Impact of Histidine-Tryptophan-Ketoglutarate Versus University of Wisconsin Solution on the Outcome of Pancreas Transplant With Cold Ischemic Time ≥12 Hours: A Retrospective Study.

OBJECTIVES: Histidine-tryptophan-ketoglutarate and University of Wisconsin solutions are currently used for pancreas graft preservation. Our hypothesis was whether the use of histidine-tryptophan-ketoglutarate solution is associated with worse pancreas graft survival than University of Wisconsin solution, in general and after prolonged cold ischemic time of ≥12 hours. MATERIALS AND METHODS: This retrospective study investigated the impact of static cold storage in histidine-tryptophan-ketoglutarate (n = 133) versus University of Wisconsin (n = 107) solution on outcomes of 240 pancreas transplant procedures. Patient and graft survival rates were compared after 1, 3, and 5 years in both groups. Serum lipase, amylase, and C-reactive protein levels and incidence of surgical complications were evaluated at postoperative week 1. A subgroup analysis of 96 grafts (52 with histidine-tryptophanketoglutarate/44 with University of Wisconsin) with pancreas graft cold ischemic time ≥12 hours was also performed. RESULTS: At mean follow-up of 75.2 ± 9.9 months, both groups demonstrated comparable short- and long-term patient survival. Overall, pancreas graft survival was slightly better in the histidine-tryptophan-ketoglutarate group (Kaplan-Meier analysis, log-rank P = .013). However, the subgroup analysis of grafts with cold ischemic time ≥12 hours showed slightly better pancreatic graft survival in the University of Wisconsin group, although not significantly (log-rank P = .95). Serum lipase and C-reactive protein levels at postoperative week 1 were higher in the histidinetryptophan-ketoglutarate group. Surgical complications were comparable. Multivariable Cox regression analysis identified neither solution as a risk factor affecting patient and graft survival. CONCLUSIONS: Although a direct comparison between histidine-tryptophan-ketoglutarate and University of Wisconsin showed better pancreas graft survival with histidine-tryptophan-ketoglutarate, the multivariable analysis showed that the perfusion solution does not significantly influence patient and graft survival. However, in the analysis of transplants with cold ischemic time ≥12 hours, pancreas graft survival was slightly better in the University of Wisconsin group, although not significantly.

Impact of donor cardiopulmonary resuscitation on the outcome of simultaneous pancreas-kidney transplantation-a retrospective study.

Previous cardiac arrest in brain-dead donors has been discussed as a potential risk factor in pancreas transplantation (PT), leading to a higher rate of organ refusal. This study aimed to assess the impact of cardiopulmonary resuscitation (CPR) in brain-dead donors on pancreas transplant outcome. A total of 518 type 1 diabetics underwent primary simultaneous pancreas-kidney (SPK) transplantation at our center between 1994 and 2018. Patients were divided into groups, depending on whether their donor had been resuscitated or not. A total of 91 (17.6%) post-CPR donors had been accepted for transplantation (mean duration of cardiac arrest, 19.4 ± 15.6 min). Those donors were younger (P < 0.001), had lower pancreas donor risk index (PDRI, P = 0.003), and had higher serum creatinine levels (P = 0.021). With a median follow-up of 167 months (IQR 82-229), both groups demonstrated comparable short- and long-term patient and graft survival. The resuscitation time (<20 min vs. ≥20 min) also showed no impact, with similar survival rates for both groups. A multivariable Cox regression analysis suggested no statistically significant association between donor CPR and patient or graft survival. Our results indicate that post-CPR brain-dead donors are suitable for PT without increasing the risk of complications.

Creatine protects the immature brain from hypoxic-ischemic injury.

OBJECTIVE: We tested the neuroprotective effects of creatine against hypoxic-ischemic injury in the immature brain. METHODS: Hippocampal slices were prepared from fetal guinea pigs at 0.9 gestation and incubated in artificial cerebrospinal fluid (aCSF) equilibrated with carbogen. Slices were subjected to oxygen-glucose deprivation (OGD) for 30 or 40 minutes. Two hours after OGD, adenosine triphosphate (ATP) and protein synthesis were analyzed. Creatine (3 mM) was applied to tissue slices of the study groups 2 hours before the insult. In a second set of experiments 7-day-old Wistar rats were anesthetized, and the left carotid artery was ligated. After 1 hour of recovery the pups were subjected to a hypoxic gas mixture (8% oxygen and 92% nitrogen) for 80 minutes. Seven days later the brains of the neonates were removed and analyzed for hypoxic-ischemic injury. The rat pups of the test group were treated with creatine (3 g/kg subcutaneously) before (-64 hours, -40 hours, and -16 hours) and after (+3 hours) the hypoxic-ischemic insult, with zero time corresponding to the start of hypoxia, whereas the animals of the control group received the solvent. RESULTS: Creatine significantly improved the recovery of protein synthesis 2 hours after OGD in hippocampal slices but had no effect on ATP levels. Whereas seven animals of the control group developed severe cystic cerebral infarction, only mild to moderate damage was observed in the rat pups of the study group. In contrast to creatine-treated pups, the volume of the ipsilateral hemisphere was considerably smaller than that of the contralateral one in control animals (104 +/- 22 versus 138 +/- 14 mL, P<.001). Except at the frontal level (A 6.0 mm), neuronal cell injury was significantly lower in the cortex of the animals that had received creatine. This was also true for the evaluated subfields in the hippocampus. CONCLUSION: We conclude that creatine protects the immature brain from hypoxic-ischemic injury.

Intracisternal application of endotoxin enhances the susceptibility to subsequent hypoxic-ischemic brain damage in neonatal rats.

Perinatal brain damage is associated not only with hypoxic-ischemic insults but also with intrauterine inflammation. A combination of antenatal inflammation and asphyxia increases the risk of cerebral palsy >70 times. The aim of the present study was to determine the effect of intracisternal (i.c.) administration of endotoxin [lipopolysaccharides (LPS)] on subsequent hypoxic-ischemic brain damage in neonatal rats. Seven-day-old Wistar rats were subjected to i.c. application of NaCl or LPS (5 microg/pup). One hour later, the left common carotid artery was exposed through a midline neck incision and ligated with 6-0 surgical silk. After another hour of recovery, the pups were subjected to a hypoxic gas mixture (8% oxygen/92% nitrogen) for 60 min. The animals were randomized to four experimental groups: 1) sham control group, left common carotid artery exposed but not ligated (n = 5); 2) LPS group, subjected to i.c. application of LPS (n = 7); 3) hypoxic-ischemic study group, i.c. injection of NaCl and exposure to hypoxia after ligation of the left carotid artery (n = 17); or 4) hypoxic-ischemic/LPS study group, i.c. injection of LPS and exposure to hypoxia after ligation of the left carotid artery (n = 19). Seven days later, neonatal brains were assessed for neuronal cell damage. In a second set of experiments, rat pups received an i.c. injection of LPS (5 microg/pup) and were evaluated for tumor necrosis factor-alpha expression by immunohistochemistry. Neuronal cell damage could not be observed in the sham control or in the LPS group. In the hypoxic-ischemic/LPS group, neuronal injury in the cerebral cortex was significantly higher than in animals that were subjected to hypoxia/ischemia after i.c. application of NaCl. Injecting LPS intracisternally caused a marked expression of tumor necrosis factor-alpha in the leptomeninges. Applying LPS intracisternally sensitizes the immature rat brain to a subsequent hypoxic-ischemic insult.

[Perinatal brain damage--from neuroprotection to neuroregeneration using cord blood stem cells]. / Frühkindliche Hirnschäden--von der Neuroprotektionzur Neuroregeneration mit Nabelschnurstammzellen.

Per year, approximately 1,000 children in Germany suffer from brain damage due to hypoxic-ischemic insults during the perinatal period. Based on the severity and localization of the insult, these children develop either spastic pareses, choreoathetosis, ataxia, or sensomotoric dysfunctions. A close cooperation between obstetricians, pediatricians, neuropediatricians, physical therapists, developmental psychologists, and other specialists is required, as the strain these disorders have on the children and their families is tremendous. The costs resulting per birthyear for the community are estimated on 1 million Euro. Clinical concepts to decrease the cerebral morbidity in perinatology departments have proven to be effective over the last decade. However, since brain damage cannot be prevented every time, it is essential that therapeutic measures, which have a neuroprotective effect after the insult, are being developed. Experimental pilots regarding these matters are promising. Current experiments are focused on the possible application of cord blood-derived stem cells for neuroregeneration.