Refining feasibility assessment of endoscopic ear surgery: a radiomics model utilizing machine learning on external auditory canal CT scans.

BACKGROUND: Feasibility assessment of endoscopic ear surgery (EES) relies solely on subjective evaluation by surgeons. OBJECTIVE: Extracting radiomic features from preoperative CT images of the external auditory canal, we aim to classify EES patients into easy and difficult groups and improve accuracy in determining surgery feasibility. METHODS: 85 patients' external auditory canal CT scans were collected and 139 radiomic features were extracted using PyRadiomics. The most relevant features were selected and three machine learning algorithms (logistic regression, support vector machine, and random forest) were compared using K-fold cross-validation (k = 5) to predict surgical feasibility. RESULTS: The best-performing machine learning model, the support vector machine (SVM), was selected to predict the difficulty of EES. The proposed model achieved a high accuracy of 86.5%, and F1 score of 84.6%. The area under the ROC curve was 0.93, indicating good discriminatory power. CONCLUSIONS AND SIGNIFICANCE: The proposed machine learning model provides a reliable and accurate method for classifying patients undergoing otologic surgery based on preoperative imaging data. The model can help clinicians to better prepare for challenging surgical cases and optimize treatment plans for individual patients.

Comparison of prognostic and treatment between T1a and T1b glottic cancer: a propensity score-matched SEER database analysis.

PURPOSE: The prognoses of T1a and T1b glottic cancers are still controversial. This study aimed to compare the prognosis difference between the two groups based on the population-based Surveillance, Epidemiology, and End Results database (SEER). METHODS: Data for patients with T1a or T1b glottic cancers were extracted from the SEER database. The bias between T1a and T1b glottic cancers was minimized with Propensity Score Matching (PSM), and disease-specific survival (DSS) was analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards models. RESULTS: A total of 5,272 patients were extracted from the database, including 847 patients with T1b glottic cancer that were 1:1 propensity score-matched with patients with T1a glottic cancer. After propensity score-matching, there was no statistical difference in disease-specific survival between T1a and T1b patients, whilst survival was impaired by old age. However, on the multivariate analysis, the T1a stage was associated with improved DSS compared with the T1b stage. CONCLUSION: Our analysis showed that T1a glottic cancers didn't have a significantly better prognosis compared with T1b after PSM. However, the DSS of T1a patients is superior to that of T1b patients in multivariate analysis.

Transcanal endoscopic management of isolated congenital middle ear malformations.

BACKGROUND: A few studies have reported transcanal endoscopic management of isolated congenital middle ear malformations (CMEMs). OBJECTIVE: The purpose of this study is to describe our surgical experience in endoscopic ear surgery for isolated CMEMs and evaluate the surgical effect of hearing reconstruction. METHODS: From January 2017 to January 2022, a retrospective study was performed on 36 patients (37 ears) with isolated CMEMs who all underwent endoscopic surgery. Demographic data, high-resolution computed tomography (HRCT) findings, intraoperative findings, surgical management and audiometric data were recorded. RESULTS: Anomalies were categorized according to the Teunissen and Cremers classification system: 8 ears were categorized as class I, 8 ears as class II, 19 ears as class III and 2 ears as class IV. The air conduction pure tone average (AC-PTA) of 37 cases was 61.5 ± 8.6 dB preoperatively and 29.6 ± 6.9 dB postoperatively (p < 0.001). The mean preoperative air-bone gap (ABG) significantly decreased from 43.1 ± 8.7 dB to 12.8 ± 5.5 dB postoperatively. 36 of 37 cases (97%) met the criteria for successful operation. CONCLUSION: Isolated CMEMs are mainly manifested as aplasia of the stapes' superstructure and dysplasia of the long process of the incus. Transcanal endoscopic surgery seems a safe technique for the management of isolated CMEMs.

A Novel Her2/VEGFR2/CD3 trispecific antibody with an optimal structural design showed improved T-cell-redirecting antitumor efficacy.

Rationale: T-cell-redirecting bispecific antibodies (bsAbs) and trispecific antibodies (tsAbs) designed to recognize different epitopes or antigens have emerged as promising cancer therapies. Current approaches are all designed to include another antibody specific to the site of the primary antibody, and the molecular structures are generally established. However, the dimensions of target molecule and epitope location play a key role in the efficiency of the immunological synapse (IS) formation and subsequent T-cell-redirecting activities, therefore the connection flexibility of these antibodies determines the geometries of different formats of these molecules and will have a major impact on the efficacy. Methods: We describe a novel recombination strategy using various linker designs to site-specifically fuse anti-Her2 (2Rs15) or anti-VEGFR2 (3VGR19) nanobodies to different positions of the anti-CD3 antibody fragment (Fab, SP34). Based on the comparison among the various antigen-specific bsAbs, we could determine the desired fusion site of each nanobody to SP34, and further ensure the optimal structure of tsAbs with synergistic dual-antigen enhanced T-cell-redirecting activities. Results: This approach allows precise control of the formation of IS between Her2- and/or VEGFR2-expressing cancer cells and T cells, to obtain the optimal structure of the Her2/VEGFR2/CD3 tsAb without the need to map antibody-binding epitopes. Optimization of Her2/VEGFR2/CD3 tsAb results in enhanced T-cell-redirecting in vitro and in vivo antitumor efficacy compared with the corresponding bsAbs alone or in combination, and the potency to overcome tumor relapse due to antigen escape or resistance to Herceptin and Cyramza therapy. Conclusion: The novel design strategy for developing tsAbs using a site-specific recombination approach represents a promising platform for immuno-oncology and in applications other than cancer therapy.

The effect of chronic exposure to a low concentration of perfluorooctanoic acid on cognitive function and intestinal health of obese mice induced by a high-fat diet.

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant associated with many adverse health risks. Evidence suggests that obese individuals may be more susceptible to environmental substances. In the present work, we explored the effects of PFOA exposure on the cognitive function and intestinal health of obese mice. Obese mice induced by a high-fat diet were exposed to PFOA (0.5 mg/kg (bw)/day) via drinking water for 100 days. After exposure to PFOA, decreased body weight, enlarged liver, abnormal behavior, impaired synapse structure, neuroinflammation, activated glial cell, decreased nerve growth factor, altered gut microbiota, and disturbed serum metabolites were observed, while the gut inflammation and intestinal barrier were not significantly influenced. These results suggest that exposure to PFOA is associated with cognitive impairment in obese mice.

Is Helicobacter pylori colonization associated with chronic tonsillitis? - A meta-analysis and systematic review.

PURPOSE: The aim of this study was to investigate the correlation between Helicobacter pylori colonization of tonsillar tissue in chronic tonsillitis and in noninfectious hyperplastic tonsils. MATERIALS AND METHODS: All included studies investigated the presence of Helicobacter pylori in tonsillar tissue removed for infectious or noninfectious factors. Included studies must have used an accepted method of testing for Helicobacter pylori. We pooled six eligible studies to perform a traditional meta-analysis. RESULTS: Six studies were included, including 462 patients. Helicobacter pylori does have a significant role in chronic tonsillitis compared with noninfectious indications for tonsillectomy for children population. Detection methods had effects on results. CONCLUSION: The positive rate of Helicobacter pylori in chronic tonsillitis group was significantly higher than that in simple noninfectious group for the pediatric population, but not for adults. We suspected that chronic tonsillitis is likely to be relevant to Helicobacter pylori.

Identifying key genes and small molecule compounds for nasopharyngeal carcinoma by various bioinformatic analysis.

ABSTRACT: Nasopharyngeal carcinoma (NPC) is one of the most prevalent head and neck cancer in southeast Asia. It is necessary to proceed further studies on the mechanism of occurrence and development of NPC.In this study, we employed the microarray dataset GSE12452 and GSE53819 including 28 normal samples and 49 nasopharyngeal carcinoma samples downloaded from the Gene Expression Omnibus(GEO) to analysis. R software, STRING, CMap, and various databases were used to screen differentially expressed genes (DEGs), construct the protein-protein interaction (PPI) network, and proceed small molecule compounds analysis, among others.Totally, 424 DEGs were selected from the dataset. DEGs were mainly enriched in extracellular matrix organization, cilium organization, PI3K-Akt signaling pathway, collagen-containing extracellular matrix, and extracellular matrix-receptor interaction, among others. Top 10 upregulated and top 10 downregulated hub genes were identified as hub DEGs. Piperlongumine, apigenin, menadione, 1,4-chrysenequinone, and chrysin were identified as potential drugs to prevent and treat NPC. Besides, the effect of genes CDK1, CDC45, RSPH4A, and ZMYND10 on survival of NPC was validated in GEPIA database.The data revealed novel aberrantly expressed genes and pathways in NPC by bioinformatics analysis, potentially providing novel insights for the molecular mechanisms governing NPC progression. Although further studies needed, the results demonstrated that the expression levels of CDK1, CDC45, RSPH4A, and ZMYND10 probably affected survival of NPC patients.

Low expression of CIP4 in predicting worse overall survival: A potential biomarker for laryngeal cancer.

Previous reports indicate that Cdc42-interacting protein-4 (CIP4) has previously been reported to plays an important role in the progression of various cancers. However, its correlation with laryngeal cancer (LC) remains unreported. Data from TCGA and GEO databases were used to evaluate the role of CIP4 in LC. Based on GEO and TCGA datasets, we analyzed the differences in CIP4 expression between normal and tumor samples. The Wilcoxon signed-rank test was used to analyze the relationship between clinical features and CIP4. Cox regression and the Kaplan-Meier analyses were used to identify the clinical characteristics associated with the overall survival. Also, the GEPIA database was used to confirm the relationship between CIP4 and overall survival. Lastly, Gene Set Enrichment Analysis (GSEA) was performed based on the TCGA dataset. CIP4 expression in LC was significantly associated with gender and tumor stage (p-values<0.05). Similar to GEPIA validation, Kaplan-Meier survival analysis demonstrated that LC with CIP4-low exhibited a worse prognosis than that with CIP4-high. Univariate analysis revealed that CIP4-high significantly correlated with better overall survival (HR: 0.522, 95% CI: 0.293-0.830, P = 0.026). Besides, multivariate analysis revealed that CIP4 remained independently associated with the overall survival (HR: 0.61, 95% CI: 0.326-0.912, P = 0.012). GSEA showed that the p53, WNT signaling, TGF-ß signaling pathways, etc. were enriched in a phenotype high CIP4 expression. In summary, the CIP4 gene is a potential prognostic molecular marker for patients diagnosed with laryngeal cancer. Moreover, the p53, WNT signaling, and TGF-ß signaling pathways are potentially associated with CIP4 in LC.

Prognostic values and clinical relationship of TYK2 in laryngeal squamous cell cancer.

ABSTRACT: Laryngeal squamous cell cancer (LSCC) is the second most common head and neck cancer with the increasing mortality. The tyrosine kinase 2 (TYK2) has previously been reported to play an important role in various cancers excepting LSCC. We used available data from the cancer genome atlas program (TCGA), gene expression omnibus, and gene expression profiling interactive analysis (GEPIA) to evaluate the role of TYK2 in LSCC.The difference of TYK2 expression level between normal and tumor samples was analyzed based on TCGA, gene expression omnibus, and GEPIA databases. The relationship between clinical features and TYK2 were analyzed using the Wilcoxon signed-rank test. We applied Cox regression and the Kaplan-Meier method to finding which clinical characteristics is associated with overall survival. Also, we used GEPIA database to validate the relationship between TYK2 and overall survival. At last, we performed gene set enrichment analysis based on TCGA data set.The expression level of TYK2 in LSCC was significantly associated with gender, lymph node status and metastasis (P-values <.05). Kaplan-Meier survival analysis, as same as GEPIA validation, demonstrated that LSCC with TYK2-low had a worse prognosis than that with TYK2-high. The univariate analysis showed that TYK2-high correlated significantly with a better overall survival (hazard ratio: 0.351, 95% confidence interval: 0.194-0.637, P < .001). The multivariate analysis revealed that TYK2 remained independently associated with overall survival (hazard ratio: 0.36, 95% confidence interval: 0.185-0.699, P = .003). Gene set enrichment analysis shows that Janus kinases-STAT signaling pathway, p53 signalling pathway and natural killer cell mediated cytotoxicity, etc are enriched in TYK2 high expression phenotype.Gene TYK2 may be a potential prognostic molecular marker for LSCC. Moreover, the Janus kinases-STAT signaling pathway and p53 signaling pathway are probably the key pathway associated with TYK2 in LC.

Survival benefit of induction chemotherapy in treatment for stage III or IV locally advanced nasopharyngeal carcinoma - An updated meta-analysis and systematic review.

PURPOSE: The purpose of this study was to investigate whether combined Induction chemotherapy (IC) with concurrent chemoradiotherapy (CCRT) for stage III or IV locally advanced nasopharyngeal carcinoma (LA-NPC) could achieve better survival benefits than CCRT alone. MATERIALS AND METHODS: Only randomized controlled trials were included in this study. There were two treatment regiments (IC + CCRT and CCRT alone) recruited for analysis. The end points of this meta-analysis were overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastases-free survival (DMFS). Then we performed a traditional meta-analysis. RESULTS: Seven studies were included, including 2628 patients. Compared with using CCRT alone, IC + CCRT has better effects on overall survival (OS) [HR = 0.75, 95% CI = 0.63-0.89], locoregional recurrence-free survival (LRFS) [HR = 0.70, 95% CI = 0.56-0.86] and distant metastasis-free survival (DMFS) [HR = 0.65, 95% CI = 0.54-0.78]. Of note, the addition of IC also increases the incidence of toxic reactions and patient discomfort. CONCLUSION: IC + CCRT provided better survival benefits than CCRT alone. However, patients also had a higher incidence of toxic reactions with combination therapy.

Which treatment is better than concurrent chemoradiotherapy about survival for stage III or IV locally advanced nasopharyngeal carcinoma? An updated Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: To speculate whether induction chemotherapy (IC) or adjuvant chemotherapy (AC) with concurrent chemoradiotherapy (CCRT) could obtain better survival benefit for stage III or IV locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Only randomized controlled trials were incorporated. There were five treatments (CCRT, IC + CCRT, CCRT + AC, IC + RT and RT alone) recruited for analysis. Overall survival (OS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) with a hazard ratio (HR) were selected as endpoints. First of all, we performed a traditional meta-analysis and subsequently conducted network meta-analysis based on the Bayesian method. RESULTS: Totally, 15 studies, including 6182 patients, were incorporated for analysis. There was a statistically significant benefits in favor of IC + CCRT, compared with CCRT alone, for OS [HR = 0.75, 95% CI = 0.63-0.89], LRFS [HR = 0.70, 95% CI = 0.56-0.86], and DMFS [HR = 0.65, 95% CI = 0.54-0.78]. What's more, we did not observed any significant differences between CCRT + AC and CCRT alone for all the endpoints. Unsurprisingly, it was RT alone that demonstrate the poorest survival benefit. Strange to say, survival benefit, between IC + CCRT and IC + RT, or between IC + CCRT and CCRT + AC, did not significantly exist. CONCLUSION: Induction chemotherapy IC + CCRT provided better survival benefit than CCRT alone. CCRT + AC failed to increase survival benefit significantly compared to CCRT alone. More research about comparing IC + CCRT with IC + RT or CCRT + AC are needed.

Exposure to Perfluorooctanoic Acid Induces Cognitive Deficits via Altering Gut Microbiota Composition, Impairing Intestinal Barrier Integrity, and Causing Inflammation in Gut and Brain.

Perfluorooctanoic acid (PFOA) is an eight-carbon perfluoroalkyl chemical and has been detected widely in many media. Although the toxic effect of PFOA has been confirmed, the influence on gut and brain has not been cleared. Male C57BL/6J mice were exposed to different concentrations (0, 0.5, 1, and 3 mg/Kg (bw)/day of PFOA for 35 days in this work. The results indicate that exposure to PFOA could damage intestinal barrier integrity and impair the synaptic structure. PFOA exposure also caused inflammation in gut and brain by increasing lipopolysaccharide, tumor necrosis factor-α, interleukin-1 beta, and cyclooxygenase-2 and decreasing interleukin-10. Interestingly, fecal microbiota transplantation treatment could attenuate a series of PFOA-induced changes to a certain extent. The results suggest that exposure to PFOA has potential deleterious effects on gut and brain, and inflammation may play an essential role in evaluating the influence induced by PFOA exposure.