Search

This paper investigates the effect of vibro-kinetic (VK) technology on psychophysiological states of users in a virtual reality context. Specifically, we investigate whether a VK seat, i.e., a seat using movement and vibration synchronized with a given media, induces psychophysiological states aligned with an optimal immersive virtual reality (VR) experience. We test our hypotheses with subjects in a seated position while experiencing a passive vehicular movement with a VR headset. Using a between-subject experiment, 45 participants were randomly assigned to a VK or a non-VK condition. Users' psychophysiological states were measured using electrodermal activity, heart rate, and user perceptions. We find evidence that VK significantly enhances the physiological activation of the user throughout the experience. Also, we find that VK seems to create a psychological state that requires less conscious autoregulation, which could suggest that users experience less cybersickness in this condition.

In this paper, we investigate the effect of a vibro-kinetic seat, i.e., a seat using movement and vibration synchronized with a given media, on psychophysiological states and head movements of users immersed in virtual reality. The aim of this study is to explore the extent to which a vibro-kinetic seat can contribute to create a more immersive virtual reality experience than with a classic seat, including fewer cybersickness discomfort symptoms. We test our hypothesis with a between-subject design where we assigned 45 participants to a specific condition: Vibro-kinetic condition (with the seat moving according to the virtual reality experience) or non-vibro-kinetic condition (where the seat was motionless). Users’ physiological states were captured using electrodermal activity and heart rate variability. Users’ head movements were captured using automatic video detection. The results suggest that the vibro-kinetic condition leads to more immersion and a better psychophysiological state to livirtual learning environmentve a more optimal virtual reality experience without cybersickness symptoms. Also, based on the head movement detection, the vibro-kinetic seat seems to contribute to increasing head movements for a large number of users, an indication of the increased presence feeling in virtual reality. Moreover, users in the vibro-kinetic condition live an enhanced experience and are more immersed in the VR experience.

International audience; Objectives : To evaluate the benefits for rheumatoid arthritis (RA) patients of switching from one tumor necrosis factor inhibitor (TNFi) to another based on reason for change (primary failure, escape or intolerance) and molecule-switching order.Methods : Between 2000 and 2008, 356 RA patients prescribed a TNFi (infliximab [IFX], etanercept [ETA] or adalimumab [ADA]) and undergoing standardized evaluation were included in this retrospective study. Detailed demographic, clinical and biological data were collected before first biologic use and ≤ 6 months later to evaluate response based on EULAR-criteria. Primary failure, escape or intolerance of first TNFi triggered switch to another TNFi, the response of which was evaluated 6 months later. Propensity score then measured any interaction with baseline variables.Results : Of the 356 RA patients, 38 switched from IFX/ADA to ETA, 26 from ETA to IFX/ADA, and eight from one monoclonal antibody (mAb; IFX/ADA) to another. Clinical parameters for switchers and non-switchers were comparable. Switchers changed therapies because of primary failure (36.1%), escape (33.3%), or intolerance (30.6%), with no difference found in these subgroups. More switchers responded to the second TNFi than the first (P < 0.01), respectively, regardless of switch (ETA to IFX/ADA: 50 vs. 23.1% [P < 0.05]; IFX/ADA to ETA: 57.9 vs. 15.8% [P < 0.001]) or reason for changing. In addition, DAS28 decreased more with the second antagonist (P < 0.001) and regardless of molecules switched (P < 0.01). Survival of the second TNFi was significantly longer with switch from mAb to the soluble receptor than vice versa (P < 0.05).Discussion : Overall, any switching from one TNFi to another, especially mAb to soluble receptor, was often beneficial for RA patients.

Nail involvement has rarely been recognized in systemic sclerosis (SSc). Indeed, only a few small series have assessed nail changes in SSc, most of which are case reports.The aims of the current case-control study were to: (1) determine the prevalence of fingernail changes in SSc; and (2) evaluate the correlation between fingernail changes and other features of SSc.In all, 129 patients with SSc and 80 healthy control subjects underwent routine fingernail examination.The prevalence of fingernail changes was 80.6% in SSc. Patients with SSc more frequently exhibited: trachyonychia (P = .006), scleronychia (P .0001), thickened nails (P .0001), brachyonychia (P = .0004), parrot beaking (P .0001), pterygium inversum unguis (P .0001), splinter hemorrhages (P .0001), and cuticle abnormalities (P .0001) than healthy control subjects. The presence of fingernail changes was associated with digital ulcers (P .0001), calcinosis cutis (P = .004), and higher values of mean nailfold videocapillaroscopy score (P = .0009).The cohort originated from a single center.This study underlines that fingernail changes are correlated with more severe forms of SSc characterized by digital microangiopathy, including digital ulcers and calcinosis cutis. Nail changes should be systematically checked in all patients with SSc, and may be included in the American College of Rheumatology/European League Against Rheumatism classification criteria for SSc.

Objective To assess the role of Toll-like receptors (TLRs) in antiphospholipid antibody (aPL)–mediated vascular abnormalities in patients with primary arterial antiphospholipid syndrome (APS). Methods Forty-eight subjects participated in the study. Arterial function and structure and TLR pathway activation were determined in patients with primary arterial APS and matched controls. The pathogenic effects of aPL isolated from patients were assessed in wild-type (WT) and TLR-knockout mice. Results APS patients had endothelial dysfunction, arterial stiffening, and hypertrophy, as evidenced by decreased brachial artery endothelium-dependent flow-mediated dilation (FMD) and increased aortic pulse wave velocity and carotid intima-media thickness (IMT), as compared with controls. Plasma samples from APS patients revealed decreased nitric oxide (NO) availability and a pro-oxidative, proinflammatory, and prothrombotic state illustrated by a decrease in nitrite and an increase in lipid peroxidation, tumor necrosis factor α levels, and tissue factor (TF) levels. Furthermore, TLR pathway activation was found in APS patients with increased TLR-2 and TLR-4 messenger RNA expression and increased protein levels of the activated TLR transduction protein interleukin-1 receptor–associated kinase 1 in peripheral blood mononuclear cells. Moreover, agonist-stimulated cell-surface expression of TLR-2 and TLR-4 in circulating monocytes was higher in APS patients than in controls. These changes were positively associated with IMT and negatively associated with FMD. Finally, aPL injection decreased mesenteric endothelium-dependent relaxation and increased TF expression in WT mice but not in TLR-2– or TLR-4–knockout mice. Conclusion This translational study supports the notion that TLR-2 and TLR-4 play a role in mediating vascular abnormalities in patients with primary arterial APS. TLRs thus constitute a promising pharmacologic target for preventing cardiovascular complications in APS.

International audience; BACKGROUND: The aims of the present study were to determine both clinical manifestations and outcome of anti-PL7 patients with antisynthetase syndrome (ASS). METHODS: The medical records of 15 consecutive anti-PL7 patients with biopsy proven ASS were retrospectively analyzed without prior selection. RESULTS: Anti-PL7 patients exhibited polymyositis (n=14) and dermatomyositis (n=1); extra-pulmonary manifestations of ASS included: Raynaud's phenomenon (40%), mechanic's hands (33.3%), joint impairment (26.7%), pericardial effusion (20%) and esophageal/gastrointestinal involvement (20%). The outcome of myositis was as follows: remission/improvement (91.7%) and deterioration (8.3%). Fourteen patients (93.3%) experienced interstitial lung disease (ILD). ILD preceded ASS diagnosis (n=5), was identified concomitantly with ASS (n=8) and occurred after ASS diagnosis (n=1). Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n=1), progressive onset of lung signs (n=11) and asymptomatic patients exhibiting abnormalities consistent with ILD on PFT and HRCT-scan (n=2). No patient had resolution of ILD, whereas 64.3% and 35.7% experienced improvement and deterioration of ILD, respectively. ILD resulted in respiratory insufficiency requiring O2 therapy in 14.3% of cases. Two patients died. Predictive parameters of ILD deterioration were: DLCO

Objective To assess the outcome of interstitial lung disease (ILD) in anti–Jo-1 patients with antisynthetase syndrome, determine predictive variables of ILD deterioration in these patients, and compare features of anti–Jo-1 patients with and without ILD. Methods Ninety-one anti–Jo-1 patients were identified by medical records search in 4 medical centers. All of these patients had undergone pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans. Results Sixty-six patients (72.5%) had ILD. Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n = 12), progressive onset of lung signs (n = 35), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT scans (n = 19). Sixteen patients had resolution of ILD; 39 and 11 patients experienced improvement and deterioration of ILD, respectively. ILD led to decreased functional status, since 29.8% of patients exhibited a marked reduction of activities due to ILD and 13.6% had respiratory insufficiency requiring oxygen therapy; 5 of 6 patients died due to ILD complications. Predictive parameters of ILD deterioration were HRCT scan pattern of usual interstitial pneumonia, respiratory muscle involvement, and age ≥55 years. Furthermore, anti–Jo-1 patients with ILD, compared with those without, more frequently exhibited mechanic's hands and lower creatine kinase levels. Conclusion Our findings confirm that ILD is a frequent complication in anti–Jo-1 patients, resulting in high morbidity. We suggest that patients with predictive factors of ILD deterioration may require more aggressive therapy. Finally, anti–Jo-1 patients with ILD, compared with those without, may exhibit a particular clinical phenotype.

International audience; OBJECTIVE: To evaluate the prevalence of baseline abnormalities in standard laboratory tests in patients with early arthritis and their impact on selection of disease-modifying antirheumatic drugs according to American College of Rheumatology (ACR) recommendations and/or of nonsteroidal anti-inflammatory drugs. METHODS: In three cohorts of patients with early arthritis (the ESPOIR, VErA, and Brittany cohorts), we evaluated the prevalence of anemia (hemoglobinN or>2N), and systemic inflammation (erythrocyte sedimentation rate [ESR]>20 and C-reactive protein [CRP]>6). RESULTS: We evaluated 1393 patients (1018 women and 375 men). Anemia was present in 363/1366 (26.5%) patients, leukopenia in 18/1372 (1.3%), and thrombocytopenia in 13/1371 (0.9%). ESR elevation was seen in 50.4% of patients and CRP elevation in 62.7%. The level of AST was above normal in 4% and of ALT in 10% of patients. No patient had severe renal dysfunction, 5.6% had moderate renal dysfunction, and 42.6% had mild renal dysfunction. Among the 1094 patients who had undergone all the tests, only 18 (1.64%, 95% confidence interval, 1-2.64) had a formal contraindication to methotrexate therapy according to ACR recommendations (4 had leukopenia, 12 had high ALT levels, and 2 had high ALT and AST levels). CONCLUSION: Patients with recent-onset arthritis often have anemia, mild or moderate renal dysfunction, and abnormal liver function. However, fewer than 2% have laboratory test abnormalities contraindicating methotrexate therapy.

International audience; ObjectivesTo date, no studies have yet assessed the characteristics of non-HCV patients with low level of cryoglobulin (≤ 0.05 g/L). The aims of the current study were thus to: 1) determine the prevalence of cryoglobulin ≤ 0.05 g/L in patients with non-HCV cryoglobulin; and 2) compare clinical features and long term outcome, including organ complications and mortality rate, between non-HCV patients with cryoglobulin level ≤ 0.05 g/L and those exhibiting cryoglobulin level > 0.05 g/L.MethodsAmong 6379 cryoglobulin testing, cryoglobulin was detected in 618 patients (9.69% of cases); of these 618 patients, 453 non-HCV patients were included in the study. The medical records of these patients were reviewed.ResultsOf the 453 non-HCV cryoglobulin-positive patients, 265 (58.6%) exhibited cryoglobulin level ≤ 0.05 g/L. We showed that patients with cryoglobulin level ≤ 0.05 g/L had: 1) less commonly: palpable purpura (p < 0.001), digital ulcers (p = 0.006), peripheral neurologic involvement (p = 0.03) and renal impairment (p = 0.03); and 2) lower median values of ESR (p < 0.001) and C-reactive protein (p = 0.001). The patients with cryoglobulin level ≤ 0.05 g/L less often experienced infections (p = 0.04) and hematological malignancies (p = 0.01); both groups did not differ regarding prevalence of connective tissue diseases and solid tumors. Mortality rate was as high as 13.6% in patients with cryoglobulin level ≤ 0.05 g/L; death was mainly due to: solid tumors (16.6%), cardiovascular complications (13.8%), hematological malignancies (11.1%), infections (8.3%), pulmonary/renal complications of cryoglobulin (8.3%) and connective tissue diseases (8.3%).ConclusionOur study shows a high prevalence of cryoglobulin level ≤ 0.05 g/L in clinical practice. Our findings further underscore that non-HCV cryoglobulin level ≤ 0.05 g/L may be responsible for severe renal and neurological complications, leading to high morbidity and mortality in these patients. Thus, our data suggest that both appropriate therapy and close follow-up may be required to improve such patients' outcome.

Objective To determine the prevalence of delayed gastric emptying using the 13C–octanoic acid breath test in unselected patients with systemic sclerosis (SSc), to evaluate whether findings of the 13C–octanoic acid breath test are associated with clinical digestive manifestations, gastric mucosal abnormalities detected by gastroscopy, motor activity dysfunction detected by antroduodenal manometry, and esophageal motor impairment and extradigestive manifestations of SSc, and to develop a risk prediction score of gastric emptying in SSc. Methods Consecutive patients with SSc (n = 57) underwent the 13C–octanoic acid breath test. All of the patients with SSc completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. Results The prevalence of delayed gastric emptying was 47.4% in patients with SSc. A marked correlation was observed between a GSS of digestive symptoms ≥5 and the presence of delayed gastric emptying (P < 0.00001). The sensitivity of a GSS ≥5 for predicting delayed gastric emptying was as high as 0.93, while the specificity was 0.73. Moreover, a GSS ≥5, mucosal gastric abnormalities, severe esophageal motor impairment, and interstitial lung disease were factors that were independently associated with the presence of delayed gastric emptying, and these variables were used to create a risk prediction score. The area under the receiver operating characteristic curve for the risk prediction score was 0.90; the sensitivity of this score for the prediction of delayed gastric emptying was 0.93, while the specificity was 0.77. Conclusion The results indicate that delayed gastric emptying occurs often in patients with SSc. Interestingly, using risk models with routine clinical characteristics, a simple risk prediction score can be calculated, allowing prediction of the occurrence of delayed gastric emptying in patients with SSc.

Objectives The aims of the present study were to (1) assess clinical features and long-term outcome in anti-Jo1-positive patients with anti-Ro52 antibody; (2) compare characteristics of anti-Jo1-positive patients with and without anti-Ro52 antibody; and (3) compare features of anti-Ro52-positive patients with and without anti-Jo1 antibody. Methods The medical records of 89 consecutive anti-Jo1-positive patients with antisynthetase syndrome (ASS) were reviewed; 36 of these patients had coexistent anti-Ro52 antibody. Furthermore, the medical records of 13 consecutive anti-Ro52-positive patients without anti-Jo1 antibody were also reviewed. Results Nine anti-Jo1-positive patients (25%) with anti-Ro-52 antibody achieved remission of ASS, whereas 19 other patients (52.8%) improved and 8 patients (22.2%) worsened their clinical status. Anti-Jo1-positive patients with anti-Ro52 antibody experienced ASS-related complications: interstitial lung disease ( n = 28), esophageal dysfunction ( n = 9), and joint manifestations ( n = 25), including periarticular hydroxyapatite calcifications and erosions of metacarpophalangeal and interphalangeal joints and wrists ( n = 3); 7 anti-Ro52-positive patients (19.4%) had cancer. Anti-Jo1-positive patients with anti-Ro52 antibody, compared with those without, more commonly experienced deterioration of myositis and joint involvement, symptomatic form of ILD, and cancer; they also had decreased survival rate ( P = 0.05). We further found that anti-Ro52-positive patients with anti-Jo1 antibody, compared with those without, were younger and more frequently exhibited ILD with poorer prognosis. Conclusions Our series underlines that the presence of anti-Ro52 antibody is associated with a particular phenotype of ASS, leading to more severe myositis and joint impairment. Moreover, the coexistence of anti-Ro52 antibody seems to be associated with an increased risk of cancer. We therefore suggest that anti-Jo1-positive patients should routinely undergo the search for anti-Ro52 antibody, as this autoantibody appears to impact patients' prognosis.

Summary Objective To report our experience using rituximab as therapy for refractory antisynthetase syndrome (ASS)-associated interstitial lung disease. Methods We retrospectively evaluated the medical records of 7 ASS patients with refractory interstitial lung disease, which had previously failed to respond to prednisone and/or other cytotoxic drugs. All 7 patients received rituximab therapy, i.e.: 1 g at days 0 and 14 and at 6-month follow-up. Data on pulmonary symptoms, pulmonary function tests and high resolution computed tomography (HRCT) scan of the lungs were collected: 1) before rituximab initiation; and 2) at 6-month and one-year follow-up after the first infusion of rituximab. Results At one-year follow-up, ASS patients had resolution ( n = 2) or improvement of pulmonary clinical manifestations. Patients also exhibited significant improvement of interstitial lung disease parameters: 1) on pulmonary function tests: FVC ( p = 0.03) and DLCO ( p = 2 × 10 −5 ); 2) and HRCT-scan of the lungs. Due to clinical resolution/improvement of interstitial lung disease, the median daily dose of oral prednisone could be reduced in these 7 ASS patients at one-year follow-up, compared with baseline (20 mg/day vs. 9 mg/day; p = 0.015). Conclusion Our findings suggest that rituximab may be a helpful therapy for refractory interstitial lung disease in patients with ASS.

Objective This study was undertaken to assess the characteristics and outcome of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/DM) and to determine variables predictive of ILD deterioration in PM/DM. Methods Among 348 consecutive patients with PM/DM, 107 patients with ILD were identified by medical records search in 4 medical centers. All patients underwent pulmonary function tests (PFTs) and pulmonary high-resolution computed tomography (HRCT) scan. Results ILD onset preceded PM/DM clinical manifestations in 20 patients, was identified concurrently with PM/DM in 69 patients, and occurred after PM/DM onset in 18 patients. Patients with ILD could be divided into 3 groups according to their presenting lung manifestations: patients with acute lung disease (n = 20), patients with progressive-course lung signs (n = 55), and asymptomatic patients with abnormalities consistent with ILD evident on PFTs and HRCT scan (n = 32). We observed that 32.7% of the patients had resolution of pulmonary disorders, whereas 15.9% experienced ILD deterioration. Factors that predicted a poor ILD prognosis were older age, symptomatic ILD, lower values of vital capacity and diffusing capacity for carbon monoxide, a pattern of usual interstitial pneumonia on HRCT scan and lung biopsy, and steroid-refractory ILD. The mortality rate was higher in patients with ILD deterioration than in those without ILD deterioration (47.1% versus 3.3%). Conclusion Our findings indicate that ILD results in high morbidity in PM/DM. Our findings also suggest that more aggressive therapy may be required in PM/DM patients presenting with factors predictive of poor ILD outcome.

Summary Objectives: The aims of this prospective study were to identify, in vitamin K antagonist (VKA)-treated patients, factors associated with INR values: (i) greater than 6.0. and (ii) ranging from 4.0 to 6.0 complicated with bleeding. We also assessed VKA-related morbidity in these patients. Methods: During a 6-month period, 3090 consecutive patients were referred to our Department of Internal Medicine, including 412 VKA-treated patients. At admission, the medical records of VKA-treated patients were reviewed for type, duration and indication of VKA therapy, previous medical history of VKA-related hemorrhage, comorbidities and concomitant medications. Results: Forty of the 412 VKA-treated patients (9.7%) exhibited oral anticoagulant related overcoagulation. VKA overcoagulation was associated with high morbidity, leading to major bleeding in 27.5% of cases; moreover, 12.5% of these patients died, death being mainly due to major bleeding. Under multivariate analysis, significant factors for VKA-related overcoagulation were as follows: previous medical history of VKA therapy-related hemorrhage (P = 0.00001) and INR levels over therapeutic range (P = 0.0006), chronic liver disease (P = 0.03), therapy with amiodarone (P = 0.009); in contrast, statin therapy was found to be a protective factor of VKA overcoagulation (P = 0.008). Conclusion: The knowledge of predictive factors of VKA-related overcoagulation seems of utmost importance to improve patients’ management. Our study underlines the fact that the potential of drug interaction should be taken into account when choosing amiodarone for patients receiving VKAs. Interestingly, long-term (>6 month) statin therapy may be a protective factor of VKA overcoagulation. Our findings, therefore, suggest that there may be no need to switch long-term users of VKA and statin to a safer alternative therapy.

The colour-word Emotional Stroop task (ES task) has been proposed to assess the interferences between emotion and attention. Using this task, first, we examined how attention (using reaction times) can be modified by emotionally relevant words in schizophrenics as compared with controls as a function of the emotional significance of the word; second, we tested the assumption that schizophrenics with the most negative symptoms will show higher impairment in relationship to negative emotional words. In general, schizophrenics were slower to react. In both groups, mean reaction times were slower for emotional as compared with neutral words. No significant differences were observed between negative and positive words either in schizophrenics (n = 21) or in controls (n = 20). Even in the most negative schizophrenic patients, there were no differences between negative and positive words. There were no significant interactions between type of stimulus and any clinical variables (PANSS negative or non negative categorization, etc.). Also, there were no statistically significant correlations between reaction times and neuroleptic dosage or anhedonia scores. In conclusion, schizophrenia patients showed the same degree of interference from emotional words as compared with controls. Moreover, patients with a higher level of negative symptoms did not differently experience positive and negative words.

Objectives. Several paradoxical adverse events (PAEs), e.g. IBDs, acute anterior uveitis (AAU) and psoriasis, have been described in patients taking anti-TNF drugs. This retrospective study aimed to describe the different PAEs that have occurred in a population of SpA patients treated with anti-TNF drugs, and to determine whether they are drug specific. Methods. Since 2000, we have followed 296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis, 12 Crohn’s disease) and 77 psoriatic arthritis] treated with at least one anti-TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients treated only with conventional DMARDs who served as controls. Considering the cumulative time of exposure to each anti-TNF agent, the frequencies of new-onset PAEs in exposed patients were calculated. Results. Respective cumulative exposure times were 287, 290 and 62 patient-years for infliximab, etanercept and adalimumab. We observed the following PAEs: five psoriasis (three under infliximab and one with etanercept or adalimumab), three AAU (1/100 patient-years, all under etanercept) and four IBD (three under etanercept and one under infliximab). There was no significant association among any of these PAEs and a specific anti-TNF agent; nor significant difference in the overall PAEs among patients receiving anti-TNF drugs or controls (P ¼ 0.303), the latter experiencing two psoriasis and three AAU. Conclusions. Undesirable side effects—IBD, AAU and psoriasis—may appear with anti-TNF drugs. Even if they are, a priori, paradoxical, no evidence supports any PAEs to be anti-TNF agent-specific in SpA.

The aim of this study was to evaluate the usefulness of serum osteocalcin (OC) levels in multiple myeloma (MM) in order to assess its significance and activity, and to predict its course. Serum OC was measurement in 117 patients with MM and 116 healthy controls matched for age and sex. Serum OC levels were weakly correlated with Karnofsky index (r=0.22; p

To investigate the involvement of angiogenesis markers in very early arthritis patients and their relevance to predict further joint destruction.Levels of Vascular Endothelial Growth Factor (VEGF), angiopoietin-1 (Ang-1), and soluble Fms-like tyrosine kinase-1 (sFlt-1) were measured by ELISA in serum samples from 310 patients having polyarthritis, evolving for less than 6 months (VErA cohort). Each angiogenesis marker was measured at baseline and one year later. X-rays of hands and feet were carried out at inclusion and after 1 year and read using the van der Heidje-modified Sharp method.At baseline and after 1 year, VEGF levels were correlated with clinical and biological parameters of inflammation. We also observed a positive correlation between sFlt-1 levels and biological inflammation (Erythrocyte Sedimentation Rate (ESR): r=0.17, p=0.006; C Reactive Protein: r=0.14, p=0.02). Angiopoietin-1 levels were correlated with ESR (r=0.12, p=0.04). Interestingly, only VEGF levels measured at baseline were correlated with Disease Activity Score measured 1 year later. Relationship between angiogenesis markers and radiographic progression was also evaluated. VEGF and Ang-1 levels measured at inclusion were related with Sharp score after one year (VEGF: r=0.21, p0.001; Ang-1: r=0.24, p0.001; Spearman's test). Moreover, VEGF levels were higher in patients with radiographic progression (p=0.002).Serum concentrations of VEGF, sFlt-1 and angiopoietin-1 were correlated to parameters of inflammation and to bone destruction in early arthritis. These results contribute to demonstrate that angiogenesis reflects disease severity and angiogenesis markers might become a new useful tool to evaluate disease activity and to estimate outcome for patients with inflammatory arthritis.

The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients. The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet. Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal clinical manifestations in SSc patients with fructose malabsorption, our findings underscore that fructose malabsorption may play a significant role in the onset of gastrointestinal symptoms in these patients. Finally, we suggest that fructose malabsorption may be due to reduced fructose absorption by enterocytes, impaired enteric microbiome, and decreased intestinal permeability.

Background Occupational exposure is reported as playing a substantial causative role in systemic sclerosis (SSc). Objective We sought to compare the characteristics of SSc in patients with and without occupational exposure to crystalline silica/solvents. Methods In all, 142 patients with SSc were enrolled in this prospective study. An expert committee performed blind evaluation of occupational exposure to crystalline silica/solvents. Results Patients exposed to crystalline silica more often exhibited: diffuse cutaneous SSc ( P = .02), digital ulcers ( P = .05), interstitial lung disease ( P = .0004), myocardial dysfunction ( P = .006), and cancer ( P = .06). Patients exposed to solvents more frequently developed: diffuse cutaneous SSc ( P = .001), digital ulcers ( P = .01), interstitial lung disease ( P = .02), myocardial dysfunction ( P = .04), and cancer ( P = .003); in addition, these patients were more frequently anti-Scl 70 positive and anticentromere negative. Under multivariate analysis, significant factors for SSc associated with exposure to silica/solvents were: male gender (odds ratio 19.31, 95% confidence interval 15.34-69.86), cancer (odds ratio 5.97, 95% confidence interval 1.55-23.01), and digital ulcers (odds ratio 2.42, 95% confidence interval 1.05-5.56). Limitations The cohort originated from a single geographic region. Conclusion Occupational exposure to crystalline silica/solvents is correlated with more severe forms of SSc characterized by: diffuse cutaneous involvement, interstitial lung disease, general microangiopathy (digital ulcers and myocardial dysfunction), and association with cancer. Occupational exposure should be systematically checked in all patients with SSc, as exposed patients seem to develop more severe forms of SSc.

Fecal calprotectin (FC) is a simple, non-invasive and reproducible test, which has been described to be highly elevated in patients with active inflammatory bowel diseases. Recently, few authors have reported increased levels of FC in SSc patients, although the relationship between FC levels and the degree of gastrointestinal involvement has not yet been determined in patients with SSc. Thus, this prospective study aimed to: 1) determine the prevalence of increased fecal calprotectin (FC) levels in unselected patients with systemic sclerosis (SSc); 2) make prediction about which SSc patients exhibit increased levels of FC; and 3) evaluate the correlation between increased levels of FC and digestive symptoms, and gastrointestinal involvement, including the presence of small intestinal bacterial overgrowth (SIBO) using glucose H2/CH4 breath test. 125 consecutive patients with SSc underwent FC levels and glucose H2/CH4 breath test. All of the patients with SSc also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. 93 (74.4%) patients had abnormal levels of FC (>50 μg/g); 68 patients (54.4%) exhibited highly elevated levels of FC (>200 μg/g). A marked correlation was found between abnormal FC levels and GSS score of digestive symptoms, esophageal involvement and delayed gastric emptying. Moreover, we found a strong association between abnormal levels of FC and the presence of SIBO on glucose H2/CH4 breath test, with the higher correlation between the presence of SIBO and the level of FC ≥275 μg/g with an area under the receiver operating characteristic curve of 0.97 ± 0.001 (CI: 0.93-0.99; p

To validate the 2010-ACR/EULAR criteria for rheumatoid arthritis (RA), taking into account the recent EULAR definition of "erosive disease", on the 310 patients comprising the very early arthritis cohort (VErA).2010-criteria performances were tested by first strictly applying its three items successively: ≥ 1 clinical synovitis/another disease(s)/score ≥ 6/10), then the typical erosion grid without obtaining a score of ≥ 6 to diagnose RA. We tested successively: no erosion (S1), ≥ 1 erosion(s) (S2), EULAR-defined erosive disease (S3). Two gold standards were used: expert diagnosis at six years and EULAR erosive disease at two years.At inclusion, median age was 52 years; median RA duration 4.2 months. 2010-ACR/EULAR criteria, including EULAR-defined erosive disease applied at baseline, classified comparable numbers of patients as the 1987 criteria (P=0.27). Using expert diagnosis at six years, more patients were classified as RA with S2 than 1987-ACR criteria (P0.04). In contrast, sensitivity and specificity indicated that 2010-ACR/EULAR-S3 criteria performed slightly but not significantly better than 1987-ACR criteria. On ROC curves, a score ≥ 6 correctly classified RA. When EULAR-defined erosion at two years was the gold standard, the 1987-ACR, the 2010-S1, -S2 and -S3 criteria performed comparably.Using the very early community-based, conservatively treated VErA cohort, the strict application of 2010-ACR/EULAR criteria using the new EULAR definition of erosive disease or not performed slightly but not significantly better than the 1987-ACR criteria.

Purpose To assess preoperative and postoperative infra-clinical macular changes in macula-off retinal detachment (RD) using third-generation optical coherence tomography (OCT3). Design Prospective observational cohort study. Methods Twenty-two nonconsecutive eyes of 22 patients with macula-off RD underwent best-corrected visual acuity measurement and OCT3 scans through the fovea before and after successful surgery. The relationship between preoperative and postoperative OCT macular characteristics, postoperative infra-clinical foveal detachment, and final visual acuity (FVA) were assessed using Kruskal-Wallis multiple comparison test and Mann-Whitney U test, respectively. Results Preoperative cystic cavities in the inner nuclear layer of the detached retina, postoperative abnormal macular profile, and postoperative lack of the junction line between photoreceptor cell inner and outer segments on OCT3 were associated with a poorer FVA ( P = .001, P = 10 −4 and P = .015, respectively). In contrast, postoperative infra-clinical foveal detachment did not influence FVA ( P = .88). Conclusions Morphologic macular analysis using OCT3 provide some new insights to understand incomplete visual recovery after successful macula-off RD surgery.

Abnormal sensory gating in schizophrenia has frequently been reported. The strength of central inhibitory pathways was measured using the P50 component of the auditory evoked potential in a conditioning-testing paradigm. The relationships between a relative decrease in P50 amplitude to repeated auditory stimuli and clinical symptoms remain controversial. Using the Positive and Negative Syndrome Scale, we studied the P50 auditory conditioning-testing paradigm in 81 schizophrenic subjects, categorized into subgroups with and without prominent negative symptoms, in comparison with 88 control subjects. We found increased ratios of testing stimuli to conditioning stimuli in both schizophrenic subgroups relative to findings in the control group. In addition, we found significantly increased mean latencies of the P50 responses to conditioning (C) and testing (T) stimuli and significantly increased T/C ratios in the subgroup with negative symptoms compared with the subgroup with non-negative symptoms.

PURPOSE To determine whether preoperative optical coherence tomography (OCT) is useful in predicting postoperative visual outcome for patients with primary macula-off rhegmatogenous retinal detachment (RD). METHODS This prospective study included 20 nonconsecutive eyes with macula-off RD and successful reattachment of the retina. Preoperative 5-mm OCT was performed through the center of the fovea. The relationship among preoperative OCT findings, main preoperative clinical variables, and final postoperative visual acuity was statistically analyzed. RESULTS Final postoperative visual acuity was negatively correlated with three preoperative OCT variables: height of RD at the central fovea (r=0.79; P

DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case-control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P=0.02, Odds ratio=4.6, 95% confidence interval 1.3-16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and we found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an intermediate phenotype associated with certain forms of psychosis.

SUMMARYThe objective of this study was to determine the diagnostic and prognostic values of antiglucose-6-phosphate isomerase (GPI) antibodies in patients with very early arthritis. Anti-GPI antibodies were measured by ELISA using purified GPI from rabbit muscle in: (i) 383 sera from healthy blood donors (n = 120), well-established rheumatoid arthritis (RA) (n = 99) and non-RA differentiated arthritis (NRADA) (n = 164) patients; (ii) 195 sera obtained from community-recruited patients with very early inflammatory arthritis (VErA cohort) that were studied for 1 year and classified as having RA (n = 116), NRADA (n = 41), and undifferentiated arthritis (UA) (n = 38) after the follow-up period. The criterion for severity was the progression of radiographic damage. Prevalence of anti-GPI antibodies was significantly higher in well-established RA patients (45·4%) compared to healthy subjects (2·5%). Anti-GPI antibodies were also present in sera from NRADA: systemic lupus erythematosus 53%, polymyositis 45·4%, adult-onset Still's disease 44%, systemic sclerosis 42·8%, spondylarthropathies 25% and primary Sjögren’s syndrome 5·8%. No significant association was found between the presence of anti-GPI antibodies and the 3 diagnostic groups from the VErA cohort. No correlation was observed between anti-GPI and autoantibodies usually associated with RA. Anti-GPI antibodies were not predictive of radiological progression in patients with very early arthritis. Thus, anti-GPI antibodies are not useful for discriminating RA from non-RA rheumatic diseases and do not constitute a predictive factor of structural damage.

SUMMARY The objective of the study was to determine the diagnostic value for rheumatoid arthritis (RA) of anti-filaggrin autoantibodies (autoAb) recognizing citrullinated recombinant rat filaggrin (ACRF) in community cases of very early arthritis. To evaluate the diagnostic value of ACRF, were studied sera from patients with different classified rheumatic diseases and healthy subjects (group 1, n= 422) and 314 community cases of very early arthritis (group 2) that were classified as RA (n = 176), non-RA (n = 63) and undifferentiated (n = 75) arthritides after 1 years of follow-up. ACRF were measured using a new ELISA, with results expressed as the difference between the OD value obtained on citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF; dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also tested. Different reactivity patterns against citrullinated and noncitrullinated filaggrin were observed. Almost all sera reacting with citrullinated but not noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that recognized both forms of filaggrin, a positive result was obtained only with RA sera. For groups 1 and 2, dACRF sensitivity was 58·4% and 30·7%, and specificity for RA was 99·5% and 98·4%, respectively. In group 2, dACRF specificity for RA was better than that of RF (92·1%), APF (95·2%), AKA (96·8%) and anti-CCP (95·2%). dACRF positive predictive value was high (98·2) and close to that given by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive correlation between AKA, APF, anti-CCP and dACRF test results, they were complementary since some sera were positive for only one test. Thus, in a community setting, anti-citrullinated rat filaggrin reactivity detected by a new ELISA, whose originality is based on the difference between serum's reactivities on the citrullinated and native forms of filaggrin, had a higher diagnostic value for RA than other autoAb.

OBJECTIVE It has been postulated that in critically ill patients, splanchnic hypoperfusion may lead to cytokine release into the systemic circulation. The presence of cytokines could trigger an inflammatory response and cause multiple organ dysfunction syndrome. Although experimental studies support this hypothesis, humans studies remain controversial. The aim of the study was to determine the relationship between splanchnic hypoperfusion and cytokine release during septic shock. DESIGN Human prospective study. SETTING Medical intensive care unit at a university hospital. PATIENTS A total of 30 patients with mean arterial pressure of

To evaluate the predictive value of clinical, biological and radiological parameters for the prognosis of rheumatoid arthritis (RA) in a community-recruited cohort.Ninety-one patients (mean age 49 yr, female/male ratio 2.9) with RA of limited duration (median 2 yr), 80% recruited from the community, were prospectively enrolled in 1996 (T1) and followed until 1999 (T2). Data collected at T1 were demographic characteristics, Ritchie articular index (RAI), extra-articular manifestations, Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP) and autoantibodies (autoAbs) [rheumatoid factors (RF), detected by latex fixation test and ELISA (IgM, IgA and IgG isotypes), anti-filaggrin, detected by immunofluorescence (anti-keratin antibodies, AKA; anti-perinuclear factor antibodies, APF) and ELISA (anti-citrullinated rat filaggrin antibodies, ACRFA), anti-Sa, anti-calpastatin recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI), anti-cardiolipin (ACL), antineutrophil cytoplasmic antibodies (ANCA), anti-annexin V (aANX V) and anti-Ro]. Hands were radiographed at T1 and T2, and read using the Sharp method as modified by van der Heijde. The main assessment criterion was progression of radiologically detected damage between T1 and T2.At T1, RA activity was mild (RAI 11/78; mean CRP 14 mg/ml), with minor functional disability (HAQ 0.8/3) and mild X-ray destruction (mean total Sharp score 9.2/280). At T1, 96% of the patients were on treatment (prednisone 72%, DMARDs 95%). The latex test detected autoAb in 46% of patients, RF-IgM was detected in 51%, RF-IgA in 36%, RF-IgG in 32%, AKA in 33%, APF in 45%, ACRFA in 45%, ACAST-C27 in 14%, ACAST-DI in 5%, anti-Sa in 22%, ACL in 3%, ANCA in 28%, aANX V in 9% and anti-Ro in 2%. At T2, the mean total Sharp score was 22.9. According to univariate analysis, T1 parameters associated with the independent variable were RAI, HAQ, CRP, latex test positivity and T1 Sharp scores. Multivariate analysis retained only latex test positivity and, to a lesser degree, joint-space narrowing score as independent predictors of radiological progression.RF is the main factor that can predict radiological progression in community cases of RA of limited duration.

To identify new autoantibody populations in patients with rheumatic diseases, a cDNA expression library was immunoscreened with a rheumatoid arthritis (RA) patient's serum which contains autoantibodies binding to uncharacterized polypeptides by Western-blotting. One clone encoding the amino-terminal region (Nt) [domain L and half of domain I] of human calpastatin was selected. Different fragments of the selected cDNA were prepared and the corresponding recombinant polypeptides were produced by in vitro translation and analysed by Western blotting. Most RA sera bound to recombinant amino-terminal region and domain I but not to domain L. This prompted us to use a recombinant polypeptide corresponding to the domain I of calpastatin as the antigen in a solid-phase ELISA to test sera from patients with various systemic rheumatic diseases and healthy controls. Anti-calpastatin domain I antibodies (ACAST-DI Ab), were detected by ELISA in RA, systemic lupus erythematosus (SLE), Sjogren's syndrome and control sera at respective frequencies of 10, 9, 0 and 1%. These Ab did not have prognostic value in early RA; high levels were significantly associated with vasculitis in SLE. Antibodies reacting with the calpastatin amino-terminal region are produced during systemic rheumatic diseases and are predominantly directed against domain I. High levels of these Ab may constitute a marker of vasculitis in SLE.

Deficit and non-deficit subtypes were examined for their concordance in 83 sibling pairs of 109 schizophrenic patients belonging to 46 multiply affected families. Using a sib-pair method, we have found that the distribution of deficit and non-deficit syndromes in sibling pairs of schizophrenic patients differed significantly from chance expectation. This familial aggregation suggests that the syndrome may be used to define phenotypes for genetic studies.

Objective. To determine whether measurements of different autoantibodies (Ab) and cytokines are useful to distinguish very early rheumatoid arthritis (RA) from other inflammatory rheumatisms. Methods. From a population-based recruitment, 32 patients with very early polyarthritis (median duration: 4 months) were studied. Evaluations at entry (M0), and at 6 (M6) and 12 months (M12). Ab tested: rheumatoid factors (RF) by agglutination methods and ELISA, antiperinuclear factor (APF), antikeratin Ab (AKA), anti-Sa and antinuclear Ab. Cytokine production (TNFα, IL2, IFNγ, IL1β, IL10) in whole blood cell culture (WBCC) was determined at M0. At M12, patients were classified as having RA (N = 15) or other rheumatic diseases. Results. At M0, AKA/APF and anti-Sa Ab frequencies were low, 13% and 7%, respectively. While most Ab detected at MO persisted, others appeared during follow-up, particularly APF, which rose from 13 to 40% at M12. At M6, IgM-RF was detected in two RA patients exclusively by ELISA. AKA/APF were found to be highly specific markers for RA (100% specificity). At some time during follow-up, two RF-negative RA patients were AKA-positive. In two patients, AKA and APF were present at M0 before they satisfied ACR criteria. IL2 and IFNγ production was significantly lower (P

OBJECTIVE: The authors address whether a possible age-at-onset cohort effect may have introduced a bias into anticipation studies of schizophrenia. METHOD: A retrospective review of the medical records of all admissions for psychotic disorders (N=877) was conducted. All subjects with a confirmed DSM-IV diagnosis of schizophrenia and age-at-onset data were included (N=419). For analyses, subjects were placed into one of three successive birth cohorts: 1905–1944 (N=96), 1945–1964 (N=200), and 1965–1984 (N=123). RESULTS: The mean age at first appearance of psychotic symptoms and, similarly, the mean age at first hospitalization significantly decreased over time in successive birth cohorts (25.3, 23.3, and 20.4 years, respectively, for age at first appearance of psychotic symptoms). CONCLUSIONS: This potential birth cohort effect for age at onset of schizophrenia needs to be incorporated into genetic models.

Several studies have reported in schizophrenia a decrease of age of onset in successive family generations, and this observation is consistent with anticipation. Anticipation is known to result from expansion of CAG repeats in several neurodegenerative disorders. Longer alleles of the KCNN3 gene, which contains a highly polymorphic CAG repeat, and encodes a neuronal small conductance calcium-activated potassium channel, have recently been shown to be over-represented in sporadic cases of schizophrenia. In this report, we tested the hypothesis of an association between longer alleles of CAG repeat in the KCNN3 gene and schizophrenia in 20 families with clinical evidence for anticipation and in 151 unrelated schizophrenic cases. No significant difference in the distributions of allele frequencies was observed between familial cases of schizophrenia and controls, and between unrelated cases and controls. Furthermore, no intergenerational CAG repeat instability was detected in the 20 families. Our results do not support the involvement of the KCNN3 (hSKCa3) gene in the etiology of schizophrenia.

263 patients (median age 65+/-10 years) with multiple myeloma were treated with cyclophosphamide-prednisone. Out of this cohort, 103 patients had progressive disease and were randomly assigned to either VAD (vincristine, doxorubicin, dexamethasone; 50 cases) or VMBCP (vincristine, BCNU, cyclophosphamide, melphalan and prednisone; 53 cases). There were no statistical differences between the two groups with the respect to clinical, biological and radiological parameters. There was no difference in survival between the VAD and VMBCP groups. The 4 months response rate was similar in the two groups (50% VAD, 56% VMBCP). With multivariate analysis for survival (Cox model), two factors had a statistically significant impact: Karnofsky index (> 60) and albuminaemia ( 60 and albuminaemia > or = 34 g/l, the median survival was 29 months v 2 months with a Karnofsky index < or = 60 and albuminaemia < 34 g/l (P

To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC).Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET₁). All included patients had a FDG PET/CT scan during RT (PET₂, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year.Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77% received RT with induction chemotherapy and 73% RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUVmax in the PET2 scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95% CI 1.25 - 3.09, p = 0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95% CI 0.73 - 0.94, p 10(-4)). A SUVmax value of 5.3 in the PET₂ scan yielded a sensitivity of 70% and a specificity of 92% for predicting tumour progression or death at 1 year.This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUVmax assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study).

Between January 1985 and July 1989 we diagnosed asymptomatic stage I multiple myeloma according to Durie and Salmon [Durie and Salmon: Cancer 36:842, 1975] in 91 patients. All patients were followed without chemotherapy. Disease progression occurred in 41 patients and the median time to progression for all patients was 48 months. In the Cox multivariate regression analysis, hemoglobin levels 25% (P or = 30 g/l for Ig G or > or = 25 g/l for Ig A (P < .01) were the only significant prognostic factors for progression. The 38 patients without any harmful factor remained free of progression for a median of more than 50 months. The 18 patients with two or three of these characteristics (high-risk group) had the shortest median time to progression of 6 months. Despite different times to progression, the response rate and survival after chemotherapy were similar for all groups of patients. Patients in the high-risk group for progression have to be frequently monitored for disease progression and might benefit from early treatment.

International audience; To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with infective endocarditis (IE) in internal medicine; and to compare clinical and biochemical features and outcome between patients exhibiting IE with and without ANCA.Fifty consecutive patients with IE underwent ANCA testing. The medical records of these patients were reviewed.Of the 50 patients with IE, 12 exhibited ANCA (24%). ANCA-positive patients with IE exhibited: longer duration between the onset of first symptoms and IE diagnosis (P = 0.02); and more frequently: weight loss (P = 0.017) and renal impairment (P = 0.08), lower levels of C-reactive protein (P = 0.0009) and serum albumin (P = 0.0032), involvement of both aortic and mitral valves (P = 0.009), and longer hospital stay (P = 0.016). Under multivariate analysis, significant factors for ANCA-associated IE were: longer hospital stay (P = 0.004), lower level of serum albumin (P = 0.02), and multiple valve involvement (P = 0.04). Mortality rate was 25% in ANCA patients; death was because of IE complications in all these patients.Our study identifies a high prevalence of ANCA in unselected patients with IE in internal medicine (24%). Our findings further underscore that ANCA may be associated with a subacute form of IE leading to multiple valve involvement and more frequent renal impairment. Because death was due to IE complications in all patients, our data suggest that aggressive therapy may be required to improve such patients’ outcome.

International audience; The aims of the present study were to: compare the characteristics between antisynthetase syndrome (ASS) patients with anti-Jo1 antibody and those with anti-PL7/PL12 antibody. The medical records of 95 consecutive patients with ASS were reviewed. Seventy-five of these patients had anti-Jo1 antibody; the other patients had anti-PL7 (n=15) or anti-PL12 (n=5) antibody. At ASS diagnosis, the prevalence of myalgia (p=0.007) and muscle weakness (p=0.02) was significantly lower in the group of anti-PL7/PL12-positive patients than in those with anti-Jo1 antibody; median value of CK (p=0.00003) was also lower in anti-PL7/PL12 patients. Anti-Jo1 positive patients developed more rarely myositis resolution (21.3% vs. 46.2%); in addition, the overall recurrence rate of myositis was higher in anti-Jo1 positive patients than in patients with anti-PL7/PL12 antibody (65.9% vs. 19.4%). Anti-Jo1-positive patients, compared with those with anti-PL7/PL12 antibody, more often experienced: joint involvement (63.3%vs. 40%) and cancer (13.3% vs. 5%). By contrast, anti-PL7/PL12 positive patients, compared with those with anti-Jo1 antibody, more commonly exhibited: ILD (90% vs. 68%); in anti-PL7/PL12 positive patients, ILD was more often symptomatic at diagnosis, and led more rarely to resolution of lung manifestations (5.6% vs. 29.4%). Finally, the group of anti-PL7/PL12 positive patients more commonly experienced gastrointestinal manifestations related to ASS (p=0.02). Taken together, although anti-Jo1 positive patients with ASS share some features with those with anti-PL7/PL12 antibody, they exhibit many differences regarding clinical phenotype and long-term outcome. Our study underscores that the presence of anti-Jo1 antibody results in more severe myositis, joint impairment and increased risk of cancer. On the other hand, the presence of anti-PL7/PL12 antibody is markedly associated with: early and severe ILD, and gastrointestinal complications. Thus, our study interestingly indicates that the finding for anti-Jo1 and anti-PL7/PL12 antibodies impacts both the long-term outcome and prognosis of patients with ASS.

The aims of this present study were to: 1) assess the characteristics of hematological malignancies in polymyositis/polymyositis (PM/DM) patients; and 2) determine predictive variables of hematological malignancies in PM/DM patients. We retrospectively reviewed the medical records of 32 patients (14 PM, 18 DM) associated with hematological malignancies. In our 32 PM/DM patients, hematological malignancy was concurrently identified (18.8%) or occurred during the course of PM/DM (31.2%); although, PM/DM more often preceded hematological malignancy onset (50%). We observed that the types of hematological malignancies varied, consisting of: B-cell lymphoma (n=20), T-cell lymphoma (n=4), Hodgkin's disease (n=2), multiple myeloma (n=1), myelodysplastic syndrome without excess of blasts (n=3), hairy cell (n=1) and acute lymphocytic leukemia (n=1). In 21 patients of our 32 patients with PM/DM-associated hematological malignancy (65.6% of cases), PM/DM paralleled the course of hematological malignancy. Finally, we observed that patients with PM/DM-associated hematological malignancies had a poor prognosis, the survival status ranging from 96.9%, 78.1% and 51.4% at 1, 3 and 5years, respectively. Interestingly, we found that patients with hematological malignancies, compared with those without were older and more frequently had DM; on the other hand, these patients less commonly exhibited: joint involvement (p=0.017), interstitial lung disease (p=0.06) and anti-Jo1 antibody (p=0.001). Taken together, our study underscores that the association between PM/DM and hematological malignancy, especially lymphoma, should not be ignored. Our findings also suggest that antisynthetase syndrome may be a protective factor of hematological malignancy in PM/DM patients.

Objectives To test the performances of combining anti-CCP second generation (CCP2) with ACR 1987 classification criteria and to diagnose early RA in a community-based very early arthritis (VErA) patient cohort. Methods The VErA cohort comprised 310 patients (median age 52 years; 68.1% women; median symptom duration 4.2 months; glucocorticoid- and DMARD naive) conservatively treated during the first 2 years. At 6 years of follow-up, a three-expert committee classified the patients into three groups: RA, other classified arthritis (OCA) or unclassified arthritis (UA). We calculated the performances of the different sets, including anti-CCP2 positivity, while retaining or deleting RF and rheumatoid nodule components with ACR 1987 criteria for early RA diagnosis. Models were subjected to receiver operating characteristics curve and logistic regression analyses to try to identify relevant sets able to classify very early RA. Results At 6 years, 149 patients were diagnosed as RA and 119 as non-RA (95 OCA and 24 UA). The original ACR 1987 criteria had 77.9% sensitivity and 64.7% specificity for the RA diagnosis at 6 years. The modified set excluding rheumatoid nodules, including anti-CCP2 positivity and retaining RF performed significantly better than ACR 1987 criteria, with 79.9% sensitivity and 64.7% specificity and with a larger area under the curve. However, in the zone of interest, i.e., ≥4/7 criteria, the curves for these sets were superimposed. Conclusions Adding anti-CCP2 positivity and deleting rheumatoid nodules failed to improve the performances of ACR 1987 classification criteria for the diagnosis of early RA.

The aim of this study was to investigate the relationship between depressive and positive symptoms, two positive symptom using scales (PANSS and SAPS) in samples defined by three schizophrenic diagnostic systems (DSMIII-R, ICD9 and Langfeldt) at difference phases of the illness and in taking into account the negative and extrapyramidal symptoms and the doses of neuroleptics. With both scales, correlations between depressive and positive symptoms were significantly negative in two diagnostic subgroups (DSMIII-R and Langfeldt) in the acute phase. These correlations were also significant when negative symptoms, subjective extrapyramidal signs and the doses of neuroleptics were partialled out. Only the extrapyramidal physician's score was intercorrelated with positive and negative symptoms. Among the positive symptoms, ‘conceptual disorganization’ (or ‘positive formal thought disorder’) and ‘suspiciousness/persecution’ were especially correlated negatively with depression. At the post-acute phase or at the residual phase, no significant correlation between depressive and positive symptoms was found in any diagnostic subgroup. These results show the necessity of taking into account the phase of illness and the diagnostic criteria in order to study depression in schizophrenia.

SummaryThe stability of symptomatology and of eleven schizophrenic diagnostic systems was studied in patients initially in an acute phase (group 1) compared to patients in a residual phase (group 2). The patients were evaluated over a period of 1 year with a standardized checklist and PANSS in both groups. The number of patients included by the Carpenter, Calego, 1CD9, New-Haven, Schneider and Vienne systems decreased significantly between admission and discharge in group 1, whereas no variation was observed in group 1 between discharge and one year later, or in group 2 over a period of 1 year. The instability of schizophrenic diagnostic systems such as New-Haven, Schneider and Vienne could be due to the variation of positive or general symptomatology. The number of patients included by Feighner or Langfeldt did not vary significantly between admission and discbarge in group 1, in spite of a significant decrease in symptomatology, probably because certain criteria, such as duration of illness, hindered the systems from changing. The results showed the importance of specifying in every study on schizophrenia the time of inclusion (admission, discharge) or the phase of illness (acute or residual phase).

Objective To identify, in conservatively treated, very early arthritis patients, predictors of ≥1 erosion(s) at 2 years, and to construct a prediction model. Methods Community-based adults (n = 310) who had never taken disease-modifying antirheumatic drugs (DMARDs) or steroids with swelling of ≥2 joints persisting for >4 weeks and lasting

Objective To assess the long-term outcome of esophageal complications in the group of patients receiving intravenous immunoglobulins (IVIG) for the treatment of severe steroid-refractory esophageal involvement related to polymyositis/dermatomyositis (PM/DM). Methods We retrospectively reviewed the medical records of 73 patients (39 with PM, 34 with DM) with steroid-resistant esophageal involvement. Esophageal involvement was evaluated by clinical and manometric investigations. Results Seventy-three patients with steroid-refractory esophageal involvement related to PM/DM received IVIG therapy (2 gm/kg monthly). The median interval between PM/DM diagnosis and the onset of esophageal complications was 6 months. The most common clinical manifestations revealing esophageal dysfunction were dysphagia (69.9%), coughing while eating (61.6%), and gastroesophageal reflux into the pharynx and/or mouth (34.2%). Twenty-five patients exhibited life-threatening esophageal complications requiring exclusive enteral feeding; 33 patients (45.2%) with esophageal impairment developed aspiration pneumonia. Sixty patients (82.2%) exhibited resolution of esophageal clinical manifestations, leading to a return to normal oral feeding and ablation of feeding enteral tubes. Four other patients (5.5%) improved, although they still experienced mild dysphagia intermittently. Because of impaired cricopharyngeal muscle relaxation, another patient successfully underwent cricopharyngeal myotomy. Eight patients died from aspiration pneumonia (n = 6) and cancer (n = 2). Muscle weakness, thoracic myopathy, and aspiration pneumonia were independent predictive factors of IVIG-treated esophageal complications in PM/DM patients. Conclusion Our findings indicate that IVIG should be considered in life-threatening esophageal impairment complicating steroid-resistant PM/DM. We also suggest that combined therapy of IVIG and high-dose steroids may be the first-line therapy in PM/DM patients with life-threatening esophageal manifestations.

A randomized trial has been performed in which 91 patients with stage III myeloma and additional severe criteria were randomly allocated to either VAD or VMBCP. No significant difference was noted between these two groups using the following criteria: response rate (VMBCP: 54%; VAD: 39%), impact on symptoms, median survival (VMBCP: 14 months, VAD: 17 months). However, toxic effects and refusal to pursue treatment were more frequent with VAD than with VMBCP (12 v 6). Therefore, in this trial, VMBCP appears to be more useful than VAD.

SummaryChronic Hallucinatory Psychosis (CHP) is typically a French disease entity initially described by G Ballet (1911) and whose diagnostic criteria were established by Pull (1987). This diagnosis is not used in English and German literature. The aim of this study was to investigate the relationship between Pull's criteria for CHP and the criteria for schizophrenia defined by 14 different diagnostic systems and schizoaffective disorders. Seventy-two non-affective psychotic patients (34 men, 38 women), aged 20 to 84, in exacerbated or stabilized phase, were interviewed by the same investigator (SD). The patient distribution between the diagnoses in the different diagnostic systems was carried out using a computerized 208-item checklist. The main results indicated that the definite CHP diagnosis was significantly related to the Catego S + (C = 0.52; P < 0.01), New-Haven, (C = 0.40; P < 0.05) and Schneider (C = 0.54; P < 0.001) systems for schizophrenia and with the depressive-schizoaffective disorder (C =0.39; P < 0.05) in the RDC system. The probable CHP diagnosis was significantly linked with the same systems and with the probable RDC (C = 0.39; P < 0.05) for schizophrenia. These results emphasize that in 13 out of the 14 diagnostic systems, schizophrenic and schizoaffective disorders overlapped with CHP in the French diagnostic system. Among these systems, four schizophrenic diagnoses were significantly linked to CHP. In contrast, the Bleuler system for schizophrenia was not related to CHP at all.

Catatonia is a common but under-diagnosed neuropsychiatric syndrome characterized by the occurrence in a single patient of concomitant affective, motor and behavioral symptoms with a hazardous outcome (called lethal catatonia: LC). Deaths by thromboembolic disease have been previously reported in LC. A 2-year prospective study was carried out to examine D-dimer levels, an early and sensitive coagulation marker, in patients with catatonic disorders. Twenty-five acute catatonic patients and 50 psychiatric control patients - matched on age, gender, psychiatric diagnosis, general psychopathology and neuroleptic medication matched - were investigated and considered in relation to D-dimer blood levels and other biological variables (serum iron, creatine phosphokinase, leukocytosis). All catatonic patients had high D-dimer levels and mean levels were significantly higher in catatonics than in non-catatonic patients, independently of age, gender, immobility, comorbid diagnosis, general psychopathology and neuroleptic medication. No significant association was observed with other biological parameters investigated. These preliminary and exploratory results suggest that catatonia is associated with early coagulation activation.

SummaryThe aim of this study was to test whether a positive and a negative component could be found in broadly defined schizophrenic patients. Therefore, 70 patients either in an exacerbated or in a stabilized phase were selected according to the criteria of at least 1 of the 4 following diagnostic systems: DSM III-R, Schneider, Carpenter, Langfeldt; principal component analyses (PCA) were carried out with the 9 global ratings of the Scales for Assessment of Negative and Positive Symptoms (SANS and SAPS) and with the Positive and Negative Syndrome Scale (PANSS). The PCA of the SANS-SAPS global ratings yielded a 3-factor solution explaining 72.14% of the total variance, depicting a negative, a positive and a disorganization component. The PCA of the PANSS provided a 5-factor solution with a total explained variance of 55.98%. The first 3 factors were similar to those of the SANS-SAPS global rating analysis. The results showed that the positive and negative components described in a homogeneous schizophrenic population could be replicated in a larger and more heterogeneous group of schizophrenic patients. The question regarding the sufficiency of the positive-negative dichotomy was strengthened by the presence of a third disorganization component which explained as much of the variance as the positive component.