Prevalence of donor-transmitted atherosclerosis—Clinical utility of intracoronary ultrasound early after heart transplantation. A single-center study

AbstractIntroductionCoronary allograft vasculopathy (CAV) is one of the main factors limiting long-term survival following orthotopic heart transplantation (HTx). Whether or not and, if so, how donor-transmitted atherosclerosis (DCA) affects the post-transplant course of the allograft recipient is still unclear. Conventional coronary angiography is a moderately accurate technique for DCA detection as it will reveal only the more gross morphological lesions. By contrast, intravascular ultrasound (IVUS) has been shown to be a much more sensitive technique for CAV and DCA detection. In our study we sought to determine the prevalence of DCA in our HTx patient population and identify main risk factors of DCA based on donor characteristics.Patients and methodsWe performed a retrospective analysis of data of 119 patients (92 men, 27 women) undergoing transplantation in our center from August 2006 through September 2012, who had survived their first post-transplant month and had coronary angiography and IVUS.ResultsDCA was present in 39 patients, and not documented in 80 patients. The main risk factors for DCA included donor age, cigarette smoking, and hypertension; the other parameters were not shown to be statistically significant. In-hospital mortality was low in both groups (DCA positive and DCA negative), with one patient dying in either group. One-year mortality rates post-HTx were likewise almost identical in both groups (15.4% and 15% in DCA positive and negative, respectively).ConclusionThe prevalence of DCA in our patients was 32.8%, with major risk factors for DCA including donor age, cigarette smoking, and hypertension. As age seems to be the strongest predictor, coronary angiography should be a routine examination in individuals aged over 40 years; the examination should be considered in younger individuals with a cluster of several of risk factors. The 1-year survival in this selected patient population was identical in both groups, the implication being that the diagnosis of DCA had no effect on 1-year survival post-HTx

The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence

There are no commercially available vaccines against human protozoan parasitic diseases, despite the success of vaccination-induced long-term protection against infectious diseases. East Coast fever, caused by the protist Theileria parva, kills one million cattle each year in sub-Saharan Africa, and contributes significantly to hunger and poverty in the region. A highly effective, live, multi-isolate vaccine against T. parva exists, but its component isolates have not been characterized. Here we sequence and compare the three component T. parva stocks within this vaccine, the Muguga Cocktail, namely Muguga, Kiambu5 and Serengeti-transformed, aiming to identify genomic features that contribute to vaccine efficacy.; We find that Serengeti-transformed, originally isolated from the wildlife carrier, the African Cape buffalo, is remarkably and unexpectedly similar to the Muguga isolate. The 420 detectable non-synonymous SNPs were distributed among only 53 genes, primarily subtelomeric antigens and antigenic families. The Kiambu5 isolate is considerably more divergent, with close to 40,000 SNPs relative to Muguga, including <8,500 non-synonymous mutations distributed among <1,700 (42.5 %) of the predicted genes. These genetic markers of the component stocks can be used to characterize the composition of new batches of the Muguga Cocktail.; Differences among these three isolates, while extensive, represent only a small proportion of the genetic variation in the entire species. Given the efficacy of the Muguga Cocktail in inducing long-lasting protection against infections in the field, our results suggest that whole-organism vaccines against parasitic diseases can be highly efficacious despite considerable genome-wide differences relative to the isolates against which they protect

Additional file 3: Table S3. of The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence

Comprehensive lists of variants identified in T. parva Serengeti-transformed and Kiambu5 stocks, relative to the reference T. parva Muguga isolate, respectively. (XLSX 71 kb

Additional file 1: Table S1. of The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence

Sequencing data statistics for three T. parva stocks. (XLSX 49 kb

Additional file 2: Table S2. of The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence

Comprehensive lists of variants identified in T. parva Serengeti-transformed and Kiambu5 stocks, relative to the reference T. parva Muguga isolate, respectively. (XLSX 65 kb

Baseline characteristics.

1<p>Categorical parameters are described by absolute number and percentage of patients in given category; continuous variables are described by median (5^th; 95^th percentile).</p>2<p>Overall statistical significance of differences among groups is based on Mann-Whitney test for continuous variables and ML chi-square test for categorical variables,</p>3<p>Creatinine clearance was estimated according to MDRD formula;</p>*<p>statistically significant.</p><p>BMI – Body mass index, TIA – Transitory ischemic attack, EF LV – Ejection fraction of left ventricle, PA systolic – Pulmonary artery systolic pressure, AVA – Aortic valve area.</p

Evaluation of additional benefit of biomarkers to clinical model (EuroSCORE) by net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) for prediction of combined safety endpoint at 30 days and combined endpoint (0–365 days) in groups of patients treated by TAVI and by SAVR and TAVI.

<p>Evaluation of additional benefit of biomarkers to clinical model (EuroSCORE) by net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) for prediction of combined safety endpoint at 30 days and combined endpoint (0–365 days) in groups of patients treated by TAVI and by SAVR and TAVI.</p

ROC analysis for prediction of endpoints in patients treated with TAVI.

<p>ROC analysis for prediction of endpoints in patients treated with TAVI.</p

Risk assessment plot of the performance comparison between reference EuroSCORE model and new EuroSCORE+MDA model for combined safety endpoint at 30 days in TAVI group (N = 29).

<p>Risk assessment plot of the performance comparison between reference EuroSCORE model and new EuroSCORE+MDA model for combined safety endpoint at 30 days in TAVI group (N = 29).</p