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Abstract Background Transplantation offers the best survival for patients with end stage organ disease. Transplant of hepatitis C virus (HCV) nucleic acid test (NAT) positive organs into negative recipients is a novel strategy that can expand the donor pool. We aim to evaluate our centre’s experience. Methods We preformed a retrospective review of anti-HCV NAT positive and negative organs into negative recipients transplanted over 27 months. Primary outcome was the success rate of eradication of HCV post-transplant. Secondary outcomes were rate of transmission of HCV, treatment adverse events, and graft failure. Results 33 anti-HCV positive organs were transplanted into negative recipients. 22 (66.7%) were NAT positive. Median recipients age was 49 years (interquartile range [IQR] 44.5–62.0) with the majority being males (57.6%). NAT positive organ transplantations included 16 kidneys, 3 livers, 1 kidney-pancreas, 1 liver-kidney, and 1 heart. The most common HCV genotype was 1a (59.1%). The median time to initiating therapy was 41.5 days. SVR12 was 100% in patients who finished therapy. There were no adverse events with therapy and no graft failure. Conclusions Anti-HCV NAT positive organ transplantation into negative recipients is safe with excellent eradication rates and no significant adverse events or graft failure. This would expand donor pool to close the gap between supply and demand.

Background: In Ontario, kidney transplants have risen by 4% annually in recent years. An understanding of how this will affect the future annual number of posttransplant follow-up visits informs how to organize and deliver care. Objective: We projected the required number of annual posttransplant follow-up nephrology visits to inform posttransplant care delivery. Design: Population-based retrospective cohort study. Setting: Linked databases from Ontario, Canada (population 14 million). Patients: Incident kidney transplant recipients from years 2008 to 2013. Measurements: Frequency, distance traveled, and current and projected visits for posttransplant follow-up. Methods: Assuming a graft survival of 13 years and using the mean number of posttransplant clinic visits in years 1, 2, and 3, we forecasted the number of clinic visits needed in the year 2027. Results: Using data from 2443 recipients, the mean (SD) number of clinic visits per recipient was 14.0 (9.2) in the first year after transplant, and 3.9 (6.2) and 3.0 (5.3) in the second and third year, respectively. If transplant rates rise by 4% per year until 2027, the estimated annual visits number will increase from 30 622 to 43 948. The median (25th, 75th percentile) distance between transplant center and patient’s home was 30 (13, 65) km. The median round-trip travel distance for these visits in the first year after transplantation was 603 km per recipient, and median driving cost was Can$344 (2017). Limitations: Regarding patient expense, limitations include that distances traveled were calculated orthodromically, and we did not account for patient cost of follow-up beyond that of vehicular travel. Regarding follow-up projections, limitations include the assumption that graft life span will not change, follow-up patterns do not differ between donor kidney type, and we did not survey stakeholders as to their preferred method of follow-up. Conclusion: We quantified the increase in posttransplant visits when regional annual rates of transplantation rise. Strategies recognizing the burden of these visits may enhance patient-centered care, as it is unclear how some patients manage costs, nor how the current health care system will manage the demand.

Background: Renal transplant recipients (RTRs) are at significantly higher risk for morbidity and mortality compared with the general population, largely attributed to cardiovascular disease (CVD). Previous estimates of CVD events have come from health care databases and retrospective studies. Objective: The objective of this study was to prospectively determine the prevalence of risk factors and incidence of CVD events in a Canadian cohort of RTRs. Design: Study of Cardiovascular Outcomes in Renal Transplantation (SCORe) was a prospective, longitudinal, multicenter observational study. Setting: Adult RTRs were recruited from 6 participating transplant sites in Ontario, Canada. Patients: Eligible patients were those receiving a living or deceased donor renal transplant. Patients who received simultaneous transplant of any other organ were excluded. Measurements: Primary outcomes included myocardial infarction (MI) defined by American College of Cardiology (ACC-MI) criteria, and major adverse cardiac events (MACE), defined as cardiovascular (CV) death, ACC-MI, coronary revascularization, and nonhemorrhagic stroke. CV events were adjudicated by a single, independent cardiologist. Methods: CV and transplant-specific risk factors that predict MACE and ACC-MI were identified by stepwise regression analysis using the Cox proportional hazards model. Results: A total of 1303 patients enrolled across 6 transplant centers were followed for 4.5 ± 1.6 years (mean ± SD). Incidence of MACE was 7.0%, with significant independent predictors/risk factors including age, diabetes, coronary revascularization, nonhemorrhagic stroke, and renal replacement therapy (RRT). ACC-MI incidence was 4.0%, with significant independent predictors/risk factors including age, coronary revascularization, and duration of RRT in excess of the median value (2.91 years). Limitations: Patients were recruited from a single province, so may not reflect the experience of RTRs in other areas of Canada. Conclusions: Using a prospective design and rigorous methodology, this study found that the incidence of CV events after renal transplantation was elevated relative to the general Canadian population and was comparable with that reported in patient registries, thus helping validate the utility of retrospective analysis in this field. SCORe highlights the importance of monitoring RTRs for traditional cardiac and transplant-specific CV risk factors to help prevent CV morbidity and mortality. Further research is needed to investigate a broader range of potential risk factors and their combined effects on incident CV events.

Ischemia reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation, leading to graft failures and lower long-term survival rate of the recipient. Several studies have demonstrated that microRNAs (miRNAs) are vital regulators of signalling pathways involved in I/R injury. The present study aims to quantify the altered expression levels of miRNA and mRNA upon I/R injury in a mouse heart transplantation model, and to investigate whether these miRNA can regulate genes involved in I/R injury. We performed heterotopic heart transplantation on mouse models to generate heart tissue samples with I/R and non-I/R (control). The expression levels of miRNAs as well as genes were measured in heart grafts by microarray and real time RT-PCR. miRNA alteration in cardiomyocytes exposed to hypoxia was also detected by qRT-PCR. We observed significant alterations in miRNA and gene expression profile after I/R injury. There were 39 miRNAs significantly downregulated and 20 upregulated up to 1.5 fold in heart grafts with I/R injury compared with the grafts without I/R. 48 genes were observed with 3 fold change and p

A DNA construct containing the cholera toxin B subunit (CTB) gene genetically fused to a nucleotide sequence encoding three copies of tandemly repeated diabetes-associated autoantigen, the B chain of human insulin, was produced and transferred into low-nicotine tobaccos by Agrobacterium. Integration of the fusion gene into the plant genome was confirmed by polymerase chain reaction (PCR). The results of immunoblot analysis verified the synthesis and assembly of the fusion protein into pentamers in transgenic tobacco. GM1–ELISA showed that the plant-derived fusion protein retained GM1–ganglioside receptor binding specificity. The fusion protein accounted for 0.11% of the total leaf protein. The production of transgenic plants expressing CTB–InsB3 offers a new opportunity to test plant-based oral antigen therapy against autoimmune diabetes by inducing oral tolerance. [ABSTRACT FROM AUTHOR]

Background. Cytomegalovirus (CMV)-seronegative recipients of renal allografts from CMV-seropositive donors (D+/R-) have a higher rate of acute rejection than other renal transplant recipients. A relationship between CMV infection/disease and chronic allograft nephropathy (CAN) has been proposed from animal studies, although human studies have been inconclusive. The objective of this study was to determine if CMV seromatching has an effect on renal allograft function and allograft survival.Methods. A retrospective single centre study was carried out in 333 first cadaveric transplant recipients from January 1, 1991 to December 31, 1997. The primary end-point was creatinine clearance at 3 years post-transplant in groups based on CMV seromatching. The secondary end-point was renal allograft survival.Results. Mean creatinine clearance 3 years post-transplant was 53.4?ml/min/1.73?m2 of body surface area. There was no significant difference in the mean creatinine clearance for groups formed on the basis of CMV seromatching. Delayed graft function and acute rejection were associated with a lower creatinine clearance at 3 years and reduced overall graft survival [hazard ratios 2.35 (1.563.54) (P<0.001) and 1.57 (1.02.46) (P = 0.046), respectively]. Considering the end-point of graft loss due to acute rejection (censoring for death with a functioning graft) identified the D+/R- group as having an increased hazard of graft loss due to acute rejection [hazard ratio 3.12 (1.168.57) (P = 0.024)].Conclusions. The D+/R- group does not appear to have poorer renal allograft function 3 years post-transplant. This group does, however, have an increased risk of early allograft loss due to acute rejection. [ABSTRACT FROM AUTHOR]