Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

Longitudinal Evaluation of Bone Mineral Density and Bone Metabolism Markers in Patients with Indolent Systemic Mastocytosis Without Osteoporosis.

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.

Prevalence, pathogenesis, and treatment options for mastocytosis-related osteoporosis.

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.

Xq27 FRAXA locus is a strong candidate for dyslexia: evidence from a genome-wide scan in French families.

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.

Perioperative intra- and extravascular volume in liver transplant recipients.

UNLABELLED: 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 oxygen fraction ratio (PaO(2)/FiO(2)). 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 PaO(2)/FiO(2) 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 PaO(2)/FiO(2). 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 PaO(2)/FiO(2).

[Psychocognitive and psychiatric disorders associated with developmental dyslexia: A clinical and scientific issue]. / Les troubles psychiatriques et psychocognitifs associés à la dyslexie de développement : un enjeu clinique et scientifique.

INTRODUCTION: Dyslexia is a complex neurodevelopemental disorder that affects 5 to 10% of school-age children. This condition consists in a specific learning disability with a neurological origin. These learning difficulties are unexpected in relation to other cognitive abilities and the provision of efficient classroom instruction. A range of neurobiological investigations suggests that disruption of the parieto-temporo-occipital systems underlies a failure of skilled reading to develop. The observation that dyslexia is both a familial and heritable problem was made early on and was confirmed by twin studies. They also suggested that both genetic and environmental factors are involved. Several loci have been implicated in dyslexia, notably on chromosomes 2, 3, 6, 15 and 18 and some candidate genes have been proposed, but no functional mutation has yet been identified. LITERATURE REVIEW: Dyslexia seldom appears isolated and dyslexic people are very likely to present other kinds of learning disabilities or psychiatric disorders. Specific language impairment, often with a mild outcome, is the most frequently associated with dyslexia. Indeed, late language development is often reported by dyslexic patients and also occurs more frequently among their siblings. Genetic linkage studies suggest some common genetic factor underlying this comorbidity. Dyscalculia is associated with dyslexia in 25% of cases, but most people with dyscalculia do not have any sign of dyslexia. The question of whether dyscalculia associated with dyslexia and dyscalculia itself rely on the same cognitive impairment is still controversial. Impaired motor development is also a common feature that affects nearly 50% of dyslexics and dyslexia is frequent among dyspraxic patients. This association raises the discussion on the role of motor impairment in dyslexia's physiopathology and the cerebellar theory of dyslexia. Beyond its link with other learning disorders, the study of dyslexia's comorbidity highlights psychopathological issues. ADHD is the most frequent psychiatric disorder associated with dyslexia. Underpinnings of this link between the two disorders seem to rely on common cognitive and genetic factors. Some authors have proposed a candidate gene ADRA2A to determine the condition including ADHD and dyslexia. In addition, dyslexics are exposed to a higher risk of anxiodepressive and behavioural disorders. Dyslexic children experience three times more behavioural disorders and one third of children with behavioural problems turn out to be affected by dyslexia. The literature study reveals inconsistent findings about depressed mood among dyslexics, but evidence of a persistent increase in the rate of anxiety disorders. The authors put forward the impact of environmental factors to explain these psychiatric comorbidities. CONCLUSION: This review emphasizes dyslexia's comorbidities because they represent an important issue, both from a scientific and clinical point of view. Indeed, for clinicians, children showing multiple learning disabilities have specific reeducation and educational needs and dyslexics have a higher risk of emotional and behavioural disorders. On the other hand, dyslexia's comorbidity study provides a powerful method for researchers to investigate the still unknown physiopathology of dyslexia.

Evaluation of new laryngoscope blade for tracheal intubation, Truview EVO2: a manikin study.

BACKGROUND AND OBJECTIVE: Difficult airways present a clinical challenge for anaesthetists. The Truphatek Truview EVO2 (Truphatek International Ltd, Netanya, Israel) is a new laryngoscope blade used for endotracheal intubation that could be used where there is difficulty in visualizing the laryngeal inlet. METHODS: Twenty anaesthetists (12 trainees and eight consultants) compared the Truphatek Truview EVO2 with a conventional Macintosh size 3 blade. The Trucorp Airsim Bronchi (Trucorp Ltd, Belfast, Northern Ireland, UK) manikin was intubated under normal conditions and under simulated difficult conditions such as tongue inflation and neck rigidity. In each scenario, the Cormack-Lehane grade, time needed for successful intubation, perceived difficulty of tracheal intubation and personal preference of blade were compared. The results were analysed with t-test (time of intubation), Wilcoxon signed-rank sum (Cormack-Lehane grade, ease of manoeuvre, preferred blade) and analysis of variance with Bonferroni correction (augmentation of difficulties in different scenarios). RESULTS: The Truview EVO2 blade allowed the best laryngeal view as judged by the Cormack-Lehane grade (P < 0.05) in two separate situations: under simulated tongue inflation and under simulated neck rigidity. However, this blade did not reduce the intubation time or the ease of tracheal tube placement with respect to conventional Macintosh blade. CONCLUSION: Compared with the classical Macintosh blade, the Truview EVO2 blade allowed a better view of the larynx, but did not facilitate endotracheal intubation in any of the difficult scenarios created with the adjustable manikin and in most scenarios in fact prolonged the intubation time.

The hairy elbows syndrome: clinical and neuroradiological findings.

The hairy elbows syndrome (HES) is a rare congenital phenotype characterized by an abnormal increase in long hairs localized on the upper limbs extensor surfaces. This feature is often associated with short stature, facial asymmetry, dysmorphisms, intrauterine growth retardation (IUGR), and mental and speech delay. We report a case with hypertricosis cubiti associated with infantile spasms, behaviour disorders and cerebral hemisphere asymmetry. Although these findings have not been previously described we are uncertain whether they are unusual or underestimated. However, it is likely that these neurological findings are strongly interrelated leading to a more severe phenotype of the syndrome.