No abstract

In this population-based prospective follow-up study, children undergoing solid organ transplantation had a highly elevated risk for fractures: The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p < 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p < 0.001) in the study group compared with the control population. Thus, screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied. Introduction:The incidence and predictors of fractures after solid organ transplantation are not well documented in the pediatric age group. Materials and Methods: A total of 196 children, which is 93% of patients surviving kidney, liver, and heart transplantation in our country, participated in a retrospective chart review at enrollment followed by a 5-year prospective follow-up study between January 1999 and December 2004. Hospital and medical records were reviewed. All children underwent clinical examinations and answered questionnaires concerning fracture history at the beginning and at the end of the prospective follow-up. Radiographs of the thoracic and lumbar spine were obtained. The fracture incidence was compared with data obtained from public health registries. Results: Seventy-five (38%) of the transplant patients suffered from a total of 166 fractures after organ transplantation. The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p < 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p < 0.001) in the study group compared with the control population. The age-and sex-adjusted hazard ratios (95% CI) were 61.3 (40.7-92.4 were the most significant independent risk factors. Conclusions: Children undergoing solid organ transplantation have a highly elevated risk for fractures. Screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied.

Occlusive vasculopathy with intimal hyperplasia and plexogenic arteriopathy are severe histopathological changes characteristic of pulmonary arterial hypertension (PAH). Although a phenotypic switch in pulmonary endothelial cells (ECs) has been suggested to play a critical role in the formation of occlusive lesions, the pathobiology of this process is poorly understood. The goal of this study was to identify novel molecular mechanisms associated with EC dysfunction and PAH-associated bone morphogenetic protein receptor 2 (BMPR2) deficiency during PAH pathogenesis. A bioinfomatics approach, patient samples, and in vitro experiments were used. By combining a metaanalysis of human idiopathic PAH (iPAH)-associated gene-expression microarrays and a unique gene expression-profiling technique in rat endothelium, our bioinformatics approach revealed a PAH-associated dysregulation of genes involving chromatin organization, DNA metabolism, and repair. Our hypothesis that altered DNA repair and loss of genomic stability play a role in PAH was supported by in vitro assays where pulmonary ECs from patients with iPAH and BMPR2-deficient ECs were highly susceptible to DNA damage. Furthermore, we showed that BMPR2 expression is tightly linked to DNA damage control because excessive DNA damage leads to rapid down-regulation of BMPR2 expression. Moreover, we identified breast cancer 1 (BRCA1) as a novel target for BMPR2 signaling and a novel modulator of pulmonary EC homeostasis. We show here that BMPR2 signaling plays a critical role in the regulation of genomic integrity in pulmonary ECs via genes such as BRCA1. We propose that iPAH-associated EC dysfunction and genomic instability are mediated through BMPR2 deficiency-associated loss of DNA damage control.

In patients with adolescent idiopathic scoliosis who undergo surgery with Harrington instrumentation, the overall long-term clinical outcome does not correlate with the radiologic outcome. However, a significant inverse correlation was found between the magnitude of the primary thoracic curve at follow-up assessment and the scores for questions on cosmetic matters in the Scoliosis Research Society questionnaire. Spine mobility is diminished as a result of spondylodesis, but the patients perform, on the average, as well as the normal population in nondynamometric trunk strength measurements.