Il‐17 promotes nitric oxide production in non‐small‐cell lung cancer

Introduction: Lung cancer is the second most frequent malignancy worldwide, but its aetiology is still unclear. Inflammatory cytokines and Th cells, including Th17, are now emerging as being involved in NSCLC pathways, thus postulating a role of IL‐17 in tumour angiogenesis by stimulating the vascular endothelial growth factor and the release of nitric oxide. Despite the fact that many biomarkers are used for chest malignancy diagnosis, data on FeNO levels and inflammatory cytokines in NSCLC are still few. Our study aimed to evaluate the relationship between pulmonary nitric oxide production and VEGF and Th17‐related cytokines in the EBC of patients affected by early‐stage NSCLC. Methods: FeNO measurement and lung function tests were performed in both patients affected by NCSLC and controls; EBC samples were also taken, and Th1 (IL‐1, IL‐6, IL‐12, IFN‐g, TNF‐a), Th17 (IL‐17, IL‐23) and Th2 (IL‐4, IL‐5, IL‐13) related cytokines were measured. Results: Th1 and Th17‐related cytokines in EBC, except for IFN‐gamma and TNF-alpha, were significantly higher in patients than in healthy controls, whereas no differences were seen for Th2‐related cytokines. FeNO at the flow rate of 50 mL/s, JawNO and CalvNO levels were significantly higher in patients affected by NSCLC compared to controls. Significant correlations were found between FeNO 50 mL/s and IL‐17, IL‐1 and VEGF. JawNO levels positively correlated with IL‐6, IL‐17 and VEGF. No correlations were found between FeNO and Th2‐related cytokines. Conclusion: This is the first report assessing a relationship between FeNO levels and Th17‐related cytokines in the EBC of patients affected by early‐stage NSCLC. IL‐17, which could promote angiogenesis through the VEGF pathway, might be indirectly responsible for the increased lung production of NO in patients with NSCLC

How does image quality affect radiologists' perceived ability for image interpretation and lesion detection in digital mammography?

OBJECTIVES: To study how radiologists' perceived ability to interpret digital mammography (DM) images is affected by decreases in image quality. METHODS: One view from 45 DM cases (including 30 cancers) was degraded to six levels each of two acquisition-related issues (lower spatial resolution and increased quantum noise) and three post-processing-related issues (lower and higher contrast and increased correlated noise) seen during clinical evaluation of DM systems. The images were shown to fifteen breast screening radiologists from five countries. Aware of lesion location, the radiologists selected the most-degraded mammogram (indexed from 1 (reference) to 7 (most degraded)) they still felt was acceptable for interpretation. The median selected index, per degradation type, was calculated separately for calcification and soft tissue (including normal) cases. Using the two-sided, non-parametric Mann-Whitney test, the median indices for each case and degradation type were compared. RESULTS: Radiologists were not tolerant to increases (medians: 1.5 (calcifications) and 2 (soft tissue)) or decreases (median: 2, for both types) in contrast, but were more tolerant to correlated noise (median: 3, for both types). Increases in quantum noise were tolerated more for calcifications than for soft tissue cases (medians: 3 vs. 4, p = 0.02). Spatial resolution losses were considered less acceptable for calcification detection than for soft tissue cases (medians: 3.5 vs. 5, p = 0.001). CONCLUSIONS: Perceived ability of radiologists for image interpretation in DM was affected not only by image acquisition-related issues but also by image post-processing issues, and some of those issues affected calcification cases more than soft tissue cases. KEY POINTS: • Lower spatial resolution and increased quantum noise affected the radiologists' perceived ability to interpret calcification cases more than soft tissue lesion or normal cases. • Post-acquisition image processing-related effects, not only image acquisition-related effects, also impact the perceived ability of radiologists to interpret images and detect lesions. • In addition to current practices, post-acquisition image processing-related effects need to also be considered during the testing and evaluation of digital mammography systems

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Il‐17 promotes nitric oxide production in non‐small‐cell lung cancer

Introduction: Lung cancer is the second most frequent malignancy worldwide, but its aetiology is still unclear. Inflammatory cytokines and Th cells, including Th17, are now emerging as being involved in NSCLC pathways, thus postulating a role of IL-17 in tumour angiogenesis by stimulating the vascular endothelial growth factor and the release of nitric oxide. Despite the fact that many biomarkers are used for chest malignancy diagnosis, data on FeNO levels and inflammatory cytokines in NSCLC are still few. Our study aimed to evaluate the relationship between pulmonary nitric oxide production and VEGF and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. Methods: FeNO measurement and lung function tests were performed in both patients affected by NCSLC and controls; EBC samples were also taken, and Th1 (IL-1, IL-6, IL-12, IFN-g, TNF-a), Th17 (IL-17, IL-23) and Th2 (IL-4, IL-5, IL-13) related cytokines were measured. Results: Th1 and Th17-related cytokines in EBC, except for IFN-gamma and TNF-alpha, were significantly higher in patients than in healthy controls, whereas no differences were seen for Th2-related cytokines. FeNO at the flow rate of 50 mL/s, JawNO and CalvNO levels were significantly higher in patients affected by NSCLC compared to controls. Significant correlations were found between FeNO 50 mL/s and IL-17, IL-1 and VEGF. JawNO levels positively correlated with IL-6, IL-17 and VEGF. No correlations were found between FeNO and Th2-related cytokines. Conclusion: This is the first report assessing a relationship between FeNO levels and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. IL-17, which could promote angiogenesis through the VEGF pathway, might be indirectly responsible for the increased lung production of NO in patients with NSCLC

The expression of TSLP receptor in chronic rhinosinusitis with and without nasal polyps.

Chronic Rhinosinusitis with or without Nasal Polyps (CRSwNP and CRSsNP) may be characterized by different cytokine profiles. Generally, Th2 cytokines and eosinophilic infiltration have been reported to be more specific of CRSwNP compared to CRSsNP, where neutrophils seem to play a major role. The epithelial cell-derived thymic stromal lymphopoietin (TSLP) has been recently identified as a key factor in Th2-inflammatory response. The aim of this study is to investigate the expression of TSLP Receptor (TSLP R) in surgical specimens obtained from patients affected by CRSwNP (n=10) and CRSsNP (n=5) by mmunohistochemical techniques (immunostaining score, IS). TSLP R expression was significantly higher in the inflammatory infiltrate and in the epithelial cells of CRSwNP, CRSsNP patients compared to the control group (IS 4.5 130.68, 4.4 131.44 and 0.43 130.3 respectively, p=0.0024 for inflammatory infiltrate and IS 5.8 130.92, 7.8 132.06 and 0.86 130.55 respectively, p=0.0018 for epithelial cells). No significant difference was observed in IS of inflammatory infiltrate and epithelial cells in CRSwNP compared to CRSsNP. Very low IS for TSLP R was found in connective tissue of all the samples, with no difference among the groups. TSLP receptor is highly expressed in CRS compared to controls and independently from the polyps suggesting an early common inflammatory pathway in the two CRS phenotypes

Eosinophilic inflammation of chronic rhinosinusitis with nasal polyps is related to OX40 ligand expression.

The aims of this study were to investigate OX40 ligand expression in sinus tissue from patients with nasal polyposis compared with patients with chronic rhinosinusitis without nasal polyps (NPs), and to determine if OX40 ligand expression is related to eosinophilic sinus infiltration. Twenty patients with chronic rhinosinusitis (11 with and nine without NPs) and seven controls were enrolled in the study. The mRNA expression of OX40 ligand and thymic stromal lymphopoietin and its receptor were analyzed. The immunoreactivity score for OX40 ligand and the eosinophil count were obtained. The mRNA expression and immunoreactivity score of OX40 ligand were higher in patients with nasal polyposis than in patients without NPs, as well as healthy controls. The mRNA expression of thymic stromal lymphopoietin and its receptor was significantly higher in nasal polyposis than in the control, but not significantly higher than in chronic rhinosinusitis without NPs. A correlation between the number of OX40 ligand-positive cells and the number of eosinophils in sinus biopsies was found only in patients with nasal polyposis. In conclusion, the thymic stromal lymphopoietin/OX40 ligand axis is up-regulated in nasal polyposis and is related to the intensity of eosinophilic inflammation

Validation of a candidate instrument to assess image quality in digital mammography using ROC analysis

PurposeTo validate a candidate instrument, to be used by different professionals to assess image quality in digital mammography (DM), against detection performance results.MethodsA receiver operating characteristics (ROC) study was conducted to assess the detection performance in DM images with four different image quality levels due to different quality issues. Fourteen expert breast radiologists from five countries assessed a set of 80 DM cases, containing 60 lesions (40 cancers, 20 benign findings) and 20 normal cases. A visual grading analysis (VGA) study using a previously-described candidate instrument was conducted to evaluate a subset of 25 of the images used in the ROC study. Eight radiologists that had participated in the ROC study, and seven expert breast-imaging physicists, evaluated this subset. The VGA score (VGAS) and the ROC and visual grading characteristics (VGC) areas under the curve (AUCROC and AUCVGC) were compared.ResultsNo large differences in image quality among the four levels were detected by either ROC or VGA studies. However, the ranking of the four levels was consistent: level 1 (partial AUCROC: 0.070, VGAS: 6.77) performed better than levels 2 (0.066, 6.15), 3 (0.061, 5.82), and 4 (0.062, 5.37). Similarity between radiologists’ and physicists’ assessments was found (average VGAS difference of 10 %).ConclusionsThe results from the candidate instrument were found to correlate with those from ROC analysis, when used by either observer group. Therefore, it may be used by different professionals, such as radiologists, radiographers, and physicists, to assess clinically-relevant image quality variations in DM