Tukua

Gracias por escuchar. En este episodio les comparto el audio de un simposio organizado por el Grupo de Enfermedades Infecciosas y Salud Global como parte del Ciclo de Videoconferencias Interactivas 2021 auspiciado por el Instituto Nacional de Salud Pùblica y coordinado por el Dr. Celso Ramos, Investigador en Ciencias adscrito a dicho instituto. El título completo del simposio es Reflexiones y Análisis sobre la pandemia de COVID-19: Lecciones aprendidas, retos y oportunidades. Les deseo lo mejor para 2022. 

En este episodio se comenta el estudio por Goebel, et al, en donde se replican los síntomas de la fibromialgia en un modelo animal mediante la transferencia de anticuerpos de pacientes con este síndrome.  Gracias por su atención a este podcast. Sus comentarios y sugerencias son bienvenidos.   El artículo comentado es el siguiente:   Goebel, A. et al. Passive transfer of fibromyalgia symptoms from patients to mice. J. Clin. Invest. 131, e144201 (2021)

Gracias por escuchar. Belimumab, un anticuerpo monoclonal humano que inhibe el factor de activación de células B (BAFF), está aprobado para su uso en pacientes con lupus eritematoso sistémico (LES) pero aún no en aquellos con nefritis lúpica. Los resultados del ensayo de fase III BLISS-LN indican que la adición de belimumab a la terapia estándar mejora los resultados renales en adultos con nefritis lúpica activa, lo que respalda su uso para esta indicación. Estas son algunas referencias útiles: Furie, R. et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N. Engl. J. Med. 383, 1117–1128 (2020) Maria, N. I. & Davidson, A. Protecting the kidney in systemic lupus erythematosus: from diagnosis to therapy. Nat. Rev. Rheumatol. 16, 255–267 (202)

¡Gracias por escuchar! Los nuevos criterios de clasificación EULAR-ACR de 2019 para el lupus eritematoso sistémico (LES) se desempeñaron bien en las cohortes de validación y derivadas iniciales. Pero, ¿superan estos criterios los criterios de clasificación previos entre género, duración de la enfermedad o etnias? Están son algunas referencias cuya lectura se recomienda: Adamichou, C. et al. In an early SLE cohort the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria classify non-overlapping groups of patients: use of all three criteria ensures optimal capture for clinical studies while their modification earlier classification and treatment. Ann. Rheum. Dis. 79, 232–241 (2020). Aringer, M. et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann. Rheum. Dis. 78, 1151–1159 (2019).   Aggarwal, R. et al. Distinctions between diagnostic and classification criteria? Arthritis Care Res. 67, 891–897 (2015). Dahlström, Ö. & Sjöwall, C. The diagnostic accuracies of the 2012 SLICC criteria and the proposed EULAR/ACR criteria for systemic lupus erythematosus classification are comparable. Lupus 28, 778–782 (2019). Johnson, S. R. et al. Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities. Ann. Rheum. Dis. 79, 1333–1339 (2020). Pons-Estel, G. J., Alarcón, G. S., Scofield, L., Reinlib, L. & Cooper, G. S. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin. Arthritis Rheum. 39, 257–268 (2010). Petri, M. et al. A Comparison of 2019 EULAR/ACR SLE classification criteria with two sets of earlier SLE classification criteria. Arthritis Care Res. https://doi.org/10.1002/acr.24263 (2020). Pons-Estel, G. J. et al. Applying the 2019 EULAR/ACR lupus criteria to patients from an established cohort: a Latin American perspective. RMD Open 6, e001097 (2020). Ugarte-Gil, M. F. et al. Applying the 2019 EULAR/ACR Lupus criteria to patients from the LUMINA cohort. Arthritis Care Res. https://doi.org/10.1002/acr.24367 (2020). Uribe, A. G., McGwin, G. Jr, Reveille, J. D. & Alarcón, G. S. What have we learned from a 10-year experience with the LUMINA (Lupus in Minorities: Nature vs. nurture) cohort? Where are we heading? Autoimmunity Rev. 3, 321–329 (2004).  

¡Gracias por escuchar! Una pregunta importante para los pacientes y médicos es si, y en qué medida, las intervenciones dietéticas, los suplementos dietéticos o la pérdida de peso pueden ayudar a prevenir la gota incidente o controlar la gota existente. En este episodio se revisará evidencia evidencia reciente en este sentido, derivada de uno de los pocos ensayos clínicos relacionados a este tema. Algunas referencia útiles: Singh, J. A., Shah, N. & Edwards, N. L. A cross-sectional internet-based patient survey of the management strategies for gout. BMC Complement. Altern. Med. 16, 90 (2016). Juraschek, S. P. et al. Effects of dietary patterns on serum urate: results from the DASH randomized trial. Arthritis Rheumatol. https://doi.org/10.1002/art.41614 (2020). Appel, L. J. et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N. Engl. J. Med. 336, 1117–1124 (1997). Jacobs, D. R. Jr. & Steffen, L. M. Nutrients, foods, and dietary patterns as exposures in research: a framework for food synergy. Am. J. Clin. Nutr. 78, 508s–513s (2003). Juraschek, S. P. et al. Effects of the Dietary Approaches to Stop Hypertension (DASH) diet and sodium intake on serum uric acid. Arthritis Rheumatol. 68, 3002–3009 (2016). Li, C., Hsieh, M. C. & Chang, S. J. Metabolic syndrome, diabetes, and hyperuricemia. Curr. Opin. Rheumatol. 25, 210–216 (2013). Stamp, L. K. et al. Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: a pilot randomized controlled trial. Arthritis Rheum. 65, 1636–1642 (2013). Stamp, L. K. et al. Lack of effect of tart cherry concentrate dose on serum urate in people with gout. Rheumatology 59, 2374–2380 (2020). Singh, J. A. et al. A randomized internet-based pilot feasibility and planning study of cherry extract and diet modification in gout. J. Clin. Rheumatol. 26, 147–156 (2019). Rai, S. K. et al. The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: prospective cohort study. BMJ 357, j1794 (2017).

Han sido muchos meses desde que nos escuchamos la última vez. En este episodio, hablaré de la evidencia que hay sobre riesgo de tromboembolismo venoso en pacientes que usan inhibidores de JAK.Estas son algunas referencias revisadas para este episodio.Les agradezco su continuado apoyo y su paciencia. Por favor difundan este podcast entre sus conocidos. Choi, H. K. et al. The risk of pulmonary embolism and deep vein thrombosis in rheumatoid arthritis: a UK population-based outpatient cohort study. Ann. Rheum. Dis. 72, 1182–1187 (2013).Cohen, S. B. et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann. Rheum. Dis. https://doi.org/10.1136/annrheumdis-2020-218510 (2020).Genovese, M. et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis. Lancet Rheumatol. 2, E347–E357 (2020).Mease, P. et al. Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data. Ann. Rheum. Dis. 79, 1400–1413 (2020).Molander, V., Bower, H. & Askling, J. Does the risk of venous thromboembolism vary with disease activity in rheumatoid arthritis? [abstract]. Ann. Rheum. Dis. 79 (Suppl. 1), 23–24 (2020).Sandborn, W. J. et al. Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme. Aliment. Pharmacol. Ther. 50, 1068–1076 (2019).Samuelson, B. T. et al. The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis. Blood Coagul. Fibrinolysis 27, 648–652 (2016).Yates, M. et al. Venous thromboembolism risk with JAK inhibitors: a meta-analysis. Arthritis Rheumatol. https://doi.org/10.1002/art.41580 (2020).Winthrop, K. L. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat. Rev. Rheumatol. 13, 234–243 (2017).Winthrop, K. et al. Integrated safety of filgotinib in patients with moderately or severely active rheumatoid arthritis receiving treatment for up to 5.5 years [abstract]. Arthritis Rheumatol. 72 (Suppl. 10), 229 (2020).

Gracias por escuchar. Este episodio es el final de la segunda temporada de Tukua y analiza algunos aspectos relacionados al papel conjunto que llevan a cabo la alimentación y la inflamación.No olviden calificar el podcast en iTunes y dejar sus comentarios en tukua.podbean.com.Hasta la siguiente temporada.

¡Gracias por escuchar! Las personas con enfermedades reumáticas requieren una consideración especial con respecto a COVID-19, causada por el SARS-CoV-2. En este episodio se presentan los primeros resultados derivados del registro RheumCOVID que está centrando su atención en como esta pandemia afecta a los pacientes atendidos por Reumatología. Les pido amablemente que dejen sus comentarios y sugerencias en tukua.podbean.com, YouTube, Facebook y sus calificaciones en iTunes. https://www.thelancet.com/pdfs/journals/lanrhe/PIIS2665-9913(20)30095-3.pdf

¡Gracias por escuchar! La artritis reumatoide (AR) es la causa más frecuente de artritis crónica en todo el mundo y representa una carga de salud y costos socioeconómicos sustanciales, problemas que aumentan con el envejecimiento de la población. En este episodio se presentarán algunas ideas sobre las áreas actuales de incertidumbre en los estudios de prevención de la AR, las lecciones que se pueden aprender de los ensayos de prevención en otros estados de enfermedad y las direcciones futuras a considerar.Estos trabajos pueden resultar de interés:Alpizar-Rodriguez D, Finckh A (2020) Is the prevention of rheumatoid arthritis possible? Clin Rheumatol:1–7.Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G, Genant HK, Peterfy C, Mitra P, Overfield S, Qi K, Westhovens R (2010) Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial). Ann Rheum Dis 69:510–516Gerlag DM, Safy M, Maijer KI, Tang MW, Tas SW, Starmans-Kool MJF, van Tubergen A, Janssen M, de Hair M, Hansson M, de Vries N, Zwinderman AH, Tak PP (2019) Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis 78:179–185van Dongen H, van Aken J, Lard LR, Visser K, Ronday HK, Hulsmans HM, Speyer I, Westedt ML, Peeters AJ, Allaart CF, Toes RE, Breedveld FC, Huizinga TW (2007) Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 56:1424–1432

La comunidad reumatológica internacional ha creado una respuesta global, coordinada y oportuna a la pandemia de COVID-19, The Global Rheumatology Alliance, para tratar de abordar el déficit de información que existe en torno a los desenlaces de la infección en pacientes con enfermedades reumáticas.  Esta alianza tiene como objetivo aprovechar la amplitud de la experiencia y el conocimiento en el médico reumatólogo y las comunidades de pacientes para avanzar en el conocimiento sobre COVID-19 en beneficio de todos los pacientes con enfermedades reumáticas. Todos tenemos el deber de contribuír con este esfuerzo sin precedentes.https://rheum-covid.org/

¡Gracias por escuchar! En este episodio hablaré acerca de los mecanismos de lesión tisular que se asocian a neumonía grave en pacientes infectados por SARS-CoV2 y el potencial de varios tratamientos antireumáticos para mejorar los desenlaces en estos pacientes.Agradezco su continuada atención y sus amables comentarios en tukua.podbean.com, youtube.com y sus calificaciones en iTunes. Estas son algunas referencias útiles:Chen J, Subbarao K: The Immunobiology of SARS. Annu Rev Immunol 2007; 25: 443-72De Lauretis A, Sestini P, Pantelidis P et al.: Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol 2013; 40: 435-46.Diao B, Wang C, Tan Y et al.: Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19). MedRxiv 2020: 2020.02.18.20024364.Fu Y, Cheng Y, Wu Y, Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virol Sin 2020 Mar 3Huang C, Wang Y, Li X et al.: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506.Li G, Fan Y, Lai Y et al.: Coronavirus infections and immune responses. J Med Virol 2020; 92: 424-32.Li H, Yang Sg, Gu L et al.: Effect of low-to- moderate-dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia. Influenza Other Respir Viruses 2017; 11: 345-54.Stebbing J, Phelan A, Griffin I et al.: COV- ID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis 2020. Zhang Y, Li J, Zhan Y et al.: Analysis of serum cytokines in patients with severe acute respiratory syndrome. Infect Immun 2004; 72: 4410-5.

¡Gracias por escuchar! En este episodio se revisan 4 publicaciones recientes que presentan evidencia en diferentes tópicos de Reumatología.Por favor dejen sus comentarios en tukua.podbean.com, youtube.com y sus calificaciones en iTunes.Estas son las referencia revisadas: Adam, S. et al. Sci. Transl Med. 12 , eaay4447 (2020)Kissel, T. eT al. Ann. Rheum. Dis. https: // doi.org/10.1136/annrheumdis-2019-216499 (2020)Smolen, JS el al. Ann. Rheum. Dis. https://doi.org/10.1136/annrheumdis-2019-216655 (2020)Kolasinski , SL et al. Arthritis Rheum. https://doi.org/10.1002/art.41142 (2019)

¡Gracias por escuchar! En este episodio se resume la evidencia que ha estado surgiendo sobre la utilidad de algunos fármacos antireumáticos en el tratamiento de COVID-19.No olviden dejar sus comentarios y sugerencias así como calificar este y otros episodios en iTunes.Estas son algunas ligas de interés:https://wb.md/3b1URQYhttp://bit.ly/3d5vS0Vhttp://bit.ly/3b2awj3http://bit.ly/31HmmM1 http://bit.ly/38UgIZfhttp://bit.ly/2U9kI2A https://reut.rs/2wglfaT 

¡Gracias por escuchar! La pandemia de COVID-19 por SARSCov2 ha generado la necesidad de considerar esta infección como parte de las comorbilidades que los pacientes con enfermedad reumática pueden presentar. En este episodio se revisa la evidencia que hay sobre infección por Coronavirus en pacientes inmunocomprometidos y las recomendaciones profilácticas para estos pacientes.Agradezco su atención y pido amablemente que dejen sus comentarios en tukua.podbean.com así como sus calificaciones en iTunes. Esta liga es de mucha utilidad:https://www.eular.org/eular_guidance_for_patients_covid19_outbreak.cfm

¡Gracias por escuchar! Los pacientes con artralgia clínicamente sospechosa tienen síntomas articulares como dolor y rigidez de las articulaciones pequeñas sin signos clínicos de artritis. Algunos de estos pacientes progresan y desarrollan una enfermedad 'verdadera', pero ¿cómo podemos diferenciar la enfermedad crónica en evolución de la enfermedad que se resolverá? En este episodio se comentará un estudio reciente que pretende ayudar con la respuesta a esta pregunta.Estas son algunas referencias de utilidad:Al-Laith, M. et al. Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol. Trials 20, 429 (2019).Brulhart, L. et al. Ultrasound is not associated withthe presence of systemic autoimmunity or symptoms in individuals at risk for rheumatoid arthritis. RMD Open. 5, e000922 (2019).Gerlag, D. M. et al. Effects of B cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann. Rheum. Dis. 78, 179–185 (2019).Kleyer, A. et al. High prevalence of tenosynovial inflammation before onset of rheumatoid arthritis and its link to progression to RA-A combined MRI/CT study. Semin. Arthritis Rheum. 46, 143–150 (2016).Kleyer, A. et al. Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann. Rheum. Dis. 73, 854–860 (2014).Raza, K. et al. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res. Ther. 7, R784–R795 (2005).Sahbudin, I. et al. The role of ultrasound-defined tenosynovitis and synovitis in the prediction of rheumatoid arthritis development. Rheumatology (Oxford). 57, 1243–1252 (2018).ten Brinck, R. M. et al. Improvement of symptoms in clinically suspect arthralgia and resolution of subclinical joint inflammation: a longitudinal study in patients that did not progress to clinical arthritis. Arthritis Res. Ther. 22, 11 (2020).van Steenbergen, H. W. et al. EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Ann. Rheum. Dis. 76, 491–496 (2017).

¡Gracias por escuchar! La inhibición de TNF mediante moléculas pequeñas recientemente descubiertas se da como un antagonismo de señalización proinflamatoria de TNF mediante el aprovechamiento exclusivo de la plasticidad conformacional del TNF trimérico. El desarrollo de este mecanismo de acción podría marcar un resurgimiento de moduladores no biológicos de interacciones proteína-proteína clínicamente relevantes en reumatología, como se revisará en este episodio.Les pido amablemente dejen sus calificaciones a este y otros episodios en iTunes así como sus  sugerencias en la sección de comentarios.He aquí las referencias revisadas:Kalliolias, G. D. & Ivashkiv, L. B. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat. Rev. Rheumatol. 12, 49–62 (2016)Davis, J. M. & Colangelo, J. Small- molecule inhibitors of the interaction between TNF and TNFR. Future Med. Chem. 5, 69–79 (2013)He, M. M. et al. Small- molecule inhibition of TNF-alpha. Science 310, 1022–1025 (2005)He, M. M. et al. Small- molecule inhibition of TNF-alpha. Science 310, 1022–1025 (2005)Jairath, V. & Feagan, B. G. Global burden of inflammatory bowel disease. Lancet Gastroenterol. Hepatol. 5, 2–3 (2020)Kingsmore, K. M., Grammer, A. C. & Lipsky, P. E. Drug repurposing to improve treatment of rheumatic autoimmune inflammatory diseases. Nat. Rev. Rheumatol. 16, 32–52 (2020)Mak, K. K. & Pichika, M. R. Artificial intelligence in drug development: present status and future prospects. Drug Discov. Today 24, 773–780 (2019)Nair, N. & Wilson, A. G. Can machine learning predict responses to TNF inhibitors? Nat. Rev. Rheumatol. 15, 702–704 (2019)Steeland, S., Libert, C. & Vandenbroucke, R. E. A new venue of TNF targeting. Int. J. Mol. Sci. 19, 1442 (2018)O’Connell, J. et al. Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer. Nat. Commun. 10, 5795 (2019)Scott, D. E., Bayly, A. R., Abell, C. & Skidmore, J. Small molecules, big targets: drug discovery faces the protein- protein interaction challenge. Nat. Rev. Drug Discov. 15, 533–550 (2016)

¡Gracias por escuchar! Los medicamentos antimaláricos, hidroxicloroquina y cloroquina, son fármacos moduladores de las enfermedades reumáticas introducidos por serendipia y empíricamente para el tratamiento de diversas enfermedades reumáticas. Ni la cloroquina ni la hidroxicloroquina se sometieron al proceso de desarrollo de fármacos convencional, pero su uso se ha convertido en parte importante de los tratamiento actuales para la artritis reumatoide, lupus eritematoso sistémico, síndrome de anticuerpos antifosfolípido y síndrome de Sjögren primario. En este episodio exploraremos sus principales características desde la perspectiva farmacológica.Les pido amablemente dejen sus comentarios en tukua.podbean.com y la calificación a este y otros episodios en iTunes.Estas son algunas referencias de utilidad:Ruiz-Irastorza, G. et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann. Rheum. Dis. 69, 20–28 (2010).Ostensen, M. et al. Pregnancy and reproduction in autoimmune rheumatic diseases. Rheumatology 50, 657–664 (2011).Akhavan, P. S. et al. The early protective effect of hydroxychloroquine on the risk of cumulative damage in patients with systemic lupus erythematosus.Ponticelli, C. & Moroni, G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert. Opin. Drug Saf. 16, 411–419 (2017).Wang, S. Q. et al. Is hydroxychloroquine effective in treating primary Sjogren’s syndrome: a systematic review and meta-analysis. BMC Musculoskelet. Disord. 18, 186 (2017).Rainsford, K. D. et al. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology 23, 231–269 (2015).Collins, K. P., Jackson, K. M. & Gustafson, D. L. Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancerrelated autophagy modulation. J. Pharmacol. Exp. Ther. 365, 447–459 (2018).Munster, T. et al. Hydroxychloroquine concentrationresponse relationships in patients with rheumatoid arthritis. Arthritis Rheum. 46, 1460–1469 (2002).Carmichael, S. J., Charles, B. & Tett, S. E. Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis. Ther. Drug Monit. 25, 671–681 (2003).Mok, C. C., Mak, A. & Ma, K. M. Bone mineral density in postmenopausal Chinese patients with systemic lupus erythematosus. Lupus 14, 106–112 (2005).Petri, M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody-positive patients. Curr. Rheumatol. Rep. 13, 77–80 (2011).Kingsbury, S. R. et al. Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis: a randomized trial. Ann. Intern. Med. 168, 385–395 (2018).Lee, W. et al. Efficacy of hydroxychloroquine in hand osteoarthritis: a randomized, double-blind, placebocontrolled trial. Arthritis Care Res. 70, 1320–1325 (2018).Rempenault, C. et al. Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann. Rheum. Dis. 77, 98–103 (2018).Ruiz-Irastorza, G. et al. Predictors of major infections in systemic lupus erythematosus. Arthritis Res. Ther. 11, R109 (2009).Flannery, E. L., Chatterjee, A. K. & Winzeler, E. A. Antimalarial drug discovery – approaches and progress towards new medicines. Nat. Rev. Microbiol. 11, 849–862 (2013).Ridley, R. G. Medical need, scientific opportunity and the drive for antimalarial drugs. Nature 415, 686–693 (2002).Minie, M. et al. CANDO and the infinite drug discovery frontier. Drug Discov. Today 19, 1353–1363 (2014).Paddon, C. J. et al. High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496, 528–532 (2013).Hale, V. et al. Microbially derived artemisinin: a biotechnology solution to the global problem of access to affordable antimalarial drugs. Am. J. Trop. Med. Hyg. 77, 198–202 (2007).Somer, M. et al. Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br. J. Clin. Pharmacol. 49, 549–554 (2000).Kormelink, T. G. et al. Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann. Rheum. Dis. 69, 2137–2144 (2010).Toimela, T., Tahti, H. & Salminen, L. Retinal pigment epithelium cell culture as a model for evaluation of the toxicity of tamoxifen and chloroquine. Ophthalmic Res. 27, 150–153 (1995).Bannwarth, B. et al. Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. Clin. Pharmacokinet. 30, 194–210 (1996).Carmichael, S. J. et al. Combination therapy with methotrexate and hydroxychloroquine for rheumatoid arthritis increases exposure to methotrexate. J. Rheumatol. 29, 2077–2083 (2002).van den Borne, B. E. et al. Combination therapy in recent onset rheumatoid arthritis: a randomized double blind trial of the addition of low dose cyclosporine to patients treated with low dose chloroquine. J. Rheumatol. 25, 1493–1498 (1998).Namazi, M. R. The potential negative impact of proton pump inhibitors on the immunopharmacologic effects of chloroquine and hydroxychloroquine. Lupus 18, 104–105 (2009).Jallouli, M. et al. Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus. Arthritis Rheumatol. 67, 2176–2184 (2015).Ezra, N. & Jorizzo, J. Hydroxychloroquine and smoking in patients with cutaneous lupus erythematosus. Clin. Exp. Dermatol. 37, 327–334 (2012).Yeon Lee, J. et al. Factors related to blood hydroxychloroquine concentration in patients with systemic lupus erythematosus. Arthritis Care Res. 69, 536–542 (2017).Borden, M. B. & Parke, A. L. Antimalarial drugs in systemic lupus erythematosus: use in pregnancy. Drug Saf. 24, 1055–1063 (2001).Costedoat-Chalumeau, N. et al. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases. Review of the literature. Autoimmun. Rev. 4, 111–115 (2005).Teng, Y. K. O. et al. An evidence-based approach to pre-pregnancy counselling for patients with systemic lupus erythematosus. Rheumatology 57, 1707–1720 (2017).Andreoli, L. et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann. Rheum. Dis. 76, 476–485 (2017).Gotestam Skorpen, C. et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann. Rheum. Dis. 75, 795–810 (2016).Izmirly, P. M. et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 126, 76–82 (2012).Saxena, A. et al. Prevention and treatment in utero of autoimmune-associated congenital heart block. Cardiol. Rev. 22, 263–267 (2014).Friedman, D. et al. No histologic evidence of foetal cardiotoxicity following exposure to maternal hydroxychloroquine. Clin. Exp. Rheumatol. 35, 857–859 (2017).Sammaritano, L. R. & Bermas, B. L. Rheumatoid arthritis medications and lactation. Curr. Opin. Rheumatol. 26, 354–360 (2014).An, J. et al. Antimalarial drugs as immune modulators: new mechanisms for old drugs. Annu. Rev. Med. 68, 317–330 (2017).An, J. et al. Cutting edge: antimalarial drugs inhibit IFN-β production through blockade of cyclic GMP-AMP synthase-DNA interaction. J. Immunol. 194, 4089–4093 (2015).van den Borne, B. E. et al. Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cellFasano, S. et al. Longterm hydroxychloroquine therapy and low-dose aspirin may have an additive effectiveness in the primary prevention of cardiovascular events in patients with systemic lupus erythematosus. J. Rheumatol. 44, 1032–1038 (2017).Towers, C. G. & Thorburn, A. Therapeutic targeting of autophagy. EBioMedicine 14, 15–23 (2016).Rand, J. H. et al. Hydroxychloroquine directly reduces the binding of antiphospholipid antibodyβ2-glycoprotein I complexes to phospholipid bilayers. Blood 112, 1687–1695 (2008).Jancinova, V., Nosal, R. & Petrikova, M. On the inhibitory effect of chloroquine on blood platelet aggregation. Thromb. Res. 74, 495–504 (1994).Bertrand, E. et al. Antiaggregation action of chloroquine. Med. Trop. 50, 143–146 (1990).Nosal, R., Jancinova, V. & Petrikova, M. Chloroquine inhibits stimulated platelets at the arachidonic acid pathway. Thromb. Res. 77, 531–542 (1995).Lazarus, M. N. et al. Incidence of cancer in a cohort of patients with primary Sjogren’s syndrome. Rheumatology 45, 1012–1015 (2006). J. Rheumatol. 21, 375–376 (1994).Wallace, D. J. et al. The relevance of antimalarial therapy with regard to thrombosis, hypercholesterolemia and cytokines in SLE. Lupus 2, S13–S15 (1993).Hjorton, K. et al. Cytokine production by activated plasmacytoid dendritic cells and natural killer cells is suppressed by an IRAK4 inhibitor. Arthritis Res. Ther. 20, 238 (2018).Willis, R. et al. Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort. Lupus 21, 830–835 (2012).Wu, S. F. et al. Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res. Ther. 19, 183 (2017).Qushmaq, N. A. & Al-Emadi, S. A. Review on effectiveness of primary prophylaxis in aPLs with and without risk factors for thrombosis: efficacy and safety. ISRN Rheumatol. 2014, 348726 (2014).Nuri, E. et al. Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syndrome. Immunol. Res. 65, 17–24 (2017).Dadoun, S. et al. Mortality in rheumatoid arthritis over the last fifty years: systematic review and meta-analysis. Joint Bone Spine 80, 29–33 (2013).van den Hoek, J. et al. Mortality in patients with rheumatoid arthritis: a 15-year prospective cohort study. Rheumatol. Int. 37, 487–493 (2017).Avina-Zubieta, J. A. et al. Risk of myocardial infarction and stroke in newly diagnosed systemic lupus erythematosus: a general population-based study. Arthritis Care Res. 69, 849–856. (2017).Srinivasa, A., Tosounidou, S. & Gordon, C. Increased incidence of gastrointestinal side effects in patients taking hydroxychloroquine: a brand-related issue? J. Rheumatol. 44, 398 (2017).Abdel-Hamid, H., Oddis, C. V. & Lacomis, D. Severe hydroxychloroquine myopathy. Muscle Nerve 38, 1206–1210 (2008).Jafri, K. et al. Antimalarial myopathy in a systemic lupus erythematosus patient with quadriparesis and seizures: a case-based review. Clin. Rheumatol. 36, 1437–1444 (2017).Khosa, S. et al. Hydroxychloroquine-induced autophagic vacuolar myopathy with mitochondrial abnormalities. Neuropathology 38, 646–652 (2018).Stein, M., Bell, M. J. & Ang, L. C. Hydroxychloroquine neuromyotoxicity. J. Rheumatol. 27, 2927–2931 (2000). Int. J. Cardiol. 157, 117–119 (2012).Sundelin, S. P. & Terman, A. Different effects of chloroquine and hydroxychloroquine on lysosomal function in cultured retinal pigment epithelial cells. APMIS 110, 481–489 (2002).Jorge, A. et al. Hydroxychloroquine retinopathy implications of research advances for rheumatology care. Nat. Rev. Rheumatol. 14, 693–703 (2018).Marmor, M. F. et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). Ophthalmology 123, 1386–1394 (2016).Yusuf, I. H. et al. The Royal College of Ophthalmologists recommendations on screening for hydroxychloroquine and chloroquine users in the United Kingdom: executive summary. Eye 32, 1168–1173 (2018). J. Rheumatol. 44 1841–1849 (2017).Padol, I. T. & Hunt, R. H. Association of myocardial infarctions with COX-2 inhibition may be related to immunomodulation towards a Th1 response resulting in atheromatous plaque instability: an evidencebased interpretation. Rheumatology 49, 837–843 (2010).Hage, M. P., Al-Badri, M. R. & Azar, S. T. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role. Ther. Adv. Endocrinol. Metab. 5, 77–85 (2014).Costedoat-Chalumeau, N. et al. Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum. 54, 3284–3290 (2006).Costedoat-Chalumeau, N. et al. A prospective international study on adherence to treatment in 305 patients with flaring SLE: assessment by drug levels and self-administered questionnaires. Clin. Pharmacol. Ther. 103, 1074–1082 (2018).Bethel, M. et al. Hydroxychloroquine in patients with systemic lupus erythematosus with end-stage renal disease. J. Investig. Med. 64, 908–910 (2016).Sperati, C. J. & Rosenberg, A. Z. Hydroxychloroquineinduced mimic of renal Fabry disease. Kidney Int. 94, 634 (2018).Yusuf, I. H., Lotery, A. J. & Ardern-Jones, M. R. Joint recommendations for retinal screening in longterm users of hydroxychloroquine and chloroquine in the United Kingdom, 2018. Br. J. Dermatol. 179, 995–996 (2018).Melles, R. B. & Marmor, M. F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol. 132, 1453–1460 (2014).Costedoat-Chalumeau, N., Isenberg, D. & Petri, M. Letter in response to the 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus by Fanouriakis et al. Ann. Rheum. Dis. https://doi.org/10.1136/annrheumdis-2019215573 (2019).

¡Gracias por escuchar! La desregulación en la formación y / o eliminación de trampas extracelulares de neutrófilos (NETs) es importante en la disregulación inmune y el daño orgánico en condiciones de inflamación crónica. En este episodio revisaré algunos estudios recientes que han demostrado cómo ciertas susceptibilidades genéticas a la autoinmunidad pueden promover la inflamación mediada por NETs y revelan su papel en el daño vascular y la aterosclerosis prematura.No olviden dejar sus comentarios y retroalimentación y calificar estos y otros episodios en iTunes.Estos son algunas referencias útiles:Gupta, S. & Kaplan, M. J. The role of neutrophils and NETosis in autoimmune and renal diseases. Nat. Rev. Nephrol. 12, 402–413 (2016).Odqvist, L. et al. Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus. Ann. Rheum. Dis. 78, 1363–1370 (2019).Carmona-Rivera, C. et al. Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2. Blood 134, 395–406 (2019).Silvestre-Roig, C. et al. Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death. Nature 569, 236–240 (2019).Wang, Y. et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J. Cell Biol. 184, 205–213 (2009).Suzuki, A. et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat. Genet. 34, 395–402 (2003).Chang, H. H. et al. The W620 polymorphism in PTPN22 disrupts its interaction with peptidylarginine deiminase type 4 and enhances citrullination and NETosis. Arthritis Rheumatol. 67, 2323–2334 (2015).Zhou, Q. et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N. Engl. J. Med. 370, 911–920 (2014).Ali, A. A. et al. Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome. Nat. Commun.10, 1916 (2019).10. Knight, J. S. et al. Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ. Res. 114, 947–956 (2014)

¡Gracias por escuchar! La disponibilidad de biosimilares para tratar enfermedades inflamatorias ha generado nuevos retos en la terapéutica de pacientes cuando se sustituye el tratamiento de un bio-original a su biosimilar (o bio comparable en México) para ahorrar costos. En este episodio hablaré acerca de la evidencia sobre la la efectividad y la seguridad del 'cambio no médico' de fármacos y sobre los beneficios de comunicar información sobre biosimilares a los pacientes de manera positiva.Recuerden que su retroalimentación y sus calificaciones en iTunes son bienvenidas. Aquí están las referencias consultadas:1. European Medicines Agency. Centrally authorised biosimilar medicines. EMA https://www.ema.europa.eu/ en/medicines/field_ema_web_categories%253Aname_ field/Human/ema_group_types/ema_medicine/field_ ema_med_status/authorised-36/ema_medicine_types/ field_ema_med_biosimilar/search_api_aggregation_ ema_medicine_types/field_ema_med_biosimilar (2019).2. US Food & Drug Administration. Biosimilar product information. FDA https://www.fda.gov/drugs/ biosimilars/biosimilar-product-information (2019).3. Dorner, T. & Kay, J. Biosimilars in rheumatology: current perspectives and lessons learnt. Nat. Rev. Rheumatol. 11, 713–724 (2015).4. Goll, G. L. et al. Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial. J. Intern. Med. 285, 653–669 (2019).5. Glintborg, B. et al. To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry. Ann. Rheum. Dis. 78, 192–200 (2019).6. Gasteiger, C. et al. The effects of message framing on patients’ perceptions and willingness to change to a biosimilar in a hypothetical drug switch. Arthritis Care Res. https://doi.org/10.1002/acr.24012 (2019).7. Jørgensen, K. K. et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, doubleblind, non-inferiority trial. Lancet 389, 2304–2316 (2017).8. Radet for Anvendelse af Dyr Sygehusmedicin. RADS anbefaling vedrørende brug af biosimilært infliximab og etanercept [RADS recommendation regarding the use of biosimilar infliximab and etanercept]. regioner.dk https://www.regioner.dk/media/3488/rads-notatom-anvendelsen-af-biosimilaere-juni-2016.pdf (2016).9. Tweehuysen, L. et al. Open-label, non-mandatory transitioning from originator etanercept to biosimilar SB4: six-month results from a controlled cohort study. Arthritis Rheumatol. 70, 1408–1418 (2018)

La hiperuricemia asintomática es una condición muy común sobre la cual se derramado mucha tinta, específicamente con relación a su manejo. En este episodio discutiré cual es el impacto clínico de la hiperuricemia asintomática, tocaré brevemente su fisiopatología y contribuiré a confundirlos en cuanto a su tratamiento.Estas son algunas de las referencias consultadas:Bursill, D. et al. Gout, hyperuricemia, and crystal- associated disease network consensus statement regarding labels and definitions for disease elements in gout. Arthritis Care Res. 71, 427–434 (2019).Richette, P. et al. 2016 updated EULAR evidence- based recommendations for the management of gout. Rheum. Dis. 76, 29–42 (2017).Sivera, F. et al. Multinational evidence-based recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative. Rheum. Dis. 73, 328–335 (2014).Dalbeth, N. et al. Discordant American College of Physicians and international rheumatology guidelines for gout management: consensus statement of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN). Rev. Rheumatol. 13, 561–568 (2017).Khanna, D. et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 64, 1431–1446 (2012).Neogi, T. & Mikuls, T. R. To treat or not to treat (to target) in gout. Intern. Med. 166, 71–72 (2017).Jensen, T. et al. Fructose and sugar: a major mediator of non-alcoholic fatty liver disease. Hepatol. 68, 1063–1075 (2018).Johnson, R. J. et al. Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: report of a scientific workshop organized by the national kidney foundation. J. Kidney Dis. 71, 851–865 (2018).Yamanaka, H. Japanese Society of Gout and Nucleic Acid Metabolism. Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides Nucleotides Nucleic Acids 30, 1018–1029 (2011).

¡Gracias por escuchar! En este episodio continuaré con la discusión sobre la aplicación de los principios de la economía del comportamiento en Reumatología.Por favor califiquen el podcast en iTunes o en tukua.podbean.com, siendo bienvenidos sus comentarios y sugerencias.

 ¡Gracias por escuchar! La Economía del Comportamiento es un campo que estudia el comportamiento irracional de los seres humanos cuando se trata de tomar una decisión o seguir un consejo. En este y en el siguiente episodio repaso como estas herramientas pueden usarse para beneficio de la relación médico paciente en el campo de la Reumatología.Les pido amablemente dejen sus comentarios y sugerencias en www.tukua.podbean.com, en iTunes o a través de su gestor de podcasts favorito.Algunas referencias:Patel, M. S. et al. Framing financial incentives to increase physical activity among overweight and obese adults: a randomized, controlled trial. Ann. Intern. Med. 164, 385–394 (2016).Schneider, T. R. et al. The effects of message framing and ethnic targeting on mammography use among low-income women. Health Psychol. 20, 256–266 (2001)Lipstein, E. A. et al. High levels of decisional conflict and decision regret when making decisions about biologics. J. Pediatr. Gastroenterol. Nutr. 63, e176–e181 (2016)Bickel, W. K., Johnson, M. W., Koffarnus, M. N., MacKillop, J. & Murphy, J. G. The behavioral economics of substance use disorders: reinforcement pathologies and their repair. Annu. Rev. Clin. Psychol. 10, 641–677 (2014).Halpern, S. D. et al. Randomized trial of four financial-incentive programs for smoking cessation. N. Engl. J. Med. 372, 2108–2117 (2015).Halpern, S. D. et al. A pragmatic trial of E-cigarettes, incentives, and drugs for smoking cessation. N. Engl. J. Med. 378, 2302–2310 (2018).Volpp, K. G. et al. Financial incentive-based approaches for weight loss: a randomized trial. JAMA 300, 2631–2637 (2008).Thorgeirsson, T. & Kawachi, I. Behavioral economics: merging psychology and economics for lifestyle interventions. Am. J. Prev. Med. 44, 185–189 (2013)Patel, M. S. et al. Using wearable devices and smartphones to track physical activity: initial activation, sustained use, and step counts across sociodemographic characteristics in a national sample. Ann. Intern. Med. 167, 755–757 (2017)Checchi, K. D., Huybrechts, K. F., Avorn, J. & Kesselheim, A. S. Electronic medication packaging devices and medication adherence: a systematic review. JAMA 312, 1237–1247 (2014).Milkman, K. L., Beshears, J., Choi, J. J., Laibson, D.& Madrian, B. C. Using implementation intentions prompts to enhance influenza vaccination rates.Halpern, S. D., Ubel, P. A. & Asch, D. A. Harnessing the power of default options to improve health care. N. Engl. J. Med. 357, 1340–1344 (2007).

¡Gracias por escuchar!Para empezar el año, este episodio lo dedicaré a hablar de como la composición corporal influye sobre la eficacia y eventos adversos asociados al uso de glucocorticoides.Agradezco su continuada atención a este podcast y les recuerdo que se pueden suscribir a el en iTunes, Spotify o usando su gestor de podcasts favorito. Como siempre su retroalimentación es bienvenida y les pido amablemente dejen su calificación a este y otros episodios en iTunes.Estas son algunas de las referencias consultadas para este episodio:van der Goes, M. C. et al. Patient and rheumatologist perspectives on glucocorticoids: an exercise to improve the implementation of the European League Against Rheumatism (EULAR) recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann. Rheum. Dis. 69, 1015–1021 (2010).Konijn, N. P. et al. The short-term effects of two high-dose, step-down prednisolone regimens on body composition in early rheumatoid arthritis. Rheumatology (Oxford) http://dx.doi.org/10.1093/ rheumatology/kew221 (2016).Buttgereit, F., Smolen, J. S., Coogan, A. N. & Cajochen, C. Clocking in: chronobiology in rheumatoid arthritis. Nat. Rev. Rheumatol. 11, 349–356 (2015).Arvidson, N. G., Gudbjornsson, B., Larsson, A. Hallgren, R. The timing of glucocorticoid administration in rheumatoid arthritis. Ann. Rheum. Dis. 56, 27–31 (1997).Cutolo, M. Glucocorticoids and chronotherapy in rheumatoid arthritis. RMD Open 2, e000203 (2016).Smith-Ryan, A. E. et al. Validity and reliability of a 4-compartment body composition model using dual energy X-ray absorptiometry-derived body volume. Clin. Nutr. http://dx.doi.org/10.1016/j. clnu.2016.05.006 (2016).Summers, G. D., Metsios, G. S., Stavropoulos- Kalinoglou, A. & Kitas, G. D. Rheumatoid cachexia and cardiovascular disease. Nat. Rev. Rheumatol. 6, 445–451 (2010).Walsmith, J. & Roubenoff, R. Cachexia in rheumatoid arthritis. Int. J. Cardiol. 85, 89–99 (2002).Arshad, A., Rashid, R. & Benjamin, K. The effect of disease activity on fat-free mass and resting energy expenditure in patients with rheumatoid arthritis versus noninflammatory arthropathies/soft tissue rheumatism. Mod. Rheumatol. 17, 470–475 (2007).Elkan, A. C., Hakansson, N., Frostegard, J., Cederholm, T. & Hafstrom, I. Rheumatoid cachexia is associated with dyslipidemia and low levels of atheroprotective natural antibodies against phosphorylcholine but not with dietary fat in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res. Ther. 11, R37 (2009).

¡Gracias por escuchar! Deseo que pasen felices fiestas y el 2020 cumpla con todas sus expectativas.Esta es la liga mencionada en este episodio:https://www.bmj.com/content/367/8227

¡Gracias por escuchar! En la última década, el cannabis ha resurgido como una potencial terapia medicinal y su uso en este contexto es cada vez más regulado a nivel global. Muchas de las aplicaciones médicas actuales de los cannabinoides incluyen enfermedades reumáticas como la artritis reumatoide y la fibromialgia, lo que lleva a la necesidad de evaluar la evidencia actual para el uso terapéutico en estas condiciones y sus posibles aplicaciones terapéuticas, como veremos en este episodio.No olviden dejar su opinión y retroalimentación, así como calificar este y otros episodios en iTunes.Estas son algunas de la referencias mas interesantes usadas en la preparación de este episodio: National Academies of Sciences, Engineering and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (The National Academies Press, 2017).Volkow, N. D., Baler, R. D., Compton, W. M. & Weiss, S. R. B. Adverse health effects of marijuana use. N. Engl. J. Med. 370, 2219–2227 (2014).Anderson, G. D. & Chan, L. N. Pharmacokinetic drug interactions with tobacco, cannabinoids and smoking cessation products. Clin. Pharmacokinet. 55, 1353–1368 (2016).Fitzcharles, M.-A. et al. Rheumatologists lack confidence in their knowledge of cannabinoids pertaining to the management of rheumatic complaints. BMC Musculoskelet. Disord. 15, 258 (2014).Iversen, L. Cannabis and the brain. Brain 126, 1252–1270 (2003).Richardson, D. et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res. Ther. 10, R43 (2008). 

En este episodio hablo acerca del IFN tipo I, un atractivo blanco terapéutico en Lupus Eritematoso Sistémico (LES), un concepto que se ha visto impulsado por los resultados positivos de ensayos clínicos recientes con anticuerpos monoclonal es anti-IFN en pacientes con LES. Estos fármacos parecen funcionar mejor en pacientes con una expresión elevada de los genes inductores de IFN, lo cual fortalece la idea de qué hay subgrupos de pacientes que pueden beneficiarse de manera preferencial.

¡Gracias por escuchar! La microbiota de los seres humanos está implicada en la patogenia de múltiples enfermedades crónicas, tanto intestinales como sistémicas. La integridad de la barrera intestinal es esencial para prevenir que la microbiota de un individuo sano desencadene respuestas inmunes adaptativas, Cuando los comensales intactos o los microorganismos patógenos escapan la barrera intestinal, múltiples mecanismos de defensa impiden el acceso bacteriano a la circulación sistémica. Sin embargo, si estos mecanismos fracasan, los ganglios linfáticos mesentéricos y el hígado representan barreras adicionales contra estos microbios fugitivos. Tales mecanismos ocurren solo durante la enfermedad intestinal o vascular, o bajo circunstancias especiales como lo son la quimioterapia o el inmunocompromiso. En este episodio exploraremos un reciente estudio por Manfredo Vieira y colaboradores, de la Universidad de Yale, publicado en Science el año pasado.Esta es la referencia del artículo: Manfredo Vieira et al., Science 359, 1156–1161 (2018)Les recuerdo amablemente que su retroalimentación es muy importante. No duden en dejar sus comentarios en esta página y sus calificaciones en iTunes. 

¡Gracias por escuchar! La semana pasada se llevó a cabo el evento académico mas grande de la Reumatología global, la reunión anual del Colegio Americano de Reumatólogos. En este episodio hago un pequeño resumen de lo que me pareció mas interesante. Debido a que este evento es masivo, esto no pretende ser una reseña comprensiva, mas bien proveer de un punto de vista sobre hacia donde se dirige nuestra especialidad.Les pido amablemente dejen su retroalimentación en esta página y su calificación en iTunes.

¡Gracias por escuchar! En este episodio comento una reciente editorial escrita por Aletaha y Smolen en donde plantean que las medidas de desenlace que actualmente se usan en ensayos clínicos que evalúan nuevas terapéuticas para Artritis Reumatoide son inadecuadas y explican los cambios que debemos asumir para ofrecer unos resultados de mejor calidad. Como siempre agradezco su calificación en iTunes y su retroalimentación por este medio. La referencia del artículo es:Aletaha D, Smolen J, Remission in rheumatoid arthritis: missing objectives by using inadequate DAS28 targets, Nature Rev Rheum; 15:633-634 (2019)

¡Gracias por escuchar! En este episodio hablaré acerca de una técnica de bioingeniería que ha demostrado una gran versatilidad para la edición del genoma, con potencial no solo de investigación sino de también diagnóstico y terapéutico. CRISPR/Cas 9 es algo de lo que cada vez se habla más y cuya comprensión nos adelanta un futuro muy prometedor para el tratamiento de las enfermedades reumática. Agradezco que dejen sus comentarios en esta página y que califiquen el podcast en iTunes. Recuerden que Tukua se encuentra disponible ahí así como en Spotify, o a través de Stitcher o su gestor de podcasts favorito.A continuación dejo una revisión útil para el estudio de este tema. Gibson G, Yang M, What rheumatologists need to know about CRISPR/Cas9, Nat Rev Rheum;13:205-16 (2017), doi:10.1038/nrrheum.2017.6

¡Gracias por escuchar! En este episodio repaso algunos conceptos relevantes sobre la dactilítis, una manifestación común en espondiloartritis. Les pido amablemente que califiquen este episodio en iTunes, o dejen sus comentarios en esta página. El podcast se encuentra disponible también en Spotify y a través de la aplicación gestora de podcasts de su elección.Abajo enlisto referencias útiles, algunas mencionadas en el episodio: Olivieri, I., Scarano, E., Padula, A., Giasi, V. & Priolo, F. Dactylitis, a term for different digit diseases. Scand. J. Rheumatol. 35, 333–340 (2006). Gladman, D. D., Ziouzina, O., Thavaneswaran, A. & Chandran, V. Dactylitis in psoriatic arthritis: prevalence and response to therapy in the biologic era. J. Rheumatol. 40, 1357–1359 (2013). Ritchlin, C. T., Colbert, R. A. & Gladman, D. D. Psoriatic arthritis. N. Engl. J. Med. 376, 957–970 (2017). Rothschild, B. M., Pingitore, C. & Eaton, M. Dactylitis: implications for clinical practice. Semin. Arthritis Rheum. 28, 41–47 (1998). Taylor, W. J. et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 54, 2665–2673 (2006). Rudwaleit, M. et al. The Assessment of Spondyloarthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann. Rheum. Dis. 70, 25–31 (2011). Brockbank, J. E., Stein, M., Schentag, C. T. & Gladman, D. D. Dactylitis in psoriatic arthritis: a marker for disease severity? Ann. Rheum. Dis. 64, 188–190 (2005). Kavanaugh, A., Helliwell, P. & Ritchlin, C. T. Psoriatic arthritis and burden of disease: patient perspectives from the population-based multinational assessment of psoriasis and psoriatic arthritis (MAPP) survey. Rheumatol. Ther. 3, 91–102 (2016). Kaeley, G. S., Eder, L., Aydin, S. Z., Gutierrez, M. & Bakewell, C. Dactylitis: a hallmark of psoriatic arthritis. Semin. Arthritis Rheum. 48, 263–273 (2018). McGonagle, D., Conaghan Philip, G. & Emery, P. Psoriatic arthritis: a unified concept twenty years on. Arthritis Rheum. 42, 1080–1086 (2001). Tinazzi, I. et al. ‘Deep Koebner’ phenomenon of the flexor tendon-associated accessory pulleys as a novel factor in tenosynovitis and dactylitis in psoriatic arthritis. Ann. Rheum. Dis. 77, 922 (2018). Pattison, E., Harrison, B. J., Griffiths, C. E., Silman, A. J. & Bruce, I. N. Environmental risk factors for the development of psoriatic arthritis: results from a case-control study. Ann. Rheum. Dis. 67, 672–676 (2008). Ng, J., Tan, A. L. & McGonagle, D. Unifocal psoriatic arthritis development in identical twins following site specific injury: evidence supporting biomechanical triggering events in genetically susceptible hosts. Ann. Rheum. Dis. 74, 948–949 (2015). Jacques, P. et al. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann. Rheum. Dis. 73, 437–445 (2014). Jacques, P. & McGonagle, D. The role of mechanical stress in the pathogenesis of spondyloarthritis and how to combat it. Best Pract. Res. Clin. Rheumatol. 28, 703–710 (2014). Thorarensen, S. M. et al. Physical trauma recorded in primary care is associated with the onset of psoriatic arthritis among patients with psoriasis. Ann. Rheum. Dis. 76, 521–525 (2017). Wilkins, R. A., Siddle, H. J., Redmond, A. C. & Helliwell, P. S. Plantar forefoot pressures in psoriatic arthritis-related dactylitis: an exploratory study. Clin. Rheumatol. 35, 2333–2338 (2016). Tan, A. L. & McGonagle, D. The need for biological outcomes for biological drugs in psoriatic arthritis. J. Rheumatol. 43, 3–6 (2016). Mumtaz, A. et al. Development of a preliminary composite disease activity index in psoriatic arthritis. Ann. Rheum. Dis. 70, 272–277 (2011). Helliwell, P. S. et al. The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project). Ann. Rheum. Dis. 72, 986–991 (2013). Ramiro, S., Smolen, J. S., Landewe, R., van der Heijde, D. & Gossec, L. How are enthesitis, dactylitis and nail involvement measured and reported in recent clinical trials of psoriatic arthritis? A systematic literature review. Ann. Rheum. Dis. 77, 782–783 (2017). Salvarani, C. et al. A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis. J. Rheumatol. 28, 2274–2282 (2001). Antoni, C. E. et al. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum. 52, 1227–1236 (2005). Clegg, D. O. et al. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum. 39, 2013–2020 (1996). Helliwell, P. S. et al. Development of an assessment tool for dactylitis in patients with psoriatic arthritis. J. Rheumatol. 32, 1745–1750 (2005). Healy, P. J. & Helliwell, P. S. Measuring dactylitis in clinical trials: which is the best instrument to use? J. Rheumatol. 34, 1302–1306 (2007). Chandran, V. et al. International multicenter psoriasis and psoriatic arthritis reliability trial for the assessment of skin, joints, nails, and dactylitis. Arthritis Rheum. 61, 1235–1242 (2009).Mease, P. et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann. Rheum. Dis. 73, 48–55 (2014). Fournie, B. et al. Extrasynovial ultrasound abnormalities in the psoriatic finger. Prospective comparative power-doppler study versus rheumatoid arthritis. Joint Bone Spine 73, 527–531 (2006). Benjamin, M. & McGonagle, D. The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites. J. Anat. 199, 503–526 (2001). Kane, D., Greaney, T., Bresnihan, B., Gibney, R. & FitzGerald, O. Ultrasonography in the diagnosis and management of psoriatic dactylitis. J. Rheumatol. 26, 1746–1751 (1999). Tinazzi, I. et al. Comprehensive evaluation of finger flexor tendon entheseal soft tissue and bone changes by ultrasound can differentiate psoriatic arthritis and rheumatoid arthritis. Clin. Exp. Rheumatol. 36, 785–790 (2018). McGonagle, D., Gibbon, W. & Emery, P. Classification of inflammatory arthritis by enthesitis. Lancet 352, 1137–1140 (1998). Olivieri, I. et al. Dactylitis in patients with seronegative spondylarthropathy. Assessment by ultrasonography and magnetic resonance imaging. Arthritis Rheum. 39, 1524–1528 (1996).Olivieri, I. et al. Toe dactylitis in patients with spondyloarthropathy: assessment by magnetic resonance imaging. J. Rheumatol. 24, 926–930 (1997). Olivieri, I. et al. Fast spin echo-T2-weighted sequences with fat saturation in dactylitis of spondylarthritis. No evidence of entheseal involvement of the flexor digitorum tendons. Arthritis Rheum. 46, 2964–2967 (2002). Healy, P. J., Groves, C., Chandramohan, M. & Helliwell, P. S. MRI changes in psoriatic dactylitis extent of pathology, relationship to tenderness and correlation with clinical indices. Rheumatology 47, 92–95 (2008). Tan, A. L. et al. High-resolution MRI assessment of dactylitis in psoriatic arthritis shows flexor tendon pulley and sheath-related enthesitis. Ann. Rheum. Dis. 74, 185–189 (2015). FitzGerald, O., Haroon, M., Giles, J. T. & Winchester, R. Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Res. Ther. 17, 115 (2015). McHugh, K. & Bowness, P. The link between HLA-B27 and SpA—new ideas on an old problem. Rheumatology 51, 1529–1539 (2012). Ritchlin, C. T. et al. Treatment recommendations for psoriatic arthritis. Ann. Rheum. Dis. 68, 1387–1394 (2009). Coates, L. C. et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis Rheum. 68, 1060–1071 (2016). Gossec, L. et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann. Rheum. Dis. 75, 499–510 (2016). Coates, L. & Helliwell, P. S. Methotrexate efficacy in the Tight Control in Psoriatic Arthritis study. J. Rheum. 43, 356–361 (2016). Rose, S., Toloza, S., Bautista-Molano, W. & Helliwell, P. S. Comprehensive treatment of dactylitis in psoriatic arthritis. J. Rheumatol. 41, 2295–2300 (2014). Kavanaugh, A. et al. Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2). Ann. Rheum. Dis. 75, 1984–1988 (2016). Mease, P. et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N. Engl. J. Med. 377, 1537–1550 (2017). Kavanaugh, A. et al. Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo-controlled trial. Arthritis Rheum. 64, 2504–2517 (2012). Kavanaugh, A. & Mease, P. Treatment of psoriatic arthritis with tumor necrosis factor inhibitors: longer-term outcomes including enthesitis and dactylitis with golimumab treatment in the Longterm Extension of a Randomized, Placebo-controlled Study (GO-REVEAL). J. Rheumatol. Suppl. 89, 90–93 (2012). Antoni, C. E. et al. Two-year efficacy and safety of infliximab treatment in patients with active psoriatic arthritis: findings of the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT). J. Rheumatol. 35, 869–876 (2008). Kavanaugh, A. et al. Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial. Ann. Rheum. Dis. 66, 498–505 (2007). Baranauskaite, A. et al. Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study. Ann. Rheum. Dis. 71, 541–548 (2012). Carron, P. et al. Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis. RMD Open 2, e000265 (2016). Nash, P. et al. Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3). Arthritis Res. Ther. 20, 47 (2018). Mease, P. et al. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann. Rheum. Dis. 77, 890–897 (2018). Mease, P. J. et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann. Rheum. Dis. 76, 79–87 (2017). Wells, A. F. et al. Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial. Rheumatology 57, 1253–1263 (2018). Gladman, D. et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N. Engl. J. Med. 377, 1525–1536 (2017). Mease, P. J. et al. Efficacy and safety of abatacept, a T cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis. Ann. Rheum. Dis. 76, 1550–1558 (2017). Genovese Mark, C. et al. Apremilast in patients with active rheumatoid arthritis: a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 67, 1703–1710 (2015). Smolen, J. S. et al. A randomised phase II study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Ann. Rheum. Dis. 76, 831–839 (2017). Kavanaugh, A. et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann. Rheum. Dis. 73, 1020–1026 (2014). Kunwar, S., Dahal, K. & Sharma, S. Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatol. Int. 36, 1065–1075 (2016). da Silva Junior, G. B., Daher Ede, F. & da Rocha, F. A. Osteoarticular involvement in sickle cell disease. Rev. Bras. Hematol. Hemoter. 34, 156–164 (2012). Braum, L. S. et al. Characterisation of hand small joints arthropathy using high-resolution MRI — limited discrimination between osteoarthritis and psoriatic arthritis. Eur. Radiol. 23, 1686–1693 (2013). Tan, A. L., Grainger, A. J., Tanner, S. F., Emery, P. & McGonagle, D. A high-resolution magnetic resonance imaging study of distal interphalangeal joint arthropathy in psoriatic arthritis and osteoarthritis: are they the same? Arthritis Rheum. 54, 1328–1333 (2006). Tuttle, K. S., Vargas, S. O., Callahan, M. J., Bae, D. S. & Nigrovic, P. A. Enthesitis as a component of dactylitis in psoriatic juvenile idiopathic arthritis: histology of an established clinical entity. Pediatr. Rheumatol. Online J. 13, 7 (2015). Nash, P. et al. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet 389, 2317–2327 (2017).Jeong, H. et al. Spondyloarthritis features in zymosan-induced SKG mice. Joint Bone Spine 85, 583–591 (2018). 

¡Gracias por escuchar! En este episodio se hablará acerca de las alternativas de tratamiento del síndrome de Sjögren primario, tanto glandular como extraglandular.Recuerden que su retroalimentación es bienvenida y les pido amablemente califiquen el podcast en iTunes. Además, Tukua se encuentra disponible en Spotify o a través del gestor de podcasts de su elección.A continuación enlisto algunos de los artículos revisados para este episodio: Vitali, C. et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria 21. proposed by the American-European ConsensusGroup. Ann. Rheum. Dis. 61, 554–558 (2002).Shiboski, S. C. et al. American College of 22. Rheumatology classification criteria for Sjögren’ssyndrome: a data-driven, expert consensus approach in the Sjögren’s International Collaborative Clinical 23. Alliance cohort. Arthritis Care Res. (Hoboken) 64, 475–487 (2012).Seror, R. et al. EULAR Sjögren’s syndrome disease activity index: development of a consensus systemic 25. disease activity index for primary Sjögren’s syndrome. Ann. Rheum. Dis. 69, 1103–1109 (2010).Seror, R. et al. Defining disease activity states and clinically meaningful improvement in primary Sjogren’s 26. syndrome with EULAR primary Sjögren’s syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann. Rheum. Dis. 75, 382–389 (2016).Seror, R. et al. EULAR Sjögren’s Syndrome Patient 27. Reported Index (ESSPRI): development of a consensus patient index for primary Sjögren’s syndrome. Ann. Rheum. Dis. 70, 968–972 (2011).Theander, E. et al. Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the 28. development of malignant lymphoma in primary Sjögren’s syndrome. Ann. Rheum. Dis. 70, 29. 1363–1368 (2011).Valim, V. et al. Recommendations for the treatment 33. of Sjögren’s syndrome. Rev. Bras. Reumatol. 55, 446–457 (in Portuguese) (2015).Furness, S., Worthington, H. V., Bryan, G., Birchenough, S. & McMillan, R. Interventions for the management of dry mouth: topical therapies. 34. Cochrane Database Syst. Rev. 12, CD008934 (2011).Steller, M., Chou, L. & Daniels, T. E. Electrical stimulation of salivary flow in patients with Sjögren’s syndrome. J. Dent. Res. 67, 1334–1337 (1988).Vivino, F. B. et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch. Intern. Med. 159, 174–181 (1999).Meijer, J. M. et al. Effectiveness of rituximab treatment in primary Sjögren’s syndrome:a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 62, 960–968 (2010).Forstot, S. L. & Foulks, G. N. Management of Dry Eye (Oxford Univ. Press, 2012).Toda, I., Shinozaki, N. & Tsubota, K. Hydroxypropyl methylcellulose for the treatment of severe dry eye associated with Sjögren’s syndrome. Cornea 15, 120–128 (1996).Marsh, P. & Pflugfelder, S. C. Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjögren syndrome. Ophthalmology 106, 811–816 (1999).Barber, L. D., Pflugfelder, S. C., Tauber, J. & Foulks, G. N. Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years. Ophthalmology 112, 1790–1794 (2005).Milin, M. et al. Sicca symptoms are associated with similar fatigue, anxiety, depression, and quality-of-life impairments in patients with and without primary Sjögren’s syndrome. Joint Bone Spine http://dx.doi. org/10.1016/j.jbspin.2015.10.005 (2016).van Leeuwen, N. et al. Psychological profiles in patients with Sjögren’s syndrome related to fatigue: a cluster analysis. Rheumatology (Oxford) 54, 776–783 (2015).Segal, B. et al. Prevalence, severity, and predictors of fatigue in subjects with primary Sjögren’s syndrome. Arthritis Rheum. 59, 1780–1787 (2008).Gottenberg, J. E. et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: the JOQUER randomized clinical trial. JAMA 312, 249–258 (2014).Hartkamp, A. et al. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjögren syndrome: a randomised controlled trial. Ann. Rheum. Dis. 67, 91–97 (2008).Theander, E., Horrobin, D. F., Jacobsson, L. T. & Manthorpe, R. Gammalinolenic acid treatment of fatigue associated with primary Sjögren’s syndrome. Scand. J. Rheumatol. 31, 72–79 (2002).Kruize, A. A. et al. Hydroxychloroquine treatment for primary Sjögren’s syndrome: a two year double blind crossover trial. Ann. Rheum. Dis. 52, 360–364 (1993).Sankar, V. et al. Etanercept in Sjögren’s syndrome: a twelve-week randomized, double-blind, placebo- controlled pilot clinical trial. Arthritis Rheum. 50, 2240–2245 (2004).Koch, M., Iro, H. & Zenk, J. Stenosis and other non- sialolithiasis-related obstructions of the major salivary gland ducts. Modern treatment concepts. HNO 58, 218–224 (in German) (2010).De Vita, S. et al. Efficacy and safety of belimumab given for 12 months in primary Sjögren’s syndrome: the BELISS open-label phase II study. Rheumatology (Oxford) (2015). Kuhn, A. et al. Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus: analysis of 1002 patients from the EUSCLE database. Br. J. Dermatol. 171, 571–579 (2014).Palm, O. et al. Clinical pulmonary involvement in primary Sjögren’s syndrome: prevalence, quality of life and mortality — a retrospective study based on registry data. Rheumatology (Oxford) 52, 173–179 (2013).Francois, H. & Mariette, X. Renal involvement in primary Sjögren syndrome. Nat. Rev. Nephrol. 12, 82–93 (2016).Evans, R. D., Laing, C. M., Ciurtin, C. & Walsh, S. B. Tubulointerstitial nephritis in primary Sjögren syndrome: clinical manifestations and response to treatment. BMC Musculoskelet. Disord. 17, 2 (2016).Gottenberg, J. E. et al. Efficacy of rituximab in systemic manifestations of primary Sjögren’s syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann. Rheum. Dis. 72, 1026–1031 (2013).Colafrancesco, S. et al. Myositis in primary Sjögren’s syndrome: data from a multicentre cohort. Clin. Exp. Rheumatol. 33, 457–464 (2015).Oddis, C. V. et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 65, 314–324 (2013).Mok, C. C., Ho, L. Y. & To, C. H. Rituximab for refractory polymyositis: an open-label prospective study. J. Rheumatol. 34, 1864–1868 (2007).Carvajal Alegria, G. et al. Epidemiology of neurological manifestations in Sjögren’s syndrome: data from the French ASSESS Cohort. RMD Open 2, e000179 (2016).Yamashita, H. et al. Diagnosis and treatment of primary Sjögren syndrome-associated peripheral neuropathy: a six-case series. Mod. Rheumatol. 23, 925–933 (2013).Chen, W. H., Yeh, J. H. & Chiu, H. C. Plasmapheresis in the treatment of ataxic sensory neuropathy associated with Sjögren’s syndrome. Eur. Neurol. 45, 270–274 (2001).Mekinian, A. et al. Efficacy of rituximab in primary Sjögren’s syndrome with peripheral nervous system involvement: results from the AIR registry. Ann. Rheum. Dis. 71, 84–87 (2012).Terrier, B. et al. Non HCV-related infectious cryoglobulinemia vasculitis: results from the French nationwide CryoVas survey and systematic review of the literature. J. Autoimmun. 65, 74–81 (2015).Singh, A. G., Singh, S. & Matteson, E. L. Rate, risk factors and causes of mortality in patients with Sjögren’s syndrome: a systematic review and meta- analysis of cohort studies. Rheumatology (Oxford) 55, 450–460 (2016).Pollard, R. P. et al. Treatment of mucosa-associated lymphoid tissue lymphoma in Sjögren’s syndrome: a retrospective clinical study. J. Rheumatol. 38, 2198–2208 (2011).Papageorgiou, A. et al. Predicting the outcome of Sjögren’s syndrome-associated non-hodgkin’s lymphoma patients. PLoS ONE 10, e0116189 (2015).Devauchelle-Pensec, V. et al. Improvement of Sjögren’s syndrome after two infusions of rituximab (anti-CD20). Arthritis Rheum. 57, 310–317 (2007).Carubbi, F. et al. Efficacy and safety of rituximab treatment in early primary Sjögren’s syndrome: a prospective, multi-center, follow-up study. Arthritis Res. Ther. 15, R172 (2013).Devauchelle-Pensec, V. et al. Which and how many patients should be included in randomised controlled trials to demonstrate the efficacy of biologics in primary Sjögren’s syndrome? PLoS ONE 10, e0133907 (2015).Jousse-Joulin, S. et al. Brief report: ultrasonographic assessment of salivary gland response to rituximab in primary Sjögren’s syndrome. Arthritis Rheumatol. 67, 1623–1628 (2015).Cornec, D. et al. Development of the Sögren’s Syndrome Responder Index, a data-driven composite endpoint for assessing treatment efficacy. Rheumatology (Oxford) 54, 1699–1708 (2015).

¡Gracias por escuchar! En este episodio se discuten las nuevas estrategias terapéuticas para el manejo del Lupus Eritematoso Sistémico. Agradezco su retroalimentación y les pido amablemente que califiquen el episodio en iTunes y en Spotify. No olviden dejar sus comentarios y sugerencias en tukua.podbean.com. Abajo enlisto las referencias bibliográficas consultadas en este episodio: Piga, M. et al. Failure to achieve lupus low disease activity state (LLDAS) six months after diagnosis is associated with early damage accrual in Caucasian patients with systemic lupus erythematosus. Arthritis. Res. Ther. 19, 247 (2017). Nossent, J. et al. Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus. Lupus 19, 949–956 (2010). Iaccarino, L. et al. Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study. J. Autoimmun. 86, 1–8 (2018). Calixto, O. J., Franco, J. S. & Anaya, J. M. Lupus mimickers. Autoimmun. Rev. 13, 865–872 (2014). Doria, A. & Briani, C. Lupus: improving long-term prognosis. Lupus 17, (166–170 (2008). Bizzarro, N. et al. Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: a 15-year longitudinal study.J. Thromb. Haemost. 5, 1158–1164 (2007). Pengo, V. et al. Efficacy and safety of rivaroxaban versus warfarin in high-risk patients with antiphospholipid syndrome: rationale and design of the Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS) trial. Lupus 25, 301–306 (2016). Arnaud, L. et al. Patient-level analysis of five international cohorts further confirms the efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies. Autoimmun. Rev. 14, 192–200 (2015). Ruiz-Irastorza, G. et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th international congress on antiphospholipid antibodies. Lupus 20, 206–218 (2011). Moroni, G. et al. Changing patterns in clinical- histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis. Ann. Rheum. Dis. 77, 1318–1325 (2018). van Vollenhoven, R. et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann. Rheum. Dis. 76, 554–561 (2017). Bertsias, G. et al. Joint European League Against Rheumatism and European Renal Association- European Dialysis and Transplant Association (EULAR/ ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann. Rheum. Dis. 71, 1771–1782 (2012). Bruce, I. N. et al. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Ann. Rheum. Dis. 74, 1706–1713 (2015). Al Sawah, S. et al. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus-the Hopkins Lupus Cohort. Lupus. Sci. Med. 2, e000066 (2015). Guiducci, C. et al. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 465, 937–941 (2010). Fischer-Betz, R. et al. Renal outcome in patients with lupus nephritis using a steroid-free regimen of monthly intravenous cyclophosphamide: a prospective observational study. J. Rheumatol. 39, 2111–2117 (2012). Merrill, J. T. et al. Lupus community panel proposals for optimising clinical trials: 2018. Lupus. Sci. Med. 5, e000258 (2018). Iaccarino, L. et al. Effects of belimumab on flare rate and expected damage progression in patients with active systemic lupus erythematosus. Arthritis Care Res. (Hoboken) 69, 115–123 (2017). Trentin, F. et al. Effectiveness, tolerability, and safety of belimumab in patients with refractory SLE: a review of observational clinical-practice-based studies. Clin. Rev. Allergy Immunol. 54, 331–343 (2018). Bruce, I. N. et al. Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care. Lupus 25, 699–709 (2016). Zhang, H. et al. Multitarget therapy for maintenance treatment of lupus nephritis. J. Am. Soc. Nephrol. 28, 3671–3678 (2017). Gladman, D. D., Iban ̃ez, D., Ruiz, I. & Urowitz, M. B. Recommendations for frequency of visits to monitor systemic lupus erythematosus in asymptomatic patients: data from an observational cohort study. Rheumatol. 40, 630–633 (2013). Hsu, C. Y. et al. Adherence to hydroxychloroquine improves long-term survival of patients with systemic lupus erythematosus. Rheumatology (Oxford) 57, 1743–1751 (2018). Chen, W. et al. Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 21, 944–952 (2012). Merrill, J. T. et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 62, 222–233 (2010). Kraaij, T., Huizinga, T. W., Rabelink, T. J. & Teng, Y. K. Belimumab after rituximab as maintenance therapy in lupus nephritis. Rheumatology (Oxford) 53, 2122–2124 (2014). Steiman, A. J. et al. Outcomes in patients with systemic lupus erythematosus with and without a prolonged serologically active clinically quiescent period. Arthritis Care Res. 64, 511–518 (2012). Moroni, G., Longhi, S., Gliglio, E., Messa, P. & Ponticelli, C. What happens after complete withdrawal of therapy in patients with lupus nephritis. Clin. Exp. Rheumatol. 31, S75–S81 (2013). Banchereau, R. et al. Personalized immunomonitoring uncovers molecular networks that stratify lupus patients. Cell 165, 551–565 (2016).

¡Gracias por escuchar! El episodio 5 difiere de los anteriores al hablar de los aspectos éticos relacionados a la investigación clínica. Este tema es importante ya que los médicos clínicos empleamos evidencia para el tratamiento de nuestros pacientes y frecuentemente desconocemos la manera en la que se conducen los investigadores en relación a la ética de los proyectos que desarrollan.No olviden calificar el episodio (y todo el podcast) en iTunes y en Spotify. Su retroalimentación es muy importante.A continuación enumero el material mencionado en el episodio: https://history.nih.gov/research/downloads/nuremberg.pdf https://www.wma.net/es/policies-post/declaracion-de-helsinki-de-la-amm-principios-eticos-para-las-investigaciones-medicas-en-seres-humanos/ https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html https://cioms.ch/ https://www.hhs.gov/ohrp/regulations-and-policy/regulations/common-rule/index.html 

¡Gracias por escuchar! En este episodio hablaré del papel que juega la inflamación en la generación de dolor en pacientes con osteoartritis. La OA tiene una morbilidad asociada sustancial y constituye un creciente problema de salud pública derivado en gran medida del envejecimiento poblacional. Los síntomas de la OA pueden ser funcionales pero se manifiestan principalmente como dolor y el manejo de la enfermedad se centra principalmente en su control.Agradezco que escuchen este podcast y les recuerdo que se encuentra disponible en el catálogo de iTunes, en Google Play (siendo accesible a través del gestor de podcasts de su dispositivo móvil), así como en Spotify. Agradezco también su retroalimentación en estas plataformas y les pido amablemente que califiquen el podcast ya que esto es importante para su continuado desarrollo.A continuación se enlistan las referencias mencionadas en este episodio: Grace, P. M., Hutchinson, M. R., Maier, S. F. & Watkins, L. R. Pathological pain and the neuroimmune interface. Nat. Rev. Immunol. 14, 217–231(2014).Owens, C. & Conaghan, P. G. Improving joint pain and function in osteoarthritis. Practitioner 260, 17–20 (2016).O’Neil, C. K., Hanlon, J. T. & Marcum, Z. A. Adverse effects of analgesics commonly used by older adults with osteoarthritis: focus on non-opioid and opioid analgesics. Am. J. Geriatr. Pharmacother. 10, 331–342 (2012).Wang, Y., Teichtahl, A. J. & Cicuttini, F. M. Osteoarthritis year in review 2015: imaging. Osteoarthritis Cartilage 24, 49–57 (2016).Haringman, J. J., Smeets, T. J., Reinders-Blankert, P. & Tak, P. P. Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis. Ann. Rheum. Dis. 65, 294–300 (2006).de Lange-Brokaar, B. J. et al. Degree of synovitis on MRI by comprehensive whole knee semi-quantitative scoring method correlates with histologic and macroscopic features of synovial tissue inflammation in knee osteoarthritis. Osteoarthritis Cartilage 22, 1606–1613 (2014).Cook, A. D., Christensen, A. D., Tewari, D., McMahon, S. B. & Hamilton, J. A. Immune cytokines and their receptors in inflammatory pain. Trends Immunol. 39, 240–255 (2018).Malfait, A. M. & Schnitzer, T. J. Towards a mechanism-based approach to pain management in osteoarthritis. Nat. Rev. Rheumatol. 9, 654–664 (2013).Bellamy, N. et al. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst. Rev. 2, CD005328 (2006).McAlindon, T. E. et al. Effect of intra-articular triamcinolone versus saline on knee cartilage volume and pain in patients with knee osteoarthritis:a randomized clinical trial. JAMA 317, 1967–1975 (2017).Aitken, D. et al. A randomised double-blind placebo-controlled crossover trial of HUMira (adalimumab) for erosive hand OsteoaRthritis — the HUMOR trial. Osteoarthritis Cartilage 26, 880–887 (2018).Cohen, S. B. et al. A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee. Arthritis Res. Ther. 13, R125 (2011).Wang, S. X. et al. Safety, tolerability, and pharmacodynamics of an anti-interleukin-1alpha/beta dual variable domain immunoglobulin in patients with osteoarthritis of the knee: a randomized phase 1 study. Osteoarthritis Cartilage 25, 1952–1961 (2017).Eitner, A., Hofmann, G. O. & Schaible, H. G. Mechanisms of osteoarthritic pain. Studies in humans and experimental models. Front. Mol. Neurosci. 10, 349 (2017).Basbaum, A. I., Bautista, D. M., Scherrer, G. & Julius, D. Cellular and molecular mechanisms of pain. Cell 139, 267–284 (2009).Ji, R. R., Xu, Z. Z. & Gao, Y. J. Emerging targets in neuroinflammation-driven chronic pain. Nat. Rev. Drug Discov. 13, 533–548 (2014).McMahon, S. B., La Russa, F. & Bennett, D. L. Crosstalk between the nociceptive and immune systems in host defence and disease. Nat. Rev. Neurosci. 16, 389–402 (2015).Pinho-Ribeiro, F. A. et al. Blocking neuronal signaling to immune cells treats streptococcal invasive infection. Cell 173, 1083–1097 (2018).Shechter, R. et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLOS Med. 6, e1000113 (2009).Willemen, H. L. et al. Monocytes/macrophages control resolution of transient inflammatory pain. J. Pain 15, 496–506 (2014).Barthel, C. et al. Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis. Arthritis Res. Ther. 11, R82 (2009).Skaper, S. D. Nerve growth factor: a neuroimmune crosstalk mediator for all seasons. Immunology 151, 1–15 (2017).Denk, F., Bennett, D. L. & McMahon, S. B. Nerve growth factor and pain mechanisms. Annu. Rev. Neurosci. 40, 307–325 (2017).Minnone, G., De Benedetti, F. & Bracci-Laudiero, L. NGF and its receptors in the regulation of inflammatory response. Int. J. Mol. Sci. 18, E1028 (2017).Bagal, S. K. et al. Discovery of potent, selective, and peripherally restricted Pan-Trk kinase inhibitors for the treatment of pain. J. Med. Chem. 61, 6779–6800 (2018).Pinho-Ribeiro, F. A., Verri, W. A. Jr & Chiu, I. M. Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol. 38, 5–19 (2017).Robinson, W. H. et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 12, 580–592 (2016).de Lange-Brokaar, B. J. et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage 20, 1484–1499 (2012).Rahmati, M., Mobasheri, A. & Mozafari, M. Inflammatory mediators in osteoarthritis: a critical review of the state-of-the-art, current prospects, and future challenges. Bone 85, 81–90 (2016).Urban, H. & Little, C. B. The role of fat and inflammation in the pathogenesis and management of osteoarthritis.Rheumatology 57, iv10–iv21 (2018).Dawes, J. M., Kiesewetter, H., Perkins, J. R.,Bennett, D. L. & McMahon, S. B. Chemokine expression in peripheral tissues from the monosodium iodoacetate model of chronic joint pain. Mol. Pain 9, 57 (2013).Driscoll, C. et al. Nociceptive sensitizers are regulated in damaged joint tissues, including articular cartilage, when osteoarthritic mice display pain behavior. Arthritis Rheumatol. 68, 857–867 (2016).Sweitzer, S. M., Hickey, W. F., Rutkowski, M. D., Pahl, J. L. & DeLeo, J. A. Focal peripheral nerve injury induces leukocyte trafficking into the central nervous system: potential relationship to neuropathic pain. Pain 100, 163–170 (2002).Hu, P., Bembrick, A. L., Keay, K. A. & McLachlan, E. M. Immune cell involvement in dorsal root ganglia and spinal cord after chronic constriction or transectionof the rat sciatic nerve. Brain Behav. Immun. 21, 599–616 (2007).Lems, W. F. Bisphosphonates: a therapeutic option for knee osteoarthritis? Ann. Rheum. Dis. 77, 1247–1248 (2018).Wenham, C. Y. et al. A randomized, double-blind, placebo-controlled trial of low-dose oral prednisolone for treating painful hand osteoarthritis. Rheumatology 51, 2286–2294 (2012).Dorleijn, D. M. J. et al. Intramuscular glucocorticoid injection versus placebo injection in hip osteoarthritis: a 12-week blinded randomised controlled trial. Ann. Rheum. Dis. 77, 875–882 (2018).McCabe, P. S. et al. Synovial fluid white blood cell count in knee osteoarthritis: association with structural findings and treatment response. Arthritis Rheumatol. 69, 103–107 (2017).Leung, Y. Y. et al. Colchicine lack of effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): a randomized controlled trial. Osteoarthritis Cartilage 26, 631–640 (2018).Kingsbury, S. R. et al. Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis: a randomized trial. Ann. Intern. Med. 168, 385–395 (2018).Lee, W. et al. Efficacy of hydroxychloroquine in hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res. 70, 1320–1325 (2018).Wenham, C. Y. et al. Methotrexate for pain relief in knee osteoarthritis: an open-label study. Rheumatology 52, 888–892 (2013).Kingsbury, S. R. et al. Significant pain reduction with oral methotrexate in knee osteoarthritis; results from a randomised controlled phase III trial of treatment effectiveness [abstract 428]. Arthritis Rheumatol. 70 (Suppl. 9), 454–455 (2018).Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).Kashyap, M. P., Roberts, C., Waseem, M. & Tyagi, P. Drug targets in neurotrophin signaling in the central and peripheral nervous system. Mol. Neurobiol. 55, 6939–6955 (2018).Bannwarth, B. & Kostine, M. Nerve growth factor antagonists: is the future of monoclonal antibodies becoming clearer? Drugs 77, 1377–1387 (2017).Baamonde, A., Lastra, A., Juarez, L., Hidalgo, A. & Menendez, L. TRPV1 desensitisation and endogenous vanilloid involvement in the enhanced analgesia induced by capsaicin in inflamed tissues. Brain Res. Bull. 67, 476–481 (2005).Hamilton, J. A., Cook, A. D. & Tak, P. P. Anti-colony- stimulating factor therapies for inflammatory and autoimmune diseases. Nat. Rev. Drug Discov. 16, 53–70 (2017).Schett, G. et al. A phase IIA study of anti-GM-CSF antibody GSK3196165 in subjects with inflammatory hand osteoarthritis [abstract 1365]. Arthritis Rheumatol. 70 (Suppl. 9), 1494 (2018).Achuthan, A. et al. Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation. J. Clin. Invest. 126, 3453–3466 (2016).Wylde, V., Hewlett, S., Learmonth, I. D. & Dieppe, P. Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants. Pain 152, 566–572 (2011).Beswick, A. D., Wylde, V., Gooberman-Hill, R., Blom, A. & Dieppe, P. What proportion of patients report long-term pain after total hip or knee replacement for osteoarthritis? A systematic review of prospective studies in unselected patients. BMJ Open 2, e000435 (2012).Li, H., Wang, R., Lu, Y., Xu, X. & Ni, J. Targeting G protein-coupled receptor for pain management. Brain Circ. 3, 109–113 (2017).

¡Gracias por Escuchar! En esta ocasión hablaré acerca del mecanismo de acción del fármaco mas importante y de mayor uso para el tratamiento de varias enfermedades, principalmente Artritis Reumatoide, el Metotrexato. Para este episodio consulté varias fuentes, tratando de presentar evidencia en humanos sobre su interesante funcionamiento. Recuerden que su retroalimentación es bienvenida y muy importante. Les pido amablemente dejen sus calificaciones y comentarios sobre el podcast en iTunes. Próximamente el podcast estará disponible en Google Play y se encuentra disponible en Spotify, pudiendo también acceder a el a través de su gestor de podcasts favorito.A continuación se encuentra una lista de las referencias consultadas para este episodio.Lopez-Olivo, M. A. et al. Methotrexate for treating rheumatoid arthritis. Cochrane Database Syst. Rev. 6, CD000957 (2014).Kavanaugh, A. et al. Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann. Rheum. Dis. 72, 64–71 (2013).Detert, J. et al. Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naive patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study. Ann. Rheum. Dis. 72, 844–850 (2013).Horslev-Petersen, K. et al. Adalimumab added to a treat-to-target strategy with methotrexate and intra- articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo- controlled trial. Ann. Rheum. Dis. 73, 654–661 (2014).O’Dell, J. R. et al. Validation of the methotrexate-first strategy in patients with early, poor-prognosis rheumatoid arthritis: results from a two-year randomized, double-blind trial. Arthritis Rheum. 65, 1985–1994 (2013).Bathon, J. M. et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N. Engl. J. Med. 343, 1586–1593 (2000).Klareskog, L. et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363, 675–681 (2004).Goekoop-Ruiterman, Y. P. et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 52, 3381–3390 (2005).Breedveld, F. C. et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis. Rheum. 54, 26–37 (2006).Soubrier, M. et al. Evaluation of two strategies (initial methotrexate monotherapy versus its combination with adalimumab) in management of early active rheumatoid arthritis: data from the GUEPARD trial. Rheumatology 48, 1429–1434 (2009).Tak, P. P. et al. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann. Rheum. Dis. 70, 39–46 (2011).de Jong, P. H. et al. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann. Rheum. Dis. 72, 72–78 (2013).Emery, P. et al. Golimumab, a human anti-tumor necrosis factor monoclonal antibody, injected subcutaneously every 4 weeks in patients with active rheumatoid arthritis who had never taken methotrexate: 1-year and 2-year clinical, radiologic, and physical function findings of a phase III, multicenter, randomized, double-blind, placebo- controlled study. Arthritis Care Res. (Hoboken) 65, 1732–1742 (2013).Takeuchi, T. et al. Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study. Ann. Rheum. Dis. 73, 536–543 (2014).Nam, J. L. et al. A randomised controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial. Ann. Rheum. Dis. 73, 1027–1036 (2014).Emery, P. et al. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active- controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann. Rheum. Dis. 74, 19–26 (2015).Whittle, S. L. & Hughes, R. A. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology 43, 267–271 (2004).Schiff, M. H., Jaffe, J. S. & Freundlich, B. Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration. Ann. Rheum. Dis. 73, 1549–1551 (2014).Hoekstra, M. et al. Splitting high-dose oral methotrexate improves bioavailability: a pharmacokinetic study in patients with rheumatoid arthritis. J. Rheumatol. 33, 481–485 (2006).Wegrzyn, J., Adeleine, P. & Miossec, P. Better efficacy of methotrexate given by intramuscular injection than orally in patients with rheumatoid arthritis. Ann. Rheum. Dis. 63, 1232–1234 (2004).Hasko, G. & Cronstein, B. Regulation of inflammation by adenosine. Front. Immunol. 4, 85 (2013).Baggott, J. E., Morgan, S. L., Sams, W. M. & Linden, J. Urinary adenosine and aminoimidazolecarboxamide excretion in methotrexate-treated patients with psoriasis. Arch. Dermatol. 135, 813–817 (1999).Varani, K. et al. A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res. Ther. 13, R197 (2011).Peres, R. S. et al. Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 112, 2509–2514 (2015).Nesher, G., Mates, M. & Zevin, S. Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis. Arthritis Rheum. 48, 571–572 (2003).Nesher, G., Osborn, T. G. & Moore, T. L. In vitro effects of methotrexate on polyamine levels in lymphocytes from rheumatoid arthritis patients. Clin. Exp. Rheumatol. 14, 395–399 (1996).Nesher, G., Osborn, T. G. & Moore, T. L. Effect of treatment with methotrexate, hydroxychloroquine, and prednisone on lymphocyte polyamine levels in rheumatoid arthritis: correlation with the clinical response and rheumatoid factor synthesis. Clin. Exp. Rheumatol. 15, 343–347 (1997).Huang, C. et al. Ornithine decarboxylase prevents methotrexate-induced apoptosis by reducing intracellular reactive oxygen species production. Apoptosis 10, 895–907 (2005).Smith, D. M., Johnson, J. A. & Turner, R. A. Biochemical perturbations of BW 91Y (3-deazaadenosine) on human neutrophil chemotactic potential and lipid metabolism. Int. J. Tissue React. 13, 1–18 (1991).Phillips, D. C., Woollard, K. J. & Griffiths, H. R. The anti-inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen species. Br. J. Pharmacol. 138, 501–511 (2003).Johnston, A., Gudjonsson, J. E., Sigmundsdottir, H., Ludviksson, B. R. & Valdimarsson, H. The anti- inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin. Immunol. 114, 154–163 (2005).Dolhain, R. J. et al. Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis. Br. J. Rheumatol. 37, 502–508 (1998).Miranda-Carus, M. E., Balsa, A., Benito-Miguel, M., Perez de Ayala, C. & Martin-Mola, E. IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis: effect of methotrexate. J. Immunol. 173, 1463–1476 (2004).Wijngaarden, S., van Roon, J. A., van de Winkel, J. G., Bijlsma, J. W. & Lafeber, F. P. Down-regulation of activating Fcγ receptors on monocytes of patients with rheumatoid arthritis upon methotrexate treatment. Rheumatology 44, 729–734 (2005).Cooper, D. L. et al. FcγRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy. PLoS ONE 7, e28918 (2012).Rudwaleit, M. et al. Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor α, increase of interleukin 10, and predicted by the initial concentration of interleukin 4. Ann. Rheum. Dis. 59, 311–314 (2000).Majumdar, S. & Aggarwal, B. B. Methotrexate suppresses NF-κB activation through inhibition of IκBα phosphorylation and degradation. J. Immunol. 167, 2911–2920 (2001).Mello, S. B., Barros, D. M., Silva, A. S., Laurindo, I. M. & Novaes, G. S. Methotrexate as a preferential cyclooxygenase 2 inhibitor in whole blood of patients with rheumatoid arthritis. Rheumatology 39, 533–536 (2000).Vergne, P. et al. Methotrexate and cyclooxygenase metabolism in cultured human rheumatoid synoviocytes. J. Rheumatol. 25, 433–440 (1998).Novaes, G. S., Mello, S. B., Laurindo, I. M. & Cossermelli, W. Low dose methotrexate decreases intraarticular prostaglandin and interleukin 1 levels in antigen induced arthritis in rabbits. J. Rheumatol. 23, 2092–2097 (1996).Leroux, J. L., Damon, M., Chavis, C., Crastes De Paulet, A. & Blotman, F. Effects of methotrexate on leukotriene and derivated lipoxygenase synthesis in polynuclear neutrophils in rheumatoid polyarthritis. Rev. Rheum. Mal. Osteoartic. 59, 587–591 (in French) (1992).Seitz, M. & Dayer, J. M. Enhanced production of tissue inhibitor of metalloproteinases by peripheral blood mononuclear cells of rheumatoid arthritis patients responding to methotrexate treatment. Rheumatology 39, 637–645 (2000).Tchetverikov, I. et al. Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with α2 macroglobulin in serum of rheumatoid arthritis patients. Ann. Rheum. Dis. 67, 128–130 (2008).Stamp, L. K. et al. Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy. Arthritis Rheum. 62, 359–368 (2010).Dervieux, T., Weinblatt, M. E., Kivitz, A. Kremer, J. M. Methotrexate polyglutamation in relation to infliximab pharmacokinetics in rheumatoid arthritis. Ann. Rheum. Dis. 72, 908–910 (2013).Wessels, J. A. et al. Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent- onset rheumatoid arthritis. Arthritis Rheum. 54, 2830–2839 (2006).Wessels, J. A. et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis. Arthritis Rheum. 56, 1765–1775 (2007).Fransen, J. et al. Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure. Pharmacogenomics 13, 1087–1094 (2012).Owen, S. A. et al. Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients. Pharmacogenomics J. 13, 227–234 (2013).Aslibekyan, S. et al. Genetic variants associated with methotrexate efficacy and toxicity in early rheumatoid arthritis: results from the treatment of early aggressive rheumatoid arthritis trial. Pharmacogenomics J.14, 48–53 (2014). 

¡Gracias por escuchar! Ahora ya se puede acceder a Tukua a través de iTunes.Agradezco sus comentarios y retroalimentación y les ruego se suscriban al podcast. A continuación se enlistan los artículos mencionados en el episodio 2. Karpouzas, G. A. et al. Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease. Ann. Rheum. Dis. 73, 1797–1804 (2014). Maki-Petaja, K. M. et al. Anti-tumor necrosis factor therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation 126, 2473–2480 (2012). The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 302, 1993–2000 (2009). van Sijl, A. M. et al. The effect of TNF-alpha blocking therapy on lipid levels in rheumatoid arthritis: a meta- analysis. Semin. Arthritis Rheum. 41, 393–400 (2011). Queiro, R. et al. Prevalence and type II diabetes- associated factors in psoriatic arthritis. Clin. Rheumatol. 37, 1059–1064 (2018). Dubreuil, M. et al. Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study. Rheumatology 53, 346–352 (2014). Siebert, S. et al. Characteristics of rheumatoid arthritis and its association with major comorbid conditions: cross-sectional study of 502 649 UK Biobank participants. RMD Open 2, e000267 (2016). Coxib and Traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 382, 769–779 (2013). Roubille, C. et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti- inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta- analysis. Ann. Rheum. Dis. 74, 480–489, (2015) Zhang, J. et al. Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis. Ann. Rheum. Dis. 75, 1813–1818 (2016)

Gracias por escuchar. Estas son los artículos a los que se hace referencia en este episodio del podcast:Ogdie, A. et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study. Ann. Rheum. Dis. 74, 326–332 (2014).Avina-Zubieta, J. A., Thomas, J., Sadatsafavi, M., Lehman, A. J. & Lacaille, D. Risk of incident cardiovascular events in patients with rheumatoidarthritis: a meta-analysis of observational studies. Ann. Rheum. Dis. 71, 1524–1529 (2012).Schieir, O., Tosevski, C., Glazier, R. H., Hogg-Johnson, S.& Badley, E. M. Incident myocardial infarction associated with major types of arthritis in the general population: a systematic review and meta-analysis. Ann. Rheum. Dis. 76, 1396–1404 (2017). 21.D’Agostino, R. B. et al. General cardiovascular risk profile for use in primary care. Circulation 117, 743–753 (2008).Arts, E. E. A. et al. Performance of four current risk 23. algorithms in predicting cardiovascular events inpatients with early rheumatoid arthritis. Ann. Rheum.Dis. 74, 668–674 (2015). 24.Crowson, C. S., Matteson, E. L., Roger, V. L., Therneau, T. M. & Gabriel, S. E. Usefulness of risk scores to estimate the risk of cardiovascular disease in patients with rheumatoid arthritis. Am. J. Cardiol. 110, 420–424 (2012). 25.Agca, R. et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms ofinflammatory joint disorders: 2015/2016 update. 26. Ann. Rheum. Dis. 76, 17–28 (2017).Gómez-Vaquero, C. et al. SCORE and REGICOR function charts underestimate the cardiovascular risk in Spanish patients with rheumatoid arthritis. Arthritis 27. Res. Ther. 15, R91 (2013).Ahlehoff, O. et al. Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J. Intern. Med. 270, 147–157 (2011).Polachek, A., Touma, Z., Anderson, M. & Eder, L. Risk of cardiovascular morbidity in patients with psoriatic arthritis: a meta-analysis of observational studies. Arthritis Care Res. 69, 67–74 (2017).Gulati, A. M. et al. On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study. Ann. Rheum. Dis. 75, 819–824 (2016).Eder, L., Wu, Y., Chandran, V., Cook, R. & Gladman, D. D. Incidence and predictors for cardiovascular events in patients with psoriatic arthritis. Ann. Rheum. Dis. 75, 1680–1686 (2016).Eder, L. et al. Gaps in diagnosis and treatment of cardiovascular risk factors in patients with psoriatic disease: an international multicenter study.J. Rheumatol. 45, 378–384 (2018).Ridker, P. M., Cushman, M., Stampfer, M. J., Tracy, R. P. & Hennekens, C. H. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N. Engl. J. Med. 336, 973–979 (1997).Ridker, P. M. et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med. 359, 2195–2207 (2008).Sever, P. S. et al. Evaluation of C-reactive protein before and on-treatment as a predictor of benefit of atorvastatin: a cohort analysis from the Anglo- Scandinavian Cardiac Outcomes Trial lipid-lowering arm. J. Am. Coll. Cardiol. 62, 717–729 (2013).Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).Ridker, P. M. et al. Low-dose methotrexate for the prevention of atherosclerotic events. N. Engl. J. Med. 380, 752–762 (2019).Szentpetery, A. et al. Higher coronary plaque burden in psoriatic arthritis is independent of metabolic syndrome and associated with underlying disease severity. Arthritis Rheumatol. 70, 396–407 (2018).Min, J. K. et al. Relationship of coronary artery plaque composition to coronary artery stenosis severity: results from the prospective multicenter ACCURACY trial. Atherosclerosis 219, 573–578 (2011).

Tukua es un proyecto dirigido a los reumatólogos hispanoparlantes y a profesionales de la medicina afines a esta especialidad y que tiene tres objetivos:1. Difundir evidencia científica del campo de la reumatología que resulte práctica, que se pueda emplear en nuestra práctica diaria y que conduzca a la mejor atención de nuestros pacientes.2. Fomentar la discusión de esta evidencia con el público que (espero) escuche y me retroalimente sobre este podcast, de manera que se genere y enriquezca la conversación profesional entre nosotros.3. Contribuír a fortalecer la reumatología a través de este medio de comunicación, en español, deseando llegue a todos los profesionales que se dedican al cuidado de los pacientes con enfermedades reumáticas.Tukua es un vocablo otomí, una etnia del centro de México, que significa Reuma; consideré que la palabra tukua no solo le brindaba cierto aire regional a este proyecto y que además era un nombre original y adecuado.