AdipoRon reduces TGFß1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFß1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFß1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

Daptomycin to bone and joint infections and prosthesis joint infections: a systematic review

ABSTRACT Backgroud: Daptomycin has been used in bone and joint infections (BJI) and prosthesis joint infections (PJI) considering spectrum of activity and biofilm penetration. However, the current experience is based on case reports, case series, cohorts, and international surveys. The aim of this systematic review was to evaluate studies about daptomycin treatment efficacy in BJI/PJI compared to other antibiotic regimens. Methods: PubMed, LILACS, Scielo and Web of Science databases were searched for articles about daptomycin and treatment of BJI and PJI from inception to March 2018. Inclusion criteria were any published researches that included patients with BJI treated with daptomycin. Diagnosis of BJI was based on clinical, laboratory and radiological findings according to IDSA guidelines. Results: From 5107 articles, 12 articles were included. Only three studies described the outcomes of patients with BJI treated with daptomycin with comparator regimen (vancomycin, teicoplanin and oxacillin). Studies presented large heterogeneity regarding device related infections, surgical procedures, and daptomycin regimens (varied from 4 mg/kg to 10 mg/kg). A total of 299 patients have been included in all studies (184 infections associated with orthopedic disposal and 115 osteomyelitis/septic arthritis). Two hundred and thirty-three patients were treated with daptomycin. The clinical cure rates on device related and non-device related infections (i.e. osteomyelitis) were 70% and 78%, respectively. Compared to all regimens evaluated, daptomycin group outcomes were non-inferior. Conclusion: Although a randomized clinical trial is needed, this systematic review tends to support daptomycin usage for bone and joint infections.

Oral steroid therapy for frozen shoulder / Terapia de esteroides orales para el hombro congelado

BACKGROUND: Since frozen shoulder is characterized by spontaneous recovery, no precise treatment strategy exists. Both conservative therapy and arthroscopic surgery is available, but the time required for recovery varies considerably. This study looks at the possible early symptom relief with oral steroid therapy. SUBJECTS AND METHODS: The subjects were 76 patients aged 33 to 73 years at the beginning of the study. The duration of the frozen shoulder was one to 15 months (mean 5.7 months) and hypertension was noted in 13 patients as a complicated disorder. A single course of steroid therapy consisted of a total dose of 105 mg of prednisolone over approximately a three-week period by the dose-tapering method. The number of courses varied with the degree of symptom relief, but the rest period between courses was always approximately four weeks. The results were assessed on the basis of the Japanese Orthopaedic Association (JOA) score, but the principal evaluations were pain and range of motion. RESULTS: The average ranges of motion before treatment were 102.8º of forward flexion 11.3º of external rotation and internal, rotation was at the buttocks. However, after one course of treatment, forward flexion was 136º, external rotation was 33.7º, and internal rotation was limited to the buttocks in only six cases. CONCLUSION: The results of oral steroid therapy for frozen shoulder were highly satisfactory. However, sufficient care is required in explaining the method of administration and the adverse effects such as the osteonecrosis of the femoral head or osteoporosis.

ANTECEDENTES: Como que el hombro congelado se caracteriza por la recuperación espontánea, no existe una estrategia de tratamiento precisa. Tanto la terapia conservadora como la cirugía artroscópica se hallan a disposición, pero el tiempo requerido para la recuperación varía considerablemente. Este estudio echa una ojeada al posible alivio de los síntomas tempranos por medio de la terapia de esteroides orales. SUJETOS Y MÉTODO: Los sujetos fueron 76pacientes en edades de 33 a 73 años al comienzo del estudio. La duración del hombro congelado fue de 1 a 15 meses (promedio 5.7 meses), y se observó hipertensión en 13 pacientes como una condición co-mórbida. Un solo tratamiento con esteroides consistía en una dosis total de 105 mg de prednisolona por un período de aproximadamente tres semanas mediante el método de reducción gradual de la dosis. El número de tratamientos varió de acuerdo con el grado de alivio del síntoma, pero el período de descanso entre tratamientos fue aproximadamente de cuatro semanas. Los resultados fueron evaluados sobre la base de la puntuación establecida por la Asociación Ortopédica del Japón (JOA), y las evaluaciones principales fueron el dolor y el alcance del movimiento. RESULTADOS: El rango promedio del movimiento antes del tratamiento fue 102.8º deflexión delantera, y 11.3º de rotación externa y la rotación interna fue en las nalgas. Sin embargo, luego de un tratamiento, la flexión delantera fue 136º, la rotación externa fue 33.7º, y la rotación interna estuvo limitada a las nalgas en sólo seis casos. CONCLUSIÓN: Los resultados de la terapia de esteroides orales para el hombro congelado, fueron altamente satisfactorias. Sin embargo, se requiere suficiente cuidado al explicar el método de administración y los efectos adversos, tales como la osteonecrosis de la cabeza del fémur o la osteoporosis.

Uso de infliximab en pacientes de un centro reumatologico / Use of infliximab in patients of a rheumatologic center

The objective of this study was to obtain post-marketing information about the use of infliximab in an ambulatory setting. We studied--retrospectively and prospectively--the case records of patients with rheumatoid arthritis (n=37), psoriatic arthritis (n=5), mixed connective tissue disease (n=1), and ankylosing spondylitis (n=2) who received infliximab (3 mg/kg) from August 2000 to January 2003. Descriptive values were given as percentage, mean or median, and standard deviation or interquartile range. Wilcoxon test was used for paired analysis of pre/post doses of corticosteroids, non-steroidal anti-inflammatory drugs, and methotrexate therapy. A p value < or = 0.05 was considered significant. Forty-five patients were included. A total of 207 infusions were administered. In 4 patients the treatment was permanently discontinued due to severe back pain during the infusion (2 cases) and serious anaphylactic reactions (2 cases). Other adverse reactions occurring during infusions were mild and successfully managed with standard treatment. A case of staphylococcal septic arthritis resolved with standard antibiotic treatment. No patient had evidence of active tuberculosis. One patient with rheumatoid arthritis and chronic renal insufficiency, received treatment with infliximab 1.9 mg/kg, every 30 days, with no changes in renal function. Due to improvement of symptoms, 14/39 (35.9%) patients could decrease the doses of corticosteroids, 15/43 (34.8%) decreased the doses of antiinflammatory drugs and 12/34 (35.3%) decreased methotrexate dosage. Although some questions remain to be elucidated, this case series shows the drug safety profile, the possibility to reduce concomitant drug doses, as well as individual approaches for situations where there are not yet guidelines available, so that rheumatologists have to make decisions based on clinical needs.

El objetivo de este estudio fue obtener informacion postmarketing sobre el uso de infliximab en un centro reumatologico de atencion ambulatoria. Se realizo un analisis retrospectivo y prospectivo de las historias clinicas de pacientes con diagnostico de artritis reumatoidea (n=37), artritis psoriasica (n=5),enfermedad mixta del tejido conectivo (n=1) y espondilitis anquilosante (n=2) que recibieron infliximab (3 mg/kg) desde agosto de 2000 a junio de 2003. El analisis descriptivo se realizo con porcentajes, media o medianay desviacion estandar o intervalo intercuartilo. La prueba de Wilcoxon se utilizo para el analisis apareado dedosis de antiinflamatorios no esteroideos y metotrexato, anterior y posterior a la administracion de infliximab. Se consideraron significativos valores de p < o = 0.05. Se incluyeron 45 pacientes a los que se les administraron un total de 207 infusiones. En 2 pacientes el infliximab se discontinuó debido a lumbalgia severa durante la infusion y en otros 2 por anafilaxia intrainfusional. Otras reacciones adversas ocurridas durante las infusiones fueron moderadas y respondieron adecuadamente al tratamiento estandar. Se presento un caso de artritis septica de rodilla por estafilococos. Un caso de artritis reumatoidea con insuficiencia renal compensada recibio infliximab en dosis de 1.9 mg/kg cada 30 dias, sin cambios en la funcion renal. Al momento, ningun paciente ha desarrollado tuberculosis activa. Debido a la mejoria clinica, se redujo la dosis de corticoides en 14/39 (35.9%) pacientes, de antiinflamatorios no esteroideos en 15/43 (34.8%) y de metotrexato en 12/34 (35.3%). En estaserie de casos se muestra el perfil de seguridad de infliximab, la posibilidad de reducir la dosis de drogas concomitantes,asi como algunos enfoques individuales sobre situaciones para las cuales no disponemos de guias basadas en la evidencia medica, y en las que los reumatologos debemos tomar decisiones segun las necesidades clinicas.

Nuevas modalidades terapéuticas en el uso de teicoplanina / [New therapeutic strategies with teicoplanin]

Teicoplanin is a glycopeptide antibiotic with similar spectrum to vancomycin. However, unlike this drug, teicoplanin can be administered by i.v. or i.m. route once daily thanks to its long half-life (88 to 182 hours). This pharmacokinetic characteristic is particularly interesting in infections that require extended antimicrobial therapy, where new therapeutic strategies may be considered. Long-term treatment with teicoplanin proved effective in the treatment of bone and joint infections due to methicillin-resistant staphylococci. Teicoplanin administered three times a week yields comparable clinical efficacy than daily administration with considerably improved cost-effectiveness. This aspect merits special attention, particularly when evaluating prolonged outpatient antibiotic therapy regimens. For synergic effects it is possible to associate teicoplanin with other antibiotics. Chronic suppressive antibiotic therapy with teicoplanin may be an alternative in carefully selected patients, particularly those carrying prosthetic devices.

Diclofenac vs nimesulida en artrosis: niveles plasmáticos y eficacia clínica / Diclofenac vs nimesulide in arthrosis: plasmatic levels and clinical efficacy

El diclofenac (liberación sostenida) y la nimesulida (fórmula convencional) son dos antiinflamatorios no esteroideos cuya dosificación es de un comprimido diario en nuestro país. Las escasas referencias en relación a la farmacocinética y duración de la acción de la nimesulida en pacientes añosos nos indujeron a diseñar el presente estudio controlado con diclofenac. Se selecionaron 20 pacientes con gonartrosis grado II-III asignándoles al azar el tratamiento A (diclofenac, liberación controlada 100mg) o B (nimesulida, presentación convencional 200mg). El estudio se desorrolló de acuerdo a un diseño doble ciego con grupos paralelos. Luego de un lavado de 7 días se comenzó con la medicación activa durante 84 días. Cada 14 días se evaluaron el dolor y otros parámetros clínicos. Se tomaron muestras de sangre los días 7, 49 y 91 a las 10 horas de la toma matutina para medir la concentración de los fármacos en plasma. Se realizaron exámenes de laboratório y al final del estudio. Ya a las dos semanas de comenzado el estudio se constataron mejorías estadísticamente significativas para los parámetros clínicos evaluados, que se mantuvieron durante todo el ensayo, en ambos tratamientos. El diclofenac y la nimesulida aumentaron su concentración plasmática durante los tres meses de estudio y se constató una aparente correlación lineal entre algunos parámetros clínicos y los niveles plasmáticos de los fármacos. La tolerancia, los exámenes de laboratório, y la apreciación clínica global del médico y del paciente para ambos grupos no mostraron diferencias estadísticamente significativas

Acetato de hidrocortisona en la artropatía hemofílica / Hidrocortisone acetate in hemophilic arthropathy

Se utilizó acetato de hidrocortisona intraarticualr en 30 articulaciones con artropatía hemofílica, en 15 adultos. Se observó que después de la primera dosis se produjo una evidente mejoría clínica en la mayoría de las articulaciones tratadas (86,5 %), que alcanza el 100 % después de la tercera dosis. No se observó hemartrosis ni otro tipo de complicaciones por la inyección intraarticualr. Los resultados obtenidos sugieren que la aplicación intraarticular de los corticosteroides podría ser de utilidad, no sólo en el tratamiento de la artropatía hemofílica con cambios radiológicos importantes, sino también en la prevención de la progresión del daño articualr en aquellos casos con estudio radiológico normal

Estudo multicêntrico nacional com tenoxicam / Brazilian multicenter trial with tenoxicam

Säo relatados os resultados obtidos em um estudo multicêntrico com o tenoxicam, novo agente antiinflamatório näo-esteróide em patologias reumáticas diversas. Participaram da investigaçäo 1.432 pacientes e 385 investigadores. Foram registrados resultados satisfatórios em 94,5% dos casos. Os eventos adversos, de leve intensidade em sua maioria, foram registrados em 13.5% dos pacientes e só constituiram causa de abandono em cinco casos. A boa tolerabilidade da droga, aliada a uma eficácia superior com apenas uma dose diária, recomendam seu emprego nas afecçöes reumáticas

Articular participation in inflammatory intestinal diseases

The association between chronic inflammatory bowel diseases (ulcerative colitis, regional enteritis, Whipple's disease) with articular had their studies expanded at the end of the 50's decade. The purpose of this study is to show the incidence and presentation form of the articular involvemente in our patients, excluding bearer of intestinal inflammatory disease, and leaving out the reactive forms to intestinal infections by Yersinia, Salmonella or Shigella. It has been analyzed a whole of 25 cases of ulcerative colitis, 2 of Whipple's disease and 2 of IgA deficiency, all of then with confirmed diagnosis by radiologic alterations, endoscopy, biopsy and immuno-electrophoresis. We noticed the articular involvement in 9 cases (4 ulcerative colitis, 3 regional enterites, 1 in Whipple's disease and 1 in IgA deficiency), aware that the most common presentation was the fugacious and migrant articular pain (arthralgy), having its beginning in most cases after the intestinal disease, with sporadic arthritis in knees and ankles. Classic participation of sacro-ileitis occured in 2 cases, one on left side and other participation, even before the intestinal occurred in 2 cases, one on left side and other sides participation, even before the intestinal manifestation

Eficácia e tolerabilidade da acemetacina no tratamento de processos reumáticos extra-articulares: estudo duplo-cego comparativo com indometacina / Efficacy and tolerability of acemetacin in the treatment of exta-articular rheumatic process: double-blind comparative study with indomethacin

No presente estudo multicêntrico, duplo-cego, randomizado, os autores compararam a eficácia e a tolerabilidade da acemetacina e da indometacina, no tratamento das bursites, tendinites e epicondilites. O estudo envolveu um total de 110 pacientes tratados durante um período de 7 dias, com 60 mg de acemetacina ou 50 mg de indometacina, 3 vezes ao dia. A eficácia terapêutica de ambas as drogas foi semelhante. Entretanto, a incidência de efeitos colaterais foi significativamente menor no grupo acemetacina em relaçäo ao grupo indometacina. Neste último, a intensidade dos efeitos colaterais foi mais freqüentemente moderada e grave que no grupo acemetacina. Os autores concluem que a acemetacina é uma boa opçäo para o controle das patologias extra-articulares por sua boa eficácia terapêutica e sua menor incidênia de efeitos colaterais

Artropatia de Clutton: relato de um caso / Clutton's arthropathy: a case report

Os autores relatam um caso de artropatia de Clutton com poliartrite e ceratouveíte parenquimatosa bilateral. O estudo radiológico evidenciou apenas aumento de partes moles e a sorologia para sífilis foi positiva. Com uso de corticosteróide oftálmico, Aspirina e penicilina, houve regressäo da lesäo ocular e melhora dos sintomas articulares

Sulindac en enfermedades periarticulares / Sulindac in extra-articular diseases

Se comunica los resultados obtenidos con sulindac* en el tratamiento de 40 pacientes con enfermedades periarticulares. Se realizaron examenes clínicos y de gabinete. La dosis diaria de sulindac fue de 300mg divididos en dos tomas (150mg por la mañana y 150 mg en la noche). La duración del tratamiento fue de 1 a 5 semanas. Tanto el efecto analgésico como en el inflamatorio fueron excelentes en 24 casos, buenos en 11, regulares en 3 y malos en 2. Se suspendió el tratamiento a dos pacientes durante la primera semana; uno por presentar dolor tipo cólico y meteorismo moderado, y el otro por gastritis severa. Estas manifestaciones desaparecieron al suspender el medicamento