Preemptive simultaneous pancreas kidney transplantation has survival benefit to patients.

Several organ allocation protocols give priority to wait-listed simultaneous kidney-pancreas (SPK) transplant recipients to mitigate the higher cardiovascular risk of patients with diabetes mellitus on dialysis. The available information regarding the impact of preemptive simultaneous kidney-pancreas transplantation on recipient and graft outcomes is nonetheless controversial. To help resolve this, we explored the influence of preemptive simultaneous kidney-pancreas transplants on patient and graft survival through a retrospective analysis of the OPTN/UNOS database, encompassing 9690 simultaneous transplant recipients between 2000 and 2017. Statistical analysis was performed applying a propensity score analysis to minimize bias. Of these patients, 1796 (19%) were transplanted preemptively. At ten years, recipient survival was significantly superior in the preemptive group when compared to the non-preemptive group (78.9% vs 71.8%). Dialysis at simultaneous kidney-pancreas transplantation was an independent significant risk for patient survival (hazard ratio 1.66 [95% confidence interval 1.32-2.09]), especially if the dialysis duration was 12 months or longer. Preemptive transplantation was also associated with significant superior kidney graft survival compared to those on dialysis (death-censored: 84.3% vs 75.4%, respectively; estimated half-life of 38.57 [38.33 -38.81] vs 22.35 [22.17 - 22.53] years, respectively). No differences were observed between both groups neither for pancreas graft survival nor for post-transplant surgical complications. Thus, our results sustain the relevance of early referral for pancreas transplantation and the importance of pancreas allocation priority in reducing patient mortality after simultaneous kidney-pancreas transplantation.

Improving safety in organ recovery transportation: Report from the ASTS/UNOS/AST/AOPO transportation safety summit.

Despite the passage of a decade since the tragic loss of an organ recovery team from the University of Michigan, there are currently no national standards governing air and ground transportation of organ recovery personnel. Consequently, the American Society of Transplant Surgeons, the Association of Organ Procurement Organizations, and the United Network for Organ Sharing jointly convened a transportation summit to review and update recommendations for national transportation standards. Expanded air transport quality assurance protocols, including a requirement for two engine turbine-powered aircraft piloted by two qualified pilots certified through onsite inspections was recommended. Ground transportation providers must ensure adequate safety restraints are available, ambulance avoided if possible, and the use of lights and sirens minimized. Finally, adequate insurance coverage for all team members, including trainees should be provided and should not rely on carrier liability insurance policies. The summit participants have committed the support of their organizations to promote and enact these regulations nationally.

Radiation dose to staff from scatter radiation in the post-anaesthetic recovery ward.

INTRODUCTION: Though recovery is a significant aspect of the post-surgical orthopaedic patient pathway, radiation dose from medical imaging to staff within the post-anaesthetic recovery unit, is not extensively researched. This study aimed to quantify the distribution of scatter radiation for common post-surgical orthopaedic examinations. METHODS: A Raysafe Xi survey meter was used to record scattered dose at various locations around an anthropomorphic phantom, with positions simulating the potential positions of nearby staff and patients. X-ray projections of the AP Pelvis, Lateral Hip, AP and lateral knee were simulated using a portable x-ray machine. Readings were tabulated and diagrams drawn representing the distribution of scatter measurements from each of the four procedures. RESULTS: Magnitude of dose was dependent on imaging parameters (ie. kVp and mAs), the area of body exposed (ie. hip or knee), and the type of projection (ie. AP or lateral). Knee exposures proved much lower than hip exposures at any distance from the radiation source. CONCLUSION: Maintaining a two-metre distance from the x-ray source was justified most profoundly by the hip exposures. Staff should have confidence that occupational limits will not be reached with adherence to the practices suggested. This study provides comprehensive diagrams and dose measurements with the aim of educating staff working around radiation.

Hierarchical steepness, counter-aggression, and macaque social style scale.

Nonhuman primates show remarkable variation in several aspects of social structure. One way to characterize this variation in the genus Macaca is through the concept of social style, which is based on the observation that several social traits appear to covary with one another in a linear or at least continuous manner. In practice, macaques are more simply characterized as fitting a four-grade scale in which species range from extremely despotic (grade 1) to extremely tolerant (grade 4). Here, we examine the fit of three core measures of social style-two measures of dominance gradients (hierarchical steepness) and another closely related measure (counter-aggression)-to this scale, controlling for phylogenetic relationships. Although raw scores for both steepness and counter-aggression correlated with social scale in predicted directions, the distributions appeared to vary by measure. Counter-aggression appeared to vary dichotomously with scale, with grade 4 species being distinct from all other grades. Steepness measures appeared more continuous. Species in grades 1 and 4 were distinct from one another on all measures, but those in the intermediate grades varied inconsistently. This confirms previous indications that covariation is more readily observable when comparing species at the extreme ends of the scale than those in intermediate positions. When behavioral measures were mapped onto phylogenetic trees, independent contrasts showed no significant consistent directional changes at nodes below which there were evolutionary changes in scale. Further, contrasts were no greater at these nodes than at neutral nodes. This suggests that correlations with the scale can be attributed largely to species' phylogenetic relationships. This could be due in turn to a structural linkage of social traits based on adaptation to similar ecological conditions in the distant past, or simply to unlinked phylogenetic closeness.

Living kidney donor follow-up: state-of-the-art and future directions, conference summary and recommendations.

In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented.

Chimeric antigen receptor T cells (CAR-T) for the treatment of T-cell malignancies.

At present, the only curative therapy for patients with T-cell malignancies is allogeneic stem cell transplant, which has associated risks and toxicities. Novel agents have been tried in relapsed T-cell acute lymphoblastic leukemia (T-ALL), but only one, with 20%-30% complete remission rates, has been approved by the US Food and Drug Administration. T-ALL is a heterogeneous disease, but it has universal overexpression of CD7 as well as several other T-cell markers, such as CD2 and CD5. T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown great potential for inducing both remissions and even long-term relapse-free survival in patients with B-cell leukemia and lymphoma. UCART7 for CD7+ T-cell malignancies is in development for treatment of relapsed T-ALL in children and adults. It may also have potential in other CD7+ hematologic malignancies that lack both effective therapies and targeted therapies. The challenges encountered and progress made in developing a novel fratricide-resistant "off-the-shelf" CAR-T (or UCART7) that targets CD7+ T-cell malignancies are discussed here.

Development of social play in hamsters: Sex differences and their possible functions.

In several rodent species social play appears to be necessary for proper deployment of species-specific patterns of aggressive and reproductive behavior. Specifically, in male Syrian hamsters (Mesocricetus auratus), play has been linked to the development of adult aggression. We quantified several types of social play behavior in same-sex peer groups of Syrian hamsters three times per week for three consecutive weeks after weaning, which included postnatal days 22-42 (PD22 to PD42). Male hamsters increased playful contact during PD36-PD42, whereas females showed peak playful contact during PD29-PD35. These findings suggest that the motivation for social play increases during mid-adolescence in males, but dissipates in females. To investigate the effects of social play deprivation, one hamster per litter remained pair-housed with its mother forthree weeks after weaning its littermates. In adulthood, both play-deprived and play-exposed animals received acute social defeat stress followed by social interaction testing. Play deprivation led to increased defeat-induced social avoidance in both males and females. In males, play deprivation increased fighting back during social defeat stress, whereas in females it reduced aggressive behavior during conditioned defeat testing. We suggest that social play deprivation disrupts neural circuits regulating aggression in a sex-specific manner, perhaps related to sex differences in territorial defense, but has similar effects on neural circuits regulating stress responsivity. Overall, these findings suggest that juvenile social play functions to promote coping with stress and appropriate social behavior in adulthood.

Clinical results from transplanting incompatible live kidney donor/recipient pairs using kidney paired donation.

CONTEXT: First proposed 2 decades ago, live kidney paired donation (KPD) was considered a promising new approach to addressing the shortage of organs for transplantation. Ethical, administrative, and logistical barriers initially proved formidable and prevented the implementation of KPD programs in the United States. OBJECTIVE: To determine the feasibility and effectiveness of KPD for the management of patients with incompatible donors. DESIGN, SETTING, AND PATIENTS: Prospective series of paired donations matched and transplanted from a pool of blood type or crossmatch incompatible donors and recipients with end-stage renal disease (6 conventional and 4 unconventional KPD transplants) at a US tertiary referral center (between June 2001 and November 2004) with expertise in performing transplants in patients with high immunologic risk. INTERVENTION: Kidney paired donation and live donor renal transplantation. MAIN OUTCOME MEASURES: Patient survival, graft survival, serum creatinine levels, rejection episodes. RESULTS: A total of 22 patients received transplants through 10 paired donations including 2 triple exchanges at Johns Hopkins Hospital. At a median follow-up of 13 months (range, 1-42 months), the patient survival rate was 100% and the graft survival rate was 95.5%. Twenty-one of the 22 patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL (range, 0.8-1.8 mg/dL) (106.1 micromol/L [range, 70.7-159.1 micromol/L]). There were no instances of antibody-mediated rejection despite the inclusion of 5 patients who were highly sensitized to HLA antigens due to previous exposure to foreign tissue. Four patients developed acute cellular rejection (18%). CONCLUSIONS: This series of patients who received transplants from a single-center KPD pool provides evidence that recipients with incompatible live donors, even those with rare blood type combinations or high degrees of HLA antigen sensitization, can receive transplants through KPD with graft survival rates that appear to be equivalent to directed, compatible live donor transplants. If these results can be generalized, broader availability of KPD to the estimated 6000 patients with incompatible donors could result in a large expansion of the donor pool.

The state of U.S. living kidney donors.

BACKGROUND AND OBJECTIVES: Increasing living kidney donation mandates ongoing assessment of living donors for future health risks and revision of national health policy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Living kidney donors as reported to the Organ Procurement and Transplant Network database from January 1988 through December 2008 were reviewed for minor medical abnormalities, presence of donor health care coverage, and occurrence of surgical complications and death. RESULTS: At donation in 2008, 19.5% were obese, 2.0% had a history of hypertension, and 3.5% had proteinuria. The median estimated GFR of living donors was 92.2 ml/min. Additionally, 12.2% of donors were reported not to have health insurance at the time of donation. By racial background, 14.9% of black and 17.0% of Hispanic donors did not have insurance at donation. Perioperative complications included blood transfusion (0.4%), reoperation (0.5%), and vascular complications (0.2%). Death occurred within 30 days of donation in 0.03% donating between October 1999 and December 2008. During those same years, overall donor death was 2.8%. CONCLUSIONS: Almost one quarter of living donors have medical conditions that may be associated with future health risk. Close follow-up and a registry of these donors are necessary. Only then will we be able to inform prospective living donors most accurately of the real risk of donation on their health and survival. Additionally, these data speak to the need for a national discussion on the provision of health insurance for living donors.

Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy.

The majority of preconditioning protocols developed to allow ABO-incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful engraftment. Our center has developed a preconditioning protocol that includes plasmapheresis (PP), low-dose CMV hyperimmune globulin (CMVIg), and anti-CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy. Our initial experience has included treatment of six recipients and successful transplantation from blood group A(1), A(2), and group B living donors. Mean (+/- SD) serum creatinine was 1.3 +/- 0.1 mg/dL among the six recipients and no episodes of antibody-mediated rejection (AMR) occurred at a median follow-up of 12 months. ABO antibody titers have remained below pretreatment levels. The absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation. The use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post-splenectomy infections.