Trasplante renal en pacientes con infección por virus de la inmunodeficiencia humana (VIH)

El pronóstico de la infección por VIH ha mejorado tras introducir el tratamiento antirretroviral de gran actividad (TARGA), no contraindicando actualmente el trasplante renal (TR). La nefropatía asociada al VIH (HIVAN) es la principal causa de enfermedad crónica terminal (ERCT) en pacientes VIH a nivel mundial. Los criterios de inclusión para TR de pacientes VIH son multidisciplinares: no infecciones oportunistas; CD4>200; carga viral indetectable. Material y métodos. Revisión de historias clínicas de 14 pacientes infectados por VIH receptores de un primera lo injerto renal (2001-2019),seleccionadossegúnrecomendacionesdelasguíasespañolasyamericanas.Lainmunosupresiónserealizósegúnlaprácticahabitualennuestropaís.TARGAseinicióinmediatamentetrasTR.Resultados.LaprincipalcausadeERCTfuelaglomerulonefritis(N=6;42,9%)seguidadeHIVAN(N=4;28,6%).El71,4%(N=10)seencontrabanenhemodiálisisprevioalTRysólo1pacientesetrasplantóensituacióndeprediálisis.Desdeelpuntodevistainmuno-virológico,lamedianadeCD4fue458células/μLytodoslospacientespresentabancargaviralindetectable.El92,9%(N=13)recibíaTARGApreTR.2pacientesprecisarontrasplantectomíaprecozyfueroneliminadosdelanálisisposterior.Conunamedianadeseguimientode61,0meses,el58,3%(7/12)delospacientespresentóunafunciónretrasadadelinjertoyel33,3%(4/12)rechazoagudo.Lamedianadecreatininaalos3mesesyenlaúltimafechadeseguimientofue1,3mg/dL(RIC0,8)y2,1(RIC7,1)respectivamente.Lasupervivenciadelinjertoydelpacientea1y3añosfuede75,0%y100%;y67,0%y89,0%,respectivamente.Conclusión.ElTResunaalternativaterapéuticasegurayefectivaenpacientesseleccionadosconVIH.TheprognosisofHIVinfectionhasimprovedwiththeintroductionofhighlyactiveantiretroviraltherapy(HAART),beingnolongeracontraindicationtotransplantation(KT).HIV-associatednephropathy(HIVAN)isthemostcommoncauseofend-stagerenaldisease(ESRD)amongHIV-infectedpatientsworldwide.TheconsensuscriteriafortheselectionofHIVpatientsfortransplantationaremultidisciplinary:noopportunisticinfections;CD4count>200;undetectableviralload.Materialandmethods.Reviewoftheclinicalchartsof14HIV-infected,recipientsofaprimaryrenalallograft(2001-2019).InclusioncriteriamettheAmericanandSpanishguidelinerecommendations.Immunosuppressiveprotocolfollowedroutinepracticeinourcountry.HAARTwasstartedduringimmediatepost-KT.Results.ThemainESRDetiologywasglomerulonephritis (6;42.9%)followedbyHIVAN(4;28.6%).RegardingrenalsubstitutivetreatmentpriortoKT,themajoritywereonhemodialysis(10;71.4%).InonepatientKTwaspre-emptive.MedianCD4countwas458cells/μLandallpatientspresentedundetectableviralload.13(92.9%)wereonHAARTpriortoKT.Twopatientsunderwentearlytransplantectomy,theremainingpatientswerefollowedforamedianof61.0months(3.7to106.2months).Delayedgraftfunctionandacuterejectionratewere58.3%(7/12)and33.3%(4/12)respectively.Mediancreatininelevelsat3monthsandatthelastfollow-upwere1.3mg/dL(IQR0.8)and2.1mg/dL(IQR7.1)respectively.Graftandpatientsurvivalat1and3yearswererespectively75.0%and100%;and67.0%and89%.Conclusions.KTcanbesafeandeffectiveinselectedHIV-infectedpatient

Mitochondrial echoes of first settlement and genetic continuity in El Salvador

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador. Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas. Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade

DIVULGA: Comunicación multimodal para la divulgación del conocimiento científico y académico en la red

La divulgación del conocimiento científico es una responsabilidad social que la Universidad debe abordar desde la perspectiva de la investigación y la innovación. El proyecto incentiva a usar la comunicación multimodal en la red para divulgar ciencia

DIVULGA.net: internacionalización de la divulgación del conocimiento científico y académico en internet

El proyecto DIVULGA.net tiene la finalidad específica de internacionalizar la difusión de conocimiento científico y académico, en una iniciativa liderada por alumnos UCM y cuyo propósito es incorporar a estudiantes de universidades extranjeras. De este modo se pueden crear sinergias que fortalezcan una red en internet de divulgación de cultura científica con los universitarios como agentes principales

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Impacto de la donación renal de vivo en la evolución de la función renal del donante

Introducción: El trasplante renal de donante vivo representa la mejor opción terapéutica para lospacientes con Insuficiencia Renal Crónica Terminal(IRC). Sin embargo, la nefrectomía conlleva ciertos riesgos a corto y largo plazo para el donante vivo. En este estudio queremos evaluar el impacto de la donación sobre la función renaldel donante.Material y Métodos: Evaluamos retrospectivamente a los donantes vivos renales en el periodo comprendido entre 2010 y 2018 en el Hospital Universitario Ramón y Cajal. Se realizó un análisis descriptivo de la muestra y se usó elanálisis de varianza (ANOVA) para comparar la edad y el IMC con el aclaramiento medido en los distintos momentos del tiempo. Así mismo, se realizó la curva de supervivencia de Kaplan-Meier en función del sexo para ver cuántos pacientes desarrollaban IRCpost-nefrectomía. Resultados: De los 39 pacientes, al año de la nefrectomía el 34,4% presentaron insuficiencia renaldefinida como un aclaramiento<60ml/min/1,73m2.Ningún paciente desarrollóIRCT. Los pacientes con mayor edad tuvieron un mayor deterioro de la función renal. No se demostrómayor deterioro de la función renal atendiendo al sexo y en los sujetos con IMC más alto.Conclusiones: La edad parece ser un factor de riesgo para la IRCmientras que el IMC y el sexoen la población estudiada,no parece que provoquen un mayor riesgo en el deterioro de la tasa de filtrado glomerular.Background: Living donor kidney transplantation represents the best therapeutic option for patients with chronic terminal renal failure. However, nephrectomy bears certain short-as well as long-term risks for the living donor. In this study we want to evaluate the impact of donation on donor renal function.Materials and Methods: We retrospectively evaluated live kidneydonors in the period between 2010 and 2018 at the Ramón y Cajal University Hospital. A descriptive analysis of the sample was carried out and it was used in analysis of variance (ANOVA) to compare the age and the BMI with the clearance measured at the different moments of time. Likewise, the Kaplan-Meier survival curve was performed according to sex to see how many patients developed post-nephrectomy renal failure(CKD).Results: Of the 39 patients, one year after the nephrectomy, 34.4% had renal failure (<60ml / min / 1.73m2). No patient ended up on ESKD. The older patients had a greater deterioration of renal function. There is no greater deterioration of renal function in subjects with higher BMI.Conclusions: Age seems to be a risk factor for renal failure while BMI and sex do not seem to cause a greater risk in the deterioration of the glomerular filtration rat

Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype arising from renal cell carcinomas. This tumor is characterized by a predominant angiogenic and immunogenic microenvironment that interplay with stromal, immune cells, and tumoral cells. Despite the obscure prognosis traditionally related to this entity, strategies including angiogenesis inhibition with tyrosine kinase inhibitors (TKIs), as well as the enhancement of the immune system with the inhibition of immune checkpoint proteins, such as PD-1/PDL-1 and CTLA-4, have revolutionized the treatment landscape. This approach has achieved a substantial improvement in life expectancy and quality of life from patients with advanced ccRCC. Unfortunately, not all patients benefit from this success as most patients will finally progress to these therapies and, even worse, approximately 5 to 30% of patients will primarily progress. In the last few years, preclinical and clinical research have been conducted to decode the biological basis underlying the resistance mechanisms regarding angiogenic and immune-based therapy. In this review, we summarize the insights of these molecular alterations to understand the resistance pathways related to the treatment with TKI and immune checkpoint inhibitors (ICIs). Moreover, we include additional information on novel approaches that are currently under research to overcome these resistance alterations in preclinical studies and early phase clinical trials

The Usefulness of Contrast-Enhanced Ultrasound in the Assessment of Early Kidney Transplant Function and Complications

Objectives: The routine diagnostic method for assessment of renal graft dysfunction is Doppler ultrasound. However, contrast-enhanced ultrasound (CEUS) may provide more information about parenchymal flow and vascular status of kidney allografts. The aim of the study was to assess the effectiveness of CEUS in the immediate post-transplant period, focusing on acute vascular complications. A brief review of available literature and a report of our initial experience is made. Material and methods: 15 kidney transplant (KT) cases with clinical suspicion of acute surgical complication were assessed with CEUS and conventional Doppler ultrasound (US). In addition, bibliographic review was conducted through PubMed, Embase, and ClinicalKey databases. Results: 10% of KT underwent CEUS, useful for detecting vascular complication or cortical necrosis in 4 (26%) and exclude them in 74%. Grafts with acute vascular complications have a delayed contrast-enhancement with peak intensity lower than normal kidneys. Perfusion defects can be clearly observed and the imaging of cortical necrosis is pathognomonic. Conclusions: CEUS is a useful tool in the characterization of renal graft dysfunction with special interest on acute vascular complications after renal transplant. It is a feasible technique for quantitative analysis of kidney perfusion, which provides information on renal tissue microcirculation and regional parenchymal flow. Exploration could be done by a urologist at the patient’s bedside while avoiding iodinated contrast