Relación entre la compatibilidad del HLA y la pérdida del injerto en trasplante renal de donante cadavérico: Un análisis por propensity score matching en Colombia / Relationship between HLA compatibility and graft loss in renal transplant from a deceased donor: An analysis by propensity score matching in Colombia

Introducción. En Colombia, solo un 24 % de los pacientes en lista recibieron un trasplante renal, la mayoría de donante cadavérico. Para la asignación de órganos se considera el HLA A-B-DR, pero la evidencia reciente sugiere que el HLA A-B no está asociado con los desenlaces del trasplante. El objetivo de este estudio fue evaluar la relevancia del HLA A-B-DR en la sobrevida del injerto de los receptores de trasplante renal. Métodos. Estudio de cohorte retrospectivo que incluyó pacientes trasplantados renales con donante cadavérico en Colombiana de Trasplantes, desde 2008 a 2023. Se aplicó un propensity score matching (PSM) para ajustar las covariables en grupos de comparación por compatibilidad y se evaluó la relación del HLA A-B-DR con la sobrevida del injerto renal por medio de la prueba de log rank y la regresión de Cox. Resultados. Se identificaron 1337 pacientes transplantados renales, de los cuales fueron mujeres un 38,7 %, con mediana de edad de 47 años y de índice de masa corporal de 23,8 kg/m2. Tras ajustar por PSM las covariables para los grupos de comparación, la compatibilidad del HLA A-B no se relacionó significativamente con la pérdida del injerto, con HR de 0,99 (IC95% 0,71-1,37) para HLA A y 0,75 (IC95% 0,55-1,02) para HLA B. Solo la compatibilidad por HLA DR fue significativa para pérdida del injerto con un HR de 0,67 (IC95% 0,46-0,98). Conclusión. Este estudio sugiere que la compatibilidad del HLA A-B no influye significativamente en la pérdida del injerto, mientras que la compatibilidad del HLA DR sí mejora la sobrevida del injerto en trasplante renal con donante cadavérico

Introduction. In Colombia, only 24% of patients on the waiting list received a renal transplant, most of them from cadaveric donors. HLA A-B-DR is considered for organ allocation, but recent evidence suggests that HLA A-B is not associated with transplant outcomes. The objective of this study was to evaluate the relevance of HLA A-B-DR on graft survival in kidney transplant recipients. Methods. Retrospective cohort study that included kidney transplant recipients with a cadaveric donor in Colombiana de Trasplantes from 2008 to 2023. A propensity score matching (PSM) was applied to adjust the covariates in comparison groups for compatibility, and the relationship of HLA A-B-DR with kidney graft survival was evaluated using the log rank test and Cox regression. Results. A total of 1337 kidney transplant patients were identified; of those, 38.7% were female, with median age of 47 years, and BMI 23.8 kg/m2. After adjusting the covariates with PSM for the comparison groups, HLA A-B matching was not significantly related to graft loss, with HR of 0.99 (95% CI 0.71-1.37) and 0.75 (95% CI 0.55-1.02), respectively. Only HLA DR matching was significant for graft loss with an HR of 0.67 (95% CI 0.46-0.98). Conclusions. This study suggests that HLA A-B matching does not significantly influence graft loss, whereas HLA DR matching does improve graft survival in renal transplantation with a cadaveric donor.

Descripción de polimorfismos genéticos en CYP3A5 y MDR-1 y su impacto en el rechazo agudo clínico de pacientes trasplantados de hígado del Hospital San Vicente Fundación Rionegro / Description of genetic polymorphisms in CYP3A5 and MDR-1 and their impact on clinical acute rejection in liver transplant patients at Hospital San Vicente Fundación Rionegro

Introducción. El tacrolimus es un medicamento inmunosupresor ampliamente usado en trasplante hepático, que presenta una gran variabilidad interindividual la cual se considera asociada a la frecuencia de polimorfismos de CYP3A5 y MDR-1. El objetivo de este estudio fue evaluar la frecuencia de los polimorfismos rs776746, rs2032582 y rs1045642 y su asociación con rechazo clínico y toxicidad farmacológica. Métodos. Se incluyeron pacientes inmunosuprimidos con tacrolimus a quienes se les realizó trasplante hepático en el Hospital San Vicente Fundación Rionegro entre 2020 y 2022, con supervivencia mayor a un mes. Se evaluaron las variables clínicas, rechazo agudo y toxicidad farmacológica. Se secuenciaron los genes de estudio mediante PCR, comparando la expresión o no en cada uno de los pacientes. Resultados. Se identificaron 17 pacientes. El 43 % de los pacientes se clasificaron como CYP3A5*1/*1 y CYP3A5*1/*3, entre los cuales se encontró asociación con aumento en la tasa de rechazo agudo clínico, al comparar con los pacientes no expresivos (100 % vs. 44 %, p=0,05); no hubo diferencias en cuanto a la toxicidad farmacológica u otros desenlaces. Se encontró el polimorfismo rs2032582 en un 50 % y el rs1045642 en un 23,5 % de los pacientes, sin embargo, no se identificó asociación con rechazo u otros eventos clínicos. Conclusiones. Se encontró una asociación entre el genotipo CYP3A5*1/*1 y CYP3A5*1/*3 y la tasa de rechazo clínico. Sin embargo, se requiere una muestra más amplia para validar estos datos y plantear modelos de medicina personalizada.

Introduction. Tacrolimus is an immunosuppressive drug widely used in liver transplantation, which presents great interindividual variability which is considered associated with the frequency of CYP3A5 and MDR-1 polymorphisms. The objective of this study was to evaluate the frequency of the rs776746, rs2032582 and rs1045642 polymorphisms and their association with clinical rejection and drug toxicity. Methods. Immunosuppressed patients with tacrolimus who underwent a liver transplant at the Hospital San Vicente Fundación Rionegro between 2020 and 2022 were included, with survival of more than one month. Clinical variables, acute rejection and pharmacological toxicity were evaluated. The study genes were sequenced by PCR, comparing their expression or not in each of the patients. Results. Seventeen patients were identified. 43% of the patients were classified as CYP3A5*1/*1 and CYP3A5*1/*3, among which an association was found with increased rates of clinical acute rejection when compared with non-expressive patients (100% vs. 44%, p=0.05). There were no differences in drug toxicity or other outcomes. The rs2032582 polymorphism was found in 50% and rs1045642 in 23.5% of patients; however, no association with rejection or other clinical events was identified. Conclusions. An association was found between the CYP3A5*1/*1 and CYP3A5*1/*3 genotype and the clinical rejection rate. However, a larger sample is required to validate these data and propose models of personalized medicine.

Desempenho do óxido nítrico na sepse: uma revisão de escopo / Desempeño del óxido nítrico en la sepsis: una revisión de alcance / Performance of nitric oxide in sepsis: a scoping review

Resumo Objetivo Mapear as evidências disponíveis sobre as ações do óxido nítrico na fisiopatologia da sepse e sua relação com a gravidade de pacientes sépticos. Método Revisão de escopo de acordo com a metodologia do Joanna Briggs Institute. Realizou-se busca por estudos que evidenciaram as ações do óxido nítrico na sepse e se o seu aumento está associado à gravidade de pacientes sépticos. Dois revisores independentes fizeram o mapeamento das informações utilizando um instrumento de extração de dados previamente elaborado. Os dados foram analisados quanto à sua relevância, sendo posteriormente extraídos e sintetizados. Resultados De 1342 estudos, 11 foram incluídos na revisão. O primeiro foi publicado em 2017 e o último, em 2022. A maioria foi desenvolvida nos Estados Unidos, na China e na Alemanha. Os estudos apresentaram informações referentes as ações do óxido nítrico, sintetizando sua biodisponibilidade e os inibidores endógenos relacionados a sua produção, além de abordarem a relação do óxido nítrico com a gravidade da sepse. Conclusão A produção de óxido nítrico fisiológico durante a sepse atua como protetor vascular, principalmente na microcirculação, porém, em altas concentrações, contribui para a disfunção vascular, que subverte a fisiologia da regulação da pressão arterial, causando profunda vasodilatação e hipotensão refratária e aumentando a gravidade de pacientes sépticos.

Resumen Objetivo Mapear las evidencias disponibles sobre las acciones del óxido nítrico en la fisiopatología de la sepsis y su relación con la gravedad de pacientes sépticos. Métodos Revisión de alcance de acuerdo con la metodología del Joanna Briggs Institute. Se realizó una búsqueda de estudios que evidenciaron las acciones del óxido nítrico en la sepsis y si su aumento estaba asociado a la gravedad de pacientes sépticos. Dos revisores independientes hicieron el mapeo de la información utilizando un instrumento de extracción de datos previamente elaborado. Los datos se analizaron respecto a su relevancia, para luego extraerlos y sintetizarlos. Resultados De 1342 estudios, se incluyeron 11 en la revisión. El primero fue publicado en 2017 y el último en 2022. La mayoría se realizó en Estados Unidos, China y Alemania. Los estudios presentaron información referente a las acciones del óxido nítrico, sintetizando su biodisponibilidad y los inhibidores endógenos relacionados con su producción, además de abordar la relación del óxido nítrico con la gravedad de la sepsis. Conclusión La producción de óxido nítrico fisiológico durante la sepsis actúa como protector vascular, principalmente en la microcirculación. Sin embargo, en altas concentraciones, contribuye a la disfunción vascular, que subvierte la fisiología de la regulación de la presión arterial, causa una profunda vasodilatación e hipotensión refractaria y aumenta la gravedad de pacientes sépticos. Registro da revisão de escopo no Open Science Framework: https://doi.org/10.17605/OSF.IO/MXDK2

Abstract Objective Map the available evidence on the actions of nitric oxide in the pathophysiology of sepsis and its relationship with the severity of sepsis in patients. Method Scoping review following the Joanna Briggs Institute methodology. A search was carried out for studies that highlighted the actions of nitric oxide in sepsis, informing whether its increase is associated with the severity of sepsis in patients. Two independent reviewers mapped the information using a previously designed data extraction instrument. The data was analyzed for its relevance and then extracted and synthesized. Results Eleven of 1342 studies were included in the review. The first of them was published in 2017 and the last in 2022. Most of them were developed in the USA, China, and Germany. Studies have reported the actions and bioavailability of nitric oxide and endogenous inhibitors related to its production, and related nitric oxide to the severity of sepsis. Conclusion The physiological production of nitric oxide during sepsis acts as a vascular protector, mainly in the microcirculation but contributes to vascular dysfunction in high concentrations, subverting the regulation of blood pressure, causing deep vasodilation and refractory hypotension, and increasing the severity of sepsis in patients. Registration of the scoping review in the Open Science Framework: https://doi.org/10.17605/OSF.IO/MXDK2

Recusa familiar para doação de córneas para transplante: fatores associados e tendência / Negativa familiar para donación de córneas para trasplante: factores asociados y tendencia / Family refusal to donate a cornea for transplantation: associated factors and trends

Resumo Objetivo Analisar a recusa familiar de doação de córnea para transplante em uma Organização de Procura de Órgãos. Métodos Estudo quantitativo do tipo transversal sobre as recusas de córnea de doadores em situação de morte encefálica. A fonte de dados foi constituída pelos Termos de Autorização de Doação de Órgãos e Tecidos firmados entre janeiro de 2001 a dezembro de 2020 em uma Organização de Procura de Órgãos. Os dados foram coletados, tabulados e analisados de forma descritiva e inferencial. O presente estudo foi aprovado pelo Comitê de Ética em Pesquisa. Resultados Dos 2.447 Termos de Autorização de Doação de Órgãos e Tecidos firmados no período, 620 (25.34%) recusaram a doação de córneas. Com relação à tendência temporal de recusas de doação de córneas, o único período que apresentou significância foi de 2001 a 2009, quando as faixas etárias de zero a 11 anos e 12 a 19 anos demonstraram tendência decrescente, e a faixa etária maior ou igual a 60 anos, mostrou-se crescente. No período total de 2001 a 2020, as faixas etárias dos 20 a 40 anos, 41 a 59 anos e maior ou igual a 60 anos apresentaram, 48%, 59% e 73%, respectivamente, menores chances de recusa da doação de córneas. Conclusão A faixa etária apresentou associação com a recusa, tendo em vista que os indivíduos de maior idade apresentaram maiores índices.

Resumen Objetivo Analizar la negativa familiar de donación de córneas para trasplante en una Organización de Búsqueda de Órganos. Métodos: Estudio cuantitativo tipo transversal sobre la negativa de córnea de donantes en situación de muerte encefálica. La fuente de datos estuvo compuesta por los Términos de Autorización de Donación de Órganos y Tejidos firmados entre enero de 2001 y diciembre de 2020 en una Organización de Búsqueda de Órganos. Se recopilaron los datos, luego se tabularon y se analizaron de forma descriptiva e inferencial. El presente estudio fue aprobado por el Comité de Ética en Investigación. Resultados De los 2447 Términos de Autorización de Donación de Órganos y Tejidos firmados en el período, 620 (25,34 %) negaron la donación de córneas. Con relación a la tendencia temporal de negativas de donación de córneas, el único período que presentó significación fue de 2001 a 2009, cuando los grupos de edad de 0 a 11 años y de 12 a 19 años demostraron una tendencia decreciente, y el grupo de edad mayor o igual a 60 años se mostró creciente. En el período total de 2001 a 2020, los grupos de edad de 20 a 40 años, de 41 a 59 años y mayor o igual a 60 años presentaron un 48 %, un 59 % y un 73 %, respectivamente, menor probabilidad de negativa de donación de córneas. Conclusión El grupo de edad presentó relación con la negativa, considerando que los individuos de mayor edad presentan mayores índices.

Abstract Objective To analyze family refusals to donate a cornea for transplantation in an Organ Procurement Organization. Methods This was a quantitative cross-sectional study on corneal donation refusals from potential brain-dead donors. The data source was based on the Terms of Authorization for Donation of Organs and Tissues signed from January 2001 to December 2020 in an Organ Procurement Organization. Data were collected, tabulated, and analyzed in a descriptive and inferential manner. The present study was approved by the Research Ethics Committee. Results Of the 2,447 Terms of Authorization for Donation of Organs and Tissues signed in the above period, 620 (25.34%) of them refused to donate a cornea. Regarding the time trend of corneal donation refusals, the period 2001-2009 was the only one that showed significance, when the 0-11 and 12-19 age groups showed a decreasing trend and that of 60 years or older showed an increasing trend. In the period 2001-2020, the age groups of 20-40, 41-59, and 60 years or older had lower rates of refusal to donate a cornea (48%, 59%, and 73%, respectively). Conclusion The age group is associated with refusal because older individuals had the highest refusal rates.

Maturation and development of fetal pig intestinal tissue in immunodeficient mice

Purpose: This study aimed to compare the degree of maturation and development of fetal pig segmental intestinal tissue with that of spheroids created by in-vitro reaggregation of dissociated fetal intestinal cells after transplantation into immunodeficient mice. Methods: Fetal pig small intestines were transplanted as segmental grafts into the omentum and subrenal capsules of immunodeficient mice or enzymatically treated to generate single cells. Spheroids made by in-vitro reaggregation of these cells were transplanted into the subrenal capsules of immunodeficient mice. The segmental grafts and spheroids were harvested four and eight weeks after transplantation, and the structural maturity and in-vivo development of these specimens were histologically evaluated. Results: The spheroids were engrafted and supplied blood vessels from the host mice, but an intestinal layered structure was not clearly observed, and there was almost no change in size. On the other hand, the segmental grafts formed deep crypts in the mucus membrane, the inner circular layer, and outer longitudinal muscles. The crypts of the transplanted grafts harvested at eight weeks were much deeper, and the smooth muscle layer and the enteric nervous system were more mature than those of grafts harvested at the fourth week, although the intestinal peristaltic wave was not observed. Conclusions: Spheroids created from fetal small intestinal cells could not form layered structures or mature sufficiently. Conversely, segmental tissues structurally matured and developed after in-vivo transplantation and are therefore potential grafts for transplantation.

Isquemia mesentérica aguda: un desafío de la medicina. Reporte de un caso

La isquemia intestinal aguda es una emergencia vascular provocada por fenómenos oclusivos y no oclusivos de la circulación mesentérica arterial y venosa, de difícil diagnóstico y pronóstico ominoso. Su incidencia va en aumento paulatino con el decurso de los años, asociada fundamentalmente al envejecimiento de la población. La tasa de mortalidad es elevada a pesar de los avances en el campo de la imagenología. Suele diagnosticarse de forma tardía, cuando está establecido el daño isquémico intestinal de carácter irreversible. El elemento imprescindible e indispensable lo constituye el tiempo que trascurre hasta la cirugía, por lo que su diagnóstico sigue siendo un reto clínico. El tratamiento exige medidas médicas intensivas, al igual que cirugía de revascularización y resección del intestino necrosado. Por desdicha, el examen físico y los hallazgos de laboratorio no son sensibles ni específicos para su diagnóstico. Teniendo en cuenta estos elementos, se presenta el caso de una paciente de 38 años con clínica difusa de vómitos, diarrea y dolor abdominal progresivo, que requirió intervención quirúrgica de urgencia con diagnóstico transoperatorio de isquemia mesentérica aguda. Durante su estancia hospitalaria se relaparotomizó en dos ocasiones, mantuvo soporte ventilatorio e inotrópico por fallo multiorgánico en la Unidad de Cuidados Intensivos, mostrando una adecuada evolución posquirúrgica. El objetivo de esta presentación es enfatizar en la clínica como elemento fundamental para abordar de forma correcta esta entidad en un medio hospitalario de limitados recursos diagnósticos imagenológicos, al abordar conceptos teóricos recientes y facilitar una adecuada actuación en la toma de decisiones.

Acute intestinal ischemia is a vascular emergency caused by occlusive and non-occlusive phenomena of the mesenteric arterial and venous circulation of difficult diagnosis and ominous prognosis. Its incidence is gradually increasing over the years, mainly associated with the ageing of the population. The mortality rate is high despite advances in the field of imaging. It is usually diagnosed late, when irreversible ischemic intestinal damage is established. The essential and indispensable element is the time that elapses until surgery, so its diagnosis continues to be a clinical challenge. Treatment requires intensive medical measures, as well as revascularization surgery and resection of the necrotic intestine. Unfortunately, physical examination and laboratory findings are neither sensitive nor specific for its diagnosis. Taking these elements into account, the authors present the case of a 38-year-old female patient with diffuse symptoms of vomiting, diarrhea and progressive abdominal pain that required emergency surgery with intraoperative diagnosis of acute mesenteric ischemia. During her hospital stay, she underwent re-laparotomy twice, maintained ventilatory and inotropic support due to multi-organ failure in the Intensive Care Unit, showing an adequate post-surgical evolution. The objective of this presentation is to emphasize in the clinic as a fundamental element to correctly address this entity in a hospital environment with limited imaging diagnostic resources by addressing recent theoretical concepts and facilitating adequate action in decision-making.

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.

Case report of scrub typhus complicated by hypokalemia and multiple organ dysfunction syndrome

ABSTRACT CONTEXT: Scrub typhus, caused by Orientia tsutsugamushi, has a wide range of clinical manifestations, including meningoencephalitis, acute renal failure, pneumonitis, myocarditis, and septic shock. However, there are no documented cases of scrub typhus with hypokalemia. In this report, we present a case of scrub typhus with hypokalemia and multiple organ failure syndrome, highlighting the importance of electrolyte imbalance in patients with scrub typhus. CASE REPORT: A 59-year-old woman presented to the emergency department with abdominal pain that had been present for 1 day. On admission, the physical examination and laboratory test results indicated that the patient had renal, liver, and circulatory failure, and hypokalemia. She developed meningitis and disseminated intravascular coagulation during hospitalization. She recovered with appropriate management, and was discharged on day 17. CONCLUSION: This report highlights the potential for atypical presentations of scrub typhus, including a previously undocumented association with hypokalemia. Although the contribution of hypokalemia to the patient's clinical course remains uncertain, this case underscores the importance of considering electrolyte imbalance in the management of patients with scrub typhus. Further research is warranted to better understand the relationship between scrub typhus and electrolyte imbalance.

Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Research progress in risk factors of post-transplantation diabetes mellitus / 器官移植

Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.

Ethic analysis of the role of incentive system in the organ donation after citizen’s death / 器官移植

Organ transplantation has demonstrated its significant values by its excellent effectiveness in health reconstruction and life survival, where organ donation is a major component in promoting the development of organ transplantation in China. In recent years, an important progress has been made in organ transplantation in China with an annually increased organ donation rate. In spite of this, there is a serious fact confronted by us that the donated organ quantity is insufficient, which may be solved by further improvement of medical science and public health policy. According to the international experience, an incentive system may improve the organ donation rate effectively although the hidden ethic property of the incentive system itself may have an essentially conflict with the altruism contained in the organ donation. Therefore, in this article, the property of the incentive system, the interaction between organ donation and incentive system and the ethic justification of the system was reviewed, aiming to provide a reference for the further development of the organ donation and transplantation business in China.

Construction and validation of a prediction model for public acceptance of kidney xenotransplantation in China / 器官移植

Objective To explore the public attitude towards kidney xenotransplantation in China by constructing and validating the prediction model based on xenotransplantation questionnaire. Methods A convenient sampling survey was conducted among the public in China with the platform of Wenjuanxing to analyze public acceptance of kidney xenotransplantation and influencing factors. Using random distribution method, all included questionnaires (n=2 280) were divided into the training and validation sets according to a ratio of 7:3. A prediction model was constructed and validated. Results A total of 2 280 questionnaires were included. The public acceptance rate of xenotransplantation was 71.3%. Multivariate analysis showed that gender, marital status, resident area, medical insurance coverage, religious belief, vegetarianism, awareness of kidney xenotransplantation and whether on the waiting list for kidney transplantation were the independent influencing factors for public acceptance of kidney xenotransplantation (all P<0.05). The area under the curve (AUC) of receiver operating characteristic (ROC) of the prediction model in the training set was 0.773, and 0.785 in the validation set. The calibration curves in the training and validation sets indicated that the prediction models yielded good prediction value. Decision curve analysis (DCA) suggested that the prediction efficiency of the model was high. Conclusions In China, public acceptance of kidney xenotransplantation is relatively high, whereas it remains to be significantly enhanced. The prediction model based on questionnaire survey has favorable prediction efficiency, which provides reference for subsequent research.

Investigation of patients’preferences regarding therapeutic drug monitoring of mycophenolic acid in solid organ transplantation / 中国药房

OBJECTIVE To investigate the preferences of patients who underwent solid organ transplantation regarding therapeutic drug monitoring （TDM） of mycophenolic acid （MPA） and explore the factors influencing patients’ decision-making process， so as to provide support for the development of individualized medication guidelines for MPA and improvement of clinical decision-making. METHODS The cross-sectional study was used to design the questionnaire on the patients’ preferences to accept MPA TDM， and involved patients who underwent solid organ transplantation and received MPA treatment at two tertiary hospitals in Beijing from April 14， 2022， to June 27， 2022. The Likert 5-level scoring method was used to score the patients’ preferences to accept MPA TDM， the influencing factors and their correlation of the patients’ preferences to accept MPA TDM were analyzed by Pearson correlation analysis and binary Logistic regression analysis， and the nonparametric test and chi-square test were used to rank and analyze the consistency of the factors affecting patients’ preference decision. RESULTS A total of 140 questionnaires were collected， and the effective recovery rate was 77.35%. The average preference score of 140 patients to receive MPA TDM was （4.01±0.65）， and the overall preference value was high. There were 116 （82.86%） patients agreed or strongly agreed with MPA TDM. Significant differences were observed in preference scores between patients who had previously undergone MPA TDM and those who had never undergone it （[ 4.30±0.53） scores vs. （3.80±0.65） scores， P＜0.001]. Additionally， patients’ preference scores were significantly influenced by their understanding level and attention level （P＜0.001）. The ranking of factors contributing to decision-making exhibited consistency （P＜0.001）. The factors were ranked in descending order of clinical efficacy， safety， comfortability， economy and time cost. CONCLUSIONS The patients who underwent solid organ transplantation hold high preferences towards MPA TDM. The primary factors influencing their decisions are their prior experience， understanding level， and attention level.

Caracterização epidemiológica e causas da não doação por potenciais doadores de órgãos em morte encefálica / Epidemiological characterization and causes of non-donation by potential brain-dead organ donors / Caracterización epidemiológica y causas de la no donación de potenciales donantes de órganos en muerte cerebral

Objetivo: analisar as características epidemiológicas e causas da não efetivação do processo de doação de órgãos e tecidos de potenciais doadores em morte encefálica. Método: estudo transversal, com dados secundários do ano de 2019, obtidos de formulários de notificação de morte encefálica de pacientes com idade igual e superior a 18 anos, analisados descritiva e inferencialmente, após aprovação pelo comitê de ética. Resultados: notificadas 231 mortes encefálicas, com maior incidência de pessoas do sexo masculino, idade média de 48 anos e notificações dos hospitais públicos. Em Campo Grande, Mato grosso do Sul, observou-se maior número de notificações e o menor tempo entre a notificação e o primeiro exame clínico (RR: 4,01; IC 2,17-7,41; p<0,001). Entre os casos de não doação, 75,8% ocorreram por contraindicação médica e recusa familiar. Conclusão: houve predomínio de adultos jovens, não doadores de órgãos, cuja negativa da família deu-se pela vontade de manter o corpo íntegro.

Objective: to analyze the epidemiological characteristics and causes of non-completion of the organ and tissue donation process from potential brain-dead donors. Method: cross-sectional study, with secondary data from 2019, obtained from brain death notification forms of patients aged 18 years and over, analyzed descriptively and inferentially, after approval by the ethics committee. Results: 231 brain deaths were reported, with a higher incidence of males, average age of 48 years and notifications from public hospitals. In Campo Grande, Mato grosso do Sul, Brazil, there was a greater number of notifications and a shorter time between notification and the first clinical examination (RR: 4.01; CI 2.17-7.41; p<0.001). Among cases of non-donation, 75.8% occurred due to medical contraindication and family refusal. Conclusion: there was a predominance of young adults, non-organ donors, whose family's refusal was due to the desire to keep the body intact.

Objetivo: analizar las características epidemiológicas y las causas de la no finalización del proceso de donación de órganos y tejidos de potenciales donantes en muerte cerebral. Método: estudio transversal, con datos secundarios del año 2019, obtenidos de formularios de notificación de muerte encefálica de pacientes de 18 años y más, analizados de manera descriptiva e inferencial, previa aprobación del comité de ética. Resultados: Se reportaron 231 muertes encefálicas, con mayor incidencia de hombres, edad promedio de 48 años y notificaciones de los hospitales públicos. En Campo Grande, Mato grosso do Sul, hubo mayor número de notificaciones y menor tiempo entre la notificación y el primer examen clínico (RR: 4,01; IC 2,17-7,41; p<0,001). Entre los casos de no donación, el 75,8% se produjo por contraindicación médica y negativa familiar. Conclusión: hubo predominio de adultos jóvenes, no donantes de órganos, cuya negativa familiar se debió al deseo de mantener el cuerpo íntegro.

Síndrome de disfunción orgánica múltiple progresiva en embarazo adolescente: reporte de caso clínico / Progressive multiple organ dysfunction syndrome in adolescent pregnancy: Case report

Introducción El embarazo adolescente es un proceso fisiológico, pero puede evolucionar con parto prematuro, patologías obstétricas o médicas graves, mortalidad o secuelas para madre e hijo/a. Nuestro objetivo es reportar el síndrome de disfunción orgánica múltiple progresiva secundario a pielonefritis y sepsis ocurrido durante el preparto, parto y puerperio de embarazo adolescente y sus secuelas. Caso clínico Adolescente de 14 años, con embarazo de 27 semanas de gestación controlado desde las 8 hasta 25 semanas. Ingresó de urgencia en unidad de alto riesgo obstétrico por signos de parto prematuro, pielonefritis e injuria renal aguda. Se inició tratamiento con cefazolina intravenosa y betametasona para maduración pulmonar, nifedipino oral y sulfato de magnesio para prevención del parto prematuro y protección neuronal fetal, evolucionando con hipotensión sostenida y shock séptico. A las 13 horas después del ingreso, fue trasladada a unidad de paciente crítico donde evolucionó con falla orgánica múltiple persistente y progresiva durante 28 días, afectando sucesivamente los sistemas cardiovascular, hematológico, respiratorio y gastrointestinal. Se trató con drogas vasoactivas, antibióticos, ventilación mecánica invasiva, ultrafiltración, hemodiálisis, drenaje pleural y colecistectomía. A las 24 horas de ingreso a cuidado intensivo, ocurrió el parto prematuro vaginal. La embarazada desarrolló enfermedad renal crónica etapa KDIGO 5 ( V) y se encuentra en espera de trasplante renal. Por su parte, la recién nacida prematura viva presentó asfixia neonatal severa, displasia broncopulmonar y encefalopatía hipóxico-isquémica. Conclusiones El embarazo adolescente complicado es una emergencia sanitaria. El diagnóstico y manejo oportuno de la pielonefritis, shock séptico y disfunción orgánica asociada a la sepsis pueden evitar mortalidad y secuelas permanentes materna y/o neonatal.

Introduction Adolescent pregnancy is a physiological process, but it can evolve with premature delivery, severe obstetric or clinical pathologies, mortality, or sequelae for mother and child. We aim to report the progressive multiple organ dysfunction syndrome secondary to pyelonephritis and sepsis during prepartum, delivery, and puerperium of adolescent pregnancy and its sequelae. Case report A 14-year-old adolescent with a pregnancy of 27 weeks of gestation controlled from 8 to 25 weeks. She was urgently admitted to the high-risk obstetric unit due to signs of preterm labor, pyelonephritis, and acute renal injury. Treatment was started with intravenous cefazolin and betamethasone for lung maturation, oral nifedipine, and magnesium sulfate to prevent preterm labor and fetal neuronal protection, evolving with sustained hypotension and septic shock. At 13 hours after admission, she was transferred to the intensive care unit, where she evolved with persistent and progressive multiple organ failure for 28 days, progressively affecting the cardiovascular, hematologic, respiratory, and gastrointestinal systems. She was treated with vasoactive drugs, antibiotics, invasive mechanical ventilation, ultrafiltration, hemodialysis, pleural drainage, and cholecystectomy. Twenty-four hours after admission to intensive care, preterm vaginal delivery occurred. She developed chronic kidney disease stage KDIGO 5 (Kidney Disease Improving Global Outcomes V) and is awaiting renal transplantation. On the other hand, the preterm newborn presented severe neonatal asphyxia, bronchopulmonary dysplasia, and hypoxic-ischemic encephalopathy. Conclusion Complicated adolescent pregnancy is a health emergency. Avoiding delays in the diagnosis and treatment of pyelonephritis, septic shock and the progressive multiple organ dysfunction syndrome can prevent mortality and permanent sequelae, both maternal and neonatal.

Bioética en donantes en asistolia 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.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study / Dapagliflozina em pacientes com doença crítica: justificativa e desenho do estudo DEFENDER

ABSTRACT Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry: NCT05558098

RESUMO Antecedentes: A doença crítica é um importante ônus permanente da assistência médica em todo o mundo e está associada a altas taxas de mortalidade. Os inibidores do cotransportador de sódio-glicose do tipo 2 têm demonstrado consistentemente benefícios nos desfechos cardiovasculares e renais. Os efeitos dos inibidores do cotransportador de sódio-glicose do tipo 2 em doenças agudas ainda não foram devidamente investigados. Métodos: O DEFENDER é um estudo de iniciativa do investigador, multicêntrico, randomizado, aberto, desenhado para avaliar a eficácia e a segurança da dapagliflozina em 500 participantes adultos com disfunção orgânica aguda hospitalizados na unidade de terapia intensiva. Os participantes aptos serão randomizados 1:1 para receber 10mg de dapagliflozina e o tratamento padrão por até 14 dias ou apenas o tratamento padrão. O desfecho primário é um composto hierárquico de mortalidade hospitalar, início de terapia renal substitutiva e tempo de internação na unidade de terapia intensiva, até 28 dias. O monitoramento da segurança será rigoroso durante todo o estudo. Conclusão: O DEFENDER é o primeiro estudo desenvolvido para investigar o uso de um inibidor do cotransportador de sódio-glicose do tipo 2 em pacientes de unidade de terapia intensiva geral com disfunção orgânica aguda. O estudo fornecerá informações relevantes sobre o uso de medicamentos dessa classe promissora em pacientes críticos. Registro ClincalTrials.gov: NCT05558098

Nefrectomía totalmente laparoscópica para donante vivo de riñón: Características y desenlaces en una institución de alta complejidad en Colombia. Serie de casos / Total laparoscopic nephrectomy for a living kidney donor: Characteristics and outcomes in a single center from Colombia. Case series

Introducción. El trasplante es la mejor opción de tratamiento para los pacientes con enfermedad renal terminal, sin embargo, existe discrepancia entre las listas de espera y la disponibilidad de órganos a partir de la donación cadavérica. Buscando aumentar el número de órganos disponibles se implementó el trasplante con donante vivo. A partir de la introducción de técnicas mínimamente invasivas para la nefrectomía, el donante vivo ha logrado cifras cercanas al 50 % de los trasplantes realizados en muchas instituciones, debido a los beneficios propios del procedimiento. El objetivo de este estudio fue describir los resultados después de la incorporación del procedimiento totalmente laparoscópico en nuestra institución. Métodos. Se hizo un análisis retrospectivo de las características de los pacientes llevados a nefrectomía para obtención de injerto por técnica totalmente laparoscópica y los resultados en un solo centro en Cali, Colombia, desde noviembre de 2019 hasta octubre de 2022. Los datos fueron obtenidos mediante la revisión de las historias clínicas electrónicas. Resultados. Se realizaron 78 nefrectomías para obtención de injerto con técnica totalmente laparoscópica. El tiempo operatorio promedio fue de 152 minutos, el sangrado promedio fue de 12 ml, la estancia hospitalaria promedio del donante fue de 2,8 días. La tasa de complicaciones fue de 7,6 % (4 pacientes con complicación Clavien-Dindo I y 2 pacientes Clavien-Dindo IIIb). No se presentó ningún caso de mortalidad. Conclusiones. La técnica totalmente laparoscópica resulta ser una técnica segura con baja tasa de morbilidad y excelentes beneficios para los donantes.

Introduction. Kidney transplant is the best treatment option for end-stage renal disease. However, the discrepancy between waiting lists and the availability of organs from cadaveric donation is well known. Organ transplantation with a living donor was implemented to increase the number of organs available. Since the introduction of minimally invasive techniques for nephrectomy, living donors have achieved figures close to 50% of transplants performed in many institutions due to the procedure's benefits. In our country, the experiences described are from the hand-assisted technique. This is the first description after incorporating the laparoscopic procedure. Methods. A retrospective analysis of the characteristics and results of all patients undergoing nephrectomy to obtain a graft using a laparoscopic technique was carried at a single center in Cali, Colombia, from November 2019 to October 2022. The electronic medical records were reviewed to obtain the data. Results. Seventy-eight nephrectomies were performed to obtain a graft with a laparoscopic technique. The mean operating time was 152 minutes, the average bleeding was 12 cc, and the average hospital stay was 2.8 days. The complication rate was 7.6% (four patients with Clavien-Dindo I complication and two Clavien-Dindo IIIb patients). There were no cases of mortality. Conclusions. The laparoscopic technique is safe, with a low morbidity rate and excellent benefits.

Factors Associated With Hypertension and Cardiovascular Parameters in Children With Infrequently Relapsing Nephrotic Syndrome

Objective: To assess the prevalence of hypertension in children with infrequently relapsing nephrotic syndrome (IRNS) and its association with dyslipidemia, and end organ damage including left ventricular hypertrophy (LVH), at relapse and after steroid induced remission. Methods: Prospective observational study conducted in 83 children aged 1-12 years with IRNS, presenting in relapse. Blood pressure, fundus examination, blood and urine investigations were done at relapse and then at 4 weeks of therapy. Echocardiography at 4 weeks was performed for assessment of LVH and relative wall thickness (RWT) for concentric geo-metry (CG). Results: 27 patients (32.5%) developed hypertension, out of which 21 patients (25.3%) had stage I hypertension. Hypertension in first episode (63.0%, P<0.01) and in previous relapses (87.5%, P<0.001) was significantly associated with hypertension in the current episode. 12 patients had a positive family history of hypertension, of which 8 (66.7%) were classified under the hypertensive group (P=0.016). Concentric geometry (CG) was found in 28% of hypertensive and 5.5% of non-hypertensive children (P=0.011). On regres-sion analysis, a lower Up:Uc at the time of relapse was found to have a protective role for development of hypertension. Conclusion: One third children with IRNS had hypertension at relapse and a high proportion of hypertensive patients had CG pattern on echocardiography.

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