Chronic Pancreas Allograft Rejection Followed by Successful HLA-Incompatible Islet Alloautotransplantation: A Novel Strategy?

The purpose of pancreas or islet transplantation is to restore glycemic control in order to mitigate diabetes-related complications and prevent severe hypoglycemia. Complications from chronic pancreas allograft rejection may lead to transplantectomy, even when the endocrine function remains preserved. We present first evidence of a successful HLA incompatible islet re-transplantation with islets isolated from a rejecting pancreas allograft after simultaneous kidney pancreas transplantation. The pancreas allograft was removed because of progressively painful pancreatic panniculitis from clinically uncontrolled chronic rejection. The endocrine function was preserved. Induction treatment for this "islet alloautotransplantation" consisted of plasmapheresis, IVIg and alemtuzumab. At 1 year, the patient retained islet graft function with good glycemic control and absence of severe hypoglycemia, despite persistent low-grade HLA donor-specific antibodies. His panniculitis had resolved completely. In our point of view, islet alloautotransplantation derived from a chronically rejecting pancreas allograft is a potential option to salvage (partial) islet function, despite preformed donor-specific antibodies, in order to maintain stable glycemic control. Thereby it protects against severe hypoglycemia, and it potentially mitigates kidney graft dysfunction and other diabetes-related complications in patients with continued need for immunosuppression and who are otherwise difficult to retransplant.

The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice.

Solid phase immunoassays improved the detection and determination of the antigen-specificity of donor-specific antibodies (DSA) to human leukocyte antigens (HLA). The widespread use of SPI in kidney transplantation also introduced new clinical dilemmas, such as whether patients should be monitored for DSA pre- or post-transplantation. Pretransplant screening through SPI has become standard practice and DSA are readily determined in case of suspected rejection. However, DSA monitoring in recipients with stable graft function has not been universally established as standard of care. This may be related to uncertainty regarding the clinical utility of DSA monitoring as a screening tool. This consensus report aims to appraise the clinical utility of DSA monitoring in recipients without overt signs of graft dysfunction, using the Wilson & Junger criteria for assessing the validity of a screening practice. To assess the evidence on DSA monitoring, the European Society for Organ Transplantation (ESOT) convened a dedicated workgroup, comprised of experts in transplantation nephrology and immunology, to review relevant literature. Guidelines and statements were developed during a consensus conference by Delphi methodology that took place in person in November 2022 in Prague. The findings and recommendations of the workgroup on subclinical DSA monitoring are presented in this article.

The Obesity Paradox in the Trauma Patient: Normal May not Be Better.

OBJECTIVE: The obesity paradox is the association of increased survival for overweight and obese patients compared to normal and underweight patients, despite an increased risk of morbidity. The obesity paradox has been demonstrated in many disease states but has yet to be studied in trauma. The objective of this study is to elucidate the presence of the obesity paradox in trauma patients by evaluating the association between BMI and outcomes. METHODS: Using the 2014-2015 National Trauma Database (NTDB), adults were categorized by WHO BMI category. Logistic regression was used to assess the odds of mortality associated with each category, adjusting for statistically significant covariables. Length of stay (LOS), ICU LOS and ventilator days were also analyzed, adjusting for statistically significant covariables. RESULTS: A total of 415,807 patients were identified. Underweight patients had increased odds of mortality (OR 1.378, p < 0.001 95% CI 1.252-1.514), while being overweight had a protective effect (OR 0.916, p = 0.002 95% CI 0.867-0.968). Class I obesity was not associated with increased mortality compared to normal weight (OR 1.013, p = 0.707 95% CI 0.946-1.085). Class II and Class III obesity were associated with increased mortality risk (Class II OR 1.178, p = 0.001 95% CI 1.069-1.299; Class III OR 1.515, p < 0.001 95% CI 1.368-1.677). Hospital and ICU LOS increased with each successive increase in BMI category above normal weight. Obesity was associated with increased ventilator days; Class I obese patients had a 22% increase in ventilator days (IRR 1.217 95% CI 1.171-1.263), and Class III obese patients had a 54% increase (IRR 1.536 95% CI 1.450-1.627). CONCLUSION: The obesity paradox exists in trauma patients. Further investigation is needed to elucidate what specific phenotypic aspects confer this benefit and how these can enhance patient care. LEVEL OF EVIDENCE: Level III, prognostic study.

Effects of thymosin on cytotoxicity and virus production in AKR mice.

The cytotoxic potential and ability to produce endogenous ecotropic virus(es) of thymic-, splenic-, and lymph node-derived lymphocytes were significantly (and differentially) altered following thymosin treatment of young (nonleukemic) and aged (preleukemic) AKR mice. Thymosin administration markedly enhanced the cytotoxic potential of both splenic and lymph node lymphocytes from aged animals, but effected a moderate increase only in the spleens of young mice. Thymosin enhanced the production of endogenous virus(es) by thymocytes from aged mice, with the opposite effect noted in young animals. Splenectomy generally reduced the cytotoxic activity and virus titers of lymphocytes from both groups, and thymosin administration further reduced the cytotoxic response. These findings probably reflect overall effects on both regulatory lymphocyte subpopulations and different endogenous viruses in young and aged mice.

72 kidney transplants at the Medical College of Georgia 1968-1976.

Seventy-two kidneys have been transplanted-47 from related donors, and 25 from cadaver donors-into 63 recipients. No donor died or experienced a complication requiring more than one extra week of hospitalization. Six recipients died. Three of the six recipients died from complications. Two of the six died only because they declined to resume hemodialysis, and one died in prison of unusual circumstances after seven and one-half years of good health and kidney function. Five patients are surviving by virtue of a second transplant. Eight patients are now on hemodialysis. Seven patients with transplants are not in excellent physical health and five other patients with excellent health and renal function are nonetheless frequently depressed and easily upset over minor physical disabilities. A majority of the recipients have been rehabilitated to a gratifying extent.

Altered mitogenic responsiveness of chronic leukemic lymphocytes and normal human lymphocytes treated with dimethyl sulfoxide.

Peripheral lymphocytes from patients with chronic lymphocytic leukemia display a delayed and lowered response to stimulation by PHA, as compared with the lymphocytes from normal donors. This response was determined by measuring the incorporation of tritiated thymidine. The addition of DMSO in concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0% (v/v) to the culture fluid of normal cell cultures that had been stimulated, with PHA elicited a 3- to 4-fold increase in the rate of incorporation of labeled thymidine at the 3-day test period. The addition of 2.0% DMSO proved to be preferentially cytotoxic to cultures of leukemic cells after 48 hours, as compared with the virtual absence of cytotoxicity for cultures of normal lymphocytes. The addition of 0.1%, 0.25%, 0.5%, and 1.0% DMSO to cultures of leukemic cells stimulated with PHA (as were normal cell cultures) resulted in a 6- to 6.5-fold increase in the rate of uptake of tritiated thymidine at 3 days.