Effects of an omega-3 fatty acid-enriched lipid emulsion on eicosanoid synthesis in acute respiratory distress syndrome (ARDS): A prospective, randomized, double-blind, parallel group study

<p>Abstract</p> <p>Background</p> <p>The use of lipid emulsions has been associated with changes in lung function and gas exchange which may be mediated by biologically active metabolites derived from arachidonic acid. The type and quantity of the lipid emulsions used could modulate this response, which is mediated by the eicosanoids. This study investigates the use of omega-3 fatty acid-enriched lipid emulsions in ARDS patients and their effects on eicosanoid values.</p> <p>Methods</p> <p>Prospective, randomized, double-blind, parallel group study carried out at the Intensive Medicine Department of Vall d'Hebron University Hospital (Barcelona-Spain). We studied 16 consecutive patients with ARDS and intolerance to enteral nutrition (14 men; age: 58 ± 13 years; APACHE II score 17.8 ± 2.3; Lung Injury Score: 3.1 ± 0.5; baseline PaO₂/FiO₂ratio: 149 ± 40). Patients were randomized into two groups: Group A (n = 8) received the study emulsion Lipoplus^®20%, B. Braun Medical (50% MCT, 40% LCT, 10% fish oil (FO)); Group B (n = 8) received the control emulsion Intralipid^®Fresenius Kabi (100% LCT). Lipid emulsions were administered for 12 h at a dose of 0.12 g/kg/h. We measured LTB₄, TXB₂, and 6-keto prostaglandin F_1αvalues at baseline [immediately before the administration of the lipid emulsions (T-0)], at the end of the administration (T-12) and 24 hours after the beginning of the infusion (T 24) in arterial and mixed venous blood samples.</p> <p>Results</p> <p>In group A (FO) LTB₄, TXB₂, 6-keto prostaglandin F_1αlevels fell during omega-3 administration (T12). After discontinuation (T24), levels of inflammatory markers (both systemic and pulmonary) behaved erratically. In group B (LCT) all systemic and pulmonary mediators increased during lipid administration and returned to baseline levels after discontinuation, but the differences did not reach statistical significance. There was a clear interaction between the treatment in group A (fish oil) and changes in LTB₄over time.</p> <p>Conclusions</p> <p>Infusion of lipids enriched with omega-3 fatty acids produces significant short- term changes in eicosanoid values, which may be accompanied by an immunomodulatory effect.</p> <p>Trial registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN63673813">ISRCTN63673813</a>.</p

Effects on hemodynamics and gas exchange of omega-3 fatty acid-enriched lipid emulsion in acute respiratory distress syndrome (ARDS): a prospective, randomized, double-blind, parallel group study

<p>Abstract</p> <p>Introduction</p> <p>We investigated the effects on hemodynamics and gas exchange of a lipid emulsion enriched with omega-3 fatty acids in patients with ARDS.</p> <p>Methods</p> <p>The design was a prospective, randomized, double-blind, parallel group study in our Intensive Medicine Department of Vall d'Hebron University Hospital (Barcelona-Spain). We studied 16 consecutive patients with ARDS and intolerance to enteral nutrition (14 men and 2 women; mean age: 58 ± 13 years; APACHE II score: 17.8 ± 2.3; Lung Injury Score: 3.1 ± 0.5; baseline PaO₂/FiO₂ratio: 149 ± 40). Patients were randomized into 2 groups: Group A (n = 8) received the study emulsion Lipoplus^®20%, B.Braun Medical (50% MCT, 40% LCT, 10% ω-3); Group B (n = 8) received the control emulsion Intralipid^®Fresenius Kabi (100% LCT). Lipid emulsions were administered during 12 h at a dose of 0.12 g/kg/h. Measurements of the main hemodynamic and gas exchange parameters were made at baseline (immediately before administration of the lipid emulsions), every hour during the lipid infusion, at the end of administration, and six hours after the end of administration lipid infusion.</p> <p>Results</p> <p>No statistically significant changes were observed in the different hemodynamic values analyzed. Likewise, the gas exchange parameters did not show statistically significant differences during the study. No adverse effect attributable to the lipid emulsions was seen in the patients analyzed.</p> <p>Conclusion</p> <p>The lipid emulsion enriched with omega-3 fatty acids was safe and well tolerated in short-term administration to patients with ARDS. It did not cause any significant changes in hemodynamic and gas exchange parameters.</p> <p>Trial registration</p> <p>ISRCTN63673813</p

Diagnósticos, produtos farmacêuticos e mulheres internadas em um manicômio

El artículo sigue una perspectiva interseccional situada, e incorpora análisis desde la sociología del diagnóstico y los estudios sociales de los fármacos. El objetivo es analizar un conjunto de fuentes de investigación compuesto por i. entrevistas semidirigidas a 15 mujeres cis que estuvieron o están internadas en un hospital neuropsiquiátrico de la provincia de Buenos Aires, Argentina, ii. entrevistas semidirigidas a 17 profesionales de los equipos tratantes, y iii. análisis de10 historias clínicas. Se analizan los diagnósticos de base que recibieron las mujeres, y su variación a lo largo de períodos prolongados de internación, como así también la relación entre los diagnósticos de ingreso y los esquemas de administración de medicación psicofarmacológica. La metodología triangula el análisis de fuentes desde métodos y técnicas cualitativas y cuantitativas.The article follows a situated intersectional perspective, and includes analyses from the sociology of diagnosis and pharmaceutical studies. The aim is to analyze a set of research sources composed of i. semi-directed interviews with 15 cis women who were or are hospitalized in a neuropsychiatric hospital in the province of Buenos Aires, Argentina, ii. semi-directed interviews with 17 professionals from the treatment teams, and iii. analysis of 10 medical records. The underlying diagnoses received by the women and their variation over prolonged periods of hospitalization are analyzed, as well as the relationship between admission diagnoses and psychopharmacological medication administration schedules. The methodology triangulates the analysis of sources from qualitative and quantitative methods and techniques.O artigo segue uma perspectiva interseccional situada e incorpora análises da sociologia do diagnóstico e dos estudos sociais das drogas. O objetivo é analisar um conjunto de fontes de pesquisa composto por: i. entrevistas semi-dirigidas com 15 mulheres cis que estavam ou estão internadas em um hospital neuropsiquiátrico da província de Buenos Aires, Argentina; ii. entrevistas semi-dirigidas com 17 profissionais das equipes de tratamento e iii. análise de 10 históricos médicos. São analisados os diagnósticos subjacentes recebidos pelas mulheres e sua variação ao longo de períodos prolongados de internação, bem como a relação entre os diagnósticos de admissão e os esquemas de administração de medicamentos psicofarmacológicos. A metodologia triangula a análise de fontes a partir de métodos e técnicas qualitativas e quantitativas.Fil: Bianchi, Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; ArgentinaFil: Sabin Paz, Macarena del Pilar. Universidad Nacional de Lanus. Departamento de Salud Comunitaria. Centro de Salud Mental Comunitaria "mauricio Goldenberg"; Argentin

A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype

Multi-trait analysis; Polygenic risk score; StrokeAnálisis de múltiples rasgos; Puntuación de riesgo poligénico; IctusAnàlisi de múltiples trets; Puntuació de risc poligènic; IctusBackground: Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification. Methods: Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value < 5 × 10−8 influencing both traits (GWAS-pairwise) with a p-value < 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort. Results: We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension. Conclusion: The loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.J. Cárcel-Márquez has received funding through an AGAUR Contract (Agència de Gestió d'Ajuts Universitaris i de Recerca; FI_DGR 2019, grant number 2020FI_B1 00157) co-financed with Fons Social Europeu (FSE) (https://agaur.gencat.cat). From Instituto de Salud Carlos III: E. Muiño is funded by a Río Hortega Contract (CM18/00198), M. Lledós is funded by a PFIS Contract (Contratos Predoctorales de Formación en Investigación en Salud, FI19/00309), C. Gallego-Fabrega is supported by a Sara Borrell Contract (CD20/00043) and Fondo Europeo de Desarrollo Regional (ISCIII-FEDER), T. Sobrino (CPII17/00027), and F. Campos (CPII19/00020) are recipients of research contracts from the Miguel Servet Program (https://www.isciii.es). This study has been funded by Instituto de Salud Carlos III PI15/01978, PI17/02089, PI18-01338, and RICORS-ICTUS RD21/0006/0006 (Instituto de Salud Carlos III), by Marató TV3 support of the Epigenesis study (https://www.ccma.cat/tv3/marato/), by the Fundació Docència i Recerca FMT grant for the Epigenesis project (https://www.mutuaterrassa.com), by Eranet-Neuron of the Ibiostroke project (AC19/00106) (https://www.neuron-eranet.eu), by Boehringer Ingelheim of the SEDMAN Study (https://www.boehringer-ingelheim.it), and GCAT Cession Research Project PI-2018-01 (http://www.gcatbiobank.org). GCAT was funded by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); and have additional suport by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529)

Extracellular Tumor-Related mRNA in Plasma of Lymphoma Patients and Survival Implications

BACKGROUND: We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. METHODOLOGY/PRINCIPAL FINDINGS: mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. CONCLUSIONS/SIGNIFICANCE: Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries