Can we predict the kidney graft survival before its performance?

RESUMEN : El trasplante renal es tratamiento de elección en los pacientes que padecen insuficiencia renal crónica, por lo que es fundamental conocer los factores predictores de muerte y de fracaso del injerto, así como su aplicación en la práctica clínica para que el injerto dure el mayor tiempo posible y con la mejor calidad de vida. Diversos factores pretrasplante y post-trasplante pueden influir en una peor supervivencia del injerto renal. Se han desarrollado múltiples modelos que combinan estos factores para predecir el riesgo de pérdida de los injertos renales. Entre estos modelos, Molnar et al desarrollaron uno en población norteamericana utilizando variables pretrasplante. El objetivo de nuestro estudio fue validar dicho modelo en una población española. Realizamos un estudio retrospectivo de todos los trasplantes renales realizados en el Hospital Universitario Marqués de Valdecilla entre 2000 y 2015. En nuestra población se demostró que el modelo predictivo de Molnar se asociaba con un mayor riesgo de pérdida del injerto a uno, tres y cinco años, pero no estaba bien calibrado ni presentaba una capacidad discrimintaviva significativa como para considerarlo útil en nuestra población.ABSTRACT : Kidney transplantation is the treatment of choice in patients with chronic kidney failure, so it is essential to study the factors predictive of death and failure of the grafts, as well as its application in clinical practice, so that the graft lasts the longest possible time and with the best quality of life. Both pretransplant and posttransplant risk factors influence the outcome of the kidney graft. Several risk prediction models have been developed to estimate the risk of graft loss. Among them, Molnar et al developed a model to predict graft survival in a US population taking into account only pretransplant variables. Our objective was to validate this model in a Spanish kidney transplant population. We carried out a retrospective study including all the kidney transplants performed in University Hospital Marqués de Valdecilla between 2000 and 2015. In our population of kidney transplant recipients, Molnar`s model related to a higher risk of graft failure at one, three and five years after transplantation, but this model did not allow to discriminate those patients who were going to lose the graft and it was not well calibrated to predict graft failure.Grado en Medicin

Blood Bacterial Profiles Associated With Human Immunodeficiency Virus Infection and Immune Recovery

[EN] Human immunodeficiency virus (HIV) infection impairs mucosal immunity and leads to bacterial translocation, fueling chronic inflammation and disease progression. While this is well established, questions remain about the compositional profile of the translocated bacteria, and to what extent it is influenced by antiretroviral therapy (ART). Using 16S ribosomal DNA targeted sequencing and shotgun proteomics, we showed that HIV increases bacterial translocation from the gut to the blood. HIV increased alpha diversity in the blood, which was dominated by aerobic bacteria belonging to Micrococcaceae (Actinobacteria) and Pseudomonadaceae (Proteobacteria) families, and the number of circulating bacterial proteins was also increased. Forty-eight weeks of ART attenuated this phenomenon. We found that enrichment with Lactobacillales order, and depletion of Actinobacteria class and Moraxellaceae and Corynebacteriacae families, were significantly associated with greater immune recovery and correlated with several inflammatory markers. Our findings suggest that the molecular cross talk between the host and the translocated bacterial products could influence ART-mediated immune recovery.This work was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013–2016, projects PI15/00345 and PI18/00154); the Fundación Asociación Española Contra el Cáncer within the European Research Era-NET aligning national/regional translational cancer research programs and activities program (grant AC17/00019) and cofinanced by the European Development Regional Fund; and Plan Estatal de I+D+i 2013–2016 (grant PT17/0019 to the Proteomics Facility of the Spanish National Center for BIotechnology)

Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor’s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.This work was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013–2016, project PI18/00154, a Gilead Fellowship (GLD16-00030), the SPANISH AIDS Research Network RD16/0025/0001project), and co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (ERDF). The present investigation was also funded by the Instituto de Salud Carlos III and the Fundación Asociación Española contra el Cáncer within the ERANET TRANSCAN-2 program, grant number AC17/00022, a crowdfunding project from the precipita platform of the Fundación Española para la Ciencia y la Tecnología (FECYT) and a restricted grant from Finch Therapeutics. The SEIMC-GESIDA Foundation supported this study with safety and data monitoring (GESIDA 9116).Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

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

The effects of provenance, climate, and chemical defense on the resistance of Pinus pinaster Aiton to Bursaphelenchus xylophilus (Steiner and Buhrer)

Abstract Key message The resistance of Pinus pinaster Aiton to pinewood nematode Bursaphelenchus xylophilus (Steiner and Buhrer) varied among populations from the Iberian Peninsula, with survival rates for inoculated seedlings ranging from 5 to 100%. These differences in resistance were paralleled by differences in some constitutive chemical defenses. Populations from the southeastern Iberian Peninsula displayed higher resistance than northern populations. Context The presence of the pinewood nematode (PWN), Bursaphelenchus xylophilus (Steiner and Buhrer), in Portugal threatens Mediterranean pine species such as Pinus pinaster Aiton. Aims We have focused on assessing the resistance of P. pinaster populations to B. xylophilus, looking for any relationship between the PWN resistance and some constitutive chemical defenses and geoclimatic parameters. Methods Two-year-old seedlings from 32 provenances and two seed orchards were evaluated in an experiment of artificial inoculation following a randomized complete block design under greenhouse conditions. We measured growth-related traits, response to B. xylophilus inoculations, and constitutive chemical compounds in needles of the evaluated seedlings and compiled geoclimatic data for each population. Mixed models, nonparametric tests, correlations, and PCA were used to analyze the data. Results Survival, wilting symptoms, morphological traits, and nematode density varied significantly among populations. Lower concentrations of constitutive polyphenols, lipid-soluble substances, and tannins were related to higher PWN resistance. Populations from the southeast of the Iberian Peninsula showed higher survival rates than those from further north. Additionally, we observed that populations to warm, dry climates showed higher resistance to B. xylophilus than populations originating from humid, temperate climates. Conclusion Higher susceptibility to PWN is related to lower growth traits, to lower levels of certain constitutive chemical compounds, and to adaptations to harsher climate