Repetitive Transcranial Magnetic Stimulation, a Novel Therapeutic Strategy for Refractory Paradoxical Vocal Fold Motion Disorder.

Paradoxical vocal fold motion disorder (PVFMD) is a condition involving the inappropriate narrowing of the larynx with symptoms of laryngeal tightness and dyspnea. A 23-year-old woman was diagnosed with PVFMD by imaging, revealing dynamically constricted, supraglottic tissue, an abnormal adduction of the vocal cords with a characteristic "posterior chink" observed. After diagnosis, laryngeal control retraining protocols and biofeedback therapy were initiated. To treat persistent symptoms, interventions such as vocal fold botulinum toxin (BoNT) injections were performed with slight improvements. Ultimately, psychiatry performed 10 repetitive transcranial magnetic stimulations (rTMS) with a right-sided, low-frequency approach to treat the patient's underlying major depressive disorder and comorbid anxious distress. Afterward, the patient's symptoms were successfully reduced with an improvement in Dyspnea Severity Index. Although most patients with PVFMD were relieved with laryngeal control therapy, some are refractory and lack the literature on the best treatment. In this case, we followed the multidisciplinary approach and individualized our novel therapeutic strategies including especially rTMS, which successfully reduced symptoms. This is the first reported case of refractory PVFMD to be treated with novel interventions, and rTMS might play a role in PVFMD mitigation.

Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration.

Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy with a steadily increasing global incidence in recent decades. The pathogenesis of PTC is poorly understood, and the present diagnostic protocols are deficient. Thus, identifying novel prognostic biomarkers to improve our understanding of the mechanisms of pathogenesis, diagnosis, and designing therapeutic strategies for PTC is crucial. In this study, we integrated 27 PTC transcriptomic datasets and identified overlapping differentially expressed genes (DEGs) and differentially expressed microRNAs, collectively known as thyroid tumor-enriched proteins (TTEPs), and TTEmiRs, respectively. Our integrated bioinformatics analysis revealed that TTEPs were associated with tumor stages, poor surgical outcomes, distant metastasis, and worse prognoses in PTC cohorts. In addition, TTEPs were found to be associated with tumor immune infiltrating cells and immunosuppressive phenotypes of PTC. Enrichment analysis suggested the association of TTEPs with epithelial-to-mesenchymal transition (EMT), cell-matrix remodeling, and transcriptional dysregulation, while the TTEmiRs (miR-146b-5p and miR-21-5p) were associated with the modulation of the immune response, EMT, migration, cellular proliferation, and stemness. Molecular docking simulations were performed to evaluate binding affinities between TTEPs and antrocinnamomin, antcin, and antrocin, the bioactive compounds from one of the most reputable Taiwan indigenous medicinal plants (Antrodia camphorata). Our results revealed that antcin exhibited higher binding efficacies toward FN1, ETV5, and NRCAM, whereas antrocin demonstrated the least. Among the targets, fibronectin (FN1) demonstrated high ligandability potential for the compounds whereas NRCAM demonstrated the least. Collectively, our results hinted at the potential of antcin for targeting TTEPs. In conclusion, this comprehensive bioinformatics analysis strongly suggested that TTEPs and TTEmiRs could be used as potential diagnostic biomarker signatures and be exploited as potential targets for therapeutics development.

Identification of DPP4/CTNNB1/MET as a Theranostic Signature of Thyroid Cancer and Evaluation of the Therapeutic Potential of Sitagliptin.

In recent years, the incidence of thyroid cancer has been increasing globally, with papillary thyroid cancer (PTCa) being the most prevalent pathological type, accounting for approximately 80% of all cases. Although PTCa has been regarded to be slow growing and has a good prognosis, in some cases, PTCa can be aggressive and progress despite surgery and radioactive iodine treatment. In addition, most cancer treatment drugs have been shown to be cytotoxic and nonspecific to cancer cells, as they also affect normal cells and consequently cause harm to the body. Therefore, searching for new targets and therapies is required. Herein, we explored a bioinformatics analysis to identify important theranostic markers for THCA. Interestingly, we identified that the DPP4/CTNNB1/MET gene signature was overexpressed in PTCa, which, according to our analysis, is associated with immuno-invasive phenotypes, cancer progression, metastasis, resistance, and unfavorable clinical outcomes of thyroid cancer cohorts. Since most cancer drugs were shown to exhibit cytotoxicity and to be nonspecific, herein, we evaluated the anticancer effects of the antidiabetic drug sitagliptin, which was recently shown to possess anticancer activities, and is well tolerated and effective. Interestingly, our in silico molecular docking results exhibited putative binding affinities of sitagliptin with DPP4/CTNNB1/MET signatures, even higher than standard inhibitors of these genes. This suggests that sitagliptin is a potential THCA therapeutic, worthy of further investigation both in vitro and in vivo and in clinical settings.

Transcriptomic discovery of a theranostic signature (SERPINE1/MMP3/COL1A1/SPP1) for head and neck squamous cell carcinomas and identification of antrocinol as a candidate drug.

Head and neck squamous cell carcinomas (HNSCC) are prevalent malignancies with a disappointing prognosis, necessitating the search for theranostic biomarkers for better management. Based on a meta-analysis of transcriptomic data containing ten clinical datasets of HNSCC and matched nonmalignant samples, we identified SERPINE1/MMP3/COL1A1/SPP1 as essential hub genes as the potential theranostic biomarkers. Our analysis suggests these hub genes are associated with the extracellular matrix, peptidoglycans, cell migration, wound-healing processes, complement and coagulation cascades, and the AGE-RAGE signaling pathway within the tumor microenvironment. Also, these hub genes were associated with tumor-immune infiltrating cells and immunosuppressive phenotypes of HNSCC. Further investigation of The Cancer Genome Atlas (TCGA) cohorts revealed that these hub genes were associated with staging, metastasis, and poor survival in HNSCC patients. Molecular docking simulations were performed to evaluate binding activities between the hub genes and antrocinol, a novel small-molecule derivative of an anticancer phytochemical antrocin previously discovered by our group. Antrocinol showed high affinities to MMP3 and COL1A1. Notably, antrocinol presented satisfactory drug-like and ADMET properties for therapeutic applications. These results hinted at the potential of antrocinol as an anti-HNSCC candidate via targeting MMP3 and COL1A1. In conclusion, we identified hub genes: SERPINE1/MMP3/COL1A1/SPP1 as potential diagnostic biomarkers and antrocinol as a potential new drug for HNSCC.

Predictive factors of increased surgical drain output after thyroid lobectomy: a retrospective study.

BACKGROUND: Thyroid lobectomy is one of the most common operations for thyroid lesions. Life-threatening complications can occur; these include post-operative bleeding with airway compression caused by hematoma. Given this risk, prophylactic drains are routinely used in our practice. The aim of this study was to identify factors that influence the total drainage volume (TDV). METHODS: From 2016 to 2017, a total of 89 consecutive patients with thyroid lobectomy performed by the same surgeon were included in the study. The demographic characteristics of the patients, TDV, fine needle aspiration cytology, hospitalization day, operation time, thyroid gland size, and blood test results were retrospectively recorded from the hospital database. Spearman's rank correlation and multivariate regression were used to analyze the association of factors with the TDV. RESULTS: The median TDV was 56 mL, and there was a positive correlation between age, weight, blood sugar, gland size, hospitalization day, operation time, and TDV. Multivariate regression analysis revealed that male sex (ß=19.684; 95% CI, 7.998-31.371; P=0.001), higher blood sugar (ß=0.173; 95% CI, 0.087-0.260; P<0.001), and larger thyroid gland size (ß=0.069; 95% CI, 0.008-0.130; P=0.027) were independent risk factors for TDV. CONCLUSIONS: The TDV primarily depends on male sex, larger thyroid gland, and higher blood sugar level. Patients with these factors should undergo meticulous hemostasis and bleeding should be carefully monitored in the perioperative period.

Clinical assessment of diode laser-assisted endoscopic intrasphenoidal vidian neurectomy in the treatment of refractory rhinitis.

For chronic rhinitis that is refractory to medical therapy, surgical intervention such as endoscopic vidian neurectomy (VN) can be used to control the intractable symptoms. Lasers can contribute to minimizing the invasiveness of ENT surgery. The aim of this retrospective study is to compare in patients who underwent diode laser-assisted versus traditional VN in terms of operative time, surgical field, quality of life, and postoperative complications. All patients had refractory rhinitis with a poor treatment response to a 6-month trial of corticosteroid nasal sprays and underwent endoscopic VN between November 2006 and September 2015. They were non-randomly allocated into either a cold instrument group or a diode laser-assisted group. Vidian nerve was excised with a 940-nm continuous wave diode laser through a 600-µm silica optical fiber, utilizing a contact mode with the power set at 5 W. A visual analog scale (VAS) was used to grade the severity of the rhinitis symptoms for quality of life assessment before the surgery and 6 months after. Of the 118 patients enrolled in the study, 75 patients underwent cold instrument VN and 43 patients underwent diode laser-assisted VN. Patients in the laser-assisted group had a significantly lower surgical field score and a lower postoperative bleeding rate than those in the cold instrument group. Changes in the VAS were significant in preoperative and postoperative nasal symptoms in each group. The application of diode lasers for vidian nerve transection showed a better surgical field and a lower incidence of postoperative hemorrhage. Recent advancements in laser application and endoscopic technique has made VN safer and more effective. We recommend this surgical approach as a reliable and effective treatment for patients with refractory rhinitis.

The association of superior attachment of uncinate process with pneumatization of middle turbinate: a computed tomographic analysis.

The frontal sinus outflow pathway is complex and can be influenced by the configuration of the uncinate process (UP). The UP can attach superior to the lamina papyracea, skull base, and middle turbinate. The factors associated with superior attachment remain unclear. This study analyzed the relationships between different types of superior UP attachment and characteristics of the surrounding structures including the agger nasi cell, skull base, and middle turbinate. This retrospective study utilized computed tomography images of 836 sides with identifiable sinus structure from 434 Taiwanese patients. Types of superior UP attachment, height of the ethmoid cribriform plate, prevalence of agger nasi cell, and degree of pneumatization of the middle turbinate were analyzed. In the current study, neither the presence of an agger nasi cell nor height of the cribriform plate had significant relationship with superior UP attachment type. However, UP attachment type was statistically significantly associated with pneumatized middle turbinate (PMT) type (p < 0.01). The PMT group had a higher incidence of UP attachment to the middle turbinate (38%) than the non-PMT group (18%). In the extensive PMT group, the incidence of UP attachment to the middle turbinate was high to 49%. In conclusion, superior UP attachment to the middle turbinate was associated with pneumatization of the middle turbinate. The UP has a greater tendency to attach to the middle turbinate in cases with more PMT.