Relationship of Hearing Loss to Parkinson's Disease, Dementia, and APOE Genotype in Adults.

Background: Hearing loss has been recognized as a risk factor for dementia and non-motor features of Parkinson's disease (PD). The apolipoprotein E (APOE) protein contributes to maintenance and repair of neuronal cell membranes, causing age-related disorders. This study aimed to analyze the impact of hearing loss on cognitive impairment, PD severity, and APOE gene expression in these patients. Methods: A total of 72 out-patients diagnosed with either PD or hearing loss were enrolled in this study. The hearing assessment included pure-tone audiometry, speech reception thresholds, and speech discrimination ability. Dementia was assessed by filling out the Clinical Dementia Rating and Mini-Mental State Examination questionnaires. The severity of PD was assessed using the Modified Hoehn and Yahr scale. Blood samples were tested for the gene expression of APOE. Results: Out of the 72 cases, there were 44 males and 28 females, with an average age of 64.4 ± 9.1 years. A total of 41 out of 72 cases had dementia and had a worse hearing threshold than those without dementia (47.1 ± 24.4 vs. 31.7 ± 22.1 dB, p = 0.006). A total of 58 patients were diagnosed with PD, with 14 of them classified as having severe symptoms (Modified Hoehn and Yahr scale > 2). Patients with severe PD were found to have a worse hearing threshold (49.6 ± 28.3 vs. 30.3 ± 17.8 dB, p = 0.028) and higher prevalence of dementia (12/14 vs. 18/44, p = 0.006). Among 10 individuals with the APOE ε4 gene, the prevalence of dementia was higher than those without the ε4 allele (9/10 vs. 32/62, p = 0.036). Conclusions: Hearing loss is common in severe PD and in dementia patients. Severe PD has a negative impact on the hearing threshold and cognitive dysfunction. Patients with APOE ε4 have a higher prevalence of dementia.

Microencapsulation of ginger essential oil using mung bean protein isolate-chitosan complex coacervates: Application in the preservation of crab meatballs and the prediction of shelf life.

Crab meatballs with more unsaturated fat tend to spoil. Ginger essential oil (GEO) with oxidation resistance was encapsulated into microcapsules (GM) by complex cohesion of mung bean protein isolate (MBPI) and chitosan (CS) in a ratio of 8:1 at pH = 6.4, encapsulation efficiency (EE) and payload (PL) of GM (D50 = 26.16 ± 0.45 µm) with high thermal stability were 78.35 ± 1.02% and 55.43 ± 0.64%. GM (0.6%, w/w) did not interfere with the original flavor of crab meatballs, and lowered values of pH, thiobarbituric acid reactive substances (TBARS) and total bacteria counts (TBC) of the products than those spiked with GEO and the control. The prediction accuracy of the logistic first-order growth kinetic equation in line with TBC (2.84%) was better than that of zero-order and Arrhenius coupled equation based on pH (7.48%) and TBARS (5.94%), but all of them could predict the shelf life of crab meatballs containing GM stored at 4-25 °C.

Multi-scale adversarial learning with difficult region supervision learning models for primary tumor segmentation.

Objective.Recently, deep learning techniques have found extensive application in accurate and automated segmentation of tumor regions. However, owing to the variety of tumor shapes, complex types, and unpredictability of spatial distribution, tumor segmentation still faces major challenges. Taking cues from the deep supervision and adversarial learning, we have devised a cascade-based methodology incorporating multi-scale adversarial learning and difficult-region supervision learning in this study to tackle these challenges.Approach.Overall, the method adheres to a coarse-to-fine strategy, first roughly locating the target region, and then refining the target object with multi-stage cascaded binary segmentation which converts complex multi-class segmentation problems into multiple simpler binary segmentation problems. In addition, a multi-scale adversarial learning difficult supervised UNet (MSALDS-UNet) is proposed as our model for fine-segmentation, which applies multiple discriminators along the decoding path of the segmentation network to implement multi-scale adversarial learning, thereby enhancing the accuracy of network segmentation. Meanwhile, in MSALDS-UNet, we introduce a difficult region supervision loss to effectively utilize structural information for segmenting difficult-to-distinguish areas, such as blurry boundary areas.Main results.A thorough validation of three independent public databases (KiTS21, MSD's Brain and Pancreas datasets) shows that our model achieves satisfactory results for tumor segmentation in terms of key evaluation metrics including dice similarity coefficient, Jaccard similarity coefficient, and HD95.Significance.This paper introduces a cascade approach that combines multi-scale adversarial learning and difficult supervision to achieve precise tumor segmentation. It confirms that the combination can improve the segmentation performance, especially for small objects (our codes are publicly availabled onhttps://zhengshenhai.github.io/).

Association of Autonomic Symptom Burden with Sudden Sensorineural Hearing Loss.

OBJECTIVE: To investigate the autonomic symptom burden in patients with sudden sensorineural hearing loss (SSNHL) and its association with the severity and prognosis. STUDY DESIGN: Observational prospective study. SETTING: Tertiary academic medical center. METHODS: Patients diagnosed with SSNHL at a single medical center completed the COMPASS 31 questionnaire, which assesses dysautonomia across 6 domains with 31 questions. A total COMPASS 31 score was calculated by summing the scores from each weighted domain. The treatment outcome was evaluated by the percentage of recovery, calculated as the hearing gain in pure tone average (PTA) after treatment divided by the pretreatment PTA difference between the 2 ears. We defined poor recovery as a percentage of recovery <80%. RESULTS: A total of 63 SSNHL patients were included. The mean COMPASS 31 score was 23.4 (SD 14). Patients with poor recovery had significantly higher COMPASS 31 scores than those with good recovery (mean 26.4 [SD 14.4] vs 16.9 [SD 10.4]; 95% confidence interval [CI] 2-17). There was a negative association between COMPASS 31 score and both hearing gain (r = -.323, 95% CI -0.082 to -0.529) and percentage of recovery (r = -.365, 95% CI -0.129 to -0.562). Multivariate analyses of independent factors indicate that patients with higher COMPASS 31 scores had a greater risk for poor recovery (OR 1.06 [95% CI 1.003-1.117]). CONCLUSION: This study highlights the association between autonomic symptom burden and poor hearing outcomes in SSNHL patients. The findings underscore the importance of evaluating autonomic function during the treatment of SSNHL.

Altered expression of imprinted genes in patients with cytogenetically normal­acute myeloid leukemia: Implications for leukemogenesis and survival outcomes.

Genomic imprinting, an epigenetic mechanism that regulates gene expression from parental chromosomes, holds substantial relevance in multiple cancers, including hematopoietic malignancies. In the present study, the expression of a panel of 16 human imprinted genes in bone marrow samples from 64 patients newly diagnosed with cytogenetically normal-acute myeloid leukemia (CN-AML) were examined alongside peripheral blood samples from 85 healthy subjects. The validated findings of the present study revealed significant upregulation of seven genes [COPI coat complex subunit gamma 2 (COPG2), H19 imprinted maternally expressed transcript (H19), insulin like growth factor 2 (IGF2), PEG3 antisense RNA 1 (PEG3-AS1), DNA primase subunit 2 (PRIM2), solute carrier family 22 member 3 SLC22A3 and Zinc finger protein 215 (ZNF215)] in patients with CN-AML (P<0.001). Notably, the expression level of H19 exhibited an inverse association with the survival duration of the patients (P=0.018), establishing it as a predictive marker for two- and five-year survival in patients with CN-AML. Kaplan-Meier analysis demonstrated that patients with lower H19 expression had superior two- and five-year survival rates compared with those with higher H19 expression. The results of the present study highlighted the association between loss of imprinting and leukemogenesis in CN-AML, underscoring the significance of H19 imprinting loss as a prognostic indicator for unfavorable two- and five-year survival in CN-AML patients.

The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer.

PURPOSE: This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell carcinoma (LAOSCC). METHODS: Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction. RESULTS: There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI <97.8). In Cox models, low GNRI remained an independent negative prognosticator of OS (HR: 1.6; 95% CI: 1.124-2.277; p = 0.009) and CSS (HR: 1.907; 95% CI: 1.219-2.984; p = 0.005). The c-index of the proposed nomogram, incorporating assorted clinicopathological factors and GNRI, had a statistically significant increase compared with the predictive nomogram constructed by the TNM staging system alone (0.692 vs. 0.637, p < 0.001)." CONCLUSION: Preoperative GNRI is an independent prognostic factor of OS and CSS in patients with LAOSCC. A multivariate nomogram that includes GNRI may better help us to accurately estimate individual survival outcomes.

Lymph node ratio as a survival predictor for head and neck squamous cell carcinoma with multiple adverse pathological features.

BACKGROUND: The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features. METHODS: In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled. RESULTS: The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016). CONCLUSION: For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.

Surface Biofunctionalization of Gadolinium Phosphate Nanobunches for Boosting Osteogenesis/Chondrogenesis Differentiation.

In order to achieve smart biomedical micro/nanomaterials, promote interaction with biomolecules, improve osteogenic/chondrogenic differentiation, exhibit better dispersion in bone implants and ultimately maximize functionality, we innovatively and successfully designed and synthesized polymer PBLG-modified GdPO4·H2O nanobunches by hydroxylation, silylation and glutamylation processes. The effects of different feeding ratios on the surface coating of GdPO4·H2O with Si-OH, the grafting γ-aminopropyltriethoxysilane (APS) and the in situ ring-opening polymerization reaction of poly(g-benzyl-L-glutamate) (PBLG) were investigated, and the physical and chemical properties were characterized in detail. When GdPO4·H2O@SiO2-APS:NCA = 4:1, the PBLG-g-GdPO4·H2O grafting rate was 5.93%, with good stability and dispersion in degradable polymeric materials. However, the MRI imaging signal was sequentially weakened as the modification process proceeded. Despite this, the biological effects had surprising findings. All the modifiers at appropriate concentrations were biocompatible and biologically active and the biomacromolecules of COL I and COL II in particular were expressed at least 3 times higher in GdPO4·H2O@SiO2 compared to the PLGA. This indicates that the appropriate surface modification and functionalization of gadolinium-containing micro/nanomaterials can promote interaction with cells and encourage bone regeneration by regulating biomacromolecules and can be used in the field of biomedical materials.

Functional and Molecular Markers for Hearing Loss and Vertigo Attacks in Meniere's Disease.

Meniere's disease (MD) is one of the most complicated diseases in the otologic clinic. The complexity of MD is partially due to the multifactorial etiological mechanisms and the heterogenous symptoms, including episodic vertigo, hearing loss, aural fullness and tinnitus. As a result, the diagnosis of MD and differentiating MD from other diseases with similar symptoms, such as vestibular migraine (VM), is challenging. In addition, it is difficult to predict the progression of hearing loss and the frequency of vertigo attacks. Detailed studies have revealed that functional markers, such as pure tone audiometry (PTA), electrocochleography (ECochG), vestibular evoked myogenic potential (VEMP), caloric test, video head impulse test (vHIT) and magnetic resonance imaging (MRI) could help to evaluate MD with different hearing levels and frequency of vertigo attacks. Investigations of molecular markers such as autoimmunity, inflammation, protein signatures, vasopressin and circadian clock genes in MD are still underway. This review will summarize these functional and molecular markers, address how these markers are associated with hearing loss and vertigo attacks in MD, and analyze the results of the markers between MD and VM.

Solar-driven methanogenesis with ultrahigh selectivity by turning down H2 production at biotic-abiotic interface.

Integration of methanogens with semiconductors is an effective approach to sustainable solar-driven methanogenesis. However, the H2 production rate by semiconductors largely exceeds that of methanogen metabolism, resulting in abundant H2 as side product. Here, we report that binary metallic active sites (namely, NiCu alloys) are incorporated into the interface between CdS semiconductors and Methanosarcina barkeri. The self-assembled Methanosarcina barkeri-NiCu@CdS exhibits nearly 100% CH4 selectivity with a quantum yield of 12.41 ± 0.16% under light illumination, which not only exceeds the reported biotic-abiotic hybrid systems but also is superior to most photocatalytic systems. Further investigation reveal that the Ni-Cu-Cu hollow sites in NiCu alloys can directly supply hydrogen atoms and electrons through photocatalysis to the Methanosarcina barkeri for methanogenesis via both extracellular and intracellular hydrogen cycles, effectively turning down the H2 production. This work provides important insights into the biotic-abiotic hybrid interface, and offers an avenue for engineering the methanogenesis process.

Presume Why Probiotics May Not Provide Protection in Inflammatory Bowel Disease through an Azoxymethane and Dextran Sodium Sulfate Murine Model.

Recent studies have shown dysbiosis is associated with inflammatory bowel disease (IBD). However, trying to restore microbial diversity via fecal microbiota transplantation (FMT) or probiotic intervention fails to achieve clinical benefit in IBD patients. We performed a probiotic intervention on a simulated IBD murine model to clarify their relationship. IBD was simulated by the protocol of azoxymethane and dextran sodium sulfate (AOM/DSS) to set up a colitis and colitis-associated neoplasm model on BALB/c mice. A single probiotic intervention using Clostridium butyricum Miyairi (CBM) on AOM/DSS mice to clarify the role of probiotic in colitis, colitis-associated neoplasm, gut microbiota, and immune cytokines was performed. We found dysbiosis occurred in AOM/DSS mice. The CBM intervention on AOM/DSS mice failed to improve colitis and colitis-associated neoplasms but changed microbial composition and unexpectedly increased expression of proinflammatory IL-17A in rectal tissue. We hypothesized that the probiotic intervention caused dysbiosis. To clarify the result, we performed inverse FMT using feces from AOM/DSS mice to normal recipients to validate the pathogenic effect of dysbiosis from AOM/DSS mice and found mice on inverse FMT did develop colitis and colon neoplasms. We presumed the probiotic intervention to some extent caused dysbiosis as inverse FMT. The role of probiotics in IBD requires further elucidation.

Expression of circadian clock genes in leukocytes of patients with Meniere's disease.

Objectives: The underlying etiology of Meniere's disease (MD) is not completely clear, but the precipitated triggers may alter the circadian clock in patients with MD. This study aims to survey the expression of circadian clock genes in peripheral blood (PB) leukocytes of MD patients. Methods: We investigated the expression of nine circadian clock genes in the PB leukocytes of patients with MD and normal controls using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: We observed significantly lower expression of PER1 gene and higher expression of CLOCK gene in MD patients than those in normal controls (p < 0.05). PER1 did not associate with the degree of dizziness handicap in the patients with MD, but a lower expression of PER1 was significantly correlated with higher pure tone average (PTA) and speech reception threshold of the affected ear (p < 0.05). Patients with PTA > 30 dB had significantly lower PER1 expression than those with PTA ≤30 dB in the affected ear (p < 0.05). Our qRT-PCR result was validated by fewer positively stained leukocytes for PER1 protein in the MD patients using the immunocytochemical study. Conclusion: Our study implies the alteration of the circadian clock in patients with MD. In particular, the downregulation of PER1 correlated with the degree of hearing loss in the affected ear. PER1 in PB leukocytes may be a potential marker for the progression of hearing loss in MD.

Clinical significance of the neural response telemetric thresholds in Mandarin-speaking cochlear implant patients.

BACKGROUND: It is unclear whether neural response telemetric (NRT) thresholds are related to lexical tonal language performance after cochlear implants (CIs). We explored the factors associated with changes in NRT thresholds and postoperative performance of CI patients. METHODS: Patients receiving nucleus 24 CIs in our hospital from November 2010 were enrolled. We analyzed medical records and NRT thresholds. Mandarin speech and tone identification were measured in CI patients for at least 1 year postoperatively. RESULTS: Seventy-two patients with an average age of 16.1 years received CIs. The postoperative NRT threshold was lower than the intraoperative threshold. The NRT threshold was higher in the early- than the late-activation group (mapping within 21 vs >21 days postoperatively, respectively). Lower intraoperative NRT thresholds and curved electrodes were significantly associated with lower postoperative NRT thresholds. In multiple linear regression analysis, only postoperative NRT thresholds significantly affected speech and tone perception, including word recognition scores, tone perception, and comprehension of easy and difficult sentences (all p < 0.05). Other clinical parameters, including age, gender, implant type, and activation timing, were not significantly associated with clinical tone or speech outcomes. CONCLUSION: Curved electrode arrays were associated with lower postoperative NRT thresholds. A lower postoperative NRT threshold might predict better performance of Mandarin-speaking CI patients. Future studies should evaluate factors that affect both postoperative NRT thresholds and lexical tonal language performance.

Applicability of Oculomotor Tests for Predicting Central Vestibular Disorder Using Principal Component Analysis.

The videonystagmography oculomotor test battery is considered useful method for diagnosing vertigo. However, its role in diagnosing central vestibular disorder has not been clarified due to variations in interpretation. Patients (n = 103) with vertigo or dizziness symptoms undergoing the oculomotor tests and brain MRI within 1 month were analyzed. Two otology specialists retrospectively interpreted the oculomotor tests, and three neurology and neuroradiology specialists determined whether central lesions were present on brain MRI. Multivariable logistic regression analysis was performed to determine the factors contributing to discordant interpretation between oculomotor tests and brain MRI. Oculomotor tests predicting central lesions were assessed using principal component analysis. The intra- and inter-rater reliability in oculomotor test interpretation was moderate to good. Age > 60 years and multiple comorbidities were significant predictors of a discordant interpretation between MRI and oculomotor tests. Positive neurological symptoms and a higher oculomotor index (according to saccade (vertical axis), smooth pursuit (horizontal axis), and gaze-evoked nystagmus (horizontal/vertical axes) tests) significantly predicted central vestibular disorder in vertigo patients. Caution is required when interpreting the results of the oculomotor test battery for diagnosis of central lesions in older patients, as well as in those with multiple comorbidities.

Shelf life extension of aquatic products by applying nanotechnology: a review.

Aquatic products are extremely perishable due to their biological composition. Conventional preservation methods such as freezing, chemical treatments, packaging, and so forth are unable to inhibit enzymatic and microbiological spoilage efficiently and/or energy intensive and/or potentially toxic. However, the demand of consumers for aquatic products with long shelf life and high quality has urged the food industries to pursuit highly effective preservation methods for shelf life extension of aquatic products. Nanotechnology-related shelf life prolongation process possess the ability to overcome the drawbacks of conventional preservation technologies due to its unique properties. In this article, the aquatic products spoilage mechanisms, recent application of nanotechnology-related preservation techniques for aquatic products as well as the risk and regulation of nanomaterials have been reviewed. It has been shown that nanotechnology-related preservation techniques can effectively extend the shelf life without impairing the quality of aquatic products. However, the safety of nanotechnology is still remained controversial, therefore, the application of nanotechnology should be considered cautiously.

Comparison of the Functional Success of Fat Myringoplasty and Perifascial Areolar Tympanoplasty in Transcanal Endoscopic Ear Surgery.

OBJECTIVES: We compared the functional outcomes of fat myringoplasty and areolar tympanoplasty through a small postauricular incision in patients who underwent transcanal endoscopic ear surgery (TEES). METHODS: The study included patients who underwent myringoplasty or type I tympanoplasty using TEES in our Department of Otolaryngology between April 2016 and May 2019. The patients were divided into 2 groups according to the type of graft material used, which was selected based on the available amount of subcutaneous fat and the surgeon's experience. RESULTS: In total, 63 patients received fat tissue grafts (group A) and 77 received areolar tissue grafts (group B). The median operative time was significantly longer in group B (132 minutes) than in group A (65 minutes); perforations were significantly larger in group B than in group A (61.0% vs 29.7% of the eardrum surface). The postoperative air conduction threshold, air-bone gap, and speech reception threshold values were significantly lower than the preoperative values in both groups. The graft success rate did not significantly differ between groups A (96.8%, 61/63) and B (96.1%, 74/77). In group A, the perforation was > 35% of the eardrum surface in 27.0% (17/63) of the patients; the graft success rate was 100% (17/17). In the remaining 46 patients (perforation > 35%), the graft success rate was 95.7% (44/46); this difference was not statistically significant. CONCLUSIONS: Transcanal endoscopic ear surgery increases the usefulness of fat myringoplasty for the repair of perforations > 35% of the eardrum surface. Postauricular fatty and areolar tissues are suitable for this simple and rapid technique, which yields excellent outcomes.

Intratympanic steroid injection versus hyperbaric oxygen therapy in refractory sudden sensorineural hearing loss: a meta-analysis.

OBJECTIVE: The present meta-analysis aims to compare the efficacy of intratympanic steroid (ITS) injection and hyperbaric oxygen (HBO) therapy as salvage treatments for refractory sudden sensorineural hearing loss (SSNHL). DATA SOURCES: Comprehensive searches were performed in PubMed, EMBASE and the Cochrane Library from the date of the database inception to June 2020. All studies reporting the use of salvage ITS and HBO treatments in refractory SSNHL patients were included. Subsequently, the full texts of the eligible studies were evaluated. METHODS: The quality and bias of the studies were assessed using the Newcastle-Ottawa Scale and Cochrane's risk of bias tools for nonrandomized and randomized studies, respectively. The data were analyzed using Comprehensive Meta-Analysis software (Version 3; Biostat, Englewood, NJ). RESULTS: Three hundred and fourteen subjects in 3 observational studies and 1 randomized controlled trial met our inclusion criteria. The pooled results demonstrated that there were no significant differences in the mean posttreatment hearing gain between the ITS and HBO groups. The changes in word discrimination and hearing gain at 250, 500, 1000, 2000, 4000 and 8000 Hz were also comparable between the two salvage treatment groups. CONCLUSIONS: The pooled results demonstrated that there were no significant differences in hearing improvements between salvage ITS injection and salvage HBO therapy after failed primary systemic steroid treatment in patients with SSNHL. However, spontaneous recovery could bias the treatment outcomes, and these results should be interpreted with caution. Clinicians may choose these salvage treatments according to personal experience and treatment availability. In cases in which specialized HBO facilities are difficult to access, salvage ITS injection can be provided with comparable responses.

Stereotactic body radiotherapy plus cetuximab for previously irradiated un-resectable head and neck cancer.

BACKGROUND: The aim of the study was to explore the treatment outcomes and prognostic factors for patients with previously irradiated but unresectable recurrent head and neck squamous cell carcinoma (rHNSCC) treated by stereotactic body radiotherapy (SBRT) plus cetuximab at a single institute in Taiwan. METHODS: From February 2016 to March 2019, 74 patients with previously irradiated but unresectable rHNSCC were treated with SBRT plus cetuximab. All patients received irradiation to the gross tumor and/or nodal area with 40-50 Gy in five fractions, with each fraction interval ≥2 days over a 2-week period by using the CyberKnife M6 machine. An18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan was performed before treatment for treatment target delineation (n = 74) and 2 months later for response evaluation (n = 60). The median follow-up time was 9 months (range 1-36 months). RESULTS: The treatment response rate was complete response: 25.0%, partial response: 41.7%, stable disease: 11.7%, and progressive disease: 21.7% based on the criteria of the Response Evaluation Criteria in Solid Tumors (n = 72) and complete metabolic response: 21.7%, partial metabolic response: 51.7%, stable metabolic disease: 13.3%, and progressive metabolic disease: 13.3% based on PET-CT (n = 60), respectively. The 1-/2-year overall survival (OS) and progression-free survival (PFS) rates were 42.8%/22.0% and 40.5%/19.0%, respectively. In the logistic regression model, a re-irradiation interval >12 months was observed to be the only significant prognostic factor for a favorable treatment response. In the Cox proportional hazards model, a re-irradiation interval >12 months and gross tumor volume (GTV) â‰¦ 50 ml were favorable prognostic factors of OS and PFS. CONCLUSION: SBRT plus cetuximab provides a promising salvage strategy for those patients with previously irradiated but unresectable rHNSCC, especially those with a re-irradiation interval >12 months or GTV â‰¦ 50 ml.

Systemic toll-like receptor 9 agonist CpG oligodeoxynucleotides exacerbates aminoglycoside ototoxicity.

The Toll-like receptor (TLR) signaling pathway is the key regulator of the innate immune system in response to systemic infection. Several studies have reported that the systemic TLR4 agonist lipopolysaccharide exacerbates aminoglycoside ototoxicity, but the influence of virus-associated TLR7 and TLR9 signaling cascades on the cochlea is unclear. The present study aimed to investigate the auditory effects of systemic TLR7 and TLR9 agonists during chronic kanamycin treatment. CBA/CaJ mice received the TLR7 agonist gardiquimod or TLR9 agonist CpG oligodeoxynucleotides (ODN) one day before kanamycin injection and on the 5th and 10th days during a 14-day course of kanamycin treatment. We observed that systemic gardiquimod or CpG ODN alone did not affect the baseline auditory brainstem response (ABR) threshold. Three weeks after kanamycin treatment, gardiquimod did not significantly change ABR threshold shifts, whereas CpG ODN significantly increased kanamycin-induced ABR threshold shifts. Furthermore, outer hair cell (OHC) evaluation revealed that CpG ODN reduced distortion product otoacoustic emission amplitudes and increased kanamycin-induced OHC loss. CpG ODN significantly elevated cochlear Irf-7, Tnf-α, Il-1, and Il-6 transcript levels. In addition, an increased number of Iba-1+ cells, which represented activated macrophages, was observed in the cochlea treated with CpG ODN. Our results indicated that systemic CpG ODN exacerbated kanamycin-induced ototoxicity and increased cochlear inflammation. This study implies that patients with underlying virus infection may experience more severe aminoglycoside-induced hearing loss if it occurs.

Quality of Life as a Mediator between Cancer Stage and Long-Term Mortality in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Radiotherapy.

BACKGROUND: Quality of life (QoL) attained before, during, or after treatments is recognized as a vital factor associated with therapeutic benefits in cancer patients. This nasopharyngeal cancer (NPC) patient longitudinal study assessed the relationship among QoL, cancer stage, and long-term mortality in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS: The European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the head and neck cancer-specific QoL questionnaire module (QLQ-HN35) were employed to evaluate four-dimensional QoL outcomes at five time points: pre- (n = 682), during (around 40 Gy) (n = 675), 3 months (n = 640), 1 year (n = 578) and 2 years post-IMRT (n = 505), respectively, for 682 newly diagnosed NPC patients treated between 2003 and 2017 at a single institute. The median followed-up time was 7.5 years, ranging from 0.3 to 16.1 years. Generalized estimating equations, multivariable proportional hazards models, and Baron and Kenny's method were used to assess the investigated effects. RESULTS: Advanced AJCC stage (III-IV) patients revealed a 2.26-fold (95% CI-1.56 to 3.27) higher covariate-adjusted mortality risk than early-stage (I-II) patients. Compared with during IMRT, advanced-stage patients had a significantly low global health QoL and a significantly high QoL-HN35 symptom by a large magnitude at pre-, 3 months, and 2 years post-IMRT. QoL scales at pre-IMRT, 1 year, and 2 years post-IMRT were significantly associated with mortality. The effect changes of mortality risk explained by global health QoL, QoL-C30, and QoL-HN35 symptom were 5.8-9.8% at pre-IMRT but at 2 years post-IMRT were 39.4-49.4% by global health QoL and QoL-HN35 symptoms. CONCLUSIONS: We concluded advanced cancer stage correlates with a long-term high mortality in NPC patients treated with IMRT and the association is partially intermediated by QoL at pre-IMRT and 2 years post-IMRT. Therefore, QoL-HN35 symptom and global health QoL-dependent medical support and care should be focused and tailored at 2 years post-IMRT.