OBJECTIVE:Sudden sensorineural hearing loss (SSNHL) is a condition with largely unknown etiology, though both vascular and genetic components have been implicated. The X-ray repair cross-complementing group 1 (XRCC1) gene, involved in DNA repair and oxidative stress response, has been linked to ischemic stroke and noise-induced hearing loss. This study aimed to investigate the association between XRCC1 single nucleotide polymorphisms (SNPs) and SSNHL risk in Taiwan. DESIGN:Prospective case-control study. SETTING:Tertiary academic medical center. MATERIALS AND METHODS:A total of 276 patients with SSNHL and 293 healthy controls were enrolled. Three XRCC1 SNPs (rs1799782, rs25489, and rs25487) were genotyped using TaqMan assays. All SNPs were tested for Hardy-Weinberg equilibrium. Associations with SSNHL risk were analyzed under dominant and recessive models using multivariate logistic regression. Clinical predictors of recovery were also evaluated. RESULTS:The TT genotype of XRCC1 rs1799782 was significantly associated with increased SSNHL risk compared with the CC genotype [adjusted odds ratio (aOR)=2.005; 95% CI=1.13-3.62; P =0.0164]. This association persisted under the recessive model (TT vs. CC+CT) (aOR=1.983; 95% CI=1.15-3.49; P =0.0134). No significant associations were observed for rs25489 and rs25487. High-tone (aOR=6.42; P = 0.0043) and flat-type (aOR=4.12; P =0.0071) audiogram patterns and longer treatment delay were linked to unfavorable clinical outcomes. XRCC1 genotypes were not predictive of treatment response. CONCLUSIONS:The TT genotype of XRCC1 rs1799782 is significantly associated with increased SSNHL susceptibility in the Taiwanese population.

ImportanceSudden sensorineural hearing loss (SSNHL) is associated with metabolic syndrome, central obesity, and albumin level. Malnutrition may adversely affect recovery in older patients with SSNHL, yet its clinical relevance remains underexplored.ObjectiveThis study investigated the associations of the geriatric nutritional risk index (GNRI) with clinical outcomes in older patients (age >65 years) with SSNHL.DesignObservational retrospective study.SettingTertiary academic medical center.ParticipantsA total of 328 patients aged over 65 years who were diagnosed with SSNHL were retrospectively enrolled. Patients were included if they had complete clinical, audiometric, and laboratory data, including serum albumin levels and anthropometrics for GNRI calculation.Intervention/ExposuresThe primary exposure was the GNRI, calculated using body weight, height, and serum albumin. All patients received steroid treatment for SSNHL.Main Outcome MeasuresThe primary outcome was hearing recovery, categorized as favorable or unfavorable based on clinical audiometric improvement.ResultsAmong older patients with SSNHL, 107 (32.62%) and 221 (67.38%) had favorable and unfavorable outcomes, respectively. Vertigo, worse initial level of hearing loss, and low GNRI were mainly associated with unfavorable hearing outcomes in older patients with SSNHL. Furthermore, low GNRI (<99) was linked to unfavorable clinical outcomes (odds ratio [OR] = 1.91, P = .0151). Multivariate logistic regression revealed that vertigo (aOR = 3.45, P = .0002), worse initial level of hearing loss (per 1 unit increase in hearing loss elevates the risk of poor hearing recovery by 2%, P = .0015), and low GNRI (aOR = 1.79, P = .0435) were associated with unfavorable clinical outcomes.ConclusionIn summary, evaluation of nutritional status plays a crucial role in improving clinical outcomes in SSNHL. Moreover, GNRI can predict clinical outcomes in older patients with SSNHL treated with steroids. Older patients with SSNHL who have vertigo, a worse initial level of hearing loss, and low GNRI exhibit unfavorable outcomes.RelevanceGNRI is a simple, accessible marker that can help identify older SSNHL patients at higher risk of poor recovery. Future prospective studies should validate its use as a prognostic tool and explore whether nutritional interventions can improve hearing outcomes.

BACKGROUND:16-hydroxycleroda-3,13-dien-15,16-olide (HCD), a compound isolated from Polyalthia longifolia var. pendula, has been identified as a PI3K inhibitor. P. longifolia var. pendula is recognized for its diverse pharmacological properties, including antimicrobial, hypotensive, anti-inflammatory, and cytotoxic activities. Considering the pivotal role of PI3K in the regulation of apoptosis in cancer cells, this study aims to investigate the apoptotic effects induced by HCD in head and neck cancer cell models. METHODS:The study focused on investigating the mechanism through which HCD induces apoptosis in oral squamous cell carcinoma (OSCC) using SCC25 and SCC180 cells. These cells were treated with HCD at IC20, IC50, and IC80 concentrations over periods of 24, 48, and 72 h. Assessments included cell viability, oxidative stress levels using MitoSOX and CellROX, and the analysis of gene and protein expressions related to apoptosis via immunofluorescence staining, flow cytometry, RT-PCR, and western blotting. RESULTS:The results demonstrated that HCD significantly increased the sub-G1 phase cell population, suppressed clonogenic activity, and promoted mitochondrial ROS production, accompanied by a reduction in glutathione levels. HCD also activated cytochrome c (cyto. c) release and Bax expression while downregulating Bcl-2 expression. Notably, in SCC25 cells, HCD induced apoptosis through the TNF-α/TNF-R and FasL/Fas death domains, leading to caspase cascade activation. Moreover, HCD showed dose-dependent growth inhibition of SCC25 cells, both alone and combined with cisplatin, by enhancing caspase-3 expression. CONCLUSION:This investigation into HCD's molecular mechanisms in OSCC cells offers insight into developing effective anticancer therapies, highlighting its role in apoptosis induction through oxidative stress, mitochondrial pathways, and death receptor signaling.

Objectives: To investigate the role of normal weight central obesity (NWCO) in the prognosis of sudden sensorineural hearing loss (SSNHL). Methods: We retrospectively investigated 807 cases of SSNHL from January of 2008 to August of 2019 from the Department of Otorhinolaryngology at Kaohsiung Medical University Hospital in southern Taiwan. We analyzed the association between overweight and obesity, NWCO, and the prognosis of SSNHL. The demographic and clinical characteristics, audiometry results, and outcomes were also reviewed. Results: The nonobese (body mass index [BMI] < 24 kg/m 2 ) and overweight and obese groups (BMI ≥ 24 kg/m 2 ) comprised 343 (42.50%) and 464 (57.50%) patients, respectively. The favorable prognosis rates in the nonobese and the overweight and obese groups were 45.48% and 45.91%, respectively, without a significant difference ( P = .9048). Multivariate logistic regression revealed that BMI (adjusted odds ratio [aOR] = 1.00, 95% CI = 0.948-1.062, P = .9165) was not significantly associated with SSNHL recovery. The normal weight noncentral obesity (NWNCO) and NWCO groups comprised 266 (77.55%) and 77 (22.45%) patients, respectively, and had favorable prognosis rates of 48.50% and 35.06%, respectively. The difference between the groups was significant ( P = .0371). Multivariate logistic regression analysis revealed that NWCO (aOR = 2.51, 95% CI = 1.292-5.019, P = .0075) was significantly associated with SSNHL recovery. Conclusions: NWCO may significantly affect the prognosis of SSNHL.

A 32-year-old male patient presented to the otolaryngology outpatient department after experiencing visible progressive facial misalignment for 3 weeks. He complained about the sunken appearance of his left eye and the asymmetric protrusion of his bilateral maxillary bone. However, he had no history of recent facial trauma, sinus surgery, or any nasal or ophthalmological symptoms. Physical examination revealed a deepening of the left superior orbital sulcus and left hypoglobus (Figure 1A). The patient's visual acuity and extraocular movements were normal. Nasal endoscopy indicated the absence of polyps, purulent secretion, edematous mucosa, or any other abnormality. Subsequent computed tomography (CT) revealed that all the walls of the left maxillary sinus were bowing inward, causing a considerable reduction in the sinus volume and a downward displacement of the orbital floor (Figure 1B,C). A diagnosis of silent sinus syndrome (SSS) was made. During endoscopic maxillary antrostomy performed under general anesthesia, total occlusion of the maxillary sinus ostium and the accumulation of mucus were discovered. Patency of the maxillary sinus was subsequently achieved. Six months after the maxillary antrostomy, the patient self-reported improved facial asymmetry (Figure 1D), and a follow-up CT scan revealed a substantial expansion of the size of the patient's maxillary sinus and an improvement in his enophthalmos (Figure 1E,F). The criteria for diagnosing SSS include spontaneous enophthalmos and/or hypoglobus, contraction of the maxillary sinus with osteomeatal complex (OMC) occlusion on CT images as well as the absence of symptoms of sinonasal inflammatory disease, orbital trauma, or any congenital deformity.1-3 The pathophysiology of SSS involves maxillary sinus hypoventilation after total OMC occlusion. Subsequent gas resorption leads to sub-atmospheric pressure, creating a vacuum that causes sinus wall retraction. Over time, the maxilla bone undergoes secondary demineralization, and the resulting negative sinus pressure causes the weakened areas to implode.4 This phenomenon was confirmed by Kass et al.5 a series of human studies. When SSS was first described in 1990s, the Caldwell-Luc procedure was the conventional surgical solution. However, the treatment trend has shifted to endoscopic surgery, which provides advantages such as reduced infection rates, a reduced risk of numbness, and improved maxillary sinus aeration. Nevertheless, the endoscopic procedure must be performed carefully to prevent orbital content from prolapsing into the maxillary sinus. A major debate is whether orbital floor reconstruction should be performed during maxillary surgery. Some surgeons prefer a one-stage approach, whereas others recommend a watch-and-wait strategy because spontaneous re-expansion and atelectasis resolution can occur to some extent after the maxillary ostium is widened.2-4 Our patient only underwent maxillary surgery, and at 6 months after the procedure, we observed the regression of enophthalmos and an increase in the maxillary sinus size. This result suggests that simultaneous endoscopic antrostomy and orbital floor reconstruction are not required. In summary, this report presents a rare clinical case of a patient who visited our institution solely because of aesthetic concerns. Furthermore, the patient was pleased with the cosmetic results achieved through accurate diagnosis and treatment. All authors declare no conflict of interest. Approval for retrospective data collection/secondary use of health information was obtained from the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20230135).

OBJECTIVES:To investigate the etiology and ossicular pathology of traumatic ossicular injury in Taiwan and examine the hearing outcomes and predictive factors between the titanium prosthesis and autologous incus groups.METHODS:We retrospectively analyzed patients with traumatic ossicular injury from 2011 to 2020 in Taiwan. Patients were divided into the titanium or autologous group according to the surgical materials used. The audiometric outcomes and predictive factors of ossiculoplasty were analyzed between groups.RESULTS:Twenty patients with ossicular chain discontinuity were enrolled (8 in the titanium group and 12 in the autologous group). The postoperative hearing threshold (26.6 ± 8.9 dB) and air-bone gap (10.3 ± 5.6 dB) improved significantly compared with the preoperative hearing threshold (50.7 ± 13.3 dB) and air-bone gap (29.9 ± 11.0 dB). The improvements in the hearing threshold and air-bone gap were not significantly different between the titanium and autologous groups. Our patients presented an improvement in hearing restoration with 65% closure of the air-bone gap in 0 to 10 dB range and 30% in 11 to 20 dB range, without sensorineural hearing loss during surgery. Univariate regression analysis revealed that vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative factors influencing the air-bone gap gain.CONCLUSIONS:Ossiculoplasty with both titanium prosthesis and autologous materials demonstrated favorable hearing recovery in traumatic ossicular injury. Vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative predictive factors of the hearing benefit after surgery.

Objective We used simple variables to construct prognostic prediction ensemble learning models for patients with sudden sensorineural hearing loss (SSNHL). Study Design Retrospectively study. Setting Tertiary medical center. Patients 1,572 patients with SSNHL. Intervention Prognostic. Main Outcome Measures We selected four variables, namely, age, days after onset of hearing loss, vertigo, and type of hearing loss. We also compared the accuracy between different ensemble learning models based on the boosting, bagging, AdaBoost, and stacking algorithms. Results We enrolled 1,572 patients with SSNHL; 73.5% of them showed improving and 26.5% did not. Significant between-group differences were noted in terms of age (p = 0.011), days after onset of hearing loss (p < 0.001), and concurrent vertigo (p < 0.001), indicating that the patients who showed improving to treatment were younger and had fewer days after onset and fewer vertigo symptoms. Among ensemble learning models, the AdaBoost algorithm, compared with the other algorithms, achieved higher accuracy (82.89%), higher precision (86.66%), a higher F1 score (89.20), and a larger area under the receiver operating characteristics curve (0.79), as indicated by test results of a dataset with 10 independent runs. Furthermore, Gini scores indicated that age and days after onset are two key parameters of the predictive model. Conclusions The AdaBoost model is an effective model for predicting SSNHL. The use of simple parameters can increase its practicality and applicability in remote medical care. Moreover, age may be a key factor influencing prognosis.

Purpose: The long-term prognosis and survival rate of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are poor, although the identification of specific biomarkers that reveal its nature and aggressiveness has improved it. Growth-related oncogene alpha (Groα) and NOD1 (nucleotide-binding oligomerization domain 1) can be used as prognosis markers to identify subgroups of HNSCC patients with low survival rates and as potential therapeutic targets for HNSCC patients. However, the mechanism associated with the Groα-mediated NOD pathway in HNSCC progression remains unclear. Method: Overall survival analysis and multiple-gene comparison were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA). qRT-PCR and RT-PCR were used to analyze mRNA expression. Microarray, immunofluorescence staining or western blot analyses were carried out to detect protein expression. Results: Groα was significantly higher in the grade 4 HNSCC tumor tissues compared with that in grade 1-3 and healthy subjects. High expression of Groα, NOD1 and RIPK2 (receptor-interacting serine-threonine kinase 2) is correlated with survival rate in HNSCC patients. Treatment of SCC25 and OECM-1 cells with Groα increased the expression of NOD1 and RIPK2 in a concentration-dependent manner. The findings herein reveal the association of Groα, NOD1 and RIPK2 biomarkers with HNSCC carcinogenesis. Moreover, Groα is the major stimulus of inflammatory mediation and promotes TNF-α (tumor necrosis factor-α) and COX-2 (cyclooxygenase-2) expression in HNSCC. Groα induces TNF-α and COX-2 expression through regulation involving ERK (extracellular signal-regulated kinase)-, JNK (C-Jun N-terminal kinase)- and p38 MAPK (mitogen-activated protein kinase)-dependent signaling pathways. Conclusions: Our findings herein constitute the first evidence that Groα is important in HNSCC progression and metastasis via the NOD1-mediated MAPK pathway, suggesting a role for Groα and NOD1 in mediating metastasis and its potential as a therapeutic target.

Background The glucocorticoid receptor gene ( NR3C1 ) encodes the receptor to which cortisol and other glucocorticoids bind. Steroids in either oral, intratympanic, or intravascular forms are the treatment of choice for sudden sensorineural hearing loss (SSNHL), but the outcome varies. The outcomes of SSNHL have been investigated for related factors, including age, initial hearing loss severity and pattern, vertigo, genetic variations, and the time between onset and treatment. The objective of the present study was to analyze the association of genetic polymorphisms of NR3C1 with the outcomes of SSNHL. Materials and methods We conducted a comparison study of 93 cases with a poor outcome (control) and 100 cases with a good outcome (case) in SSNHL patients. Six single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Results The heterozygous AT genotype of rs17100289 was associated with a poor outcome in comparison with the major homozygous AA genotype after adjustments for age and sex (OR = 0.50; 95% CI 0.26–0.95; P = 0.035) in SSNHL patients. The CT genotype of rs4912912 was also associated with a poor outcome compared with the major homozygous TT genotype after the adjustments (OR = 0.47; 95% CI 0.24–0.92; P = 0.026). Conclusion These results suggest that NR3C1 genetic polymorphisms may influence the outcomes of SSNHL. Graphical Abstract Keywords Nuclear receptor subfamily 3 Group C member 1 ( , ) , Genetic polymorphism , Outcomes , Steroid receptor gene , sudden sensorineural hearing loss

Background: Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from the same patients. Methods: The present study is a retrospective study performed in an academic medical center. Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth. Results: Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma. Conclusion: Our data suggests that CRT and AnxA2 downregulation are seen in cholesteatoma compared to retroauricular skin. We speculate that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma.

Background The glucocorticoid receptor gene ( NR3C1) encodes the receptor to which cortisol and other glucocorticoids bind. Steroids in either oral, intratympanic, or intravascular forms are the treatment of choice for sudden sensorineural hearing loss (SSNHL), but the outcome varies. The outcomes of SSNHL have been investigated for related factors, including age, initial hearing loss severity and pattern, vertigo, genetic variations, and the time between onset and treatment. The objective of the present study was to analyze the association of genetic polymorphisms of NR3C1 with the outcomes of SSNHL. Materials and methods We conducted a comparison study of 93 cases with a poor outcome (control) and 100 cases with a good outcome (case) in SSNHL patients. Six single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Results The heterozygous AT genotype of rs17100289 was associated with a poor outcome in comparison with the major homozygous AA genotype after adjustments for age and sex (OR = 0.50; 95% CI 0.26–0.95; P = 0.035) in SSNHL patients. The CT genotype of rs4912912 was also associated with a poor outcome compared with the major homozygous TT genotype after the adjustments (OR = 0.47; 95% CI 0.24–0.92; P = 0.026). Conclusion These results suggest that NR3C1 genetic polymorphisms may influence the outcomes of SSNHL. Graphical Abstract

Background The survival rate of head and neck squamous cell carcinoma (HNSCC) patients with secondary primary malignancy (SPM) showed no significant improvement for decades, however, the impact of advances in diagnostic tools is rarely mentioned. This study investigated the clinical characteristic of HNSCC with SPM over a 27-year period especially from the perspective of diagnostic tools. Methods This study evaluated 157 HNSCC patients with SPM. The patients were divided into two groups according to the time of SPM diagnosis (Group A:1992–2003; Group B: 2004–2014). Age, gender, stage of first primary malignancy (FPM), SPM interval, overall survival, and disease-free survival were compared between groups. Results Group B had significantly more SPM developed rate (p = 0.002), more SPM patients with advanced stage of FPM (p = 0.001), synchronous SPM (p = 0.006), and shorter SPM interval (p<0.001) compared to Group A. The survival rate in Group B was not significantly better than Group A. Conclusion Among patients diagnosed with HNSCC recently, more SPMs are diagnosed in a shorter time interval and in a more advanced stage. The overall advances in diagnostic tools cannot significantly improve SPM survival, however, it enables more patients to receive corresponding treatment.

Total thyroidectomy (TT) in patients with Graves’ disease is challenging even for an experienced thyroid surgeon. This study aimed to investigate the accumulation of experience and applying newly developed devices on major complications and voice outcomes after surgery of a single surgeon over 30 years. This study retrospectively reviewed 90 patients with Graves’ disease who received TT. Forty-six patients received surgery during 1990–1999 (Group A), and 44 patients received surgery during 2010–2019 (Group B). Major complications rates were compared between Group A/B, and objective voice parameters were compared between the usage of energy-based devices (EBDs) within Group B. Compared to Group B, Group A patients had higher rates of recurrent laryngeal nerve palsy (13.0%/1.1%, p = 0.001), postoperative hypocalcemia (47.8%/18.2%, p = 0.002), and postoperative hematoma (10.9%/2.3%, p = 0.108). Additionally, Group A had one permanent vocal cord palsy, four permanent hypocalcemia, and one thyroid storm, whereas none of Group B had these complications. Group B patients with EBDs had a significantly better pitch range (p = 0.015) and jitter (p = 0.035) than those without EBDs. To reduce the major complications rate, inexperienced thyroid surgeons should remain vigilant when performing TT for Graves’ disease. Updates on surgical concepts and the effective use of operative adjuncts are necessary to improve patient safety and voice outcome.

Squamous cell carcinoma (SCC) is the most common malignant tumor of the head and neck and generally detected in the late stages when the cancer has advanced, and therefore has a poor prognosis and survival rate. A high expression of growth-related oncogene alpha (Groα) is associated with tumor metastasis and invasion and the poor survival rate of patients. Microarray reveals that Groα exhibits a cancer-specific response in HNSCC. Quantitative real-time PCR (qRT-PCR) results concerning the mRNA expression of Groα in HNSCC tissues; indicate that Groα was more highly expressed in HNSCC than in non-cancerous matched tissue (NCMT). The serum of HNSCC patients and healthy subjects demonstrates that the expression of Groα in the HNSCC patients significantly exceeded than in healthy subjects. Furthermore, exposure Groα to stimulated the proliferation, clonogenicity and migration with HNSCC cells (SCC4, SCC9, SCC25 and OECM-1), yielding a stronger response than in non-malignant HaCaT and DOK cells. A high expression of Groα and its receptors CXCR1/2 (chemokine (C-X-C motif) receptor) in HNSCC tissues are highly correlated with tumor progression stage and metastasis. Following the treatment of SCC25 and OECM-1 cells with Groα, β-catenin, matrix metalloproteinases (MMP)-2, MMP-7 and MMP-9 expressions significantly increased but E-cadherin expression was slightly decreased, suggesting that the EMT and metastasis processes were activated by Groα. These findings constitute the first evidence that Groα promotes epithelial mesenchymal transition (EMT) and MMPs expressions in HNSCC via activating CXCR1/2, suggesting a role for Groα in mediating metastasis and its potential as a therapeutic target.

A recurrent laryngeal nerve (RLN) injury resulting in vocal fold paralysis and dysphonia remains a major source of morbidity after thyroid and parathyroid surgeries. Intraoperative neural monitoring (IONM) is increasingly accepted as an adjunct to the standard practice of visual RLN identification. Endotracheal tube (ET) surface recording electrode systems are now widely used for IONM; however, the major limitation of the clinical use of ET-based surface electrodes is the need to maintain constant contact between the electrodes and vocal folds during surgery to obtain a high-quality recording. An ET that is malpositioned during intubation or displaced during surgical manipulation can cause a false decrease or loss of electromyography (EMG) signal. Since it may be difficult to distinguish from an EMG change caused by a true RLN injury, a false loss or decrease in EMG signal may contribute to inappropriate surgical decision making. Therefore, researchers have investigated alternative electrode systems that circumvent common causes of poor accuracy in ET-based neuromonitoring. Recent experimental and clinical studies have confirmed the hypothesis that needle or adhesive surface recording electrodes attached to the thyroid cartilage (transcartilage and percutaneous recording) or attached to the overlying neck skin (transcutaneous recording) can provide functionality similar to that of ET-based electrodes, and these recording methods enable access to the EMG response of the vocalis muscle that originates from the inner surface of the thyroid cartilage. Studies also indicate that, during surgical manipulation of the trachea, transcartilage, percutaneous, and transcutaneous anterior laryngeal (AL) recording electrodes could be more stable than ET-based surface electrodes and could be equally accurate in depicting RLN stress during IONM. These findings show that these AL electrodes have potential applications in future designs of recording electrodes and support the use of IONM as a high-quality quantitative tool in thyroid and parathyroid surgery. This article reviews the major recent developments of newly emerging transcartilage, percutaneous, and transcutaneous AL recording techniques used in IONM and evaluates their contribution to improved voice outcomes in modern thyroid surgery.

Background Sudden sensorineural hearing loss (SSNHL) is a disease with an unknown etiology; damage to the auditory nerve from inflammation due to viral infection or vascular incidents has been implicated. According to several studies, cytokines, including interleukins, are associated with SSNHL in terms of serum expression and genetic polymorphisms. Interleukin-1 (IL-1) plays a key role in inflammation and may be associated with SSNHL. This study analyzed the association of single nucleotide polymorphisms (SNPs) of IL-1 receptor (IL-1R) genes with SSNHL in Taiwan. Methods We conducted a case–control study involving 401 patients with SSNHL and 730 healthy controls. Four SNPs (IL-1R type 1 gene [ IL1R1 ] [rs3917225 and rs2234650] and IL-1R type 2 gene [ IL1R2 ] [rs4141134 and rs2071008]) were selected. The genotypes were determined using the TaqMan assay. The Hardy–Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated. Results The TT genotype of rs2234650 had an adjusted odds ratio (OR) of 2.988 (95% confidence interval [95% CI] 1.27–6.82) ( P = 0.012) compared with the CC genotype in patients with SSNHL. The SNP rs2234650 was associated with SSNHL in the recessive model (TT vs. CC + CT, P = 0.0206, OR = 2.681). The CT genotype of rs4141134 had an adjusted OR of 3.860 (95% CI 2.01–7.44; P < 0.0001) compared with the TT genotype, in patients with SSNHL. The SNP rs4141134 was associated with SSNHL under the dominant model (CC + CT vs. TT, P < 0.0001, OR = 4.087). Conclusion These findings suggest that IL1R1 and IL1R2 gene polymorphisms may contribute to an increased risk of SSNHL in Taiwan.

BACKGROUND:Exosomes are critical mediators of intercellular communication and could be involved in many human diseases; however, little is known about the role of exosomes in nasal polyps (NP).METHODS:Exosomes in nasal lavage fluids (NLF) were isolated by ultracentrifugation. Exosome identity was validated by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and specific exosomal markers. The exosome proteome was revealed by LC-MS/MS, and the expression of the candidate exosomal protein, mucin 5AC, was confirmed by Western blot analysis and immunohistochemistry (IHC). Cellular uptake of the exosomes was monitored by fluorescence confocal microscopy and the ensuing effects on COX-2, VEGF and MMP-2/MMP-9 were determined by Western blotting, ELISA and gelatin zymography, respectively.RESULTS:Mass spectrometry analysis and subsequent verification by Western blotting identified that mucin 5AC was significantly upregulated in exosomes from NLFs of NP patients. Moreover, the expression of mucin 5AC was increased in the tissue specimens of the NP patients. Functional assays suggest that the mucin 5 AC-enriched exosomes could be effectively taken up by chronic rhinosinusitis without NP (CRSsNP)-derived fibroblasts, the control cells, resulting in a significant increase in the expression of COX-2, VEGF and MMP-9.CONCLUSIONS:Mucin 5AC, the major airway mucin, cannot only be carried and transferred by nasal exosomes, but may also promote tissue remodeling and angiogenesis and thus could be a potential therapeutic target of NP.

Technological advances in thyroid surgery have rapidly increased in recent decades. Specifically, recently developed energy-based devices (EBDs) enable simultaneous dissection and sealing tissue. EBDs have many advantages in thyroid surgery, such as reduced blood loss, lower rate of post-operative hypocalcemia, and shorter operation time. However, the rate of recurrent laryngeal nerve (RLN) injury during EBD use has shown statistically inconsistent. EBDs generate high temperature that can cause iatrogenic thermal injury to the RLN by direct or indirect thermal spread. This article reviews relevant medical literatures of conventional electrocauteries and different mechanisms of current EBDs, and compares two safety parameters: safe distance and cooling time. In general, conventional electrocautery generates higher temperature and wider thermal spread range, but when applying EBDs near the RLN adequate activation distance and cooling time are still required to avoid inadvertent thermal injury. To improve voice outcomes in the quality-of-life era, surgeons should observe safety parameters and follow the standard procedures when using EBDs near the RLN in thyroid surgery.

Objective Delayed facial palsy is a complication of otologic surgery. Tympanoplasty is commonly employed in chronic otitis media. We compared the incidence and characteristics of delayed facial palsy and hearing restoration between endoscopic and microscopic tympanoplasty for the treatment of simple chronic otitis media. Study Design Retrospective cohort study. Setting Tertiary medical center. Subjects and Methods We retrospectively analyzed 468 patients who underwent type I tympanoplasty from January 2009 to April 2017. Patients were divided into transcanal endoscopic ear surgery and microscopic ear surgery groups. Their epidemiological profiles were reviewed and the outcomes of tympanoplasty were analyzed. Blood sample tests for herpes simplex virus and varicella-zoster virus immunoglobulin M and immunoglobulin G were arranged in patients with delayed facial palsy. Results Transcanal endoscopic ear surgery exhibited similar benefits to microscopic ear surgery in graft-taking rate and hearing restoration but had a shorter operation time (P < .01). Eight patients (1.71%) developed delayed facial palsy, but no statistically significant difference was observed between the 2 surgical approaches. All patients tested negative for varicella-zoster virus and herpes simplex virus immunoglobulin M and positive for immunoglobulin G of the same viruses; however, the titer did not exhibit a 4-fold increase, implying that patients did not have active viral infections. Conclusion Transcanal endoscopic ear surgery is an ideal alternative for simple tympanoplasty. The incidence of delayed facial palsy was not significantly different between the 2 approaches. Because of the favorable prognosis and the absence of direct serological evidence supporting viral reactivation, treatment with antivirals may not be required.

Prolonged treatment with cisplatin (CDDP) frequently develops chemoresistance. We have previously shown that p22phox, an endoplasmic reticulum (ER) membrane protein, confers CDDP resistance by blocking CDDP nuclear entry in oral squamous cell carcinoma (OSCC) cells; however, the underlying mechanism remains unresolved. Using a fluorescent dye-labeled CDDP, here we show that CDDP can bind to p22phox in both cell-based and cell-free contexts. Subsequent detection of CDDP-peptide interaction by the Tris-Tricine-based electrophoresis revealed that GA-30, a synthetic peptide matching a region of the cytosolic domain of p22phox, could interact with CDDP. These results were further confirmed by liquid chromatography–mass spectrometry (LC–MS) analysis, from which MA-11, an 11-amino acid subdomain of the GA-30 domain, could largely account for the interaction. Amino acid substitutions at Cys50, Met65 and Met73, but not His72, significantly impaired the binding between CDDP and the GA-30 domain, thereby suggesting the potential CDDP-binding residues in p22phox protein. Consistently, the p22phox point mutations at Cys50, Met65 and Met73, but not His72, resensitized OSCC cells to CDDP-induced cytotoxicity and apoptosis. Finally, p22phox might have binding specificity for the platinum drugs, including CDDP, carboplatin and oxaliplatin. Together, we have not only identified p22phox as a novel CDDP-binding protein, but further highlighted the importance of such a drug-protein interaction in drug resistance.