Donor noradrenaline use is associated with better allograft survival in recipients of pancreas transplantation.

INTRODUCTION: Outcomes following pancreas transplantation are suboptimal and better donor selection is required to improve this. Vasoactive drugs (VaD) are commonly used to correct the abnormal haemodynamics of organ donors in intensive care units. VaDs can differentially affect insulin secretion positively (dobutamine) or negatively (noradrenaline). The hypothesis was that some VaDs might induce beta-cell stress or rest and therefore impact pancreas transplant outcomes. The aim of the study was to assess relationships between VaD use and pancreas transplant graft survival. METHODS: Data from the UK Transplant Registry on all pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Univariable- and multivariable-adjusted Cox regression analyses determined risks of graft failure associated with VaD use. RESULTS: In 2,183 pancreas transplants, VaDs were used in the following numbers of donors: dobutamine 76 (3.5%), dopamine 84 (3.8%), adrenaline 161 (7.4%), noradrenaline 1,589 (72.8%) and vasopressin 1,219 (55.8%). In multivariable models, adjusted for covariates and the co-administration of other VaDs, noradrenaline use (vs non-use) was a strong predictor of better graft survival (hazard ratio [95% confidence interval] 0.77 [0.64-0.94], p = 0.01). CONCLUSIONS: Noradrenaline use was associated with better graft survival in models adjusted for donor and recipient variables - this may be related to inhibition of pancreatic insulin secretion initiating pancreatic beta-cell 'rest'. Further research is required to replicate these findings and establish whether relationships are causal. Identification of alternative methods of inducing beta-cell rest could be valuable in improving graft outcomes.

Future imaging modalities for the assessment of pancreas allografts a scan of the horizon.

Pancreas transplantation (PT) allows improved glycaemic control for patients with complicated type 1 diabetes mellitus and is most commonly performed simultaneously with a renal transplant. Imaging modalities are critical for the assessment of pancreatic graft dysfunction, as clinical assessment and hyperglycaemia lack robust sensitivity for the transplant clinician. Biopsy represents the most conclusive standard of PT graft assessment but is challenging due to its invasive nature and the potential morbidity associated with the procedure. Innovative imaging technologies offer the opportunity to apply these modalities to improve PT outcomes while using non-invasive technologies to provide a diagnostic sensitivity that traditionally only biopsies can provide. Early graft dysfunction has traditionally been investigated with Computed tomography (CT) and ultrasound (US) scans. We explore adjuncts to these modalities including the application of contrast enhanced ultrasound (CEUS) for routine post-operative graft assessment to inform post-operative treatment strategies. There is currently a dearth of imaging modalities to reliably monitor long term graft function, but the use of innovative functional imaging techniques and how they can be applied to PT is discussed. Perfusion CT and glucose stimulated magnetic resonance imaging (MRI) to detect whole organ function are examined. In addition, early phase developments in beta-cell specific imaging methods to quantify beta-cell mass longitudinally are described. The clinical applications of such tools including Mn2+-enhanced MR and GLP-1R targeted PET/CT are reviewed and may demonstrate opportunities to provide the transplant clinician with greater information to support improved patient care.

Systematic review to assess the possibility of return of cerebral and cardiac activity after normothermic regional perfusion for donors after circulatory death.

BACKGROUND: Normothermic regional perfusion (NRP) is a novel technique that aids organ recovery from donors after circulatory death (DCDs). However, ethical concerns exist regarding the potential return of spontaneous cerebral and cardiac activity (ROSCCA). This study aimed to determine the likelihood of ROSCCA in NRP-DCDs of abdominal organs. METHODS: Extracorporeal cardiopulmonary resuscitation (ECPR) for refractory out-of-hospital cardiac arrest (OOHCA) was identified as a comparator for NRP-DCDs and as a validation cohort. A systematic search identified all articles relating to NRP-DCDs and ECPR-OOHCA. Rates of ROSCCA and survival outcomes (ECPR-OOHCA only) were recorded and analysed according to the duration of no perfusion. RESULTS: In NRP-DCDs, 12 of 410 articles identified by database searching were eligible for inclusion. There were no instances of ROSCCA recorded among 493 donors. In ECPR-OOHCA, eight of 947 screened articles were eligible for inclusion (254 patients). Where the absence of perfusion exceeded 5 min in ECPR-OOHCA, there were no survivors with a favourable neurological outcome. CONCLUSION: ROSCCA is unlikely following commencement of NRP and has not occurred to date. Strict observance of the 5-min interval following asystole provides satisfactory assurance that ROSCCA will not occur following NRP.

Renal Allograft Failure After Ipilimumab Therapy for Metastatic Melanoma: A Case Report and Review of the Literature.

Transplant recipients are at an increased risk of malignant melanoma, a result of chronic immunosuppression. Ipilimumab is a newer biological agent targeting T lymphocytes to potentiate an immune response against melanoma, and the use of this agent results in a new adverse effect profile that the clinician must be aware of while a patient is on therapy. We report the case of a male renal transplant recipient who developed graft failure while treated with ipilimumab and minimal immunosuppressive therapy for metastatic ocular melanoma, with biopsy evidence of glomerulonephritis and acute rejection. We highlight the immunological side effects that can manifest from ipilimumab therapy and conclude that it did influence graft function in this patient. Our case illustrates the importance of weighing the risks and benefits to graft function and long-term survival as well as the importance of considering other treatment modalities in this specific group of melanoma patients.

Randomized clinical trial of the use of glyceryl trinitrate patches to aid arteriovenous fistula maturation.

BACKGROUND: Arteriovenous fistulas are critical for haemodialysis, but maturation rates remain poor. Experimental and anecdotal evidence has supported the use of transdermal glyceryl trinitrate (GTN) patches. The aim of this RCT was to determine whether use of a GTN patch aids arteriovenous fistula maturation. METHODS: Patients referred for arteriovenous fistula formation were eligible. The GTN or placebo patch was applied immediately after surgery and left in situ for 24 h. The primary outcome measure was the change in venous diameter at 6 weeks after fistula formation. The secondary outcome measure was clinical fistula patency at 6 weeks. RESULTS: Of 200 patients recruited (533 screened), 101 were randomized to the placebo group and 99 to the GTN group. Of these, 81 and 86 respectively completed surgery, and had follow-up data available at 6 weeks. Improvements in venous diameter were similar in the two groups: mean(s.d.) increase 2·3(1·9) mm in the placebo group compared with 2·2(1·8) mm in the GTN group (P = 0·704). The fistula failure rate did not differ significantly between the two groups: 23 per cent for placebo and 28 per cent for GTN (P = 0·596). CONCLUSION: GTN transdermal patches used for 24 h after surgery did not improve arteriovenous fistula maturation. REGISTRATION NUMBER: NCT01685710 (http://www.clinicaltrials.gov).

A prospective cohort study of risk prediction in simultaneous pancreas and kidney transplantation.

INTRODUCTION: Current risk prediction scoring systems in pancreas transplantation are limited to organ factors and are specific to predicting graft outcome. They do not consider recipient factors or inform regarding recipient morbidity. The aim of this study was to assess the utility of commonly used general surgical risk prediction models (P-POSSUM [Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity], MODS [multiple organ dysfunction score], Charlson co-morbidity index, revised cardiac risk index, ASA [American Society of Anesthesiologists] grade and Waterlow score), and to correlate them with total length of hospital stay (LOS) and critical care unit (CCU) LOS, important surrogate markers of patient outcome. METHODS: All risk prediction scores were calculated prospectively for all simultaneous pancreas and kidney (SPK) transplant recipients from November 2011 to October 2013, and correlated with outcome measures. RESULTS: Overall, 57 SPK transplant recipients were analysed. The mean age was 42.0 years (standard deviation [SD]: 7.60 years), 27 (52%) were male and the mean body mass index was 25.43kg/m(2) (SD: 3.11kg/m(2)). The mean pancreas and kidney cold ischaemic times were 703 minutes (SD: 182 minutes) and 850 minutes (SD: 192 minutes) respectively. The median total LOS and mean CCU LOS was 17 days (range: 8-79 days) and 7 days (SD: 4.04 days) respectively. When correlated with risk prediction scores, Waterlow score was the only significant predictor of total LOS and CCU LOS (p<0.001 [Spearman's correlation] and p=0.001 [Pearson's correlation] respectively). CONCLUSIONS: Preoperative risk prediction plays an important part in planning perioperative care. To date, no validated risk prediction scoring system exists for SPK transplantation. This prospective study indicates that Waterlow score identifies high risk individuals and has value in the prediction of outcome following SPK transplantation.

Complex kidneys for complex patients: the risk associated with transplantation of kidneys with multiple arteries into obese patients.

Conflicting evidence surrounds clinical outcomes in obese individuals after transplantation; nonetheless, many are denied the opportunity to receive a transplant. Allografts with complex vascular anatomy are regularly used in both deceased and living donor settings. We established the risk of transplanting kidneys with multiple renal arteries into obese recipients. A retrospective analysis of data from 1095 patients undergoing renal transplantation between January 2004 and July 2013 at a single centre was conducted. Of these, 24.2% were obese (body mass index >30 kg/m(2)), whereas 25.1% of kidneys transplanted had multiple arteries, thereby making the transplantation of kidneys of complex anatomy into obese recipients a relatively common clinical occurrence. Vessel multiplicity was associated with inferior 1-year graft survival (85.8.% vs 92.1%, P = .004). Obese patients had worse 1-graft survival compared to those of normal BMI (86.8% vs 93.8%, P = .001). The risk of vascular complications and of graft loss within a year after transplantation were greater when grafts with multiple arteries were transplanted into obese recipients as compared to their nonobese counterparts (RR 2.00, CI 95% 1.07-3.65, and RR 1.95, CI 95% 1.02-3.65). Additionally, obese patients faced significantly higher risk of graft loss if receiving a kidney with multiple arteries compared to one of normal anatomy (RR 1.97, 95% CI 1.02-3.72). Thus, obese patients receiving complex anatomy kidneys face poorer outcomes, which should be considered when allocating organs, seeking consent, and arranging for aftercare.

Successful management of a ruptured mycotic pseudoaneurysm following pancreas transplantation using bovine pericardial patch: a case report.

Arterial mycotic pseudoaneurysms are a rare complication of pancreas transplantation. Rupture results in catastrophic hemorrhage with a high risk of mortality. Definitive management is complicated by an extensive arterial defect within a contaminated surgical field. Synthetic vascular grafts often fail due to subsequent graft infection whereas primary repair often results in arterial stenosis. Arterial ligation may be required to prevent exsanguination. A 41-year-old man, type 1 diabetic with associated renal failure, underwent successful simultaneous pancreas and kidney transplantation. He presented, 9 months following transplantation, with life-threatening rectal bleeding secondary to a ruptured mycotic pseudoaneurysm. This was successfully managed with a bovine pericardial patch (BPP) repair of the arterial defect and enteric diversion following graft pancreatectomy. He remains well with no vascular insufficiency 18 months following the procedure. A ruptured mycotic pseudoaneurysm following transplantation carries a significant risk of mortality and represents a surgical challenge as conventional techniques using synthetic materials often fail due to the contaminated field. A BPP offers good handling characteristics, excellent hemostatic properties and a favorable profile of infection risk in comparison with synthetic grafts. This case highlights its use as a treatment for a post-transplantation ruptured mycotic pseudoaneurysm.

Anti-tuberculosis prophylaxis following renal transplantation: acceptable variations?

BACKGROUND: Guidelines suggest tuberculosis (TB) prophylaxis in renal transplant recipients originating in endemic areas or in those at risk from non-endemic countries. Concern remains that these guidelines may fail to provide adequate prophylaxis for a cohort of patients who remain at potential risk. We aimed to determine variation patterns among different transplant units within the United Kingdom (UK) with regard to TB prophylaxis policy. METHODS: The renal pharmacist at each of the 25 UK renal transplant centers was contacted. Specific information was obtained relating to drug prophylaxis given, duration of treatment, as well as which transplant recipients were eligible for treatment. RESULTS: A 96% response rate (24/25 centers) was achieved. Prophylaxis regimens varied from no prophylaxis to isoniazid 300 mg given life-long. The most common duration of treatment was 6 months post transplantation (at 7 centers). Variations existed in the concurrent use of pyridoxine. A wide discrepancy was seen in the determination of who should receive prophylaxis, with no clear association with frequency of TB incidence in the region. CONCLUSIONS: A marked discrepancy exists among national renal transplant units in pharmacologic prophylaxis for TB, as well in the selection of individuals for this treatment.

Transcranial Doppler ultrasonography-directed intravenous glycoprotein IIb/IIIa receptor antagonist therapy to control transient cerebral microemboli before and after carotid endarterectomy.

BACKGROUND: Patients with a transient focal neurological deficit, critical carotid stenosis and/or microemboli detected by transcranial Doppler ultrasonography (TCD) have a significant risk of stroke. The effect of tirofiban, a selective glycoprotein IIb/IIIa inhibitor, was assessed in patients with microembolic signals on TCD after transient ischaemic attacks or carotid endarterectomy (CEA). METHODS: Thirty-three patients with microemboli on TCD (13 symptomatic preoperative, 19 postoperative, one both) were treated with tirofiban between 2002 and 2007. All patients had carotid stenosis greater than 70 per cent. TCD monitoring was used during and after tirofiban therapy. RESULTS: The median (range) rate of microemboli decreased from 22 (4-260) per h before surgery and 81 (44-216) per h after surgery to 0 (0-9) per h in both groups (P < 0.001, Mann-Whitney U test). This occurred rapidly (preoperative median 30 min; postoperative median 45 min) and was well tolerated in all patients, with no serious adverse effects. CONCLUSION: Cerebral microemboli were controlled by tirofiban both before and after CEA. Further study is required to compare the relative efficacy of tirofiban and dextran.