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1.
Artigo em Inglês | MEDLINE | ID: mdl-31642912

RESUMO

OBJECTIVES: The reversibility of interstitial lung disease (ILD) in SSc is difficult to assess by current diagnostic modalities and there is clinical need for imaging techniques that allow for treatment stratification and monitoring. 18F-Fluorodeoxyglucose (FDG) PET/CT scanning may be of interest for this purpose by detection of metabolic activity in lung tissue. This study aimed to investigate the potential role of 18F-FDG PET/CT scanning for the quantitative assessment of SSc-related active ILD. METHODS: 18F-FDG PET/CT scans and high resolution CT scans of eight SSc patients, including five with ILD, were analysed. For comparison, reference groups were included: eight SLE patients and four primary Sjögren's syndrome (pSS) patients, all without ILD. A total of 22 regions of interest were drawn in each patient at apical, medial and dorsobasal lung levels. 18F-FDG uptake was measured as mean standardized uptake value (SUVmean) in each region of interest. Subsequently, basal/apical (B/A) and medial/apical (M/A) ratios were calculated at patient level (B/A-p and M/A-p) and at tissue level (B/A-t and M/A-t). RESULTS: SUVmean values in dorsobasal ROIs and B/A-p ratios were increased in SSc with ILD compared with SSc without ILD (P = 0.04 and P = 0.07, respectively), SLE (P = 0.003 and P = 0.002, respectively) and pSS (P = 0.03 and P = 0.02, respectively). Increased uptake in the dorsobasal lungs and increased B/A-t ratios corresponded to both ground glass and reticulation on high resolution CT. CONCLUSION: Semi-quantitative assessment of 18F-FDG PET/CT is able to distinguish ILD from non-affected lung tissue in SSc, suggesting that it may be used as a new biomarker for SSc-ILD disease activity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31539063

RESUMO

OBJECTIVES: To gain insight into SSc patients' perspective on quality of care and to survey their preferred quality indicators. METHODS: An online questionnaire about healthcare setting, perceived quality of care (CQ index) and quality indicators, was sent to 2093 patients from 13 Dutch hospitals. RESULTS: Six hundred and fifty patients (mean age 59 years, 75% women, 32% limited cutaneous SSc, 20% diffuse cutaneous SSc) completed the questionnaire. Mean time to diagnosis was 4.3 years (s.d. 6.9) and was longer in women compared with men (4.8 (s.d. 7.3) vs 2.5 (s.d. 5.0) years). Treatment took place in a SSc expert centre for 58%, regional centre for 29% or in both for 39% of patients. Thirteen percent of patients was not aware of whether their hospital was specialized in SSc. The perceived quality of care was rated with a mean score of 3.2 (s.d. 0.5) (range 1.0-4.0). There were no relevant differences between expert and regional centres. The three prioritized process indicators were: good patient-physician interaction (80%), structural multidisciplinary collaboration (46%) and receiving treatment according to SSc guidelines (44%). Absence of disease progression (66%), organ involvement (33%) and digital ulcers (27%) were the three highest rated outcome indicators. CONCLUSION: The perceived quality of care evaluated in our study was fair to good. No differences between expert and regional centres were observed. Our prioritized process and outcome indicators can be added to indicators suggested by SSc experts in earlier studies and can be used to evaluate the quality of care in SSc.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30517706

RESUMO

Objective: To investigate the relationship between remission and health-related quality of life (HRQoL) in patients with SLE in a longitudinal observational cohort. Methods: HRQoL was measured at cohort visits using the physical and mental component score (PCS and MCS, respectively) of the Short Form 36 questionnaire. Definitions of Remission in SLE remission categories (no remission/remission on therapy/remission off therapy) were applied. Determinants of PCS and MCS were identified with simple linear regression analyses. Association between remission and HRQoL was assessed using generalized estimating equation models. Results: Data from 154 patients with 2 years of follow-up were analysed. At baseline 60/154 (39.0%) patients were in either form of remission. Patients in remission had higher Short Form 36 scores in all subdomains compared with patients not in remission. PCS was positively associated with remission and employment, and negatively associated with SLICC damage index, ESR, medication, patient global assessment and BMI. MCS was positively associated with Caucasian ethnicity and negatively associated with patient global assessment. In generalized estimating equation analysis, a gradual and significant increase of PCS was observed from patients not in remission (mean PCS 36.0) to remission on therapy (41.8) to remission off therapy (44.8). No significant difference in MCS was found between remission states. Conclusion: we show a strong and persistent association between remission and PCS, but not MCS. These results support the relevance (construct validity) of the Definition of Remission in SLE remission definitions and the further development of a treat-to-target approach in SLE.

5.
RMD Open ; 4(Suppl 1): e000782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402270

RESUMO

Systemic sclerosis (SSc) is an orphan disease characterised by autoimmunity, fibrosis of the skin and internal organs, and vasculopathy. SSc may be associated with high morbidity and mortality. In this narrative review we summarise the results of a systematic literature research, which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines or recommendations. Only in the domains 'Vascular & Ulcers' (ie, non-pharmacological approach to digital ulcer), 'PAH' (ie, screening and treatment), 'Treatment' and 'Juveniles' (ie, evaluation of juveniles with Raynaud's phenomenon) evidence-based and consensus-based guidelines could be included. Hence there is a preponderance of unmet needs in SSc referring to the diagnosis and (non-)pharmacological treatment of several SSc-specific complications. Patients with SSc experience significant uncertainty concerning SSc-related taxonomy, management (both pharmacological and non-pharmacological) and education. Day-to-day impact of the disease (loss of self-esteem, fatigue, sexual dysfunction, and occupational, nutritional and relational problems) is underestimated and needs evaluation.

6.
BMJ Open ; 8(8): e020479, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127049

RESUMO

INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disease characterised by inflammation, fibrosis and vasculopathy. Digital ulcers (DUs) are a frequent manifestation of vasculopathy in patients with SSc. Despite recent advances in pharmacological treatments, DU still have major health and economic implications. As there is currently no proven therapeutic strategy to promote DU healing, new treatments are urgently needed. Mesenchymal stem or stromal cells (MSCs) may provide a novel therapy for DU in SSc, because of their immunomodulatory and vasculoregenerative properties. Allogeneic MSC therapy involves functionally competent MSCs from healthy donors and may be used as 'off-the-shelf' available treatment. This study will evaluate whether allogeneic MSC therapy is a safe and potentially efficacious treatment for DU of SSc. METHODS AND ANALYSIS: The MANUS (Mesenchymal stromal cells for Angiogenesis and Neovascularization in digital Ulcers of Systemic Sclerosis) Trial is a double-blind randomised placebo-controlled trial. 20 patients with SSc with refractory DU will be randomised to receive eight intramuscular injections with either placebo or 50*106 MSCs. The primary outcome is the toxicity of the treatment at 12 weeks after administration. Secondary outcomes include (serious) adverse events, number and time to healing of DU, pain, reported hand function, quality of life and SSc disease activity. We will also evaluate changes in nailfold capillaroscopy pattern, as well as biochemical parameters and biomarkers in peripheral blood and skin biopsies. Follow-up visits will be scheduled at 48 hours and 2, 4, 8, 12, 24 and 52 weeks post-treatment. If the results confirm safety, feasibility and potential efficacy, a large multicentre randomised controlled trial with longer follow-up will be initiated focusing on efficacy. ETHICS AND DISSEMINATION: The study has been approved by the Dutch Central Committee on Research Concerning Human Subjects (protocol no: NL51705.000.15). The results will be disseminated through patient associations and conventional scientific channels. TRIAL REGISTRATION NUMBER: NCT03211793; Pre-results.

8.
Rheumatology (Oxford) ; 57(4): 631-638, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29329443

RESUMO

Objectives: Excessive bone formation is an important hallmark of AS. Recently it has been demonstrated that axial bony lesions in AS patients can be visualized using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F-fluoride uptake in clinically active AS patients is related to focal bone formation in spine biopsies and is sensitive to change during anti-TNF treatment. Methods: Twelve anti-TNF-naïve AS patients [female 7/12; age 39 years (SD 11); BASDAI 5.5 ± 1.1] were included. 18 F-fluoride PET-CT scans were performed at baseline and in two patients, biopsies were obtained from PET-positive and PET-negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually by two blinded expert readers. In addition, 18F-fluoride uptake was quantified using the standardized uptake value corrected for individual integrated whole blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined according to a ⩾ 20% improvement in Assessment of SpondyloArthritis international Society criteria at 24 weeks. Results: At baseline, all patients showed at least one axial PET-positive lesion. Histological analysis of PET-positive lesions in the spine confirmed local osteoid formation. PET-positive lesions were found in the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes (20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12 weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased significantly in the costovertebral (mean SUVAUC -1.0; P < 0.001) and SI joints (mean SUVAUC -1.2; P = 0.03) in contrast to non-responders. Conclusions: 18F-fluoride PET-CT identified bone formation, confirmed by histology, in the spine and SI joints of AS patients and demonstrated alterations in bone formation during anti-TNF treatment.


Assuntos
Antirreumáticos/uso terapêutico , Fluordesoxiglucose F18/farmacologia , Osteogênese/fisiologia , Coluna Vertebral/diagnóstico por imagem , Espondilite Anquilosante/diagnóstico por imagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Idoso , Biópsia , Feminino , Seguimentos , Humanos , Imagem Tridimensional , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacologia , Espondilite Anquilosante/tratamento farmacológico , Adulto Jovem
9.
Joint Bone Spine ; 85(2): 219-226, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28363827

RESUMO

OBJECTIVES: To validate the IFN response gene (IRG) set for the prediction of non-response to rituximab in rheumatoid arthritis (RA) and assess the predictive performance upon combination of this gene set with clinical parameters. METHODS: In two independent cohorts of 93 (cohort I) and 133 (cohort II) rituximab-starting RA patients, baseline peripheral blood expression of eight IRGs was determined, and averaged into an IFN score. Predictive performance of IFN score and clinical parameters was assessed by logistic regression. A multivariate prediction model was developed using a forward stepwise selection procedure. Patients with a decrease in disease activity score (ΔDAS28)≥1.8 after 6 months of therapy were considered responders. RESULTS: The mean IFN score was higher in non-responders compared to responders in both cohorts, but this difference was most pronounced in patients who did not use prednisone, as described before. Univariate analysis in cohort I showed that baseline DAS28, IFN score, DMARD use and negativity for IgM-RF and/or ACPA were associated with rituximab non-response. The multivariate model consisted of DAS28, IFN score and DMARD use, which showed an area under the curve (AUC) of 0.82. In cohort II, this model revealed a comparable AUC in PREDN-negative patients (0.78), but AUC in PREDN-positive patients was significantly lower (0.63), which seemed due to effect modification of the IFN score by prednisone. CONCLUSIONS: Combination of predictive parameters provided a promising model for the prediction of non-response to rituximab, with possibilities for optimization via definition of the exact interfering effect of prednisone on IFN score. TRIAL REGISTRATION (COHORT II, SMART TRIAL): NCT01126541, registered 18 May 2010.

10.
Rheumatology (Oxford) ; 57(3): 555-562, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29029294

RESUMO

Objectives: Several chronic inflammatory diseases are associated with cardiovascular disease, but the risk in ANCA-associated vasculitis is poorly quantified. The aim of the present study was to review the evidence for an increased cardiovascular risk, including ischaemic heart disease, cerebrovascular accidents and peripheral arterial disease, in patients with ANCA-associated vasculitis. Methods: A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses. The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies comparing vasculitis patients with at least one control group. Summary estimates were derived with a random-effects model and reported as relative risks. Results: One thousand three hundred and seventy-five studies were identified. Seven studies were included, comprising almost 14 000 ANCA-associated vasculitis patients vs general population controls in six studies and chronic kidney disease patients in one study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% CI: 1.23, 2.22) for all cardiovascular events, 1.60 (95% CI: 1.39, 1.84) for ischaemic heart disease and 1.20 (95% CI: 0.98, 1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates. Conclusion: This meta-analysis of observational studies supports an increase in cardiovascular risk in patients with ANCA-associated vasculitis of ∼65%, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Doenças Cardiovasculares/epidemiologia , Idoso , Doenças Cardiovasculares/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Fatores de Risco
11.
BMC Nephrol ; 18(1): 378, 2017 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-29287588

RESUMO

BACKGROUND: In ANCA-associated vasculitis the acute phase of the disease is often preceded by prodromal symptoms. The aim of the present study was to analyze the relation between the duration of the prodromal phase and renal damage. METHODS: Patients with ANCA-associated vasculitis and renal involvement from a retrospective single-center cohort were divided into two equal groups based on the duration of the prodromal phase. The prodromal phase was defined as the time between first vasculitis related symptoms and the date of diagnosis. Clinical characteristics at diagnosis and renal items on the vasculitis damage index at 6 months were compared between the two groups. In addition, the relation between a long prodromal phase and 3-year end-stage renal disease and mortality as a composite outcome was studied. RESULTS: A total of 72 patients were included (age 64 ± 12 years; 74% male; 96% Caucasian). At diagnosis, in patients with a prodromal phase ≤22 weeks versus >22 weeks estimated glomerular filtration rate and proteinuria did not differ significantly (35 (interquartile range 50) versus 30 (50) ml/min p = 0.84; 75% versus 87%, p = 0.21 respectively). Furthermore, Birmingham Vasculitis Activity Scores were comparable (7 (3), p = 0.71). At 6 months, a long prodromal phase was associated with proteinuria (odds ratio 5.38, 95% confidence interval (CI) 1.47-19.62), but not with an estimated glomerular filtration rate ≤ 50 ml/min (odds ratio 0.89, 95% CI 0.33-2.37) in multivariable analyses. In addition, a long prodromal phase was associated with end-stage renal disease/mortality (hazard ratio 5.22, 95% CI 1.13-24.20). CONCLUSIONS: A long prodromal phase was associated with proteinuria and 3-year end-stage renal disease/mortality, but not with a reduced renal function at 6 months. These results underline the importance of an early diagnosis in ANCA-associated vasculitis patients in order to improve renal outcomes.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Rim/fisiopatologia , Sintomas Prodrômicos , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Países Baixos/epidemiologia , Estudos Retrospectivos , Fatores de Risco
12.
RMD Open ; 3(2): e000502, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29119006

RESUMO

Objective: To evaluate if COmbinatie therapie Bij Reumatoïde Artritis (COBRA)-light therapy is cost-effective in treating patients with early rheumatoid arthritis (RA) compared with COBRA therapy. Methods: This economic evaluation was performed next to the open-label, randomised non-inferiority COBRA-light trial in 164 patients with early RA. Non-responders to COBRA or COBRA-light received etanercept (50 mg/week) for 3-6 months. The societal perspective analysis took medical direct, non-medical direct and indirect costs into account. Costs were measured with patient cost diaries for the follow-up period of 52 weeks. Bootstrapping techniques estimated uncertainty around the cost-effectiveness ratios, presented in cost-effectiveness planes. Results: 164 patients were randomised to either COBRA or COBRA-light strategy. At week 52, COBRA-light proved to be non-inferior to COBRA therapy on all clinical outcome measures. The results of the base-case cost-utility analysis (intention-to-treat analyses) revealed that COBRA-light strategy is more expensive (k€9.3 (SD 0.9) compared with COBRA (k€7.2 (SD 0.8)), but the difference in costs were not significant (k€2.0; 95% CI -0.3 to 4.4). Also, both strategies produced similar quality-adjusted life-years (QALYs). The sensitivity analyses showed robustness of these results. In a per-protocol sensitivity analysis, in which costs of etanercept were assumed to be provided as prescribed according to protocol, both arms had much higher costs: COBRA-light: k€11.5 (8.3) compared with k€8.5 (6.8) for COBRA, and the difference in costs was significant (k€2.9; 0.6 to 5.3). Conclusions: In the base-case cost-utility analysis, the two strategies produced similar QALYs for similar costs. But it is anticipated that if protocol had been followed correctly, the COBRA-light strategy would have been more costly due to additional etanercept costs, for a limited health gain. Given the limited added benefit and high costs of starting etanercept in the presence of low disease activity in our trial, such a strategy needs better justification than is available now. Trial registration number: 55552928, Results.

13.
J Immunol Res ; 2017: 8245879, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29094052

RESUMO

Objective: To investigate disease activity around and during pregnancy and pregnancy outcome in women with systemic lupus erythematosus (SLE) considering antiphospholipid antibody status. Moreover, differences between first and consecutive pregnancies were examined. Methods: Pregnancies > 16 weeks gestation of SLE patients receiving joint care from rheumatologists and gynecologists in two tertiary centers in the Netherlands between 2000 and 2015 were included. Disease activity, flare rate, and pregnancy outcomes and complications were assessed. Results: Ninety-six women (84% Caucasian) with 144 pregnancies were included. The median SLE(P)DAI score was 2 before, during, and after pregnancy. Flare rates were 6.3%, 20.1%, and 15.3%, respectively. Severe hypertensive disorder of pregnancy, intrauterine fetal death, preterm birth, and small-for-gestational age infants occurred in 18.1%, 4.1%, 32.7%, and 14.8%, respectively. Complication rates were similar in the first and consecutive pregnancies. Half of the women did not experience any pregnancy complication whereas 42.7% developed a complication during all pregnancies. Mean number of pregnancies was 2.4 and live births 1.7. Conclusion: In this SLE population with low disease activity, pregnancy complications were present irrespective of antiphospholipid antibody status. Furthermore, there were no differences in complication rates between the first and consecutive pregnancies as seen in healthy mothers. This information is useful for patient counseling.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Adulto , Anticorpos Antifosfolipídeos/metabolismo , Estudos de Coortes , Aconselhamento , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Países Baixos , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Adulto Jovem
14.
Rheumatology (Oxford) ; 56(9): 1586-1596, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28859326

RESUMO

Objective: To assess the efficacy and safety of initial COBRA-light vs COBRA therapy in RA patients after a 4-year follow-up period. Methods: In the COBRA-light trial, 162 consecutive patients with recent-onset RA were randomized to either COBRA-light (prednisolone and MTX) or COBRA therapy (prednisolone, MTX and SSZ) for 1 year. After 1 year, treatment was continued without protocol, and adjusted by the treating physician according to clinical judgement, preferably with a treat-to-target strategy. Four years after trial initiation, all patients were invited to participate in the COBRA-light extension study, in which patients were interviewed and physically examined, patient reported outcomes were assessed, radiographs were made and clinical records were examined for comorbidities and medication use. Results: In the extension study, 149 out of 162 (92%) original trial patients participated: 72 COBRA-light and 77 COBRA patients. Initial COBRA-light and COBRA therapy showed similar effect on disease activity, physical functioning, radiological outcome and Boolean remission over the 4-year follow-up period. In addition, both treatment groups showed similar survival and major comorbidities, although the power to detect differences was limited. Besides protocolled differences in prednisolone, MTX and SSZ use, the use of other synthetic and biologic DMARDs and intra-articular and intramuscular glucocorticoid injections was similar in both treatment groups over the 4-year period. Conclusion: Early RA patients initially treated with COBRA-light or COBRA therapy had similar efficacy and safety outcomes over a 4-year follow-up period.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Comorbidade , Progressão da Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Radiografia , Índice de Gravidade de Doença , Sulfassalazina/administração & dosagem , Sulfassalazina/efeitos adversos , Sulfassalazina/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento
15.
PLoS One ; 12(8): e0181847, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28800625

RESUMO

BACKGROUND: 18F-FDG-PET(/CT) is increasingly used in studies aiming at quantifying atherosclerotic plaque inflammation. Considerable methodological variability exists. The effect of data acquisition and image analysis parameters on quantitative uptake measures, such as standardized uptake value (SUV) and target-to-background ratio (TBR) has not been investigated extensively. OBJECTIVE: The goal of this study was to explore the effect of several data acquisition and image analysis parameters on quantification of vascular wall 18F-FDG uptake measures, in order to increase awareness of potential variability. METHODS: Three whole-body emission scans and a low-dose CT scan were acquired 38, 60 and 90 minutes after injection of 18F-FDG in six rheumatoid arthritis patients with high cardiovascular risk profiles.Data acquisition (1 and 2) and image analysis (3, 4 and 5) parameters comprised:1. 18F-FDG uptake time, 2. SUV normalisation, 3. drawing regions/volumes of interest (ROI's/VOI's) according to: a. hot-spot (HS), b. whole-segment (WS) and c. most-diseased segment (MDS), 4. Background activity, 5. Image matrix/voxel size.Intraclass correlation coefficients (ICC's) and Bland Altman plots were used to assess agreement between these techniques and between observers. A linear mixed model was used to determine the association between uptake time and continuous outcome variables. RESULTS: 1. Significantly higher TBRmax values were found at 90 minutes (1,57 95%CI 1,35-1,80) compared to 38 minutes (1,30 95%CI 1,21-1,39) (P = 0,024) 2. Normalising SUV for BW, LBM and BSA significantly influences average SUVmax (2,25 (±0,60) vs 1,67 (±0,37) vs 0,058 (±0,013)). 3. Intraclass correlation coefficients were high in all vascular segments when SUVmax HS was compared to SUVmax WS. SUVmax HS was consistently higher than SUVmax MDS in all vascular segments. 4. Blood pool activity significantly decreases in all (venous and arterial) segments over time, but does not differ between segments. 5. Image matrix/voxel size does not influence SUVmax. CONCLUSION: Quantitative measures of vascular wall 18F-FDG uptake are affected mainly by changes in data acquisition parameters. Standardization of methodology needs to be considered when studying atherosclerosis and/or vasculitis.


Assuntos
Fluordesoxiglucose F18/química , Inflamação/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Placa Aterosclerótica/patologia
16.
J Rheumatol ; 44(10): 1453-1457, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28668810

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic immune-mediated disease of unknown etiology. Among its clinical manifestations, pulmonary involvement is the leading cause of mortality in patients with SSc. However, the genetic factors involved in lung complication are not well defined. We aimed to review the association of the MIF gene, which encodes a cytokine implicated in idiopathic pulmonary hypertension among other diseases, with the susceptibility and clinical expression of SSc, in addition to testing the association of this polymorphism with SSc-related pulmonary involvement. METHODS: A total of 4392 patients with SSc and 16,591 unaffected controls from 6 cohorts of European origin were genotyped for the MIF promoter variant rs755622. An inverse variance method was used to metaanalyze the data. RESULTS: A statistically significant increase of the MIF rs755622*C allele frequency compared with controls was observed in the subgroups of patients with diffuse cutaneous SSc (dcSSc) and with pulmonary arterial hypertension (PAH) independently (dcSSc: p = 3.20E-2, OR 1.13; PAH: p = 2.19E-02, OR 1.32). However, our data revealed a stronger effect size with the subset of patients with SSc showing both clinical manifestations (dcSSc with PAH: p = 6.91E-3, OR 2.05). CONCLUSION: We reviewed the association of the MIF rs755622*C allele with SSc and described a phenotype-specific association of this variant with the susceptibility to develop PAH in patients with dcSSc.


Assuntos
Predisposição Genética para Doença , Hipertensão Pulmonar/genética , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Esclerodermia Difusa/genética , Alelos , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Hipertensão Pulmonar/etiologia , Esclerodermia Difusa/complicações
17.
Rheumatology (Oxford) ; 56(8): 1407-1416, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28460084

RESUMO

Objective: The aim was to investigate the association between autoantibodies (autoAbs) and neuropsychiatric (NP) involvement in patients with SLE and to evaluate whether any autoAb or a combination of these autoAbs could indicate the underlying pathogenic process. Methods: Using a multiplexed protein array for 94 antigens, we compared the serum autoAb profiles of 69 NPSLE patients, 203 SLE patients without NP involvement (non-NPSLE) and 51 healthy controls. Furthermore, we compared the profiles of NPSLE patients with clinical inflammatory (n = 38) and ischaemic (n = 31) NP involvement. Results: In total, 75 IgG and 47 IgM autoAbs were associated with SLE patients in comparison with healthy controls. Comparing NPSLE with non-NPSLE and healthy control sera, 9 IgG (amyloid, cardiolipin, glycoprotein 2, glycoprotein 210, heparin, heparan sulphate, histone H2A, prothrombin protein and vimentin) and 12 IgM (amyloid, cardiolipin, centromere protein A, collagen II, histones H2A and H2B, heparan sulphate, heparin, mitochondrial 2, nuclear Mi-2, nucleoporin 62 and vimentin) autoAbs were present at significantly different levels in NPSLE. The combination of IgG autoAbs against heparan sulphate, histone H2B and vimentin could differentiate NPSLE from non-NPSLE (area under the curve 0.845, 99.97% CI: 0.756, 0.933; P < 0.0001). Compared with non-NPSLE, four IgG and seven IgM autoAbs were significantly associated with inflammatory NPSLE. In ischaemic NPSLE, three IgG and three IgM autoAbs were significantly different from non-NPSLE patients. Conclusion: In our cohort, the presence of high levels of anti-heparan sulphate and anti-histone H2B combined with low levels of anti-vimentin IgG autoAbs is highly suggestive of NPSLE. These results need to be validated in external cohorts.


Assuntos
Autoanticorpos/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Adulto , Autoanticorpos/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Heparitina Sulfato/imunologia , Histonas/imunologia , Humanos , Imunoglobulina G/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Masculino , Pessoa de Meia-Idade , Análise Serial de Proteínas , Vimentina/imunologia
18.
Rheumatology (Oxford) ; 56(6): 1008-1012, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28340004

RESUMO

Objectives: The aims were to assess the prevalence of malnutrition and to validate bioelectrical impedance analysis (BIA) against whole-body DXA for the assessment of body composition in patients with SSc. Methods: Malnutrition was defined as BMI <18.5 kg/m 2 or unintentional weight loss >10% in combination with a fat-free mass index (FFMI) <15 kg/m 2 for women or <17 kg/m 2 for men or BMI <20.0 kg/m 2 (age <70 years) or <22 kg/m 2 (age >70 years). Body composition was assessed in 72 patients with whole-body DXA (Hologic, Discovery A) and BIA (Bodystat Quadscan 400). The manufacturer's equation and the Geneva equation were used to estimate FFM and fat mass. The agreement between BIA and whole-body DXA was assessed with Bland-Altman analysis and intraclass correlation coefficient. Results: Malnutrition was found in 8.3% (n = 6) and low FFMI in 20.8% (n = 15) of patients. The mean difference in FFM between BIA and DXA applying the Geneva equation was 0.02 ( s . d . 2.4) kg, intraclass correlation coefficient 0.97 (95% CI: 0.95, 0.98). Limits of agreement were ±4.6 kg. The manufacturer's equation was less adequate to predict FFM. Conclusion: This study shows a relatively low prevalence of malnutrition in comparison with other studies, but a high prevalence of low FFMI, underlining the necessity of measuring body composition in SSc patients with a standardized and validated method. A good validity of BIA in determining FFM was found at a group level, while at an individual level the FFM may vary by 4.6 kg.


Assuntos
Composição Corporal/fisiologia , Desnutrição/patologia , Escleroderma Sistêmico/patologia , Absorciometria de Fóton , Adulto , Idoso , Impedância Elétrica , Feminino , Humanos , Masculino , Desnutrição/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroderma Sistêmico/complicações
20.
Rheumatology (Oxford) ; 56(9): 1472-1478, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28199724

RESUMO

Objective: To assess the 10-year cardiovascular (CV) risk score and to identify treatment and undertreatment of CV risk factors in patients with established RA. Methods: Demographics, CV risk factors and prevalence of cardiovascular disease (CVD) were assessed by questionnaire. To calculate the 10-year CV risk score according to the Dutch CV risk management guideline, systolic blood pressure was measured and cholesterol levels were determined from fasting blood samples. Patients were categorized into four groups: indication for treatment but not treated; inadequately treated, so not meeting goals (systolic blood pressure ⩽140 mmHg and/or low-density lipoprotein ⩽2.5 mmol/l); adequately treated; or no treatment necessary. Results: A total of 720 consecutive RA patients were included, 375 from Reade and 345 from the Antonius Hospital. The mean age of patients was 59 years (s.d. 12) and 73% were female. Seventeen per cent of the patients had a low 10-year CV risk (<10%), 21% had an intermediate risk (10-19%), 53% a high risk (⩾20%) and 9% had CVD. In total, 69% had an indication for preventive treatment (cholesterol-lowering or antihypertensive drugs). Of those, 42% received inadequate treatment and 40% received no treatment at all. Conclusion: Optimal CV risk management remains a major challenge and better awareness and management are urgently needed to reduce the high risk of CVD in the RA population.


Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/etiologia , Idoso , Anti-Hipertensivos/uso terapêutico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Estudos Transversais , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Medição de Risco/métodos , Fatores de Risco , Gestão de Riscos/métodos , Gestão de Riscos/normas
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