Rheumatoid arthritis monotherapy in the Jak inhibitors Era. Current prevalence and associated factors in a multicenter study.

BACKGROUND: Combined therapy constitutes the standard of care in RA. Jak inhibitors (Jaki) have shown efficacy in monotherapy, a modality used in cases where it is not possible to use Disease-Modifying Anti Rheumatic Drugs (csDMARDs). OBJECTIVES: To estimate the prevalence (total and by drug), reason for using and the increase over the time of bDMARDs or tsDMARDs as monotherapy after the availability of the Jaki. To analyze the differential characteristics between patients with monotherapy vs combined therapy. METHODS: Cross-sectional multicenter study. Consecutive patients with a diagnosis of RA (ACR/EULAR 2010) under treatment with bDMARDs or tsDMARDs started from 2013 were included. Socio-demographic, clinic, and therapeutic data were collected. RESULTS: A total of 505 RA patients were included. Since 2013, the prevalence of monotherapy usage was (any) 49%. The drugs used as monotherapy were Jaki in 41% and TNF-blockers in 30%. The leading causes of monotherapy use were intolerance/adverse events (62%), medical decision or lack of adherence (37.7%). The highest socioeconomic level and a better functional status at diagnosis were predictors of monotherapy use. The use of the second line of treatments and less polypharmacy were independent factors associated with this therapeutic modality. CONCLUSIONS: The current prevalence of monotherapy in RA was 49%, the Jaki were the most used drug in this modality. Monotherapy increases from year to year. There are differential characteristics in patients using monotherapy.

Prognostic factors associated with advanced chronic kidney disease in a cohort of patients with ANCA vasculitis and renal involvement.

OBJECTIVE: The aim of this study was to evaluate prognostic factors associated with advanced chronic kidney disease (ACKD) in a cohort of patients with ANCA-associated vasculitis and renal involvement. METHODS: Observational retrospective study. We included patients with biopsy-proven ANCA glomerulonephritis (GN) diagnosed between 2001 and 2016, with at least 1-year follow-up. Data were recorded at diagnosis, end of induction, after 12 months of treatment, and at the end of follow-up. We analysed clinical-analytical data and renal histopathology, as well as treatments, dialysis requirement, relapses and death. Univariate analysis was performed to identify factors associated with long-term ACKD (eGFR < 30 ml/min). Multivariate analysis using an alternative outcome (eGFR at the end of follow-up) was performed. Diagnostic accuracy for ACKD of each predictor variable was compared using AUC of ROC curves. RESULTS: Sixty patients were included: 17 GPA, 14 MPA, 5 EGPA, and 24 RLV. Forty-six patients were women (76.7%). Mean age at diagnosis was 67.8 years (SD 13.1), and median follow-up time was 4.2 years (IQR 2.2-6.8). At the end of follow-up, 12 patients (20.0%) had an eGFR < 30 ml/min. Univariate analysis showed a statistically significant association of ACKD with sclerotic class biopsy (OR 7.17, 95% CI 1.34-38.31), 12-month proteinuria (OR 5.16, 95% CI 1.16-22.87), and creatinine at diagnosis (OR 1.24, 95% CI 1.02-1.52), end of induction (OR 15.40, 95% CI 2.41-98.28), and after 12 months (OR 19.25, 95% CI 2.75-134.92). In the multivariate analysis, eGFR at baseline (< 0.001), after 6 months (< 0.001) and 12 months of treatment (< 0.001), remained statistically associated with eGFR at the end of follow-up. The best diagnostic accuracy in ROC curves was shown by serum creatinine at the end of induction treatment (AUC 0.93) and after 12 months (AUC 0.94). CONCLUSION: In this cohort of patients with ANCA GN, creatinine and eGFR at baseline and after 6 and 12 months of treatment were the best predictors of ACKD at the end of follow-up.

Relación entre fibromialgia y sarcopenia: el papel del abordaje nutricional / Fibromyalgia and sarcopenia relation: the role of nutritional approach

Introducción: la fibromialgia (FM) es un síndrome caracterizado por la presencia de dolor musculoesquelético crónico y generalizado, de origen no articular, que puede llegar a ser invalidante y afectar la esfera biológica, psicológica y social del paciente. Estado del arte: no se han publicado recomendaciones nutricionales específicas para las personas con FM y también existe un vago conocimiento acerca de los parámetros relacionados con la evaluación de la composición corporal (masa musculoesquelética, masa grasa, agua corporal, etc.) y la alteración en la fuerza muscular (p. ej., dinapenia, por dinamometría de mano, flexión de la rodilla, entre otras), así como la evaluación en términos de sarcopenia. Discusión: pocos estudios publicados hasta el momento describen en profundidad la composición corporal de las personas con FM. La mayoría se centran casi exclusivamente en la descripción del peso y el índice de masa corporal (IMC), por lo que existe poco conocimiento acerca de otros parámetros de relevancia, como por ejemplo aquellos relacionados con masa y fuerza muscular o masa grasa. La alimentación se menciona en varias publicaciones, pero no existen guías o pautas específicas de recomendaciones nutricionales para esta población. Algunos pacientes adoptan diversas dietas, estrategias o planes alimentarios sin ningún tipo de orientación de los profesionales de la salud, e incluso a veces, siguiendo fuentes de información no fiables, poniendo en riesgo su salud. Las publicaciones científicas no evalúan la asociación o el impacto del estado nutricional y la inadecuada alimentación en la calidad de vida. Conclusiones: en las personas con FM, conocer el estado nutricional, más allá del peso, determinando la composición corporal y la prevalencia de dinapenia o sarcopenia o ambas permitiría realizar un abordaje nutricional más adecuado. Este conocimiento podría ser coadyuvante en la terapéutica, logrando una mejoría en su desempeño físico y una mejor calidad de vida. (AU)

Introduction: fibromyalgia (FM) is a syndrome charcaterized by the presence of chronic, and generalized musculoskeletal pain, not articular in origin, which can become disabling and affect the biological, psychological, and social sphere of the patient. State of the art: no specific nutritional recommendations have been published for people with FM and there is also a vague knowledge regarding parameters related to body composition assessment (skeletal muscle mass, body fat mass, water, etc.) and loss of muscle strength (for example, dynapenia, by handgrip, knee flexion, among others), as well as assessment in terms of sarcopenia. Discussion: there are few studies published so far that completely describe the body composition in people with FM. Most of them focus almost exclusively on weight and body mass index (BMI), so there is a lack of knowledge about other descriptive parameters, such as those related to muscle mass and strength or fat mass. Diet is mentioned in several publications, but there are no specific guidelines for nutritional recommendations for this population. Some patients follow several diets, strategies or eating plans without health care professionals' guidance, and sometimes even following unreliable sources of information, putting themselves at risk. Scientific publications do not evaluate the association or impact of nutritional status and inadequate nutrition on quality of life in FM. Conclusions: in people with FM, knowledge of the nutritional status, beyond weight, determining body composition and the prevalence of dynapenia and/or sarcopenia would allow a more accurate nutritional approach. This knowledge could be helpful for the treatment, achieving an improvement in their physical performance and a better quality of life. (AU)

Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples.

Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.

Sarcopenia y su relevancia en la práctica clínica / Sarcopenia and its relevance in clinical practice

La sarcopenia se define como una combinación de baja fuerza y masa muscular con alteración funcional del músculo, que afecta a poblaciones de diferentes edades por diversos motivos. La prevalencia global en adultos mayores se ha estimado en 10% (IC 95%: 8-12%) en hombres y 10% (IC 95%: 8-13%) en mujeres. Recientemente ha cobrado importancia su detección en enfermedades reumáticas, particularmente las inflamatorias. En esta revisión narrativa hemos considerado: a) recomendaciones para el diagnóstico de la sarcopenia; b) herramientas útiles para la práctica clínica y la investigación; c) su relación con las enfermedades reumáticas. Según el último Consenso Europeo de Sarcopenia la búsqueda debe comenzar cuando el paciente reporta síntomas y/o signos (debilidad, lentitud al caminar, desgaste muscular, pérdida de masa muscular, etc.). Para los adultos mayores se recomienda el cuestionario SARC-F como herramienta de tamizaje. Varias pruebas establecen los puntos de corte que deben utilizarse para diagnosticar la baja fuerza muscular, la disminución en la masa muscular y la alteración en el rendimiento físico. La relevancia de diagnosticar precozmente la sarcopenia se basa en el impacto clínico, económico y social que tiene, incluyendo la funcionalidad y calidad de vida de las personas, muy importante en aquellas con enfermedades reumatológicas.

Sarcopenia is defined as a combination of low muscle strength and mass with muscle function impairment that affects the population at different age ranges for different reasons. The global prevalence at the elderly was estimated at 10% (95% CI: 8-12%) in men and 10% (95% CI: 8-13%) in women. In recent years, the detection of sarcopenia in rheumatic diseases has become relevant. The aim of this revision was to develop a review regarding: a) recommendations for the diagnosis of sarcopenia; b) most useful tools for detection in clinical practice and research; c) relationship with some rheumatic diseases. According to the latest European Sarcopenia Consensus, in clinical practice, the search must start when the patient reports symptoms and signs (weakness, slow walking, muscle wasting, disease that leads to muscle loss, etc.). For the elderly population the SARC-F test is recommended as a screening tool. Several tests have established cut-off points to be used to diagnose low muscle strength, decrease in muscle mass or physical performance impairment. The relevance of early diagnosis of sarcopenia is based on the clinical, economic, social impact and also on functionality and quality of life in people, particularly in those with rheumatic diseases.

Frecuencia de infección por SARS-CoV-2 en asistentes a un congreso médico en la Ciudad Autónoma de Buenos Aires. Datos del Congreso Argentino de Reumatología 2021 / Frequency of SARS-CoV-2 infection in attendees at a medical congress in the Autonomous City of Buenos Aires. Data from the Argentine Congress of Rheumatology 2021

Introducción: en el contexto de la pandemia por SARS-CoV-2, la Sociedad Argentina de Reumatología (SAR) organizó su congreso "híbrido" (presencial y virtual), en diciembre de 2021, en concordancia con la condición epidemiológica. El objetivo principal de este trabajo fue describir la frecuencia de nuevos casos de infección luego de asistir al Congreso y la opinión de los médicos sobre los aspectos de bioseguridad del evento, y como objetivo secundario, analizar las características de los asistentes durante la pandemia por SARS-CoV-2. Materiales y métodos: estudio transversal a través de una encuesta online, autoadministrada y anónima. Se encuestaron a los concurrentes (médicos y no médicos) al Congreso (presencial o virtual). La primera encuesta fue al momento de la inscripción y la segunda luego de 14 días de culminado, solo para los médicos. Se realizó un análisis descriptivo de los resultados. Resultados: 1.322 individuos se inscribieron al Congreso; 1.039 (98,9%) eran médicos. 1.051 (79,5%) completaron la primera encuesta y 501 (48,2%) contestaron la segunda. Mientras 428 (85,4%) asistieron presencialmente, la virtualidad la eligieron aquellos con más años de ejercicio (p=0,023), con comorbilidades (p=0,03) y quienes tuvieron una internación previa por SARS-CoV-2 (p=0,05). Del total, 1.028 (97,8%) estaban vacunados. El 84,6% tuvo una opinión favorable sobre la modalidad "híbrida". Cinco (1,2%) presentaron síntomas de infección por SARS-CoV-2 y tres (0,7%) tuvieron confirmación diagnóstica. Conclusiones: cinco personas registraron la infección sintomática después del evento. Las medidas de bioseguridad tomadas fueron las aconsejadas por el Ministerio de Salud de la Nación y la opinión de los médicos sobre las mismas fueron favorables.

Introduction: in the context of the pandemic due to SARS-CoV-2, the Argentine Society of Rhematology organized its "hybrid" congress (face-to-face and virtual), on December 2021, in accordance with the epidemiological condition. The main objective of this work was to describe the frequency of new cases of infection after attending the Congress and the opinion of doctors on the biosafety aspects of the event, and as a secondary objective, to analyze the characteristics of those attending the Congress during the pandemic. by SARS-CoV-2. Materials and methods: cross-sectional study, through an online, self-administered and anonymous survey. The attendees (physician and non- physician) to the congress (face-to-face or virtual) were surveyed. The first survey was at the time of registration and the second after 14 days of finish, only for physicians. A descriptive analysis of the results was performed. Results: 1,322 subjects registered for Congress; 1,039 (98.9%) were physicians. 1,051 (79.5%) completed the first survey and 501 (48.2%) answered the second. While 428 (85.4%) attended in person, virtuality was chosen by those with more years of practice (p=0.023), with comorbidities (p=0.03) and those who had a previous hospitalization for SARS-CoV-2 (p =0.05). Of the total, 1,028 (97.8%) were vaccinated. 84.6% had a favorable opinion about the "hybrid" modality. Five (1.2%) presented symptoms of SARS-CoV-2 infection and three (0.7%) had diagnostic confirmation. Conclusions: five subjects had symptoms and three confirmed infections. The biosafety measures taken were those recommended by the Ministry of Health and the opinion of the colleagues about them was favorable.

Subthalamic Beta Activity in Parkinson's Disease May Be Linked to Dorsal Striatum Gray Matter Volume and Prefrontal Cortical Thickness: A Pilot Study.

Background: Excessive oscillations at beta frequencies (13-35 Hz) in the subthalamic nucleus (STN) represent a pathophysiological hallmark of Parkinson's disease (PD), which correlates well with parkinsonian symptoms and is reduced in response to standard disease treatments. However, the association of disease-specific regional gray matter (GM) atrophy or cortical thickness (CT) with the presence of STN beta oscillatory activity has been poorly investigated but is of relevance given the potential of these variables for extracting information about PD pathophysiology. This exploratory study investigated the involvement of regional GM volume and CT in the basal ganglia-cortical network and its potential association with the presence of STN beta oscillatory activity in PD. Methods: We acquired preoperative GM densities on T1-weighted magnetic resonance imaging scans and we carried out regional estimation of GM volume and CT. LFP activities from the STN were recorded post-operatively in 7 cognitively preserved PD patients off dopaminergic medication undergoing deep-brain stimulation surgery. Oscillatory beta power was determined by power spectral density of 4-min resting state STN LFP activity. Spearman partial correlations and regression analysis were used to screen the presence of STN beta power for their relationship with GM volume and CT measurements. Results: After controlling for the effects of age, educational level, and disease duration, and after correcting for multiple testing, enhanced STN beta power showed significant and negative correlations between, first, volume of the right putamen and left caudate nucleus, and second, smaller CT in frontal regions involving the left rostral middle frontal gyrus (MFG) and left medial orbitofrontal gyrus. A lower volume in the right putamen and a lower CT in the left MFG demonstrated the strongest associations with increased STN beta power. Conclusions: These tentative results seem to suggest that STN LFP beta frequencies may be mainly linked to different but ongoing parallel neurodegenerative processes, on the one hand, to GM volume reduction in dorsal striatum, and on the other hand, to CT reduction of prefrontal-"associative" regions. These findings could further delineate the brain structural interactions underpinning the exaggerated STN beta activity commonly observed in PD patients.

Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC.

Most colorectal cancer (CRC) patients die as a consequence of metastasis. Mitochondrial dysfunction could enhance cancer development and metastatic progression. We aimed to evaluate the adaptations associated with mitochondrial function in tumor tissues from stages III and IV of human CRC and whether they could ultimately be used as a therapeutic target in metastatic colorectal cancer (mCRC). We analyzed the protein levels by Western blotting and the enzymatic activities of proteins involved in mitochondrial function, as well as the amount of mitochondrial DNA (mtDNA), by real-time PCR, analyzing samples of non-tumor adjacent tissue and tumor tissue from stages III and IV CRC patients without radio- or chemotherapy treatment prior to surgery. Our data indicate that the tumor tissue of pre-metastatic stage III CRC exhibited an oxidant metabolic profile very similar to the samples of non-tumor adjacent tissue of both stages. Notable differences in the protein expression levels of ATPase, IDH2, LDHA, and SIRT1, as well as mtDNA amount, were detected between the samples of non-tumor adjacent tissue and tumor tissue from metastatic CRC patients. These findings suggest a shift in the oxidative metabolic profile that takes place in the tumor tissue once the metastatic stage has been reached. Tumor tissue oxidative metabolism contributes to promote and maintain the metastatic phenotype, with evidence of mitochondrial function impairment in stage IV tumor tissue.

Treating the skin with biologics in patients with psoriasis decreases the incidence of psoriatic arthritis.

OBJECTIVES: To compare the incidence of psoriatic arthritis (PsA) in patients with psoriasis (PsO) according to different treatments for their skin: topics/no treatment, conventional disease-modifying antirheumatic drugs (DMARDs) (cDMARDs) or biological DMARDs (bDMARDs). METHODS: Patients with PsO without PsA followed at a university hospital were included in this retrospective cohort study. Patients were classified according to their treatment in topics (topics, phototherapy or no treatment), cDMARDs (methotrexate and cyclosporine) and bDMARDs (tumour necrosis factor inhibitors (TNFi), interleukin 17 inhibitors (IL-17i) and IL-12-23i ((interleukin (IL) 12/IL-23 inhibitor))) groups. Incident cases of PsA were attributed to one treatment if developed during the administration of that treatment. A Cox proportional hazards model was used to evaluate the adjusted risk of PsA development by treatment group. RESULTS: 1719 patients with PsO contributed a total of 14 721 patient/years (py). 1387 (81%) patients were in the topics, 229 (13%) in cDMARDs and 103 (6%) in the bDMARDs group. During follow-up, 239 patients (14%) developed PsA (231 under topics, six under cDMARDs and two under bDMARDs). Global incidence was 1.6 per 100 py. The risk of developing PsA in patients with PsO treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94; p=0.0111), compared with topics, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96; p=0.1007). Adjusted Cox proportional hazards regression analysis showed that male sex, nail involvement and higher body max index were associated with increased risk of developing PsA, while biologics use was protective (HR: 0.19; 95% CI 0.05 to 0.81). CONCLUSION: Treatment with biologics in patients with PsO reduced the risk of PsA development.

APR-246 combined with 3-deazaneplanocin A, panobinostat or temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells.

Glioblastoma is the most malignant brain tumor and presents high resistance to chemotherapy and radiotherapy. Surgery, radiotherapy and chemotherapy with temozolomide are the only treatments against this tumor. New targeted therapies, including epigenetic modulators such as 3­deazaneplanocin A (DZ­Nep; an EZH2 inhibitor) and panobinostat (a histone deacetylase inhibitor) are being tested in vitro, together with temozolomide. The present study combined APR­246 with DZ­Nep, panobinostat and teomozolomide in order to explore the possibility of restoring p53 function in mutated cases of glioblastoma. Following the Chou­Talalay method it was demonstrated that APR­246 acts in an additive manner together with the other compounds, reducing clonogenicity and inducing apoptosis in glioblastoma cells independently of p53 status.

Osteoporotic fractures in rheumatoid arthritis patients in Argentina: a matched retrospective cohort study

Abstract Background: To compare the incidence of osteoporotic fractures in patients with rheumatoid arthritis (RA) with matched controls from a university hospital. Methods: Consecutive RA patients (n = 100) were matched (age and sex) with controls (1:2). The follow-up period began at the index date, defined as the date of diagnosis for RA patients and the date of the first medical claim at the Health Management Organization (HMO) for non-RA patients. Fracture incidence rates per 1000 persons-years (PY) for distinct types of fractures were calculated. Multivariate cox regression analysis was performed to identify factors associated with fractures. Results: One hundred RA patients were followed for a total of 975.1 patients-years and 200 controls for 1485.7 patients-years. No difference was found in the overall fracture incidence rate per 1000 PY between RA and controls (19.5, 95% CI 12.7-28.6 vs 12.1, 95% CI 7.7-18.7, p =0.07). In the Cox regression analysis, only age (HR 1.06, 95% CI 1.02-1.11, p = 0.006) and history of a prior fracture (HR 9.85, 95% CI 2.97-32.64, p < 0.001) were associated with fractures after the index date. The stratified analysis of the fractures by location showed that only the vertebral fractures were more frequent in RA patients compared with controls (12.9 per 1000 PY, 95% CI 8.9-25.8, vs. 3.4, 95% CI 1.4-8.1, respectively, p =0.01). Conclusion: Patients with RA didn't show an overall increased risk of osteoporotic fractures compared with matched controls, but vertebral fractures were more frequently observed in patients with RA.

Performance of Ultrasonography Compared to Conventional Radiography for the Diagnosis of Osteoarthritis in Patients With Knee Pain.

Purpose: To investigate the performance of ultrasonography (US) for the detection of knee osteoarthritis (OA) in patients suffering from knee pain, compared to conventional radiographs. Methods: Cross-sectional study performed at a university teaching hospital. Consecutive patients complaining of unilateral or bilateral mechanical knee pain who signed an informed consent were included. All patients underwent simultaneously an ultrasonographic and a radiographic evaluation of the knee. Exclusion criteria were age under 18 years, prior diagnosis of knee OA, diagnosis of inflammatory arthritis, history of knee surgery or trauma, severe knee deformities, and corticosteroid injection within the last 2 months. The diagnostic properties of US for the detection of knee OA were evaluated using radiological data as the reference method. Evaluated test properties were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the positive and negative likelihood ratio (LR+ and LR-). Results: Three-hundred twenty-two knees (281 patients) were included. Radiographic degenerative changes were present in 56.8% (183) of the evaluated knees. Regarding the diagnostic properties of the US, the presence of either osteophytes or the compromise of the femoral hyaline cartilage had the best sensitivity to detect OA (95%), with a NPV of 92% and a LR- of 0,07, while the combined identification of osteophytes and compromise of the femoral hyaline cartilage had the best specificity (94%), with 94% PPV and a LR+ of 13. Conclusion: US demonstrated an excellent sensitivity with an adequate specificity for the detection of radiographic knee OA.

Asociación entre Artritis Reumatoidea y otras enfermedades autoinmunes / Association between Rheumatoid Arthritis and other autoimmune diseases

Objetivos: Determinar la frecuencia de enfermedades autoinmunes (EAI) en pacientes con Artritis Reumatoidea (AR) y comparar la frecuencia de EAI entre pacientes con AR y sin AR ni otra EAI reumatológica. Material y Métodos: Estudio multicéntrico, observacional, analítico, retrospectivo. Se incluyeron pacientes consecutivos con AR (ACR/EULAR 2010) y como grupo control pacientes con diagnóstico inicial de Osteoartritis primaria (OA). Resultados: Se incluyeron 1549 pacientes: 831 con AR (84% mujeres, edad media 55.2 años [DE 13.6]) y 718 con OA (82% mujeres, edad media 67 años [DE 11.1]). La frecuencia de EAI en el grupo AR fue del 22% (n=183). Estos presentaron mayor frecuencia de EAI reumatológicas (9.4 vs 3.3%, p< 0.001), y menor frecuencia de EAI no reumatológicas que aquellos con OA (15.3 vs 20.5, p=0.007). La EAI reumatológica más prevalente fue el Síndrome de Sjögren, el cual fue más frecuente en el grupo AR (87.2 vs 29.2%, p< 0,001). La frecuencia de EAI reumatológicas en los pacientes con AR fue mayor en la forma erosiva (11 vs 6.8%, p=0.048). Conclusión: La frecuencia de EAI en los pacientes con AR fue del 22%, en quienes predominaron las de etiología reumatológica mientras que, las no reumatológicas predominaron en pacientes con OA.

Objectives: To determine the frequency of autoimmune diseases (AID) in Rheumatoid Arthritis (RA) patients and to compare this frequency between patients with and without RA or other rheumatologic AID. Methods: Multicenter, observational, analytical, retrospective study. Consecutive patients with diagnosis of RA (ACR/EULAR 2010) were included. Patients with initial diagnosis of primary ostearthritis (OA) were used as control group. Results: A total of 1549 patients were included: 831 RA (84% women, mean age 55.2 [±13.6]) and 718 OA (82% women, mean age 67 [± 11.1]). The frequency of AID in the RA group was 22% (n=183). RA patients showed higher frequency of rheumatologic AID (9.4 vs 3.3%, p< 0.001), and lower frequency of non-rheumatologic AID than OA patients (15.3 vs 20.5%, p= 0.007). The most prevalent rheumatic AID was Sjögren's Syndrome, which was more frequent in the AR group (87.2 vs 29.2%, p<0.001). The frequency of rheumatologic AID in RA patients was higher in those with erosive RA (11 vs 6.8%, p=0.048). Conclusion: The frequency of AID in RA patients was 22%. Rheumatologic AID were more frequent in RA patients, whereas non-rheumatologic AID prevailed in OA patients.

Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells.

Alpha-Synuclein (aSyn) is a chameleon-like protein. Its overexpression and intracellular deposition defines neurodegenerative α-synucleinopathies including Parkinson's disease. Whether aSyn up-regulation is the cause or the protective reaction to α-synucleinopathies remains unresolved. Remarkably, the accumulation of aSyn is involved in cancer. Here, the neuroblastoma SH-SY5Y cell line was genetically engineered to overexpress aSyn at low and at high levels. aSyn cytotoxicity was assessed by the MTT and vital-dye exclusion methods, observed at the beginning of the sub-culture of low-aSyn overexpressing neurons when cells can barely proliferate exponentially. Conversely, high-aSyn overexpressing cultures grew at high rates while showing enhanced colony formation compared to low-aSyn neurons. Cytotoxicity of aSyn overexpression was indirectly revealed by the addition of pro-oxidant rotenone. Pretreatment with partially reduced graphene oxide, an apoptotic agent, increased toxicity of rotenone in low-aSyn neurons, but, it did not in high-aSyn neurons. Consistent with their enhanced proliferation, high-aSyn neurons showed elevated levels of SMP30, a senescence-marker protein, and the mitosis Ki-67 marker. High-aSyn overexpression conferred to the carcinogenic neurons heightened tumorigenicity and resistance to senescence compared to low-aSyn cells, thus pointing to an inadequate level of aSyn stimulation, rather than the aSyn overload itself, as one of the factors contributing to α-synucleinopathy.

Antioxidant enzymes change in different non-metastatic stages in tumoral and peritumoral tissues of colorectal cancer.

Antioxidant defences and oxidative stress are related to development, progression and malignancy of colorectal cancer. However, their role in early stages of cancer remains unknown. More and more recent studies have revealed that non-tumour adjacent tissue is not a normal tissue. Thus, our aim was to analyse protein levels of MnSOD (Manganese Superoxide Dismutase), acMnSOD (Acetylated Manganese superoxide Dismutase), SIRT3 (Sirtuin 3), CuZnSOD (Cupper Zinc Superoxide Dismutase), CAT (Catalase), GPx (Glutathione Peroxidase), and GRd (Glutathione Reductase) both in tumour and non-tumour adjacent tissue from colorectal cancer patients by western blot. Non-tumour adjacent tissue seemed to have higher levels of antioxidant enzymes that detoxify hydrogen peroxide compared to tumour tissue. In contrast, tumour tissue had higher levels of MnSOD and acMnSOD. Furthermore, most of the proteins analysed showed significant differences between stage I and II in both non-tumour adjacent and tumour tissue. This could indicate that antioxidant enzymes, especially MnSOD, play a crucial role in early stages of colorectal cancer in both tissues, so they could be analysed as novel biomarkers to improve colorectal cancer diagnosis.

The synergistic effect of DZ­NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells.

Current treatment against glioblastoma consists of surgical resection followed by temozolomide, with or without combined radiotherapy. Glioblastoma frequently acquires resistance to chemotherapy and/or radiotherapy. Novel therapeutic approaches are thus required. The inhibition of enhancer of zeste homolog 2 (EZH2; a histone methylase) and histone deacetylases (HDACs) are possible epigenetic treatments. Temozolomide, 3­deazaneplanocin A (DZ­Nep; an EZH2 inhibitor) and panobinostat (an HDAC inhibitor) were tested in regular and temozolomide­resistant glioblastoma cells to confirm whether the compounds could behave in a synergistic, additive or antagonistic manner. A total of six commercial cell lines, two temozolomide­induced resistant cell lines and two primary cultures derived from glioblastoma samples were used. Cell lines were exposed to single treatments of the drugs in addition to all possible two­ and three­drug combinations. Colony formation assays, synergistic assays and reverse transcription­quantitative PCR analysis of apoptosis­associated genes were performed. The highest synergistic combination was DZ­Nep + panobinostat. Triple treatment was also synergistic. Reduced clonogenicity and increased apoptosis were both induced. It was concluded that the therapeutic potential of the combination of these three drugs in glioblastoma was evident and should be further explored.

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Evaluation of Learned Helplessness, Perceived Self-efficacy, and Functional Capacity in Patients With Fibromyalgia and Rheumatoid Arthritis.

OBJECTIVES: The aims of this study were to compare learned helplessness (LH) and perceived self-efficacy (SE) in patients with fibromyalgia (FM) and rheumatoid arthritis (RA) and to assess their correlation with functional disability, level of perceived pain, and fatigue. METHODS: This multicenter, cross-sectional study included consecutive patients (aged ≥18 years) with RA, according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and FM, according to 2010 American College of Rheumatology criteria. Learned helplessness was measured by the Rheumatology Attitude Index, Spanish version; SE with the Arthritis Self-efficacy Scale, Spanish version; functional capacity with the Health Assessment Questionnaire (HAQ), Argentine version; depression with Center for Epidemiological Studies-Depression Scale 7-item version and perceived pain and fatigue by the visual analog scale. Disease activity was measured by the Clinical Disease Activity Index (CDAI) and disease impact with the Fibromyalgia Impact Questionnaire (FIQ). RESULTS: A total of 215 patients, 100 with FM and 115 with RA, were included. Mean age was 59 (SD, 14) years and 58 (SD, 13) years for FM and RA, patients respectively. Whereas LH and depression were significantly higher, SE was significantly lower in FM patients. We found a positive correlation between LH and HAQ, pain, depression, fatigue, FIQ, and CDAI in FM and RA patients. We observed a negative correlation between SE and HAQ, pain, depression, fatigue, FIQ (FM), and CDAI (RA) in both groups. CONCLUSIONS: Both LH and SE correlate significantly with functional capacity, perceived pain, disease activity, and disease impact in RA and FM patients. Learned helplessness was higher in patients with active disease or high disease impact, as opposed to those in remission or with low disease impact, and the reverse was true for SE. Patients with FM had significantly more LH, pain, fatigue, and depression and less SE compared with those with RA.

Non-tumor adjacent tissue of advanced stage from CRC shows activated antioxidant response.

Colorectal cancer (CRC) is a leading cause of malignant cancer-related morbidity and mortality, with a higher incidence in developed countries and a high mortality rate mainly attributable to metastases. The aim of the present study was to determine the metabolic adaptations related to oxidative stress in tumor tissue from advanced stages (III and IV) of CRC and whether they could be used as potential biomarkers for clinical applications. To tackle this aim, we have analyzed the protein expression levels related to oxidative stress and the enzymatic activities of MnSOD and catalase, comparing samples of non-tumor adjacent tissue and tumor tissue of CRC patients in stages III and IV. The results showed no differences between stage III and IV in tumor tissues for any of the proteins studied. However, some differences were found between samples of non-tumor adjacent tissue and tumor tissue for some of the antioxidant enzymes. Overwhelmingly, the greatest differences were detected when comparing samples of non-tumor adjacent tissue from stage III and stage IV. To the best of our knowledge, this is the first study where differences between the non-tumor adjacent tissues of CRC patients from different cancer stages were determined. This study suggests that the parameters analyzed should be evaluated as biomarkers for the evolution of CRC. Furthermore, tumor tissue status should not be of sole importance for the prognosis of CRC, as the non-tumor adjacent tissues could also merit consideration.

Tenosinovitis subclínica detectada por ecografía en pacientes con artritis reumatoidea en remisión clínica sostenida / Subclinical tenosynovitis detected by ultrasound in patients with rheumatoid arthritis under sustained clinical remission

El objetivo fue evaluar la prevalencia de tenosinovitis detectada por ecografía-doppler en pacientes con Artritis Reumatoidea (AR) en remisión clínica sostenida, determinar su asociación con las características de la enfermedad y determinar si la presencia de tenosinovitis ecográfica podría agregar información a la sinovitis para definir remisión ecográfica. Se incluyeron 60 pacientes con AR en remisión clínica (DAS28 <2,6, CDAI <2,8 y/o SDAI <3,3) sostenida a quienes se les realizó una ecografía con señal doppler de poder (DP). Un reumatólogo entrenado evaluó en forma bilateral: 1°-6° compartimentos extensores a nivel del carpo, 2°-5° tendones flexores de los dedos de las manos, tibial posterior, peroneo lateral corto y largo. A nivel articular se evaluaron en forma bilateral: carpo, 2°-5° metacarpofalángicas y 2°-5° interfalángicas proximales. Se definió remisión ecográfica a la ausencia de sinovitis en escala de grises (EG) grado ≥2 y la ausencia de señal DP a nivel articular o tendinoso. Se detectó tenosinovitis por EG grado ≥2 y señal DP ≥1 en 14 (23%; IC 95%: 12-34) y 13 (21,7%; IC 95%: 10-32) pacientes, respectivamente. Los tendones más frecuentemente afectados fueron: 6° compartimento extensor del carpo, tibial posterior y 3° tendón flexor tibial posterior. En el análisis multivariado, la única variable que se asoció con la presencia de tenosinovitis por ecografía-doppler fue la ERS (OR: 1,11; IC 95%: 1,02-1,22). Veintinueve pacientes (48,3%; IC 95%: 35-60) presentaron sinovitis subclínica y no fueron clasificados como AR en remisión ecográfica. La adición de la información brindada por la presencia de tenosinovitis subclínica, permitió clasificar 6 pacientes más sin remisión ecográfica, arrojando un total de 35 pacientes (58,3%; IC 95%: 45-70) (p=0,272).

The aims were to evaluate prevalence of ultrasound (US) tenosynovitis in Rheumatoid Arthritis (RA) patients in sustained clinical remission, its association with disease features and to assess whether the presence of tenosynovitis could add information to synovitis to define ultrasound (US) remission. Sixty consecutive RA patients in sustained (≥12 months) clinical remission (DAS28 <2.6, CDAI <2.8 and/or SDAI <3.3) were included. All patients underwent US examination by the same experienced rheumatologist. The following were bilaterally assessed: 1st-6th extensor tendon compartments at wrist level, 2nd-5th finger flexor tendons, posterior tibial, peroneal tendons, wrists, 2nd-5th metacarpophalangeal and 2nd-5th proximal interphalangeal. US remission was defined as the absence of synovitis on gray scale (GS ≥2) and the absence of power doppler (PD) signal at both joint and tendon level. Grey scale ≥2 and PD tenosynovitis were detected in 14 (23%; 95% CI: 12-34) and 13 (21.7%; 95% CI: 10-32) RA patients in clinical remission, respectively. The most frequent involved tendons were: 6th extensor wrist compartment, 3rd finger flexor and posterior tibials. In multivariate analysis, the only feature associated with the presence of subclinical tenosynovitis was erythrosedimentation rate (ESR)(OR: 1.11; 1.02-1.22). Twenty-nine (48.3%; 95% CI: 35-60) patients had subclinical synovitis and were not classified as in US remission. Adding the information of subclinical tenosynovitis, 6 more patients would have been classified as not in US remission, yielding a total of 35 patients (58.3%; 95% CI: 45-70) (p=0.272).