 vs. 55.2%, p = 0.007). After adjusting for HLA mismatch, a pre-transplant PACT score was persistently associated with lower odds of acute rejection (Odds Ratio 0.119, 95% Confidence Interval 0.027–0.52, p = 0.005). In PACT subsection analysis, the lack of family availability (OR 0.08, 95% CI 0.01–0.97, p = 0.047) and risk for psychopathology (OR 0.34, 95% CI 0.13–0.87, p = 0.025) were associated with a low PACT score and post-transplant non-adherence.Conclusions: Our study highlights the importance of standardized psychosocial assessments and the potential use of PACT in risk stratifying pre-transplant candidates

Kidney Donor Profile Index Is a Reliable Alternative to Liver Donor Risk Index in Quantifying Graft Quality in Liver Transplantation.

Background:The most established metric for estimating graft survival from donor characteristics in liver transplantation is the liver donor risk index (LDRI). The LDRI is calculated from donor and transplant-related variables, including cold ischemic time. Because cold ischemic time is unknown at the time of organ offer, LDRI is not available for organ acceptance decisions. In contrast, the kidney donor profile index (KDPI) is derived purely from donor variables known at the time of offer and thus calculated for every deceased donor in the United States. The similarity in donor factors included in LDRI and KDPI led us to hypothesize that KDPI would reliably approximate LDRI in estimating graft survival in liver transplantation. Methods:The United Network of Organ Sharing registry was queried for adults who underwent deceased donor liver transplantation from 2002 to 2016. The cohort was divided into quintiles of KDPI and LDRI, and graft survival was calculated according to Kaplan Meier. Hazard ratios for LDRI and KDPI were estimated from Cox proportional hazards models, and Uno's concordance statistic was compared. Results:In our analysis of 63 906 cases, KDPI closely approximated LDRI in estimating liver graft survival, with an equivalent concordance statistic of 0.56. Conclusions:We conclude that KDPI can serve as a reasonable alternative to LDRI in liver acceptance decisions

Review article: the pathogenesis of diverticular disease - current perspectives on motility and neurotransmitters

International audienceBackground: Low fibre diet, structural abnormalities and ageing are traditional aetiological factors implicated in the development of Diverticular Disease (DD). More recently, motility disorders are implicated in its causation leading to speculation that neurotransmitters play a role in mediating these disturbances. Aims: To draw together studies on the role of neurotransmitters in the development of DD and its symptoms. Methods: Medline, GoogleScholar and Pubmed were searched for evidence on this subject using the terms neurotransmitters, motility, Diverticular Disease and pathogenesis. Articles relevant to the subject were cited and linked references also reviewed. Results: Serotonin which has been found to be an excitatory colonic neurotransmitter has been found in early studies to be increased in colonic enterochromaffin cells. Acetylcholine which is thought to be an excitatory neurotransmitter and cholinergic activity has also seen to be increased in DD. These findings may suggest that an increase in excitatory neurotransmitters may result in the hypersegmentation thought to cause pulsion diverticula. Similarly, a decrease of Nitric Oxide which is inhibitory is found Conclusions: There is some evidence that neurotransmitters may play a role in the motility disturbances seen in DD however a clear role is yet to be ascertained