Safety and efficacy of restarting immune checkpoint inhibitors in non-small cell lung cancer patients following immune-related adverse events: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to evaluate the safety and efficacy of restarting immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) after experiencing immune-related adverse events (irAEs). METHODS: A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library was conducted to identify studies investigating the safety and efficacy of restarting ICIs in NSCLC patients after irAEs. Outcome measures, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) after ICI restarting, were extracted. Meta-analysis was performed using the R meta-package. RESULTS: Four studies involving a total of 326 subjects were included, comprising 137 patients who restarted ICI treatment after irAEs and 189 patients who did not restart ICI treatment. The results revealed that ICI restarting was associated with an increased ORR (OR = 2.36, 95% CI 1.49-3.84), prolonged PFS (HR = 0.60, 95% CI 0.42-0.86), and prolonged OS (HR = 0.65, 95% CI 0.43-0.99) compared to non-restarting. The incidence of irAEs after ICI restarting was 45% (95% CI 0.27-0.63). CONCLUSION: Restarting ICI treatment after discontinuation due to previous irAEs appears to be a reasonable option for NSCLC patients. However, a comprehensive assessment of the potential benefits and risks to individual patients is crucial, and close monitoring of irAEs is warranted.

Comparison of Gray-scale Inversion to Improve Detection of Pulmonary Nodules on Chest X-rays Between Radiologists and a Deep Convolutional Neural Network.

Detection of pulmonary nodules on chest x-rays is an important task for radiologists. Previous studies have shown improved detection rates using gray-scale inversion. The purpose of our study was to compare the efficacy of gray-scale inversion in improving the detection of pulmonary nodules on chest x-rays for radiologists and machine learning models (ML). We created a mixed dataset consisting of 60, 2-view (posteroanterior view - PA and lateral view) chest x-rays with computed tomography confirmed nodule(s) and 62 normal chest x-rays. Twenty percent of the cases were separated for a testing dataset (24 total images). Data augmentation through mirroring and transfer learning was used for the remaining cases (784 total images) for supervised training of 4 ML models (grayscale PA, grayscale lateral, gray-scale inversion PA, and gray-scale inversion lateral) on Google's cloud-based AutoML platform. Three cardiothoracic radiologists analyzed the complete 2-view dataset (n=120) and, for comparison to the ML, the single-view testing subsets (12 images each). Gray-scale inversion (area under the curve (AUC) 0.80, 95% confidence interval (CI) 0.75-0.85) did not improve diagnostic performance for radiologists compared to grayscale (AUC 0.84, 95% CI 0.79-0.88). Gray-scale inversion also did not improve diagnostic performance for the ML. The ML did demonstrate higher sensitivity and negative predictive value for grayscale PA (72.7% and 75.0%), grayscale lateral (63.6% and 66.6%), and gray-scale inversion lateral views (72.7% and 76.9%), comparing favorably to the radiologists (63.9% and 72.3%, 27.8% and 58.3%, 19.5% and 50.5% respectively). In the limited testing dataset, the ML did demonstrate higher sensitivity and negative predictive value for grayscale PA (72.7% and 75.0%), grayscale lateral (63.6% and 66.6%), and gray-scale inversion lateral views (72.7% and 76.9%), comparing favorably to the radiologists (63.9% and 72.3%, 27.8% and 58.3%, 19.5% and 50.5%, respectively). Further investigation of other post-processing algorithms to improve diagnostic performance of ML is warranted.

LHX1 as a potential biomarker regulates EMT induction and cellular behaviors in uterine corpus endometrial carcinoma.

OBJECTIVES: To investigate the expression of LHX1 and its role as a biomarker in the diagnosis and prognosis of Uterine Corpus Endometrial Carcinoma (UCEC). METHODS: The Cancer Genome Atlas (TCGA) database was used to detect the expression level of LHX1 in UCEC cells and tissues, and to find out the effect of LHX1 on prognosis. Co-expressed genes were then identified by Spearman correlation analysis, and the protein-protein interaction network was constructed using Cytoscape software. The R "clusterProfiler" package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A series of in vitro experiments were performed to evaluate LHX1 expression and detect UCEC cell proliferation, invasion, and migration. Western blotting was used to determine the effect of LHX1 on expression levels of Epithelial-Mesenchymal Transition (EMT)-related proteins. RESULTS: LHX1 was upregulated in UCEC tissues and correlated with poor overall survival and disease-specific survival outcomes. Functional enrichment analysis suggested that genes co-expressed with LHX1 were enriched in cell adhesion. The expression of LHX1 was positively correlated with the expression levels of genes related to EMT induction and invasion. LHX1 can enhance the proliferation, migration, and invasion activities of UCEC cells in vitro, and alter the expression levels of EMT-related proteins. CONCLUSION: LHX1 expression was highly upregulated in UCEC cells and tissues, which was correlated with the prognosis of patients with UCEC. LHX1 may regulate UCEC progression at least in part by modulating EMT induction.

How the "Are We Drinking Ourselves Sick?" Communication Campaign Built Support for Policy Action on Sugary Drinks in Jamaica.

Background: This study assesses the effectiveness of a campaign "Are We Drinking Ourselves Sick?" that ran nationally in Jamaica in four phases from 2017 to 2019 to increase knowledge about the harms of sugary drinks, shift attitudes, and build support for policy actions to address sugary drink consumption, including a tax and a ban in schools. Methods: Campaign impact was measured in representative cross-sectional household surveys of adults ages 18 to 55. A baseline survey was conducted before the launch of the campaign (n = 1430). Evaluation surveys were conducted mid-campaign (n = 1571) and post-campaign (n = 1500). Campaign impact was assessed by comparing changes across survey periods on key knowledge, attitudinal and policy support outcome indicators. The independent association between campaign awareness and outcomes was analyzed using logistic regression analyses. Results: The campaign was recalled by more than 80% of respondents and was well-received with 90% or more respondents describing it as believable and relevant. There was a decline in knowledge on the harms of sugary drinks from the baseline to post-campaign period, notably on risks of diabetes (adjusted odds ratio or AOR = 0.62, p < 0.001), overweight and obesity (AOR = 0.58, p < 0.001), and heart disease (AOR = 0.79, p < 0.003). However, post-campaign awareness was independently associated in logistic regression analysis with improved knowledge of the harms of sugary drinks, including risks of diabetes (AOR = 1.45, p = 0.019), overweight or obesity (AOR = 1.65, p = 0.001), and heart disease (AOR = 1.44, p = 0.011). Support for government action remained high across survey waves (≥90%), and campaign awareness was independently associated with increased policy support for sugary drinks taxes (Mid-campaign: AOR = 1.43, p = 0.019; post-campaign: AOR = 1.46, p = 0.01) and restrictions on sugary drinks in schools (AOR = 1.55, p = 0.01). Conclusion: This study demonstrates the role that media campaigns can play in maintaining knowledge and concern about the health harms of sugary drinks and increasing support for policy passage.

Coronary Artery Changes in Patients with Multisystem Inflammatory Syndrome in Children: Los Angeles Experience.

We compared cardiac findings in patients with multisystem inflammatory syndrome in children and Kawasaki disease in the first 6 months of the 2020 coronavirus disease pandemic to patients with Kawasaki disease during 2016-2019. We saw a high rate of coronary aneurysms in 2020, with a similar rate of coronary involvement but greater volume and incidence of cardiac dysfunction compared with previous years.

LHX1 as a potential biomarker regulates EMT induction and cellular behaviors in uterine corpus endometrial carcinoma

Abstract Objectives: To investigate the expression of LHX1 and its role as a biomarker in the diagnosis and prognosis of Uterine Corpus Endometrial Carcinoma (UCEC). Methods: The Cancer Genome Atlas (TCGA) database was used to detect the expression level of LHX1 in UCEC cells and tissues, and to find out the effect of LHX1 on prognosis. Co-expressed genes were then identified by Spearman correlation analysis, and the protein-protein interaction network was constructed using Cytoscape software. The R "clusterProfiler" package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A series of in vitro experiments were performed to evaluate LHX1 expression and detect UCEC cell proliferation, invasion, and migration. Western blotting was used to determine the effect of LHX1 on expression levels of Epithelial-Mesenchymal Transition (EMT)-related proteins. Results: LHX1 was upregulated in UCEC tissues and correlated with poor overall survival and disease-specific survival outcomes. Functional enrichment analysis suggested that genes co-expressed with LHX1 were enriched in cell adhesion. The expression of LHX1 was positively correlated with the expression levels of genes related to EMT induction and invasion. LHX1 can enhance the proliferation, migration, and invasion activities of UCEC cells in vitro, and alter the expression levels of EMT-related proteins. Conclusion: LHX1 expression was highly upregulated in UCEC cells and tissues, which was correlated with the prognosis of patients with UCEC. LHX1 may regulate UCEC progression at least in part by modulating EMT induction.

Heart Rate and Heart Rate Difference Predicted the Efficacy of Metoprolol on Postural Tachycardia Syndrome in Children and Adolescents.

OBJECTIVE: To evaluate the ability of heart rate (HR) and HR difference during head-up tilt test (HUTT) and to predict clinical improvement related to metoprolol treatment in children and adolescents with postural tachycardia syndrome (POTS). STUDY DESIGN: This was a retrospective cohort study. A total of 53 subjects (27 male, aged 6-12 years old, mean age 11.79 ± 1.50 years old) with POTS treated with metoprolol were involved from July 2012 to September 2019. In total, 52 subjects who underwent health examination during the same period were matched as the control group. Subjects in both groups underwent HUTT. The HR distance between 5 minutes and 0 minutes (HR difference 5) and between 10 minutes and 0 minutes (HR difference 10) during HUTT was calculated. RESULTS: The POTS group was significantly greater than the control group in HR 5, HR 10, HR difference 5, and HR difference 10 (P < .01). There was no statistical difference in HR 0 between the 2 groups (P > .05). In total, 53 subjects with POTS were followed up for 96.0 (IQR, 40.5, 134.5) days during treatment with metoprolol. HUTT results demonstrated that 58.49% of subjects with POTS had a response and symptom scores were reduced after intervention. HR and HR difference were useful in predicting the efficacy of metoprolol on POTS. When HR 5, HR 10, HR difference 5, and HR difference 10, respectively, were ≥110, 112, 34, and 37 beats/min, the sensitivity and specificity were 82.50% and 69.23%, 84.62% and 69.70%, 85.29% and 89.47%, and 97.56% and 64.86%, respectively. CONCLUSIONS: HR and HR difference are helpful to predict the efficacy of metoprolol on POTS in children and adolescents.