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Objective Among specific autoantibodies in DM, the anti–small ubiquitin-like modifier activating enzyme (SAE) antibody is rare. We aim to describe the clinical characteristics, cancer prevalence, and muscle pathology of anti-SAE–positive DM. Methods Patients with a diagnosis of DM and sera positive for the anti-SAE antibody were recruited from 19 centres in this retrospective observational study. The available muscular biopsies were reviewed. We conducted a comparison with anti-SAE–negative DM and a review of the literature. Results Of the patients in the study (n = 49), 84% were women. Skin involvement was typical in 96% of patients, with 10% having calcinosis, 18% ulceration and 12% necrosis; 35% presented with a widespread skin rash. Muscular disease affected 84% of patients, with mild weakness [Medical Research Council (MRC) scale 4 (3, 5)], although 39% of patients had dysphagia. Muscular biopsies showed typical DM lesions. Interstitial lung disease was found in 21% of patients, mainly with organizing pneumonia pattern, and 26% of patients showed dyspnoea. Cancer-associated myositis was diagnosed in 16% of patients and was responsible for the majority of deaths, its prevalence being five times that of the general population. IVIG therapy was administered to 51% of the patients during the course of the disease. Comparison with anti-SAE–negative DM (n = 85) showed less and milder muscle weakness (P = 0.02 and P = 0.006, respectively), lower creatinine kinase levels (P Conclusion Anti-SAE positive DM is a rare subgroup associated with typical skin features but a potentially diffuse rash, a mild myopathy. Interstitial lung disease defines an organizing pneumonia pattern. Cancer associated DM prevalence is five times that of the general population. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT04637672.

International audience; BackgroundCardiac uptake on technetium-99m whole-body scintigraphy (WBS) is almost pathognomonic of transthyretin cardiac amyloidosis. The rare false positives are often related to light-chain cardiac amyloidosis. However, this scintigraphic feature remains largely unknown, leading to misdiagnosis despite characteristic images. A retrospective review of all WBSs in a hospital database to detect those with cardiac uptake may allow the identification of undiagnosed patients.ObjectivesThe authors sought to develop and validate the first deep learning–based model that automatically detects significant cardiac uptake (≥Perugini grade 2) on WBS from large hospital databases in order to retrieve patients at risk of cardiac amyloidosis.MethodsThe model is based on a convolutional neural network with image-level labels. The performance evaluation was performed with C-statistics using a 5-fold cross-validation scheme stratified so that the proportion of positive and negative WBSs remained constant across folds and using an external validation data set.ResultsThe training data set consisted of 3,048 images: 281 positives (≥Perugini 2) and 2,767 negatives. The external validation data set consisted of 1,633 images: 102 positives and 1,531 negatives. The performance of the 5-fold cross-validation and external validation was as follows: 98.9% (± 1.0) and 96.1% for sensitivity, 99.5% (± 0.4) and 99.5% for specificity, and 0.999 (SD = 0.000) and 0.999 for the area under the curve of the receiver-operating characteristic curves. Sex, age

Background Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving mycophenolic acid (MPA) may have a less favourable outcome from COVID-19 infection. Our aim was to investigate whether MPA treatment is associated with severe infection and/or death. Methods IRMD patients with and without MPA treatment with highly suspected/confirmed COVID-19 were included in this observational multicentre study. The primary outcome was death rate from COVID-19 with secondary objectives to determine the severity of infection and length of hospital stay. Outcome comparisons were made using regression models with and without adjustment on prespecified confounding factors. ORs, sub-HR (sHR) and 95% CIs were calculated using patients not treated with MPA as a reference group. Results Of the 1977 patients, 1928 were not treated with MPA (393 were MPA eligible), and 49 patients were treated with MPA. MPA-treated patients had more severe disease, longer hospital stays and higher death rate from COVID-19 than non-MPA patients (OR 8.02 (95% CI 3.35 to 19.20), p Conclusion MPA therapy is not associated with a more severe COVID-19 infection. However, due to increased vulnerability of developing a severe form of COVID-19, careful consideration should be taken with iRMD patients likely to be treated with MPA. Trial registration number NCT04353609.

We report the case of an 80-year-old woman who presented one episode of cardiopulmonary arrest and two episodes of acute airway obstruction. We found in this patient the presence of tracheomalacia caused by megaesophagus compression secondary to achalasia probably responsible for episodes of acute airway obstruction and cardiopulmonary arrest.

ObjectiveA new adult-onset autoinflammatory syndrome has been described, named VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic). We aimed to compare the clinical characteristics, the laboratory features and the outcomes between idiopathic-relapsing polychondritis (I-RP) and VEXAS-relapsing polychondritis (VEXAS-RP).MethodsPatients from French retrospective multicentre cohort of RP were separated into two groups: a VEXAS-RP and an I-RP.ResultsCompared with patients with I-RP (n=40), patients with VEXAS-RP (n=55) were men (96% vs 30%, pConclusionWe report the largest cohort of VEXAS-RP, characterised by high prevalence of male sex, fever, skin lesion, ocular involvement, pulmonary infiltration, heart involvement, older age and MDS association.

International audience

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International audience; Background/Aim: Multiple myeloma (MM) is characterized by high production of immunoglobulins resulting in a constant source of endoplasmic reticulum (ER)-stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF) was identified as a possible circulating biomarker that could help in monitoring ER-stress mediated diseases. Materials and Methods: To assess the relevance of MANF in MM, we performed in silico and in vitro analysis in malignant cell lines including the myeloma cell line RPMI 8226. Serum MANF concentration was compared between healthy subjects (n=60), patients with MM (n=68), or those with monoclonal gammopathy of undetermined significance (MGUS) (n=73). Results: MANF mRNA expression was upregulated in the RPMI 8226 cell line, and higher secretion of MANF was measured in RPMI 8226 supernatant. Serum MANF levels were not significantly different between MM or MGUS patients and those in age-and sex-matched healthy controls. Conclusion: MANF was not validated as a biomarker of interest in MM patients. Its potential implication in myeloma pathogenesis should be investigated.

The ZMM28 protein encoded by the zmm28 gene is endogenous to maize. DP202216 maize was genetically modified to increase and extend expression of the zmm28 gene relative to native zmm28 gene expression, resulting in plants with enhanced grain yield potential. Evaluation of the history of safe use (HOSU) is one component of the safety assessment framework for a newly expressed protein in a GM crop. The deduced amino acid sequence of the introduced ZMM28 protein in DP202216 maize is identical to the ZMM28 protein in nonmodified conventional maize. The ZMM28 protein has also been found in selected varieties of sweet corn kernels, and closely related proteins are found in other commonly consumed food crops. Concentrations of the ZMM28 protein in event DP202216 maize, conventional maize, and sweet corn are reported. This information supports, in part, the evaluation of HOSU, which can be leveraged in the safety assessment of the ZMM28 protein. Additional studies will be considered in the food and feed safety assessment of the DP202216 maize event.

We saw an increase in this condition related to emergence of Streptococcus pneumoniae serotype 23B., We conducted a retrospective study on all cases of pneumococcal septic arthritis (SA) in patients >18 years of age reported to the Picardie Regional Pneumococcal Network in France during 2005–2016. Among 1,062 cases of invasive pneumococcal disease, we observed 16 (1.5%) SA cases. Although SA is uncommon in adult patients, the prevalence of pneumococcal SA in the Picardie region increased from 0.69% during 2005–2010 to 2.47% during 2011–2016 after introduction of the pneumococcal 13-valent conjugate vaccine. We highlight the emergence of SA cases caused by the 23B serotype, which is not covered in the vaccine.

International audience; Objectives: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE.Methods: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders.Results: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83).Conclusions: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

Background To determine whether the use of disease‐modifying antirheumatic drugs (DMARDs) is linked to the risk of COVID‐19 among patients with inflammatory rheumatic diseases (IRDs). Methods We performed a disproportionality analysis of the World Health Organization pharmacovigilance database between January 1, 2020, and June 10, 2020. The frequency of COVID‐19 reports for all DMARD classes identified was compared with that for all other reports for all other drugs and quoted as the reporting odds ratio (ROR) (95% confidence interval [CI]). Results Among 980,446 individual case‐safety reports voluntarily recorded in the database, 398 identified COVID‐19 in DMARD‐treated patients with IRDs. There were 177 (44.5%) patients with rheumatoid arthritis (RA), 120 (30.1%) with ankylosing spondylitis (AS), 93 (23.4%) with psoriatic arthritis (PsA), and 8 (2.0%) with juvenile idiopathic arthritis. Most of the cases of COVID‐19 occurred in patients taking anti‐TNF agents (84.2%), resulting in a significant disproportionality signal (ROR [95% CI]: 8.31 [7.48–9.23]) – particularly in patients with RA, AS or PsA. A significant inverse disproportionality was found for the anti‐IL‐6 agent tocilizumab (ROR [95% CI]: 0.12 [0.02–0.88]) and JAK inhibitors (ROR [95% CI]: 0.33 [0.19–0.58]) in patients with RA – suggesting that these two drug classes are safer in the context of RA. Conclusion Our results are in line with the literature on a potentially better safety profile for anti‐IL‐6 agents and JAK inhibitors. The WHO pharmacovigilance data suggest that COVID‐19 is significantly more frequent in patients with IRDs treated with TNF inhibitors.

Summary Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. Findings Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66–6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46–0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55–3·19, p=0·53). Interpretation Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. Funding None.

Objective Adult-onset Still's disease (AOSD) is a rare inflammatory disease that may be life-threatening if complicated by cardiac problems. We performed a retrospective multicenter study to describe the manifestations, treatments and outcomes of cardiac involvement in AOSD. Methods We reviewed the medical databases of eight centers. All AOSD patients identified as fulfilling Yamagushi's or Fautrel's criteria were included in the study. Cardiac involvement, clinical manifestations, laboratory features, the course of the disease and treatments were evaluated. Results We included 96 AOSD patients in this study: 28 (29%) had documented cardiac involvement (AOSD + C group) and 68 (71%) had no cardiac involvement (control group). Cardiac complications were observed at diagnosis in 89% of cases. It were pericarditis (n = 17), tamponade (n = 5), myocarditis (n = 5) and non-infectious endocarditis (n = 1). Levels of leukocytes, neutrophils and C-reactive protein were significantly higher (p = 0.02, p = 0.02 and p = 0.002, respectively in the AOSD + C group than in the control group. Admission to intensive care, and the use of biotherapy were more frequent during follow-up in the AOSD + C group than the control group (p = 0.0001 and p = 0.03 respectively). Cardiac involvement was associated with refractory form in multivariate analyzed (p = 0.01). Corticosteroids were effective with or without methotrexate in 71% of patients but not in severe involvement as myocarditis or tamponade. Conclusion Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis.

This study examined an extended theory of planned behaviour (TPB), incorporating additional social influences, for predicting parents’ and carers’ decisions to visit the library with their young ch...

Currently, no research has systematically investigated the beliefs underpinning caregivers' intentions to visit public libraries with their young children. Drawing from the theory of planned behaviour, this study adopted a three-phase program of formative research to examine the decision making processes of parents and carers with young children living in a low socio-economic area. Phase 1 identified seven behavioural, five normative, and ten control beliefs as modal salient beliefs held by parents and carers. Phase 2 identified a variety of key behavioural, normative, and control beliefs as significant predictors of intention to visit the library with their young child. Phase 3 elicited the reasons underpinning these key beliefs guiding parents' and carers' intentions, identifying 34 reasons that could be used in messages to promote library visits. The results provide useful information that intervention designers, councils, and library services can use to encourage library use among parents and carers with young children.

The ipd072Aa gene from Pseudomonas chlororaphis encodes the IPD072Aa protein which confers protection against certain coleopteran pests when expressed in genetically modified (GM) plants. A weight of evidence approach was used to assess the safety of the IPD072Aa protein. This approach considered the history of safe use of the source organism and bioinformatic comparison of the protein sequence with known allergenic and toxic proteins. The IPD072Aa protein was assessed for resistance to degradation in the presence of simulated gastric fluid containing pepsin as well as heat stability. There was no hazard identified with the IPD072Aa protein. Furthermore, an acute oral toxicity study found no evidence of adverse effects. Collectively, these studies support the human health safety assessment of the IPD072Aa protein.

Introduction Le Virus de l’Hepatite C (VHC) affecterait 185 millions de personnes dans le monde. Environ 50 % des patients VHC chroniques developperaient des complications neurologiques dont les plus decrites sont les neuropathies, les AVC, les encephalomyelites et les troubles cognitifs. Observation Nous rapportons le cas d’une patiente de 80 ans (45 kg, 1,58 m) aux antecedents d’hypertension arterielle, maladie de Willebrand de type II, hepatite C (Genotype 1b, consideree comme guerie depuis 2 ans apres traitement par SOFOSBUVIR et daclatasvir), cryoglobulinemie et syndrome sec adressee initialement pour alteration de l’etat general. A l’examen clinique on retrouvait une amyotrophie diffuse et importante notamment au niveau des muscles inter-osseux associee a des fasciculations linguales, une dysphonie et des troubles de la deglutition. Tres vite, le diagnostic de Sclerose laterale amyotrophique (SLA) fut suspecte puis confirme par les donnees de l’EMG. La patiente fut mise sous RILUZOLE. Malheureusement, l’evolution fut rapidement fatale en 4 mois avec deces des suite d’une pneumopathie d’inhalation. Discussion Plusieurs etudes ont montre la presence de l’ARN du VHC dans des cellules astrocytaires et microgliales chez des patients infectes par le VHC de maniere chronique. D’autres etudes ont montre la presence de recepteurs du VHC au niveau de la barriere hemato-encephalique. Cependant, a l’heure actuelle, les mecanismes physiopathologiques en jeux dans les complications neurologiques du VHC restent meconnus. Conclusion Nous rapportons le deuxieme cas d’association SLA-VHC. Au vu des donnees actuelles, il nous est impossible de dire si cette association est fortuite ou si la SLA peut faire partie comme des complications neurologiques de l’infection chronique au VHC.

To compare clinical and imaging characteristics of patients with giant cell arteritis (GCA) and upper extremity (UE) arterial involvement to patients with Takayasu arteritis (TAK).A cohort of patients seen at the Mayo Clinic with TAK diagnosed between 1984 and 2009 and a cohort of patients with GCA and UE arterial involvement diagnosed between 1999 and 2008 were studied.The TAK cohort consisted of 125 patients (91% female); the mean age (±SD) at diagnosis was 30.9 (±10) years. The cohort of patients with GCA and UE involvement comprised of 120 patients (80% female); the mean age (±SD) at diagnosis was 67.8 (±7.5) years. The mean time from onset of symptoms to diagnosis was significantly longer in TAK (3.2 years) than GCA (0.5 years), p0.001. UE claudication was reported in 40% with TAK and 53% with GCA, p = 0.04. UE blood pressure discrepancy was present in 65% with TAK versus 28% with GCA, p0.001. Involvement of the thoracic aorta, abdominal aorta, carotid arteries, innominate artery, mesenteric artery, and left renal artery was more frequently observed in TAK (p0.05). Among patients with luminal changes of the thoracic aorta, stenotic/occlusive lesions were predominant in TAK (81% compared to 0% in GCA), whereas aneurysmal disease was more common in GCA (100% compared with 19% in TAK, p0.001).Patients with GCA and UE involvement differ from patients with TAK in clinical and imaging characteristics. Aortic aneurysms were more common in GCA, while stenotic changes of the aorta were more common in TAK, suggesting different pathophysiologic mechanisms or vascular response to injury.

Objectives The prevalence of atherosclerotic risk factors and disease in Takayasu's arteritis (TAK) has not been well defined. We aimed to assess the frequency of cardiovascular (CV) risk factors and the incidence of CV events (CVEs) in patients with TAK from two ethnically different populations. Methods Patients with TAK followed at Mayo Clinic, Rochester, MN, USA and Marmara University, Istanbul, Turkey were included in this retrospective study. Patients with TAK were compared with age-, sex- and calendar year-matched controls from the same geographical region without TAK. The 2008 Framingham 10-year general CV risk score (FRS) was used for the evaluation of CV risk at the time of TAK incidence/index date. Results In total, 191 patients with TAK and 191 non-TAK controls were included. Hypertension and the prevalence of lipid-lowering treatments were significantly more frequent in TAK. Prior to the incidence/index date, occurrence of CVE was significantly higher in TAK. The FRS was significantly higher in TAK compared with non-TAK at incidence/index date. The cumulative incidence of CVE was 15.4% at 10 years in TAK vs 5.8% in non-TAK; the risk of CVE was increased among patients with TAK (hazard ratio = 4.36; 95% CI: 1.25, 15.13). Conclusion CV risk factors are more common in patients with TAK, particularly hypertension. The FRS is higher in patients with TAK at the time of diagnosis. The cumulative incidence of CVE was also significantly higher during follow-up in TAK. Our results suggest that patients with TAK should undergo careful assessment of CV risk factors, and an aggressive risk modification approach is warranted.

To evaluate cardiopulmonary (CP) involvement in patients with Takayasu's arteritis (TAK) and assess the impact on disease outcomes.A retrospective cohort of patients with newly diagnosed TAK from 1984 to 2009 was assembled. Demographics, baseline disease characteristics, relapse events, surgeries and mortality were abstracted from direct medical record review. Angiograms, advanced imaging and cardiac studies were reviewed for evidence of CP involvement. Cox models with time-dependent covariates were used to assess the association between CP involvement and outcomes.A total of 124 patients with TAK were identified. Forty-five (36%) patients had at least one objective CP abnormality observed within 6 months of TAK diagnosis. Age at diagnosis was higher in those with CP involvement than those without (34.6 vs 30.1 yrs; p=0.04). Baseline characteristics and symptoms were similar, except shortness of breath, which was more frequently observed at TAK diagnosis in patients with CP involvement compared to those without (53% vs 21%; p=0.001). Composite CP involvement was not associated with risk of first surgery [Hazard ratio (95% CI): 1.21 (0.64-2.30); p=0.56]. However, pulmonary hypertension (PH) on echocardiogram was significantly associated with risk of first surgery [HR (95% CI): 12.9 (1.86- 89.14); p=0.01]. CP involvement was not significantly associated with mortality [HR (95% CI): 2.51 (0.45- 14.02); p=0.29].Cardiopulmonary abnormalities in TAK are common at the time of initial presentation. In this population, the presence of PH predicted a 13-fold increased risk for vascular or valvular surgery. In this cohort, the presence of CP involvement did not increase mortality.

Introduction En reaction a une infection bacterienne, les polynucleaires neutrophiles circulants augmentent tandis que les lymphocytes diminuent par redistribution et majoration de leur apoptose. L’objectif de notre etude etait d’evaluer si le Rapport Neutrophiles sur Lymphocytes (RNL) permettait de differencier une etiologie bacterienne d’une autre cause devant une fievre et/ou un syndrome inflammatoire chez un patient hospitalise dans un service de medecine interne, et ainsi de confirmer les resultats d’une etude retrospective menee dans le meme service sur l’annee 2014. Materiels et methodes Nous avons realise une etude prospective des patients hospitalises pour une fievre et/ou un syndrome inflammatoire (proteine C reactive, CRP superieure a 5 mg/l) dans un medecine interne entre avril 2016 et juin 2017, et mesure le RNL, la CRP et la procalcitonine (PCT). Resultats 184 patients ont ete inclus avec 82 infections bacteriennes, 23 maladies autoimmunes,16 cancers, 4 maladies thromboemboliques, 4 arthrites microcristallines, 2 infections virales, 9 infection virales, une pneumocystose, une candidemie et 24 patients sans etiologie retrouvee. L’âge moyen etait de 71 ans avec 54,6 % de femmes. Le RNL median dans les infections bacteriennes etait a 7, significativement plus eleve que dans les autres causes, p = 0,002. Ce resultat etait confirme apres exclusion des patients sans etiologie (RNL a 7 [4–13,5] dans les infections bacteriennes versus 4,6 [2,8–6,9] pour les autres causes, p = 0,003) et en analyse de sensibilite (RNL a 7 [4–13,5] versus 4,5 [2,7–7,1], p = 0,001). Nous avons determine par l’indice de Youden le seuil optimal de RNL permettant d’obtenir les meilleures sensibilite (Se) et specificite (Sp) : un seuil a 7 donnait une Se a 51 % et une Sp a 75 %. Notre etude retrospective retrouvait un seuil a 8. Concernant la PCT le seuil optimal retrouve etait a 0,3 μg/l, avec une Se a 59 % et une Sp a 74 %. Si l’on comparait les differents marqueurs biologiques, l’aire sous la courbe ROC (AROC) de la PCT etait a 0,71, de la CRP a 0,67 et du RNL a 0,64, non significativement differentes (p = 0,12). Conclusion Nous avons confirme dans une cohorte prospective que le RNL etait significativement plus eleve dans les infections bacteriennes par rapport aux autres etiologies, pour les patients hospitalises pour une fievre et/ou un syndrome inflammatoire en medecine interne. La valeur optimale de RNL retrouvee etait a 7, proche de celle determinee dans l’etude retrospective (a 8). Les AROC de la CRP, de la PCT et du RNL n’etaient pas significativement differentes. La CRP et la PCT bien que plus couteuses n’etait donc pas superieures au RNL dans ce contexte. Ce marqueur semble donc une aide diagnostique precieuse pour differencier une etiologie bacterienne dans un service de medicine interne.

Drowning, a largely preventable problem, continues to be a serious issue worldwide, with young men particularly at risk. Alcohol and drugs are often present among young males and, particularly for males aged 18-34 years, alcohol is considered to be a significant risk factor for drowning. The current study aimed to understand the motivations guiding the intentions of young Australian men to engage in drinking and swimming, a behaviour not yet examined systematically. A cross-sectional correlational design was adopted to investigate the ability of the theory of planned behaviour (TPB) and additional variables to predict males' intentions to drink and swim. Males (N = 211) aged 18-34 years (Mage = 23.93, SD = 4.01) completed a survey either on-line or paper-based. The survey assessed the TPB constructs of attitude, subjective norm, and perceived behavioural control (PBC); and additional variables of group norms, anticipated regret, objective (i.e. swimming ability) and perceived (i.e. perceived severity and perceived susceptibility) risk perceptions, and past behaviour. Support was found for the TPB constructs of attitude and subjective norm, but not PBC, as well as the additional constructs of group norm, anticipated regret, objective risk, and past behaviour in predicting males' intentions to drink and swim; explaining an overall 76 % of variance. Knowledge gained from this study will help to inform resultant interventions designed to discourage alcohol use in, on, or around water and, thus, prevent drownings in this at risk group. Language: en

To describe the clinical features, treatment, and outcomes in a longitudinal cohort of patients with Takayasu arteritis (TAK).We retrospectively studied patients with newly diagnosed TAK evaluated from January 1, 1984, through December 31, 2009.The cohort included 126 patients who were predominantly white (85/103; 82.5%) and female (115/126; 91%). The median age at diagnosis was 31.6 years (interquartile range, 22.9-39.8 years). Median delay in diagnosis was 17.5 months (interquartile range, 7-41.8 months). Thirty-one patients (25%) were 40 years or older at diagnosis. Median delay in diagnosis for patients 40 years or older was 44.8 months compared with 28.3 months for those younger than 40 years (P.001). Limb claudication was the presenting symptom in 64 of 123 patients (52%). Hata type V arteriographic abnormalities were the most common (57/100; 57%). Renal artery abnormalities were observed in 24 of 41 patients (58%) with new-onset hypertension. Inflammatory markers were elevated at diagnosis in 85 of 119 patients (71%). Vascular interventions were performed in 69 patients (55%). Seventy-nine patients (63%) were followed up for more than 1 year (median follow-up, 5.5 years; interquartile range, 2.9-10.0 years). In this subset, treatment consisted of corticosteroids in 73 patients (92%) and additional immunosuppressants in 52 patients (66%). At 5 years, 96% experienced at least one remission of any duration. The overall survival was 97% at 10 years and 86% at 15 years. Mortality was increased compared with the general population (standardized mortality ratio, 3.0; 95% CI, 1.0-8.9).There continues to be an unacceptably long delay in the diagnosis of TAK. Awareness of TAK in patients older than 40 years is needed. Morbidity was high despite immunosuppressive treatment. Survival was decreased in this cohort.

Interstitial lung disease (ILD) has been reported in 3 to 11% of patients with primary Sjogren's syndrome (pSS). The aims of this retrospective multicenter study were to: 1) analyze characteristics and outcome of ILD in pSS; and 2) evaluate predictive factors associated with ILD onset and deterioration. Twenty-one of 263 patients with pSS (8%) developed ILD. ILD onset preceded pSS diagnosis (n=5), was concurrently identified in association with pSS (n=6) and developed after pSS onset (n=9). Presenting ILD manifestations were: acute/subacute (n=11) onset of ILD, symptomatic progressive onset of ILD (n=5), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT-scan (n=5). ILD therapy included: steroids (n=21), cyclophosphamide (n=1), azathioprine (n=4) and rituximab (n=1). The course of ILD was as follows: improvement (15.8%), stabilization (47.4%) or deterioration (36.8%). Predictive parameters of ILD onset were: older age (p=0.044), Raynaud's phenomenon (p=0.001) and esophageal involvement (p=0.001). Factors associated with ILD deterioration were: older age (p=0.038) and esophageal involvement (p=0.038). Thus, this study underscores the poor outcome of ILD during pSS; thus, systematic screening of pulmonary involvement is required in pSS patients, resulting in both diagnosis and management at early stage of ILD. We also suggest that patients presenting predictive factors of ILD deterioration may need a closer follow-up and a more aggressive therapy.

Objectives To evaluate the utility of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for the diagnosis of giant cell arteritis (GCA) and to determine the frequency of normal ESR and CRP at diagnosis of GCA. Methods All patients undergoing temporal artery biopsy (TAB) between 2000 and 2008 were identified. Only subjects with both ESR and CRP at the time of TAB were included. The medical records of all patients were reviewed. Results We included 764 patients (65% women), mean age 72.7 (±9.27) years, who underwent TAB. Biopsy was consistent with GCA in 177 patients (23%). Elevated CRP and elevated ESR provided a sensitivity of 86.9% and 84.1%, respectively, for a positive TAB. The odds ratio of a concordantly elevated ESR and CRP for positive TAB was 3.06 (95% CI 2.03, 4.62), whereas the odds ratio for concordantly normal ESR and CRP was 0.49 (95% CI 0.29, 0.83). Seven patients (4%) with a positive TAB for GCA had a normal ESR and CRP at diagnosis. Compared with GCA patients with elevated markers of inflammation, a greater proportion of these patients had polymyalgia rheumatica symptoms (P = 0.008), whereas constitutional symptoms, anemia and thrombocytosis, were observed less often (P Conclusions CRP is a more sensitive marker than ESR for a positive TAB that is diagnostic of GCA. There may be clinical utility in obtaining both tests in the evaluation of patients with suspected GCA. A small proportion of patients with GCA may have normal inflammatory markers at diagnosis.

Giant cell arteritis (GCA) is an inflammatory vasculopathy that involves large- and medium-sized arteries and can cause vision loss, stroke and aneurysms. GCA occurs in people aged >50 years and is more common in women. A higher incidence of the disease is observed in populations from Northern European countries. Polymyalgia rheumatica (PMR) is a periarticular inflammatory process manifesting as pain and stiffness in the neck, shoulders and pelvic girdle. PMR shares the same pattern of age and sex distribution as GCA. The pathophysiology of PMR and GCA is not completely understood, but the two conditions may be related and often occur concurrently. A delay in the diagnosis should be avoided because of the risk of vascular ischaemic complications due to GCA. The diagnosis should be considered in patients aged >50 years presenting with symptoms such as new headache, visual disturbances, jaw claudication or symptoms of PMR. GCA can also present as a systemic inflammatory syndrome with fever of unknown origin. Marked elevation of acute-phase reactants, recognizable in higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, is often seen in both PMR and GCA. However, some patients can present with a normal ESR. Confirmation of the diagnosis of GCA by temporal artery biopsy is important because clinical findings and laboratory tests are not specific, and because a diagnosis of GCA commits patients to long-term treatment with corticosteroids. The role of imaging techniques for the diagnosis of GCA remains unclear, but these modalities can be helpful in assessing the extent of vascular involvement, especially when extra-cranial disease is present. In PMR, subdeltoid and subacromial bursitis can be identified by imaging techniques, especially ultrasound or MRI. The clinical manifestations of GCA and PMR respond dramatically within 12–48 hours of starting corticosteroid treatment. The initial corticosteroid dosage commonly used in GCA is oral prednisone 40–60 mg/day, and for patients with PMR a dosage of 15–20 mg/day is often sufficient. A prolonged course of treatment is necessary, and corticosteroids are gradually tapered, guided by regular clinical evaluation and ESR (and/or CRP) measurement. Methotrexate is the best studied corticosteroid-sparing agent in GCA, and may be useful for patients with frequent disease relapses and/or corticosteroid-related toxicity. Retrospective studies favour aspirin (acetylsalicylic acid) as an effective adjuvant treatment for reducing the ischaemic complications of GCA. The long-term course of corticosteroid therapy frequently exposes elderly patients with PMR/GCA to various adverse effects, which can be attenuated with appropriate prophylactic measures. Co-morbid diseases and polypharmacy can pose particular challenges in the geriatric population. In general, the life expectancy of patients with GCA does not appear to be shortened, whereas the morbidity associated with the disease and its treatment is well recognized.

Introduction Le lymphome de Hodgkin (LH) est rare, son diagnostic est le plus souvent evoque devant des signes non specifiques. La biopsie ganglionnaire reste la pierre angulaire du diagnostic. Les syndromes paraneoplasiques seraient presents dans Observation Homme de 65 ans adresse pour faiblesse des membres inferieurs, amyotrophie et chutes a repetition s’aggravant depuis deux ans. L’EMG etait en faveur d’une neuropathie motrice a blocs de conduction proximaux. Le bilan d’extension retrouvait des traces d’IgM monoclonale kappa sans anomalies significatives du myelogramme ni de la biopsie osteomedullaire. Le reste des examens etaient sans anomalies. Un traitement par immunoglobulines intraveineuses (IgIV) avait partiellement ameliore la symptomatologie. Deux mois plus tard, apparition de lesion eczematiformes et hyper-keratosiques diffuses avec lesions fissuraires des paumes et des plantes. Une biopsie cutanee etait realisee en faveur d’une ichtyose. Un traitement par corticoides et acitretine fut initie et les IgIV poursuivies. Sept mois plus tard, recidive des lesions cutanees et nouvelle aggravation de la neuropathie. Un scanner thoraco-abdomino-pelvien retrouvait de nombreuses adenopathies axillaires, mesenteriques et lombo-aortiques. Une TEP au 18-FDG retrouvait une fixation des adenopathies. Une biopsie d’adenopathie inguinale fut realisee retrouvant un LH de type « cellularite mixte ». Un traitement par 8 cycles d’adriblastine, bleomycine, vinblastine et deticene (ABVD) fut initie. Discussion Actuellement le patient est en remission, n’a pas presente de nouvelles lesions cutanees, cependant la neuropathie persiste sous IgIV mensuelles. Devant la chronologie des symptomes, nous avons retenu le diagnostic de neuropathie motrice et ichtyose paraneoplasiques revelant un LH. Conclusion A notre connaissance, ce cas est le premier associant ces deux syndromes para-neoplasie chez un meme patient atteint de lymphome.

Introduction Les conditions du metier d’agriculteur ont ete transformees et les risques n’ont jamais ete evalues correctement en France. L’union europeenne vient de re-autoriser l’emploi de certains produits phytosanitaires alors que les etudes demeurent tres parcellaires. Objectifs Tester la prevalence des troubles neuromusculaires chez les agriculteurs actifs ou retraites. Methodes Tous les patients hospitalises dans le service de medecine interne conventionnelle entre 09/2015 et 09/2017 ont ete inclus, leur(s) profession(s), exposition, symptomes et pathologies recueillis avec leur consentement. Les facteurs de risque et les elements confondants ont ete enregistres, les associations ont ete analysees en test du Chi2 et les odds ratio (OR) calcules avec l’aide du logiciel SAS. Resultats Au total, 2207 patients, 108 agriculteurs, 2099 non-agriculteurs. Au total, 25,93 % des agriculteurs versus 17,58 % des temoins presentaient une pathologie neuromusculaire (p = 0,028). Les agriculteurs presentaient plus d’exposition aux phytosanitaires (71,30 % vs 2,62 %, p = 5,10–80), plus de neuropathies peripheriques (14,81 % vs 5,91 %, p = 0,0009), plus de Parkinson (4,63 % vs 2,19 %, p = 0,1), plus de myalgies (8,33 % vs 4,19 %, p = 0,04), et plus d’uveites (6,48 % vs 2,53 %, p = 0,01). Discussion Il aurait mieux valu realiser notre etude dans la population generale ou avec les donnees de la Mutuelle sociale agricole, mais toutes nos demandes ont ete refusees. Conclusion Neuropathies peripheriques, uveites et myalgies sont significativement plus frequentes chez les agriculteurs, et la maladie de Parkinson semble plus frequente.

Acetolactate synthase (ALS) enzymes have been isolated from numerous organisms including soybeans (Glycine max; GM-ALS) and catalyze the first common step in biosynthesis of branched chain amino acids. Expression of an ALS protein (GM-HRA) with two amino acid changes relative to native GM-ALS protein in genetically modified soybeans confers tolerance to herbicidal active ingredients and can be used as a selectable transformation marker. The safety assessment of the GM-HRA protein is discussed. Bioinformatics comparison of the amino acid sequence did not identify similarities to known allergenic or toxic proteins. In vitro studies demonstrated rapid degradation in simulated gastric fluid (

The glyphosate acetyltransferase (gat) gene from Bacillus licheniformis was subjected to multiple rounds of gene shuffling to optimize kinetics of corresponding GAT proteins to acetylate the herbicide active ingredient glyphosate. Genetically modified soybeans expressing the gat4601 gene (356043 soybeans) are tolerant to the application of glyphosate. The current manuscript reports the outcome of the allergenicity and toxicity assessment for the GAT4601 protein. Bioinformatic comparison of the amino acid sequence of GAT4601 did not identify similarities to known allergenic or toxic proteins. In vitro studies conducted with heterologously produced GAT4601 protein demonstrated that it was rapidly degraded in simulated gastric fluid containing pepsin (< 30 s) and in simulated intestinal fluid containing pancreatin (< 2 min) and completely inactivated at temperatures above 56 degrees C. The GAT4601 protein expressed in planta is not glycosylated and similar protein profiles were observed in flour extracts from 356043 soybeans and nontransgenic near isoline comparator soybeans (Jack) using serum from soy allergic persons. No evidence of adverse effects was observed in mice following acute oral exposure to 2000 mg/kg of GAT4601 protein or in a repeated dose dietary exposure study at doses of 800-1000 mg/kg/day. This comprehensive assessment demonstrates that the GAT4601 protein does not present a risk for adverse effects in humans when used in the context of agricultural biotechnology.

Maize line 1507, containing event DAS-Ø15Ø7-1 (1507), is a genetically modified (GM) maize plant that expresses the cry1F gene from Bacillus thuringiensis (Bt) sbsp. aizawai and the phosphinothricin-N-acetyltransferase (pat) gene from Streptomyces viridochromogenes throughout the plant including in the grain expression of the Cry1F protein confers in planta resistance to the European corn borer (ECB; Ostrinia nubilalis Hübner: Crambidae) and other lepidopteran pests. Expression of the PAT protein confers tolerance to the herbicidal active ingredient glufosinate-ammonium. The current study evaluated the nutritional performance of rats fed diets containing 1507 maize grain in a subchronic rodent feeding study. The grains in this study, 1507, its near-isogenic control (33P66), and a non-GM commercial hybrid (33J56) contained similar amounts of proximates, amino acids, minerals, anti-nutrients, and secondary metabolites. The subchronic feeding study compared standard toxicology response variables in rats fed diets containing 1507 maize grain with those in rats fed diets containing non-GM maize grains. All diets were prepared according to the specifications of PMI Nutrition International, LLC Certified Rodent LabDiet 5002 (PMI) 5002). Diets were fed ad libitum to Sprague-Dawley rats for approximately 90 days. In-life response variables included indicators of dietary performance and weekly evaluations for clinical signs of toxicity. No toxicologically significant differences were observed in the nutritional performance variables, clinical and neurobehavioral signs, ophthalmology, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis), organ weights, and gross and microscopic pathology between any pair of treatment groups. These results demonstrate that 1507 maize grain is as safe and as nutritious as non-GM maize grain.

This study investigates the merits of the Developmental Needs Meeting Strategy (DNMS), a relatively new ego state therapy. The DNMS is based on the assumption that many presenting problems are due to wounded ego states stuck in childhood because of unmet developmental needs. DNMS protocols endeavor to identify and heal the wounded child parts most responsible for a presenting problem. When internal Resource ego states, which serve as competent caregivers, meet the wounded ego states' developmental needs, the wounded ego states become unstuck and heal. Eight participants were recruited from the private practice caseloads of 3 DNMS therapists. All participants reported significant improvement in the targeted problems, with gains maintained at follow-up. These findings suggest that the DNMS has therapeutic potential.

Maize (Zea mays) is a widely cultivated cereal that has been safely consumed by humans and animals for centuries. Transgenic or genetically engineered insect-resistant and herbicide-tolerant maize, are commercially grown on a broad scale. Event TC1507 (OECD unique identifier: DAS-O15O7-1) or the Herculex®(#) I trait, an insect-resistant and herbicide-tolerant maize expressing Cry1F and PAT proteins, has been registered for commercial cultivation in the US since 2001. A science-based safety assessment was conducted on TC1507 prior to commercialization. The safety assessment addressed allergenicity; acute oral toxicity; subchronic toxicity; substantial equivalence with conventional comparators, as well as environmental impact. Results from biochemical, physicochemical, and in silico investigations supported the conclusion that Cry1F and PAT proteins are unlikely to be either allergenic or toxic to humans. Also, findings from toxicological and animal feeding studies supported that maize with TC1507 is as safe and nutritious as conventional maize. Maize with TC1507 is not expected to behave differently than conventional maize in terms of its potential for invasiveness, gene flow to wild and weedy relatives, or impact on non-target organisms. These safety conclusions regarding TC1507 were acknowledged by over 20 regulatory agencies including United States Environment Protection Agency (US EPA), US Department of Agriculture (USDA), Canadian Food Inspection Agency (CFIA), and European Food Safety Authority (EFSA) before authorizing cultivation and/or food and feed uses. A comprehensive review of the safety studies on TC1507, as well as some benefits, are presented here to serve as a reference for regulatory agencies and decision makers in other countries where authorization of TC1507 is or will be pursued.

This article describes the use of the Developmental Needs Meeting Strategy (DNMS) for the treatment of dissociative identity disorder (DID). The DNMS is an ego state therapy which guides a client's own internal resources to meet developmental needs that were not met in childhood. After 17 months of DNMS treatment, a client with DID reported a near total elimination in frequency and severity of symptoms of depression, anxiety and suicidal thoughts, her Trauma Symptom Inventory scores indicated no trauma-related symptoms, and her Multidimensional Inventory of Dissociation scores indicated she no longer met the diagnostic criteria for DID. She was functioning well without any medication. Further research concerning this treatment strategy is warranted.

Introduction Le lymphome intravasculaire est une maladie rare dont l’incidence annuelle est estimee a 0,5 cas pour 100 000 habitants [1] . Il se caracterise par une proliferation de lymphocytes B atypiques dans la lumiere des petits vaisseaux. Le diagnostic est difficile en raison de presentations non specifiques dependantes des organes affectes et habituellement sans adenopathies. Des manifestations neurologiques centrales sont presentes dans 42 % a 75 % des cas [2] , [3] . Au vu de ces difficultes, la maladie est souvent disseminee au moment du diagnostic engendrant un pronostic pejoratif malgre des prises en charge therapeutiques agressives. Observation Nous presentons le cas d’une patiente de 39 ans initialement adressee pour cephalees, vertiges, aphasie motrice et paresthesies du membre inferieur gauche. L’IRM cerebrale montrait des stenoses etagees et distales de l’artere cerebrale posterieure droite, la presence d’hypersignaux T2 FLAIR et diffusion en nappe sous-corticaux bilateraux, associes a un hyposignal T2 echo de gradient a ce niveau et conclut a un aspect en faveur d’une vascularite. La ponction lombaire retrouvait 6 elements, 3 hematies et des protides a 1,76 g/L. Apres avoir ecarte une vascularite systemique, une endocardite, une cause infectieuse, une pathologie tumorale, le diagnostic de vascularite primitive du systeme nerveux central fut retenu. La patiente recut 3 bolus de methylprednisolone ayant engendres une remission complete des symptomes. Deux mois plus tard, la patiente fut hospitalisee dans un etat de confusion et de dyspnee associe a un syndrome tetra-pyramidal, des troubles praxiques, un syndrome frontal et des cephalees. L’IRM cerebrale realisee retrouvait une nette majoration des hypersignaux T2 FLAIR avec hyposignaux T2 echo de gradient en leur sein. Il existait alors une cytolyse hepatique, une cholestase et une thrombopenie. Le scanner thoraco-abdomino-pelvien montrait quelques lesions en verre depoli des apex pulmonaires. Un TEP scanner au 18-FDG fut realise retrouvant une fixation diffuse des medullaire osseuses sans autres anomalies de fixation. La realisation d’un myelogramme, d’une biopsie osteomedullaire et d’une ponction biopsie hepatique confirmerent le diagnostic de lymphome B a grandes cellules. A noter que l’arteriographie cerebrale realisee entre temps sous corticotherapie s’est revelee normale. Une chimiotherapie par rituximab, cyclpophosphamide, doxorubicine, oncovin et prednisone (R-CHOP) fut rapidement mise en place. Malheureusement l’issue fut defavorable avec deces de la patente suite a un œdeme cerebral majeur avec engagement le lendemain de la chimiotherapie. Conclusion Le lymphome intravasculaire est un diagnostic rare et difficile a cause de ses multiples presentations aspecifiques pouvant mimer de nombreuses pathologies y compris des vascularites cerebrales. C’est un defi diagnostique majeur pour le clinicien car son evolution necessite une prise en charge therapeutique agressive et rapide. Rapidite souvent compromise devant la difficulte diagnostique initiale assombrissant le pronostic de la maladie.

Replicating a study done 15 years ago, the authors mailed a survey to psychiatrists, psychologists, psychotherapists, and marriage and family counselors who were listed in the San Antonio Yellow Pages to get information about their perceptions of the incidence of unethical practice. Results show a shift in perceived unethical practice over the 15-year time frame.