Glioblastoma: a comprehensive approach combining bibliometric analysis, Latent Dirichlet Allocation, and HJ-Biplot : Glioblastoma insights and trends: a 49-year bibliometric analysis.

Glioblastoma is a common and aggressive malignant central nervous system tumor in adults. This study aims to evaluate and analyze the scientific results, collaboration countries, main research topics, and topics over time reported about glioblastoma. A bibliometric analysis of glioblastoma publications was performed mainly using R and Multbiplot software for author, journal, and resume. Associated statistic methods Latent Dirichlet Allocation (LDA) and HJ-Biplot. Inclusion criteria were research articles from the PubMed database published in English between 1973 and December 2022. A total of 64,823 documents with an annual growth rate of 8.27% indicates a consistent increase in research output over time. The results for the number of citations and significant publications showed Cancer Res, J Neuro-Oncol, and Neuro-Oncology are the most influential journals in the field of glioblastoma. The countries that concentrated research were the tumor United States, China, Germany, and Italy. Finally, there has been a marked growth in studies on prognosis and patient survival, therapies, and treatments for glioblastoma. These findings reinforce the need for increased global resources to address glioblastoma, particularly in underdeveloped countries. Glioblastoma research's exponential growth reflects sustained interest in early diagnosis and patient survival.

Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells.

Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.

A Comparative Study on Graft and Overall Survival Rates Between Diabetic and Nondiabetic Kidney Transplant Patients Through Survival Analysis.

Background: Patients with diabetes mellitus (DM) have worse graft and overall survival, but recent evidence suggests that the difference is no longer significant. Objective: To compare the outcomes between patients with end-stage kidney disease due to DM (ESKD-DM) and ESKD due to nondiabetic etiology (ESKD-non-DM) who underwent kidney transplantation (KT) up to 10 years of follow-up. Design: Survival analysis of a retrospective cohort. Setting and Patients: All patients who underwent KT at the Hospital Universitario San Ignacio, Colombia, between 2004 and 2022. Measurements: Overall and graft survival in ESKD-DM and ESKD-non-DM who received KT. Patients who died with functional graft were censored for the calculation of kidney graft survival. Methods: Log-rank test, Cox proportional hazards model, and competing risk analysis were used to compare overall and graft survival in patients with ESKD-DM and ESKD-non-DM who underwent KT. Results: A total of 375 patients were included: 60 (16%) with ESKD-DM and 315 (84%) with ESKD-non-DM. Median follow-up was 83.3 months. Overall survival was lower in patients with ESKD-DM at 5 (75.0% vs 90.8%, P < .001) and 10 years (55.0% vs 86.7%, P < .001). Cardiovascular death was higher in patients with diabetes (27.3% vs 8.2%, P = .021). Death-censored graft survival was similar in both groups (96.7% vs 93.3% at 5 years, P = .324). On multivariate analysis, the factors associated with global survival were DM (hazard ratio [HR] = 2.11, 95% confidence interval [CI] = 1.23-3.60, P = .006), recipient age (HR = 1.05, 95% CI = 1.02-1.08, P < .001), delayed graft function (HR = 2.07, 95% CI = 1.24-3.46, P = .005), and donor age (HR = 1.03, 95% CI = 1.01-1.05, P = .002). In the competing risk analysis, DM was associated with mortality only in the cardiovascular death group (sub-hazard ratio [SHR] = 6.06, 95% CI = 1.01-36.4, P = .049). Limitations: Change in diabetes treatment received over time and adherence to glycemic targets were not considered. The sample size is relatively small, which limits the precision of our estimates. The Kidney Donor Profile Index and the occurrence of treated acute rejection were not included in the regression models. Conclusion: Overall survival is lower in patients with diabetes, possibly due to older age and cardiovascular comorbidities. Therefore, patients with diabetes should be followed more closely to control cardiovascular risk factors. However, there is no difference in graft survival.

Contexte: Les patients diabétiques (DB) sont ceux qui présentent les pires résultats de greffe et de survie globale, mais des données récentes suggèrent que la différence n'est désormais plus significative. Objectif: Comparer les résultats des patients atteints d'insuffisance rénale terminale causée par le DB (IRT-DB) et ceux des patients non-diabétiques (IRT-nonDB) pour une période de 10 ans après une transplantation rénale (TR). Conception: Analyse de la survie d'une cohorte rétrospective. Sujets et cadre de l'étude: Tous les patients qui ont subi une TR à l'Hôpital Universitario San Ignacio (Colombie) entre 2004 et 2022. Mesures: La survie globale et la survie du greffon chez les patients IRT-DB et IRT-nonDB après une TR. Les patients décédés avec un greffon fonctionnel ont été censurés pour le calcul de la survie du greffon. Méthodologie: Le test logarithmique par rangs, un modèle de régression à effet proportionnel de Cox et une analyse des risques concurrents ont été utilisés pour comparer la survie globale et la survie du greffon des patients atteints d'IRT-DB et d'IRT-nonDB après une TR. Résultats: Au total, 375 patients ont été inclus à l'étude, soit 60 patients (16 %) atteints d'IRT-DB et 315 (84 %) atteints d'IRT-nonDB. La durée médiane du suivi était de 83,3 mois. La survie globale était plus faible chez les patients atteints d'IRT-DB à 5 ans (75,0 c. 90,8 %; p<0,001) et à 10 ans (55,0 % c. 86,7 %; p<0,001). Les décès de causes cardiovasculaires ont été plus nombreux chez les patients diabétiques (27,3 % c. 8,2 %; p=0,021). La survie du greffon censurée pour le décès était similaire pour les deux groupes (96,7 % c. 93,3 % à 5 ans, p=0,324). Dans l'analyse multivariée, les facteurs associés à la survie globale étaient le DB (RR=2,11; IC95 : 1,23-3,60; p=0,006), l'âge du receveur (RR=1,05; IC95 : 1,02-1,08; p<0,001), le retard de fonction du greffon (RR = 2,07; IC95 : 1,24-3,46; p = 0,005) et l'âge du donneur (RR = 1,03; IC95 : 1,01-1,05; p=0,002). Dans l'analyse des risques concurrents, le DB a été associé à la mortalité uniquement dans le groupe de patients décédés de causes cardiovasculaires (RRS=6,06; IC95 : 1,01-36,4; p=0,049). Limites: Les modifications dans le traitement du diabète au fil du temps et l'observance des cibles glycémiques n'ont pas été prises en compte. La taille de l'échantillon est relativement faible, ce qui limite la précision des estimations. L'indice de profil du donneur (Kidney Donor Profile Index­KDPI) et la survenue d'un rejet aigu traité n'ont pas été inclus dans les modèles de régression. Conclusion: La survie globale est plus faible chez les patients diabétiques, peut-être en raison de l'âge avancé et des comorbidités cardiovasculaires de ces patients. Les patients diabétiques devraient par conséquent faire l'objet d'un suivi plus rapproché afin de surveiller les facteurs de risque cardiovasculaire. Aucune différence n'a cependant été observée pour la survie du greffon.

A Computational Approach to Predict the Role of Genetic Alterations in Methyltransferase Histones Genes With Implications in Liver Cancer.

Histone methyltransferases (HMTs) comprise a subclass of epigenetic regulators. Dysregulation of these enzymes results in aberrant epigenetic regulation, commonly observed in various tumor types, including hepatocellular adenocarcinoma (HCC). Probably, these epigenetic changes could lead to tumorigenesis processes. To predict how histone methyltransferase genes and their genetic alterations (somatic mutations, somatic copy number alterations, and gene expression changes) are involved in hepatocellular adenocarcinoma processes, we performed an integrated computational analysis of genetic alterations in 50 HMT genes present in hepatocellular adenocarcinoma. Biological data were obtained through the public repository with 360 samples from patients with hepatocellular carcinoma. Through these biological data, we identified 10 HMT genes (SETDB1, ASH1L, SMYD2, SMYD3, EHMT2, SETD3, PRDM14, PRDM16, KMT2C, and NSD3) with a significant genetic alteration rate (14%) within 360 samples. Of these 10 HMT genes, KMT2C and ASH1L have the highest mutation rate in HCC samples, 5.6% and 2.8%, respectively. Regarding somatic copy number alteration, ASH1L and SETDB1 are amplified in several samples, while SETD3, PRDM14, and NSD3 showed a high rate of large deletion. Finally, SETDB1, SETD3, PRDM14, and NSD3 could play an important role in the progression of hepatocellular adenocarcinoma since alterations in these genes lead to a decrease in patient survival, unlike patients who present these genes without genetic alterations. Our computational analysis provides new insights that help to understand how HMTs are associated with hepatocellular carcinoma, as well as provide a basis for future experimental investigations using HMTs as genetic targets against hepatocellular carcinoma.

Lung Cancer Gene Regulatory Network of Transcription Factors Related to the Hallmarks of Cancer.

The transcriptomic analysis of microarray and RNA-Seq datasets followed our own bioinformatic pipeline to identify a transcriptional regulatory network of lung cancer. Twenty-six transcription factors are dysregulated and co-expressed in most of the lung cancer and pulmonary arterial hypertension datasets, which makes them the most frequently dysregulated transcription factors. Co-expression, gene regulatory, coregulatory, and transcriptional regulatory networks, along with fibration symmetries, were constructed to identify common connection patterns, alignments, main regulators, and target genes in order to analyze transcription factor complex formation, as well as its synchronized co-expression patterns in every type of lung cancer. The regulatory function of the most frequently dysregulated transcription factors over lung cancer deregulated genes was validated with ChEA3 enrichment analysis. A Kaplan-Meier plotter analysis linked the dysregulation of the top transcription factors with lung cancer patients' survival. Our results indicate that lung cancer has unique and common deregulated genes and transcription factors with pulmonary arterial hypertension, co-expressed and regulated in a coordinated and cooperative manner by the transcriptional regulatory network that might be associated with critical biological processes and signaling pathways related to the acquisition of the hallmarks of cancer, making them potentially relevant tumor biomarkers for lung cancer early diagnosis and targets for the development of personalized therapies against lung cancer.

Risk Factors for Urologic Complications After Kidney Transplantation and Impact in Graft Survival.

Background and Purpose: Kidney transplantation (KT) is the best therapy for chronic kidney disease (CKD). Major urologic complications (MUCs) are the second etiology associated to morbidity and graft loss following KT, after rejection episodes. The objective of this study was to estimate the incidence, risk factors and impact on graft survival associated to urological complications in KT patients. Patients and Methods: A retrospective cohort based on electronic patient files of kidney transplant recipients from Colombiana de Trasplantes was created for the period August 2008 to September 2019. Initiation of follow-up was defined as the date of transplantation up to 3 years post-transplantation. Incidence of ureteral stenosis, ureteral obstruction, and ureteral leak was measured. A logistic regression multivariate model was adjusted to determine the associated factors to MUCs (yes/no). Patient and graft survival time were analyzed using a Kaplan-Meier method. Results: A total of 1584 KT patients were included in the cohort. MUCs were present in 195 (12.6%) KT patients. We found that dialysis duration (OR: 1.004; p = 0.02) remained significant for the incidence of MUCs in KT patients of deceased donors. Probability of graft and patient survival at 3 years of follow-up was 90.5% and 85.5%, respectively. No significant difference was found on graft and patient survival in KT patients with or without MUCs. Conclusion: MUCs are frequent complications for KT. We did not observe significant differences in graft or patient survival according to the presence of MUCs. The identification of MUCs and risk factors may guide transplant teams for future surgical and clinical decisions.

[Transplant patient and kidney graft survival in a retrospective cohort in Mexico]. / Supervivencia del paciente trasplantado y del injerto renal en una cohorte retrospectiva en México.

Background: Knowledge of the functionality of the graft and patient survival is essential to assess the success of kidney transplantation. Objective: To determine the survival of transplanted patients by type of donor and the functionality of kidney grafts in a cohort in Mexico. Material and methods: Kidney transplant cohort from 2013 to 2017 in Mexico. 790 patients followed up for one year were analyzed to assess the survival of transplanted patients by type of donor and the functionality of kidney grafts. For this, measures of central tendency and dispersion were used, as well as Kaplan-Meier survival tables with SPSS, version 25. Results: Out of the 790 patients, 518 were from living donors (65.56%) with patient survival of 97.88% and graft function of 93.24% at 12 months of follow-up; 272 patients received the graft from a deceased donor with patient survival of 91.18% and renal graft function of 84.19%. Conclusions: There is still a difference of almost 5% in the survival of the recipient patient from a living donor compared to a deceased donor. For the functionality of the kidney graft, this difference is > 7%. Cadaveric donation has increased; however, even at low figures is of approximately 35% in Mexico.

Introducción: el conocimiento de la funcionalidad del injerto y la supervivencia del paciente es fundamental para valorar el éxito del trasplante renal. Objetivo: determinar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales en una cohorte en México. Material y métodos: cohorte de trasplante renal de 2013 a 2017 en México. Se analizaron 790 pacientes seguidos por un año para valorar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales. Para ello se usaron medidas de tendencia central y dispersión, así como tablas de supervivencia de Kaplan-Meier con SPSS, versión 25. Resultados: de los 790 pacientes, 518 fueron de donante vivo (65.56%) con supervivencia del paciente de 97.88% y de funcionalidad del injerto de 93.24% a 12 meses de seguimiento; 272 pacientes recibieron el injerto de donante fallecido con supervivencia del paciente de 91.18% y funcionalidad del injerto renal de 84.19%. Conclusiones: aún existe una diferencia de casi 5% en la supervivencia del paciente receptor de un donante vivo en referencia con un donante fallecido. Para la funcionalidad del injerto renal esta diferencia es > 7%. La donación cadavérica ha aumentado; sin embargo, incluso en cifras bajas es de aproximadamente el 35% en México.

Supervivencia del paciente trasplantado y del injerto renal en una cohorte retrospectiva en México / Transplant patient and kidney graft survival in a retrospective cohort in Mexico

Introducción: el conocimiento de la funcionalidad del injerto y la supervivencia del paciente es fundamental para valorar el éxito del trasplante renal. Objetivo: determinar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales en una cohorte en México. Material y métodos: cohorte de trasplante renal de 2013 a 2017 en México. Se analizaron 790 pacientes seguidos por un año para valorar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales. Para ello se usaron medidas de tendencia central y dispersión, así como tablas de supervivencia de Kaplan-Meier con SPSS, versión 25. Resultados: de los 790 pacientes, 518 fueron de donante vivo (65.56%) con supervivencia del paciente de 97.88% y de funcionalidad del injerto de 93.24% a 12 meses de seguimiento; 272 pacientes recibieron el injerto de donante fallecido con supervivencia del paciente de 91.18% y funcionalidad del injerto renal de 84.19%. Conclusiones: aún existe una diferencia de casi 5% en la supervivencia del paciente receptor de un donante vivo en referencia con un donante fallecido. Para la funcionalidad del injerto renal esta diferencia es > 7%. La donación cadavérica ha aumentado; sin embargo, incluso en cifras bajas es de aproximadamente el 35% en México

Background: Knowledge of the functionality of the graft and patient survival is essential to assess the success of kidney transplantation. Objective: To determine the survival of transplanted patients by type of donor and the functionality of kidney grafts in a cohort in Mexico. Material and methods: Kidney transplant cohort from 2013 to 2017 in Mexico. 790 patients followed up for one year were analyzed to assess the survival of transplanted patients by type of donor and the functionality of kidney grafts. For this, measures of central tendency and dispersion were used, as well as Kaplan-Meier survival tables with SPSS, version 25. Results: Out of the 790 patients, 518 were from living donors (65.56%) with patient survival of 97.88% and graft function of 93.24% at 12 months of follow-up; 272 patients received the graft from a deceased donor with patient survival of 91.18% and renal graft function of 84.19%. Conclusions: There is still a difference of almost 5% in the survival of the recipient patient from a living donor compared to a deceased donor. For the functionality of the kidney graft, this difference is > 7%. Cadaveric donation has increased; however, even at low figures is of approximately 35% in Mexico

[ABO incompatible living donor kidney transplantation in a center in Córdoba, Argentina]. / Trasplante renal donante vivo ABO incompatible en un centro de Córdoba, Argentina.

The ABO incompatible (ABOi) living donor (LD) kidney transplant allows increasing the number of donors and reducing the time on the waiting list. The objectives of this study were to compare graft survival, patient survival, rejection risk factors and complications during the first year p ost-transplantation in patients who received an ABOi LD kidney transplant between 2014 and 2019 in our institution, matched according to sex, age and immunological risk with a control group of ABO compatible (ABOc) LD kidney transplants in the same period. Thirteen patients were included in each group. No significant differences were found between ABOi and ABOc in the incidence of delayed graft function (n = 0 vs. 1), bleeding (0 vs. 0), infections (13 vs. 13), cellular rejection (1 vs. 3) and humoral rejection (4 vs. 3) in the first year after transplantation. The rejection rate in ABOi do not seem to be related to blood incompatibility. No risk factors associated with rejection were found. Overall survival of patients was 100% in both groups, and graft survival was 92.3% in ABOi and 100% in ABOc (p = 1). ABOi kidney transplantation is an adequate feasible option in our environment for those who do not have compatible donors.

El trasplante renal con donante vivo (DV) ABO incompatible (ABOi) permite aumentar el número de donantes y reducir el tiempo en lista de espera. Los objetivos de este estudio fueron: comparar la supervivencia del injerto, del paciente, los factores de riesgo de rechazo y las complicaciones durante el primer año post-trasplante en los pacientes que recibieron un trasplante DV ABOi entre 2014 y 2019 en nuestra institución, emparejados según sexo, edad y riesgo inmunológico con un grupo control de trasplantados DV ABO compatibles (ABOc) en el mismo periodo. Se incluyeron 13 pacientes en cada grupo. No se hallaron diferencias significativas entre los ABOi vs ABOc en la incidencia de retardo de la función del injerto (n = 0 vs. 1), sangrado (0 vs. 0), infecciones (13 vs. 13), rechazo celular (1 vs. 3) y rechazo humoral (4 vs. 3) en el primer año posttrasplante. La tasa de rechazo en los pacientes ABOi no parece tener relación con la incompatibilidad sanguínea, ni se hallaron otros factores de riesgo asociados a rechazo. La supervivencia global de los pacientes fue del 100% en ambos grupos, y la del injerto fue del 92.3% en ABOi y 100% en ABOc (p = 1). El trasplante renal ABOi es una adecuada opción factible en nuestro medio para quienes que no cuentan con donantes compatibles.

Sobrevida del paciente adulto mayor y del injerto en trasplante renal / Patient and graft survival in the elderly kidney transplant recipients

Resumen Introducción: el trasplante renal es considerado la terapia más efectiva para el tratamiento de la enfermedad renal crónica (ERC). Recientemente, el trasplante renal ha aumentado en los pacientes mayores de 60 años, dado que presenta ventajas relevantes reportadas en la literatura mundial como un menor riesgo de morir, en comparación con pacientes de la misma edad que continúan en diálisis. Objetivo: evaluar la sobrevida del injerto y del paciente adulto mayor en una cohorte de pacientes con trasplante renal. Materiales y métodos: analizamos retrospectivamente una cohorte de 193 pacientes mayores de 60 años, quienes recibieron trasplante renal en el periodo comprendido entre 2008 a 2019 en nuestros centros de trasplante. Se analizaron variables sociodemográficas y clínicas para determinar la sobrevida del injerto y del paciente a 1, 5 y 10 años postrasplante, mediante el método de Kaplan-Meier. Se realizó un modelo de regresión de Cox para evaluar los potenciales factores de riesgo para pérdida del injerto renal en el primer año postrasplante. Resultados: la media de edad de los pacientes fue de 64,62 ± 3,82 años. La sobrevida del injerto censurada por muerte fue del 90 %, 86 % y 75 % en los años 1, 5 y 10 postrasplante, respectivamente, y la sobrevida del injerto no censurada fue del 82 %, 63 % y 43 %, respectivamente y en el mismo orden, en los mismos periodos documentados. Las principales causas de mortalidad fueron infecciones y enfermedad cardiovascular. La sobrevida del paciente adulto mayor fue del 89 %, 70 % y 55 % en los años 1, 5 y 10 postrasplante, respectivamente. Los factores de riesgo asociados a pérdida del injerto renal en el primer año postrasplante fueron: edad mayor a 70 años (HR 4,2; 95 % CI 1,1-15,3), sexo femenino (HR 2,7; 95 % CI 1,01-7,3) y no adherencia al tratamiento (HR 8,1; 95 % CI 2,1-30,7). Conclusión: los pacientes adultos mayores trasplantados tuvieron desenlaces adecuados en el trasplante renal. Es importante definir herramientas de evaluación del paciente adulto mayor que sean objetivas en el pretrasplante, donde la edad no sea una barrera de acceso al trasplante renal para esta población.

Abstract Background: Kidney transplantation is considered the most effective renal replacement therapy for chronic kidney disease. Recently, kidney transplantation is increasing in elderly recipients. Aged patients who have a kidney transplant have relevant advantages compared to dialysis reported in the literature such as better survival. Objective: We aimed to assess graft and patient survival in a cohort of elderly kidney transplant recipients. Materials and Methods: We retrospectively analyzed a cohort of 193 patients older than 60 years who received a kidney transplant from 2008 to 2019 in our transplant centers. Our study included sociodemographic and clinical variables to determine patient and graft survival at 1, 5 and 10 years after kidney transplantation using the Kaplan-Meier method. Cox regression analysis was used to evaluate the potential risk factors for graft loss during the first year of transplantation. Results: The mean recipient age was 64.62 ± 3.82 years old. The 1, 5 and 10-year death-censored graft survival rates were 90%, 86% and 75% and uncensored graft survival probability was 82%, 63% and 43% at 1, 5 and 10 years, respectively. The main mortality causes were infections and cardiovascular disease. Patient survival was 89%, 70% and 55% at 1, 5 and 10 years, respectively. Independent graft loss risk factors in the first year posttransplant were: age >70 (HR 4.2; 95% CI 1.1-15.3), female sex (HR 2.7; 95% CI 1.01-7.3) and non-compliance (HR 8.1; 95% CI 2.1-30.7). Conclusion: We found that older patients experience good outcomes following renal transplantation. There is a need to determine suitable older recipients based on objective selection criteria where age should not be a barrier to the kidney transplant.

Trasplante renal donante vivo ABO incompatible en un centro de Córdoba, Argentina / ABO incompatible living donor kidney transplantation in a center in Córdoba, Argentina

Resumen El trasplante renal con donante vivo (DV) ABO incompatible (ABOi) permite aumentar el número de donantes y reducir el tiempo en lista de espera. Los objetivos de este estudio fueron: comparar la supervivencia del injerto, del paciente, los factores de riesgo de rechazo y las complicaciones durante el primer año post-trasplante en los pacientes que recibieron un trasplante DV ABOi entre 2014 y 2019 en nuestra ins titución, emparejados según sexo, edad y riesgo inmunológico con un grupo control de trasplantados DV ABO compatibles (ABOc) en el mismo periodo. Se incluyeron 13 pacientes en cada grupo. No se hallaron diferencias significativas entre los ABOi vs ABOc en la incidencia de retardo de la función del injerto (n = 0 vs. 1), sangrado (0 vs. 0), infecciones (13 vs. 13), rechazo celular (1 vs. 3) y rechazo humoral (4 vs. 3) en el primer año post-trasplante. La tasa de rechazo en los pacientes ABOi no parece tener relación con la incompatibilidad sanguínea, ni se hallaron otros factores de riesgo asociados a rechazo. La supervivencia global de los pacientes fue del 100% en ambos grupos, y la del injerto fue del 92.3% en ABOi y 100% en ABOc (p = 1). El trasplante renal ABOi es una adecuada opción factible en nuestro medio para quienes que no cuentan con donantes compatibles.

Abstract The ABO incompatible (ABOi) living donor (LD) kidney transplant allows increasing the number of donors and reducing the time on the waiting list. The objectives of this study were to compare graft survival, patient survival, rejection risk factors and complications during the first year p ost-transplantation in patients who received an ABOi LD kidney transplant between 2014 and 2019 in our institution, matched according to sex, age and immunological risk with a control group of ABO compatible (ABOc) LD kidney transplants in the same period. Thirteen patients were included in each group. No significant differences were found between ABOi and ABOc in the incidence of delayed graft function (n = 0 vs. 1), bleeding (0 vs. 0), infections (13 vs. 13), cellular rejection (1 vs. 3) and humoral rejection (4 vs. 3) in the first year after transplantation. The rejection rate in ABOi do not seem to be related to blood incompatibility. No risk factors associated with rejection were found. Overall survival of patients was 100% in both groups, and graft survival was 92.3% in ABOi and 100% in ABOc (p = 1). ABOi kidney trans plantation is an adequate feasible option in our environment for those who do not have compatible donors.

Ivabradine plus conventional treatment vs conventional treatment alone in reducing the mean heart rate in heart transplant recipients: A randomized clinical trial.

The absence of afferent nerves for heart rate (HR) regulation leaves the transplanted heart under the influence of its internal and hormonal control. The HR of heart transplantation (HTx) recipients varies from to 90-110 bpm, indicating a lack of vagal parasympathetic tone. We hypothesized that the reduction in mean HR using an If-channel antagonist (ivabradine) could be effective and safe in HTx recipients. The primary objective of this open-label randomized clinical trial was to compare the mean HR at 3, 6, 12, 18, 24, 30, and 36 months after randomization between an ivabradine plus conventional treatment group (IG) and conventional treatment alone group (CG). The secondary objectives were reduction in mortality, graft dysfunction, and ventricular mass. All patients were randomized between 1 and 12 months after HTx. Ivabradine started at randomization. Of the 35 patients, 54.28% were in the CG and 45.72% in the IG. There were no significant between-group differences in demographics. Over time, the HR differences between the groups became significant (P < .01). There were no significant between-group differences in mortality, graft dysfunction, and ventricular mass. We conclude that ivabradine could effectively and consistently reduce the HR in HTx recipients.

Caracterización de la evolución clínica del trasplante renal en pacientes con virus de la hepatitis C positivo / Characterization of the clinical course of kidney transplantation in patients with positive hepatitis C virus

Introducción: La infección por el virus de la hepatitis C es un evento común en los receptores de trasplante renal que la arrastran desde su estancia en los tratamientos de hemodiálisis previos al implante. La positividad al virus C se ha asociado a una evolución desfavorable después del trasplante, dado por una mayor frecuencia de complicaciones clínicas, metabólicas e inmunológicas que repercuten de forma negativa tanto en la supervivencia del injerto como del paciente. Objetivos: Caracterizar la evolución clínica de los pacientes trasplantados de riñón con virus de la hepatitis C positivo y determinar la evolución de este grupo de enfermo de acuerdo a variables demográficas, clínicas y de supervivencia. Método: Estudio analítico, transversal, retrospectivo en pacientes trasplantados renales del Hospital Clínico Quirúrgico Hermanos Ameijeiras, desde el año 2005 al 2017. Se excluyeron los menores de 15 años, los retrasplantes, los trasplantes dobles y los combinados o cuando no se pudo obtener la información. Se comparan las variables escogidas entre enfermos que llegan al trasplante con serología positiva al virus C, (HVC positivos), con los HVC negativos. Resultados: Del total de 156 enfermos, 65 por ciento (102) fueron HVC positivos, no se encontraron diferencias entre grupo en cuanto a edad y sexo de receptores y donantes, así como tampoco en el tratamiento inmunosupresor utilizado. El donante vivo se empleó menos en los HVC positivos donde se encontraron más enfermos con poliquistosis renal. La necrosis tubular aguda (NTA) y el rechazo fueron más frecuentes en los HVC positivos, siendo la primera estadísticamente significativa, p=0,0421, también resultaron significativamente más frecuente en el grupo HVC positivo, la proteinuria, p=0,041, la elevación de enzimas hepáticas, p=0,047 y la diabetes postrasplante, p=0,047. La supervivencia del injerto y los pacientes fue menor en los HVC positivos. Conclusiones: En este estudio la hepatitis por virus C impacta negativamente en la evolución del injerto y propicia la aparición de algunas complicaciones clínicas, lo que sin dudas pudiera influir en una menor expectativa de vida tanto para el injerto como para el enfermo(AU)

Introduction: Hepatitis C virus infection is a common event in kidney transplant recipients that has dragged it along since their stay in hemodialysis treatments prior to implantation. Positivity to virus C has been associated with an unfavorable evolution after transplantation, due to higher frequency of clinical, metabolic and immunological complications that negatively affect both graft and patient survival. Objectives: To describe the clinical evolution of kidney transplant patients with positive hepatitis C virus and to determine the evolution of this group of patients according to demographic, clinical and survival variables. Method: An analytical, cross-sectional, retrospective study in kidney transplant patients at Hermanos Ameijeiras Hospital was carried out from 2005 to 2017. This study excluded children under 15 years of age, re-transplants, double and combined transplants or when it was not possible to gather the information. The variables chosen among patients who arrive at transplantation with positive serology for virus C (positive HCV) were compared with negative HCV. Results: One hundred and fifty six patients were the total, 65 percent (102) were HVC positive, no differences were found between groups in terms of age and sex of recipients and donors, nor in the immunosuppressive treatment used. The living donor was less used in positive HVC where more patients with polycystic kidney disease were found. Acute tubular necrosis (ATN) and rejection were more frequent in positive HVC, the former being statistically significant, p = 0.0421, proteinuria, p = 0.041, elevation was also significantly more frequent in the positive HVC group of liver enzymes, p = 0.047 and post-transplant diabetes, p = 0.047. Graft and patient survival was lower in positive HCV. Conclusions: In this study, hepatitis C virus has negative impact on the evolution of the graft and favors the appearance of some clinical complications, which undoubtedly could influence a shorter life expectancy for both the graft and the patient(AU)

Impact of Combinations of Donor and Recipient Ages and Other Factors on Kidney Graft Outcomes.

As the availability of kidneys for transplantation continues to be outpaced by its growing demand, there has been an increasing utilization of older deceased donors in the last decades. Considering that definition of factors that influence deceased donor kidney transplant outcomes is important for allocation policies, as well as for individualization of post-transplant care, the purpose of this study was determine the risks for death censored graft survival and for patient survival conferred by older age of the donor in the context of the age of the recipient and of risk factors for graft and/or patient survival. The investigation was conducted in a single-center cohort of 5,359 consecutive first kidney transplants with adult deceased donors performed on non-prioritized adult recipients from January 1, 2002, to December 31, 2017. Death censored graft survival and patient survival were lower in older donors, whereas graft survival was higher and patient survival was lower in old recipients. The analyses of combinations of donor and recipient ages showed that death censored graft survival was lower in younger recipients in transplants from 18 to 59-year old donors, with standard or extended criteria, but no difference in graft survival was observed between younger and older recipients when the donor was ≥ 60-year old. Patient survival was higher in younger recipients in transplants with younger or older donors. Two to six HLA-A,B,DR mismatches, when compared to 0-1 MM, conferred risk for death-censored graft survival only in transplants from younger donors to younger recipients. Pre-transplant diabetes conferred risk for patient survival only in 50-59-year old recipients, irrespectively, of the age of the donor. Time on dialysis ≥ 10 years was a risk factor for patient survival in transplants with all donor-recipient age combinations, except in recipients with ≥ 60 years that received a kidney from an 18-49-year old donor. In conclusion, the results obtained in this study underline the importance of analyzing the impact of the age of the donor taking into consideration different scenarios.

Renal transplantation recipient patients survival.

INTRODUCTION: The Bajío High Specialty Regional Hospital started operating in 2007 to tackle the health demands of 5.8 million inhabitants. It has 184 beds and a transplant unit with 26 beds. In 2008, the renal transplant program launched activities. OBJECTIVE: To describe the survival of kidney transplant receptor patients and of the grafted kidney at the Bajío High Specialty Regional Hospital. METHODS: Retrospective cohort study, where consecutive transplants carried out between 2008 and 2016 were included. Statistical analysis was performed using the Kaplan-Meier method. RESULTS: A total of 837 transplants were analyzed. Graft survival censored for death, with a functional graft at 1 and 5 years, was 94.6% and 78.9%. Patient survival at 1 and 5 years was 95.4% and 88.1%. CONCLUSIONS: The renal transplant program is one of the the best programs established in Mexico, both for the number of deceased-donor kidney transplants performed and for the patient and graft survival achieved. These data indicate that the renal transplant program has had a sustained development.

INTRODUCCIÓN: El Hospital Regional de Alta Especialidad del Bajío inició sus funciones en 2007 para atender la demanda de salud de 5.8 millones de habitantes, cuenta con 184 camas y una unidad de trasplantes con 26 camas. En 2008 inició actividades el programa de trasplante renal. OBJETIVO: Presentar la supervivencia de los pacientes receptores de trasplante renal y del riñón injertado en el Hospital Regional de Alta Especialidad del Bajío, Guanajuato, México. MÉTODO: Estudio de cohorte retrospectivo en el que se incluyeron los trasplantes consecutivos realizados entre 2008 y 2016. El análisis estadístico se efectuó con el método de Kaplan-Meier. RESULTADOS: Se analizaron 837 trasplantes. La supervivencia del injerto censurada para muerte con injerto funcional a uno y cinco años fue de 94.6 y 78.9 %. La supervivencia del paciente a uno y cinco años fue de 95.4 y 88.1 %. CONCLUSIONES: El programa de trasplante renal constituye uno de los mejor establecidos en México, tanto por el número de trasplantes renales de donante fallecido realizados como por la supervivencia obtenida de paciente e injerto. Los datos indican que el programa de trasplante renal ha tenido un desarrollo sostenido.

Supervivencia de los pacientes receptores de trasplante renal / Renal transplantation recipient patients survival

Resumen Introducción: El Hospital Regional de Alta Especialidad del Bajío inició sus funciones en 2007 para atender la demanda de salud de 5.8 millones de habitantes, cuenta con 184 camas y una unidad de trasplantes con 26 camas. En 2008 inició actividades el programa de trasplante renal. Objetivo: Presentar la supervivencia de los pacientes receptores de trasplante renal y del riñón injertado en el Hospital Regional de Alta Especialidad del Bajío, Guanajuato, México. Método: Estudio de cohorte retrospectivo en el que se incluyeron los trasplantes consecutivos realizados entre 2008 y 2016. El análisis estadístico se efectuó con el método de Kaplan-Meier. Resultados: Se analizaron 837 trasplantes. La supervivencia del injerto censurada para muerte con injerto funcional a uno y cinco años fue de 94.6 y 78.9 %. La supervivencia del paciente a uno y cinco años fue de 95.4 y 88.1 %. Conclusiones: El programa de trasplante renal constituye uno de los mejor establecidos en México, tanto por el número de trasplantes renales de donante fallecido realizados como por la supervivencia obtenida de paciente e injerto. Los datos indican que el programa de trasplante renal ha tenido un desarrollo sostenido.

Abstract Introduction: The Bajío High Specialty Regional Hospital started operating in 2007 to tackle the health demands of 5.8 million inhabitants. It has 184 beds and a transplant unit with 26 beds. In 2008, the renal transplant program launched activities. Objective: To describe the survival of kidney transplant receptor patients and of the grafted kidney at the Bajío High Specialty Regional Hospital. Methods: Retrospective cohort study, where consecutive transplants carried out between 2008 and 2016 were included. Statistical analysis was performed using the Kaplan-Meier method. Results: A total of 837 transplants were analyzed. Graft survival censored for death, with a functional graft at 1 and 5 years, was 94.6% and 78.9%. Patient survival at 1 and 5 years was 95.4% and 88.1%. Conclusions: The renal transplant program is one of the the best programs established in Mexico, both for the number of deceased-donor kidney transplants performed and for the patient and graft survival achieved. These data indicate that the renal transplant program has had a sustained development.

Microbiota Profile and Impact of Fusobacterium nucleatum in Colorectal Cancer Patients of Barretos Cancer Hospital.

Microbial diversity has been pointed out as a major factor in the development and progression of colorectal cancer (CRC). We sought to explore the richness and abundance of the microbial community of a series of colorectal tumor samples treated at Barretos Cancer Hospital, Brazil, through 16S rRNA sequencing. The presence and the impact of Fusobacterium nucleatum (Fn) DNA in CRC prognosis was further evaluated by qPCR in a series of 152 CRC cases. An enrichment for potentially oncogenic bacteria in CRC was observed, with Fusobacterium being the most abundant genus in the tumor tissue. In the validation dataset, Fn was detected in 35/152 (23.0%) of fresh-frozen tumor samples and in 6/57 (10.5%) of paired normal adjacent tissue, with higher levels in the tumor (p = 0.0033). Fn DNA in the tumor tissue was significantly associated with proximal tumors (p = 0.001), higher depth of invasion (p = 0.014), higher clinical stages (p = 0.033), poor differentiation (p = 0.011), MSI-positive status (p < 0.0001), BRAF mutated tumors (p < 0.0001), and the loss of expression of mismatch-repair proteins MLH1 (p < 0.0001), MSH2 (p = 0.003), and PMS2 (p < 0.0001). Moreover, the presence of Fn DNA in CRC tissue was also associated with a worse patient cancer-specific survival (69.9 vs. 82.2% in 5 years; p = 0.028) and overall survival (63.5 vs. 76.5%; p = 0.037). Here we report, for the first time, the association of F. nucleatum presence with important clinical and molecular features in a Brazilian cohort of CRC patients. Tumor detection and classification based on the gut microbiome might provide a promising approach to improve the prediction of patient outcome.

A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets.

BACKGROUND & AIMS: A causal link has recently been established between epigenetic alterations and hepatocarcinogenesis, indicating that epigenetic inhibition may have therapeutic potential. We aimed to identify and target epigenetic modifiers that show molecular alterations in hepatocellular carcinoma (HCC). METHODS: We studied the molecular-clinical correlations of epigenetic modifiers including bromodomains, histone acetyltransferases, lysine methyltransferases and lysine demethylases in HCC using The Cancer Genome Atlas (TCGA) data of 365 patients with HCC. The therapeutic potential of epigenetic inhibitors was evaluated in vitro and in vivo. RNA sequencing analysis and its correlation with expression and clinical data in the TCGA dataset were used to identify expression programs normalized by Jumonji lysine demethylase (JmjC) inhibitors. RESULTS: Genetic alterations, aberrant expression, and correlation between tumor expression and poor patient prognosis of epigenetic enzymes are common events in HCC. Epigenetic inhibitors that target bromodomain (JQ-1), lysine methyltransferases (BIX-1294 and LLY-507) and JmjC lysine demethylases (JIB-04, GSK-J4 and SD-70) reduce HCC aggressiveness. The pan-JmjC inhibitor JIB-04 had a potent antitumor effect in tumor bearing mice. HCC cells treated with JmjC inhibitors showed overlapping changes in expression programs related with inhibition of cell proliferation and induction of cell death. JmjC inhibition reverses an aggressive HCC gene expression program that is also altered in patients with HCC. Several genes downregulated by JmjC inhibitors are highly expressed in tumor vs. non-tumor parenchyma, and their high expression correlates with a poor prognosis. We identified and validated a 4-gene expression prognostic signature consisting of CENPA, KIF20A, PLK1, and NCAPG. CONCLUSIONS: The epigenetic alterations identified in HCC can be used to predict prognosis and to define a subgroup of high-risk patients that would potentially benefit from JmjC inhibitor therapy. LAY SUMMARY: In this study, we found that mutations and changes in expression of epigenetic modifiers are common events in human hepatocellular carcinoma, leading to an aggressive gene expression program and poor clinical prognosis. The transcriptional program can be reversed by pharmacological inhibition of Jumonji enzymes. This inhibition blocks hepatocellular carcinoma progression, providing a novel potential therapeutic strategy.

Sexual acquisition of HIV infection after solid organ transplantation: Late presentation and potentially fatal complications.

INTRODUCTION: While the growing knowledge on HIV among solid organ transplant recipients (SOT) is limited to either pretransplant infection or allograft transmission, there are only sparse reports describing HIV-infection after transplantation through sexual route, the primary mode of transmission in the general population. METHODS: From two different centers, we report nine new cases of HIV infection in SOT recipients attributed to sexual acquisition: eight cases of kidney-transplant recipients and one heart-transplant recipient. FINDINGS: There were nine cases of post-transplant HIV-infection detected among 14 526 transplants performed 1998 to 2015. In 6/9 cases, infection was contracted 5 years after SOT. All but one patient had stable allograft function under immunosuppressive therapy. The main trigger to diagnosis was late CMV disease and sexually transmitted diseases; five patients had CDC-stage 3 HIV infection. In 7/9 patients, virologic response and CD4 recovery were achieved within 3 months after starting antiretroviral therapy (ART). After an average of 3.6 years post diagnosis, 5/9 patients remained alive with well-controlled infection and functioning allograft. CONCLUSION: Sexual acquisition of HIV infection after SOT represents a difficult challenge, as it may occur in any kind of transplant and at any time. The course of infection resembles that of the general population, with life-threatening infectious complications, but good response to ART. Assessment of lifestyle and risk behavior is paramount, as indications may be not disclosed without direct questioning.