RESUMEN

BACKGROUND AND AIMS: Ustekinumab is an effective treatment for inflammatory bowel diseases. However, some patients do not respond to conventional doses. The aim of the study was to evaluate the effectiveness of intravenous maintenance Ustekinumab in patients with secondary failure. METHODS: Single-center, retrospective study in adult patients with intravenous maintenance ustekinumab. The reduction of biochemical activity markers, ustekinumab trough levels and clinical indices of activity were evaluated. Biological remission was defined as the percentage decrease fecal calprotectin ≥ 80% and/or final fecal calprotectin ≤ 250 and C reactive protein < 5mg/L. RESULTS: 31 patients were included: Crohn's disease 77.4%. All included patients were bio-exposed and 61.3% had carried ≥ 2 biologics. Pre-intravenous maintenance mean Harvey-Bradshaw Index was 6.5±4,38 vs 5±3,1 at week 8 (p=0.024) vs 4.1±3.1 at week 24 (p=0.019). The median ustekinumab trough levels pre-intravenous maintenance were 1.40µg/ml [IQR 2.3] vs 5.35µg/ml [IQR 4.1] at week 8 (p<0.001) vs 4.8µg/ml [IQR 3.9] at week 24 (p<0.001). The pre-intravenous maintenance median fecal calprotectin was 809µg/g [IQR: 2256] vs 423µg/g [IQR: 999] at week 8 (p=0.025) vs 333µg/g [508] (p=0.001) at week 24. At the end of follow-up 48% went into biological remission. The presence of perianal disease was associated with lower biological remission (70.6% vs 27.3%, p=0.025). Median intravenous ustekinumab maintenance time was 8.55 [IQR 23.9] months. In 83.9% of patients no serious infections or malignancy were documented. CONCLUSIONS: The use of maintenance intravenous ustekinumab appears to be an effective and safe strategy that can be evaluated as a salvage treatment especially in highly bioexposed patients.

RESUMEN

Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic (PK/PD) parameters is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised paediatric host. In neonates and children, infections account for a high percentage of hospital admissions, and anti-infectives are the most used drugs. However, paediatric PK/PD studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals-usually used off-label in paediatrics-to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the PK parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, paediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring. The aim of this document, developed jointly by the Spanish Society of Hospital Pharmacy and the Spanish Society of Paediatric Infectious Diseases, is to describe the available evidence on the indications for therapeutic drug monitoring (TDM) of antibiotics and antifungals in newborn and paediatric patients, and to provide practical recommendations for TDM in routine clinical practice to optimise their dosing, efficacy and safety. Of antibiotics and antifungals in the paediatric population.

Asunto(s)

RESUMEN

Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic parameters, is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised host. In neonates and children, infections account for a high percentage of hospital admissions and anti-infectives are the most used drugs. However, pediatric pharmacokinetic and pharmacodynamic studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals -usually used off-label in pediatrics- to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the pharmacokinetic parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, pediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring. The aim of this document, developed jointly between the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Pediatric Infectious Diseases (SEIP), is to describe the available evidence on the indications for therapeutic drug monitoring of antibiotics and antifungals in newborn and pediatric patients and to provide practical recommendations for therapeutic drug monitoring in routine clinical practice to optimize pharmacokinetic and pharmacodynamic parameters, efficacy and safety of antibiotics and antifungals in the pediatric population.

Asunto(s)

RESUMEN

Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic (PK/PD) parameters is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised paediatric host. In neonates and children, infections account for a high percentage of hospital admissions, and anti-infectives are the most used drugs. However, paediatric PK/PD studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals-usually used off-label in paediatrics-to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the PK parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, paediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring. The aim of this document, developed jointly by the Spanish Society of Hospital Pharmacy and the Spanish Society of Paediatric Infectious Diseases, is to describe the available evidence on the indications for therapeutic drug monitoring (TDM) of antibiotics and antifungals in newborn and paediatric patients, and to provide practical recommendations for TDM in routine clinical practice to optimise their dosing, efficacy and safety. Of antibiotics and antifungals in the paediatric population.

Asunto(s)

RESUMEN

Introducción: Las características y complejidad de la diabetes mellitus tipo 2 motivan la necesidad de un abordaje multi e interdisciplinario. El estudio persigue caracterizar las representaciones sociales de la diabetes mellitus tipo 2 que posee un grupo de pacientes adultos, residentes en Área Metropolitana de Buenos Aires, Argentina Método: Estudio cuantitativo, descriptivo, corte transversal. Se aplicó cuestionario sociodemográfico elaborado ad hoc y técnica de palabras asociadas. Participaron 90 pacientes adultos, reclutados principalmente del servicio de diabetológica del Hospital de Clínicas "José de San Martin" dependiente de la Universidad de Buenos Aires. Resultados: El núcleo de la representación social estuvo integrado por palabras referidas al impacto y malestar emocional que causa esta patología; la identidad de la enfermedad y la necesidad de cuidado de la salud. La periferia contuvo los siguientes temas, de mayor a menor importancia: obesidad, complicaciones de la diabetes, plan alimentario, tratamiento médico y medicación. En menor medida, se mencionaron elementos como actividad física y sedentarismo. De manera tangencial, surgieron los elementos de desinformación y sexualidad. Discusión: La representación social de la diabetes mellitus tipo 2 en pacientes se caracteriza por reflejar, en su núcleo, el temor, impacto y malestar que causa esta enfermedad. La reproducción del discurso médico mediante los temas referidos a factores de riesgo, complicaciones y tratamiento, conforman el sistema periférico de la representación. Elementos importantes tales como actividad física, sedentarismo, desinformación y sexualidad, son poco mencionados. Se destaca la importancia de la salud mental, como una problemática central a abordar en este tipo de patologías. También se sugiere implementación de educación terapéutica.

Introduction: Characteristics and complexity of type 2 diabetes generates the need for a multi and interdisciplinary approach. The aim of the study is to characterize social representations of type 2 diabetes in a group of adult patients, living in the Metropolitan Area of Buenos Aires, Argentina. Method: Descriptive and cross-sectional design. An ad-hoc sociodemographic questionnaire and the associated words technique were applied. 90 adult patients participated, recruited mainly from a diabetes service of a public hospital. Results: The core of the social representation was made up of words referring to the impact and emotional discomfort caused by this pathology, the identity of the disease and the need for health care. The periphery contained the following topics, from most to least important: obesity, diabetes complications, eating plan, medical treatment, and medication. Elements such as physical activity and sedentary lifestyle were mentioned to a lesser extent. Also, misinformation and sexuality were mentioned tangentially. Discussion: Social representation of type 2 diabetes in patients is characterized by reflecting at its core, the fear, impact and discomfort that this disease causes. The reproduction of medical discourse, through topics related to risk factors, complications and treatment, make up the peripheral system of representation. Important elements such as physical activity, sedentary lifestyle, misinformation and sexuality are rarely mentioned. The importance of mental health is highlighted as a central problem to be addressed in this type of pathology. Also, it's suggested the implementation of therapeutic education.

RESUMEN

The catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening clinical condition that represents the most severe clinical presentation of the antiphospholipid syndrome (APS). It was first described in 1992 in a group of patients that presented with multiorgan involvement and microangiopathic features of APS. Most of the current knowledge of CAPS comes from the analysis of all cases collected at the "CAPS Registry" that was created in 2000 to perform studies on this condition. Most cases are triggered by a prothrombotic situation that leads to a multiorgan thrombosis and a cytokine storm. The analysis of cases included in the "CAPS Registry" has shown that the triple therapy with anticoagulation, glucocorticoids, and plasma exchange and/or intravenous immunoglobulins is associated to a better prognosis of CAPS. The improvement of the knowledge allowed a decrease from the 50% mortality rate reported in the first series to 25-30% in the most recent publications.

Asunto(s)

RESUMEN

All contemporary psychotherapies agree that (failing) emotion regulation is central to psychological disorders and that psychotherapy is about improving emotion regulation. In his research on the "emotion-laden" complex Jung put an emphasis on the role of failing emotion regulation in contributing to psychological disorders as well as to change in the process of psychotherapy, but he left this field of research and took a very different direction in favour of his archetype concept. Psychodynamic approaches generally argue that changes in emotion regulation are accomplished through corrective emotional experiences in the therapeutic relationship. Insights from affective neurosciences and attachment research have had a major influence on how the therapeutic relationship is constructed in contemporary psychodynamic approaches. There is a lack of similar developments in analytical psychology, which leads to substantial differences between the models of Jungian psychotherapy in contrast to other contemporary psychodynamic approaches. The implications of these differences for the practice of psychotherapy and especially the role of the therapeutic relationship are pointed out.

Toutes les psychothérapies actuelles s'accordent sur le fait que la régulation (défaillante) de l'émotion est au centre des désordres psychologiques et que la psychothérapie vise à améliorer la régulation de l'émotion. Dans sa recherche sur le « complexe à haute charge émotionnelle ¼, Jung a mis l'accent sur le rôle de la régulation défaillante de l'émotion comme participant aux désordres psychologiques ainsi qu'au changement dans le processus de psychothérapie. Mais il a abandonné ce champ de recherche et pris une direction très différente, y préférant son concept de l'archétype. Les approches psychodynamiques plaident généralement en faveur de l'idée que les changements dans la régulation de l'émotion sont atteints par les expériences émotionnelles corrective dans la relation thérapeutique. Des apports venant des neurosciences affectives et des recherches sur l'attachement ont eu une influence majeure sur comment la relation thérapeutique est construite dans les approches psychodynamiques actuelles. De tels développements font défaut dans la psychologie analytique, ce qui conduit à des différences considérables entre les modèles de psychothérapie jungienne en contraste avec les autres approches psychodynamiques actuelles. L'article souligne les conséquences de ces différences dans la pratique de la psychothérapie, tout particulièrement en ce qui concerne le rôle de la relation thérapeutique.

Todas las psicoterapias contemporáneas coinciden en que la regulación (fallida) de las emociones es central a los trastornos psicológicos y que la psicoterapia consiste en mejorar la regulación de las emociones. En su investigación sobre el complejo "de tonalidad afectiva", Jung hizo hincapié en el rol de una fallida regulación emocional en el desarrollo de los trastornos psicológicos, así como al cambio en el proceso de psicoterapia, pero abandonó este campo de investigación y tomó una dirección muy diferente en favor de su concepto de arquetipo. En general, los enfoques Psicodinámicos sostienen que los cambios en la regulación de las emociones se logran a través de experiencias emocionales correctivas en la relación terapéutica. Los conocimientos de las neurociencias afectivas y la investigación sobre el apego han tenido una gran influencia en cómo comprender la conformación de la relación terapéutica en los abordajes psicodinámicos contemporáneos. Faltan desarrollos similares en la psicología analítica, lo que conduce a diferencias sustanciales entre los modelos de la psicoterapia Junguiana en contraste con otros enfoques psicodinámicos contemporáneos. Se señalan las implicaciones de estas diferencias para la práctica de la psicoterapia y se destaca especialmente el rol de la relación terapéutica.

RESUMEN

Introducción: la falta de adherencia farmacológica, siendo un problema de salud pública es una de las principales causas de incremento de la morbimortalidad, discapacidad y costos sanitarios en los pacientes con enfermedades crónicas no transmisibles. Objetivo: describir la prevalencia de la no adherencia al tratamiento farmacológico de los pacientes adultos con patología crónica que asistieron a un centro médico de la ciudad de Tunja, desde septiembre a noviembre del año 2022. Materiales y métodos: estudio observacional de corte transversal que incluyó adultos mayores de 18 años con enfermedad crónica no transmisible en el servicio de consulta externa de un centro de salud de baja complejidad, se recolectó los datos de las historias clínicas, se utilizó estadística descriptiva y Odds Ratio para análisis de asociación. Resultados: se analizaron 216 pacientes. La prevalencia de no adherencia al tratamiento farmacológico fue del 75%, el promedio de edad de pacientes con patología crónica fue 65,5 años, el sexo femenino representó el 56,9%, la mayoría de los casos tuvieron hipertensión arterial sistémica (94,4%), más de la mitad presentaron comorbilidades (73,1%) y el 45,3% estaban polimedicados. Los factores relacionados con la no adherencia farmacológica según el test de Morisky-Green fueron edad menor a 60 años (p=0,033), sexo masculino (p=0,045), consumo de alcohol (p=0,003) y tabaco (p=0,003), ausencia de comorbilidades (p=0,008) y no polifarmacia (p=0,004). Conclusión: la no adherencia farmacológica presentó una prevalencia, por encima a la reportada en la literatura y el principal factor asociado fue el consumo de tabaco. Los resultados obtenidos proporcionan conocimientos para nuevas investigaciones (AU)

Introduction: lack of pharmacological adherence, being a public health problem, is one of the main causes of increased morbidity and mortality, disability and health costs in patients with chronic non-communicable diseases. Objective: to describe the prevalence of non-adherence to pharmacological treatment in adult patients with chronic pathology who attended a medical center in the city of Tunja, from September to November 2022. M aterials and methods: cross-sectional observational study that included adults over 18 years of age with chronic non-communicable disease in the outpatient service of a low-complexity health center, data was collected from medical records, descriptive statistics were used and Odds Ratio for association analysis. Results: 216 patients were analyzed. The prevalence of non-adherence to pharmacological treatment was 75%, the average age of patients with chronic pathology was 65.5 years, the female sex represented 56.9%, the majority of cases had systemic arterial hypertension (94,4%), more than half had comorbidities (73.1%) and 45.3% were polypharmacy. The factors related to pharmacological non-adherence according to the Morisky-Green test were age under 60 years (p=0.033), male sex (p=0.045), alcohol consumption (p=0.003) and tobacco (p=0.003), absence of comorbidities (p=0.008) and no polypharmacy (p=0.004). Conclusion: pharmacological non-adherence had a high prevalence above that reported in the literature and the main associated factor was tobacco consumption. The results obtained provide knowledge for new research (AU)

Asunto(s)

RESUMEN

The objective of regulatory authorities is to ensure a favorable risk-benefit balance for medicines in their licensed indication, without seeking to establish their place in the therapeutic armamentarium beyond that. The licensed indication covers heterogeneous subpopulations and often does not sufficiently specify the characteristics of the patients who may benefit. The regulatory information does not always show the benefit over the standard treatments; moreover, it only reacts to the conditions specified in the developer's application, and lacks an assessment of the clinical relevance of the benefit and its uncertainties. Many cases highlight the need to establish a more specific therapeutic benefit scenario than the licensed indication. For example, abemaciclib was approved in the adjuvant setting for high-risk patients with early breast cancer, but the appropriate level of risk and how to assess it needs to be specified. Also, pembrolizumab is approved for neoadjuvant plus adjuvant treatment in lung cancer; but it remains to be analyzed whether it is superior to nivolumab in neoadjuvant treatment alone, which involves less treatment and economic burden. As therapeutic positioning is always a necessary decision, whether made at a national, regional, local or individual level, it must be made in the most appropriate way. The absence of a multidisciplinary discussion and consensus, relying only on individual decisions to determine positioning from the outset, underestimates information gaps, inter-individual variability and the influence of drug promotion. It can be harmful and costly. To properly manage the introduction of new medicines, it is essential to establish their benefit scenario in a multidisciplinary way. This, together with consideration of the clinical benefit provided versus the appropriate alternatives and the uncertainties of the benefit, constitutes the objective of the clinical assessment and the basis for designing a well-focused economic analysis. This allows policy makers to make the most appropriate decisions on pricing and funding new treatments. In an ideal situation, the benefit scenario considered for the new medicine would coincide with the one established for funding, but costs that are difficult to bear may lead to restrictions and affect the final positioning after the economic and budgetary impact assessment.

RESUMEN

INTRODUCTION: Digital health or "e-health" is a set of applications based on information and communication technologies (ICTs) that can be used to promote self-care and medication adherence in patients with chronic diseases. The aim of this study was to carry out a review of systematic reviews (meta-review) on efficacy studies of e-health interventions to promote adherence to antiretroviral therapy (ART) in people living with HIV/AIDS. METHODOLOGY: A review of systematic reviews ("meta-review") was performed using the Medline-PubMed database on efficacy studies of e-health components to promote adherence to ART, in patients with HIV/AIDS, proposing a structured search strategy (PICO question). A selection process for systematic reviews was conducted based on inclusion and exclusion criteria. Subsequently, the corresponding data were extracted, and the analysis was accomplished in descriptive tables. RESULTS: A total of 29 systematic reviews were identified, from which 11 were selected. These reviews comprised 55 RCTs with different e-health interventions and enrolled a total of 15,311 HIV/AIDS patients. Studies included a total of 66 comparisons (experimental group vs. control group) in indirect adherence measurements based on different measurement techniques (36 statistically significant); 21 comparisons of viral load (VL) measurements (10 statistically significant); and 8 comparisons of CD4+ cell count measurements (3 statistically significant). m-Health was the most studied component followed by the telephone call and e-learning. CONCLUSION: Evidence was found that supports that some e-health interventions are effective in promoting adherence to ART and improving health outcomes in patients with HIV/AIDS, although it is identified that more studies are needed for more robust evidence.

Asunto(s)

Asunto(s)

RESUMEN

Contextualização: A suplementação de zinco tem sido recomendada para o tratamento e a prevenção de muitas doenças, mas já foi demonstrado que os achados in vitro não são os mesmos evidenciados na clínica, havendo carência de evidências científicas em humanos, relativa ao real benefício dessa suplementação para o organismo humano. Objetivos: Sumarizar as evidências de revisões sistemáticas da Cochrane, referentes à efetividade da suplementação de zinco para tratamento e prevenção de doenças. Métodos: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca na Cochrane Library (2024), sendo utilizado o descritor "ZINC". Todas as revisões sistemáticas de ensaios clínicos foram incluídas. O desfecho primário de análise foi a melhora clínica, a redução dos sintomas ou a prevenção da doença. Resultados: Quatorze estudos foram incluídos, totalizando 221 ensaios clínicos e 265.113 participantes. Discussão: há evidência de benefício do zinco na anemia falciforme (redução de crises e infecções); na prevenção de diarreia aguda ou persistente em regiões com taxas elevadas de desnutrição; na prevenção da diarreia e melhora no crescimento de crianças de 6 meses a 12 anos de idade; na redução da mortalidade e no ganho de peso a curto prazo em prematuros; e na redução da incidência e prevalência de pneumonia em crianças de 2 a 59 meses de idade. É necessário cautela, pois não há robustez dos resultados e o nível de evidência é limitado. Conclusão: Há evidência de efetividade do zinco em algumas intervenções, mas a evidência é limitada, sugerindo-se a realização de novos estudos prospectivos de qualidade.

Asunto(s)

RESUMEN

El objetivo de este estudio fue describir las alternativas terapéuticas ortodóncico-quirúrgicas más utilizadas en la actualidad para el manejo de la displasia cleidocraneal en pacientes en crecimiento. Se realizó una búsqueda de literatura durante mayo de 2023 en las bases de datos Pubmed, Epitemonikos, Dentistry & Oral Sciences Source y LILACS sobre reporte de casos que presentaran estrategias de tratamiento ortodóncico-quirúrgico en pacientes menores de 18 años con displasia cleidocraneal. Seis artículos cumplieron con los criterios de inclusión. De ellos se obtuvieron siete reportes de casos. Las edades de los pacientes fluctúan entre los 10 y 16 años. Las estrategias de tratamiento consisten en al menos dos etapas de tratamiento ortodóncico quirúrgicas que involucran la extracción de dientes primarios y supernumerarios y la exposición quirúrgica de dientes permanentes retenidos para permitir su erupción y/o su tracción ortodóncica. Algunos casos son finalizados con cirugía Ortognática (Osteotomía Le Fort I de avance maxilar). La extracción de dientes primarios y supernumerarios, fenestración y tracción ortodóncica de los dientes permanentes retenidos y la cirugía ortognática al finalizar el crecimiento (cuando sea necesario) se propone actualmente como la mejor alternativa terapéutica para el tratamiento de pacientes con displasia cleidocraneal.

The objective of this study was to describe the orthodontic-surgical therapeutic alternatives most used nowadays, for the management of CCD in growing patients. A literature search for case reports was carried out through May, 2023 in PubMed, Epitemonikos, Dentistry & Oral Sciences Source and LILACS databases. We included case reports that presented complete orthodontic-surgical treatment strategies in patients with DCC under 18 years of age. Six articles met the inclusion criteria and seven case reports were identified. The age of cases ranged from 10 to 16 years. Treatment strategies consisted of at least two stages of surgical orthodontic treatment involving extraction of primary and supernumerary teeth and surgical exposure of impacted permanent teeth to allow spontaneous eruption or orthodontic traction. Some cases were completed with orthognathic surgery. Extraction of primary and supernumerary teeth, fenestration and orthodontic traction of retained permanent teeth and orthognathic surgery at the end of growth (when necessary) is currently proposed as the best therapeutic alternative for the treatment of patients with DCC.

RESUMEN

Resumen El carcinoma sarcomatoide primario hepático es un tumor agresivo que representa el 0.4-0.7% de todas las neoplasias primarias hepáticas. Se asocia a hepa topatía por virus hepatotropos, es más prevalente en la población asiática y en su histología se evidencian componentes de carcinoma y sarcoma. No posee carac terísticas clínicas ni imagenológicas patognomónicas y su diagnóstico se realiza en base a los hallazgos de la anatomía patológica e inmunohistoquímica. La cirugía en estadio localizado representa la única modalidad terapéutica con impacto en la sobrevida. Reportamos el caso de una paciente de 72 años, coreana, con an tecedentes de hepatopatía crónica por virus B, a quien se le diagnosticó un carcinoma sarcomatoide hepático primario con metástasis ósea y ganglionares.

Abstract Primary hepatic sarcomatoid carcinoma is a very ag gressive tumor, representing 0.4-0.7% of all primary he patic neoplasms. The disease is associated with liver dis ease due to hepatotropic viruses and is more prevalent in Asians. Histology shows sarcomatous and carcinoma components. It does not have pathognomonic clinical or imaging characteristics and its diagnosis is based on the pathological and immunohistochemistry findings. Surgery could prolong survival in localized stages. We report the case of a 72-year-old Korean patient with a history of chronic liver disease due to B virus, who was diagnosed with primary hepatic sarcomatoid carcinoma with bone and lymph node metastases.

RESUMEN

Diagnosis and treatment of ocular syphilis can be challenging due to the wide spectrum of clinical presentations of this sexually transmitted disease. In some cases of syphilitic panuveitis, pars plana vitrectomy (PPV) can be useful in management since it plays an important role in improving fundus examination allowing treatment of possible retinal associated lesions when vitreous inflammation is intense. We present 3 cases of patients with ocular syphilis that underwent a therapeutic PPV, vitreous sample was taken and analyzed in two of them.

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, with epidemiological studies indicating a 25% prevalence. NAFLD is considered to be a progressive disease that progresses from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), then to liver fibrosis, and finally to cirrhosis or hepatocellular carcinoma (HCC). Existing research has mostly elucidated the etiology of NAFLD, yet its particular molecular processes remain uncertain. Long non-coding RNAs (LncRNAs) have been linked in a wide range of biological processes in recent years, with the introduction of microarray and high-throughput sequencing technologies, and previous studies have established their tight relationship with several stages of NAFLD development. Existing studies have shown that lncRNAs can regulate the signaling pathways related to hepatic lipid metabolism, NASH, NASH-related fibrosis and HCC. This review aims to provide a basic overview of NAFLD and lncRNAs, summarize and describe the mechanisms of lncRNAs action involved in the development of NAFLD, and provide an outlook on the future of lncRNAs-based therapy for NAFLD. (AU)

La enfermedad del hígado graso no alcohólico (NAFLD) es la enfermedad hepática más común en el mundo, con estudios epidemiológicos que indican una prevalencia del 25%. La NAFLD se considera una enfermedad progresiva que avanza de esteatosis hepática simple a esteatohepatitis no alcohólica (NASH), luego a fibrosis hepática y, finalmente, a cirrosis o carcinoma hepatocelular (HCC). La investigación existente ha dilucidado principalmente la etiología de NAFLD. Sin embargo, sus procesos moleculares particulares siguen siendo inciertos. Los ARN largos no codificantes (lncRNA) se han relacionado en una amplia gama de procesos biológicos en los últimos años, con la introducción de microarrays y tecnologías de secuenciación de alto rendimiento, y estudios previos han establecido su estrecha relación con varias etapas del desarrollo de NAFLD. Los estudios existentes han demostrado que los lncRNA pueden regular las vías de señalización relacionadas con el metabolismo lipídico hepático, NASH, fibrosis relacionada con NASH y HCC. Esta revisión tiene como objetivo proporcionar una visión general básica de NAFLD y lncRNA, resumir y describir los mecanismos de acción de lncRNA involucrados en el desarrollo de NAFLD, y proporcionar una perspectiva sobre el futuro de la terapia basada en lncRNA para NAFLD. (AU)

Asunto(s)

RESUMEN

El tratamiento de la enfermedad inflamatoria intestinal (EII) ha sufrido una gran transformación tras la introducción de los fármacos biológicos. Gracias a ellos, los objetivos del tratamiento han evolucionado desde la respuesta y remisión clínica a objetivos más ambiciosos, como la remisión endoscópica o radiológica. Sin embargo, aunque los biológicos son muy eficaces, un porcentaje importante de pacientes no obtendrá una respuesta inicial o la perderá a lo largo del tiempo. Sabemos que existe una relación directa entre las concentraciones valle del biológico y su eficacia terapéutica, que cuanto más exigente sea el objetivo terapéutico serán necesarios niveles superiores del fármaco y que es frecuente la exposición insuficiente al mismo. La monitorización terapéutica de medicamentos biológicos, así como los modelos farmacocinéticos, nos brindan la posibilidad de ofrecer un enfoque personalizado del abordaje en pacientes con EII. Durante los últimos años se ha acumulado información relevante respecto a su utilidad durante o después de la inducción, así como en el mantenimiento del tratamiento biológico, en estrategias reactivas o proactivas y antes de la retirada o desintensificación del esquema.El objetivo de este documento es establecer recomendaciones sobre la utilidad de la monitorización terapéutica de biológicos en pacientes con EII, en los diferentes escenarios de la práctica clínica e identificar las áreas donde su utilidad es evidente, prometedora o controvertida. (AU)

The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common.Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation.The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial. (AU)

Asunto(s)

RESUMEN

Antecedentes y justificación: La estrategia de la aproximación concentración-dosis (C/D) y los distintos perfiles del tacrolimus (Tac), según los polimorfismos del citocromo P450 (CYPs) se centran en el metabolismo de Tac y se plantean como herramientas para el seguimiento de los pacientes trasplantados. El objetivo de este estudio es comparar la exposición al Tac analizado según ambas estrategias. Materiales y métodos: Se han incluido 425 pacientes trasplantados renales. El cálculo del cociente concentración Tac/dosis (C/D) permitió dividir la población en terciles y clasificar los pacientes según su tasa de metabolismo del Tac en tres grupos (rápida, intermedia y lenta). Con base en los polimorfismos del CYP3A4 y A5, los pacientes se agruparon en metabolizadores rápidos (portadores del CYP3A5*1 y CYP34A *1/*1), intermedios (CYP3A5*3/3 y CYP3A4*1/*1) y lentos (CYP3A5 *3/*3 y portadores del CYP3A4*22). Resultados: Al comparar los pacientes de cada grupo metabolizador según los dos criterios, coincidieron 47% (65/139) de los metabolizadores rápidos, 85% (125/146) de los intermedios y solo 12% (17/140) de los lentos. Se observaron concentraciones de Tac estadísticamente menores en los metabolizadores rápidos y concentraciones mayores en los lentos, comparándolos con el grupo intermedio según el cociente C/D o según polimorfismos. Los metabolizadores rápidos requirieron alrededor de 60% más de dosis de Tac que los intermedios a lo largo del seguimiento, mientras que los lentos aproximadamente 20% menos de dosis que los intermedios. Los metabolizadores rápidos clasificados por ambos criterios presentan un porcentaje mayor de veces con valores de concentración de Tac en sangre infraterapéuticos... (AU)

Background and justification: The strategy of the concentration–dose (C/D) approach and the different profiles of tacrolimus (Tac) according to the cytochrome P450 polymorphisms (CYPs) focus on the metabolism of Tac and are proposed as tools for the follow-up of transplant patients. The objective of this study is to analyse both strategies to confirm whether the stratification of patients according to the pharmacokinetic behaviour of C/D corresponds to the classification according to their CYP3A4/5 cluster metabolizer profile. Materials and methods: Four hundred and twenty-five kidney transplant patients who received Tac as immunosuppressive treatment have been included. The concentration/dose ratio (C/D) was used to divided patients in terciles and classify them according to their Tac metabolism rate (fast, intermediate, and slow). Based on CYP3A4 and A5 polymorphisms, patients were classified into three metabolizer groups: fast (CYP3A5*1 and CYP34A*1/*1 carriers), intermediate (CYP3A5*3/3 and CYP3A4*1/*1) and slow (CYP3A5*3/*3 and CYP3A4*22 carriers). Results: When comparing patients included in each metabolizer group according to C/D ratio, 47% (65/139) of the fast metabolizers, 85% (125/146) of the intermediate and only 12% (17/140) of the slow also fitted in the homonym genotype group. Statistically lower Tac concentrations were observed in the fast metabolizers group and higher Tac concentrations in the slow metabolizers when compared with the intermediate group both in C/D ratio and polymorphisms criteria. High metabolizers required approximately 60% more Tac doses than intermediates throughout follow-up, while poor metabolizers required approximately 20% fewer doses than intermediates. Fast metabolizers classified by both criteria presented a higher percentage of times with sub-therapeutic blood Tac concentration values... (AU)

Asunto(s)

RESUMEN

Se estima que el 96% de los recién nacidos (RN) con encefalopatía hipóxico-isquémica (EHI) nacen en entornos con recursos limitados (ERL) sin capacidad para ofrecer el estándar asistencial vigente desde hace cerca de 15 años en los países con altos recursos y que incluye hipotermia terapéutica, neuromonitorización continua electroencefalográfica y resonancia magnética, además de un control intensivo de las constantes vitales y del equilibrio homeostático. Esta situación no parece estar cambiando; sin embargo y aún con estas limitaciones, el conocimiento actualmente disponible permite mejorar la asistencia de los pacientes con EHI atendidos en ERL. El propósito de esta revisión sistematizada es ofrecer, bajo el término «código EHI», recomendaciones de prácticas asistenciales basadas en evidencia científica y factibles en ERL, que permitan optimizar la atención del RN con EHI y ayuden potencialmente a reducir los riesgos asociados a la comorbilidad y a mejorar los resultados neuroevolutivos. El contenido del código EHI se agrupó en nueve epígrafes: 1) prevención de la EHI, 2) reanimación, 3) primeras seis horas de vida, 4) identificación y graduación de la EHI, 5) manejo de las convulsiones, 6) otras intervenciones terapéuticas, 7) disfunción multiorgánica, 8) estudios complementarios, y 9) atención a la familia. (AU)

It is estimated that 96% of infants with hypoxic-ischaemic encephalopathy (HIE) are born in resource-limited settings with no capacity to provide the standard of care that has been established for nearly 15 years in high-resource countries, which includes therapeutic hypothermia, continuous electroencephalographic monitoring and magnetic resonance imaging in addition to close vital signs and haemodynamic monitoring. This situation does not seem to be changing; however, even with these limitations, currently available knowledge can help improve the care of HIE patients in resource-limited settings. The purpose of this systematic review was to provide, under the term «HIE Code», evidence-based recommendations for feasible care practices to optimise the care of infants with HIE and potentially help reduce the risks associated with comorbidity and improve neurodevelopmental outcomes. The content of the HIE code was grouped under 9 headings: 1) prevention of HIE, 2) resuscitation, 3) first 6hours post birth, 4) identification and grading of encephalopathy, 5) seizure management, 6) other therapeutic interventions, 7) multiple organ dysfunction, 8) diagnostic tests and 9) family care. (AU)

Asunto(s)