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Background Capsule endoscopy is a widely recognized method to study the small bowel, including in patients with Crohn's disease (CD). The Lewis score (LS) is a valuable tool in this setting, able to assess inflammatory activity. PF-543 supplier TOP100, a new software tool of the RAPID Reader®, emerged to assist in the time-consuming capsule reading process, by automatically selecting 100 images that will most likely contain abnormalities.Aim Evaluate the agreement between TOP100 and classic reading (CR) in determining LS in the setting of CD.Methods Retrospective study including consecutive patients undergoing small bowel capsule endoscopy (SBCE) for suspected or established CD. One experienced reader performed CR and calculated the LS. Another experienced reader, blinded to the CR results, reviewed all SBCE videos using TOP100 and calculated the LS.Results One hundred and fifteen patients were included. SBCE detected significant inflammatory activity (LS ≥135) in 64 patients (55.7%). We verified a strong agreement between the two methods of capsule reading (Kappa = 0.83, p  less then  .001), with an agreement on 89.6% of the cases. The agreement was superior in moderate-to-severe inflammatory activity (Kappa = 0.92, p  less then  .001). All cases of moderate-to-severe activity detected by CR were identified by TOP100 as significant inflammatory activity. A good agreement was verified in all tertiles (p  less then  .001).Conclusions Although the classical review of the entire video remains the gold standard, the TOP100 has been shown to be a useful tool in assisting the reader in a prompt calculation of LS, in particular for identifying patients with moderate-to-severe inflammatory disease.Aim Evaluate quality of life (QoL) in patients with advanced non-small cell lung cancer treated with second or third line nab-paclitaxel ± durvalumab. Patients & methods Longitudinal QoL was assessed using Lung Cancer Symptom Scale, EuroQoL Five-Dimensions Five-Levels and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core. Results QoL was generally stable through eight treatment cycles (both arms). Clinically meaningful improvement from baseline was noted in Lung Cancer Symptom Scale (overall constitutional score and three-item index [nab-paclitaxel + durvalumab]) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core (global health status/QoL and emotional functioning [both arms] and pain [nab-paclitaxel + durvalumab]) analyses. EuroQoL Five-Dimensions Five-Levels domains were stable/improved or completely resolved at least once in 19-56% and 9-51% of patients, respectively. Conclusion While QoL trends were promising, additional data are required to support these regimens in this setting.Oxidative stress is recognised as a key factor that can lead to cellular senescence and aging. Carbon monoxide (CO) is produced by haemoxygenase-1 (HO-1), which exerts cytoprotective effects in aging-related diseases, whereas the effect of CO on cellular senescence and aging has not been elucidated. In the current study, we clearly demonstrated that CO delays the process of cellular senescence and aging through regulation of miR-34a and Sirt1 expression. CO reduced H2O2-induced premature senescence in human diploid fibroblast WI-38 cells measured with SA-β-Gal-staining. Furthermore, CO significantly decreased the expression of senescence-associated secretory phenotype (SASP), including TNF-α IL-6, and PAI-1 and increased the transcriptional levels of antioxidant genes, such as HO-1 and NQO1. Moreover, CO apparently enhanced the expression of Sirt1 through down-regulation of miR-34a. Next, to determine whether Sirt1 mediates the inhibitory effect of CO on cellular senescence, we pre-treated WI-38 cells with the Sirt1 inhibitor Ex527 and a miR-34a mimic followed by the administration of H2O2 and evaluated the expression of SASP and antioxidant genes as well as ROS production. According to our results, Sirt1 is crucial for the antiaging and antioxidant effects of CO. Finally, CO prolonged the lifespan of Caenorhabditis elegans and delayed high-fat diet-induced liver aging. Taken together, these findings demonstrate that CO reduces cellular senescence and liver aging through the regulation of miR-34a and Sirt1.Objectives The early identification of patients with a high risk of developing delayed neurological sequelae (DNS) can improve the quality of care in carbon monoxide (CO) poisoning cases. The aim of this study is to investigate whether the serum netrin-1 levels measured at presentation to the emergency department (ED) predicted the development of DNS after acute CO intoxication.Methods This prospective observational study was conducted between 1 August 2018 and 31 July 2019 in a single tertiary hospital. The patients with acute CO intoxication and serum netrin-1 levels measured at the time of ED presentation were included in the study. All patients were followed up for six weeks regarding the development of DNS. The patients were divided into two groups, including those who developed DNS (DNS group) and those who did not (non-DNS group).Results A total of 183 patients were included in the study, and 54 (29.5%) developed DNS. The median serum netrin-1 level at ED presentation was significantly lower in the DNS group (391.5 pg/mL [263.0-550.5]) than in the non-DNS group (626.0 pg/mL [505.9-755.6]) (p less then .001). Multivariate analysis revealed that a low serum netrin-1 level (adjusted odds ratio [AOR] 8.02, 95% CI 2.45-26.20), low Glasgow coma scale (GCS) score at ED presentation (AOR 0.81, 95% CI 0.68-0.97), long CO exposure time (AOR 1.96, 95% CI 1.49-2.56), and the presence of acute brain lesions (AOR 8.24, 95% CI 2.37-28.58) on diffusion-weighted imaging were independent predictors of DNS. Serum netrin-1 levels less than 432 pg/mL predicted the development of DNS with a sensitivity of 68.5% (95% CI 54.4%-80.5%) and a specificity of 86.0% (95% CI 78.8%-91.5%).Conclusions Low serum netrin-1 levels were significantly associated with the development of DNS. Therefore, serum netrin-1 at ED presentation can help identify patients at risk of developing DNS following discharge.

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