The impact of EGFR T790M mutation status following the development of Osimertinib resistance on the efficacy of Osimertinib in non-small cell lung cancer: A meta-analysis.

BACKGROUND: Previous studies have suggested that loss of the EGFR T790M gene mutation may contribute to the development of resistance to Osimertinib in non-small cell lung cancer (NSCLC). AIMS: This study aims to assess the relationship between the clinical effectiveness of Osimertinib in NSCLC patients and the T790M mutation status following resistance to Osimertinib and examine differences between plasma and tissue tests and between Asian and non-Asian groups. METHODS: The PubMed, Web of Science, Cochrane, and EMBASE databases were comprehensively searched for studies on the association between T790M mutation status and the efficacy of Osimertinib between January 2014 and November 2023. Meta-analysis was carried out using Review Manager 5.4 software. RESULTS: After evaluating 2727 articles, a total of 14 studies were included in the final analysis. Positive correlations between EGFR T790M mutation status after Osimertinib resistance and longer PFS (HR: 0.44, 95% CI: 0.30-0.66), longer OS (HR: 0.3, 95% CI: 0.10-0.86), longer TTD (HR: 0.69, 95% CI: 0.45-1.07), and improved clinical outcomes including PFS and TTD subgroups (HR: 0.58, 95% CI: 0.47-0.73) were observed. Subgroup analysis revealed that, compared with the blood tests, the results of the T790M mutation tests by the tissue are more significant (HR: 0.24, 95% CI: 0.11-0.52 for tissue tests; HR: 0.47, 95% CI: 0.22-1.00 for plasma tests), and the PFS of Osimertinib were similar for Asian and non-Asian patients (HR: 0.46, 95% CI: 0.31-0.68 for Asians; HR: 0.12, 95% CI: 0.01-1.27 for non-Asians). CONCLUSIONS: Persistence of the T790M gene mutation after the development of Osimertinib resistance is associated with higher therapeutic benefits of Osimertinib in NSCLC patients. The results of tissue detection are more significant than those of plasma detection.

Comparison of osimertinib plus bevacizumab against osimertinib alone in NSCLC harboring EGFR mutations: a systematic review and meta-analysis.

Background: Frequent failures observed in some trials comparing the efficacy and safety of osimertinib plus bevacizumab to osimertinib monotherapy in advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) alterations have brought questions. Objectives: To evaluate the efficacy and safety of these two treatment regimens in advanced NSCLC patients harboring EGFR mutations. Design: This study is a systematic review and meta-analysis. Data sources and methods: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases were extensively searched for relevant randomized controlled trials (RCTs) on 14 May 2023. Two researchers independently screened the literature, assessed quality, and extracted data. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The secondary outcomes were adverse events (AEs) and PFS stratified by patients' characteristics. STATA 17.0 software (StataCorp LLC, USA) was adopted for meta-analysis. Results: A total of four RCTs involving 390 patients were included. Overall, the risk of bias across the studies was moderate to low. Pooled results showed that compared to osimertinib alone, the addition of bevacizumab to osimertinib failed to show prolongation of PFS [hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.78-1.27], OS (HR = 1.01, 95% CI: 0.73-1.41), or improvement of the ORR (risk ratio = 1.12, 95% CI: 0.90-1.38), while an increased incidence of some AEs was observed, such as nausea, oral mucositis, hypertension, and proteinuria. Notably, combination treatment did significantly prolong the PFS in the subset of smokers (HR = 0.64, 95% CI: 0.44-0.94). A mild trend toward PFS benefit under the combined regimen was also noted in patients with brain metastases and first-line treatment, though not reaching statistical significance. Conclusion: Based on the available evidence, the addition of bevacizumab to osimertinib could not provide additional survival benefits with higher but manageable toxicity for EGFR-mutant NSCLC patients. Osimertinib monotherapy remains the prioritized treatment. Further investigation is warranted.

Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the highly aggressive malignancy types of head and neck squamous cell carcinomas; genes involved in the development of LSCC still need exploration. METHODS: We downloaded expression profiles of 96 (85 in advanced stage and 11 in early stage) LSCC patients from TCGA-HNSC. Function enrichment and protein-protein interactions of genes in significant modules were conducted. Univariate and multivariate Cox regression analyses were performed to explore potential prognostic biomarkers for LSCC. The expression levels of genes at different stages were compared and visualized via boxplots. Immune infiltration was examined by the CIBERSORTx web-based tool and depicted with ggplot2. Gene set enrichment analysis (GSEA) was utilized to analyze functional enrichment terms and pathways. Immunohistochemical staining (IHC) was used to verify the expression of genes in the LSCC samples. RESULTS: We identified 25 modules, including 3 modules significantly related to tumor stages of LSCC via weighted gene co-expression network analysis (WGCNA). UIMC1, NPM1, and DCTN4 in the module 'cyan', TARS in the module 'darkorange', and COPB2 and RYK in the module 'lightyellow' showed statistically significant relation to overall survival. The expression of COPB2, DCTN4, RYK, TARS, and UIMC1 indicated association with the change of fraction of immune cells in LSCC patients; two genes, COPB2 and RYK, indicated different expression in various tumor stages of LSCC. Finally, COPB2 and RYK showed high-expression in tumor tissues of advanced LSCC patients. CONCLUSIONS: Our study provided a potential perceptive in analyzing progression of LSCC cells and exploring prognostic genes.

Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation.

BACKGROUND: Refractory otomycosis is a common condition that is difficult to treat. OBJECTIVES: This study aimed to evaluate the effectiveness of 1% topical voriconazole drops in the treatment of otomycosis. METHODS: This retrospective analysis was conducted from November 2017 to November 2019. Patients who had refractory otomycosis without tympanic membrane perforation confirmed by microbial culture and fluorescent staining were included in the study. All patients were treated with 1% topical voriconazole drops hourly at daytime for 2 weeks. Evaluation of effectiveness was conducted 1 month after the completion of topical voriconazole treatment. Before and after topical voriconazole treatment, hearing tests were performed in all patients. RESULTS: Fifty-five patients were included in this study. The reasons for refractoriness were resistant recurrence to imidazole drugs (50 cases, 90.9%) and difficulty in cleaning the external auditory canal (5 cases, 9.1%). The most common strain was Aspergillus terreus (50.9%), followed by Aspergillus flavus (29.1%), Aspergillus niger (10.9%), and Aspergillus fumigatus (9.1%). After 2 weeks of treatment with 1% topical voriconazole drops, otomycosis in all patients was resolved. There was no significant change in bone conduction before and after topical voriconazole treatment (paired t-test, P = 0.5023; linear correlation analysis, R2 = 0.98; equation, y = 1.003x-0.284). Adverse effects, such as blurred vision and phototoxicity, were not observed in any patient. CONCLUSIONS: Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation within 2 weeks.

An epidemiological survey of laryngopharyngeal reflux disease at the otorhinolaryngology-head and neck surgery clinics in China.

PURPOSE: Using the Reflux Symptom Index (RSI), this nationwide study aimed to investigate the incidence, diagnostic status, risk factors, and common symptoms of adult laryngopharyngeal reflux disease (LPRD) at otorhinolaryngology-head and neck surgery (OHNS) clinics in China. METHODS: This multicenter cross-sectional survey began at the different institutions ranged from July to October 2017, and the duration was 12 months. A total of 90,440 eligible patients were finally enrolled from 72 medical institutions in China. All these patients completed the questionnaire based on RSI. In this study, LPRD was defined as RSI > 13. RESULTS: There were 9182 with LPRD among the 90,440 eligible participants (10.15%). However, only 1294 had a history of LPRD diagnosis among those with LPRD (14.09%). There were regional differences in the frequency of LPRD (P < 0.001). The proportions of patients with LPRD in males (vs. females), middle- and old-aged patients (vs. young), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking) were significantly higher (all P < 0.001). Middle and old age, current smoking, and drinking history were independent predictors of LPRD (all P < 0.001, OR 1.240, 1.261, and 1.481, respectively). "Sensations of something stuck in throat or a lump in throat", "clearing throat", and "excess throat mucus or postnasal drip" were the most frequent clinical symptoms in patients with LPRD. CONCLUSIONS: LPRD has a high incidence at the OHNS clinics in China. However, the diagnostic status of this disease is not optimistic. Older age, smoking, and drinking history were risk factors for LPRD.

The effect of the standard length of the first prescription on the adherence to sublingual immunotherapy for patients with allergic rhinitis.

BACKGROUND: Poor adherence to sublingual immunotherapy (SLIT) has become a major cause of unsatisfactory clinical efficacy for patients with allergic rhinitis (AR). This study was designed to identify the effect of different first prescription lengths on the adherence to SLIT. METHODS: The clinical data of 306 patients with AR who started SLIT between January 2017 and June 2018 were retrospectively reviewed. Patients were divided into 3 groups according to the length of their first prescription (group A: less than 3 months, group B: 3 to 6 months, group C: more than 6 months). The numbers of adherent or nonadherent patients in each group and the main reasons of nonadherence were analyzed. RESULTS: Groups A, B, and C included 102, 161, and 43 patients, respectively. The average lengths of the first prescription for group A, B, and C were 62.52 ± 17.63, 102.21 ± 9.22, and 189.07 ± 17.97 days. There were significance differences among the 3 groups (p < 0.05). There were 42 (41.18%), 112 (69.57%), and 37 (86.05%) adherent patients in group A, B, and C. There were 60 (58.82%), 49 (30.43%), and 6 (13.95%) nonadherent patients in group A, B, and C. There were significant differences in the proportions of adherent and nonadherent patients among the 3 groups (p < 0.05). The following reasons were cited for nonadherence to SLIT: the long course of SLIT; inconvenience of getting the prescription; ineffectiveness; side effects; and other reasons. CONCLUSION: Under certain conditions, 6 months is recommended as the standard length for the first prescription, which can significantly improve adherence to SLIT in patients with AR.

Cerumen impaction was composed of abnormal exfoliation of keratinocytes that was correlated with infection.

OBJECTIVE: This study investigated the exact composition and tried to be helpful in explaining the etiologic mechanism of cerumen impaction in the external auditory canal (EAC). METHODS: A hundred impacted cerumen samples and 15 normal cerumen samples were collected by manual removal and divided into 2 groups. All samples were examined via microbial culture, hematoxylin-eosin staining, periodic acid-Schiff staining, and fungal fluorescent staining. RESULTS: Eighty-eight patients in group 1 were in the habit of using cotton buds. Forty-seven impacted cerumen samples tested positive for microbes, while only 1 sample of normal cerumen tested positive for microbes (p < .05). The most commonly isolated bacterium and fungus was Staphylococcus aureus and Aspergillus terreus respectively. All cerumen samples were composed of exfoliated keratinocytes and microorganisms assessed via pathologic examination. However, unlike normal cerumen, impacted cerumen contained nucleated keratinocytes and infiltrated neutrophils. Recurrent impaction was found only among patients who tested mold culture-positive. CONCLUSION: Impacted cerumen is composed of abnormal exfoliated keratinocytes that was correlated with microbial-induced neutrophil-mediated inflammation. Mold infection is highly correlated with recurrent cerumen impaction. Microbial culture of removed impacted cerumen is strongly recommended. Ear cleaning with cotton buds, particularly when the EAC is wet might be one of the important causes of cerumen impaction which is need further studied. LEVEL OF EVIDENCE: 2b.

Tanshinone IIA suppress the proliferation of HNE-1 nasopharyngeal carcinoma an in vitro study.

Nasopharyngeal carcinoma (NPC) at present is considered to be one of the fatal diseases detected commonly in the people belonging to Southeast Asia and southern China. According to the WHO reports among the detected cases of NPC worldwide, 80% are from China. The present study investigates the effect of tanshinone IIA on the migration and invasion potential of HNE-1NPC cells and studied the detailed mechanism involved. Effect of the tanshinone IIA on viability of the HNE-1NPC cells was analyzed by MTS assay. Cell matrigel invasion and wound-healing motility assays, respectively were used for the analysis of invasion and migration potential of HNE-1 cells. Tanshinone IIA inhibited the viability of HNE-1cells in a dose dependent manner. Migration and invasion potential of the tanshinone IIA treated cells was reduced significantly (P < 0.05) compared to the control cells after 48 h. Analysis of the proteins involved in migration and invasion revealed a significant decrease in the expression of matrix metalloproteinase (MMP)-2 and MMP-9 on treatment with tanshinone IIA. It also inhibited the p65 and p50 expression in the nuclear fractions of HNE-1 cells after 48 h. Thus, tanshinone IIA inhibits migration and invasion potential of the HNE-1NPC cells through reduction in the expression of matrix metalloproteinases. Therefore, tanshinone IIA can be used for the treatment of NPC.

The effects of functional polymorphisms in the TGFß1 gene on nasopharyngeal carcinoma susceptibility.

OBJECTIVE: Transforming growth factor ß1 (TGFß1) promotes tumor growth and metastasis in the later stage of cancer development. In this study, we explored whether TGFß1 polymorphisms were associated with increased risk of nasopharyngeal carcinoma (NPC) in a Chinese population. DESIGN: Case-control study. SETTING: Hospitals of the Department of Otorhinolaryngology-Head and Neck Surgery. SUBJECTS AND METHODS: Two single nucleotide polymorphisms of TGFß1 gene promoter -509C/T (rs1800469) and 869T/C (Leu 10 Pro, rs1800470) at exon 1 were analyzed in 522 NPC patients and 712 age- and sex-matched controls in a Chinese population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Functional relevance of the polymorphism was determined by biochemical assays. RESULTS: The -509T allele carriers were associated with a significantly reduced risk of NPC as compared with the noncarriers (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53-0.89 and OR, 0.50; 95% CI, 0.31-0.67, respectively). Moreover, -509C-containing TGFß1 promoter drove an ~1.7-fold increase in reporter expression, compared with the -509T-containing counterpart in both CNE-1 and CNE-2 cell lines. The TGFß1 -509 CC genotype carriers had a higher TGFß1 mRNA level than the TGFß1 -509TT genotype carriers did (P < .01). However, no significant association was observed between the 869T/C polymorphism and risk of NPC. CONCLUSION: These findings indicate that the -509C/T polymorphism in TGFß1 may play a vital role in mediating individual susceptibility to NPC.