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 / Characteristics of children and adolescents with chronic lung diseases referred for assessment by the Uruguayan lung transplant team in 2003 - 2023 / Características de crianças e adolescentes com doenças pulmonares crônicas referidas para avaliação pela equipe uruguaia de transplante pulmonar no período 2003 - 2023

Introducción: el trasplante pulmonar se ha consolidado en los últimos años como una opción terapéutica para niños y adolescentes con enfermedad pulmonar grave en la que han fracasado otros tratamientos. Este procedimiento otorga una buena calidad de vida y una supervivencia prolongada, similar a la del trasplante realizado en pacientes adultos. La indicación general para el trasplante pulmonar es la insuficiencia respiratoria progresiva, y potencialmente letal, debida a una enfermedad pulmonar parenquimatosa o vascular. La selección de candidatos a trasplante es compleja, requiriendo condiciones médicas y socioambientales específicas. Objetivos: analizar las características clínicas de los pacientes pediátricos con enfermedades pulmonares crónicas derivados para evaluación por el equipo de trasplante pulmonar de Uruguay. Analizar las características clínicas y sobrevida de los pacientes trasplantados pulmonares pediátricos uruguayos. Material y métodos: estudio descriptivo y retrospectivo de todos los pacientes menores de 19 años derivados al equipo de trasplante pulmonar entre 2003 y 2023. Datos obtenidos de la base del programa y mediante revisión de historias clínicas. Resultados: se incluyeron 30 pacientes (15 de sexo masculino). La media de edad de los pacientes derivados fue de 13,4 ± 3,6 años. Las etiologías de los pacientes derivados fueron 17/30 (56,6%) fibrosis quística, 4/30 (13,3%) bronquiolitis obliterante postrasplante de médula ósea, 4/30 (13,3%) hipertensión pulmonar, 3/30 (10%) bronquiolitis obliterante posinfecciosa y 2/30 (6,6%) enfermedad pulmonar intersticial difusa. Ingresaron en lista de trasplante 14 pacientes, de los cuales 9 se trasplantaron, 1 se mantiene en lista de espera y 4 fallecieron a la espera del trasplante. Del resto de los pacientes derivados para evaluación: 7 pacientes se encuentran aún en evaluación. Fueron excluidos por razones psicosociales o causas médicas 2 pacientes. Dos pacientes tuvieron pérdida de seguimiento y otros 5 fallecieron durante la evaluación. Las etiologías de los pacientes trasplantados pediátricos fueron fibrosis quística (3/9), bronquiolitis obliterante postrasplante de médula ósea (3/9) e hipertensión pulmonar (3/9). De los pacientes trasplantados, 5 fallecieron (2 en el posoperatorio y 3 fallecieron por sepsis entre 1-2 años postrasplante). Los restantes pacientes están en seguimiento postrasplante hace un mes, 2, 7 y 9 años. No se han encontrado diferencias estadísticamente significativas en la sobrevida condicional cuando se compararon pacientes adultos y pediátricos. Conclusiones: los resultados en los pacientes trasplantados en cuanto a características y causas de mortalidad son comparables con los reportados internacionalmente. La mortalidad postrasplante fue algo mayor que en otros estudios, pero creemos que existe sesgo por el bajo número de pacientes. Dados los resultados mencionados, planteamos que el trasplante sigue siendo una alternativa terapéutica válida en nuestro medio. Los desafíos de este tratamiento incluyen la disponibilidad limitada de órganos de donantes adecuados, la toxicidad de los medicamentos inmunosupresores necesarios para prevenir el rechazo, la prevención y el tratamiento de la bronquiolitis obliterante, así como maximizar el crecimiento, el desarrollo y la calidad de vida de los receptores.

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.

Actualización en fibrosis quística: uso de exacaftor/tezacaftor/ivacaftor/en pacientes con fibrosis quística port-trasplante pulmonar / Use of exacaftor/tezacaftor/ivacaftor in cystic patients post lung transplantation

El uso de moduladores de CFTR en pacientes con fibrosis quística post trasplante pulmonar es un tema todavía controversial. Varias publicaciones reportan los beneficios del modulador elexacaftor/tezacaftor/ivacaftor en los síntomas extrapulmonares de la fibrosis quística, especialmente enfermedad sinusal, síntomas gastrointestinales y diabetes. Un número alto de pacientes debe discontinuar el tratamiento por mala tolerancia, sin embargo, no se describen interacciones de importancia con el tratamiento inmunosupresor. Se debe considerar para su uso los riesgos versus beneficios en forma individual en cada paciente.

The use of CFTR modulators in patients with cystic fibrosis after lung transplantation is still a controversial issue. Several publications report the benefits of the use of the modulator elexacaftor/tezacaftor/ivacaftor on extrapulmonary symptoms of cystic fibrosis, especially sinus disease, gastrointestinal symptoms and diabetes. A high number of patients must discontinue treatment due to poor tolerance; however, no significant interactions with immunosuppressive treatment have been described. The individual risk-benefit of each patient should be considered for its use.

Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients aged over 65 years / 医学前沿

The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged ≽ 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65-70 years (111 recipients, group 65-70) and ≽ 70 years (55 recipients, group ≽ 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group ≽ 70 (30.9% vs. 14.4% in group 65-70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65-70) and 7.3% (group ≽ 70) of patients. Kaplan-Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.

Características clínicas y resultados de pacientes con fibrosis quística con enfermedad pulmonar avanzada: experiencia en 10 años del Instituto Nacional del Tórax / Clinical features and outcomes of cystic fibrosis patients with advanced lung disease: experience of 10 years at the Instituto Nacional del Tórax

La enfermedad pulmonar avanzada (EPAV) es la principal causa de morbimortalidad en pacientes con Fibrosis Quística (FQ). Objetivo: describir características clínicas de pacientes con FQ con EPAV y mortalidad en el seguimiento. Método: Estudio descriptivo, retrospectivo de pacientes con FQ y EPAV: VEF1 4 años de vida. Un 75% era portador de infección crónica por Pseudomonas. Un 68% era dependiente de oxígeno y un 18% de ventilación mecánica no invasiva. El 70 % tuvo 2 o más hospitalizaciones el último año de seguimiento. De 27 pacientes derivados a trasplante, 7 se trasplantaron, 3 fallecieron en lista para trasplante, 9 presentaron alguna contraindicación: 4 de ellos por desnutrición y 5 por mala adherencia y escasa red de apoyo. En el seguimiento un 32% (n = 14) falleció, 93% de causa respiratoria. Conclusión: Un 39% de los pacientes tenían EPAV cuyo diagnóstico de FQ en promedio fue a los 11,2 años (SD ± 13 a). Las barreras de ingreso a lista para trasplante fueron: desnutrición, mala adherencia y falta de red de apoyo. Esta es una población con una elevada mortalidad.

Advanced cystic fibrosis lung disease (ACFLD) is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Objective: to describe clinical characteristics of patients with CF with ACFLD and mortality during follow-up. Method: Descriptive, retrospective study of patients with CF and ACFLD: FEVi < 40%, oxygen dependent, and/or referred to a lung transplantprogram. Clinical, microbiological, functional, genetic and mortality characteristics were collected. Results: Of 111 controlled patients, 39% met criteria for ACFLD. 52% were men and the mean age was 29,8 years- old. The average BMI was 19.9 kg/m2, 72% had pancreatic insufficiency and 87% had a genetic study, being the DF508 mutation the most frequent (67%). The average age of diagnosis was 11.2 years (SD ± 13 years), being in 54,5% over the age of 4 years. 75% had chronic Pseudomonas infection. 68% were oxygen dependent and 18% on noninvasive mechanical ventilation. In the last year of follow-up 70% had 2 or more hospitalizations. Of 27 patients who have been referred for transplantation, 7 underwent lung transplantation, 3 died waiting on the transplant list, 9 had contraindications: 4 due to malnutrition and 5 to poor adherence and poor support network. 32% (n = 14) of the ACFLD patients died, 93% due to respiratory causes. Conclusion: 39% of the patients had ACFLD. The average age for CF diagnosis was 11.2 years (SD ± 13 years) Barriers to entering the transplant list are: malnutrition, poor adherence, and lack of a support network. This is a population with a high mortality.

Approach and anesthetic management for kidney transplantation in a patient with bilateral lung transplantation: case report

Abstract Lung transplantation is the last resort for end-stage lung disease treatment. Due to increased survival, lung recipients present an increased likelihood to be submitted to anesthesia and surgery. This case report describes a 23-year-old female patient with history of lung transplantation for cystic fibrosis, with multiple complications, and chronic kidney disease, and who underwent kidney transplantation under general anesthesia. Understanding the pathophysiology and changes related to immunosuppressive therapy is essential to anesthetic technique planning and safety, and for perioperative management. The success of both anesthesia and surgery requires a qualified multidisciplinary team due to the rarity of the clinical scenario and high incidence of associated morbidity and mortality.

O enfermeiro no processo de captação de coração e pulmão em um centro transplantador / La enfermera en el proceso de captura de corazón y pulmón en un centro de trasplantes / The nurse's performance in the heart and lung capture process in transplantation center

Objetivo:Descrever as atividades implementadas pelo enfermeiro no processo de captação de coração e pulmão em um centro transplantador brasileiro e sua implicação no aumento do número de transplantes realizados. Métodos: Estudo descritivo e observacional, com foco no organograma instituído sobre as atividades do enfermeiro para avaliação e o aceite do doador. Resultados:Com a formação da unidade, exclusivamente dedicada ao processo captação/transplante, houve entre os meses de agosto de 2013 e dezembro de 2021, um aumento de 138,18% na realização de transplantes cardíacos adultos, 76,54% nos transplantes pediátricos e/ou cardiopatias congênitas e 63,22% nos procedimentos de pulmão,quando comparado ao mesmo período dos anos anteriores.Conclusão: O estudo descreve pela primeira vez a importância da atuação do enfermeiro na implementação de um programa de transplantes de sucesso e como suas ações contribuíram para o aumento do número de procedimentos realizados e podem servir de modelo para outros centros.(AU)

Objective: To describe the activities performed by nurses in the heart and lung harvesting process in a Brazilian transplant center and their implication in the increase in the number of transplants performed. Methods: Descriptive and observational study, focusing on the organizational chart established on the activities of nurses for the evaluation and acceptance of the donor. Results: With the formation of the unit, exclusively dedicated to the capture/transplantation process, between August 2013 and December 2021, there was an increase of 138.18% in adult heart transplants, 76.54% in pediatric transplants and/ or congenital heart disease and 63.22% in lung procedures, when compared to the same period in previous years. Conclusion: The study describes for the first time the importance of nurses' performance in the implementation of a successful transplant program and how their actions contributed to the increase in the number of procedures performed and can serve as a model for other centers.(AU)

Objetivo: Describir las actividades realizadas por enfermeros en el proceso de extracción de corazón y pulmón en un centro de trasplante brasileño y su implicación en el aumento de trasplantes realizados. Métodos: Estudio descriptivo y observacional, con foco en el organigrama establecido sobre las actividades de los enfermeros para la evaluación y aceptación del donante. Resultados: Con la formación de la unidad, dedicada exclusivamente al proceso de captación/trasplante, entre agosto de 2013 y diciembre de 2021, hubo un aumento del 138,18% en trasplantes cardíacos adultos, 76,54% en trasplantes pediátricos y/o cardiopatías congénitas y 63,22% % en procedimientos pulmonares, en comparación con años anteriores. Conclusión: El estudio describe por primera vez la importancia de la actuación de los enfermeros en la implementación de un programa de trasplante exitoso y cómo sus acciones contribuyeron para el aumento del número de procedimientos realizados y pueden servir de modelo para otros centros.(AU)

Trasplante pulmonar: una perspectiva desde la inmunología / Lung transplantation: a perspective from immunology

Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.

Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.

Incidência de reações adversas associadas ao uso de inibidores de calcineurina em pacientes submetidos ao transplante pulmonar / Incidence of adverse reactions associated with the use of calcineurin inhibitors in patients undergoing lung transplantation

Introdução: O uso de terapia imunossupressora é de extrema importância no transplante pulmonar, entretanto existem diversas reações adversas (RAMs) associadas ao seu uso. Neste trabalho buscamos descrever a incidência de perda de função renal (FR), diabetes mellitus (DM), hipertensão arterial sistêmica (HAS) e hipercolesterolemia associadas ao uso de ICN na população de transplantados pulmonares do Hospital de Clínicas de Porto Alegre após 1 ano de transplante.Metodologia: Estudo de coorte retrospectivo, conduzido no Hospital de Clínicas de Porto Alegre. Foram incluídos os pacientes transplantados de pulmão no período de 2016 a 2018.Resultados: Após um ano do transplante 56,5% (13/23) tiveram uma perda de FR em comparação ao basal, mas com valores ainda dentro da normalidade e 30,4% (7/23) perderam FR. A diferença de FR antes e após o transplante foi estatisticamente significativa com p < 0,001, no entanto não foi observado diferença entre os ICN (p = 0,499). Entre as variáveis: DM, HAS e Hipercolesterolemia, apenas o desenvolvimento de HAS foi estaticamente significativo quando comparado ao período pré-transplante (p < 0,001).Conclusão: Nossos dados demonstraram importante perda de FR após uso de imunossupressores ICN, corroborando com dados já publicados, no entanto, não foi possível identificar associação com ICN específico, sugerindo que benefícios na intercambialidade de terapias entre os ICN na tentativa de preservação da FR devem ser melhor estudados. Diante da possibilidade de desenvolvimento de RAMs associadas ao uso de imunossupressores, destacamos a importância da inserção do farmacêutico clínico nas equipes de transplante.

Introduction: Immunosuppressive therapy is extremely important in lung transplantation, but there are several adverse drug reactions (ADRs) associated with its use.Objective: To report the incidence of loss of renal function (RF), diabetes mellitus (DM), systemic arterial hypertension (SAH), and hypercholesterolemia associated with the use of calcineurin inhibitors (CNIs) in the population of lung transplant recipients at Hospital de Clínicas de Porto Alegre at 1 year after transplant. Methods: We conducted a retrospective cohort study of patients undergoing a lung transplant at Hospital de Clínicas de Porto Alegre from 2016 to 2018.Results: At 1 year after transplant, 56.5% (13/23) had loss of RF compared with baseline, but the values remained within the normal range, whereas 30.4% (7/23) had complete loss of RF. There was a statistically significant difference in RF before and after transplant (p < 0.001), but not in CNIs (p = 0.499). Among the variables DM, SAH, and hypercholesterolemia, only the development of SAH was statistically significant compared with the pre-transplant period (p < 0.001).Conclusion: Our data demonstrated an important loss of RF after the use of CNI immunosuppressants, which is consistent with published data. However, no association was identified with the type of CNI, suggesting that the benefits of the interchangeability of CNI therapies aimed at preserving RF should be further studied. Given the potential occurrence of ADRs associated with the use of immunosuppressants, we highlight the importance of the presence of a clinical pharmacist in the transplant team.

Estrategias para aumentar la disponibilidad de órganos destinados a trasplante pulmonar. Enfoque desde Argentina / Strategies to increase the availability of organs destined for lung transplantation. Approach from Argentina

Resumen Ante la escasez de donantes pulmonares, el aumento de los pacientes en lista de espera y el aumento de las muertes en lista de espera existen varias estrategias que buscan resolver estos problemas. Las estrategias de promoción son necesarias, continuas y transver sales a todo el proceso. Las de procuración implican mejora continua en la calidad de atención médica, siendo muy costo-efectivas en nuestro contexto. Las de distribución ya se emplean y han generado mejoras en el acceso al trasplante; deben ser constantemente evaluadas. Las de selección involucran mejoras a expensas de mayores costos a veces con consecuencias negativas, por lo que deben ser evaluadas caso a caso. El uso de EVLP es efectivo, aunque pareciera no ser una intervención costo-efectiva en nuestro medio debiendo emplearse otras estrategias previamente. La utilización de donantes a corazón parado es efectiva aunque requiere de una inversión en el sistema logístico que no parece ser viable por el momento en Argentina.

Abstract Given the shortage of lung donors and the increase in patients and deaths on the waiting lists, there are several strategies that could be carried out. Promotion strategies are necessary, continuous and transversal to the entire process. Strategies that attempt to enhance organ procurement involve continuous improvement in the quality of healthcare, which is highly profitable in our context. Interventions on grafts distribution are already in use and have generated improvements in access to lung transplantation. Laxity in the selection criteria generates higher costs, sometimes with negative consequences, so a case-by-case selection must be applied. Ex vivo lung perfusion is effective, although it does not appear to be a cost-effective intervention in our country, other strategies must be implemented previously. The use of non-heart-beating lung donors requires an investment in a logistics system that nowadays does not seem viable in Argentina.

Delayed chest closure for oversized lung allograft in lung transplantation: a retrospective analysis from turkey

Abstract Introduction: The aim of this study was to evaluate the delayed chest closure (DCC) results in patients who underwent lung transplantation. Methods: Sixty patients were evaluated retrospectively. Only bilateral lung transplantations and DCC for oversized lung allograft (OLA) were included in the study. Six patients who underwent single lung transplantation, four patients who underwent lobar transplantation, two patients who underwent retransplantation, and four patients who underwent DCC due to bleeding risk were excluded from the study. Forty-four patients were divided into groups as primary chest closure (PCC) (n=28) and DCC (n=16). Demographics, donor characteristics, and operative features and outcomes of the patients were compared. Results: The mean age was 44.5 years. There was no significant difference between the demographics of the groups (P>0.05). The donor/recipient predicted total lung capacity ratio was significantly higher in the DCC group than in the PCC group (1.06 vs. 0.96, P=0.008). Extubation time (4.3 vs. 3.1 days, P=0.002) and intensive care unit length of stay (7.6 vs. 5.2 days, P=0.016) were significantly higher in the DCC group than in the PCC group. In the DCC group, postoperative wound infection was significantly higher than in the PCC group (18.6% vs. 0%, P=0.19). Median survival was 14 months in all patients and there was no significant difference in survival between the groups (16 vs. 13 months, P=0.300). Conclusion: DCC is a safe and effective method for the management of OLA in lung transplantation.

Experiencia en trasplante pulmonar pediátrico en Chile / Experience with pediatric lung transplantation in Chile

El trasplante de pulmón (TP) es una opción para pacientes pediátricos con enfermedades pulmonares terminales. OBJETIVO: Evaluar resultados y sobrevida de pacientes pediátricos trasplantados de pulmón. MÉTODOS: Análisis retrospectivo de registros clínicos de pacientes TP ≤ 15 años de Clínica Las Condes. Se analizaron datos demográficos, tipo de trasplante, función pulmonar basal y post trasplante, complicaciones precoces y tardías y sobrevida. RESULTADOS: Nueve pacientes < 15 años de edad se han trasplantado. La edad promedio fue 12,7 años. La principal indicación fue fibrosis quística (7 pacientes). El IMC promedio fue de 17,6 y todos estaban con oxígeno domiciliario. El 77% utilizó soporte extracorpóreo intraoperatorio. Las principales complicaciones precoces fueron hemorragia y la disfunción primaria de injerto mientras que las tardías fueron principalmente las infecciones y la disfunción crónica de injerto. Cuatro pacientes han fallecido y la sobrevida a dos años fue de 85%. El trasplante les permitió una reinserción escolar y 3 lograron completar estudios universitarios. CONCLUSIÓN: El trasplante pulmonar es una alternativa para niños con enfermedades pulmonares avanzadas mejorando su sobrevida y calidad de vida.

Lung transplantation (TP) is a treatment option in children with terminal lung diseases. OBJECTIVE: To evaluate the results and survival of pediatrics lung transplant patients. METHODS: Retrospective analysis of clinical records of lung transplantation of patients ≤ 15 years from Clínica Las Condes, Santiago, Chile. Demographic data, type of transplant, baseline and post transplant lung function, early and late complications and survival rate were analyzed. RESULTS: Nine patients ≤ 15 years-old were transplanted. The average age at transplant was 12.7 years. The main indication was cystic fibrosis (7 patients). The average BMI was 17.6 and all the patients were with home oxygen therapy. 77% used extracorporeal intraoperative support. Average baseline FEV1 was 25.2% with progressive improvement in FEV1 of 77% in the first year. The main early complications were hemorrhage and primary graft dysfunction, while late complications were infections and chronic graft dysfunction. Four patients have died and the estimated 2 years survival was 85%. They achieved school reinsertion and three managed to complete university studies. CONCLUSION: Lung transplantation is an alternative for children with advanced lung diseases improving their survival and quality of life.

Trasplante pulmonar ex vivo: primera experiencia en Chile y Latinoamérica / Lung transplant with ex vivo lung perfusion, Chilean and Latin American first experience

Background: The number of patients waiting for a lung transplant worldwide greatly exceeds the number of available donors. Ex vivo lung perfusion is a useful tool that allows marginal donor lungs to be evaluated and reconditioned for a successful lung transplantation. Aim: To describe the first Chilean and Latin American experience in ex vivo lung perfusion for marginal donor lungs before transplantation. Material and Methods: Descriptive analysis of all ex vivo lung perfusion conducted for marginal donor lungs at a private clinic, from April 2019 to October 2020. High risk donor lungs and rejected lungs from other transplantation centers were included. The "Toronto Protocol" was used for ex vivo lung perfusion. Donor lung characteristics and recipient outcomes were studied. Results: During the study period, five ex vivo lung perfusions were performed. All lungs were reconditioned and transplanted. No complications were associated. There were no primary graft dysfunctions and only one chronic allograft dysfunction. There was no mortality during the first year. The median arterial oxygen partial pressure/fractional inspired oxygen ratio increased from 266 mm Hg in the donor lung to 419 after 3 hours of ex vivo lung perfusion (p = 0.043). Conclusions: ex vivo lung perfusion is a safe and useful tool that allows marginal donor lungs to be reconditioned and successfully transplanted.

Soporte ventilatorio no invasivo como puente hacia el trasplante pulmonar: reporte de un caso / Bridging to lung transplant using noninvasive ventilatory support: a case report

El soporte ventilatorio no invasivo es una herramienta que ha demostrado mejorar la sobrevida de pacientes con falla muscular de la bomba respiratoria y el manejo de enfermedades pulmonares crónicas, incluso la ventilación no invasiva nocturna ha servido de puente hacia el trasplante pulmonar. Se presenta el caso de una adolescente de 14 años con enfermedad pulmonar crónica hipoxémica severa y falla ventilatoria secundaria, que requirió ventilación prolongada y traqueostomía en espera de trasplante pulmonar. Luego de reevaluar indemnidad de la vía aérea fue decanulada a soporte ventilatorio no invasivo, con uso alternado de mascarilla nasal nocturna y pieza bucal diurna, permitiendo descanso muscular respiratorio eficiente, y mejoría de flujo de tos con técnicas de apilamiento de aire. Este plan permitió una decanulación segura y realizar soporte continuo ventilatorio no invasivo con un programa de rehabilitación cardiorrespiratorio. Generalmente, el soporte ventilatorio no invasivo se utiliza en trastornos primarios de la bomba respiratoria. En este caso, se indicó para enfermedad pulmonar crónica hipoxémica, mostrando claros beneficios con oxigenación adecuada, buen rendimiento cardiovascular con mejor tolerancia al ejercicio y entrenamiento en el escenario de preparación al trasplante pulmonar.

Noninvasive Ventilatory Support has demonstrated to improve survival of patients with ventilatory pump muscle failure and nocturnal noninvasive ventilation is useful in chronic lung disease, even bridging to lung transplant. We present a 14 years old girl with severe hypoxemic chronic lung disease and secondary ventilatory failure, who required continuous long-term ventilation and underwent a tracheostomy waiting for lung transplant. After reevaluated the airway patency the patient was decannulated to Noninvasive Ventilation Support, alternating nocturnal nasal mask with diurnal mouth piece in order to provide efficient respiratory muscle rest, made air stacking and improved cough flow. This plan allows safe decannulation to continuous Noninvasive Ventilatory Support tailoring a rehabilitation cardiorespiratory program. Usually, Noninvasive Ventilation Support is prescribed for primary respiratory pump muscles failure, but in this case, it was applied for a hypoxemic chronic lung disease. Clear benefits were observed leading to appropriate oxygenation, good cardiovascular performance with better tolerance to exercise for training in the preparatory scenario of a lung transplant.

Early stage of antibody-mediated rejection after lung transplantation： A case report and literature review / 中南大学学报(医学版)

Antibody-mediated rejection (AMR) is a rare and serious complication after lung transplantation, with no characteristic of pathological manifestation, no systematic standard treatment, and the poor efficacy and prognosis. We reported a case of early AMR after lung transplantation and the relevant literature has been reviewed. A male patient presented with symptoms of cold 99 days after transplantation and resolved after symptomatic treatment. He admitted to the hospital 14 days later because of a sudden dyspnea and fever. Anti-bacteria, anti-fungi, anti-virus, and anti-pneumocystis carinii treatment were ineffective, and a dose of 1 000 mg methylprednisolone did not work too. The patient's condition deteriorated rapidly and tracheal intubation was done to maintain breathing. Serum panel reactive antibody and donor specific antibody showed postive in humen leukocyte antigen (HLA) II antibody. Pathological examination after transbronchial transplantation lung biopsy showed acute rejection. Clinical AMR was diagnosed combined the donor-specific antibody with the pathological result. The patient was functionally recovered after combined treatment with thymoglobuline, rituximab, plasmapheresis, and immunoglobulin. No chronic lung allograft dysfunction was found after 3 years follow up. We should alert the occurrence of AMR in lung transplantation recipient who admitted to hospital with a sudden dyspnea and fever while showed no effect after common anti-infection and anti-rejection treatment. Transbronchial transplantation lung biopsy and the presence of serum donor-specific antibody are helpful to the diagnosis. The treatment should be preemptive and a comprehensive approach should be adopted.

Acute kidney injury following adult lung transplantation / 中华医学杂志(英文版)

BACKGROUND@#Acute kidney injury (AKI) is a common and serious complication following lung transplantation (LTx), and it is associated with high mortality and morbidity. This study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical outcomes.@*METHODS@#This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019. The outcomes were AKI incidence, risk factors, mortality, and kidney recovery. Multivariate analysis was performed to identify independent risk factors. Survival analysis was presented using the Kaplan-Meier curves.@*RESULTS@#AKI occurred in 137 of the 191 patients (71.7%), with transient AKI in 43 (22.5%) and persistent AKI in 94 (49.2%). AKI stage 1 occurred in 27/191 (14.1%), stage 2 in 46/191 (24.1%), and stage 3 in 64/191 (33.5%) of the AKI patients. Renal replacement therapy (RRT) was administered to 35/191 (18.3%) of the patients. Male sex, older age, mechanical ventilation (MV), severe hypotension, septic shock, multiple organ dysfunction (MODS), prolonged extracorporeal membrane oxygenation (ECMO), reintubation, and nephrotoxic agents were associated with AKI (P < 0.050). Persistent AKI was independently associated with pre-operative pulmonary hypertension, severe hypotension, post-operative MODS, and nephrotoxic agents. Severe hypotension, septic shock, MODS, reintubation, prolonged MV, and ECMO during or after LTx were related to severe AKI (stage 3) (P < 0.050). Patients with persistent and severe AKI had a significantly longer duration of MV, longer duration in the intensive care unit (ICU), worse downstream kidney function, and reduced survival (P < 0.050).@*CONCLUSIONS@#AKI is common after LTx, but the pathogenic mechanism of AKI is complicated, and prerenal causes are important. Persistent and severe AKI were associated with poor short- and long-term kidney function and reduced survival in LTx patients.

Accuracy of echocardiography and chest tomography for pulmonary hypertension screening in patients awaiting lung transplantation / Acurácia do ecocardiograma e da tomografia de tórax para rastreamento de hipertensão pulmonar em pacientes aguardando transplante de pulmão

ABSTRACT Objective To examine the accuracy of a pulmonary hypertension screening strategy based on a combination of echocardiographic data and tomographic measurements (pulmonary artery diameter and pulmonary artery diameter to ascending aorta diameter ratio) in patients with chronic lung disease referred for lung transplantation. Methods A retrospective observational study with patients with pulmonary emphysema or fibrosis referred for transplantation between 2012 and 2016. Pulmonary hypertension was defined as mean pulmonary artery pressure ≥25mmHg, or between 21 and 24mmHg, with pulmonary vascular resistance >3 Wood units on right heart catheterization. Tomographic measurements were made by two independent radiologists. Results This sample comprised 13 patients with emphysema and 19 patients with pulmonary fibrosis. Of these, 18 had pulmonary hypertension. The level of agreement in tomographic measurements made by radiologists was high (intraclass correlation coefficients 0.936 and 0.940, for pulmonary artery diameter and pulmonary artery diameter to ascending aorta diameter ratio, respectively). Areas under the ROC curves constructed for pulmonary artery diameter, pulmonary artery diameter to ascending aorta diameter ratio, and pulmonary artery systolic pressure as predictors of pulmonary hypertension were 0.540, 0.629 and 0.783, respectively. The sensitivity, specificity and negative predictive value of pulmonary artery systolic pressure ≥40mmHg were 67%, 79% and 65%, respectively. The combined criterion (pulmonary artery diameter to ascending aorta diameter ratio >1 and/or pulmonary artery systolic pressure ≥40mmHg) achieved sensitivity of 72%, specificity of 79%, and a negative predictive value of 69%. Conclusion Measurements of pulmonary artery and ascending aorta diameter were highly reproducible. The association of pulmonary artery and aortic diameter >1 and/or pulmonary artery systolic pressure ≥40mmHg improved the sensitivity and the negative predictive value for pulmonary hypertension screening. This strategy demands prospective validation to assess safety and cost-effectiveness.

RESUMO Objetivo Avaliar a acurácia de uma estratégia de rastreamento de hipertensão pulmonar baseada na combinação de dados de ecocardiograma com as medidas derivadas da tomografia computadorizada (diâmetro da artéria pulmonar e razão entre diâmetro da artéria pulmonar e diâmetro da aorta ascendente) em pacientes pneumopatas crônicos encaminhados para transplante pulmonar. Métodos Estudo observacional retrospectivo realizado com pacientes com enfisema e fibrose pulmonar avaliados para transplante entre 2012 e 2016. Definiu-se hipertensão pulmonar como pressão arterial pulmonar média ≥25mmHg, ou entre 21 a 24mmHg, com resistência vascular pulmonar >3 unidades Wood no cateterismo direito. As medidas tomográficas foram realizadas por dois radiologistas independentes. Resultados Foram incluídos 13 pacientes com enfisema e 19 com fibrose pulmonar, sendo 18 com hipertensão pulmonar. Houve alta concordância entre os radiologistas em relação às medidas tomográficas (coeficientes de correlação intraclasse para diâmetro da artéria pulmonar de 0,936 e diâmetro da artéria pulmonar/diâmetro da aorta ascendente de 0,940). As áreas abaixo da curva ROC de diâmetro da artéria pulmonar, diâmetro da artéria pulmonar/diâmetro da aorta ascendente, e pressão sistólica da artéria pulmonar como preditores de hipertensão pulmonar foram 0,540, 0,629 e 0,783, respectivamente. A sensibilidade, especificidade e valor preditivo negativo da pressão de sistólica de artéria pulmonar ≥40mmHg foram 67%, 79% e 65%, respectivamente. O critério combinado de diâmetro da artéria pulmonar/diâmetro da aorta ascendente >1 e/ou pressão sistólica da artéria pulmonar ≥40mmHg mostrou sensibilidade de 72%, especificidade de 79%, e valor preditivo negativo de 69%. Conclusão Os diâmetros da artéria pulmonar e da aorta ascendente foram altamente reprodutíveis. A associação entre diâmetro da artéria pulmonar e diâmetro da aorta ascendente >1 e/ou pressão sistólica da artéria pulmonar ≥40mmHg melhorou a sensibilidade e o valor preditivo negativo para rastreamento de hipertensão pulmonar. Essa estratégia requer validação prospectiva para se avaliarem segurança e custo-efetividade.

Fatores solúveis de células-tronco mesenquimais (FS-CTM) como uma ferramenta potencial para reduzir a inflamação nos pulmões de doadores após choque hipovolêmico / Soluble factors of mesenchimal stem cells (FS-MSC) as a potential tool to reduce inflammation in donor's lungs after hypovolemic shock

RESUMO Objetivo A escassez de pulmões viáveis ainda é um grande obstáculo para o transplante. As vítimas de trauma, que constituem potenciais doadores de pulmão, comumente apresentam choque hipovolêmico que acarreta inflamação e deterioração pulmonar e rejeição após o transplante. Buscando melhorar o enxerto pulmonar, testaram-se novas abordagens ao tratamento do doador. Este estudo foca o tratamento com células-tronco mesenquimais (CTMs) ou fatores solúveis produzidos pelas CTMs (FS-CTMs), usando um modelo com ratos para doadores de pulmão após choque hemorrágico. Métodos Quarenta e oito ratos foram divididos em quatro grupos: Controle (n=12), animais sem indução de choque hipovolêmico; Choque (n=12), animais submetidos a choque hipovolêmico (pressão arterial média de 40 mmHg); CTM (n=12), animais submetidos a choque hipovolêmico e tratados com CTMs; e FS (n=12), animais submetidos a choque hipovolêmico e tratados com FS-CTMs. Os animais foram submetidos a um procedimento de choque hipovolêmico (40 mmHg) com 50 minutos de duração. Os animais tratados foram monitorados por 115 minutos. Realizamos análise histopatológica do tecido pulmonar e quantificação dos marcadores inflamatórios (TNF-α, IL-1β, IL-6, IL-10, iCAM e vCAM) no tecido pulmonar e leucócitos no sangue periférico (LSPs). Resultados O choque hemorrágico resultou em taxas mais altas de LSPs e infiltrado de neutrófilos nos pulmões. Os animais do grupo FS apresentaram menor densidade de neutrófilos em comparação com os animais dos grupos Choque e CTM (p<0,001). Não foram observadas diferenças entre os grupos quanto aos níveis de citocinas no tecido pulmonar. Conclusão Os pulmões dos ratos submetidos a choque hemorrágico e tratados com FS-CTM apresentaram inflamação reduzida indicada por uma diminuição do infiltrado de neutrófilos nos pulmões.

ABSTRACT Objective The shortage of viable lungs is still a major obstacle for transplantation. Trauma victims who represent potential lung donors commonly present hypovolemic shock leading to pulmonary inflammation and deterioration and rejection after transplantation. Seeking to improve lung graft, new approaches to donor treatment have been tested. This study focuses on treatment with mesenchymal stem cells (MSCs) or soluble factors produced by MSCs (FS-MSC) using a rat model for lung donors after hemorrhagic shock. Methods Forty-eight rats were divided into four groups: Sham (n=12), animals without induction of hypovolemic shock; Shock (n=12), animals submitted to hypovolemic shock (mean arterial pressure 40 mmHg); MSC (n=12), animals submitted to hypovolemic shock and treated with MSCs, and FS (n=12), animals submitted to hypovolemic shock and treated with FS-MSC. The animals were subjected to a 50-minute hypovolemic shock (40 mmHg) procedure. The treated animals were monitored for 115 minutes. We performed histopathology of lung tissue and quantification of inflammatory markers (TNF-α, IL-1β, IL-6, IL-10, iCAM and vCAM) in lung tissue and peripheral blood leukocytes (PBLs). Results Hemorrhagic shock resulted in higher PBLs and neutrophil infiltrate in the lungs. FS animals had lower neutrophil density comparing with Shock and MSC animals (p<0.001). No differences in the cytokine levels in lung tissue were observed between the groups. Conclusions The lungs of rats submitted to hemorrhagic shock and treated with FS-MSC showed reduced inflammation indicated in a decrease in lung neutrophil infiltrate.