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Alemtuzumab induction with tacrolimus maintenance monotherapy and short-course steroid use provides a simple, safe, and effective immunosuppressive regimen for renal transplantation.

IntroductionImmunohistochemical staining for C4d in peritubular capillaries has been part of antibody-mediated rejection (AbMR) definition in the Banff Classification for Allograft Pathology since 2003. However, it has limited sensitivity and specificity, therefore the clinical significance of C4d-positive biopsies without evidence of rejection (C4d+ WER) is unknown. We investigated the transcript levels of genes associated with AbMR in C4d+ WER biopsies from both ABO-compatible and incompatible renal transplant patients.MethodsRNA was extracted from formalin-fixed paraffin-embedded renal transplant biopsies (n = 125) and gene expression analysis of 35 AbMR-associated transcripts carried out using the NanoString nCounter system.ResultsAbMR-associated transcripts were significantly increased in samples with AbMR or suspicious AbMR. A subgroup of 17 of 35 transcripts that best distinguished AbMR from C4d-negative biopsies without evidence of rejection was used to study C4d+ WER samples. There was no differential expression between C4d-negative and C4d+ WER from both ABO-incompatible and -compatible transplants. The geometric mean of 17 differentially expressed genes was used to assign the C4d+ WER biopsies a high- or low-AbMR transcript score. Follow-up biopsies showed AbMR within 1 year of initial biopsy in 5 of 7 high-AbMR transcript patients but only 2 of 46 low-AbMR transcript patients. In multivariate logistic regression analysis, elevated transcript levels in a C4d+ WER biopsy were associated with increased odds for biopsy-proven AbMR on follow-up (P = 0.032, odds ratio 16.318), whereas factors including donor-specific antibody (DSA) status and time since transplantation were not.ConclusionGene expression analysis in C4d+ WER samples has the potential to identify patients at higher risk of developing AbMR.

Abstract:This research explores the experiences of five professional practitioners from disciplines including teaching, youth work, sport and health who had become lecturers in Higher Education. Their experiences are considered using Interpretative Phenomenological Analysis and tentative conclusions are reached on the meaning of such experiences for the individuals. The work extends previous studies (Shreeve 2010(Shreeve , 2011 Gourlay 2011a Gourlay , 2011bBoyd & Harris 2010) to consider the relationship between knowledge and influence and how institutional preference for knowledge gained from research impacts on the validity of knowledge derived from professional experience. The research finds shared feelings associated with inauthenticity and loss arising from concerns that the contribution of the professional in Higher Education is undervalued. The research challenges the assumption that professional practitioners adopt the professional identity of a lecturer in Higher Education instead finding that they create their own professional identities in the liminal space between the professional and academic domains, but points to difficulties associated with constructed nature of such professional identities within the institutional structure of a Higher Education institution.

AIMTo analyse the risk factors and outcomes of delayed graft function (DGF) in patients receiving a steroid sparing protocol.METHODSFour hundred and twenty-seven recipients of deceased donor kidney transplants were studied of which 135 (31.6%) experienced DGF. All patients received monoclonal antibody induction with a tacrolimus based, steroid sparing immunosuppression protocol.RESULTSFive year patient survival was 87.2% and 94.9% in the DGF and primary graft function (PGF) group respectively, P = 0.047. Allograft survival was 77.9% and 90.2% in the DGF and PGF group respectively, P < 0.001. Overall rejection free survival was no different between the DGF and PGF groups with a 1 and 5 year rejection free survival in the DGF group of 77.7% and 67.8% compared with 81.3% and 75.3% in the PGF group, P = 0.19. Patients with DGF who received IL2 receptor antibody induction were at significantly higher risk of rejection in the early post-transplant period than the group with DGF who received alemtuzumab induction. On multivariate analysis, risk factors for DGF were male recipients, recipients of black ethnicity, circulatory death donation, preformed DSA, increasing cold ischaemic time, older donor age and dialysis vintage.CONCLUSIONAlemtuzumab induction may be of benefit in preventing early rejection episodes associated with DGF. Prospective trials are required to determine optimal immunotherapy protocols for patients at high risk of DGF.