Contaminación de líquido de preservación en trasplante renal. Reporte y revisión de la literatura

Chronic kidney disease is a public health problem with high morbidity and mortality, kidney transplantation being one of the current therapeutic alternatives. In12 published works concerning the contamination of the preservation fluid in kidney transplant, four case reports, and eight prevalence studies. The prevalence of preservation liquid contamination for any microorganism ranged from17.43% to 59.72%, while for those limited to the Candida sp report, the frequency varied from 1.69% to 8.57%. In the case reports, all were associated with Candida infection, with renal artery arteritis and graft loss as the most frequent complications. In our institution, of a total of 59 transplant patients, at least one microorganism was isolated in 20 cases (28.17%). Preservation fluid contamination is a frequent phenomenon in kidney transplantation. However, since no publications are describing the complications associated with infection by other microorganisms, we could say that contamination by Candida sp, despite not having a high prevalence, it is clinically the most relevant.La enfermedad renal crónica es un problema de salud pública con una alta morbilidad y mortalidad. El trasplante renal es una de las actuales alternativas terapéuticas. Se incluyen en este artículo 12 trabajos publicados referentes a la contaminación del líquido de preservación en trasplante renal, 4 reportes de caso, y 8 estudios de prevalencia. En este estudio la prevalencia de contaminación de líquido de preservación para cualquier microorganismo varió entre 17,43 % a 59,72 %, mientras que para los limitados al reporte de Candida sp, la frecuencia varió de 1,69 % a 8,57 %. En los reportes de caso, todos fueron asociados a la infección por Candida sp, con arteritis de la arteria renal y pérdida del injerto como las complicaciones más frecuentes. En nuestra institución, Hospital de Especialidades de las Fuerzas Armadas N°1, de un total de 59 pacientes trasplantados se aisló al menos un microorganismo en 20 casos (28,17 %). Con estos resultados sugerimos que la contaminación del líquido de preservación es un fenómeno frecuente en trasplante renal, sin embargo al no poseer publicaciones en las que se describan las complicaciones asociadas a la infección por otros microorganismos, creemos que la contaminación por Candida sp, a pesar de no tener una gran frecuencia, es clínicamente la más relevante

Descripción de la ferropenia en pacientes con enfermedad renal crónica terminal en hemodiálisis, Quito, Ecuador

Introduction: Anemia and iron deficiency are very prevalent conditions in hemodialysis and have been associated with an increase in morbidity and mortality. Objective: Describe the characteristics of iron deficiency and anemia in patients with end-stage renal disease on hemodialysis, and analyze the parameters of the blood count to predict iron deficiency in them. Materials and methods: A cross-sectional descriptive study carried out in the hemodialysis unit of the Specialties Hospital of the Armed Forces No. 1 and CLINEF Norte, Quito, Ecuador, during December 2018 and January 2019. The analysis was based on the comparison of two groups, ferropenic and non-ferropenic patients. Results: We included 268 patients with an average age of 59.16 years; 89 patients (33.21%) were ferropenic. However, they presented normal hematimetric parameters in most of them. We also found that 80.22% of the patients included were anemic, with little frequency of microcytosis and hypochromia. Among them, 33.21% were ferropenic, being hemoglobin a poor marker of iron deficiency. Additionally, to predict ferropenia, and not to have ferritin or transferrin saturation, we find especially useful the mean corpuscular hemoglobin, mean corpuscular volume, erythrocyte distribution width, and Srivastava index, however the predictive value increases when including the syderemia as in our proposed model. Conclusions: Given the high frequency of anemia without hypochromia or microcytosis in patients with end-stage renal disease on hemodialysis, even in iron deficiency, regular evaluation of ferric metabolism is essential, as well as the analysis of the blood count with a focus on the dialysis patient.Introducción: la anemia y ferropenia son condiciones muy prevalentes en hemodiálisis asociadas al incremento en la morbimortalidad. Objetivo: describir las características de la ferropenia y anemia de pacientes con enfermedad renal terminal en hemodiálisis, y analizar los parámetros del hemograma para predecir la deficiencia de hierro en ellos. Materiales y métodos: estudio descriptivo transversal realizado en la unidad de hemodiálisis del Hospital de Especialidades de las Fuerzas Armadas N°1 y CLINEF Norte, Quito, Ecuador, durante diciembre de 2018 y enero de 2019. El análisis se basó en la comparación de dos grupos, pacientes ferropénicos y no ferropénicos. Resultados: se incluyeron 268 pacientes con edad promedio de 16 y 59 años; 89 pacientes (33,21 %) fueron ferropénicos, sin embargo presentaron parámetros hematimétricos normales en la mayoría de ellos. Encontramos además que el 80,22 % de los pacientes incluidos eran anémicos, con poca frecuencia de microcitosis e hipocromía. Entre ellos, el 33,21 % fueron ferropénicos, siendo la hemoglobina un pobre marcador de ferropenia. Adicionalmente, para predecir ferropenia, y de no contar con ferritina o saturación de transferrina, encontramos útil la hemoglobina corpuscular media, el volumen corpuscular medio, el ancho de distribución eritrocitaria y el índice de Srivastava, sin embargo el valor predictivo se incrementó al incluir la sideremia como en nuestro modelo propuesto. Conclusiones: dada la alta frecuencia de anemia sin hipocromía o microcitosis en los pacientes con enfermedad renal terminal en hemodiálisis, incluso en ferropenia, es fundamental la evaluación regular del metabolismo férrico, así como el análisis del hemograma con enfoque en el paciente dialítico

Novel genes and sex differences in COVID-19 severity

[EN] Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.S

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

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

Osteoimmunology of Oral and Maxillofacial Diseases : Translational Applications Based on Biological Mechanisms

The maxillofacial skeleton is highly dynamic and requires a constant equilibrium between the bone resorption and bone formation. The field of osteoimmunology explores the interactions between bone metabolism and the immune response, providing a context to study the complex cellular and molecular networks involved in oro-maxillofacial osteolytic diseases. In this review, we present a framework for understanding the potential mechanisms underlying the immuno-pathobiology in etiologically-diverse diseases that affect the oral and maxillofacial region and share bone destruction as their common clinical outcome. These otherwise different pathologies share similar inflammatory pathways mediated by central cellular players, such as macrophages, T and B cells, that promote the differentiation and activation of osteoclasts, ineffective or insufficient bone apposition by osteoblasts, and the continuous production of osteoclastogenic signals by immune and local stromal cells. We also present the potential translational applications of this knowledge based on the biological mechanisms involved in the inflammation-induced bone destruction. Such applications can be the development of immune-based therapies that promote bone healing/regeneration, the identification of host-derived inflammatory/collagenolytic biomarkers as diagnostics tools, the assessment of links between oral and systemic diseases; and the characterization of genetic polymorphisms in immune or bone-related genes that will help diagnosis of susceptible individuals.Peer reviewe

A massacre of early Neolithic farmers in the high Pyrenees at Els Trocs, Spain

International audienceViolence seems deeply rooted in human nature and an endemic potential for such is today frequently associated with differing ethnic, religious or socioeconomic backgrounds. Ethnic nepotism is believed to be one of the main causes of inter-group violence in multi-ethnic societies. At the site of Els Trocs in the Spanish pyrenees, rivalling groups of either migrating early farmers or farmers and indigenous hunter-gatherers collided violently around 5300 BCE. This clash apparently resulted in a massacre of the Els Trocs farmers. The overkill reaction was possibly triggered by xenophobia or massive disputes over resources or privileges. In the present, violence and xenophobia are controlled and sanctioned through social codes of conduct and institutions. So that, rather than representing an insurmountable evolutionary inheritance, violence and ethnic nepotism can be overcome and a sustainable future achieved through mutual respect, tolerance and openness to multi-ethnic societies