Ototoxicity among cisplatin, carboplatin, and oxaliplatin in zebrafish model.

Platinum-based antineoplastic drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various cancers. Ototoxicity is a common adverse effect of platinum-based drugs. Ototoxicity leads to irreversible hearing impairment. We hypothesize that different platinum-based drugs exhibit varying ototoxic concentrations, time effects, and ototoxic mechanisms. We tested this hypothesis by using a zebrafish model (pvalb3b: TagGFP) to assess the viability of hair cells collected from zebrafish larvae. Cisplatin, carboplatin, and oxaliplatin were administered at dosages of 100, 200, or 400 µM, and the ototoxic effects of these drugs were assessed 1, 2, or 3 h after administration. Fm4-64 and a TUNEL assay were used to label the membranes of living hair cells and to detect cell apoptosis, respectively. We observed that >50% of hair cells were damaged at 1 h after cisplatin (100 µM) exposure, and this ototoxic effect increased at higher dosages and over time. Owing to the smaller ototoxic effects of carboplatin and oxaliplatin, we conducted higher-strength and longer-duration experiments with these drugs. Neither carboplatin nor oxaliplatin was obviously ototoxic, even at 1600 µM and after 6 h. Moreover, only cisplatin damaged the membranes of the hair cells. Cell apoptosis and significantly increased antioxidant gene expression were observed in only the cisplatin group. In conclusion, cisplatin significantly damages sensory hair cells and has notable dosage and time effects. Carboplatin and oxaliplatin are less ototoxic than cisplatin, likely due to having different ototoxic mechanisms than cisplatin.

Facial canal dehiscence, dural exposure, and labyrinthine fistula in middle ear cholesteatoma and mastoiditis.

PURPOSE: To analyze the prevalence and associations of facial canal dehiscence (FCD), dural exposure, and labyrinthine fistula in chronic otitis media (COM) with and without cholesteatoma. METHODS: This was a retrospective study performed in an academic medical center. Patients who received tympanoplasty with mastoidectomy for COM with and without cholesteatoma were included. The prevalence of FCD, dural exposure, and labyrinthine fistula in COM with and without cholesteatoma (mastoiditis) and their relationships were analyzed. RESULTS: A total of 189 patients, including 107 (56.6%) females and 82 (43.4%) males, with 191 ears were included. There were 149 cases (78.0%) of cholesteatoma and 42 patients (22.0%) with mastoiditis. FCD was noted in 27.5% of patients with cholesteatoma and 9.5% of patients with mastoiditis. Dural exposure was found in 21 patients (14.1%) with cholesteatoma and 4 patients (9.5%) with mastoiditis. Eleven patients (7.4%) with cholesteatoma and 1 patient (2.4%) with mastoiditis had labyrinthine fistula. Patients with a labyrinthine fistula had nearly a fivefold greater chance (OR = 4.924, 95% CI = 1.355-17.896, p = 0.015) of having FCD than those without a fistula. There was a positive correlation between dural exposure and labyrinthine fistula (P = 0.011, Fisher's exact test). CONCLUSION: FCD, dural exposure, and labyrinthine fistula are common complications in COM. These complications are more frequently observed in patients with cholesteatoma than in patients with mastoiditis. Surgeons should pay more attention to the treatment of COM.

Association of sudden sensorineural hearing loss with dementia: a nationwide cohort study.

BACKGROUND: Impaired cochlear blood perfusion and microvascular damage can cause sudden sensorineural hearing loss (SSHL), which is a potential risk factor for dementia. This study explored the association between SSHL and dementia. METHODS: This retrospective cohort study used a random sample of 1000,000 individuals from Taiwan's National Health Insurance Research Database. We identified 3725 patients newly diagnosed with SSHL between January 1, 2000, and December 31, 2009, and propensity score matching according to age, sex, index year, comorbidities, and medications was used to select the comparison group of 11,175 patients without SSHL. Participants were stratified by age (<65 and ≧65 years) and sex for the subgroup analyses. The outcome of interest was all cause dementia (ICD-9-CM codes 290.0, 290.4, 294.1, 331.0). Both groups were followed up until December 31, 2010, for diagnoses of dementia. Cox regression models were used to estimate the hazard ratio (HR) of dementia. RESULTS: During the average 5-year follow-up period, the incidence rate of dementia in the SSHL cohort was 6.5 per 1000 person-years compared with 5.09 per 10,000 person-years in the comparison group. After adjustment for potential confounders, patients with SSHL were 1.39 times more likely to develop dementia than those without SSHL (95% confidence interval = 1.13-1.71). When stratified by patients' age and sex, the incidence of dementia was 1.34- and 1.64-fold higher in patients with SSHL aged ≥65 years (P = .013) and in women (P = .001), respectively, compared with the comparison group. Women with SSHL who were < 65 years old had the highest risk (2.14, 95% CI = 1.17-4.11, P = .022). In addition, a log-rank test revealed that patients with SSHL had significantly higher cumulative incidence of dementia than those without SSHL (P = .002). CONCLUSIONS: Patients with SSHL, especially women aged < 65 years, were associated with higher risk of dementia than those without SSHL. Thus, clinicians managing patients with SSHL should be aware of the increased risk of dementia.

Atrial deformation correlated with functional capacity in mitral stenosis patients.

BACKGROUND: Left atrial (LA) dysfunction, expressed as impaired LA deformation using two-dimensional (2D) strain imaging, has been observed in association with rheumatic mitral stenosis (MS). However, the clinical role of speckle tracking echocardiography (STE)-derived LA strain has rarely been studied in MS. AIM: This study aimed to identify the determinants of New York Heart Association (NYHA) functional class in patients with mitral stenosis and to investigate the relationship between left atrial deformation as measured by two-dimensional STE-derived LA strain and heart failure symptoms. METHODS: Sixty-nine consecutive patients (20 males and 49 females; mean age: 61 ± 14 years) with rheumatic MS were evaluated using comprehensive 2D and color Doppler echocardiography including STE-derived LA strain (LAS) and peak positive filling strain rate (LASRr) during the LA reservoir phase. Those results were then correlated with NYHA functional class. RESULTS: There were 15 (22%) patients in functional class I, 42 (61%) in functional class II, and 12 (17%) in functional class III. There were no significant differences in mitral valve area, pressure gradient, pulmonary artery pressure, LA emptying fraction, or left ventricular ejection fraction between functional classes. Upon multivariate analysis (controlling for diuretics usage), LAS (ß = -0.233, P = .045) and LASRr (ß = -0.277, P = .014) were independent factors in determining NYHA functional class. CONCLUSIONS: In stable patients with MS, NYHA functional class independently correlated with LAS and LASRr. Left atrial (LA) deformation correlated with heart failure symptoms in patients with MS.

Cilostazol as an add-on therapy for patients with Alzheimer's disease in Taiwan: a case control study.

BACKGROUND: Combination therapy using acetylcholinesterase inhibitors (AChEIs) and cilostazol is of unknown efficacy for patients with Alzheimer's disease (AD). METHODS: We explored the therapeutic responses by using a case-control study, which was conducted in Taiwan. We enrolled 30 participants with stable AD who were receiving cilostazol (50 mg) twice per day as an add-on therapy combined with AChEIs, and 30 participants as controls who were not receiving cilostazol as an add-on therapy. The therapeutic responses were measured using neuropsychological assessments and analyzed in relation to cilostazol use, apolipoprotein E genotype, and demographic characteristics. Mini-mental state examination (MMSE) and clinical dementia rating sum of boxes (CDR-SB) were administered at the outset of the study and 12 months later. Multiple logistic regression analysis was used to estimate the association between the therapeutic response and cilostazol use. RESULTS: For the therapeutic indicator of cognition, Cilostazol use (adjusted odds ratio (aOR) = 0.17, 95% confidence interval (CI) = 0.03-0.80), initial CDR-SB score (aOR = 2.06, 95% CI = 1.31-3.72), and initial MMSE score (aOR = 1.41, 95% CI = 1.11-1.90), but not age, sex, education, or ApoE ε4 status, were significantly associated with poor therapeutic outcomes. For the therapeutic indicator of global status, no significant association was observed between the covariates and poor therapeutic outcomes. CONCLUSIONS: Cilostazol may reduce the decline of cognitive function in stable AD patients when applied as an add-on therapy.

Symptom severity of patients with advanced cancer in palliative care unit: longitudinal assessments of symptoms improvement.

BACKGROUND: This study assessed the symptom severity of patients with advanced cancer in a palliative care unit and explored the factors associated with symptom improvement. METHODS: This study was conducted in a palliative care unit in Taiwan between October 2004 and December 2009. Symptom intensity was measured by the "Symptom Reporting Form", and graded on a scale of 0 to 4 (0 = none, and 4 = extreme). These measures were assessed on the 1(st), 3(rd), 5(th), and 7(th) Day in the palliative care unit. The study data comprised routine clinical records and patients' demographic data. Generalized estimating equation (GEE) was used to assess the symptom improvement, and investigate the factors associated with the symptom reporting form scores. RESULTS: Among the 824 recruited patients with advanced cancer, pain (78.4%), anorexia (64.4%) and constipation (63.5%) were the most common and severe symptom. After controlling for other factors in the multivariate GEE model, the day of palliative care administration was a significant factor associated with all of the scales, except Days 7 on the dyspnoea and oedema scales and Day 5 on the anxiety scale. In addition, patients aged ≥ 65 years exhibited significantly lower scores on the pain, sleep disturbance, depression, and anxiety scales than did those aged < 65 years. Moreover, female patients exhibited higher scores on the vomiting, anorexia, oedema, depression, and anxiety scales than did male patients. Furthermore, patients with gastrointestinal tract cancer exhibited higher scores on the constipation, vomiting, anorexia, oedema, depression, and anxiety scales and lower scores on the dyspnoea scale than did those with lung cancer. Patients with breast cancer exhibited higher scores on the oedema scale and lower scores on the anxiety scale. Patients with genitourinary cancer exhibited higher scores on the vomiting and oedema scales and lower scores on the dyspnoea scale. Patients with head, neck, and oral cancer exhibited lower scores on the oedema scale alone. CONCLUSION: The symptom severity declined during the first week in the palliative care unit. In addition, differences in sex and primary cancer sites may contribute to varying degrees of symptom improvement.

Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population.

Perception of hearing impairment and the willingness to use hearing aids in an elderly population in southern Taiwan: A community-based study.

OBJECTIVES: To estimate the prevalence and severity of hearing impairment (HI), the self-perception of HI, and the willingness to use a hearing aid (HA) in the elderly population in southern Taiwan. DESIGN: This community-based study was performed in a metropolitan hospital. A questionnaire about the perception of HI and the willingness to use a HA was used. The severity of HI in speech-frequency pure-tone average (PTA) was evaluated. The associations between sex, age, severity of HI, self-perception of HI, and the willingness to use a HA were analysed. STUDY SAMPLE: A total of 599 volunteers were recruited from the health management center; 324 (54.1%) males and 275 (45.9%) females, who were 65 years of age or older. RESULTS: The prevalence of HI >25 dBHL in the elderly was 78%. The predicted levels for elderly persons to perceive HI and hearing difficulties were 34.38 dBHL and 54.38 dBHL, respectively. Males and younger participants were more willing to use HA. The primary reasons for refusing HA use were discomfort (25.1%) and a self-perception that the HA was unnecessary (19.7%). CONCLUSIONS: The prevalence of HI was high among the elderly population in southern Taiwan. Age and sex were the determinants of HA use.

Autophagy is deficient and inversely correlated with COX-2 expression in nasal polyps: a novel insight into the inflammation mechanism.

BACKGROUND: Nasal polyposis is characterised by persistent inflammation of the upper airways. Autophagy has been implicated in many chronic inflammatory diseases. Whether autophagy plays a role in nasal polyp (NP) inflammation is completely unknown and deserves investigation. METHODS: LC3 and COX-2 expression, the common autophagy and inflammation indicators, respectively, was analysed by immunoblotting in fresh tissues of NP and control nasal mucosa (NM). Primary cultures of NP-derived fibroblasts (NPDFs) and NMDFs were established for in vitro studies. Autophagy was induced by amino acid starvation and LC3 ectopic overexpression or inhibited by 3-methyladenine in the fibroblasts. Inflammation was induced by IL1-ß and TNF-α. LC3 and COX-2 expression was confirmed in NP specimens by immunohistochemistry. RESULTS: LC3 expression was decreased while COX-2 expression was significantly increased in fresh NP tissues compared with the NM control. In NMDFs and NPDFs, autophagy induction by starvation and LC3 overexpression downregulated COX-2 expression. Conversely, autophagy inhibition by 3-methyladenine enhanced COX-2 expression. However, IL1-ß and TNF-α had no effect on autophagy. Immunohistochemical studies on the NP specimens showed that most displayed low LC3 expression, whereas COX-2 was highly expressed in >50% of the specimens. Examination of two consecutive NP sections from the same tissue blocks revealed a negative correlation between LC3 and COX-2 expression. CONCLUSION: Autophagy is deficient in NP tissues and COX-2 is negatively regulated by autophagy in NP-derived fibroblasts. Since COX-2 is essential for the production of pro-inflammatory mediators, this study might help interpret persistent mucosal inflammation in NP. Attenuation of inflammation by restoring autophagy might be a therapeutic strategy for treating NP.

Endoscopic atticotomy for attic cholesteatomas using piezosurgery.

BACKGROUND: Attic cholesteatomas can be exenterated by transcanal endoscopic ear surgery (TEES). In the limited operative field of exclusive transcanal endoscopic atticotomy, surgeons use either a piezosurgery scalpel or a drilling system to remove the posterior lateral bony wall of the epitympanum. We aimed to investigate the feasibility of using piezosurgery or microdrill for endoscopic atticotomy during exenteration of attic cholesteatomas. METHODS: This study is a retrospective chart review of patients diagnosed with attic cholesteatoma, who were treated by exclusive TEES. The superior and posterior external auditory canal bones were excised using a piezosurgery scalpel or microdrill. Preoperative and postoperative hearing thresholds were measured by pure-tone audiometry. RESULTS: The postoperative follow-up duration varied from 6 to 37 months. There were no significant differences in age, sex, laterality of the affected ear, and preoperative bone conduction thresholds between the piezosurgery scalpel and microdrill groups. The operative duration was longer in the piezosurgery group than in the microdrill group (135.6 ± 19.5 minutes vs 117.3 ± 29.1 minutes, p = 0.042). Seven of 30 (23.3%) patients in the microdrill group, but none in the piezosurgery group, had a friction injury from the drilling. Postoperative testing at higher frequencies of 2000, 3000, and 4000 Hz showed no deterioration in the bone conduction threshold in the piezosurgery group. CONCLUSION: Endoscopic atticotomy performed using a piezosurgery scalpel is potentially safer but slower than using a microdrill for exenteration of attic cholesteatomas.

Predictive Factors and Audiometric Outcome Comparison Between Titanium Prosthesis and Autologous Incus in Traumatic Ossicular Injury.

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.

Prognosis Prediction of Sudden Sensorineural Hearing Loss Using Ensemble Artificial Intelligence Learning Models.

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.

Normal Weight Central Obesity is a Poor Prognostic Factor for Sudden Sensorineural Hearing Loss.

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/m2) and overweight and obese groups (BMI ≥ 24 kg/m2) 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.

Upregulation of phosphorylated HSP27, PRDX2, GRP75, GRP78 and GRP94 in acquired middle ear cholesteatoma growth.

Cholesteatoma is a destructive and expanding growth of keratinizing squamous epithelium in the middle ear or petrous apex. The molecular and cellular processes of the pathogenesis of acquired middle ear cholesteatoma have not been fully understood. In this study, comparative proteomic analysis was conducted to investigate the roles of specific proteins in the pathways regarding keratinocyte proliferation in cholesteatoma. The differential proteins were detected by comparing the two-dimension electrophoresis (2-DE) maps of the epithelial tissues of 12 attic cholesteatomas with those of retroauricular skins. There were 14 upregulated proteins in the epithelial tissues of cholesteatoma in comparison with retroauricular skin. The modulation of five crucial proteins, HSP27, PRDX2, GRP75, GRP78 and GRP94, was further determined by RT-PCR, Western blot and immunohistochemistry. Phosphorylation of HSP27 at Ser-82 was identified by mass spectroscopy. The results of this study suggested that phosphorylated HSP27 is the end expression of two potential signal-transduction pathways, and together with PRDX2, they are very likely involved in the proliferation of keratinocytes in cholesteatoma. Upregulations of GRP75, GRP78 and GRP94 in keratinocytes may be able to counter endoplasmic reticulum stress, to inhibit cell apoptosis, to prevent protein unfolding and to promote cholesteatoma growth.

Glucocorticoid receptor (NR3C1) genetic polymorphisms and the outcomes of sudden sensorineural hearing loss.

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.

Growth Regulated Oncogene-α Upregulates TNF-α and COX-2 and Activates NOD1/RIPK2 mediated-MAPK Pathway in Head and Neck Squamous Cell Carcinoma.

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.

The differential impact of Type D personality on the prognosis of patients with stable coronary artery disease.

OBJECTIVE: This study investigated the association between Type D personality and prognoses in stable coronary artery disease (CAD) patients by mode of endpoints, age, and methodological debates to explain substantial heterogeneity among Type D studies. DESIGN: The prospective study was designed to recruit 590 stable CAD patients in Taiwan. Main outcome measures: Demographic and clinical characteristics, and the 14-item Type D scale-Taiwanese version were recorded at discharge. RESULTS: Hierarchical logistic regression analyses showed, regardless of the methodological debates, Type D personality was significantly associated with MACEs though not non-cardiac outcomes in stable CAD patients after adjusting for possible confounders. Furthermore, Type D personality was especially associated with MACEs in stable CAD patients with younger age (<65 y), rather than older age (≥65 y). Subgroup analysis also showed the adverse effect of Type D personality on MACEs was larger among males, those living in the rural region, those with PTCA or stent, those with heart failure, hypertension, diabetes, and those who were smokers. CONCLUSIONS: Regardless of whether the methodological debate is dichotomous or continuous, Type D personality was significantly associated with MACEs in stable CAD patients, some of whom had younger age, were males, smokers, or had comorbidities.

Downregulation of Calreticulin and Annexin A2 Expression in Acquired Middle Ear Cholesteatoma by 2-DE Analysis.

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.

Heat shock protein 70 gene polymorphisms in sudden sensorineural hearing loss.

BACKGROUND: Heat shock proteins protect cells and tissues against different types of damage. Previous studies have revealed that the serum level of heat shock protein 70 (HSP70) increases in sudden sensorineural hearing loss (SSNHL) patients. We hypothesized that genetic variants of the HSP70 gene are associated with susceptibility to SSNHL. METHODS: We conducted a case-control study with 160 SSNHL cases and 178 controls. Three tagging single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. A haplotype analysis was also performed. RESULTS: All three SNPs were in Hardy-Weinberg equilibrium. The CT genotype of rs2075800 exhibited an adjusted odds ratio of 0.59 (95% confidence interval 0.37-0.94; p = 0.027). The T allele of SNP rs2075800 was associated with SSNHL under the dominant model (p = 0.019; odds ratio 0.59). Haplotype analysis of the three SNPs demonstrated that the haplotype TGC (rs2075800/rs1043618/rs2763979) was statistically significant (p = 0.0137). CONCLUSIONS: These results suggest that HSP70 gene polymorphisms influence the susceptibility to the development of SSNHL in the Taiwanese population.

Cochlear Implantation Hearing Outcome in Ménière's Disease.

OBJECTIVE: The aim of this study was to evaluate the hearing outcome of cochlear implantation in patients deafened by Ménière's disease. STUDY DESIGN: Retrospective single-institution study. SETTING: Tertiary medical center. METHODS: Our institutional database of 1400 patients with cochlear implants was reviewed to identify cases with deafness due to Ménière's disease. Twenty-nine patients were identified: 24 with unilateral and 5 with sequential bilateral cochlear implants. Pre- and postoperative speech recognition scores and medical data were extracted from the medical record and analyzed. RESULTS: Overall the mean difference between pre- and postoperative speech recognition after >1 year was 56% (95% CI, 47.08%-64.92%). The mean preoperative monosyllabic word score was 9.5%, and the mean postoperative scores at 1 month, 3 months, 6 months, 1 year, and >1 year were 37.1%, 46.1%, 54.1%, 59.1%, and 66.8%, respectively. Cochlear implantation resulted in improved word scores in all patients regardless of prior medical or surgical treatment (endolymphatic sac, labyrinthectomy). The mean postoperative hearing improvement in patients aged <70 and ≥70 years was 65.26% (95% CI, 54.79%-75.73%) and 40.00% (95% CI, 27.22%-52.77%). Postoperative word scores in patients with bilateral cochlear implants were not significantly different between the first and second implanted ears or between the monoaural and binaural testing conditions. CONCLUSION: Cochlear implant in patients deafened by Ménière's disease significantly improves word recognition scores regardless of whether medical or surgical treatment is used prior to implantation. The potential improvement in word recognition scores decreases after age 70 years.