Long-term immune response accompanies clinical outcomes in severe asthmatics treated with anti-IL-5/IL-5R biologics

This work was supported by ISCIII - Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria - Spanish Health Research Fund) grants PI21/00896 and FI19/00067; Ciber de Enfermedades Respiratorias (CIBERES); SEAIC grants 22A07; BASEAS STUDY (Basophils in EosinophilicAsthma) Study Code ESR-20-20764 AstraZeneca International; Comunidad de Madrid grant PEJ2021-AI_BMD-22320 and FEDER funds (Fondo Europeo de Desarrollo Regiona

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

Meta-analysis of functional neuroimaging and cognitive control studies in schizophrenia: preliminary elucidation of a core dysfunctional timing network

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile

Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2

Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required

Tratamiento quirúrgico de los hemangiomas

El planteamiento terapéutico ante los hemangiomas ha cambiado ligeramente estos últimos años, pasando de mantener una actitud general conservadora a ser más agresivos en algunos casos. Las alteraciones inestéticas crónicas que pueden originar los hemangiomas, el trauma psicosocial que pueden desencadenar en la niñez, junto con un mejor conocimiento del comportamiento de este tipo de lesiones y el avance en técnicas quirúrgicas más seguras y eficaces, han sido los factores fundamentales de este cambio de actitud. El presente trabajo se centra en el tratamiento quirúrgico de los hemangiomas, explicando las indicaciones que tienen según la etapa de evolución en que se encuentren y las técnicas quirúrgicas empleadas para resecar la lesión con la mínima morbilidad. Así mismo, se tratan de forma detallada aquellas lesiones que, por presentar una localización anatómica facial concreta, requieren un tratamiento quirúrgico especial. Palabras clave. Hemangioma. Cirugía. Láser

VP61.01: MRI versus ultrasound expert evaluation for detecting malignancy in adnexal masses classified as inconclusive by IOTA Simple Rules

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Assessing the reproducibility of the IOTA simple ultrasound rules for classifying adnexal masses as benign or malignant using stored 3D volumes

OBJECTIVE: To analyze the reproducibility of the IOTA simple ultrasound rules for classifying adnexal masses as benign or malignant among examiners with different level of expertise using stored 3D volumes of adnexal masses. STUDY DESIGN: Five examiners, with different levels of experience and blinded to each other, evaluated 100 stored 3D volumes from adnexal masses and looked for the presence or absence of malignant or benign features according to the IOTA definitions. Multiplanar view and virtual navigation were used. All examiners had to assess the 3D volume of each adnexal mass and classify it as benign or malignant. To analyze intra-observer agreement each examiner performed the assessment twice with a two-week interval between the first and second assessments. To analyze the inter-observer agreement, the second assessment from each examiner was used. Reproducibility was assessed calculating the weighted Kappa index. RESULTS: Intra-observer reproducibility was moderate or good for all observers (Kappa index ranging from 0.59 to 0.74). Inter-observer reproducibility was moderate to good (Kappa index range: 0.46-0.67). CONCLUSIONS: The simple rules are reasonably reproducible among observers with different level of expertise when assessed in stored 3D volumes

External validation of IOTA simple descriptors and simple rules for classifying adnexal masses

Objective: To assess the diagnostic performance of a three-step strategy proposed by the International Ovarian Tumor Analysis (IOTA) Group for discriminating between benign and malignant adnexal masses. Methods: This was a prospective observational study, performed at two tertiary-care university hospitals, of women diagnosed with an adnexal mass on transvaginal or transabdominal ultrasound between December 2012 and December 2014. Women were scheduled for an ultrasound evaluation, which was initially performed by non-expert examiners. The examiner had to classify the mass using ‘simple descriptors’ (first step) and, if not possible, using ‘simple rules’ (second step). For inconclusive masses, an expert examiner classified the mass according to their subjective impression (third step). Masses were managed expectantly, with serial follow-up examinations, or surgically, according to ultrasound findings and clinical symptoms. Histology was used as the reference standard. Masses that were managed expectantly with at least 1 year of follow-up were considered as benign for analytical purposes. Women with less than 1 year of follow-up were not included in the study. Results: Six hundred and sixty-six women were included (median age, 41 (range, 18–81) years) of whom 514 were premenopausal and 152 were postmenopausal. Based on the three-step strategy, 362 women had surgical removal of the mass (53 malignant and 309 benign), 71 masses resolved spontaneously and 233 persisted. Four hundred and forty-eight (67.3%) of 666 masses could be classified using simple descriptors and, of the 218 that could not, 147 (67.4%) were classified using simple rules. Of the remaining 71 masses, the expert examiner classified 45 as benign, 12 as malignant and 14 as uncertain. Overall sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of the three-step strategy were 94.3%, 94.9%, 18.6 and 0.06, respectively. Conclusion: The IOTA three-step strategy, based on the sequential use of simple descriptors, simple rules and expert evaluation, performs well for classifying adnexal masses as benign or malignant