ClinCirc identifies alterations of the circadian peripheral oscillator in critical care patients.

BackgroundAssessing circadian rhythmicity from infrequently sampled data is challenging; however, these types of data are often encountered when measuring circadian transcripts in hospitalized patients.MethodsWe present ClinCirc. This method combines 2 existing mathematical methods (Lomb-Scargle periodogram and cosinor) sequentially and is designed to measure circadian oscillations from infrequently sampled clinical data. The accuracy of this method was compared against 9 other methods using simulated and frequently sampled biological data. ClinCirc was then evaluated in 13 intensive care unit (ICU) patients as well as in a separate cohort of 29 kidney-transplant recipients. Finally, the consequences of circadian alterations were investigated in a retrospective cohort of 726 kidney-transplant recipients.ResultsClinCirc had comparable performance to existing methods for analyzing simulated data or clock transcript expression of healthy volunteers. It had improved accuracy compared with the cosinor method in evaluating circadian parameters in PER2:luc cell lines. In ICU patients, it was the only method investigated to suggest that loss of circadian oscillations in the peripheral oscillator was associated with inflammation, a feature widely reported in animal models. Additionally, ClinCirc was able to detect other circadian alterations, including a phase shift following kidney transplantation that was associated with the administration of glucocorticoids. This phase shift could explain why a significant complication of kidney transplantation (delayed graft dysfunction) oscillates according to the time of day kidney transplantation is performed.ConclusionClinCirc analysis of the peripheral oscillator reveals important clinical associations in hospitalized patients.FundingUK Research and Innovation (UKRI), National Institute of Health Research (NIHR), Engineering and Physical Sciences Research Council (EPSRC), National Institute on Academic Anaesthesia (NIAA), Asthma+Lung UK, Kidneys for Life.

Comparison of Ipsilateral and Contralateral Simultaneous Pancreas and Kidney Transplantation: A Single-Center Analysis with 5-Year Outcome.

BACKGROUND It is routine to implant the pancreas on the right and the renal graft on the left iliac fossa during a simultaneous kidney and pancreas transplant (cSPK). Ipsilateral placement of both organs on the same side raises concerns that the pancreas graft might compromise the distally placed kidney. However, ipsilateral SPK (iSPK) can be faster than the conventional contralateral graft placement and allows for preservation of the other side for future transplants. MATERIAL AND METHODS In a single unit, 67 SPK transplantations (cSPK n=49, iSPK n=18) were performed from 2008 to 2011. The decision for graft placement was made during the procedure. Donor and recipient demographics, surgical complications, reoperations, surgical time, and patient and graft survival with 5-year follow-up were compared between the 2 groups. RESULTS Duration of operation was shorter in the iSPK group. Recipient and donor demographics were comparable, apart from more females receiving ipsilateral graft placement. The broader female pelvis was probably the determining factor contributing to this outcome. The iSPK group included marginally younger recipients. The ipsilateral group also demonstrated a trend to improved survival of patient, pancreas, and kidney graft, at 1- and 5-year follow-up. There was no difference in complication rates between the 2 groups. CONCLUSIONS There were no significant differences in overall outcomes. iSPK is a safe procedure, which proves similar patient and graft survival as with cSPK. Both procedures have comparable surgical complication rates. iSPK is a safe and quicker procedure that allows for preservation of the contralateral side for potential subsequent transplants.

A single-center experience of post-transplant lymphomas involving the central nervous system with a review of current literature.

BACKGROUND: Central Nervous System (CNS) lymphoma is a rare presentation of post-transplantation lymphoproliferative disorder (PTLD). METHODS: This single center retrospective study reviewed presentations, management and outcomes of CNS lymphomas in kidney transplant patients transplanted 1968 to 2015, and reviews relevant current literature. RESULTS: We identified 5773 adult kidney transplant recipients of who 90 had a PTLD diagnosis confirmed. CNS disease was diagnosed in 6/90 (7%). Median age at presentation was 60 years and time from transplant 4.5 years. Immunosuppression at diagnosis included mycophenolate mofetil and prednisolone without calcineurin inhibitor in 5/6 patients. Histological analysis diagnosed monomorphic disease in 5/6, and one polymorphic case with tissue positive for Epstein-barr virus (EBV) in 5/6 cases. Despite this 2/4 EBV positive cases had no detectable EBV in peripheral blood or CSF at diagnosis. Treatment strategies included reduction in immunosuppression in all, chemotherapy (n=5), radiotherapy (n=3), Cytotoxic T-Lymphocytes and Craniotomy (n=2). Patient survival was 40% at 1 year with CTL treated patients surviving beyond three years from diagnosis. CONCLUSION: This study supports observational data suggesting MMF treated patients without CNI may have increased risk of disease. Peripheral blood screening for EBV DNAemia does not seem helpful in early identification of those at risk.

Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol.

INTRODUCTION: High intrapatient variability (IPV) in tacrolimus trough levels has been shown to be associated with higher rates of renal transplant failure. There is no consensus on what level of IPV constitutes a risk of graft loss. The establishment of such a threshold could help to guide clinicians in identifying at-risk patients to receive targeted interventions to improve IPV and thus outcomes. METHODS AND ANALYSIS: A multicentre Transplant Audit Collaborative has been established to conduct a retrospective study examining tacrolimus IPV and renal transplant outcomes. Patients in receipt of a renal transplant at participating centres between 2009 and 2014 and fulfilling the inclusion criteria will be included in the study. The aim is to recruit a minimum of 1600 patients with follow-up spanning at least 2 years in order to determine a threshold IPV above which a renal transplant recipient would be considered at increased risk of graft loss. The study also aims to determine any national or regional trends in IPV and any demographic associations. ETHICS AND DISSEMINATION: Consent will not be sought from patients whose data are used in this study as no additional procedures or information will be required from participants beyond that which would normally take place as part of clinical care. The study will be registered locally in each participating centre in line with local research and development protocols. It is anticipated that the results of this audit will be disseminated locally, in participating NHS Trusts, through national and international meetings and publications in peer-reviewed journals.