Using surface molecule expression on lymphocytes to classify septic shock patients

1 page.-- Letter.The present study was supported by grants S-BIO-0189/2006 MITIC/TIMEDIC from Comunidad de Madrid and 98/1431 Fondo de Investigaciones Sanitarias, CIBERehd, and by a research prize awarded by the Fundación Lilly.Peer reviewe

Eating Disorder Awareness Campaigns:Thematic and Quantitative Analysis Using Twitter

Background: Health awareness initiatives are frequent but their efficacy is a matter of controversy. We have investigated the effect of the Eating Disorder Awareness Week and Wake Up Weight Watchers campaigns on Twitter. Objective: We aimed to examine whether the Eating Disorder Awareness Week and Wake Up Weight Watchers initiatives increased the volume and dissemination of Twitter conversations related to eating disorders and investigate what content generates the most interest on Twitter. Methods: Over a period of 12 consecutive days in 2018, we collected tweets containing the hashtag #wakeupweightwatchers and hashtags related to Eating Disorder Awareness Week (#eatingdisorderawarenessweek, #eatingdisorderawareness, or #EDAW), with the hashtag #eatingdisorder as a control. The content of each tweet was rated as medical, testimony, help offer, awareness, pro-ana, or anti-ana. We analyzed the number of retweets and favorites generated, as well as the potential reach and impact of the hashtags and the characteristics of contributors. Results: The number of #wakeupweightwatchers tweets was higher than that of Eating Disorder Awareness Week and #eatingdisorder tweets (3900, 2056, and 1057, respectively). The content of tweets was significantly different between the hashtags analyzed (P<.001). Medical content was lower in the awareness campaigns. Awareness and help offer content were lower in #wakeupweightwatchers tweets. Retweet and favorite ratios were highest in #wakeupweightwatchers tweets. Eating Disorder Awareness Week achieved the highest impact, and very influential contributors participated. Conclusions: Both awareness campaigns effectively promoted tweeting about eating disorders. The majority of tweets did not promote any specific preventive or help-seeking behaviors

AM3 (Inmunoferón®) as an adjuvant to hepatitis B vaccination in hemodialysis patients

AM3 (Inmunoferón®) as an adjuvant to hepatitis B vaccination in hemodialysis patients.BackgroundPatients with end-stage renal disease (ESRD) undergoing hemodialysis have severe alterations in cell-mediated immunity (CMI) that increases their risk of contracting chronic hepatitis B virus (HBV) infection and decreases their protective responses to HBV vaccine. In an effort to improve the humoral response to an accelerated HBV vaccine protocol in these patients, the ability of an immunomodulator, AM3, to improve seroconversion was investigated.MethodsA total of 269 patients were enrolled in a multicenter trial. All patients received a DNA recombinant vaccine (40 μg HBsAg/dose/day) on days 0, 10, 21, and 90. AM3 or placebo (3 g/day) was given orally for 30 consecutive days beginning 15 days prior to the first vaccine dose. Anti-HBsAg titers were measured on days 120 and 270 after the beginning of the trial.ResultsAfter one month, 207 patients could be evaluated and 132 patients after six months. The placebo and AM3-treated groups had comparable seroconversion and protective response rates one month after the final vaccine dose. The AM3 treatment group, but not the placebo group, maintained these protective titers up to six months after the final vaccine dose. At this time, the percentage of high responders (anti-HBsAg>100 IU/L) and mean anti-HBsAg titers in the AM3 group was significantly higher than in the placebo group.ConclusionsAM3 is a safe and easily tolerated oral agent that potentiates long-term serological immunity to hepatitis B in hemodialysis patients after vaccination

Terapia dirigida en tumores sólidos

El manejo diagnóstico y terapéutico de los pacientes con tumores malignos ha progresado intensamente durante los últimos años. La incorporación de conocimientos y técnicas de diferentes ciencias biológicas a la oncología ha contribuido a mejorar el modo de enfocar, aliviar y curar al enfermo que padece una neoplasia. Las células se convierten en cancerosas en un proceso de dos etapas consecutivas: proliferación descontrolada y/o supervivencia alterada y adquisición de capacidad invasiva y metastásica. Este proceso de desarrollo y diseminación de las células neoplásicas se produce dentro del organismo del paciente con capacidad defensiva constituida por el sistema inmune a la que supera e, incluso, utiliza en su propio crecimiento. Los nuevos fármacos de diseño molecular tienen como objetivo fundamental el control de la proliferación aunque una de sus grandes desventajas es que raramente existe una sola alteración genética responsable del desarrollo y progresión del cáncer, por lo que se necesita la utilización de varias moléculas en un mismo paciente para conseguir el control tumoral. En la actualidad existen diversos agentes multiselectivos dirigidos contra varias dianas moleculares con excelente perfil de respuesta. En el presente capítulo se analizan las principales vías de abordaje molecular terapéutico en tumores sólidos, con especial hincapié en las terapias que utilizan biomarcadores predictivos EGFR, la terapia antiangiogénica y los inhibidores de la ruta PI3K/AKT/mTOR

Histopathological study of JNK in venous wall of patients with chronic venous insufficiency related to osteogenesis process

Chronic venous insufficiency (CVI) is one of the most common vascular pathologies worldwide. One of the risk factors for the development of CVI is aging, which is why it is related to senile changes. The main trigger of the changes that occur in the venous walls in CVI is blood flow reflux, which produces increased hydrostatic pressure, leading to valve incompetence. The cellular response is one of the fundamental processes in vascular diseases, causing the activation of cell signalling pathways such as c-Jun N-terminal kinase (JNK). Metabolic changes and calcifications occur in vascular pathology as a result of pathophysiological processes. The aim of this study was to determine the expression of JNK in venous disease and its relationship with the role played by the molecules involved in the osteogenic processes in venous tissue calcification. This was a cross-sectional study that analyzed the greater saphenous vein wall in 110 patients with (R) and without venous reflux (NR), classified according to age. Histopathological techniques were used and protein expression was analysed using immunohistochemistry techniques for JNK and markers of osteogenesis (RUNX2, osteocalcin (OCN), osteopontin (OPN)). Significantly increased JNK, RUNX2, OCN, OPN and pigment epithelium-derived factor (PEDF) protein expression and the presence of osseous metaplasia and amorphous calcification were observed in younger patients (<50 years) with venous reflux. This study shows for the first time the existence of an osteogenesis process related to the expression of JNK in the venous wall.This study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016) and cofinanced by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF) and B2017/BMD-3804 MITIC-C

Early alterations of B cells in patients with septic shock

Abstract Introduction It has recently been proposed that B lymphocytes are involved in sepsis pathogenesis. The goal of this study is to investigate potential abnormalities in a subset distribution and activation of circulating B lymphocytes in patients with septic shock. Methods This observational prospective study was conducted in a medical-surgical ICU. All patients with septic shock were eligible for inclusion. B-cell phenotypes (CD19+CD69+, CD19+CD23+, CD19+CD5+, CD19+CD80, CD19+CD86+, CD19+CD40 and CD19+CD95+) were assessed by quantitative flow cytometry upon admission to the ICU and 3, 7, 14 and 28 d later. Results Fifty-two patients were included. Thirty-six healthy volunteers matched for age and sex were used as controls. The patients had lymphopenia that was maintained during 28 d of follow-up. In patients with septic shock who died, the percentage of CD19+CD23+ was lower during the 7 d of follow-up than it was in survival patients. Moreover, the percentage of CD80+ and CD95+ expression on B cells was higher in patients who died than in survivors. Receiver operating characteristic curve analysis showed that a CD19+CD23+ value of 64.6% at ICU admission enabled discrimination between survivors and nonsurvivors with a sensitivity of 90.9% and a specificity of 80.0% (P = 0.0001). Conclusions Patients with septic shock who survive and those who don't have different patterns of abnormalities in circulating B lymphocytes. At ICU admission, a low percentage of CD23+ and a high of CD80+ and CD95+ on B cells were associated with increased mortality of patients with septic shock. Moreover, a drop in circulating B cells persisted during 28 d of ICU follow-up.This work was partially funded by grants from Fondo de Investigación de la Seguridad Social, Ministerio de Economia y Competitividad (MEC) (Spain), Consejeria de Educación, Comunidad de Madrid, MITIC-CM (S-2010/BMD-2502) and Instituto de Salud Carlos III, MEC (PI051871, CIBERehd).Peer Reviewe

Clinical relevance of the severe abnormalities of the T cell compartment in septic shock patients

8 pages, 2 figures.-- PMID: 19243622 [PubMed].[Introduction] Given the pivotal role of T lymphocytes in the immune system, patients with septic shock may show T cell abnormalities. We have characterised the T cell compartment in septic shock and assess its clinical implications.[Methods] T lymphocytes from the peripheral blood of 52 patients with septic shock and 36 healthy control subjects were analysed on admission to the intensive care unit, baseline, and 3, 7, 14 and 28 days later. T cell phenotypes (CD3+CD4+/CD3+CD8+, CD45RA+/CD45RO+, CD62L+/CD28+) were assessed by quantitative flow cytometry.[Results] CD3+, CD3+CD4+ and CD3+CD8+ lymphocyte counts were significantly lower in patients with septic shock than control subjects. In surviving patients, CD3+CD4+ lymphocytes had normalised after 14 days, yet CD3+CD8+ numbers were still low. Non effector CD45RA+CD45RO- subsets of CD3+CD4+ and CD3+CD8+ were persistently low during patient follow up. CD3+CD8+CD28+ and CD3+CD8+CD62L+ were reduced in patients versus controls and survivors versus nonsurvivors in the first three days. A prediction receptor operative curve revealed that for the CD3+CD8+CD28+ subset, a cutoff of 136 cells/ml showed 70% sensitivity and 100% specificity for predicting death and the area under the curve was 0.84 at admission. Corresponding values for CD3+CD8+CD62L+ were 141 cells/ml, 60% sensitivity, 100% specificity and an area under the curve of 0.75.[Conclusions] A severe redistribution of T lymphocyte subsets is found in septic shock patients. A different kinetic pattern of T cell subset involvement is observed in surviving and nonsurviving patients, with lower numbers of circulating CD3+CD8+CD28+ and CD3+CD8+CD62L+ associated with a better disease outcome.This study was supported by grants S-BIO-0189/2006 MITIC/TIMEDIC from Comunidad de Madrid, Fondo de Investigaciones Sanitarias, CIBERehd and by a research prize awarded by the Fundación Lilly.Peer reviewe

Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder

Background: Major Depressive Disorder (MDD) is associated with both proinflammatory and adaptive immune response abnormalities. Regulatory T lymphocytes (Tregs), a subtype of CD4+ T cells, are relevant for maintaining immune-inflammatory system homeostasis and control of inflammation such as the kind potentially induced by the interactions between the intestinal microbiome and gut mucosa. We investigated the Treg population and its distribution along their stages of differentiation/activation, as well as its function in MDD patients without concomitant diseases. We also studied the potential association between Treg alterations, intestinal barrier damage, and bacterial translocation. Methods: 30 MDD patients and 20 healthy controls were studied. The levels of circulating CD25FoxP3+ Tregs and their distribution on the naïve (TN), effector (TE), central (TCM), and effector memory(TEM) differentiation/activation stages were analyzed using polychromatic flow cytometry. Chemokine receptors (CCR) 2, 5, and 6, and the intracytoplasmic IL-10 expression by the Tregs were also analyzed. The serum IL-10 was measured using Luminex. The serum levels of zonulin and the intestinal fatty acid-binding protein (I-FABP), both markers of gut barrier function, and the LPS-binding protein (LBP), a marker of bacterial translocation, were measured using an enzyme-linked immunosorbent assay. Results: MDD patients had increased number of circulating Tregs cells with enhanced number of Tregs at the TN, TE, TCM, and TEM stages. The percentage of Tregs cells at TN stage was significantly higher in MDD patients. The percentage of Tregs that expressed CCR2 and CCR6 was increased as well as those expressing IL-10. MDD patients had significantly increased levels of circulating I-FABP and LBP. MDD patients with high LBP levels had a significant reduction in the number of circulating Tregs compared to normal-LBP MDD patients. Conclusions: MDD patients showed an expansion of circulating Tregs and their CD25highFoxP3+ and CD25lowFoxP3+ subsets throughout the different stages of CD4+ T lymphocyte differentiation/activation. Tregs also showed an increased frequency of cells expressing CCR6 and CCR2. IL-10 Treg production was also enhanced in MDD patients that concurrently had increased serum IL-10 levels. However, this Treg expansion was blunted in MDD patients with gut barrier damage and increased bacterial translocation.Instituto de Salud Carlos IIIComunidad de Madri

Abnormal Distribution and Function of Circulating Monocytes and Enhanced Bacterial Translocation in Major Depressive Disorder

Introduction: Major depressive disorder (MDD) patients experience a systemic inflammatory stage. Monocytes play an important role in innate inflammatory responses and may be modulated by bacterial translocation. Our aim was to investigate the subset distribution and function of circulating monocytes, levels of proinflammatory cytokines, gut barrier damage, and bacterial translocation in MDD patients. Methods: Twenty-two MDD patients without concomitant diseases and 14 sex- and age-matched healthy controls were studied. The levels of circulating CD14++CD16- (classical), CD14++CD16++ (intermediate) and CD14- CD16++ (nonclassical) monocytes and the intracytoplasmic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 expression in the presence or absence of lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. The serum TNF-α, IL-1β, IL-6, and IL-10 levels were measured by Luminex. LPS-binding protein (LBP), intestinal fatty acidbinding protein (I-FABP), and zonulin were measured by enzyme-linked immunosorbent assay (ELISA). Results: MDD patients had a significant increase in the frequency of intermediate monocytes and a significant decrease in the frequency of classical monocytes compared to those in the healthy controls. MDD patients had a significantly increased percentage of classical monocytes that expressed IL-1β, intermediate monocytes that expressed IL-1β and IL6 and nonclassical monocytes that expressed IL-1β, and decreased levels of nonclassical monocytes that expressed IL6 compared to those in the healthy controls. MDD patients had significantly increased levels of circulating TNF-α, IL-1β, LBP, and I-FABP compared to those in the healthy controls. MDD patients with high LBP levels had a significant reduction in the number of circulating monocytes compared to that in the normal-LBP MDD patients, which can be mainly ascribed to a decrease in the number of intermediate and nonclassical monocytes. Conclusions: We have demonstrated that compared to the healthy controls, MDD patients show a marked alteration in circulating monocytes, with an expansion of the intermediate subset with increased frequency of IL-1β and IL-6 producing cells. These patients also exhibited a systemic proinflammatory state, which was characterized by the enhanced serum TNF-α and IL-1β levels compared to those in the healthy controls. Furthermore, MDD patients showed increased LBP and I-FABP levels compared to those in healthy controls, indicating increased bacterial translocation and gut barrier damage