Unexplained fever after pancreas transplantation.

BACKGROUND: Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. METHODS: We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas-kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. RESULTS: Twenty-three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post-transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy-proven rejection, graft loss, death, or documented infections compared to UF-free patients during the first-year post-transplant. CONCLUSION: UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first-year post-transplant.

Evaluation of a pharmacy managed heparin protocol for extracorporeal membrane oxygenation patients.

INTRODUCTION: Unfractionated heparin is the preferred anticoagulant in extracorporeal membrane oxygenation (ECMO) patients. However, there is a lack of consensus on its titration and monitoring. The objective of this study was to describe the efficacy and safety of a pharmacy managed heparin protocol utilizing activated partial thromboplastin time (aPTT) in comparison to our standard physician-managed activated clotting time (ACT)-based anticoagulation in ECMO patients. METHODS: Patients administered a heparin drip while on ECMO were included in the study. The primary endpoints were the incidence of hemorrhagic and thrombotic complications. RESULTS: A total of 122 adult patients were identified who were on ECMO with heparin anticoagulation; sixty-one patients were managed with each of the physician-managed ACT and pharmacy managed aPTT protocols. No statistically significant difference was observed between the physician ACT and the pharmacy aPTT groups in overall hemorrhagic (69% vs 80%, p=0.145) or thrombotic complications (41% vs 39%, p=0.853). CONCLUSION: There was a similar rate of thrombotic and bleeding events between the two study groups. A pharmacy managed heparin protocol utilizing aPTT monitoring appears to be a safe and effective method of providing anticoagulation in adult ECMO patients.

Comparison of Acellular Solutions for Ex-situ Perfusion of Amputated Limbs.

INTRODUCTION: Hypothermic ex-situ machine perfusion (MP) has been shown to be a promising alternative to static cold storage (SCS) for preservation of solid organs for transplantation and vascularized composite allotransplantation. Perfusion with blood-based perfusion solutions in austere environments is problematic due to their need for appropriate storage and short shelf life, making it impractical for military and emergency use. Acellular perfusion has been shown to be effective, but the ideal perfusate solution for MP of amputated limbs is yet to be determined. The purpose of this study is to evaluate the efficacy of alternative perfusate solutions, such as dextran-enriched Phoxilium, Steen, and Phoxilium in ex-vivo hypothermic MP of amputated limbs in a porcine model. MATERIALS AND METHODS: Amputated forelimbs from Yorkshire pigs (n = 8) were preserved either in SCS (n = 2) at 4°C for 12 hours or machine-perfused at 10°C for 12 hours with oxygenated perfusion solutions (n = 6) at a constant flow rate. The perfusates used include modified Steen-solution, Phoxilium (PHOX), or Phoxilium enriched with dextran-40 (PHODEX). The perfusate was exchanged after 1 and 6 hours of perfusion. Machine data were recorded continuously. Perfusate samples for clinical chemistry, blood gas analysis, and muscle biopsies were procured at specific timepoints and subsequently analyzed. In this semi in-vivo study, limb replantation has not been performed. RESULTS: After amputation, every limb was successfully transferred and connected to our perfusion device. The mean total ischemia time was 77.5 ± 5.24 minutes. The temperature of the perfusion solution was maintained at 10.18 ± 2.01°C, and perfusion pressure at 24.48 ± 10.72 mmHg. Limb weight increased by 3% in the SCS group, 36% in the PHODEX group, 25% in the Steen group, and 58% in the PHOX group after 12 hours. This increase was significant in the PHOX group compared with the SCS group. All perfusion groups showed a pressure increase of 10.99 mmHg over time due to edema. The levels of HIF-1a decreased over time in all groups except the Steen and the PHODEX group. The biomarkers of muscle injury in the perfusate samples, such as creatine kinase and lactate-dehydrogenase, showed a significant difference between groups, with highest values in the PHODEX group. No significant differences were found in the results of the blood gas analysis. CONCLUSION: With the exception of significantly higher levels of creatine kinase and lactate dehydrogenase, MP with dextran-enriched Phoxilium provides similar results as that of the commercially available perfusates such as Steen, without the need for cold storage, and at circa 5% of the cost of the Steen solution. Further large-scale replantation studies are necessary to evaluate the efficacy of dextran-enriched Phoxilium as an alternate perfusate solution.

Alemtuzumab as a Therapy for Chronic Lung Allograft Dysfunction in Lung Transplant Recipients With Short Telomeres.

Alemtuzumab, a monoclonal antibody targeting CD52 that causes lymphocyte apoptosis, is a form of advanced immunosuppression that is currently used as a therapy for refractory acute cellular rejection and chronic lung allograft dysfunction in lung transplant recipients (1-3). Side effects of alemtuzumab include bone marrow suppression, infection, and malignancy. Whether alemtuzumab can be safely used in allograft recipients that have an increased propensity for bone marrow suppression due to telomeropathies is unknown. In a retrospective case series, we report outcomes associated with alemtuzumab in three lung allograft recipients with short telomere lengths, comparing endpoints such as leukopenia, transfusion needs, infection, hospitalization and survival to those of 17 patients without known telomeropathies that received alemtuzumab. We show that the use of alemtuzumab in lung transplant recipients with short telomeres is safe, though is associated with an increased incidence of neutropenia, thrombocytopenia and anemia requiring packed red blood cell transfusions. Alemtuzumab appears to be an acceptable advanced immunosuppressive therapy in patients with telomeropathies, though given the design and scope of this study, the actual clinical effect needs further evaluation in larger trials.