Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.

Introduction: This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). Methods: The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. Results: A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Discussion: Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

Visual manifestations in giant cell arteritis: identification of risk factors from the ARTESER Registry.

OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.

Utility of applying a diagnostic algorithm in giant cell arteritis based on the level of clinical suspicion. / Utilidad de la aplicación de un algoritmo diagnóstico en la arteritis de células gigantes en función del grado de sospecha clínica.

INTRODUCTION: To reach the diagnosis of giant cell arteritis (GCA), signs, symptoms, laboratory tests, imaging findings, and occasionally anatomopathological results from temporal artery biopsy are evaluated. This study describes the results of an algorithm analysis based on clinical and ultrasound evaluation of patients with suspected GCA, highlighting its diagnostic utility by contrasting its use in different clinical suspicion scenarios. METHOD: Prospective multicenter study evaluating patients referred with suspected GCA through a preferential circuit (fast track), grouping them according to low or high clinical suspicion of GCA. Each of these scenarios is evaluated by biopsy and ultrasound for all patients, resulting in positive, indeterminate, or negative outcomes, yielding six possible groups. Potential areas of improvement are explored, emphasizing that, following a negative or indeterminate ultrasound, 18-FDG-PET-CT could be recommended. We analyze the results and application of a diagnostic algorithm, confirming its efficiency and applicability based on whether there is high or low clinical suspicion. RESULTS: Sixty-nine patients (41 in the high suspicion group and 28 in the low suspicion group). There were 41 new diagnoses of GCA: 35 in the high suspicion group and 6 in the low suspicion group. Using ultrasound alone, the initial algorithm has an overall diagnostic efficiency of 72.5%, which improves to 80.5% when including 18F-FDG-PET/CT. The negative predictive value of ultrasound in patients with low clinical suspicion is 84.6%, and the positive predictive value of ultrasound in patients with high suspicion is 100%, improving sensitivity from 57.1% to 80.8% with 18F-FDG-PET/CT in this scenario. Temporal artery biopsy was performed on all patients, with no differences in sensitivity or specificity compared to ultrasound. In cases where all three tests - ultrasound, biopsy, and 18F-FDG-PET/CT - are performed, sensitivity increases to 92.3% in patients with high clinical suspicion. CONCLUSION: In situations of high clinical suspicion, the algorithm provides sufficient information for the diagnosis of GCA if ultrasound is positive. A negative ultrasound is sufficient to rule out the diagnosis in the context of low clinical suspicion. 18-FDG-PET-CT may be useful in patients with high suspicion and negative or indeterminate ultrasound results.

Increase of Circulating Monocyte-Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage.

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte−PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte−PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.

A description of Chilean food and nutrition health policies / Una descripción de las políticas de nutrición y alimentación en Chile

ABSTRACT BACKGROUND: Chile has implemented numerous successful food and nutrition initiatives since the early 20th century, aiming to address malnutrition in all its forms. AIM: To summarize the major nutrition and food-related policies, strategies, and programs implemented in Chile, using the NOURI-SHING Framework. MATERIAL AND METHODS: The NOURISHING framework proposes a methodology for reporting, monitoring, and categorizing actions to promote healthier eating in three main domains: food environment, food system and behavior change communication. The data collection was carried out reviewing the databases of the Chilean Ministries of Health, Education and Social Development, and the Parliament. Information about nutrition related public health policies, strategies or programs was obtained from peer reviewed articles, official reports, official State websites, as well as interviews with former and current stakeholders. RESULTS: Chile has mandatory nutritional labeling that was updated to front-of-package warning labels about critical nutrients. In addition, the advertising of unhealthy foods and breast milk substitutes is restricted, among other food and nutrition policies. Nevertheless, strategies related to mass and social media communication campaigns, or periodic education and information interventions still need to be implemented. CONCLUSIONS: Using the NOURISHING framework, a comprehensive summary and description of nutrition and food public health policies implemented in Chile is described. An overview of the policy changes required according to the nutritional needs of the population and the nutritional transition in Chile is provided.

ANTECEDENTES: Chile ha implementado numerosas iniciativas sobre nutrición y alimentación desde el comienzo del siglo 20, para combatir la malnutrición en todas sus formas. OBJETIVO: Recopilar las principales políticas y programas sobre nutrición y alimentación implementados en Chile utilizando la estructura NOURISHING. MATERIAL Y MÉTODOS: La estructura NOURISHING propone un método para informar, monitorear y categorizar las acciones destinadas hacia una alimentación más saludable en tres dominios: ambiente nutricional, sistemas de alimentación y comunicación para lograr cambios de comportamiento. Se recolectó información desde bases de datos de los Ministerios de Salud, Educación y Desarrollo Social y del Congreso. La información acerca de políticas, programas o estrategias de salud pública se obtuvo de artículos revisados por pares, informes oficiales, sitios de internet del Estado y de entrevistas con quienes están o estuvieron involucrados en estos programas. RESULTADOS: Dentro de las políticas de nutrición y alimentos en Chile, se destaca el sistema obligatorio de etiquetado nutricional que ha evolucionado hacia la incorporación de advertencias en envases de alimentos señalando la presencia de nutrientes críticos. En Chile también se ha restringido la publicidad de alimentos no saludables y sustitutos de leche materna, entre otras políticas. Sin embargo, aún falta implementar campañas de comunicación y educación masiva sobre nutrición y alimentación saludable. CONCLUSIONES: Utilizando la estructura NOURISHING entregamos un resumen y descripción de los programas de nutrición y alimentación implementados en Chile en las últimas décadas. Se entrega una visión general de los cambios requeridos de acuerdo con las necesidades de la población y la transición nutricional que se ha experimentado.

Sarilumab (IL-6R antagonist) in critically ill patients with cytokine release syndrome by SARS-CoV2.

ABSTRACT: Blocking IL-6 pathways with sarilumab, a fully human anti-IL-6R antagonist may potentially curb the inflammatory storm of SARS-CoV2. In the present emergency scenario, we used "off-label" sarilumab in 5 elderly patients in life-threatening condition not candidates to further active measures. We suggest that sarilumab can modulate severe COVID-19-associated Cytokine Release Syndrome.

Situación de salud bucal de párvulos chilenos en un contexto comunitario / Oral health situation of Chilean children in a community context

INTRODUCCIÓN: Determinar la situación de salud bucal en párvulos ingresados a un programa promocional-preventivo en la comuna de Melipilla durante el año 2018. MATERIAL Y MÉTODOS: Estudio transversal realizado en 860 párvulos de entre dos a cinco años de edad matriculados en 17 establecimientos educacionales de la comuna, ubicados en zona urbana y rural. La experiencia de caries dental como variable dependiente y sexo, edad y zona geográfica del establecimiento educacional (urbano-rural) como variable independiente fueron medidas en un contexto comunitario (en aula). Estudio aprobado por Comité Científico de Ética de Universidad Finis Terrae y Servicio de Salud Metropolitano Occidente. RESULTADOS: El estudio abarcó al 88,5% de los párvulos matriculados, con promedio de edad de 3,76 ± 1,06 años. El 53,5% correspondieron a niñas. Un 34,1% (IC:95% 30,74:37,48) presentó caries dental, sin diferencias por sexo, zona geográfica, si por edad. A mayor edad, mayor daño por caries dental. Cada párvulo en promedio presentó un diente primario con caries (diente cariado:1,14 ± 2,28). El tercio de la población más afectada por caries dental presentó en promedio tres dientes primarios con daño. DISCUSIÓN: Los resultados muestran un elevado daño por caries dental cuyo inicio es temprano; esto pone de manifiesto la necesidad de avanzar en el desarrollo de políticas públicas de salud bucal destinadas a la primera infancia. (AU)

INTRODUCTION: To determine the oral health situation in the infants admitted to a pro-motional-preventive program in the municipality of Melipilla during the year 2018.MATERIAL AND METHODS: Cross-sectional study conducted with 860 infants between two to five years of age enrolled in 17 educational establishments in the community, located in urban and rural settings. The incidence of cavities as related to the variables of sex, age and geographical area of the educational establishment (urban-rural) as an independent variables were measured in a community context (in the classroom). Study approved by the Scientific Committee of Ethics of the Finis Terrae University and the Western Metropolitan Health Service.RESULTS: The study covered 88.5% of the enrolled children of 3.76 ± 1.06 years with an average age of 3,76 ± 1,06. 53.5% were girls. 34.1% (IC:95% 30,74:37,48) had cavities, without differences by sex or geographical area, but by age. The older you get, the more damage you get from tooth decay. Each toddler had on average one primary tooth with cavities (decayed tooth: 1.14 ± 2.28). One third of the population most affected by cavities presented on average three primary teeth with damage.DISCUSSION: The results show a high damage by cavities whose onset is early; This highlights the need to improve the development of public oral health policies aimed at early childhood. (AU)

Primary vertebral tumor of axis: A clinical and surgical challenge. / Tumor vertebral primario de axis: un desafío clínico y quirúrgico.

We report the case of a 17-year-old male presented to the emergency department with a six weeks history of neck pain and no neurogical deficit. Computed tomography and magnetic resonance imaging revealed an expansile lesion in the axis, with soft tissue and spinal cavity invasion, without mielopathy signs. Tomography-guided mass biopsy was taken. Waiting for histopathologic results, the pacient developed acute tetraparesis and sphincter incompetence. Magnetic resonance revealed that the bone mass had grown with epidural compromise, mielopathy and new vertebral lesions. Medular decompression with laminectomy, excision of the posterior elements of axis with the involved soft tissue mass and occipito-cervical fixation was performed. Neurological recovery was complete. Inmunochemistry revealed an Ewing Sarcoma. Chemoteraphy treatment was given, with partial response. Primary Ewing sarcoma of atlas-axis is a rare entity with poor prognosis. Multidisciplinary approach treatment is needed, with a total surgical resection if it is possible, a real challenge for the surgeon.

Garantía Explícita en Salud Oral en adulto de 60 años: impacto en la percepción de la calidad de vida / Explicit Oral Health Guarantee for Adults 60 Years of Age: impact on their perception of quality of life

OBJETIVO: Evaluar la Garantía Explícita en Salud Oral en el Adulto de 60 años (GES-60 años) desde la percepción de la calidad de vida. MÉTODO: Se realizó una evaluación antes y después de la prestación del programa GES-60, sin grupo control. Se utilizó el cuestionario Geriatric Oral Health Assessment Index (GOHAI) para cuantificar los cambios en la percepción de la calidad de vida como un indicador de resultado del programa. Se aplicó el test no paramétrico de Wilcoxon para datos emparejados en STATA 12.0. RESULTADOS: Participaron 103 adultos en el estudio y 85,5% fueron mujeres. Al término del programa GES-60 se presentaron mejoras significativas en la valoración global de la percepción de la calidad de vida relacionada con salud oral, como también en cada una de las dimensiones, particularmente en términos de la limitación psicológica. CONCLUSIÓN: Existe una significativa contribución del programa en el mejoramiento de la percepción de la calidad de vida de la población intervenida.

OBJECTIVE: To evaluate the Explicit Guarantee in Oral Health for Adults 60 years of Age (GES-60) on the basis of their perception of quality of life. METHOD: Evaluations were conducted before and after users participated in the GES-60 program, without a control group. The Geriatric Oral Health Assessment Index (GOHAI) was used to quantify changes in the perception of quality of life as an indicator of the program's results. The nonparametric Wilcoxon test was used to analyze matched data in STATA 12.0. RESULTS: A total of 103 adults participated in the study, and 85.5% were women. At the end of the GES-60 program, there were significant improvements in the overall assessment of the participants' perception of quality of life related to oral health, in each of the dimensions, particularly in terms of psychological limitations. CONCLUSION: The program significantly improves the target population's perception of quality of life.

miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli.

Regulation of miR-146a abundance and its role in intestinal inflammation and particularly in intestinal epithelial cells (IECs) has been poorly studied. Here we study the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using IEC lines and models of colitis (trinitrobenzenesulfonic acid (TNBS), dextran sulfate sodium (DSS) and the CD4 + CD62L + T cell transfer model). Specific bacterial antigens and cytokines (LPS, flagelin and IL-1ß/TNF) stimulate miR-146a expression, while peptidoglycan, muramyldipeptide and CpG DNA have no effect. Overexpression of miR-146a by LPS depends on the activation of the TLR4/MyD88/NF-kB and Akt pathways. Accordingly, the induction of miR-146a is lower in TLR4, but not in TLR2 knock out mice in both basal and colitic conditions. miR-146a overexpression in IECs induces immune tolerance, inhibiting cytokine production (MCP-1 and GROα/IL-8) in response to LPS (IEC18) or IL-1ß (Caco-2). Intestinal inflammation induced by chemical damage to the epithelium (DSS and TNBS models) induces miR-146a, but no effect is observed in the lymphocyte transfer model. Finally, we found that miR-146a expression is upregulated in purified IECs from villi vs. crypts. Our results indicate that miR-146a is a key molecule in the interaction among IECs, inflammatory stimuli and the microbiota.

Evolución temporal de los egresos hospitalarios por enfermedades infecciosas en Chile, 2004-2014 / Temporal trend of hospital discharges due to infectious diseases in Chile, 2004-2014

Resumen Introducción: Las enfermedades de origen infeccioso son importantes productoras de morbilidad y mortalidad. Objetivo: Describir la tendencia temporal de las tasas de los episodios de hospitalización por enfermedades infecciosas en Chile entre los años 2004 y 2014. Métodos: Estudio descriptivo usando el Registro Nacional de Egresos hospitalarios, identificando los episodios de hospitalización por enfermedades infecciosas incluyendo parasitarias. Se calcularon las tasas de egresos hospitalarios y se estandarizaron por edad. Mediante regresión de Poisson se estimó el porcentaje de cambio anual (PCA). Resultados: Los episodios de hospitalización por enfermedades infecciosas han disminuido (PCA de −4%). Las mujeres presentan menos episodios que los hombres. La magnitud de las tasas según grupos etarios, es mayor para personas de 0-9 años, y de 80 años y más. Conclusiones: En la última década hubo una reducción de episodios de egreso hospitalario por enfermedades infecciosas.

Background: Infectious diseases are important causes of burden of illness and mortality. Aim: To describe the temporal trends of hospital discharges due to infectious in Chile from 2004 to 2014. Methods: Descriptive study. National Hospital Discharge Registry were used. We included all hospital discharges with main diagnosis of infectious diseases including parasitic diseases. Rates were calculated and standardized. The anual percentage change (APC) was estimated by Poisson regression. Results: During a stated period of time in hospitalization of infectious diseases decreased (APC −4%). Women had fewer hospital discharged compared to men. Patients aged between 0 and 9 years and those who aged 80 years and older showed greater rates than other age groups. Conclusions: Chile has experimented a reduction in hospital discharges due to infectious diseases.

The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab.

BACKGROUND: IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses. METHODS: Heparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients. RESULTS: Three statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90-183)pg/ml, in g2 12.3(4.4-24)pg/ml, and in g3 60.1(30-146)pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5-15), g2 = 12(8-20), and g3 23(16-26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups. CONCLUSIONS: RA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.

Mortality trend of gallbladder cancer in Araucanía Region, Chile, 2004-2014. / Tendencia de la mortalidad por cáncer de vesícula en la Región de la Araucanía, Chile, 2004-2014.

BACKGROUND: Chile has the highest mortality rate for gallbladder cancer in the Andean region. The areas most affected by this cancer are found in southern Chile. OBJECTIVE: To describe the mortality rate trends for gallbladder cancer in the Araucanía region between 2004 and 2014. METHODS: Ecological observational descriptive study. The cases were identified by the codes ICD-10: C-23. The population at risk was obtained from the projections of the National Institute of Statistics of Chile. The mortality rate was modeled using the Poisson regression method, including age, time, and interaction between the two variables. The annual percentage change (APC) was used as a summary measure. RESULTS: In 2014, the Araucanía region had a standardized mortality rate of 10.36 per 100,000 inhabitants, while in the country it was 6.13 per 100,000. At the country level, the temporal evolution of mortality due to gallbladder cancer presented an annual percentage change of 9.1% (incidence rate ratio = 0.91 p-value <0.05), while in Araucanía the decrease was 7 % (incidence rate ratio = 0.93 p-value= 0.16), which is not statistically significant. The mortality rate was 2.68 times higher in women than in Araucanía men (p-value <0.05), a result similar to that of the country. At the national level, the trend according to age group shows a decrease for all groups, being the one of greater magnitude in those people from 45 to 54 years with an annual percent change of -5.36%, these results are not observed in the Araucanía. CONCLUSIONS: Mortality from gallbladder cancer shows a decreasing trend in the period studied for the whole country; however, this is not so for the Araucanía region, which maintains a higher mortality rate than that of the country.

INTRODUCCIÓN: Chile presenta la mayor tasa de mortalidad por cáncer de vesícula de la región andina. Las zonas más afectadas por este cáncer se encuentran al sur del país. OBJETIVO: Describir la tendencia de la tasa de mortalidad por cáncer de vesícula en Región de la Araucanía, entre los años 2004 y 2014. MÉTODOS: Estudio descriptivo observacional de tipo ecológico. Se utilizaron las defunciones por cáncer de vesícula ocurridas entre los años 2004 y 2014 en la Región de la Araucanía y en Chile. Los casos se identificaron utilizando el código CIE-10: C-23. La población en riesgo se obtuvo de las proyecciones del Instituto Nacional de Estadística de Chile. La tasa de mortalidad se modelizó a través del método de regresión de Poisson, utilizando como variables explicativas el tiempo, la edad y la interacción entre estas. Se empleó el porcentaje de cambio anual como medida de resumen. RESULTADOS: En el año 2014 la Región de la Araucanía presentó una tasa de mortalidad por cáncer de vesícula estandarizada de 10,36 por 100 000 habitantes, mientras que en el país fue de 6,13 por 100 000. En Chile, la evolución temporal de la mortalidad por cáncer de vesícula presenta una disminución con un porcentaje de cambio anual de 9,1% (razón de tasas de incidencia: 0,91; p <0,05), mientras que en la Araucanía la disminución fue de un 7% (razón de tasas de incidencia 0,93 p =0,16), no siendo estadísticamente significativo. La tasa de mortalidad fue 2,68 veces mayor en mujeres que en hombres de la Araucanía (p <0,05), resultado similar al del país. A nivel nacional, la evolución según grupo etario muestra un descenso para todos los grupos. La disminución de mayor magnitud se produce en aquellas personas de 45 a 54 años, con un porcentaje de cambio anual de -5,36%. Estos resultados no se observan en la Araucanía. CONCLUSIONES: La mortalidad por cáncer de vesícula tiene una tendencia decreciente en el período estudiado para el país. Sin embargo, no arroja resultados significativos para la Región de la Araucanía, manteniéndose la tasa de mortalidad superior a la nacional.

Simultaneous Electrochemical Speciation of Oxidized and Reduced Glutathione. Redox Profiling of Oxidative Stress in Biological Fluids with a Modified Carbon Electrode.

The simultaneous electrochemical quantification of oxidized (GSSG) and reduced glutathione (GSH), biomarkers of oxidative stress, is demonstrated in biological fluids. The detection was accomplished by the development of a modified carbon electrode and was applied to the analysis of biological fluids of model organisms under oxidative stress caused by lead intoxication. Nanocomposite molecular material based on cobalt phthalocyanine (CoPc) and multiwalled carbon nanotubes functionalized with carboxyl groups (MWCNTf) was developed to modify glassy carbon electrodes (GCE) for the detection of reduced and oxidized glutathione. The morphology of the nanocomposite film was characterized by scanning electron microscopy (SEM) and profilometry. The electrochemical behavior of the modified electrode was assessed by cyclic voltammetry (CV) to determine the surface coverage (Γ) by CoPc. The electrocatalytic behavior of the modified electrode toward reduced (GSH) and oxidized (GSSG) forms of glutathione was assessed by CV studies at physiological pH. The obtained results show that the combined use of CoPc and MWCNTf results in an electrocatalytic activity for GSH oxidation and GSSG reduction, enabling the simultaneous detection of both species. Differential pulse voltammetry reveals detection limits of 100 µM for GSH and 8.3 µM for GSSG, respectively. The potential interference from ascorbic acid, cysteine, glutamic acid, and glucose was also studied, and the obtained results show limited effects from these species. Finally, the hybrid electrode was used for the determination of GSH and GSSG in rat urine and plasma samples, intoxicated or not by lead. Both glutathione forms were detected in these complex biological matrixes without any pretreatment. Our results portray the role of GSH and GSSG as markers of oxidative stress in live organisms under lead intoxication.

Queimaduras por tentativa de suicídio e homicídio e a sua associação com o prognóstico / Burns caused by attempted suicide and homicide and its association with prognosis / Quemaduras por intento de suicidio y homicidio y su asociación con el pronóstico

Objetivo: Descrever as características clínicas e epidemiológicas de pacientes vítimas de queimaduras infligidas intencionalmente internados em uma unidade de terapia intensiva de um centro de tratamento especializado em queimaduras de um hospital universitário. Método: Foi realizado um estudo longitudinal retrospectivo na unidade de Terapia Intensiva de um Centro de Tratamento de Queimados. A amostragem foi de conveniência de todos os pacientes adultos queimados internados consecutivamente no período de maio de 2011 a novembro de 2013. Foram coletados dados clínicos e do diagnóstico da queimadura, além de escores prognósticos. Resultados: Dos 178 pacientes incluídos no estudo, 19,7% tiveram lesões intencionais, sendo 10,7% ocasionadas por tentativa de suicídio e 9,0% por tentativa de homicídio. As lesões autoinfligidas e por agressão foram mais graves quando comparadas a lesões acidentais. A média da superfície corpórea queimada total foi maior nas lesões intencionais (39,2%; DP=21,6%) comparada às acidentais (25,3%, DP=15,6%; p<0,001) e a lesão inalatória foi mais frequente nas intencionais (71,43%) do que nas acidentais (38,4%; p<0,001). A taxa de mortalidade foi maior nas queimaduras intencionais (65,7%) comparada aos acidentes (30,7%; p<0,001). As mulheres foram o principal grupo de risco associado às queimaduras intencionais (p<0,001). As variáveis clínicas e prognósticos apresentaram resultados semelhantes entre os pacientes com queimaduras por tentativa de suicídio e homicídio. Conclusões: Identificou-se que as lesões intencionais são um fator de risco para o pior prognóstico e mortalidade de pacientes queimados.

Objective: To describe the clinical and epidemiological features of burn victims inflicted intentionally admitted to an intensive care unit of a specialized burn center at a university hospital. Method: Retrospective longitudinal study conducted in the intensive care unit of a Burn Treatment Center. Convenience sampling of all burned adult patients consecutively admitted from May 2011 to November 2013. Clinical data and burn diagnosis as well as prognostic scores were collected. Results: Of the 178 patients included in the study 19.7% had intentional injuries, 10.7% caused by attempted suicide and 9.0% attempted homicide. Self-inflicted injury and assault resulted in more serious injury compared to accidental injuries. The average of the total burned body area was higher in intentional injuries (39.2% and standard deviation ­ SD=21.6%) compared with accidental (25.3%, SD=15.6%, p<0.001) and inhalation injury was more frequent in intentional (71.43%) than in accidental (38.4%; p<0.001). The mortality rate was higher in intentional burns (65.7%) compared to accidents (30.7%; p<0.001). Women had higher risk associated intentional burns (p<0.001). Clinical and prognostic variables showed similar results among patients with burns of attempted suicide and homicide. Conclusions: It was found that intentional injuries are a risk factor for poor prognosis and mortality in burned patients.

Objetivo: Describir las características clínicas y epidemiológicas de pacientes víctimas de quemaduras infligidas intencionalmente internados en una unidad de cuidados intensivos de un centro de tratamiento especializado para quemaduras de un hospital universitario. Método: Estudio retrospectivo longitudinal en la unidad de cuidados intensivos de un centro de tratamiento especializado para quemaduras. El muestreo fue de conveniencia, de todos los pacientes adultos quemados internados consecutivamente a partir de mayo de 2011 hasta noviembre de 2013. Se recogieron datos clínicos y del diagnóstico de quemaduras, así como las puntuaciones de pronóstico. Resultados: De los 178 pacientes incluidos en el estudio, 19,7% tenían lesiones intencionales, siendo 10,7% por tentativa de suicidio y 9,0% por tentativa de homicidio. Las lesiones autoinfligidas y por agresión resultaron en lesiones más graves cuando comparadas a lesiones accidentales. El promedio de la superficie total del cuerpo quemado fue mayor en las lesiones intencionales (39,2%; DE=21,6%) en comparación a las accidentales (25,3%; DE=15,6%, p<0,001) y la lesión por inhalación fue más frecuente en las intencionales (71,43%) que en las accidentales (38,4%; p<0,001). La tasa de mortalidad fue mayor en las quemaduras intencionales (65,7%) en comparación a los accidentes (30,7%; p<0,001). Las mujeres fueron el principal grupo de riesgo asociado a quemaduras intencionales (p<0,001). Las variables clínicas y pronóstico presentaron resultados similares entre los pacientes con quemaduras de intento de suicidio y homicidio. Conclusiones: Se identificó que las lesiones intencionales son un factor de riesgo para peor pronóstico y mortalidad en pacientes quemados.

Polymorphisms in genes involved in the mechanism of action of methotrexate: are they associated with outcome in rheumatoid arthritis patients?

BACKGROUND: Methotrexate (MTX) is the first-line treatment option for newly diagnosed rheumatoid arthritis (RA) patients. However, 50-70% of the patients respond to treatment and 30% suffer toxicity. AIM: To identify pharmacogenetic markers of outcome in RA patients treated with MTX. PATIENTS & METHODS: We analyzed 27 genetic variants in DHFR, TYMS, MTHFR, ATIC and CCND1 genes. RESULTS: We included 124 RA patients treated with MTX monotherapy. In multivariate analyses two variants in the MTHFR gene were associated with response, rs17421511 (p = 0.024) and rs1476413 (p = 0.0086), as well as one in the DHFR gene, rs1643650 (p = 0.026). The ATIC rs16853826 variant was associated with toxicity (p = 0.039). CONCLUSION: MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy.

Adalimumab regulates intracellular TNFα production in patients with rheumatoid arthritis.

INTRODUCTION: Adalimumab is a fully human anti-tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients. METHODS: We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors. RESULTS: Before starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P < 0.001). When we added in vitro TNFα to healthy donor culture cells, levels of iTNFα+ CD14+ cells decreased, suggesting that the TNFα signal was responsible for the iTNFα+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFα and a progressive increase in iTNFα+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNFα+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNFα+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFα. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNFα+ CD14+ cells to levels measured before treatment. CONCLUSIONS: Our findings suggest that adalimumab treatment in RA patients can return iTNFα levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.

Calidad de vida relacionada con salud oral en mayores de 14 años en la comunidad San Juan bautista, isla Robinson Crusoe, Chile / Quality of life related to oral health in subjects 14 Years or Older, San Juan Bautista community, Robinson Crusoe Island, Chile

El aislamiento geográfico y condiciones medioambientales hacen a la población de Juan Fernández altamente vulnerable, siendo relevante conocer la calidad de vida relacionada con salud oral. Se realizó un estudio transversal en 137 habitantes mayores de 14 años. Se aplicó OHIP-14 para medir calidad de vida relacionada con salud oral previo consentimiento informado. El análisis estadístico fue realizado STATA 12.0. Un 51,8% es población femenina, con una edad media de 42,26 (DE 16,5). Un 91,97%, percibe que la salud oral afecta su calidad de vida, siendo levemente mayor en mujeres. Las molestias psicológicas son una manifestación en 80,29% de los encuestados. Un 75,91% percibe incomodidad por dolor en su boca, 62,77% manifiesta problemas de incapacidad psicológica. Existe mayor impacto en la calidad de vida relacionada con salud oral a medida que aumenta la edad. Por cada año de vida, el valor del OHIP-14 aumenta 0,07 (IC:95% 0,04­0,1). Los resultados obtenidos sugieren la necesidad de generar políticas públicas que consideren la salud oral desde una perspectiva integral, con énfasis en poblaciones altamente vulnerables considerando la mejora en la calidad de vida como un resultado a esperar

Geographic isolation and environmental conditions make the population of Robinson Crusoe Island, in the Juan Fernández archipielago highly vulnerable. It is therefore relevant to know the quality of life related to oral health (QOLRTO). In this report a cross sectional study in 137 inhabitants over 14 years of age was carried out. OHIP-14 was applied to measure QOLRTO, after informed consent was obtained. Statistical analysis was made in STATA 12.0. The population is 51.8% female, mean age 42.26 (SD 16.5) being similar in both sexes. Of the subjects studied, 91.97% perceived that oral health affects their quality of life, being slightly higher in women. Psychological distress was a manifestation in 80.29% of subjects, while 75.91% perceived discomfort and mouth pain, and 62.77% reported psychological disability issues. There is a greater impact of oral health issues with increasing age. For each year of life, the value of the OHIP-14 increased 0.07 (CI 95%, 0.04 to 0.1). The results suggest that public health policies that include a comprehensive oral health perspective, with emphasis on highly vulnerable populations should be considered

Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis.

The denomination of inflammatory bowel disease comprises a group of chronic inflammatory diseases of the digestive tract, ulcerative colitis and Crohn's disease being the most important conditions. Bile acids may play a role both in etiology and pharmacology of this disease. Thus, although deoxycholic acid is regarded as a proinflammatory agent ursodeoxycholic acid, which is currently being used to treat certain types of cholestasis and primary biliary cirrhosis, because of their choleretic, cytoprotective and immunomodulatory effects, it has been reported to exert an anti-inflammatory activity. We aim to confirm and characterize the intestinal antiinflammatory activity of ursodeoxycholic acid. The experimental model trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats has been used. Animal status was characterized by a number of macroscopic and biochemical parameters. Oral administration of ursodeoxycholic acid was able to ameliorate experimental colonic inflammation. This occurred only at a relatively high dose (50 mg/kg day), whereas ursodeoxycholic acid was without significant effect at doses of 10 and 25 mg/kg day. The therapeutic effect was evidenced, among others, by a higher body weight recovery, a diminished affected to total mucosal area and lower alkaline phosphatase activity in treated vs. control (TNBS treated) animals. These results indicate that, at the appropriate dose, ursodeoxycholic acid is a potentially useful drug to reduce intestinal inflammation and could be envisaged to be incorporated in the treatment of inflammatory bowel diseases.