Prevalence and clinical characteristics of patients with rheumatoid arthritis with interstitial lung disease using unstructured healthcare data and machine learning

Artritis reumatoide; Epidemiologia; Fibrosi pulmonarRheumatoid arthritis; Epidemiology; Pulmonary fibrosisArtritis reumatoide; Epidemiología; Fibrosis pulmonarObjectives Real-world data regarding rheumatoid arthritis (RA) and its association with interstitial lung disease (ILD) is still scarce. This study aimed to estimate the prevalence of RA and ILD in patients with RA (RAILD) in Spain, and to compare clinical characteristics of patients with RA with and without ILD using natural language processing (NLP) on electronic health records (EHR). Methods Observational case–control, retrospective and multicentre study based on the secondary use of unstructured clinical data from patients with adult RA and RAILD from nine hospitals between 2014 and 2019. NLP was used to extract unstructured clinical information from EHR and standardise it into a SNOMED-CT terminology. Prevalence of RA and RAILD were calculated, and a descriptive analysis was performed. Characteristics between patients with RAILD and RA patients without ILD (RAnonILD) were compared. Results From a source population of 3 176 165 patients and 64 241 683 EHRs, 13 958 patients with RA were identified. Of those, 5.1% patients additionally had ILD (RAILD). The overall age-adjusted prevalence of RA and RAILD were 0.53% and 0.02%, respectively. The most common ILD subtype was usual interstitial pneumonia (29.3%). When comparing RAILD versus RAnonILD patients, RAILD patients were older and had more comorbidities, notably concerning infections (33.6% vs 16.5%, p<0.001), malignancies (15.9% vs 8.5%, p<0.001) and cardiovascular disease (25.8% vs 13.9%, p<0.001) than RAnonILD. RAILD patients also had higher inflammatory burden reflected in more pharmacological prescriptions and higher inflammatory parameters and presented a higher in-hospital mortality with a higher risk of death (HR 2.32; 95% CI 1.59 to 2.81, p<0.001). Conclusions We found an estimated age-adjusted prevalence of RA and RAILD by analysing real-world data through NLP. RAILD patients were more vulnerable at the time of inclusion with higher comorbidity and inflammatory burden than RAnonILD, which correlated with higher mortality.The RA-WILD study was fully supported by Bristol-Myers Squibb Company. Award/grant number not applicable

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum TimeCourse

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.This research was partially funded by FOREUM—Foundation for Research in Rheumatolog

Nuevas estrategias en el diagnóstico del cáncer asociado a las dermatomiositis y polimiositis

El diagnóstico de cáncer constituye un indicador de mal pronóstico en pacientes con dermatomiositis (DM) y polimiositis (PM) y se relaciona, además, con una parte importante de la mortalidad observada en estas entidades. Se estima que entre un 15% y un 30% de las DM y PM tienen un comportamiento paraneoplásico. La afectación inflamatoria del músculo y/o la piel parece originarse a partir de una reacción inmunológica cruzada entre antígenos del tejido tumoral (frente a los que se inicia la respuesta inmunitaria) y del músculo. Aunque en la mayor parte de estos casos la neoplasia y la miositis se diagnostican a la vez, un porcentaje significativo de neoplasias no pueden ser diagnosticadas en una primera evaluación, haciéndose únicamente clínicamente evidentes meses o años después del inicio de la miositis. La ausencia de marcadores para determinar que DM y PM tienen una etiología paraneoplásica constituye uno de los principales problemas en la evaluación de estos pacientes, y dificulta la realización de un diagnóstico precoz de las neoplasias que aparece con posterioridad al debut de la miositis, las cuales no es infrecuente que se presenten en forma de enfermedad diseminada. La presente tesis doctoral se ha diseñado con el objetivo de profundizar en esta problemática a partir de la realización de tres estudios independientes que pretenden evaluar posibles marcadores clínicos y serológicos de DM o PM paraneoplásica y la utilidad de nuevas técnicas diagnósticas para el cribado inicial de neoplasia en estas entidades. En un primer lugar se ha procedido al estudio del fenómeno del cáncer en una serie histórica de 85 pacientes con DM (65) y PM (20) atendidos en el servicio de Medicina Interna del Hospital Vall d'Hebron de Barcelona. Tras realizar un análisis descriptivo de la frecuencia de cáncer en la cohorte y valorar las características clínicas asociadas a esta condición, se ha investigado mediante la implementación de técnicas de inmunoprecipitación de proteinas la presencia del nuevo anticuerpo anti-p155, determinándose su grado de relación con las neoplasias. Mediante este estudio se ha conseguido aportar a la bibliografía la segunda serie más larga (hasta la fecha de publicación) de pacientes adultos con DM en los que se ha evaluado esta asociación. Los resultados obtenidos han confirmado en nuestra serie una frecuencia de neoplasia y un comportamiento clínico de las mismas similar al observado en la bibliografía. Se ha identificado también la presencia del anticuerpo anti-p155 en un 23% de pacientes con DM, describiéndose, de forma concordante con lo previamente reportado, una intensa asociación del mismo con aquellas miositis en las que se asume un origen paraneoplásico. En un segundo lugar, mediante una revisión sistemática y un metanálisis de todos los trabajos publicados sobre el tema se ha investigado la utilidad de la determinación del anticuerpo anti-p155 como test diagnóstico de miositis paraneoplásica. Mediante este estudio se ha podido caracterizar mejor y definir las propiedades de este anticuerpo cuando se utiliza para esta finalidad, quedando patente su potencial relevancia clínica en el cribado de neoplasia y la planificación de estrategias de seguimiento en estas entidades. Finalmente, se ha evaluado mediante un estudio prospectivo multicéntrico la utilidad del FDG-PET/TC para la detección precoz de neoplasias en pacientes con un diagnóstico reciente de DM y PM, demostrándose que esta exploración tiene una sensibilidad y especificidad similar a la observada con las estrategias de cribado convencionales. A partir de los resultados anteriores se propone finalmente una nueva estrategia de evaluación de neoplasia de pacientes con DM y PM tanto al inicio de la enfermedad como en su seguimiento.Dermatomyositis (DM) and polymyositis (PM) are often associated with cancer, which considerably determine the prognosis and is one of the main causes of mortality in this population. The incidence of cancer in published series of patients with idiopathic inflammatory myopathy (IIM) ranges from 15% to 30%. Inflammation in skin and muscle in patients with cancer-associated myositis (CAM) is supposed to appear as a paraneoplastic phenomenon secondary to an immune response directed to similar antigens present both in cancer and muscle tissues. As cancer can develop before, concurrently, or subsequent to the onset of IIM, cancer screening is now mandatory routine practice in patients with IIM. Nevertheless, there is no consensus as to the method or frequency with which patients should be tested to rule out neoplasm at diagnosis or during the follow-up. Clinical, analytical, and treatment response features that have been proposed as positive and negative predictive markers of malignancy are of uncertain usefulness in clinical practice. The aim of this doctoral thesis is to go in depth this topic through three different studies where clinical and new serologic and imaging techniques for CAM diagnosis are evaluated. In the first study we analyze the presence of cancer and the new myositis-specific autoantibody anti-p155 (determined by protein immunoprecipitation assays with HeLa cells) in a large cohort of patients with IIM and describe a number of clinical, serologic and laboratory features of CAM and p155-positive patients. The incidence of CAM in our series is similar than previously reported (19% in the complete cohort and 22% in DM group). Only the shawl sign shows a significant association with CAM. Anti-p155 is present in 23% of DM patients with a clear association with CAM, with an odds ratio of 23 (95% confidence interval, 5,23-101,2). The second study is a systematic review and meta-analysis of the published studies on this subject (including our first study) to ascertain the accuracy of anti-p155 for diagnosing CAM in DM. In this study the diagnostic value of anti-p155 for detecting paraneoplastic DM has been more precisely characterized, with a sensitivity and specificity of 78% and 89% respectively. Our data indicate an important potential role for negative anti-p155 results, which indicate a low probability of CAM in adult DM patients, and supports the usefulness of this antibody for diagnosing CAM and guiding patient management. The third study is a multicenter, 3-year prospective study including 55 consecutive patients with IIM, where the value of whole-body [18F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/TC) for diagnosing occult malignant disease in patients with myositis is compared to broad conventional cancer screening. According to our results FDG-PET/TC is not superior to broad convencional screening to diagnose occult cancer in myositis. Finally a new algorithm for the diagnosis of malignancy in myositis is proposed

Nuevas estrategias en el diagnóstico del cáncer asociado a las dermatomiositis y polimiositis

Descripció del recurs: el 01 setembre 2012El diagnóstico de cáncer constituye un indicador de mal pronóstico en pacientes con dermatomiositis (DM) y polimiositis (PM) y se relaciona, además, con una parte importante de la mortalidad observada en estas entidades. Se estima que entre un 15% y un 30% de las DM y PM tienen un comportamiento paraneoplásico. La afectación inflamatoria del músculo y/o la piel parece originarse a partir de una reacción inmunológica cruzada entre antígenos del tejido tumoral (frente a los que se inicia la respuesta inmunitaria) y del músculo. Aunque en la mayor parte de estos casos la neoplasia y la miositis se diagnostican a la vez, un porcentaje significativo de neoplasias no pueden ser diagnosticadas en una primera evaluación, haciéndose únicamente clínicamente evidentes meses o años después del inicio de la miositis. La ausencia de marcadores para determinar que DM y PM tienen una etiología paraneoplásica constituye uno de los principales problemas en la evaluación de estos pacientes, y dificulta la realización de un diagnóstico precoz de las neoplasias que aparece con posterioridad al debut de la miositis, las cuales no es infrecuente que se presenten en forma de enfermedad diseminada. La presente tesis doctoral se ha diseñado con el objetivo de profundizar en esta problemática a partir de la realización de tres estudios independientes que pretenden evaluar posibles marcadores clínicos y serológicos de DM o PM paraneoplásica y la utilidad de nuevas técnicas diagnósticas para el cribado inicial de neoplasia en estas entidades. En un primer lugar se ha procedido al estudio del fenómeno del cáncer en una serie histórica de 85 pacientes con DM (65) y PM (20) atendidos en el servicio de Medicina Interna del Hospital Vall d'Hebron de Barcelona. Tras realizar un análisis descriptivo de la frecuencia de cáncer en la cohorte y valorar las características clínicas asociadas a esta condición, se ha investigado mediante la implementación de técnicas de inmunoprecipitación de proteinas la presencia del nuevo anticuerpo anti-p155, determinándose su grado de relación con las neoplasias. Mediante este estudio se ha conseguido aportar a la bibliografía la segunda serie más larga (hasta la fecha de publicación) de pacientes adultos con DM en los que se ha evaluado esta asociación. Los resultados obtenidos han confirmado en nuestra serie una frecuencia de neoplasia y un comportamiento clínico de las mismas similar al observado en la bibliografía. Se ha identificado también la presencia del anticuerpo anti-p155 en un 23% de pacientes con DM, describiéndose, de forma concordante con lo previamente reportado, una intensa asociación del mismo con aquellas miositis en las que se asume un origen paraneoplásico. En un segundo lugar, mediante una revisión sistemática y un metanálisis de todos los trabajos publicados sobre el tema se ha investigado la utilidad de la determinación del anticuerpo anti-p155 como test diagnóstico de miositis paraneoplásica. Mediante este estudio se ha podido caracterizar mejor y definir las propiedades de este anticuerpo cuando se utiliza para esta finalidad, quedando patente su potencial relevancia clínica en el cribado de neoplasia y la planificación de estrategias de seguimiento en estas entidades. Finalmente, se ha evaluado mediante un estudio prospectivo multicéntrico la utilidad del FDG-PET/TC para la detección precoz de neoplasias en pacientes con un diagnóstico reciente de DM y PM, demostrándose que esta exploración tiene una sensibilidad y especificidad similar a la observada con las estrategias de cribado convencionales. A partir de los resultados anteriores se propone finalmente una nueva estrategia de evaluación de neoplasia de pacientes con DM y PM tanto al inicio de la enfermedad como en su seguimiento.Dermatomyositis (DM) and polymyositis (PM) are often associated with cancer, which considerably determine the prognosis and is one of the main causes of mortality in this population. The incidence of cancer in published series of patients with idiopathic inflammatory myopathy (IIM) ranges from 15% to 30%. Inflammation in skin and muscle in patients with cancer-associated myositis (CAM) is supposed to appear as a paraneoplastic phenomenon secondary to an immune response directed to similar antigens present both in cancer and muscle tissues. As cancer can develop before, concurrently, or subsequent to the onset of IIM, cancer screening is now mandatory routine practice in patients with IIM. Nevertheless, there is no consensus as to the method or frequency with which patients should be tested to rule out neoplasm at diagnosis or during the follow-up. Clinical, analytical, and treatment response features that have been proposed as positive and negative predictive markers of malignancy are of uncertain usefulness in clinical practice. The aim of this doctoral thesis is to go in depth this topic through three different studies where clinical and new serologic and imaging techniques for CAM diagnosis are evaluated. In the first study we analyze the presence of cancer and the new myositis-specific autoantibody anti-p155 (determined by protein immunoprecipitation assays with HeLa cells) in a large cohort of patients with IIM and describe a number of clinical, serologic and laboratory features of CAM and p155-positive patients. The incidence of CAM in our series is similar than previously reported (19% in the complete cohort and 22% in DM group). Only the shawl sign shows a significant association with CAM. Anti-p155 is present in 23% of DM patients with a clear association with CAM, with an odds ratio of 23 (95% confidence interval, 5,23-101,2). The second study is a systematic review and meta-analysis of the published studies on this subject (including our first study) to ascertain the accuracy of anti-p155 for diagnosing CAM in DM. In this study the diagnostic value of anti-p155 for detecting paraneoplastic DM has been more precisely characterized, with a sensitivity and specificity of 78% and 89% respectively. Our data indicate an important potential role for negative anti-p155 results, which indicate a low probability of CAM in adult DM patients, and supports the usefulness of this antibody for diagnosing CAM and guiding patient management. The third study is a multicenter, 3-year prospective study including 55 consecutive patients with IIM, where the value of whole-body [18F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/TC) for diagnosing occult malignant disease in patients with myositis is compared to broad conventional cancer screening. According to our results FDG-PET/TC is not superior to broad convencional screening to diagnose occult cancer in myositis. Finally a new algorithm for the diagnosis of malignancy in myositis is proposed

PET Scan: Nuclear Medicine Imaging in Myositis

Purpose of Review Positron emission tomography (PET) combined with computed tomography (CT) has proven useful as a cancer screening technique in patients with inflammatory myopathy, mainly dermatomyositis. In this review, we focus on advances in this direction and other potential applications of PET/CT in patients with inflammatory myopathy. Recent Findings Cancer screening by PET/CT seems suitable and cost-effective in patients with myositis. It has also shown value as a hybrid technique for diagnosing myositis versus controls and could be of interest for differentiating between polymyositis and sporadic inclusion body myositis. Quantification of muscle activity by PET/CT seems reliable. Preliminary data suggest that it could also be used to diagnose and measure the activity of the disease in the lung. Summary PET/CT should be in the toolbox of physicians managing patients with myositis. The multiple applications of PET/CT include its value for cancer screening, measuring the activity of the disease in muscle, and helping to differentiate between myositis phenotypes. The possibility to diagnose and monitor inflammatory lung activity remains to be demonstrated in welldesigned studies

Correlations between traits related to the ability to exploit soil resources (vertically) and traits related to the ability to exploit light (horizontally).

<p>Correlations between traits related to the ability to exploit soil resources (vertically) and traits related to the ability to exploit light (horizontally).</p

Anti-MDA5 Antibodies in a Large Mediterranean Population of Adults with Dermatomyositis

A new myositis-specific autoantibody directed against melanoma differentiation-associated gene 5 (anti-MDA5) has been described in patients with dermatomyositis (DM). We report the clinical characteristics of patients with anti-MDA5 in a large Mediterranean cohort of DM patients from a single center, and analyze the feasibility of detecting this autoantibody in patient sera using new assays with commercially available recombinant MDA5. The study included 117 white adult patients with DM, 15 (13%) of them classified as clinically amyopathic dermatomyositis (CADM). Clinical manifestations were analyzed, with special focus on interstitial lung disease and its severity. Determination of anti-MDA5 antibodies was performed by a new ELISA and immunoblot technique. In sera, from 14 (12%) DM patients (8 CADM), MDA5 was recognized by ELISA, and confirmed by immunoblot. Eight of the 14 anti-MDA5-positive patients (57.14%) presented rapidly-progressive interstitial lung disease (RP-ILD) versus 3 of 103 anti-MDA5-negative patients (2.91%) (P < 0.05; OR: 44.4, 95% CI 9.3-212). The cumulative survival rate was significantly lower in anti-MDA5-positive patients than in the remainder of the series (P < 0.05). Patients with anti-MDA5-associated ILD presented significantly lower 70-month cumulative survival than antisynthetase-associated ILD patients. Among the cutaneous manifestations, only panniculitis was significantly associated with the presence of anti-MDA5 antibodies (P < 0.05; OR: 3.85, 95% CI 1.11-13.27). These findings support the reliability of using commercially available recombinant MDA5 for detecting anti-MDA5 antibodies and confirm the association of these antibodies with RP-ILD in a large series of Mediterranean patients with DM