RESUMO
OBJECTIVES: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt. METHODS: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups. RESULTS: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%). CONCLUSION: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104. TRIAL REGISTRATION NUMBER: NCT03649061. CTR PILOT APPROVAL BELGIUM: S59474, EudraCT number: 2017-004054-41.
Assuntos
Antirreumáticos , Artrite Reumatoide , Quimioterapia Combinada , Etanercepte , Glucocorticoides , Metotrexato , Humanos , Etanercepte/uso terapêutico , Etanercepte/administração & dosagem , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Antirreumáticos/administração & dosagem , Glucocorticoides/uso terapêutico , Glucocorticoides/administração & dosagem , Resultado do Tratamento , Idoso , Adulto , Indução de Remissão , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.
Assuntos
Difosfonatos , Osteíte Deformante , Humanos , Difosfonatos/efeitos adversos , Osteíte Deformante/complicações , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/genética , Proteína Sequestossoma-1/genética , Ácido Zoledrônico/uso terapêutico , Testes Genéticos , BiomarcadoresRESUMO
Osteogenesis imperfecta is a rare congenital disease of connective tissue characterized by recurrent fractures and progressive skeletal deformities which may impact on gait. The aims of this prospective study were to identify gait deviations in children with osteogenesis imperfecta compared to age-matched controls and establish relationships with clinical features. We evaluated 22 patients with different types of osteogenesis imperfecta using three-dimensional gait analysis. The incidence and location of frac- tures, fracture at birth, age at first fracture, use of intramedullary rodding and number of surgical in- terventions in the lower extremities, bone mineral density, hypermobility and number of injections of bisphosphonates were recorded for each patient. Step length was lower in the osteogenesis imperfecta group compared with the control group. Kinematics showed that sagittal pelvic and transversal hip range of motion were higher in the osteogenesis imperfecta group, whereas sagittal knee range of motion during swing phase was reduced. Regarding kinetics, hip flexion moment and hip negative power peak were significantly decreased in the osteogenesis imperfecta group. Mechanical and energetic parameters were considered as normal. The principal component analysis revealed that the bone mineral density was increased in children who had received more in- jections of bisphosphonates and these had also less deficit in kinematic parameters. Main modifications in gait parameters were observed in spatiotemporal, kinematic and kinetic data. More studies are necessary to allow stratification of severity of the osteogenesis imperfecta disease, help improve its challenging multidisciplinary treatment and ob- jectively assess treatment outcomes.
Assuntos
Osteogênese Imperfeita , Criança , Difosfonatos/uso terapêutico , Marcha , Análise da Marcha , Humanos , Recém-Nascido , Osteogênese Imperfeita/complicações , Estudos ProspectivosRESUMO
Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Osteíte Deformante , Proteína Sequestossoma-1 , Proteínas Adaptadoras de Transdução de Sinal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Osteíte Deformante/epidemiologia , Osteíte Deformante/genética , Proteína Sequestossoma-1/genética , Ácido ZoledrônicoRESUMO
INTRODUCTION: Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. METHODS AND ANALYSIS: People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events. ETHICS AND DISSEMINATION: The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable. TRIAL REGISTRATION NUMBER: ISRCTN11616770.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteíte Deformante/genética , Osteíte Deformante/prevenção & controle , Proteína Sequestossoma-1/genética , Ácido Zoledrônico/uso terapêutico , Adulto , Ansiedade/etiologia , Depressão/etiologia , Testes Genéticos , Humanos , Dor Musculoesquelética/etiologia , Mutação , Osteíte Deformante/complicações , Osteíte Deformante/diagnóstico por imagem , Qualidade de Vida , Cintilografia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year. METHODS: The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD-inexperienced patients with ERA were stratified into a high-risk or low-risk group based upon presence of erosions, disease activity, rheumatoid factor and anticitrullinated protein antibodies. High-risk patients were randomised to a COBRA Classic (MTX + sulfasalazine + prednisone step-down from 60â mg), COBRA Slim (MTX + prednisone step-down from 30â mg) or COBRA Avant Garde (MTX + leflunomide + prednisone step-down from 30â mg) scheme. Low-risk patients were randomised to MTX tight step-up (MTX-TSU) or COBRA Slim. Primary outcome was the proportion of patients in 28 joint disease activity score calculated with C-reactive protein remission at week 52 in an intention-to-treat analysis. Secondary outcomes were safety and effectiveness (ClinicalTrial.gov identifier NCT01172639). RESULTS: 98 COBRA Classic, 98 COBRA Slim (high risk), 93 COBRA Avant Garde, 47 MTX-TSU and 43 COBRA Slim (low risk) patients were evaluated. Remission was achieved in 64.3% (63/98) COBRA Classic, 60.2% (59/98) COBRA Slim (high risk) and 62.4% (58/93) COBRA Avant Garde patients at W52 (p=0.840); and in 57.4% (27/47) MTX-TSU and 67.4% (29/43) COBRA Slim (low risk) patients (p=0.329). Less adverse events occurred per patient with COBRA Slim (high risk) compared with COBRA Classic or COBRA Avant Garde (p=0.038). Adverse events were similar in MTX-TSU and COBRA Slim (low risk) patients (p=0.871). At W52, 76.0% patients were on DMARD monotherapy, 5.2% used GCs and 7.5% biologicals. CONCLUSIONS: MTX with a moderate-dose GC remission induction scheme (COBRA Slim) seems an effective, safe, low-cost and feasible initial treatment strategy for patients with ERA regardless of their prognostic profile, provided a treat-to-target approach is followed. TRIAL REGISTRATION NUMBERS: EudraCT-number 2008-007225-39 and NCT01172639; Results.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Proteína C-Reativa/metabolismo , Quimioterapia Combinada/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Isoxazóis/uso terapêutico , Leflunomida , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prognóstico , Indução de Remissão , Fatores de Risco , Índice de Gravidade de Doença , Sulfassalazina/uso terapêuticoRESUMO
INTRODUCTION: Considering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial. METHODS: Disease-modifying antirheumatic drug-naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti-citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3.2). Patients were randomized to 15 mg of MTX weekly (MTX with tight step-up (MTX-TSU)) or 15 mg of MTX weekly with prednisone bridging, starting at 30 mg and tapered to 5 mg daily from week 6 (COmbinatie therapie bij Reumatoïde Artritis (COBRA Slim)). A TSU approach was applied. Outcomes assessed were DAS28(CRP)-determined remission, cumulative disease activity, Health Assessment Questionnaire (HAQ) scores and adverse events (AEs) after 16 treatment weeks. RESULTS: We analyzed 43 COBRA Slim and 47 MTX-TSU patients and found that 65.1% in the COBRA Slim group and 46.8% in the MTX-TSU group reached remission (P = 0.081). Mean ± standard deviation area under the curve values of DAS28(CRP) were 13.84 ± 4.58 and 11.18 ± 4.25 for the MTX-TSU and COBRA Slim patients, respectively (P = 0.006). More COBRA Slim patients had an HAQ score of 0 (51.2% versus 23.4%, P = 0.006) at week 16. Therapy-related AEs between groups did not differ. CONCLUSION: In patients with low-risk eRA, MTX with step-down glucocorticoid bridging seems more efficacious than MTX step-up monotherapy, with a comparable number of AEs observed over the first 16 treatment weeks. TRIAL REGISTRATION: EU Clinical Trials Register Identifier: EudraCT number 2008-007225-39 . Registered 5 November 2008.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/análise , Glucocorticoides/uso terapêutico , Metotrexato/uso terapêutico , Adulto , Idoso , Área Sob a Curva , Artrite Reumatoide/sangue , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Keratin (K)19, a biliary/hepatic progenitor cell (HPC) marker, is expressed in a subset of hepatocellular carcinomas (HCC) with poor prognosis. The underlying mechanisms driving this phenotype of K19-positive HCC remain elusive. DESIGN: Clinicopathological value of K19 was compared with EpCAM, and α-fetoprotein, in a Caucasian cohort of 242 consecutive patients (167 surgical specimens, 75 needle biopsies) with different underlying aetiologies. Using microarrays and microRNA profiling the molecular phenotype of K19-positive HCCs was identified. Clinical primary HCC samples were submitted to in vitro invasion assays and to side population analysis. HCC cell lines were transfected with synthetic siRNAs against KRT19 and submitted to invasion and cytotoxicity assays. RESULTS: In the cohort of surgical specimens, K19 expression showed the strongest correlation with increased tumour size (p<0.01), decreased tumour differentiation (p<0.001), metastasis (p<0.05) and microvascular invasion (p<0.001). The prognostic value of K19 was also confirmed in a set of 75 needle biopsies. Profiling showed that K19-positive HCCs highly express invasion-related/metastasis-related markers (eg, VASP, TACSTD2, LAMB1, LAMC2, PDGFRA), biliary/HPC markers (eg, CD133, GSTP1, NOTCH2, JAG1) and members of the miRNA family 200 (eg, miR-141, miR-200c). In vitro, primary human K19-positive tumour cells showed increased invasiveness, and reside in the chemoresistant side population. Functionally, K19/KRT19 knockdown results in reduced invasion, loss of invadopodia formation and decreased resistance to doxorubicin, 5-fluorouracil and sorafenib. CONCLUSIONS: Giving the distinct invasive properties, the different molecular profile and the poor prognostic outcome, K19-positive HCCs should be considered as a seperate entity of HCCs.
Assuntos
Carcinoma Hepatocelular/fisiopatologia , Queratina-19/fisiologia , Neoplasias Hepáticas/fisiopatologia , Antígenos de Neoplasias/fisiologia , Biomarcadores/análise , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Moléculas de Adesão Celular/fisiologia , Linhagem Celular Tumoral , Molécula de Adesão da Célula Epitelial , Técnicas de Silenciamento de Genes , Humanos , Queratina-19/análise , Neoplasias Hepáticas/química , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Invasividade Neoplásica/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , alfa-Fetoproteínas/fisiologiaRESUMO
OBJECTIVES: Fatigue is an important aspect of spondyloarthritis (SpA). However the influencing factors of fatigue in SpA are unclear. The objective of this study was to explore if fatigue is related to disease activity or to patient characteristics. METHODS: This was a retroelective observational study (Cochin COSPA study) in one tertiary-referral centre. The primary outcome was fatigue, evaluated on a 0-100mm Visual Analogue Scale (VAS). The covariates were demographic characteristics, disease subtype (axial vs. peripheral) and disease-related factors, e.g. Bath Disease Activity Index (BASDAI), patient global assessment (VAS), Bath Functional Index (BASFI). To explain fatigue, univariate then multivariate logistic regressions were conducted (with fatigue analysed as above or below 50 mm), as well as multiple linear regressions with the different covariates. RESULTS: Two hundred and sixty-six SpA patients were analysed. Sixty-one percent were male; mean age and disease duration were 44.5±13.5 years and 16.8±11.7 years, respectively. Mean VAS fatigue was 49.3±32.7mm; 49.6% of patients had fatigue VAS>50mm. Logistic regression showed high fatigue was associated with disease: BASDAI and BASFI (p<0.0001), as well as female gender (p=0.025) and aerobic exercise (p=0.005), but there was no difference in the subtypes of SpA. In multivariate analysis, the single factor explaining fatigue was patient global assessment (p<0.001 and odds ratio =1.35). By linear regression, demographic variables explained 2.8% of the variance, whereas disease characteristics and activity explained 44.6%. CONCLUSIONS: Fatigue levels were high in SpA patients whatever the subtype and appeared more strongly related to the disease than to patient-related variables, thus confirming its usefulness as an outcome measure.
Assuntos
Fadiga/epidemiologia , Espondilartrite/epidemiologia , Adulto , Estudos Transversais , Fadiga/diagnóstico , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Paris/epidemiologia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Inquéritos e Questionários , Centros de Atenção Terciária , Fatores de TempoRESUMO
OBJECTIVE: To assess the effects on bone mineral density (BMD) of prolonged anti-tumor necrosis factor (anti-TNF) therapy in patients with spondyloarthritis (SpA); to compare the BMD changes to those observed in SpA patients not treated with anti-TNF; and to identify the predictors of these changes. METHODS: Fifty-nine patients with SpA according to the European Spondylarthropathy Study Group criteria who were treated with anti-TNF therapy for at least 4 years were included. Thirty-four patients with SpA from an international longitudinal observational study (OASIS cohort) were used as a control group. Lumbar spine and hip BMD were measured by dual-energy x-ray absorptiometry at baseline, after 1 year, and after at least 4 years. RESULTS: Over an average 6.5 years' followup, the increase in BMD was 11.8% (± 12.8%) at the lumbar spine (p < 0.0001) and 3.6% (± 9.3%) at the great trochanter (p = 0.0001) in patients treated with anti-TNF. At the lumbar spine, the increase was similar in patients with and those without syndesmophytes. BMD changes were significantly higher in the anti-TNF group than in the control group at lumbar spine (p < 0.0001), at femoral neck (p = 0.002), and at trochanter (p = 0.011), but not at total hip (p = 0.062). Multivariate analysis showed that the predictors of lumbar spine BMD changes in the total population were the use of anti-TNF (p < 0.0001) and, in the anti-TNF therapy group, the 1-year lumbar spine BMD change (p = 0.007). CONCLUSION: This study shows that prolonged anti-TNF therapy increases lumbar spine and trochanter BMD. This effect should be taken into account before introducing antiosteoporotic treatment in these patients.
Assuntos
Antirreumáticos/farmacologia , Densidade Óssea/efeitos dos fármacos , Articulação do Quadril/efeitos dos fármacos , Vértebras Lombares/efeitos dos fármacos , Espondilartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Quimioterapia Combinada , Etanercepte , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Humanos , Imunoglobulina G/farmacologia , Imunoglobulina G/uso terapêutico , Infliximab , Vértebras Lombares/diagnóstico por imagem , Masculino , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Radiografia , Receptores do Fator de Necrose Tumoral/uso terapêutico , Espondilartrite/diagnóstico por imagem , Resultado do TratamentoRESUMO
OBJECTIVES: To assess bone mineral density (BMD) at lumbar spine and hip in a large cohort of patients with early inflammatory back pain (IBP) suggestive of axial spondyloarthritis (SpA), and to assess systemic and bone inflammation (according to MRI) as risk factors of low BMD. PATIENTS AND METHODS: 332 (52.4% male) patients with IBP suggestive of axial SpA defined by Calin or Berlin criteria were recruited; they had lumbar spine and hip BMD and body composition measurements. Low BMD was defined by Z≤-2 (at least one site). Clinical, biological (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and imaging (x-rays, spine and sacroiliac joint MRI) parameters were compared in patients with and without low BMD (Z≤-2). Significant parameters in univariate analysis were tested in multivariate models. RESULTS: Patients (mean age 33.8 years) had a short duration of axial symptoms (mean 1.6 years); 71.4% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA and HLA-B27 was present in 62.1%. 43 (13.0%) had low BMD (88% male). Multivariate logistic regression showed that parameters significantly associated with low BMD (any site) were the presence of bone marrow oedema (inflammatory lesions) on MRI (OR 4.63, p=0.001), either ESR or CRP (OR 2.60, p=0.037) and male gender (OR 9.60, p=0.0004). CONCLUSIONS: This study conducted in a large cohort of young adults with early IBP suggestive of SpA shows that 13.0% of patients have a low BMD and that the main risk factor associated with low BMD was inflammation on MRI.
Assuntos
Dor nas Costas/etiologia , Edema/complicações , Osteoporose/etiologia , Espondilartrite/complicações , Absorciometria de Fóton/métodos , Adolescente , Adulto , Dor nas Costas/epidemiologia , Dor nas Costas/fisiopatologia , Sedimentação Sanguínea , Densidade Óssea/fisiologia , Doenças Ósseas/complicações , Doenças Ósseas/diagnóstico , Doenças Ósseas/epidemiologia , Doenças Ósseas/fisiopatologia , Proteína C-Reativa/metabolismo , Estudos de Coortes , Edema/diagnóstico , Edema/epidemiologia , Edema/fisiopatologia , Feminino , França/epidemiologia , Articulação do Quadril/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Fatores de Risco , Espondilartrite/epidemiologia , Espondilartrite/fisiopatologia , Adulto JovemRESUMO
OBJECTIVES: Heel pain is a common but poorly studied feature of spondyloarthritis (SpA). The aims of this study were to assess the prevalence and clinical features of heel pain in a cohort of patients with SpA. METHODS: This was a retrolective single centre observational study in 2010. Patients with SpA as defined by Amor's criteria were recruited. The data collected were: demographic and disease characteristics, history of heel pain, age at first heel pain, localisation, nature and intensity of pain and treatments. The analyses were descriptive. RESULTS: A total of 275 SpA patients (mean age 44.6±13.5 yrs, mean disease duration 16.7±11.8 yrs, 61.5% men) were assessed. A history of heel pain was reported in 130 patients (47.1%), and was the first symptom of SpA in 15.7% of all patients. Heel pain was frequent in both axial (89/201, 44.3%) and peripheral disease (27/56, 48.2%). Distribution was more frequently inferior (88, 69.3%) than posterior (61, 48.0%) (p<0.0001), and frequently bilateral: simultaneously (41.9%) rather than alternatively (29.1%) (p=0.03). Main clinical symptoms were: morning pain on weight bearing (83.6%), but also night pain (34.4%), and/or patient-described swelling (24.2%). Heel pain was frequently recurrent (74.2%), intense (70.3%), source of a limp (71.6%), and often resistant to non-steroidal anti-inflammatory drugs (NSAIDs) (54/108, 50%). Tumour necrosis factor blockers were efficacious on heel pain in 72/94 (76.6%) of cases. CONCLUSIONS: This study confirmed heel pain as a frequent symptom in both axial and peripheral SpA. It occurred early in the disease course and it was frequently recurrent and resistant to NSAIDs.
Assuntos
Artralgia/epidemiologia , Artralgia/patologia , Calcanhar/patologia , Espondilartrite/epidemiologia , Espondilartrite/patologia , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artralgia/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Espondilartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVES: Hip involvement is a classic feature of spondyloarthritis (SpA). The aim of the present paper is to study the prevalence, clinical and radiological features of hip involvement, and the association with criteria for severity, in a cohort of patients with SpA in a tertiary care centre. DESIGN: retrospective single centre observational study in 2010 of patients with definite SpA who underwent direct interview by a physician. Hip involvement was defined as hip pain considered related to SpA inflammation and confirmed radiographically. Other data collection: demographic data, SpA characteristics, treatments performed for hip involvement. ANALYSIS: prevalence of hip involvement was analysed according to disease duration (Kaplan-Meyer). Multivariate Cox analysis compared patients with vs. without hip involvement over time. RESULTS: In all, 275 SpA patients were assessed. The median age was 45 (IQR 35-55) years, the median SpA symptom duration 14 (7-25) years, 61% (169) were men, and 79% were HLA-B27 positive. Hip involvement was found in 18% (49) SpA patients, with already 13% after 5 years of disease duration and with frequent bilateral involvement (61%). Hip involvement was associated with non-Caucasian origin (p=0.05). Thirty-three percent (16/49) needed surgery (23 total joint replacements in all) with good functional results. CONCLUSIONS: Hip involvement is a frequent manifestation in SpA (18%), often bilateral, and associated with non-Caucasian origin. One third of the patients needed total joint replacement. Physicians should be wary of hip pain in SpA patients and implement rapid diagnostic procedures in such cases.
Assuntos
Artralgia/epidemiologia , Artralgia/patologia , Articulação do Quadril/patologia , Espondilartrite/epidemiologia , Espondilartrite/patologia , Adulto , Artralgia/cirurgia , Artrite/epidemiologia , Artrite/patologia , Artroplastia de Quadril/estatística & dados numéricos , Estudos Transversais , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVES: Dactylitis is a common but little studied feature of spondylarthritis (SpA). Our objective was to assess the prevalence of dactylitis among a cohort of patients with spondylarthritis in a tertiary care centre and to describe the clinical characteristics of dactylitis. METHODS: This was a prospective single centre observational study carried out in 2010. The patients included had been diagnosed as having definite SpA based on Amo's criteria. Each patient was interviewed by a physician. The data collected included prevalence of dactylitis and its clinical characteristics, effectiveness of the different treatments, and association with severe manifestations of SpA, and analysed by descriptive analysis. RESULTS: 275 consecutive SpA patients were assessed: mean age 43.2±13.5 years, mean disease duration 14.0±11.8 years, 169 (61.4%) were men. In all, 59 patients (21.5%) suffered from SpA-associated dactylitis. The localisation of dactylitis was toes in 46 patients (78.0%) and/or fingers in 25 patients (42.4%). The most frequent localisations were the second toe and the second finger. Dactylitis was the first symptom of SpA in 14 patients (5.1%), and 28.8% (n=17) of dactylitis appeared within the first 5 years of disease. Dactylitis was present in 35.1% (n=13) of patients with undifferenciated SpA and in 30.6% (n=15) of patients with psoriatic arthritis. It was significantly associated with history of peripheral arthritis or heel pain. In our population, there was no correlation between dactylitis and HLA B27 status or sex and it was not a marker of severity of disease. CONCLUSIONS: Dactylitis is a frequent manifestation in SpA (21.5%) particularly in peripheral disease and it may be the first manifestation of the disease with localisation being more frequent in the toes.
Assuntos
Deformidades Adquiridas do Pé/epidemiologia , Deformidades Adquiridas da Mão/epidemiologia , Inflamação/epidemiologia , Espondilartrite/epidemiologia , Adulto , Estudos Transversais , Feminino , Dedos , Deformidades Adquiridas do Pé/diagnóstico , Deformidades Adquiridas do Pé/terapia , Deformidades Adquiridas da Mão/diagnóstico , Deformidades Adquiridas da Mão/terapia , Humanos , Inflamação/diagnóstico , Inflamação/terapia , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Prevalência , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Espondilartrite/terapia , Dedos do PéRESUMO
OBJECTIVE: To evaluate the performance of the Assessment in Spondyloarthritis International Society (ASAS) criteria (axial or peripheral) against the Amor and European Spondylarthropathy Study Group criteria in established spondyloarthritis (SpA). METHODS: Rheumatologist-diagnosed patients with SpA were retrospectively classified according to the different criteria sets. Clinical characteristics of patients fulfilling all 3 criteria were compared with those who did not, by nonparametric statistics. RESULTS: ASAS classified 90% of the 231 patients, with 169 (73%) fulfilling all 3 criteria sets. Multivariate analysis showed the 62 patients not fulfilling all criteria sets were older at symptom onset (p < 0.001) and less likely to have inflammatory back pain (p < 0.001), peripheral arthritis (p < 0.001), or elevated C-reactive protein levels (p = 0.034). CONCLUSION: ASAS criteria can be used in established disease.
Assuntos
Classificação Internacional de Doenças/normas , Doenças Reumáticas/classificação , Doenças Reumáticas/diagnóstico , Sociedades Médicas/normas , Espondilartrite/classificação , Espondilartrite/diagnóstico , Adulto , Estudos de Coortes , Diagnóstico Diferencial , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Reumáticas/epidemiologia , Espondilartrite/epidemiologiaRESUMO
OBJECTIVES: Work status is an important outcome in SpA. The objective was to assess work instability and its determinants in a cohort of patients with SpA, using the AS-work instability scale (AS-WIS). METHODS: We performed a cross-sectional monocentre study. Patients were definite SpA patients with paid work. Work instability was measured by the AS-WIS. Its determinants were assessed by correlations with SpA scores (BASDAI, BASFI and patient's global assessment) and patients with low work instability (AS-WIS score < 11) were compared with those with moderate to high instability, through backward logistic regression. RESULTS: In all, 156 patients were assessed: mean (s.d.) age 41 (11) years, mean disease duration 15 (11) years; 71 (45.5%) were on TNF blockers. The mean AS-WIS score was 9.5 (5.5); 55 (35%) patients had moderate and 8 (5%) patients had high work instability. Correlations of the AS-WIS score with SpA scores were significant but moderate (BASDAI R = 0.42, BASFI R = 0.41, patient's global assessment R = 0.53; P < 0.0001). In multivariate analysis, high patient's global assessment was the only element associated with moderate to high work instability; demographic characteristics and treatments were not significant elements. CONCLUSION: Work instability was found to be high and its main determinant was patient's global assessment. The predictive validity of the AS-WIS in terms of job retention should be further assessed.
Assuntos
Avaliação da Deficiência , Emprego/estatística & dados numéricos , Perfil de Impacto da Doença , Espondilite Anquilosante/fisiopatologia , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espondilite Anquilosante/diagnósticoRESUMO
OBJECTIVES: Anterior chest wall pain is a common but little studied feature of spondyloarthritis. The objectives of our study were to assess the prevalence of anterior chest wall pain and to describe its clinical characteristics in a cohort of spondyloarthritis patients in a tertiary care center. STUDY DESIGN: retrolective single center observational study in 2010 (COSPA). Consecutive patients with definite spondyloarthritis according to Amor's criteria were included. DATA COLLECTION: each patient underwent direct interview by a physician. Prevalence of anterior chest wall pain, according to spondyloarthritis subtype and its date of appearance, localization and nature were collected. RESULTS: In all, 275 consecutive spondyloarthritis patients were assessed. Among them, 102 patients (37.1%) suffered from spondyloarthritis-associated anterior chest wall pain. It was the first symptom of spondyloarthritis in 3.6% of cases. The prevalence after 5 and 10 years following the diagnosis of spondyloarthritis was 26.0% and 35.5%, respectively. Pain was usually in the upper chest and acute, increased by respiratory movements and movements of the arm; pain during the night was less frequent (41.0%). A flare lasted on average 5 weeks; recurrences were frequent (75%). Non-steroidal anti-inflammatory drugs and anti-tumor necrosis factor agents were reported as effective in 49.3% and 80.0% of cases, respectively. CONCLUSION: Anterior chest wall pain was a frequent manifestation in spondyloarthritis. It occurred early in the disease course, but the risk persisted after disease onset. Better knowledge of the clinical characteristics of this symptom may help physicians for diagnosis and follow-up.
Assuntos
Dor no Peito/epidemiologia , Dor no Peito/etiologia , Espondilartrite/complicações , Parede Torácica , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Dor no Peito/tratamento farmacológico , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Radiografia , Cintilografia , Estudos Retrospectivos , Parede Torácica/diagnóstico por imagem , Parede Torácica/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVES: To evaluate expert treatment selection for early rheumatoid arthritis and to validate a prediction model for rapid radiographic progression (RRP) in daily practice. METHODS: Patients received initial combination therapy with steroids (ICTS) or disease-modifying antirheumatic drug monotherapy (IMT) after informal evaluation of prognostic factors, followed by a tight control strategy. Changes in Sharp/van der Heijde score (total Sharp score (TSS)) of >5 units over 1 year (=RRP) were documented. The mean change in TSS and proportion with RRP were compared between groups. Based on the 28 swollen joint count, rheumatoid factor titre and C reactive protein/erythrocyte sedimentation rate, patients were placed in the ASPIRE prediction matrix, yielding a RRP risk. Numbers needed to treat (NNT) intensively to avoid one RRP after 1 year were calculated. RESULTS: The mean change in TSS after 1 year and the proportion with RRP was lower in the ICTS group (n=37) than in the IMT group (n=43). The mean calculated risk of RRP was higher in patients with radiographic progression. The mean NNT intensively to prevent RRP was lower in the ICTS group than in the IMT group. The positive predictive value of NNT for RRP prevention was 12.6%, but the negative predictive value reached 100%. CONCLUSION: ICTS seems more effective in preventing RRP than IMT. The predictive matrix model could be helpful in preventing overtreatment in practice.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Seleção de Pacientes , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Técnicas de Apoio para a Decisão , Progressão da Doença , Quimioterapia Combinada , Métodos Epidemiológicos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RadiografiaRESUMO
We analyzed global gene expression patterns of 91 human hepatocellular carcinomas (HCCs) to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with patient survival. This association was validated via 5 independent supervised learning methods. We also identified the genes most strongly associated with survival by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification, suggesting an etiological involvement of these processes in accelerating the progression of HCC. In conclusion, the biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g., HIF1a) for selective treatment of HCC patients. Supplementary material for this article can be found on the HEPATOLOGY Web site (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html)
Assuntos
Carcinoma Hepatocelular/classificação , Perfilação da Expressão Gênica , Neoplasias Hepáticas/classificação , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidadeRESUMO
In animals, the combination of oxidative liver damage and inhibited hepatocyte proliferation increases the numbers of hepatic progenitors (oval cells). We studied different murine models of fatty liver disease and patients with nonalcoholic fatty liver disease or alcoholic liver disease to determine whether oval cells increase in fatty livers and to clarify the mechanisms for this response. To varying degrees, all mouse models exhibit excessive hepatic mitochondrial production of H(2)O(2), a known inducer of cell-cycle inhibitors. In mice with the greatest H(2)O(2) production, mature hepatocyte proliferation is inhibited most, and the greatest number of oval cells accumulates. These cells differentiate into intermediate hepatocyte-like cells after a regenerative challenge. Hepatic oval cells are also increased significantly in patients with nonalcoholic fatty liver disease and alcoholic liver disease. In humans, fibrosis stage and oval cell numbers, as well as the number of intermediate hepatocyte-like cells, are strongly correlated. However, cirrhosis is not required for oval cell accumulation in either species. Rather, as in mice, progenitor cell activation in human fatty liver diseases is associated with inhibited replication of mature hepatocytes. The activation of progenitor cells during fatty liver disease may increase the risk for hepatocellular cancer, similar to that observed in the Solt-Farber model of hepatocarcinogenesis in rats.