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Background Chronic rhinosinusitis affects approximately 5%-2% of the general population worldwide. Steroid implants after endoscopic sinus surgery (ESS) have drawn considerable interest for their cost savings, but relevant guidelines indicate that evidence on this topic is of low quality with high heterogeneity. The purpose of this study was to examine the efficacy of steroid implants after ESS by synthesizing relevant randomized controlled trials (RCTs). Methods Two authors independently assessed the eligibility of potential references from five biomedical databases. They further extracted relevant data from the included studies, including (a) mean, standard deviation, or standard error for Lund-Kennedy endoscopic (LKE) score and Perioperative Sinus Endoscopy (POSE) score and (b) events and sample sizes of each group for further intervention. Data were pooled in a random-effects model, and results were presented as the weighted mean difference (WMD) or risk ratio (RR) with 95% confidence interval (CI) and I2 . Results Eleven RCTs (n = 853) were included and showed that the steroid implant group had lower LKE scores (WMD, -1.19; 95% CI, -1.75 to -0.62; I2 = 0%) and POSE scores (WMD, -1.62; 95% CI, -2.47 to -0.76; I2 = 48%) than the placebo implant group at postoperative week 2. Moreover, the reoperation rate in the steroid implant group was also lower than in the placebo implant group (RR, 0.49; 95% CI, 0.30 to 0.80; I2 = 0%). However, no significant difference was observed in the postoperative oral steroid requirement between both groups. Conclusions Collectively, steroid implant decreases LKE and POSE among patients receiving ESS in the short term, but long-term effects remain unclear. Patient-based outcomes are worth further discussion in the future.

Introduction: Packing of the nasal cavity has traditionally been used for postoperative bleeding control and decreasing synechia formation in patients undergoing nasal surgeries. Although absorbable nasal packing has been gaining popularity in the recent years, nonabsorbable nasal packing is still often used in nasal surgeries in various parts of the world. It is known to be associated with pain and discomfort especially upon and during removal, and previous reviews have only evaluated the effects of local anesthetic infiltration of nasal packing in septal surgeries. Objective: To evaluate the effect of infiltrating nasal packing with local anesthetics in postoperative pain and anxiety following sinonasal surgeries Materials and methods: We searched the PubMed and Embase databases from their earliest record to April 27, 2019, randomized controlled trials and prospective controlled trials for review, and included only randomized controlled trials for data analysis. We included studies using topical anesthetics-infiltrated nasal packing following sinonasal surgeries and evaluated the effectiveness compared to placebo packing in pain reduction during postoperative follow up, as well as the effectiveness in anxiety reduction. Results: Among 15 studies included for review, 9 studies involving 765 participants contributed to the meta-analysis. In terms of pain reduction, our analysis showed significant standard mean differences regarding effectiveness at postoperative 1, 12, 24 h interval for all surgical groups combined, in the sinus surgery group, as well as during nasal packing removal. There was no consistent evidence to support the effectiveness in anxiety reduction. Conclusions: Our study supports anesthetics infiltration of nasal packing as an effective method in managing pain in patients with nasal packing after sinonasal surgeries. However, the level of evidence is low. More high-quality randomized controlled trials are needed to establish its effectiveness in reducing anxiety. We believe this review is of great clinical significance due to the vast patient population undergoing sinonasal surgeries. Postoperative local hemorrhage remains the greatest concern for ear nose and throat surgeons due to the rich vasculature of the nose and sinuses. Sinonasal packing provides structural support and serves as an important measure for hemostasis and synechia formation. Although absorbable packing has been gaining popularity in the recent years, nonabsorable packing materials are still used in many countries due to lower cost. Infiltration of nasal packing with local anesthetic provides a solution to the discomfort, nasal pressure and nasal pain experienced commonly by the patients as evidenced by our analysis. Resumo Introdução: O tamponamento da cavidade nasal tem sido usado tradicionalmente para controle do sangramento pós-operatório e diminuição da formação de sinéquia em pacientes submetidos a cirurgias nasais. Embora o tamponamento nasal absorvível tenha ganhado popularidade nos últimos anos, o tampão nasal não absorvível ainda é frequentemente usado em várias partes do mundo. Sabe-se que o tamponamento está associado a dor e desconforto, especialmente na sua remoção, e revisões anteriores avaliaram apenas os efeitos do tampão com anestésico local em cirurgias do septo nasal. Objetivo: Avaliar o efeito do tamponamento nasal infiltrado com anestésicos locais na dor e ansiedade pós-operatórias após cirurgias nasosinusais. Material e métodos: Para a revisão, pesquisamos nos bancos de dados PubMed e Embase desde o registro mais antigo até 27 de abril de 2019, incluímos ensaios clínicos controlados e randomizados, a ensaios clínicos prospectivos controlados e apenas ensaios clínicos controlados e randomizados para análise de dados. Incluímos estudos que usaram tamponamento nasal infiltrado com anestésicos tópicos após cirurgias nasosinusais e avaliamos a eficácia em comparação com o tamponamento com placebo na redução da dor durante o acompanhamento pós-operatório, bem como os efeitos na redução da ansiedade. Resultados: Entre os 15 estudos incluídos, 9, que envolveram 765 participantes, contribuíram para a metanálise. Em termos de redução da dor, nossa análise mostrou diferenças médias padrão significantes em relação à eficácia no pós-operatório nos intervalos de 1, 12, 24 horas para todos os grupos cirúrgicos combinados, no grupo da cirurgia sinusal e durante a remoção do tamponamento nasal. Não houve evidências consistentes para apoiar a eficácia na redução da ansiedade. Conclusões: Nosso estudo apoia o uso de tamponamentos nasais infiltrados com anestésicos locais como um método eficaz no tratamento da dor em pacientes após cirurgias nasosinusais. No entanto, o nível de evidência é baixo. São necessários mais ensaios clínicos randomizados de alta qualidade para estabelecer sua eficácia na redução da ansiedade. Acreditamos que esta revisão seja de grande significado clínico devido à vasta população submetida a cirurgias nasosinusais. A hemorragia local pós-operatória continua a ser a maior preocupação para os cirurgiões otorrinolaringológicos devido à rica vasculatura do nariz e seios nasais. O tamponamento nasosinusal fornece suporte estrutural e serve como uma medida importante para a hemostasia e formação de sinéquias. Embora o tamponamento absorvível tenha ganhado popularidade nos últimos anos, os materiais de tamponamento não absorvíveis ainda são usados em muitos países devido ao menor custo. A infiltração do tamponamento nasal com anestésicos locais fornece uma solução para desconforto, pressão e dor nasal comumente referida pelos pacientes, como evidenciado por nossa análise.

Background Health care systems and physicians need to conform to budgets and streamline resources to provide cost-effective quality care. Although endoscopic tympanoplasty (ET) has been performed for decades, no studies on the cost-effectiveness of ET and microscopic tympanoplasty (MT) for treating chronic otitis media have been published. The present study aimed to compare the cost-effectiveness of ET and MT for treating chronic otitis media. Methods This study was performed using a Cohort-style Markov decision-tree economic model with a 30-year time horizon. The economic perspective was that of a third-party payer (Taiwan National Health Insurance System). Two treatment strategies were compared, namely ET and MT. The primary outcome was the incremental cost per quality-adjusted life year (QALY). Probabilities were obtained from meta-analyses. Costs were obtained from the published literature and Taiwan National Health Insurance System database. Multiple sensitivity analyses were performed to account for data uncertainty. Results The reference case revealed that the total cost of ET was $NT 20,901 for 17.08 QALY per patient. By contrast, the total cost of MT was $NT 21,171 for 17.15 QALY per patient. The incremental cost effectiveness ratio for ET versus that of MT was $NT 3703 per QALY. The cost-effectiveness acceptability curve indicated that ET was comparable to MT at a willingness-to-pay threshold of larger than $NT 35,000 per QALY. Conclusion This cost-effectiveness analysis indicates that ET is comparable to MT for treating chronic otitis media in Taiwan. This result provides the latest information for physicians, the government, and third-party payers to select proper clinical practice.

Objective The tympanomeatal flap elevation technique has been used in tympanoplasty for decades; however, this procedure has disadvantages. In recent years, endoscopic transcanal myringoplasty (ETM) has been increasingly practiced and has yielded positive results.This study compares the efficacy of ETM and endoscopic type I tympanoplasty (ETT) in repairing medium-sized perforations of the tympanic membrane. Methods This retrospective medical record review included patients undergoing surgery for medium-sized perforations of the tympanic membrane from January 1, 2013 to August 1, 2015. We divided our patients into 2 groups: the ETM group and ETT group. The main outcome measure was comparison of the graft take rates and hearing results between ETM and ETT. Results A total of 113 patients were enrolled in this study; of these patients, 64 underwent ETM and 49 received ETT. The overall graft take rates and improvement of air–bone gaps were comparable between the groups. However, the patients in the ETM group had shorter operative times and fewer follow-up visits over 3 months than those in the ETT group did. Conclusion We recommend that ETM (instead of ETT) be used for repairing medium-sized perforations of the tympanic membrane.

Background: The learning curve for endoscopic tympanoplasty has never been quantitatively reported. The present study depicted the learning curve for endoscopic tympanoplasty and evaluated how many procedures an otologist requires to attain proficiency in this technique. Methods: We reviewed the medical charts of consecutive patients who underwent endoscopic tympanoplasty between January 1, 2013 and June 1, 2015. We enrolled patients with simple perforations of the tympanic membrane and excluded those with ossicular chain disease. The main outcome was learning curves for endoscopic tympanoplasty, which illustrated changes in the mean operative time and graft success rate according to the patient numbers. We subsequently estimated and verified the threshold value using statistical methods. Results: A total of 221 procedures were included. For the learning curve of the mean operative time, the time gradually decreased from 75 minutes to 55 minutes. After the 150th patient, the mean operative time stabilized to < 60 minutes. For the learning curve of the graft success rate, the rate sharply increased from 75% to 95%. After the 50th patient, the graft success rate reached a plateau and fluctuated between 85% and 100%. We subsequently verified that the 50th and 150th patients were appropriate threshold values. Moreover, the graft success rate of perforations < 50% was significantly higher than that of perforations > 50%. Conclusion: These curves illustrate significant progress of the surgeon during the first 50 patients, considering the graft success rate, reaching an advanced level after the 150th patient, considering the mean operating time.

We examined the overall survival rates of a national cohort to determine optimal treatments and prognostic factors for patients with metachronous second primary head and neck squamous cell carcinomas (mspHNSCCs) at different stages and sites. We analyzed data of mspHNSCC patients collected from the Taiwan Cancer Registry database. The patients were categorized into four groups based on the treatment modality: Group 1 (control arm; chemotherapy [CT] alone), Group 2 (reirradiation [re‐RT] alone with intensity‐modulated radiotherapy [IMRT]), Group 3 (concurrent chemoradiotherapy alone [irradiation with IMRT]), and Group 4 (salvage surgery with or without RT or CT). We enrolled 1741 mspHNSCC patients without distant metastasis. Multivariate Cox regression analyses revealed that Charlson comorbidity index (CCI) ≥6, stage of second HNSCC, stage of first HNSCC, and duration from first primary HNSCC of

Objectives Microscopic tympanoplasty has been the standard surgery for repairing perforated tympanic membranes since the 1950s, but endoscopic tympanoplasty has been increasingly practiced since the late 1990s. In this study, we compared the efficacies of endoscopic and microscopic tympanoplasty. Data Sources PubMed, Embase, MEDLINE, and the Clinical Trial Register. Review Methods We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We included clinical studies that compared the efficacies of endoscopic and microscopic tympanoplasty. We assessed the risk of bias and calculated the pooled relative risk (RR) estimates with 95% confidence interval (CI). Results We identified four studies (involving 266 patients in total) that met the inclusion criteria. The pooled tympanic membrane closure rates and hearing results of endoscopic and microscopic tympanoplasty were comparable (85.1% vs. 86.4%, respectively; RR: 0.98; 95% CI: 0.85 to 1.11; I2 = 0) (mean difference of improvements of air-bone gaps: −2.73; 95% CI: −6.73 to 1.28; I2 = 80%). The pooled canalplasty rate of endoscopic tympanoplasty was significantly lower than that of microscopic tympanoplasty. Patients receiving endoscopic tympanoplasty had a more desirable cosmetic result than did those receiving microscopic tympanoplasty. Conclusions Our up-to-date review evidences the comparable tympanic membrane closure rates and hearing results for endoscopic and microscopic tympanoplasty. Patients receiving endoscopic tympanoplasty have a lower canalplasty rate and more desirable cosmetic result than do those receiving microscopic tympanoplasty. Laryngoscope, 127:1890–1896, 2017

Objective Endoscopic transcanal myringoplasty (ETM) has been an emerging technique for repairing tympanic perforations since the late 1990s. Objective outcomes (ie, graft success rates and hearing results) of patients who received ETM are well documented; however, subjective outcomes of these patients have rarely been reported. Hence, this study evaluated subjective and objective outcomes of patients who received ETM for repairing tympanic perforations. Study Design Prospective study. Setting Tertiary care university hospital. Patients and Methods Patients who underwent ETM for perforations of the tympanic membrane were included. We evaluated subjective variables of patients receiving ETM as the primary outcome and objective variables as the secondary outcome. Results In total, 91 ears that underwent ETM were included. The mean pain scale score was 0.1 (range, 0-2) on postoperative day 3. The mean duration of pain medication was 2.0 (range, 0-3) days. The mean number of days required to resume routine activities was 1.0 (range, 1-2) days. The overall graft success was determined postoperatively at 3 months in 80 of 91 ears (87.9%). Closure of the air-bone gap to within 20 dB was achieved in 79 (86.8%) ears. Conclusion In this study, patients who received ETM had mild postoperative pain and resumed routine activities early. These patients also exhibited favorable graft success rates and hearing results at 3 months postoperatively. On the basis of our results, we conclude that patients who receive ETM for the repair of tympanic perforations have favorable short-term subjective and objective outcomes.

Since the 1950s, microscopic myringoplasty has been the standard surgery for repairing a perforated tympanic membrane. In addition to conventional microscopic myringoplasty, endoscopic myringoplasty has been an emerging technique since the late 1990s. This study evaluated the efficacy of endoscopic transcanal myringoplasty for repairing tympanic perforations and examined the minimally invasive feature of this technique (no postauricular incision, no canalplasty).We retrospectively reviewed the medical records of patients who underwent endoscopic transcanal myringoplasty for perforations of the tympanic membrane. The main outcome was the overall rate of graft success of endoscopic transcanal myringoplasty.A total of 181 patients were included in the analysis. The overall graft success was determined in 163 of 181 patients (92.8%). The mean preoperative and postoperative air-bone gaps were 19.3dB and 7.8dB, respectively, revealing a significant improvement of 11.5dB (Cohen's d, 1.27; 95% CI, 1.03-1.50; P0.05; paired t test) in the air-bone gap. The rate of graft success with partial visualization of the perforation margin was comparable to that with complete visualization of the perforation margin. Larger sizes of perforations were significantly associated with lower rates of graft success (P0.01).Our study revealed that the rate of graft success and hearing results of endoscopic transcanal myringoplasty and microscopic myringoplasty are comparable for repairing perforations of the tympanic membrane. Visualization of the perforation margin by otoscopy did not affect the rate of graft success. However, endoscopic transcanal myringoplasty is less invasive because this technique does not require postauricular incision, canalplasty, and general anesthesia.

Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and β-catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells. The Wnt signaling transducers such as β-catenin and TCF-4 were decreased in honokiol-treated SP cells, while the β-catenin degradation promoting kinase GSK-3α/β was increased. Consistently, the protein levels of β-catenin downstream targets such as c-Myc and Cyclin D1 were also downregulated. Furthermore, the β-catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT.

Honokiol, an active compound ofMagnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such asABCG2,ABCC5,EpCAM,OCT-4,CD133,CD44, andβ-catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells. The Wnt signaling transducers such asβ-catenin and TCF-4 were decreased in honokiol-treated SP cells, while theβ-catenin degradation promoting kinase GSK-3α/βwas increased. Consistently, the protein levels ofβ-catenin downstream targets such asc-MycandCyclin D1were also downregulated. Furthermore, theβ-catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT.

Repairing anterior perforations of the tympanic membrane has been challenging for otolaryngologists. Therefore, devising a simple and effective technique for performing the repair is crucial.To assess the results of endoscopic transcanal myringoplasty for repairing anterior perforations of the tympanic membrane.This medical record review included 59 patients who underwent endoscopic transcanal myringoplasty from January 1, 2013, to June 1, 2015, at PoJen General Hospital, Taipei, Taiwan. Patients with ossicular chain disease and cholesteatoma or inadequate follow-up were excluded. Patients were followed up for 6 months, and final follow-up was completed on January 1, 2016.The main outcome was the rate of overall graft success after endoscopic transcanal myringoplasty. Secondary outcomes included hearing results and prognostic factors.The study sample included the medical records of 59 patients (30 men [51%]; 29 women [49%]; mean [SD] age, 49.5 [13.1] years) who underwent endoscopic transcanal myringoplasty. Overall, 55 patients (93%) had a successful graft at 6 postoperative months. The mean (SD) preoperative and postoperative air-bone gaps were 15.9 (9.4) and 5.4 (7.0) dB, respectively, revealing a significant mean (SD) improvement of 10.3 (7.6) dB (Cohen d, 1.27; 95% CI, 0.90-1.63; P .001, paired t test) in the gap. The postoperative air-bone gap in 46 patients (78%) was less than 10 dB; in 12 patients (20%), 10 to 20 dB; and in 1 patient (2%), more than 20 dB. Postoperative otorrhea significantly affected the graft success rate (odds ratio, 52.00; 95% CI, 4.08-662.55; P .01, χ2 test). The visualization of the perforation margin (complete or partial) was not significantly associated with the graft success rate. However, partial visualization of the perforation margin significantly prolonged the mean (SD) operative time (complete vs partial, 59.2 [13.7] vs 68.1 [14.1] minutes; Cohen d, 0.64; 95% CI, 0.12-1.18; P = .02, t test).The rate of graft success and hearing outcomes for endoscopic transcanal myringoplasty are comparable with those of microscopic myringoplasty for repairing anterior perforations of the tympanic membrane. However, the present technique is simpler because postauricular incision, canalplasty, and general anesthesia are not required. Thus, endoscopic transcanal myringoplasty should be considered for repairing anterior perforations of the tympanic membrane.

Supplemental Digital Content is available in the text, For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival. Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0–148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments). We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31–0.35), 0.34 (0.31–0.36), and 0.37 (0.28–0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82–1.55), 0.67 (0.62–0.73), and 0.49 (0.46–0.53) for CCI scores of ≥10, 5 to 9, and

The aim of the present study was to report a rare case of single-clone, immunoglobulin heavy chain (IgH)-rearranged mucosa-associated lymphoid tissue (MALT) lymphoma in the conjunctiva, with nasal cavity dissemination through the nasolacrimal duct. A 24-year-old female was diagnosed with MALT lymphoma of the nasal cavity at the Department of Otolaryngology, Wan Fang Medical Center, Taipei Medical University (Tapei, Taiwan) in October 2008. A biopsy of the relapsing conjunctival lesion revealed a MALT lymphoma by pathological staining, while a single-clone, IgH-rearranged tumor lesion in the nasal cavity and conjunctiva was confirmed using continuous sinus computed tomography scans and polymerase chain reaction. Tumor lesions were negative for Helicobacter pylori and Chlamydia infection, but exhibited bilateral neck lymph node dissemination. A combination of radiation therapy (a total dosage of 46.8 Gray, in two phases covering the left lacrimal sac, nasal cavity and bilateral neck region) and topical ciprofloxacin plus steroid (0.3% ciprofloxacin 4 times a day and betamethasone eye ointment before sleep for 1 month) was provided as an effective therapeutic strategy, and no recurrence was found in the next 3 years. The nasolacrimal duct serves as a channel for conjunctival tumor spreading and is easily neglected. IgH-involved translocation in MALT lymphoma is a factor in the progression of the disease, and aggressive combination therapy is essential for a high-risk, disseminated IgH-rearranged MALT lymphoma.

Microtia is characterized as an incomplete auricular development and surgical reconstruction for microtia is still limited even with emerging developments. This study aimed to apply bionanomaterials (PRP/collagen scaffold) for human auricular neocartilage reconstruction by using microtia chondrocytes. The results showed that PRP (TGF-β1 750 pg/mL and 1 ng/mL) increased cell viability of microtia chondrocytes during in vitro 9-day cultures. Additionally, chondrogenic-specific mRNA of Aggrecan and type II collagen (Col II) was significantly and continuously expressed with PRP treatment during the 21-day in vitro expansion. Tissue engineering of auricular neocartilage was performed by seeding microtia chondrocytes in bionanomaterials (PRP/collagen scaffold) 3-dimensional (3D) cultures. Immunohistochemistry (IHC) of Col II showed intensive signals between cells and matrix after 4-week cultures. Conclusion. Our results demonstrated that PRP promotes proliferation and redifferentiation of microtia chondrocytes and provides regenerative potentials in auricular neocartilage reconstruction.

The immunohistochemical method and electron spin resonance (ESR) spin trapping assay were employed to detect the localization and biochemical activity of superoxide dismutases (SODs) in the rat nasal mucosa. Manganese SOD and copper-zinc SOD were immunohistochemically illustrated to be richly expressed in the epithelial cells and the subepithelial glands of nasal mucosa. The olfactory vesicles also showed positive immunostaining for manganese SOD and copper-zinc SOD. ESR spin trapping assay revealed that SOD activity in the mucosa of olfactory areas was significantly higher than in the mucosa of respiratory areas; however, the ratio of SOD activity in the mitochondrial fraction to SOD activity in the cytosolic fraction was similar, approximating 17:83 in the mucosa of both the olfactory and respiratory areas. The predominant localization of SODs in epithelial cells of nasal mucosa suggests the importance of mucosal epithelium in protecting nasal mucosa against cytotoxic superoxide (O2-) radicals. Epithelial goblet cells and the connective tissue of lamina propria, which showed no positive immunostaining for SODs, are considered to be vulnerable to oxidative insults implicated in the generation of O2- radicals. The higher SODs activity in the mucosa of olfactory areas implies that there is a different requirement of SOD in mucosa of the respiratory and olfactory areas on scavenging microenvironmental O2- radicals.

A modified immunoglobulin peroxidase bridge sequence method was used to detect the localization of manganese superoxide dismutase (MnSOD), a superoxide radical (O2−) scavenging enzyme locating in mitochondrial matrix, in the vestibular labyrinth of pigmented rats. Strong positive MnSOD immunostaining was demonstrated in the dark cell regions of the ampullae, utricle, and common crus. The result provides for the first time direct evidence demonstrating the existence of mitochondrial O2−scavengers in the vestibular labyrinth and illustrates that the specific sites for vestibular MnSOD immunolocalization are the dark cell regions. This site specificity of MnSOD immunolocalization suggests that dark cell regions may possess high metabolic activity and may encounter constant threat from O2−. We assume MnSOD is needed in protecting some physiologic functions of the dark cell regions. Cell types showing negative MnSOD immunostaining may conceivably be relatively vulnerable to acute O2−damage.

Background and Objective: Local persistent infection by Porphyromonas gingivalis leads to inflammatory systemic diseases, such as atherosclerosis. We have reported previously that avirulent P. gingivalis fimbriae-dependent invasion into endothelial cells might be involved in progression of atherosclerosis. Although interleukin-6 (IL-6) regulates progression of atherosclerosis, little is known about the relationship of P. gingivalis fimbriae-dependent invasion to IL-6 regulation in endothelial cells. Material and Methods: We examined the secretion of IL-6 and the expression of the IL-6 signal transducer gp130 in human umbilical vein endothelial cells (HUVEC) infected with the wild-type FDC381 strain of P. gingivalisand a fimbriae-deficient mutant (fimA) by enzyme-linked immunosorbent assay, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry (fluorescence-activated cell sorting, FACS) analysis. Results: Coculture of HUVEC with P. gingivalis resulted in increase of IL-6 secretion at 24 h postinfection. Interestingly, the increase was inhibited significantly in HUVEC infected with the P. gingivalis fimA mutant. In addition, the increase of IL-6 secretion induced by P. gingivalis infection was significantly impaired by the meiosis specific kinase 1 inhibitor, PD98059, or the nuclear factor κB inhibitor, Bay11-7082. Furthermore, we demonstrated that gp130 expression increased with P. gingivalis infection. Importantly, gp130 expression was significantly impaired by P gingivalis fimA mutant infection compared with wild-type P. gingivalis infection, as assessed by both quantitative RT-PCR and FACS analysis. Conclusion: Our findings indicate that P. gingivalis fimbriae are important factors in the autocrine regulation of IL-6, by increasing gp130 in endothelial cells.

Objective Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC)–based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration. Methods A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage-forming ability. Results Coculture of hPi-GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor β superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp-hMSCs acquired neocartilage-forming potential within the collagen scaffold. Conclusion These findings help define the molecular markers of chondrogenesis and more accurately delineate the stages of chondrogenesis during chondrocytic differentiation of human MSCs. The results indicate that human MSCs committed to the chondroprogenitor stage of chondrocytic differentiation undergo detailed chondrogenic changes. This model of in vitro chondrogenesis of human MSCs represents an advance in cell-based transplantation for future clinical use.

Supplemental Digital Content is available in the text, The use of induction chemotherapy (CT) is controversial. We compared the survival of head and neck cancer patients receiving docetaxel- or platinum-based induction CT before concomitant chemoradiotherapy (CCRT) with the survival of those receiving upfront CCRT alone. Data from the National Health Insurance and cancer registry databases in Taiwan were linked and analyzed. We enrolled patients who had head and neck cancer between January 1, 2002 and December 31, 2011. Follow-up was from the index date to December 31, 2013. We included head and neck patients diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0–148.9 who were aged >20 years, at American Joint Committee on Cancer clinical cancer stage III or IV, and receiving induction CT or platinum-based CCRT. The exclusion criteria were a cancer history before head and neck cancer diagnosis, distant metastasis, AJCC clinical cancer stage I or II, receipt of platinum and docetaxel before radiotherapy, an age 8 weeks before RT, induction CT alone before RT, cetuximab use, adjuvant CT within 90 days after RT completion, an RT dose

Supplemental Digital Content is available in the text, Patients with head and neck cancer are treated through surgery, radiotherapy (RT), and chemotherapy (CT). Carotid artery damage and neurotoxicity were previously observed in these patients. This study estimated the dementia risk associated with different treatment modalities in a head and neck cancer population with long-term follow-up. Taiwan's National Health Insurance claims database and a cancer registry database from the Collaboration Center of Health Information Application were linked for the present analysis. Patients with head and neck cancer, treated from January 1, 2002 to December 31, 2010, were included in the study. The follow-up duration was the period from the index date to December 31, 2012. Inclusion criteria were head and neck cancer; an age >20 years; and having undergone surgery, CT, concurrent CT, or surgery with adjuvant treatment. Exclusion criteria were another cancer diagnosed before the head and neck cancer, death or being diagnosed with dementia within 2 years after the treatment of the head and neck cancer, stroke before the index date, distant metastasis, in situ carcinoma, sarcoma, head and neck cancer recurrence, an unknown sex, and an age 65 years and having undergone RT with or without CT were risk factors (P 6660 cGy exhibited a 1.69-fold (95% CI 0.97–2.95, P = 0.063) higher dementia risk compared with those who received a total radiation dose

Chondrocytes are useful as a cell culture system for studying arthritic degeneration in tissue engineered cartilage. However, primary chondrocytes have short in vitro lifespan and rapid shift of collagen phenotype. In this study, we used a high dosage of retroviral vector LXSN16E6E7 to transduce human primary chondrocytes and obtained an actively proliferating cell line, designated hPi, which expresses HPV-16 E6/E7 mRNA in early passages. Parental primary chondrocytes cease to grow after five passages, whereas hPi could be propagated beyond 100 passages without requiring additional cell elements in defined medium. After 48 passages, hPi can also give many profiles similar to those of parental primary chondrocyte, including type II collagen in mRNA and protein level, aggrecan in mRNA level, lacunae in type I collagen matrices, and morphology with GAG-specific Alcian blue staining. hPi has shown neoplastic transformation, as examined by NOD-SCID mice tumorgenicity assays for 3 months. Our results indicated that human primary chondrocytes could be immortalized by transduction with HPV-16 E6/E7, preserving stable cartilage-specific differentiation markers. The established chondrocyte cell line could provide a novel model to engineer cartilage in vitro and in vivo for cartilage repair research and clinical application. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

There has been recent increasing interest in the involvement of superoxide radicals (O2-) and their scavenging enzymes, the superoxide dismutases, in the patho-physiology of certain diseases. Since mitochondria are significant intracellular sources of O2- and important targets of oxidant injury, determining the intracochlear localization of mitochondrial O2- scavenging enzyme may provide important insight into the pathogenesis of injury due to cochlear oxidants. In order to locate the mitochondrial O2- scavenging enzyme, manganese superoxide dismutase (MnSOD), the authors used a modified immunoglobulin peroxidase bridge sequence method to detect MnSOD in paraffin-embedded, formalin-fixed rat cochleas. Site-specific immunolocalization of MnSOD could be demonstrated in the cochlear labyrinth, suggesting that the generation of intracochlear O2- was possibly implicated in the metabolically active sites and sites rich in vascularity. This study also provided a useful probe for detecting MnSOD immunohistochemically from ethylenediamine tetra-acetic acid-treated materials without requiring an antigen retrieval procedure.

We present a case of superficial siderosis (SS) of the central nervous system (CNS) with an unruptured intracranial aneurysm to illustrate that the commonly encountered unexplainable progressive sensorineural hearing loss (SNHL) can be an important sign for the early awareness of this rare disorder. The literature on SS is reviewed and the pathogenesis of SS is discussed.