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Systemic Mastocytosis has been long identified as a potential cause of osteoporosis; nevertheless, data regarding longitudinal variation of bone mineral density (BMD) in patients with indolent systemic mastocytosis (ISM) are missing . We studied BMD variation at lumbar spine and proximal hip after 30-month (±6 months) follow-up in a large cohort of patients (83) with ISM without osteoporosis, supplementated with vitamin D and/or calcium when needed. We also analyzed the correlation between variation of BMD, basal serum tryptase levels and bone turnover markers (BTM). Sixty-four percent of our population was male; mean age was 52.1 (±11.5) years. Vitamin D insufficiency (serum levels of 25-OH-vitamin D, 25OHD, lower than 75 nmol/L) was found in more than 70 % of patients. After a follow-up of 30 ± 6 months with only vitamin D (5000-7500 IU weekly of oral cholecalciferol) or calcium (500 mg/die) supplementation when needed, we observed 2.1 % increase in BMD at lumbar spine, with no significant changes at hip. At the end of follow-up, almost 60 % of patients showed 25OHD serum levels still lower than recommended, despite vitamin D supplementation. Reduction in BMD after follow-up significantly correlated with high C-telopeptide of type I collagen serum levels at the time of diagnosis. In patients with ISM without osteoporosis, a routinary BMD evaluation within a time <2 years is not justified, except in the presence of elevated BTM. In these patients, vitamin D supplementation is frequently needed. [ABSTRACT FROM AUTHOR]

Mastocytosis is a rare condition characterized by abnormal mast cell proliferation and a broad spectrum of manifestations, including various organs and tissues. Osteoporosis is one of the most frequent manifestations of systemic mastocytosis, particularly in adults. Osteoporosis secondary to systemic mastocytosis is a cause of unexplained low bone mineral density that should be investigated when accompanied by suspicious clinical elements. Bone involvement is often complicated by a high recurrence of fragility fractures, mainly vertebral, leading to severe disability. The mechanism of bone loss is the result of different pathways, not yet fully discovered. The main actor is the osteoclast with a relative or absolute predominance of bone resorption. Among the stimuli that drive osteoclast activity, the most important one seems to be the RANK-RANKL signaling, but also histamine and other cytokines play a significant role in the process. The central role of osteoclasts made bisphosphonates, as anti-resorptive drugs, the most rational treatment for bone involvement in systemic mastocytosis. There are a few small studies supporting this approach, with large heterogeneity of drug and administration scheme. Currently, zoledronate has the best evidence in terms of gain in bone mineral density and bone turnover suppression, two surrogate markers of anti-fracture efficacy. [ABSTRACT FROM AUTHOR]

Dyslexia is a frequent neurodevelopmental learning disorder. To date, nine susceptibility loci have been identified, one of them being DYX9, located in Xq27. We performed the first French SNP linkage study followed by candidate gene investigation in dyslexia by studying 12 multiplex families (58 subjects) with at least two children affected, according to categorical restrictive criteria for phenotype definition. Significant results emerged on Xq27.3 within DYX9. The maximum multipoint LOD score reached 3,884 between rs12558359 and rs454992. Within this region, seven candidate genes were investigated for mutations in exonic sequences ( CXORF1, CXORF51, SLITRK2, FMR1, FMR2, ASFMR1, FMR1NB), all having a role during brain development. We further looked for 5′UTR trinucleotide repeats in FMR1 and FMR2 genes. No mutation or polymorphism co-segregating with dyslexia was found. This finding in French families with Dyslexia showed significant linkage on Xq27.3 enclosing FRAXA, and consequently confirmed the DYX9 region as a robust susceptibility locus. We reduced the previously described interval from 6.8 (DXS1227-DXS8091) to 4 Mb also disclosing a higher LOD score. [ABSTRACT FROM AUTHOR]

Abstract: Assessing adequate volemia to avoid fluid overload and pulmonary edema perioperatively in liver transplantation (LT) is a challenge both for the anesthetist and the intensivist. Volumetric preload indices, such as intrathoracic blood volume index (ITBVI), measured by transpulmonary thermodilution, and continuous end-diastolic volume index (EDVI), measured by pulmonary artery thermodilution, were shown to better reflect preload than central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP). An ITBVI increase soon after the graft reperfusion influenced pulmonary perfusion without an alteration of extravascular lung water index (EVLWI) and without impaired oxygenation. This study was designed to evaluate relationships between CVP, PAOP, ITBVI, EDVI, and stroke volume index (SVI) within 48 hours after LT. We also investigated the relationship between EVLWI and arterial partial pressure of oxygen and inspired oxigen fraction ratio (PaO2/FiO2). Methods: We enrolled 125 patients (103 men and 22 women) undergoing LT. All patients were monitored with the PiCCO system (Pulsion Medical System) and with advanced pulmonary artery catheter connected to the Vigilance System. Hemodynamic-volumetric data were collected upon intensive care unit admission and every 8 hours up to 48 hours. Univariate and multivariate regression models were fitted to assess associations between SVI and EDVI, ITBVI, and filling pressures after adjusting for the right ventricular ejection fraction (RVEF, categorized as ≤30, 31–40, or >40) and the phase of the observation period. We also assessed associations between PaO2/FiO2 and EVLWI. Results: SVI was associated with EDVI, ITBVI, and RVEF. The models showing the best fit to the data were those including EDVI and ITBVI. Neither CVP nor PAOP showed correlation with SVI. EVLWI inversely correlated with PaO2/FiO2. Conclusions: In the first 48 hours after LT, ITBVI and EDVI were associated with SVI assessment, whereas CVP and PAOP were not related. EVLWI significantly inversely correlated with PaO2/FiO2. [Copyright &y& Elsevier]