Trypanosoma cruzi strains cause different myocarditis patterns in infected mice

Aims. Chagas disease pathology is dependent on the infecting T. cruzi strain. However, the relationship between the extent and type of myocarditis caused by different T. cruzi strains in the acute and chronic phases of infection has not been studied in detail. To address this, we infected mice with three genetically distant T. cruzi strains as well as infected in vitro different cell types. Methods and Results. Parasitemia was detected in mice infected with the Y and VFRA strains, but not with the Sc43 strain; however, only the Y strain was lethal. When infected with VFRA, mice showed higher inflammation and parasitism in the heart than with Sc43 strain. Y and VFRA caused homogeneous pancarditis with inflammatory infiltrates along the epicardium, whereas Sc43 caused inflammation preferentially in the auricles in association with intracellular parasite localization. We observed intramyocardic perivasculitis in mice infected with the VFRA and Y strains, but not with Sc43, during the acute phase, which suggests that endothelial cells may be involved in heart colonization by these more virulent strains. In in vitro infection assays, the Y strain had the highest parasite-cell ratio in epithelial, macrophage and endothelial cell lines, but Y and VFRA strains were higher than Sc43 in cardiomyocytes. Conclusions. This study supports parasite variability as a cause for the diverse cardiac outcomes observed in Chagas disease, and suggests that endothelial cells could be involved in heart infection during the acute phase.This work was partially supported by grants from “Fondo de Investigaciones Sanitarias” (PS09/00538 and PI12/00289); “Ministerio de Ciencia e Innovación” (SAF2010-18733); The European Union (ChagasEpiNet); “Comunidad de Madrid” S2010/BMD-2332; RED RECAVA RD06/0014/1013;RED RICET RD12/0018/004 and an institutional grant from “Fundación Ramon Areces

Evaluación del ISTH-BAT en los trastornos plaquetarios congénitos: correlación clínica, laboratorio y molecular

CO-153 Introducción: Los trastornos plaquetarios congénitos (TPC) son un grupo heterogéneo de enfermedades raras, que se clasifican en trombocitopenias hereditarias (THs) y en trombocitopatías hereditarias (TFPs). Su identificación inicial y su diagnóstico final son complejos. Éste, se basa en la la historia clínica, la exploración física, pruebas de laboratorio fenotípicas y la confirmación de la alteración molecular subyacente. Por otra parte, la valoración de la clínica hemorrágica suele ser subjetiva, por lo que la Sociedad Internacional de Trombosis y Hemostasia (ISTH) recomienda la utilización de escalas de sangrado (bleeding assessment tools, BAT). Los objetivos de nuestros estudios fueron a) evaluar la clínica hemorrágica con el ISTH-BAT en pacientes diagnosticados de TPC, b) su comparación entre THs y TFPs y c) su relación con las pruebas funcionales y moleculares. Métodos: Estudio retrospectivo de 138 pacientes con TPC incluidos en el proyecto nacional “Caracterización funcional y molecular de los TPC” de la SETH. La clínica hemorrágica se evaluó mediante el ISTHBAT, obteniendo un score de sangrado (BS). El diagnóstico fenotípico se realizó mediante hemograma y frotis de sangre periférica, la función plaquetaria mediante agregometría de transmisión de luz (LTA) y citometría de flujo (CMF) y el diagnóstico molecular mediante secuenciación ..

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Mycobacterial Infection in Systemic Lupus Erythematosus: Clinical Significance and Associated Factors. Data from the Registry of Patients with SLE of the Spanish Society of Rheumatology (RELESSER)

Pathophysiology and treatment of rheumatic disease

Lupus Impact Tracker Responds to Changes in Low Disease Activity and Remission Outcomes in a Large Spanish Lupus Registry Cohort

International audienc