Seguridad de equipos de procuramiento de órganos y tejidos en Chile. ¿Qué esperamos?

Las tasa de trasplantes en Chile es baja en comparación con otros países. Si bien se han hecho importantes avances para aumentar este número, existe poca claridad en cuanto a protocolos de seguridad de los equipos de procuramiento de órganos. A nivel internacional existen diferentes tragedias que han marcado este trabajo, la más conocida es la ocurrida en Michigan, donde un equipo médico perdió la vida al caer sobre el lago en un transporte por un trasplante de pulmón. Años después de la tragedia se conocieron los reiterados reclamos por parte del personal médico en relación a la falta de seguridad durante los traslados. Si bien el procuramiento de órganos tiene un riesgo asociado inherente, este se debe mantener al mínimo. Para avanzar en esto se confeccionó una guía de seguridad donde participaron las organizaciones de trasplante más importantes de Estados Unidos. Se emitieron recomendaciones, donde se regula el transporte aéreo, terrestre, seguros y el futuro de esta actividad. En Chile la orientación técnica que regula el procuramiento, no especifica ninguno de estos puntos y no existe información pública disponible, dejando la seguridad a disposición de las instituciones locales. Si bien es importante reconocer el esfuerzo nacional por mejorar el número de trasplantes año a año, es necesario avanzar en mejorar la seguridad de los equipos de procuramiento, y no esperar que ocurra una tragedia, para generar cambios necesarios, particularmente en un país con una geografía desafiante como Chile.

The transplant rate in Chile is low compared to other countries. Although significant advances have been made to increase this number, there is little clarity regarding safety protocols for organ procurement teams. Internationally, various tragedies have marked this work, the most famous being the one that occurred in Michigan, where a medical team lost their lives when they crashed into a lake during transport for a lung transplant. Years after the tragedy, repeated complaints by medical personnel came to light concerning the lack of safety during transfers. Although organ procurement inherently carries associated risks, these should be kept to a minimum. In 2020, a safety guide was created to make progress with participation from the most crucial transplant organizations in the United States. Recommendations were issued regulating air and ground transportation, insurance, and the future of transplant activity. In Chile, technical guidelines that regulate procurement need to specify crucial safety metrics, and there is no publicly available information or recommendations, leaving safety to the discretion of local institutions. While it is essential to recognize the national effort to improve the number of transplants year after year, it is necessary to advance in improving the safety of procurement teams and not wait for a tragedy to occur to generate the required changes, particularly in a country with challenging geography like Chile.

Is Iron Overload Associated with Worse Outcomes in Patients with Chronic Liver Disease Undergoing Liver Transplantation?

ABSTRACT Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 person-months; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Effects of Changweiqing （肠胃清） on Transplanted Tumor Growth of Colorectal Cancer Cells and Expression of STAT3 and Bcl-2 Gene Splicing Isoforms / 中医杂志

ObjectiveTo explore the possible mechanism of Changweiqing （肠胃清） in the treatment of colorectal cancer. MethodsHCT 116 cancer cells were used to prepare intestinal cancer cells with silenced polypyrimidine region binding protein 3 （PTBP3） gene and stably transfected cells with overexpressed PTBP3 gene. Stably transfected cells with silenced PTBP3， stably transfected cells with overexpressed PTBP3 and untransfected cancer cells were injected into the armpit of 72 nude mice to construct three different subcutaneous transplanted tumor models of colorectal cancer cells， including the silenced model， the overexpressed model and the control model， with 24 mice per model. Mice of each transplanted tumor modelwere randomly divided into Changweiqing （CWQ） group， oxaliplatin （OXA） group and normal saline （NS） group， with 8 mice in each group. The CWQ groups were given intragastric administration of 35.9625 g/kg of Changweiqing oral liquid and were intraperitoneally injected with 0.2ml of normal saline； the NS groups were given 0.5ml of normal saline by gavage， and intraperitoneal injection of 0.2ml of normal saline； the OXA groups were intraperitoneally injected with 5 mg/kg （0.2 ml） of oxaliplatin and given 0.5ml of normal saline by gavage. Each group was given intragastric administration once a day and intraperitoneal injection three times a week. After 31 days， the weight of subcutaneous tumors in each group was measured， and the tumor inhibition rate of the groups in each model were measured. Immunohistochemistry and other methods were used to detect the expression level of cell proliferation cell nuclear antigen Ki67 and apoptosis index. Real-time PCR and Western Blot were used to detect mRNA and protein expressions of PTBP3， signal transducer and activator of transcription 3 （STAT3） splicing isoform α （STAT3α）， STAT3 splicing isoform β （STAT3β）， B-cell lymphoma/leukemia-2 （Bcl-2） splicing isoform α （Bcl-2α）， and Bcl-2 splicing isoform β （Bcl-2β） in subcutaneous tumor cells in each group. ResultsFor all three transplanted tumor models， the weight of the subcutaneous tumors and Ki67 expression level of subcutaneous tumor tissue in all CWQ groups and OXA groups were lower than those of the corresponding NS groups， while the apoptosis level were higher （P＜0.05 or P＜0.01）. The mRNA and protein expressions of PTBP3， STAT3α， and Bcl-2α in the subcutaneous tumor tissues of the silenced model CWQ group and the overexpressed model CWQ group were lower than those of the corresponding NS groups， while the mRNA and protein expression levels of STAT3β and Bcl-2β were higher （P＜0.05 or P＜0.01）. All there groups of silenced model had lower subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α in subcutaneous tumor tissue， as well as higher apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all groups of control model； all groups of overexpressed model had higher subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α ， while lower apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all control model groups （P＜0.05 or P＜0.01）. In the control model， compared with the NS group， The tumor inhibition rate of all OXA groups was higher than that of corresponding CWQ groups， respectively. Compared to that of each control model group， the tumor inhibition rate was positive value of each silenced model group， and negative value of each overexpressed model group. ConclusionPTBP3 can promote the proliferation and inhibit apoptosis of intestinal cancer cells， upregulate the expression of STAT3α and Bcl-2α， and downregulate the expression of STAT3β and Bcl-2β in intestinal cancer cells. The meachnism of action of Changweiqing in the treatment of colorectal cancer maybe related to the inhibition of PTBP3， and regulation of the expression of STAT3α， STAT3β， Bcl-2α， and Bcl-2β.

Understanding the dynamics of deceased organ donation and utilization in Colombia / Examen de la dinámica de la donación y utilización de órganos de personas fallecidas en Colombia / Entendendo a dinâmica da doação e do aproveitamento de órgãos de pessoas falecidas na Colômbia

ABSTRACT Objective. To obtain a comprehensive overview of organ donation, organ utilization, and discard in the entire donation process in Colombia. Methods. A retrospective study of 1 451 possible donors, distributed in three regions of Colombia, evaluated in 2022. The general characteristics, diagnosis, and causes of contraindication for potential donors were described. Results. Among the 1 451 possible donors, 441 (30.4%) fulfilled brain death criteria, constituting the potential donor pool. Families consented to organ donation in 141 medically suitable cases, while 60 instances utilized legal presumption, leading to 201 eligible donors (13.9%). Of those, 160 (11.0%) were actual donors (in whom operative incision was made with the intent of organ recovery or who had at least one organ recovered). Finally, we identified 147 utilized donors (10.1%) (from whom at least one organ was transplanted). Statistically significant differences were found between age, sex, diagnosis of brain death, and donor critical pathway between regions. A total of 411 organs were transplanted from 147 utilized donors, with kidneys being the most frequently procured and transplanted organs, accounting for 280 (68.1%) of the total. This was followed by 85 livers (20.7%), 31 hearts (7.5%), 14 lungs (3.4%), and 1 pancreas (0.2%). The discard rate of procured deceased donors was 8.1%. Conclusions. About one-tenth of donors are effectively used for transplantation purposes. Our findings highlight areas of success and challenges, providing a basis for future improvements in Colombia.

RESUMEN Objetivo. Presentar una descripción integral de la donación, utilización y descarte de órganos en todo el proceso de donación en Colombia. Métodos. Estudio retrospectivo de 1 451 donantes posibles, distribuidos en tres regiones de Colombia, que fueron evaluados en el 2022. Se describen las características generales, el diagnóstico y las causas de contraindicación de los donantes potenciales. Resultados. De los 1 451 donantes posibles, 441 (30,4%) cumplían con los criterios de muerte encefálica y constituyeron el conjunto de donantes potenciales. Las familias consintieron la donación de órganos en 141 casos aptos desde el punto de vista médico, mientras que en 60 casos se recurrió a la presunción legal, con lo que se llegó a 201 donantes aptos (13,9%). De estos, 160 (11,0%) fueron donantes reales (en los que se les practicó una incisión quirúrgica para la extracción de órganos o se obtuvo al menos un órgano). En última instancia, hubo 147 donantes utilizados (10,1%) (de los que se trasplantó al menos un órgano). Se observaron diferencias estadísticamente significativas entre las regiones en cuanto a edad, sexo, diagnóstico de muerte encefálica y vía crítica del donante. Se trasplantaron un total de 411 órganos procedentes de 147 donantes utilizados; los riñones fueron los órganos obtenidos y trasplantados con mayor frecuencia, ya que supusieron 280 (68,1%) del total de órganos, seguidos del hígado (85, 20,7%), el corazón (31 , 7,5%), los pulmones (14, 3,4%) y el páncreas (1, 0,2%). La tasa de descarte de los donantes fallecidos disponibles fue del 8,1%. Conclusiones. Aproximadamente una décima parte de los donantes son utilizados, de hecho, para realizar trasplantes. Estos datos destacan las áreas en las que se han obtenido buenos resultados y aquellas en las que se presentan desafíos, lo cual proporciona una base para futuras mejoras en Colombia.

RESUMO Objetivo. Obter uma visão geral e abrangente da doação, do aproveitamento e do descarte de órgãos em todo o processo de doação na Colômbia. Métodos. Estudo retrospectivo de 1 451 possíveis doadores em três regiões da Colômbia que foram avaliados em 2022. Foram descritas as características gerais, o diagnóstico e os motivos para a contraindicação de potenciais doadores. Resultados. Dentre os 1 451 possíveis doadores, 441 (30,4%) preencheram os critérios de morte encefálica, formando o grupo de potenciais doadores. Em 141 casos considerados clinicamente aptos, as famílias consentiram com a doação de órgãos, e em 60 casos utilizou-se o princípio da presunção legal, resultando em 201 doadores elegíveis (13,9%). Desses, 160 (11,0%) foram doadores efetivos (ou seja, doadores nos quais foi feita uma incisão cirúrgica com a intenção de remover um órgão ou pessoas com pelo menos um órgão removido). Por fim, foram identificados 147 doadores utilizados (10,1%) (ou seja, que doaram pelo menos um órgão que foi transplantado). Foram encontradas diferenças estatisticamente significantes entre idade, sexo, diagnóstico de morte encefálica e itinerário crítico de doação entre as regiões. Um total de 411 órgãos foram transplantados de 147 doadores utilizados. Os rins foram os órgãos mais frequentemente removidos e transplantados, representando 280 (68,1%) do total, seguido de 85 fígados (20,7%), 31 corações (7,5%), 14 pulmões (3,4%) e 1 pâncreas (0,2%). A taxa de descarte de doadores falecidos com órgãos removidos foi de 8,1%. Conclusões. Cerca de um décimo dos doadores são efetivamente usados para fins de transplante. Nossos achados destacam áreas de sucesso e desafios, oferecendo uma base para futuras melhorias na Colômbia.

Frequency of skin diseases in renal transplant recipients and patients with chronic kidney disease in a tertiary center: a cross-sectional study

ABSTRACT BACKGROUND: The prevalence of chronic kidney disease (CKD) has increased in the recent decades, along with the number of patients in the terminal stages of this disease, requiring transplantation. Some skin disorders are more frequent in patients with CKD and in renal transplant recipients (RTR). OBJECTIVES: To evaluate the frequency of skin diseases in RTR and patients with CKD receiving conservative treatment. DESIGN AND SETTING: This observational cross-sectional study recruited consecutive patients with CKD and RTR from a nephrology clinic at a teaching hospital in Brazil between 2015 and 2020. METHODS: Quantitative, descriptive, and analytical approaches were used. The sample was selected based on convenience sampling. Data were collected from dermatological visits and participants' medical records. RESULTS: Overall, 308 participants were included: 206 RTR (66.9%, median age: 48 years, interquartile range [IQR] 38.0-56.0, 63.6% men) and 102 patients with CKD (33.1%, median age: 61.0 years, IQR 50.0-71.2, 48% men). The frequency of infectious skin diseases (39.3% vs. 21.6% P = 0.002) were higher in RTR than in patients with CKD. Neoplastic skin lesions were present in nine (4.4%) RTR and in only one (1.0%) patient with CKD. Among the RTR, the ratio of basal cell carcinoma to squamous cell carcinoma was 2:1. CONCLUSIONS: This study revealed that an increased frequency of infectious skin diseases may be expected in patients who have undergone kidney transplantation. Among skin cancers, BCC is more frequently observed in RTR, especially in those using azathioprine.

Características de los niños y adolescentes con enfermedades pulmonares crónicas derivados para evaluación por equipo de trasplante pulmonar de Uruguay en el período 2003 - 2023

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Summary: Introduction: lung transplantation has been recently consolidated as a therapeutic option for children and adolescents with severe lung disease when other treatments have failed. This procedure provides a good quality of life and additional survival, similar to that of transplantation in adult patients. The general indication for lung transplantation is progressive, potentially fatal respiratory failure due to parenchymal or vascular lung disease. The selection of transplant candidates is complex, requiring specific medical and socio-environmental conditions. Objectives: to analyze the clinical characteristics of pediatric patients with chronic lung diseases referred for evaluation by the Uruguayan lung transplant team. To analyze the clinical characteristics and survival of Uruguayan pediatric lung transplant patients. Material and methods: descriptive and retrospective study of all patients under 19 years of age referred to the lung transplant team between 2003 and 2023. The data was obtained from the program's database and through medical records' review. Results: 30 patients were included (15 male). The mean age of the referred patients was 13.4 ± 3.6 years. Etiologies were 17/30 (56.6%) cystic fibrosis, 4/30 (13.3%) bronchiolitis obliterans post-bone marrow transplant, 4/30 (13.3%) pulmonary hypertension, 3 /30 (10%) post-infectious bronchiolitis obliterans, and 2/30 (6.6%) diffuse interstitial lung disease. 14 patients were placed on the transplant list, of which 9 were transplanted, 1 remains on the waiting list and 4 died while waiting for the transplant. Of the rest of the patients referred for evaluation: 7 patients are still under evaluation. 2 patients were excluded for psychosocial reasons or medical reasons. 2 patients could not be followed-up and other 5 died during the evaluation. The etiologies of the pediatric transplant patients were cystic fibrosis (3/9), post-bone marrow transplant bronchiolitis obliterans (3/9), and pulmonary hypertension (3/9). Of the transplanted patients, 5 died (two in the post-operative period, and three died from sepsis between 1-2 years post-transplant). The remaining patients are in post-transplant follow-up for 1 month, 2, 7 and 9 years. No statistically significant differences in conditional survival were found when comparing adult and pediatric patients. Conclusions: results in transplanted patients in terms of characteristics and causes of mortality are comparable with those reported internationally. Post-transplant mortality was somewhat higher than in other studies, but we believe that there is bias due to the low number of patients. Given the results above, we propose that transplantation continues to be a valid therapeutic alternative in our country. The challenges of this treatment include the limited availability of suitable donor organs, the toxicity of immunosuppressive medications necessary to prevent rejection, prevention and treatment of bronchiolitis obliterans, as well as maximizing the growth, development and quality of life of the receivers.

Introdução: o transplante pulmonar consolidou-se nos últimos anos como opção terapêutica para crianças e adolescentes com doença pulmonar grave, nas quais outros tratamentos falharam. Esse procedimento proporciona boa qualidade de vida e sobrevida prolongada, semelhante ao transplante realizado em pacientes adultos. A indicação geral para transplante pulmonar é insuficiência respiratória progressiva e potencialmente fatal devido a doença pulmonar parenquimatosa ou vascular. A seleção de candidatos a transplantes é complexa, exigindo condições médicas e socioambientais específicas. Objetivos: analisar as características clínicas de pacientes pediátricos com doenças pulmonares crônicas encaminhados para avaliação pela equipe uruguaia de transplante pulmonar. Analisar as características clínicas e a sobrevida de pacientes pediátricos uruguaios transplantados pulmonares. Material e métodos: estudo descritivo e retrospectivo de todos os pacientes menores de 19 anos encaminhados à equipe de transplante pulmonar entre 2003 e 2023. Os dados foram obtidos no banco de dados do programa e por meio de revisão de prontuários. Foram incluídos 30 pacientes (15 do sexo masculino). A média de idade dos pacientes encaminhados foi de 13,4 ± 3,6 anos. As etiologias dos pacientes encaminhados foram 17/30 (56,6%) fibrose cística, 4/30 (13,3%) bronquiolite obliterante pós-transplante de medula óssea, 4/30 (13,3%) hipertensão pulmonar, 3/30 (10%) pós -bronquiolite obliterante infecciosa e 2/30 (6,6%) doença pulmonar intersticial difusa. Foram colocados na lista de transplante 14 pacientes, dos quais 9 foram transplantados, 1 permanece em lista de espera e 4 faleceram enquanto aguardavam o transplante. Do restante dos pacientes encaminhados para avaliação: 7 pacientes ainda estão em avaliação, 2 pacientes foram excluídos por motivos psicossociais ou médicos. 2 pacientes foram perdidos no acompanhamento e outros 5 faleceram durante a avaliação. As etiologias dos pacientes transplantados pediátricos foram fibrose cística (3/9), bronquiolite obliterante pós-transplante de medula óssea (3/9) e hipertensão pulmonar (3/9). Dos pacientes transplantados, 5 faleceram (dois no pós-operatório e três por sepse entre 1-2 anos pós-transplante). Os demais pacientes estão em acompanhamento pós-transplante por 1 mês, 2, 7 e 9 anos. Não foram encontradas diferenças estatisticamente significativas na sobrevida condicional quando comparamos pacientes adultos e pediátricos. Conclusões: os resultados em pacientes transplantados em termos de características e causas de mortalidade são comparáveis aos relatados internacionalmente. A mortalidade pós-transplante foi um pouco maior do que em outros estudos, mas acreditamos que exista viés devido ao baixo número de pacientes. Diante dos resultados acima mencionados, propomos que o transplante continue sendo uma alternativa terapêutica válida em nosso meio. Os desafios deste tratamento incluem a disponibilidade limitada de órgãos de doadores adequados, a toxicidade dos medicamentos imunossupressores necessários para prevenir a rejeição, prevenção e tratamento da bronquiolite obliterante, bem como maximizar o crescimento, desenvolvimento e qualidade de vida dos receptores.

Mobile game: educational technology for home care of patients undergoing liver transplantation / Juego móvil: tecnología educativa para la atención domiciliaria de patients sometidos a trasplante de hígado / Mobile game: tecnologia educacional para cuidados domiciliares do paciente submetido ao transplante hepático

ABSTRACT Objective: to develop and validate an educational game capable of supporting health education actions for patients undergoing liver transplantation. Method: this is a study of a technological product, based on the User-Centered Design framework, carried out in a reference hospital for liver transplantation. Participants were patients undergoing liver transplantation, nurses and information technology professionals. Data collection took place through semi-structured interviews and a questionnaire, using Brazilian standards for usability assessment. Data analysis occurred through content analysis, based on the calculation model for the System Usability Scale. Results: seventeen patients participated, including seven nurses and four information technology professionals. The game is made up of five paths with the main care to be carried out at home. Each path presents steps to be followed with its rules. As for validation, the overall mean was 1.38. Usability assessment by patients had a mean of 80 points, while by professionals it was above 75%. Conclusion: it is considered that the aforementioned tool is capable of being used in practice by users. Furthermore, this was adjusted to meet the needs of patients undergoing liver transplantation to support and manage home care.

RESUMEN Objetivo: desarrollar y validar un juego educativo capaz de apoyar acciones de educación en salud para pacientes sometidos a trasplante de hígado. Método: estudio de un producto tecnológico, basado en el marco del Diseño Centrado en el Usuario, realizado en un hospital de referencia para trasplante hepático. Los participantes fueron pacientes sometidos a trasplante de hígado, enfermeras y profesionales de tecnologías de la información. La recolección de datos se realizó a través de entrevistas semiestructuradas y cuestionario, utilizando estándares brasileños para la evaluación de la usabilidad. El análisis de los datos ocurrió a través del análisis de contenido, basado en el modelo de cálculo de la System Usability Scale. Resultados: participaron 17 pacientes, entre ellos siete enfermeras y cuatro profesionales de tecnologías de la información. El juego se compone de cinco recorridos cuyo cuidado principal se realizará en casa. Cada camino presenta pasos a seguir con sus reglas. En cuanto a la validación, la media general fue de 1,38. La valoración de la usabilidad por parte de los pacientes tuvo una media de 80 puntos, mientras que la de los profesionales superó el 75%. Conclusión: se considera que la herramienta antes mencionada es susceptible de ser utilizada en la práctica por los usuarios. Además, esto se ajustó para satisfacer las necesidades de los pacientes sometidos a trasplante de hígado para apoyar y gestionar la atención domiciliaria.

RESUMO Objetivo: desenvolver e validar jogo educativo capaz de subsidiar ações de educação em saúde ao paciente submetido ao transplante hepático. Método: estudo de produto tecnológico, sustentado no referencial doDesign Centrado no Usuário, realizado em hospital de referência em transplante hepático. Participantes foram pacientes submetidos ao transplante hepático, enfermeiros e profissionais da tecnologia da informação. A coleta de dados ocorreu por meio de entrevista semiestruturada e questionário, utilizando as normas brasileiras para avaliação da usabilidade. A análise dos dados ocorreu por meio de análise de conteúdo, com base no modelo de cálculo para a escala de System Usability Scale. Resultados: participaram 17 pacientes, dos quais, sete enfermeiros e quatro profissionais da tecnologia da informação. O jogo é formado por cinco caminhos com os principais cuidados a serem desenvolvidos em domicílio. Cada caminho apresenta etapas a serem seguidas com suas regras. Quanto à validação, a média geral foi de 1,38. A avaliação da usabilidade pelos pacientes teve média de 80 pontos, já pelos profissionais foi acima de 75%. Conclusão: considera-se que a referida ferramenta está apta para ser usada na prática pelos usuários. Ainda, essa foi ajustada para atender às necessidades dos pacientes submetidos ao transplante hepático para apoiar e gerenciar os cuidados em domicílio.

Construction and validation of educational technology on post-liver transplant for family caregivers / Construcción y validación de tecnología educativa sobre el período posterior a trasplantes hepáticos destinada a cuidadores familiares / Construção e validação de tecnologia educacional sobre o pós-transplante hepático para o familiar cuidador

ABSTRACT Objective: to construct and validate an educational booklet on post-liver transplant for family caregivers. Method: a methodological study carried out in two stages from August 2021 to July 2023: 1) Construction of the educational booklet aimed at liver transplant patient's family caregivers; and 2) Content and face validation by expert judges and semantic validity with the target audience. For the experts to analyze the validity data, the Content Validity Index was used (≥0.78 per item and ≥0.80 in total), as well as the Exact Binomial Distribution test (p>0.05 and 0.80) and the Intraclass Correlation Coefficient (95%) for greater reliability. In the semantic evaluation, the IRaMuTeQ software was used to guide the analysis of the interviews, using Descending Hierarchical Classification and Word Cloud. Results: after the bibliographic survey, four axes guided the construction of the booklet. The total Content Validity Index was 0.99 (p>0.05), with excellent reliability (ICC=0.946). The total Face Validity Index was 0.93 (p>0.05), with good reliability (ICC=0.766). In terms of semantics, the analytical categories pointed to a satisfactory level of perception and understanding of the booklet by the target audience. Conclusion: the technology is innovative, including caregivers in the education process, and is relevant to post-transplant care. The validation process shows the feasibility of understanding the booklet and the need to use it to improve home care.

RESUMEN Objetivo: construir y validar un folleto educativo sobre el período posterior a trasplantes hepáticos destinado a cuidadores familiares. Método: estudio metodológico realizado en dos etapas entre agosto de 2021 y julio de 2023: 1) Construcción del folleto educativo destinado a cuidadores familiares de pacientes sometidos a trasplantes hepáticos; y 2) Validación del contenido y la apariencia a cargo de jueces especialistas, además de la validez semántica con el público objetivo. Para el análisis de los datos de validez a cargo de los especialistas se utilizó el Índice de Validez de Contenido (≥ 0,78 por ítem y ≥ 0,80 en el total), además de la prueba Exacta de Distribución Binomial (p>0,05 y 0,80) y del Coeficiente de Correlación Intraclase (95%) para mayor confiabilidad. En la evaluación semántica se empleó el programa de software IRaMuTeQ para guiar el análisis de las entrevistas, por medio de la Clasificación Jerárquica Descendente y de una Nube de palabras. Resultados: después del relevamiento bibliográfico se identificaron cuatro ejes que guiaron la construcción del folleto. El Índice de Validez de Contenido total fue 0,99 (p>0,05), con excelente confiabilidad (CCI=0,946). El Índice de Validez de Apariencia total fue 0,93 (p>0,05), con buen nivel de confiabilidad (CCI=0,766). En el caso de la semántica, las categorías analíticas analizadas señalaron un nivel satisfactorio de percepción y comprensión del folleto entre el público objetivo. Conclusión: la tecnología demuestra ser innovadora, incluyendo a los cuidadores en el proceso de educación, además de ser relevante para la atención que debe proporcionarse después del trasplante. El proceso de validación denota la viabilidad de la comprensión expuesta en el folleto y la necesidad de emplearlo para mejorar los cuidados domiciliarios.

RESUMO Objetivo: construir e validar uma cartilha educativa sobre o pós-transplante hepático para o familiar cuidador. Método: estudo metodológico, realizado em duas etapas durante o período de agosto de 2021 a julho de 2023: 1) Construção da cartilha educativa voltada ao familiar cuidador do paciente transplantado hepático e 2) Validação de conteúdo e aparência pelos juízes especialistas e de validade semântica junto ao público-alvo. Para análise dos dados de validade pelos especialistas foi utilizado o Índice de Validade de Conteúdo, ≥ 0,78 por item e ≥ 0,80 no total, além do teste Exato de Distribuição Binomial (p>0,05 e 0,80) e do Coeficiente de Correlação Intraclasse (95%) para maior confiabilidade. Na avaliação semântica, foi utilizado o software IRaMuTeQ para nortear a análise das entrevistas, por meio da Classificação Hierárquica Descendente e da Nuvem de Palavras. Resultados: após o levantamento bibliográfico, quatro eixos nortearam a construção da cartilha. O Índice de Validade de Conteúdo total foi de 0,99 (p>0,05), com excelente confiabilidade (CCI=0,946). O Índice de Validade de Aparência total foi de 0,93 (p>0,05) e boa confiabilidade (CCI=0,766). Na semântica, as categorias analíticas analisadas apontaram um nível satisfatório de percepção e compreensão da cartilha pelo público-alvo. Conclusão: a tecnologia mostra-se inovadora, incluindo os cuidadores no processo de educação, sendo relevante para o cuidado pós-transplante. O processo de validação denota a viabilidade da compreensão exposta na cartilha e a necessidade de utilização dela para a melhoria do cuidado domiciliar.

Estrategias de telesalud en la atención de personas con enfermedad renal crónica: revisión integradora / Telehealth strategies in the care of people with chronic kidney disease: integrative review / Estratégias de telessaúde no atendimento às pessoas com doença renal crônica: revisão integrativa

Objetivo: evaluar las evidencias sobre estrategias de telesalud en la atención de personas con enfermedad renal crónica. Método: revisión integradora de la literatura. La búsqueda de estudios primarios se realizó en seis bases de datos: PubMed/MEDLINE, Web of Science, EMBASE, CINAHL, LILACS y Scopus. La muestra estuvo compuesta por 48 artículos publicados entre 2000 y 2021, la estrategia de telesalud fue aplicada mediante equipo multidisciplinario, médico, enfermero, farmacéutico, nutricionista y trabajador social. De los artículos se extrajo el tipo de estudio, país, estrategia aplicada, escenario, población y profesional. Los estudios fueron seleccionados mediante la lectura de título y resumen (fase 1) y, posteriormente, mediante la lectura completa (fase 2), se los categorizó por estrategia de telesalud. El resumen de resultados se presentó de forma descriptiva y los estudios se clasificaron según el nivel de evidencia. Resultados: el domicilio fue el más representativo en las terapias de diálisis y tratamiento conservador. Se identificaron seis categorías de estrategias de telesalud: dispositivos de monitoreo remoto, teleconsulta, plataforma digital, aplicaciones, estrategias multimodales y contacto telefónico. Conclusión: el uso de esas estrategias para la atención de personas con enfermedad renal crónica tiene diferentes formatos e implementaciones, las mismas son factibles para dicha población en cualquier etapa de la enfermedad y pueden ser aplicadas por diferentes profesionales de la salud especialmente en el ámbito domiciliario. La evidencia ha demostrado que la telesalud favorece la reducción de costos, la accesibilidad a ubicaciones remotas, un mejor seguimiento de la diálisis con resultados positivos sobre el control de los síntomas, la reducción de riesgos y capacitación del paciente.

Objective: to evaluate the evidence about telehealth strategies in caring for people with chronic kidney disease. Method: integrative literature review. The search for primary studies was carried out in six databases: PubMed/MEDLINE, Web of Science, EMBASE, CINAHL, LILACS, and Scopus. The sample consisted of 48 articles published between 2000 and 2021. The telehealth strategy was applied by a multidisciplinary team of doctors, nurses, pharmacists, nutritionis, and social workers. The type of study, country, strategy applied, setting, population, and professional were extracted from the articles. The studies were selected by reading the title and abstract (phase 1) and then reading them in full (phase 2), categorizing them by telehealth strategy. The results were summarized descriptively and the studies were classified according to their level of evidence. Results: the home was the most representative in dialysis and conservative treatment. Six categories of telehealth strategies were identified: remote monitoring devices, teleconsultation, digital platforms, apps, multimodality strategies, and telephone contact. Conclusion: using these strategies for the care of people with chronic kidney disease presents different forms and implementations, being feasible for the renal population at any stage of the disease and applicable by different health professionals with an emphasis on the home environment. The evidence shows that telehealth favors lower cost, accessibility to remote locations, and better monitoring of dialysis with positive resul in symptom control, risk reduction, and patient training.

Objetivo: analisar as evidências sobre as estratégias de telessaúde no atendimento às pessoas com doença renal crônica. Método: revisão integrativa da literatura. A busca pelos estudos primários foi realizada em seis bases de dados: PubMed/MEDLINE, Web of Science, EMBASE, CINAHL, LILACS e Scopus. A amostra foi composta por 48 artigos publicados entre 2000 e 2021, a estratégia de telessaúde foi aplicada por equipe multidisciplinar, médico, enfermeiro, farmacêutico, nutricionista e assistente social. Foram extraídos dos artigos o tipo de estudo, país, estratégia aplicada, cenário, população e profissional. Os estudos foram selecionados por leitura de título e resumo (fase 1) e, após, por leitura completa (fase 2), com sua categorização por estratégia de telessaúde. A síntese dos resultados foi apresentada de forma descritiva e os estudos classificados de acordo com o nível de evidência. Resultados: o domicílio foi o de maior representatividade nas terapias dialíticas e tratamento conservador. Foram identificadas seis categorias de estratégias de telessaúde: dispositivos de monitoramento remoto, teleconsulta, plataforma digital, aplicativos, estratégias multimodalidades e contato telefônico. Conclusão: a utilização dessas estratégias para o atendimento de pessoas com doença renal crônica apresenta diferentes formatos e implementações, sendo viável à população renal em quaisquer fases da doença e aplicável por diferentes profissionais de saúde com ênfase no ambiente domiciliar. As evidências apontaram que a telessaúde favorece a diminuição de custos, acessibilidade aos locais afastados, melhor monitoramento da diálise com resultados positivos no controle dos sintomas, redução dos riscos e treinamento do paciente.

Fallo intestinal crónico secundario a síndrome de intestino corto: papel actual de la cirugía, la rehabilitación médica y el trasplante intestinal. Informe evolutivo a 16 años de manejo multidisciplinario / Chronic intestinal failure due to short bowel syndrome: current role of surgery, medical rehabilitation, and intestinal transplantation. A progress report after 16 years of multidisciplinary management

RESUMEN Antecedentes: la insuficiencia intestinal, en su grado más grave, se conoce como fallo intestinal crónico (FIC). Las últimas décadas han sido testigo de la incorporación, evolución y perfeccionamiento de tratamientos que, en su conjunto, se denominan rehabilitación intestinal y abarcan tanto procedimientos quirúrgicos como tratamientos médicos que, llevados a cabo por equipos multi e interdisciplinarios, alcanzan altas tasas de éxito. Objetivo: describir los resultados de 16 años en el tratamiento de pacientes con FIC secundario a síndrome de intestino corto (SIC), y la evolución del papel de la cirugía, la rehabilitación médica y el trasplante. Material y métodos: análisis retrospectivo de una base de datos prospectiva de pacientes con fallo intestinal crónico secundario a SIC entre febrero de 2006 y marzo de 2022. Resultados: se incluyeron 492 pacientes (368 adultos-A y 124 pediátricos-P). Grupo A: 111 pacientes recibieron cirugía de reconstrucción autóloga del tracto gastrointestinal (CRATGI), 16 péptido semisintético similar al glucagón de tipo 2 (sGLP-2); el 83% logró la rehabilitación, con un 77% de supervivencia a 10 años; el 6,8% (17 pacientes) requirió trasplante intestinal (TxI), con un 89% de independencia de la nutrición parenteral (NP) al año y supervivencia post-TxI del 29% a los 10 años. Grupo B: 18 recibieron CRATGI; 9, enteroplastia serial transversa (STEP); y 6, sGLP-2; el 52% se rehabilitó, con una supervivencia del 69% a los 10 años; 28 pacientes recibieron TxI, con 69% de independencia de nutrición parenteral (NP) al año y supervivencia del 39% a los 10 años. Conclusión: los resultados presentados resaltan el papel central de la cirugía y la rehabilitación médica para alcanzar la suficiencia intestinal.

ABSTRACT Background: Severe intestinal insufficiency is known as chronic intestinal failure (CIF). In recent decades, medical treatments and surgical procedures have been incorporated, developed and improved under the name intestinal rehabilitation. When performed by multiand interdisciplinary teams, these treatments have high success rates. Objective: The aim of present study is to describe the 16-year outcomes in the management of patients with CIF secondary to short bowel syndrome (SBS) and the role of surgery, medical rehabilitation, and transplantation. Material and methods: We conducted a retrospective analysis on a prospective database of patients treated with chronic intestinal failure due to SBS between February 2006 and March 2022. Results: A total of 492 patients (368 adults (Group A) and 124 pediatric patients (Group B)] were included. Group A: 111 patients underwent autologous gastrointestinal reconstruction surgery (AGIRS), 16 were treated with semisynthetic glucagon-like peptide-2 (sGLP2); 83% achieved rehabilitation, with 77% survival at 10 years; 6.8% (17 patients) required intestinal transplantation (ITx), with 89% independence from parenteral nutrition (PN) at 1 year and post-ITx survival of 29% at 10 years. Group B: 18 patients underwent AGIRS; 9 underwent serial transverse enteroplasty (STEP); and 6 received sGLP2; 52% were rehabilitated, with 69% survival at 10 years; 28 patients received ITx, with 69% independence from PN at 1 year and 39% survival at 10 years. Conclusion: These results highlight the central role of surgery and medical rehabilitation in the recovery of intestinal function.

Evolución y factores de riesgo de mortalidad en una cohorte pediátrica con enfermedad renal crónica en Paraguay: estudio multicéntrico

Contexto: la enfermedad renal crónica (ERC) tiene una alta morbimortalidad y un alto costo de tratamiento. Entre sus causas principales en Pediatría se describen las anomalías congénitas del riñón y las vías urinarias (CAKUT, por sus siglas en inglés) Objetivo: determinar la evolución y los factores asociados a mortalidad de una cohorte pediátrica atendida en dos hospitales de referencia nacional, con el fin de elaborar estrategias para el manejo precoz y multidisciplinario de esta enfermedad y, de esa manera, optimizar los recursos para reducir la morbimortalidad de la enfermedad. Metodología: estudio de cohorte retrospectivo de pacientes de dos hospitales de referencia entre enero del 2000 y diciembre del 2020, en el cual se estudiaron: edad, sexo, seguro social, ingreso fijo, causa de la ERC, estadio de la ERC al ingreso y al final de estudio, requerimiento y tipo de diálisis, trasplante y óbito, donde el estadio de la ERC se clasificó según las guías K/DOQI (Kidney Disease Quality Iniciative). Por su parte, se relacionó óbito con edad, sexo, ingreso fijo, seguro social, estadio de ERC y requerimiento de diálisis. Se destaca que el análisis se realizó con el programa Epi Info (Atlanta), el cual usa estadística descriptiva y la prueba de chi cuadrado para establecer asociaciones con óbito a un nivel de significancia de 0,05. Resultados: se estudió a 187 pacientes de entre 2 y 17 años de edad, 96 mujeres y 91 varones, donde la mayoría eran mayores de10 años (44,9 %). Entre las causas de ERC más frecuentes se encuentran las anomalías congénitas (CAKUT) (54,5 %) y las indeterminadas (16,6 %); el estadio de ERC al ingreso estuvo repartido entre I (2,1 %), II (16 %), III (25,7 %), IV (8 %), y V (48,1 %); además, el 59,4 % requirió diálisis, el 87,3 % hemodiálisis, el 12,6 % diálisis peritoneal y 13,3 % recibieron un trasplante; por último, la mortalidad fue del 24,5 %, lo cual se asoció con el estadio de ERC al ingreso y el requerimiento de diálisis. Conclusiones: este estudio de cohorte demostró mejores resultados en la evolución de los niños con ERC diagnosticados en estadios tempranos. El diagnóstico y tratamiento precoces ayudan a mejorar la morbimortalidad.

Background: Chronic kidney disease (CKD) has high morbidity and mortality and high cost of treatment. Among the main causes are congenital anomalies of the kidney and urinary tract (CAKUT). Purpose: To determine the evolution and factors associated with mortality in a pediatric cohort attended in two national referral hospitals, in order to develop strategies for early and multidisciplinary management of this disease and, thus, optimize resources to reduce morbidity and mortality of the disease. Methodology: Retrospective cohort study of patients in two reference hospitals between January 2000 and December 2020. Age, sex, social security, fixed income, cause of CKD, CKD stage at admission and at the end of study, requirement and type of dialysis, transplant and death were studied. CKD stage was classified according to the K/DOQI (Kidney Disease Quality Initiative) guidelines. Death was related to age, sex, fixed income, social security, CKD stage, and dialysis requirement. Data analysis was performed with the Epi Info program (CDC, Atlanta), using descriptive statistics, and the chi-square test to establish associations with death at a significance level of 0.05. Results: 187 patients between 2 and 17 years of age 96 women and 91 men, were studied. Most of the patients were older than 10 years (44.9%). Among the most frequent causes of CKD are congenital anomalies (CAKUT) (54.5%) and undetermined (16,6%). CKD stage at admission was I (2,1%), II (16%), III (25,7%), IV (8%), and V (48.1%). 59.4% required dialysis, hemodialysis (87.3%), peritoneal dialysis (12.7%), 13.3% underwent kidney transplant. Mortality rate was 24.5%, which was associated with CKD stage at admission and dialysis requirement. Conclusions: This cohort study demonstrated better outcomes in children with CKD diagnoses at its early stages. The early diagnosis and treatment help to improve the morbidity and mortality.

Neumonía por Pneumocystis jirovecii asociada a hemorragia alveolar difusa en un paciente con trasplante renal / Pneumocystis jirovecii pneumonia associated with diffuse alveolar hemorrhage in a renal transplant patient. Case report

La neumonía por Pneumocystis jirovecii es una enfermedad fúngica oportunista descrita principalmente en pacientes con VIH, sin embargo, tras la introducción de la TARV, ha incrementado su incidencia en pacientes con inmunosupresión no asociada a VIH, como neoplasias hematológicas y trasplantes de órganos sólidos. Presentamos el caso de un varón de 17 años, receptor de un trasplante renal, con inmunosupresión prolongada con corticoesteroides, con cuadro clínico de tos, disnea y fiebre. La TC mostró micronódulos pulmonares centrolobulillares y vidrio esmerilado. El LBA fue compatible con hemorragia alveolar difusa (HAD), con RPC positiva para P. jirovecii. Se descartaron otras infecciones y enfermedades autoinmunes. Recibió tratamiento con cotrimoxazol con buena evolución clínica y mejoría radiológica. Si bien las causas más frecuentes de HAD son etiologías autoinmunes como enfermedades reumatológicas o vasculitis, es prioritario descartar causas infecciosas, incluyendo P. jirovecii, ya que el tratamiento dirigido puede tener un impacto significativo en la mortalidad en este grupo de pacientes.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection, described mainly in HIV patients, however, after the introduction of ART, its presentation has increased in patients with non-HIV immunosuppression, such as hematological cancers, solid or hematopoietic stem cell transplantation. We report the case of a 17-year-old male, kidney transplant patient, with prolonged immunosuppression with corticoesteroids, with history of cough, dyspnea, and fever. Chest CT evidences centrilobular pulmonary micronodules with ground glass. BAL was performed compatible with diffuse alveolar hemorrhage, with positive PCR for P. jirovecii. Other infections and autoimmune disease were ruled out. He received treatment with cotrimoxazole with clinical improvement of the patient, and follow up chest CT at the end of treatment showed decrease of pulmonary infiltrates. Although the most frequent causes of DAH are autoimmune etiologies such as rheumatic diseases or vasculitis, it is a priority to rule out infectious causes, including P. jirovecii, since targeted treatment could have a significant impact on mortality outcomes in this group of patients.

Trasplante cardíaco y autólogo de células progenitoras hematopoyéticas en pacientes con amiloidosis AL / Cardiac and autologous stem cell transplantation hematopoietic in patients with AL amyloidosis

Resumen Objetivo: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. Método: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. Resultados: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. Conclusiones: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.

Abstract Objective: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. Method: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. Results: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. Conclusions: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.

Use of sirolimus as an adjuvant therapy for kidney transplant recipients with high-risk cutaneous squamous cell carcinomas: a prospective non-randomized controlled study / Uso do sirolimo como terapia adjuvante para receptores de transplante renal com carcinoma espinocelular cutâneo de alto risco: um estudo prospectivo controlado não randomizado

ABSTRACT Introduction: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability. Methods: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion. Results: Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable. Conclusions: This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.

RESUMO Introdução: Pesquisas anteriores demonstraram benefícios da conversão tardia para inibidores de mTOR contra carcinomas espinocelulares cutâneos (CECs) em receptores de transplante renal (RTR), apesar da baixa tolerabilidade. Este estudo investigou se a conversão gradual para monoterapia com sirolimo sem dose de ataque modificou o curso da doença com melhor tolerabilidade. Métodos: Esse estudo prospectivo exploratório incluiu RTR não sensibilizados com mais de 12 meses pós-transplante, uso contínuo de terapia imunossupressora baseado em inibidor de calcineurina (CNI) associado a micofenolato de sódio ou azatioprina, com lesões de CECs de mau prognóstico. Comparou-se densidades de incidência de CECs de alto risco durante 3 anos após conversão para monoterapia com sirolimo à um grupo não randomizado com CECs classificados conforme os mesmos critérios de gravidade do grupo sirolimo, mas inadequado/não disposto à conversão. Resultados: Foram incluídos 44 pacientes (83% homens, idade média 60 ± 9,7 anos, 62% com fototipo de pele II, tempo médio pós-transplante 9 ± 5,7 anos). 25 pacientes foram convertidos para SRL e 19 indivíduos mantidos em CNI. Foi observado tendência de diminuição da densidade de incidência de todos CECs no grupo SRL e de aumento no grupo CNI (1,49 a 1,00 lesões/paciente-ano; 1,74 a 2,08 lesões/paciente-ano; p = 0,141). A densidade de incidência de lesões moderadamente diferenciadas diminuiu significativamente no grupo SRL enquanto aumentou significativamente no grupo CNI (0,31 a 0,11 lesões/paciente-ano; 0,25 a 0,62 lesões/paciente-ano; p = 0,001). No grupo SRL não houve descontinuação do sirolimo, nenhum episódio de rejeição aguda e nenhuma formação de DSA de novo. Função renal permaneceu estável. Conclusões: Esse estudo sugere que a monoterapia com sirolimo pode ser útil como terapia adjuvante de CECs de alto risco em RTR. A estratégia de conversão usada foi bem tolerada e segura em relação aos principais desfechos do transplante a médio prazo.

Infecciones bacterianas durante el primer mes post trasplante hepático. Experiencia de 12 años en un único centro. Montevideo-Uruguay / Bacterial infections during the first month after liver transplantation. 12 years experience in a single center. Montevideo-Uruguay

INTRODUCCIÓN: Las infecciones bacterianas en trasplante hepático (TH) son una de las principales causas de morbimortalidad. OBJETIVO: Caracterizar las complicaciones infecciosas bacterianas en el primer mes postrasplante. Pacientes y MÉTODOS: Estudio retrospectivo entre los años 2009-2020. RESULTADOS: 225 pacientes recibieron un TH. 80 (35,5%) desarrollaron al menos un episodio de infección bacteriana en el primer mes postrasplante hepático. Hubo 105 episodios de infección bacteriana con una incidencia de 46,6%. El foco más frecuente fue el abdominal (48,6%) y el microorganismo predominante fue Klebsiella spp. De los 104 aislamientos, el 57,6% presentaron un perfil MDR/XDR. Los pacientes que desarrollaron una complicación infecciosa presentaron menor sobrevida al alta hospitalaria en comparación con los que no la presentaron 87,5 versus 94,5% [OR 4,18 (IC 95%: 1,5-11,6)]. En el análisis multivariado la reintervención quirúrgica precoz [OR 4,286 (IC 95%: 1,911-9,61)], mostró un riesgo significativo de desarrollar una complicación infecciosa bacteriana en el primer mes postrasplante. CONCLUSIONES: Tres de cada 10 pacientes presentaron una infección bacteriana en el primer mes postrasplante con una alta incidencia de bacilos gramnegativos MDR/XDR. Los pacientes que desarrollaron una complicación infecciosa presentaron una menor sobrevida al alta. La reintervención quirúrgica precoz se identificó como un factor predisponente de infección temprana.

BACKGROUND: Bacterial infections are one of the main causes of morbidity and mortality in liver transplant recipients (LT). Aim: To characterize bacterial infectious complications in the first month an after a liver transplant. METHODS: Retrospective analysis of a cohort of liver transplant recipients who presented at least one bacterial infectious complication in the first month after transplant between 2009 and 2020. RESULTS: 225 patients were analyzed. 80 (35.5%) had a least one documented bacterial infection during the first month after transplant. 105 bacterial infections were documented, with an incidence of 46.6%. The most frequent origin was intra-abdominal (48.6%) and the predominant isolated microorganism was Klebsiella spp. Among 104 isolated microorganisms 57.6% showed MDR/XDR profile. Patients who developed a bacterial infectious complication had a shorter overall survival (OS) after discharge from hospital (87.5% vs 94.5%) [OR 4.18 (IC 95%: 1.5-11,6)]. When multivariate analysis of predisposing factors was performed early surgical reoperation was the only variable associated with an increased risk of developing a bacterial complication in the first month [OR 4.286 (IC 95%: 1.911-9.61)]. CONCLUSIONS: Three out of 10 patients developed a bacterial infectious complication during the first month after liver transplant with a high incidence of gram-negative bacillus MDR/XDR. Patients who presented infectious complications had a shorter OS after discharge, and early reoperation was identified as a predisposing factor of early infectious complications.

Anti-Hla Donor-Specific Antibodies Are Associated to Infection and Not to the Engraftment Rate in Outpatient Haploidentical Hematopoietic Cell Transplantation

ABSTRACT Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor's antigens. Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT. Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient's anti-HLA DSA test results. Data for anti-HLA-A, -B, -C, and -DR were analyzed. Recipients with DSA ≥ 500 MFI were considered positive, and those with < 500 were considered negative; the same was adopted for MFI ≥ 1000. Results: Post-transplant infection was higher in recipients with DSA ≥ 500 MFI (84.6%, p = 0.041). First-year mortality was higher in DSA-positive patients ≥ 500 MFI, p = 0.004, and DSA ≥ 1000 MFI, p = 0.022, than in DSA-negative recipients. Graft failure in the first 100 days was not associated with DSA ≥ 500 or ≥ 1000 MFI. There was no difference in acute (a-GVHD) or chronic (c-GVHD) graft versus host disease between DSA-positive and negative patients. Conclusions: There was no association of anti-HLA DSA at MFI ≥ 500 and ≥ 1000 with graft failure, however, increased infection and 1st-year mortality were documented in related haplo-HCT at the MFI cutoffs studied. (REV INVEST CLIN. 2023;75(5):249-58)

Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients

ABSTRACT Introduction: Chronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD. Objective and Method: Due to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD. Results: Our results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls. Conclusion: Moreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD.

Bioética en donantes en asistolia controlada / Bioethics in controlled asystole donor / Bioética no doador em assistolia controlada

Las campañas de prevención y promoción de salud, así como los avances en las medidas terapéuticas destinadas a los pacientes neurocríticos, han logrado reducir la incidencia de pacientes con injuria encefálica aguda (IEA) que evolucionan a la muerte encefálica (ME). Sin embargo, en la mayoría de los países de América Latina, los órganos perfusibles aptos para trasplante (TX) provienen de donantes fallecidos en ME. La donación en asistolia (DA), y en particular la donación en asistolia controlada (DAC), constituye una opción aceptada y válida para la obtención de órganos que contribuiría a la disminución de las listas de espera para trasplante. Durante el proceso de DAC, se aplican conceptos con fuerte impronta bioética cuya aplicación resulta fundamental en el momento de la toma de decisiones. El presente artículo tiene el objetivo de analizar dichos conceptos con la finalidad de otorgar herramientas válidas al equipo asistencial para aquellos procesos en los que existe deliberación moral, como ocurre en la donación de órganos en asistolia controlada, considerada parte integral de los cuidados al final de la vida.

Campaigns for health prevention and promotion, along with advancements in therapeutic measures for neurocritical patients, have succeeded in reducing the incidence of patients with acute brain injury (ABI) progressing to brain death (BD). However, in most Latin American countries, suitable perfusable organs for transplantation (TX) come from deceased donors in brain death (BD). Donation after circulatory death (DCD), particularly controlled donation after circulatory death (cDCD), represents an accepted and valid option for organ procurement that would contribute to reducing transplant waiting lists. During the cDCD process, strong bioethical principles are applied, and their implementation is crucial when making decisions. The purpose of this article is to analyze these concepts, aiming to provide valid tools to the healthcare team for processes involving moral deliberation, such as controlled circulatory death organ donation, considered an integral part of end-of-life care.

As campanhas de prevenção e promoção da saúde, bem como os avanços na medidas terapêuticas voltadas para pacientes neurocríticos conseguiram reduzir a incidência de pacientes com lesão cerebral aguda que evoluem para morte encefálica (ME). No entanto, na maioria dos países latino-americanos, os órgãos que podem ser perfundidos adequados para transplante (TX) vêm de doadores falecidos em ME. A doação em assistolia e em particular a doação em assistolia controlada (DAC),é uma opção aceita e válida para a obtenção de órgãos, o que contribuiria para a redução das listas de espera para transplantes. Durante o processo DAC, são aplicados conceitos com forte cunho bioético, que são fundamentais na o momento da tomada de decisão. Este artigo tem como objetivo analisar esses conceitos, com o objetivo de oferecer ferramentas válidas à equipe de saúde, para os processos em que há deliberação moral como ocorre na doação de órgãos em assistolia controlada considerada parte integrante dos cuidados de fim de vida.

Single-center "Argentine" analysis of post-transplant lymphoproliferative disorders: incidence, histopathological characteristics and EBV status

ABSTRACT Introduction: Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations occurring after solid organ or bone marrow transplantation. The primary aims of our study were to characterize cumulative incidence of PTLDs, clinical and pathological features according to the Epstein-Barr virus (EBV) status and survival. Methods: This was a retrospective cohort study on adult and pediatric patients, from January 2001 to December 2017. The cumulative incidence of PTLD was calculated by analyzing all the patients transplanted at our hospital, based on the database of the Organ Donation and Ablation Authority of Argentina (INCUCAI). The Kaplan-Meier method was used to plot the survival. Results: Fifty-eight cases of biopsy-confirmed PTLD were identified and 12 cases of clinical data were incomplete and these patients were excluded. The median age at the time of the PTLD diagnosis was 17.5 years (interquartile range [IQR] 9 - 57). The median interval between transplant and PTLD diagnosis was 39 months (IQR 9 - 113). The most commonly transplanted organ was the liver (24 cases, 52.2%), followed by kidney (20 cases, 43.5%). The Epstein-Barr encoding region in situ hybridization (EBER ISH) was positive in 29 (69.8%) of the 43 evaluable biopsies. The PTLD cumulative incidence was 1.84% (95%CI 1.77 - 1.91) for solid organ and 0.84% (95%CI 0.48 - 1.2) for bone marrow transplant patients. The overall survival rate at 5 years was 0.77 (95%CI 0.61 - 0.87). Subgroups by the EBV EBER status, transplant type, PTLD subtype and age group (adult vs. pediatric) showed no statistically significant association with the overall survival. Conclusion: The PTLD incidence was similar to that of previous series and the EBER did not appear as a relevant factor in our patient survival.

Risk of skin cancer in kidney, liver and heart recipients: A nationwide population-based study in Taiwan

Background: Previous population-based studies in western countries had revealed increased skin cancer risk among transplant recipients compared to the general population. However, population-based studies in Asia on skin cancer among recipients of different transplanted organs were lacking in the literature. Aims: This study aims to estimate skin cancer risk among recipients in Taiwan, examine the association between each specific type of skin cancer and each type of transplanted organ, and compare skin cancer risk between different immunosuppressive regimens. Methods: This population-based retrospective cohort study identified 7550 patients with heart, lung, kidney or liver transplantation and 30,200 controls matched for gender, age and comorbidity index from the National Health Insurance Research Database in Taiwan between 2000 and 2015. Using multivariable Cox proportional hazard models, we estimated the hazard ratios and 95% confidence intervals for the correlation of skin cancer with organ transplantation as well as immunosuppressive regimen. Results: Organ transplant recipients in Taiwan had an increased risk of skin cancer with adjusted hazard ratios of 4.327 (95% confidence intervals 2.740–6.837, P < 0.001), with the greatest risk, observed among heart recipients (adjusted hazard ratios 6.348, 95% confidence intervals 3.080–13.088, P < 0.001). The risk of non-melanoma skin cancer and melanoma was 4.473 (95% confidence intervals 2.568–7.783, P < 0.001) and 3.324 (95% confidence intervals 1.300–8.172, P < 0.001), respectively. When comparing immunosuppressants, those with calcineurin inhibitors carried the highest risk of skin cancer (adjusted hazard ratios 4.789, 95% confidence intervals 3.033–7.569, P < 0.001), followed by those with antimetabolites (adjusted hazard ratios 4.771, 95% confidence intervals 3.025–7.541, P < 0.001). Limitations: We could not evaluate confounding behavioural risk factors of skin cancers that were not documented in the database, nor could we recognize patients’ compliance with immunosuppressants. Conclusion: Organ recipients have a greater risk of skin cancer. Clinicians should inform recipients of the importance of photoprotection and regular dermatologic follow-up