Guillaume Lefèvre

Survival and Prognostic Factors in Systemic Sclerosis-Associated Pulmonary Hypertension A Systematic Review and Meta-Analysis

OBJECTIVEnPulmonary hypertension (PH) is a frequent and life-limiting complication of systemic sclerosis (SSc). However, data on survival rates and their evolution over time, as well as prognostic factors in SSc complicated by PH, are still conflicting. The aim of this study was to conduct a systematic review and meta-analysis of cohort studies to assess pooled survival and prognostic factors for survival in patients with SSc-associated PH.nnnMETHODSnFor this systematic review and meta-analysis, we searched the Medline and EMBase databases (January 1960 to January 2012). All cohort studies in which survival and/or prognostic factors for SSc-associated PH were reported were included in the analysis. We calculated the pooled survival rates and analyzed their evolution over time and identified prognostic factors for survival.nnnRESULTSnTwenty-two studies were included, representing a total of 2,244 patients with SSc-associated PH. The pooled 1-, 2-, and 3-year survival rates were 81% (95% confidence interval [95% CI] 79-84%), 64% (95% CI 59-69%), and 52% (95% CI 47-58%), respectively. Meta-regression did not reveal a significant change in survival over time, while baseline hemodynamic measures of PH severity were significantly correlated with survival. In patients with SSc complicated by pulmonary arterial hypertension (PAH), age, male sex, diffusing capacity for carbon monoxide (DLCO), pericardial effusion, and the parameters classically associated with the severity of idiopathic PAH, including the 6-minute walk distance, mean pulmonary artery pressure, cardiac index, and right atrial pressure, were significant prognostic factors. DLCO and pericardial effusion were the only prognostic factors in patients with interstitial lung disease-related PH.nnnCONCLUSIONnOur meta-analysis revealed a poor pooled 3-year survival rate of 52% in patients with SSc-associated PH. Baseline hemodynamic measures of PAH severity, but not the period of time during which patients were included in the studies, correlated significantly with survival in patients with SSc-associated PAH. All of the prognostic factors typically observed in idiopathic PAH, including the 6-minute walk distance and right atrial pressure, were also prognostic factors in SSc-associated PAH.

Patient-level analysis of five international cohorts further confirms the efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies.

We performed an individual patient meta-analysis to determine whether aspirin has a significant protective effect on the risk of first thrombosis among patients with antiphospholipid antibodies (aPL). Five international cohort studies with available individual patient-level data, reporting on primary prophylaxis with continuous treatment with low-dose aspirin in patients with aPL were included. The main outcome was the occurrence of a first thrombotic in patients with aPL treated with low-dose aspirin compared to those not treated with low-dose aspirin. Pooled Hazard Ratios (HRs) and 95%CIs were calculated using frailty models. We pooled data from 497 subjects and 79 first thrombotic events (3469 patient-years of follow-up). After adjustment on cardiovascular risk factors, aPL profiles, and treatment with hydroxychloroquine, the HR for the risk of a first thrombosis of any type in aPL carriers treated with low-dose aspirin versus those not treated with aspirin was 0.43 (95%CI 0.25-0.75). Subgroup analysis showed a protective effect of aspirin against arterial (HR: 0.43 [95%CI: 0.20-0.93]) but not venous (HR: 0.49 [95%CI: 0.22-1.11]) thrombosis. Subgroup analysis according to underlying disease revealed a protective effect of aspirin against arterial thrombosis for systemic lupus erythematosus (SLE) (HR: 0.43 [95%CI: 0.20-0.94]) and asymptomatic aPL carriers (HR: 0.43 [95%CI 0.20-0.93]). We found no independent protective effect of hydroxychloroquine. This individual patient data meta-analysis shows that the risk of first thrombotic event as well of first arterial thrombotic event is significantly decreased among SLE patients and asymptomatic aPL individuals treated by low-dose aspirin.

Prevalence of Anti–RNA Polymerase III Antibodies in Systemic Sclerosis: New Data From a French Cohort and a Systematic Review and Meta‐Analysis

Studies assessing the prevalence of anti–RNA polymerase III (anti–RNAP III) antibodies in systemic sclerosis (SSc) have yielded a wide range of results. The aim of the present study was to describe a new SSc cohort tested for presence of anti–RNAP III and perform a systematic review and meta‐analysis to assess the prevalence of anti–RNAP III in patients worldwide and the potential factors of variability.

18F-FDG PET/CT in patients with amyloid light-chain amyloidosis: case-series and literature review.

Objectives: To describe FDG-PET/CT in amyloid light-chain (AL) amyloidosis. Methods: We describe a French multicenter study which included patients with AL amyloidosis who had undergone a FDG-PET/CT during follow-up. Results: Ten patients with AL amyloidosis (median age 62 years [59–85]) were analyzed. AL amyloidosis was of λ-type in 7/10 cases (70%) and localized amyloidosis in 4/10 cases (40%). AL amyloidosis was primary in 7/10 (70%) cases and associated with Waldenstrom’s macroglobulinemia (n = 2) and plasmocytoma (n = 1) in the remaining cases. Median delay between diagnosis and PET was 1 month [0–51]. PET was positive in seven (70%) patients and showed a median FDG SUV of 6.5 [4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15]. FDG uptakes with positive PET were localized in seven patients, namely in the nasopharynx (n = 3), bronchopulmonary (n = 2), duodenal, cutaneous, bone, joint and muscular areas (n = 1, each). FDG uptakes on PET were concordant with the known organ impairment in 6/7 cases (86%) and showed unknown nasopharyngeal and mesenteric localization in one case each. PET was negative in the patient with cardiac amyloidosis and two patients with pulmonary amyloidosis. Conclusion: High FDG uptake may be present in patients with AL amyloidosis, however prospective studies are needed in order to determine the place of FDG PET in AL amyloidosis.

The lymphoid variant of hypereosinophilic syndrome: study of 21 patients with CD3-CD4+ aberrant T-cell phenotype.

AbstractThe CD3-CD4+ aberrant T-cell phenotype is the most described in the lymphoid variant of hypereosinophilic syndrome (L-HES), a rare form of HES. Only a few cases have been reported, and data for these patients are scarce. To describe characteristics and outcome of CD3-CD4+ L-HES patients, we conducted a national multicentric retrospective study in the French Eosinophil Network. All patients who met the recent criteria of hypereosinophilia (HE) or HES and who had a persistent CD3-CD4+ T-cell subset on blood T-cell phenotyping were included. Clinical and laboratory data were retrospectively collected by chart review. CD3-CD4+ L-HES was diagnosed in 21 patients (13 females, median age 42 years [range, 5–75 yr]). Half (48%) had a history of atopic manifestations. Clinical manifestations were dermatologic (81%), superficial adenopathy (62%), rheumatologic (29%), gastrointestinal (24%), pulmonary (19%), neurologic (10%), and cardiovascular (5%). The median absolute CD3-CD4+ T-cell count was 0.35u2009G/L (range, 0.01–28.3), with a clonal TCR&ggr;&dgr; rearrangement in 76% of patients. The mean follow-up duration after HES diagnosis was 6.9 ± 5.1 years. All patients treated with oral corticosteroids (CS) (nu2009=u200918) obtained remission, but 16 required CS-sparing treatments. One patient had a T-cell lymphoma 8 years after diagnosis, and 3 deaths occurred during follow-up.In conclusion, clinical manifestations related to CD3-CD4+ T cell-associated L-HES are not limited to skin, and can involve all tissue or organs affected in other types of HE. Contrary to FIP1L1-PDGFRA chronic eosinophilic leukemia patients, CS are always effective in these patients, but CS-sparing treatments are frequently needed. The occurrence of T-cell lymphoma, although rare in our cohort, remains a major concern during follow-up.

Cardiac biomarkers in systemic sclerosis: contribution of high-sensitivity cardiac troponin in addition to N-terminal pro-brain natriuretic peptide.

To measure plasma concentrations of high‐sensitivity cardiac troponin T (HS‐cTnT) and N‐terminal pro–brain natriuretic peptide (NT‐proBNP) in patients with systemic sclerosis (SSc; scleroderma) and age‐ and sex‐matched healthy control subjects, and to examine the contribution of traditional cardiovascular risk factors and SSc features to the concentrations of these 2 cardiac biomarkers.

Tocilizumab in Giant Cell Arteritis: A Multicenter Retrospective Study of 34 Patients

Objective. To report the efficacy and safety of tocilizumab (TCZ) for giant cell arteritis (GCA). Methods. A retrospective multicenter study that included 34 patients receiving TCZ for GCA. Results. TCZ was effective in all but 6 patients, who still had mild symptoms. Mean glucocorticoid dose was tapered. One patient died and 3 patients had to stop TCZ therapy because of severe adverse events. Twenty-three patients stopped treatment; 8 of these experienced relapses after a mean of 3.5 ± 1.3 months. Conclusion. TCZ is effective in GCA. However, side effects occur. Whether this treatment has only a suspensive effect remains to be determined.

Inflammation and disease activity are associated with high circulating cardiac markers in rheumatoid arthritis independently of traditional cardiovascular risk factors.

Objective. To measure concentrations of high-sensitivity cardiac troponin (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) and to examine correlates. Methods. The plasma concentrations of HS-cTnT and NT-proBNP were measured in consecutive patients with RA and compared to values obtained from age-matched and sex-matched healthy controls. Results. We included 236 unrelated patients with RA (192 females, 57 ± 13 yrs) and 213 controls (170 females, 55 ± 15 yrs). Seventy-one patients with RA were free of cardiovascular (CV) risk factors. HS-cTnT and NT-proBNP concentrations were significantly higher in the total cohort of patients with RA (p = 0.03 and p < 0.0001, respectively) and in the subgroup free of CV risk factors (p = 0.02 and p < 0.0001, respectively) compared to controls. In addition, both the total cohort of patients with RA and the subgroup free of CV risk factors were more likely to have levels above the cutoff concentrations of HS-cTnT (p = 0.003 and p = 0.007, respectively) and NT-proBNP (p = 0.0001 and p < 0.0001, respectively) than controls. Patients with RA and increased C-reactive protein (CRP) levels had higher HS-cTnT (p = 0.03) and NT-proBNP (p = 0.02) concentrations. HS-cTnT levels positively correlated with the 28-joint Disease Activity Score (DAS28-CRP; r = 0.2, p = 0.020). Multivariate logistic regression analysis indicated that increased HS-cTnT levels were independently associated with a DAS28-CRP > 5.1 (OR 11.8; 95% CI 1.6–35.5) and a body mass index > 30 kg/m2 (OR 2.7; 95% CI 1.3–5.5). Conclusion. HS-cTnT and NTproBNP are increased in patients with RA, independent of CV risk factors. The association between HS-cTnT, NT-proBNP, and CRP, together with the correlation between HS-cTnT and disease activity, support the link between myocardial injury/dysfunction and inflammation.

In Antisynthetase Syndrome, ACPA Are Associated With Severe and Erosive Arthritis: An Overlapping Rheumatoid Arthritis and Antisynthetase Syndrome

AbstractAnticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The clinical significance of ACPA in patients with antisynthetase syndrome (ASS), a systemic disease characterized by the association of myositis, interstitial lung disease, polyarthralgia, and/or polyarthritis, has not yet been evaluated with regard to phenotype, prognosis, and response to treatment. ACPA-positive ASS patients were first identified among a French multicenter registry of patients with ASS. Additionally, all French rheumatology and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were asked to report their observations of ASS patients with ACPA. The 17 collected patients were retrospectively studied using a standardized questionnaire and compared with 34 unselected ACPA-negative ASS patients in a case–control study. All ACPA-positive ASS patients suffered from arthritis versus 41% in the control group (Pu200a<u200a0.0001). The number of swollen joints was significantly higher (7.0u200a±u200a5.0 vs 2.9u200a±u200a3.9, Pu200a<u200a0.005), with a distribution resembling that of RA. Radiographic damages were also more frequent in ACPA-positive ASS patients (87% vs 11%, Pu200a<u200a0.0001). Aside from a significantly higher transfer factor for carbon monoxide in ACPA–ASS patients, lung, muscle, and skin involvements had similar incidences, patterns, and severity in both groups. Although Nonbiologic treatments were similarly used in both groups, ACPA-positive patients received biologics more frequently (59% vs 12%, Pu200a<u200a0.0008), mostly due to refractory arthritis (nu200a=u200a9). Eight patients received anti-Cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) with good efficacy and tolerance, whereas 2 of the 5 patients treated with antitumor necrosis factor drugs had worsened myositis and/or interstitial lung disease. After a >7-year mean follow-up, extra-articular outcomes and survival were not different. ACPA-positive ASS patients showed an overlapping RA–ASS syndrome, were at high risk of refractory erosive arthritis, and might experience ASS flare when treated with antitumor necrosis factor drugs. In contrast, other biologics such as anti-CD20 mAb were effective in this context, without worsening systemic involvements.

High-sensitivity cardiac troponin assays: answers to frequently asked questions.

Cardiac troponin (cTn) assays have quickly gained in analytical sensitivity to become what are termed high-sensitivity cardiac troponin (hs-cTn) assays, bringing a flurry of dense yet incomplete literature data. The net result is that cTn assays are not yet standardized and there are still no consensus-built data on how to use and interpret cTn assay results. To address these issues, the authors take cues and clues from multiple disciplines to bring responses to frequently asked questions. In brief, the effective use of hs-cTn hinges on knowing: specific assay characteristics, particularly precision at the 99th percentile of a reference population; factors of variation at the 99th percentile value; and the high-individuality of hs-cTn assays, for which the notion of individual kinetics is more informative than straight reference to normal values. The significance of patterns of change between two assay measurements has not yet been documented for every hs-cTn assay. Clinicians need to work hand-in-hand with medical biologists to better understand how to use hs-cTn assays in routine practice.