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).

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.