Eosinophilic Esophagitis (EoE) is an inflammatory esophageal disease which is increasing in prevalence. The diagnostic gold-standard involves manual review of a patient's biopsy tissue sample by a clinical pathologist for the presence of 15 or greater eosinophils within a single high-power field (400x magnification). Diagnosing EoE can be a cumbersome process with added difficulty for assessing the severity and progression of disease. We propose an automated approach for quantifying eosinophils using deep image segmentation. A U-Net model and post-processing system are applied to generate eosinophil-based statistics that can diagnose EoE as well as describe disease severity and progression. These statistics are captured in biopsies at the initial EoE diagnosis and are then compared with patient metadata: clinical and treatment phenotypes. The goal is to find linkages that could potentially guide treatment plans for new patients at their initial disease diagnosis. A deep image classification model is further applied to discover features other than eosinophils that can be used to diagnose EoE. This is the first study to utilize a deep learning computer vision approach for EoE diagnosis and to provide an automated process for tracking disease severity and progression.
Autoradiographic methods were used to determine the distribution of autonomic receptors in airway smooth muscle of ferret from trachea to terminal bronchioles; [3H]dihydroalprenolol, [3H]prazosin, and [3H]quinuclidinyl benzilate were used to label beta-adrenergic, alpha-adrenergic, and muscarinic receptors, respectively, using experimental conditions that gave maximal specific receptor binding. Marked differences were found in the longitudinal distribution of each receptor and in distribution of the various receptors in each caliber airway. Beta-receptors were present in high density throughout the airways, with the highest density in bronchioles. Alpha-receptors were sparse in large airways, but numerous in small bronchioles, whereas cholinergic receptors were numerous in bronchial smooth muscle, sparse in proximal bronchioles, and almost absent from distal bronchioles. This method may be useful in studying alterations of autonomic receptors distribution in small and large airways after experimental manipulation and in disease.
Early mortality after percutaneous coronary intervention (PCI) is relatively rare. Current risk prediction models for this event are outdated. We sought to derive a 30-day mortality risk score after PCI.The score was derived from a pooled database of 21 randomised clinical trials using a logistic regression model incorporating clinical and angiographic variables. The score was validated in a separate unrestricted study population, the Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents (ADAPT-DES) registry. Of 32,882 eligible patients, 75% had data for all 19 variables used for score derivation. The independent predictors of 30-day mortality were age, presentation with ACS, diabetes mellitus, use of first-generation drug-eluting stents, left main or left anterior descending artery lesion, prior myocardial infarction (MI), and suboptimal flow in the artery before or after PCI. The median [interquartile range] score in the derivation cohort was 5 [3, 6] and overall mortality was 0.49%, ranging from 0.08% to 1.64% with scores of 0-16. The 30-day mortality rate was approximately tenfold higher in patients with a score at or above versus below the median of 5 (0.86% versus 0.08%, p<0.0001). Discrimination in both cohorts was very good (C statistic=0.848 and 0.828, respectively), and calibration was satisfactory.A novel risk score incorporating eight readily available clinical and angiographic variables had high discrimination for 30-day death after PCI across a wide range of clinical scenarios.
Abstract Inhaled corticosteroids (ICS) are the mainstay of treatment for asthma, but their role in chronic obstructive pulmonary disease (COPD) is debated. Recent randomised controlled trials (RCTs) conducted in patients with COPD and frequent or severe exacerbations demonstrated a significant reduction (~25%) in exacerbations with ICS in combination with dual bronchodilator therapy (triple therapy). However, the suggestion of a mortality benefit associated with ICS in these trials has since been rejected by the European Medicines Agency and US Food and Drug Administration. Observational evidence from routine clinical practice demonstrates that dual bronchodilation is associated with better clinical outcomes than triple therapy in a broad population of patients with COPD and infrequent exacerbations. This reinforces guideline recommendations that ICS-containing maintenance therapy should be reserved for patients with frequent or severe exacerbations and high blood eosinophils (~10% of the COPD population), or those with concomitant asthma. However, data from routine clinical practice indicate ICS overuse, with up to 50–80% of patients prescribed ICS. Prescription of ICS in patients not fulfilling guideline criteria puts patients at unnecessary risk of pneumonia and other long-term adverse events and also has cost implications, without any clear benefit in disease control. In this article, we review the benefits and risks of ICS use in COPD, drawing on evidence from RCTs and observational studies conducted in primary care. We also provide a practical guide to prescribing ICS, based on the latest global treatment guidelines, to help primary care providers identify patients for whom the benefits of ICS outweigh the risks.
The ability of three different peptides, substance P (SP), FMLP and melittin, to activate eosinophils purified from the peritoneal cavity of human serum-treated guinea pigs was investigated. Degranulation (eosinophil peroxidase, EPO), oxidative burst (O2-), [Ca2+]i mobilization, and arachidonic acid metabolism (thromboxane B2, TXB2) were used as indices of eosinophil activation. SP (100 nM to 100 microM), FMLP (1 to 100 microM) and melittin (10 nM to 100 microM) induced EPO release but only FMLP (1 to 100 microM) led to an elevation of [Ca2+]i. The melittin- and SP-induced EPO secretion occurred at both cytotoxic and noncytotoxic concentrations as assessed by lactate dehydrogenase release. In addition, the effect of SP was not inhibited by the SP analogue (D-Pro4, D-Trp7,9,10)SP(4-11) and SP failed to promote the generation and subsequent release of TXA2. In contrast, FMLP (10 to 100 microM) stimulated the release of TXB2 from guinea pig eosinophils that was selectively inhibited by pretreatment of the cells with BOC-FMLP. On an equimolar basis (1 microM), melittin was approximately fivefold more active at promoting TXB2 release than FMLP. The results indicate that eosinophils respond to the three peptides, SP, melittin, and FMLP in differential fashion. We conclude that activation of guinea pig eosinophils by FMLP is likely to be receptor-mediated whereas the actions of SP and melittin may act through nonspecific peptide-membrane phospholipid interactions.
