Pancreatic autoantibodies after pancreas–kidney transplantation – do they matter?

Type 1 diabetes recurrence has been documented in simultaneous pancreas–kidney transplants (SPKT), but this diagnosis may be underestimated. Antibody monitoring is the most simple, noninvasive, screening test for pancreas autoimmune activity. However, the impact of the positive autoimmune markers on pancreas graft function remains controversial. In our cohort of 105 SPKT, we studied the cases with positive pancreatic autoantibodies. They were immunosuppressed with antithymocyte globulin, tacrolimus, mycophenolate, and steroids. The persistence or reappearance of these autoantibodies after SPKT and factors associated with their evolution and with graft outcome were analyzed. Pancreatic autoantibodies were prospectively monitored. Serum samples were collected before transplantation and at least once per year thereafter. At the end of the follow‐up (maximum 138 months), 43.8% of patients were positive (from pre‐transplant or after recurrence) for at least one autoantibody – the positive group. Antiglutamic acid decarboxylase was the most prevalent (31.4%), followed by anti‐insulin (8.6%) and anti‐islet cell autoantibodies (3.8%). Bivariate analysis showed that the positive group had higher fasting glucose, higher glycated hemoglobin (HbA1c), lower C‐peptide levels, and a higher number of HLA‐matches. Analyzing the sample divided into four groups according to pre‐/post‐transplant autoantibodies profile, the negative/positive group tended to present the higher HbA1c values. Multivariate analysis confirmed the significant association between pancreas autoimmunity and HbA1c and C‐peptide levels. Positivity for these autoantibodies pre‐transplantation did not influence pancreas survival. The unfavorable glycemic profile observed in the autoantibody‐positive SPKT is a matter of concern, which deserves further attention.     

Transplant tourism – a dangerous journey?

Polcari AJ, Hugen CM, Farooq AV, Holt DR, Hou SH, Milner JE. Transplant tourism – a dangerous journey?
Clin Transplant 2011: 25: 633–637. © 2010 John Wiley & Sons A/S. Abstract: Introduction: While the ethical aspects of transplant tourism have received much attention recently, less has been written about the medical safety of this practice. We retrospectively evaluated the outcomes of patients who purchased organs internationally and presented to our center for follow‐up care. Methods: Baseline demographic characteristics were recorded. Post‐operative outcomes including patient survival, graft survival, five‐yr graft function, and complications were assessed. Results: Eight patients who purchased international organs for transplant were identified. The country of transplant was China (n = 3), Pakistan (n = 3), India (n = 1), and the Philippines (n = 1). All patients were born in either Asia or the Middle East and traveled to the region of their ethnicity for transplantation. The mean time to presentation was 49 d post‐operatively. The overall one‐ and two‐yr patient survival rates were 87% and 75%, respectively. One patient died of miliary tuberculosis and another of Acinetobacter baumanii sepsis. There was one case of newly acquired hepatitis B infection. At last follow‐up, all six surviving patients had functioning grafts with a mean creatinine level of 1.26 mg/dL at five yr. Conclusion: Although intermediate‐term graft function is acceptable, the early morbidity and mortality among transplant tourists is high. These results suggest that the associated risks may not justify the trip.     

Chemokines and the inflammatory response following cardiopulmonary bypass – a new target for therapeutic intervention? – a review

This 10-year Medline search of English-language articles describing experimental and clinical studies on chemokines, cardiopulmonary bypass (CPB) and systemic or multiorgan failure revealed that chemokines are significantly involved in the pathogenesis of post-CPB syndrome. The post-CPB inflammatory response depends upon recruitment and activation of inflammatory cells. Leucocyte recruitment is a well-orchestrated process that involves several protein families, including pro-inflammatory cytokines, adhesion molecules and chemokines. Current anti-inflammatory therapies mostly act on the cells that have already been recruited. A more efficient therapy might be the prevention of excessive recruitment of particular leucocyte populations by antagonizing chemokine receptors which might act upstream of the current anti-inflammatory agents. The chemokines, which are a cytokine subfamily of chemotactic cytokines, participate in recognizing, recruiting, removing and repairing inflammation. As chemokines target specific leucocyte subsets, antagonism of a single chemokine ligand or receptor would be expected to have a circumscribed effect, thereby endowing the antagonist with a limited side-effect profile. Chemokines should be considered as possible targets for therapeutic intervention.     

Chronic wounds – is cellular ‘reception’ at fault? Examining integrins and intracellular signalling

As with all physiologic processes, chronic wounds are associated with unique intracellular and cellular/extracellular matrix (ECM) receptor types and signalling messages. These cellular receptors mediate responses of the epidermis to provisional wound matrix and change in form and number in cases of impaired wound healing. Integrins are the major cell‐surface receptors for cell adhesion and migration and epidermal keratinocytes express several integrins that bind ECM ligands in provisional wound ECM. Integrin receptors and more particularly integrin clusters and focal adhesion points appear to influence epidermal and dermal cell matrix interactions, cell motility, cell phenotype and ultimate healing trajectory. In chronic wounds, a variety of changes in receptors have been identified: decreased integrin α5β1 receptors affect the integration of fibronectin and subsequent keratinocyte migration; integrin αvβ6 stimulate transforming growth factor (TGF)‐β and may increase the susceptibility to ulceration and fibrosis; however, TGF‐β signal receptors have been found to be dysfunctional in many chronic wounds; additionally receptor interactions result in increased senescent cells including fibroblasts, myofibroblasts and even keratinocytes – this produces a degradative ECM and wound bed and corrosive chronic wound fluid. The activation or inhibition of integrin receptors by various agents may provide an excellent means of influencing wound healing. This process offers an earlier intervention into the wound healing cascade promoting intrinsic healing and elaboration of growth factors and ECM proteins, which may be more cost effective than the traditional attempts at extrinsic addition of these agents.     

A 10 min “no‐touch” time – is it enough in DCD? A DCD Animal Study

Donation after cardiac death (DCD) is under investigation because of the lack of human donor organs. Required times of cardiac arrest vary between 75s and 27min until the declaration of the patients' death worldwide. The aim of this study was to investigate brain death in pigs after different times of cardiac arrest with subsequent cardiopulmonary resuscitation (CPR) as a DCD paradigm. DCD was simulated in 20 pigs after direct electrical induction of ventricular fibrillation. The "no-touch" time varied from 2min up to 10min; then 30min of CPR were performed. Brain death was determined by established clinical and electrophysiological criteria. In all animals with cardiac arrest of at least 6min, a persistent loss of brainstem reflexes and no reappearance of bioelectric brain activity occurred. Reappearance of EEG activity was found until 4.5min of cardiac arrest and subsequent CPR. Brainstem reflexes were detectable until 5min of cardiac arrest and subsequent CPR. According to our experiments, the suggestion of 10min of cardiac arrest being equivalent to brain death exceeds the minimum time after which clinical and electrophysiological criteria of brain death are fulfilled. Therefore shorter "no-touch" times might be ethically acceptable to reduce warm ischemia time.