ESVM guidelines:the diagnosis and management of Raynaud's phenomenon

Regarding the clinical diagnosis of Raynaud's phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud's phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud's phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment

TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis

Objective : Innate lymphoid cells-2 (ILC2) were shown to be involved in the development of lung or hepatic fibrosis. We sought to explore the functional and phenotypic heterogeneity of ILC2 in skin fibrosis within systemic sclerosis (SSc). Methods : Blood samples and skin biopsies from healthy donor or patients with SSc were analysed by immunostaining techniques. The fibrotic role of sorted ILC2 was studied in vitro on dermal fibroblast and further explored by transcriptomic approach. Finally, the efficacy of a new treatment against fibrosis was assessed with a mouse model of SSc. Results : We found that ILC2 numbers were increased in the skin of patients with SSc and correlated with the extent of skin fibrosis. In SSc skin, KLRG1− ILC2 (natural ILC2) were dominating over KLRG1+ ILC2 (inflammatory ILC2). The cytokine transforming growth factor-β (TGFβ), whose activity is increased in SSc, favoured the expansion of KLRG1- ILC2 simultaneously decreasing their production of interleukin 10 (IL10), which regulates negatively collagen production by dermal fibroblasts. TGFβ-stimulated ILC2 also increased myofibroblast differentiation. Thus, human KLRG1- ILC2 had an enhanced profibrotic activity. In a mouse model of SSc, therapeutic intervention-combining pirfenidone with the administration of IL10 was required to reduce the numbers of skin infiltrating ILC2, enhancing their expression of KLRG1 and strongly alleviating skin fibrosis. Conclusion : Our results demonstrate a novel role for natural ILC2 and highlight their inter-relationships with TGFβ and IL10 in the development of skin fibrosis, thereby opening up new therapeutic approaches in SSc

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Chronic kidney disease and the short-term risk of mortality and amputation in patients hospitalized for peripheral artery disease

International audienceObjective: The aim of the present study was to determine the prevalence of chronic kidney disease (CKD) and its prognostic value in patients hospitalized for lower extremity peripheral artery disease (PAD).Methods: Data from the COhorte des Patients ARTériopathes registry, a prospective multicenter, observational study of consecutive patients hospitalized for PAD in academic hospitals of southwestern France, were analyzed. All the subjects were in Rutherford grade ≥ 3, and 55.6% were in grade ≥ 5-6. Associations between CKD and 1-year mortality, as well as amputation rates, were evaluated by Cox analysis. Kaplan-Meier survival curves were analyzed according to estimated glomerular filtration rate (eGFR).Results: From May 2004 to January 2009, we enrolled 1010 patients. They were classified into four groups according to the eGFR: 21.7% were in group 1 (≥ 90 mL/min per 1.73 m(2)), 34% in group 2 (60-89 mL/min per 1.73 m(2)), 32.2% in group 3 (30-59 mL/min per 1.73 m(2)), and 12.1% in group 4 (<30 mL/min per 1.73 m(2) including dialysis). All-cause mortality was 25.1% at 1 year. The rate of major amputation was 26.3%. Mortality rates were, respectively, at 16%, 18%, 31.7%, and 44.3% (P < .0001) in groups 1 to 4. The major amputation rates were at 23.7%, 21.5%, 28%, and 40.2% (P = .0006), respectively. The presence of severe CKD (group 4) was associated with all-cause mortality (hazard ratio, 1.84; 95% confidence interval, 1.02-3.32; P = .044). In contrast, the risk of amputation was not associated with CKD after adjustments to risk factors.Conclusions: The prevalence of CKD in patients hospitalized for PAD is high. CKD is an independent predictor of 1-year mortality, but is not an independent predictor of limb amputation

Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men

International audienceBackground & aims: Blond orange juice is the most consumed fruit juice in the world. It is a source of hesperidin, a bioavailable flavonoid reported to exhibit potential vascular protective actions. However, the specific impact on vascular function of Citrus phytomicronutrients, is unknown. For the first time, we investigated the effects of blond orange juice compared with a control beverage mimicking the composition of orange juice (including Vitamin C but no phytomicronutrients), on antioxidant markers, cardiovascular risk factors and endothelial function. Methods: Twenty five male volunteers with two cardiovascular risk factors (age over 50 years and LDL-cholesterol between 130 and 190 mg/L) were enrolled in a randomized cross-over study. They received 3 times daily 200 mL of either blond orange juice or control beverage for 4 weeks, spaced by a 5-week wash-out. Endothelial function (flow mediated dilatation and plasma markers), oxidative status, lipid profile and inflammatory markers were assessed. Results: Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species. A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed. This allows further experiments demonstrating the specific effect of phytomicronutrients from orange juice. Conclusions: These findings suggest that daily intake of nutritionally relevant dose of blond orange juice may contribute for a significant antioxidant effect through the phytochemicals contained in. Orange juice may be associated to other healthy foods to achieve a significant effect on the vascular function. This study is recorded in ClinicalTrials.com as NCT00539916. (C) 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

Is VLSM a valid tool for determining the functional anatomy of the brain? Usefulness of additional Bayesian network analysis

International audienc

J Rheumatol

OBJECTIVE: Tocilizumab (TCZ), an IL-6 receptor antagonist, is approved for giant cell arteritis (GCA) as a cortisone-sparing strategy and in refractory patients. This study assessed the real-world efficacy, safety, and long-term outcomes of GCA patients treated with TCZ. METHODS: We conducted a multicenter retrospective observational study at three French centers. All patients ≥ 50 years, meeting the American College of Rheumatology (ACR) criteria, and had received at least one dose of TCZ were included. Relapse was defined by therapeutic escalation, such as increased doses of CS, resumption of CS after weaning, or introduction or intensification of adjuvant therapy. RESULTS: Between 2013 and 2019, 43 patients were included. Patients were followed-up in median 511 days between GCA diagnosis and inclusion with 34/43 (72%) patients experiencing relapses. At inclusion, median age was 77 years and median dose of corticosteroid (CS) was 15 mg/day. After inclusion, the mean cumulative dose of CS was 2.1g/year versus 9.4g/year before inclusion (p\textbackslashtextless2.10(7)) with 12/43 (28%) patients experiencing relapses on TCZ. Among 29 patients undergoing TCZ discontinuation, 18 (62%) experienced relapse. Factors associated with relapse after inclusion were introduction of TCZ \textbackslashtextgreater 6 months after diagnosis (p=0,005), absence of ischemic signs at diagnosis (p=0,006), relapse rate \textbackslashtextgreater0.8/year (p=0.03) and absence of CS tapering ≤ 5 mg/day (p=0,03) before inclusion. Serious adverse events occurred in 18/43 patients (42%), including four deaths. CONCLUSION: Our results confirm the effectiveness of TCZ for CS-sparing, but after discontinuation of treatment, TCZ allows for a prolonged remission in less than 50% of patients. Attention must be paid to the tolerance of this long-term treatment in this elderly and heavily treated population