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PURPOSE: Acquired QT prolongation is frequent and leads to a higher mortality rate in critically ill patients. KardiaMobile 1L® (KM1L) is a portable, user-friendly single lead, mobile alternative to conventional 12-lead electrocardiogram (12-L ECG) that could be more readily available, potentially facilitating more frequent QTc assessments in intensive care units (ICU); however, there is currently no evidence to validate this potential use. METHODS: We conducted a prospective diagnostic test study comparing QT interval measurement using KM1L with conventional 12-L ECG ordered for any reason in patients admitted to an ICU. We compared the mean difference using a paired t-test, agreement using Bland-Altman analysis, and Lin's concordance coefficient, numerical precision (proportion of QT measurements with <10 ms difference between KM1L and conventional 12-L ECG), and clinical precision (concordance for adequate discrimination of prolonged QTc). RESULTS: We included 114 patients (61.4% men, 60% cardiovascular etiology of hospitalization) with 131 12-L ECG traces. We found no statistical difference between corrected QT measurements (427 ms vs. 428 ms, p = .308). Lin's concordance coefficient was 0.848 (95% CI 0.801-0.894, p = .001). Clinical precision was excellent in males and substantial in females (Kappa 0.837 and 0.781, respectively). Numerical precision was lower in patients with vasoactive drugs (-13.99 ms), QT-prolonging drugs (13.84 ms), antiarrhythmic drugs (-12.87 ms), and a heart rate (HR) difference of ≥5 beats per minute (bpm) between devices (-11.26 ms). CONCLUSION: Our study validates the clinical viability of KM1L, a single-lead mobile ECG device, for identifying prolonged QT intervals in ICU patients. Caution is warranted in patients with certain medical conditions that may affect numerical precision.

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Background: Controversies exist on whether the presence of cardiovascular risk factors and their association with major cardiovascular events (MACE) is different between men and women. Most of the evidence comes from high-income countries, hindering extrapolation of sociocultural and demographic factors of other regions. Objective: To evaluate sex differences in the prevalence of cardiovascular risk factors and the incidence of MACE and diabetes in Colombian adults. Methods: We performed a survival analysis from women and men aged 35-70 belonging to the Prospective Urban Rural Epidemiology-Colombia prospective study. Incidence rates for MACE composite (myocardial infarction, stroke, heart failure, death) and each outcome and diabetes were calculated. Kaplan-Meier curves and log-rank tests were performed. The association between demographic, behavioral, and metabolic variables with MACE and diabetes were evaluated with Cox proportional hazards models. Results: 7,552 participants (50±9.7 years) were included; 64% were women. Women had higher hypertension prevalence, body mass index, levels of total cholesterol, LDL-c, and HDL-c but lower triglycerides levels. Women were more sedentary but fewer smokers or active alcohol consumers and had higher educational levels. After 12-year mean follow-up (SD 2.3), the incidence rate of MACE composite was higher in men [4.2 (3.6-4.9) vs. 3.2 (2.8-3.7) cases per 1000 person-years]. Diabetes had the greatest association with MACE (HR = 2.63 95%CI:1.85;3.76), followed by hypertension (HR = 1.75 95%CI:1.30;2.35), low relative grip strength (HR = 1.53 95%CI:1.15;2.02), smoking (HR = 1.47 95%CI: 1.11;1.93), low physical activity (HR = 1.42 95%CI: 1.03;1.96). When evaluating risk factors by sex, only an increased waist-to-hip ratio was more strongly associated with MACE in men (p-interaction <0.05). Conclusions: The composite MACE outcome was higher in men despite having a lower overall burden of risk factors. The risk factors contribution was similar, leading us to reconsider the need to carrying out differentiated cardiovascular risk prevention and management campaigns, at least in our region.

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Case description: A 61-year-old male patient with uncontrolled rheumatoid arthritis presented acute coronary syndrome on three occasions, less than 48 hours after infliximab infusion. Clinical findings: He presented with ST-elevation myocardial infarction on two occasions and non-ST-elevation acute coronary syndrome on one, with the identification of multivessel coronary disease. Treatment and outcome: Coronary intervention was performed with thrombus aspiration, medicated stent implantation, medicated balloon angioplasty, discontinuation of infliximab, and modification and optimization of cardiovascular pharmacological management. Clinical relevance: Patients with rheumatoid arthritis have subclinical cardiovascular disease and increased cardiovascular risk. The evidence regarding the relationship between infliximab and ischemic heart disease is controversial. A wide clinical spectrum of cardiac involvement with infliximab infusion is found in case reports, ranging from stable angina to ST-segment elevation acute coronary syndrome. The pathophysiology is not elucidated, with hypotheses proposing plaque rupture, allergic reactions, and vasoconstriction as possible disease mechanisms. The direct association between infliximab infusion and acute coronary syndrome needs more clinical research to optimize the management and prognosis of patients presenting with this type of complication.

Descripción del caso: Paciente masculino de 61 años con artritis reumatoide no controlada, en manejo con infliximab, quién presentó en tres oportunidades síndrome coronario agudo menos de 48 horas posterior a la aplicación del medicamento. Hallazgos clínicos: Presentó infarto con elevación del ST en dos ocasiones y síndrome coronario agudo sin elevación del ST en una oportunidad, encontrándose enfermedad coronaria multivaso. Tratamiento y resultado: Se realizó intervención coronaria con tromboaspiración, implante de stents medicados y angioplastia con balón medicado, suspensión del infliximab y modificación y optimización de manejo farmacológico cardiovascular. Relevancia clínica: Los pacientes con artritis reumatoide tienen enfermedad cardiovascular subclínica y mayor riesgo cardiovascular. La evidencia respecto a la relación entre infliximab y cardiopatía isquémica es controversial. En reportes de caso se encuentra un amplio espectro clínico de compromiso cardíaco con la infusión de infliximab, que va desde la angina estable hasta el síndrome coronario agudo con elevación del segmento ST. La fisiopatología no está claramente dilucidada, con hipótesis que proponen la ruptura de placa, reacciones alérgicas y la vasoconstricción como posibles mecanismos de enfermedad. La asociación directa entre la infusión de infliximab y el síndrome coronario agudo necesita más investigación clínica con el fin de optimizar el manejo y pronóstico de los pacientes que presentan este tipo de complicaciones.

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Case description: A 61-year-old male patient with uncontrolled rheumatoid arthritis presented acute coronary syndrome on three occasions, less than 48 hours after infliximab infusion. Clinical findings: He presented with ST-elevation myocardial infarction on two occasions and non-ST-elevation acute coronary syndrome on one, with the identification of multivessel coronary disease. Treatment and outcome: Coronary intervention was performed with thrombus aspiration, medicated stent implantation, medicated balloon angioplasty, discontinuation of infliximab, and modification and optimization of cardiovascular pharmacological management. Clinical relevance: Patients with rheumatoid arthritis have subclinical cardiovascular disease and increased cardiovascular risk. The evidence regarding the relationship between infliximab and ischemic heart disease is controversial. A wide clinical spectrum of cardiac involvement with infliximab infusion is found in case reports, ranging from stable angina to ST-segment elevation acute coronary syndrome. The pathophysiology is not elucidated, with hypotheses proposing plaque rupture, allergic reactions, and vasoconstriction as possible disease mechanisms. The direct association between infliximab infusion and acute coronary syndrome needs more clinical research to optimize the management and prognosis of patients presenting with this type of complication.

Descripción del caso: Paciente masculino de 61 años con artritis reumatoide no controlada, en manejo con infliximab, quién presentó en tres oportunidades síndrome coronario agudo menos de 48 horas posterior a la aplicación del medicamento. Hallazgos clínicos: Presentó infarto con elevación del ST en dos ocasiones y síndrome coronario agudo sin elevación del ST en una oportunidad, encontrándose enfermedad coronaria multivaso. Tratamiento y resultado: Se realizó intervención coronaria con tromboaspiración, implante de stents medicados y angioplastia con balón medicado, suspensión del infliximab y modificación y optimización de manejo farmacológico cardiovascular. Relevancia clínica: Los pacientes con artritis reumatoide tienen enfermedad cardiovascular subclínica y mayor riesgo cardiovascular. La evidencia respecto a la relación entre infliximab y cardiopatía isquémica es controversial. En reportes de caso se encuentra un amplio espectro clínico de compromiso cardíaco con la infusión de infliximab, que va desde la angina estable hasta el síndrome coronario agudo con elevación del segmento ST. La fisiopatología no está claramente dilucidada, con hipótesis que proponen la ruptura de placa, reacciones alérgicas y la vasoconstricción como posibles mecanismos de enfermedad. La asociación directa entre la infusión de infliximab y el síndrome coronario agudo necesita más investigación clínica con el fin de optimizar el manejo y pronóstico de los pacientes que presentan este tipo de complicaciones.

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Close and frequent follow-up of heart failure (HF) patients improves clinical outcomes. Mobile telemonitoring applications are advantageous alternatives due to their wide availability, portability, low cost, computing power, and interconnectivity. This study aims to evaluate the impact of telemonitoring apps on mortality, hospitalization, and quality of life (QoL) in HF patients. We conducted a registered (PROSPERO CRD42022299516) systematic review of randomized clinical trials (RCTs) evaluating mobile-based telemonitoring strategies in patients with HF, published between January 2000 and December 2021 in 4 databases (PubMed, EMBASE, BVSalud/LILACS, Cochrane Reviews). We assessed the risk of bias using the RoB2 tool. The outcome of interest was the effect on mortality, hospitalization risk, and/or QoL. We performed meta-analysis when appropriate; heterogeneity and risk of publication bias were evaluated. Otherwise, descriptive analyses are offered. We screened 900 references and 19 RCTs were included for review. The risk of bias for mortality and hospitalization was mostly low, whereas for QoL was high. We observed a reduced risk of hospitalization due to HF with the use of mobile-based telemonitoring strategies (RR 0.77 [0.67; 0.89]; I2 7%). Non-statistically significant reduction in mortality risk was observed. The impact on QoL was variable between studies, with different scores and reporting measures used, thus limiting data pooling. The use of mobile-based telemonitoring strategies in patients with HF reduces risk of hospitalization due to HF. As smartphones and wirelessly connected devices are increasingly available, further research on this topic is warranted, particularly in the foundational therapy.

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Beyond the temporal-spatial identification of the noxious stimulus and the characterization of its attributes, pain perception involves the retrieval of memories related to previous painful experiences, the use of adaptive learning, as well as the individual's ability to process and obtain knowledge, which adds a cognitive dimension to this complex sensation. The present review aims to define the neuronal substrates involved in pain processing and cognition, to understand how these processes interact to help modulate pain, and to consider the effect of some analgesic treatments on cognitive performance. Some of the anatomical substrates that are in charge of processing and modulating pain are also involved with certain cognitive processes, such as attention and the generation of expectations, which could be advantageous, and could even represent the foundations of a complemen- tary analgesic option, which eventually might be useful in intolerant or refractory patients or could even help to reduce the prescribed doses of the drugs typically used for pain management.

Más allá de la identificación temporo-espacial del estímulo nocivo y de la caracterización de sus atributos, la percepción del dolor supone la recuperación de recuerdos relacionados con experiencias dolorosas previas, el uso de aprendizaje adaptativo, así como la capacidad del individuo para procesar y obtener conocimientos, lo cual añade una dimensión cognitiva a esta compleja sensación. La presente revisión tiene como objetivos definir los sustratos neuronales implicados en el procesamiento del dolor y en la cognición, entender cómo esos procesos interactúan para contribuir a modular el dolor y considerar el efecto de algunos tratamientos analgésicos en el desempeño cognitivo. Parte de los sustratos anatómicos que tienen a su cargo el procesamiento y la modulación del dolor, también están relacionados con ciertos procesos cognitivos, como la atención y la generación de expectativas, lo cual podría resultar ventajoso, e incluso podría representar las bases de una opción analgésica complementaria que, eventualmente sería de utilidad en pacientes intolerantes o fármaco-resistentes, o hasta podría coadyuvar a disminuir las dosis prescritas de los fármacos típicamente empleados para el manejo del dolor.

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La hepatopatía congestiva comprende el espectro de manifestaciones a nivel del hígado, con injuria inducida como consecuencia de la congestión venosa hepática por una alteración en el flujo venoso del tracto de salida hepático. La etiología más frecuente es la falla cardiaca derecha, que por aumento de la presión venosa central, lleva retrógradamente al aumento de la presión venosa hepática, disminución del flujo hepático y disminución de la saturación de oxígeno, con congestión a nivel sinusoidal y particular compromiso de los hepatocitos de la zona 3. Generalmente tiene una presentación subclínica en cuanto a manifestaciones hepáticas que son enmascaradas por los signos y síntomas de falla cardiaca. El diagnóstico comprende la suma de hallazgos serológicos, imagenológicos e histológicos, luego de una exclusión de otras patologías con posible injuria hepática. El tratamiento se basa en el manejo de la falla cardiaca de base, y el pronóstico a su vez, queda supeditado a la fase de la enfermedad cardiaca de base. Se realizó una búsqueda de la literatura con el fin de construir una revisión de esta entidad, con conceptos actualizados a partir de la evidencia reciente.

Congestive liver disease comprises the spectrum of manifestations secondary to liver injury as a consequence of hepatic venous congestion due to a disturbance in the hepatic venous outflow. The most frequent cause is right heart failure, which, due to an increase in central venous pressure, leads retrogradely to an increase in hepatic venous pressure, a decrease in liver inflow and a decrease in oxygen saturation, with sinusoidal congestion and characteristic compromise of zone 3 hepatocytes. Its presentation is usually subclinical in terms of liver manifestations, masked by the signs and symptoms of heart failure. The diagnosis includes the sum of serological, imaging and histological findings, after exclusion of other entities involving liver injury. Treatment is based on the management of the underlying heart failure and the prognosis is as well dependent on the stage of the underlying heart disease. A literature search was carried out in order to create a review of this entity with updated concepts based on recent evidence.

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The development of chronic pain after surgery or persistent postoperative pain is a significant public health problem that affects between 10%-56% of patients undergoing surgical intervention. It produces great restrictions of mobility, limitation of daily activities, dependence on opioids, anxiety, depression, a great alteration of the quality of life and important legal and medical-economic consequences. There is a very close correlation between acute postoperative pain, and persistent postoperative pain. For this reason, pain must be treated effectively in its acute phase to reduce the incidence of chronic pain after surgery. There are risk factors that predispose to its appearance and that must be known by the anesthesiologist. In an individualized and meticulous pre-anesthetic consultation, these risk factors can be detected, as well as the presence of surgical procedures related to chronic pain, with the purpose of the therapeutic approach of the first ones if necessary, and a good planning of the anesthetic and analgesic technique, which reduces the participation of the second, in the chronicity of acute pain. The role of the anesthesiologist in the pre-anesthetic consultation is essential for the planning of preventive and multimodal analgesia that, together with other resources, should reduce the incidence of persistent postoperative pain.

El desarrollo del dolor crónico después de la cirugía o dolor posoperatorio persistente, es un problema de salud pública significativo que afecta entre el 10%-56% de los pacientes sometidos a una intervención quirúrgica. Produce grandes restricciones de la movilidad, limitación de las actividades de vida diaria, dependencia a los opioides, ansiedad, depresión, una gran alteración de la calidad de vida e importantes consecuencias legales y médico-económicas. Hay una correlación muy estrecha entre el dolor agudo posoperatorio, y el dolor posoperatorio persistente. Por esa razón, el dolor debe ser tratado de manera eficaz en su fase aguda para disminuir la incidencia del dolor crónico posterior a la cirugía. Existen factores de riesgo que predisponen a su aparición y que deben ser conocidos por el anestesiólogo. En una consulta pre-anestésica individualizada y minuciosa, se podrán detectar estos factores de riesgo, como también la presencia de procedimientos quirúrgicos relacionados con el dolor crónico, con la finalidad del abordaje terapéutico de los primeros de ser necesario, y una buena planificación de la técnica anestésica y analgésica, que disminuya la participación de los segundos, en la cronicidad del dolor agudo. El rol del anestesiólogo en la consulta pre-anestésica, es fundamental para la planificación de la analgesia preventiva y multimodal que junto a otros recursos deberían disminuir la incidencia del dolor postoperatorio persistente.

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METHODS: A multicenter cross-sectional study involving seven referral centers from three cities of Argentina was undertaken. Patients with a diagnosis of ulcerative colitis (UC), Crohn's disease (CD), or indeterminate colitis (IBDU/IC) were invited to answer an anonymous survey, which included a 5-point Likert scale to evaluate adherence to therapies. Independent variables associated with inadequate adherence were evaluated. RESULTS: Overall, 447 UC/IBDU and 135 CD patients were enrolled. Median age was 37 years (range 21-72); 39.8% were male; median time from diagnosis was 6 years (0.5-35). 91.4% were under treatment with at least one oral medication; 50.3% of patients reported inadequate adherence to oral medications. Patients with UC/IBDU had a lower risk of inadequate adherence when compared to patients with CD (OR 0.57 (0.37-0.87)). 21.8% reported inadequate adherence to biologics; subcutaneous administration was significantly associated with inadequate adherence to biologics (OR 4.8 (1.57-14.66)). CONCLUSION: Inadequate treatment adherence is common among patients with IBD, and potentially modifiable factors were identified.

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Introduction: The HLA region strongly associates with autoimmune diseases, such as type 1 diabetes. An alternative way to test classical HLA alleles is by using tag SNP. A set of tag SNP for several classical HLA alleles has been reported as associated with susceptibility or resistance to this disease in Europeans. Objective: We aimed at validating the methodology based on tag SNP focused on the inference of classical HLA alleles, and at evaluating their association with type 1 diabetes mellitus in a sample of 200 families from Antioquia. Materials and methods: We studied a sample of 200 families from Antioquia. Each family had one or two children with T1D. We genotyped 13 SNPs using tetra-primer ARMS-PCR or PCRRFLP. In addition, we tested the validity of the tag SNP reported for Europeans in 60 individuals from a population of Colombians living in Medellín (CLM) from the 1000 Genomes Project database. Statistical analyses included the Hardy-Weinberg equilibrium, the transmission disequilibrium and the linkage disequilibrium tests. Results: The linkage disequilibrium was low in reported tag SNP and classical HLA alleles in this CLM population. Association analyses revealed both risk and protection factors to develop type 1 diabetes mellitus. Appropriate tag SNPs for the CLM population were determined by using the genotype information available in the 1000 Genome Project database. Conclusions: Although linkage disequilibrium patterns in this CLM population were different from those reported in Europeans, we did find strong evidence of the role of HLA in the development of type 1 diabetes mellitus in the study population.

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Resumen Introducción. La región del antígeno leucocitario humano (Human Leukocyte Antigen, HLA) se ha asociado claramente con enfermedades autoinmunitarias, como la diabetes mellitus de tipo 1. Los polimorfismos representativos de un solo nucleótido (tag Single Nucleotide Polymorphism, tag SNP) constituyen una forma alternativa de evaluar los alelos clásicos del HLA. En la población europea se ha reportado un grupo de tag SNP para múltiples alelos clásicos relacionados con la predisposición o la resistencia frente a dicha enfermedad. Objetivo. Validar la metodología basada en los tag SNP enfocada en la inferencia de alelos HLA clásicos, y evaluar su asociación con la diabetes mellitus de tipo 1 en una muestra de familias antioqueñas. Materiales y métodos. Se estudió una muestra de 200 familias antioqueñas con uno a dos hijos afectados por diabetes mellitus de tipo 1. Se genotipificaron 13 SNP mediante el ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction) con cuatro iniciadores, o mediante la PCR-RFLP (PCR-Restriction Fragment Length Polymorphism). Además, se evaluó la validez de los tag SNP de 1.000 genomas reportados en europeos en una muestra de 60 individuos de la población colombiana de Medellín. Se hicieron las pruebas de desequilibrio de la transmisión, de desequilibrio de ligamiento y de equilibrio de Hardy-Weinberg. Resultados. En la población de estudio no se encontró suficiente desequilibrio de ligamiento entre los SNP y los alelos clásicos evaluados, por lo cual no fue posible inferir los alelos clásicos del HLA para el conjunto de familias con diabetes mellitus de tipo 1. El estudio de asociación evidenció que esta región aporta factores tanto de riesgo como de protección para el desarrollo de la enfermedad. Los tag SNP apropiados para la muestra de estudio se determinaron usando los SNP ubicados en la región HLA en la base de datos del 1000 Genomes Project en la mencionada población. Conclusiones. Los patrones de desequilibrio de ligamiento en la población estudiada fueron diferentes a los reportados para la población europea. A pesar de esto, se encontró evidencia clara sobre el papel de la región HLA en el riesgo de padecer diabetes mellitus de tipo 1 en la población de estudio.

abstract Introduction: The HLA region strongly associates with autoimmune diseases, such as type 1 diabetes. An alternative way to test classical HLA alleles is by using tag SNP. A set of tag SNP for several classical HLA alleles has been reported as associated with susceptibility or resistance to this disease in Europeans. Objective: We aimed at validating the methodology based on tag SNP focused on the inference of classical HLA alleles, and at evaluating their association with type 1 diabetes mellitus in a sample of 200 families from Antioquia. Materials and methods: We studied a sample of 200 families from Antioquia. Each family had one or two children with T1D. We genotyped 13 SNPs using tetra-primer ARMS-PCR or PCRRFLP. In addition, we tested the validity of the tag SNP reported for Europeans in 60 individuals from a population of Colombians living in Medellín (CLM) from the 1000 Genomes Project database. Statistical analyses included the Hardy-Weinberg equilibrium, the transmission disequilibrium and the linkage disequilibrium tests. Results: The linkage disequilibrium was low in reported tag SNP and classical HLA alleles in this CLM population. Association analyses revealed both risk and protection factors to develop type 1 diabetes mellitus. Appropriate tag SNPs for the CLM population were determined by using the genotype information available in the 1000 Genome Project database. Conclusions: Although linkage disequilibrium patterns in this CLM population were different from those reported in Europeans, we did find strong evidence of the role of HLA in the development of type 1 diabetes mellitus in the study population.

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OBJECTIVE: To describe the percentile distribution of waist circumference (WC) by sex and age in a representative sample of children and adolescents of lower-middle and low socioeconomic status in Santiago, Chile. METHODS: A cross-section of 3022 primary-school students between the ages of 6 and 14 from middle-low and low-class schools of Santiago. Ten schools from the Primary Education Society (SIP) in Santiago, Chile, were selected at random. WC was measured under standardized procedures as instructed by the WHO (midpoint between lower costal margin and iliac crest). The population was categorized between percentiles 10 and 90 and divided by sex and age. RESULTS: WC tends to increase with age in both males and females, but no significant differences were found in the percentiles by age for boys and girls at any age range (p>0.05). In our sample, comparing Chilean children with other populations (British, Australian, European-American, African-American, Mexican - American and Colombian), Chilean children have shown a significantly greater WC (p<0.05). CONCLUSIONS: We present new WC reference values for Chilean children according to sex and age from a representative sample of Chilean population. These can be considered as a new anthropometric assessment tool for estimating cardiometabolic risk in Chilean children.

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Celiac crisis is a severe and potentially fatal complication of celiac disease. Unusual at present, it has been described mainly in children younger than 2-years-old, but reports in adults do exist. We report a 26-years-old lady with tetany and bleeding diathesis at presentation. In spite of it rareness, it is important to consider celiac crisis among the multiple manifestations of celiac disease.

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BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.

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BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.(AU)

Antecedentes. La glicoproteína P (P-gp), un producto del gen MDR-1, es una bomba de eflujo transmembranainvolucrada en el transporte de drogas, descripta por primera vez en el cáncer refractario. En el intestino normal, P-gp se detecta sobre las célulasepiteliales superficiales, pero no se la ha descripto en el epitelio de las criptas. El papel de P-gp y su expresiónintestinal en la colitis ulcerosa (CU) refractaria a esteroides es controvertido. Objetivo. Comparar elpatrón de inmunotinción de P-gp en células epiteliales colónicas de pacientes con CU refractaria vs.respondedora a esteroides. Métodos. Se estudió P-gp por inmunohistoquímica en biopsias rectales obtenidasde 19 pacientes con CU activa, incluyendo muestras prequirúrgicas de 11 pacientes refractarios que fueronsometidos a una colectomía y muestras de 8 respondedores. Ideamos un score de 5 puntos (0-4), según elporcentaje de superficie epitelial con inmunotinción positiva en el epitelio superficial y críptico (áreas apical,lateral y citoplásmica). Resultados. Comparados con los respondedores, los pacientes refractarios a esteroides tenían scores de inmunotinción significativamente mayores en el epitelio superficial, tanto en lasáreas celulares apical (2.8+0.5 vs. 1.1+0.5, p=0.023) como citoplásmica (2.7+0.5 vs. 1.2+0.5, p=0.032). Se detectó frecuentemente inmunotinción positiva en el epitelio superficial en los pacientes refractarios (apical: 9/11 casos, citoplásmica: 10/11 casos), pero la misma se observó sólo en 4/8 respondedores. P-gp también sedetectó en áreas similares del epitelio de las criptas en 6/11 pacientes refractarios, en tanto que fue infrecuenteen el grupo de los 8 respondedores (1 caso en el área apical y 2 en la citoplásmica). Fuerón estudiadasbiopsias de la mucosa de la anastomosis pouch ileal - anal, obtenidas varios años después del procedimeinto quirúrgico, observándose un patrón de...(AU)

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BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.(AU)

Antecedentes. La glicoproteína P (P-gp), un producto del gen MDR-1, es una bomba de eflujo transmembranainvolucrada en el transporte de drogas, descripta por primera vez en el cáncer refractario. En el intestino normal, P-gp se detecta sobre las célulasepiteliales superficiales, pero no se la ha descripto en el epitelio de las criptas. El papel de P-gp y su expresiónintestinal en la colitis ulcerosa (CU) refractaria a esteroides es controvertido. Objetivo. Comparar elpatrón de inmunotinción de P-gp en células epiteliales colónicas de pacientes con CU refractaria vs.respondedora a esteroides. Métodos. Se estudió P-gp por inmunohistoquímica en biopsias rectales obtenidasde 19 pacientes con CU activa, incluyendo muestras prequirúrgicas de 11 pacientes refractarios que fueronsometidos a una colectomía y muestras de 8 respondedores. Ideamos un score de 5 puntos (0-4), según elporcentaje de superficie epitelial con inmunotinción positiva en el epitelio superficial y críptico (áreas apical,lateral y citoplásmica). Resultados. Comparados con los respondedores, los pacientes refractarios a esteroides tenían scores de inmunotinción significativamente mayores en el epitelio superficial, tanto en lasáreas celulares apical (2.8+0.5 vs. 1.1+0.5, p=0.023) como citoplásmica (2.7+0.5 vs. 1.2+0.5, p=0.032). Se detectó frecuentemente inmunotinción positiva en el epitelio superficial en los pacientes refractarios (apical: 9/11 casos, citoplásmica: 10/11 casos), pero la misma se observó sólo en 4/8 respondedores. P-gp también sedetectó en áreas similares del epitelio de las criptas en 6/11 pacientes refractarios, en tanto que fue infrecuenteen el grupo de los 8 respondedores (1 caso en el área apical y 2 en la citoplásmica). Fuerón estudiadasbiopsias de la mucosa de la anastomosis pouch ileal - anal, obtenidas varios años después del procedimeinto quirúrgico, observándose un patrón de...(AU)

Assuntos

RESUMO

BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.

Antecedentes. La glicoproteína P (P-gp), un producto del gen MDR-1, es una bomba de eflujo transmembranainvolucrada en el transporte de drogas, descripta por primera vez en el cáncer refractario. En el intestino normal, P-gp se detecta sobre las célulasepiteliales superficiales, pero no se la ha descripto en el epitelio de las criptas. El papel de P-gp y su expresiónintestinal en la colitis ulcerosa (CU) refractaria a esteroides es controvertido. Objetivo. Comparar elpatrón de inmunotinción de P-gp en células epiteliales colónicas de pacientes con CU refractaria vs.respondedora a esteroides. Métodos. Se estudió P-gp por inmunohistoquímica en biopsias rectales obtenidasde 19 pacientes con CU activa, incluyendo muestras prequirúrgicas de 11 pacientes refractarios que fueronsometidos a una colectomía y muestras de 8 respondedores. Ideamos un score de 5 puntos (0-4), según elporcentaje de superficie epitelial con inmunotinción positiva en el epitelio superficial y críptico (áreas apical,lateral y citoplásmica). Resultados. Comparados con los respondedores, los pacientes refractarios a esteroides tenían scores de inmunotinción significativamente mayores en el epitelio superficial, tanto en lasáreas celulares apical (2.8+0.5 vs. 1.1+0.5, p=0.023) como citoplásmica (2.7+0.5 vs. 1.2+0.5, p=0.032). Se detectó frecuentemente inmunotinción positiva en el epitelio superficial en los pacientes refractarios (apical: 9/11 casos, citoplásmica: 10/11 casos), pero la misma se observó sólo en 4/8 respondedores. P-gp también sedetectó en áreas similares del epitelio de las criptas en 6/11 pacientes refractarios, en tanto que fue infrecuenteen el grupo de los 8 respondedores (1 caso en el área apical y 2 en la citoplásmica). Fuerón estudiadasbiopsias de la mucosa de la anastomosis pouch ileal - anal, obtenidas varios años después del procedimeinto quirúrgico, observándose un patrón de...

Assuntos

RESUMO

BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.

RESUMO

The gold standard to quantify Crohn's disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.

Assuntos