H&N : 115 citations

Items: 115
Select item 31242489
1.
Chemotherapy. 2019 Jun 26:1-9. doi: 10.1159/000500714. [Epub ahead of print]
Efficacy and Safety of Cetuximab plus Radiotherapy in Cisplatin-Unfit Elderly Patients with Advanced Squamous Cell Head and Neck Carcinoma: A Retrospective Study.
Addeo R1, Caraglia M2, Vincenzi B3, Luce A2, Montella L4, Mastella A5, Mazzone S6, Ricciardiello F7, Carraturo M8, Del Prete S4, Sperlongano P9.
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Abstract
INTRODUCTION:
Concurrent platinum-based chemoradiation currently represents the standard treatment for advanced head and neck cancer (HNC), but it induces a significant toxicity, in particular among elderly patients. Elderly and unfit patients have been underrepresented in clinical trials and there is a need for tailored guidelines.

METHODS:
A retrospective review of clinical data of HNC patients treated at the Operative Oncology Unit of the San Giovanni di Dio Hospital in Frattamaggiore (Naples, Italy) was performed. At study entry, a comprehensive assessment including absolute contraindications for cisplatin use, as well as comorbidities, socioeconomic status, BMI, and weight loss, was performed. The treatment included high-dose radiotherapy plus weekly cetuximab (initially at a dose of 400 mg/m2of body surface area and thereafter at 250 mg weekly during the whole radiotherapy). The aim of this study was to evaluate the activity and toxicity of this schedule in a series of patients aged older than 69 years.

RESULTS:
Between May 30, 2013, and March 30, 2015, sixty-four patients (age range, 69-87 years; median age, 73.7 years; male/female ratio, 46/18) were treated. The overall response rate was 67% in this series of patients. The disease control rate was 76%. Disease progression was recorded in 25% of the patients. The median duration of loco-regional control was 17 months (range, 15.8-17.7 months). PFS was 14.8 months (range, 13.9-15.5 months). The overall survival was 34 months, with a median follow-up of 41.0 months (range, 31.1-36.8 months). The main grade 3/4 adverse events were acne rash in 52% and radiation dermatitis in 32% of the cases.

CONCLUSION:
Cetuximab plus radiotherapy appears to be feasible and active in elderly patients unsuitable for cisplatin treatment. The treatment was supported by a favorable toxicity profile.

© 2019 S. Karger AG, Basel.

KEYWORDS:
Advanced head and neck cancer; Cetuximab; Chronic alcoholism; Comorbidities; Elderly; Radiotherapy

PMID: 31242489 DOI: 10.1159/000500714
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Select item 31242479
2.
ORL J Otorhinolaryngol Relat Spec. 2019 Jun 26:1-11. doi: 10.1159/000499473. [Epub ahead of print]
Pigmented Villonodular Synovitis Presenting as Unilateral Hearing Loss: Review of the Literature and Case Report.
Brant JA1, Kaufman AC2, Luu N3, Grady SM4, O Apos Malley BW1, Ruckenstein MJ1.
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Abstract
BACKGROUND/AIMS:
To review the existing literature on pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ) and report a rare case of PVNS of the TMJ presenting with unilateral hearing loss.

METHODS:
Review of the existing literature and a description of personal experience with PVNS of the TMJ presenting with unilateral hearing loss.

RESULTS:
Review of the existing literature revealed 76 reported cases of PVNS of the TMJ. The most common presenting symptom was of a slowly enlarging mass or swelling of the preauricular area, with dysfunctional TMJ also frequently reported. All patients underwent surgical excision with some pursuing radiation as adjuvant therapy. Presented Patient: A 46-year-old man presented with several months of unilateral subjective hearing loss and aural fullness. Imaging revealed a mass centered along the superior TMJ with expansion through the squamous temporal bone and extra-axial intracranial extension into the middle cranial fossa. Imaging characteristics and fine-needle aspiration biopsy were consistent with PVNS.

INTERVENTION:
The patient underwent near-total excision of the mass via frontotemporal craniectomy and lateral temporal bone resection.

FOLLOW-UP:
At the 16-month follow-up there was no evidence of disease recurrence.

CONCLUSION:
PVNS of the TMJ represents a rare entity that can present with a variety of symptoms including unilateral hearing loss.

© 2019 S. Karger AG, Basel.

KEYWORDS:
Pigmented villonodular synovitis; Temporomandibular joint; Unilateral hearing loss

PMID: 31242479 DOI: 10.1159/000499473
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Select item 31242384
3.
Mol Pharm. 2019 Jun 26. doi: 10.1021/acs.molpharmaceut.9b00422. [Epub ahead of print]
MicroSPECT/CT Imaging of Cell-Line and Patient-Derived EGFR-Positive Tumor Xenografts in Mice with Panitumumab Fab Modified with Hexahistidine Peptides to Enable Labeling with 99mTc (I) Tricarbonyl Complex.
Ku A, Chan C, Aghevlian S, Cai Z, Cescon D, Bratman SV, Ailles L, Hedley DW, Reilly RM.
Abstract
We aimed to investigate the feasibility of conjugating synthetic hexahistidine peptides (His6) peptides to panitumumab Fab (PmFab) to enable labeling with [99mTc(H2O)3(CO)3]+ complex and study these radioimmunoconjugates for imaging EGFR-overexpressing tumor xenografts in mice by microSPECT/CT. Fab were reacted with a 10-fold excess of sulfo-SMCC to introduce maleimide functional groups for reaction with the terminal thiol on peptides [CGYGGHHHHHH] that harbored the His6 motif. Modification of Fab with His6 peptides was assessed by SDS-PAGE/Western blot and the number of His6 peptides introduced was quantified by a radiometric assay incorporating 123I-labeled peptides into the conjugation reaction. Radiolabeling was achieved by incubation of PmFab-His6 in PBS, pH 7.0, with [99mTc(H2O)3(CO)3]+ in a 1.4 MBq/µg ratio. The complex was prepared by adding [99mTcO4]- to an Isolink® kit (Mallinckrodt). Immunoreactivity was assessed in a direct (saturation) binding assay using MDA-MB-468 human triple-negative breast cancer (TNBC) cells. Tumor and normal tissue uptake and imaging properties of 99mTc-PmFab-His6 (70 μg; 35-40 MBq) injected i.v. (tail vein) were compared to irrelevant 99mTc-Fab 3913 in NOD/SCID mice engrafted subcutaneously (s.c.) with EGFR-overexpressing MDA-MB-468 or PANC-1 human pancreatic ductal carcinoma (PDCa) cell-line derived xenografts (CLX) at 4 h and 24 h post injection (p.i.). In addition, tumor imaging studies were performed with 99mTc-PmFab-His6 in mice with patient-derived tumor xenografts (PDX) of TNBC, PDCa and head and neck squamous cell carcinoma (HNSCC). Biodistribution studies in non-tumor bearing Balb/c mice were performed to project the radiation absorbed doses for imaging studies in humans with 99mTc-PmFab-His6. PmFab was derivatized with 0.80 ± 0.03 His6 peptides. Western blot and SDS-PAGE confirmed the presence of His6 peptides. 99mTc-PmFab-His6 was labeled to high radiochemical purity (≥95%) and the Kd for binding to EGFR on MDA-MB-468 cells was 5.5 ± 0.4 × 10e-8 mol/L. Tumor uptake of 99mTc-PmFab-His6 at 24 h p.i. was significantly (P<0.05) higher than irrelevant 99mTc-Fab 3913 in mice with MDA-MB-468 tumors (14.9 ± 3.1 %ID/g vs. 3.0 ± 0.9 %ID/g) and in mice with PANC-1 tumors (5.6 ± 0.6 vs. 0.5 ± 0.1 %ID/g). In mice implanted orthotopically in the pancreas with the same PDCa PDX, tumor uptake at 24 h p.i. was 4.2 ± 0.2 %ID/g. Locoregional metastases of these PDCa tumors in the peritoneum exhibited slightly and significantly lower uptake than the primary tumors (3.1 ± 0.3 vs. 4.2 ± 0.3 %ID/g; P=0.02). In mice implanted with different TNBC or HNSCC PDX, tumor uptake at 24 h p.i. was variable and ranged from 3.7-11.4 %ID/g and 3.8-14.5 %ID/g, respectively. MicroSPECT/CT visualized all CLX and PDX tumor xenografts at 4 and 24 h p.i. Dosimetry estimates revealed that in humans, the whole body dose from administration of 740-1,110 MBq of 99mTc-PmFab-His6 would be 2-3 mSv, which is less than for a 99mTc-medronate bone scan (4 mSv).

PMID: 31242384 DOI: 10.1021/acs.molpharmaceut.9b00422
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Select item 31242294
4.
Jpn J Clin Oncol. 2019 Jun 26. pii: hyz091. doi: 10.1093/jjco/hyz091. [Epub ahead of print]
Treatment results of 99 patients undergoing open partial hypopharyngectomy with larynx preservation.
Shinozaki T1, Hayashi R1, Okano W1, Tomioka T1, Higashino T2.
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Abstract
OBJECTIVE:
Hypopharyngeal cancers frequently go undetected until advanced stages. However, recent advances in endoscopic technology have enabled earlier detection of hypopharyngeal cancer. We evaluated the effectiveness of larynx-preserving surgery for hypopharyngeal cancer.

METHODS:
We retrospectively analyzed 99 patients with hypopharyngeal squamous cell carcinoma who underwent partial hypopharyngectomy with larynx preservation between September 1992 and December 2009 at the National Cancer Center Hospital East. Of these, 91 patients underwent larynx-preserving surgery as initial treatment; eight patients underwent salvage surgery for recurrent disease after previous radiotherapy. Also, 9 of our patients had undergone previous radiotherapy in the head and neck for a different cancer. Before surgery, the TNM stage and tumor location was recorded. Free-flap reconstruction was performed in 60 patients, while the hypopharyngeal mucosa was closed without a free flap in 39 patients.

RESULTS:
The 5-year overall survival rate in our cohort was 66.9%, and 59 patients are currently alive without recurrence. Thirty-three patients died due to primary recurrence (n = 5), regional recurrence (n = 10), distant metastasis (n = 9), postoperative death (n = 1), and unrelated disease (n = 8). Laryngeal function could not be preserved in 19 patients, 2 of whom had undergone previous radiotherapy, and 7 of whom had undergone both previous radiotherapy and other salvage surgeries.

CONCLUSION:
Partial hypopharyngectomy can preserve laryngeal function in patients with pharyngeal cancer with careful patient selection.

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

KEYWORDS:
hypopharyngeal cancer; open procedure; partial pharyngectomy; past radiation

PMID: 31242294 DOI: 10.1093/jjco/hyz091
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Select item 31242251
5.
PLoS One. 2019 Jun 26;14(6):e0218964. doi: 10.1371/journal.pone.0218964. eCollection 2019.
Risk of sudden sensorineural hearing loss in patients with dysrhythmia: A nationwide population-based cohort study.
Luan CW1, Chang JJ2, Hsu CM1, Tsai MS1, Chang GH1, Huang EI1, Fang KH3, Lin MH4, Liu CY4, Yang YH5, Tsai YT1.
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Abstract
OBJECTIVE:
Whether dysrhythmia is a risk factor of sudden sensorineural hearing loss (SSNHL) remains unclear. In this study, we aimed to investigate the risk of developing SSNHL among patients with dysrhythmia in different age and gender groups by using population-based data in Taiwan.

METHODS:
We conducted a matched cohort study by analyzing data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. 41,842 newly diagnosed dysrhythmia patients and 83,684 comparison subjects without dysrhythmia were selected from claims. The incidence of sudden sensorineural hearing loss at the end of 2013 was determined in both groups. Univariate and multivariate logistic regression analyses were used to investigate the risk of SSNHL among patients with dysrhythmia.

RESULTS:
The incidence of SSNHL was 1.30-fold higher in the dysrhythmia group compared with the control group (53.2 versus 40.9 per 100,000 person-years), and using Cox proportional hazard regressions, the adjusted hazard ratio (HR) was 1.40 (95% confidence interval [CI], 1.15-1.70). Gender-stratified analysis revealed a significantly higher risk of SSNHL in patients with dysrhythmia than in those without dysrhythmia for both men and women (HR = 1.34, 95% CI = 1.02-1.76, P = 0.039, HR = 1.35, 95% CI = 1.02-1.78, P = 0.035, respectively). Age-stratified analysis revealed remarkable associations between dysrhythmia and SSNHL among those aged less than 40 years and more than 65 years (HR = 2.18, 95% CI = 1.03-4.64, P = 0.043 and HR = 1.54, 95% CI = 1.14-2.09, P = 0.006, respectively).

CONCLUSIONS:
Our findings support dysrhythmia as an independent risk factor for SSNHL. Based on the study results, clinicians managing patients with dysrhythmia should be aware of the increased risk of developing SSNHL, especially among patients aged <40 and >65 years, and counsel patients to seek medical advice immediately if they experience any acute change in their hearing ability.

PMID: 31242251 DOI: 10.1371/journal.pone.0218964
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Conflict of interest statement
Select item 31242137
6.
Ear Hear. 2019 Jul/Aug;40(4):1025-1034. doi: 10.1097/AUD.0000000000000685.
Effect of Audibility and Suprathreshold Deficits on Speech Recognition for Listeners With Unilateral Hearing Loss.
Bost TJM1, Versfeld NJ1, Goverts ST1,2.
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Abstract
OBJECTIVES:
We examined the influence of impaired processing (audibility and suprathreshold processes) on speech recognition in cases of sensorineural hearing loss. The influence of differences in central, or top-down, processing was reduced by comparing the performance of both ears in participants with a unilateral hearing loss (UHL). We examined the influence of reduced audibility and suprathreshold deficits on speech recognition in quiet and in noise.

DESIGN:
We measured speech recognition in quiet and stationary speech-shaped noise with consonant-vowel-consonant words and digital triplets in groups of adults with UHL (n = 19), normal hearing (n = 15), and bilateral hearing loss (n = 9). By comparing the scores of the unaffected ear (UHL+) and the affected ear (UHL-) in the UHL group, we were able to isolate the influence of peripheral hearing loss from individual top-down factors such as cognition, linguistic skills, age, and sex.

RESULTS:
Audibility is a very strong predictor for speech recognition in quiet. Audibility has a less pronounced influence on speech recognition in noise. We found that, for the current sample of listeners, more speech information is required for UHL- than for UHL+ to achieve the same performance. For digit triplets at 80 dBA, the speech recognition threshold in noise (SRT) for UHL- is on average 5.2 dB signal to noise ratio (SNR) poorer than UHL+. Analysis using the speech intelligibility index (SII) indicates that on average 2.1 dB SNR of this decrease can be attributed to suprathreshold deficits and 3.1 dB SNR to audibility. Furthermore, scores for speech recognition in quiet and in noise for UHL+ are comparable to those of normal-hearing listeners.

CONCLUSIONS:
Our data showed that suprathreshold deficits in addition to audibility play a considerable role in speech recognition in noise even at intensities well above hearing threshold.

PMID: 31242137 DOI: 10.1097/AUD.0000000000000685
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Select item 31242136
7.
Ear Hear. 2019 Jul/Aug;40(4):757-765. doi: 10.1097/AUD.0000000000000679.
Impact of Bilateral Vestibulopathy on Spatial and Nonspatial Cognition: A Systematic Review.
Dobbels B1, Peetermans O2, Boon B2, Mertens G1,2, Van de Heyning P1,2, Van Rompaey V1,2.
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Abstract
OBJECTIVES:
Hearing loss is considered an independent risk factor for dementia. Growing evidence in animal and human studies suggest that not only hearing loss but also vestibular loss might result in cognitive deficits. The objective of this study is to evaluate the presence of spatial and nonspatial cognitive deficits in patients with bilateral vestibulopathy. As different causes of bilateral vestibulopathy are associated with hearing loss, the objective is to evaluate if these cognitive deficits are due to the vestibular loss of the patients with bilateral vestibulopathy, or to their hearing loss, or both.

DESIGN:
We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. (1) Data sources: MEDLINE and the Cochrane Library. (2) Study selection: Cross-sectional studies investigating cognitive performances in human patients with bilateral vestibulopathy confirmed by quantitative vestibular testing. (3) Data extraction: Independent extraction of articles by three authors using predefined data fields, including patient- and control characteristics and cognitive outcomes.

RESULTS:
Ten studies reporting on 126 patients with bilateral vestibulopathy matched the inclusion criteria. Cognitive domains evaluated in patients with bilateral vestibulopathy included visuospatial abilities, memory, language, attention, and executive function. In only three studies, hearing performance of the included patients was briefly described. Nearly all studies demonstrated a significant impairment of spatial cognition in patients with bilateral vestibulopathy. In the few papers investigating nonspatial cognition, worse outcome was demonstrated in patients with bilateral vestibular loss performing cognitive tasks assessing attentional performance, memory, and executive function.

CONCLUSIONS:
Strong evidence exists that patients with bilateral vestibulopathy suffer from impaired spatial cognition. Recent studies even suggest impairment in other cognitive domains than spatial cognition. However, in all previous studies, conclusions on the link between cognitive performance and vestibular loss were drawn without taken hearing loss into consideration as a possible cause of the cognitive impairment.

PMID: 31242136 DOI: 10.1097/AUD.0000000000000679
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Select item 31241859
8.
Clin Otolaryngol. 2019 Jun 26. doi: 10.1111/coa.13397. [Epub ahead of print]
The Correlation Analysis of Intralabyrinthine Hemorrhage Magnetic Resonance Imaging with Hearing Loss and Prognosis:A Retrospective Analysis of 207 cases.
Li J1, Wang M2, Sun L1, Zhao H1, Song G3, Tian J1, Hu N1, Li M4, Dou W4, Qu J4, Wang H2, Gong R1,5.
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Abstract
Recently, a few studies that evaluated sudden deafness caused by intralabyrinthine hemorrhage (ILH) on three-dimensional fluid-attenuated inversion recovery (3D FLAIR) images. But, there has been no report yet about the volume of ILH on living body, especially the relationship between the relative volume of ILH and the degree of hearing loss as well as the prognosis. We found that there was a positive correlation between the relative volume of ILH and the degree of hearing loss (r =0.476, P = 0.003) as well as the prognosis (r = 0.628, P = 0.000). Therefore, the relative volume of ILH is suggested to serve as a novel objective prognostic factor in SSNHL. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:
fluid-attenuated inversion recovery; intralabyrinthine hemorrhage; magnetic resonance imaging; prognosis; sudden sensorineural hearing loss

PMID: 31241859 DOI: 10.1111/coa.13397
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Select item 31241775
9.
Int J Cancer. 2019 Jun 26. doi: 10.1002/ijc.32536. [Epub ahead of print]
Assessing tumor heterogeneity using ctDNA to predict and monitor therapeutic response in metastatic breast cancer.
Ma F1, Guan Y2,3, Yi Z1, Chang L2,3, Li Q1, Chen S1, Zhu W1, Guan X1, Li C4, Qian H4, Xia X5, Yang L2,3, Zhang J6,7, Husain H8, Liao Z9, Futreal A7, Huang J10, Yi X2,3, Xu B1.
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Abstract
Tumor heterogeneity was associated with treatment outcome of metastatic cancers but few studies have examined whether tumor heterogeneity in circulating tumor DNA (ctDNA) can be used to predict treatment outcome. ctDNA analysis was performed in 37 HER2-positive metastatic breast cancer patients treated with pyrotinib. Patients with high tumor heterogeneity had significantly worse PFS outcomes, with a median PFS of 30.0 weeks versus 60.0 weeks for patients with low tumor heterogeneity (hazard ratio [HR], 2.9; P = 0.02). Patients with trunk resistance mutations receiving pyrotinib monotherapy had worse outcomes (HR, 4.5; P = 0.03), with a median PFS of 7.8 weeks versus 27.4 weeks for those with branch resistance mutations or without any resistance mutations in baseline ctDNA. Longitudinal monitoring of 21 patients during treatment showed that the molecular tumor burden index ([mTBI] a measure of the percentage of ctDNA in samples) was positively correlated with tumor size as evaluated by computed tomography (P < 0.0001, Pearson r = 0.52) and detected disease progression 8-16 weeks earlier. Our current findings suggested that ctDNA could be used to assess tumor heterogeneity and predict treatment outcomes. Furthermore, the mTBI is better for assessing therapeutic response than single gene mutations and might supplement the current therapeutic response evaluation system. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:
PFS; cell-free circulating tumor DNA (ctDNA); metastasis breast cancer; trunk/branch resistance mutations; tumor heterogeneity

PMID: 31241775 DOI: 10.1002/ijc.32536
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Select item 31241771
10.
Laryngoscope. 2019 Jun 26. doi: 10.1002/lary.28064. [Epub ahead of print]
The Alberta Reconstructive Technique: An Occlusion-Driven and Digitally Based Jaw Reconstruction.
Seikaly H1,2, Idris S1, Chuka R2, Jeffrey C1,2, Dzioba A1, Makki F1, Logan H2, O'Connell DA1,2, Harris J1, Ansari K1, Biron V1, Cote D1, Osswald M1,2, Nayar S1,2, Wolfaardt J1.
Author information
Abstract
OBJECTIVES/HYPOTHESIS:
The free flap reconstructive protocols of the jaws have been refined over the years and presently are based on bone-driven approaches that generally use the lower border of the mandible or the anterior surface of the maxilla as the templates for reconstruction because these contours are deemed important to the eventual cosmetic outcomes of patients. The ultimate goal of functional jaw reconstruction, however, is the reconstruction of the dental occlusion and oral rehabilitation. The purpose of the present study was to evaluate the Alberta reconstructive technique (ART), which is a new approach of occlusion-driven jaw reconstruction with digitally planned immediate osseointegrated implant installation.

STUDY DESIGN:
Prospective cohort study.

METHODS:
This research study considers the ART's safety, effectiveness, accuracy, timeliness of reconstruction, aesthetic appeal, and cost-effectiveness in comparison with the standard bone-driven and delayed osseointegrated implant installation (BDD) protocol.

RESULTS:
The ART procedures were as safe and more effective at achieving full occlusal reconstruction and oral rehabilitation. The ART cohort of patients achieved oral rehabilitation in 21.4 month as compared to 73.1 months for the BDD cohort. There were no differences in the aesthetic appeal the two groups. The ART cost an average of $22,004 less than BDD and we calculated the quality adjusted life years gain to be between 2.14 and 4.04 in favour of ART.

CONCLUSIONS:
The ART is a good option for patients with jaw defects. It provides a safe, effective, accurate, aesthetic, and cost-effective reconstruction that restores form and function in a timely manner.

LEVEL OF EVIDENCE:
2b Laryngoscope, 2019.

© 2019 The American Laryngological, Rhinological and Otological Society, Inc.

KEYWORDS:
Alberta reconstructive technique; Mandibular; digital surgical planning; fibular free flap; maxillary; occlusion-driven reconstruction; osseointegrated implants; reconstruction; surgical design and simulation

PMID: 31241771 DOI: 10.1002/lary.28064
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Select item 31241769
11.
Laryngoscope. 2019 Jun 26. doi: 10.1002/lary.28153. [Epub ahead of print]
An Innovative Approach to Airway Foreign Body Management in an Extremely Premature Neonate.
Hodge SE1, Kilpatrick L1, Zdanski C1.
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Abstract
This case report is a retrospective review of a challenging though ultimately successful removal of an airway foreign body in a 2-day-old premature female born at 23 weeks and 4 days gestation. A segment of a 5-F surfactant catheter was cut and accidentally dislodged in the distal airway within the lumen of the patient's endotracheal tube. Ultimately, visualization was obtained using a 1.6-mm KARL STORZ sialoendoscope, and retrieval was performed using sialoendoscopy forceps passed via the working channel of the sialoendoscope while maintaining ventilation. This case represents an innovative approach to complex airway foreign body management utilizing sialoendoscopy instruments. Laryngoscope, 2019.

© 2019 The American Laryngological, Rhinological and Otological Society, Inc.

KEYWORDS:
Airway foreign body; pediatric; sialoendoscopy

PMID: 31241769 DOI: 10.1002/lary.28153
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Select item 31241531
12.
Clin J Sport Med. 2019 Jul;29(4):292-297. doi: 10.1097/JSM.0000000000000512.
Clinical Utility of Oculomotor and Electrophysiological Measures in Identifying Concussion History.
Ledwidge PS1,2,3, Patterson JN2,4, Molfese DL1,2, Honaker JA2,4,5.
Author information
Abstract
OBJECTIVE:
To examine whether oculomotor and electrophysiological measures improve the clinical performance of the typical concussion protocol for classifying collegiate athletes with a history of concussion.

DESIGN:
Cross-sectional.

SETTING:
University Athletic Medicine and Research Facility.

PARTICIPANTS:
Forty-five varsity collegiate athletes.

INDEPENDENT VARIABLES:
Collegiate varsity athletes with or without a history of a diagnosed concussion.

MAIN OUTCOME MEASURES:
Multivariate receiver operating curve and area under the curve (AUC) analyses tested the clinical performance of the typical concussion protocol (symptoms, postural control, neuropsychological abilities). We examined differences in clinical performance between this protocol and after adding reflexive saccade and event-related potential (ERP) indices. Hypotheses were formed after data collection.

RESULTS:
Significant AUCs were demonstrated for the typical concussion protocol (model 1: AUC = 0.75, P = 0.007), after adding reflexive saccade eye excursion gain (model 2: AUC = 0.80, P = 0.001), and ERPs (model 3: AUC = 0.79, P = 0.002). The AUC for reflexive saccades and ERPs was significant (model 4: AUC = 0.70, P = 0.030). Model 2's increased clinical performance compared with model 1 was nonsignificant, χ(2) = 1.871, P = 0.171.

CONCLUSIONS:
All 4 models demonstrated adequate sensitivity and specificity for classifying athletes with a previous concussion. Adding reflexive saccades and ERPs did not significantly increase clinical performance of the typical concussion protocol. Future research should determine the clinical utility of saccades and ERPs for acute postconcussion assessments.

PMID: 31241531 DOI: 10.1097/JSM.0000000000000512
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Select item 31241381
13.
Acta Oncol. 2019 Jun 26:1-7. doi: 10.1080/0284186X.2019.1627413. [Epub ahead of print]
Relationship between patient and physician-rated xerostomia and dose distribution to the oral cavity and salivary glands for head and neck cancer patients after radiotherapy.
Kaae JK1,2,3, Johnsen L4, Hansen CR2,4, Kristensen MH5, Brink C2,4, Eriksen JG6.
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Abstract
Introduction: Xerostomia is a frequent complication after curative intended radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Assessment of xerostomia is commonly done by the physician. The aim of this study is to investigate the relation between patient and physician-rated xerostomia and to predict the degree of xerostomia from patients with self-reported xerostomia based on delivered doses to the oral cavity, parotid, and submandibular glands. Material and methods: During a 2-year period, consecutive HNSCC patients attending the follow-up clinic were included. All included patients had self-reported xerostomia, and completed the disease-specific EORTC QLQ-H&N35 questionnaire. The physician assessed the degree of xerostomia with the DAHANCA toxicity scale and was blinded for the EORTC score. Oral cavity, parotid, and submandibular glands (OAR) were delineated on the planning CT according to international guidelines. DVH were extracted from treatment plans. Logistic regression tested the relation between mean doses, patient characteristics, and xerostomia scores. Differences between DVH values and scoring of xerostomia were analyzed with a Kruskal-Wallis test. The relation between xerostomia and dose distributions was further investigated using principal component analysis (PCA). Results: In total, 109 patients were included in the study. A weak correlation was seen between patient and physician-rated toxicity (p = .001), however, in general patients reported more toxicity than physicians. For EORTC score ≥2, the multi-variable analysis was significant for doses to the oral cavity, tobacco status and use of xerogenic medication. Neither the DVH analysis nor the PCA found any clear distinction between xerostomia scores for EORTC or DAHANCA and investigated OARs. Conclusion: Patients tended to report higher scores of xerostomia than the physician. PCA indicated a complex relation between doses to the OAR and xerostomia scores, showing e.g., that reducing doses in one organ was on the expense of increased dose to another organ.

KEYWORDS:
Radiotherapy; dose volume distribution; head and neck cancer; xerostomia

PMID: 31241381 DOI: 10.1080/0284186X.2019.1627413
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Select item 31241377
14.
Acta Oncol. 2019 Jun 26:1-7. doi: 10.1080/0284186X.2019.1627416. [Epub ahead of print]
Towards FLASH proton therapy: the impact of treatment planning and machine characteristics on achievable dose rates.
van de Water S1, Safai S1, Schippers JM1,2, Weber DC1,3,4, Lomax AJ1,5.
Author information
Abstract
Background: This study aimed at evaluating spatially varying instantaneous dose rates for different intensity-modulated proton therapy (IMPT) planning strategies and delivery scenarios, and comparing these with FLASH dose rates (>40 Gy/s). Material and methods: In order to quantify dose rates in three-dimensions, we proposed the 'dose-averaged dose rate' (DADR) metric, defined for each voxel as the dose-weighted mean of the instantaneous dose rates of all spots (i.e., pencil beams). This concept was applied to four head-and-neck cases, each planned with clinical (4 fields) and various spot-reduced IMPT techniques: 'standard' (4 fields), 'arc' (120 fields) and 'arc-shoot-through' (120 fields; 229 MeV only). For all plans, different delivery scenarios were simulated: constant beam intensity, variable beam intensity for a clinical Varian ProBeam system, varied per energy layer or per spot, and theoretical spot-wise variable beam intensity (i.e., no monitor/safety limitations). DADR distributions were calculated assuming 2-Gy or 6-Gy fractions. Results: Spot-reduced plans contained 17-52 times fewer spots than clinical plans, with no deterioration of plan quality. For the clinical plans, the mean DADR in normal tissue for 2-Gy fractionation was 1.7 Gy/s (median over all patients) at maximum, whereas in standard spot-reduced plans it was 0.7, 4.4, 7.1, and 12.1 Gy/s, for the constant, energy-layer-wise, spot-wise, and theoretical spot-wise delivery scenarios, respectively. Similar values were observed for arc plans. Arc-shoot-through planning resulted in DADR values of 3.0, 6.0, 14.1, and 24.4 Gy/s, for the abovementioned scenarios. Hypofractionation (3×) generally resulted in higher dose rates, up to 73.2 Gy/s for arc-shoot-through plans. The DADR was inhomogeneously distributed with highest values at beam entrance and at the Bragg peak. Conclusion: FLASH dose rates were not achieved for conventional planning and clinical spot-scanning machines. As such, increased spot-wise beam intensities, spot-reduced planning, hypofractionation and arc-shoot-through plans were required to achieve FLASH compatible dose rates.

PMID: 31241377 DOI: 10.1080/0284186X.2019.1627416
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Select item 31241364
15.
Endocr Pract. 2019 Jun 26. doi: 10.4158/EP-2019-0078. [Epub ahead of print]
UPSTROKE TIME PER CARDIAC CYCLE IS ASSOCIATED WITH CARDIOVASCULAR PROGNOSIS IN TYPE 2 DIABETES.
Chang LH1,2,3, Hwu CM2,4, Chu CH2,5, Won JGS2,4, Chen HS2,4, Lin LY2,4.
Author information
Abstract
Objective Upstroke time per cardiac cycle (UTCC) in the lower extremities has been found to be predictive of cardiovascular mortality in the general population. Therefore, the purpose of the study was to test the associations between increasing UTCC and outcomes in patients with type 2 diabetes. Design and methods A total of 452 patients with type 2 diabetes (age: 67.5±8.6 years; male: 54%) registered in share-care program participated in the study at an out-patient clinic in Taipei Veterans General Hospital across a mean of 5.8 years. Primary outcomes were all-cause mortality hospitalization for coronary artery disease, stroke, revascularization, amputation and diabetic foot syndrome. Secondary end-point outcome was all-cause mortality. Results Increment of UTCC associations with primary and secondary outcome were undertaken prior to baseline characteristic adjustments. A UTCC of 20.1% exhibited the greatest area under curve (AUC), sensitivity, and specificity balance to predict composite events in receiver operating curves (AUC: 0.63, p=0.001; sensitivity: 67.7%; specificity: 54.9%). Sixty-four composite events and 17 deaths were identified from medical records. UTCC ≥ 20.1% was associated with the occurrence of composite events and an increased risk of mortality. For composite events, an adjusted hazard ratio (HR) of 2.45 and 95% confidence interval (CI) of 1.38-4.35 (p=0.002) were calculated. For all-cause mortality, an adjusted HR of 1.91 and 95% CI of 0.33-10.99 (p=0.467) were calculated. Conclusions Increasing UTCC was associated with cardiovascular outcomes in patients with type 2 diabetes. Therefore, UTCC is advocated as a noninvasive screening tool for ambulatory patients with type 2 diabetes.

KEYWORDS:
cardiovascular outcomes; type 2 diabetes mellitus; upstroke time per cardiac cycle

PMID: 31241364 DOI: 10.4158/EP-2019-0078
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Select item 31241284
16.
Cent Eur J Public Health. 2019 Jun;27(2):106-109. doi: 10.21101/cejph.a5565.
Environmental and behavioural head and neck cancer risk factors.
Vučičević Boras V1, Fučić A2, Baranović S3, Blivajs I4, Milenović M5, Bišof V5,6, Rakušić Z5,7, Ceppi M8, Bruzzone M8.
Author information
Abstract
OBJECTIVES:
The high incidence of head and neck cancer (HNC), significantly associated with living environment and behaviour, can be prevented more efficiently. The aim of this study was to evaluate the environmental and behavioural risk factors for HNC.

METHODS:
Using a detailed questionnaire on social status, education, living and occupational environment exposures, family cancer and lifestyle, HNC patients (103 cases, 76.7% of men) were compared with control subjects (244 subjects, 73% of men) balanced by age: mean (standard deviation) 63.8 (9.3) and 63.8 (9.0) for cases and controls, respectively.

RESULTS:
The results of this study showed that smoking and low education were significant risk factors for HNC regardless of sex. Family HNC and breast cancer were significant predictors of HNC risk.

CONCLUSION:
The study confirmed previous results that smoking and low education are significantly associated with HNC. Additionally, results pointed to significant HNC and breast cancer risk in HNC patient's families that may have originated from passive smoking or a smoking habit stemming from social environments that support it. Better dissemination programmes regarding smoking risks for children and adults are needed, targeting not only individuals but also families.

KEYWORDS:
aetiology; education; family cancer; head and neck cancer; smoking

PMID: 31241284 DOI: 10.21101/cejph.a5565
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Select item 31240981
17.
Acta Otolaryngol. 2019 Jun 26:1-5. doi: 10.1080/00016489.2019.1631479. [Epub ahead of print]
Smoking or poor oral hygiene do not predispose to peritonsillar abscesses via changes in oral flora.
Sanmark E1, Wikstèn J1, Välimaa H2,3, Blomgren K1.
Author information
Abstract
Aim: The purpose of this prospective study was to determine if there is a difference in number and distribution of salivary bacteria between patients with tonsillar infection and healthy volunteers. Background: The etiology of peritonsillar abscess (PTA) is unclear. Smoking, periodontal disease, and infection of minor salivary glands have been suggested as predisposing factors for PTA. Material and methods: Patients with acute tonsillitis (AT) (n = 54), peritonsillitis (PT) (n = 36), PTA (n = 58), and healthy volunteers (n = 52) were prospectively recruited and evaluated. Saliva bacteria were analyzed with flow cytometry. Patients and their treating physicians completed a questionnaire about patients' current disease, smoking habits, alcohol consumption, and oral health. Results: There were no differences in the total number of saliva bacteria between patients with acute throat infection and healthy volunteers (p = .104) or between AT, PT, and PTA patients (p = .273). Smoking habits, alcohol consumption, oral hygiene, or prior antibiotics had no effect on total amount of salivary bacteria in patients with acute throat infection. Conclusions: The effects of smoking on salivary bacteria do not seem to be the mechanism that promotes development of PTA in smokers.

KEYWORDS:
Salivary bacteria; flow cytometry; tonsillar infection

PMID: 31240981 DOI: 10.1080/00016489.2019.1631479
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Select item 31240949
18.
Future Oncol. 2019 Jun 26. doi: 10.2217/fon-2018-0772. [Epub ahead of print]
Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy.
Bossi P1, Botta L2, Bironzo P3, Sonetto C3, Musettini G4, Sbrana A4, Di Giannantonio V5, Locati LD5, Di Maio M6, Antonuzzo A4.
Author information
Abstract
Aim: Reporting toxicities of targeted therapies (TTs) and immunotherapy in oncology requires special attention. Materials & methods: We identified TTs and immunotherapies approved by the US FDA for solid malignancies in the adult population. Publications were reviewed according to a 24-point score based on the Consolidated Standards of Reporting Trials guidance. Results: We identified 81 trials (>45,000 patients). The experimental drug was studied as single agent in 51% of the cases; setting of disease was mainly (95%) advanced/metastatic. Lowest scores in adverse event (AE) description regarded: reporting recurrent/late toxicities and duration of the AEs (>90%), time of occurrence and indication of all-grade AEs (>75%). Conclusions: Suboptimal reporting of AEs in trials leading to approval of TTs and immunotherapy was shown. Improving AE descriptions should be a priority in ongoing trials.

KEYWORDS:
Systematic Review; immunotherapy; targeted treatments; toxicities

PMID: 31240949 DOI: 10.2217/fon-2018-0772
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Select item 31240853
19.
J Biophotonics. 2019 Jun 25:e201900145. doi: 10.1002/jbio.201900145. [Epub ahead of print]
Photobiomodulation using low level 808 nm diode laser rescues cochlear synaptopathy after acoustic overexposure in rat.
Lee JH1,2, Lee MY1,2,3, Chung PS1,2,3, Jung JY1,2,3.
Author information
Abstract
A certain degree of noise can cause hearing problems without a permanent change in the hearing threshold, which is called hidden hearing loss and results from partial loss of auditory synapses. Photobiomodulation (PBM) enhances neural growth and connections in the peripheral nervous systems. In this study, we assessed whether PBM could rescue cochlear synaptopathy after acoustic overexposure in rat. PBM was performed for 7 days after noise exposure. The ABRs were acquired before and after noise exposure using a tone and a paired-click stimulus. Auditory response to paired click sound with short time interval was performed to evaluate auditory temporal processing ability. In the result, hearing threshold recovered 2 weeks after noise exposure in both groups. Peak wave 1 amplitude of the ABR and ABR recovery threshold did not recover in the noise only group, whereas it fully recovered in the noise + PBM group. The number of synaptic ribbons was significantly different in the control and noise only groups, while there was no difference between the control and noise + PBM group. These results indicate that PBM rescued peak wave 1 amplitude and maintained the auditory temporal processing ability resulting from a loss of synaptic ribbons after acoustic overexposure. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:
Photobiomodulation; cochlear synaptopathy; noise-induced hearing loss; paired-click ABR

PMID: 31240853 DOI: 10.1002/jbio.201900145
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Select item 31240818
20.
Head Neck. 2019 Jun 25. doi: 10.1002/hed.25849. [Epub ahead of print]
Second primary tumors in patients with a head and neck paraganglioma.
Contrera KJ1, Yong V2, Reddy CA3, Berber E4, Lorenz RR1.
Author information
Abstract
BACKGROUND:
There are conflicting recommendations and possibly overuse of imaging for surveillance of second primary tumors for patients with a history of head and neck paraganglioma.

METHODS:
Retrospective cohort study of 234 adults with head and neck paragangliomas (1990-2010) followed for a mean of 7.5 ± 8.4 years.

RESULTS:
The rate of second paraganglioma was 1.7% after 5 years and 5.1% after 10 years, yielding an incidence of 6.65 per 1000 person-years. Only 1.3% of patients (2.59 per 1000 person-years) ever had a second paraganglioma in the chest, abdomen, or pelvis. Patients with a hereditary paraganglioma (hazard ratio [HR] = 4.84, 95% confidence interval [CI]: 1.52-15.43) or carotid body tumor (HR = 3.55, 95% CI: 1.15-10.99) were at greater risk.

CONCLUSIONS:
The incidence rate of a second primary paragangliomas is low but increases with hereditary disease. These results question the utility of repeated imaging outside of the neck to screen for second paragangliomas.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:
glomus tumor; imaging; paraganglioma; second primary tumor; surveillance

PMID: 31240818 DOI: 10.1002/hed.25849
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Select item 31240808
21.
Head Neck. 2019 Jun 25. doi: 10.1002/hed.25844. [Epub ahead of print]
Utilization of rehabilitation services in patients with head and neck cancer in the United States: A SEER-Medicare analysis.
Wang JR1, Nurgalieva Z1, Fu S2, Tam S1, Zhao H2, Giordano SH2, Hutcheson KA1, Lewis CM1.
Author information
Abstract
BACKGROUND:
Head and neck cancer (HNC) and its treatment lead to functional impairments. Rehabilitation by speech-language pathology (SLP) and occupational/physical therapy (OT/PT) can decrease morbidity.

METHODS:
The Surveillance, Epidemiology and End Results-Medicare data for patients with HNC diagnosed between 2002 and 2011 was utilized to evaluate posttreatment rehabilitation.

RESULTS:
In 16 194 patients, the overall utilization rate was 20.7% for SLP and 26.2% for OT/PT services. Treatment modality was significantly associated rehabilitation utilization. Compared to patients treated with primary surgery, those treated with primary radiotherapy had significantly lower odds of OT/PT utilization. Patients treated with surgery plus adjuvant treatment and primary concurrent chemoradiation had higher odds of SLP utilization compared to patients treated with surgery alone.

CONCLUSIONS:
Rehabilitation services appeared to be underutilized by patients with HNC in the United States and vary with treatment modality. There is a need to improve integration of rehabilitation services into the HNC care continuum.

SUMMARY:
Rehabilitation services are underutilized by patients with HNC during posttreatment surveillance in the United States. Treatment modality significantly impacts rehabilitation utilization patterns.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:
head and neck cancer; occupational therapy; physical and rehabilitation medicine; rehabilitation research; speech-language pathology; survivorship

PMID: 31240808 DOI: 10.1002/hed.25844
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Grant support
Select item 31240807
22.
Head Neck. 2019 Jun 25. doi: 10.1002/hed.25850. [Epub ahead of print]
Simultaneous tracheal and esophageal reconstruction for thyroid cancer involving trachea and esophagus using a free bipaddled posterior tibial artery perforator flap.
Liu J1, Ren J1, Lv D1, Wang J1, Deng D1, Li L1, Wang H1, Chen F1.
Author information
Abstract
BACKGROUND:
Simultaneous tracheal and esophageal reconstruction after tumor resection is a great challenge. Here we present an innovative operative technique to simultaneously reconstruct tracheal and esophageal defects, in which a free posterior tibial artery perforator flap was made into a free bipaddled flap to cover both tracheal and esophageal defects.

METHODS:
A free bipaddled posterior tibial artery perforator flap was utilized to conduct simultaneous tracheal and esophageal reconstruction for a 72-year-old female patient with papillary thyroid carcinoma and massive trachea and esophagus invasion, who underwent radical resection.

RESULTS:
Satisfactory breathing and swallowing functions were gained independent of nasal feeding and tracheotomy. Voice was still hoarse due to tumor invasion of left recurrent laryngeal nerve. During a period of 2-year follow-up, no sign of tumor recurrence was observed.

CONCLUSION:
A free bipaddled posterior tibial artery perforator flap could be a decent choice for simultaneous reconstruction of large tracheal and esophageal defects.

© 2019 The Authors. Head & Neck published by Wiley Periodicals, Inc.

KEYWORDS:
esophageal reconstruction; free bipaddled posterior tibial artery perforator flap; simultaneous reconstruction; thyroid cancer; tracheal reconstruction

PMID: 31240807 DOI: 10.1002/hed.25850
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Select item 31240588
23.
Ann Surg Oncol. 2019 Jun 25. doi: 10.1245/s10434-019-07505-6. [Epub ahead of print]
Focused Ultrasound Surveillance of Lymph Nodes Following Lymphoscintigraphy Without Sentinel Node Biopsy: A Useful and Safe Strategy in Elderly or Frail Melanoma Patients.
Ipenburg NA1,2, Thompson JF3,4,5, Uren RF4,6, Chung D4,6, Nieweg OE3,4,5.
Author information
Abstract
BACKGROUND:
Sentinel node (SN) biopsy (SNB) has become standard of care in clinically localized melanoma patients. Although it is minimally invasive, advanced age and/or comorbidities may render SNB inadvisable in some patients. Focused ultrasound follow-up of SNs identified by preoperative lymphoscintigraphy may be an alternative in these patients. This study examines the outcomes in patients managed in this way at a major melanoma treatment center.

METHODS:
All patients with clinically localized cutaneous melanoma who underwent lymphoscintigraphy and in whom SNB was intentionally not performed due to advanced age and/or comorbidities were included.

RESULTS:
Between 2000 and 2009, 160 patients (5.2% of the total) underwent lymphoscintigraphy without SNB because of advanced age and/or comorbidities. Compared with the 2945 patients who had a SNB, the 160 patients were older, had thicker melanomas that were more often located in the head and neck region, and had more SNs in more nodal regions. Of the 160 patients, 150 (94%) were followed with ultrasound examination of their SNs at each follow-up visit; this identified 33% of the nodal recurrences before they became clinically apparent. Compared with SN-positive patients who were treated by completion lymph node dissection, observed patients who developed nodal recurrence had more involved nodes when a delayed lymphadenectomy was performed. Melanoma-specific survival, recurrence-free survival, and distant recurrence-free survival rates were similar, while regional lymph node-free survival was worse.

CONCLUSIONS:
Lymphoscintigraphy with focused ultrasound follow-up of SNs is a reasonable management alternative to SNB in patients who are elderly and/or have substantial comorbidities.

PMID: 31240588 DOI: 10.1245/s10434-019-07505-6
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Select item 31240480
24.
Curr Treat Options Oncol. 2019 Jun 25;20(8):65. doi: 10.1007/s11864-019-0664-z.
Approach to the Patient with Recurrent/Metastatic Disease.
Guigay J1, Sâada-Bouzid E2, Peyrade F2, Michel C2.
Author information
Abstract
For most of patients with a recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), the treatment remains palliative: The main objective is to reduce the symptoms related to the locoregional relapse, prolong life while maintaining quality of life, which is a big challenge. The systemic treatment needs to be adapted to the performance status, comorbidities, and sequelae of patients. For fit patients, the combination of platinum-based chemotherapy and cetuximab (EXTREME) is the standard of care in first-line treatment since 2008, as no other targeted therapy has been approved in this setting until now. The replacement of 5-FU with a taxane (docetaxel) in the EXTREME regimen has been explored in the large randomized international study TPExtreme which results are awaited in a few months. Depending on the study results on survival, response rate, and tolerance, the TPEx regimen may become a treatment option for patients with R/M HNSCC. Unfit patients are usually treated with platinum-free combinations or with the monotherapies which are recommended in second-line setting (methotrexate, taxanes, cetuximab). However, the irruption of new immunotherapies (e.g., checkpoint inhibitors (CPI)) is changing the guidelines. The tolerance of anti-PD-1 CPI is better than that of chemotherapy, and they seem to be a good option for unfit patients. Anti-PD-1 nivolumab and pembrolizumab are now approved for platinum refractory patients, providing prolonged survival in the case of response, and improvement in quality of life. New options arise in first-line setting with pembrolizumab alone or combined with chemotherapy. Patients with a high PD-L1 biomarker level seem to benefit more from immunotherapy. Other situations (e.g., PD-L1-low, PD-L1-negative, high tumor burden) may more likely to benefit from other combinations, such as cetuximab plus chemotherapy, to avoid local failures and life-threatening fast progression. In terms of perspectives, chemo-free and CPI-free approaches, using other immune oncology agents, should be the next steps.

KEYWORDS:
Advances; Recurrent/metastatic disease; Review; Standards; Treatment

PMID: 31240480 DOI: 10.1007/s11864-019-0664-z
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Publication type
Select item 31240457
25.
Eur Arch Otorhinolaryngol. 2019 Jun 25. doi: 10.1007/s00405-019-05526-1. [Epub ahead of print]
Total laryngopharyngectomy with circumferential reconstruction: Helsinki institutional study.
Zarins J1, Aro K2, Bäck L2, Atula T2, Vuola J3, Lassus P3, Keski-Säntti H2.
Author information
Abstract
PURPOSE:
Surgical complications after total laryngopharyngectomy (TLP) are common, reconstruction is challenging, and patients often lose their ability to swallow and speak. To evaluate these aspects, we analysed outcome after TLP.

METHODS:
We reviewed all patients who underwent TLP and subsequent circumferential pharyngeal reconstruction through 2004-2017 at the Helsinki University Hospital.

RESULTS:
For the 26 eligible patients, TLP was the primary treatment for 11 and salvage surgery for 15, followed by reconstruction with free flaps in 22 patients and pedicled flaps in 4. An early (≤ 30 days) pharyngocutaneous fistula developed in seven patients (27%; median time 13 days; range 6-26), and a late (> 30 days) fistula in five patients (19%; median time 370 days; range 46-785). In addition, ten patients (39%) developed an oesophageal stricture. Four patients (15%) resumed full oral feeding. A speech prosthesis was inserted for 15 patients (58%) and most of them could produce intelligible speech. We found acceptable survival figures for patients undergoing TLP both as a primary treatment and as salvage procedure: the overall survival at 1 year was 82% and 67%, and at 5 years 33% and 27%, respectively. Disease-specific survival at 1 year was 90% and 70%, and that at 5 years was 45% and 43%, respectively.

CONCLUSIONS:
Despite fair survival, TLP carries a high risk for postoperative complications with limited functional outcome, thus necessitating cautious patient selection and surgical experience.

KEYWORDS:
Fistula; Free flaps; Hypopharynx cancer; Larynx cancer; Stricture; Survival

PMID: 31240457 DOI: 10.1007/s00405-019-05526-1
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Select item 31240456
26.
Eur Arch Otorhinolaryngol. 2019 Jun 20. doi: 10.1007/s00405-019-05513-6. [Epub ahead of print]
Evaluation of the information given to patients undergoing total pharyngolaryngectomy and quality of life: a prospective multicentric study.
Bozec A1, Schultz P2, Gal J3, Chamorey E3, Chateau Y3, Dassonville O4, Poissonnet G4, Peyrade F5, Saada E5, Guigay J5, Benezery K6, Leysalle A6, Santini L7, Giovanni A7, Messaoudi L2, Fakhry N7.
Author information
Abstract
BACKGROUND:
Providing cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate the information given to patients undergoing total pharyngolaryngectomy (TPL) as well as the evolution and predictors of patient quality of life (QoL).

METHODS:
We conducted a prospective multicentric study on patients undergoing TPL for a locally advanced laryngeal/hypopharyngeal cancer. All patients completed the EORTC QLQ-INFO25, QLQ-C30, and QLQ-H&N35 questionnaires, before and after surgery.

RESULTS:
This study enrolled 46 patients. Between the pre- and post-therapeutic periods, we observed no significant changes in the global QLQ-INFO25 and QLQ-C30 scores. However, we found a significant deterioration in 4 QLQ-INFO25 scales/items and in social functioning, as well as an increase of sense, speech, and social contact problems. N-stage and professional activity were significant predictors of preoperative QLQ-INFO25 scores. Younger age was significantly associated with financial difficulties, whereas professional activity and lower education level were significant predictors of xerostomia and swallowing problems, respectively.

CONCLUSION:
In patients undergoing TPL, we observed significant changes in QLQ-INFO25 scores between the pre- and post-treatment periods and, particularly, a deterioration of patient satisfaction with the information received. Several clinical factors were identified as significant predictors of QLQ-INFO25 and QoL scores.

KEYWORDS:
Head and neck cancer; Information; Quality of life; Satisfaction; Total laryngectomy

PMID: 31240456 DOI: 10.1007/s00405-019-05513-6
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Select item 31240455
27.
Eur Arch Otorhinolaryngol. 2019 Jun 25. doi: 10.1007/s00405-019-05525-2. [Epub ahead of print]
Comprehensive analysis of gene expression and DNA methylation for human nasopharyngeal carcinoma.
Li H1, Wang FL2, Shan LP3, An J1, Liu ML1, Li W1, Zhang JE4, Wu PP5.
Author information
Abstract
PURPOSE:
Nasopharyngeal carcinoma (NPC) is one of the most malignant head and neck carcinomas with unique epidemiological features. In this study, we aimed to identify the novel NPC-related genes and biological pathways, shedding light on the potential molecular mechanisms of NPC.

METHODS:
Based on Gene Expression Omnibus (GEO) database, an integrated analysis of microarrays studies was performed to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in NPC compared to normal control. The genes which were both differentially expressed and differentially methylated were identified. Functional annotation and protein-protein interaction (PPI) network construction were used to uncover biological functions of DEGs.

RESULTS:
Two DNA methylation and five gene expression datasets were incorporated. A total of 1074 genes were up-regulated and 939 genes were down-regulated in NPC were identified. A total of 719 differential methylation CpG sites (DMCs) including 1 hypermethylated sites and 718 hypomethylated sites were identified. Among which, 11 genes were both DEGs and DMGs in NPC. Pathways in cancer, p53 signaling pathway and Epstein-Barr virus infection were three pathways significantly enriched pathways in DEmRNAs of NPC. The PPI network of top 50 DEGs were consisted of 191 nodes and 191 edges.

CONCLUSIONS:
Our study was helpful to elucidate the underlying mechanism of NPC and provide clues for therapeutic methods.

KEYWORDS:
Differentially expressed genes; Integrated analysis; Methylation; Nasopharyngeal carcinoma; PPI network

PMID: 31240455 DOI: 10.1007/s00405-019-05525-2
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Select item 31240454
28.
Eur Arch Otorhinolaryngol. 2019 Jun 25. doi: 10.1007/s00405-019-05528-z. [Epub ahead of print]
Profiling of heat shock proteins 27 and 70 in adenoids of children.
Min HJ1,2, Park JS1, Kim CE1, Kim KS3.
Author information
Abstract
PURPOSE:
Heat shock protein (HSP)27 and 70 are molecular chaperones that may have immunomodulatory functions. We determined if and at what levels each are expressed in the adenoids of pediatric subjects. We also examined tissue distributions, associated clinical characteristics, and antibacterial effects.

METHODS:
Western blot, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry were applied to adenoidal tissues and lavage fluids obtained from children (N = 40) undergoing adenotonsillectomy.

RESULTS:
Via western blot and ELISA, both HSP27 and 70 were regularly detected in adenoidal tissue and in lavage fluid samples. HSP27 was highly expressed in epithelium, whereas HSP70 showed strong subepithelial positivity and bore a significant relation to adenoidal size. Assayed levels of HSP27 and 70 correlated inversely, and their addition to culture media independently increased bacterial numbers (Staphylococcus aureus). Upon the precipitation of each from adenoidal lavage fluids, bacterial counts declined.

CONCLUSIONS:
HSP27 and 70 are readily expressed in the adenoids of children and may be implicated in immunologic responses.

KEYWORDS:
Adenoid; HSP 27; HSP 70; Heat shock protein

PMID: 31240454 DOI: 10.1007/s00405-019-05528-z
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Grant support
Select item 31240326
29.
Cancer Immunol Immunother. 2019 Jun 25. doi: 10.1007/s00262-019-02362-4. [Epub ahead of print]
High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer.
Carpén T1,2, Sorsa T3,4, Jouhi L5, Tervahartiala T3, Haglund C6,7, Syrjänen S8,9, Tarkkanen J10, Mohamed H10, Mäkitie A5,11,12, Hagström J10,7, Mattila PS5.
Author information
Abstract
BACKGROUND:
An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC.

MATERIALS AND METHODS:
A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS).

RESULTS:
High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels.

CONCLUSION:
Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.

KEYWORDS:
HPV; MMP-8; Oropharyngeal cancer; Prognosis; Survival; TIMP-1

PMID: 31240326 DOI: 10.1007/s00262-019-02362-4
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Select item 31240221
30.
Biomed Res Int. 2019 May 23;2019:6917084. doi: 10.1155/2019/6917084. eCollection 2019.
The Pull-Back Technique for the 532 Slim Modiolar Electrode.
Riemann C1, Sudhoff H1, Todt I1.
Author information
Abstract
INTRODUCTION:
The distance between the modiolus and the electrode array is one factor that has become the focus of many discussions and studies. Positioning the electrode array closer to the spiral ganglion with the goal of reducing the current spread has been shown to improve hearing outcomes. The perimodiolar electrode arrays can be complemented with a surgical manoeuvre called the pull-back technique. This study focuses its attention on the recently developed 532 slim modiolar electrode.

OBJECTIVE:
To investigate the intracochlear movements and pull-back technique for the 532 slim modiolar electrode.

MATERIAL AND METHODS:
A decapping procedure of the cochlea was performed on 5 temporal bones. The electrode array was inserted, and the intracochlear movements were microscopically examined and digitally captured. Three situations were analysed: the initial insertion, the overinsertion, and the pull-back position. The position of the three white markers of the electrode array in relation to the round window (RW) was evaluated while performing these three actions.

RESULTS:
The initial insertion achieved an acceptable perimodiolar position of the electrode array, but a gap was still observed between the mid-portion of the array and the modiolus (the first white marker was seen in the RW). When we inserted the electrode more deeply, the mid-portion of the array was pushed away from the modiolus (the second and third white markers were seen in the RW). After applying the pull-back technique, the gap observed during the initial insertion disappeared, resulting in an optimal perimodiolar position (the first white marker was once again visible in the RW).

CONCLUSION:
This temporal bone study demonstrated that when applying the pull-back technique for the 532 slim modiolar electrode, a closer proximity to the modiolus was achieved when the first white marker of the electrode array was visible in the round window.

PMID: 31240221 PMCID: PMC6556256 DOI: 10.1155/2019/6917084
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Select item 31239854
31.
Evid Based Complement Alternat Med. 2019 May 26;2019:1318639. doi: 10.1155/2019/1318639. eCollection 2019.
Analysis of Factors Influencing the Efficiency of Acupuncture in Tinnitus Patients.
Lin TY1,2, Yang SW2,3, Lee YS4,5, Wu PW2,3, Young CK2,3, Li TH1, Chou WL1.
Author information
Abstract
An effective acupuncture treatment must comprehend the influence of various factors, but studies in this aspect remain limited. This study aimed to identify relevant factors and search for the best practical method of acupuncture for patients with tinnitus. The study was a retrospective review of patients' data with a prospective design who had subjective idiopathic tinnitus and received acupuncture between May 2012 and August 2017. Patients' demographics, tinnitus characteristics, previous diseases, underlying diseases, oral habits, audiograms, acupuncture sessions, and acupoints were recorded and analyzed. A visual analog scale (VASloudness) was used for measuring the loudness of tinnitus, and the Clinical Global Impression-Improvement scale (CGI-I) was used for assessing the suffering of patients. Good treatment responses in patients were defined as the magnitude of change from the baseline VASloudness for ≥ 30% plus CGI-I ≤ 3 points. In total, 107 patients were enrolled. Most factors were not significantly associated with the treatment effectiveness of acupuncture in tinnitus patients. Only the combination of acupoints and the number of acupuncture sessions reached statistically significant differences. Further analyzing these two factors, we confirmed that the combination of periauricular and distal acupuncture and 17 to 24 acupuncture sessions contributed to a considerably better outcome. This result would serve as a reference for clinical acupuncturists to select an appropriate acupuncture strategy in the treatment of tinnitus.

PMID: 31239854 PMCID: PMC6556279 DOI: 10.1155/2019/1318639
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Select item 31239839
32.
J Oncol. 2019 May 23;2019:6273438. doi: 10.1155/2019/6273438. eCollection 2019.
Efficacy and Safety of Gefitinib in Patients with Advanced Head and Neck Squamous Cell Carcinoma: A Meta-Analysis of Randomized Controlled Trials.
Tang X1, He J2, Li B3, Zheng Y4, Li K1, Zou S1, Chen L5.
Author information
Abstract
BACKGROUND:
Trials on assessing the benefits of EGFR inhibitors in head and neck squamous cell carcinoma (HNSCC) patients have gradually been published. Nevertheless, the benefits of gefitinib in advanced HNSCC are still unknown.

METHODS:
The Cochrane library, PubMed, and EMBASE databases were systematically searched from the inception dates to 17 July 2017, 18 July 2017, and 19 July 2017, respectively. The keywords "head and neck" and gefitinib were used to retrieve in articles and abstracts. An additional search for recently published randomized trials was performed from July 17, 2017, to April 18, 2018. Then we assessed the risk of bias of the included studies based on the Cochrane "Risk of Bias" tool. Quantitative analysis was carried out to evaluate the overall survival (OS), progression free survival (PFS), overall response rate (ORR), and grade 3-4 adverse effects by Review Manager 5.0.2 and the quality-of-life was analyzed in the included studies.

RESULTS:
Seven randomized controlled trials and a total number of 1287 patients were involved. There were no significant differences in OS, PFS, or ORR between gefitinib and no gefitinib group (HR 1.07, 95% CI 0.93 to 1.22, and P=0.35; HR 0.84, 95% CI 0.69 to 1.04, and P=0.11; RR 1.04, 95% CI 0.90 to 1.20, and P =0.60, respectively). However, gefitinib alone was equivalent to chemotherapeutics (i.e., methotrexate; methotrexate + fluorouracil) in ORR in patients with recurrent HNSCC, and a trend of improvement in QOL in gefitinib group was showed. Toxicities revealed no differences except for diarrhea and skin toxicity (p=0.0003; p=0.03, respectively).

CONCLUSION:
For patients with advanced HNSCC, gefitinib cannot prolong the OS and PFS or improve ORR, and odds of skin toxicity and diarrhea increased. However, gefitinib alone is equivalent to methotrexate or methotrexate + fluorouracil and tends to improve QOL for recurrent patients.

PMID: 31239839 PMCID: PMC6556337 DOI: 10.1155/2019/6273438
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Select item 31239825
33.
Rev Urol. 2019;21(1):15-20.
Immunotherapy in Urological Tumors.
Sharma A1, Suleyman N2, Jones O2, Vasdev N.
Author information
Abstract
The past decade has seen significant improvement in our understanding of tumor biological features, which has led to use of anti-programmed-death 1 (PD-1) and anti-PD-ligand-1 (PD-L1) agents and cytotoxic T lymphocytes antigen 4 (CTLA-4) inhibitors in a multitude of cancers. These immunotherapeutic agents have shown activity in melanoma, lung, head and neck, colorectal, urological, and other cancers. This article details the use of immunotherapy agents in urothelial, renal, prostate, and testicular tumors.

KEYWORDS:
Cell wall-derived therapies; Cytokines; Immune checkpoint inhibitors; Immunotherapy; Recombinant BCG; Urological tumors

PMID: 31239825
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Select item 31239790
34.
Med Devices (Auckl). 2019 May 28;12:193-202. doi: 10.2147/MDER.S197919. eCollection 2019.
Nasal sound pressure as objective verification of implant in active transcutaneous bone conduction devices.
Reinfeldt S1, Rigato C1, Håkansson B1, Fredén Jansson KJ1, Eeg-Olofsson M2.
Author information
Abstract
Objective: Active transcutaneous bone conduction devices consist of an external audio processor and an internal implant under intact skin. During the surgical procedure, it is important to verify the functionality of the implant before the surgical wound is closed. In a clinical study with the new bone conduction implant (BCI), the functionality of the implant was tested with an electric transmission test, where the output was the nasal sound pressure (NSP) recorded in the ipsilateral nostril. The same measurement was performed in all follow-up visits to monitor the implant's functionality and transmission to bone over time. The objective of this study was to investigate the validity of the NSP method as a tool to objectively verify the implant's performance intraoperatively, as well as to follow-up the implant's performance over time. Design: Thirteen patients with the BCI were included, and the NSP measurement was part of the clinical study protocol. The implant was electrically stimulated with an amplitude-modulated signal generator using a swept sine 0.1-10 kHz. The NSP was measured with a probe tube microphone in the ipsilateral nostril. Results: The NSP during surgery was above the noise floor for most patients within the frequency interval 0.4-5 kHz, showing NSP values for expected normal transmission of a functioning implant. Inter-subject comparison showed large variability, but follow-up results showed only minor variability within each subject. Further investigation showed that the NSP was stable over time. Conclusion: The NSP method is considered applicable to verify the implant's functionality during and after surgery. Such a method is important for implantable devices, but should be simplified and clinically adapted. Large variations between subjects were found, as well as smaller variability in intra-subject comparisons. As the NSP was found to not change significantly over time, stable transmission to bone, and implant functionality, were indicated.

KEYWORDS:
bone conduction; bone conduction implant; ear-canal sound pressure; nasal sound pressure; objective intraoperative verification

PMID: 31239790 PMCID: PMC6553998 DOI: 10.2147/MDER.S197919
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Conflict of interest statement
Select item 31239690
35.
Ther Clin Risk Manag. 2019 Jun 4;15:683-688. doi: 10.2147/TCRM.S199630. eCollection 2019.
Improved perioperative quality of life in endoscopic sinus surgery by application of enhanced recovery after surgery.
Wu X1, Kong W1, Zhu Q2, Wang W1, Xu H1, Zhou S3, Yang Q1.
Author information
Abstract
Background: Endoscopic sinus surgery (ESS) has been the definitive treatment for chronic rhinosinusitis (CRS), but the complications caused perioperatively may affect patients' quality of life (QoL). This study aims to evaluate the effects of enhanced recovery after surgery (ERAS) on improving perioperative QoL in ESS. Materials and methods: Seventy-four patients with chronic rhinosinusitis with nasal polyps (CRSwNP) met the criteria for inclusion. Participants undergoing ESS were randomly divided into an ERAS group and a control group, and QoL assessment was performed using the Chinese version of the 22-item Sinonasal Outcomes Test (SNOT-22). Measurements were administered at baseline, and on postoperative day 1 (POD1), POD3 and POD6. Complications such as nausea/emesis, hemorrhage, aspiration and dizziness were also recorded. Results: The preoperative global SNOT-22 scores (mean ± SD) were 39.89±4.86 in the ERAS group and 40.52±3.61 in the control group (t=0.643, P=0.522). On POD1, the global SNOT-22 scores increased significantly to 51.77±5.59 and 62.02±3.86 (t=9.218, P<0.01), and on POD3 they increased to 48.22±6.22 and 51.11±5.14, respectively (t=2.179, P<0.05). However, the scores recovered to 39.39±4.73 and 40.13±3.31 in the respective groups on POD6, which were lower than but not statistically significant different from the baseline (t=0.786, P=0.434). There were statistically significant improvements across all subdomains of SNOT-22 for patients in the two groups only in POD1 (all P<0.05). The ERAS group did not have an increased incidence of complications such as nausea/emesis (χ 2=0.223, P>0.05), hemorrhage, aspiration and dizziness compared to the control group. Conclusion: ERAS could improve perioperative QoL in patients with CRSwNP undergoing ESS, and SNOT-22 can be used for ERAS evaluation as a patients' outcome report.

KEYWORDS:
SNOT-22; chronic rhinosinusitis; enhanced recovery after surgery; quality of life

PMID: 31239690 PMCID: PMC6556532 DOI: 10.2147/TCRM.S199630
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Select item 31239676
36.
Int J Nanomedicine. 2019 Jun 6;14:4211-4227. doi: 10.2147/IJN.S195336. eCollection 2019.
Dexamethasone-loaded injectable silk-polyethylene glycol hydrogel alleviates cisplatin-induced ototoxicity.
Chen Y1,2,3, Gu J1,2,3, Liu J4, Tong L1, Shi F5, Wang X4, Wang X1,2,3, Yu D1,2,3, Wu H1,2,3.
Author information
Abstract
Background: Cisplatin is an extensively used anti-neoplastic agent for the treatment of various solid tumors. However, a high incidence of severe ototoxicity is accompanied by its use in the clinic. Currently, no drugs or therapeutic strategies have been approved for the treatment of cisplatin-induced ototoxicity by the FDA. Purpose: The purpose of this study was to investigate the otoprotective effects of dexamethasone (DEX)-loaded silk-polyethylene hydrogel (DEX-SILK) following round window membrane administration in the cisplatin-induced ototoxicity mouse model. Methods: The morphology, gelation kinetics, viscosity and secondary structure of the DEX-SILK hydrogel were analyzed. DEX concentration in the perilymph was tested at different time points following hydrogel injection on the RWM niche. Cultured cells (HEI-OC1), organ of Corti explants (C57/BL6, P0-2), and cisplatin-induced hearing loss mice model (C57/BL6) were used as in vitro and in vivo models for investigating the otoprotective effects of DEX-SILK hydrogel against cisplatin. Results: Encapsulation of DEX with a loading of 8% (w/v) did not significantly change the silk gelation time, and DEX was evenly distributed in the Silk-PEG hydrogel as visualized by scanning electron microscopy (SEM). The concentration of Silk majorly influenced DEX distribution, morphological characteristics, viscosity, and gelation time. The optimized DEX-SILK hydrogel (8% w/v loading, 15% silk concentration, 10 μl) was administered directly onto the RWM of the guinea pigs. The DEX concentration in the perilymph was maintained above 1 μg/ml for at least 21 days for the DEX-SILK, while it was maintained for less than 6 h in the control sample of free DEX. DEX-SILK (5-60 ng/ml) exhibited significant protective effects against cisplatin-induced cellular ototoxicity and notably reduced the production of reactive oxygen species (ROS). Eventually, pretreatment with DEX-SILK effectively preserved outer hair cells in the cultured organ of Corti explants and demonstrated significant hearing protection at 4, 8, and 16 kHz in the cisplatin-induced hearing loss mice as compared to the effects noted following pretreatment with DEX. Conclusion: These results demonstrated the clinical value of DEX-SILK for the therapy of cisplatin-induced ototoxicity.

KEYWORDS:
cisplatin-induced hearing loss; dexamethasone; round window membrane; silk-polyethyleneglycol hydrogel

PMID: 31239676 PMCID: PMC6559256 DOI: 10.2147/IJN.S195336
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Conflict of interest statement
Select item 31239594
37.
Nagoya J Med Sci. 2019 May;81(2):249-258. doi: 10.18999/nagjms.81.2.249.
Exploration of coping styles in male patients with head and neck cancer: a prospective cohort study.
Sato N1, Kimura H1, Adachi Y2, Nishio N3, Ando M4, Tokura T1, Nagashima W5, Kishi S1, Yamauchi A1, Yoshida K6, Hiramatsu M3, Fujimoto Y3, Ozaki N1.
Author information
Abstract
Majority of head and neck cancer (HNC) patients are male, and more than 85% of patients with HNC have the habit of smoking and drinking. Due to the specific demographic characteristics, HNC patients are anticipated to have specific coping styles, affecting psychological distress, survival, and quality of life. We explored the subscales of the Mental Adjustment to Cancer (MAC) Scale in male patients with HNC, and then examined the correlation between revised subscales of the MAC scale and anxiety/depression. Participants were 150 male inpatients with HNC, and their demographic and medical data were obtained. Coping style was assessed by MAC scale. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Out of 40 items in the original MAC scale, 19 items were excluded by factor analysis, and the remaining 21 items were divided into three factors: Negative Adjustment, Positive Adjustment, and Abandonment. Negative and Positive Adjustments were similar to the copings of mixed gender patients with heterogeneous cancers, and Abandonment was a new subscale specific to male patients with HNC. This subscale had a weak positive correlation with anxiety and depression. Male HNC patients revealed a specific coping style of Abandonment, related with psychological distress. We believe that an understanding of the Abandonment coping style revealed in our study will improve the psychological support offered to male patients with HNC.

KEYWORDS:
anxiety; coping; depression; head and neck cancer; oncology

PMID: 31239594 PMCID: PMC6556458 DOI: 10.18999/nagjms.81.2.249
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Select item 31239523
38.
Sci Rep. 2019 Jun 25;9(1):9273. doi: 10.1038/s41598-019-45385-8.
Auditory metabolomics, an approach to identify acute molecular effects of noise trauma.
Ji L1, Lee HJ2, Wan G1, Wang GP1, Zhang L2, Sajjakulnukit P2, Schacht J1, Lyssiotis CA3, Corfas G4.
Author information
Abstract
Animal-based studies have provided important insights into the structural and functional consequences of noise exposure on the cochlea. Yet, less is known about the molecular mechanisms by which noise induces cochlear damage, particularly at relatively low exposure levels. While there is ample evidence that noise exposure leads to changes in inner ear metabolism, the specific effects of noise exposure on the cochlear metabolome are poorly understood. In this study we applied liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based metabolomics to analyze the effects of noise on the mouse inner ear. Mice were exposed to noise that induces temporary threshold shifts, synaptopathy and permanent hidden hearing loss. Inner ears were harvested immediately after exposure and analyzed by targeted metabolomics for the relative abundance of 220 metabolites across the major metabolic pathways in central carbon metabolism. We identified 40 metabolites differentially affected by noise. Our approach detected novel noise-modulated metabolites and pathways, as well as some already linked to noise exposure or cochlear function such as neurotransmission and oxidative stress. Furthermore, it showed that metabolic effects of noise on the inner ear depend on the intensity and duration of exposure. Collectively, our results illustrate that metabolomics provides a powerful approach for the characterization of inner ear metabolites affected by auditory trauma. This type of information could lead to the identification of drug targets and novel therapies for noise-induced hearing loss.

PMID: 31239523 DOI: 10.1038/s41598-019-45385-8
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Select item 31239411
39.
Phys Med Biol. 2019 Jun 26. doi: 10.1088/1361-6560/ab2c95. [Epub ahead of print]
Automatic segmentation of the mandible from computed tomography scans for 3D virtual surgical planning using the convolutional neural network.
Qiu B1, Guo J2, Kraeima J3, Glas HH3, Borra RJH4, Witjes MJH3, van Ooijen PMA5.
Author information
Abstract
Segmentation of mandibular bone in CT scans is crucial for 3D virtual surgical planning of craniofacial tumor resection and free flap reconstruction of the resection defect, in order to obtain a detailed surface representation of the bones. A major drawback of most existing mandibular segmentation methods is that they require a large amount of expert knowledge for manual or partially automatic segmentation. In fact, due to the lack of experienced doctors and experts, high quality expert knowledge is hard to achieve in practice. Furthermore, segmentation of mandibles in CT scans is influenced seriously by metal artifacts and large variations in their shape and size among individuals. In order to address these challenges we propose an automatic mandible segmentation approach in CT scans, which considers the continuum of anatomical structures through different planes. The approach adopts the architecture of the U-Net and then combines the resulting 2D segmentations from three orthogonal planes into a 3D segmentation. We implement such a segmentation approach on two head and neck datasets and then evaluate the performance. Experimental results show that our proposed approach for mandible segmentation in CT scans exhibits high accuracy.

© 2019 Institute of Physics and Engineering in Medicine.

KEYWORDS:
3D virtual surgical planning; automatic mandible segmentation; convolutional neural network; oral and maxillofacial surgery

PMID: 31239411 DOI: 10.1088/1361-6560/ab2c95
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Select item 31239321
40.
Clin Cancer Res. 2019 Jun 25. pii: clincanres.3944.2018. doi: 10.1158/1078-0432.CCR-18-3944. [Epub ahead of print]
Nivolumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: Efficacy and Safety in CheckMate 141 by Prior Cetuximab Use.
Ferris RL1, Licitra L2, Fayette J3, Even C4, Blumenschein GR5, Harrington KJ6, Guigay J7, Vokes EE8, Saba NF9, Haddad RI10, Ramkumar S11, Russell J12, Brossart P13, Tahara M14, Colevas AD15, Concha-Benavente F16, Lynch M17, Li L18, Gillison ML19.
Author information
Abstract
PURPOSE:
Cetuximab, which modulates immune responses, may affect the efficacy of subsequent immunotherapy. Here, we assessed outcomes with nivolumab, by prior cetuximab exposure, in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) who had experienced progression within 6 months of platinum-containing chemotherapy.

EXPERIMENTAL DESIGN:
In the randomized, open-label, phase III CheckMate 141 trial, patients were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator's choice (IC) of single-agent chemotherapy, with stratification by prior cetuximab exposure. The primary endpoint was overall survival (OS); additional endpoints were progression-free survival, objective response rate, and safety.

RESULTS:
In patients with prior cetuximab exposure, the median OS was 7.1 months with nivolumab versus 5.1 months with IC (HR, 0.84; 95% CI, 0.62-1.15); OS benefit with nivolumab was maintained across most demographic subgroups. In patients without prior cetuximab exposure, the median OS was 8.2 months with nivolumab versus 4.9 months with IC (HR, 0.52; 95% CI, 0.35-0.77); OS benefit with nivolumab was maintained across patient baseline subgroups including tumor programmed death ligand 1 (PD-L1) expression (<1% or ≥1%). Grade 3-4 treatment-related adverse event rates favored nivolumab versus IC in both subgroups.

CONCLUSIONS:
Nivolumab appeared to improve efficacy versus IC regardless of prior cetuximab use, supporting its use in patients with R/M SCCHN with or without prior cetuximab exposure. The reduction in risk of death with nivolumab compared with IC was greater in patients without prior cetuximab exposure versus with prior cetuximab exposure.

Copyright ©2019, American Association for Cancer Research.

PMID: 31239321 DOI: 10.1158/1078-0432.CCR-18-3944
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Select item 31239287
41.
Mol Cancer Res. 2019 Jun 25. pii: molcanres.1191.2018. doi: 10.1158/1541-7786.MCR-18-1191. [Epub ahead of print]
Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma.
Domingo-Vidal M1, Whitaker-Menezes D1, Martos-Rus C1, Tassone P2, Snyder CM3, Tuluc M4, Philp N4, Curry J2, Martinez-Outschoorn U5.
Author information
Abstract
Head and neck squamous cell carcinoma (HNSCC) is comprised of metabolically linked distinct compartments. Cancer-associated fibroblasts (CAFs) and non-proliferative carcinoma cells display a glycolytic metabolism, whilst proliferative carcinoma cells rely on mitochondrial oxidative metabolism fueled by the catabolites provided by the adjacent CAFs. Metabolic coupling between these reprogrammed compartments contributes to HNSCC aggressiveness. In the current study, we examined the effects of cigarette smoke-exposed CAFs on metabolic coupling and tumor aggressiveness of HNSCC. Cigarette smoke (CS) extract was generated by dissolving cigarette smoke in growth media. Fibroblasts were cultured in CS or control media. HNSCC cells were co-cultured in vitro and co-injected in vivo with CS- or control fibroblasts. We found that CS induced oxidative stress, glycolytic flux and MCT4 expression, and senescence in fibroblasts. MCT4 upregulation was critical for fibroblast viability under CS conditions. The effects of CS on fibroblasts were abrogated by antioxidant treatment. Co-culture of carcinoma cells with CS-fibroblasts induced metabolic coupling with upregulation of the marker of glycolysis MCT4 in fibroblasts and markers of mitochondrial metabolism MCT1 and TOMM20 in carcinoma cells. CS-fibroblasts increased CCL2 expression and macrophage migration. Co-culture with CS-fibroblasts also increased two features of carcinoma cell aggressiveness: resistance to cell death and enhanced cell migration. Co-injection of carcinoma cells with CS-fibroblasts generated larger tumors with reduced apoptosis than control co-injections, and upregulation of MCT4 by CS exposure was a driver of these effects. We demonstrate that a tumor microenvironment exposed to CS is sufficient to modulate metabolism and cancer aggressiveness in HNSCC. Implications: Cigarette smoke shifts cancer-stroma towards glycolysis and induces head and neck cancer aggressiveness with a mitochondrial profile linked by catabolite transporters and oxidative stress.

Copyright ©2019, American Association for Cancer Research.

PMID: 31239287 DOI: 10.1158/1541-7786.MCR-18-1191
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Select item 31239229
42.
Br J Oral Maxillofac Surg. 2019 Jun 22. pii: S0266-4356(19)30226-8. doi: 10.1016/j.bjoms.2019.06.005. [Epub ahead of print]
Comparison of outcomes of treatment for ranula: a proportion meta-analysis.
Chung YS1, Cho Y2, Kim BH3.
Author information
Abstract
Treatment for ranula is classified into three categories depending on how the leaking saliva is managed: removal of the leaking site by intraoral or transcervical resection of the sublingual gland; formation of a drainage tract through the wall of the pseudocyst by micromarsupialisation or marsupialisation; or sealing of the site of the leak by inducing fibrosis with a sclerosing agent. Resection of the sublingual gland is probably the option most likely to be curative for both oral and plunging ranula considering their pathophysiology. Although alternative treatments have been introduced to avoid the invasiveness of resection of the gland, their outcomes have been inconsistent. The objective of this study therefore was to help decision-making by providing more integrated rates of cure, consistency of treatment, and morbidity, depending on types of treatment used in previous series of cases. We used proportion meta-analysis of 39 such published series, and the most curative treatment for oral ranula was intraoral resection of the sublingual gland. Micromarsupialisation and its modification showed cure rates comparable with those of resection of the gland, but these were moderately inconsistent. In the treatment of plunging ranula, there was no significant difference in cure rate between the intraoral and transcervical approaches, although they both showed higher cure rates than injection of OK-432. Comparisons of morbidity were available for patients who had developed nerve dysfunction and haematoma after the intraoral and transcervical approaches and there was no significant difference between the two, though the morbidity was higher after the transcervical than that after the intraoral approach. In conclusion, intraoral resection of the sublingual gland is sufficient treatment with a tendency to have fewer complications than that in the transcervical approach.

Copyright © 2019 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:
Oral ranula; Plunging ranula; proportion meta-analysis

PMID: 31239229 DOI: 10.1016/j.bjoms.2019.06.005
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Select item 31239146
43.
Prog Brain Res. 2019;248:65-90. doi: 10.1016/bs.pbr.2019.04.014. Epub 2019 May 24.
Mathematical models for dynamic, multisensory spatial orientation perception.
Clark TK1, Newman MC2, Karmali F3, Oman CM4, Merfeld DM5.
Author information
Abstract
Mathematical models have been proposed for how the brain interprets sensory information to produce estimates of self-orientation and self-motion. This process, spatial orientation perception, requires dynamically integrating multiple sensory modalities, including visual, vestibular, and somatosensory cues. Here, we review the progress in mathematical modeling of spatial orientation perception, focusing on dynamic multisensory models, and the experimental paradigms in which they have been validated. These models are primarily "black box" or "as if" models for how the brain processes spatial orientation cues. Yet, they have been effective scientifically, in making quantitative hypotheses that can be empirically assessed, and operationally, in investigating aircraft pilot disorientation, for example. The primary family of models considered, the observer model, implements estimation theory approaches, hypothesizing that internal models (i.e., neural systems replicating the behavior/dynamics of physical systems) are used to produce expected sensory measurements. Expected signals are then compared to actual sensory afference, yielding sensory conflict, which is weighted to drive central perceptions of gravity, angular velocity, and translation. This approach effectively predicts a wide range of experimental scenarios using a small set of fixed free parameters. We conclude with limitations and applications of existing mathematical models and important areas of future work.

© 2019 Elsevier B.V. All rights reserved.

KEYWORDS:
Computational; Internal models; Sensory conflict; Vestibular; Visual-vestibular integration

PMID: 31239146 DOI: 10.1016/bs.pbr.2019.04.014
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Select item 31239144
44.
Prog Brain Res. 2019;248:329-340. doi: 10.1016/bs.pbr.2019.02.005. Epub 2019 Jun 11.
Model of optokinetic responses involving two different visual motion processing pathways.
Miura K1, Takemura A2, Taki M3, Kawano K2.
Author information
Abstract
To understand visual motion processing underlying the optokinetic response (OKR), we developed a biomimetic model that reproduces the findings from behavioral experiments. We recorded OKRs induced by drifting gratings with different spatiotemporal frequencies from humans and non-human primates. The characteristics of the initial open-loop responses and the closed-loop eye velocity gains were analyzed using a model developed in this study. The model consists of two pathways with different dynamics. One mediates the transient response (transient pathway) and the other the sustained response (sustained pathway). Each pathway has a different spatiotemporal frequency dependence. Assuming there are different visual sensitivities for these pathways, one tuned to lower spatial and higher temporal frequencies on the retina and the other tuned to stimulus velocity, we successfully reproduced the course of OKRs. Our results suggest that two different neural circuitries/populations contribute to visual processing in the different stages of OKRs.

© 2019 Elsevier B.V. All rights reserved.

KEYWORDS:
Computer simulation; Eye movements; Human; Monkey; Motion vision

PMID: 31239144 DOI: 10.1016/bs.pbr.2019.02.005
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Select item 31239135
45.
Prog Brain Res. 2019;248:241-248. doi: 10.1016/bs.pbr.2019.04.028. Epub 2019 May 23.
The functional head impulse test: Comparing gain and percentage of correct answers.
Versino M1, Colnaghi S2, Corallo G3, Mandalà M4, Ramat S5.
Author information
Abstract
OBJECTIVES:
The video head impulse test (vHIT) provides as output a gain value that summarizes the behavior of the vestibulo-ocular reflex as the ratio of a measure of eye movement to the corresponding measure of head movement and is not directly informative of the functional effectiveness of the motor response. The functional HIT (fHIT) is based on the ability to recognize the orientation of a Landolt C optotype that briefly appears on a computer screen during passive head impulses imposed by the examiner over a range of head accelerations; accordingly fHIT is a functional measurement of the vestibular-ocular reflex since it measures the capability to keep clear vision and to read during head movement.

METHODS:
We compared the results of the fHIT with those of the vHIT and the results of the Dizziness Handicap Inventory (DHI) questionnaire in a group of 27 vestibular neuritis patients recorded acutely and at 3-months follow-up.

RESULTS:
Both the vHIT and fHIT exams correctly classified all patients as abnormal on the affected side when tested in the acute phase. After a 3-month follow-up, both were able to show that compensation phenomena had occurred. Otherwise the data from the two techniques were not correlated. More specifically, the fHIT detected more abnormalities than the vHIT, for head rotation toward the healthy side, both in the acute phase and after 3 months, and for head rotation toward the affected side after 3 months. The asymmetry indices, that compare the performance of the healthy to the affected side, also were larger for the fHIT than for the vHIT both at onset and after 3 months. There was no significant correlation between the different vHIT and fHIT parameters and indices, or with the DHI values after 3 months.

CONCLUSIONS:
The fHIT data are able to detect a difference between the healthy and the affected side in the acute phase, and they show an improvement after 3 months. fHIT detects more abnormalities than vHIT, but both these techniques lack a correlation with the DHI score.

© 2019 Elsevier B.V. All rights reserved.

KEYWORDS:
Dizziness Handicap Inventory; Functional HIT; Head impulse test; Vestibulo-ocular reflex

PMID: 31239135 DOI: 10.1016/bs.pbr.2019.04.028
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Select item 31239133
46.
Prog Brain Res. 2019;248:209-223. doi: 10.1016/bs.pbr.2019.04.029. Epub 2019 Jun 11.
Spatial orientation: Model-based approach to multi-sensory mechanisms.
Kheradmand A1, Otero-Millan J2.
Author information
Abstract
Perception of spatial orientation is generated through multimodal sensory integration. In this process, there are systematic errors with changes in the head or body position, which reflect challenges for the brain in maintaining a common sensory reference frame for spatial orientation. Here, we focus on this multisensory aspect of spatial orientation. We review a Bayesian spatial perception model that can be used as a framework to study sensory contributions to spatial orientation during lateral head tilts and probe neural networks involved in this process.

© 2019 Elsevier B.V. All rights reserved.

KEYWORDS:
Bayesian; SVV; Sensory integration; Spatial orientation; Subjective visual vertical

PMID: 31239133 DOI: 10.1016/bs.pbr.2019.04.029
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Select item 31239095
47.
Auris Nasus Larynx. 2019 Jun 22. pii: S0385-8146(19)30283-4. doi: 10.1016/j.anl.2019.06.003. [Epub ahead of print]
The usefulness of abscess tonsillectomy followed by intraoral drainage for parapharyngeal abscess concomitant with peritonsillar abscess in the elderly.
Ohori J1, Iuchi H2, Nagano H2, Umakoshi M2, Matsuzaki H2, Kurono Y2.
Author information
Abstract
Parapharyngeal abscess (PPA) may cause life-threatening complications and peritonsillar abscess (PTA) and tonsillitis frequently precede PPA. The optimal management of PPA caused by PTA has been the subject of debate with respect to the surgical approach. We present three cases of PPA concomitant with PTA in elderly patients. In two cases, the abscesses in parapharyngeal space were drained by abscess tonsillectomy followed by intraoral incision of the tonsillar bed. On the other hand, the third case did not undergo abscess tonsillectomy because of his refusal of surgery and needed extraoral drainage after the aggravation of PPA. Based on the experience of those three cases, it was suggested that abscess tonsillectomy followed by intraoral incision of the tonsillar bed might be a useful surgical approach for the drainage of PPA concomitant with PTA, especially in elderly patients.

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

KEYWORDS:
Abscess tonsillectomy; Intraoral drainage; Parapharyngeal abscess; Peritonsillar abscess

PMID: 31239095 DOI: 10.1016/j.anl.2019.06.003
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Select item 31239082
48.
Int J Oral Maxillofac Surg. 2019 Jun 22. pii: S0901-5027(19)31173-7. doi: 10.1016/j.ijom.2019.06.003. [Epub ahead of print]
Dealing with vascular anomalies during radial forearm free flap harvest: report of two cases and review of the literature.
Breik O1, Selbong U2, Laugharne D2, Jones K2.
Author information
Abstract
Radial forearm free flap reconstruction for head and neck cancer is very common, and it is widely considered a workhorse flap. Although this flap has a relatively reliable anatomy, surgeons need to be aware of possible anatomical variations and how to deal with them. This paper presents the cases of two patients who underwent oral reconstruction, in whom anomalies of the radial artery were identified while raising a radial forearm free flap. Case 1 demonstrates the dominant branch of the radial artery joining the common interosseous artery approximately 9 cm from the first wrist crease. Case 2 demonstrates abnormal distal branching of the radial artery approximately 4 cm from the first wrist crease. Reconstruction with the flap was successful in both cases. A literature review of reported anomalies of the radial artery is presented, and how to deal with such vascular anomalies is discussed.

Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:
aberrant radial artery; anomalies; radial artery; radial forearm

PMID: 31239082 DOI: 10.1016/j.ijom.2019.06.003
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Select item 31238980
49.
J Exp Clin Cancer Res. 2019 Jun 25;38(1):278. doi: 10.1186/s13046-019-1254-4.
Long noncoding RNA MYOSLID promotes invasion and metastasis by modulating the partial epithelial-mesenchymal transition program in head and neck squamous cell carcinoma.
Xiong HG1,2, Li H1, Xiao Y1, Yang QC1, Yang LL1, Chen L1, Bu LL1, Zhang WF1,2, Zhang JL3,4, Sun ZJ5,6.
Author information
Abstract
BACKGROUND:
Partial epithelial mesenchymal transition (p-EMT) was found to play a potential role in the initial stage of metastasis in human head and neck squamous cell carcinoma (HNSCC). Some long noncoding RNAs (lncRNAs) have been reported to function as promoters or inhibitors of cancer metastasis. This study aimed to identify p-EMT-related lncRNAs in HNSCC.

METHODS:
Differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DEGs) in HNSCC obtained from The Cancer Genome Atlas (TCGA) were screened out by using the "edgeR" package. DE-lncRNAs in the Oral squamous cell carcinoma (OSCC) lncRNA microarray dataset GSE84805 were screened out by using the "limma" package. Slug-related lncRNAs were determined by Pearson correlation analysis (|Pearson correlation coefficient| ≥ 0.4, p < 0.01) based on TCGA. Survival analysis were performed for the overlapping DE-lncRNAs by using the "Survival" package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of MYOSLID. RT-qPCR and In Site Hybridization (ISH) were used to explore the MYOSLID expression and its clinical significance in HNSCC specimens. Immunohistochemical staining, siRNA, wound healing assay, transwell assay, and western blot were used to explore the biological function and potential molecular mechanisms.

RESULTS:
MYOSLID was identified as a Slug-related lncRNA and with prognostic value among the 9 overlapping DE-lncRNAs. GO and KEGG analyses revealed that MYOSLID was closely related to important biological processes and pathways that regulate cancer metastasis. The results of univariate and multivariate Cox regression analysis based on TCGA and HNSCC tissue microarray data suggested MYOSLID was an independent prognostic factor. MYOSLID expression in HNSCC was closely correlated with Slug, PDPN and LAMB3. The knockdown of MYOSLID in OSCC cell line significantly inhibited cell migration and invasion compared to those in the control cells. In addition, the knockdown of MYOSLID significantly reduced Slug, PDPN and LAMB3 expression levels. However, the knockdown of MYOSLID had no effect on the expression levels of the EMT biomarkers E-cadherin and Vimentin.

CONCLUSIONS:
Our study revealed that MYOSLID expression was closely related to the p-EMT program in HNSCC, and it might be a new predictive biomarker for aggressive HNSCC.

KEYWORDS:
Long non-coding RNA; MYOSLID; Partial epithelial to mesenchymal transition; Prognostic biomarkers

PMID: 31238980 DOI: 10.1186/s13046-019-1254-4
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Select item 31238894
50.
BMC Cancer. 2019 Jun 25;19(1):624. doi: 10.1186/s12885-019-5816-9.
Expression of toll-like receptors in non-endemic nasopharyngeal carcinoma.
Ruuskanen M1, Leivo I2, Minn H3, Vahlberg T4, Haglund C5,6, Hagström J6,7, Irjala H8.
Author information
Abstract
BACKGROUND:
Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer.

METHODS:
In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome.

RESULTS:
We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2nucl/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative).

CONCLUSIONS:
TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.

KEYWORDS:
Epstein-Barr virus; Head and neck cancer; Human papillomavirus; Nasopharyngeal carcinoma; Toll-like receptor

PMID: 31238894 DOI: 10.1186/s12885-019-5816-9
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Select item 31238308
51.
Fetal Diagn Ther. 2019 Jun 25:1-6. doi: 10.1159/000500455. [Epub ahead of print]
Fetoscopy-Assisted Percutaneous Decompression of the Distal Trachea and Lungs Reverses Hydrops Fetalis and Fetal Distress in a Fetus with Laryngeal Atresia.
Nicolas CT1,2, Lynch-Salamon D1, Bendel-Stenzel E1,3, Tibesar R1, Luks F4, Eyerly-Webb S1, Lillegard JB5,6,7.
Author information
Abstract
We present a case of prenatal hydrops secondary to congenital high airway obstruction syndrome (CHAOS) that was treated with fetoscopy-assisted needle decompression. A 22-year-old G3P2 woman presented after a 21-week ultrasound demonstrated CHAOS. The fetus developed hydrops at 25 weeks, characterized by abdominal ascites, pericardial effusion, and scalp edema. Fetal MRI showed complete obstruction of the glottis and subglottic airway, suggestive of laryngeal atresia. At 27 weeks, due to the progression of the hydrops, operative fetoscopy was proposed and performed. Fetal laryngoscopy confirmed fusion of the vocal cords and laryngeal atresia. The atretic segment was a solid cartilaginous block, preventing intubation. Using the fetoscope to stabilize the fetal head and neck, we performed ultrasound-guided percutaneous needle drainage of the cervical trachea through the anterior fetal neck. We removed 17 mL of viscous fluid from the lower trachea, resulting in immediate lung decompression. Two weeks later, ultrasound confirmed hydrops resolution. The patient was delivered and tracheostomy performed at 30 weeks via an ex utero intrapartum treatment (EXIT) procedure after progression of preterm labor. At 27 days of life, the infant was stable on minimal ventilator support. To our knowledge, this is the first successful report of an ultrasound-guided percutaneous tracheal decompression through the anterior neck of a fetus with CHAOS secondary to laryngeal atresia.

© 2019 S. Karger AG, Basel.

KEYWORDS:
CHAOS; Congenital high airway obstruction syndrome; EXIT; Ex utero intrapartum treatment; Fetal surgery; Fetoscopy; Laryngeal atresia

PMID: 31238308 DOI: 10.1159/000500455
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Select item 31238303
52.
ORL J Otorhinolaryngol Relat Spec. 2019 Jun 25:1-10. doi: 10.1159/000496829. [Epub ahead of print]
Predictive Significance of Radiographic Density of Sinus Opacity and Bone Thickness in Unilateral Maxillary Sinus Mycetoma.
Huang Z1, Xu H2, Xiao N1, Li Y1, Dong Y1, Li Y1, Zhou B3.
Author information
Abstract
OBJECTIVES:
To identify the optimal cutoff value in Hounsfield units (HU) of maxillary sinus (MS) opacity and bone thickness (neo-osteogenesis) of MS as radiological predictors for mycetoma.

METHODS:
One hundred and sixty-four patients, including 59 patients with unilateral MS mycetoma, 31 with unilateral odontogenic maxillary sinusitis, 44 with chronic rhinosinusitis and 30 with rhinitis, who underwent sinus or turbinate surgery were recruited. The bone thickness, HU of the MS posterolateral wall and sinus opacity were evaluated using computed tomography scan.

RESULTS:
The bone thickness of the MS posterolateral wall in the mycetoma group was significantly higher than that in the odontogenic sinusitis and chronic rhinosinusitis (CRS) groups (p < 0.0001). The HU of the sinus opacity in the mycetoma group were significantly higher than those in the odontogenic and CRS groups (p < 0.0001). An optimal cutoff HU of sinus opacity >101.17 yielded a sensitivity of 96.6 and specificity of 100% for the diagnosis of MS mycetoma. An optimal cutoff of bone thickness >0.305 cm yielded a sensitivity of 84.7 and specificity of 60% for the diagnosis of MS mycetomas.

CONCLUSIONS:
The radiographic density measurement of MS opacification has a high predictive value for the diagnosis of MS mycetoma while radiographic neo-osteogenesis has not.

© 2019 S. Karger AG, Basel.

KEYWORDS:
Bone thickness; Computed tomography; Mycetoma; Odontogenic maxillary sinusitis; Predictor; ROC curve; Radiographic density

PMID: 31238303 DOI: 10.1159/000496829
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Select item 31238052
53.
Life Sci. 2019 Jun 22:116597. doi: 10.1016/j.lfs.2019.116597. [Epub ahead of print]
LncRNA SNHG3 regulates laryngeal carcinoma proliferation and migration by modulating the miR-384/WEE1 axis.
Wang L1, Su K2, Wu H2, Li J2, Song D2.
Author information
Abstract
LncRNA SNHG3 (SNHG3) is involved in tumor development and progression, but little is known about how SNHG3 functions in laryngeal carcinoma (LC). Real time-PCR (RT-PCR) was used to estimate the expression of SNHG3 in LC tissues and cell lines TU212 and TU686. Cell viability, migration, and invasion were evaluated. Our results showed increased SNHG3 in LC tissues and cell lines. Loss of function of SNHG3 reduced cell viability, migration, and invasion of TU212 and TU686 cells. Western blot analyses demonstrated that the protein levels of MMP2 and MMP9 decreased after SNHG3 silencing. Additionally, bioinformatics software predicted that SNHG3 could sponge miR-384 at the 3'-UTR with complementary binding sites, which was validated by a dual-luciferase reporter assay. RT-PCR analysis revealed that knockdown of SNHG3 upregulated miR-384 expression and that overexpression of miR-384 decreased SNHG3. Furthermore, a dual-luciferase reporter assay showed that miR-384 could bind to the 3'-UTR of WEE1, and inhibition of miR-384 markedly increased WEE1 expression. The mRNA and protein levels of WEE1 were downregulated upon deletion of SNGH3. Suppression of WEE1 partly abolished the tumorigenic migration and invasion potential of the miR-384 inhibitor in migration and invasion. Inhibition of miR-384 partially reversed the biological activities of SNHG3 in TU212 and TU686 cells. Collectively, our results indicate that SNHG3 regulated LC cell migration and invasion via the miR-384/WEE1 axis.

Copyright © 2019. Published by Elsevier Inc.

KEYWORDS:
Laryngeal carcinoma; Migration; SNHG3; WEE1; miR-384

PMID: 31238052 DOI: 10.1016/j.lfs.2019.116597
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Select item 31238024
54.
J Am Coll Radiol. 2019 Jun 22. pii: S1546-1440(19)30697-0. doi: 10.1016/j.jacr.2019.05.045. [Epub ahead of print]
Feeding the Data Monster: Data Science in Head and Neck Cancer for Personalized Therapy.
Marcu LG1, Boyd C2, Bezak E3.
Author information
Abstract
OBJECTIVE:
Head and neck carcinomas are clinically challenging malignancies due to tumor heterogeneities and resilient tumor subvolumes that require individualized treatment planning and delivery for an improved outcome. Although current approaches to diagnosis and therapy have boosted locoregional control, the long-term survival in this patient group remains unchanged over the last decades. A new approach to head and neck cancer management is therefore needed to better identify patient subgroups that are responsive to specific therapies. The aim of this article is to review the current status of knowledge and practice utilizing big data toward personalized therapy in head and neck cancers based on CT and PET imaging modalities.

METHODS:
Literature published in English since 2000 was searched using Medline. Additional articles were retrieved via pearling of identified literature. Publications were reviewed and summarized in tabulated format.

RESULTS:
Studies based on big data in head and neck cancer are limited; however, the field of radiomics is under continuous development and provides valuable input for personalized treatment. Using PET/PET CT biomarkers for patient treatment individualization and response prediction seems promising, especially in regards to detection of hypoxia and clonogenic cancer stem cells. Literature shows that macroscopic changes in medical images (whether structural or functional) are correlated with biologic and biochemical changes within a tumor.

CONCLUSION:
Current trends in data science suggest that the ideal model for decision support in head and neck cancers should be based on human-machine collaboration, namely on: (1) software-based algorithms, (2) physician innovation collaboratives, and (3) clinician mix optimization.

Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.

KEYWORDS:
Head and neck cancer; human papilloma virus; outcome prediction; patient stratification; radiomics

PMID: 31238024 DOI: 10.1016/j.jacr.2019.05.045
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Select item 31237991
55.
Int Forum Allergy Rhinol. 2019 Jun 25. doi: 10.1002/alr.22355. [Epub ahead of print]
Predictive value of computed tomography in the recurrence of chronic rhinosinusitis with nasal polyps.
Meng Y1, Zhang L1,2,3, Lou H1, Wang C1.
Author information
Abstract
BACKGROUND:
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a nasal disease with a high tendency for recurrence. The aim of this study was to compare the use of computed tomography (CT) scan with other clinical parameters in predicting the recurrence of CRSwNP.

METHODS:
A total of 272 consecutive CRSwNP patients undergoing endoscopic functional sinus surgery were recruited. The demographic characteristics and clinical parameters, including CT scores, level of exhaled nitric oxide, and peripheral eosinophilia, were recorded. The degree of infiltration of inflammatory cells in the sinus mucosa was evaluated.

RESULTS:
Two hundred thirty of the 272 patients completed the study (118 patients with recurrence and 112 patients with no recurrence). The average follow-up time was 24 months after the first surgery. The 2 groups were not significantly different with respect to age, gender distribution, comorbid allergy, exhaled oral fractional exhaled nitric oxide levels, nasal obstruction/runny nose/headache/facial pain scores, Lund-Mackay score, peripheral eosinophil percentage, and peripheral eosinophil absolute count. The onset of surgical history and asthma, visual analog scores of CRS, anosmia score, ratio of total ethmoid sinus scores for both sides and maxillary sinus score for both sides (E/M ratio), Lund-Kennedy score, tissue eosinophil percentage, and tissue eosinophil absolute count were significantly higher in the recurrence group. The E/M ratio showed high accuracy as a predictor for CRSwNP recurrence. The cut-off point of 2.55 for E/M ratio indicated the highest predictive value of CRSwNP recurrence.

CONCLUSION:
The E/M ratio is a useful predictor for the recurrence of CRSwNP in the Chinese population.

© 2019 ARS-AAOA, LLC.

KEYWORDS:
chronic rhinosinusitis; computed tomography; diagnosis; nasal polyps; recurrence

PMID: 31237991 DOI: 10.1002/alr.22355
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Select item 31237963
56.
Histopathology. 2019 Jun 25. doi: 10.1111/his.13944. [Epub ahead of print]
Immune microenvironment and expression of PD-L1, PD-1, cancer testis antigen PRAME and MHC I in salivary duct carcinoma.
Xu B1, Jungbluth AA1, Frosina D1, Alzumaili B1, Aleynick N1, Slodkowska E2, Higgins K3, Ho A4, Morris L5, Ghossein R1, Katabi N1.
Author information
Abstract
AIMS:
Salivary duct carcinoma (SDC) is an aggressive salivary malignancy that has high mortality rates and is often resistant to chemotherapy. Anti-PD1/PD-L1 checkpoint inhibitors have led to dramatic improvement in various cancers. Other immunotherapeutic approaches e.g. cancer vaccines have shown promising results. Cancer testis antigens (CTAs), e.g. PRAME, are regarded as promising vaccine targets due to their tumor-specific expression pattern.

METHODS AND RESULTS:
We analyzed the immunoexpression of PD-L1, PD-1, major histocompatibility complex class I (MHC I) and PRAME in 53 SDCs. The immunoexpression of PD-L1 in tumor cells (TC) and immune cells (IC), PD-1 in IC, PRAME in TC, and MHC I in TC were analyzed, and were correlated with outcome. PRAME expression was observed in 83% of SDCs. No PRAME staining was present in normal salivary gland tissue. Using the three established diagnostic algorithms proposed for head and neck squamous cell carcinoma, being CPS≥1, TC%≥1%, and TC%≥25%: 35 (66%), 17 (32%) and 3 cases (6%) were deemed positive for PD-L1, respectively. PD-1-positive IC was noted in 35 (66%) of cases. MHC I downregulation was seen in 82% SDCs. There was a significant correlation among PD-L1 expression in IC, PD-1 in IC and PRAME in TC. PD-L1 expression in TC and lack of PD-1-expression in IC were associated with decreased disease specific survival in SDC.

CONCLUSIONS:
Alterations of tumor immune microenvironment is common in SDCs, including expression of PD-1/PD-L1 and PRAME, which opens the doors to potential novel immune therapy, e.g. cancer vaccination and PD-1/PD-L1 blockade in these tumors. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:
CTA; MHC I; PD-1; PD-L1; PRAME; salivary duct carcinoma

PMID: 31237963 DOI: 10.1111/his.13944
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Select item 31237767
57.
Am J Rhinol Allergy. 2019 Jun 25:1945892419860634. doi: 10.1177/1945892419860634. [Epub ahead of print]
Differential Expression of Extracellular Matrix Components in Nasal Polyp Endotypes.
Feng X1,2, Payne SC3,4,5, Borish L3,4,6,7, Steinke JW3,4,6.
Author information
KEYWORDS:
allergic fungal sinusitis; aspirin-exacerbated respiratory disease; chronic rhinosinusitis; collagen; eosinophils; extracellular matrix; fibronectin; laminin; nasal polyps; vessels

PMID: 31237767 DOI: 10.1177/1945892419860634
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Select item 31237699
58.
Laryngoscope. 2019 Jun 25. doi: 10.1002/lary.28154. [Epub ahead of print]
Primary odynophonia: When pain is out of proportion to dysphonia.
Kim SI1, Atkinson C1, Harris AH1, Tibbetts K1, Mau T1.
Author information
Abstract
OBJECTIVES/HYPOTHESIS:
Odynophonia is generally regarded as a symptom of a voice disorder. However, a subset of patients with odynophonia have debilitating pain out of proportion to the relatively mild degree of dysphonia and are not responsive to voice therapy. The goals of this study were to 1) describe the symptomatology of this subset of patients and differentiate it from typical odynophonia, 2) propose alternate models to explain this phenomenon of primary odynophonia, and 3) present a new treatment paradigm based on the proposed models.

STUDY DESIGN:
Case series.

METHODS:
Inclusion criteria were complaint of persistent pain associated with voicing, normal vocal fold mobility, complete glottic closure, and limited or lack of response of pain to voice therapy. Presenting symptoms, voice evaluation, and treatment outcomes were reviewed.

RESULTS:
Eleven patients fit the inclusion criteria. The degree of pain did not follow the trajectory of vocal improvement with therapy. The pain was stagnant or worsened with voice exercises. The most dramatic improvement came about in one patient who received false vocal fold Botox injections, and another who received thyrohyoid lidocaine/triamcinolone injection. We propose that these patients had developed primary odynophonia, in which the pain had become self-sustaining and no longer responded to correction of hyperfunctional vocal behavior. The mechanism of pain persistence may involve superior laryngeal neuralgia, cartilaginous or ligamentous inflammation, and/or central sensitization.

CONCLUSIONS:
A minority of patients have primary odynophonia distinct from typical odynophonia. Direct treatment of pain may be advisable prior to or in conjunction with voice therapy.

LEVEL OF EVIDENCE:
4 Laryngoscope, 2019.

© 2019 The American Laryngological, Rhinological and Otological Society, Inc.

KEYWORDS:
Odynophonia; muscle tension dysphonia; painful talking; painful voice; superior laryngeal neuralgia

PMID: 31237699 DOI: 10.1002/lary.28154
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Select item 31237040
59.
J Eur Acad Dermatol Venereol. 2019 Jun 25. doi: 10.1111/jdv.15759. [Epub ahead of print]
Differences between pure desmoplastic melanoma and superficial spreading melanoma in terms of survival, distribution and other clinicopathologic features.
Howard MD1,2, Wee E3, Wolfe R2, McLean CA1,4, Kelly JW1, Pan Y1.
Author information
Abstract
BACKGROUND:
Pure desmoplastic melanoma (pDM) is an uncommon subtype of malignant melanoma with comparative high rates of local recurrence and low rates of sentinel lymph node positivity. The melanoma specific survival (MSS) of pDM compared to other melanoma subtypes is unclear, with conflicting reports and lack of multivariable analyses.

OBJECTIVES:
We aimed to describe clinicopathological characteristics of a cohort of patients with pDM and to compare the MSS of pDM with superficial spreading melanoma (SSM).

METHODS:
A prospective cohort study was performed of all primary invasive cutaneous pDM with known tumour location and thickness reviewed at a tertiary referral centre over 21 years.

RESULTS:
119 primary cutaneous invasive pDMs from 3570 total invasive cutaneous melanomas were included. Compared to 2,272 SSMs, and due largely to their greater average thickness, patients with pDM had worse MSS (unadjusted hazard ratio, HR, 2.56, 95% confidence interval, CI, 1.56 to 4.22). After adjustment for clinicopathologic factors (including thickness, ulceration, mitotic rate, age and sex), there was evidence that patients with pDM had an improved MSS (adjusted HR, 0.49; 95% CI, 0.28 to 0.87). Median thickness of head and neck pDM was greater than non-head and neck pDM (p<0.001). There was reduced univariable MSS in head and neck pDM compared to the rest of the body.

CONCLUSIONS:
Decreased univariable MSS of patients with pDM compared to SSM was explained by the increased frequency of adverse clinicopathologic features at diagnosis, in particular the greater Breslow thickness of pDM. After adjustment, patients with pDM had half the chance of melanoma specific death compared to SSM. Head and neck pDM were thicker at diagnosis compared to the rest of the body, which may account for its poorer survival compared to the rest of the body. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:
clinicopathologic; desmoplastic melanoma; melanoma; pure DM; survival; tumour location

PMID: 31237040 DOI: 10.1111/jdv.15759
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Select item 31236943
60.
Med Phys. 2019 Jun 25. doi: 10.1002/mp.13679. [Epub ahead of print]
Modeling of multiple planning target volumes for head and neck treatments in knowledge-based treatment planning.
Zhang J1, Ge Y2, Sheng Y1, Yin FF1, Wu QJ1.
Author information
Abstract
PURPOSE:
The purpose of this study is to develop an accurate and reliable dose volume histogram (DVH) prediction method for external beam radiation therapy plans with multiple planning target volumes (PTVs).

MATERIALS AND METHODS:
We present a novel DVH prediction workflow, including new features and a modeling methodology, that makes better use of multiple PTVs: (1) We propose a generalized feature to characterize the geometric relationship of OARs with respect to two or more PTVs with different prescribed dose levels; (2) We incorporate a novel data augmentation method to improve the data distribution in the feature space; (3) A similarity metric that leverages such information is subsequently used to select a subset of similar cases from the training dataset for model building; (4) Finally, a DVH prediction model is trained with these selected cases. To evaluate this new modeling workflow, we used 120 head and neck (HN) cases to tune the model, and used a separate dataset consisting of 148 cases for validation. The proposed model has been compared with the conventional knowledge-based model in terms of model prediction accuracy, which was measured by the root mean squared error (RMSE) between the predicted DVHs and the actual clinical plan DVHs. Furthermore, 25 randomly selected plans were re-planned guided by the proposed model and evaluated against clinical plans using clinical evaluation criteria.

RESULTS:
The proposed modeling workflow significantly improved DVH prediction accuracy for brainstem (p<0.001), cord (p<0.001), larynx (p=0.004), mandible (p<0.001), oral cavity (p=0.011), parotid (p<0.001), and pharynx (p=0.001). Cases re-planned with the guidance of the proposed model spared OARs significantly better by clinical evaluation criteria. The re-planned cases showed a 15% increase in the number of satisfied criteria, compared with clinical plans.

CONCLUSIONS:
The proposed modeling workflow generates DVH predictions with improved accuracy and robustness when multiple PTVs exist in a plan. It has demonstrated that the improvement in the DVH prediction model translates into better plan quality in knowledge-based planning. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:
DVH prediction; Knowledge-based planning; intensity modulated radiation therapy; modeling; treatment planning

PMID: 31236943 DOI: 10.1002/mp.13679
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Select item 31236917
61.
Br J Surg. 2019 Jun 25. doi: 10.1002/bjs.11216. [Epub ahead of print]
Meta-analysis of routine calcium/vitamin D3 supplementation versus serum calcium level-based strategy to prevent postoperative hypocalcaemia after thyroidectomy.
Sanabria A1,2, Rojas A2, Arevalo J2.
Author information
Abstract
BACKGROUND:
The aim was to assess the effectiveness of routine administration of calcium +/- vitamin D3 compared with a serum calcium level-based strategy to prevent symptomatic hypocalcaemia after thyroidectomy.

METHODS:
RCTs comparing routine supplementation of calcium +/- vitamin D3 with treatment based on serum calcium levels measured after total thyroidectomy, published between 1980 and 2017, were identified in MEDLINE, Embase, LILACS and Google Scholar databases. Risk of bias was evaluated using the Cochrane Collaboration tool. Risk differences were calculated by random-effects meta-analysis. Meta-regression and cumulative meta-analysis were used to explore the best therapeutic approach.

RESULTS:
Fifteen studies with 3037 patients were included, and seven treatment comparisons were made. Routine supplementation with calcium + vitamin D3 offered a lower risk of symptomatic (risk difference (RD) -0·25, 95 per cent c.i. -0·32 to -0·18) and biochemical (RD -0·24, -0·31 to -0·17) hypocalcaemia than treatment based on measurement of calcium levels. The number needed to treat was 4 (95 per cent c.i. 3 to 6) for symptomatic hypocalcaemia. No publication bias was found; although heterogeneity was high for some comparisons, sensitivity analysis did not change the main results.

CONCLUSION:
Routine postoperative administration of calcium + vitamin D3 is effective in decreasing the rate of symptomatic and biochemical hypocalcaemia.

© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.

PMID: 31236917 DOI: 10.1002/bjs.11216
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Publication type
Select item 31236741
62.
Int J Clin Oncol. 2019 Jun 24. doi: 10.1007/s10147-019-01496-w. [Epub ahead of print]
Phonatory function in patients with well-differentiated thyroid carcinoma following meticulous resection of tumors adhering to the recurrent laryngeal nerve.
Miyamaru S1, Kumai Y2, Murakami D2, Kodama N3, Miyamoto T2, Yumoto E4, Orita Y2.
Author information
Abstract
BACKGROUND:
Well-differentiated thyroid carcinomas (WDTCs) sometimes adhere firmly to the recurrent laryngeal nerve (RLN), while allowing normal mobility of the vocal fold (VF). Meticulous dissection of the adhered tumor from the RLN is known to be effective, preserving VF mobility and oncological safety. However, phonatory function following this preservation procedure has yet to be evaluated sufficiently. The objective of this study was to examine phonatory function following the preservation procedure.

METHODS:
Ten patients with WDTCs, demonstrating normal preoperative VF mobility with tumors adhering to the RLN, underwent the preservation procedure between 2000 and 2013 (preservation group). During the same period, nine patients with WDTCs demonstrating normal VF mobility underwent resection and reconstruction of the tumor-invaded RLNs (reconstruction group). Phonatory function, including maximum phonation time (MPT), mean flow rate (MFR), jitter, shimmer, harmonics-to-noise ratio, and GRBAS scale score, was evaluated and compared statistically between the two groups.

RESULTS:
The mean values of MPT and MFR in the preservation group were at normal levels. Both G and B scores of GRBAS scale were at near-normal levels. Additionally, the mean B score of the GRBAS scale was significantly better in the preservation group than in the reconstruction group.

CONCLUSIONS:
When normal VF mobility is observed preoperatively, meticulous resection for preserving RLN would contribute to maintain not only normal level of MPT and MFR, but also to provide better B score of GRBAS scale than RLN resection followed by immediate reconstruction.

KEYWORDS:
Phonatory function; Recurrent laryngeal nerve; Well-differentiated thyroid carcinoma

PMID: 31236741 DOI: 10.1007/s10147-019-01496-w
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Select item 31236579
63.
Ann Oncol. 2019 Jun 24. pii: mdz197. doi: 10.1093/annonc/mdz197. [Epub ahead of print]
Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD1 antibody in phase Ib/II clinical trial NCT02915432.
Wang F1, Wei XL1, Wang FH1, Xu N2, Shen L3, Dai GH4, Yuan XL5, Chen Y6, Yang SJ7, Shi JH8, Hu XC9, Lin XY10, Zhang QY11, Feng JF12, Ba Y13, Liu YP14, Li W15, Shu YQ16, Jiang Y17, Li Q18, Wang JW19, Wu H20, Feng H20, Yao S20, Xu RH1.
Author information
Abstract
BACKGROUND:
High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized PD-1 antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.

PATIENTS AND METHODS:
We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In Cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/Kg d1, Q2W) as a monotherapy. In Cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 BID, d1-d14, Q3W as first-line treatment. Primary endpoint was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.

RESULTS:
In Cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group [14.6 vs 4.0 months, HR = 0.48 (96% CI 0.24 to 0.96), p=0.038], while PD-L1 overexpression did not correlate with significant survival benefit. 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.

CONCLUSIONS:
Toripalimab has demonstrated a manageable safety profile and promising anti-tumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.

TRIAL REGISTRATION:
ClinicalTrials.gov NCT02915432.

© The Author 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

KEYWORDS:
Gastric cancer; Immunotherapy; Programmed death ligand-1; Tumor mutational burden

PMID: 31236579 DOI: 10.1093/annonc/mdz197
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Secondary source ID
Select item 31236537
64.
OTO Open. 2019 Mar 13;3(1):2473974X19830635. doi: 10.1177/2473974X19830635. eCollection 2019 Jan-Mar.
Semiautomated Motion Tracking for Objective Skills Assessment in Otologic Surgery: A Pilot Study.
Kanumuri VV1,2, Ameen B1, Tarabichi O1, Kozin ED1,2, Lee DJ1,2.
Author information
Abstract
Perioperative teaching and feedback of technical performance are essential during surgical training but are limited by competing demands on faculty time, resident work-hour restrictions, and desire for efficient operating room utilization. The increasing use of high-definition video microscopy and endoscopy in otolaryngology offers opportunities for trainees and faculty to evaluate performance outside the operating room but still requires faculty time. Our hypothesis is that automated motion tracking via video analysis offers a way forward to provide more consistent and objective feedback for surgical trainees. In this study, otolaryngology trainees at various levels were recorded performing a cortical mastoidectomy on cadaveric temporal bones using standard surgical instrumentation and high-definition video cameras coupled to an operating microscope. Videos were postprocessed to automatically track the tip of otologic dissection instruments. Data were analyzed for key metrics potentially applicable to the global rating scale used in the Accreditation Council for Graduate Medical Education's Objective Structured Assessments of Technical Skills.

KEYWORDS:
motion tracking; objective surgical skills tracking

PMID: 31236537 PMCID: PMC6572917 DOI: 10.1177/2473974X19830635
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Select item 31236536
65.
OTO Open. 2019 Feb 11;3(1):2473974X19826943. doi: 10.1177/2473974X19826943. eCollection 2019 Jan-Mar.
Speech and Language Outcomes in Patients with Ankyloglossia Undergoing Frenulectomy: A Retrospective Pilot Study.
Daggumati S1, Cohn JE2, Brennan MJ2, Evarts M2, McKinnon BJ3, Terk AR3.
Author information
Abstract
Ankyloglossia is a controversial topic with no standardized treatment guidelines. A retrospective chart review was conducted to identify children who underwent lingual frenulectomy for speech and language impairment. Impairment severity was recorded pre- and postoperatively as mild, mild to moderate, moderate, moderate to severe, or severe. Variables were tested with chi-square analysis for their statistical relationship to improvements in speech and language. Children with preoperative moderate and moderate-to-severe speech and language impairment attained better speech and language outcomes after frenulectomy as compared with children with mild and mild-to-moderate impairment (100% vs 82%, P = .015). Sutured closure after frenulectomy was associated with better speech and language improvements (100% vs 83%, P = .033). One could consider observation of patients with mild and mild-to-moderate speech and language impairments. Sutured closure might result in better improvements in speech and language impairments. This pilot study sheds light on the potential impact of a larger study currently underway.

KEYWORDS:
ankyloglossia; frenulectomy; frenulum; pediatric otolaryngology; speech; tongue-tie

PMID: 31236536 PMCID: PMC6572914 DOI: 10.1177/2473974X19826943
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Select item 31236534
66.
OTO Open. 2019 Feb 1;3(1):2473974X18823002. doi: 10.1177/2473974X18823002. eCollection 2019 Jan-Mar.
Arterial Pseudoaneurysm following Radiotherapy in Patients with a History of Nasopharyngeal Carcinoma.
Choby G1, Tangbumrungtham N2, Dodd R3, Patel ZM4.
Author information
KEYWORDS:
NPC; ORN; carotid; embolization; epistaxis; nasopharyngeal carcinoma; osteoradionecrosis; pseudoaneurysm

PMID: 31236534 PMCID: PMC6572923 DOI: 10.1177/2473974X18823002
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Publication type
Select item 31236533
67.
OTO Open. 2019 Jan 30;3(1):2473974X18821931. doi: 10.1177/2473974X18821931. eCollection 2019 Jan-Mar.
Spontaneous Otogenic Pneumocephalus: Reporting a Unique Site of Dehiscence.
Stewart M1, Farrell C2, Pelosi S3.
Author information
KEYWORDS:
altitude changes; petrous apex; spontaneous otogenic pneumocephalus; temporal bone

PMID: 31236533 PMCID: PMC6572922 DOI: 10.1177/2473974X18821931
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Publication type
Select item 31236529
68.
OTO Open. 2019 Jan 4;3(1):2473974X18818415. doi: 10.1177/2473974X18818415. eCollection 2019 Jan-Mar.
Oral Human Papillomavirus Infection and Head and Neck Squamous Cell Carcinoma in Rural Northwest Cameroon.
Rettig EM1, Gooi Z2, Bardin R3, Bogale M4, Rooper L5, Acha E4, Koch WM1,4.
Author information
Abstract
OBJECTIVE:
Oral human papillomavirus (HPV) infection is the precursor for a growing subset of oropharyngeal squamous cell carcinomas (OPSCCs) in the developed world. This study was designed to characterize oral HPV infection and OPSCC in a region with high rates of HPV-driven cervical cancer.

STUDY DESIGN:
Cross-sectional cohort study, retrospective case series.

SETTING:
Northwest Cameroon referral hospital.

SUBJECTS AND METHODS:
Individuals infected with human immunodeficiency virus attending an outpatient clinic were evaluated for oral HPV infection with oral swabs or rinses that were tested for 51 HPV types. HNSCCs diagnosed and/or treated at the same hospital from 2011 to 2017 were retrospectively reviewed to ascertain demographic and tumor characteristics, and available OPSCCs were tested for HPV.

RESULTS:
The oral HPV infection study population comprised 101 participants. Most (69%) were female and never-smokers (84%). Participants had median 4 lifetime sexual partners (interquartile range, 3-7; range, 1-100). Five participants (5%) had oral HPV infection; one had 2 HPV types. HPV types detected were HPV68 (n = 2), HPV82 (n = 2), HPV32 (n = 1), and unknown (n = 1). No significant demographic or behavioral differences were detected among individuals with vs without oral HPV infection. OPSCCs comprised just 8% (n = 11) of 131 HNSCCs in the retrospective study population. Two of 7 OPSCCs were HPV positive.

CONCLUSION:
The low prevalence of OPSCC observed in northwest Cameroon together with the rarity of oral HPV infection suggests low rates of HPV-driven oropharyngeal carcinogenesis in the region. Future research should examine how geographic differences in oral HPV infection are influenced by cultural norms and affect HPV-OPSCC epidemiology.

KEYWORDS:
Africa; Cameroon; epidemiology; head and neck cancer; human immunodeficiency virus; human papillomavirus; oropharyngeal cancer

PMID: 31236529 PMCID: PMC6572919 DOI: 10.1177/2473974X18818415
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Select item 31236528
69.
OTO Open. 2019 Jan 4;3(1):2473974X18805431. doi: 10.1177/2473974X18805431. eCollection 2019 Jan-Mar.
Angioedema Involving the Larynx after Starting Apixaban.
Williamson A1, Vaughn CA1, Tulunay-Ugur OE1.
Author information
KEYWORDS:
angioedema; apixaban; dabigatran; laryngeal edema; larynx; rivaroxaban

PMID: 31236528 PMCID: PMC6572916 DOI: 10.1177/2473974X18805431
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Publication type
Select item 31236471
70.
Laryngoscope Investig Otolaryngol. 2019 May 7;4(3):353-358. doi: 10.1002/lio2.270. eCollection 2019 Jun.
Head-Up Sleep May Cure Patients With Intractable Benign Paroxysmal Positional Vertigo: A six-Month Randomized Trial.
Horinaka A1,2, Kitahara T1, Shiozaki T1, Ito T1, Wada Y1, Yamanaka T1, Nario K1,2.
Author information
Abstract
OBJECTIVES:
The aim of the present study was to assess head-position management for intractable idiopathic benign paroxysmal positional vertigo (BPPV) when lying down. We hypothesized that head-up sleep (HUS) could prevent free-floating otoliths from entering the semicircular canals.

STUDY DESIGN:
A prospective two-arm multicenter randomized controlled trial.

METHODS:
BPPV was diagnosed in 611 patients (611/1,520; 40.2%) according to the 2015 diagnostic guidelines issued by the International Classification of Vestibular Disorders. Among them, 201 patients were intractable (201/611; 32.9%), 88 of whom were idiopathic and subsequently enrolled in the study. Patients randomly received intervention with HUS at greater than 45° (n = 44) or head-down sleep (HDS; n = 44) when lying down. Before treatment, they completed several examinations, including subjective visual vertical (SVV). The specific diagnoses for the 88 patients with BPPV included horizontal type cupula (n = 40), horizontal type canal (n = 13), posterior type (n = 26), and probable and/or atypical BPPV (n = 9).

RESULTS:
Patient backgrounds did not differ significantly between the HUS and HDS groups. Visual analog scale (VAS) scores of vertiginous sensation were significantly lower in the HUS group than in the HDS group at both the third month and sixth month post-treatment. Positional/positioning nystagmus observed just before treatment disappeared significantly more often in the HUS group than in the HDS group until the sixth post-treatment month. Further, especially in HUS group, VAS scores in SVV- group (n = 24) were significantly lower than those in the SVV+ group (n = 20) sixth month post-treatment.

CONCLUSIONS:
Controlling free-floating otoliths is not easy due to aging of the otolith organs. Repeatedly returning the endless free-floating debris from the canals to the utricle through physical means is not a good strategy. Therefore, HUS when lying down at home could be recommended as an initial treatment for patients with intractable idiopathic BPPV.

LEVEL OF EVIDENCE:
1b.

KEYWORDS:
Intractable idiopathic BPPV; free‐floating otolith; head‐up pillows; semicircular canals; subjective visual vertical

PMID: 31236471 PMCID: PMC6580063 DOI: 10.1002/lio2.270
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Select item 31236470
71.
Laryngoscope Investig Otolaryngol. 2019 May 7;4(3):347-352. doi: 10.1002/lio2.267. eCollection 2019 Jun.
Facial nerve venous malformation: A radiologic and histopathologic review of 11 cases.
Guerin JB1, Takahashi EA1, Lane JI1, Hoxworth JM2, Weindling SM3, Blessing MM4, Jentoft ME5, Carlson ML6, Neff BA6, Wood CP1.
Author information
Abstract
OBJECTIVE:
The purpose of this article was to provide a combined pathologic and radiologic review of previous pathologically diagnosed facial nerve "hemangiomas" to confirm that these lesions are most characteristic of venous malformations rather than neoplasms.

STUDY DESIGN:
Retrospective radiologic, clinical, and histopathologic review of all patients with a previous pathologically diagnosed facial nerve hemangioma of the temporal bone who underwent computed tomography or magnetic resonance imaging (MRI) were included. A consensus radiologic review for characteristic features and pathologic analysis was performed.

MATERIALS AND METHODS:
A panel of 4 neuroradiologists retrospectively analyzed CT and MRI exams for 11 facial nerve hemangiomas and provided a consensus agreement on the characteristic imaging features. Concurrently, two neuropathologists reevaluated archived tissue specimens from these lesions and applied additional immunohistochemical and histochemical stains including D240, CD31, smooth muscle actin (SMA), Verhoeff Van Gieson (VVG) and glucose transporter 1 (GLUT1).

RESULTS:
Lesions were composed of dilated vascular spaces with a simple, CD31-positive endothelial lining and a smooth muscle component. All lesions were negative for markers found in arterial and lymphatic malformations and infantile hemangiomas. They had characteristic radiologic features previously ascribed to facial nerve hemangiomas. Namely, these lesions are typically T1 isointense or hypointense and T2 hyperintense relative to cerebral cortex and heterogeneously enhance on MRI. Bony canal expansion and erosion, intralesional calcification, and intracranial extension are common.

CONCLUSIONS:
On the basis of this radiologic and pathologic review, these lesions are best characterized as venous malformations.

LEVEL OF EVIDENCE:
4.

KEYWORDS:
Facial nerve; geniculate hemangioma; temporal bone; venous malformation

PMID: 31236470 PMCID: PMC6580060 DOI: 10.1002/lio2.267
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Select item 31236469
72.
Laryngoscope Investig Otolaryngol. 2019 May 10;4(3):341-346. doi: 10.1002/lio2.273. eCollection 2019 Jun.
Functional Modules of Pharyngeal Swallowing Mechanics.
Hosseini P1, Tadavarthi Y1, Martin-Harris B2,3,4, Pearson WG Jr5,6.
Author information
Abstract
OBJECTIVES:
The present retrospective cohort study aims to test the hypothesis that elements of swallowing mechanics including hyoid movement, laryngeal elevation, tongue base retraction, pharyngeal shortening, pharyngeal constriction, and head and neck extension can be grouped into functional modules, and that these modules are predictably altered in disease states.

METHODS:
Modified barium swallow video clips of a thick and a thin liquid swallow from 40 normal patients and 10 dysphagic post-treatment oropharyngeal head-and-neck cancer (HNC) patients were used in this study. Coordinate locations of 12 anatomical landmarks mapping pharyngeal swallowing mechanics were tracked on every frame during the pharyngeal phase of each swallow using a custom-made MATLAB tool. Morphometric modularity hypothesis testing was performed on these coordinate data to characterize the modular elements of swallowing function in each cohort using MorphoJ software.

RESULTS:
The elements of normal swallowing can be grouped into four functional modules including bolus propulsion, pharyngeal shortening, airway protection, and head and neck posture. Modularity in HNC patient showed an intact airway protection module but altered bolus propulsion and pharyngeal shortening modules. To cross-validate the alteration in modules, a post hoc analysis was performed, which showed significantly increased vallecular (P < .04) and piriform (P < .05) residue but no significant change in aspiration status in the HNC cohort versus controls.

CONCLUSIONS:
This study suggests that while pharyngeal swallowing mechanics is highly complex, the system is organized into functional modules, and that changes in modularity impacts swallowing performance. This approach to understanding swallowing function may help the patient care team better address swallowing difficulties.

LEVEL OF EVIDENCE:
2b.

KEYWORDS:
Deglutition; dysphagia; functional modularity; swallowing mechanics

PMID: 31236469 PMCID: PMC6580054 DOI: 10.1002/lio2.273
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Select item 31236466
73.
Laryngoscope Investig Otolaryngol. 2019 May 20;4(3):319-322. doi: 10.1002/lio2.275. eCollection 2019 Jun.
Syntopy of vagus nerve in the carotid sheath: A dissectional study of 50 cadavers.
Hojaij F1, Rebelo G1, Akamatsu F1, Andrade M1, Camargo C2, Cernea C3, Jacomo A1.
Author information
Abstract
BACKGROUND:
Vagus nerve anatomical position inside the carotid sheath is not clear in the literature. Nevertheless, monitoring laryngeal nerves during thyroid surgeries may damage big vessels in the carotid sheath (jugular vein; carotid artery). This gap led to an unprecedent cross sectional study of vagus syntopy using the carotid artery as anatomical mark.

METHODS:
Fifty cadavers less than 24 hours postmortem were studied. The vagus nerve was spotted, reproducing the patterns performed in thyroidectomies.

RESULTS:
On the right side, vagus nerve was posterior to the common carotid artery in 64% of the cases. On the left side, it was anterior, in 68% of the dissections. Comparing both sides, there was no symmetry in this syntopy. No influence of ethnic or anthropometric characteristics was observed.

CONCLUSION:
The vagus nerve is more frequently posterior to the common carotid artery on the right side and, anterior, on the left side.

LEVEL OF EVIDENCE:
4.

KEYWORDS:
Vagus nerve; anatomy; carotid sheath

PMID: 31236466 PMCID: PMC6580062 DOI: 10.1002/lio2.275
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Select item 31236465
74.
Laryngoscope Investig Otolaryngol. 2019 May 15;4(3):314-318. doi: 10.1002/lio2.268. eCollection 2019 Jun.
Does perioperative oxandrolone improve nutritional status in patients with cachexia related to head and neck carcinoma?
Osmolak AM1, Klatt-Cromwell CN1,2, Price AM1, Sanclement JA1, Krempl GA1.
Author information
Abstract
BACKGROUND:
Cancer cachexia affects up to over 50% of advanced head and neck cancer (HNC) patients. To date, the potential utility of anabolic steroids in perioperative cachectic HNC patients has not been determined.

METHODS:
Retrospective review of pre- and post-oxandrolone administration prealbumin levels in 18 perioperative HNC patients between October 2007 and October 2014 at a tertiary academic medical center.

RESULTS:
The median pretreatment prealbumin was 88.5 mg/L. The median post-treatment prealbumin was 227 mg/L. The median interval improvement of the prealbumin level was 131.5 mg/L. The median differences between the pretreatment and post-treatment prealbumin levels were found to be statistically significant (P < .001). Subjective improvement in wound healing was also observed.

CONCLUSIONS:
Perioperative administration of oxandrolone resulted in objective improvements in prealbumin levels and subjective improvements in surgical wounds. Oxandrolone administered 10 mg twice daily (BID) for 10 days may be a useful adjunct in the perioperative care of nutritionally deficient HNC patients who are at risk for or have demonstrated impaired wound healing.

LEVEL OF EVIDENCE:
3.

KEYWORDS:
Head and neck cancer; anabolic steroids; cancer cachexia; oxandrolone; prealbumin

PMID: 31236465 PMCID: PMC6580053 DOI: 10.1002/lio2.268
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Select item 31236463
75.
Laryngoscope Investig Otolaryngol. 2019 May 7;4(3):307-309. doi: 10.1002/lio2.263. eCollection 2019 Jun.
Aberrant innominate artery: A possible hazard during total laryngectomy.
Nijkamp J1, Jaafar RBJ1, Postma L2, Snoeijs M3, Qiu Shao SS4, Tan B1.
Author information
Abstract
BACKGROUND:
Surgical management in laryngeal carcinoma remains a challenge with countless unexpected complications. Great vessel anomalies such as anomaly of the innominate artery carry high risk of morbidity and mortality if not managed properly.

METHODS:
We present our first experience with an aberrant innominate artery during total laryngectomy which complicated the whole surgical procedure and tracheostoma placement.

RESULTS:
We decided to place a pectoralis major muscle flap to separate and cover up the aberrant vessel from the trachea and end-stoma which ultimately did not lead to major complications postoperatively and postradiation therapy.

CONCLUSION:
Aberrant innominate artery is an extremely rare entity and failure of recognizance can lead to hazardous complications. Preoperative angiography needs to be done if there are high suspicions of aberrant vessels in the operative field. Careful dissection of the head and neck region, and prompt decision making are mandatory to manage such cases.

LEVELS OF EVIDENCE:
Case Report.

KEYWORDS:
Aberrant innominate artery; laryngeal carcinoma; total laryngectomy

PMID: 31236463 PMCID: PMC6580061 DOI: 10.1002/lio2.263
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Select item 31236462
76.
Laryngoscope Investig Otolaryngol. 2019 May 2;4(3):300-306. doi: 10.1002/lio2.262. eCollection 2019 Jun.
Patient-reported outcomes for dental health, shoulder-neck dysfunction, and overall quality of life after treatment with radiation for head and neck cancer.
Verma N1, Tan X2, Knowles M3, Bernard S4, Chera B3.
Author information
Abstract
OBJECTIVES:
The current exploratory cross-sectional study was designed to examine and characterize survivorship issues among patients treated with radiation for head and neck cancer with regard to dental health, shoulder-neck dysfunction, and overall quality of life (QOL).

METHODS:
Patients (N = 58) being seen for follow-up at a radiation oncology clinic at least 1 year beyond the end of treatment completed three survey questionnaires regarding general QOL as well as dental health issues and shoulder-neck dysfunction. The questionnaires were scored and univariate analyses were performed using the variables of age, radiation dosage, definitive radiation + neck dissection versus definitive surgery + postoperative radiation, and chemotherapy.

RESULTS:
Median follow-up was 2.5 years. Of 58 patients, 35% reported having more problems with their general dental health as compared to before treatment and 38% reported having pain at night in the neck/shoulder after treatment. With regard to pretreatment counseling, 79% of patients reported being counseled about their dental health prior to treatment, while 31% reported being counseled about possible shoulder-neck dysfunction. Patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation reported more functional and symptomatic issues.

CONCLUSION:
Patients treated with radiation for head and neck cancer face a number of survivorship issues, including problems with dental health and shoulder-neck dysfunction, and are not necessarily thoroughly counseled about these issues prior to treatment. Patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation may experience more survivorship issues.

LEVEL OF EVIDENCE:
IV.

KEYWORDS:
Head and neck cancer; dental health; quality of life; shoulder‐neck dysfunction; survivorship

PMID: 31236462 PMCID: PMC6580067 DOI: 10.1002/lio2.262
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Select item 31236461
77.
Laryngoscope Investig Otolaryngol. 2019 Apr 22;4(3):292-299. doi: 10.1002/lio2.265. eCollection 2019 Jun.
Effect of early tracheostomy in mechanically ventilated patients.
Dochi H1, Nojima M2, Matsumura M1, Cammack I3, Furuta Y1.
Author information
Abstract
OBJECTIVE:
To investigate the effect of the timing of tracheostomy in patients who required prolonged mechanical ventilation using two methods: analysis of early versus late tracheostomy and landmark analysis.

STUDY DESIGN:
Retrospective cohort study.

METHODS:
Patients who were emergently intubated and admitted into the intensive care unit or high dependency unit between January 2011 and August 2016, with or without tracheostomy, were included. In the early and late tracheostomy analysis, all patients were divided into early (≤10 days, n = 88) and late (>10 days, n = 132) groups. In the landmark analysis, 198 patients requiring ventilation for more than 10 days were divided into early tracheostomy (≤10 days, n = 57) and nonearly tracheostomy (>10 days, n = 141) groups. We compared 60-day ventilation withdrawal rate and 60-day mortality.

RESULTS:
Early tracheostomy was a significant factor for early ventilation withdrawal, as shown by log-rank test results (early and late tracheostomy: P = .001, landmark: P = .021). Multivariable analysis showed that the early group was also associated with a higher chance of ventilation withdrawal in each analysis (early and late tracheostomy: adjusted hazard ratio [aHR] = 1.69, 95% confidence interval [CI] = 1.20-2.39, P = .003; landmark: aHR = 1.61, 95% CI = 1.06-2.38, P = .027). Early tracheostomy, however, was not associated with improved 60-day mortality (early and late tracheostomy: aHR = 0.88, 95% CI = 0.46-1.69, P = .71; landmark: aHR = 1.46; 95% CI = 0.58-3.66; P = .42).

CONCLUSION:
For patients requiring ventilation, performing tracheostomy within 10 days of admission was independently associated with shortened duration of mechanical ventilation; 60-day mortality was not associated with the timing of tracheostomy.

LEVEL OF EVIDENCE:
2b.

KEYWORDS:
Early tracheostomy; landmark analysis; mechanical ventilation; withdrawal

PMID: 31236461 PMCID: PMC6580064 DOI: 10.1002/lio2.265
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Select item 31236190
78.
World Allergy Organ J. 2019 Jun 13;12(6):100038. doi: 10.1016/j.waojou.2019.100038. eCollection 2019.
Identification of rare variants of allergic rhinitis based on whole genome sequencing and gene expression profiling: A preliminary investigation in four families.
Zhang Y1,2,3, Li J2, Zhao Y2, Wang C1,2, Zhang L1,2,3.
Author information
Abstract
BACKGROUND:
Despite the success of genome-wide association studies for allergic rhinitis (AR), no definitive causal variants have been identified, and a substantial portion of the heritability of the disease is yet to be discovered.

METHODS:
Four families, each with at least 1 parent and one child suffering from dust mite (DM) AR, were recruited, and whole-genome sequencing was performed on samples from 9 eligible individuals from these families. Conjoint analysis was performed for existing gene expression profiling data in the literature and the whole genome sequencing data obtained for these individuals; for presence of family-specific variants segregating with AR and the pathways involved. Similar analyses were also performed with data obtained for 96 sporadic house dust mite (HDM) AR patients and 96 healthy controls.

RESULTS:
Three rare variants in three genes (FLT1_c.603A ​> ​T; VEGFB_c.322A ​> ​C; and ITGA2_c.502+1G ​> ​A), which are involved in Focal Adhesion pathway, were identified in affected, but not unaffected, subjects in two families. VEGFB_c.322A ​> ​C and/or ITGA2_c.502+1G ​> ​A were further detected in all DM AR patients but not in any healthy individuals in 1 family; which was further investigated for members. The 3 identified variants were not found in any of the sporadic DM AR patients or healthy controls.

CONCLUSION:
Despite the relatively small sample size, this study has identified several potentially functional rare variants in AR candidate genes, and it provides a platform for future work in larger numbers of families and sporadic individuals for a better understanding of the genetic basis of AR.

KEYWORDS:
Allergic rhinitis; FLT1; Gene expression profiling; ITGA2; Rare variants; VEGFB; Whole genome sequencing

PMID: 31236190 PMCID: PMC6581771 DOI: 10.1016/j.waojou.2019.100038
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Select item 31236144
79.
Dis Markers. 2019 May 19;2019:3857853. doi: 10.1155/2019/3857853. eCollection 2019.
An Oncogenic Role for Four-Jointed Box 1 (FJX1) in Nasopharyngeal Carcinoma.
Chai SJ1, Ahmad Zabidi MM1,2, Gan SP1, Rajadurai P3, Lim PVH4, Ng CC2, Yap LF1, Teo SH1, Lim KP1, Patel V1, Cheong SC1.
Author information
Abstract
Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer prevalent in Southern China and Southeast Asia. The current knowledge on the molecular pathogenesis of NPC is still inadequate to improve disease management. Using gene expression microarrays, we have identified the four-jointed box 1 (FJX1) gene to be upregulated in primary NPC tissues relative to nonmalignant tissues. An orthologue of human FJX1, the four-jointed (fj) gene in Drosophila and Fjx1 in mouse, has reported to be associated with cancer progression pathways. However, the exact function of FJX1 in human is not well characterized. The overexpression of FJX1 mRNA was validated in primary NPC tissue samples, and the level of FJX1 protein was significantly higher in a subset of NPC tissues (42%) compared to the normal epithelium, where no expression of FJX1 was observed (p = 0.01). FJX1 is also found to be overexpressed in microarray datasets and TCGA datasets of other cancers including head and neck cancer, colorectal, and ovarian cancer. Both siRNA knockdown and overexpression experiments in NPC cell lines showed that FJX1 promotes cell proliferation, anchorage-dependent growth, and cellular invasion. Cyclin D1 and E1 mRNA levels were increased following FJX1 expression indicating that FJX1 enhances proliferation by regulating key proteins governing the cell cycle. Our data suggest that the overexpression of FJX1 contributes to a more aggressive phenotype of NPC cells and further investigations into FJX1 as a potential therapeutic target for NPC are warranted. The evaluation of FJX1 as an immunotherapy target for NPC and other cancers is currently ongoing.

PMID: 31236144 PMCID: PMC6545767 DOI: 10.1155/2019/3857853
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Select item 31235758
80.
Sci Rep. 2019 Jun 24;9(1):9130. doi: 10.1038/s41598-019-45589-y.
HER3 targeting potentiates growth suppressive effects of the PI3K inhibitor BYL719 in pre-clinical models of head and neck squamous cell carcinoma.
Meister KS1, Godse NR1, Khan NI1, Hedberg ML1, Kemp C1, Kulkarni S1, Alvarado D2, LaVallee T2, Kim S1, Grandis JR3, Duvvuri U4.
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Abstract
BYL719 is a PI3K inhibitor that has demonstrated efficacy in the treatment of head and neck squamous cell carcinoma. BYL719 exerts its therapeutic effect by suppressing AKT and other proliferative signaling mechanisms. Despite PI3K inhibition and AKT suppression, residual activity of protein S6, a core marker of proliferative activation, has been observed. HER3, either via dimerization or activation by its ligand neurgeulin (NRG), is known to activate PI3K. Thus, we hypothesized that co-targeting HER3 and PI3K would lead to greater suppression of the PI3K-AKT signaling pathway and greater tumor suppression than with BYL719 alone. We investigated biochemical expression and activation of the HER3-PI3K-AKT-S6 pathway in HNSCC cell lines and patient-derived xenografts (PDXs). Antitumor effects of HER3 and PI3K inhibitors alone and in combination were evaluated in cell culture and murine models. Treatment of HNSCC cell lines with BYL719 significantly reduced AKT activation and suppressed tumor growth. However, S6 was persistently activated despite suppression of AKT. Combination treatment with KTN3379, a monoclonal antibody targeted against HER3, and BYL719 led to enhanced suppression of in vitro and in vivo cancer growth and durable suppression of AKT and S6. Therefore, inhibition of HER3 with KTN3379 enhanced the effects of PI3K inhibition in pre-clinical HNSCC models. These data support co-targeting HER3 and PI3K for the treatment of HSNCC.

PMID: 31235758 DOI: 10.1038/s41598-019-45589-y
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Select item 31235699
81.
Nat Commun. 2019 Jun 24;10(1):2764. doi: 10.1038/s41467-019-10680-5.
Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer.
Yoo SK1,2,3, Song YS4,5, Lee EK6, Hwang J7, Kim HH4, Jung G4, Kim YA8, Kim SJ9, Cho SW4, Won JK10, Chung EJ11, Shin JY1,3, Lee KE1,9, Kim JI1,7, Park YJ12,13, Seo JS14,15,16,17,18.
Author information
Abstract
Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAFV600E and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.

PMID: 31235699 DOI: 10.1038/s41467-019-10680-5
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Select item 31235478
82.
Mol Cell Biol. 2019 Jun 24. pii: MCB.00086-19. doi: 10.1128/MCB.00086-19. [Epub ahead of print]
The miRNA to miRNA regulation of Programmed Cell Death 4 (PDCD4).
Ajuyah P1, Hill M2, Ahadi A2, Lu J2, Hutvagner G2, Tran N3,4.
Author information
Abstract
The regulation of tumour suppressor genes by microRNAs is often demonstrated as a one miRNA to one target relationship. However, given the large number of miRNA sites within a 3' untranslated region (UTR), most targets likely undergo miRNA cooperation or combinatorial action. Programmed Cell Death 4 (PDCD4), an important tumour suppressor, prevents neoplastic events, and is commonly downregulated in cancer. This study investigates the relationship between miR-21 and miR-499 in regulating PDCD4. This was explored using miRNA overexpression, mutational analysis of the PDCD4 3'UTR to assess regulation at each miRNA site, and IC50 calculations for combinatorial behaviour. We demonstrate that the first miR-499 binding site within PDCD4 is inactive, but the two remaining sites are both required for PDCD4 suppression. Additionally, the binding of miR-21 to PDCD4 influenced miR-499 activity through an increase in its silencing potency, and stabilization of its mature form. Furthermore, adjoining miRNA sites greater than 35 nt apart could potentially regulate thousands of 3'UTRs, similar to that observed between miR-21 and miR-499. The regulation of PDCD4 serves as a unique example of regulatory action by multiple miRNAs. This relationship was predicted to occur on thousands of targets and may represent a wider mode of miRNA regulation.

Copyright © 2019 Ajuyah et al.

PMID: 31235478 DOI: 10.1128/MCB.00086-19
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83.
Respir Med Res. 2019 Apr 10;75:1-4. doi: 10.1016/j.resmer.2019.03.001. [Epub ahead of print]
Diagnostic of mediastinal lymphadenopathy in extrathoracic cancer: A place for EBUS-TBNA in real life practice?
Fournier C1, Hermant C2, Gounant V3, Escarguel B4, Thibout Y5, Lachkar S6, Raspaud C7, Vergnon JM5.
Author information
Abstract
INTRODUCTION:
Mediastinal lymphadenopathy in patients with extrathoracic malignancy is common. To obtain tissue proof of metastatic spread, EBUS-TBNA is an alternative to mediastinoscopy or thoracoscopy, but there are limited data about its diagnostic performance. The aim of this study was to determine the diagnostic accuracy of EBUS-TBNA for the evaluation of mediastinal lymphadenopathy in patients with extrathoracic cancers.

METHODS:
We performed a multicenter retrospective study based on an online questionnaire to collect data from January 2011 to December 2012 in all patients with proven extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases who underwent EBUS-TBNA for diagnosis.

RESULTS:
Hundred and eighty-five patients were included. Extrathoracic malignancies observed were urological (43), breast (35), gastrointestinal (33), head and neck (30), melanoma (11), lymphoma (6), and others (27). EBUS-TBNA confirmed malignancy in 93 patients (50.3%): concordant metastases in 67 (36.2%); new lung cancer in 25 (13.5%); and 1 unidentified cancer. The diagnostic accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were respectively 54.6%, 68.4%, 100%, 53.3%, and 100%.

CONCLUSION:
Mediastinoscopy remain the reference, but EBUS-TBNA may be considered as first line investigation in patients with suspected mediastinal lymph node metastases and extrathoracic malignancy. It prevented a surgical procedure in 50.3% of patients.

Copyright © 2019. Published by Elsevier Masson SAS.

KEYWORDS:
EBUS-TBNA; Extrathoracic malignancy; Lymph node; Mediastinal lymphadenopathy; Mediastinoscopy

PMID: 31235451 DOI: 10.1016/j.resmer.2019.03.001
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Select item 31235417
84.
Clin Nutr. 2019 Jun 13. pii: S0261-5614(19)30257-2. doi: 10.1016/j.clnu.2019.05.029. [Epub ahead of print]
Chewing capacity and ideal cardiovascular health in adulthood: A cross-sectional analysis of a population-based cohort study.
Rangé H1, Perier MC2, Boillot A3, Offredo L2, Lisan Q4, Guibout C2, Thomas F5, Danchin N5, Boutouyrie P6, Jouven X2, Bouchard P7, Empana JP2.
Author information
Abstract
BACKGROUND AND AIMS:
To study the association between chewing capacity-a prerequisite for eating- and the level of cardiovascular health (CVH).

METHODS:
This is a cross-sectional analysis conducted on 5430 study participants from the Paris Prospective Study 3 that were subjected to an oral examination by trained dentists at study recruitment between 2008 and 2012. Chewing capacity was determined by the number of functional tooth units (FTUs), and ≥ 5FTUs defined adequate chewing capacity. Subjects were categorized into poor, intermediate, or ideal CVH for the 4 behavioural (smoking status, body mass index, physical activity, diet) and the 3 biological (total cholesterol, fasting glycemia, and blood pressure) factors according to the American Heart Association Life's Simple 7. Multinomial logistic regression was used to explore the association between the number of FTUs (exposure) and ideal or intermediate vs. poor CVH (main outcome).

RESULTS:
10.31% of the study participants had an ideal CVH and 7% presented an impaired chewing capacity (<5 FTUs). Subjects with at least 5 FTUs (OR = 2.37; 95% CI: 1.37-4.12) were more likely to have an ideal global CVH, after adjustment for age, sex, marital status, education, deprivation, depressive status, and dental plaque. This association existed for the behavioural but not the biological CVH, with the strongest association being observed with the diet metric.

CONCLUSION:
This is the first study suggesting that adults with a preserved chewing capacity have an increased likelihood to be at an ideal behavioural CVH.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS:
Cardiovascular diseases; Chewing capacity; Epidemiology; Functional tooth units; Nutrition

PMID: 31235417 DOI: 10.1016/j.clnu.2019.05.029
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Select item 31235195
85.
J Voice. 2019 Jun 22. pii: S0892-1997(19)30093-1. doi: 10.1016/j.jvoice.2019.05.008. [Epub ahead of print]
Efficacy of Voice Therapy in Improving Vocal Function in Adults Irradiated for Laryngeal Cancers: A Pilot Study.
Angadi V1, Dressler E2, Kudrimoti M3, Valentino J4, Aouad R4, Gal T4, Stemple J5.
Author information
Abstract
BACKGROUND:
Radiation therapy (XRT) for laryngeal cancers causes acute and chronic vocal dysfunction. Although these deleterious effects of XRT are well-established, there is a dearth of research with respect to effective voice rehabilitation following XRT for laryngeal cancers.

OBJECTIVE:
To obtain preliminary data on the efficacy of voice rehabilitation, using vocal function exercises (VFEs) in improving vocal function in adults irradiated for laryngeal cancer. The comparison treatment group (VH) received vocal hygiene counseling.

STUDY DESIGN:
Randomized clinical trial.

METHODS:
Participants were randomized to the VFE + VH or VH group. Both interventions lasted 6 weeks. The primary outcome measure was improvement in VHI scores. Secondary outcome measures included auditory-perceptual assessments, acoustic and aerodynamic measures, and laryngeal imaging.

RESULTS:
Ten participants were recruited for the study. The VFE + VH (n = 6) group demonstrated a statistically significant improvement in the primary outcome measure (P = 0.03), as well as select parameters of all secondary outcome measures. The VH (n = 4) group did not demonstrate a statistically significant improvement in primary or secondary outcome measures.

CONCLUSIONS:
This study offers preliminary data for the utility of VFEs in the irradiated laryngeal cancer population. However, findings in the VFE + VH group lack generalizability, secondary to sample heterogeneity, and limited sample size.

Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

KEYWORDS:
Radiation therapy; Vocal Function Exercises; Vocal hygiene; Voice disorders; Voice therapy

PMID: 31235195 DOI: 10.1016/j.jvoice.2019.05.008
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Select item 31235078
86.
Auris Nasus Larynx. 2019 Jun 21. pii: S0385-8146(19)30200-7. doi: 10.1016/j.anl.2019.05.009. [Epub ahead of print]
Adrenal insufficiency following nivolumab therapy in patients with recurrent or metastatic head and neck cancer.
Kagoshima H1, Hori R2, Kojima T1, Okanoue Y1, Fujimura S1, Taguchi A1, Shoji K1.
Author information
Abstract
Nivolumab, an anti-programmed cell death-1 monoclonal antibody, is currently used to treat many types of advanced cancers including recurrent and metastatic head and neck cancer. However, there are increasing reports concerning immune-related adverse events related to nivolumab therapy. Here, we report three patients who presented with adrenal insufficiency following nivolumab therapy. Two were diagnosed as having isolated adrenocorticotropic hormone (ACTH) deficiency and one was diagnosed as having primary adrenal insufficiency. All three patients complained of progressive fatigue and appetite loss, so we measured their blood cortisol and ACTH levels and diagnosed them as having adrenal deficiency. Treatment with nivolumab was discontinued for all three patients, and replacement therapy using hydrocortisone was successful after a few days in all cases. Two patients subsequently resumed nivolumab therapy because their general condition had improved. Complaints of fatigue and appetite loss during cancer treatment are common and tend to be regarded as unimportant. Although adrenal insufficiency due to nivolumab is relatively rare, complaints of these symptoms could lead to the detection of adrenal insufficiency at an early stage. The present report highlights the importance of the early recognition of adrenal insufficiency.

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

KEYWORDS:
Adrenal insufficiency; Immune-related adverse events; Nivolumab

PMID: 31235078 DOI: 10.1016/j.anl.2019.05.009
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Select item 31234932
87.
J Otolaryngol Head Neck Surg. 2019 Jun 24;48(1):29. doi: 10.1186/s40463-019-0352-9.
Opioid prescribing practices following elective surgery in Otolaryngology-Head & Neck Surgery.
Biskup M1, Dzioba A2, Sowerby LJ2, Monteiro E3, Strychowsky J2.
Author information
Abstract
BACKGROUND:
Prescription opioid abuse has become a major issue across the world and especially in North America. Canada has the second highest number of opioid prescriptions per capita in the world, second only to the United States, with numbers continuing to rise in recent years. Surgeons play a critical role in this discussion as they are responsible for the management of post-operative pain in their patients. The objective of this study is to evaluate the opioid prescribing practices of Otolaryngologists-Head and Neck Surgeons in Canada and determine factors that may influence these practices.

METHODS:
The online survey was distributed to members of the Canadian Society of Otolaryngology-Head and Neck Surgery. Questions surveyed the respondents' demographics and opioid prescribing practices for common pediatric and adult elective surgeries.

RESULTS:
The survey was sent to 670 surgeons and trainees and 121 responses were received (18%). There was representation across all subspecialties with a mix of community and academic surgeons. The most commonly prescribed opioid was Codeine/Acetaminophen, 48.2% (n = 53), in the adult population, and Morphine, 47.1% (n = 41), in the pediatric population. The median total oral morphine equivalents prescribed across all adult surgeries was 123.75 mg (24.75 doses). The surgery with the highest oral morphine equivalents prescribed was tonsillectomy/adenoidectomy for both adult and pediatric patients, with a median of 150 mg (30 doses) for adults and 4.5 mg/kg (23 doses) for pediatrics. Gender, training years, year in residency, or reported level of conservatism did not predict the dose prescribed to either adult or pediatric patients. Due to the relatively low response rate, the generalizability of these results is unclear.

CONCLUSIONS:
Our study demonstrates a wide variability in opioid prescriptions across procedures and within each individual procedure. This variability reflects the lack of guidelines available for post-operative opioid prescribing and suggests that some Otolaryngologists may be prescribing higher doses of opioids than required. Opportunities for improving patient safety and resource stewardship regarding optimal prescribing practices should be explored.

KEYWORDS:
Analgesia; Narcotic; Opioid; Opioid epidemic; Otolaryngology; Post-operative pain; Prescribing patterns

PMID: 31234932 DOI: 10.1186/s40463-019-0352-9
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Select item 31234735
88.
Otolaryngol Head Neck Surg. 2019 Jun 25:194599819858594. doi: 10.1177/0194599819858594. [Epub ahead of print]
Outcomes of Vocal Fold Motion Impairment and Dysphagia after Pediatric Cardiothoracic Surgery: A Systematic Review.
Orzell S1, Joseph R2, Ongkasuwan J3, Bedwell J3, Shin J4, Raol N5.
Author information
Abstract
OBJECTIVE:
The objective of this study was to systematically review the literature regarding vocal fold motion impairment (VFMI), respiratory outcomes, and swallowing outcomes in children following congenital heart surgery (CHS).

DATA SOURCES:
PubMed, Embase, Medline, and CINAHL databases.

REVIEW METHODS:
Data sources were searched from inception to November 30, 2018. Studies that described recovery of VFMI and swallowing function following CHS were included, and a qualitative analysis was performed.

RESULTS:
A total of 1371 studies were identified, of which 8 met inclusion criteria for VFMI and 5 met inclusion criteria for swallowing outcomes. Studies including patients who underwent isolate patent ductus arteriosus ligation were excluded. VFMI was present in 8% to 59% of subjects, and rates of recovery ranged from 9% to 96% at 6 months to 6 years of follow-up. Inability to maintain an oral diet occurred in 14% to 100% of subjects with VFMI and 11% to 61% without VFMI following surgery. Tolerance of an oral diet without tube feeding was present in 66% to 75% of subjects with VFMI and 88% to 100% without VFMI at 24 days to 3.2 years of follow-up. Limited data suggest that time to extubation is longer in VFMI subjects, but overall hospital length of stay and mortality may not be affected by VFMI status.

CONCLUSIONS:
Data evaluating dysphagia and VFMI after CHS are limited. Most studies suggest significant improvement in swallowing function, while rate of recovery of VFMI is variable. Future prospective studies with standardized screening and follow-up are needed to better elucidate outcomes to help develop algorithms for identification and management of VFMI after CHS.

KEYWORDS:
congenital heart surgery; dysphagia; dysphonia; pediatric; recovery; vocal fold motion impairment

PMID: 31234735 DOI: 10.1177/0194599819858594
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Select item 31234699
89.
J Pharm Pract. 2019 Jun 24:897190019857407. doi: 10.1177/0897190019857407. [Epub ahead of print]
Successful Long-Term Prophylactic Treatment With Subcutaneous C1 Esterase Inhibitor in a Patient With Hereditary Angioedema.
Hahn J1, Nordmann-Kleiner M1, Trainotti S1, Hoffmann TK1, Greve J1.
Author information
Abstract
BACKGROUND:
Hereditary angioedema (HAE) patients suffer from recurrent swellings. Current standard therapy consists of C1 esterase inhibitor (C1-INH) and bradykinin receptor B2 antagonists. Severe courses require prophylactic treatment. For such patients, it has been demonstrated that the intravenous (IV) administration of C1-INH [C1-INH(IV)] is safe and effective. A new prophylactic option is subcutaneous (SC) treatment with C1-INH.

METHODS AND CASE:
We present the case of an HAE patient placed on prophylactic C1-INH(IV) therapy due to frequent attacks when managed with on-demand therapy. An implanted port allowed the periodical and safe application of medication until the device was explanted due to an infection. Due to the poor venous access, repeated IV application failed. Therefore, we began a SC treatment with 1500 IU C1-INH [C1-INH(SC)] as long-term prophylaxis and analyzed the clinical course over 16 months.

RESULTS:
Under the SC prophylaxis, the number of attacks were reduced to 1/month in comparison to 4.33/month with no prophylactic treatment and 1.83/month with C1-INH(IV). No severe attacks and no attack within the upper airway occurred over the 16 months of C1-INH(SC) treatment. As a result, quality of life improved, as measured by the Angioedema quality of life questionaire (AE-QoL).

CONCLUSION:
Self-administered SC prophylactic use of C1-INH over a period of 16 months seems to be a well tolerated and efficient. The patient's quality of life improved, and by learning self-application, the patient gained independence.

KEYWORDS:
C1 inhibitor; bradykinin; hereditary angioedema; subcutaneous; therapy

PMID: 31234699 DOI: 10.1177/0897190019857407
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Select item 31192932
90.
Medicine (Baltimore). 2019 Jun;98(24):e15951. doi: 10.1097/MD.0000000000015951.
Oncologic outcomes of IMRT versus CRT for nasopharyngeal carcinoma: A meta-analysis.
Luo MS1, Huang GJ2, Liu HB3.
Author information
Abstract
BACKGROUND:
Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Asia particularly southern China. Comparisons of outcomes of conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT) have been still debated. This meta-analysis was carried out to compare oncologic outcomes of CRT and IMRT in the treatment of NPC.

METHODS:
A literature search was performed through PubMed, Embase, and the Cochrane library databases from their inceptions to November 10, 2018. Two authors assessed the included studies and extracted data independently. Relative studies that compared oncologic outcomes between CRT and IMRT for NPC were included.

RESULTS:
A total of 13 eligible studies were included, which contained 1 RCT, 1 prospective study, and 11 retrospective studies. Our meta-analysis showed that IMRT has increased overall survival (OR = 0.51, 95% CI = 0.41-0.65, P < .00001), locoregional control rate (OR = 0.59, 95% CI = 0.52-0.67, P < .00001), disease-free survival (OR = 0.77, 95% CI = 0.65-0.91, P = .002), and metastasis-free survival (OR = 0.71, 95% CI = 0.54-0.94, P = .01) in comparison with CRT.

CONCLUSION:
The results of this meta-analysis indicate IMRT should be a better option for the treatment of NPC because patients who underwent IMRT may benefit from increased overall survival, locoregional control rate, disease-free survival, and metastasis-free survival compared with CRT.

PMID: 31192932 PMCID: PMC6587629 DOI: 10.1097/MD.0000000000015951
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Select item 31192928
91.
Medicine (Baltimore). 2019 Jun;98(24):e15923. doi: 10.1097/MD.0000000000015923.
Effect of comprehensive nursing intervention in preventing postoperative pain, complications, and psychological pressure in the otolaryngology department.
Luan RL1, Zhu MX, Sun HY.
Author information
Abstract
This study aims to analyze the influence of comprehensive nursing intervention on the postoperative pain, complications, and psychological pressure of otolaryngology patients.A total of 300 otolaryngology patients in our hospital from February 2016 to October 2017 were selected and randomly divided into 2 groups using the random number table: control group (n = 150), patients were given routine nursing; experimental group (n = 150), patients were given comprehensive nursing intervention. Postoperative pain, complications, and psychological pressure between the 2 groups were analyzed.Residual pain in the experimental group at 3 months after the operation was lower than that in the control group (P < .05). The postoperative complications in the experimental group was lower than that in the control group (P < .05). The acute psychological pressure score and the psychological pressure self-test score in the experimental group were both lower than that in the control group (P < .05).Comprehensive nursing intervention for otolaryngology patients was associated to relieving pain after the operation and psychological pressure of patients in the short and long term. Besides, comprehensive nursing intervention for otolaryngology patients was associated with a lower risk of complications.

PMID: 31192928 PMCID: PMC6587606 DOI: 10.1097/MD.0000000000015923
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Select item 30829278
92.
Indian J Cancer. 2018 Oct-Dec;55(4):399-403. doi: 10.4103/ijc.IJC_325_18.
Nicotinic acetylcholine receptor gene polymorphism is not associated with tobacco-related oral squamous cell carcinoma.
Rajesh D1, Azeem Mohiyuddin SM2, Balakrishna S1, Kutty AVM1.
Author information
Abstract
BACKGROUND:
Nicotinic acetylcholine receptor is implicated in carcinogenesis indirectly through increasing nicotine dependence and directly through its impact on cell-cycle regulation. Functional polymorphism in nicotinic acetylcholine receptor alpha-5 subunit gene (CHRNA5 c.1192G>A; rs16969968) is associated with nicotine dependence and risk of lung cancer.

AIM:
The aim of this study was to evaluate the association of CHRNA5 c.1192G>A polymorphism with the risk of oral squamous cell carcinoma (OSCC).

SETTINGS AND DESIGN:
This was a rural teaching hospital-based case-control study.

MATERIALS AND METHODS:
A total of 100 histopathologically confirmed cases of OSCC patients and 100 age- and gender-matched healthy individuals were genotyped for CHRNA5 c.1192G>A polymorphism by polymerase chain reaction-restriction fragment length polymorphism method. Allele and genotype frequencies among case and control groups were compared by Chi-squared test (Fisher's exact).

RESULTS:
The frequency of CHRNA5 c.1192A allele was 22% in OSCC patients and 26% in control individuals. The difference in the distribution of alleles and genotypes between case and control groups was not significant (P > 0.05).

CONCLUSIONS:
CHRNA5 c.1192G>A polymorphism is not associated with the risk of developing OSCC.

KEYWORDS:
CHRNA5 gene; genetic susceptibility; nicotinic acetylcholine receptor; oral squamous cell carcinoma

PMID: 30829278 DOI: 10.4103/ijc.IJC_325_18
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MeSH terms, Substances
Select item 30701397
93.
Ann Biomed Eng. 2019 Apr;47(4):1000-1011. doi: 10.1007/s10439-019-02217-0. Epub 2019 Jan 30.
A Bag of Wavelet Features for Snore Sound Classification.
Qian K1,2, Schmitt M3, Janott C4,5, Zhang Z6,5, Heiser C7, Hohenhorst W8, Herzog M9, Hemmert W4, Schuller B3,6,5.
Author information
Abstract
Snore sound (SnS) classification can support a targeted surgical approach to sleep related breathing disorders. Using machine listening methods, we aim to find the location of obstruction and vibration within a subject's upper airway. Wavelet features have been demonstrated to be efficient in the recognition of SnSs in previous studies. In this work, we use a bag-of-audio-words approach to enhance the low-level wavelet features extracted from SnS data. A Naïve Bayes model was selected as the classifier based on its superiority in initial experiments. We use SnS data collected from 219 independent subjects under drug-induced sleep endoscopy performed at three medical centres. The unweighted average recall achieved by our proposed method is 69.4%, which significantly ([Formula: see text] one-tailed z-test) outperforms the official baseline (58.5%), and beats the winner (64.2%) of the INTERSPEECH COMPARE Challenge 2017 Snoring sub-challenge. In addition, the conventionally used features like formants, mel-scale frequency cepstral coefficients, subband energy ratios, spectral frequency features, and the features extracted by the OPENSMILE toolkit are compared with our proposed feature set. The experimental results demonstrate the effectiveness of the proposed method in SnS classification.

KEYWORDS:
Bag-of-audio-words; Drug-induced sleep endoscopy; Obstructive sleep apnea; Snore sound; Wavelets

PMID: 30701397 DOI: 10.1007/s10439-019-02217-0
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Select item 30586022
94.
Pain. 2019 Apr;160(4):965-972. doi: 10.1097/j.pain.0000000000001473.
Role of anxiety in young children's pain memory development after surgery.
Fischer S1, Vinall J2, Pavlova M1, Graham S1,3, Jordan A4, Chorney J5, Rasic N2, Brookes JT6,7, Hoy M6, Yunker WK6,7, Noel M8.
Author information
Abstract
Pediatric pain is common, and memory for it may be distressing and have long-lasting effects. Children who develop more negatively biased memories for pain (ie, recalled pain is higher than initial pain report) are at risk of worse future pain outcomes. In adolescent samples, higher child and parent catastrophic thinking about pain was associated with negatively biased memories for postsurgical pain. This study examined the influence of child and parent anxiety on the development of younger children's postsurgical pain memories. Seventy-eight children undergoing a tonsillectomy and one of their parents participated. Parents reported on their anxiety (state and trait) before surgery, and trained researchers observationally coded children's anxiety at anaesthesia induction. Children reported on their postsurgical pain intensity and pain-related fear for 3 days after discharge. One month after surgery, children recalled their pain intensity and pain-related fear using the same scales previously administered. Results revealed that higher levels of postsurgical pain and higher parent trait anxiety predicted more negatively biased memories for pain-related fear. Parent state anxiety and child preoperative anxiety were not associated with children's recall. Children who developed negatively biased pain memories had worse postsurgical pain several days after surgery. These findings underscore the importance of reducing parental anxiety and effective postsurgical pain management to potentially buffer against the development of negatively biased pain memories in young children.

PMID: 30586022 DOI: 10.1097/j.pain.0000000000001473
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Select item 30559083
95.
Clin Lung Cancer. 2019 Mar;20(2):e163-e170. doi: 10.1016/j.cllc.2018.11.001. Epub 2018 Nov 15.
Radiologic Criteria in Predicting Pathologic Less Invasive Lung Cancer According to TNM 8th Edition.
Katsumata S1, Aokage K2, Nakasone S1, Sakai T3, Okada S3, Miyoshi T3, Tane K1, Hayashi R4, Ishii G5, Tsuboi M3.
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Abstract
PURPOSE:
The Japan Clinical Oncology Group Study 0201 has proposed radiologic criteria on thin-slice computed tomography to diagnose pathologic less invasive lung adenocarcinoma that could be a candidate for sublobar resection based on the previous tumor, node, metastasis classification system (TNM). The aim of this study was to propose the new radiologic criteria for predicting pathologic less invasive cancer according to the 8th edition TNM.

PATIENTS AND METHODS:
We analyzed 744 patients who had peripheral clinical Tis-T1cN0M0 non-small-cell lung cancer of 3 cm or less and underwent complete resection by lobectomy from 2003 to 2011. We defined lung cancer with no nodal involvement and no vessel invasion pathologically as a pathologic less invasive cancer and investigated the radiologic criteria on the basis of the solid component size and by the consolidation-to-tumor (C/T) ratio (calculated with the maximum solid component diameter divided by the maximum tumor diameter) by using preoperative thin-slice computed tomography to predict them with a specificity of 97% or more, and evaluated overall survival.

RESULTS:
Patients with clinical Tis/T1mi/T1a disease had no pathologic invasive cancer except for one patient (specificity, 99%). From the investigation with the C/T ratio, only the criterion of C/T ratio 0.5 or less met the standard (specificity, 100%). The final specificity after combining these criteria was 99.6%, and they showed excellent prognosis (5-year overall survival rate, 96.2%).

CONCLUSION:
Lung cancer with clinical Tis/T1mi/T1a or a C/T ratio of 0.5 or less can be completely cured by sublobar resection with sufficient margin because of its less invasive nature pathologically.

Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS:
Consolidation-to-tumor ratio; Ground-glass opacity; Limited resection; Non–small-cell lung cancer; Thin-slice computed tomography

PMID: 30559083 DOI: 10.1016/j.cllc.2018.11.001
[Indexed for MEDLINE]
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Select item 30523622
96.
Cancer Treat Res. 2019;177:81-103. doi: 10.1007/978-3-030-03502-0_4.
Molecular Biology of EBV in Relationship to HIV/AIDS-Associated Oncogenesis.
Lang F1,2, Pei Y1,2, Lamplugh ZL1,2, Robertson ES3,4,5.
Author information
Abstract
Herpesvirus-induced disease is one of the most lethal factors which leads to high mortality in HIV/AIDS patients. EBV, also known as human herpesvirus 4, can transform naive B cells into immortalized cells in vitro through the regulation of cell cycle, cell proliferation, and apoptosis. EBV infection is associated with several lymphoma and epithelial cancers in humans, which occurs at a much higher rate in immune deficient individuals than in healthy people, demonstrating that the immune system plays a vital role in inhibiting EBV activities. EBV latency infection proteins can mimic suppression cytokines or upregulate PD-1 on B cells to repress the cytotoxic T cells response. Many malignancies, including Hodgkin Lymphoma and non-Hodgkin's lymphomas occur at a much higher frequency in EBV positive individuals than in EBV negative people during the development of HIV infection. Importantly, understanding EBV pathogenesis at the molecular level will aid the development of novel therapies for EBV-induced diseases in HIV/AIDS patients.

KEYWORDS:
EBV; HIV/AIDS; Latent infection; Lymphoma; Oncogenesis

PMID: 30523622 DOI: 10.1007/978-3-030-03502-0_4
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Select item 30343004
97.
Clin Lung Cancer. 2019 Jan;20(1):43-47. doi: 10.1016/j.cllc.2018.09.015. Epub 2018 Sep 24.
Local Consolidation Therapy (LCT) After First Line Tyrosine Kinase Inhibitor (TKI) for Patients With EGFR Mutant Metastatic Non-small-cell Lung Cancer (NSCLC).
Elamin YY1, Gomez DR2, Antonoff MB3, Robichaux JP1, Tran H1, Shorter MK1, Bohac JM1, Negrao MV1, Le X1, Rinsurogkawong W4, Lewis J4, Lacerda L1, Roarty EB1, Swisher SG3, Roth JA3, Zhang J1, Papadimitrakopoulou V1, Heymach JV5.
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Abstract
INTRODUCTION:
Although most NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutations have an impressive initial response, the vast majority has residual disease and develops acquired resistance after 9 to 14 months of EGFR tyrosine kinase (TKI) therapy. We recently reported a phase II trial showing that, for patients with molecularly unselected oligometastatic NSCLC who did not progress after first-line systemic therapy, local consolidation therapy (LCT) with surgery or radiation improved progression-free survival (PFS), compared with maintenance therapy alone. Herein, we report a retrospective analysis of LCT after TKI in patients with metastatic EGFR mutant NSCLC.

PATIENTS AND METHODS:
We identified patients with metastatic EGFR mutant NSCLC treated with TKI plus LCT or with TKI alone in the MD Anderson GEMINI (Genomic Marker-Guided Therapy Initiative) database and in our recently published LCT trial. PFS was compared between LCT plus TKI and TKI only treated patients using the log-rank test.

RESULTS:
We identified 129 patients with EGFR mutant NSCLC who were treated with first-line TKI and 12 that were treated with TKI followed by LCT. Among the 12 patients treated with TKI plus LCT, 8 patients had oligometastatic disease (defined as ≤ 3 metastases), and 4 patients had > 3 metastases. LCT regimens were hypofractionated radiotherapy or stereotactic ablative body radiotherapy for 11 patients and surgery for 1 patient. TKI followed by LCT resulted in a significantly longer PFS (36 months) compared with TKI alone (PFS, 14 months; log-rank P = .0024).

CONCLUSIONS:
Our data suggests that first-line TKI plus LCT is a promising therapeutic strategy for patients with EGFR mutant NSCLC that merits further investigation.

Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS:
EGFR mutant NSCLC; Local ablative therapy; Local consolidation therapy; Residual disease; Targeted therapy

PMID: 30343004 DOI: 10.1016/j.cllc.2018.09.015
[Indexed for MEDLINE]
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Select item 30261765
98.
Expert Rev Clin Immunol. 2018 Nov;14(11):957-964. doi: 10.1080/1744666X.2018.1530113. Epub 2018 Oct 8.
Recent advances in the diagnosis of allergic rhinitis.
Wang X1,2, Du K1, She W2, Ouyang Y2, Sima Y1, Liu C1, Zhang L1,2.
Author information
Abstract
Allergic rhinitis (AR) is a disorder with high prevalence worldwide. Identification of clinically relevant allergens is the key step for the diagnosis, allergen avoidance and allergen specific immunotherapy for AR. Areas covered: With the new findings of mechanisms of AR and the development of technology, much progress has been achieved in the diagnosis of AR recently. We review the recent advances about local IgE, in vivo and in vitro tests, cytological diagnosis and nitric oxide (NO) in the diagnosis of AR. Expert commentary: AR is traditionally diagnosed with the combined evaluation of history and allergen sensitization by in vivo skin prick tests and in vitro allergen specific IgE in serum, to confirm the correlation between clinical history and potential allergens. Nasal provocation test and local IgE measurement can be used to diagnose local AR. Allergen microarray has the ability to detect more potential allergens. Basophil activation and mast cell activation tests can be used in allergen diagnosis and to modify the response to immunotherapy, while cytological diagnosis is useful in the differential diagnosis of AR and non-AR. Nasal NO has been confirmed to be an optimal biomarker to discriminate between AR and non-AR.

KEYWORDS:
Allergic rhinitis; IgE; cytology; diagnosis; nitric oxide; skin prick tests

PMID: 30261765 DOI: 10.1080/1744666X.2018.1530113
[Indexed for MEDLINE]
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Select item 30225564
99.
World J Surg. 2019 Feb;43(2):519-526. doi: 10.1007/s00268-018-4787-3.
Appropriateness of Subadventitial Resection for Invasion of the Carotid Artery by Papillary Thyroid Carcinoma.
Moritani S1.
Author information
Abstract
BACKGROUND:
Selection of surgical treatment for patients with papillary thyroid carcinoma (PTC) that includes great vessel invasion is challenging. We investigated the efficacy of tumor excision, with regard to safety of the surgical procedure and prognosis among patients with PTC invasion of the carotid or vertebral artery.

METHODS:
This study is a retrospective review of patients who underwent surgical excision for PTC at our institution, between 1981 and 2010, with 49 patients treated for carotid artery invasion and nine for vertebral artery invasion.

RESULTS:
Twenty patients with carotid artery invasion receiving initial treatment underwent subadventitial resection. Among 29 relapsing patients with carotid artery invasion, subadventitial resection was performed in 27 and en-block resection and reconstruction in the other two. In patients with carotid artery invasion, locoregional recurrence was identified in 14 patients, with the recurrence specific to the carotid artery in one case and distant recurrence in 15. The 10-year disease-specific survival rate was shorter among relapsing patients (21.7%) than among those receiving an initial treatment (69.3%). At 8 years after surgery, however, the survival rates were comparable between the two groups. Of the nine patients with vertebral artery invasion, two received initial treatment, with either preservation or reconstruction of the vertebral artery. The other six cases were tumor recurrences, treated by tumor and vertebral artery resection. Vertebral artery invasion was associated with carotid artery invasion in five patients and subclavian artery invasion in four.

CONCLUSIONS:
Carotid artery invasion by PTC did not extend beyond the adventitia of the artery in the majority of patients. Most patients with vertebral artery invasion required tumor excision with vertebral artery resection.

PMID: 30225564 DOI: 10.1007/s00268-018-4787-3
[Indexed for MEDLINE]
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Select item 29675997
100.
J Neurochem. 2018 Aug;146(4):459-473. doi: 10.1111/jnc.14451. Epub 2018 Jul 23.
Hearing vulnerability after noise exposure in a mouse model of reactive oxygen species overproduction.
Morioka S1,2, Sakaguchi H2, Yamaguchi T3, Ninoyu Y1, Mohri H1, Nakamura T1, Hisa Y2,4, Ogita K3, Saito N1, Ueyama T1.
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Abstract
Previous studies have convincingly argued that reactive oxygen species (ROS) contribute to the development of several major types of sensorineural hearing loss, such as noise-induced hearing loss (NIHL), drug-induced hearing loss, and age-related hearing loss. However, the underlying molecular mechanisms induced by ROS in these pathologies remain unclear. To resolve this issue, we established an in vivo model of ROS overproduction by generating a transgenic (TG) mouse line expressing the human NADPH oxidase 4 (NOX4, NOX4-TG mice), which is a constitutively active ROS-producing enzyme that does not require stimulation or an activator. Overproduction of ROS was detected at the cochlea of the inner ear in NOX4-TG mice, but they showed normal hearing function under baseline conditions. However, they demonstrated hearing function vulnerability, especially at high-frequency sounds, upon exposure to intense noise, which was accompanied by loss of cochlear outer hair cells (OHCs). The vulnerability to loss of hearing function and OHCs was rescued by treatment with the antioxidant Tempol. Additionally, we found increased protein levels of the heat-shock protein 47 (HSP47) in models using HEK293 cells, including H2 O2 treatment and cells with stable and transient expression of NOX4. Furthermore, the up-regulated levels of Hsp47 were observed in both the cochlea and heart of NOX4-TG mice. Thus, antioxidant therapy is a promising approach for the treatment of NIHL. Hsp47 may be an endogenous antioxidant factor, compensating for the chronic ROS overexposure in vivo, and counteracting ROS-related hearing loss.

© 2018 International Society for Neurochemistry.

KEYWORDS:
ROS ; Hsp47; NOX4; antioxidant; hearing loss; transgenic mouse model

PMID: 29675997 DOI: 10.1111/jnc.14451
[Indexed for MEDLINE]
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Select item 29645361
101.
Int Forum Allergy Rhinol. 2018 Jul;8(7):837-849. doi: 10.1002/alr.22107. Epub 2018 Apr 12.
Perioperative analgesia for patients undergoing endoscopic sinus surgery: an evidence-based review.
Svider PF1, Nguyen B1,2, Yuhan B1,2, Zuliani G1, Eloy JA3,4,5,6, Folbe AJ2,7.
Author information
Abstract
BACKGROUND:
Misuse and diversion of prescription opioids have been critical in facilitating the opioid epidemic. Our objective was to perform a systematic evidence-based review delineating perioperative regimens (including opioid alternatives) evaluated for endoscopic sinus surgery.

METHODS:
PubMed/MEDLINE, Cochrane Library, and EmBase databases were evaluated for studies detailing analgesics employed after endoscopic sinus surgery. Studies were assessed for level of evidence. Bias risk was evaluated using the Cochrane Bias tool and GRADE criteria. Medication, administration, adverse effects, pain scores, and rescue analgesic consumption were evaluated. A summary of evidence detailing benefits, harm, and cost was prepared.

RESULTS:
Thirty-two studies encompassing 1812 patients were included. The GRADE criteria determined the overall evidence to be of moderate quality. Perioperative acetaminophen had few adverse events and reduced immediate need for opioid rescue after sinus surgery; studies evaluating acetaminophen demonstrate a preponderance of benefit over harm. Nonsteroidal anti-inflammatory drugs (NSAIDs) also reduce postoperative opioid consumption, although a small portion of patients undergoing sinus surgery harbor the potential for NSAID intolerance. The aggregate level of evidence for studies evaluating NSAIDs was grade A, whereas the aggregate grade of evidence for several other agents was grade B.

CONCLUSION:
There is evidence supporting the use of NSAIDs and gabapentin for the control of pain after endoscopic sinus surgery. Acetaminophen, α-agonists, and local anesthetics are also viable options for postoperative analgesia. Familiarity with these data is essential to facilitate the use of opioid alternatives. Further large-scale, multi-institutional, randomized trials are needed to provide conclusive recommendations for these perioperative analgesics.

© 2018 ARS-AAOA, LLC.

KEYWORDS:
endoscopic sinus surgery; endoscopic skull base surgery; endoscopy; pain control; pain management; perioperative analgesia

PMID: 29645361 DOI: 10.1002/alr.22107
[Indexed for MEDLINE]
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Select item 29633540
102.
Int Forum Allergy Rhinol. 2018 Jul;8(7):777-782. doi: 10.1002/alr.22112. Epub 2018 Apr 6.
Factor analysis of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis.
Mattos JL1, Schlosser RJ1,2, DeConde AS3, Hyer M4, Mace JC5, Smith TL5, Soler ZM1.
Author information
Abstract
BACKGROUND:
Olfactory-specific quality of life (QOL) can be measured using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS), which examines various aspects of olfactory dysfunction. It is unknown if certain factors of the QOD-NS differentially impact QOL.

METHODS:
Patients with chronic rhinosinusitis (CRS) completed the QOD-NS, 22-item Sino-Nasal Outcome Test (SNOT-22), Medical Outcomes Study Short Form 6-D (SF-6D) health utility measure, and Patient Health Questionnaire-2 (PHQ-2) depression screen. Exploratory factor analysis of the QOD-NS was performed. Associations between QOD-NS factors and other QOL metrics were analyzed before and after endoscopic sinus surgery (ESS).

RESULTS:
Outcomes were examined on 132 patients. The QOD-NS contains 4 distinct factors. There was no difference in associations between the different factors and baseline clinical characteristics. ESS had greatest effect size (d) on factors 2 and 4 (d = 0.29 and 0.27, respectively, p < 0.05). Postsurgical changes in the SF-6D and SNOT-22 had the strongest correlation with factor 2 scores (r = 0.29 and 0.34, respectively, p < 0.05), and changes in the PHQ-2 had the strongest correlation to factor 3 (r = 0.24, p < 0.05). Abnormal QOD-NS scores at baseline were associated with effect size increases of 50% to 100% (p < 0.05).

CONCLUSION:
The QOD-NS measures 4 distinct factors. Eating-related questions had the greatest improvement after ESS. Health utility and CRS-specific QOL improvement most strongly associated with factor 2, while PHQ-2 changes are most highly associated with factor 3, suggesting a differential impact of the factors of the QOD-NS on varying aspects of QOL.

© 2018 ARS-AAOA, LLC.

KEYWORDS:
QOD; eating; olfaction; quality of life; sinusitis; taste

PMID: 29633540 PMCID: PMC6035764 [Available on 2019-07-01] DOI: 10.1002/alr.22112
[Indexed for MEDLINE]
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Select item 29569385
103.
Int Forum Allergy Rhinol. 2018 Jul;8(7):783-789. doi: 10.1002/alr.22113. Epub 2018 Mar 23.
Taste impairment in chronic rhinosinusitis.
Othieno F1, Schlosser RJ1,2, Rowan NR1, Storck KA1, Mattos JL3, Smith TL4, Soler ZM1.
Author information
Abstract
BACKGROUND:
Though many patients with chronic rhinosinusitis (CRS) describe disturbances in smell and taste, there have been no studies specifically assessing taste impairment in CRS. This study sought to objectively assess taste dysfunction in CRS patients and determine whether taste impairment correlates with olfactory dysfunction. Additionally, this investigation sought to determine the impact of taste dysfunction on quality of life (QOL) in CRS and identify the clinical factors that influence taste.

METHODS:
Sixty-eight CRS patients were prospectively enrolled and completed several QOL surveys in relation to taste, smell, overall sinus-specific QOL, and depression. Validated taste strips were used to determine gustatory dysfunction pertaining to sweet, sour, salty, and bitter. Olfactory testing was assessed using the Sniffin' Sticks Test while both Lund-Kennedy and Olfactory Cleft Endoscopy Scoring (OCES) systems were used for endoscopic evaluation.

RESULTS:
The overall prevalence of dysgeusia was 28%, with scores significantly lower for sour compared to other subgroups. No correlation was observed between taste scores and objective olfactory metrics including olfaction tests and OCES. Taste scores were better in younger patients (r = 0.28, p = 0.02), female patients (p = 0.004), and never smokers compared to former smokers (p = 0.01). Taste scores did not correlate with patient-reported outcome measures or CRS disease severity metrics.

CONCLUSION:
Taste dysfunction is a common complaint in CRS. This cohort shows prevalence of gustatory loss to be about 28% using ideal normative values. This dysfunction correlated with male gender, smoking history, and older age. Taste dysfunction did not correlate with measured olfactory outcomes.

TRIAL REGISTRATION:
ClinicalTrials.gov NCT02720653.

© 2018 ARS-AAOA, LLC.

KEYWORDS:
chronic rhinosinusitis; olfaction disorders; quality of life; taste; taste perception

PMID: 29569385 PMCID: PMC6582951 [Available on 2019-07-01] DOI: 10.1002/alr.22113
[Indexed for MEDLINE]
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Select item 29543388
104.
Int Forum Allergy Rhinol. 2018 Jul;8(7):850-856. doi: 10.1002/alr.22116. Epub 2018 Mar 15.
Hereditary angioedema education in otolaryngology residencies: survey of program directors.
Patel VA1, Siddique L1, Stahl L1, Carr MM2.
Author information
Abstract
BACKGROUND:
The objective of this work was to assess resident education regarding contemporary management of hereditary angioedema using a web-based survey.

METHODS:
An 11-item, multiple-choice, electronic questionnaire was sent to all 106 accredited otolaryngology training programs in November 2016. Questions focused on resident education, management principles, and formalized assessment.

RESULTS:
A total of 34 program directors responded, representing 32% of otolaryngology residences. Ninety-seven percent believed otolaryngology residents should be knowledgeable in the management of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE). Specifically, 38% and 26% of program directors felt their residents were comfortable and very comfortable in C1-INH-HAE management, respectively. Of those surveyed, 18% have educational simulation activities and a protocol in place for C1-INH-HAE management. Forty-seven percent of respondents felt their training program provided adequate education and exposure to C1-INH-HAE. Over the last 5 years, 45% felt residents were exposed to 1 to 5 cases of C1-INH-HAE. Sixty-seven percent of residents were trained in the management of C1-INH-HAE through in-person lectures. Seventy-one percent of programs had no formal assessment of resident competency in C1-INH-HAE management.

CONCLUSION:
This study is the first to offer insight into C1-INH-HAE education and management principles in otolaryngology training programs. Surveyed program directors believe residents need a strong knowledge base in the management of C1-INH-HAE but less than half feel their trainees acquire the necessary exposure to this emergent disease process. Future research efforts in this area should aim to determine optimal educational activities as well as how to best incorporate this into otolaryngology residency curricula.

© 2018 ARS-AAOA, LLC.

KEYWORDS:
curriculum; education; hereditary angioedema; otolaryngology; patient care; quality improvement; residency; survey; training; universities

PMID: 29543388 DOI: 10.1002/alr.22116
[Indexed for MEDLINE]
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Select item 29485754
105.
Int Forum Allergy Rhinol. 2018 Jul;8(7):790-796. doi: 10.1002/alr.22108. Epub 2018 Feb 27.
Management of long-lasting phantosmia: a systematic review.
Saltagi MZ1, Rabbani CC1,2, Ting JY1,2, Higgins TS3,4.
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Abstract
BACKGROUND:
Interest in the pathophysiology and management of phantom smells has increased rapidly over the last decade. A PubMed search for the term "phantosmia" demonstrated a near-doubling of articles published on phantosmia within the past 7 years. We aimed to systematically review the literature on the management of phantosmia.

METHODS:
The PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990, using terms combined with pertinent Boolean search operators. We included articles evaluating management of phantosmia written in the English language, with original data and a minimum of 6 months of follow-up, on at least 2 patients and with well-defined and measurable outcomes.

RESULTS:
A total of 2151 unique titles were returned upon the initial search. Of these, 146 abstracts were examined, yielding 7 articles meeting the inclusion criteria. All articles were predominantly level 4 evidence. One prospective level 3 study was included. The studies included a total of 96 patients, with follow-up ranging from 6 months to 11 years. Endpoints were primarily based on subjective patient responses. Management options included observation and medical and surgical therapy. Olfactory mucosa excision was the only surgical intervention studied, with short-term symptomatic improvement in 10 of 11 patients. Forty-one patients were treated medically, which included antipsychotic, antimigraine, and antiseizure medications, transcranial stimulation, and topical cocaine application.

CONCLUSION:
Despite increasing interest in the treatment of phantosmia and reports of successful therapies, there remains a paucity of data and lack of consensus regarding optimal management of this difficult condition.

© 2018 ARS-AAOA, LLC.

KEYWORDS:
olfaction; olfactory disorders; olfactory excision; parosmia; phantom smell

PMID: 29485754 DOI: 10.1002/alr.22108
[Indexed for MEDLINE]
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Select item 29485750
106.
Int Forum Allergy Rhinol. 2018 Jul;8(7):831-836. doi: 10.1002/alr.22106. Epub 2018 Feb 27.
A challenge-response endoscopic sinus surgery specific checklist as an add-on to standard surgical checklist: an evaluation of potential safety and quality improvement issues.
Sommer DD1, Arbab-Tafti S1, Farrokhyar F2,3, Tewfik M4, Vescan A5, Witterick IJ5, Rotenberg B6, Chandra R7, Weitzel EK8, Wright E9, Ramakrishna J1.
Author information
Abstract
BACKGROUND:
The goal of this study was to develop and evaluate the impact of an aviation-style challenge and response sinus surgery-specific checklist on potential safety and equipment issues during sinus surgery at a tertiary academic health center. The secondary goal was to assess the potential impact of use of the checklist on surgical times during, before, and after surgery. This initiative is designed to be utilized in conjunction with the "standard" World Health Organization (WHO) surgical checklist. Although endoscopic sinus surgery is generally considered a safe procedure, avoidable complications and potential safety concerns continue to occur. The WHO surgical checklist does not directly address certain surgery-specific issues, which may be of particular relevance for endoscopic sinus surgery.

METHODS:
This prospective observational pilot study monitored compliance with and compared the occurrence of safety and equipment issues before and after implementation of the checklist. Forty-seven consecutive endoscopic surgeries were audited; the first 8 without the checklist and the following 39 with the checklist. The checklist was compiled by evaluating the patient journey, utilizing the available literature, expert consensus, and finally reevaluation with audit type cases. The final checklist was developed with all relevant stakeholders involved in a Delphi method.

RESULTS:
Implementing this specific surgical checklist in 39 cases at our institution, allowed us to identify and rectify 35 separate instances of potentially unsafe, improper or inefficient preoperative setup. These incidents included issues with labeling of topical vasoconstrictor or injectable anesthetics (3, 7.7%) and availability, function and/or position of video monitors (2, 5.1%), endoscope (6, 15.4%), microdebrider (6, 15.4%), bipolar cautery (6, 15.4%), and suctions (12, 30.8%).

CONCLUSION:
The design and integration of this checklist for endoscopic sinus surgery, has helped improve efficiency and patient safety in the operating room setting.

© 2018 ARS-AAOA, LLC.

KEYWORDS:
challenge-response; checklist; complications; prevention; safety; sinus surgery

PMID: 29485750 DOI: 10.1002/alr.22106
[Indexed for MEDLINE]
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Select item 29461689
107.
Int Forum Allergy Rhinol. 2018 Jul;8(7):817-824. doi: 10.1002/alr.22099. Epub 2018 Feb 20.
Clinical associations between allergies and rapid eye movement sleep disturbances.
Berson SR1, Klimczak J2, Prezio EA3, Hu S2, Abraham M4.
Author information
Abstract
BACKGROUND:
Allergic rhinitis, an immunoglobulin E inflammatory condition including nasal congestion, obstruction, sneezing, pruritus, and fatigue symptoms, has significant impact on quality of life and impairs sleep. Sleep-disordered breathing (SDB) patients often have normal all-night apnea-hypopnea (AHI) or respiratory-disturbance (RDI) indices on polysomnography (PSG). We hypothesized that the rapid eye motion-respiratory disturbance index (REM-RDI) may be a novel predictor of allergic status.

METHODS:
A retrospective analysis of 100 patients compared REM-RDI results in 67 allergen-positive patients with 33 nonallergic patients who presented with nasal blockage. Subjects completed STOP-Bang©, 22-item Sino-Nasal Outcome Test (SNOT-22)©, and Epworth Sleepiness Scale© questionnaires and underwent skin-prick testing (SPT) and PSGs including REM-RDI values. Using multivariate logistic regression models, we evaluated relationships between allergic status and sleep parameters while controlling for possible confounders including body mass index (BMI).

RESULTS:
Using REM-RDI as the outcome of interest, allergen-positive patients were 3.92 times more likely to have REM-RDI values in a moderate/severe range (≥15 events/hour); and patients with moderate/severe REM-RDI values were more likely to be allergen positive (p < 0.05). Allergic status was not significantly related to all-night AHI, RDI, or REM-AHI. BMI was not significantly related to REM-RDI. STOP-Bang© was related to allergy status (p = 0.02) and REM-RDI (p < 0.01). Allergic patients had increased REM latency and less total amount of REM.

CONCLUSION:
We revealed significant bidirectional associations between allergen positivity and increased REM-RDI values independent of BMI, AHI, RDI, and REM-AHI. Allergic inflammation and REM-RDI data may play important roles in diagnosing and treating fatigued SDB patients and as objective perioperative safety and outcomes measures.

© 2018 The Authors International Forum of Allergy & Rhinology, published by ARSAAOA, LLC.

KEYWORDS:
AR; QOL; SNOT-22; SPT; allergens; allergic rhinitis; evidence-based medicine, skin-prick test; nasal airflow dynamics; quality of life

PMID: 29461689 PMCID: PMC6055599 DOI: 10.1002/alr.22099
[Indexed for MEDLINE] Free PMC Article
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Select item 29458150
108.
Free Radic Biol Med. 2018 May 20;120:342-355. doi: 10.1016/j.freeradbiomed.2018.02.025. Epub 2018 Feb 17.
PINK1 Protects Auditory Hair Cells and Spiral Ganglion Neurons from Cisplatin-induced Ototoxicity via Inducing Autophagy and Inhibiting JNK Signaling Pathway.
Yang Q1, Sun G2, Yin H1, Li H3, Cao Z4, Wang J5, Zhou M2, Wang H6, Li J7.
Author information
Abstract
Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1) gene encodes a serine/threonine kinase, which acts as a molecular sensor of mitochondrial health necessary for mitochondrial quality control. The present study was designed to examine whether PINK1 expressed in C57BL/6 murine cochlea and HEI-OC1 cells and, if so, to investigate the possible mechanisms underlying the action of PINK1 in cisplatin-induced death of sensory hair cells (HCs) and spiral ganglion neurons (SGNs) in vitro. The expression pattern of PINK1, formation of parkin particles, and autophagy were determined by immunofluorescent staining. The expressions of PINK1, LC3B, cleaved-caspase 3 and p-JNK were measured by Western blotting. The levels of reactive oxygen species (ROS) were evaluated by DCFH-DA and Mito-Sox Red staining. The mitochondrial membrane potential was detected by Tetramethylrhodamine methyl ester perchlorate (TMRM) and Rhodamine 123. Cell viability and apoptosis were examined by CCK8 assay, TUNEL staining and Annexin V Apoptosis Detection Kit, respectively. We found that PINK1 was widely expressed in the cytoplasm in HCs, SGNs, stria vascularis of C57BL/6 cochlea and HEI-OC1 cells and, notably, the expression level in cochlear HCs and SGNs of postnatal day 4 (P4) mice was higher than that in adult mice. Moreover, treatment with 30 μM cisplatin elicited the formation of ROS, which, in turn, led to PINK1 activation, parkin recruitment, autophagy formation and JNK pathway relevant to apoptosis in HEI-OC1 cells, HCs, and SGNs. Meanwhile, co-treatment with ROS scavenger N-acetyl-L-cysteine (NAC) or H2O2 consumer catalase-polyethylene glycol (PEG-catalase) inhibited parkin recruitment, alleviated autophagy formation, and mitigated JNK pathway related apoptosis. In addition, PINK1 silencing resulted in a lower level of autophagy, but, a higher mortality in HEI-OC1 cells treated with cisplatin. Taken together, data from this work reveal that PINK1 possesses the protective effect via induction of autophagy and resistance of apoptosis under cisplatin stimulus in sensory HCs and SGNs, implying that PINK1 might serve as an important regulator of cisplatin-elicited ototoxicity.

Copyright © 2018. Published by Elsevier Inc.

KEYWORDS:
Apoptosis; Autophagy; Cisplatin; Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1); ROS

PMID: 29458150 DOI: 10.1016/j.freeradbiomed.2018.02.025
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109.
Ann Hum Genet. 2018 Mar;82(2):102-108. doi: 10.1111/ahg.12230. Epub 2017 Nov 17.
Silenced DMBT1 promotes nasal mucosa epithelial cell growth.
Lu X1, Xu Y1, Zhao Y1, Tao Q1, Wu J1.
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Abstract
OBJECTIVE:
The aim of this study was to investigate the role of the deleted in malignant brain tumors 1 (DMBT1) gene in the development of nasal polyps, as well as related mechanisms.

METHODS:
A stable human nasal mucosa epithelial cell (HNEpC) line with low expression of DMBT1 was generated. Three groups were established: a control group (HNEpCs without any treatment), a control short interference RNA (shRNA) group (HNEpCs transfected with an empty vector), and a DMBT1 shRNA group (HNEpCs with silenced DMBT1). Cell viability, apoptosis, and cell cycle distribution were measured after incubation. Expression of p53, signal transducer and activator of transcription 3 (STAT3), protein kinase B (AKT) and extracellular signal-regulated kinase1/2 (ERK1/2) was detected by western blotting.

RESULTS:
Compared with the control cell line, HNEpCs with silenced DMBT1 had increased viability and decreased apoptosis. Moreover, after DMBT1 silence, cell numbers were decreased significantly in the G1 phase and increased in the G2 and S phases. DMBT1 silence was associated with increased AKT expression and decreased p53 expression, but it did not alter expression of ERK1/2 or STAT3 (P > 0.05). Compared with the control cell line, HNEpCs transfected with an empty vector did not have altered cell viability, apoptosis, cell cycle distribution or expression of AKT, p53, ERK1/2, or STAT3 (P > 0.05).

CONCLUSION:
DMBT1 plays an important role in the growth and division of nasal epithelial cells. The possible mechanism might involve DMBT1 regulating the AKT-p53 pathway to promote cell viability and reduce apoptosis of nasal epithelial cells.

© 2017 John Wiley & Sons Ltd/University College London.

KEYWORDS:
AKT; DMBT1, human nasal epithelial cells; p53

PMID: 29148567 DOI: 10.1111/ahg.12230
[Indexed for MEDLINE]
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110.
Am J Med. 2018 Feb;131(2):e57-e58. doi: 10.1016/j.amjmed.2017.10.017. Epub 2017 Oct 24.
Mucocutaneous Secondary Syphilis: 'The Great Imitator'.
Sakthivel P1, Kakkar A2, Sharma SC3, Panda S3.
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PMID: 29079400 DOI: 10.1016/j.amjmed.2017.10.017
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Select item 28982584
111.
Am J Med. 2018 Feb;131(2):146-147. doi: 10.1016/j.amjmed.2017.09.013. Epub 2017 Oct 2.
First, Rule Out Cancer: Giant Lipoma.
Ralli M1, de Vincentiis M2, Greco A2.
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PMID: 28982584 DOI: 10.1016/j.amjmed.2017.09.013
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112.
Sci Rep. 2017 Sep 18;7(1):11773. doi: 10.1038/s41598-017-11779-9.
Variations in oral microbiota associated with oral cancer.
Zhao H1, Chu M1, Huang Z1, Yang X2, Ran S1, Hu B3, Zhang C4, Liang J5.
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Abstract
Individual bacteria and shifts in microbiome composition are associated with human disease, including cancer. To unravel the connections underlying oral bacterial dysbiosis and oral squamous cell carcinoma (OSCC), cancer lesion samples and anatomically matched normal samples were obtained from the same patients. We then profiled the bacteria within OSCC lesion surface samples at the species level using next-generation sequencing to comprehensively investigate bacterial community composition and functional genes in these samples. Significantly greater bacterial diversity was observed in the cancer samples than in the normal samples. Compared with previous studies, we identified many more taxa demonstrating remarkably different distributions between the groups. In particular, a group of periodontitis-correlated taxa, including Fusobacterium, Dialister, Peptostreptococcus, Filifactor, Peptococcus, Catonella and Parvimonas, was significantly enriched in OSCC samples. Additionally, several operational taxonomic units (OTUs) associated with Fusobacterium were highly involved in OSCC and demonstrated good diagnostic power. Our study revealed drastic changes in surface bacterial communities of OSCC. The findings enrich knowledge of the association between oral bacterial communities and oral cancer.

PMID: 28924229 PMCID: PMC5603520 DOI: 10.1038/s41598-017-11779-9
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113.
Cerebellum. 2018 Apr;17(2):122-131. doi: 10.1007/s12311-017-0878-1.
The Floccular Syndrome: Dynamic Changes in Eye Movements and Vestibulo-ocular Reflex in Isolated Infarction of the Cerebellar Flocculus.
Yacovino DA1,2, Akly MP3,4, Luis L5, Zee DS6.
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Abstract
The cerebellar flocculus is a critical structure involved in the control of eye movements. Both static and dynamic abnormalities of the vestibulo-ocular reflex (VOR) have been described in animals with experimental lesions of the flocculus/paraflocculus complex. In humans, lesions restricted to the flocculus are rare so they can become an exceptional model to contrast with the clinical features in experimental animals or in patients with more generalized cerebellar diseases. Here, we examined a 67-year-old patient with an acute vestibular syndrome due to an isolated infarct of the right flocculus. We evaluated him multiple times over 6 months-to follow the changes in eye movements and vestibular function-with caloric testing, video-oculography and head-impulse testing, and the anatomical changes on imaging. Acutely, he had an ipsilateral-beating spontaneous nystagmus, bilateral gaze-evoked nystagmus, borderline impaired smooth pursuit, and a complete contraversive ocular tilt reaction. The VOR gain was reduced for head impulses directed contralateral to the lesion, and there was also an ipsilesional caloric weakness. All abnormalities progressively improved at follow-up visits but with a considerable reduction in volume of the affected flocculus on imaging. The vestibular and ocular motor findings, qualitatively similar to a previously reported patient, further clarify the "acute floccular syndrome" in humans. We also add new information about the pattern of recovery from such a lesion with corresponding changes in the size of the affected flocculus on imaging.

KEYWORDS:
Acute vestibular syndrome (AVS); Cerebellum; Flocculus; Head impulse test; Infarct; Magnetic resonance imaging (MRI); Vestibulo-ocular reflex (VOR)

PMID: 28844105 DOI: 10.1007/s12311-017-0878-1
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114.
J Allergy Clin Immunol Pract. 2017 Jul - Aug;5(4):1122-1124. doi: 10.1016/j.jaip.2016.11.028. Epub 2016 Dec 23.
Unilateral Nasal Congestion and Headache: Renal Cell Carcinoma Metastasis to the Sinuses.
Jean T1, Pourang D2, Gabikian P3, Lim JY4, Samant S2.
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PMID: 28024970 DOI: 10.1016/j.jaip.2016.11.028
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115.
ACS Nano. 2017 Jan 24;11(1):112-125. doi: 10.1021/acsnano.6b04930. Epub 2016 Dec 21.
Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules.
Nakhleh MK1, Amal H1, Jeries R1, Broza YY1, Aboud M1, Gharra A1, Ivgi H1, Khatib S1, Badarneh S1, Har-Shai L2, Glass-Marmor L2, Lejbkowicz I2, Miller A2, Badarny S3, Winer R3, Finberg J4, Cohen-Kaminsky S5, Perros F5, Montani D5, Girerd B5, Garcia G5, Simonneau G5, Nakhoul F6, Baram S7, Salim R7, Hakim M8, Gruber M9, Ronen O9, Marshak T9, Doweck I9, Nativ O10, Bahouth Z10, Shi DY11, Zhang W11, Hua QL11, Pan YY11, Tao L11, Liu H11, Karban A12, Koifman E12, Rainis T13, Skapars R14, Sivins A14, Ancans G14, Liepniece-Karele I14, Kikuste I14,15, Lasina I14, Tolmanis I15, Johnson D16, Millstone SZ17, Fulton J18, Wells JW17, Wilf LH19, Humbert M5, Leja M14,15, Peled N20, Haick H1.
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Abstract
We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

KEYWORDS:
breath; carbon nanotube; diagnosis; disease; nanoparticle; noninvasive; sensor; volatile organic compound

PMID: 28000444 PMCID: PMC5269643 DOI: 10.1021/acsnano.6b04930
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