A rare rib lesion due to parosteal osteosarcoma: a case report

Masses which develop on the surface of the rib bones are rare. The differential diagnosis includes benign and malignant lesions.

http://bit.ly/2RY1ZIg

Safety and reproducibility of Nasal Allergen Challenge

Abstract

Background

The nasal allergen challenge (NAC) is a useful tool for the diagnosis of allergic rhinitis (AR) and local allergic rhinitis (LAR), and might serve to design and monitor allergen immunotherapy. Nevertheless, data about its safety and reproducibility is scarce.

Objective

To investigate the safety and reproducibility of NAC in pediatric and adult rhinitis patients with/without asthmatic symptoms, and in healthy controls.

Methods

A retrospective evaluation of the NACs conducted in our Unit for 2005‐2017 and monitored by acoustic rhinometry and nasal‐ocular symptoms was performed to analyze the safety of two methods for allergen application (metered spray & micropipette) and NAC protocols (NAC with single or multiple allergens/session (NAC‐S & NAC‐M)). The adverse events (AE), spirometry values, and rescue medication required for AE were recorded. The reproducibility was examined by a prospective analysis of three repeated NAC‐S performed at 1‐2‐month interval in AR, LAR and non‐allergic rhinitis patients, and in healthy controls.

Results

A total of 11499 NACs were performed in 518 children and 5830 adults. Only four local AE occurred, and 99.97% of NACs were well tolerated. The reproducibility and positive and negative predictive values of three consecutive NAC‐S performed in 710 subjects were 97.32%, 100%, and 92.91% respectively. There were no false positive results in the 710 analyzed subjects. Safety and reproducibility were comparable between the methods of allergen application and the rhinitis phenotypes.

Conclusion

The NAC is a safe and highly reproducible diagnostic test ready to be used in the clinical practice in both children and adults with or without asthma.

This article is protected by copyright. All rights reserved.

http://bit.ly/2R7NUmR

Contribution of airway eosinophils in airway wall remodeling in asthma: role of MMP‐10 and MET

Abstract

Background

Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma.

Methods

We analyzed the transcriptomic data from bronchial biopsies of 81 moderate‐to‐severe asthma patients of the U‐BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA. Transcription binding site analysis used the PRIMA algorithm. Localisation of proteins was by immunohistochemistry.

Results

Using stringent false discovery rate analysis, MMP‐10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils (HE) compared to low mucosal (LE) numbers. Immunohistochemical analysis confirmed increased expression of MMP‐10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less‐stringent conditions (raw p‐value <0.05, log2Fold Change>0.5), we defined a 73‐gene set characteristic of the HE compared to the LE group. 33/73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CC‐chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organisation correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS‐1 and SOX family proteins that showed positive correlation with MMP10 and MET expression.

Conclusion

Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP‐10 likely play an important role in these processes.

This article is protected by copyright. All rights reserved.

http://bit.ly/2WaDpmy

Dysregulated fatty acid metabolism in nasal polyp‐derived eosinophils from patients with chronic rhinosinusitis

Abstract

Background

Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in peripheral blood‐derived eosinophils from patients with severe asthma. However, functional characteristics of eosinophils present in allergic inflammatory tissues remains largely uncharacterized.

Methods

We established a method for isolating CD69^hi CCR3^low CXCR4^‐ siglec‐8^int eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (NP‐EOS). Multi‐omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze NP‐EOS as compared with peripheral blood‐derived eosinophils from healthy subjects (PB‐EOS).

Results

Lipidomic analysis revealed impaired synthesis of prostaglandins and 15‐lipoxygenase (15‐LOX)‐derived mediators, and selective upregulation of leukotriene D₄ production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (GGT5, DPEP2, and 15‐LOX) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of PB‐EOS with eosinophil activators IL‐5, GM‐CSF, and agonists of TLR2 and NOD2 mimicked the observed changes in lipid metabolism.

Conclusion

Inflammatory tissue‐derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.

This article is protected by copyright. All rights reserved.

http://bit.ly/2R88e7F

Diffuse Alveolar Hemorrhage Caused by Warfarin after Rifampicin Discontinuation

An 83-year-old man under warfarin therapy presented for assessment of prolonged prothrombin time and cough. High-resolution computed tomography findings of the chest showed diffuse alveolar hemorrhage. His international normalized ratio (INR) was 11.89. He had been treated with rifampicin for a persistent infection, but this had been discontinued about two months before admission. Rifampicin suppresses the anticoagulant activity of warfarin, which can lead to a need for increased doses of warfarin to achieve and maintain a therapeutic INR. More frequent INR monitoring is needed even after discontinuing rifampicin.

http://bit.ly/2Tar67S

A novel histopathological scoring system for patients with oral squamous cell carcinoma

Abstract

Objectives

Tumor invasion into blood and/or lymphatic vessels, perineural invasion, and histopathological grading are evaluated to assess the biological aggressiveness of oral squamous cell carcinoma (OSCC). We aim to assess the prognostic impact of a novel scoring system, based upon the aforementioned histological parameters.

Materials and methods

Retrospective chart review of 334 patients with treatment-naive squamous cell carcinoma of the oral cavity. Statistical analysis was performed using univariate and multivariate analysis. Histological grade G1 or G2 were assigned 0 points and G3 or G4 1 point. Invasion of the lymphatic vessels, blood vessels, or perineural space was given 1 point. Zero points were given, when invasion was not detectable. The final score was conducted through addition of each parameter. Therefore, our scoring system ranged between 0 and 4 points.

Results

T-classification (p < 0.001), N-classification (p < 0.001), UICC stage (p < 0.001), extracapsular spread (p < 0.001), locoregional recurrence (p < 0.001), and overall survival (p < 0.001) were significantly associated with the OSCC-Histoscore. In multivariate analysis, T-classification (p = 0.001), N-classification (p = 0.039), resection margins (p = 0.038), and OSCC-Histoscore (p < 0.001) were independent prognostic markers for overall survival rate.

Conclusion

Our presented OSCC-Histoscore serves as a strong independent prognostic parameter for 5-year overall survival (OS) and predicts OS better than T-classification, N-classification, and resection margins.

Clinical relevance

Our presented histoscore improves prediction of the overall survival of patients with OSCC.

http://bit.ly/2sGAEMg

Role and Mechanism of Galactose-Alpha-1,3-Galactose in the Elicitation of Delayed Anaphylactic Reactions to Red Meat

Abstract

Purpose of Review

The alpha-Gal (α-Gal) syndrome is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-alpha-1,3-galactose (α-Gal). In this article, we review the presence of α-Gal in food and non-food sources; we discuss the evolutionary context of the antibody response to α-Gal and highlight immune responses to α-Gal and other carbohydrates.

Recent findings

IgE antibodies have been associated with delayed allergy to red meat. In addition to food, drugs, and other products of animal origin are increasingly perceived as a risk for patients sensitized to α-Gal. The link between tick bites and anti-α-Gal IgE-antibody production that has been established first by epidemiological studies has now been confirmed in mouse models.

Summary

The anti-α-Gal immune response is complex and characterized by a unique feature. IgM and IgG antibodies have been found to confer protection against pathogens whereas the IgE-response to α-Gal is detrimental and causes severe reactions upon exposure to mammalian meat and other products.

http://bit.ly/2FHeqT2