PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial

INTRODUCTION: Patients with advanced cirrhosis have enteric bacterial dysbiosis and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxaemia, inducing innate immune dysfunction which predisposes to infection, and development of complications such as bleeding, sepsis and hepatic encephalopathy. This feasibility study aims to assess the safety of administering faecal microbiota transplantion to patients with cirrhosis and explore the effect of the intervention on their prognosis by achieving restoration of a healthy gut microbiome. METHODS AND ANALYSIS: A PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation is a single-centre, randomised, single-blinded, placebo-controlled study evaluating faecal microbiota transplantation (FMT) against placebo. Patients with advanced but stable cirrhosis with a Model for End-Stage Liver Disease score between 10 and 16 will be recruited. Twenty-four patients will be randomised to FMT plus standard of care (as per our institutional practice) and eight patients to placebo in a ratio of 3:1. Patients will be evaluated at baseline before the study intervention is administered and at 7, 30 and 90 days post-intervention to assess safety and adverse events. FMT/placebo will be administered into the jejunum within 7 days of baseline. The primary outcome measure will be safety and feasibility as assessed by recruitment rates, tolerability and safety of FMT treatment. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient occurred on 23 May 2018. ETHICS AND DISSEMINATION: Research Ethics approval was given by the London South East Research Ethics committee (ref 17/LO/2081). TRIAL REGISTRATION NUMBER: NCT02862249 and EudraCT 2017-003629-13

Added value of patient-reported outcome measures (PROMs) after an acute stroke and early predictors of 90 days PROMs

Outcomes; Stroke; Value based health careResultats; Ictus; Atenció de la salut basada en valorsResultados; Ictus; Atención de la salud basado en valoresIntroduction Value-based health care represents a patient-centered approach by valuing Patient-Reported Outcome Measures (PROMs). Our aim was to describe the additional value of PROMs after an acute stroke over conventional outcome measures and to identify early predictors of poor PROMs. Methods Acute stroke patients discharged from a tertiary care hospital followed by a web/phone-based PROMs collection program in the post hospitalization phase. Main PROMs involve anxiety and depression (HADS) (each defined by HADS ≥ 10) and global physical (PHY-) and mental (M-) health (PROMIS-10). PROMIS cut-off raw values of normality were: PHY-PROMIS ≥ 13 and M-PROMIS ≥ 11. An overall health status (OHS) from 0 to 100 was also determined. PROMs related to the different modified Rankin Scale (mRS) grades were defined. Early predictors of PROMs were evaluated. Results We included 1321 stroke patients, mean age 75 (± 8.6) and 55.7% male; 77.7% returned home. Despite a favorable mRS at 3 months (< 3), a relevant rate of patients considered without symptoms or with mild disability showed unfavorable results in the measured PROMs (8% unfavorable OHS, 15% HAD-depression, 12.1% HAD-anxiety, 28.7% unfavorable M-PROMIS and 33.1% unfavorable PHY-PROMIS results). Along follow-up, only PHY-PROMIS and OHS showed significant improvement (p < 0.01 and 0.03, respectively). The multivariate analysis including discharge variables showed that female sex, higher discharge mRS and discharge to socio-rehabilitation-center (SRC) were independent predictors of unfavorable results in PROMs (p < 0.01). When adding 7 days PROMs results, they emerged as the strongest predictors of 3 months PROMs. Conclusions A high proportion of stroke patients show unfavorable results in PROMs at 3 months, even those with favorable mRS, and most results obtained by PROMs during follow-up continued to indicate alterations. Female sex, mRS and discharge to SRC predicted unfavorable results in PROMs, but the strongest predictors of 3 months PROMs were the results of the 7 days PROMs

Impact of obstructive sleep apnea on the levels of placental growth factor (PlGF) and their value for predicting short-term adverse outcomes in patients with acute coronary syndrome

Background Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. Methods A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. Results Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment. Conclusions The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term followup. Trial Registration ClinicalTrials.gov NCT0133508

Abordagem por Competências no Currículo Escolar em Cabo Verde: Desfazendo Equívocos para uma Mudança Significativa nas Políticas e Práxis Educacionais

A abordagem curricular por competências, enquanto fenómeno recente no discurso educativo em Cabo Verde, corre o risco de não passar de mero modismo, sem se traduzir numa inovação efectiva ao nível das práxis educacionais, se não for correctamente compreendida pelos diversos actores envolvidos na obra educativa e, em particular, nos processos de deliberação, gestão e realização dos currículos escolares. O presente artigo procura esclarecer alguns equívocos que em Cabo Verde, como em outras latitudes, acompanham a defesa da pedagogia por competências. Assim, importa elucidar que a abordagem curricular por competências vem aprofundar, entre outras, as abordagens por conteúdos e por objectivos e não, pura e simplesmente, substituí-las, por serem, alegadamente, tradicionais. Outrossim, no contexto da educação escolar, as competências não devem ser encaradas numa perspectiva redutora, focalizada na transferibilidade de conhecimentos para o mercado de trabalho, mas, fundamentalmente, no sentido da mobilização do conhecimento escolar para a resolução dos problemas nos diversos contextos ou situações da vida, que não se esgota no mercado

Evolución de la calidad de vida relacionada con la salud (CVRS) en niños/as escolares de las ciudades de Córdoba y Bahía Blanca

1 p.El uso del indicador CVRS se incrementa en la clínica y la investigación pediátrica. Su seguimiento permite conocer el sentido y la magnitud de los cambios en cada dimensión de la salud. Objetivo: Describir la evolución de la CVRS en un período de 6 meses en niños/as de 9 a 12 años, de escuelas de Córdoba y Bahía Blanca según sexo y desarrollo puberal (DP).http://www.sap.org.ar/docs/congresos/2013/conarpe/resumenes.pdfFil: Jouglard, Ezequiel Francisco. Universidad Nacional del Sur. Departamento de Ciencias de la Salud; Argentina.Fil: Fueyo Lavin, Julieta. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Salud Pública. Centro de Investigación Epidemiológica y en Servicios de Salud; Argentina.Fil: Mamondi, Verónica. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Salud Pública. Centro de Investigación Epidemiológica y en Servicios de Salud; Argentina.Fil: Rivera, Carolina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Salud Pública. Centro de Investigación Epidemiológica y en Servicios de Salud; Argentina.Fil: Pogany, Lourdes. Hospital Nacional de Pediatría Garrahan; Argentina.Fil: Sanchez, María Camila. Servicio de Gastroenterología Infantil del Hospital Italiano de Buenos Aires; Argentina.Fil: Prina, Martina. Hospital Nacional de Pediatría Garrahan; Argentina.Fil: Roizen, Mariana. Hospital Nacional de Pediatría Garrahan; Argentina.Fil: Esand, María Eugenia. Universidad Nacional del Sur. Departamento de Ciencias de la Salud; Argentina.Fil: Berra, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ciencias de la Salud; Argentina.Pediatrí

Induction of transplantation tolerance converts potential effector T cells into graft-protective regulatory T cells

Naturally occurring FOXP3+CD4+ Treg have a crucial role in self-tolerance. The ability to generate similar populations against alloantigens offers the possibility of preventing transplant rejection without indefinite global immunosuppression. Exposure of mice to donor alloantigens combined with anti-CD4 antibody induces operational tolerance to cardiac allografts, and generates Treg that prevent skin and islet allograft rejection in adoptive transfer models. If protocols that generate Treg in vivo are to be developed in the clinical setting it will be important to know the origin of the Treg population and the mechanisms responsible for their generation. In this study, we demonstrate that graft-protective Treg arise in vivo both from naturally occurring FOXP3+CD4+ Treg and from non-regulatory FOXP3−CD4+ cells. Importantly, tolerance induction also inhibits CD4+ effector cell priming and T cells from tolerant mice have impaired effector function in vitro. Thus, adaptive tolerance induction shapes the immune response to alloantigen by converting potential effector cells into graft-protective Treg and by expanding alloreactive naturally occurring Treg. In relation to clinical tolerance induction, the data indicate that while the generation of alloreactive Treg may be critical for long-term allograft survival without chronic immunosuppression, successful protocols will also require strategies that target potential effector cells

Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease

Background: Galectin-9 (Gal-9) induces apoptosis in activated T helper 1 (T(H)1) cells as a ligand for T cell immunoglobulin mucin-3 (Tim-3). Gal-9 also inhibits the G1 phase cell cycle arrest and hypertrophy in db/db mice, the hallmark of early diabetic nephropathy, by reversing the high glucose-induced up-regulation of cyclin dependent kinase inhibitors such as p27(Kip1) and p21(Cip1). Methods: We investigated the serum levels of Gal-9 in the patients with type 2 diabetes and various stages of chronic kidney disease (CKD) (n = 182). Results: Serum Gal-9 levels in the patients with type 2 diabetes were 131.9 +/- 105.4 pg/ml and Log(10)Gal-9 levels significantly and positively correlated with age (r = 0.227, p = 0.002), creatinine (r = 0.175, p = 0.018), urea nitrogen (r = 0.162, p = 0.028) and osmotic pressure (r = 0.187, p = 0.014) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.188, p = 0.011). Log(10)Gal-9 levels increased along with the progression of GFR categories of G1 to G4, and they were statistically significant by Jonckheere-Terpstra test (p = 0.012). Log(10)Gal-9 levels remained similar levels in albuminuria stages of A1 to A3. Conclusion: The elevation of serum Gal-9 in the patients with type 2 diabetes is closely linked to GFR and they may be related to the alteration of the immune response and inflammation of the patients with type 2 diabetes and CKD