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AKI has a high mortality rate, may lead to chronic kidney disease, and effective therapies are lacking. Micro-RNAs (miRNAs) regulate biologic processes by potently inhibiting protein expression, and pre-clinical studies have explored their roles in AKI. We conducted a systematic review and meta-analysis of miRNAs as therapeutics in pre-clinical AKI. Study screening, data extraction, and quality assessments were performed by 2 independent reviewers. Seventy studies involving 42 miRNA species were included in the analysis. All studies demonstrated significant effects of the miRNA intervention on kidney function and/or histology, with most implicating apoptosis and phosphatase and tensin homolog (PTEN) signaling. Fourteen studies (20.0%) examined the effect of miRNA-21 in AKI, and meta-analysis demonstrated significant increases in serum creatinine and kidney injury scores with miR-21 antagonism and pre-conditioning. No studies reported on adverse effects of miRNA therapy. Limitations also included lack of model diversity (100% rodents, 61.4% ischemia–reperfusion injury), and predominance of male sex (78.6%). Most studies had an unclear risk of bias, and the majority of miRNA-21 studies were conducted by a single team of investigators. In summary, several miRNAs target kidney function and apoptosis in pre-clinical AKI models, with data suggesting that miRNA-21 may mediate protection and kidney repair.Systematic review registration ID: CRD42019128854.

Female sex protects against development of acute kidney injury (AKI). While sex hormones may be involved in protection, the role of differential gene expression is unknown. We conducted gene profiling in male and female mice with or without kidney ischemia–reperfusion injury (IRI). Mice underwent bilateral renal pedicle clamping (30 min), and tissues were collected 24 h after reperfusion. RNA-sequencing (RNA-Seq) was performed on proximal tubules (PTs) and kidney endothelial cells. Female mice were resistant to ischemic injury compared with males, determined by plasma creatinine and neutrophil gelatinase-associated lipocalin (NGAL), histologic scores, neutrophil infiltration, and extent of apoptosis. Sham mice had sex-specific gene disparities in PT and endothelium, and male mice showed profound gene dysregulation with ischemia–reperfusion compared with females. After ischemia PTs from females exhibited smaller increases compared with males in injury-associated genes lipocalin-2 (Lcn2), hepatitis A virus cellular receptor 1 (Havcr1), and keratin 18 (Krt18), and no up-regulation of SRY-Box transcription factor 9 (Sox9) or keratin 20 (Krt20). Endothelial up-regulation of adhesion molecules and cytokines/chemokines occurred in males, but not females. Up-regulated genes in male ischemic PTs were linked to tumor necrosis factor (TNF) and Toll-like receptor (TLR) pathways, while female ischemic PTs showed up-regulated genes in pathways related to transport. The data highlight sex-specific gene expression differences in male and female PTs and endothelium before and after ischemic injury that may underlie disparities in susceptibility to AKI.

Background Acute kidney injury (AKI) causes significant morbidity and mortality in humans, and there are currently no effective treatments to enhance renal recovery. MicroRNAs (miRNAs) are short chain nucleotides that regulate protein expression and have been implicated in the pathogenesis of AKI. Recently, preclinical studies in vivo have uncovered a therapeutic role for administration of specific miRNAs in AKI. However, the overall benefits of this strategy in preclinical studies have not been systematically reviewed, and the potential for translation to human studies is unclear. Aim The primary aim is to conduct a systematic review of the therapeutic properties of miRNAs in preclinical studies of AKI. The secondary aim is to determine potential adverse effects of miRNA administration in these studies. Methods A comprehensive search strategy will identify relevant studies in AKI in vivo models, using the MEDLINE, EMBASE, OVID, PUBMED, and Web of Science databases. The search strategy will include terms for mammalian (non-human) AKI models, including injury related to ischemia/reperfusion, nephrotoxicity, sepsis, contrast agents, cardio-pulmonary bypass, and hemorrhagic shock. Interventions will be defined as direct administration of exogenous miRNAs or antagonists of miRNAs, as well as maneuvers that alter expression of miRNAs that are mechanistically linked to AKI outcomes. The primary outcomes will be indices of kidney function and structure, and there will be no restriction on comparator interventions. Two independent investigators will initially screen abstracts, and selected articles that meet eligibility criteria will be reviewed for data abstraction and analysis. The SYRCLE RoB tool for animal studies will determine risk of bias, and meta-analysis will be performed as appropriate. The GRADE methodology will assess the quality of evidence. Discussion The administration of selective miRNA mimics or antagonists exerts beneficial effects in mammalian models of AKI, although multiple obstacles must be addressed prior to translation to human clinical trials. The proposed systematic review will document key miRNA candidates, and determine effect size estimates and sources of outcome bias. The review will also identify gaps in knowledge and guide future directions in AKI research. Systematic review registration PROSPERO CRD42019128854

Acute kidney injury (AKI) is a common complication of hospitalization with high morbidity and mortality for which no effective treatments exist and for which current diagnostic tools have limitations for earlier identification. MicroRNAs (miRNAs) are small non-coding RNAs that have been implicated in the pathogenesis of AKI, and some miRNAs have shown promise as therapeutic tools in animal models of AKI. However, less is known about the role of miRNAs in human AKI.To evaluate the role of miRNAs in human subjects with AKI.Systematic review and meta-analysis.Quantification of miRNA levels from human blood, urine, or kidney biopsy samples, and measures of renal function as defined in the study protocol.A comprehensive search strategy for Ovid MEDLINE All, Embase, Web of Science, and CENTRAL will be developed to identify investigational studies that evaluated the relationship between miRNA levels and human AKI. Primary outcomes will include measurements of kidney function and miRNA levels. Study screening, review and data extraction will be performed independently by 2 reviewers. Study quality and certainty of evidence will be assessed with validated tools. A narrative synthesis will be included and the possibility for meta-analysis will be assessed according to characteristics of clinical and statistical heterogeneity between studies.These include (1) lack of randomized trials of miRNAs for the prevention or treatment of human AKI, (2) quality of included studies, and (3) sources of clinical and statistical heterogeneity that may affect strength and reproducibility of results.Previous studies of miRNAs in different animal models of AKI have generated strong interest on their use for the prevention and treatment of human AKI. This systematic review will characterize the most promising miRNAs for human research and will identify methodological constraints from miRNA research in human AKI to help inform the design of future studies.PROSPERO CRD42020201253.L’insuffisance rénale aiguë (IRA) est une complication fréquente des hospitalisations avec morbidité et mortalité élevées. Il n’existe aucun traitement efficace contre l’IRA et les outils diagnostiques actuels qui permettent son dépistage précoce comportent des limites. Les microARN (miARN) sont de petits ARN non codants ayant été impliqués dans la pathogenèse de l’IRA; certains d’entre eux se sont révélés prometteurs comme outils thérapeutiques dans les modèles animaux de l’IRA. Le rôle des miARN dans l’IRA chez l’humain est cependant moins connu.Évaluer le rôle des miARN chez les sujets humains atteints d’IRA.Examen systématique et méta-analyze.La quantification des taux de miARN chez l’humain à partir d’échantillons de sang, d’urine ou de biopsie rénale, et mesure de la fonction rénale telle que définie dans le protocole de l’étude.Une stratégie de recherche exhaustive des bases de données Ovid MEDLINE All, Embase, Web of Science et CENTRAL sera élaborée afin de répertorier les études expérimentales ayant évalué la relation entre les taux de miARN et l’IRA chez l’humain. Les principaux critères d’évaluation comprendront la mesure de la fonction rénale et des taux de miARN. Deux examinateurs procéderont de façon indépendante à la sélection des études, à leur examen et à l’extraction des données. La qualité des études et la robustesse des données seront évaluées à l’aide d’outils validés. Une synthèse descriptive sera incluse et la possibilité d’une méta-analyze sera évaluée en fonction des caractéristiques de l’hétérogénéité clinique et statistique entre les études.Les limites de l’étude concernent notamment (i) le manque d’essais randomisés examinant les miARN pour la prévention ou le traitement de l’IRA humaine; (ii) la qualité des études incluses; et (iii) les sources d’hétérogénéité clinique et statistique susceptibles d’affecter la robustesse et la reproductibilité des résultats.Des études antérieures sur les miARN dans différents modèles animaux de l’IRA ont suscité un vif intérêt pour leur utilization dans la prévention et le traitement de l’IRA chez l’humain. Cet examen systématique caractérisera les miARN les plus prometteurs pour la recherche sur l’IRA humaine et définira les contraintes méthodologiques de telles études, ce qui aidera à orienter la conception des études futures.

Acute kidney injury (AKI) carries high morbidity and mortality, and effective treatments are lacking. Preclinical models support involvement of micro-RNAs (miRs) in AKI pathogenesis, although effects on the kidney transcriptome are unclear. We previously showed that injection of cord blood endothelial colony forming cell-derived exosomes, enriched in miR-486-5p, prevented ischemic AKI in mice. To further define this, we studied direct effects of miR-486-5p in mice with kidney ischemia-reperfusion injury. RNA-Seq was used to compare the impact of miR-486-5p and exosomes on the transcriptome of proximal tubules and kidney endothelial cells 24 hours after ischemia-reperfusion. In mice with AKI, injection of miR-486-5p mimic increased its levels in proximal tubules and endothelial cells, and improved plasma creatinine, histological injury, neutrophil infiltration, and apoptosis. Additionally, miR-486-5p inhibited expression of its target phosphatase and tensin homolog, and activated protein kinase B. In proximal tubules, miR-486-5p or exosomes reduced expression of genes associated with ischemic injury and the tumor necrosis factor (TNF) pathway, and altered distinct apoptotic genes. In endothelial cells, genes associated with metabolic processes were altered by miR-486-5p or exosomes, although TNF pathway genes were not affected. Thus, our results suggest that miR-486-5p may have therapeutic potential in AKI.

Background:Biological therapies have marked a difference in the treatment of many autoimmune conditions. As all treatments, they have their side effects although little evidence of long-term effects has been reported.Objectives:Analyze retrospectively the appearance of infections that required hospitalization and other side effects in patients treated with biological therapies over the past 10 years.Methods:Biological drugs dispensed in our center to non-cancer patients from 2008 to 2018 were reviewed. Health records were collected from our database and all statistical analyzes were performed with the SPSS program.Results:24 different biological drugs applied to 34 medical conditions; 847 treatments were dispensed over a total of 555 patients. The median age was 44 years with a mean duration of 3.6 years of treatment. The most commonly used drug were adalimumab (n = 280, 33%), infliximab (n = 119, 12%), etanercept (n = 97.13%), rituximab (n = 63, 7%), vedolizumab (n = 47, 5.5%) and omalizumab (n = 43.5%). The rest of the drugs were administered The underlying conditions included Crohn’s Disease (n = 262, 31%), rheumatoid arthritis (n = 133, 16%), ulcerative colitis (n = 118, 14%), spondyloarthropathies (n = 86, 10%), psoriatic arthritis (n = 56, 7%), psoriasis (n = 49, 6%), asthma (n = 34, 4%), nephropathies (n = 19, 2%) and vasculitis (n = 13, 1.5%). The rest were pathologies with During treatment, infection requiring hospitalization occurred in 10.2% (n = 86). The most frequent focus of infection was respiratory (n = 23, 27%), abdominal (n = 19, 22%), soft tissue-bone (n = 17 cases, 20%), urinary (n = 7, 8%) and tuberculosis (n = 4, 5%). No case of hepatitis reactivation was observed. At the time of hospital admission, 46% of patients were only under biological therapy, 21% had another non-corticosteroid immunosuppressant, 17% were associated with corticosteroid, and 15% had triple therapy (corticosteroids, another immunosuppressant and the biological drug). The drugs associated with more infections were: abatacept 20%, rituximab 16% and adalimumab 13%.During the study period, 14 deaths (1.7%) were observed; being the cause cancer-related (n=5), infection (n=5), the disease itself for which was receiving biological treatment (n=2), and endocrine metabolic causes (n=2).At the end of the review, 48% of the treatments were still in use, while 52% had stopped for various reasons: 20% ineffectiveness, 12% side effects, 12% maintained complete remission. The remaining low percentage was due to death, pregnancy, or study entry.The side effects that led to a change in treatment was: non-immune hematological disorders in 4.1% (14% of tocilizumab, 7% of rituximab and 6% of vedolizumab), immune disorders in 3.8% (6% of secukinumab, 5% of tocilizumab and 4.5% of certolizumab), nervous system involvement in 2.4% (11.5% of golimumab,10% of abatacept, 5% of tocilizumab), debut or worsening of heart failure in 1.4% (9, 5% of tocilizumab, 2.5% of etanercept and 1.4% of adalimumab) and cancer-related in 0.7% (2% of infliximab, 1.7% of etanercept).Conclusion:In these 10 years of follow-up and and evaluating 847 treatments, there were 10% hospitalizations due to infections (n = 86) causing death in 5 patients. In light of these results, and pending an exhaustive statistical analysis, we did not find high frequencies of serious side effects in our series. Very little long-term evidence exists on the safety of these drugs.References:[1]Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2011(2):CD008794. Published 2011 Feb 16.Disclosure of Interests:None declared.

Administration of human cord blood endothelial colony-forming cells (ECFCs) or their exosomes protects mice against kidney ischemia/reperfusion injury. Here we studied the microRNA (miRNA) content of ECFC exosomes and the role of miRNA transfer in kidney and endothelial cell protection. ECFC exosomes were enriched in miR-486-5p, which targets the phosphatase and tensin homolog (PTEN) and the Akt pathway. In cultured endothelial cells exposed to hypoxia, incubation with ECFC exosomes increased miR-486-5p, decreased PTEN, and stimulated Akt phosphorylation. Exposure of hypoxic endothelial cells to conditioned medium from ECFCs pretreated with anti-miR-486-5p blocked increases in miR-486-5p and phosphorylated Akt, restored expression of PTEN, and enhanced apoptosis. Coculture of endothelial cells with ECFCs enhanced endothelial miR-486-5p levels. Targeting of PTEN by miR-486-5p was observed in endothelial cells, and PTEN knockdown blocked apoptosis. In mice with ischemic kidney injury, infusion of ECFC exosomes induced potent functional and histologic protection, associated with increased kidney miR-486-5p levels, decreased PTEN, and activation of Akt. Infusion of exosomes from ECFCs transfected with anti-miR-486-5p had no protective effect. Thus, delivery of ECFC exosomes reduces ischemic kidney injury via transfer of miR-486-5p targeting PTEN. Exosomes enriched in miR-486-5p could represent a therapeutic tool in acute kidney injury.

Endothelial colony forming cell (ECFC)-derived exosomes protect mice against ischemic kidney injury, via transfer of microRNA-(miR)-486-5p. Mechanisms mediating exosome recruitment to tissues are unclear. We hypothesized that ECFC exosomes target ischemic kidneys, involving interaction between exosomal CXC chemokine receptor type 4 (CXCR4) and stromal cell-derived factor (SDF)-1α. Ischemia-reperfusion was induced in mice by bilateral renal vascular clamp, with intravenous infusion of exosomes at reperfusion. Optical imaging determined exosome biodistribution, and miR-486-5p was measured by real-time PCR. Human umbilical vein endothelial cells (HUVECs) were cultured to study the CXCR4/SDF-1α interaction. Targeting of administered exosomes to ischemic kidneys was detected 30 min and 4 hrs after reperfusion. Exosomes increased miR-486-5p levels only in kidneys, within proximal tubules, glomeruli, and endothelial cells. Uptake of fluorescently-labeled exosomes into HUVECs, and exosomal transfer of miR-486-5p were enhanced by hypoxia, effects blocked by neutralizing antibody to SDF-1α or by the CXCR4 inhibitor plerixafor. Infusion of ECFC exosomes prevented ischemic kidney injury in vivo, an effect that was not observed when exosomes were pre-incubated with plerixafor. These data indicate that ECFC exosomes selectively target the kidneys after ischemic injury, with rapid cellular transfer of miR486-5p. Targeting of exosomes may involve interaction of CXCR4 with endothelial cell SDF-1α.

The administration of certain progenitor cells is protective in experimental acute kidney injury (AKI), and mechanisms may involve the release of paracrine factors. Endothelial colony-forming cells (ECFCs) are endothelial precursor cells with a high proliferative capacity and pro-angiogenic potential. We examined the effects of human umbilical cord blood-derived ECFCs and their extracellular vesicles in a mouse model of ischemic AKI and in cultured human umbilical vein endothelial cells subjected to hypoxia/reoxygenation. In mice with ischemic AKI, administration of ECFCs (i.v.) at the time of reperfusion significantly attenuated increases in plasma creatinine, tubular necrosis, macrophage infiltration, oxidative stress, and apoptosis, without cell persistence in the kidneys. In cultured human umbilical vein endothelial cells, hypoxia/reoxygenation stimulated apoptosis. This effect was inhibited by incubation with conditioned medium or exosomes (40- to 100-nm diameter) derived from ECFCs, but not by microparticles (100- to 1000-nm diameter) or vesicle-depleted conditioned medium. Administration of exosomes (i.v.) directly to mice with ischemic AKI attenuated renal injury, as assessed by plasma creatinine, tubular necrosis, and apoptosis. Taken together, these studies indicate protective effects of human cord blood-derived ECFCs in experimental AKI and suggest that ECFC-derived exosomes may mediate the protective response via inhibition of endothelial cell apoptosis.

European Psychiatry - In Press.Proof corrected by the author Available online since vendredi 28 octobre 2016

Summary CA125, a tumor marker normally used to follow the clinical course of ovarian cancer, also may have a role in lymphoma. All available series were analyzed using the standard reference value 35 U/ml, but age and sex may influence serum CA125 (sCA125) levels. We aim to study the prognostic value of serum CA125 (sCA125) levels in diffuse large B-cell lymphoma (DLBCL), considering the influence of age and sex on sCA125 levels. We investigated the relationship between sCA125 and clinical outcome after treatment in 42 patients with DLBCL, comparing both the standard (35 U/ml) and a new age and sex adjusted (sex/age-adjusted) reference value proposed by our group. We found that patients with elevated sCA125 levels had significantly more adverse prognostic factors at diagnosis, lower CR rates, higher relapse rates and worse survival. In the low-risk IPI categories, the presence of elevated sCA125 defined a particularly high-risk subgroup with poorer 3-year PFS when compared with patients with normal sCA125 levels. The use of a sex/age-adjusted reference value for sCA125 may increase the sensitivity to identify those patients with elevated sCA125 levels truly related to DLBCL activity.

The occurrence and spatial distribution of alkylphenols (4-tert-octylphenol, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol) and bisphenol A were examined in five estuaries along the Northwest coastal area of Spain. As far as we know, no previous works about this topic could be found in the literature. A total of 98 seawater samples were collected during May 2011–July 2012 and analyzed by a highly sensitive DLLME–LC–MS/MS methodology recently developed. Results indicated nonylphenol was the most ubiquitous compound with maximal concentration of 0.337 μg L−1 (Ría de Vigo). The environmental quality standards (EQS) established in Directive 2013/39/EU for 4-tert-octylphenol were slightly exceeded in some sampling points. Fishing harbours, water treatment plant and industrial discharges were supposed as the main sources of contamination. Low and medium ecological risk was determined in all estuaries. Possible endocrine effects on biota and population were estimated in terms of estrogenic activity and daily intake respectively, and no risk was found in any case., SI

BackgroundThe aim of this randomized clinical trial follow-up at three months was to evaluate the effectiveness of an educational intervention with a focus on diet and physical activity (PA) to change the amount of PA, body mass index (BMI) and the waist circumference (WC) in patients with severe mental illness.MethodsWe recruited 332 outpatients with severe mental disorders undergoing treatment with antipsychotic medication from Mental Healthcare Centers of Barcelona. They were randomly assigned to an intervention or a control group. The patients in the intervention group participated in a group PA and diet educational program. The blinded measurements at 0 and 3 months were: the level of PA (IPAQ questionnaire), BMI, WC, blood pressure, dietary habits (PREDIMED questionnaire), quality of life (SF-36 questionnaire) and laboratory parameters (cholesterol, triglycerides, glucose).ResultsThe average age was 46.7 years and 55% were males. Schizophrenia had been diagnosed in 67.1% of them. At 3 months, the average weekly walking METs rose significantly in the IG 266.05 METs (95%CI: 16.86 to 515.25; P = 0.036). The total MET average also rose although not significantly: 191.38 METs (95%CI: 1.38 to 381.38; P = 0.086). However, the BMI decreased significantly more in the CG, by 0.26 kg/m2 (95%CI: 0.02 to 0.51; P = 0.038), than in the IG. There were no significant differences in the WC.ConclusionsThe short-term results suggest that the intervention increases the level of PA, but does not improve physical or laboratory parameters.Trial registrationClinicaltrials.gov NCT01729650 (effectiveness of a physical activity and diet program in patients with psychotic disorder [CAPiCOR]).

The administration of certain progenitor cells is protective in experimental acute kidney injury (AKI), and mechanisms may involve the release of paracrine factors. Endothelial colony-forming cells (ECFCs) are endothelial precursor cells with a high proliferative capacity and pro-angiogenic potential. We examined the effects of human umbilical cord blood-derived ECFCs and their extracellular vesicles in a mouse model of ischemic AKI and in cultured human umbilical vein endothelial cells subjected to hypoxia/reoxygenation. In mice with ischemic AKI, administration of ECFCs (i.v.) at the time of reperfusion significantly attenuated increases in plasma creatinine, tubular necrosis, macrophage infiltration, oxidative stress, and apoptosis, without cell persistence in the kidneys. In cultured human umbilical vein endothelial cells, hypoxia/reoxygenation stimulated apoptosis. This effect was inhibited by incubation with conditioned medium or exosomes (40- to 100-nm diameter) derived from ECFCs, but not by microparticles (100- to 1000-nm diameter) or vesicle-depleted conditioned medium. Administration of exosomes (i.v.) directly to mice with ischemic AKI attenuated renal injury, as assessed by plasma creatinine, tubular necrosis, and apoptosis. Taken together, these studies indicate protective effects of human cord blood-derived ECFCs in experimental AKI and suggest that ECFC-derived exosomes may mediate the protective response via inhibition of endothelial cell apoptosis.

For the first time, 13 polycyclic aromatic hydrocarbons (PAHs) have been identified in samples of surface sediments at 17 stations on the Vigo estuary (northwest Spain) and its adjacent shelf. The separation and quantification of the analyzed compounds were performed using high-performance liquid chromatography, and a fluorescence detector with wavelength programming. The values found, for the sum of the 13 PAHs, varied between 28 and 2,150 w g/kg dry weight. These concentrations may be considered to be between very low and medium when compared with other estuaries. A concentration gradient with lower values on the continental shelf, that increase as the distance to the city of Vigo decreases, may be appreciated. Variations also can be noted in the participation of each PAH in the total sum, as a consequence of the differing degradability levels of each compound.

Serum protein and immunoglobulin G (IgG) levels were measured from 16 healthy mouflons (Ovis orientalis musimon) and from 28 roe deer (Capreolus capreolus) in French and Catalonian populations. Electrophoretic patterns were described for each species. The only significant gender-related difference was increased β-globulins in French roe deer males. Significantly increased α 1 -globulin levels and decreased IgG levels occurred in the young Catalonian roe deer compared with adults from the same group. Values for total proteins, β-globulins, γ-globulin, and IgG were significantly higher in the French roe deer, while albumin and albumin/globulin ratio were higher in the Catalonian roe deer. Both populations had the same relative migration distances of the various protein fractions of the electrophoresis.

Familial Hemophagocytic Lymphohistiocytosis type 3 (FHL3) is a genetic disorder caused by mutations in UNC13D gene, coding the granule priming factor Munc13-4 that intervenes in NK and T cell cytotoxic function. Here we report the case of a 17-month-old girl with prolonged symptomatic EBV infectious mononucleosis and clinical symptoms of hemophagocytic syndrome. In vitro functional analysis pointed to a degranulation defect. The genetic analysis of UNC13D gene identified initially a heterozygous mutation (c.753 + 1G > T) in the donor splice-site that resulted in exon 9 skipping (maternal allele). Mutations in other genes were considered, but additional analysis of UNC13D cDNA revealed in the paternal allele a heterozygous transition from G to A (c.2448 − 13G > A) at the 3′ acceptor splice-site in intron 25, generating a new acceptor splice-site that leads to a frameshift and a premature STOP codon. Allele specific amplification of the cDNA confirmed the absence of a functional mRNA from the paternal allele. This case illustrates an atypical compound heterozygous UNC13D mutation affecting the RNA splicing that generates a typical FHL3 phenotype.

The time to positivity (TTP) of blood cultures has been associated with increased mortality in bacteremia caused by several microorganisms. The aim of this study is to evaluate the relationship between TTP and prognosis, clinical presentation and extended spectrum B-lactamase (ESBL)-production in patients with Escherichia coli bacteremia. This is a retrospective observational study involving 226 adult patients with E. coli bacteremia. Data collected included underlying diseases, clinical presentation, prognosis factors, TTP, ESBL-production and outcome. Thirty-one (14%) patients had severe sepsis and 29 (13%) septic shock at presentation. Thirty-three (14%) strains were ESBL-producers. Thirty-nine (17%) patients died during admission and 17 (7.5%) within 48 hours. The median TTP was 8.3 hours (range, 0.42–76.5). It was significantly shorter in patients with septic shock (6.23 h, range 1.12–47.29 h vs. 8.51 h, range 0.42–76.50 h; p = 0.018). Rapid growth of E. coli, Pitt index >1.5, non-urinary source and Charlson score >2 were selected as independent risk factors of in-hospital mortality by the multivariate analysis. ESBL-production was not associated with modifications in TTP. Lower TTP is an independent risk factor for septic shock and poor outcome in episodes of E. coli bacteremia. The TTP in E. coli bacteremia is not significantly modified by ESBL-production.

Se presenta un caso de traqueítis bacteriana en una niña de 6 años y medio. La forma clínica de presentación fue la de un crup intenso con fiebre alta y pródromos catarrales en los días previos, que no respondió al tratamiento inicial con adrenalina inhalada y corticoides y precisó intubación orotraqueal a las pocas horas del ingreso. La visualización de secreciones purulentas fluyendo de la tráquea en el momento de la intubación, con epiglotis de aspecto normal, orientó el diagnóstico de traqueítis bacteriana, que fue confirmado por el crecimiento de Haemophilus influenzae en el cultivo de dichas secreciones. Se administró tratamiento con ceftriaxona por vía intravenosa durante 14 días y ventilación mecánica durante 7 días.La fiebre alta y las secreciones traqueales purulentas persistieron durante los 5 primeros días de tratamiento. A los 2 días de desaparición de dichos signos, y previa laringotraqueobroncoscopia normal, se extubó con éxito. Tras 2 semanas de ingreso fue dada de alta con exploración física normal, y no se han observado complicaciones posteriores.Se revisan aspectos clínicos, diagnósticos y terapéuticos de una enfermedad que puede conllevar un compromiso vital y que debe considerarse en el diagnóstico diferencial de todo crup grave. : We present a case of bacterial tracheitis in a 6.5-year-old girl. Clinical signs and symptoms consisted of severe croup with high-grade fever, which were preceded by upper respiratory tract prodrome. Initial treatment with steroids and nebulized epinephrine was unsuccessful. The patient was intubated a few hours after admission. Thick purulent secretions emerging from the trachea and the normal appearance of the epiglottis suggested the diagnosis of bacterial tracheitis, which was confirmed by isolation of Haemophilus influenzae in the culture of the tracheal secretions. The patient was administered a 14-day course of endovenous ceftriaxone and was kept on mechanical ventilation for 7 days. Fever and purulent tracheal secretions continued for the next 5 days. After 48 hours without these signs, laryngotracheobronchoscopy ruled out residual obstruction. Extubation was successfully performed. Fourteen days later physical examination showed no abnormalities and the patient was discharged. No complications were found during follow-up. The clinical, diagnostic and therapeutic aspects of this potentially life-threatening entity that should taken into account in the differential diagnosis of severe croup are discussed.

CA125, a tumor marker normally used to follow the clinical course of ovarian cancer, also may have a role in lymphoma. All available series were analyzed using the standard reference value 35 U/ml, but age and sex may influence serum CA125 (sCA125) levels. We aim to study the prognostic value of serum CA125 (sCA125) levels in diffuse large B-cell lymphoma (DLBCL), considering the influence of age and sex on sCA125 levels. We investigated the relationship between sCA125 and clinical outcome after treatment in 42 patients with DLBCL, comparing both the standard (35 U/ml) and a new age and sex adjusted (sex/age-adjusted) reference value proposed by our group. We found that patients with elevated sCA125 levels had significantly more adverse prognostic factors at diagnosis, lower CR rates, higher relapse rates and worse survival. In the low-risk IPI categories, the presence of elevated sCA125 defined a particularly high-risk subgroup with poorer 3-year PFS when compared with patients with normal sCA125 levels. The use of a sex/age-adjusted reference value for sCA125 may increase the sensitivity to identify those patients with elevated sCA125 levels truly related to DLBCL activity.

Summary Haematological and blood biochemical parameters of 15 capercaillie {Tetrao urogallus) reared in captivity have been determined. Statistically significant age differences were observed in the following parameters: haemoglobin, MCHC, total bilirubin, triglycerides, alkaline phosphatase, potassium and total proteins.

In an animal model, the effect of a high dose of conventional heparin (2 IU/g s.c. twice a day) and a low-molecular-weight heparin (LMWH; Fragmin, 1 anti-Xa U/g once a day) was compared with that of placebo on the mineral bone mass in the femur of rats. After 33 days of treatment no differences were found in the weight of the femur. But heparin-treated rats exhibited a lower density (1,249 ± 0.046 g/ml as compared with that in control rats (p = 0.00007) and also in LMWH-treated rats (p = 0.001). Similarly, statistically significant differences have been found in ash contents. They were higher in control rats than in heparin-treated rats (p = 0.0002), and also slightly higher than in LMWH-treated rats (p = 0.01). Our findings suggest that LMWH may have a lower osteopenic effect than that of conventional heparin.

Background The literature reveals that approximately 20% of healthcare professionals fail to document drug allergies (DA) in the electronic records. Breakdowns in the documentation of allergies can lead to medicines errors (MEs). Purpose The aims of this study were to examine patient DA profiles documented in the electronic records and to determine MEs associated with DAs. Material and methods Retrospective observational study including all adult patients admitted to our hospital on February 24, 2014. Discharge prescriptions and patient DA profiles entered into the different (non-integrated) electronic records were reviewed. Results 258 patients were included in the study. In all patients, a history of an allergic reaction to drugs or not was reported in at least one electronic record: 55% in the patient’s admission prescriptions, 60% in the nursing consumption form and 46.4% in the electronic prescription system. Nevertheless, only in 3% of the cases was it reported in all of the records. In 13.2% of the cases, there were discrepancies between different electronic records. DAs were recorded in 60 patients. The drugs most frequently involved were penicillin (50%) and metamizole (25%). 11 MEs were identified in which a drug was prescribed for a patient with a documented DA. In 6 cases the medicine didn’t reach the patient and was prevented by a pharmacist in four cases. In the other 5, the medicine reached the patients. Fortunately, there was no evidence of any reactions following the administration of the drugs. Conclusion The existence of different non-integrated electronic records favours inadequately recorded DAs, discrepancies and MEs related to DA. Pharmacists can play an active role in getting adequate DA recording systems into hospitals and improving inpatient safety. References and/or acknowledgements I thank Dra. Ana Perez for helpful comments. No conflict of interest.

Background Patient safety is an important component of healthcare quality. The Hospital Survey on Patient Safety Culture (HSOPSC) designed by the Agency for Healthcare Research and Quality is a validated tool used to assess the patient safety culture in hospitals. However, few studies have been performed exclusively in Pharmacy Departments. Purpose The aims of the study were to evaluate the patient safety culture of healthcare professionals in a Pharmacy Department, to analyse the strengths and opportunities for improvement and to compare with a multicentre study (n = 2,503) carried out in national hospitals by the Ministry of Health, Social Services and Equality in 2008. Material and methods Descriptive and cross-sectional study. The national adaptation HSOPSC was delivered to all staff of the Pharmacy Department. It included 12 dimensions related to patient safety culture, the number of events reported during last year and professional profile of the responders. Results The response rate was 70.7% (n = 28), half of whom were pharmacists (14/15) and the other 50’0% included technicians, pharmacy assistants, nurses and administrative staff members (14/26). The global score of patient safety culture in our service was 7.5 (on a 10-point scale) and there were no significant differences among professional profiles. 47.8% of responders reported >2 events last year and there were significant differences between pharmacists (57.1%) and non-pharmacists (33.3%). The most highly-scoring dimension was ‘Organisational learning and continuous improvement’ (84.2%). The worst qualified was ‘Staffing’ (38.7%). In the comparative study, the global score of patient safety culture was 7 and the highest and the worst dimensions were the same (82% and 27.6%, respectively). Conclusion Patient safety culture in our department is notable and slightly higher than comparison national hospitals. The HSOPSC allowed us to detect the main strengths and opportunities for improvement in order to design patient safety strategies. References and/or acknowledgements No conflict of interest.

OBJECTIVES: To find the distribution of coronary risk (CR) in the various groups of hypertense patients in the Joint National Committee (JNC VI), using both the Framingham and Sheffield tables, and to assess whether there is a relationship between the different scales used. DESIGN: Descriptive study. SETTING: Tortosa Oeste Health District, Tarragona. Spain. PARTICIPANTS: Rural population between 30 and 74 years old with Hypertension, but without any background of cardiovascular pathology. MAIN MEASUREMENTS: The variables studied corresponded to the Anderson table in the Framingham study, the Sheffield table and the JNC VI one. Concordance was assessed with the kappa coefficient. RESULTS: 148 hypertense patients with an average age of 62, 63.5% of whom were women, were studied. 23% had high CR on the Framingham, and 42.1% on the Sheffield. Distribution of the sample according to the stratification of the JNC VI was: A, 16.2%; B, 51.4%, and C, 32.4%. High risk on the Framingham in the various groups of the JNC VI was: A, 0%; B, 9.2%, and C, 56.3% (kappa, 0.533). High risk on the Sheffield in the groups of the JNC VI ran at: A, 4.2%; B, 41.3%, and C, 66.7% (kappa, 0.324). CONCLUSIONS: There was moderate concordance between the Framingham tables and the JNC VI for calculation of CR in our population.

We present a case of bacterial tracheitis in a 6.5 year old girl. Clinical signs and symptoms consisted of severe croup with high grade fever, which were preceded by upper respiratory tract prodrome. Initial treatment with steroids and nebulized epinephrine was unsuccessful. The patient was intubated a few hours after admission. Thick purulent secretions emerging from the trachea and the normal appearance of the epiglottis suggested the diagnosis of bacterial tracheitis, which was confirmed by isolation of Haemophilus influenzae in the culture of the tracheal secretions. The patient was administered a 14 day course of endovenous ceftriaxone and was kept on mechanical ventilation for 7 days. Fever and purulent tracheal secretions continued for the next 5 days. After 48 hours without these signs, laryngotracheobronchoscopy ruled out residual obstruction. Extubation was successfully performed. Fourteen days later physical examination showed no abnormalities and the patient was discharged. No complications were found during followup. The clinical, diagnostic and therapeutic aspects of this potentially life threatening entity that should taken into account in the differential diagnosis of severe croup are discussed.

Seven species of Spanish ungulates were tested for the presence of homologous immunoglobulin G (IgG) with a gel-diffusion test using bovine, ovine, caprine and porcine IgG antisera. Homologous ovine and caprine IgG were detected in sera from chamois (Rupicapra pyrenaica), Spanish ibex (Capra pyrenaica hispanica), mouflon (Ovis orientalis musimon), red deer (Cervus elaphus), fallow deer (Dama dama) and roe deer (Capreolus capreolus). Homologous porcine IgG was detected in wild boar (Sus scrofa) serum. Immunoelectrophoretic assays were performed to compare the electrophoretic mobility of IgG from domestic and wild species.

Three groups of chamois (Rupicapra pyrenaica) and three groups of Spanish ibex (Capra pyrenaica) were established to study the effects of sarcoptic mange on serum proteins and immunoglobulin G (IgG) levels. The first group of chamois consisted of 22 healthy Pyrenean chamois (R. pyrenaica pyrenaica) from a non-infested area, the second group consisted of 20 healthy Cantabrian chamois (R. p. parva) from an area where sarcoptic mange has been reported since 1994 and the third group consisted of 16 Cantabrian chamois from the same area but naturally infested by Sarcoptes scabiei. The first group of Spanish ibex was 39 healthy animals from a sarcoptic mange non-infested area, the second group was 23 healthy animals from a sarcoptic mange infested area and the third group consisted of 20 animals from the same area but naturally infested with the parasite. Blood samples were taken after killing the animals as part of hunting programmes. Values for total proteins, gamma-globulin and IgG were higher in infested and healthy chamois from the infested area compared to healthy chamois from the non-infested area, and IgG levels were higher in infested chamois compared to healthy-exposed chamois. Values for alpha2-globulin were higher in healthy Cantabrian chamois. In Spanish ibex, albumin, alpha2-globulin and IgG levels were lower in the healthy Spanish ibex from the non-infested area than in healthy animals from an infested area. The differences found in the chamois were indicative of the establishment of a humoral antibody response in the animals in contact with the disease. As the IgG levels were not significantly different between healthy and infested Spanish ibex from the same area, a different pattern of chronic infection with humoral response to the disease was suggested.

The characteristics of semirigid cavity confer to the skull and their content a special behavior, with regard to the other organs of the economy and they become the increases of pressure the interior in this space a threat against the appropriate evolution of the patients with intracranial pathologies of etiologies dissimilar.We make a study of the bibliography published on the topic, besides our personal approach with regard to the elements that we have been able to evaluate in our practices in clinic daily. We carried out a wide revision of the topic being exposed the physiopathological factors that intervene in to the maintenance of a homeostasis intracranial, the influence of the vital functions on this pressure and other aspects of importance. The clinical manifestations specify of this syndrome they are baskets after carrying out an analysis of their physiopathology.In this paper we exposes the methods for their menstruation as well as the importance of the use of these evidences in the establishment of an appropriate treatment. The modernized therapy of this entity, as well as the foundations of their application.

Reye's syndrome is a metabolic encephalopathy of infancy which is often fatal. Epidemiological studies have shown associated factors including having taken Aspirin for viral illness. Some patients with this disorder may have preexisting organic acidemia such as dicarboxylic aciduria.To study the behavior of Reye's syndrome in a group of patients during the years 1990-1996 in a provincial paediatric hospital and review variables such as age, sex, race, prodromal illness, previous consumption of Aspirin, hospital stay, mortality, diagnosis of dicarboxylic aciduria, etc.We selected patients with Reye's syndrome seen during the period mentioned and considered the above variables.All 10 patients seen with Reye's syndrome were boys. Their ages were between 3 months and 2 years. Most (nine) of the patients were Caucasian. All patients had influenza as the prodromal illness, and all took Aspirin as an antipyretic. There was considerable variation in the length of their stay in the hospital. In our series there was a high mortality and only two patients survived. One boy had dicarboxylic aciduria.The fatal character of Reye's syndrome has been shown, as has its relation to the use Aspirin. In our environment there seems to be a tendency for Caucasian boys to be affected.

Two cases of haemonchosis occurred in the Spanish ibex (Capra pyrenaica) population of the National Hunting Reserve of Tortosa and Beseit, northeastern Spain, in July 1992 and May 1993. The animals were cachectic and recumbent and had an acute hemorrhagic, macrocytic and hypochromic anemia; which was related to a high infection of 2,016 and 1,863 Haemonchus contortus, respectively, in the abomasum of the animals.

Background The paediatric population is a dynamic group, with major changes in pharmacokinetics and pharmacodynamics. Unfortunately, most medications commonly used in children do not have an approved labelling for use in these patients and are not available in appropriate formulations. Purpose To analyse extemporaneous formulas compounded in a Pharmacy Department for pediatric patients during 2009. Materials and methods Descriptive retrospective study of pediatric extemporaneous formulas made during 2009 in a 400-beds general hospital with 68 pediatric beds. Doctor9s orders, compounding formula register book and standardised protocols were consulted in order to obtain the data. Each unit produced was considered as a formula. Results 2158 pediatric extemporaneous formulas were made for 139 patients (50% girls), which corresponds to 8% of all compounded formulations developed. Patients9 average age was 28 months. 29% of them were younger than 1 month, 25% between 1 and 5 months, 10% between 6 and 12 months, 20% between 1 and 5 years and 16% were older than 5 years. 76% of extemporaneous formulas were solid oral formulas, 18% liquid oral formulas, 5% were sterile parenteral preparations and only 1% were topical formulas. 36 different active ingredients were used. The most common formulas were redosed oral nutrition, followed by bosentan, omeprazole and methimazole capsules and liposomal amphotericin B preparations. 25% of the patients needed more than one different extemporaneous formula. Conclusions Pharmaceutical compounding is essential to provide the appropriate doses or dosage forms that paediatric patients require. The compounding pharmacist is instrumental in assisting the medical staff with developing these new treatments and compounded formulations to treat these patients. It would be desirable that drug manufacturers could produce strengths and dosage forms appropriate for children.