Residual venous obstruction, alone and in combination with D-dimer, as a risk factor for recurrence after anticoagulation withdrawal following a first idiopathic deep vein thrombosis in the prolong study.

OBJECTIVE: This study aims to assess the predictive value of residual venous obstruction (RVO) for recurrent venous thrombo-embolism (VTE) in a study using D-dimer to predict outcome. DESIGN: This is a multicentre randomised open-label study. METHODS: Patients with a first episode of idiopathic VTE were enrolled on the day of anticoagulation discontinuation when RVO was determined by compression ultrasonography in those with proximal deep vein thrombosis (DVT) of the lower limbs. D-dimer was measured after 1 month. Patients with normal D-dimer did not resume anticoagulation while patients with abnormal D-dimer were randomised to resume anticoagulation or not. The primary outcome measure was recurrent VTE over an 18-month follow-up. RESULTS: A total of 490 DVT patients were analysed (after excluding 19 for different reasons and 118 for isolated pulmonary embolism (PE)). Recurrent DVT occurred in 19% (19/99) of patients with abnormal D-dimer who did not resume anticoagulation and 10% (31/310) in subjects with normal D-dimer (adjusted hazard ratio: 2.1; p = 0.02). Recurrences were similar in subjects either with (11%, 17/151) or without RVO (13%, 32/246). Recurrent DVT rates were also similar for normal D-dimer, with or without RVO, and for abnormal D-dimer, with or without RVO. CONCLUSIONS: Elevated D-dimer at 1 month after anticoagulation withdrawal is a risk factor for recurrence, while RVO at the time of anticoagulation withdrawal is not.

Systemic-onset juvenile idiopathic arthritis: the changing life of a rare disease.

Systemic-onset juvenile idiopathic arthritis (SoJIA), sometimes called Still's disease, is a systemic inflammatory disease classified within the spectrum of juvenile idiopathic arthritis (JIA). It is an orphan disease with often a chronic course and a major impact on the affected children and their families. This disorder is unique in terms of clinical manifestations, prognosis and response to conventional immunosuppressants. The objectives of this review are to describe SoJIA and emphasise the recent advances in the pathogenesis and treatment, which have transformed the care and the prognosis of this potentially life-threatening paediatric condition.

Urinary low-molecular-weight protein excretion in pediatric idiopathic nephrotic syndrome.

BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most common causes of idiopathic nephrotic syndrome (INS). We have evaluated the reliability of urinary neutrophil-gelatinase-associated lipocalin (uNGAL), urinary alpha1-microglobulin (uα1M) and urinary N-acetyl-beta-D-glucosaminidase (uβNAG) as markers for differentiating MCD from FSGS. We have also evaluated whether these proteins are associated to INS relapses or to glomerular filtration rate (GFR). METHODS: The patient cohort comprised 35 children with MCD and nine with FSGS; 19 healthy age-matched children were included in the study as controls. Of the 35 patients, 28 were in remission (21 MCD, 7 FSGS) and 16 were in relapse (14 MCD, 2 FSGS). The prognostic accuracies of these proteins were assessed by receiver operating characteristic (ROC) curve analyses. RESULTS: The level of uNGAL, indexed or not to urinary creatinine (uCreat), was significantly different between children with INS and healthy children (p = 0.02), between healthy children and those with FSGS (p = 0.007) and between children with MCD and those with FSGS (p = 0.01). It was not significantly correlated to proteinuria or GFR levels. The ROC curve analysis showed that a cut-off value of 17 ng/mg for the uNGAL/uCreat ratio could be used to distinguish MCD from FSGS with a sensitivity of 0.77 and specificity of 0.78. uβNAG was not significantly different in patients with MCD and those with FSGS (p = 0.86). Only uα1M, indexed or not to uCreat, was significantly (p < 0.001) higher for patients in relapse compared to those in remission. CONCLUSIONS: Our results indicate that in our patient cohort uNGAL was a reliable biomarker for differentiating MCD from FSGS independently of proteinuria or GFR levels.

Complications of systemic juvenile idiopathic arthritis: risk factors and management recommendations.

Systemic juvenile idiopathic arthritis (SJIA) is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. Systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that SJIA is an autoinflammatory disorder. IL-1 and IL-6 play a major role in the pathogenesis of SJIA, and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. However, complications of SJIA, including macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation, continue to be a major issue in SJIA patients' care. Translational research leading to a profound understanding of the cytokine crosstalk in SJIA and the identification of risk factors for SJIA complications will help to improve long-term outcome.

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures.

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4pmol/L) and aBMD values at the total hip (0.989 vs 0.971g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

The difference of disease perception by juvenile idiopathic arthritis patients and their parents : analysis of the JAMAR questionnaire.

BACKGROUND: The JAMAR (Juvenile Arthritis Multidimensional Assessment Report) has been developed to evaluate the perception of the patient and his parents on different items: well-being, pain, functional status, quality of life, disease activity, disease course, side effects of medication, therapeutic compliance and satisfaction with illness outcome. Our aim was to compare disease's perception by JIA patients and their parents. METHODS: We included into the study 100 consecutive patients over 7 years of age. We asked both parent and child to complete the JAMAR questionnaire. For each patient we recorded demographic and disease related data. We examined the level of disagreement between children and parents for the quantitative items of the JAMAR: VAS Pain, VAS Disease Activity, VAS Well Being, Juvenile Arthritis Functional Score, HRQoL. Then we looked for a relation between discordance-rate and demographic and clinical variables. RESULTS: Children and parents' median scores for all five items were similar. Individual dyads agreement was low, with a large amount of pairs (80) discordant for at least one item. We found higher MD VAS and JADAS in more discordant dyads, suggesting that when the disease is more active discordance between child and parent increase. CONCLUSION: The JAMAR questionnaire is an important tool that helps clinicians to detect divergent child and parent's disease perceptions. It is essential that both patients and parents fill the JAMAR questionnaire for a complete clinical and psychosocial evaluation.

Continuing Medical Education Self-Assessment Questions Vol. 50, No. 1 - January 2014. Actual evidence in the medical approach to adolescents with idiopathic scoliosis

Idiopathic scoliosis (IS) is a three-dimensional deformity of the spine and trunk. The most common form involve ado- lescents (AIS). The prevalence for AIS is 2-3% of the population, with 1 out of 6 patients requiring treatment of which 25% progress to surgery. Physical and rehabilitation medicine (PRM) plays a primary role in the so-called conservative treatment of adolescents with AIS, since all the therapeutic tools used (exercises and braces) fall into the PRM domain. According to a Cochrane systematic review there is evidence in favor of bracing, even if it is of low quality. Another shows that there is evidence in favor of exercises as an adjunctive treatment, but of low quality. Three meta-analysis have been published on bracing: one shows that bracing does not reduce surgery rates, but studies with bracing plus exercises were not included and had the highest effectiveness; another shows that full time is better than part-time bracing; the last focuses on observational studies following the SRS criteria and shows that not all full time rigid bracing are the same: some have the highest effectiveness, others have less than elastic and nighttime bracing. Two very important RCTs failed in recruitment, showing that in the field of bracing for scoliosis RCTs are not accepted by the patients. Consensuses by the international Society on Scoliosis Orthopedic and Rehabilitation Treatment (SOSORT) show that there is no agree- ment among experts either on the best braces or on their biomechanical action, and that compliance is a matter of clinical more than patients' behavior (there is strong agreement on the management criteria to achieve best results with bracing). A systematic review of all the existing studies shows effectiveness of exercises, and that auto-correction is the main goal of exercises. A systematic review shows that there are no studies on manual treatment. Research on conservative treat- ment of AIS has continuously decreased since the 1980s, but this trend changed only recently. The SOSORT Guidelines offers the actual standard of conservative care.

Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study.

STUDY OBJECTIVES: Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population. METHODS: We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview. RESULTS: An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls. CONCLUSIONS: We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other hypersomniacs, without any change in alcohol dependence or abuse frequency. Although disruption of hypocretin signaling in rodents reduces drug-seeking behaviors, our results do not support that hypocretin deficiency constitutes a protective factor against the development of drug addiction in humans.

Pédiatrie [Pediatry].

During the previous year, several changes occurred in paediatric patient's management. The new PALS recommendations redefine the rhythm and the rate between cardiac massage and ventilation as well as the indications for defibrillation. The choice of the test for Helicobacter Pylori depends on the age of the patient and on the clinical situation. New anti-hypertensive drugs allow to limit the progression of chronic renal disease with hyper-tension and/or proteinuria. The choice between immunoglobulins, steroids, splenectomy and rituximab to treat chronic thrombocytopenic purpura treatment is a therapeutic challenge. Finally, a new approach is presented for diagnosis and treatment of iron overload in chronic hemoglobinopathies.

Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons.

Evolutionary survival of a species is largely a function of its reproductive fitness. In mammals, a sparsely populated and widely dispersed network of hypothalamic neurons, the gonadotropin-releasing hormone (GnRH) neurons, serve as the pilot light of reproduction via coordinated secretion of GnRH. Since it first description, human GnRH deficiency has been recognized both clinically and genetically as a heterogeneous disease. A spectrum of different reproductive phenotypes comprised of congenital GnRH deficiency with anosmia (Kallmann syndrome), congenital GnRH deficiency with normal olfaction (normosmic idiopathic hypogonadotropic hypogonadism), and adult-onset hypogonadotropic hypogonadism has been described. In the last two decades, several genes and pathways which govern GnRH ontogeny have been discovered by studying humans with GnRH deficiency. More importantly, detailed study of these patients has highlighted the emerging theme of oligogenicity and genotypic synergism, and also expanded the phenotypic diversity with the documentation of reversal of GnRH deficiency later in adulthood in some patients. The underlying genetic defect has also helped understand the associated nonreproductive phenotypes seen in some of these patients. These insights now provide practicing clinicians with targeted genetic diagnostic strategies and also impact on clinical management.