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Cell
. 2019 Oct 31;179(4):864-879.e19. doi: 10.1016/j.cell.2019.10.001.
Stress-Induced Metabolic Disorder in Peripheral CD4 + T Cells Leads to Anxiety-like Behavior
Ke-Qi Fan 1, Yi-Yuan Li 1, Hao-Li Wang 1, Xin-Tao Mao 1, Jin-Xin Guo 1, Fei Wang 1, Ling-Jie Huang 2, Yi-Ning Li 1, Xiang-Yu Ma 3, Zheng-Jun Gao 1, Wei Chen 4, Dan-Dan Qian 5, Wen-Jin Xue 5, Qian Cao 2, Lei Zhang 2, Li Shen 1, Long Zhang 1, Chao Tong 1, Jiang-Yan Zhong 1, Wei Lu 5, Ling Lu 6, Ke-Ming Ren 2, Guisheng Zhong 7, Yuan Wang 4, Mingliang Tang 5, Xin-Hua Feng 1, Ren-Jie Chai 8, Jin Jin 9
Affiliations expand
PMID: 31675497 DOI: 10.1016/j.cell.2019.10.001
Abstract
Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.

Keywords: AdorA1; IRF-1; T cell; amygdala; anxiety; leukotriene B4; purine metabolism; stress; xanthine.

Copyright © 2019 Elsevier Inc. All rights reserved.

Comment in
The Immune-Mind Connection.
Hang S, Huh JR.
Cell. 2019 Oct 31;179(4):803-805. doi: 10.1016/j.cell.2019.10.012.
PMID: 31675492
T cells with fragmented mitochondria frazzle the mind.
Bordon Y.
Nat Rev Immunol. 2020 Jan;20(1):5. doi: 10.1038/s41577-019-0246-0.
PMID: 31700159 No abstract available.
Cited by 3 articles
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2
Review Cancer Lett
. 2019 Sep 28;460:54-64. doi: 10.1016/j.canlet.2019.06.012. Epub 2019 Jun 22.
Tumor-derived Extracellular Vesicles in Breast Cancer: From Bench to Bedside
Hong-Xia Wang 1, Olivier Gires 2
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PMID: 31233837 DOI: 10.1016/j.canlet.2019.06.012
Abstract
Tumor-derived extracellular vesicles (TEVs) released from various tumor cell types comprise endosome-derived exosomes and microvesicles (MVs), which originate from plasma membrane budding. TEVs incorporate a myriad of biomolecules such as proteins, DNAs, metabolites and microRNAs, which can be transferred from cell-to-cell. Besides their role in the disposal of biomolecules, TEVs serve to orchestrate fundamental processes of normal and malignant development, including breast cancer (BC). As such, TEVs are important constituents of the tumor microenvironment (TME) that act as communication shuttles through transduction of encapsulated molecular cargos from a parent to a recipient cell and through direct interaction with target cells. Emerging evidence suggests that TEVs support BC development and disease progression by fostering invasion, angiogenesis, pre-metastatic niche preparation, escape from immune surveillance, and induction of resistance to treatment. Although there is a long way to go in order to translate the current knowledge into actual clinical applications, TEVs represent promising candidates for diagnostic biomarkers, therapeutic carriers and targets. In the present review, we will summarize the current knowledge on TEVs in BC.

Keywords: Exosomes; Extracellular vesicles; Liquid biopsy; Metastatic breast cancer; Microvesicles; Tumor microenvironment.

Copyright © 2019 Elsevier B.V. All rights reserved.

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Review Clin Cancer Res
. 2019 Mar 15;25(6):1709-1717. doi: 10.1158/1078-0432.CCR-18-2581. Epub 2018 Nov 9.
The Reciprocity Between Radiotherapy and Cancer Immunotherapy
Yifan Wang # 1, Zhi-Gang Liu # 2 3, Hengfeng Yuan 4 5, Weiye Deng 1, Jing Li 6, Yuhui Huang 7, Betty Y S Kim 5, Michael D Story 1, Wen Jiang 8 6
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PMID: 30413527 PMCID: PMC6420874 DOI: 10.1158/1078-0432.CCR-18-2581
Free PMC article
Abstract
The clinical success of immune checkpoint inhibitors in treating metastatic and refractory cancers has generated significant interest in investigating their role in treating locally advanced diseases, thus requiring them to be combined with standard treatments in the hope of producing synergistic antitumor responses. Radiotherapy, in particular, has long been hypothesized to have actions complementary to those of immune checkpoint blockade, and a growing body of evidence indicates that cancer immunotherapy may also have radiosensitizing effects, which would provide unique benefit for locoregional treatments. Recent studies have demonstrated that when immune cells are activated by immunotherapeutics, they can reprogram the tumor microenvironment in ways that may potentially increase the radiosensitivity of the tumor. In this review, we highlight the evidence that supports reciprocal interactions between cancer immunotherapy and radiotherapy, where in addition to the traditional notion that radiation serves to enhance the activation of antitumor immunity, an alternative scenario also exists in which T-cell activation by cancer immunotherapy may sensitize tumors to radiation treatment through mechanisms that include normalization of the tumor vasculature and tissue hypoxia. We describe the empirical observations from preclinical models that support such effects and discuss their implications for future research and trial design.

©2018 American Association for Cancer Research.

Conflict of interest statement
Conflict of Interest: The authors declare no conflict of interests

Cited by 3 articles3 figures
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Meta-Analysis BMC Pharmacol Toxicol
. 2019 Nov 29;20(1):72. doi: 10.1186/s40360-019-0363-1.
Antihistamine Effects and Safety of Fexofenadine: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Cheng-Zhi Huang 1 2, Zhi-Hui Jiang 3, Jian Wang 1, Yue Luo 4 5, Hua Peng 6
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PMID: 31783781 PMCID: PMC6884918 DOI: 10.1186/s40360-019-0363-1
Free PMC article
Abstract
Background: As a new generation antihistamine, fexofenadine has been widely used in allergic diseases. However, there is still a lack of collective evidence regarding the antihistamine effects and safety profiles of fexofenadine relative to other antihistamine drugs and placebo. Therefore, we aimed to systematically evaluate the antihistamine effects and safety of fexofenadine.

Methods: An electronic literature search of randomized controlled trials (RCTs) was performed using Embase, Cochrane and PubMed from establishment to January 1st, 2018. RCTs comparing the antihistamine effects or safety (adverse events, sedative effects, and cognitive/psychomotor function) of fexofenadine with either other antihistamines or placebo for healthy subjects and patients with allergy were selected.

Results: Fifty-one studies of 14,551 participants met the inclusion criteria. When compared with the first-generation antihistamines, fexofenadine produced significantly lower adverse events frequency (OR = 0.446; 95% CI: 0.214 to 0.929, P = 0.031), significantly lower sedative effects frequency (OR = 0.265; 95% CI: 0.072 to 0.976, P = 0.046) and significantly less change of all cognitive/psychomotor function. When compared with the second-generation antihistamines, fexofenadine produced significantly marginal sedative effects (OR = 0.59; 95% CI, 0.38 to 0.93; P = 0.02) and significantly less change of most of the cognitive/psychomotor function. When compared with placebo, fexofenadine produced more significant antihistamine effects.

Conclusions: Fexofenadine has a positive antihistamine effect, which is probably no worse than the second-generation antihistamines. Fexofenadine probably has a favorable safety profile, which is more likely better than that of the first-generation antihistamines. There is lack of data to support that fexofenadine has a better overall safety profile compared to the second-generation antihistamines, however, some presently available evidence on sedative effects and certain aspects of cognitive/psychomotor function favors fexofenadine. Therefore, fexofenadine may be worthy of recommendation for safety related workers.

Keywords: Antihistamines; Fexofenadine; Meta-analysis; Randomized controlled trial; Systematic review.

Conflict of interest statement
The authors declare that they have no competing interests.

72 references10 figures
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5
Multicenter Study Head Neck
. 2019 Jan;41(1):16-29. doi: 10.1002/hed.25192. Epub 2018 Dec 3.
Salvage Laryngectomy and Laryngopharyngectomy: Multicenter Review of Outcomes Associated With a Reconstructive Approach
Microvascular Committee of the American Academy of Otolaryngology-Head & Neck Surgery*
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PMID: 30508265 DOI: 10.1002/hed.25192
Abstract
Background: Surgeons have developed various reconstructive techniques to minimize the rate of pharyngocutaneous fistula and optimize functional outcome after salvage laryngectomy or laryngopharyngectomy.

Methods: Multicenter retrospective review at 33 institutions of 486 patients with a history of squamous cell carcinoma (SCC) of the larynx or hypopharynx previously treated with primary chemoradiotherapy (CRT) who required salvage surgery. Outcomes evaluated were overall fistula rate, fistula requiring reoperation, and 12-month speech and swallowing function.

Results: Primary closure of the hypopharynx was associated with a statistically higher overall fistula rate and fistula requiring reoperation compared to reconstruction with vascularized tissue augmentation. Vascularized tissue augmentation with muscle led to worse 12-month "understandability of speech" and "nutritional mode" scores compared to vascularized tissue augmentation without muscle.

Conclusion: Vascularized tissue augmentation reduces the overall fistula rate and fistula requiring reoperation but vascularized tissue augmentation with muscle may impair speech and swallowing outcomes.

Keywords: hypopharyngeal reconstruction; hypopharyngeal squamous cell carcinoma; laryngeal squamous cell carcinoma; microvascular; pharyngocutaneous fistula; recurrent laryngeal cancer; salvage laryngectomy.

© 2019 Wiley Periodicals, Inc.

Cited by 2 articles
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6
Cancer
. 2019 Dec 15;125(24):4462-4470. doi: 10.1002/cncr.32458. Epub 2019 Sep 22.
Chinese Nonmedicinal Herbal Diet and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study
Chuyang Lin 1 2, Su-Mei Cao 1 3, Ellen T Chang 4 5, Zhiwei Liu 6, Yonglin Cai 7 8, Zhe Zhang 9 10, Guomin Chen 11, Qi-Hong Huang 12, Shang-Hang Xie 1 3, Yu Zhang 3, Jingping Yun 3, Wei-Hua Jia 3, Yuming Zheng 7 8, Jian Liao 13, Yufeng Chen 6, Longde Lin 10, Qing Liu 1 3, Ingemar Ernberg 14, Guangwu Huang 9 10, Yi Zeng 11, Yi-Xin Zeng 3 15, Hans-Olov Adami 6 16, Weimin Ye 1 3 6
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PMID: 31544233 PMCID: PMC6891117 (available on 2020-12-15) DOI: 10.1002/cncr.32458
Free PMC article
Abstract
Background: An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated.

Methods: This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake.

Results: Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79).

Conclusions: Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.

Keywords: case-control studies; herbal diet; herbs; nasopharyngeal carcinoma.

© 2019 American Cancer Society.

Conflict of interest statement
Conflicts of Interest: None.

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7
Radiother Oncol
. 2019 Dec;141:247-255. doi: 10.1016/j.radonc.2019.06.034. Epub 2019 Aug 17.
Evofosfamide Sensitizes Esophageal Carcinomas to Radiation Without Increasing Normal Tissue Toxicity
Linda Spiegelberg 1, Stefan J van Hoof 2, Rianne Biemans 1, Natasja G Lieuwes 1, Damiënne Marcus 1, Raymon Niemans 1, Jan Theys 1, Ala Yaromina 1, Philippe Lambin 1, Frank Verhaegen 2, Ludwig J Dubois 3
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PMID: 31431383 PMCID: PMC6913516 DOI: 10.1016/j.radonc.2019.06.034
Free PMC article
Abstract
Background and purpose: Esophageal cancer incidence is increasing and is rarely curable. Hypoxic tumor areas cause resistance to conventional therapies, making them susceptible for treatment with hypoxia-activated prodrugs (HAPs). We investigated in vivo whether the HAP evofosfamide (TH-302) could increase the therapeutic ratio by sensitizing esophageal carcinomas to radiotherapy without increasing normal tissue toxicity.

Materials and methods: To assess therapeutic efficacy, growth of xenografted esophageal squamous cell (OE21) or adeno (OE19) carcinomas was monitored after treatment with TH-302 (50 mg/kg, QD5) and irradiation (sham or 10 Gy). Short- and long-term toxicity was assessed in a gut mucosa and lung fibrosis irradiation model, sensitive to acute and late radiation injury respectively. Mice were injected with TH-302 (50 mg/kg, QD5) and the abdominal area (sham, 8 or 10 Gy) or the upper part of the right lung (sham, 20 Gy) was irradiated. Damage to normal tissues was assessed 84 hours later by histology and blood plasma citrulline levels (gut) and for up to 1 year by non-invasive micro CT imaging (lung).

Results: The combination treatment of TH-302 with radiotherapy resulted in significant tumor growth delay in OE19 (P = 0.02) and OE21 (P = 0.03) carcinomas, compared to radiotherapy only. Irradiation resulted in a dose-dependent decrease of crypt survival (P < 0.001), mucosal surface area (P < 0.01) and citrulline levels (P < 0.001) in both tumor and non-tumor bearing animals. On the long-term, irradiation increased CT density in the lung, indicating fibrosis, over time. TH-302 did not influence the radiation-induced short-term and long-term toxicity, confirmed by histological evaluation.

Conclusion: The combination of TH-302 and radiotherapy might be a promising approach to improve the therapeutic index for esophageal cancer patients.

Keywords: Esophageal cancer; Long-term lung fibrosis; Radiotherapy; Short-term gut toxicity; TH-302; Therapeutic index.

Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.

Conflict of interest statement
None.

48 references7 figures
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8
Otol Neurotol
. 2019 Aug;40(7):e747-e752. doi: 10.1097/MAO.0000000000002325.
A Validated Questionnaire to Assess the Severity of Persistent Postural-Perceptual Dizziness (PPPD): The Niigata PPPD Questionnaire (NPQ)
Chihiro Yagi 1, Yuka Morita, Meiko Kitazawa, Yoriko Nonomura, Tatsuya Yamagishi, Shinsuke Ohshima, Shuji Izumi, Kuniyuki Takahashi, Arata Horii
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PMID: 31219964 PMCID: PMC6641087 DOI: 10.1097/MAO.0000000000002325
Free PMC article
Abstract
Objective: To establish a questionnaire to diagnose and assess the severity of persistent postural-perceptual dizziness (PPPD).

Study design: Retrospective chart review.

Setting: Tertiary referral center.

Patients: Fifty PPPD patients and 50 consecutive control patients with other vestibular disorders.

Interventions: Patients answered questions on three exacerbating factors of PPPD (upright posture/walking, movement, and visual stimulation), and each factor was evaluated using four questions scoring the severity from 0 (none) to 6 (unbearable). Somatic and psychological distress was evaluated by the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS), respectively.

Main outcome measures: The questionnaire's reliability was tested by Cronbach's alpha, and it was validated by examining the differences in the questionnaire's scores between PPPD patients and controls. The area under the curve (AUC) of the receiver operating characteristic curve for each factor was calculated.

Results: Cronbach's alpha coefficient was >0.8 for all factors, except the movement factor. There were no significant differences in the VAS and HADS scores between the two groups. However, the combined and individual questionnaire scores for each factor were higher in PPPD patients than in controls, indicating the questionnaire's high validity. The AUC was widest for the visual stimulation factor (0.830), and a score of 9 (full score 24) had the best sensitivity (82%) and specificity (74%) for discriminating PPPD patients from controls.

Conclusions: We developed a questionnaire that exhibited high reliability and validity in evaluating PPPD severity. The visual stimulation factor may be the most characteristic among the three exacerbating factors.

Conflict of interest statement
The authors disclose no conflicts of interest.

12 references3 figures
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9
Int Forum Allergy Rhinol
. 2019 Sep;9(9):986-992. doi: 10.1002/alr.22377. Epub 2019 Jul 8.
Clinical Validation of the Olfactory Detection Threshold Module of the Snap & Sniff® Olfactory Test System
Richard L Doty 1, Crystal Wylie 1, Mark Potter 1, Rachel Beston 1, Brooke Cope 1, Kelsey Majam 1
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PMID: 31283113 DOI: 10.1002/alr.22377
Abstract
Background: Quantitative olfactory testing is essential to determine the validity and nature of a patient's complaint, accurately monitor changes in function over time (including influences of pharmacological, surgical, or immunological interventions), detect malingering, and establish disability compensation. This work describes the clinical validation of an advanced rapid odor detection threshold test that standardizes odorant delivery and eliminates unsanitary sniff bottles, the need for blindfolds, and the possibility of touching an odorant stimulus to the nose.

Methods: Snap & Sniff® single-staircase phenyl ethyl alcohol detection thresholds (S&S-Ts) were assessed bilaterally in 736 patients with chemosensory complaints; 421 received both bilateral and unilateral testing. The results were correlated with scores from the University of Pennsylvania Smell Identification Test (UPSIT) and the Smell Threshold Test (STT), a widely-used standardized threshold test. Test-retest reliability data were obtained for 50 patients.

Results: S&S-Ts were highly reliable (Spearman r = 0.84), correlated with the other olfactory test measures (rs > 0.65, ps < 0.0001), and required significantly shorter administration times than the STT (<10 minutes). Bilateral thresholds were systematically lower than unilateral thresholds, a phenomenon independent of presentation order but dependent upon the better functioning side of the nose. The S&S-Ts were sensitive to age and sex. No systematic left:right nasal side threshold differences were evident.

Conclusion: The present study validates the use of Snap & Sniff® technology in the clinic setting. High test-retest reliability and brief administration times were evident. The S&S-T test allows for a reliable, valid, inexpensive, and rapid clinical means for quantitatively assessing human olfactory sensitivity.

Keywords: age; anosmia; hyposmia; odor detection; olfaction; psychophysics; reliability; sex differences; threshold; validity.

© 2019 ARS-AAOA, LLC.

40 references
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10
Observational Study Head Neck
. 2019 Jan;41(1):110-115. doi: 10.1002/hed.25480. Epub 2018 Dec 11.
Compartmental Surgery for Oral Tongue and Floor of the Mouth Cancer: Oncologic Outcomes
Cesare Piazza 1, Alberto Grammatica 2, Nausica Montalto 2, Alberto Paderno 2, Francesca Del Bon 2, Piero Nicolai 2
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PMID: 30536781 DOI: 10.1002/hed.25480
Abstract
Background: Oral tongue/floor of mouth squamous cell carcinoma (OTFMSCC) with a depth of invasion (DOI) > 10 mm involves extrinsic muscles and lingual neurovascular/lymphatic bundles. "Compartmental" hemiglossopelvectomy (CHGP) was developed to improve loco-regional control by "en bloc" removal of tumor and its pathways of spread.

Methods: We conducted a retrospective observational study on 45 CHGPs performed at a single institution for OTFMSCC with a DOI > 10 mm at CT/MR. Group A (n = 35) included naïve patients, and group B (n = 10) recurrent cancers. We evaluated 2-year overall survival (OS), disease-free survival (DFS), local control (LC), and loco-regional control (LRC).

Results: Two-year OS, DFS, LC, and LRC were 80%, 91%, 100%, and 94% for group A, and 27%, 26%, 67%, and 36% for group B, respectively. Salvage surgery and positive margins were significantly associated with worse prognosis.

Conclusion: CHGP is a reliable oncologic approach in primary surgery for advanced OTFMSCC. In recurrent cancers, survival remains poor.

Keywords: compartmental surgery; floor of mouth; hemiglossopelvectomy; oral tongue; squamous cell carcinoma.

© 2018 Wiley Periodicals, Inc.

Cited by 2 articles
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11
Head Neck
. 2019 Jan;41(1):185-197. doi: 10.1002/hed.25471. Epub 2018 Dec 14.
Role and Regulation of Proapoptotic Bax in Oral Squamous Cell Carcinoma and Drug Resistance
Manzar Alam 1, Tanushree Kashyap 1, Prajna Mishra 2, Aditya K Panda 1, Siddavaram Nagini 3, Rajakishore Mishra 1
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PMID: 30549344 DOI: 10.1002/hed.25471
Abstract
Background: Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive.

Methods: A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients were used. The status of Bax was analyzed at DNA/mRNA/protein levels and the results were correlated with p53 and Akt expression in tissue samples/cisplatin-resistant oral tongue SCC (SCC9/SCC4-CisR) cell line.

Results: Frequent progressive decrease of Bax expression with infrequent promoter methylation, polymorphisms G(-248)A, and mutations was observed in OSCC progression/resistance. Furthermore, by targeting Akt pathway, induction of Bax-dependent cell death was observed and this was further enhanced with nimbolide treatment in SCC9/SCC4-CisR cells.

Conclusion: Hence, the Bax gene alteration and its deregulation through p53/Akt pathway are important for OSCC progression and drug resistance. Akt Inhibitor VIII and nimbolide synergistically induce Bax, and it is therefore beneficial for chemosensitizing cisplatin-resistant human OSCC.

Keywords: Akt; Bax; Bcl-2; GSK3α; GSK3β; OSCC; chemoradiation resistance; drug resistance; oral cancer; oral squamous cell carcinoma; p53.

© 2018 Wiley Periodicals, Inc.

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12
Review Int Forum Allergy Rhinol
. 2019 Sep;9(9):1054-1062. doi: 10.1002/alr.22373. Epub 2019 Jun 28.
Hyams Grading as a Predictor of Metastasis and Overall Survival in Esthesioneuroblastoma: A Meta-Analysis
Khodayar Goshtasbi 1, Arash Abiri 1, Mehdi Abouzari 1, Ronald Sahyouni 1, Beverly Y Wang 2, Bobby A Tajudeen 3, Frank P K Hsu 4, Gilbert Cadena 4, Edward C Kuan 1
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PMID: 31251848 DOI: 10.1002/alr.22373
Abstract
Background: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, represents up to 3% of all sinonasal neoplasms. Hyams histologic grading is a promising tool in predicting metastases and establishing prognoses for this complex tumor.

Methods: A systematic literature search was performed in the PubMed, Ovid MEDLINE, and Cochrane databases. ENB patients with Hyams I-II or III-IV were categorized as low-grade Hyams (LGH) or high-grade Hyams (HGH), respectively. Binary and continuous random-effects models were applied to calculate odds ratios (ORs) for the incidences of neck and distal metastases as well as for 5- and 10-year overall survival rates.

Results: Of the 57 screened articles published from 1993 to 2018, 16 (525 patients) and 21 (563 patients) provided data for tumor metastases and overall survival rates, respectively. Neck metastasis was observed in 18.2% of HGH vs 7.9% of LGH patients. Distant metastasis was noted in 20.7% of HGH vs 8.9% of LGH patients. LGH patients had 5- and 10-year overall survival rates of 81.2% and 64.0%, respectively, as compared with 60.9% and 40.6%, respectively, for HGH patients. In comparing HGHs vs LGHs, the collective ORs for neck and distant metastases were 2.08 (95% confidence interval [CI], 1.09-3.99; p = 0.03) and 2.37 (95% CI, 1.07-5.26; p = 0.03), respectively. Moreover, in comparing LGHs vs HGHs, collective ORs for 5- and 10-year overall survival rates were 3.39 (95% CI, 2.09-5.49; p < 0.001) and 3.03 (95% CI, 1.82-5.06; p < 0.001), respectively.

Conclusion: HGH ENBs, compared with LGH ENBs, are more likely to metastasize to neck or distal targets and to have lower overall survival rates.

Keywords: esthesioneuroblastoma; meta-analysis; metastasis; olfactory neuroblastoma; survival.

© 2019 ARS-AAOA, LLC.

56 references
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13
Meta-Analysis Otol Neurotol
. 2019 Aug;40(7):851-857. doi: 10.1097/MAO.0000000000002274.
What Is the Role of Hyaluronic Acid Ester in Myringoplasty? Systematic Review and Meta-Analysis
Wai Keat Wong 1, Eric H Luu
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PMID: 31246888 DOI: 10.1097/MAO.0000000000002274
Abstract
Objective: To reveal odds of tympanic membrane closure and postoperative hearing outcomes for myringoplasty utilizing hyaluronic acid ester via systematic review and meta-analysis.

Data sources: 1) Search of English articles in PubMed/Medline, Embase, and Cochrane databases published between January 1, 1998 and March 31, 2018.

Study selection: Inclusion criteria: 1) English language; 2) clinical studies; 3) reported posttreatment perforation status, hearing outcomes, or complications.

Exclusion criteria: hyaluronic acid used for middle ear packing or topical application of hyaluronic acid solution.

Data extraction: Number of patients, surgical technique, mean age, overall rate of tympanic membrane closure, success rate based on size of perforation, mean air-bone gap improvement, and postoperative speech scores and complications.

Data synthesis: Ten studies encompassing 531 patients met criteria. Reported success rates for closure of chronic perforation ranged from 70.0 to 92.7% (mean, 85.21%). Smaller perforation predicted success in complete closure. Mean air-bone gap closure was 10.6 dB (4-24 dB). There were five complications reported. Meta-analysis was performed on five studies. No difference was noted in the success rates between hyaluronic acid ester myringoplasty and conventional tympanoplasty using fascia or perichondrium, with an overall closure rates of 89.8 and 89.4%, respectively (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.59-1.82, p = 0.896). A higher closure rate was seen in hyaluronic acid ester myringoplasty (87.9%) when compared with fat graft myringoplasty (70.8%), (OR 3.01, 95% CI 1.42-6.35, p = 0.004).

Conclusions: Hyaluronic acid (HA) ester myringoplasty appears to be safe and effective at attaining complete closure of tympanic membrane perforation, although there exists significant selection bias and inconsistent reporting among existing papers.

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14
Toxicology
. 2019 Sep 1;425:152245. doi: 10.1016/j.tox.2019.152245. Epub 2019 Jul 19.
Methylmercury Exposure Induces ROS/Akt Inactivation-Triggered Endoplasmic Reticulum Stress-Regulated Neuronal Cell Apoptosis
Yao-Pang Chung 1, Cheng-Chieh Yen 2, Feng-Cheng Tang 3, Kuan-I Lee 4, Shing-Hwa Liu 5, Chin-Ching Wu 6, Shang-Shu Hsieh 4, Chin-Chuan Su 7, Chun-Ying Kuo 7, Ya-Wen Chen 8
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PMID: 31330229 DOI: 10.1016/j.tox.2019.152245
Abstract
Epidemiological studies have positively linked mercury exposure and neurodegenerative diseases (ND). Methylmercury (MeHg), an organic form of mercury, is a ubiquitous and potent environmental neurotoxicant that easily crosses the blood-brain barrier and causes irreversible injury to the central nervous system (CNS). However, the molecular mechanisms underlying MeHg-induced neurotoxicity remain unclear. Here, the present study found that Neuro-2a cells underwent apoptosis in response to MeHg (1-5 μM), which was accompanied by increased phosphatidylserine (PS) exposure on the outer cellular membrane leaflets, caspase-3 activity, and the activation of caspase cascades and poly (ADP-ribose) polymerase (PARP). Exposure of Neuro-2a cells to MeHg also triggered endoplasmic reticulum (ER) stress, which was identified via several key molecules (including: glucose-regulated protein (GRP)78, GRP94, C/EBP homologous protein (CHOP) X-box binding protein(XBP)-1, protein kinase R-like ER kinase (PERK), eukaryotic initiation factor 2α (eIF2α), inositol-requiring enzyme(IRE)-1, activation transcription factor(AFT)4, and ATF6. Transfection with GRP78-, GRP94-, CHOP-, and XBP-1-specific small interfering (si)RNA significantly suppressed the expression of these proteins, and attenuated cytotoxicity and caspase-12, -7, and -3 activation in MeHg-exposed cells. Furthermore, MeHg dramatically decreased Akt phosphorylation, and the overexpression of activation of Akt1 (myr-Akt1) could significantly prevent MeHg-induced Akt inactivation, as well as apoptotic and ER stress-related signals. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively prevented MeHg-induced neuronal cell reactive oxygen species (ROS) generation, apoptotic and ER stress-related signals, and Akt inactivation. Collectively, these results indicate that MeHg exerts its cytotoxicity in neurons by inducing ROS-mediated Akt inactivation up-regulated ER stress, which induces apoptosis and ultimately leads to cell death.

Keywords: Akt; Apoptosis; Endoplasmic reticulum stress; Methylmercury; Neurotoxicity; Reactive oxygen species.

Copyright © 2019 Elsevier B.V. All rights reserved.

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15
Comparative Study Eur Arch Otorhinolaryngol
. 2019 Dec;276(12):3461-3466. doi: 10.1007/s00405-019-05604-4. Epub 2019 Aug 22.
Clinical Characteristics of Acinic Cell Carcinoma and Secretory Carcinoma of the Parotid Gland
Tetsuya Terada 1, Ryo Kawata 2, Keiki Noro 2, Masaaki Higashino 2, Shuji Nishikawa 2, Shin-Ichi Haginomori 2, Yoshitaka Kurisu 3, Hiroko Kuwabara 3, Yoshinobu Hirose 3
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PMID: 31440815 DOI: 10.1007/s00405-019-05604-4
Abstract
Purpose: Mammary analogue secretory carcinoma (SC) of the parotid gland is a relatively uncommon cancer associated with the ETV6-NTRK3 fusion product similar to breast cancer. The clinical characteristics and outcome of treatment were reviewed for patients with this tumor at our hospital.

Methods: In this retrospective case series, 24 patients with a diagnosis of acinic cell carcinoma (AcCC) of the parotid gland were classified as having either SC or AcCC based on analysis of the ETV6-NTRK3 fusion gene. These two groups were compared with respect to their clinical and imaging characteristics (MRI/US), cytologic findings, accuracy of fine-needle aspiration cytology and frozen section, treatment outcomes, and immunohistochemical findings.

Results: Based on re-classification by ETV6-NTRK3 fusion gene analysis, the diagnosis was SC in 14 patients and AcCC in 10 patients. The SC group had a significantly higher proportion of male patients and was also significantly younger than the AcCC group. Imaging studies revealed that SC was significantly more likely to show internal heterogeneity. Correct grading of both tumors was comparable by fine needle aspiration, with the rate being 60% for AcCC and 50% for SC. Diagnosis by frozen section biopsy diagnosis obtained the correct grade in 90% of the AcCC group and 93% of the SC group.

Conclusions: In 24 patients previously diagnosed with AcCC, re-analysis of the ETV6-NTRK3 fusion product indicated that 14 patients actually had SC. Although AcCC and SC show similarities of their biological aggressiveness and prognosis, patients with SC were significantly more likely to be male and younger.

Keywords: Acinic cell carcinoma; ETV6; Parotid carcinoma; Secretory carcinoma.

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16
Comparative Study Int J Audiol
. 2019 Nov;58(11):704-716. doi: 10.1080/14992027.2019.1621396. Epub 2019 Jun 1.
Electrophysiological Characteristics in Children With Listening Difficulties, With or Without Auditory Processing Disorder
Tone Stokkereit Mattsson 1 2, Ola Lind 3, Turid Follestad 4, Kjell Grøndahl 5, Wayne Wilson 6, Jude Nicholas 7 8, Ståle Nordgård 2 9, Stein Andersson 10
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PMID: 31154863 DOI: 10.1080/14992027.2019.1621396
Abstract
Objective: To determine if the auditory middle latency responses (AMLR), auditory late latency response (ALLR) and auditory P300 were sensitive to auditory processing disorder (APD) and listening difficulties in children, and further to elucidate mechanisms regarding level of neurobiological problems in the central auditory nervous system. Design: Three-group, repeated measure design. Study sample: Forty-six children aged 8-14 years were divided into three groups: children with reported listening difficulties fulfilling APD diagnostic criteria, children with reported listening difficulties not fulfilling APD diagnostic criteria and normally hearing children. Results: AMLR Na latency and P300 latency and amplitude were sensitive to listening difficulties. No other auditory evoked potential (AEP) measures were sensitive to listening difficulties, and no AEP measures were sensitive to APD only. Moderate correlations were observed between P300 latency and amplitude and the behavioural AP measures of competing words, frequency patterns, duration patterns and dichotic digits. Conclusions: Impaired thalamo-cortical (bottom up) and neurocognitive function (top-down) may contribute to difficulties discriminating speech and non-speech sounds. Cognitive processes involved in conscious recognition, attention and discrimination of the acoustic characteristics of the stimuli could contribute to listening difficulties in general, and to APD in particular.

Keywords: Auditory processing disorder (APD); behavioural measures; electrophysiology; paediatric.

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17
J Clin Endocrinol Metab
. 2019 Sep 1;104(9):3713-3725. doi: 10.1210/jc.2018-02686.
Transcriptome Analyses Identify a Metabolic Gene Signature Indicative of Dedifferentiation of Papillary Thyroid Cancer
Ben Ma 1 2, Hongyi Jiang 1 2, Duo Wen 1 2, Jiaqian Hu 1 2, Litao Han 1 2, Wanlin Liu 1 2, Weibo Xu 1 2, Xiao Shi 1 2, Wenjun Wei 1 2, Tian Liao 1 2, Yulong Wang 1 2, Zhongwu Lu 1 2, Yu Wang 1 2, Qinghai Ji 1 2
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PMID: 30942873 DOI: 10.1210/jc.2018-02686
Abstract
Context: Metabolic reprogramming is a common feature of tumorigenesis. It remains unknown concerning the expression pattern of metabolism-associated genes in dedifferentiated thyroid cancer (DDTC).

Objective: This study aimed to identify a useful signature to indicate dedifferentiation of papillary thyroid cancer (PTC).

Design and setting: We used one discovery and two validation cohorts to screen out aberrant metabolic genes in DDTC, and further used The Cancer Genome Atlas (TCGA) cohort to search for independent risk factors for the low-differentiated phenotype of PTC as a signature of dedifferentiation. The prediction of the signature for DDTC was validated in the TCGA cohort and the combined Gene Expression Omnibus cohort. We also analyzed the correlations of the signature risk score with clinicopathological features of PTC. Gene set enrichment analyses were performed in the TCGA cohort.

Results: Significant enrichment of metabolic pathways correlated with differentiation status of PTC. A signature of metabolic genes including LPCAT2, ACOT7, HSD17B8, PDE8B, and ST3GAL1 was discovered and validated across three cohorts. The signature was not only predictive of DDTC but also significantly associated with BRAFV600E mutation (P < 0.001), T3/T4 stage (P < 0.001), extrathyroidal extension (P < 0.001), lymph node metastasis (P < 0.001), and tumor/lymph node/metastasis III/IV stage (P < 0.001) in PTC. Downregulations of LPCAT2 expression (P = 0.009) and ST3GAL1 expression (P = 0.005) increased risks of decreased disease-free survival for patients. Furthermore, the signature was implicated in a number of oncogenic biological pathways.

Conclusions: Our findings suggest that metabolic deregulations mediate dedifferentiation of PTC, and that the metabolic gene signature can be used as a biomarker for DDTC.

Copyright © 2019 Endocrine Society.

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18
Toxicology
. 2019 Sep 1;425:152252. doi: 10.1016/j.tox.2019.152252. Epub 2019 Jul 23.
Cadmium Exposure Induces Pancreatic β-Cell Death via a Ca 2+-triggered JNK/CHOP-related Apoptotic Signaling Pathway
Cheng-Chin Huang 1, Chun-Ying Kuo 2, Ching-Yao Yang 3, Jui-Ming Liu 4, Ren-Jun Hsu 5, Kuan-I Lee 1, Chin-Chuan Su 2, Chin-Ching Wu 6, Ching-Ting Lin 7, Shing-Hwa Liu 8, Chun-Fa Huang 9
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PMID: 31348969 DOI: 10.1016/j.tox.2019.152252
Abstract
Cadmium (Cd) is known to be ranked the 7th hazardous substance in the Substance Priority List by Agency for Toxic Substances and Disease Registry. The experimental and epidemiological data have suggested that Cd is linked to the development of diabetes mellitus (DM). The molecular mechanism of Cd on the pancreatic β-cell cytotoxicity still remains unclear. Evidence has pointed toward that Ca2+ is an important regulator of toxic insult-induced β-cell cytotoxicity. The role of Ca2+ in the Cd-induced β-cell cytotoxicity is still unknown. In this study, we found that Cd exposure significantly inhibited insulin secretion and cell viability in the pancreatic β-cell-derived RIN-m5F cells. Cd exposure induced apoptotic events, including the increased populations of apoptotic cells and sub-G1 hypodiploid cells, and caspase-3/-7/-9 and poly (ADP-ribose) polymerase (PARP) activation, which largely depended on the activation of c-Jun N-terminal kinase (JNK) and C/EBP homologous protein (CHOP). Transfection with siRNAs for JNK and CHOP or pretreatment with specific pharmacological inhibitor of JNK (SP600125) in β-cells effectively prevented the Cd-induced insulin secretion dysfunction and apoptosis. JNK-specific siRNA dramatically suppressed Cd-induced JNK phosphorylation and CHOP protein expression, but JNK phosphorylation could not be inhibited by CHOP-specific siRNA. Furthermore, Cd exposure significantly increased the intracellular calcium ([Ca2+]i) levels. Buffering the Ca2+ response with BAPTA/AM effectively abrogated the Cd-induced [Ca2+]i elevation, insulin secretion dysfunction, apoptosis, and protein expression of JNK phosphorylation and CHOP activation. Taken together, these findings demonstrated that Cd exposure exerts β-cell death via a [Ca2+]i-dependent JNK activation-activated downstream CHOP-related apoptotic signaling pathway.

Keywords: Apoptosis; C/EBP homologous protein (CHOP); Cadmium; Intracellular calcium; c-Jun N-terminal kinase (JNK); β-cells.

Copyright © 2019 Elsevier B.V. All rights reserved.

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19
J Tissue Eng Regen Med
. 2019 May;13(5):835-845. doi: 10.1002/term.2835. Epub 2019 Apr 9.
Collagen Sponge Scaffolds Containing Growth Factors for the Functional Regeneration of Tracheal Epithelium
Ryosuke Nakamura 1, Tatsuya Katsuno 1, Morimasa Kitamura 1, Masaru Yamashita 1, Takuya Tsuji 1, Ryo Suzuki 1, Yo Kishimoto 1, Atsushi Suehiro 1, Ichiro Tateya 1, Tatsuo Nakamura 2, Koichi Omori 1
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PMID: 30808067 DOI: 10.1002/term.2835
Abstract
Tracheal epithelia have barrier and mucociliary clearance functions that prevent invasion of extraneous particles and infectious materials. Hence, following tracheal reconstructions, functional and morphological regeneration of epithelia is required to prevent respiratory declines and infectious diseases. Although growth factors (GFs) promote the regeneration of tracheal epithelial morphologies, it remains unclear whether tracheal grafts containing GFs are beneficial for regeneration of tracheal epithelial functions. Thus, we fabricated collagen sponge scaffolds containing insulin-like GF-1 (IGF-1) and the basic fibroblast, hepatocyte, and epidermal GFs (bFGFs, HGFs, and EGFs, respectively), and we evaluated the effects of the grafts on the functional regeneration of tracheal epithelia. Partial tracheal defects were imposed surgically, and collagen sponges containing IGF-1, bFGF, HGF, or EGF were then transplanted to defect sites. Subsequent immunofluorescence studies suggested that EGF and bFGF contribute to regular distributions of tight junction molecules, and tracer permeability assays suggested that EGF and bFGF promote regeneration of barrier function. Increased ciliogenesis was also observed using scanning electron microscopy in reconstructed regions treated with EGF- and bFGF-supplemented collagen sponges. However, bFGF-supplemented collagen sponges led to greater microsphere transport than did EGF-supplemented sponges. The present data suggested that collagen sponge scaffold containing bFGF promotes functional regeneration of tracheal epithelial tissues.

Keywords: EGF; airway; bFGF; barrier function; cilia; reconstruction; tight junction.

© 2019 John Wiley & Sons, Ltd.

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20
Int Forum Allergy Rhinol
. 2019 Sep;9(9):1046-1053. doi: 10.1002/alr.22379. Epub 2019 Jul 17.
Sinonasal Mucoepidermoid Carcinoma: A Review of the National Cancer Database
Vasiliki Triantafillou 1, Ivy W Maina 1, Edward C Kuan 2, Michael A Kohanski 1, Charles C Tong 1, Neil N Patel 1, Ryan M Carey 1, Alan D Workman 1, James N Palmer 1, Nithin D Adappa 1, Jason A Brant 1
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Affiliations
1Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
2Department of Otolaryngology-Head and Neck Surgery, Irvine Medical Center, University of California, Orange, CA.
PMID: 31314958 DOI: 10.1002/alr.22379
Abstract
Background: Primary sinonasal mucoepidermoid carcinoma (SN-MEC) is a malignancy arising from seromucinous glands of the nasal cavity and paranasal sinuses. Given its rarity, few large-scale studies have been performed. In this study we describe the incidence and determinants of survival of patients with SN-MEC leveraging the National Cancer Database (NCDB).

Methods: This was a retrospective, population-based cohort study of patients diagnosed with SN-MEC between 2004 and 2012 within the NCDB. The main outcome measure was overall survival (OS).

Results: A total of 164 patients were identified. The cohort was composed of 47.6% males. Mean age at diagnosis was 59.7 years. The maxillary sinus was the most common primary site, accounting for 45.7% of cases. Eleven percent of patients presented with nodal disease, whereas 2.1% had distant metastases. Stage IV disease was seen in 30.4% of cases. A total of 79.8% of the patients underwent surgery, 61.0% received radiation therapy, and 15.1% had chemotherapy. OS at 1, 2, and 5 years was 83%, 77.0%, and 57%, respectively. On multivariate analysis, Medicaid insurance status (hazard ratio [HR], 7.29; 95% confidence interval [CI], 1.74-30.57), advanced tumor size (HR, 4.94; 95% CI, 1.19-20.5), and advanced nodal disease (N1: HR, 9.48; 95% CI, 1.66-54.23; N2B: HR, 19.3; 95% CI, 1.07-350.64) were associated with worse OS.

Conclusion: Mucoepidermoid carcinoma is the most common salivary gland malignancy but a rare sinonasal malignancy, with 5-year survival for SN-MEC approximating 50%. A significant proportion of patients present with advanced disease. Both socioeconomic factors and tumor characteristics are associated with survival.

Keywords: NCDB; National Cancer Database; sinonasal carcinoma; sinonasal mucoepidermoid carcinoma; survival.

© 2019 ARS-AAOA, LLC.

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21
Int Forum Allergy Rhinol
. 2019 Sep;9(9):977-985. doi: 10.1002/alr.22357. Epub 2019 Jul 31.
Olfactory Dysfunction Persists After Smoking Cessation and Signals Increased Cardiovascular Risk
Jesse K Siegel 1, Kristen E Wroblewski 2, Martha K McClintock 3, Jayant M Pinto 4
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PMID: 31365791 PMCID: PMC6730657 (available on 2020-09-01) DOI: 10.1002/alr.22357
Free PMC article
Abstract
Background: Olfaction plays a critical role in health and function in older adults, and impaired sense of smell is a strong predictor of morbidity and mortality. Smoking cigarettes causes olfactory impairment, but the mechanism of damage and ability to recover after cessation are unknown. We investigated the relationship between time since quitting and olfactory dysfunction in order to elucidate the mechanism(s) by which smoking damages the olfactory system and to inform patient counseling.

Methods: Using longitudinal data from the National Social Life Health and Aging Project (n = 3528 older adults, including 1526 former smokers), we analyzed the association between odor identification performance and time since smoking cessation using multivariate ordinal logistic regression, adjusting for cognition and demographic variables. To test whether vascular disease plays a role, we also assessed the relationship between olfactory decline and incidence of heart attack and heart disease.

Results: Former smokers who quit ≤15 years before testing had significantly impaired olfaction compared to never smokers (p = 0.04), but those who quit >15 years prior did not. Olfactory decline over 5 years showed modest evidence toward predicting increased incidence of heart attack or heart disease (p = 0.08).

Conclusion: Olfactory impairment in smokers persists 15 years after quitting, which is consistent with a vascular mechanism of impairment. Indeed, olfactory decline is a predictor of the development of cardiovascular disease. Taken together, these data suggest that olfactory loss may be a useful sign of underlying vascular pathology. Further investigation of olfactory loss as an early biomarker for cardiovascular disease is warranted.

Keywords: aging; atherosclerosis; heart disease; myocardial infarction; smell; smoking cessation; tobacco.

© 2019 ARS-AAOA, LLC.

Conflict of interest statement
Financial disclosures/conflicts of interest:

None

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22
Head Neck
. 2019 Jan;41(1):177-184. doi: 10.1002/hed.25506. Epub 2018 Dec 7.
Depth of Invasion as a Predictor of Nodal Disease and Survival in Patients With Oral Tongue Squamous Cell Carcinoma
Samantha Tam 1, Moran Amit 1, Mark Zafereo 1, Diana Bell 2, Randal S Weber 1
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PMID: 30537401 DOI: 10.1002/hed.25506
Abstract
Background: Depth of invasion (DOI) in oral cavity cancer is important in determining prognosis. This study aims to determine optimal cut-points of DOI for detection of occult disease and survival.

Methods: A retrospective cohort study was completed of previously untreated early stage lateral oral tongue cancer. DOI cut-points were computed. Multiple logistic regression and multivariate Cox proportional hazards models were used to assess predictors of occult nodal disease and overall survival (OS) and disease-specific survival (DSS).

Results: Occult nodal disease was found in 55 (26%) of the 212 patients. DOI of 7.25 mm was most predictive for occult nodal disease and 8 mm for OS and DSS. DOI was an independent predictor of OS and DSS.

Conclusion: The optimal DOI cut-point for detection of occult nodal metastasis was 7.25 and 8 mm for OS and DSS at 5 years. DOI is an independent predictor of OS and DSS.

Keywords: lymph node excision; mouth neoplasms; prognosis; squamous cell carcinoma; tongue neoplasms.

© 2018 Wiley Periodicals, Inc.

Cited by 4 articles
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23
Int Forum Allergy Rhinol
. 2019 Sep;9(9):1063-1068. doi: 10.1002/alr.22368. Epub 2019 Jul 1.
Transnasal Prelacrimal Approach to the Inferior Intraconal Space: A Feasibility Study
Lifeng Li 1 2, Nyall R London Jr 2 3 4, Samuel Silva 5, Daniel Prevedello 2 5, Ricardo L Carrau 2 5
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Affiliations
1Department of Otolaryngology-Head & Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
2Department of Otolaryngology-Head & Neck Surgery, The James Cancer Hospital at the Wexner Medical Center of The Ohio State University, Columbus, OH.
3Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD.
4National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH), Bethesda, MD.
5Department of Neurological Surgery, The James Cancer Hospital at the Wexner Medical Center of The Ohio State University, Columbus, OH.
PMID: 31261443 DOI: 10.1002/alr.22368
Abstract
Background: Endonasal access to the inferomedial and inferolateral intraconal space via the orbital floor has not been reported. The primary purpose of this study was to assess the feasibility of accessing the inferior intraconal space through the orbital floor via a transnasal prelacrimal approach. Secondarily, it aims to highlight anatomical relationships of neurovascular structures in this space, as a requirement to prevent complications.

Methods: Six cadaveric heads (12 sides) were dissected using a transnasal prelacrimal approach. The orbital floor, medial to the infraorbital canal, was removed and the periorbita opened to expose the inferior rectus muscle. The inferomedial and inferolateral intraconal space was accessed alongside the medial and lateral border of inferior rectus muscle, respectively. Various anatomical relationships of adjacent neurovascular structures were recorded, and the distances among the recti muscles and optic nerve were also measured.

Results: The infraorbital nerve is located at the inferolateral aspect of inferior rectus muscle. In the inferomedial intraconal space, we identified the inferomedial muscular trunk of the ophthalmic artery, optic nerve, and branches of the oculomotor nerve; whereas the inferolateral intraconal space contained the inferolateral muscular trunk of ophthalmic artery, branches of the oculomotor and nasociliary nerve, and abducens nerve. Distances from the medial, inferior, and lateral recti muscles to the optic nerve were (mean ± standard deviation) 4.70 ± 1.18 mm, 5.60 ± 0.93 mm, and 7.98 ± 1.99 mm, respectively. Distances from the inferior rectus muscle to the inferior borders of medial and lateral recti muscles were 4.45 ± 1.23 mm and 8.77 ± 1.80 mm.

Conclusion: It is feasible to access the inferior intraconal space through the orbital floor via a transnasal prelacrimal approach. The access may be subdivided into inferomedial and inferolateral corridors according to the entry point at the medial or lateral border of the inferior rectus muscle. Neurovascular structures in the inferior intraconal space are visualized directly, which should enhance their preservation.

Keywords: inferior rectus muscle; intraconal space; maxillary sinus; orbital floor; prelacrimal approach.

© 2019 ARS-AAOA, LLC.

Cited by 1 article27 references
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24
J Autoimmun
. 2019 Feb;97:29-39. doi: 10.1016/j.jaut.2018.10.005. Epub 2018 Nov 9.
Changes in the Composition of the Upper Respiratory Tract Microbial Community in Granulomatosis With Polyangiitis
Peter Lamprecht 1, Nicole Fischer 2, Jiabin Huang 3, Lia Burkhardt 4, Marc Lütgehetmann 5, Fabian Arndt 6, Ida Rolfs 7, Anja Kerstein 8, Christof Iking-Konert 9, Martin Laudien 10
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PMID: 30420263 DOI: 10.1016/j.jaut.2018.10.005
Free article
Abstract
Dysbiosis¸ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of many chronic inflammatory and autoimmune diseases. To assess the composition of the microbial upper respiratory tract (URT) community in patients with granulomatosis with polyangiitis (GPA), we used culture-independent high-throughput methods. In this prospective clinical study, nasal swabs were collected from patients with GPA, patients with rheumatoid arthritis (RA, disease control), and healthy controls. Nasal bacterial taxa were assessed using V3-V4 region 16S rRNA amplicon sequencing. Staphylococcus aureus, Haemophilus influenza, and entero- and rhinoviruses were detected using qPCR. Unbiased metagenomic RNA sequencing (UMERS) was performed in a subset of samples to determine the relative abundance of bacterial, fungal, and viral species. A trend toward reduced microbiome diversity was detected in GPA samples compared with healthy controls. The abundance of bacterial taxa and microbial richness were significantly decreased in GPA samples compared with RA samples. The relative abundance of bacterial families shifted, with increased Planococcaceae and decreased Moraxellaceae, Tissierellaceae, Staphylococcaceae, and Propionibacteriaceae in GPA and RA. Further, decreased abundance of Corynebacteriaceae, and Aerococcaceae was observed in GPA samples. Significantly more colonization of S. aureus was seen in the nasal microbiome of GPA compared with RA and healthy control samples. H. influenzae colonization was also observed in GPA samples. UMERS detected the presence of rhinoviral sequences in some GPA samples. Thus, our study uncovered changes in the URT microbial composition in patients with GPA and RA, suggesting that both immunosuppression and disease background affect the URT microbiome. Complex alterations of host-microbiome interactions in the URT could influence chronic endonasal inflammation in GPA.

Keywords: ANCA; ANCA-associated vasculitis; Autoimmune disease; Granulomatosis with polyangiitis; Microbiome; Upper respiratory tract.

Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cited by 4 articles
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25
Otol Neurotol
. 2019 Aug;40(7):957-964. doi: 10.1097/MAO.0000000000002284.
Prognostic Factors of Long-Term Hearing Preservation in Small and Medium-Sized Vestibular Schwannomas After Microsurgery
Zirong Huo 1 2 3, Jianqing Chen 1 2 3, Zhaoyan Wang 1 2 3, Zhihua Zhang 1 2 3, Hao Wu 1 2 3
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PMID: 31058754 DOI: 10.1097/MAO.0000000000002284
Abstract
Objective: The authors evaluated the long-term hearing outcomes of patients with vestibular schwannoma (VS) to explore appropriate surgical treatment.

Study design: Retrospective study.

Setting: Tertiary referral center.

Patients: A total of 138 patients diagnosed with small and medium-sized VS with serviceable hearing from January 2006 to December 2015.

Interventions: All patients underwent microsurgery via retrosigmoid (RSA) or middle cranial fossa approach (MFA) and were followed up for over 2 years.

Main outcome measures: Pre- and postoperative hearing, including pure tone audiometry, speech discrimination score, and auditory brainstem response (ABR), were analyzed.

Results: The mean tumor size and volume were 16.6 ± 3.4 mm and 1711.8 ± 918.5 mm, respectively. Preoperative hearing levels were Class A in 42, Class B in 67, and Class C in 29 patients. Patients with a tumor from the superior vestibular nerve (SVN) had better hearing at diagnosis. Postoperative hearing levels were Class A, B, C, and D for 28, 17, 32, and 61 patients. Hearing outcomes were significantly better in patients with normal intraoperative I wave on ABR. Hearing loss within 6 months had a positive effect on postoperative hearing. Better preoperative hearing and tumors from SVN were correlated with better postoperative hearing outcomes. Tumor size, cystic variation, or extension to the fundus of internal auditory canal had no influence on hearing preservation.

Conclusions: Better preoperative hearing, shorter hearing loss period, tumors from SVN, and normal intraoperative I wave are prognostic factors for serviceable hearing. RSA and MFA are effective and safe for tumor removal and hearing preservation.

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26
Comparative Study Int Forum Allergy Rhinol
. 2019 Sep;9(9):953-957. doi: 10.1002/alr.22386. Epub 2019 Jul 23.
Sinus Irrigation Penetration After Balloon Sinuplasty vs Functional Endoscopic Sinus Surgery in a Cadaveric Model
Oliver Gantz 1, Arman Danielian 2, Alison Yu 2, Elisabeth H Ference 1, Edward C Kuan 3, Bozena Wrobel 1
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PMID: 31336043 DOI: 10.1002/alr.22386
Abstract
Background: Nasal irrigation is a cornerstone of treatment for chronic rhinosinusitis. The purpose of this study was to quantify irrigation penetration to the sinuses following balloon sinuplasty and functional endoscopic sinus surgery (FESS).

Methods: Balloon sinuplasty followed by FESS was performed on 4 cadaver heads. Using a high-volume, high-flow bottle, each head was irrigated with fluorescein-dyed water prior to and following each procedure, and recorded by rigid endoscopy through trephinations. Three blinded, fellowship-trained rhinologists reviewed videos and scored the extent of staining (using an accepted scale of 0 to 3) for each site.

Results: The mean score prior to any procedure was maxillary sinus 1.67, frontal sinus 1.29, and nasal cavity 1.71. After balloon sinuplasty the mean was maxillary 2.25, frontal 2.04, and nasal cavity 2.17. After FESS the mean was maxillary 2.75, frontal 2.08, and nasal cavity 2.63. There was a statistically significant increase for both maxillary (p = 0.005) and frontal sinuses (p = 0.006) following balloon sinuplasty. There was a statistically significant increase following FESS compared to balloon for the maxillary sinus (p = 0.003), but not the frontal sinus (p = 0.96). Interrater reliability was good, with Cronbach's alpha of 0.85.

Conclusion: Irrigation improved in all sinuses following balloon sinuplasty and FESS. There was further improvement to the maxillary sinus after FESS; however, there was no difference in irrigation to the frontal sinuses following FESS compared to balloon sinuplasty. Extended frontal sinus approaches such as the Modified Lothrop procedure should be considered if more extensive access for irrigation is required.

Keywords: endoscopy; frontal sinus; maxillary sinus; nasal lavage; paranasal sinuses.

© 2019 ARS-AAOA, LLC.

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27
Eur Arch Otorhinolaryngol
. 2019 Dec;276(12):3513-3517. doi: 10.1007/s00405-019-05626-y. Epub 2019 Sep 7.
The Association Between Video-Nystagmography and Sensory Organization Test of Computerized Dynamic Posturography in Patients With Vestibular Symptoms
Shany G Gofrit 1 2, Ophir Ilan 3 4, Yulia Mayler 4, Ron Eliashar 3 4, Tali Bdolah-Abram 3, Marrigje Aagje de Jong 4, Menachem Gross 5 6
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PMID: 31494697 DOI: 10.1007/s00405-019-05626-y
Abstract
Objective: Vertigo is a complex symptom which imposes diagnostic and treatment challenges. Laboratory evaluation of vertigo includes video-nystagmography (VNG) and computerized dynamic posturography (CDP) for the evaluation of different aspects of this complaint. There are vague indications for each test and potential disagreements between them. The aim of this study is to examine the association between the test results of the VNG and sensory organization test (SOT) of CDP in patients referred for both vestibular tests.

Methods: Retrospective data regarding 56 patients age 17-82 years were collected. Patients suffered vestibular complaints and were referred for VNG and CDP evaluation on the same day. The level of agreement between VNG (including caloric test) and the vestibular input of the SOT for each patient was calculated.

Results: Among the study group, 10 showed abnormal caloric test results, of which 3 (5.4%) had normal vestibular input in the SOT, and 7 (12.5%) had impaired input (p = 0.724). Spontaneous nystagmus was recorded in 13 patients by VNG, of which 2(3.6%) had normal vestibular input and 11(19.6%) had impaired vestibular input (p = 0.056).

Conclusions: This study shows no statistically significant association between the VNG test and SOT test results. Our results emphasize the difference between the tested aspects in each laboratory test, and the need to define specific indications for each of them. There is a marginally significant association between impaired vestibular input and spontaneous nystagmus, demonstrating the non-localizing nature of this sign.

Keywords: Computerized dynamic posturography; Dizziness; Sensory organization test; Vertigo; Video-nystagmography.

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28
Cancer
. 2019 Nov 1;125(21):3738-3748. doi: 10.1002/cncr.32366. Epub 2019 Jul 9.
Tumor Characteristics Associated With Engraftment of Patient-Derived Non-Small Cell Lung Cancer Xenografts in Immunocompromised Mice
Yungchang Chen 1 2, Ran Zhang 1, Li Wang 1, Arlene M Correa 1, Apar Pataer 1, Yi Xu 1, Xiaoshan Zhang 1, Chenghui Ren 1, Shuhong Wu 1, Qing H Meng 3, Junya Fujimoto 4, Vanessa B Jensen 5, Mara B Antonoff 1, Wayne L Hofstetter 1, Reza J Mehran 1, George Pisimisis 1, David C Rice 1, Boris Sepesi 1, Ara A Vaporciyan 1, Garrett L Walsh 1, Stephen G Swisher 1, Jack A Roth 1, John V Heymach 6, Bingliang Fang 1
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PMID: 31287557 DOI: 10.1002/cncr.32366
Abstract
Background: Patient-derived xenograft (PDX) models increasingly are used in translational research. However, the engraftment rates of patient tumor samples in immunodeficient mice to PDX models vary greatly.

Methods: Tumor tissue samples from 308 patients with non-small cell lung cancer were implanted in immunodeficient mice. The patients were followed for 1.5 to approximately 6 years. The authors performed histological analysis of PDXs and some residual tumor tissues in mice with failed PDX growth at 1 year after implantation. Quantitative polymerase chain reaction and enzyme-linked immunoadsorbent assay were performed to measure the levels of Epstein-Barr virus genes and human immunoglobulin G in PDX samples. Patient characteristics were compared for PDX growth and overall survival as outcomes using Cox regression analyses. Disease staging was based on the 7th TNM staging system.

Results: The overall engraftment rate for PDXs from patients with non-small cell lung cancer was 34%. Squamous cell carcinomas had a higher engraftment rate (53%) compared with adenocarcinomas. Tumor samples from patients with stage II and stage III disease and from larger tumors were found to have relatively high engraftment rates. Patients whose tumors successfully engrafted had worse overall survival, particularly those individuals with adenocarcinoma, stage III or stage IV disease, and moderately differentiated tumors. Lymphoma formation was one of the factors associated with engraftment failure. Human CD8-positive and CD20-positive cells were detected in residual samples of tumor tissue that failed to generate a PDX at 1 year after implantation. Human immunoglobulin G was detected in the plasma of mice that did not have PDX growth at 14 months after implantation.

Conclusions: The results of the current study indicate that the characteristics of cancer cells and the tumor immune microenvironment in primary tumors both can affect engraftment of a primary tumor sample.

Keywords: neoplasia; non-small cell lung cancer (NSCLC); tumor microenvironment tumor models; xenografts.

© 2019 American Cancer Society.

Cited by 1 article42 references
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29
J Infect Dis
. 2019 Sep 13;220(8):1312-1324. doi: 10.1093/infdis/jiz318.
High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach
Sarah Mollerup 1, Maria Asplund 1, Jens Friis-Nielsen 2, Kristín Rós Kjartansdóttir 1, Helena Fridholm 1, Thomas Arn Hansen 1, José Alejandro Romero Herrera 2 3, Christopher James Barnes 1, Randi Holm Jensen 1, Stine Raith Richter 1, Ida Broman Nielsen 1, Carlotta Pietroni 1, David E Alquezar-Planas 1, Alba Rey-Iglesia 1, Pernille V S Olsen 1, Ewa Rajpert-De Meyts 4, Line Groth-Pedersen 5, Christian von Buchwald 6, David H Jensen 6, Robert Gniadecki 7, Estrid Høgdall 8, Jill Levin Langhoff 8, Imre Pete 9, Ildikó Vereczkey 9, Zsolt Baranyai 10, Karen Dybkaer 11, Hans Erik Johnsen 12, Torben Steiniche 13, Peter Hokland 14, Jacob Rosenberg 15, Ulrik Baandrup 16, Thomas Sicheritz-Pontén 2 17, Eske Willerslev 1, Søren Brunak 2 3, Ole Lund 2, Tobias Mourier 1, Lasse Vinner 1, Jose M G Izarzugaza 2, Lars Peter Nielsen 18, Anders Johannes Hansen 1
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PMID: 31253993 PMCID: PMC6743825 DOI: 10.1093/infdis/jiz318
Free PMC article
Abstract
Background: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data.

Methods: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads.

Results: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found.

Conclusions: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.

Keywords: cancer; enrichment; human; virome.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Cited by 1 article50 references4 figures
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30
Multicenter Study Int Forum Allergy Rhinol
. 2019 Sep;9(9):1000-1009. doi: 10.1002/alr.22374. Epub 2019 Jun 27.
Socioeconomic Status Impacts Postoperative Productivity Loss and Health Utility Changes in Refractory Chronic Rhinosinusitis
Daniel M Beswick 1, Jess C Mace 2, Zachary M Soler 3, Luke Rudmik 4, Jeremiah A Alt 5, Kristine A Smith 6, Kara Y Detwiller 2, Vijay R Ramakrishnan 1, Timothy L Smith 2
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PMID: 31246360 PMCID: PMC6718304 (available on 2020-09-01) DOI: 10.1002/alr.22374
Free PMC article
Abstract
Background: Social determinants of health can have a substantial impact on treatment outcomes. Prior study has shown that socioeconomic status influences the likelihood of improvement in quality-of-life (QOL) following endoscopic sinus surgery (ESS). However, the impact of socioeconomic factors on changes in productivity loss and health utility after ESS remains unknown.

Methods: Adult patients (≥18 years of age) with chronic rhinosinusitis (CRS) who underwent ESS were prospectively enrolled into a multi-institutional cohort study. Productivity losses were calculated using the human capital approach and monetized using U.S. government-estimated wage rates. Health utility values (HUVs) were derived from the Medical Outcomes Study Short-Form-12 survey using University of Sheffield algorithms. Independent socioeconomic factors of interest included: age, gender, ethnicity, insurance status, educational attainment, and household income categorized via the Thompson-Hickey model.

Results: A total of 229 patients met inclusion criteria, and 163 (71%) provided postoperative follow-up. All subjects reported significant, within-subject improvement in both mean monetized productivity loss (p < 0.001) and HUV postoperatively (p < 0.001). Using paired sample statistics, patients with lowest income (≤$25,000/year) and with Medicare insurance did not report significant improvement in productivity loss (p ≥ 0.112) or HUV (p ≥ 0.081), although sample size limitations may have contributed to this finding. Patients in higher income tiers ($25,001 to $100,000/year and $100,001+/year) and those with employer-provided/private health insurance reported significant postoperative improvements in productivity loss and HUV (all p ≤ 0.003).

Conclusion: Socioeconomic factors, including income and insurance provision, may impact improvements in productivity loss and HUV following ESS. Further research to validate these findings, ascertain mechanisms behind these results, and improve these outcomes is warranted.

Trial registration: ClinicalTrials.gov NCT02720653.

Keywords: chronic disease; endoscopic sinus surgery; evidence-based medicine; outcome assessment (health care); patient reported outcome measure; quality of life; sinusitis.

© 2019 ARS-AAOA, LLC.

Conflict of interest statement
Potential Conflicts of Interest: None

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31
Cell Cycle
. 2019 May;18(9):949-962. doi: 10.1080/15384101.2019.1598727. Epub 2019 Apr 23.
Fibroblasts Rescue Oral Squamous Cancer Cell From Metformin-Induced Apoptosis via Alleviating Metabolic Disbalance and Inhibiting AMPK Pathway
Zhuoyuan Zhang 1 2, Xiao Liang 3, Yaping Fan 1, Zhenjie Gao 4, Laurence A Bindoff 3 5, Daniela Elena Costea 6 7, Longjiang Li 1 2
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PMID: 31014173 PMCID: PMC6527302 DOI: 10.1080/15384101.2019.1598727
Free PMC article
Abstract
Metformin is an antidiabetic drug widely used for the treatment of type 2 diabetes. Growing evidence suggests that it may exert antitumor effects in vivo and in vitro. However, even with the promising potency on defeating cancer cells, the pre-clinical and epidemiological studies of metformin on various kinds of cancers are not satisfactory, and the reasons and underlying mechanisms remain unknown. Since cancer is a complex system, dependent on a promoting microenvironment, we hypothesize that the interactions between cancer cells and their neighborhood fibroblasts are essential for metformin resistance. To test this, we used a cell co-culture model closely mimicking the in vivo interactions and metabolic exchanges between normal stromal cells (NOFs) and oral squamous cancer cells (OSCC). Here we show that while metformin can significantly inhibit cell growth and induce apoptosis of OSCC cultured alone in a dose-dependent manner through activating p-AMPKT172 and modulating Bcl-2, Bax, and cleaved PARP. However, when OSCC are co-cultured with NOFs the metformin effects on OSCC cells are annihilated. NOFs are rescuing OSCC from metformin - induced apoptosis, at least partially, through inhibiting the activity of AMPK and PARP, maintaining mitochondrial membrane potential and increasing the oxidative stress. Our results indicate that metformin effects on oral cancer cells are modulated by the microenvironment and that this has to be taken into consideration in the context of developing a new combination of drugs for oral cancer treatment.

Keywords: Metabolic reprogramming; Metformin; ROS; apoptosis; autophagy; co-culture.

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32
Otol Neurotol
. 2019 Aug;40(7):878-882. doi: 10.1097/MAO.0000000000002257.
Preservation of Vestibular Function and Residual Hearing After Round Window Cochlear Implantation
Konrad Johannes Stuermer 1, Heinz Dieter Kluenter 1, Ruth Lang-Roth 1, David Schwarz 1, Karl-Bernd Hüttenbrink 1, Andreas Anagiotos 2
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PMID: 31219963 DOI: 10.1097/MAO.0000000000002257
Abstract
Objective: To examine the possible correlation between the loss of short-term residual hearing and vestibular function after cochlear implantation (CI).

Study design: Retrospective patient review.

Setting: Academic tertiary referral center.

Patients: One hundred twenty patients with normal vestibular function (VF) in the caloric testing and residual hearing (RH) at the frequencies 250, 500, and 1000 Hz on the surgery side between 2008 and 2016 were included in the study.

Intervention: Primary CI on the first side via round window with a conventional full-length electrode.

Main outcome measures: Changes of RH and VF 7 weeks after surgery were analyzed. Preservation of RH was defined as measurable postoperative thresholds at the frequencies 250, 500, and 1000 Hz in the pure-tone audiogram. Preservation of the VF after CI was assessed both by an absolute and relative threshold in the caloric testing.

Results: Seven weeks after implantation, the preservation of RH was achieved in 52 (43.3 %) patients and the preservation of VF in 95 (79.2 %) patients on the operated side. There was no significant statistical correlation between these two parameters.

Conclusion: The loss of RH was more than twice as frequent as the loss of VF. However, no statistical correlation between the failure of the two inner ear functions was found. The exact causes are still unknown, but our data could give an indication that there may be different underlying pathomechanisms.

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33
Eur Arch Otorhinolaryngol
. 2019 Dec;276(12):3477-3486. doi: 10.1007/s00405-019-05625-z. Epub 2019 Sep 9.
Evaluation of Virtual Surgical Planning Systems and Customized Devices in Fibula Free Flap Mandibular Reconstruction
Jacques Blanc 1, Carine Fuchsmann 2, Veronica Nistiriuc-Muntean 3, Pierre Jacquenot 4, Pierre Philouze 2, Philippe Ceruse 2 5
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PMID: 31501989 DOI: 10.1007/s00405-019-05625-z
Abstract
Purpose: The purpose of this study was to evaluate the accuracy of virtual planning using customized surgical devices (VP3D) in fibula free flap mandibular reconstruction.

Methods: Fourteen patients received VP3D and 16 patients underwent conventional surgery (CS). Virtual planning was compared to postoperative scans using cephalometric and three-dimensional (3D) measurements. Operative times of both VP3D and CS groups were compared.

Results: Comparisons of cephalometric measurements revealed no significant difference between virtual planning and postoperative scans. 3D analysis demonstrated a high level of virtual planning accuracy. In the VP3D group, total operative time gain was 88 min (p < 0.001) and total ischemia time gain was 36 min (p = 0.04).

Conclusion: Virtual surgical planning using customized devices enables 'tailored' surgery that is accurate and reliable and results in operative and ischemia time gain.

Clinical trial: NCT03869723.

Keywords: Fibula flap; Mandibular defect; Pre-bent plate; Reconstruction; Virtual planning.

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34
Endocrine
. 2019 Nov;66(2):278-287. doi: 10.1007/s12020-019-02000-0. Epub 2019 Jul 12.
Ultrasound Characterization for Thyroid Nodules With Indeterminate Cytology: Inter-Observer Agreement and Impact of Combining Pattern-Based and Scoring-Based Classifications in Risk Stratification
Cesar A Lam 1, Melissa J McGettigan 2, Zachary J Thompson 3, Laila Khazai 4, Christine H Chung 5, Barbara A Centeno 4, Bryan McIver 5, Pablo Valderrabano 5 6
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PMID: 31300961 DOI: 10.1007/s12020-019-02000-0
Abstract
Background: The American Thyroid Association (ATA) sonographic patterns stratify the risk of malignancy of cytologically indeterminate thyroid nodules (ITNs). This study aimed to (1) assess inter-observer agreement for sonographic features and patterns; (2) identify potential sources of disagreement; and (3) evaluate whether the number of suspicious features risk-stratifies non-ATA and high-suspicion patterns.

Methods: Three observers independently reviewed the ultrasound images of 463 ITNs with histological follow-up consecutively evaluated between October 2008 and June 2015 at an academic cancer center. Each observer evaluated individual sonographic features. ATA sonographic patterns were derived from the interpretation of sonographic features. Nodules not fitting into any of the proposed patterns were clustered into a non-ATA pattern.

Results: The inter-observer agreement for ATA sonographic patterns and echogenicity was fair, moderate for margins, good for composition and echogenic foci, and very good for extrathyroidal extension and lymph node metastasis. The interpretation of each sonographic feature was significantly different between observers, and there was complete disagreement in at least one of the features in 104 (22%) nodules. A total of 169 nodules (37%) were classified into the non-ATA pattern. The number of suspicious features allowed risk stratifying nodules with non-ATA and high-suspicion sonographic patterns. Most Non-invasive Follicular Thyroid Neoplasms with Papillary-like Nuclear Features had 0-1 suspicious features and none had >2.

Conclusions: Echogenicity interpretation was the greatest source of disagreement. The number of suspicious features risk-stratifies ITNs with non-ATA or high-suspicion patterns. Future studies attempting to objectivize the interpretation of echogenicity and heterogeneity are needed.

Keywords: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP); Thyroid cancer; Thyroid cytology; Thyroid nodules; Thyroid ultrasound.

Cited by 1 article28 references
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35
Head Neck
. 2019 Jan;41(1):162-169. doi: 10.1002/hed.25493. Epub 2018 Dec 15.
Effect of Radiotherapy on the Chemical Composition of Root Dentin
Lívia Bueno Campi 1, Fabiane Carneiro Lopes 1, Luís Eduardo Silva Soares 2, Alexandra Mussolino de Queiroz 3, Harley Francisco de Oliveira 4, Paulo César Saquy 1, Manoel Damião de Sousa-Neto 1
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PMID: 30552849 DOI: 10.1002/hed.25493
Abstract
Background: The radiotherapy can directly affect the bond strength of the adhesive materials, interfering in the prognosis of restorative treatments, which may be caused by chemical changes in dentin structure.

Methods: Twenty inferior homologues premolars were distributed in 2 groups (in vitro study) (n = 10): nonirradiated and irradiated. The specimens were submitted to the analysis of phosphate (ν1 PO4 3- ;ν2 PO4 3- ;ν4 PO4 3- ), carbonate (ν3 CO3 2- ), amide I, CH2 , amide III, and amide I/III ratio by confocal Raman spectroscopy. Data were submitted to statistical analysis (T test, P < .05).

Results: In intracanal dentin, the irradiated group had lower ν4 PO4 3- values (1.23 ± 0.06) compared to nonirradiated group (1.40 ± 0.18) (P < .05), with no difference for ν1 PO4 3- and ν2 PO4 3 peaks (P > .05). The irradiated (1.56 ± 0.06) had lower carbonate, amide III (1.05 ± 0.19), and amide I/III ratio values (0.19 ± 0.06) compared to nonirradiated group (1.42 ± 0.10, 1.28 ± 0.24, and 0.31 ± 0.10, respectively) (P < .05). For medium dentin irradiated group (1.30 ± 0.12) had lower phosphate values compared to nonirradiated group (1.48 ± 0.22) (P < .05). In cementum, there was no statistical difference between the groups.

Conclusion: The radiotherapy was able to cause changes in ν4 PO4 3- , carbonate, and amide III peaks of root dentin.

Keywords: collagen; confocal Raman spectroscopic; dentin; radiotherapy; tooth root.

© 2018 Wiley Periodicals, Inc.

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36
Otol Neurotol
. 2019 Aug;40(7):965-971. doi: 10.1097/MAO.0000000000002288.
EPO Attenuates Cisplatin-Induced Ototoxicity in HEI-OC1 Auditory Cell Via the Nrf2-ARE Signaling Pathway
Changling Sun 1, Ying Yao 2, Chenwei Zhang 3, Desheng Tong 4, Bingxue Xie 5 2
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PMID: 31135681 DOI: 10.1097/MAO.0000000000002288
Abstract
Hypothesis: Erythropoietin (EPO) may protect against cisplatin-induced ototoxicity in HEI-OC1 auditory cell line.

Background: Cisplatin is a widely used chemotherapeutic agent for the treatment of human solid tumors limited by its high incidence of ototoxicity. Currently, there are no clinical solutions. EPO has been reported to have varieties of neuroprotective effects. However, nothing has yet been reported on its potential to prevent cisplatin ototoxicity in auditory cell lines and possible mechanism.

Methods: HEI-OC1 cells were incubated with 20 μM of cisplatin for 48 hours, after application of various concentrations of EPO for 24 hours. Cell viability was determined using a Cell Counting Kit-8 (CCK-8) assay. Oxidative stress and apoptosis were assessed by reactive oxygen species (ROS) measurement, Hoechst 33258 staining, and flow cytometry (FC). Western blot (WB) and real-time quantitative PCR were used to detect nuclear factor erythroid 2-related factor 2 (Nrf2), NAD (P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), Bcl-2 and Bcl-xl protein and mRNA expression levels.

Results: Pretreatment with 40, 8, and 1.6 ng/mL of EPO for 24 hours before application of 20 μM cisplatin increased cell viability in HEI-OC1 cells. Besides, EPO enhanced the expression of Nrf-2, HO-1, and NQO1. Moreover, upregulation of the expression of Bcl-2 and bcl-xl were also observed.

Conclusion: Our results suggest that EPO alleviates cisplatin-induced ototoxicity by activating Nrf2-ARE signaling.

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37
FASEB J
. 2019 Sep;33(9):10577-10592. doi: 10.1096/fj.201800220RR. Epub 2019 Jun 26.
Down-regulation of ATF1 Leads to Early Neuroectoderm Differentiation of Human Embryonic Stem Cells by Increasing the Expression Level of SOX2
Shang-Chih Yang 1 2, Jan-Jan Liu # 2, Cheng-Kai Wang # 1 2, Yu-Tsen Lin # 2, Su-Yi Tsai 3, Wei-Ju Chen 2, Wei-Kai Huang 2, Po-Wen A Tu 4, Yu-Chen Lin 3, Ching-Fang Chang 2, Chih-Lun Cheng 2, Hsuan Lin 2 4, Chien-Ying Lai 2, Chun-Yu Lin 2, Yi-Hsuan Lee 2, Yen-Chun Chiu 2, Chiao-Ching Hsu 2, Shu-Ching Hsu 5 6, Michael Hsiao 2, Scott C Schuyler 7 8, Frank Leigh Lu 4, Jean Lu 1 2 9 10 11
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PMID: 31242772 PMCID: PMC6704446 (available on 2020-06-26) DOI: 10.1096/fj.201800220RR
Free PMC article
Abstract
We reveal by high-throughput screening that activating transcription factor 1 (ATF1) is a novel pluripotent regulator in human embryonic stem cells (hESCs). The knockdown of ATF1 expression significantly up-regulated neuroectoderm (NE) genes but not mesoderm, endoderm, and trophectoderm genes. Of note, down-regulation or knockout of ATF1 with short hairpin RNA (shRNA), small interfering RNA (siRNA), or clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) was sufficient to up-regulate sex-determining region Y-box (SOX)2 and paired box 6 (PAX6) expression under the undifferentiated or differentiated conditions, whereas overexpression of ATF1 suppressed NE differentiation. Endogenous ATF1 was spontaneously down-regulated after d 1-3 of neural induction. By double-knockdown experiments, up-regulation of SOX2 was critical for the increase of PAX6 and SOX1 expression in shRNA targeting Atf1 hESCs. Using the luciferase reporter assay, we identified ATF1 as a negative transcriptional regulator of Sox2 gene expression. A novel function of ATF1 was discovered, and these findings contribute to a broader understanding of the very first steps in regulating NE differentiation in hESCs.-Yang, S.-C., Liu, J.-J., Wang, C.-K., Lin, Y.-T., Tsai, S.-Y., Chen, W.-J., Huang, W.-K., Tu, P.-W. A., Lin, Y.-C., Chang, C.-F., Cheng, C.-L., Lin, H., Lai, C.-Y., Lin, C.-Y., Lee, Y.-H., Chiu, Y.-C., Hsu, C.-C., Hsu, S.-C., Hsiao, M., Schuyler, S. C., Lu, F. L., Lu, J. Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2.

Keywords: early development; gatekeeper; high-throughput screen.

Conflict of interest statement
The authors thank Dr. Douglas A. Melton (Harvard University, Boston, MA, USA), Dr. Yoshiaki Tsuji (North Carolina State University, Raleigh, NC, USA), Dr. Cheng-Wen Wu (Academia Sinica), Dr. Joanne Jeou-Yuan Chen (Academia Sinica), Dr. Han-Chung Wu (Academia Sinica), Dr. Chih-Cheng Chen (Academia Sinica), Dr. Hung-Chih Kuo (Academia Sinica), and Dr. Ching Hwa Tsai (National Taiwan University) for assistance in this study. The authors also thank Dr. Yu-Chi Chou (RNAi Core Facility, Academia Sinica) and Dr. Sin-Jhong Cheng [Neuroscience Core Facility (AS-CFII-108-106), Academia Sinica] for technical support and the Data Science Statistical Cooperation Center of Academia Sinica (AS-CFII-108-117) for statistical support. This study was supported by the National Health Research Institute (NHRI-EX106-10415SI), the National Science Council (NSC 102-2321-B-001-013, 102-2321-B-039-002, 102-2325-B-039-002, 102-2320-B-008-002, and 102-2311-B-182-004), The Ministry of Health and Welfare (MOHW102-TD-PB-111-NSC105), Chang Gung Memorial Hospital (BMRPC59 and CMRPD1F0353), and the Taiwan Ministry of Science and Technology (103-2321-B-001-064, 104-2320-B-001-005, 104-0210-01-09-02, 105-0210-01-13-01,105-2320-B-001-026-MY2, 106-0210-01-15-02, 107-0210-01-19-01, 107-2320-B-002-026, and AS-Summit-108). The authors declare no conflicts of interest.

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38
Int Forum Allergy Rhinol
. 2019 Sep;9(9):1069-1076. doi: 10.1002/alr.22380. Epub 2019 Jul 19.
Discriminant Analysis Followed by Unsupervised Cluster Analysis Including Exosomal Cystatins Predict Presence of Chronic Rhinosinusitis, Phenotype, and Disease Severity
Michelle M Miyake 1, Alan D Workman 1, Angela L Nocera 1 2, Dawei Wu 3, Sarina K Mueller 4, Kristen Finn 1, Mansoor M Amiji 2, Benjamin S Bleier 1
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PMID: 31322841 DOI: 10.1002/alr.22380
Abstract
Background: Cystatins are epithelial protease inhibitors that participate in sinonasal immunity and inflammation. Nasal mucus-derived exosomes (NMDEs) are small vesicles secreted by epithelial cells that carry protein cargo reflective of their host cell. NMDEs have been used as a noninvasive biomarker source to study chronic rhinosinusitis with nasal polyps (CRSwNP) proteomics with superior sensitivity to whole mucus. The purpose of this study was to noninvasively quantify exosomal cystatins in a heterogenous population to determine their utility in predicting phenotype and disease severity.

Methods: This was an Institutional Review Board-approved study in which NMDEs were purified from 105 patients undergoing sinonasal surgery by ultracentrifugation. Demographic and clinical variables were collected and phenotypes were assigned a priori. Linear discriminant analysis was executed based on normalized Cystatin values as phenotype predictor variables. Unsupervised cluster analysis was performed using Ward's linkage followed by Duda/Hart Je(2)/Je(1) index cluster stopping rules. Analysis of variance (ANOVA), Welch's test, and Fisher's exact tests were used for continuous and categorical variables.

Results: NMDE Cystatin-2 expression segregated by phenotype (mean ± standard error [SEM]): control (23.4 ± 4.2 pg/µg, n = 32); CRS without NP (CRSsNP) (56.6 ± 8.3 pg/µg, n = 33); and CRSwNP (130.5 ± 16.7 pg/µg, n = 40) (p < 0.0001). Seven clusters were identified among patients where the highest NMDE Cystatin-2 levels clustered with asthma, tissue eosinophilia, and aspirin-exacerbated respiratory disease (AERD).

Conclusion: Cystatin levels in NMDEs predict CRS phenotype and disease severity. As a "liquid biopsy," noninvasive NMDE collection offers a promising opportunity to study disease pathophysiology, discriminate disease states, and potentially reveal novel therapeutic targets.

Keywords: chronic rhinosinusitis; cluster analysis; exosome; nasal polyps; sinonasal mucus.

© 2019 ARS-AAOA, LLC.

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39
Int Forum Allergy Rhinol
. 2019 Sep;9(9):1017-1022. doi: 10.1002/alr.22367. Epub 2019 Jun 27.
Central Compartment Involvement in Aspirin-Exacerbated Respiratory Disease: The Role of Allergy and Previous Sinus Surgery
John M DelGaudio 1, Joshua M Levy 1, Sarah K Wise 1
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PMID: 31246375 PMCID: PMC6748623 (available on 2020-09-01) DOI: 10.1002/alr.22367
Free PMC article
Abstract
Background: Evidence for a relationship between allergy and chronic rhinosinusitus with nasal polyps (CRSwNP) is equivocal. Central compartment (CC) atopic disease is a nasal inflammatory condition related to inhalant allergy. CC involvement is common in aspirin-exacerbated respiratory disease (AERD), a subset of CRSwNP, and we hypothesize it is related to allergic status.

Methods: This study was a retrospective analysis of a single-institution database for the January 2016 to February 2019 time period. Data regarding endoscopic CC findings, clinical allergy history, and results of allergy testing were collected. Statistical analysis was performed, with significance set at p < 0.05.

Results: Seventy-two AERD patients met the inclusion criteria. Fifty-nine patients had CC involvement (53 bilateral, 6 unilateral). For patients with documented allergy status, 100% of patients with endoscopic CC disease had clinical allergic rhinitis (AR), and 45 of 48 (93.8%) had positive allergy testing. Thirteen patients had no CC involvement (4 with clinical AR; 3 of 7 with positive allergy testing). CC endoscopic findings in AERD were significantly associated with clinical allergy (p < 0.0001, phi = 0.771). Overall, patients with CC involvement averaged 3.8 surgeries vs 3.2 for those without CC involvement (p = not statistically significant). However, patients with septal involvement averaged 4.2 surgeries vs 2.0 for those without septal involvement (p = 0.004). As the number of sinus surgeries increases, middle turbinate (MT) resection (r = 0.300, p = 0.022) and septal involvement (r = 0.372, p = 0.004) significantly increase. All patients with MT resection had septal disease, whereas none without CC disease had MT resection.

Conclusion: Most AERD patients exhibit AR, and this correlates with CC disease. As the number of surgeries increases, MT resection may predispose to polyposis of the septum.

Keywords: allergic rhinitis; allergy; aspirin-exacerbated respiratory disease; chronic rhinosinusitis; chronic sinusitis; endoscopic sinus surgery; nasal polyp.

© 2019 ARS-AAOA, LLC.

Conflict of interest statement
Potential conflict of interest: J.M.D.: Spirox, grant support; Medtronic, consultant. S.K.W: OptiNose, scientific advisory board; SinopSys Surgical, scientific advisory board; Stryker, consultant; and NeurENT, consultant.

Cited by 1 article
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40
Carcinogenesis
. 2019 Oct 16;40(10):1251-1259. doi: 10.1093/carcin/bgz035.
DIAPH2 Alterations Increase Cellular Motility and May Contribute to the Metastatic Potential of Laryngeal Squamous Cell Carcinoma
M Kostrzewska-Poczekaj 1, E Byzia 1, N Soloch 1, M Jarmuz-Szymczak 1 2, J Janiszewska 1, E Kowal 1, J Paczkowska 1, K Kiwerska 1 3, M Wierzbicka 1 4, A Bartochowska 4, A Ustaszewski 1, G Greczka 4, R Grenman 5, K Szyfter 1, M Giefing 1 4
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PMID: 30793164 DOI: 10.1093/carcin/bgz035
Abstract
Low 5-year survival rate in laryngeal squamous cell carcinoma (LSCC) is to large extent attributable to high rate of recurrences and metastases. Despite the importance of the latter process, its complex genetic background remains not fully understood. Recently, we identified two metastasis-related candidate genes, DIAPH2 and DIAPH3 to be frequently targeted by hemizygous/homozygous deletions, respectively, in LSCC cell lines. They physiologically regulate such processes as cell movement and adhesion, hence we found it as a rationale, to study if tumor LSCC specimens harbor mutations of these genes and whether the mutations are associated with metastasizing tumors. As a proof of concept, we sequenced both genes in five LSCC cell lines derived from lymph node metastases assuming there the highest probability of finding alterations. Indeed, we identified one hemizygous deletion (c.3116_3240del125) in DIAPH2 targeting the FH2 domain. Moreover, we analyzed 95 LSCC tumors (53 N0 and 42 N+) using the Illumina platform and identified three heterozygous single nucleotide variants in DIAPH2 targeting conserved domains exclusively in N+ tumors. By combining these results with cBioPortal data we showed significant enrichment of DIAPH2 mutations (P = 0.036) in N+ tumors. To demonstrate the consequences of DIAPH2 inactivation, CRISPR/Cas9 editing was used to obtain a heterozygous DIAPH2+/- mutant HEK-293T cell line. Importantly, the edited line shows a shift from 'proliferation' to 'migration' phenotype typically observed in metastasizing cells. In conclusion, we report that DIAPH2 alterations are present primarily in metastasizing specimens of LSCC and suggest that they may contribute to the metastatic potential of the tumor.

© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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41
Meta-Analysis Head Neck
. 2019 Jan;41(1):256-261. doi: 10.1002/hed.25414. Epub 2018 Dec 18.
Racial Disparities and Human Papillomavirus Status in Oropharyngeal Cancer: A Systematic Review and Meta-Analysis
Nicholas R Lenze 1, Douglas R Farquhar 1, Angela L Mazul 2, Maheer M Masood 1, Jose P Zevallos 3
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PMID: 30561088 DOI: 10.1002/hed.25414
Abstract
Background: This study used a meta-analysis to quantify the degree to which the racial disparity in overall survival for black versus white Americans with oropharyngeal squamous cell carcinoma (OPSCC) persists after adjusting for human papillomavirus (HPV) status.

Methods: PubMed/MEDLINE, Cochrane Database of Systematic Reviews, and CINAHLA were searched through November 2017. The PRISMA statement was followed. The pooled hazard ratio (HR) was calculated using a random-effects model.

Results: Five studies met the inclusion criteria and had suitable data for pooling into the meta-analysis (N = 1153). The pooled HR for overall survival in black versus white Americans with OPSCC after adjusting for HPV status was calculated to be 1.45 (95% confidence interval, 0.87-2.40).

Conclusions: The difference in survival for black versus white Americans with OPSCC is not significant after adjusting for HPV status but still trends in the direction of a disparity. Additional studies are needed to better characterize this disparity.

Keywords: health status disparities; human papillomavirus; meta-analysis; oropharyngeal cancer; survival.

© 2018 Wiley Periodicals, Inc.

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42
Head Neck
. 2019 Jan;41(1):56-63. doi: 10.1002/hed.25356. Epub 2018 Dec 10.
Oncologic Outcomes in Patients With 1-cm to 4-cm Differentiated Thyroid Carcinoma According to Extent of Thyroidectomy
Jung Bum Choi 1, Seul Gi Lee 2, Min Jhi Kim 2, Tae Hyung Kim 2, Eun Jeong Ban 2, Cho Rok Lee 2, Jandee Lee 2, Sang-Wook Kang 2, Jong Ju Jeong 2, Kee-Hyun Nam 2, Woong Youn Chung 2, Cheong Soo Park 3
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PMID: 30536465 DOI: 10.1002/hed.25356
Abstract
Background: Recent guidelines advocate unilateral thyroidectomy for low-risk 1-cm to 4-cm differentiated thyroid cancer (DTC). This study was designed to examine the association between the extent of thyroidectomy and oncologic outcomes in patients with 1-cm to 4-cm DTC.

Materials and methods: From April 1978 to December 2011, 16 057 patients with DTC underwent thyroidectomy at Yonsei University Hospital. Among them, 5266 (32.8%) patients were classified as having 1-cm to 4-cm DTC and were enrolled in this study. Clinicopathologic features and prognostic results (disease-free survival [DFS] and disease-specific survival [DSS] rates) were analyzed by retrospective medical record review. The mean follow-up duration was 57.3 ± 58.1 months.

Results: Of tumor subtypes in the study group, papillary thyroid carcinoma was the most common (97.5%) and follicular thyroid carcinoma occurred at a rate of 2.5%. In this study, the mean tumor size was 1.84 ± 0.74 cm. Patients had extrathyroidal extension (69.3%), multiplicity (35.1%), bilaterality (26.4%), central lymph node metastasis (53.0%), and lateral neck node metastases (19.9%). Of the 5266 patients, 4292 (81.5%) underwent total thyroidectomy and 974 (18.5%) had lobectomies. Recurrence rates in the total thyroidectomy and lobectomy groups were 5.7% and 9.4%, respectively. The lobectomy group had lower DFS (P = .007) and higher DSS (P = .034) than the total thyroidectomy group. A multivariate analysis for DFS revealed that tumor size, N classification, and extent of thyroidectomy were independent risk factors. On multivariate analysis, independent risk factors for DSS were age, sex, tumor size, and M classifications.

Conclusion: Although extent of thyroidectomy does not affect DSS, total thyroidectomy is beneficial for reducing recurrence in patients with 1-cm to 4-cm DTC. However, if such tumors have such low-risk features as being unifocal, intrathyroidal, and lymph node metastasis-negative, extent of thyroidectomy does not affect oncologic outcome and lobectomy may be sufficient.

Keywords: differentiated thyroid carcinoma; oncologic outcome; prognosis; thyroid cancer; thyroidectomy extent.

© 2018 Wiley Periodicals, Inc.

Cited by 2 articles
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43
Head Neck
. 2019 Jan;41(1):146-153. doi: 10.1002/hed.25483. Epub 2018 Dec 12.
High-dose Versus Standard-Dose Radiation Therapy for Cervical Esophageal Cancer: Retrospective Single-Institution Study
Tae Hyung Kim 1, Ik Jae Lee 2, Ji-Hyun Kim 3, Chang Geol Lee 1, Yong Chan Lee 4, Jun Won Kim 2
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PMID: 30548508 DOI: 10.1002/hed.25483
Abstract
Background: To evaluate the role of definitive radiotherapy using higher-than-standard-dose radiation of 50 Gy for carcinoma of the cervical esophagus (CCE).

Methods: We reviewed 79 patients with stage I-III CCE, treated between 2000 and 2012. Patients received 5-fluorouracil/cisplatin-based chemotherapy concurrently and were divided into high-dose (≥59.4 Gy, n = 44) and standard-dose (<59.4 Gy, n = 35) groups.

Results: The median follow-up was 35 months for surviving patients. The high-dose group had significantly better 3-year local (90.0% vs 60.4%, P = .001) and locoregional (70.4% vs 45.3%, P = .04) control. Progression-free (45.4% vs 37.5%, P = .32) and overall (58.4% vs 49.1%, P = .69) survival rates were not different. High-dose radiation was an independent prognostic factor for locoregional control (P = .04). No differences in late toxicities (esophageal stenosis or tracheoesophageal fistula) were observed.

Conclusion: High-dose radiation for CCE improves local and locoregional control, without increasing severe toxicities.

Keywords: cervical esophageal carcinoma; chemoradiation; dose escalation.

© 2018 Wiley Periodicals, Inc.

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44
Eur Arch Otorhinolaryngol
. 2019 Dec;276(12):3435-3442. doi: 10.1007/s00405-019-05598-z. Epub 2019 Aug 14.
Efficacy of Hemithyroidectomy in Papillary Thyroid Carcinoma With Minimal Extrathyroidal Extension
Yong Bae Ji 1, Chang Myeon Song 1, Donghwan Kim 1, Eui-Suk Sung 2, Dong Won Lee 3, Min Sung Chung 4, Kyung Tae 5
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PMID: 31414221 DOI: 10.1007/s00405-019-05598-z
Abstract
Purpose: This study aimed to compare the oncologic outcomes of hemithyroidectomy with total thyroidectomy in clinically node-negative (cN0) papillary thyroid carcinoma (PTC) with minimal extrathyroidal extension (ETE).

Methods: Among 1826 PTC patients who underwent thyroidectomy from Jan 2001 to Dec 2014, there were 255 with unilateral cN0 PTC with minimal ETE and of equal to or less than 2 cm in size; these 255 patients were included in this study. We excluded patients who had tumor size > 2 cm, bilateral tumors, clinically positive nodes, maximal or no ETE, gross invasion of sternothyroid muscle, recurrent cancers or distant metastases. Total thyroidectomy was performed in 173 of the 255 patients, and hemithyroidectomy in 82 of them. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: sex, age, tumor size, multiplicity and central neck dissection.

Results: In the baseline data of the 255 patients, female, age and tumor size were significantly higher in the total thyroidectomy group as was Stage III, whereas T and N classification did not differ in the two groups. Propensity score matching generated two matched groups of 66 patients each, in which the significant differences between the two groups seen in the baseline analysis disappeared. In the matched samples, recurrence rate (3.0% vs. 1.5%, p = 1.0) and recurrence-free survival curves did not differ between total thyroidectomy and hemithyroidectomy.

Conclusions: Hemithyroidectomy can be recommended for cN0 PTC 1 cm or less with minimal ETE. Also it can be considered for cN0 PTC 11-20 mm with minimal ETE.

Keywords: Extrathyroidal extension; Hemithyroidectomy; Papillary thyroid carcinoma; Propensity score matching; Recurrence.

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45
Int Forum Allergy Rhinol
. 2019 Sep;9(9):1041-1045. doi: 10.1002/alr.22364. Epub 2019 Jun 7.
Lateral Nasal Wall Extension of the Nasoseptal Flap for Skull-Base and Medial Orbital Wall Defects
Justin McCormick 1, Mark Allen 1, Joshua J Kain 1, Jaime A Pena-Garcia 1, Do-Yeon Cho 1, Kristen O Riley 2, Bradford A Woodworth 1
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PMID: 31173672 DOI: 10.1002/alr.22364
Abstract
Background: Sinonasal and skull-base tumors that previously required open resection can often be completely resected via an endonasal approach. The nasoseptal flap (NSF) is the workhorse vascularized tissue flap for the endoscopic reconstruction of large skull-base defects from tumor resections. The objective of the current article is to describe a novel modification of the NSF for simultaneous reconstruction of skull-base and medial orbital wall defects.

Methods: An extension of the standard NSF to include mucosa of the lateral nasal wall was developed for closure of simultaneous skull-base and medial orbital wall defects. Outcomes including successful cerebrospinal fluid (CSF) leak closure, orbital edema, and postoperative cosmesis are reported. Eyelid edema was characterized according to the Surgeon Periorbital Rating of Edema and Ecchymosis (SPREE) scale.

Results: Three patients underwent reconstruction using the modified NSF (average age 75 years). The average defect size of the skull base was 3.6 ± 0.1 cm by 2.3 ± 0.2 cm. The average defect size of the medial orbit was 2.7 ± 0.1 cm by 2.6 ± 0.1 cm. All defects were successfully covered intraoperatively using the lateral nasal wall extension of the NSF. Two patients developed mild eyelid edema, whereas 1 individual had no noticeable swelling (SPREE classification 2, 2, and 1). All patients were successfully sealed at last clinical follow up (average 28 weeks).

Conclusion: The modification of the NSF described here provides excellent coverage for reconstruction of large anterior skull-base defects and simultaneous medial orbital wall defects.

Keywords: cerebrospinal fluid leak; extended nasoseptal flap; nasoseptal flap; skull-base reconstruction; skull-base repair; skull-base resection; skull-base tumor.

© 2019 ARS-AAOA, LLC.

24 references
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46
Review Int Forum Allergy Rhinol
. 2019 Sep;9(9):1023-1029. doi: 10.1002/alr.22381. Epub 2019 Jul 10.
Adenosine-induced Transient Hypotension for Carotid Artery Injury During Endoscopic Skull-Base Surgery: Case Report and Review of the Literature
Judd H Fastenberg 1, Tomas Garzon-Muvdi 2, Victor Hsue 3, Erin K Reilly 1, Pascal Jabbour 2, Mindy R Rabinowitz 1, Marc R Rosen 1, James J Evans 2, Gurston N Nyquist 1, Christopher J Farrell 2
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PMID: 31291066 DOI: 10.1002/alr.22381
Abstract
Background: As the management of ventral skull-base pathology has transitioned from open to endonasal treatment, there has been an increased focus on the prevention and endoscopic endonasal management of internal carotid artery (ICA) and major vascular injury. The use of adenosine to induce transient hypotension or flow arrest has been previously described during intracranial aneurysm surgery; however, there have been no reports of the technique being used during endonasal skull-base surgery to achieve hemostasis following major vascular injury.

Methods: Case report (n = 1) and literature review.

Results: A 25-year-old female underwent attempted endoscopic endonasal resection of an advanced right-sided chondrosarcoma. During resection of the tumor, brisk arterial bleeding was encountered consistent with focal injury to the right cavernous ICA. Stable vascular hemostasis could not be achieved with tamponade. An intravenous bolus dose of adenosine was administered to induce a transient decrease in systemic blood pressure and facilitate placement of the muscle patch over the direct site of vascular injury. The patient subsequently underwent endovascular deconstruction of the right ICA.

Conclusion: This is the first reported use of adenosine to induce transient hypotension for a major vascular injury sustained during endonasal skull-base surgery. Based on well-established safety data from neurosurgical application, adenosine has the potential to be used as a safe and effective adjunctive technique in similar endonasal circumstances and may represent an additional tool in the armamentarium of the skull-base surgeon. Surgeons should consider having adenosine available when a risk of ICA injury is anticipated.

Keywords: anterior skull-base; endoscopic endonasal approach to the pituitary; endoscopic skull-base surgery; major vascular injury; skull-base repair.

© 2019 ARS-AAOA, LLC.

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47
Asian Pac J Cancer Prev
. 2020 May 1;21(5):1399-1407. doi: 10.31557/APJCP.2020.21.5.1399.
Accelerated Radiotherapy With Concurrent Chemotherapy in Locally Advanced Head and Neck Cancers: Evaluation of Response and Compliance
Karim Mashhour 1, Hisham Atef 1, Ahmed Selim 1, Mostafa A Moez 2, Hussam Zawam 1, Yasser Abo-Madyan 3
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PMID: 32458648 DOI: 10.31557/APJCP.2020.21.5.1399
Free article
Abstract
Purpose: Concurrent chemo-radiotherapy (CCRT) is the primary treatment modality for locally advanced head and neck squamous cell cancer patients (LAHNSCC). Intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) and concurrent chemotherapy is not broadly implicated in our region mainly because of the lack of experience. This study aims at evaluating the response and compliance of this approach in our patients.

Methods: Forty patients with LAHNSCC were included and 50% received induction chemotherapy. All the patients were treated with IMRT-SIB radiotherapy for 70Gy over 33 daily fractions. Weekly cisplatin (40mg/m2) was administered during the radiation course.

Results: With median follow-up of 1.5 years, LC was achieved in 82.5% of cases and distant control rate was 90%. More than 5 interrupted radiation sessions and GTV volume > 50 cc significantly affected LRC (P= 0.02 and 0.001 respectively). Eighty percent of cases experienced grade 3 or 4 toxicities. Induction chemotherapy and PTV-70 volume >150 cc significantly affected the degree of toxicities (P=0.018 and 0.0001 respectively).The 2 years disease free survival (DFS) was 77%. ECOG PS, large GTV volume (> 50 cc) and RT interruption (>5 sessions) had negative impact on DFS (P= 0.041, 0.002 and 0.001 respectively). The 2 years overall survival (OS) was 87%. Radiation interruption (> 5 sessions) was the only factor which had significant detrimental effect on OS (P= 0.001).

Conclusion: Induction chemotherapy seems to have a negative impact on patient's compliance to CCRT. Bulky tumors and prolonged radiation interruptions were associated with significantly lower LRC, DFS and OS.

Keywords: IMRT; SIB; Toxicity; compliance.

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48
Int Forum Allergy Rhinol
. 2019 Sep;9(9):971-976. doi: 10.1002/alr.22371. Epub 2019 Jul 1.
Effects of Sphenoid Surgery on Nasal Irrigation Delivery
Jessica W Grayson 1, Marina Cavada 1 2, Eugene Wong 1 3, Benjamin Lien 1, Marin Duvnjak 1 3, Raewyn Campbell 2 4, Larry Kalish 1 5, Raymond Sacks 1 2 6 5, Richard J Harvey 1 2
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PMID: 31259472 DOI: 10.1002/alr.22371
Abstract
Background: Nasal irrigation is an important component of medical management in chronic rhinosinusitis. Nasal irrigations facilitate topical medication of therapies and lavage of mucin. In this study we aim to compare the influence of increasing surgical sphenoid openings on the distribution, force, and clearance of nasal irrigations.

Methods: A study was performed on fresh-frozen adult cadaver heads. The surgical ostium was modified on one side via a simple sphenoidotomy, a sphenoid sinusectomy (type 1), and sphenoid sinusectomy (type 3a). The nasal cavity was irrigated using a 240-mL squeeze bottle with 0.1% fluoroscein. An endoscope passed through the contralateral side through the sphenoid septum recorded the irrigation. Videos were recorded and blindly assessed. The distribution was defined as either no irrigation, less than one third of the sinus, less than or equal to two thirds of the sinus, or the complete sinus. The force was defined as minimal, minor, or major. The clearance was defined as no residual, less than one third of volume, less than or equal to two thirds of volume, and more than two thirds volume. Ordinal correlation scores were assessed using the Kendall tau-B test.

Results: Nine specimens (sphenoid sinuses) were assessed (44.4% female; age, 75.0 ± 12.7 years). The use of a sphenoid sinusectomy or larger produced better distribution (percent specimens with more than one third: 100% vs 59%, p < 0.01), more force (percent major: 83% vs 29%, p < 0.01), and better clearance (percent with one third or less remaining: 56% vs 18%, p < 0.01).

Conclusion: Increasing sphenoid ostial size improves nasal irrigation penetration. We propose that greater sphenoid sinusectomy size allows for improved lavage and irrigation penetration. Complete removal of the anterior face appears to mitigate pooling of irrigation.

Keywords: nasal irrigation; sphenoethmoidectomy; sphenoid; sphenoidectomy; sphenoidotomy.

© 2019 ARS-AAOA, LLC.

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49
Head Neck
. 2020 Jun;42(6):1179-1186. doi: 10.1002/hed.26202. Epub 2020 May 7.
Changing Practice Patterns in Head and Neck Oncologic Surgery in the Early COVID-19 Era
Kimberley L Kiong 1, Theresa Guo 1, Christopher M K L Yao 1, Neil D Gross 1, Matthew M Hanasono 2, Renata Ferrarotto 3, David I Rosenthal 4, Jeffrey N Myers 1, Ehab Y Hanna 1, Stephen Y Lai 1 4
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PMID: 32459061 DOI: 10.1002/hed.26202
Abstract
Background: The novel coronavirus 2019 (COVID-19) pandemic has changed health care, challenged by resource constraints and fears of transmission. We report the surgical practice pattern changes in a Head and Neck Surgery department of a tertiary cancer care center and discuss the issues surrounding multidisciplinary care during the pandemic.

Methods: We report data regarding outpatient visits, multidisciplinary treatment planning conference, surgical caseload, and modifications of oncologic therapy during this pandemic and compared this data to the same interval last year.

Results: We found a 46.7% decrease in outpatient visits and a 46.8% decrease in surgical caseload, compared to 2019. We discuss the factors involved in the decision-making process and perioperative considerations.

Conclusions: Surgical practice patterns in head and neck oncologic surgery will continue to change with the evolving pandemic. Despite constraints, we strive to prioritize and balance the oncologic and safety needs of patients with head and neck cancer in the face of COVID-19.

Keywords: SARS-CoV2; oncology; otolaryngology.

© 2020 Wiley Periodicals, Inc.

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50
Otol Neurotol
. 2019 Aug;40(7):892-899. doi: 10.1097/MAO.0000000000002275.
Age Dependent Cost-Effectiveness of Cochlear Implantation in Adults. Is There an Age Related Cut-off?
Roman D Laske 1 2, Michael Dreyfuss 3, Alan Stulman 3, Dorothe Veraguth 1 2, Alexander M Huber 1 2, Christof Röösli 1 2
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PMID: 31157721 DOI: 10.1097/MAO.0000000000002275
Abstract
Objective: To analyze the impact of age at implantation on the cost-effectiveness of cochlear implantation (CI).

Study design: Cost-utility analysis in an adapted Markov model.

Setting: Adults with profound postlingual hearing loss in a "high income" country.

Intervention: Unilateral and sequential CI were compared with hearing aids (HA).

Main outcome measure: Incremental cost-effectiveness ratio (ICER), calculated as costs per quality adjusted life year (QALY) gained (in CHF/QALY), for individual age and sex combinations in relation to two different willingness to pay thresholds. 1 CHF (Swiss franc) is equivalent to 1.01 USD.

Results: When a threshold of 50,000 CHF per QALY is applied, unilateral CI in comparison to HA is cost-effective up to an age of 91 for women and 89 for men. Sequential CI in comparison to HA is cost-effective up to an age of 87 for women and 85 for men. If a more contemporary threshold of 100,000 CHF per QALY is applied, sequential CI in comparison to unilateral CI is cost-effective up to an age of 80 for women and 78 for men.

Conclusions: Performing both sequential and unilateral CI is cost-effective up to very advanced ages when compared with hearing aids.

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51
Int J Pediatr Otorhinolaryngol
. 2020 Feb;129:109759. doi: 10.1016/j.ijporl.2019.109759. Epub 2019 Oct 31.
Allergic Rhinitis and Asthma Assessment of Risk Factors in Pediatric Patients: A Systematic Review
Domenico Testa 1, Matteo DI Bari 1, Michele Nunziata 1, Generoso DE Cristofaro 1, Giuseppe Massaro 1, Giuseppina Marcuccio 2, Gaetano Motta 1
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PMID: 31734564 DOI: 10.1016/j.ijporl.2019.109759
Abstract
Allergic rhinitis (AR) is the most prevalent allergic disease in children and can be associated with asthma (A); this association can have significant effect on child's quality of life. The objective of this work was to systematically review existing literature on the risk factors of AR and A in children to better understand the link between these two diseases. We performed a literature search over the last 25 years in PubMed and Medline. Inclusion criteria comprised English language papers containing original human data with greater than 30 subjects and papers that statistically analyze the relationship between AR and A and the risk factor(s), in children population. A statistically significant correlation was found between children with AR and A and ambient Polycyclic Aromatic Hydrocarbons exposure, live in an industrialized city with elevated traffic, dampness and moulds exposure, electric cooking, male gender, single nucleotide polymorphisms in PTNP22 gene and CTLA-4 gene, fast food and margarine products consumption, use of paracetamol in last year, history of tuberculosis, parental atopy, high total serum IgE, antibiotics in uterus and infections in uterus exposure, history of formula feeding and caesarian section. A strong and complex link between AR and A was accounted: A represents a major risk factor for the onset of AR, that correlates with more severe asthmatic symptoms. Even the onset of A in a child with AR worsen it. The interaction of genetic and environmental risk factors and the consequent epigenetic, microbiota and immunological changes, were found to led to the development of AR and A in children, with both atopic and non-atopic pathways. Close monitoring of evidenced risk factors may help with an early recognize and treat A in patients with AR.

Keywords: Allergic rhinitis; Asthma; Child.

Copyright © 2019 Elsevier B.V. All rights reserved.

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52
Cancer Lett
. 2019 Oct 1;461:144-152. doi: 10.1016/j.canlet.2019.07.011. Epub 2019 Jul 17.
Humanized anti-CD271 Monoclonal Antibody Exerts an Anti-Tumor Effect by Depleting Cancer Stem Cells
Shinkichi Morita 1, Mai Mochizuki 2, Kouichi Wada 3, Rie Shibuya 2, Mao Nakamura 4, Kazunori Yamaguchi 4, Tomoko Yamazaki 5, Takayuki Imai 6, Yukinori Asada 6, Kazuto Matsuura 6, Kazuo Sugamura 4, Yukio Katori 7, Kennichi Satoh 8, Keiichi Tamai 9
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PMID: 31325530 DOI: 10.1016/j.canlet.2019.07.011
Abstract
CD271, known as a neurotrophin receptor, is expressed in various cancers such as hypopharyngeal cancer (HPC) and melanoma. We recently reported that CD271 is a cancer-stem-cell biomarker of HPC, and that its expression is essential for cancer-cell proliferation and is correlated with a poor prognosis in this disease. Here, to develop a therapeutic antibody to CD271, we established a humanized anti-CD271 monoclonal antibody (hCD271 mA b). hCD271 mA b bound to the cysteine-rich domain 1 (CRD1) of human CD271 with high affinity (KD = 1.697 × 10-9 M). In vitro, hCD271 mA b exerted antibody-dependent cell-mediated cytotoxicity (ADCC) activity against SP2/0-CD271 (human CD271-transduced mouse cell line). Treatment with hCD271 mA b also exerted anti-tumor activity in graft models of three cell lines (HPCM2 (patient-derived xenograft cell line of hypopharyngeal cancer), MeWo-Luc (melanoma cell line), and SP2/0-CD271) in mice, resulting in smaller tumors compared to controls and reduced numbers of CD271-positive cells. Collectively, these data suggest that an antibody targeting CD271 is a promising therapeutic strategy.

Keywords: Antibody therapy; Antibody-dependent cellular toxicity; CD271; Hypopharyngeal cancer; Melanoma.

Copyright © 2019 Elsevier B.V. All rights reserved.

Cited by 1 article
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53
Clinical Trial Int J Audiol
. 2019 Dec;58(12):945-955. doi: 10.1080/14992027.2019.1657243. Epub 2019 Sep 5.
The Bone Conduction Implant - A Review and 1-year Follow-Up
Bo Håkansson 1, Sabine Reinfeldt 1, Ann-Charlotte Persson 2, Karl-Johan Fredén Jansson 1, Cristina Rigato 1, Malou Hultcrantz 3, Måns Eeg-Olofsson 4
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PMID: 31710259 DOI: 10.1080/14992027.2019.1657243
Abstract
Objective: The objective of this study is to evaluate its safety and effectiveness of the bone conduction implant (BCI) having an implanted transducer and to review similar bone conduction devices.Design: This is a consecutive prospective case series study where the patients were evaluated after 1, 3, 6 and 12 months. Outcome measures were focussed on intraoperative and postoperative safety, the effectiveness of the device in terms of audiological performance and patient's experience.Study sample: Sixteen patients with average age of 40.2 (range 18-74) years have been included. Thirteen patients were operated in Gothenburg and three in Stockholm.Results: It was found that the procedure for installing the BCI is safe and the transmission condition was stable over the follow-up time. No serious adverse events or severe adverse device effects occurred. The hearing sensitivity, speech in noise and the self-assessment as compared with the unaided condition improved significantly with the BCI. These patients also performed similar or better than with a conventional bone conduction reference device on a softband.Conclusions: In summary, it was found that the BCI can provide a safe and effective hearing rehabilitation alternative for patients with mild-to-moderate conductive or mixed hearing impairments.

Keywords: Bone conduction; active transcutaneous; hearing aid; implanted transducer.

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54
Clinical Trial J Bone Miner Res
. 2019 Feb;34(2):375-386. doi: 10.1002/jbmr.3594. Epub 2018 Nov 5.
FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice
Isabelle Schrauwen 1, Arnaud Pj Giese 2, Abdul Aziz 3 4, David Tino Lafont 5, Imen Chakchouk 1, Regie Lyn P Santos-Cortez 1, Kwanghyuk Lee 1, Anushree Acharya 1, Falak Sher Khan 3, Asmat Ullah 3, Deborah A Nickerson 6, Michael J Bamshad 6 7, Ghazanfar Ali 8, Saima Riazuddin 2, Muhammad Ansar 3, Wasim Ahmad 3, Zubair M Ahmed 2, Suzanne M Leal 1
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PMID: 30395363 PMCID: PMC6489482 DOI: 10.1002/jbmr.3594
Free PMC article
Abstract
Polydactyly is a common congenital anomaly of the hand and foot. Postaxial polydactyly (PAP) is characterized by one or more posterior or postaxial digits. In a Pakistani family with autosomal recessive nonsyndromic postaxial polydactyly type A (PAPA), we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. We found that FAM92A is expressed in the developing mouse limb and E11.5 limb bud including the progress zone and the apical ectodermal ridge, where it strongly localizes at the cilia level, suggesting an important role in limb patterning. The identified variant leads to a loss of the FAM92A/Chibby1 complex that is crucial for ciliogenesis and impairs the recruitment and the colocalization of FAM92A with Chibby1 at the base of the cilia. In addition, we show that Fam92a-/- homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. In conclusion, we present a new nonsyndromic PAPA ciliopathy due to a loss-of-function variant in FAM92A. © 2018 American Society for Bone and Mineral Research.

Keywords: CHIBBY1; CILIOPATHY; FAM92A; PAPA; POSTAXIAL POLYDACTYLY.

© 2018 American Society for Bone and Mineral Research.

Conflict of interest statement
Disclosures

All authors state that they have no conflicts of interest.

Cited by 3 articles6 figures
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55
Comparative Study Head Neck
. 2019 Jan;41(1):154-161. doi: 10.1002/hed.25463. Epub 2018 Dec 11.
Different Outcomes in Sporadic Versus Familial Medullary Thyroid Cancer
Katerina Saltiki 1, George Simeakis 1, Elli Anagnostou 1, Evangelia Zapanti 1, Eleni Anastasiou 1, Maria Alevizaki 1
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PMID: 30548085 DOI: 10.1002/hed.25463
Abstract
Background: Medullary thyroid carcinoma (MTC) has varying clinical course with familial cases (fMTC) diagnosed earlier than sporadic MTC (spMTC).

Methods: A total of 273 MTCs (familial: n = 110 [40.3%], males: 38.5%) were followed for 1-35 years (median 5.0 years). Fifty one of the familial cases were operated because of positive findings at genetic screening. Disease extent at diagnosis and follow-up was recorded.

Results: Mean age at diagnosis was: fMTC = 33.85 ± 16.5 years (range 4-74) and spMTC = 52.6 ± 14.0 years (range 16-81, P < .001). This difference remained when genetic screening cases were excluded. fMTCs had more frequently multifocality, smaller size, and more favorable stage at diagnosis (stages I and II: 60.9% vs 47.9%, stage III: 30.0% vs 23.9%, stage IV: 9.1% vs 28.9%, P = .01). fMTC had lower preoperative and postoperative calcitonin, more frequently remission (59.1% vs 47.2%) and less frequently progressive disease (8.2% vs 35.0%, P < .001). After excluding genetic screening cases, no difference in stage at diagnosis was observed. Outcome was more favorable in fMTC compared to sporadic (P = .002); the 10-year probability of lack of progression of disease differed significantly between fMTCs and spMTCs (86.4% vs 65.0%, P < .001).

Conclusion: After excluding genetic screening cases, although stage at diagnosis is similar, disease outcome remains worse in sporadic compared to fMTCs.

Keywords: familial; hereditary; medullary thyroid cancer; outcome; sporadic.

© 2018 Wiley Periodicals, Inc.

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56
Nucleic Acids Res
. 2020 Jan 8;48(D1):D856-D862. doi: 10.1093/nar/gkz830.
DNMIVD: DNA Methylation Interactive Visualization Database
Wubin Ding 1, Jiwei Chen 1, Guoshuang Feng 2 3, Geng Chen 1, Jun Wu 1, Yongli Guo 2 3, Xin Ni 2 3, Tieliu Shi 1 2 4
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PMID: 31598709 PMCID: PMC6943050 DOI: 10.1093/nar/gkz830
Free PMC article
Abstract
Aberrant DNA methylation plays an important role in cancer progression. However, no resource has been available that comprehensively provides DNA methylation-based diagnostic and prognostic models, expression-methylation quantitative trait loci (emQTL), pathway activity-methylation quantitative trait loci (pathway-meQTL), differentially variable and differentially methylated CpGs, and survival analysis, as well as functional epigenetic modules for different cancers. These provide valuable information for researchers to explore DNA methylation profiles from different aspects in cancer. To this end, we constructed a user-friendly database named DNA Methylation Interactive Visualization Database (DNMIVD), which comprehensively provides the following important resources: (i) diagnostic and prognostic models based on DNA methylation for multiple cancer types of The Cancer Genome Atlas (TCGA); (ii) meQTL, emQTL and pathway-meQTL for diverse cancers; (iii) Functional Epigenetic Modules (FEM) constructed from Protein-Protein Interactions (PPI) and Co-Occurrence and Mutual Exclusive (COME) network by integrating DNA methylation and gene expression data of TCGA cancers; (iv) differentially variable and differentially methylated CpGs and differentially methylated genes as well as related enhancer information; (v) correlations between methylation of gene promoter and corresponding gene expression and (vi) patient survival-associated CpGs and genes with different endpoints. DNMIVD is freely available at http://www.unimd.org/dnmivd/. We believe that DNMIVD can facilitate research of diverse cancers.

© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cited by 1 article29 references2 figures
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57
Case Reports Acta Neurochir (Wien)
. 2019 Sep;161(9):1937-1942. doi: 10.1007/s00701-019-04009-w. Epub 2019 Jul 12.
Avoidance of Scapular Winging While Approaching Tumors of the Middle Scalene Region
Ross C Puffer 1, Jonathan Stone 2, Robert J Spinner 2
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PMID: 31300885 DOI: 10.1007/s00701-019-04009-w
Abstract
Background: Large tumors arising from the middle scalene region can displace the middle scalene muscle and distort regional anatomy, placing nerves at risk. Understanding the surgical anatomy of these nerves is key to approaching pathology of the middle scalene muscle and avoiding damage to the dorsal scapular, long thoracic, and spinal accessory nerves, each of which can cause scapular winging and associated morbidity if injured.

Methods: IRB approval was obtained for this study, allowing cases with relevant pathology to be reviewed and presented to highlight the relevant surgical technique. Anatomical depictions were created to correlate intraoperative images with known anatomical relationships.

Results: Key to this approach is consideration of the regional anatomy in a standard supraclavicular approach, the superficial plane, containing the anterior scalene muscle and brachial plexus, and the oblique plane containing the middle scalene muscle, long thoracic, spinal accessory, and dorsal scapular nerves. Identification and mobilization of each of these structures prior to lesion removal can not only provide likely boundaries of the tumor, but also allow for protection of the nerves to avoid injury that may lead to scapular winging with associated morbidity and functional impairment of the upper extremity.

Conclusions: Lesions of the middle scalene region often split two important anatomical planes, the superficial and deep, creating an advantageous surgical corridor through an anterolateral approach. Through early identification of known anatomy, these two planes can be developed, and a safe approach to the lesion of the middle scalene region can be exploited.

Keywords: Approach; Brachial; Plexus; Scapular; Technique; Winging.

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58
Cells
. 2020 May 21;9(5):E1281. doi: 10.3390/cells9051281.
YRNAs: New Insights and Potential Novel Approach in Head and Neck Squamous Cell Carcinoma
Kacper Guglas 1 2, Tomasz Kolenda 1 3, Maciej Stasiak 4, Magda Kopczyńska 1 3, Anna Teresiak 1, Matthew Ibbs 5 6, Renata Bliźniak 1, Katarzyna Lamperska 1
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PMID: 32455790 DOI: 10.3390/cells9051281
Free article
Abstract
YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren's syndrome. Deregulation of YRNAs has been confirmed in many cancer types, but not in head and neck squamous cell carcinoma (HNSCC). The main aim of this study was to determine the biological role of YRNAs in HNSCC, the expression of YRNAs, and their usefulness as potential HNSCC biomarkers. Using quantitative reverse transcriptase (qRT)-PCR, the expression of YRNAs was measured in HNSCC cell lines, 20 matched cancer tissues, and 70 FFPETs (Formaline-Fixed Paraffin-Embedded Tissue) from HNSCC patients. Using TCGA (The Cancer Genome Atlas) data, an analysis of the expression levels of selected genes, and clinical-pathological parameters was performed. The expression of low and high YRNA1 expressed groups were analysed using gene set enrichment analysis (GSEA). YRNA1 and YRNA5 are significantly downregulated in HNSCC cell lines. YRNA1 was found to be significantly downregulated in patients' tumour sample. YRNAs were significantly upregulated in T4 stage. YRNA1 showed the highest sensitivity, allowing to distinguish healthy from cancer tissue. An analysis of TCGA data revealed that expression of YRNA1 was significantly altered in the human papilloma virus (HPV) infection status. Patients with medium or high expression of YRNA1 showed better survival outcomes. It was noted that genes correlated with YRNA1 were associated with various processes occurring during cancerogenesis. The GSEA analysis showed high expression enrichment in eight vital processes for cancer development. YRNA1 influence patients' survival and could be used as an HNSCC biomarker. YRNA1 seems to be a good potential biomarker for HNSCC, however, more studies must be performed and these observations should be verified using an in vitro model.

Keywords: GSEA; HNSCC; RNY; Ro60 associated YRNA; YRNA; biomarker; cancer; small non-coding RNA.

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59
Otol Neurotol
. 2019 Aug;40(7):e739-e746. doi: 10.1097/MAO.0000000000002305.
Poly-Lactic Acid-Based Biopolymer Formulations Are Safe for Sustained Intratympanic Dexamethasone Delivery
Francis Rousset 1 2, Vivianne Beatrix Christina Kokje 2, Marta Da Costa Coelho 1 2, Thibault Mugnier 3, Emilie Belissa 3, Doris Gabriel 3, Robert Gurny 3, Karl Heinz Krause 1 2, Pascal Senn 2
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PMID: 31295207 DOI: 10.1097/MAO.0000000000002305
Abstract
Hypothesis and background: The clinical treatment of sudden sensorineural hearing loss currently relies on the administration of steroids, either systemically or via intratympanic injections. Intratympanic injections bypass the hemato-cochlear barrier, reducing its systemic side effects. The efficacy of the injections is limited through rapid drug clearance via the Eustachian tube, and through nonoptimal properties of slow-release drug carriers. A new slow-release drug delivery vehicle based on hexyl-substituted-poly-lactic-acid (HexPLA), with the highest possible safety profile and complete bio-degradability, has been evaluated for safety and efficacy in a standardized guinea pig model of intratympanic injection.

Methods: A total of 83 animals received through retrobullar injection either empty Nile-red-colored HexPLA vehicle, 5%-dexamethasone-HexPLA, 5%-dexamethasone suspension, or a sham operation. Long-term residence time of vehicle, biocompatibility, click- and pure-tone hearing thresholds, and dexamethasone levels in the perilymph were prospectively assessed.

Results: At 1 week after injection, HexPLA vehicle was morphologically present in the middle ear and perilymph levels in the 5%-dexamethasone-HexPLA were on average 2 to 3 μg/ml and one order of magnitude higher compared with those of the 5%-dexamethasone suspension group. No significant postoperative morphological or functional changes were observed up to 3 months postdelivery.

Conclusions: HexPLA is safe, fully biocompatible, and efficient for sustained high-dose, intratympanic delivery of dexamethasone at least for 1 week and therefore of high interest for the treatment of sudden sensorineural hearing loss and other acute inner ear diseases. Due to the favorable chemical properties, a wide range of other drugs can be loaded into the vehicle further increasing its potential value for otological applications.

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60
Phys Med Biol
. 2020 May 27. doi: 10.1088/1361-6560/ab9705. Online ahead of print.
Pulsed Focused Ultrasound Lowers Interstitial Fluid Pressure and Increases Nanoparticle Delivery and Penetration in Head and Neck Squamous Cell Carcinoma Xenograft Tumors
Ali Mohammadabadi 1, Ruby N Huynh 2, Aniket S Wadajkar 3, Rena G Lapidus 4, Anthony J Kim 3, Christopher B Raub 5, Victor Frenkel 6
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PMID: 32460260 DOI: 10.1088/1361-6560/ab9705
Abstract
Nanocarriers offer a promising approach to significantly improve therapeutic delivery to solid tumors as well as limit the side effects associated with anti-cancer agents. However, their relatively large size can negatively affect their ability to efficiently penetrate into more interior tumor regions, ultimately reducing therapeutic efficacy. Poor penetration of large agents such as nanocarriers is attributed to factors in the tumor microenvironment such as elevated interstitial fluid pressure (IFP) and fibrillar collagen in the extracellular matrix. Our previous studies reported that pretreatment of solid tumor xenografts with nondestructive pulsed focused ultrasound (pFUS) can improve the delivery and subsequent therapy of a variety of therapeutic formulations in different tumor models, where the results were associated with an expanded extracellular spaces (ECS), an increase in hydraulic conductivity, and decrease in tissue stiffness. Here, we demonstrate the inverse relationship between IFP and the penetration of systemically administered nanoparticle (NP) probes, where IFP increased from the tumor periphery to their center. Furthermore, we show that pretreatment with pFUS can safely reduce IFP and improve NP delivery; especially into the center of the tumors. These results coincide with effects generated in the fibrillar collagen network microstructure in the ECS as determined by quantitative polarized light microscopy. Whole tumor and histomorphometric analysis, however, did not show significant differences in collagen area fraction or collagen feature solidity, as well as tumor cross-sectional area and aspect ratio, as result of the treatments. We present a biophysical model connecting the experimental results, where pFUS-mediated cytoarchitectural changes are associated with improved redistribution of the interstitial fluid and lower IFP. The resulting improvement in NP delivery supports our previous therapeutic studies and may have implications for clinical applications to improve therapeutic outcomes in cancer therapy.

Keywords: Head and Neck Squamous Cell Carcinoma; fibrillar collagen microstructure; focused ultrasound; interstitial fluid pressure; nanoparticle probes.

© 2020 Institute of Physics and Engineering in Medicine.

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61
Asian Pac J Allergy Immunol
. 2018 Mar;36(1):1-7. doi: 10.12932/AP0850.
Reversible Immune Abnormality and Regulatory T Cells in Offspring of Der P 1-exposed Female Mice
Lu Tan 1, Zezhang Tao 1 2, Yonggang Kong 1 2, Yu Xu 1 2
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PMID: 28802026 DOI: 10.12932/AP0850
Free article
Abstract
Background: Maternal allergic diseases have an important influence on the origin of allergic rhinitis (AR) in offspring, but the mechanism and the duration of the maternal effect are unknown. Previous researches prompted the important roles of Tregs and Foxp3 DNA methylation in the development of allergic diseases.

Objective: To investigate the immune state and Tregs in the offspring of Der p 1-exposed female mice.

Method: BALB/c female mice were exposed to Der p1 to construct the mouse AR model, then mated with normal male mice. Offspring were kept in an allergen-free environment after birth. At postnatal weeks 3, 5 and 8, mice were culled for testing.

Result: Compared with the offspring of PBS-exposed female mice (N-N), the offspring of Der p 1-exposed female mice (A-N) showed increased IL-4 and decreased IL-10 levels in serum at postnatal weeks 3 and 5. Correspondingly, the percentage of Tregs in spleen CD4+ cells declined significantly at postnatal week 5 in A-N. Further analysis of the methylation status of spleen lymphocytes revealed hypermethylation of the Foxp3 promoter in A-N mice at postnatal weeks 3 and 5. However, by 8 weeks of age, all abnormalities in cytokines, Treg counts and Foxp3 DNA methylation in A-N mice had returned to normal levels.

Conclusion: Under the influence of maternal AR, offspring have an abnormal immune state at birth. However, without exposure to allergens, the immune state in AR offspring recovered by maturity. Changes in Tregs and Foxp3 DNA methylation may be the mechanism for this reversible immune abnormality in AR offspring.

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62
Int Forum Allergy Rhinol
. 2019 Sep;9(9):1010-1016. doi: 10.1002/alr.22365. Epub 2019 Jun 17.
Association Between Chronic Rhinosinusitis and Osteoporosis: A Case-Control Study Using a National Sample Cohort
Hyo Geun Choi 1, Gyu Kong 1 2
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PMID: 31207164 DOI: 10.1002/alr.22365
Abstract
Background: The purpose of this study was to further clarify the relationship between chronic rhinosinusitis (CRS) and osteoporosis in a Korean population.

Methods: The Korean National Health Insurance Service-National Sample Cohort, with subjects ≥50 years old, was assessed for the time period 2002-2013. In total, 68,459 osteoporosis participants were matched with 68,459 control participants at a ratio of 1:1 with respect to age, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia. We analyzed previous histories of CRS with/without nasal polyp in the osteoporosis and control groups. CRS and osteoporosis were included using codes from the International Classification of Diseases-tenth edition and claim codes. Crude and adjusted odds ratios (ORs) were analyzed using conditional logistic regression analyses. The 95% confidence intervals (CIs) were then calculated. Subgroup analyses were performed according to age and sex.

Results: The rate of CRS with/without nasal polyp was higher in the osteoporosis group (3.0% [2078 of 68,459]) compared with the control group (2.0% [1344 of 68,459]) (p < 0.001). The adjusted OR of CRS with/without nasal polyp was 1.47 (95% CI, 1.37-1.58; p < 0.001) in the osteoporosis group. The results of the subgroup analyses were consistent.

Conclusion: The ORs of CRS were increased in osteoporosis participants. This relation was consistent in all age and sex groups.

Keywords: chronic rhinosinusitis; epidemiology; nested case-control studies; osteoporosis; rhinosinusitis; sinusitis.

© 2019 ARS-AAOA, LLC.

Cited by 1 article52 references
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63
Cancer Commun (Lond)
. 2019 Nov 4;39(1):68. doi: 10.1186/s40880-019-0409-1.
Chromosome Band 11q23 Deletion Predicts Poor Prognosis in Bone Marrow Metastatic Neuroblastoma Patients Without MYCN Amplification
Zhi-Xia Yue 1, Tian-Yu Xing 1, Chao Gao 1, Shu-Guang Liu 1, Wen Zhao 1, Qian Zhao 1, Xi-Si Wang 1, Mei Jin 1, Xiao-Li Ma 2
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PMID: 31685009 PMCID: PMC6829843 DOI: 10.1186/s40880-019-0409-1
Free PMC article
Abstract
Background: Interphase fluorescence in situ hybridization (FISH) of bone marrow cells has been confirmed to be a direct and valid method to assess the v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification in patients with bone marrow metastatic neuroblastoma. MYCN amplification alone, however, is insufficient for pretreatment risk stratification. Chromosome band 11q23 deletion has recently been included in the risk stratification of neuroblastoma. In the present study, we aimed to evaluate the biological characteristics and prognostic impact of 11q23 deletion and MYCN amplification in patients with bone marrow metastatic neuroblastoma.

Methods: We analyzed the MYCN and 11q23 statuses of 101 patients with bone marrow metastatic neuroblastoma using interphase FISH of bone marrow cells. We specifically compared the biological characteristics and prognostic impact of both aberrations.

Results: MYCN amplification and 11q23 deletion were seen in 12 (11.9%) and 40 (39.6%) patients. The two markers were mutually exclusive. MYCN amplification occurred mainly in patients with high lactate dehydrogenase (LDH) and high neuron-specific enolase (NSE) levels (both P < 0.001), and MYCN-amplified patients had more events (tumor relapse, progression, or death) than MYCN-normal patients (P = 0.004). 11q23 deletion was associated only with age (P = 0.001). Patients with MYCN amplification had poorer outcomes than those with normal MYCN (3-year event-free survival [EFS] rate: 8.3 ± 8.0% vs. 43.8 ± 8.5%, P < 0.001; 3-year overall survival [OS] rate: 10.4 ± 9.7% vs. 63.5% ± 5.7%, P < 0.001). 11q23 deletion reflected a poor prognosis only for patients with normal MYCN (3-year EFS rate: 34.3 ± 9.5% vs. 53.4 ± 10.3%, P = 0.037; 3-year OS rate: 42.9 ± 10.4% vs. 75.9 ± 6.1%, P = 0.048). Those with both MYCN amplification and 11q23 deletion had the worst outcome (P < 0.001).

Conclusions: Chromosome band 11q23 deletion predicts poor prognosis only in bone marrow metastatic neuroblastoma patients without MYCN amplification. Combined assessment of the two markers was much superior to single-marker assessment in recognizing the patients at a high risk of disease progression.

Keywords: 11q23 deletion; Bone marrow metastasis; Event-free survival; Fluorescence in situ hybridization; Lactate dehydrogenase; MYCN amplification; Neuroblastoma; Neuron-specific enolase; Overall survival.

Conflict of interest statement
The authors declare that they have no competing interests.

34 references2 figures
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64
Case Reports Head Neck
. 2019 Jan;41(1):E1-E10. doi: 10.1002/hed.25380. Epub 2018 Dec 16.
Initial Experience With Image-Guided Surgical Navigation in Transoral Surgery
Joseph A Paydarfar 1 2, Xiaotian Wu 2, Ryan J Halter 2 3
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PMID: 30556235 PMCID: PMC6339594 DOI: 10.1002/hed.25380
Free PMC article
Abstract
Background: Surgical navigation using image guidance may improve the safety and efficacy of transoral surgery (TOS); however, preoperative imaging cannot be accurately registered to the intraoperative state due to deformations resulting from placement of the laryngoscope or retractor. This proof of concept study explores feasibility and registration accuracy of surgical navigation for TOS by utilizing intraoperative imaging.

Methods: Four patients undergoing TOS were recruited. Suspension laryngoscopy was performed with a CT-compatible laryngoscope. An intraoperative contrast enhanced CT scan was obtained and registered to fiducials placed on the neck, face, and laryngoscope.

Results: All patients were successfully scanned and registered. Registration accuracy within the pharynx and larynx was 1 mm or less. Target registration was confirmed by localizing endoscopic and surface structures to the CT images. Successful tracking was performed in all 4 patients.

Conclusion: For surgical navigation during TOS, although a high level of registration accuracy can be achieved by utilizing intraoperative imaging, significant limitations of the existing technology have been identified. These limitations, as well as areas for future investigation, are discussed.

Keywords: 3D printing; image-guided surgical navigation; intraoperative imaging; laryngoscopy; transoral laser microsurgery; transoral robotic surgery; transoral surgery.

© 2018 Wiley Periodicals, Inc.

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65
J Biomater Appl
. 2019 Mar;33(8):1053-1059. doi: 10.1177/0885328218822636. Epub 2019 Jan 16.
Acellular Dermal Matrix Contributes to Epithelialization in Patients With Chronic Sinusitis
Zhong Bing 1, Liu Feng 1, Chun-Shu Wu 1, Jin-Tao Du 1, Ya-Feng Liu 1, Shi-Xi Liu 1
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PMID: 30651053 DOI: 10.1177/0885328218822636
Abstract
Background: Nasal endoscopic surgery is widely used for nasal diseases, including sinusitis and tumors. However, scar hyperplasia, nasal irritation, scab, and nasal obstruction delay nasal mucosal recovery, with prolonged cleaning exacerbating the patient's financial burden. Here, we presented a novel approach for the treatment of nasal mucosal defects, termed acellular dermal matrix.

Methods: A total of 31 patients with bilateral chronic sinusitis (maxillary sinusitis and ethmoid sinusitis) underwent nasal surgery and nasal mucosal repair in September-October 2016. We divided the nasal cavities of each patient into control and acellular dermal matrix groups, randomly selected one side for nasal mucosal repair by surgery. A suitable acellular dermal matrix size was selected according to the defect in each patient. After pruning, the acellular dermal matrix was placed on the wound surface and filled with gelatin sponge. All patients were followed up for 14 weeks to compare nasal mucosal epithelialization between the control and acellular dermal matrix groups. Results：No obvious complications and adverse reactions were observed after nasal surgery. Lund-Kennedy scores in the acellular dermal matrix group were significantly decreased compared with the control group at 8 (0 (0, 1) vs. 2 (2, 4); P<0.05) weeks. Epithelialization time of eight weeks in the acellular dermal matrix groups was significantly decreased than the control group of 14 weeks.

Conclusion: Acellular dermal matrix provides a growth framework for the healthy mucosa on the wounded surface and reduces postoperative epithelialization time.

Keywords: Lund-Kennedy score; Nasal endoscopic surgery; acellular dermal matrix; chronic sinusitis; epithelialization.

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66
J Sci Med Sport
. 2020 May 3;S1440-2440(19)31441-0. doi: 10.1016/j.jsams.2020.04.019. Online ahead of print.
Examining Ski Area Padding for Head and Neck Injury Mitigation
Irving S Scher 1, Lenka L Stepan 2, Jasper E Shealy 2, Ryan W Hoover 3
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PMID: 32456978 DOI: 10.1016/j.jsams.2020.04.019
Abstract
Objectives: The injury mitigation capabilities of foam, ski-area padding was examined for headfirst impacts.

Design and methods: A custom-made pendulum impactor system was constructed using an instrumented, partial 50th-percentile-male Hybrid-III anthropomorphic testing device (ATD). For each test, the ATD was raised 1.0m, released, and swung into a 20-cm diameter wooden pole. Test trials were conducted with the wooden pole covered by ski area padding (five conditions of various foam types and thicknesses) or unpadded. Linear (linear acceleration and HIC15) and angular (angular velocity, angular acceleration, and BrIC) kinematics were examined and used to estimate the likelihood of severe brain injury. Cervical spine loads were compared to the injury assessment reference values for serious injury. Further tests were conducted to examine the changes produced by the addition of a snowsport helmet.

Results: 38 test trials were recorded with a mean (±sd) impact speed of 4.2 (±0.03) m/s. Head, resultant linear acceleration, HIC15, and associated injury likelihoods were tempered by ski area padding at the impact speed tested. Ski area padding did not reduce brain injury likelihood from rotational kinematics (p>0.05 for all comparisons) or reduce the cervical spine compression below injury assessment reference values. The addition of a helmet did not reduce significantly the likelihoods of brain or cervical spine injury.

Conclusions: At the impact speed tested, ski area padding provided limited impact protection for the head (for linear kinematics) but did not protect against severe brain injuries due to rotational kinematics or serious cervical spine injuries.

Keywords: Head injuries; Neck injuries; Padding; Polyurethane foam; Skiing; Snowboarding.

Copyright © 2020 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

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67
Int J Pediatr Otorhinolaryngol
. 2020 Feb;129:109757. doi: 10.1016/j.ijporl.2019.109757. Epub 2019 Oct 31.
Outcomes of Audiometric Testing in Children With Auditory Neuropathy Spectrum Disorder
Joseph B Meleca 1, Gina Stillitano 1, Maxwell Y Lee 2, Whitney Lyle 3, Yi-Chun Carol Liu 4, Samantha Anne 5
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PMID: 31704576 DOI: 10.1016/j.ijporl.2019.109757
Abstract
Introduction: Auditory Neuropathy Spectrum Disorder (ANSD) is characterized by hearing loss ranging from normal to profound. Additionally, results are confounded by commonly fluctuating hearing thresholds in ANSD. As such, we sought to evaluate results of audiometric testing on children with ANSD and the impact of age and time on testing results.

Methods: Retrospective chart review on children <18 years of age diagnosed with ANSD at two tertiary care academic institutions. Data analyzed included initial audiogram with speech detection thresholds (SDT) and pure tone averages (PTA) as well as most recent unaided audiogram SDT and PTA.

Results: 75 ANSD patients were analyzed, of which 32 (42.7%) were female. Bilateral and unilateral ANSD was seen in 55 (73.3%) and 20 (26.7%), respectively. A total of 130 ears with ANSD were assessed with 80 (61.5%) meeting inclusion criteria. Of these patients, the median age in years at first audiogram and most recent audiogram were 1.94 (0.45-13.68) and 4.22 (0.97-14.61), respectively. The median ages at which an SDT and PTA could first be acquired on the audiogram in ANSD patients were 1.94 (0.50-13.68) and 2.86 (0.45-13.68), respectively. The average SDT/PTA at the initial and most recent audiogram were 47.5/45.7 and 49.4/53.0 dB, respectively. SDT to PTA within the same audiogram exhibited strong correlation (r = 0.82, p < 0.001). Similarly, comparison of initial SDT to SDT at a later time interval showed strong correlation (r = 0.73, p < 0.001). SDT and PTA at initial audiogram and PTA at later time demonstrated lower correlation but was still statistically significant (r = 0.49, p < 0.009 and r = 0.51, p < 0.044, respectively). Individual PTA was associated with age (r = -0.56, p < 0.001).

Conclusions: SDT and PTA within the same audiogram and initial SDT to SDT acquired at a later time correlate strongly in audiometric testing in children with ANSD. Although not as strong, initial SDT and PTA still correlate with PTA at a later time interval. These findings suggest that audiometric results yielding a reliable SDT and frequency specific information necessary to calculate the PTA is not typically obtained until 2-3 years old. However, once this information is obtained, the child's hearing is fairly stable but may fluctuate over time.

Keywords: ANSD; Audiometry; Auditory neuropathy spectrum disorder; Pure tone average; Speech detection threshold.

Copyright © 2019 Elsevier B.V. All rights reserved.

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68
Otol Neurotol
. 2019 Aug;40(7):927-935. doi: 10.1097/MAO.0000000000002299.
Endaural Laser-Assisted Single-Stage Inside-Out Cholesteatoma Surgery (LASIC) to Treat Advanced Congenital Cholesteatoma
Chang Ho Lee 1, Mi Kyung Kim, Hyoung-Mi Kim, Cheongse Won, Tae Hyun Shin, So Young Kim
Affiliations expand
PMID: 31295203 DOI: 10.1097/MAO.0000000000002299
Abstract
Objectives: Investigation of endaural laser-assisted single-stage inside-out cholesteatoma surgery (LASIC) to treat advanced congenital cholesteatoma (ACC) by a modified staging system based on ossicle status.

Study design: A retrospective case review.

Setting: A university hospital otology referral clinic.

Patients: Two hundred consecutive pediatric patients with ACC were enrolled.

Interventions: Endaural LASIC and postoperative temporal bone computed tomography (CT).

Main outcome measures: Residual or recurrent CC and audiological outcomes.

Results: LASIC was feasible in 98.0% of patients. Single-stage ossiculoplasty was performed in 95.5% of patients. Hearing preservation to less than 20 dB was 59.2% and to the preoperative hearing level was 84.5%. Mastoid invasion did not result in worse recidivism or hearing loss (HL) but further invasion of the stapes superstructure (stage IV) significantly elevated both the recidivism (16.7%) and the risk for HL (to 84.8%) (p = 0.001). Ossicle preservation LASIC was frequently possible in stage III posterior type (75.6%), whereas it was rarely possibly (15.4%) in the anterior type. Incudostapedial joint (ISJ) invasion in the absence of cochleariform process (CP) invasion (III-posterior) did not increase the incidence of HL (6.1%) or recidivism (2.4%). However, simultaneous invasion of the CP and ISJ (III-anterior) elevated the risk of HL by 46.2% by ossicle removal, although recidivism was not increased (3.8%).

Conclusions: Endaural LASIC for ACC achieved satisfactory recidivism (overall 7.5%, 16.7% in stage IV) comparable to early CC (17.2%). An ossicle status-based staging system was more efficient for correlation with audiologic and surgical outcomes of CC than that of mastoid invasion.

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69
Eur Arch Otorhinolaryngol
. 2019 Dec;276(12):3425-3434. doi: 10.1007/s00405-019-05597-0. Epub 2019 Sep 11.
Lymph Node Ratio (LNR) as a Complementary Staging System to TNM Staging in Salivary Gland Cancer
Bo-Wen Lei 1 2, Jia-Qian Hu 1 2, Peng-Cheng Yu 1 2, Yu-Long Wang 1 2, Wen-Jun Wei 1 2, Ji Zhu 2 3 4, Xiao Shi 1 2, Ning Qu 1 2, Zhong-Wu Lu 5 6, Qing-Hai Ji 7 8
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PMID: 31511971 PMCID: PMC6858905 DOI: 10.1007/s00405-019-05597-0
Free PMC article
Abstract
Purpose: The role of lymph node ratio (LNR, ratio of metastatic to examined nodes) in the staging of multiple human malignancies has been reported. We aim to evaluate its value in salivary gland cancer (SGC).

Methods: Records of SGC patients from Surveillance, Epidemiology, and End Results database (SEER, training set, N = 4262) and Fudan University Shanghai Cancer Center (FUSCC, validating set, N = 154) were analyzed for the prognostic value of LNR. Kaplan-Meier survival estimates, the Log-rank χ2 test and Cox proportional hazards model were used for univariate and multivariate analysis. Optimal LNR cutoff points were identified by X-tile.

Results: Optimal LNR cutoff points classified patients into four risk groups, R0, R1 (≤ 0.17), R2 (0.17-0.56) and R3 (> 0.56), corresponding to 5-year cause-specific survival in SEER patients of 88.6%, 57.2%, 53.1% and 39.7%, disease-free survival in FUSCC patients of 69.2%, 63.3%, 34.6% and 0%, and disease-specific survival in FUSCC patients of 92.3%, 90.0%, 71.4% and 0%, respectively. Compared with TNM staging, TNM + R staging showed smaller AIC values and higher C-index values in the Cox regression model in both patient sets.

Conclusions: LNR classification should be considered as a complementary system to TNM staging and LNR classification based clinical trials deserve further research.

Keywords: Lymph node ratio; Prognosis; Radiotherapy; Salivary gland cancer; TNM staging.

Conflict of interest statement
The authors declare that they have no conflict of interest.

Cited by 1 article21 references2 figures
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70
Saudi Med J
. 2019 Dec;40(12):1209-1217. doi: 10.15537/smj.2019.12.24747.
Platelet-rich Plasma Can Release Nutrient Factors to Promote Facial Nerve Crush Injury Recovery in Rats
Liheng Li 1, Jing Cai, Yang Yuan, Yanyan Mao, Lei Xu, Yuechen Han, Jianfeng Li, Haibo Wang
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PMID: 31828272 DOI: 10.15537/smj.2019.12.24747
Free article
Abstract
To evaluate the effects of platelet-rich plasma (PRP) on promoting neural repair after facial nerve compression in rats and the mechanism by which this occurs. Methods: Adult Wistar rats (n=100) were divided into 3 groups: healthy controls, surgery-only, and surgery+PRP groups. The rats underwent nerve crush injury to establish a facial palsy model. The blood from the rats was used to prepare the PRP for application to the injury site. The evaluation methods included vibrissae movement, eyelid closure, and electrophysiology. Electron microscopy, immunohistochemistry, and real-time polymerase chain reaction (PCR) were used to detect nutrient factor expression in the brain and nerve sections. This study was conducted in Shandong Provincial ENT Hospital Affiliated to Shandong University, Shandong, China between January and November 2018. Results: Platelet-rich plasma promotes the recovery of vibrissae movement, eyelid closure, and electrophysiological function in a rat model of nerve crush injury. Hematoxylin and eosin staining, toluidine blue staining, and electron microscopy showed significant recovery of Schwann cells and axons in the PRP group. Polymerase chain reaction results showed that PRP releases growth factors, which include nerve growth factor and brain-derived neurotrophic factor. Immunohistochemistry also demonstrated higher levels of S-100 protein expression in the PRP group compared to the other groups. Conclusions: Platelet-rich plasma releases nutrient factors in the brainstem, and the use of PRP can promote injury recovery.

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71
Ann Otol Rhinol Laryngol
. 2020 Jun;129(6):599-604. doi: 10.1177/0003489420903329. Epub 2020 Jan 29.
Factors Correlating to Burnout Among Otolaryngology Residents
Leighton Reed 1, Madhu Mamidala 1, Rosemary Stocks 1, Anthony Sheyn 1
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PMID: 31994410 DOI: 10.1177/0003489420903329
Abstract
Objectives: Physicians have high rates of burnout with an Otolaryngology burnout rate of 42%. The most studied burnout correlation is increased work hours. More recently, mindfulness training programs have been shown to decrease burnout and increase self-compassion. Regarding burnout studies specific to Otolaryngology residents, there have been few in the past decade. This study explores correlations between burnout and procedure involvement, non-clinical responsibilities and mindfulness practices along with gathering updated work hours data.

Methods: A single survey question was shown to be a reliable substitute for Maslach Burnout Inventory in assessing burnout. A survey was sent to all US Otolaryngology residents to investigate the correlation of burnout to post-graduate year, work hours, procedure involvement, non-clinical responsibilities, and mindfulness practices. Residents were asked to answer questions regarding their previous year of training.

Results: Overall burnout was 50%. PGY-1 and PGY-5 were completed with a low burnout rate compared to other years. Increased work hours were confirmed to increase burnout. Increased involvement in procedures, decreased exercise, and increased time completing paperwork correlated with increased burnout. No other factors including mindfulness correlated with increased or decreased burnout. However, only 20% who practiced mindfulness training had this training offered by their department or university.

Conclusion: Annals of Otology, Rhinology & Laryngology A 50% burnout rate is a concerning rate. Increased work hours and PGY-2 through PGY-4 correlated with increased burnout. Accessibility to mindfulness training was low. As mindfulness training is a proven activity to decrease burnout, more departments could benefit from providing these experiences to their residents.

Keywords: burnout; mental health; resident.

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72
Cancers (Basel)
. 2020 May 22;12(5):E1324. doi: 10.3390/cancers12051324.
An Integrated Genomic Strategy to Identify CHRNB4 as a Diagnostic/Prognostic Biomarker for Targeted Therapy in Head and Neck Cancer
Yi-Hsuan Chuang 1, Chia-Hwa Lee 2 3 4, Chun-Yu Lin 1 5 6, Chia-Lin Liu 7, Sing-Han Huang 1, Jung-Yu Lee 1, Yi-Yuan Chiu 1, Jih-Chin Lee 1 8, Jinn-Moon Yang 1 5 6 9 10
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PMID: 32455963 DOI: 10.3390/cancers12051324
Free article
Abstract
Although many studies have shown the association between smoking and the increased incidence and adverse prognosis of head and neck squamous cell carcinoma (HNSCC), the mechanisms and pharmaceutical targets involved remain unclear. Here, we integrated gene expression signatures, genetic alterations, and survival analyses to identify prognostic indicators and therapeutic targets for smoking HNSCC patients, and we discovered that the FDA-approved drug varenicline inhibits the target for cancer cell migration/invasion. We first identified 18 smoking-related and prognostic genes for HNSCC by using RNA-Seq and clinical follow-up data. One of these genes, CHRNB4 (neuronal acetylcholine receptor subunit beta-4), increased the risk of death by approximately threefold in CHRNB4-high expression smokers compared to CHRNB4-low expression smokers (log rank, p = 0.00042; hazard ratio, 2.82; 95% CI, 1.55-5.14), former smokers, and non-smokers. Furthermore, we examined the functional enrichment of co-regulated genes of CHRNB4 and its 246 frequently occurring copy number alterations (CNAs). We found that these genes were involved in promoting angiogenesis, resisting cell death, and sustaining proliferation, and contributed to much worse outcomes for CHRNB4-high patients. Finally, we performed CHRNB4 gene editing and drug inhibition assays, and the results validate these observations. In summary, our study suggests that CHRNB4 is a prognostic indicator for smoking HNSCC patients and provides a potential new therapeutic drug to prevent recurrence or distant metastasis.

Keywords: drug repurposing; head and neck squamous cell carcinoma (HNSCC); nicotine; prognostic biomarker; smoking.

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73
Head Neck
. 2019 Jan;41(1):139-145. doi: 10.1002/hed.25487. Epub 2018 Dec 12.
Long-term Changes in Vocal Function After Supracricoid Partial Laryngectomy With Cricohyoidoepiglottopexy for Laryngeal Cancer
Satoru Miyamaru 1, Ryosei Minoda 1 2, Narihiro Kodama 1 3
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PMID: 30548357 DOI: 10.1002/hed.25487
Abstract
Background: The purpose of this study was to assess changes in vocal function over time following supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP).

Methods: A total of 17 patients who underwent SCL-CHEP for laryngeal squamous cell carcinoma between 2007 and 2015 were reviewed. We examined maximum phonation time (MPT), mean airflow rate (MFR), voice intensity, the grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, Voice Handicap Index-10 (VHI-10), and voice-related quality of life (V-RQOL) scores. To assess changes over time in these parameters, we set 3 evaluation periods after surgery: within the first 12 months (term A), 13-36 months (term B), and after 37 months (term C).

Results: The mean MPT, MFR, G and B GRBAS subscale, VHI-10, and V-RQOL scores improved significantly over time postoperatively.

Conclusion: Multiple vocal function parameters improved significantly with time due to self-adaptation to a newly created glottis after surgery.

Keywords: improvement over time; laryngeal cancer; long-term change; postoperative vocal function; supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP).

© 2018 Wiley Periodicals, Inc.

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74
JMIR Public Health Surveill
. 2020 May 21;6(2):e19702. doi: 10.2196/19702.
Correlations of Online Search Engine Trends With Coronavirus Disease (COVID-19) Incidence: Infodemiology Study
Thomas S Higgins 1 2, Arthur W Wu 3, Dhruv Sharma 4, Elisa A Illing 4, Kolin Rubel 4, Jonathan Y Ting 4, Snot Force Alliance
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PMID: 32401211 DOI: 10.2196/19702
Free article
Abstract
Background: The coronavirus disease (COVID-19) is the latest pandemic of the digital age. With the internet harvesting large amounts of data from the general population in real time, public databases such as Google Trends (GT) and the Baidu Index (BI) can be an expedient tool to assist public health efforts.

Objective: The aim of this study is to apply digital epidemiology to the current COVID-19 pandemic to determine the utility of providing adjunctive epidemiologic information on outbreaks of this disease and evaluate this methodology in the case of future pandemics.

Methods: An epidemiologic time series analysis of online search trends relating to the COVID-19 pandemic was performed from January 9, 2020, to April 6, 2020. BI was used to obtain online search data for China, while GT was used for worldwide data, the countries of Italy and Spain, and the US states of New York and Washington. These data were compared to real-world confirmed cases and deaths of COVID-19. Chronologic patterns were assessed in relation to disease patterns, significant events, and media reports.

Results: Worldwide search terms for shortness of breath, anosmia, dysgeusia and ageusia, headache, chest pain, and sneezing had strong correlations (r>0.60, P<.001) to both new daily confirmed cases and deaths from COVID-19. GT COVID-19 (search term) and GT coronavirus (virus) searches predated real-world confirmed cases by 12 days (r=0.85, SD 0.10 and r=0.76, SD 0.09, respectively, P<.001). Searches for symptoms of diarrhea, fever, shortness of breath, cough, nasal obstruction, and rhinorrhea all had a negative lag greater than 1 week compared to new daily cases, while searches for anosmia and dysgeusia peaked worldwide and in China with positive lags of 5 days and 6 weeks, respectively, corresponding with widespread media coverage of these symptoms in COVID-19.

Conclusions: This study demonstrates the utility of digital epidemiology in providing helpful surveillance data of disease outbreaks like COVID-19. Although certain online search trends for this disease were influenced by media coverage, many search terms reflected clinical manifestations of the disease and showed strong correlations with real-world cases and deaths.

Keywords: Baidu; COVID-19; China; Google Trends; Italy; New York; SARS-CoV-2; Spain; Washington; big data; coronavirus; digital health; epidemiology; infodemiology; infoveillance.

©Thomas S Higgins, Arthur W Wu, Dhruv Sharma, Elisa A Illing, Kolin Rubel, Jonathan Y Ting, Snot Force Alliance. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 21.05.2020.

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75
Otol Neurotol
. 2019 Aug;40(7):920-926. doi: 10.1097/MAO.0000000000002293.
Hypotympanic Sound Baffle for Amelioration of Pulsatile Tinnitus Due to Carotid and Jugular Bulb Dehiscence
George S Liu 1, Nikolas H Blevins, Yona Vaisbuch
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PMID: 31295200 DOI: 10.1097/MAO.0000000000002293
Abstract
Objective: To share our experience with treating pulsatile tinnitus by insulating a dehiscent carotid artery with a hypotympanic sound baffle, and compare outcomes with a similar resurfacing approach for jugular bulb wall anomalies.

Study design: Retrospective case series.

Setting: Tertiary academic medical center.

Patients: Adult patients with troublesome pulsatile tinnitus with radiologic evidence of carotid artery dehiscence or jugular bulb wall anomaly within the temporal bone.

Intervention: Hypotympanic exposure of vessel followed by resurfacing using hydroxyapatite cement (carotid dehiscence) or autologous tissue (jugular bulb wall anomalies).

Main outcomes measures: Alleviation or reduction of pulsatile tinnitus.

Results: Two patients presented with unilateral, debilitating pulsatile tinnitus and history and imaging consistent with carotid dehiscence and underwent hypotympanic resurfacing with hydroxyapatite cement. Both had considerable initial improvement of tinnitus, and 40% resolution of tinnitus with improved quality of life at an average follow-up of 13.5 months. Two patients with jugular bulb dehiscence/diverticulum treated by resurfacing had complete elimination of symptoms at an average follow up of 17.3 months. There were no major adverse outcomes (permanent hearing loss, vascular injury, or intracranial hypertension).

Conclusion: Creation of a hypotympanic sound baffle offers promise as a means of reducing pulsatile tinnitus emanating from a dehiscent carotid artery transmitted to the tympanum, with substantial improvement in reported functional ability. Treatment of venous etiologies of pulsatile tinnitus with similar techniques demonstrates higher success rates, which may be attributable to incomplete resurfacing of carotid artery dehiscence along its extent towards the petrous apex due to safety concerns.

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76
Oral Oncol
. 2020 May 24;108:104772. doi: 10.1016/j.oraloncology.2020.104772. Online ahead of print.
New Prediction tool-LIST-with Improved Prediction Accuracy for 30-day Readmission Rates in Patients With Head and Neck Cancer After Major Cancer Surgery
Chun-Hao Yin 1, Bor-Hwang Kang 2, Wen-Shan Liu 3, Li-Fei Pan 4, Hsiu-Min Chen 1, Ching-Chih Lee 5
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PMID: 32460230 DOI: 10.1016/j.oraloncology.2020.104772
Abstract
We hope to establish a new readmission prediction score for patients with head and neck cancer (HNC) after major cancer surgery. A retrospective cohort study was conducted from the clinical and cancer registry data at Kaohsiung Veterans General Hospital. We included the data of patients with newly diagnosed HNC who underwent surgical treatment between Nov 2010 and Dec 2017. Multivariate logistic regression was performed to determine independent factors for 30-day readmission rate and establish a new prediction score. We compared the discriminatory ability of our new prediction score, HOSPTIAL score, and LACE index using linear trend chi-square test, the Akaike information criterion (AIC), and c-statistic. The 487 patients with HNC who underwent major surgery were discharged from the medical center. Of these patients, 40 (8.2%) were readmitted to the same hospital within 30 days. Our prediction score, namely LIST (representing leukocytosis, Charlson comorbidity index score of > 0, length of stay of top 33% for the total population, and advanced tumor stage) was derived through multivariate logistic regression. Compared with the HOSPITAL score and LACE index, LIST had a higher linear trend chi-square value (27.8 vs 4.3 and 6.3), higher prediction accuracy (0.743 vs 0.586 and 0.589), and lower AIC value (251 vs 274 and 272). The LIST can estimate 30-day readmission rates in patients with HNC. More intensive discharge planning and transition of care along with patient education can be applied to this high-risk group before discharge.

Keywords: HOSPITAL score; Head and neck cancer; LACE index; Readmission.

Copyright © 2020 Elsevier Ltd. All rights reserved.

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77
Turk J Pharm Sci
. 2019 Jun;16(2):169-174. doi: 10.4274/tjps.galenos.2018.20981. Epub 2019 Mar 27.
Decreased Protein Kinase C Expression in the Cochlear Fibroblasts of Diabetic Rat Models Induced by Curcumin
Tengku Siti Hajar Haryuna 1, Farhat Farhat 1, Siska Indriany 1
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PMID: 32454710 PMCID: PMC7227959 DOI: 10.4274/tjps.galenos.2018.20981
Free PMC article
Abstract
Objectives: Microcirculation and hemodynamic disturbances, including in the cochlea, are commonly found in diabetic patients. A study on diabetic rats discovered histopathological changes in outer hair cells and the spiral ganglion and mitochondrial damage in the ear. Hyperglycemia can increase the activation of protein kinase C (PKC). Curcumin as an antioxidant also affects the regulation of PKC and Ca2+. The aim of this study was to determine the role of curcumin in decreasing PKC expression in the cochlear fibroblasts of diabetic rats.

Materials and methods: An experimental study was performed on 24 Wistar rats divided into the following 6 groups: group 1: control group; group 2: diabetic group without curcumin administration; groups 3 and 4: diabetic groups with curcumin administration (200 mg/kg and 400 mg/kg for 3 days, respectively); groups 5 and 6: diabetic groups with curcumin administration (200 mg/kg and 400 mg/kg for 8 days, respectively). Cochlear tissues were taken from all groups and immunohistochemistry-stained, and the PKC expression scores were analyzed with one-way ANOVA (a significance level of 0.05).

Results: Significant differences in PKC expression (p<0.05) were found between group 1 and group 2, and group 2 and groups 3, 4, 5, and 6. There was no significant difference in PKC expression regarding the different doses and the duration of curcumin administration.

Conclusion: Curcumin can reduce PKC expression in the cochlear fibroblasts of diabetic rats.

Keywords: Diabetes mellitus; cochlea; curcumin; fibroblast; protein kinase C.

©Copyright 2019 Turk J Pharm Sci, Published by Galenos Publishing House.

Conflict of interest statement
Conflict of Interest: No conflict of interest was declared by the authors.

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78
Head Neck
. 2019 Jan;41(1):72-78. doi: 10.1002/hed.25372. Epub 2018 Dec 7.
Sclerosis of the Arytenoid Cartilage and Glottic Carcinoma: A Clinical-Pathological Study
Marco Lucioni 1, Marco Lionello 1, Piernicola Machin 2, Federica Sovran 3, Fabio Canal 2, Andy Bertolin 1, Giuseppe Rizzotto 1
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PMID: 30536660 DOI: 10.1002/hed.25372
Abstract
Background: Given the relevance of any tumor invasion of the arytenoid cartilage or crico-arytenoid unit to the planning open partial horizontal laryngectomy (OPHL) for laryngeal squamous cell carcinoma (LSCC), it is important to have a reliable radiological test to assess impairments of these structures.

Methods: We retrospectively compared the endoscopic, radiological, and pathological findings in patients with glottic LSCC who underwent OPHL.

Results: The endoscopic finding of a reduced (impaired or absent) vocal cord motility proved more sensitive, with better positive and negative predictive values, but less specific than the radiological finding of complete arytenoid sclerosis in detecting histologically assessable infiltration of the arytenoid cartilage.

Conclusions: Endoscopy retains a key role in the preoperative workup for glottic LSCC. CT evidence of complete sclerosis of the arytenoid cartilage is related to a dangerous contiguity of the tumor to the cartilage.

Keywords: arytenoid; infiltration; motility; partial laryngectomy; sclerosis.

© 2018 Wiley Periodicals, Inc.

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79
Expert Opin Drug Saf
. 2020 May 27. doi: 10.1080/14740338.2020.1775811. Online ahead of print.
Safety Evaluation of Pembrolizumab for Treating Recurrent Head and Neck Squamous Cell Carcinoma
Antoine Desilets 1, Denis Soulières 2
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PMID: 32458764 DOI: 10.1080/14740338.2020.1775811
Abstract
Programmed death 1 (PD-1) blockade has changed the therapeutic landscape of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with convincing overall response rates and overall survival benefits when compared to chemotherapy alone. The toxicity profile of pembrolizumab appears to be similar to that of other PD-1 or PD-L1 inhibitors, with frequent diarrhoea, hypothyroidism or cutaneous rash cases, and rare cases of grade 3 to 5 pneumonitis.Areas covered: In this article, the pharmacokinetics and mechanism of action of pembrolizumab will be covered, as well as the rationale behind tumour PD-L1 scoring. Safety and efficacy data surrounding pembrolizumab use will be presented. A tentative comparative analysis with other PD-1 (nivolumab) and PD-L1 (durvalumab) inhibitors will also be performed.Expert opinion: Superior OS for pembrolizumab as first-line monotherapy was demonstrated in the CPS ≥ 20 and CPS ≥ 1 populations, with favourable toxicity profile when compared to the EXTREME regimen. Patient selection through adequate PD-L1 scoring is thus essential in order to limit upfront exposure to combination chemotherapy. Further trials are currently investigating the safety of PD-L1 inhibitors, alone or in combination with anti-CTLA-4 therapies.

Keywords: PD-1 inhibitor; checkpoint inhibitor; head and neck cancer; immunotherapy; pembrolizumab.

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80
Review Exp Biol Med (Maywood)
. 2019 Mar;244(3):227-240. doi: 10.1177/1535370219826031. Epub 2019 Feb 13.
Role of Genomic Instability in Human Carcinogenesis
Jung Joo Moon 1, Alexander Lu 1, Chulso Moon 1 2
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PMID: 30760030 PMCID: PMC6425100 DOI: 10.1177/1535370219826031
Free PMC article
Abstract
This review provides various genetic and cell line data previously published in a way to explain how cellular stress can lead into genetic instability.

Keywords: Gene mutations; MYC; cellular stress; oncogene; p53; tumor suppressor gene.

Cited by 1 article4 figures
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81
Review Int J Audiol
. 2019 Dec;58(12):816-823. doi: 10.1080/14992027.2019.1654622. Epub 2019 Aug 23.
Literature Overview on P3 Measurement as an Objective Measure of Auditory Performance in Post-Lingually Deaf Adults With a Cochlear Implant
Laure Jacquemin 1 2, Griet Mertens 1 2, Winfried Schlee 3, Paul Van de Heyning 1 2, Annick Gilles 1 2 4
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PMID: 31441664 DOI: 10.1080/14992027.2019.1654622
Abstract
Objective: Cochlear implantation results in restoration of hearing, potential cortical reorganisation and the reallocation of attentional resources to the auditory system. Hence, the distorted cortical activity of patients with profound sensorineural hearing loss may be partially reversed. The measurement of auditory event-related potentials (ERPs) forms a promising electrophysiological evaluation of the central auditory nervous system. In particular, the P3 component is hypothesised to be a differential indicator of subjective auditory discrimination. This overview discusses the association between the cortical P3 component and the performance on auditory tests in post-lingually deaf adults using a CI. Moreover, the current article proposes important guidelines on eliciting, recording and analysing ERPs in CI users.Design: The literature search was conducted in PubMed.Study sample: Articles were included if they focussed on the relationship between P3 and auditory performance of an adult CI population.Results: The higher-order processing of speech in quiet and in noise of adult CI users is correlated with the ERP components, including the P3, shedding light on neurophysiological foundations for auditory performance differences.Conclusions: There is a need for replicating studies with larger sample sizes to fully comprehend the relationship between P3 and the auditory performance of CI users.

Keywords: Event-related potentials; P3; auditory performance; cochlear implant; speech perception.

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82
Ann Otol Rhinol Laryngol
. 2020 Jun;129(6):585-590. doi: 10.1177/0003489419901139. Epub 2020 Jan 24.
Malignant Otitis Externa Is Associated With Diabetes: A Population-Based Case-Control Study
Tzong-Hann Yang 1 2 3, Sudha Xirasagar 4, Yen-Fu Cheng 2 5 6 7, Chuan-Song Wu 1, Yi-Wei Kao 8, Ben-Chang Shia 8, Herng-Ching Lin 9 10
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PMID: 31976744 DOI: 10.1177/0003489419901139
Abstract
Objective: Despite studies reporting a possible association between malignant otitis externa (MOE) and diabetes, there are no large-scale population-based empirical studies. This nationwide, population-based case-control study explored the association of MOE occurrence with previously diagnosed diabetes.

Methods: Data were retrieved from Taiwan's National Health Insurance Research Database, 753 patients with MOE (cases) and 2 259 propensity score-matched patients without MOE (controls). Multiple logistic regressions were conducted to examine the association of MOE with previously diagnosed diabetes.

Results: In total, 728 (24.2%) out of 3 012 sample patients had diabetes prior to the index date. Chi-square test revealed a significant difference in diabetes prevalence among cases and controls (54.8% vs 13.9%, p < 0.001). Simple logistic regression showed the odds ratio for prior diabetes among cases versus controls was 7.50 (95% CI, 6.22~9.03). The adjusted odds ratio of prior diabetes for cases versus controls was 10.07 (95% CI, 8.15~12.44) after adjusting for patient demographics and medical co-morbidities.

Conclusions: This study found an association between MOE and diabetes. One clinical practice implication of our study is that when a patient with diabetes complains of otalgia or otorrhea, and physical examination shows swelling of the ear canal or granulation growth, physicians should consider the possibility of MOE.

Keywords: diabetes; epidemiology; malignant otitis externa.

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83
Ann Otol Rhinol Laryngol
. 2020 Jun;129(6):605-610. doi: 10.1177/0003489420903067. Epub 2020 Jan 29.
Multi-Institutional Regional Otolaryngology Bootcamp
Brian P Cervenka 1, Tsung-Yen Hsieh 1, Sharon Lin 1, Arnaud Bewley 1
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PMID: 31994404 DOI: 10.1177/0003489420903067
Abstract
Introduction: In order to increase junior resident physician proficiency and improve patient safety, simulation-based procedural training courses, or bootcamps, have been become an emerging educational tool.

Objectives: To compare pre- and post-course confidence levels and to assess station efficacy after completion of our single day bootcamp.

Methods: We developed the University of California (UC) Davis otolaryngology bootcamp, a single day course including six cadaveric task trainer stations and four simulations. The six task trainer stations included (1) Epistaxis, (2) Cricothyrotomy/tracheostomy, (3) Peritonsillar abscess/auricular hematoma, (4) Nasal bone reduction/zygoma reduction/lateral canthotomy/canalicular trauma and probing, (5) Local nerve blocks, and (6) Soft tissue reconstruction. The simulations comprised of airway fire during tracheostomy, pediatric respiratory code during airway evaluation, dislodged pediatric tracheostomy tube in the ICU, and angioedema in the emergency department with inability to intubate or ventilate. Junior residents from multiple locoregional institutions were recruited to participate. Pre- and post-course Likert surveys assessing participant confidence and station efficacy were collected and analyzed.

Results: There was a statistically significant increase in resident confidence levels for all task trainer stations. All stations had a station efficacy Likert score average of 4 "very effective" or 5 "most effective."

Conclusion: A multi-institutional, locoregional, simulation-based bootcamp can be a valuable adjunct to junior resident training. It can promote camaraderie, pool limited resources, and may be cost-effective.

Keywords: bootcamp; otolaryngology; resident education; simulation; surgical training.

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84
Head Neck
. 2019 Jan;41(1):230-238. doi: 10.1002/hed.25516. Epub 2018 Dec 15.
Novel ANO5 Mutation c.1067G>T (p.C356F) Identified by Whole Genome Sequencing in a Big Family With Atypical Gnathodiaphyseal Dysplasia
Binghui Zeng 1 2 3, Junkun Liao 1 2, Hanqing Zhang 1 2, Sha Fu 4, Weixiong Chen 1 2, Guokai Pan 1 2, Qunxing Li 1 2, Weiliang Chen 1 2, Soldano Ferrone 5, Binghao Wu 6, Sheng Sun 7, Jiali Hu 8, Michael Ho-Young Ahn 5, Zhaoyu Lin 1 2, Dongsheng Yu 3, Zhanpeng Ou 1 2, Xinhui Wang 5, Fengbo Mo 5, Nasi Huang 5 9, James A Hamilton 9, Jinsong Li 1 2, Song Fan 1 2 5
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PMID: 30554457 DOI: 10.1002/hed.25516
Abstract
Background: Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied.

Methods: Sanger sequencing, whole-genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed.

Results: A family with patients with fibro-osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through WGS, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed.

Conclusions: The novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro-osseous lesions.

Keywords: ANO5; SH3BP2; cherubism; gnathodiaphyseal dysplasia; whole-genome sequencing.

© 2018 Wiley Periodicals, Inc.

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85
J Voice
. 2020 May 22;S0892-1997(20)30163-6. doi: 10.1016/j.jvoice.2020.04.028. Online ahead of print.
Development and Validation of the Thyroidectomy-Related Voice and Symptom Questionnaire (TVSQ)
Yeon-Shin Hwang 1, Mi-Ran Shim 1, Geun-Jun Kim 1, Dong-Hyun Lee 1, Inn-Chul Nam 1, Jun-Ook Park 1, Sang-Yeon Kim 2, Young-Hak Park 1, Ja-Sung Bae 3, So-Hee Lee 3, Jeong-Soo Kim 3, Dong-Il Sun 4
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PMID: 32451255 DOI: 10.1016/j.jvoice.2020.04.028
Abstract
Objectives: Common symptoms after thyroidectomy include voice change and throat and neck discomfort. But no common questionnaire has been developed. This study was performed to evaluate the reliability and validity of the Thyroidectomy-related Voice and Symptom Questionnaire (TVSQ).

Methods: Fourty items of the TVSQ were divided into 20 items related to the "voice change" and "throat and neck discomfort" subcategories, using item generation. Through a reduction process, 20 items were removed and 20 items were used. For the patients after thyroidectomy, we evaluated the reliability and validity of each of the 20 items through item discrimination, test-retest reliability, concurrent validity, and external validity by comparing normal group and laryngeal disease patients. Also, the patients were compared before as well as 2 and 4 weeks after thyroidectomy.

Results: Item discrimination assessment showed a significant correlation between TVSQ total score and both the TVSQ "voice change" score (r = 0.908**) and TVSQ "throat and neck discomfort" score (r = 0.862**). Test-retest reliability assessment showed a significant correlation between TVSQ total scores at 2 and 4 weeks postoperatively (r = 0.764**). Concurrent validity assessment revealed that the TVSQ showed high correlations with other voice questionnaires (Voice Handicap Index, Reflux Finding Index, and Vocal Track Discomfort Scale; r = 0.538**-0.830**). External validity assessment revealed that the TVSQ was suitable for patients after thyroidectomy (P < 0.000**).

Conclusions: Validity and reliability tests revealed that the TVSQ was suitable for assessment of the subjective feelings of patients with voice change and throat and neck discomfort after thyroidectomy.

Keywords: TVSQ; Throat and neck discomfort after thyroidectomy; Thyroidectomy questionnaire; Validity and reliability of Thyroidectomy-related Voice and Symptom Questionnaire; Voice change after thyroidectomy.

Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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86
Head Neck
. 2020 May 27. doi: 10.1002/hed.26266. Online ahead of print.
Identification of Genes Associated With Cancer Stem Cell Characteristics in Head and Neck Squamous Cell Carcinoma Through Co-Expression Network Analysis
Su Pei 1, Long Chen 1, Yunli Yang 1, Xiaodong Zhu 1
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PMID: 32459022 DOI: 10.1002/hed.26266
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a type of invasive malignancy and the seventh most common cancer in the worldwide. Cancer stem cells (CSCs) are self-renewal cells in tumors and can produce heterogeneous tumor cells, which play an important role in the development of HNSCC. In our research, we aimed to identify genes related to the CSCs characteristics in HNSCC.

Methods: Messenger RNA (mRNA) expression-based stiffness index (mRNAsi) can be used as a quantitative characterization of CSCs. We used one-class logistic regression machine learning algorithm (OCLR) to calculate the mRNAsi and investigate the relationship between mRNAsi and clinical characteristics of HNSCC. Then, a weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network was constructed to screen hub genes related to mRNAsi of HNSCC.

Results: The results indicated that the score of mRNAsi in HNSCC tissues is higher than in paracancer tissues, while the mRNAsi was not statistically correlated with the prognosis and clinical characteristics of HNSCC. Six positive and six negative hub genes related to mRNAsi of HNSCC were selected, which may act as therapeutic targets for inhibiting CSCs within HNSCC.

Conclusions: In conclusion, our research selected 12 hub genes related to mRNAsi of HNSCC through weighted gene co-expression network analysis. These genes may become therapeutic targets to inhibit the CSCs of HNSCC in the future.

Keywords: CSCs characteristic; HNSCC; TCGA; WGCNA; mRNAsi.

© 2020 Wiley Periodicals, Inc.

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87
Dysphagia
. 2020 May 26. doi: 10.1007/s00455-020-10138-7. Online ahead of print.
Prevalence of Dysphagia in China: An Epidemiological Survey of 5943 Participants
Mengqing Zhang 1, Chao Li 1, Fang Zhang 1, Xiaoxiao Han 1, Qinglu Yang 1, Tuo Lin 2, Huichang Zhou 3, Min Tang 4, Jungui Zhou 5, Hongling Shi 6, Yanping Hui 7, Mingfeng Xiong 8, Ling Pang 9, Baolan Wang 10, Zhen Feng 11, Zhanfei Li 12, Changbing Cao 13, Xiao Lu 14, Yuanyuan Ding 15, Shukun Shen 16, Zhengyue Xu 17, Fan Yu 18, Chen Chen 19, Ling Meng 20, Guiqing Liao 21, Jinxin Zhang 22, Ayodele Sasegbon 23, Zulin Dou 24
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PMID: 32458145 DOI: 10.1007/s00455-020-10138-7
Abstract
Objective: To determine the prevalence of dysphagia among an older population and patients with stroke, head and neck cancers (HNCs) or neurodegenerative diseases (NDDs) in China, to identify the factors associated with this condition, and to explore the relationship between dysphagia and nutritional status.

Methods: This study included participants 65 years and older living in the community or in nursing homes and patients who had sustained a stroke, HNC, or NDD also recruited in hospitals from 14 provinces of China. The presence of dysphagia was determined by use of a questionnaire, water swallowing test, and/or a videofluoroscopic swallowing study. Logistic regression analysis was used to assess the possible associated risk factors. Body mass index was assessed as an indicator of malnutrition.

Results: A total of 5943 persons met the inclusion criteria and 2341 (39.4%) were identified with dysphagia, including the following: 51.14% of patients with stroke, 34.4% in HNCs, 48.3% in NDDs, and 19.2% of otherwise healthy older adults. The elderly with comorbidity (OR = 2.90, p < 0.01) and stroke patients (OR = 2.27, p < 0.01) were significantly more likely to exhibit signs of dysphagia. Dysphagic participants were at significantly greater risk of malnutrition (OR = 1.91, p < 0.01) compared to those without dysphagia.

Conclusion: Dysphagia is prevalent in China among older individuals and people who have suffered a stroke, HNCs, or NDDs. The prevalence of dysphagia increases steadily with increasing age and presence of comorbid disease. People with dysphagia are more likely to suffer from malnutrition.

Keywords: Chinese elderly; Comorbidity; Deglutition; Deglutition disorders; Dysphagia; Epidemiology.

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88
Head Neck
. 2019 Jan;41(1):225-229. doi: 10.1002/hed.25488. Epub 2018 Dec 9.
Superior Detection of Metastatic Cystic Lymphadenopathy in Patients With Papillary Thyroid Cancer by Utilization of Thyroglobulin Washout
Helmi Khadra 1, Hossam Mohamed 1, Zaid Al-Qurayshi 2, Andrew Sholl 3, Mary Killackey 1, Emad Kandil 1
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PMID: 30536535 DOI: 10.1002/hed.25488
Abstract
Background: Fine-needle aspiration (FNA) cytology has been the standard of care in the workup of cervical lymph nodes (LNs) in patients with recurrent papillary thyroid cancer (PTC) and suspicious cervical LNs. Recently, FNA thyroglobulin (TG) washout measurement has been proposed as an adjunct in the management of these patients. We hypothesize that using FNA-TG washout for suspicious cervical LNs would increase the accuracy of diagnosing metastatic disease especially in cystic and highly vascular cervical LN in patients with recurrent PTC.

Methods: This is a retrospective study of a prospectively collected database for patients with thyroid cancer who underwent preoperative FNA followed by selective neck dissection by one surgeon at an academic institution. FNA-cytology and FNA-TG washout were performed simultaneously. A total of 138 patients were included in our study, of which 92 (66.7%) had undergone surgical intervention. Results of both methods were then correlated with the final surgical pathology.

Results: FNA-cytology alone showed a sensitivity of 80.0%, specificity of 100.0% with a negative predictive value (NPV) of 60.0%. By contrast, FNA-TG washout had a sensitivity of 95.8%, specificity of 90.5% with a NPV of 86.4%. Combination of the FNA-cytology with FNA-TG washout of cystic/highly vascular LN increased the accuracy of diagnosis with a sensitivity of 98.2%, specificity of 100.00% with a NPV of 95.0%. All 14 malignant cervical LNs with false-negative FNA-cytology showed elevated FNA-TG washout, 10 (71.4%) of which were cystic in nature and 4 were highly vascular on ultrasonography.

Conclusion: FNA-TG washout increases the diagnostic accuracy in detecting metastatic disease in patients with recurrent thyroid cancer. FNA-TG washout may be of special diagnostic importance in cystic or highly vascular LNs, which might have falsely negative cytology.

Level of evidence: 2B.

Keywords: cystic lymph nodes; papillary thyroid cancer; thyroglobulin washout; vascular lymph nodes.

© 2018 Wiley Periodicals, Inc.

Cited by 1 article
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89
Eur Arch Otorhinolaryngol
. 2019 Dec;276(12):3507-3511. doi: 10.1007/s00405-019-05621-3. Epub 2019 Sep 12.
Ethnic Differences of Children With Foreign Body Aspiration: A Need for Preventive Education
Ohad Ronen 1, Florencia Kanelo 2, Deborah Shor 2, Maureen Ashkar 2, Ilana Kepten 2
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PMID: 31515661 DOI: 10.1007/s00405-019-05621-3
Abstract
Introduction: Only in 2005 was a product labeling law passed in Israel that requires food companies to mark a choking hazard. We wished to investigate the influence of the hazard warning on the number of foreign body aspirations (FBA) in Israel, as well as the racial differences in the prevalence of and death rates from FBA.

Materials and methods: All the medical records of patients under the age of 14 who arrived at our center's emergency department between the years 2007 and 2015 with suspected FBA were retrospectively reviewed. Population data was extracted from the Central Bureau of Statistics.

Results: Overall, 90 children arrived at the hospital with suspected FBA during 2007-2015. Forty-six (51%) of the patients were males, the mean age was 3.5 years. Seventy-one bronchoscopies were performed due to high suspicious presence of a foreign body. The most common objects aspirated were different types of nuts and seeds. In all cases, the patient's parents witnessed the aspiration of the foreign body. Most children (77, 86%) were of Arab ethnicity. The yearly prevalence of FBA in children 0-4 years of Arab ethnicity was 16.6:100,000 compared to 6.0:100,000 in the non-Arab population (p < 0.001).

Conclusion: FBA is still a common injury in our region. Since most cases are preventable, efforts should be targeted among the population at higher risk, which are parents of children under the age of 4 and parents of Arab ethnicity. We believe that national effort and support for preventive education are needed.

Keywords: Children; Ethnic group; Foreign body aspiration.

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90
Ear Hear
. 2020 May 21. doi: 10.1097/AUD.0000000000000885. Online ahead of print.
Relationship Between Corrective Saccades and Measures of Physical Function in Unilateral and Bilateral Vestibular Loss
Kristal M Riska 1, Jordan Bellucci 2, Doug Garrison 1, Courtney Hall 3 4
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PMID: 32453218 DOI: 10.1097/AUD.0000000000000885
Abstract
Objectives: Following the loss of vestibular function, some patients functionally improve and are minimally bothered by their loss of peripheral function while others remain more symptomatic and are unable to return to their activities of daily living. To date, the mechanisms for functional improvement remain poorly understood. The purpose of the present study was to examine the association between corrective saccades and measures of handicap, dynamic visual acuity, gait, and falls.

Design: A retrospective chart review was performed to identify patients who were diagnosed with unilateral or bilateral vestibular hypofunction and who also completed a baseline vestibular rehabilitation evaluation. A total of 82 patients with unilateral vestibular hypofunction and 17 patients with bilateral vestibular hypofunction were identified. The video head impulse test results for each patient were grouped based on the type of presenting saccades. Specifically, the saccade grouping included the following: (1) covert, (2) overt, or (3) a combination of both types of saccades.

Results: The results show that covert saccades are associated with better performance on measures of dynamic visual acuity, gait, and balance in patients with unilateral vestibular hypofunction. Patients exhibiting overt saccades or combination of both covert and overt saccades were more often found to have an abnormal gait speed and be characterized as being at risk for falls using the Dynamic Gait Index. We observed no differences in physical function for those patients with bilateral vestibular hypofunction as a function of saccade grouping.

Conclusions: When comparing saccade groups (covert, overt, or combination of both), patients with unilateral vestibular hypofunction and covert saccades demonstrated better performance on standard baseline physical therapy measures of dynamic visual acuity and gait and balance. We did not observe any significant associations between saccade group and physical function in patients with bilateral vestibular hypofunction; however, additional studies are needed with adequate sample sizes. Our findings may suggest that corrective saccade latency in patients with unilateral vestibular hypofunction is related to measures of physical function. The extent to which saccade latency has the potential to be a useful target for vestibular rehabilitation is still to be determined and may be promising target to improve functional outcomes.

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91
J Int Med Res
. 2019 Dec;47(12):6315-6336. doi: 10.1177/0300060519885570. Epub 2019 Nov 19.
The Top 100 Most Influential Articles in Allergic Rhinitis From 1970 to 2018: A Bibliometric Analysis
Qingwu Wu 1, Rui Zheng 1, Weihao Wang 1, Huijun Qiu 1, Xuekun Huang 1, Qintai Yang 1
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PMID: 31741403 PMCID: PMC7045673 DOI: 10.1177/0300060519885570
Free PMC article
Abstract
Objective: This study aimed to identify the top 100 most influential articles in the field of allergic rhinitis (AR).

Methods: Web of Science was queried for 1970 to 2018. Articles were sorted in descending order of the citation count. All titles and abstracts were screened to identify the top 100 articles.

Results: The top 100 most influential articles in AR were identified. The earliest article was published in 1975, and the most recent in 2015. The most prolific decade was the 2000s, with 59 articles published. Twenty-nine journals contributed to the top 100 articles, with the Journal of Allergy and Clinical Immunology contributing most of the articles (n = 34). The top three countries of article origin were the United States (n = 34), followed by the United Kingdom and France (n = 14 each). The type of article covered clinical research (n = 68), reviews (n = 22), and basic research (n = 10). For the clinical research articles, there were 6 studies with level 1 evidence, 25 with level 2 evidence, 11 with level 3 evidence, and 26 with level 4 evidence.

Conclusions: This study identified the top 100 most influential articles in the area of AR. Recognition of important historical contributions to this field may guide future investigations into AR.

Keywords: Allergic rhinitis; bibliometric; citation analysis; immunity therapy; influential article; landmark study.

Cited by 1 article18 references2 figures
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92
J Dance Med Sci
. 2020 Jun 15;24(2):66-72. doi: 10.12678/1089-313X.24.2.66.
Injury Profile of Hip-Hop Dancers
Olga Tjukov 1, Tobias Engeroff 2, Lutz Vogt 2, Winfried Banzer 2, Daniel Niederer 2
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PMID: 32456761 DOI: 10.12678/1089-313X.24.2.66
Abstract
This study assessed the injury incidence, mechanisms, and associated potential risk factors for hip-hop, popping, locking, house, and breaking dance styles. Data were collected from June to November 2015. The retrospective cohort study included 146 dancers (female: N = 67; age = 20 ± 4.2 years; males: N = 79; age = 22.9 ± 5.8 years) who completed a questionnaire that collected data concerning training hours, injuries, self-reported injury causes, treatment, and recovery time over the last 5 years. For the last 5 years, 52% (N = 76) of the dancers reported 159 injuries and, in the year prior to the survey, 31.5% (N = 46) reported a total of 75 injuries. Overall, 0.61 injuries (5 years) and 1.156 injuries (1 year) per 1,000 hours exposure time occurred. For breaking, 1.286 injuries (5 years) and 2.456 injuries (1 year) per 1,000 hours exposure time were calculated, while the other dance styles accumulatively reached 0.151 injuries (5 years) and 0.318 injuries (1 year) per 1,000 hours of exposure time. Breakers reported most injuries at the upper extremities, followed by the lower extremities, trunk, and head and neck region. Most injuries in hip-hop occurred at the lower extremities, mainly affecting the knees, followed by groin and ankle. Injuries experienced by popping and locking dancers only involved the lower extremities. In house, the lower extremities were affected most frequently, followed by the trunk. A total of 65.3% of the dancers experienced time loss, with a duration of 12.7 ± 21.3 weeks. Breakers experience significantly more injuries than dancers of the other styles. Injury risk among dancers of all the styles studied can be considered low compared to soccer players, swimmers, and long-distance runners.

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93
Comparative Study Ann Otol Rhinol Laryngol
. 2020 Jun;129(6):556-564. doi: 10.1177/0003489419900201. Epub 2020 Jan 10.
Outcomes Assessment of Multi-Level Sleep Surgery in Syndromic Versus Non-Syndromic Children
Suqrat Munawar 1, Alexander P Marston 1, Terral Patel 1, Shaun A Nguyen 1, David R White 1
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PMID: 31920116 DOI: 10.1177/0003489419900201
Abstract
Objectives: Analyze the differences in length of stay, cost, disposition, and demographics between syndromic and non-syndromic children undergoing multi-level sleep surgery.

Methods: Children with sleep disordered breathing or obstructive sleep apnea that had undergone sleep surgeries were isolated from the 1997 to 2012 editions of the Kids' Inpatient Database, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Children were then classified as syndromic or non-syndromic and stratified by level of sleep surgery (tonsillectomy & adenoidectomy, tonsillectomy & adenoidectomy plus other site surgery, other site surgery). Length of stay and cost were reported with Kruskal-Wallis one-way analysis of variance, disposition with binomial logistic regression, and demographics with chi-square.

Results: Syndromic children compared to non-syndromic children were more likely to have surgery beyond just tonsillectomy & adenoidectomy and also had a longer length of stay, higher total cost and non-routine disposition (all P < .001). Syndromic children undergoing tonsillectomy and adenoidectomy plus other site surgery had a longer length of stay compared to syndromic children undergoing tonsillectomy & adenoidectomy (6.00 days vs 3.63 days, P < .001). However, no similar statistically significant difference in length of stay was found in non-syndromic children (2.01 days vs 2.87 days, P > .05).

Conclusion: The potential risks/benefits need to be weighed carefully before undertaking sleep surgery in syndromic children. They experience a longer length of stay, higher cost, and non-routine disposition when compared to non-syndromic children. This is especially true when considering the transition from tonsillectomy & adenoidectomy to tonsillectomy & adenoidectomy plus other site surgery, as syndromic children experience a longer length of stay and non-syndromic children do not.

Keywords: adenoidectomy; multi-level sleep surgery; obstructive sleep apnea; sleep disordered breathing; syndromic; tonsillectomy.

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94
Case Reports J Int Med Res
. 2019 Dec;47(12):6356-6364. doi: 10.1177/0300060519885289. Epub 2019 Nov 19.
Process of Ectopic Tooth Formation in the Maxillary Sinus: Follow-Up Observation of One Case
Jinfeng Liu 1, Mo Zhou 1, Qitong Liu 2, Xiaolin He 1, Ningyu Wang 1
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PMID: 31741404 PMCID: PMC7045658 DOI: 10.1177/0300060519885289
Free PMC article
Abstract
Objective: This study was performed to investigate the process of ectopic tooth formation.

Methods: A patient with an ectopic tooth was followed for 6 years. The tooth size and mineralization were evaluated by paranasal sinus computed tomography every 3 years.

Results: The ectopic tooth was present in the nasal crest of the maxilla and did not change significantly during the 6-year follow-up period. However, the patient developed a new ectopic tooth in the maxillary sinus (ETm). This tooth, located in the posterior wall of the left maxillary sinus, initially appeared as a small region of soft tissue on computed tomography. After 3 years, the area of mixed density had significantly increased, and some of it had significantly mineralized to form an ETm. After 6 years, the ETm had further mineralized and enlarged in situ. The width between the left and right sides of the ETm in 2018 (9.08 ± 2.09 mm) was significantly larger than that in 2015 (7.51 ± 2.18 mm), indicating that ETm formation is a gradual process of mineralization.

Conclusion: Ectopic teeth can gradually form by in situ mineralization after adolescence, suggesting that ectopic teeth are genetically regulated and result from a programmed formation process occurring at a specific time point.

Keywords: Ectopic teeth; computed tomography; follow-up studies; maxillary sinus; mineralization; supernumerary teeth.

22 references3 figures
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95
Review Neurosurg Rev
. 2020 May 26. doi: 10.1007/s10143-020-01316-0. Online ahead of print.
Safety and Effectiveness of Endoscopic Endonasal Intracranial Aneurysm Clipping: A Systematic Review
Rafael Martinez-Perez 1, Douglas A Hardesty 2 3, Giuliano Silveira-Bertazzo 2, Thiago Albonette-Felicio 2, Ricardo L Carrau 2 3, Daniel M Prevedello 4 5
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PMID: 32458275 DOI: 10.1007/s10143-020-01316-0
Abstract
Once considered far-fetched, endoscopic endonasal clipping (EEC) has been reported as a feasible alternative route for treating intracranial aneurysms located in the midline. Appropriately, debates regarding EEC applicability have arisen amongst the neurosurgical community. We aim to define the safety, effectiveness, and current state-of-art in the use of EEC for intracranial aneurysms. Two databases (PubMed, Cochrane) were queried for intracranial aneurysms that underwent EEC between inception and 2019. Literature review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data regarding clinical presentation, radiological imaging, and outcome were extracted and analyzed from selected publications. Nine studies with 27 patients (8 males, 19 females), harboring 35 aneurysms (9 ruptured, 26 nonruptured), met the predetermined inclusion criteria. Patient age range is from 34 to 70 (median = 50) years old. Four aneurysms were considered not suitable for EEC during the procedure, and two aneurysms required additional treatment, leading to an overall treatment success (obliteration) rate of 86%. Complications occurred in 7 patients (26%), including CSF leakage in 5 patients (18%) and ischemic complications in 4 (15%). Among the cases reported, complications occurred more frequently in posterior circulation aneurysms in comparison with anterior circulation aneurysms (62.5 vs 10.5%). Ischemic complications occurred in 4 out of 8 posterior circulation aneurysms. Although feasible, EEC is associated with a significant risk of complications, with rates identified that are significantly higher than established open clipping or endovascular management. The current data suggest that transcranial clipping and endovascular occlusion are still the primary indication for treating intracranial aneurysms.

Keywords: Clipping; Endoscopy; Minimally invasive; Transnasal; Transphenoidal.

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96
Review Cell Mol Life Sci
. 2020 May;77(10):1933-1945. doi: 10.1007/s00018-019-03373-1. Epub 2019 Nov 13.
Vertebrate Cranial Mesoderm: Developmental Trajectory and Evolutionary Origin
Bhakti Vyas 1 2, Nitya Nandkishore 1 3, Ramkumar Sambasivan 4
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PMID: 31722070 DOI: 10.1007/s00018-019-03373-1
Abstract
Vertebrate cranial mesoderm is a discrete developmental unit compared to the mesoderm below the developing neck. An extraordinary feature of the cranial mesoderm is that it includes a common progenitor pool contributing to the chambered heart and the craniofacial skeletal muscles. This striking developmental potential and the excitement it generated led to advances in our understanding of cranial mesoderm developmental mechanism. Remarkably, recent findings have begun to unravel the origin of its distinct developmental characteristics. Here, we take a detailed view of the ontogenetic trajectory of cranial mesoderm and its regulatory network. Based on the emerging evidence, we propose that cranial and posterior mesoderm diverge at the earliest step of the process that patterns the mesoderm germ layer along the anterior-posterior body axis. Further, we discuss the latest evidence and their impact on our current understanding of the evolutionary origin of cranial mesoderm. Overall, the review highlights the findings from contemporary research, which lays the foundation to probe the molecular basis of unique developmental potential and evolutionary origin of cranial mesoderm.

Keywords: Cardiopharyngeal field; Head mesoderm; Head muscles; Mesoderm development; Vertebrate head evolution.

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97
Laryngoscope
. 2020 May 26. doi: 10.1002/lary.28759. Online ahead of print.
Influences of CD8 + Tregs on Peripheral Blood Mononuclear Cells From Allergic Rhinitis Patients
Lin Lin 1, Fei Dai 1, Jinjin Wei 1, Zheng Chen 1
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PMID: 32453455 DOI: 10.1002/lary.28759
Abstract
Objectives: CD8+ (or CD4+ ) CD25+ fork-head box transcription factor (Foxp3)+ regulatory T cells (CD8+ or CD4+ Tregs) all play a significant role in immune homeostasis and tolerance. However, the role of CD8+ Tregs in allergic rhinitis (AR) have not been clearly elucidated. The present study was aimed to assess the influence of CD8+ Tregs on peripheral blood mononuclear cells (PBMCs) from AR patients.

Study design: Prospective cross-sectional study.

Methods: Patients with AR were enrolled. PBMCs were obtained, and CD4+ and CD8+ Tregs were separated from PBMCs and cultured in vitro. We examined percentages of these Tregs in total CD4+ or CD8+ T cells, respectively. After that, we evaluated levels of interleukin (IL)-10 and transforming growth factor (TGF)-β in Tregs cultures. Finally, we administered CD4+ and CD8+ Tregs from AR patients into PBMCs cultures and examined contents of IL-4 and IL-5.

Results: The percentages of CD4+ or CD8+ Tregs in the total CD4+ or CD8+ T cells from PBMCs in AR patients were reduced compared to normal subjects. However, IL-10 and TGF-β and their mRNAs were increased in CD4+ and CD8+ Tregs cultures from AR patients, and there were no significant differences in their levels between these two Tregs cultures. IL-4 and IL-5 were increased in AR subjects' PBMCs compared to normal ones and decreased after the AR CD4+ or CD8+ Tregs administration. However, there were no statistical differences in IL-4 and IL-5 concentrations between these two Tregs treatments.

Conclusions: The findings demonstrate that CD8+ Tregs may alleviate inflammatory responses in AR condition.

Level of evidence: 3 Laryngoscope, 2020.

Keywords: CD4+ tregs; CD8+ tregs; PBMCs; allergic rhinitis.

© 2020 The American Laryngological, Rhinological and Otological Society, Inc.

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98
Case Reports Mol Genet Genomic Med
. 2019 Jun;7(6):e685. doi: 10.1002/mgg3.685. Epub 2019 Apr 23.
Identification of a Complex Genomic Rearrangement in TMPRSS3 by Massively Parallel Sequencing in Chinese Cases With Prelingual Hearing Loss
Xinlei Li 1, Bo Tan 1, Xiaoqian Wang 2, Xiaofei Xu 1, Cuicui Wang 1, Mingjun Zhong 1, Qiuling Zhao 1, Zhongwei Bao 1, Weihua Peng 1, Lei Zhang 1, Jing Cheng 1, Yu Lu 1, Peina Wu 2, Huijun Yuan 1
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PMID: 31016883 PMCID: PMC6565588 DOI: 10.1002/mgg3.685
Free PMC article
Abstract
Background: Genetic variants in TMPRSS3 have been causally linked to autosomal recessive nonsyndromic hearing loss (HL) at the DFNB8 and DFNB10 loci. These variants include both single nucleotide and copy number variations (CNVs). In this study, we aim to identify the genetic cause in three Chinese subjects with prelingual profound sensorineural HL.

Methods: We applied targeted genomic enrichment and massively parallel sequencing to screen 110 genes associated with nonsyndromic HL in the three affected subjects. CNVplex® analysis and polymerase chain reaction (PCR) were performed for CNV detection.

Results: We identified biallelic variations in TMPRSS3 including a novel complex genomic rearrangement and a novel missense mutation, c.551T>C. We have mapped the breakpoints of the genomic rearrangement and showed that it consisted of two deletions and an inversion encompassing exon 3 to exon 9 of TMPRSS3.

Conclusion: Our study expanded the mutational spectrum of TMPRSS3 to include complex genomic rearrangements. It showcased the importance of an integrative approach to investigate CNVs and their contribution to HL.

Keywords: TMPRSS3; copy number variation; hearing loss; massively parallel sequencing; rearrangement.

© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Conflict of interest statement
None declared.

16 references3 figures
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99
J Biomed Mater Res A
. 2019 Mar;107(3):552-560. doi: 10.1002/jbm.a.36571. Epub 2018 Nov 19.
Combinational Effects of Mechanical Forces and Substrate Surface Characteristics on Esophageal Epithelial Differentiation
Yanru Wu 1, Yun Gyeong Kang 2, Hana Cho 3, In Gul Kim 3, Eun-Jae Chung 3, Jung-Woog Shin 1 2 4
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PMID: 30390394 DOI: 10.1002/jbm.a.36571
Abstract
Even the efficacy of substrate and mechanical stimuli in addition to biochemical cues have been recognized in many studies of stem cell differentiation, few studies have been reported on the differentiation into esophageal epithelial cells. Therefore, the aim of this study was set to propose a method of differentiating stem cells into esophageal epithelial cells according to biochemical reagent concentration, substrate properties, and mechanical forces. After the concentration of all-trans retinoic acid was determined as 5 μM by a baseline experiment, the degree of differentiation was compared in three different kinds of substrates: cover glass, polyurethane (PU) membrane, and electrospun PU sheet (ePU). Then, on the substrate showing the more positive results, that is, ePU, two types of mechanical forces, intermittent hydrostatic pressure (IHP), and shear stress (SS), were applied individually at different magnitudes for the latter 7 days of an overall incubation period of 14 days. Following various biological assays, the lower IHP (50 mmHg) resulted in greater positive effects than the others. Even with cessation of the mechanical force, the relevant markers were remarkably increased. Although the range of factors regulating differentiation was limited, this study nonetheless demonstrated the combinational effects of mechanical force along with substrate type for the first time in related studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 552-560, 2019.

Keywords: electrospun sheet; esophageal epithelial differentiation; mechanical forces; polyurethane membrane; stem cells.

© 2018 Wiley Periodicals, Inc.

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