RESUMO
OBJECTIVES: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. METHOD: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. RESULTS: Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5). CONCLUSIONS: Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01656278.
Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Osteíte , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Produtos Biológicos/uso terapêutico , Edema/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Imageamento por Ressonância Magnética , Osteíte/diagnóstico por imagem , Osteíte/tratamento farmacológico , Osteíte/etiologia , Indução de Remissão , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
In 41 primary Sjögren's syndrome patients we compared fatty acid levels within erythrocyte phospholipids, plasma phospholipids, plasma triglycerides and plasma cholesterol esters, with the immunopathological and clinical disease status. Docosahexaenoic acid was the essential fatty acid (EFA), the levels of which correlated (inversely) most closely with the clinical disease status (r=-0.33 to -0.50). Levels of dihomogammalinolenic acid and eicosapentaenoic acid correlated inversely to levels of IgM rheumatoid factors (r=-0.33) and anti-SSA/Ro antibodies (r=-0.40) respectively. Moreover, levels of anti-SSA/Ro antibodies (r=-0.34-0.40) correlated with levels of the proinflammatory arachidonic acid. Sigma n-3 EFA/sigma n-6 EFA ratios correlated significantly to the quantitative estimates of immunopathological and clinical disease status. Our data are in agreement with current understanding of pro- and anti-immunoinflammatory roles within EFA metabolism, and support the rationale for intervention studies.
Assuntos
Ácidos Graxos Essenciais/sangue , Síndrome de Sjogren/classificação , Ácido 8,11,14-Eicosatrienoico/metabolismo , Adulto , Idoso , Autoanticorpos/sangue , Ésteres do Colesterol/sangue , Ácidos Docosa-Hexaenoicos/metabolismo , Eritrócitos/química , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/sangue , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Triglicerídeos/sangueRESUMO
In spite of our continuously improved pathobiological understanding, there is still no consensus on terminology and disease criteria in Sjögren's syndrome (SS). This survey points out discrepencies in the current description of the syndrome, and argues for a new classification model. We suggest that the present nomenclatures for the global disease (Sjögren's disease) and disease subsets (primary and secondary SS) be retained until additional pathobiological insights give rise to new and descriptive terms. We do find evidence, however, to support a new terminology and classification of the main immunoinflammatory manifestations of primary SS. Accordingly, three "exocrine" and four "non-exocrine" subgroups of disease manifestations are here defined. The usefulness of the proposed model should be evaluated in clinical studies and in a debate engaging all of the medical specialities involved.
Assuntos
Síndrome de Sjogren/classificação , Terminologia como Assunto , Doenças Autoimunes/classificação , Doenças Autoimunes/patologia , Doenças Autoimunes/fisiopatologia , Glândulas Exócrinas/patologia , Glândulas Exócrinas/fisiopatologia , Humanos , Síndrome de Sjogren/patologia , Síndrome de Sjogren/fisiopatologiaRESUMO
STUDY DESIGN: This prospective triple-blind randomized study of 99 patients concerned the use of free fat transplantation for operation for lumbar disc herniation. OBJECTIVE: To subsequently examine the patients after median 376 days who were subjected to enhanced computed tomographic scan. SUMMARY OF BACKGROUND DATA: In studies on experiments with animals, the degree of intraspinal scar tissue has shown to be reduced in connection with free fat transplantation. Scar tissue is seen frequently after operation for lumbar disc herniation, but it is uncertain whether the scar tissue can lead to symptoms. METHODS: The clinical outcome was scored using the Low Back Pain Rating Scale. Enhanced computed tomographic scan was assessed regarding the degree of scar tissue and survival of fat transplant. RESULTS: There was no different in the clinical outcome between the two groups. Significantly fewer patients had dural scarring in the group who had a fat transplantation, but there was no difference regarding the degree of radicular scarring. The transplant was shown on computed tomographic scan at the follow-up examination in 66% of the patients who had a fat transplantation. CONCLUSIONS: Free fat transplantation can reduced the degree of dural scar tissue after operation for lumbar disc herniation but does not result in a clinically better outcome.
Assuntos
Tecido Adiposo/transplante , Discotomia/efeitos adversos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Adulto , Idoso , Cicatriz/diagnóstico por imagem , Cicatriz/etiologia , Cicatriz/prevenção & controle , Feminino , Seguimentos , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Análise de Regressão , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Sixty-two patients with chronic low back pain occurring 14-60 months after undergoing discectomy for the first time were randomized to two physical treatment groups: 24 sessions of intensive dynamic back exercises with hyperextension or 24 sessions of intensive dynamic back exercises without hyperextension. At the conclusion of therapy and at one-year follow-up, no difference was seen between the randomized groups, with regard to the combined assessments of pain, disability and objective measurements. A difference for back exercises without hyperextension to be superior to the other treatment regimen was statistically significant at the three-month follow-up. In the patient's qualitative assessment of treatment outcome there were seen no significant differences between back exercises with or without hyperextension. There was a similar and significant improvement of the isometric endurance of back muscles in both groups, but the flexibility of the spine was significantly improved only in the group using hyperextension exercises. The overall response rate of an earlier published investigation was reproduced. It is concluded that chronic back patients after first time discectomy may benefit from an intensive rehabilitation protocol including intensive exercises. The added use of hyperextension exercises does not confer any independent benefit. Furthermore, the training had to continue for more than 2-3 months before a statistical significant decrease in back pain was reported in the patient pain diary.
Assuntos
Dor nas Costas/reabilitação , Terapia por Exercício , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/reabilitação , Adulto , Idoso , Dor nas Costas/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Inquéritos e QuestionáriosRESUMO
Establishing a model for classification of the clinical disease manifestations in primary Sjögren's syndrome is a challenge with important implications for handling individual patients and for describing and analyzing patient materials. Based on the pathobiology of primary SS we define three (1-3) "exocrine" and four (4-7) "nonexocrine" subgroups of disease manifestations. Accordingly, 1) "surface exocrine disease" includes the diagnostic features from eyes (keratoconjunctivitis sicca) and mouth (xerostomia), and the manifestations from upper airways (rhinitis sicca, xerotracheitis) and skin (xeroderma). Involvement of the excretory parenchyma of the lungs, hepatobiliary system, pancreas, intestinal tract and kidneys is designated 2) "internal organ exocrine disease". These manifestations are potentially severe, do not lead to subjective dryness, and none of them are diagnostic for the disease. We suggest 3) "monoclonal B-lymphocyte disease" (lymphoma) to be an exocrine disease manifestation because it originates mostly from the immunoinflammatory foci of the autoimmune exocrinopathy. The nonexocrine manifestations are subgrouped into: 4) "inflammatory vascular disease" (vasculitis and perivasculitis), 5) "noninflammatory vascular disease" (Raynaud), 6) "mediator-induced disease" (hematologic cytopenia, fever and fatigue) and 7) "autoimmune endocrine disease". Subdividing the seven subgroups leads to a third order of classification in which single and separate manifestations are placed. The descriptive and analytic power of the proposed model for classification of disease manifestations in primary Sjögren's syndrome should be evaluated in clinical studies.
Assuntos
Síndrome de Sjogren/classificação , Oftalmopatias/etiologia , Oftalmopatias/patologia , Oftalmopatias/fisiopatologia , Humanos , Doenças da Boca/etiologia , Doenças da Boca/patologia , Doenças da Boca/fisiopatologia , Síndrome de Sjogren/patologia , Síndrome de Sjogren/fisiopatologia , Dermatopatias/etiologia , Dermatopatias/patologia , Dermatopatias/fisiopatologiaRESUMO
Primary Sjögren's syndrome (pSS) is increasingly acknowledged as a disease entity with consistent pathogenesis and clinical presentation. This has encouraged proposals for uniform nomenclature, as well as for classification of disease subsets and clinical disease manifestations. The purpose of this literature survey is to analyse present pathogenetic and clinical data on pSS from the viewpoint of their usability for developing criteria for activity and damage. It appears that the routinely used tests for evaluating clinical disease manifestations in pSS probably measure both activity and damage. Moreover, no immunopathogenic marker has been shown to adequately represent all aspects of disease activity in pSS. The survey demonstrates the need for longitudinal studies in which potential markers of disease activity and damage are validated.
Assuntos
Síndrome de Sjogren/fisiopatologia , Biomarcadores , Humanos , Síndrome de Sjogren/classificação , Terminologia como AssuntoRESUMO
The aim of this prospective triple-blind randomized study was to determine if a free fat transplant used in operation in lumbar disc herniation could reduce the degree of intraspinal scar tissue and to evaluate whether the scar tissue could lead to symptoms. Ninety-nine patients were subsequently examined after median 376 days. The clinical outcome was scored using the Low Back Pain Rating Scale. Enhanced CT-scanning was assessed regarding the degree of scar tissue and survival of the fat transplant. There was no difference in the clinical outcome between the two groups. Significantly fewer had dural scarring in the group who had a free fat transplantation, but there was no difference regarding the degree of radicular scarring. The transplant was shown on CT-scan at the follow-up examination in 66% of the patients who had a fat transplantation. Free fat transplantation can reduce the degree of dural scar tissue after operation for lumbal disc herniation, but does not result in a clinically better outcome.
Assuntos
Tecido Adiposo/transplante , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Deslocamento do Disco Intervertebral/diagnóstico , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos ProspectivosRESUMO
Primary Sjögren's syndrome is a chronic systemic rheumatic disease characterized as an autoimmune exocrinopathy or autoimmune epithelitis thereby suggesting a pathogenesis leading to tissue specific autoimmune lesion. The development of internationally approved criteria for the classification and diagnosis of Sjögren's syndrome has been a major scientific task for nearly two decades with consensus now approaching. In contrast, an international dialogue on how to develop additional common criteria for the assessment of disease activity, organ damage and outcome in Sjögren's syndrome has just recently been initiated. Such assessment criteria would provide useful measures for patient management and are mandatory for comparing efficacy between different clinical trials. The lack of common assessment criteria may be explained by missing uniform diagnostic criteria, by the multispeciality and systemic nature of the disease and the difficulties in separating out what is activity and what is damage in Sjögren's syndrome. Attempts are now made to overcome these problems. The purpose of this paper is to give a brief introduction to the concepts of disease activity, damage and outcome in Sjogren's syndrome with reference to the results obtained from a recent workshop on assessment tools in Sjögren's syndrome held in Oxford, England in March 2000.
Assuntos
Qualidade de Vida , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Monitorização Fisiológica/métodos , Prognóstico , Índice de Gravidade de DoençaRESUMO
A new model for classifying the clinical disease manifestations of primary Sjögren's syndrome is introduced. Three "exocrine' and four "nonexocrine' subgroups of disease manifestations are defined. Accordingly, "surface exocrine disease' includes the diagnostic features from eyes, mouth, and the manifestations from the upper airways, skin and genital tract. Involvement of the excretory parenchyma of the lungs, hepatobiliary system, pancreas, gastrointestinal tract and kidneys is designated "internal organ exocrine disease'. We suggest "monoclonal B lymphocyte disease' to be an exocrine disease manifestation because it originates mostly from the immunoinflammatory foci of the autoimmune exocrinopathy. The nonexocrine manifestations are subgrouped into "inflammatory vascular disease'. "noninflammatory vascular disease', "mediator-induced disease' and "autoimmune endocrine disease'.
Assuntos
Síndrome de Sjogren/classificação , Autoimunidade , Glândulas Exócrinas , Humanos , Inflamação , Modelos Biológicos , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Síndrome de Sjogren/fisiopatologiaRESUMO
The purpose of this study was to explore the clinical and pathogenic significance of vitamin D metabolites in primary Sjögren's syndrome (primary SS). We measured blood concentrations of 25-hydroxyvitamin D (25 OH D) and calcitriol (1,25(OH)2D)vc in 41 patients and correlated the results with blood levels of various immune activation products, as well as with patients' clinical status. Levels of 25 OH D were slightly decreased as compared to normal controls and the reduced levels of 25 OH D were stable over the observed period of 2 years. Levels of 25 OH D correlated inversely with levels of soluble interleukin-2 receptor, status indices for global disease, total exocrine disease, surface exocrine disease, internal organ exocrine disease, and mediator-induced disease. Levels of 1,25(OH)2D varied considerably and compared to normal control values. Levels of 1,25(OH)2D did not correlate with clinical/immunopathological status. In conclusion the inverse correlations found between levels of 25 OH D and measures of clinical and immunoinflammatory status support the notion that vitamin D metabolism may be involved in the pathogenesis of primary SS.
Assuntos
Síndrome de Sjogren/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D/sangueRESUMO
OBJECTIVES: The clinical features of 80 patients with primary Sjögren's syndrome (PSS) were revised in order to evaluate the descriptive and analytical facilities of a newly proposed model for classification of the exocrine and nonexocrine disease manifestations in PSS. DESIGN: Retrospective, long-term (median 7.5 years follow-up) observational, clinical study. SETTING: Patients were recruited from our Department, which is a tertiary referral centre for PSS patients. SUBJECTS: Eighty patients fulfilling the Copenhagen criteria for keratoconjunctivitis sicca and/or xerostomia and followed between 1972 and 1991 were studied. RESULTS: All patients had 'surface exocrine disease' and in 31% this was the only disease manifestation. 'Internal organ exocrine disease' was found in 25% of the patients, whilst 2.5% developed 'monoclonal B lymphocyte disease' (non-Hodgkin's lymphoma). 28% displayed 'inflammatory vascular disease', 25% 'noninflammatory vascular disease', 41% "mediator-induced disease' and 2.5% 'autoimmune endocrine disease' (thyroiditis). In patients with 'internal organ exocrine disease' the frequencies of "mediator-induced disease' (70%; P < 0.01) and 'inflammatory vascular disease, (50%; P < 0.03) were significantly higher than expected by chance. The level of immunoinflammatory activity (assessed by plasma IgG, serum ANA and focus scoring of minor labial salivary gland biopsies) correlated with the extent of clinical disease as assessed by the model. CONCLUSIONS: We conclude that this theoretically based model for classification of disease manifestations in PSS contains descriptive and analytic powers which may assist the clinical handling of these patients.
Assuntos
Síndrome de Sjogren/classificação , Idoso , Autoimunidade , Biomarcadores/sangue , Diagnóstico Diferencial , Glândulas Exócrinas , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Retrospectivos , Síndrome de Sjogren/sangue , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Síndrome de Sjogren/fisiopatologiaRESUMO
Quantitative and qualitative assessment of the clinical disease manifestations in 41 primary Sjögren's syndrome (pSS) patients was performed according to a new classification model. Frequencies of subgrouped disease manifestations were as follows: 1) surface exocrine disease: 100%, 2) internal organ exocrine disease: 63%, 3) monoclonal B lymphocyte disease: 5%, 4) inflammatory vascular disease: 71%, 5) non-inflammatory vascular disease: 59%, 6) mediator induced disease: 98%. Summary scores for severity of surface exocrine disease correlated to the summary scores of all other disease manifestations (p = 0.02), to the summary scores of internal organ exocrine disease (p = 0.003), and to the summary scores of mediator induced disease (p = 0.03). Blood leucocyte counts showed significant negative correlations to levels of plasma IgG, serum IgA-RF, IgM-RF, anti-SSA/SSB antibodies, IL-6, and IL-1Ra. We conclude that the model made detailed analysis of the clinical presentation of pSS possible, and thus may assist in elucidating important pathobiological aspect of the disease.
Assuntos
Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Proteínas Sanguíneas/análise , Estudos Transversais , Citocinas/sangue , Feminino , Humanos , Sistema Imunitário/imunologia , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/sangue , Síndrome de Sjogren/classificaçãoRESUMO
To determine the value of "Low Back Pain Rating Scale" as a postal questionnaire, a retrospective study was undertaken of patients who had undergone first-time lumbar disc surgery 14-72 months previously. Rate of response was 86% (261/304). From the results, it was concluded that 87% of the patients felt that a satisfactory surgical outcome was obtained; 67% had minor or major functional restrictions of their daily activities; 65% experienced significant low-back symptoms in the period prior to follow-up examination; and 57% experienced sciatica. Thirty-seven patients were receiving pensions in the postoperative period due to continued back pain. "Low Back Pain Rating Scale" used as a postal questionnaire was found to be useful in determining general overall assessment status in patients who had undergone lumbar surgery. This evaluation method could be used as a quality control in future studies regarding this patient group.
Assuntos
Dor nas Costas/epidemiologia , Avaliação da Deficiência , Deslocamento do Disco Intervertebral/cirurgia , Laminectomia/efeitos adversos , Vértebras Lombares/cirurgia , Ciática/epidemiologia , Adulto , Dor nas Costas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/epidemiologia , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
In a retrospective study, 18 preoperative demographic and physical variables were evaluated for their preoperative prognostic value in 261 patients, following first-time lumbar disc surgery. Special reference was given to the Spengler and Finneson index-scores. "Low Back Pain Rating Scale" was used as the outcome assessment instrument. Comprehensive statistical analysis was undertaken in order to separate only the contingently independent variables. Gender was a highly significant prognostic factor. Other independently statistically significant prognostic factors include dermatomal hypoalgesia, smoking, and the Finneson index score. Results of the study are discussed with reference to the available literature.
Assuntos
Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5/137), rheumatoid arthritis (1/21), and systemic lupus erythematosus (1/58). Sera from healthy donors and patients with chronic infections were negative, except for one Salmonella typhimurium antibody positive serum. Autoantibodies to annexin XI were found to relate to thrombosis, but not to other clinical or laboratory features. A relation between antibodies to annexins and thrombosis has so far only been known for annexin V.