Citations

AbstractIntroductionSolid organ transplant recipients have a higher frequency of tuberculosis (TB) than the general population, with mortality rates of approximately 30%. Although donor‐derived TB is reported to account for <5% of TB in solid organ transplants, the source of Mycobacterium tuberculosis infection is infrequently determined.MethodsWe report 3 new cases of pulmonary TB in lung transplant recipients attributed to donor infection, and review the 12 previously reported cases to assess whether cases could have been prevented and whether any cases that might occur in the future could be detected and investigated more quickly. Specifically, we evaluate whether opportunities existed to determine TB risk on the basis of routine donor history, to expedite diagnosis through routine mycobacterial smears and cultures of respiratory specimens early post transplant, and to utilize molecular tools to investigate infection sources epidemiologically.FindingsOn review, donor TB risk was present among 7 cases. Routine smears and cultures diagnosed 4 asymptomatic cases. Genotyping was used to support epidemiologic findings in 6 cases.ConclusionValidated screening protocols, including microbiological testing and newer technologies (e.g., interferon‐gamma release assays) to identify unrecognized M. tuberculosis infection in deceased donors, are warranted.

ABSTRACTBackgroundVariants within the leucine‐rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine‐rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late‐onset sporadic disorders like Parkinson's disease.MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine‐rich repeat kinase 2 gene across 23 different sites in 15 countries.ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K‐R1398H‐K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups.ConclusionsEstablishing individual patient‐based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. © 2013 International Parkinson and Movement Disorder Society

The Fontan procedure represents the final stage of the transition to single ventricle physiology. Conversion of very complex congenital heart anatomy, such as hypoplastic left heart syndrome, double-outlet right ventricle or double-inlet left ventricle, to a single ventricle has grown in popularity as morbidity and mortality have improved. As these patients grow, survivors are at risk for impaired ventricular dysfunction, plastic bronchitis, protein-losing enteropathy and late failure. Late failing Fontan patients represent a particularly vexing scenario for clinicians, as the only durable treatment option is cardiac transplantation. However, in the short-term, some of these patients require support beyond medical management, with mechanical circulatory support via extracorporeal life support or a ventricular assist device. We report the successful bridge of an adolescent female post-Fontan conversion with late severe cardiac failure. The patient was initially resuscitated with extracorporeal life support, transitioned to a single Berlin Heart EXCOR® ventricular assist device and, subsequently, underwent successful cardiac transplantation.

Background— Despite complete interruption of antegrade coronary artery flow in the setting of a chronic total occlusion (CTO), clinical recognition of myocardial infarction is often challenging. Using cardiac MRI, we investigated the frequency and extent of myocardial infarction in patients with CTO, and assessed their relationship with regional systolic function and the extent of angiographic collateral flow. Methods and Results— We included 170 consecutive patients (median age, 62 years) with angiographically documented CTO. Regional late gadolinium enhancement and wall motion score index were assessed by cardiac MRI with the use of a 17-segment model. Angiographic collateral flow was assessed by the collateral connection grade and the Rentrop score. Evidence of previous myocardial infarction was found in 25% of patients by ECG Q waves, in 69% by regional wall motion abnormality, and in 86% of patients by late gadolinium enhancement. Increased angiographic collateral flow was associated with a lower frequency of Q waves on ECG, and a lower regional wall motion score index, late gadolinium enhancement volume (%), and degree of late gadolinium enhancement transmurality (all P <0.001), as well. Conclusions— The frequency of myocardial infarction in territories subtended by CTO is significantly higher than previously recognized. The degree of myocardial injury downstream epicardial CTO is inversely correlated with the degree of angiographic collaterals.

Background Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive. Methods and results We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort. Conclusions Our study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.