PANLAR Consensus Recommendations for the Management in Osteoarthritis of Hand, Hip, and Knee.

OBJECTIVE: The objective of this consensus is to update the recommendations for the treatment of hand, hip, and knee osteoarthritis (OA) by agreeing on key propositions relating to the management of hand, hip, and knee OA, by identifying and critically appraising research evidence for the effectiveness of the treatments and by generating recommendations based on a combination of the available evidence and expert opinion of 18 countries of America. METHODS: Recommendations were developed by a group of 48 specialists of rheumatologists, members of other medical disciplines (orthopedics and physiatrists), and three patients, one for each location of OA. A systematic review of existing articles, meta-analyses, and guidelines for the management of hand, hip, and knee OA published between 2008 and January 2014 was undertaken. The scores for Level of Evidence and Grade of Recommendation were proposed and fully consented within the committee based on The American Heart Association Evidence-Based Scoring System. The level of agreement was established through a variation of Delphi technique. RESULTS: Both "strong" and "conditional" recommendations are given for management of hand, hip, and knee OA and nonpharmacological, pharmacological, and surgical modalities of treatment are presented according to the different levels of agreement. CONCLUSIONS: These recommendations are based on the consensus of clinical experts from a wide range of disciplines taking available evidence into account while balancing the benefits and risks of nonpharmacological, pharmacological, and surgical treatment modalities, and incorporating their preferences and values. Different backgrounds in terms of patient education or drug availability in different countries were not evaluated but will be important.

Osteoarthritis in Latin America: Study of Demographic and Clinical Characteristics in 3040 Patients.

BACKGROUND: Latin America is a heterogeneous region made up of different populations, cultures, latitudes, altitudes, and immigrants from different areas and ethnic groups. OBJECTIVE: The purpose of this study is to describe the clinical and demographic profile of patients with osteoarthritis (OA) evaluated by a selected group of rheumatologists in 13 Latin American countries. METHODS: A descriptive, observational, cross-sectional study was conducted in 13 Latin American countries of patients with symptomatic OA. Data were collected over a 3-month period using an ad hoc questionnaire to evaluate the clinical and demographic features of OA seen by rheumatologists. RESULTS: Among the 3040 patients, their average age was 62.5 years, and female-to-male ratio was 4.8:1. Patients with body mass index of greater than 30 kg/m or obesity was found in 38.2%. Approximately 88% had primary OA. Joints with OA were as follows: knee 31.2%, hand 9.5%, hand and knee 22.9%, proximal and distal interphalangeal joints (erosive OA) 6.5%, axial 6.6%, and hip 1.3%. Approximately 88.5% had radiographic severity of grade 2 or 3 on Kellgren-Lawrence scale (0-4). Nonsteroidal anti-inflammatory drugs were the predominant OA treatment included in combinations with glucosamine sulfate/chondroitin and viscosupplementation. Associated comorbidities included hypertension (39%), obesity (36.3%), diabetes mellitus (12%), and without comorbidity (12.7%). CONCLUSIONS: This is 1 of the largest population studies that evaluated the characteristics of OA in 3040 patients evaluated by rheumatologists in 13 Latin American countries. This study provides important data for each Latin American country to develop new health care planning in management of OA.

Granulocyte-macrophage colony stimulating factor is anabolic and interleukin-1beta is catabolic for rat articular chondrocytes.

OBJECTIVE: To study the effects of GM-CSF and IL-1beta, both implicated in tissue damage in arthritis, on articular chondrocyte proliferation and metabolism, and to explore their agonist/antagonist effects. METHODS: Chondrocytes were obtained from 1-month-old rats. First-passage monolayers were incubated for 24 h with or without GM-CSF and/or IL-1beta, and labeled with 3H-thymidine, 35S-SO4 and 14C-proline. Proteoglycan and collagen synthesis were analyzed by liquid chromatography and SDS-PAGE. Gene expression was measured by RT-PCR. RESULTS: IL-1beta exerts potent, and GM-CSF weak, inhibitory effects on DNA synthesis. GM-CSF strongly stimulates, and IL-1beta inhibits, proteoglycan and collagen synthesis. IL-1beta suppresses the effect of GM-CSF, and increases the release of radioactive molecules from pre-labeled cartilage fragments; GM-CSF decreases the IL-1beta-induced effect. Interestingly, both cytokines induce the expression of each other's gene. CONCLUSIONS: IL-1beta appears to be a catabolic and anti-anabolic agent for chondrocytes, whereas GM-CSF is mainly anabolic, and blocks the IL-1beta-induced catabolic effect. It is postulated that both agents are implicated in inflammation: IL-1beta promotes tissue catabolism and destruction, whereas GM-CSF enhances tissue reconstruction.

A Central Role for JNK/AP-1 Pathway in the Pro-Oxidant Effect of Pyrrolidine Dithiocarbamate through Superoxide Dismutase 1 Gene Repression and Reactive Oxygen Species Generation in Hematopoietic Human Cancer Cell Line U937.

Pyrrolidine dithiocarbamate (PDTC) known as antioxidant and specific inhibitor of NF-κB was also described as pro-oxidant by inducing cell death and reactive oxygen species (ROS) accumulation in cancer. However, the mechanism by which PDTC indices its pro-oxidant effect is unknown. Therefore, we aimed to evaluate the effect of PDTC on the human Cu/Zn superoxide dismutase 1 (SOD1) gene transcription in hematopoietic human cancer cell line U937. We herein show for the first time that PDTC decreases SOD1 transcripts, protein and promoter activity. Furthermore, SOD1 repression by PDTC was associated with an increase in oxidative stress as evidenced by ROS production. Electrophoretic mobility-shift assays (EMSA) show that PDTC increased binding of activating protein-1 (AP-1) in dose dependent-manner suggesting that the MAPkinase up-stream of AP-1 is involved. Ectopic NF-κB p65 subunit overexpression had no effect on SOD1 transcription. In contrast, in the presence of JNK inhibitor (SP600125), p65 induced a marked increase of SOD1 promoter, suggesting that JNK pathway is up-stream of NF-κB signaling and controls negatively its activity. Indeed, using JNK deficient cells, PDTC effect was not observed nether on SOD1 transcription or enzymatic activity, nor on ROS production. Finally, PDTC represses SOD1 in U937 cells through JNK/c-Jun phosphorylation. Taken together, these results suggest that PDTC acts as pro-oxidant compound in JNK/AP-1 dependent-manner by repressing the superoxide dismutase 1 gene leading to intracellular ROS accumulation.

Frecuencia de infecciones en los pacientes con patología reumatológica del IAHULA Mérida 2016-2017

Introducción: Las infecciones se ha señalado que son causa de la descompensación de algunas enfermedades del tejido conectivo. Objetivos: Describir la frecuencia de infecciones asociadas a las diversas patologías reumatológicas en los pacientes que acuden al Hospital Universitario de Los Andes. Métodos: Estudio retrospectivo en el que se revisaron 3 328 historias clínicas pertenecientes a los pacientes del servicio de Reumatología. Resultados: La mayor parte de los pacientes eran del género femenino. La principal patología reumatológica fue artritis reumatoide, seguido del lupus eritematoso sistémico, artrosis en 3 lugar y finalmente otras entidades. Las principales infecciones fueron las del tracto urinario, en segunda instancia piel y partes blandas, en tercer lugar neumonías y en último lugar las no incluidas anteriormente. En cuanto al uso de la terapéutica y el tipo de patología reumatológica se encontró significancia estadística P 0,001. En cuanto al tipo de infección y la patología reumatológica en la cual se presentó dicho evento el valor de P fue 0,724. La principal causa de hospitalización en los 4 grupos de pacientes fue debido a causas infecciosas con un valor de P de 0,001. Discusión: Las infecciones fueron la principal causa de hospitalización en estos pacientes. La infección es causa de morbimortalidad importante en los pacientes reumatológicos. Conclusiones: Se recomienda en base a las observaciones obtenidas en el presente estudio, se evalúen a través de sistemas de estratificación los riesgos para el desarrollo de infecciones en los pacientes reumatológicos y así generar estrategias que disminuyan su frecuencia.

Introduction: Infections have been reported to be the cause of the decompensation of some connective tissue diseases. Objectives: To describe the frequency of infections associated with the rheumatological pathologies in patients of the University Hospital of the Andes. Methods: Retrospective study in which 3 328 clinical histories belonging to the patients of the Rheumatology service were reviewed. Results: Most of the patients were female. The main rheumatological pathology was Rheumatoid Arthritis, followed by Systemic Lupus Erythematosus, Arthrosis in third place and finally other entities. The main infections were those of the urinary tract, secondly skin and soft tissues, thirdly Pneumonia and lastly not previously included. Regarding the use of therapeutics and the type of rheumatological pathology, statistical significance was found P 0.001. Regarding the type of infection and the rheumatological pathology in which the event was presented, the P value was 0.724. The main cause of hospitalization in the 4 groups of patients was due to infectious causes with a p-value of 0.001. Discussion: Infections were the main cause of hospitalization in these patients. Infection is an important cause of morbidity and mortality in rheumatological patients. Conclusions: It is recommended based on the observations obtained in the present study, the risks for the development of infections in rheumatological patients be evaluated through stratification systems and generate strategies that decrease their frequency.

Determinación sérica de cobre, cinc y relación sérica CU/ZN en pacientes con artritis reumatoide / Determination serum copper, zinc and serum ratio Cu / Zn in patients with rheumatoid arthritis

El presente estudio tiene por objetivo comparar los niveles séricos de cobre (Cu), cinc (Zn) y el cociente molar Cu/Zn en 129 pacientes con artritis reumatoide (RA), en 94 individuos sanos como grupo control (GC) y 21 pacientes con enfermedades reumáticas no artríticas (NER), como la fibromialgia, espondilitis anquilosante entre otras. Las concentraciones séricas de Cu y Zn fueron analizadas por espectroscopía de absorción atómica en llama acoplada a un sistema de inyección en flujo continuo (EAA/FIA). Los resultados muestran un incremento significativo (p<0,05), del cobre sérico en los pacientes con AR en comparación con los otros grupos (NER y GC), este aumento fue directamente proporcional a la actividad inflamatoria de la enfermedad. El nivel medio de cinc sérico mostró una disminución progresiva. Asimismo, el detrimento sérico del cinc está relacionado con la evolución de la enfermedad o la pérdida de capacidad funcional del paciente con los niveles alterados de cobre observados en pacientes con AR activo y en etapa temprana de la enfermedad (p<0,05). Los cocientes molares de Cu/Zn fueron de 1,88; 1,14 y 1,18 para la AR, GC, y NER, respectivamente, demostrando que su modificación es más notoria que evaluar cada oligoelemento por separado. Estos hallazgos sugieren que existe una redistribución tanto del cobre como del cinc en muchos compartimientos del cuerpo, como respuesta inflamatoria. Por lo que niveles séricos de Cu, Zn y Cu/Zn molar puede ser un criterio valioso para la evaluación clínica y posiblemente, para el estudio y seguimiento de los pacientes con AR.

The aim of this study was to measure the serum levels of copper (Cu) and zinc (Zn) in 129 patients with rheumatoid arthritis (RA), in 94 healthy subjects (HS) and in 21 patients with non-rheumatic diseases (NRD) such as osteoarthritis, fibromyalgia, and ankylosing spondylitis. Serum concentrations of Cu and Zn were measured by flow injection analysis/flame atomic absorption spectroscopy (FIA/FAAS). The Cu/Zn molar ratio in serum also was evaluated in these patients. The result shown that the average concentration of serum copper in patients with RA was significantly increased (p <0.05), on comparing with other patients. This increase was directly proportional to staging or disease progression while zinc concentration was significantly lower in patients with RA, but no differences were found between the stages of the disease. The values of Cu/Zn ratio were 1.88, 1.14 and 1.18, for AR, HS, and NRD patients, respectively. In conclusion, in patients with RA serum copper tend to increase and serum Zn tend to decrease and Cu/Zn molar ratio increases significantly (p<0.05). In conclusion, our results suggest that serum Cu, Zn and Cu/Zn molar ratio could be valuable criteria for clinical evaluation and possibly follow-up study of patients with RA.

Efecto condroprotector del hialuronato de sodio en la artrosis experimental en conejos. Valoración morfológica y por microscopia electrónica de barrido / Chondroprotector effects of hyaluronan in experimental osteoarthritis. Morphologic and scanning microscope evaluation

Objetivo: Estudiar los efectos del hialuronato de sodio en la artrosis experimental por meniscectomía parcial en conejos. Material y método: Se administró hialuronato de sodio por vía intraarticular a un grupo de conejos en fase temprana y tardía de la enfermedad, cada grupo con sus respectivos controles. Se valoraron los aspectos morfológicos (macroscópicos y microscópicos), y se determinaron las concentraciones relativas de calcio en el cartílago, línea ósea subcondral y hueso por microscopia de barrido. Resultados: Los grupos de conejos que recibieron el hialuronato de sodio presentaron una reducción entre dos y 5 veces en la extensión de la lesión cartilaginosa, una disminución del tamaño de los ostreófitos y un descenso de los valores relativos de calcio en el espacio subcondral con respecto al grupo de conejos que no recibieron tratamiento. Conclusión: El hialuronato de sodio administrado por vía intrarticular parece capaz de reducir en estudios de artrosis experimental la extensión y gravedad de la lesión artrósica en todos los niveles (AU)