Patrones de tratamiento con agentes biológicos, eficacia y sobrevida a largo plazo en pacientes con espondiloartritis axial: Impacto de los factores sociodemográficos en Latinoamérica / Patterns of treatment with biological agents, efficacy and long-term survival in patients with axial spondyloarthritis: Impact of sociodemographic factors in Latin America

Objetivos: Evaluar y comparar la eficacia y la sobrevida a largo plazo de las Drogas Modificadoras de la Enfermedad-biológicas (DME-b) en Espondiloartritis Axial (EsPax) mediante el índice LUNDEX y determinar las variables asociadas a la discontinuación de las mismas. Material y métodos: Estudio multicéntrico de corte transversal. Se incluyeron pacientes con EsPax en tratamiento con DME-b. Se registraron variables sociodemográficas, terapéuticas y clínicas. Se consignaron fechas de inicio del tratamiento con DME-b, tratamiento concomitante, suspensión o cambio de tratamiento, y causas de suspensión. La eficacia terapéutica se definió según BASDAI a los 6, 12 meses y luego anualmente a partir del inicio de la DME-b. Se calculó el índice LUNDEX en estos períodos. Análisis estadístico: Estadística descriptiva. Test de Student y test Chi² o test exacto de Fisher. Curvas de Kaplan-Meier y Log-Rank. Análisis de regresión proporcional de Cox. Resultados: Se estudiaron 101 pacientes con EsPax, 80,2% varones, con una edad mediana de 42 años (RIC 35-54,5) y un tiempo mediano de evolución de la enfermedad de 19,3 años (RIC 9,4-28,8). El 26,7% de los pacientes no tenían seguro de salud. Los agentes anti-TNFα utilizados como 1º DME-b en orden de frecuencia fueron: Etanercept (ETN) 44,6%, Adalimumab (ADA) 41,6%, Infliximab 7,9% y Certolizumab 5,9%. En el 32,7% de los casos, la DME-b se administró en combinación con una droga modificadora de enfermedad convencional. La sobrevida media fue de 66,2 meses (IC 95%: 51,8-80,5). Debido a que ETN y ADA se utilizaron en el 85% de los pacientes estudiados, se realizaron comparaciones solamente entre estos agentes. El tiempo medio de supervivencia acumulada fue significaticamente menor para ETN versus ADA (X 53,18±8,8 vs X 74,8±8,9, Log-Rank p=0,02), siendo la causa principal de suspensión, la falta de provisión de la medicación. El tiempo promedio de supervivencia para aquellos que no tenían seguro de salud fue significativamente menor X 31,9 meses (IC 95%: 19-45) con respecto a aquellos pacientes con dicho seguro X 72,3 meses (IC 95%: 55,3-89,3), p=0,03. Luego de ajustar por factores confundidores, la falta de un seguro de salud fue la única variable asociada en forma independiente con menor supervivencia del DME-b (HR 2,54, IC 95%: 1,18-5,75). El LUNDEX global fue del 52,7% a los 6 meses y del 46,9% a los 12 meses. Conclusiones: La sobrevida promedio del 1º DME-b fue de 5,5 años. La falta de cobertura de salud fue la única variable que influyó negativamente en la sobrevida del tratamiento con el 1º DME-b en pacientes con EsPax.

Objectives: To evaluate and compare the efficacy and long-term survival of biological disease-modifying drugs (b-DMARDs) in Axial Spondyloarthritis (axSpA) using the LUNDEX index and to determine the variables associated with the discontinuation of these drugs. Material and methods: Cross-sectional multicenter study. Patients with axSpA in treatment with b-DMARDs were included. Sociodemographic, therapeutic and clinical variables were recorded. The dates of initiation of treatment with b-DMARDs, concomitant treatment, suspension or change of treatment, and causes of suspension were recorded. Therapeutic efficacy was defined according to BASDAI at 6, 12 months and then annually from the initiation of b-DMARDs. The LUNDEX index was calculated in these periods. Statistical analysis: Descriptive statistics. Student's test and Chi² test or Fisher's exact test. Curves of Kaplan-Meier and Log-Rank. Proportional regression analysis of Cox. Results: 101 patients with axSpA were studied, 80.2% men, with a median age of 42 years (IQR 35-54.5) and a median disease duration of 19.3 years (IQR 9.4-28.8). 26.7% of patients didn´t have health insurance. The frequency of the anti-TNFα agent used as 1st b-DMARD was: Etanercept (ETA) 44.6%, Adalimumab (ADA) 41.6%, Infliximab 7.9%, and Certolizumab 5.9%. In 32.7% of the cases, the b-DMARD was administered in combination with a c-DMARD (conventional disease-modifying drug). The mean survival was 66.2 months (95% CI: 51.8-80.5). As ETA and ADA were used in 85% of the patients, comparisons were made only between these two agents. The mean survival time was significantly lower for ETA vs ADA (X 53.18 ±8.8 vs X 74.8±8.9, Log-Rank p=0.02), being the main cause of suspension, the lack of drug provision. The average survival time for those who didn´t have health insurance was significantly lower X 31.9 months (95% CI: 19-45) in comparison to those patients who had health insurance X 72.3 months (95% CI: 55.3-89.3), p=0.03. After adjusting for confounding factors, the lack of health insurance was the only variable independently associated with a lower survival of the b-DMARD (HR 2.54, 95% CI: 1.18 to 5.75). The global LUNDEX was 52.7% at 6 months and 46.9% at 12 months. Conclusions: The average survival of the 1st b-DMARD was 5.5 years. The lack of health insurance was the only variable that negatively influenced the survival of the treatment with the 1st b-DMARD in patients with axSpA.

Prevalencia y características de uveítis como manifestación extraarticular en Espondiloartritis Axial / Prevalence and characteristics of uveitis as an extra-articular manifestation in Axial Spondyloarthritis

Introducción: La Uveítis Anterior Aguda (UAA) es la manifestación extraarticular más frecuente en la Espondiloartritis axial (EsPax), con una prevalencia global de 32,7%. El objetivo de este estudio fue determinar la prevalencia de UAA en una cohorte Argentina de pacientes con EsPax, describir sus características clínicas, frecuencia de episodios, respuesta al tratamiento y pronóstico a largo plazo, así como su asociación con características generales de la enfermedad. Material y métodos: Se realizó un estudio de corte transversal. Se incluyeron pacientes con diagnóstico de EsPax (criterios ASAS 2009) de la cohorte ESPAXIA (Estudio de Espondiloartritis Axial IREP Argentina). Se consignaron datos sociodemográficos, características de la enfermedad y tratamientos recibidos; números de episodios de uveítis, año de aparición, características del mismo, tratamiento realizado y complicaciones. Se registró rigidez matinal, medidas de movilidad axial por Bath Ankylosing Spondylitis Metrological Index (BASMI), número de articulaciones tumefactas, sitios de entesitis por medio de Maastricht AS Enthesitis Score (MASES), eritrosedimentación (ERS), proteína C reactiva (PCR) y presencia de HLA-B27. Se empleó Escala Visual Numérica (EVN) para evaluar el dolor, dolor nocturno, actividad de la enfermedad según el paciente y el médico. Se administraron autocuestionarios: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) y Ankylosing Spondylitis Quality of Life (ASQoL). Se calculó Simplified Ankylosing Spondylitis Disease Activity Score con ERS y PCR (SASDAS ERS/PCR). Análisis estadístico: Estadística descriptiva. Test T de Student, test de Chi² y análisis de regresión logística múltiple. Se consideró significativo un valor de p<0,05. Resultados: Se incluyeron 231 pacientes con EsPax, 174 de sexo masculino (75,3%) con una mediana de edad de 46 años (RIC 36-57) y mediana de tiempo de evolución de la enfermedad de 20,5 años (RIC 10,5-30,5). Sesenta pacientes (26%) presentaron al menos un episodio de uveítis, siendo la primera manifestación de la enfermedad en 22 (37,9%) de ellos. La UAA fue la forma más frecuente, observándose en 59 pacientes (98,3%). El promedio de episodios de UAA fue 4,78 (DS 5,64). Las recurrencias fueron unilaterales en 48,8% de los casos. El tratamiento recibido fue local en 42 (79,2%) de los pacientes. Doce pacientes (22,2%) presentaron secuelas luego del primer episodio, siendo la disminución de la agudeza visual y cataratas las más frecuentes (16,7% y 5,6%, respectivamente). Las variables asociadas independientemente con UAA fueron mayor tiempo de evolución de la enfermedad (24,91±14,2 años vs 20,7±13,2 años, p=0,038) y positividad de HLA-B27, (69% vs 47,4%, p=0,006). Conclusión: La prevalencia de uveítis en nuestra cohorte fue del 26%. Fue significativamente más frecuente en pacientes HLA-B27 (+) y con mayor tiempo de evolución de la enfermedad.

Background: Acute Anterior Uveitis (AAU) is the most frequent extra-articular manifestation in axial Spondyloarthritis (axSpA), with an overall prevalence of 32.7%. The aim of this study was to determine the prevalence of AAU in an Argentinian cohort of patients with axSpA and to describe their clinical characteristics, frequency of episodes, response to treatment and long-term prognosis, as well as their association with general disease characteristics. Methods: A cross-sectional study was carried out. We included patients with axSpA according to ASAS 2009 criteria from ESPAXIA cohort (Estudio de Espondiloartritis Axial IREP Argentina). Sociodemographic data, characteristics of the disease, and treatments received; numbers of episodes of uveitis, incidence date, and its characteristics, treatment and complications were consigned. Morning stiffness, axial mobility (BASMI), enthesitis (MASES), ESR, CRP and HLA-B27 were registered. Pain, night pain, patient and physician global assessment were evaluated by Numerical Visual Scale (NVA). BASDAI, BASFI and ASQoL self-questionnaires were administered. Statistical analysis: Descriptive statistics. Student's T-test, Chi² test and multiple logistic regression analysis. A p value <0.05 was considered significant. Results: Two hundred and thirty one patients with axSpA were included, 174 male (75.3%) with a median age of 46 years (IQR 36-57) and median disease duration of 20.5 years (IQR 10.5-30.5). Sixty patients (26%) had at least one episode of uveitis, being the first manifestation of the disease in 22 (37.9%) of them. Acute anterior uveitis was the most frequent form, and it was observed in 59 patients (98.3%). The mean number of episodes was 4.78 (SD 5.64). Recurrences were unilateral in 48.8% of cases. They received local therapy in 42 (79.2%) of the patients. Twelve patients (22.2%) presented a complication after the first episode, being the decrease in visual acuity and cataracts, the most frequent ones (16.7% and 5.6%, respectively). The presence of uveitis was significantly associated with longer disease duration (24.9 years vs 20.7 years, p=0.038) and with the positivity for HLA-B27, (69% vs 47.4%, p=0.006) and these variables were maintained in the multivariate analysis, after adjusting for other variables. Conclusion: The prevalence of uveitis in our cohort was 26%. It was significantly more frequent in patients HLA-B27 (+) and with longer disease duration.

Ki-67 expression in anal intraepithelial neoplasia in AIDS.

CONTEXT: AIDS is one of the most important risk factors for progression and recurrence of anogenital condyloma. In a previous work, we observed that patients with warts and high-grade AIN (HAIN) had recurrences more frequently than did patients with warts without AIN. The mechanisms of this increased incidence of high-grade lesions in AIDS are not known. OBJECTIVE: We studied the expression of the proliferative marker Ki-67 by immunohistochemical methods, in specimens of anal condyloma from HIV+ patients to clarify whether its expression can be associated to the grade of AIN. DESIGN: A retrospective study of histological specimens. SETTING: University referral unit. SAMPLE: 34 patients were divided into two groups: (1) condylomas with low grade AIN (LAIN), with 25 patients; and (2) condylomas with HAIN, with 9 patients. In this latter group we examined two areas: 2A (HAIN area) and 2B (LAIN area). MAIN MEASUREMENTS: The immunohistochemical reaction for Ki-67 was done on histological sections. Slices were lightly stained with hematoxylin, to help us in Ki-67 positive cell counting. The percentage of Ki-67 marked nuclei was calculated. We applied one-way variance analysis for statistics. RESULTS: The mean number of Ki-67 positive cells in group 1 was 19.68 +/- 10.99; in group 2 (area A) it was 46.73 +/- 10.409; and in area B it was 36.43 +/- 14.731. There were statistical differences between groups 1 and 2A and between groups 1 and 2B. Ki-67 positive cells predominated in the lower layer in LAIN. Positive Ki-67 cells were found in all layers in group 2A, and in group 2B they predominated in the two lower or in all layers of the epithelium. CONCLUSIONS: Our results suggest that LAIN areas (using routine staining techniques) in HAIN can have a biological behavior more similar to HAIN.

Imunidade anti-rábica contra amostras de vírus de rua / Immunity against rabies street virus isolates

Avaliou-se a imunidade anti-rábica em camundongos e cobaias imunizados com vacina inativada tipo Fuenzalida & Palacios e modificada, amostra SAD (Street Alabama Dufferin). A imunidade foi testada pelo emprego de seis amostras de vírus isoladas de procedência humana, canina, bovina, eqüina, suína, e do morcego hematófago Desmodus rotundus (E. Geoffroy, 1810) em Minas Gerais de 1993 a 1995. A multiplicaçäo e titulaçäo dos vírus de rua e dos fixos CVS-24 (Challenge Vírus Standard) e DR-19 (Desmodus rotundus) foram realizados em camundongos de 21 dias de idade. Utilizaram-se os testes de Habel e Koprowski, recomendados pela OMS, para testar o grau de proteçäo conferido pelas vacinas, diante do desafio com as amostras de vírus rábico de rua e fixo. As vacinas avaliadas conferiram proteçäo de 70 por cento e 100 por cento de acordo com as amostras de vírus empregadas no desafio

Miopatia miotubular: estudo clinico, etrophysiological and histological study so. / Myotubular myopathy: clinical,elecof a case

Sao apresentados os resultados dos exames clinicos, eletrofisiologicos e do estudo do ponto motor, da imunofluorescencia, da histoquimica e da ultramicroscopia da biopsia muscular de um caso de miopatia miotubular. Sao discutidos estes resultados em relacao aos achados de 56 casos desta molestia consignados na literatura ate 1978, sendo cada enfase a etiopatogenia

[McArdle's disease: a case report]. / Doença de McArdle: registro de caso.

This disease was described by McArdle as an inherited autosomal recessive affection characterized by glycogen storage with normal chain in the skeletal muscles, due to absence of myophosphorylase activity. Under a clinical aspect, excessive fatigability, cramps and myoglobinuria appear following physical exercise. A case of this disease in a 36-year-old male patient is reported. Failure of elevation of venous blood lactate after physical effort under anaerobic conditions, as well as muscle histochemistry, made diagnosis confirmation possible. The authors comment on the differential diagnosis between McArdle's disease and the other causes of myoglobinuria, specially phosphofructokinase and carnitine-palmityl-transferase deficiency.

[Ocular myopathy, Kiloh-Nevin type; study of a case with histochemical and ultrastructural changes]. / Miopatia ocular tipo Kiloh-Nevin; estudo de um caso com alteracões histoquímicas e ultraestruturais.

A non-familiar case of Kiloh-Nevin ocular myopathy with important histochemical and ultrastructural abnormalities is reported. The patient, a 43 year-old male presented with 10 year long, pregressive ocular ophtalmoplegia, myasthenic symptoms and severe muscular pain, an uncommon finding in this type of myopathy. The histochemical study showed muscular atrophy, mainly in type I fibres and a great amount of ragged-red fibres. Of particular interest, in this case, was the ultrastructural finding of severe mitochondrial abnormalities with a lot of inclusions in the cristae matrix; nevertheless these changes are not specific. The authors suggest a possible abnormality in the neuro-muscular transmission system and a genetically controlled enzimatic factor as responsible for the aethiology and pathogenesis of the Kiloh-Nevin ocular myopathy.