To investigate the validity of the global APS score (GAPSS) to predict thrombosis in patients with autoimmune diseases.
This prospective cohort study included consecutive patients with aPL or SLE. ...aPL, aPS-PT and GAPSS were determined. A Cox proportional hazards model assessed the validity of GAPSS and identified other potential independent predictors of thrombosis.
One hundred and thirty-seven patients 43.5 (s.d. 15.4) years old; 107 women were followed up for a mean duration of 43.1 (s.d. 20.7) months. Mean GAPSS was significantly higher in patients who experienced a thrombotic event compared with those without 10.88 (s.d. 5.06) vs 8.15 (s.d. 5.31), respectively, P = 0.038. In univariate analysis, age hazard ratio (HR) = 1.04 (95% CI 1.01, 1.08) and GAPSS above 16 HR = 6.86 (95% CI 1.90, 24.77) were each significantly associated with thrombosis during follow-up, while history of arterial thrombosis HR = 2.61 (95% CI 0.87, 7.82) failed to reach significance. Among aPL assays, IgG aPS/PT--a component of the GAPSS--was significantly associated with thrombosis HR = 2.95 (95% CI 1.02, 8.51). In multivariate analysis, GAPSS above 16 remained the only significant predictor of thrombosis HR = 6.17 (95% CI 1.70, 22.40).
This first external validation study confirmed that GAPSS can predict thrombosis in patients with aPL and associated autoimmune diseases.
Hereditary hemorrhagic telangiectasia (HHT) disease is a rare genetic disorder with symptoms and complications that can significantly affect patients' daily lives. To date, no scale has been ...validated to assess the specific symptoms of this disease on the quality of life (QOL) of HHT patients. This makes it difficult for clinicians to accurately measure the quality of life of patients with HHT. The present study aims to develop and validate a QOL measurement tool specific to HHT disease: the QOL questionnaire in HHT (QoL-HHT). A quantitative, non-interventional, multi-center study involving HHT patients in twenty French HHT expert centers was conducted. A calibration sample of 415 HHT patients and a validation sample of 228 HHT patients voluntarily participated in the study. Data were analyzed using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), Exploratory Structural Equation Modeling (ESEM) analyses, reliability analyses, and correlational analyses. The EFA, CFA and ESEM results allowed us to provide evidence of the factorial structure of a questionnaire composed of 24 items measuring 6 domains of QOL: Physical limitations, social relationships, concern about bleeding, relationship with the medical profession, experience of symptoms, and concern about the evolution of the disease. Cronbach's alpha coefficients (> 0.70) demonstrated reliable internal consistency of all the QoL-HHT scores (dimensions). The results of the test-retest provided further evidence of the reliability of the QOL-HHT scores over time. Correlational analyses provided evidence for the convergent validity of the QoL-HHT scores. We developed a simple and quick self-assessment tool to measure quality of life specific to HHT disease. This study demonstrated reliability and validity of our QoL-HHT scores. It is a very promising tool to evaluate the impact of HHT disease on all aspects of the quality of life of HHT patients in order to offer them individualized medico-psycho-social support.
Abstract
Objective
Pulmonary arterial hypertension (PAH) is a leading cause of death in MCTD. We aimed to describe PAH in well-characterized MCTD patients.
Methods
MCTD patients enrolled in the ...French Pulmonary Hypertension Registry with a PAH diagnosis confirmed by right heart catheterization were included in the study and compared with matched controls: MCTD patients without PAH, SLE patients with PAH and SSc patients with PAH. Survival rates were estimated by the Kaplan–Meier method and risk factors for PAH in MCTD patients and risk factors for mortality in MCTD-PAH were sought using multivariate analyses.
Results
Thirty-six patients with MCTD-PAH were included in the study. Comparison with MCTD patients without PAH and multivariate analysis revealed that pericarditis, polyarthritis, thrombocytopenia, interstitial lung disease (ILD) and anti-Sm antibodies were independent predictive factors of PAH/PH in MCTD. Estimated survival rates at 1, 5 and 10 years following PAH diagnosis were 83%, 67% and 56%, respectively. MCTD-PAH presentation and survival did not differ from SLE-PAH and SSc-PAH. Multivariate analysis revealed that tobacco exposure was an independent factor predictive of mortality in MCTD-PAH.
Conclusion
PAH is a rare and severe complication of MCTD associated with a 56% 10-year survival. We identified ILD, pericarditis, thrombocytopenia and anti-Sm antibodies as risk factors for PAH in MCTD and tobacco exposure as a predictor of mortality in MCTD-PAH.
Abstract
Background
Bevacizumab—a humanized monoclonal antibody—has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been ...conducted.
Methods
This study is a double‐blind multicenter randomized phase 2 trial with a 1:1 active‐treatment‐to‐placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3‐month period before and after treatment.
Results
A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention‐to‐treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (
p
= 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (
p
= 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (
p
= 0.03). Fifty‐nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm.
Conclusion
Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.
pulmonary arterial hypertension (PAH) is a leading cause of death in mixed connective tissue disease (MCTD). We aimed to describe PAH in well-characterized MCTD patients.
MCTD patients enrolled in ...the French Pulmonary Hypertension Registry with a PAH diagnosis confirmed by right heart catheterization were included in the study and compared with matched controls: MCTD patients without PAH, systemic lupus erythematous (SLE) patients with PAH, and systemic sclerosis (SSc) patients with PAH. Survival rates were estimated by the Kaplan-Meier method and risk factors for PAH in MCTD patients and risk factors for mortality in MCTD-PAH were sought using multivariate analyses.
thirty-six patients with MCTD-PAH were included in the study. Comparison with MCTD patients without PAH and multivariate analysis revealed that pericarditis, polyarthritis, thrombocytopenia, interstitial lung disease (ILD), and anti-Sm antibodies were independent predictive factors of PAH/PH in MCTD. Estimated survival rates at 1 year, 5 years, and 10 years, following PAH diagnosis were 83%, 67%, and 56%, respectively. MCTD-PAH presentation and survival did not differ from SLE-PAH and SSc-PAH. Multivariate analysis revealed that tobacco exposure was an independent factor predictive of mortality in MCTD-PAH.
PAH is a rare and severe complication of MCTD, associated with a 56% 10-year survival. We identified ILD, pericarditis, thrombocytopenia, and anti-Sm antibodies as risk factors for PAH in MCTD and tobacco exposure as predictor of mortality in MCTD-PAH.
Myotonic dystrophy type 1 (DM1) is characterized by an unstable expansion of a CTG repeat resulting in altered mRNA biogenesis. Benign or malignant tumours are increasingly reported. The aim of the ...study was to evaluate the risk of tumor in a cohort of patients DM1.
We retrospectively reviewed the medical records of every DM1 patient admitted in our neuromuscular center. Diagnoses of cancer and age at diagnosis were noted. The relative risk of a selected cancer was calculated using the data of the cancer registry obtained from the French "Institut de Veille Sanitaire".
A total of 109 French DM1 patients, aged 44.1±13.0 years, were studied, and 14 malignant tumours were observed, with a significant relative risk (RR) of thymoma, of gynaecologic cancers, of lung cancers.
While this cohort is small, our findings nevertheless suggest an increased risk of particular cancers in DM1. The toxic effects of mutant RNA may possibly affect oncogene expression or growth factor signalling pathways in cells. Clinical practice should include cancer screening and prevention of risk factors in DM1 patients.
To measure the association between SLE remission and scores of patients-reported outcome (PRO) measures.
We performed a prospective cohort study of SLE patients with a 2-year follow-up, using Lupus ...Patient-Reported Outcome (LupusPRO), Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus Quality of Life (SLEQOL) and 36-item Short Form (SF-36) questionnaires. Remission was defined as remission off treatment (ROFT) and remission on treatment (RONT) according to the definitions of remission in SLE consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT vs no remission and lupus low disease activity state (LLDAS) vs no LLDAS.
A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: lupus symptoms (LLDAS: +5 points on the 0-100 scale, RONT: +9, ROFT: +5), lupus medication (LLDAS: +5, RONT: +8, ROFT: +9), pain vitality (LLDAS: +6, RONT: +9, ROFT: +6) of LupusPRO; role emotional (LLDAS: +5, RONT: +8), role physical (RONT: +7 and ROFT: +7), bodily pain (RONT: +6), mental health (RONT: +5) and social functioning (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQoL and SLEQOL domains.
RONT, ROFT and LLDAS were associated with significant and clinically relevant higher QoL in most PRO domains of the LupusPRO (disease specific) and SF-36 (generic) questionnaires, but not with LupusQoL and SLEQOL disease-specific questionnaires.
Abstract
Objectives
Mediation analyses were conducted to measure the extent to which musculoskeletal (MSK) flares and depression affected physical health through excessive fatigue.
Methods
Mediation ...analyses were performed in a large multicentre cohort of SLE patients. Domains of the LupusQoL and SLEQOL questionnaires were selected as outcomes, MSK flares according to the SELENA-SLEDAI flare index (SFI-R) score and depression defined by Center for Epidemiologic Studies-Depression scale (CES-D) scale as exposures and different fatigue domains from MFI-20 and LupusQoL questionnaires as mediators. For each model, total, direct, indirect effects and proportion of effect mediated by fatigue (i.e. proportion of change in health-related quality of life) were determined.
Results
Of the 336 patients, 94 (28%) had MSK flares at inclusion and 99 (29.5%) were considered with depression. The proportion of the total effect of MSK flares on physical health impairment explained by fatigue ranged from 59.6% to 78% using the LupusQOL ‘Physical health’ domain and from 51.1% to 73.7% using the SLEQOL ‘Physical functioning’ domain, depending on the fatigue domain selected. The proportion of the total effect of depression on physical health impairment explained by fatigue ranged from 68.8% to 87.6% using the LupusQOL ‘Physical health’ domain and from 79.3% to 103.2% using the SLEQOL ‘Physical functioning’ domain, depending on the fatigue domain selected.
Conclusions
The effect of MSK flares and depression on physical health impairment is largely mediated by fatigue. Thus, the patient’s perception of disease activity as measured by physical health is largely influenced by fatigue. In addition, fatigue has a significant negative impact on quality of lifeof SLE patients with depression.
Trial registration
ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904812.
Heart valve disease (HVD) is the most frequent cardiac manifestation in patients with antiphospholipid syndrome (APS), with prevalence of 30 %. The definition is based on the presence of thickening ...or vegetation of the valves (mainly mitral and aortic) as described by Libman and Sacks for patients with systemic lupus erythematosus (SLE). Transthoracic and/or transoesophageal echocardiography (TTE and TEE, respectively) enable early and accurate diagnosis and help avoid misdiagnosis as rheumatic valve disease. The presence of antiphospholipid antibodies (aPL) in SLE patients is associated with a threefold greater risk of HVD, confirming the crucial importance of these antibodies in the pathogenic process, leading to thrombotic manifestations on valves because of hypercoagulability. Natural history is characterized by worsening of HVD over time with an increased risk for stroke. APS patients undergoing valve-replacement surgery are at high risk of thrombotic and bleeding complications. Thus aPL-associated HVD has affects clinical management of APS patients.
Background
Susac syndrome (SuS) is a rare occlusive microvessel disease of the brain, retina and inner ear. We aimed to determine whether brain lesion load at the acute phase predicts poor outcomes ...in SuS.
Methods
A prospective national cohort study was conducted from December 2012 to December 2019 in 20 centres in France. Patients included at the principal investigator's center with available brain magnetic resonance imaging (MRI) at diagnosis were analyzed. MRI was reviewed by an experienced neuroradiologist blinded to clinical status. The size, topography and number of hyperintense lesions on diffusion‐weighted imaging (DWI‐HL) were analyzed at diagnosis and during follow‐up. Outcomes involved descriptive characteristics of patients at onset and last follow‐up.
Results
Twenty‐three patients (38.1 18.8–56.5 years, 16 females) were prospectively studied. The triad (i.e., brain, eye and ear involvement) was complete at onset in 17 patients. Brain MRI was performed 1.1 (0.1–3.4) months after the first symptom. All patients had DWI‐HL at the acute phase. Patients were separated into two groups according to the number of DWI‐HL on first MRI: a first group of patients (n=15) displaying low brain lesion load (<50 DWI‐HL per patient) and a second group of patients (n=8) displaying high brain lesion load (≥100 DWI‐HL). The median follow‐up was 57.9 (9.7–98) months. Clinical features, treatment, relapse rate, time to disappearance of DWI‐HL, disabilities and professional outcome did not differ according to brain lesion load.
Conclusion
Brain lesion load assessed by DWI at the acute phase is not associated with risks of disability in SuS.
Prospective analysis of magnetic resonance imaging (MRI) hyperintense lesions on diffusion‐weighted imaging (DWI‐HL) was performed at diagnosis and during follow‐up in a large cohort of patients with Susac syndrome (SuS). Brain DWI‐HL load at diagnosis varies over a broad range, but despite a worrisome presentation in most cases, is not associated with baseline features or outcome.
PDF
