1
Oral Oncol
. 2019 Oct;97:62-68. doi: 10.1016/j.oraloncology.2019.08.007. Epub 2019 Aug 14.
Treatment Trends in Oropharyngeal Carcinoma: Surgical Technology Meets the Epidemic
T J Gal 1, Jon A Slezak 2, Alexandra E Kejner 2, Quan Chen 3, Bin Huang 4
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PMID: 31421473 DOI: 10.1016/j.oraloncology.2019.08.007
Abstract
Objective: To characterize temporal trends in treatment patterns for oropharyngeal carcinoma, and to evaluate the emerging role of surgical therapy in the era of transoral robotic surgery (TORS).
Methods: Patients with oropharynx cancer between 2004 and 2016 identified using the National Cancer Database. Demographics and primary treatment modalities were obtained. Treatment was classified as surgery alone, surgery with radiation/chemotherapy, or primary radiation/chemotherapy. Annual distribution of cases treated by the various modalities was tabulated by site and early (I/II) versus late (III/IV) stage disease (AJCC 7th edition). The "TORS era" was defined as beginning in 2010.
Results: 149,534 patients were identified. The majority (56.8%) were treated with radiation ± chemotherapy. 53,069 patients had surgery as part of treatment, 72.6% (N = 38,533) of which received adjuvant therapy. 5293 TORS procedures were performed between 2010 and 2016 with trends away from open and other endoscopic procedures. Despite a 31.0% increase in the number of cases treated surgically from before TORS (2009) to 2016, the percentage of cases treated surgically decreased from 35.0% to 32.7%, with a 44.2% increase in non-surgical therapy. Increases in the percentage of patients treated surgically were observed for base of tongue tumors (24.3-25.2%) and early stage disease (59.9-62.2%).
Conclusion: Despite the increase in the overall number of patients with oropharynx cancer, the percentages of patients treated surgically remains relatively stable. Notable increases were observed for base of tongue tumors and early stage disease.
Keywords: Chemotherapy; Human papillomavirus; National cancer database; Oropharyngeal cancer; Radiation therapy; Robotic surgery.
Copyright © 2019 Elsevier Ltd. All rights reserved.
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2
Oral Oncol
. 2019 Oct;97:69-75. doi: 10.1016/j.oraloncology.2019.07.022. Epub 2019 Aug 17.
Accuracy of Computer-Assisted Mandibular Reconstructions With Free Fibula Flap: Results of a Single-Center Series
Femke Goormans 1, Yi Sun 2, Michel Bila 3, Joseph Schoenaers 1, Joris Geusens 1, Heinz-Theo Lübbers 4, Wim Coucke 5, Constantinus Politis 3
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PMID: 31430641 DOI: 10.1016/j.oraloncology.2019.07.022
Free article
Abstract
Objectives: We evaluated the accuracy of computer-assisted mandibular reconstructions.
Patients and methods: We retrospectively reviewed data for 26 patients who had mandibular reconstruction with a microvascular free fibula flap, January 2015 to June 2018. Postoperative mandible models were obtained from computed tomography scans. After registering the models to the corresponding preoperative plan, we performed comparative measurements. Patients were grouped by condylar involvement and subdivided based on number of fibular segments used for reconstruction. For each segment, we measured length and osteotomy angles. For the final postoperative outcome, we compared intercoronoid, intergonial, and anteroposterior distances and intersegmental plane shift.
Results: Means (SD) for deviation of each osteotomy angle and fibular segment length were 1.98° (2.98) and 1.78 mm (2.69), respectively, remaining constant across subgroups. Other mean values were as follows: intercoronoid distance deviation, 3.86 mm (range, 0.20-11.21 mm); intergonial distance deviation, 3.14 mm (range, 0.05-8.28 mm); anteroposterior distance deviation, 2.92 mm (range, 0.03-8.49 mm); and intersegmental plane shift, 11.00° (range, 2.76-24.15°). Where the condyle was preserved, the intercoronoid and intergonial deviation means differed significantly (respectively 5.02 mm and 4.88 mm, both P < 0.05) for one-segmented and three-segmented fibular reconstructions. Furthermore, reconstructions involving the condylar region compared with condyle preservation showed significantly different intersegmental plane shifts (7.18°; P < 0.05).
Conclusion: Computer-assisted surgery provides cutting guides for obtaining accurate fibular segments, but current fixation methods lead to inaccuracies and reproducibility errors. In multisegmental transfer with condylar involvement, computer-assisted fixation is recommended to ensure accuracy of the preoperative plan.
Keywords: Computer-aided design; Computer-aided manufacturing; Data accuracy; Fibula; Head and neck neoplasms; Imaging, three-dimensional; Mandibular reconstruction; Printing, three-dimensional; Surgery; Surgical fixation devices.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
Cited by 1 article
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3
Exp Cell Res
. 2019 Oct 15;383(2):111508. doi: 10.1016/j.yexcr.2019.111508. Epub 2019 Jul 26.
In Vitro Humanized 3D Microfluidic Chip for Testing Personalized Immunotherapeutics for Head and Neck Cancer Patients
Ahmed Al-Samadi 1, Benedek Poor 2, Katja Tuomainen 3, Ville Liu 3, Aini Hyytiäinen 3, Ilida Suleymanova 3, Karri Mesimaki 4, Tommy Wilkman 4, Antti Mäkitie 5, Päivi Saavalainen 2, Tuula Salo 6
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PMID: 31356815 DOI: 10.1016/j.yexcr.2019.111508
Abstract
Objectives: Immunotherapy and personalized medicine therapeutics are emerging as promising approaches in the management of head and neck squamous cell carcinoma (HNSCC). In spite of that, there is yet no assay that could predict individual response to immunotherapy.
Methods: We manufactured an in vitro 3D microfluidic chip to test the efficacy of immunotherapy. The assay was first tested using a tongue cancer cell line (HSC-3) embedded in a human tumour-derived matrix "Myogel/fibrin" and immune cells from three healthy donors. Next, the chips were used with freshly isolated cancer cells, patients' serum and immune cells. Chips were loaded with different immune checkpoint inhibitors, PD-L1 antibody and IDO 1 inhibitor. Migration of immune cells towards cancer cells and the cancer cell proliferation rate were evaluated.
Results: Immune cell migration towards HSC-3 cells was cancer cell density dependent. IDO 1 inhibitor induced immune cells to migrate towards cancer cells both in HSC-3 and in two HNSCC patient samples. Efficacy of PD-L1 antibody and IDO 1 inhibitor was patient dependent.
Conclusion: We introduced the first humanized in vitro microfluidic chip assay to test immunotherapeutic drugs against HNSCC patient samples. This assay could be used to predict the efficacy of immunotherapeutic drugs for individual patients.
Keywords: Head and neck cancer; IDO1; Immunotherapy; In vitro; Microfuidic chip; PD-L1; Personalized medicine.
Copyright © 2019 Elsevier Inc. All rights reserved.
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4
Review Neuroimaging Clin N Am
. 2020 Aug;30(3):295-309. doi: 10.1016/j.nic.2020.04.002.
Technical Improvements in Head and Neck MR Imaging: At the Cutting Edge
Gregory Avey 1
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PMID: 32600632 DOI: 10.1016/j.nic.2020.04.002
Abstract
Head and neck MR imaging is technically challenging because of magnetic field inhomogeneity, respiratory and swallowing motion, and necessity of high-resolution imaging to trace key anatomic structures. These challenges have been answered by advances in MR imaging technology, including isovolumetric three-dimensional imaging, robust fat-water separation techniques, and novel deep learning-based reconstruction algorithms. New applications of MR imaging have been advanced and functional imaging has been improved. Improvements in acquisition and reconstruction technique facilitate novel applications of morphologic and functional imaging. This results in opportunities to improve diagnosis, staging, and treatment selection through application of advanced MR imaging techniques.
Keywords: Compressed sensing; Deep learning; Dixon; Head and neck; MR imaging; PET/MR imaging; ZTE.
Copyright © 2020 Elsevier Inc. All rights reserved.
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5
Review Laryngoscope
. 2020 Jan;130(1):45-51. doi: 10.1002/lary.27850. Epub 2019 Feb 1.
A Contemporary Review of Machine Learning in Otolaryngology-Head and Neck Surgery
Matthew G Crowson 1, Jonathan Ranisau 2, Antoine Eskander 1 3, Aaron Babier 2, Bin Xu 4, Russel R Kahmke 5, Joseph M Chen 1, Timothy C Y Chan 2
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PMID: 30706465 DOI: 10.1002/lary.27850
Abstract
One of the key challenges with big data is leveraging the complex network of information to yield useful clinical insights. The confluence of massive amounts of health data and a desire to make inferences and insights on these data has produced a substantial amount of interest in machine-learning analytic methods. There has been a drastic increase in the otolaryngology literature volume describing novel applications of machine learning within the past 5 years. In this timely contemporary review, we provide an overview of popular machine-learning techniques, and review recent machine-learning applications in otolaryngology-head and neck surgery including neurotology, head and neck oncology, laryngology, and rhinology. Investigators have realized significant success in validated models with model sensitivities and specificities approaching 100%. Challenges remain in the implementation of machine-learning algorithms. This may be in part the unfamiliarity of these techniques to clinician leaders on the front lines of patient care. Spreading awareness and confidence in machine learning will follow with further validation and proof-of-value analyses that demonstrate model performance superiority over established methods. We are poised to see a greater influx of machine-learning applications to clinical problems in otolaryngology-head and neck surgery, and it is prudent for providers to understand the potential benefits and limitations of these technologies. Laryngoscope, 130:45-51, 2020.
Keywords: Machine learning; and rhinology; artificial intelligence; head and neck oncology; laryngology; neural networks; neurotology.
© 2019 The American Laryngological, Rhinological and Otological Society, Inc.
Cited by 3 articles40 references
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6
Theranostics
. 2019 Apr 13;9(9):2424-2438. doi: 10.7150/thno.30941. eCollection 2019.
EBV(LMP1)-induced Metabolic Reprogramming Inhibits Necroptosis Through the Hypermethylation of the RIP3 Promoter
Feng Shi 1 2 3, Min Zhou 1 2 3, Li Shang 4, Qianqian Du 1 2 3, Yueshuo Li 1 2 3, Longlong Xie 1 2 3, Xiaolan Liu 1 2 3, Min Tang 1 2 3, Xiangjian Luo 1 2 3, Jia Fan 5, Jian Zhou 5, Qiang Gao 5, ShuangJian Qiu 5, Weizhong Wu 5, Xin Zhang 6, Ann M Bode 7, Ya Cao 1 2 3 8 9
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PMID: 31131045 PMCID: PMC6525991 DOI: 10.7150/thno.30941
Free PMC article
Abstract
EBV infection is a recognized epigenetic driver of carcinogenesis. We previously showed that EBV could protect cancer cells from TNF-induced necroptosis. This study aims to explore the epigenetic mechanisms allowing cancer cells with EBV infection to escape from RIP3-dependent necroptosis. Methods: Data from the TCGA database were used to evaluate the prognostic value of RIP3 promoter methylation and its expression. Western blotting, real-time PCR, and immunochemistry were conducted to investigate the relationship between LMP1 and RIP3 in cell lines and NPC tissues. BSP, MSP and hMeDIP assays were used to examine the methylation level. Induction of necroptosis was detected by cell viability assay, p-MLKL, and Sytox Green staining. Results: RIP3 promoter hypermethylation is an independent prognostic factor of poorer disease-free and overall survival in HNSCC patients, respectively. RIP3 is down-regulated in NPC (a subtype of HNSCC). EBV(LMP1) suppresses RIP3 expression by hypermethylation of the RIP3 promoter. RIP3 protein expression was inversely correlated with LMP1 expression in NPC tissues. Restoring RIP3 expression in EBV(LMP1)-positive cells inhibits xenograft tumor growth. The accumulation of fumarate and reduction of α-KG in EBV(LMP1)-positive cells led to RIP3 silencing due to the inactivation of TETs. Decreased FH activity caused fumarate accumulation, which might be associated with its acetylation. Incubating cells with fumarate protected NPC cells from TNF-induced necroptosis. Conclusion: These results demonstrate a pathway by which EBV(LMP1)-associated metabolite changes inhibited necroptosis signaling by DNA methylation, and shed light on the mechanism underlying EBV-related carcinogenesis, which may provide new options for cancer diagnosis and therapy.
Keywords: Epstein-Barr virus; Fumarate.; Nasopharyngeal carcinoma; Necroptosis; Receptor-interacting protein 3.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interest exists.
Cited by 3 articles46 references8 figures
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7
JAMA Netw Open
. 2019 Sep 4;2(9):e199292. doi: 10.1001/jamanetworkopen.2019.9292.
Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk
Xue Xu 1 2 3 4, Jianqiang Li 1, Jinfeng Zou 5, Xiaowen Feng 2 3 4 6, Chao Zhang 7, Ruiqing Zheng 2 3 4 8, Weixiang Duanmu 7, Arnab Saha-Mandal 2 3, Zhong Ming 1, Edwin Wang 2 3 4 9 10 11
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PMID: 31483464 PMCID: PMC6727785 DOI: 10.1001/jamanetworkopen.2019.9292
Free PMC article
Abstract
Importance: Only a small fraction of patients with cancer receiving immune checkpoint therapy (ICT) respond, which is associated with tumor immune microenvironment (TIME) subtypes and tumor-infiltrating lymphocytes (TILs).
Objective: To examine whether germline variants of natural killer (NK) cells, a key component of the immune system, are associated with TIME subtypes, the abundance of TILs, response to ICT, clinical outcomes, and cancer risk.
Design, setting, and participants: This genetic association study explored TIME subtypes and examined the association of the germline genomic information of patients with cancer with TIME subtypes, abundance of TILs, response to ICT, prognosis, and cancer risk. Clinical information, tumor RNA sequencing, and whole-exome sequencing (WES) data of paired normal samples of patients with 13 common cancers (n = 5883) were obtained from the Cancer Genome Atlas. The WES data of individuals with no cancer (n = 4500) were obtained from the database of Genotypes and Phenotypes. Data collection and analysis took place in March 2017.
Main outcomes and measures: Associations between the number of germline defective genes in NK cells and survival time and the abundance of TILs.
Results: Based on tumor RNA sequencing data, tumors were stratified into TIME-rich, TIME-intermediate, and TIME-poor subtypes. Tumors of TIME-rich subtype had more TILs (TIL-NK cells in TIME-rich head and neck squamous cell carcinoma [HNSC] tumors: t = 4.85; 95% CI of the difference, 0.01-0.03; P = 2.19 × 10-6) compared with TIME-intermediate HNSC tumors (t = 3.70; 95% CI of the difference, 0.01-0.03; P < .001), better prognosis (patients with HNSC: hazard ratio, 0.65; 95% CI, 0.41-1.02; P = .054) compared with TIME-intermediate and TIME-poor subtypes, and better ICT response (patients with melanoma: odds ratio [OR], 4.45; 95% CI, 0.99-27.08; P = .04). Patients with TIME-rich tumors had significantly fewer inherited defective genes in NK cells than patients with TIME-intermediate and TIME-poor tumors (patients with HNSC: OR, 0.49; 95% CI, 0.26-1.07; P = .005). Similarly, patients with cancer had significantly more inherited defective genes in NK cells than individuals with no cancer (patients with HNSC: OR, 19.09; 95% CI, 4.30-315.96; P = 6.21 × 10-4). Among 11 of 13 common cancers, the number of heritable defective genes in NK cells was significantly negatively associated with survival (patients with HNSC: hazard ratio, 1.77; 95% CI, 1.18-2.66; P = .005), abundance of TILs (patients with HNSC: R = -0.25; 95% CI, -0.65-2.17; P = 0.02), and response to ICT (patients with melanoma: OR, 4.45; 95% CI, 0.99-27.08; P = .04).
Conclusions and relevance: These results suggest that individuals who have more inherited defective genes in NK cells had a higher risk of developing cancer and that these inherited defects were associated with TIME subtypes, recruitment of TILs, ICT response, and clinical outcomes. The findings have implications for identifying individuals at risk for developing cancer of many types based on germline variants of NK cells and for improving existing ICT and chimeric antigen receptor-T cell therapy by adoptive transfer of healthy NK cells to patients with TIME-intermediate and TIME-poor tumors.
Conflict of interest statement
Conflict of Interest Disclosures: None reported.
Cited by 5 articles35 references5 figures
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8
Cancers (Basel)
. 2020 Jun 24;12(6):E1670. doi: 10.3390/cancers12061670.
Acquisition of Cisplatin Resistance Shifts Head and Neck Squamous Cell Carcinoma Metabolism Toward Neutralization of Oxidative Stress
Wangjie Yu 1, Yunyun Chen 2, Nagireddy Putluri 3, Cristian Coarfa 3 4 5, Matthew J Robertson 5, Vasanta Putluri 5, Fabio Stossi 3 5 6, Julien Dubrulle 3 5 6, Michael A Mancini 3 5 6, Jonathan C Pang 1, Trung Nguyen 1, Dodge Baluya 7, Jeffrey N Myers 2, Stephen Y Lai 2, Vlad C Sandulache 1
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PMID: 32599707 DOI: 10.3390/cancers12061670
Abstract
Background: Cisplatin (CDDP) is commonly utilized in the treatment of advanced solid tumors including head and neck squamous cell carcinoma (HNSCC). Cisplatin response remains highly variable among individual tumors and development of cisplatin resistance is common. We hypothesized that development of cisplatin resistance is partially driven by metabolic reprogramming. Methods: Using a pre-clinical HNSCC model and an integrated approach to steady state metabolomics, metabolic flux and gene expression data we characterized the interaction between cisplatin resistance and metabolic reprogramming. Results: Cisplatin toxicity in HNSCC was driven by generation of intra-cellular oxidative stress. This was validated by demonstrating that acquisition of cisplatin resistance generates cross-resistance to ferroptosis agonists despite the fact that cisplatin itself does not trigger ferroptosis. Acquisition of cisplatin resistance dysregulated the expression of genes involved in amino acid, fatty acid metabolism and central carbon catabolic pathways, enhanced glucose catabolism and serine synthesis. Acute cisplatin exposure increased intra-tumoral levels of S-methyl-5-thiadenosine (MTA) precursors and metabotoxins indicative of generalized oxidative stress. Conclusions: Acquisition of cisplatin resistance is linked to metabolic recovery from oxidative stress. Although this portends poor effectiveness for directed metabolic targeting, it supports the potential for biomarker development of cisplatin effectiveness using an integrated approach.
Keywords: amino acid; cisplatin; fatty acid; ferroptosis; head and neck cancer; oxidative stress.
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9
Appl Ergon
. 2020 Feb;83:102679. doi: 10.1016/j.apergo.2018.04.013. Epub 2018 May 4.
The Ipswich Microbreak Technique to Alleviate Neck and Shoulder Discomfort During Microscopic Procedures
Ananth Vijendren 1, Gavin Devereux 2, Aaron Tietjen 2, Kathy Duffield 3, Vincent Van Rompaey 4, Paul Van de Heyning 4, Matthew Yung 3
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PMID: 29735161 DOI: 10.1016/j.apergo.2018.04.013
Abstract
Neck and shoulder disorders are a considerable health problem amongst frequent microscope users. We aimed to investigate the neck and shoulder discomfort experienced during prolonged microscopic activity and to assess the benefits of minibreaks. A prospective crossover study was performed on 17 healthy volunteers sitting still while looking down a bench with and without the Ipswich Microbreak Technique (IMT). We used a subjective measure of time to fatigue and pain in the neck and shoulder regions as well as objective readings from a surface electromyogram (sEMG). The IMT delayed the sensation of pain in the neck and shoulder region while reducing the overall sEMG muscle activation. In conclusion, IMT is a useful strategy in reducing and delaying the pain in neck and shoulder from prolonged working under the microscope. This technique can be incorporated in other activities that involve a sustained stationary position.
Keywords: Micropauses; Microscope; Mini-breaks; Neck pain; Work-related musculoskeletal disorders.
Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.
Cited by 1 article
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10
World J Surg Oncol
. 2020 Jun 27;18(1):145. doi: 10.1186/s12957-020-01923-7.
BRAF V600E Mutation, BRAF-activated Long Non-Coding RNA and miR-9 Expression in Papillary Thyroid Carcinoma, and Their Association With Clinicopathological Features
Chenlei Shi 1, Jia Cao 2, Tiefeng Shi 3, Meihua Liang 1, Chao Ding 1, Yichen Lv 1, Weifeng Zhang 1, Chuanle Li 1, Wenchao Gao 4, Gang Wu 1, Jianting Man 1
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PMID: 32593310 DOI: 10.1186/s12957-020-01923-7
Free article
Abstract
Background: The incidence of thyroid cancer is increasing worldwide. This study investigated the association of B-type RAF kinase (BRAF)V600E mutation status, the expression of BRAF-activated long non-coding RNA (BANCR) and microRNA miR-9, and the clinicopathological features of papillary thyroid carcinoma (PTC).
Methods: Clinicopathological data for PTC patients (n = 51) diagnosed and treated between 2018 and 2019 were collected. Carcinoma and adjacent normal tissue samples were analyzed for the presence of the BRAFV600E mutation and/or expression of BANCR and miR-9.
Results: Larger tumor, higher rate of bilateral tumors and multifocality, extracapsular invasion, and lateral lymph node metastasis (LNM) were observed in PTC patients with BRAF V600E mutation. Patients with higher BANCR expression had a higher rate of extracapsular invasion and lateral LNM in carcinoma tissue and a lower frequency of bilateral tumors and multifocality in normal adjacent tissue. Patients with higher miR-9 expression had a lower rate of central and lateral LNM in carcinoma tissue and higher rates of bilateral tumor location and multifocality in normal adjacent tissue. Patients with BRAFV600E mutation have a higher rate of BANCR overexpression and tended to have a lower rate of miR-9 overexpression (P = 0.057), and a negative association was observed between BANCR and miR-9 expression in carcinoma tissue.
Conclusions: BRAFV600E mutation and the BANCR and miR-9 expression were closely associated with the tumor size, bilateral tumor location, multifocality, extracapsular invasion, and lateral LNM. PTC patients with these clinicopathological characteristics, BRAFV600E mutation, and high BANCR expression and low miR-9 expression needed earlier surgical treatment and are recommended for total thyroidectomy in primary surgery for reducing the risk of recurrence. These findings provide new insight into the molecular basis for PTC and can inform strategies for the management of PTC.
Keywords: BRAF V600E mutation; BRAF-activated long non-coding RNA; Papillary thyroid carcinoma; miR-9.
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11
Otolaryngol Head Neck Surg
. 2020 Mar;162(3):367-374. doi: 10.1177/0194599819900762. Epub 2020 Jan 21.
Otitis Media Middle Ear Effusion Identification and Characterization Using an Optical Coherence Tomography Otoscope
Diego Preciado 1 2, Ryan M Nolan 3, Radhika Joshi 1 2, Gina M Krakovsky 1, Anqi Zhang 3, Nickolas A Pudik 3, Nankee K Kumar 2, Ryan L Shelton 3, Stephen A Boppart 3, Nancy M Bauman 1
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PMID: 31959053 PMCID: PMC7289273 (available on 2021-03-01) DOI: 10.1177/0194599819900762
Free PMC article
Abstract
Objective: To determine the feasibility of detecting and differentiating middle ear effusions (MEEs) using an optical coherence tomography (OCT) otoscope.
Study design: Cross-sectional study.
Setting: US tertiary care children's hospital.
Subjects and methods: Seventy pediatric patients undergoing tympanostomy tube placement were preoperatively imaged using an OCT otoscope. A blinded reader quiz was conducted using 24 readers from 4 groups of tiered medical expertise. The primary outcome assessed was reader ability to detect presence/absence of MEE. A secondary outcome assessed was reader ability to differentiate serous vs nonserous MEE.
Results: OCT image data sets were analyzed from 45 of 70 total subjects. Blinded reader analysis of an OCT data subset for detection of MEE resulted in 90.6% accuracy, 90.9% sensitivity, 90.2% specificity, and intra/interreader agreement of 92.9% and 87.1%, respectively. Differentiating MEE type, reader identification of nonserous MEE had 70.8% accuracy, 53.6% sensitivity, 80.1% specificity, and intra/interreader agreement of 82.9% and 75.1%, respectively. Multivariate analysis revealed that age was the strongest predictor of OCT quality. The mean age of subjects with quality OCT was 5.01 years (n = 45), compared to 2.54 years (n = 25) in the remaining subjects imaged (P = .0028). The ability to capture quality images improved over time, from 50% to 69.4% over the study period.
Conclusion: OCT otoscopy shows promise for facilitating accurate MEE detection. The imageability with the prototype device was affected by age, with older children being easier to image, similar to current ear diagnostic technologies.
Keywords: acute otitis media; imaging; middle ear effusion; optical coherence tomography; otitis media; otitis media with effusion; otoscopy; pediatric.
Cited by 2 articles
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12
J Int Med Res
. 2020 Jun;48(6):300060520927918. doi: 10.1177/0300060520927918.
Histological Transformation of Lung Adenocarcinoma to Small Cell Lung Cancer With Mutant C797S Conferring Acquired Resistance to Osimertinib
Xiaohui Ren 1, Xinfeng Cai 2, Jing Li 1, Xia Zhang 1, Jianfei Yu 3, Xin Song 4, Henghui Zhang 5, Xia Song 1
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PMID: 32600081 DOI: 10.1177/0300060520927918
Abstract
Epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer may initially respond to EGFR tyrosine kinase inhibitors (TKIs), but may subsequently become resistant; however, the resistance mechanisms remain unclear. We report a rare case of acquired resistance to osimertinib associated with transformation to small cell lung cancer (SCLC) with cis-C797S mutation. A man with recurrent lung adenocarcinoma harboring an EGFR exon 19 deletion received erlotinib for 10 months following curative surgery and adjuvant chemotherapy. However, he switched to osimertinib after repeat biopsy showed EGFR exon 19 deletion and T790M mutation leading to erlotinib resistance. His disease progressed after 15 months and repeat biopsy showed SCLC. Next-generation sequencing of peripheral blood detected EGFR exon 19 deletion, T790M mutation, cis-C797S mutation, and RB1 inactivation. The tumor was reduced after four cycles of etoposide and cisplatin and his respiratory symptoms improved. However, computed tomography after six cycles of chemotherapy showed multiple bilateral lung lesions, and single-photon emission computed tomography showed bone metastasis. The patient received paclitaxel plus cisplatin for two cycles with partial response. Because heterogeneous genetic and phenotypic mechanisms of TKI-resistance may occur at different times and locations, histopathological and molecular testing both provide evidence to support appropriate treatment.
Keywords: C797S; Osimertinib; acquired resistance; epidermal growth factor receptor tyrosine kinase inhibitor; histological transformation; lung adenocarcinoma; small cell lung carcinoma.
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13
Clinical Trial Eur J Cancer
. 2020 Jan;124:178-185. doi: 10.1016/j.ejca.2019.10.025. Epub 2019 Nov 30.
Concurrent Cisplatin or Cetuximab With Radiotherapy for HPV-positive Oropharyngeal Cancer: Medical Resource Use, Costs, and Quality-Adjusted Survival From the De-ESCALaTE HPV Trial
David A Jones 1, Pankaj Mistry 2, Matthew Dalby 2, Tessa Fulton-Lieuw 3, Anthony H Kong 3, Janet Dunn 2, Hisham M Mehanna 3, Alastair M Gray 4
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PMID: 31794928 PMCID: PMC6947474 DOI: 10.1016/j.ejca.2019.10.025
Free PMC article
Abstract
Background: The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence.
Materials and methods: Resource use and HRQoL data were collected at intervals from the baseline to 24 months post treatment (PT). Health care costs were estimated using UK-based unit costs. Missing data were imputed. Differences in mean EQ-5D-5L utility index and adjusted cumulative quality-adjusted life years (QALYs) were compared using the Wilcoxon signed-rank test and linear regression, respectively. Mean resource usage and costs were compared through two-sample t-tests.
Results: 334 patients were randomised to cisplatin (n = 166) or cetuximab (n = 168). Two-year overall survival (97·5% vs 90·0%, HR: 3.268 [95% CI 1·451 to 7·359], p = 0·0251) and recurrence rates (6·4% vs 16·0%, HR: 2·67 [1·38 to 5·15]; p = 0·0024) favoured cisplatin. No significant differences in EQ-5D-5L utility scores were detected at any time point. At 24 months PT, mean difference was 0·107 QALYs in favour of cisplatin (95% CI: 0·186 to 0·029, p = 0·007) driven by the mortality difference. Health care costs were similar across all categories except the procurement cost and delivery of the systemic agent, with cetuximab significantly more expensive than cisplatin (£7779 [P < 0.001]). Consequently, total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab (mean difference £7547 [95% CI: £6512 to £8582]).
Conclusions: Cisplatin chemoradiotherapy provided more QALYs and was less costly than cetuximab bioradiotherapy, remaining standard of care for nonsurgical treatment of HPV-positive OPSCC.
Keywords: Cetuximab; Chemoradiotherapy; Cisplatin; Costs; Human papillomavirus; Oropharyngeal squamous cell carcinoma; Overall survival; Quality of life; Recurrence; Resource use.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Hisham Mehanna reports personal fees from Warwickshire Head Neck Clinic Ltd, AstraZeneca, MSD, Sanofi Pasteur, and Merck; grants from GlaxoSmithKline Biologicals, MSD, Sanofi Pasteur, Silence Therapeutics, GlaxoSmithKline, AstraZeneca, and several academic funders including the National Institute for Health Research (NIHR) Health Technology Assessment Unit, Cancer Research UK, and the Medical Research Council; and travel expenses from Sanofi Pasteur, MSD, and Merck, outside the submitted work.
All other authors declare no conflict of interests.
Cited by 1 article26 references3 figures
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14
Br J Cancer
. 2020 Jun 30. doi: 10.1038/s41416-020-0943-2. Online ahead of print.
EGFR/Ras-induced CCL20 Production Modulates the Tumour Microenvironment
Andreas Hippe 1, Stephan Alexander Braun 1 2, Péter Oláh 1 3, Peter Arne Gerber 1, Anne Schorr 1, Stephan Seeliger 4, Stephanie Holtz 1, Katharina Jannasch 5, Andor Pivarcsi 6, Bettina Buhren 1, Holger Schrumpf 1, Andreas Kislat 1, Erich Bünemann 1, Martin Steinhoff 7, Jens Fischer 8, Sérgio A Lira 9, Petra Boukamp 10, Peter Hevezi 11, Nikolas Hendrik Stoecklein 12, Thomas Hoffmann 13, Frauke Alves 5, Jonathan Sleeman 14 15, Thomas Bauer 16, Jörg Klufa 16, Nicole Amberg 16 17, Maria Sibilia 16, Albert Zlotnik 18, Anja Müller-Homey 19, Bernhard Homey 20
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PMID: 32601464 DOI: 10.1038/s41416-020-0943-2
Abstract
Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.
Methods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.
Results: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.
Conclusion: We propose that the chemokine axis CCL20-CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.
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15
Eur Ann Otorhinolaryngol Head Neck Dis
. 2020 Jun 26;S1879-7296(20)30147-2. doi: 10.1016/j.anorl.2020.06.008. Online ahead of print.
Pasteurella Multocida Acute Epiglottitis
L Jan 1, P Boute 2, F Mouawad 3
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PMID: 32600824 DOI: 10.1016/j.anorl.2020.06.008
Abstract
Introduction: Apart from cases related to direct inoculation, pasteurellosis is a rare opportunistic infection occurring in predisposed subjects. Close contact with domestic animals, usually cats, is generally reported. Localized ENT forms are possible and are due to oropharyngeal carriage.
Case report: We present the case of a patient with no notable history, who presented with laryngeal dyspnea and hyperthermia leading to a diagnosis of acute epiglottitis. Bacteremia was detected and blood cultures were positive for Pasteurella multocida. Treatment consisted of the standard treatment for acute epiglottitis with hospitalisation and intravenous antibiotics.
Discussion: This patient presented a history of animal exposure, but no other known risk factors. The activity spectrum of antibiotic therapy for epiglottitis should include H. influenzae and this case illustrates the diversity of the micro-organisms potentially involved. Immunosuppression or another chronic disease does not appear to be a prerequisite for ENT infection.
Keywords: Epiglottitis; Pasteurella multocida; Septicemia; Zoonosis.
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
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16
Otolaryngol Head Neck Surg
. 2020 Mar;162(3):392-399. doi: 10.1177/0194599819900014. Epub 2020 Feb 4.
Prediction of Apnea-Hypopnea Index Using Sound Data Collected by a Noncontact Device
Jeong-Whun Kim 1, Taehoon Kim 2, Jaeyoung Shin 3, Kyogu Lee 3, Sunkyu Choi 4, Sung-Woo Cho 1
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PMID: 32013710 DOI: 10.1177/0194599819900014
Abstract
Objective: To predict the apnea-hypopnea index (AHI) in patients with obstructive sleep apnea (OSA) using data from breathing sounds recorded using a noncontact device during sleep.
Study design: Prospective cohort study.
Setting: Tertiary referral hospital.
Subject and methods: Audio recordings during sleep were performed using an air-conduction microphone during polysomnography. Breathing sounds recorded from all sleep stages were analyzed. After noise reduction preprocessing, the audio data were segmented into 5-second windows and sound features were extracted. Estimation of AHI by regression analysis was performed using a Gaussian process, support vector machine, random forest, and simple linear regression, along with 10-fold cross-validation.
Results: In total, 116 patients who underwent attended, in-laboratory, full-night polysomnography were included. Overall, random forest resulted in the highest performance with the highest correlation coefficient (0.83) and least mean absolute error (9.64 events/h) and root mean squared error (13.72 events/h). Other models resulted in somewhat lower but similar performances, with correlation coefficients ranging from 0.74 to 0.79. The estimated AHI tended to be underestimated as the severity of OSA increased. Regarding bias and precision, estimation performances in the severe OSA subgroup were the lowest, regardless of the model used. Among sound features, derivative of the area methods of moments of overall standard deviation demonstrated the highest correlation with AHI.
Conclusion: AHI was fairly predictable by using data from breathing sounds generated during sleep. The prediction model may be useful not only for prescreening but also for follow-up after treatment in patients with OSA.
Keywords: machine learning; obstructive sleep apnea; respiratory sound.
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17
Elife
. 2020 Jun 30;9:e55249. doi: 10.7554/eLife.55249.
Generation of Inner Ear Hair Cells by Direct Lineage Conversion of Primary Somatic Cells
Louise Menendez 1 2 3, Talon Trecek 1 2, Suhasni Gopalakrishnan 1 2 3, Litao Tao 1 2, Alexander L Markowitz 3 4, Haoze V Yu 1 2, Xizi Wang 1 2, Juan Llamas 1 2, Chichou Huang 5, James Lee 5, Radha Kalluri 3 4, Justin Ichida 1 2 3, Neil Segil 1 2 4
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PMID: 32602462 DOI: 10.7554/eLife.55249
Free article
Abstract
The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular dysfunction. Their paucity and inaccessibility has limited the search for otoprotective and regenerative strategies. Growing hair cells in vitro would provide a route to overcome this experimental bottleneck. We report a combination of four transcription factors (Six1, Atoh1, Pou4f3, and Gfi1) that can convert mouse embryonic fibroblasts, adult tail-tip fibroblasts and postnatal supporting cells into induced hair cell-like cells (iHCs). iHCs exhibit hair cell-like morphology, transcriptomic and epigenetic profiles, electrophysiological properties, mechanosensory channel expression, and vulnerability to ototoxin in a high-content phenotypic screening system. Thus, direct reprogramming provides a platform to identify causes and treatments for hair cell loss, and may help identify future gene therapy approaches for restoring hearing.
Keywords: developmental biology; inner ear; mouse; ototoxin; regeneration; regenerative medicine; reprogramming; screening; sensory hair cell; stem cells.
Plain Language Summary
Worldwide, hearing loss is the most common loss of sensation. Most cases of hearing loss are due to the death of specialized hair cells found deep inside the ear. These hair cells convert sounds into nerve impulses which can be understood by the brain. Hair cells naturally degrade as part of aging and can be damaged by other factors including loud noises, and otherwise therapeutic drugs, such as those used in chemotherapy for cancer. In humans and other mammals, once hair cells are lost they cannot be replaced. Hair cells have often been studied using mice, but the small number of hair cells in their ears, and their location deep inside the skull, makes it particularly difficult to study them in this way. Scientists are seeking ways to grow hair cells in the laboratory to make it easier to understand how they work and the factors that contribute to their damage and loss. Different cell types in the body are formed in response to specific combinations of biological signals. Currently, scientists do not have an efficient way to grow hair cells in the laboratory, because the correct signals needed to create them are not known. Menendez et al. have now identified four proteins which, when activated, convert fibroblasts, a common type of cell, into hair cells similar to those in the ear. These proteins are called Six1, Atoh1, Pou4f3 and Gfi1. Menendez et al. termed the resulting cells induced hair cells, or iHCs for short, and analyzed these cells to identify those characteristics that are similar to normal hair cells, as well as their differences. Importantly, the iHCs were found to be damaged by the same chemicals that specifically harm normal hair cells, suggesting they are useful test subjects. The ability to create hair cells in the laboratory using more easily available cells has many uses. These cells can help to understand the normal function of hair cells and how they become damaged. They can also be used to test new drugs to assess their success in preventing or reversing hearing loss. These findings may also lead to genetic solutions to curing hearing loss.
© 2020, Menendez et al.
Conflict of interest statement
LM, TT, LT, AM, HY, XW, JL, RK, JI, NS No competing interests declared, SG Currently employed at a for-profit corporation, Allogene. This company has no competing technology, nor is it involved in this research. CH, JL Employed by a for-profit company that will benefit from the software development that they contributed to this project.
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18
Otolaryngol Head Neck Surg
. 2020 Mar;162(3):343-345. doi: 10.1177/0194599820901684. Epub 2020 Jan 21.
A Surgical Simulator for Tympanostomy Tube Insertion Incorporating Capacitive Sensing Technology to Track Instrument Placement
Vilija J Vaitaitis 1, Michael E Dunham 1, Yong-Chan Kwon 2, Wyatt C Mayer 1, Adele K Evans 1, Amari J Baker 2, Kyla D Walker 2, Gabriel D Cespedes 2, Abishek Stanley 2, Michelle Opiri 2
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PMID: 31961771 DOI: 10.1177/0194599820901684
Abstract
We describe a device engineered for realistic simulation of myringotomy and tympanostomy tube insertion that tracks instrument placement and objectively measures operator proficiency. A 3-dimensional computer model of the external ear and cartilaginous external auditory canal was created from a normal maxillofacial computed tomography scan, and models for the bony external auditory canal and tympanic cavity were created with computer-aided design software. Physical models were 3-dimensionally printed from the computer reconstructions. The external auditory canal and tympanic cavity surfaces were coated with conductive material and wired to a capacitive sensor interface. A programmable microcontroller with custom embedded software completed the system. Construct validation was completed by comparing the run times and total sensor contact times of otolaryngology faculty and residents.
Keywords: 3D printing; capacitive sensing; surgical simulator; surgical training; tympanostomy tube.
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19
Review Otolaryngol Head Neck Surg
. 2020 Feb;162(2):177-180. doi: 10.1177/0194599819897067. Epub 2019 Dec 24.
Navigating the Informed Consent Process When Using Innovative Surgery
Daniel Wehrmann 1, Glenn E Green 1, Kevin J Weatherwax 2, Andrew G Shuman 1 3
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PMID: 31874066 DOI: 10.1177/0194599819897067
Abstract
No abstract available
Keywords: expanded access; research ethics; surgical innovation.
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20
Allergy
. 2020 Jun 26. doi: 10.1111/all.14471. Online ahead of print.
ARIA-EAACI Statement on Asthma and COVID-19 (June 2, 2020)
Jean Bousquet 1 2 3, Marek Jutel 4, Cezmi A Akdis 5, Ludger Klimek 6, Oliver Pfaar 7, Kari C Nadeau 8, Thomas Eiwegger 9, Anna Bedbrook 3, Ignacio J Ansotegui 10, Josep M Anto 11 12 13 14, Claus Bachert 15 16 17 18, Eric D Bateman 19, Kazi S Bennoor 20, Emilia Camelia Berghea 21, Karl-Christian Bergmann 1, Hubert Blain 22 23, Mateo Bonini 24 25, Sinthia Bosnic-Anticevich 26, Louis-Philippe Boulet 27, Luisa Brussino 28, Roland Buhl 29, Paulo Camargos 30, G Walter Canonica 31, Victoria Cardona 32, Thomas Casale 33, Sharon Chinthrajah 8, Mübeccel Akdis 5, Tomas Chivato 34, George Christoff 35, Alvaro A Cruz 36, Wienczyslawa Czarlewski 37, Stefano Del Giacco 38, Hui Du 39, Yehia El-Gamal 40, Wytske J Fokkens 41, Joao A Fonseca 42 43 44 45, Yadong Gao 39, Mina Gaga 46, Bilun Gemicioglu 47, Maia Gotua 48, Tari Haahtela 49, David Halpin 50, Eckard Hamelmann 51, Karin Hoffmann-Sommergruber 52, Marc Humbert 53, Nataliya Ilina 54, Juan-Carlos Ivancevich 55, Guy Joos 56, Musa Khaitov 54, Bruce Kirenga 57, Edward F Knol 58, Fanny W Ko 59, Seppo Koskinen 60, Marek L Kowalski 61, Helga Kraxner 62, Dmitri Kudlay 54, Piotr Kuna 63, Maciej Kupczyk 63, Violeta Kvedariene 64, Amir H Abdul Latiff 65, Lan T Le 66, Michael Levin 67, Desiree Larenas-Linnemann 68, Renaud Louis 69, Mohammad R Masjedi 70, Erik Melén 71, Florin Mihaltan 72, Branislava Milenkovic 73, Yousser Mohammad 74, Mario Morais-Almeida 75, Joaquim Mullol 76, Leyla Namazova 77, Hugo Neffen 78, Elisabete Nunes 79, Paul O'Byrne 80, Robyn O'Hehir 81, Liam O'Mahony 82, Ken Ohta 83, Yoshitaka Okamoto 84, Gabrielle L Onorato 3, Petr Panzner 85, Nikos G Papadopoulos 86, Gianni Passalacqua 87, Vincenzo Patella 88, Ruby Pawankar 89, Nhân Pham-Thi 90, Bernard Pigearias 91, Todor A Popov 92, Francesca Puggioni 31, Frederico S Regateiro 93, Giovanni Rolla 28, Menachem Rottem 94, Boleslaw Samolinski 95, Joaquin Sastre 96, Jurgen Schwarze 97, Aziz Sheikh 98, Nicola Scichilone 99, Manuel Soto-Quiros 100, Milan Sova 101, Stefania Nicola 28, Rafael Stelmach 102, Charlotte Suppli-Ulrik 103, Luis Taborda-Barata 104 105, Teresa To 106, Peter-Valentin Tomazic 107, Sanna Toppila-Salmi 49, Ioanna Tsiligianni 108 109, Omar Usmani 110, Arunas Valiulis 111 112, Maria Teresa Ventura 113, Giovanni Viegi 114, Theodor Vontetsianos 115, De Yun Wang 116, Sian Williams 117, Gary Wk Wong 118, Arzu Yorgancioglu 119, Mario Zernotti 120, Mihaela Zidarn 121, Torsten Zuberbier 1, Ioana Agache 122
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PMID: 32588922 DOI: 10.1111/all.14471
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Oral Oncol
. 2019 Oct;97:62-68. doi: 10.1016/j.oraloncology.2019.08.007. Epub 2019 Aug 14.
Treatment Trends in Oropharyngeal Carcinoma: Surgical Technology Meets the Epidemic
T J Gal 1, Jon A Slezak 2, Alexandra E Kejner 2, Quan Chen 3, Bin Huang 4
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PMID: 31421473 DOI: 10.1016/j.oraloncology.2019.08.007
Abstract
Objective: To characterize temporal trends in treatment patterns for oropharyngeal carcinoma, and to evaluate the emerging role of surgical therapy in the era of transoral robotic surgery (TORS).
Methods: Patients with oropharynx cancer between 2004 and 2016 identified using the National Cancer Database. Demographics and primary treatment modalities were obtained. Treatment was classified as surgery alone, surgery with radiation/chemotherapy, or primary radiation/chemotherapy. Annual distribution of cases treated by the various modalities was tabulated by site and early (I/II) versus late (III/IV) stage disease (AJCC 7th edition). The "TORS era" was defined as beginning in 2010.
Results: 149,534 patients were identified. The majority (56.8%) were treated with radiation ± chemotherapy. 53,069 patients had surgery as part of treatment, 72.6% (N = 38,533) of which received adjuvant therapy. 5293 TORS procedures were performed between 2010 and 2016 with trends away from open and other endoscopic procedures. Despite a 31.0% increase in the number of cases treated surgically from before TORS (2009) to 2016, the percentage of cases treated surgically decreased from 35.0% to 32.7%, with a 44.2% increase in non-surgical therapy. Increases in the percentage of patients treated surgically were observed for base of tongue tumors (24.3-25.2%) and early stage disease (59.9-62.2%).
Conclusion: Despite the increase in the overall number of patients with oropharynx cancer, the percentages of patients treated surgically remains relatively stable. Notable increases were observed for base of tongue tumors and early stage disease.
Keywords: Chemotherapy; Human papillomavirus; National cancer database; Oropharyngeal cancer; Radiation therapy; Robotic surgery.
Copyright © 2019 Elsevier Ltd. All rights reserved.
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2
Oral Oncol
. 2019 Oct;97:69-75. doi: 10.1016/j.oraloncology.2019.07.022. Epub 2019 Aug 17.
Accuracy of Computer-Assisted Mandibular Reconstructions With Free Fibula Flap: Results of a Single-Center Series
Femke Goormans 1, Yi Sun 2, Michel Bila 3, Joseph Schoenaers 1, Joris Geusens 1, Heinz-Theo Lübbers 4, Wim Coucke 5, Constantinus Politis 3
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PMID: 31430641 DOI: 10.1016/j.oraloncology.2019.07.022
Free article
Abstract
Objectives: We evaluated the accuracy of computer-assisted mandibular reconstructions.
Patients and methods: We retrospectively reviewed data for 26 patients who had mandibular reconstruction with a microvascular free fibula flap, January 2015 to June 2018. Postoperative mandible models were obtained from computed tomography scans. After registering the models to the corresponding preoperative plan, we performed comparative measurements. Patients were grouped by condylar involvement and subdivided based on number of fibular segments used for reconstruction. For each segment, we measured length and osteotomy angles. For the final postoperative outcome, we compared intercoronoid, intergonial, and anteroposterior distances and intersegmental plane shift.
Results: Means (SD) for deviation of each osteotomy angle and fibular segment length were 1.98° (2.98) and 1.78 mm (2.69), respectively, remaining constant across subgroups. Other mean values were as follows: intercoronoid distance deviation, 3.86 mm (range, 0.20-11.21 mm); intergonial distance deviation, 3.14 mm (range, 0.05-8.28 mm); anteroposterior distance deviation, 2.92 mm (range, 0.03-8.49 mm); and intersegmental plane shift, 11.00° (range, 2.76-24.15°). Where the condyle was preserved, the intercoronoid and intergonial deviation means differed significantly (respectively 5.02 mm and 4.88 mm, both P < 0.05) for one-segmented and three-segmented fibular reconstructions. Furthermore, reconstructions involving the condylar region compared with condyle preservation showed significantly different intersegmental plane shifts (7.18°; P < 0.05).
Conclusion: Computer-assisted surgery provides cutting guides for obtaining accurate fibular segments, but current fixation methods lead to inaccuracies and reproducibility errors. In multisegmental transfer with condylar involvement, computer-assisted fixation is recommended to ensure accuracy of the preoperative plan.
Keywords: Computer-aided design; Computer-aided manufacturing; Data accuracy; Fibula; Head and neck neoplasms; Imaging, three-dimensional; Mandibular reconstruction; Printing, three-dimensional; Surgery; Surgical fixation devices.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
Cited by 1 article
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3
Exp Cell Res
. 2019 Oct 15;383(2):111508. doi: 10.1016/j.yexcr.2019.111508. Epub 2019 Jul 26.
In Vitro Humanized 3D Microfluidic Chip for Testing Personalized Immunotherapeutics for Head and Neck Cancer Patients
Ahmed Al-Samadi 1, Benedek Poor 2, Katja Tuomainen 3, Ville Liu 3, Aini Hyytiäinen 3, Ilida Suleymanova 3, Karri Mesimaki 4, Tommy Wilkman 4, Antti Mäkitie 5, Päivi Saavalainen 2, Tuula Salo 6
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PMID: 31356815 DOI: 10.1016/j.yexcr.2019.111508
Abstract
Objectives: Immunotherapy and personalized medicine therapeutics are emerging as promising approaches in the management of head and neck squamous cell carcinoma (HNSCC). In spite of that, there is yet no assay that could predict individual response to immunotherapy.
Methods: We manufactured an in vitro 3D microfluidic chip to test the efficacy of immunotherapy. The assay was first tested using a tongue cancer cell line (HSC-3) embedded in a human tumour-derived matrix "Myogel/fibrin" and immune cells from three healthy donors. Next, the chips were used with freshly isolated cancer cells, patients' serum and immune cells. Chips were loaded with different immune checkpoint inhibitors, PD-L1 antibody and IDO 1 inhibitor. Migration of immune cells towards cancer cells and the cancer cell proliferation rate were evaluated.
Results: Immune cell migration towards HSC-3 cells was cancer cell density dependent. IDO 1 inhibitor induced immune cells to migrate towards cancer cells both in HSC-3 and in two HNSCC patient samples. Efficacy of PD-L1 antibody and IDO 1 inhibitor was patient dependent.
Conclusion: We introduced the first humanized in vitro microfluidic chip assay to test immunotherapeutic drugs against HNSCC patient samples. This assay could be used to predict the efficacy of immunotherapeutic drugs for individual patients.
Keywords: Head and neck cancer; IDO1; Immunotherapy; In vitro; Microfuidic chip; PD-L1; Personalized medicine.
Copyright © 2019 Elsevier Inc. All rights reserved.
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4
Review Neuroimaging Clin N Am
. 2020 Aug;30(3):295-309. doi: 10.1016/j.nic.2020.04.002.
Technical Improvements in Head and Neck MR Imaging: At the Cutting Edge
Gregory Avey 1
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PMID: 32600632 DOI: 10.1016/j.nic.2020.04.002
Abstract
Head and neck MR imaging is technically challenging because of magnetic field inhomogeneity, respiratory and swallowing motion, and necessity of high-resolution imaging to trace key anatomic structures. These challenges have been answered by advances in MR imaging technology, including isovolumetric three-dimensional imaging, robust fat-water separation techniques, and novel deep learning-based reconstruction algorithms. New applications of MR imaging have been advanced and functional imaging has been improved. Improvements in acquisition and reconstruction technique facilitate novel applications of morphologic and functional imaging. This results in opportunities to improve diagnosis, staging, and treatment selection through application of advanced MR imaging techniques.
Keywords: Compressed sensing; Deep learning; Dixon; Head and neck; MR imaging; PET/MR imaging; ZTE.
Copyright © 2020 Elsevier Inc. All rights reserved.
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5
Review Laryngoscope
. 2020 Jan;130(1):45-51. doi: 10.1002/lary.27850. Epub 2019 Feb 1.
A Contemporary Review of Machine Learning in Otolaryngology-Head and Neck Surgery
Matthew G Crowson 1, Jonathan Ranisau 2, Antoine Eskander 1 3, Aaron Babier 2, Bin Xu 4, Russel R Kahmke 5, Joseph M Chen 1, Timothy C Y Chan 2
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PMID: 30706465 DOI: 10.1002/lary.27850
Abstract
One of the key challenges with big data is leveraging the complex network of information to yield useful clinical insights. The confluence of massive amounts of health data and a desire to make inferences and insights on these data has produced a substantial amount of interest in machine-learning analytic methods. There has been a drastic increase in the otolaryngology literature volume describing novel applications of machine learning within the past 5 years. In this timely contemporary review, we provide an overview of popular machine-learning techniques, and review recent machine-learning applications in otolaryngology-head and neck surgery including neurotology, head and neck oncology, laryngology, and rhinology. Investigators have realized significant success in validated models with model sensitivities and specificities approaching 100%. Challenges remain in the implementation of machine-learning algorithms. This may be in part the unfamiliarity of these techniques to clinician leaders on the front lines of patient care. Spreading awareness and confidence in machine learning will follow with further validation and proof-of-value analyses that demonstrate model performance superiority over established methods. We are poised to see a greater influx of machine-learning applications to clinical problems in otolaryngology-head and neck surgery, and it is prudent for providers to understand the potential benefits and limitations of these technologies. Laryngoscope, 130:45-51, 2020.
Keywords: Machine learning; and rhinology; artificial intelligence; head and neck oncology; laryngology; neural networks; neurotology.
© 2019 The American Laryngological, Rhinological and Otological Society, Inc.
Cited by 3 articles40 references
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6
Theranostics
. 2019 Apr 13;9(9):2424-2438. doi: 10.7150/thno.30941. eCollection 2019.
EBV(LMP1)-induced Metabolic Reprogramming Inhibits Necroptosis Through the Hypermethylation of the RIP3 Promoter
Feng Shi 1 2 3, Min Zhou 1 2 3, Li Shang 4, Qianqian Du 1 2 3, Yueshuo Li 1 2 3, Longlong Xie 1 2 3, Xiaolan Liu 1 2 3, Min Tang 1 2 3, Xiangjian Luo 1 2 3, Jia Fan 5, Jian Zhou 5, Qiang Gao 5, ShuangJian Qiu 5, Weizhong Wu 5, Xin Zhang 6, Ann M Bode 7, Ya Cao 1 2 3 8 9
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PMID: 31131045 PMCID: PMC6525991 DOI: 10.7150/thno.30941
Free PMC article
Abstract
EBV infection is a recognized epigenetic driver of carcinogenesis. We previously showed that EBV could protect cancer cells from TNF-induced necroptosis. This study aims to explore the epigenetic mechanisms allowing cancer cells with EBV infection to escape from RIP3-dependent necroptosis. Methods: Data from the TCGA database were used to evaluate the prognostic value of RIP3 promoter methylation and its expression. Western blotting, real-time PCR, and immunochemistry were conducted to investigate the relationship between LMP1 and RIP3 in cell lines and NPC tissues. BSP, MSP and hMeDIP assays were used to examine the methylation level. Induction of necroptosis was detected by cell viability assay, p-MLKL, and Sytox Green staining. Results: RIP3 promoter hypermethylation is an independent prognostic factor of poorer disease-free and overall survival in HNSCC patients, respectively. RIP3 is down-regulated in NPC (a subtype of HNSCC). EBV(LMP1) suppresses RIP3 expression by hypermethylation of the RIP3 promoter. RIP3 protein expression was inversely correlated with LMP1 expression in NPC tissues. Restoring RIP3 expression in EBV(LMP1)-positive cells inhibits xenograft tumor growth. The accumulation of fumarate and reduction of α-KG in EBV(LMP1)-positive cells led to RIP3 silencing due to the inactivation of TETs. Decreased FH activity caused fumarate accumulation, which might be associated with its acetylation. Incubating cells with fumarate protected NPC cells from TNF-induced necroptosis. Conclusion: These results demonstrate a pathway by which EBV(LMP1)-associated metabolite changes inhibited necroptosis signaling by DNA methylation, and shed light on the mechanism underlying EBV-related carcinogenesis, which may provide new options for cancer diagnosis and therapy.
Keywords: Epstein-Barr virus; Fumarate.; Nasopharyngeal carcinoma; Necroptosis; Receptor-interacting protein 3.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interest exists.
Cited by 3 articles46 references8 figures
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7
JAMA Netw Open
. 2019 Sep 4;2(9):e199292. doi: 10.1001/jamanetworkopen.2019.9292.
Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk
Xue Xu 1 2 3 4, Jianqiang Li 1, Jinfeng Zou 5, Xiaowen Feng 2 3 4 6, Chao Zhang 7, Ruiqing Zheng 2 3 4 8, Weixiang Duanmu 7, Arnab Saha-Mandal 2 3, Zhong Ming 1, Edwin Wang 2 3 4 9 10 11
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PMID: 31483464 PMCID: PMC6727785 DOI: 10.1001/jamanetworkopen.2019.9292
Free PMC article
Abstract
Importance: Only a small fraction of patients with cancer receiving immune checkpoint therapy (ICT) respond, which is associated with tumor immune microenvironment (TIME) subtypes and tumor-infiltrating lymphocytes (TILs).
Objective: To examine whether germline variants of natural killer (NK) cells, a key component of the immune system, are associated with TIME subtypes, the abundance of TILs, response to ICT, clinical outcomes, and cancer risk.
Design, setting, and participants: This genetic association study explored TIME subtypes and examined the association of the germline genomic information of patients with cancer with TIME subtypes, abundance of TILs, response to ICT, prognosis, and cancer risk. Clinical information, tumor RNA sequencing, and whole-exome sequencing (WES) data of paired normal samples of patients with 13 common cancers (n = 5883) were obtained from the Cancer Genome Atlas. The WES data of individuals with no cancer (n = 4500) were obtained from the database of Genotypes and Phenotypes. Data collection and analysis took place in March 2017.
Main outcomes and measures: Associations between the number of germline defective genes in NK cells and survival time and the abundance of TILs.
Results: Based on tumor RNA sequencing data, tumors were stratified into TIME-rich, TIME-intermediate, and TIME-poor subtypes. Tumors of TIME-rich subtype had more TILs (TIL-NK cells in TIME-rich head and neck squamous cell carcinoma [HNSC] tumors: t = 4.85; 95% CI of the difference, 0.01-0.03; P = 2.19 × 10-6) compared with TIME-intermediate HNSC tumors (t = 3.70; 95% CI of the difference, 0.01-0.03; P < .001), better prognosis (patients with HNSC: hazard ratio, 0.65; 95% CI, 0.41-1.02; P = .054) compared with TIME-intermediate and TIME-poor subtypes, and better ICT response (patients with melanoma: odds ratio [OR], 4.45; 95% CI, 0.99-27.08; P = .04). Patients with TIME-rich tumors had significantly fewer inherited defective genes in NK cells than patients with TIME-intermediate and TIME-poor tumors (patients with HNSC: OR, 0.49; 95% CI, 0.26-1.07; P = .005). Similarly, patients with cancer had significantly more inherited defective genes in NK cells than individuals with no cancer (patients with HNSC: OR, 19.09; 95% CI, 4.30-315.96; P = 6.21 × 10-4). Among 11 of 13 common cancers, the number of heritable defective genes in NK cells was significantly negatively associated with survival (patients with HNSC: hazard ratio, 1.77; 95% CI, 1.18-2.66; P = .005), abundance of TILs (patients with HNSC: R = -0.25; 95% CI, -0.65-2.17; P = 0.02), and response to ICT (patients with melanoma: OR, 4.45; 95% CI, 0.99-27.08; P = .04).
Conclusions and relevance: These results suggest that individuals who have more inherited defective genes in NK cells had a higher risk of developing cancer and that these inherited defects were associated with TIME subtypes, recruitment of TILs, ICT response, and clinical outcomes. The findings have implications for identifying individuals at risk for developing cancer of many types based on germline variants of NK cells and for improving existing ICT and chimeric antigen receptor-T cell therapy by adoptive transfer of healthy NK cells to patients with TIME-intermediate and TIME-poor tumors.
Conflict of interest statement
Conflict of Interest Disclosures: None reported.
Cited by 5 articles35 references5 figures
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8
Cancers (Basel)
. 2020 Jun 24;12(6):E1670. doi: 10.3390/cancers12061670.
Acquisition of Cisplatin Resistance Shifts Head and Neck Squamous Cell Carcinoma Metabolism Toward Neutralization of Oxidative Stress
Wangjie Yu 1, Yunyun Chen 2, Nagireddy Putluri 3, Cristian Coarfa 3 4 5, Matthew J Robertson 5, Vasanta Putluri 5, Fabio Stossi 3 5 6, Julien Dubrulle 3 5 6, Michael A Mancini 3 5 6, Jonathan C Pang 1, Trung Nguyen 1, Dodge Baluya 7, Jeffrey N Myers 2, Stephen Y Lai 2, Vlad C Sandulache 1
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PMID: 32599707 DOI: 10.3390/cancers12061670
Abstract
Background: Cisplatin (CDDP) is commonly utilized in the treatment of advanced solid tumors including head and neck squamous cell carcinoma (HNSCC). Cisplatin response remains highly variable among individual tumors and development of cisplatin resistance is common. We hypothesized that development of cisplatin resistance is partially driven by metabolic reprogramming. Methods: Using a pre-clinical HNSCC model and an integrated approach to steady state metabolomics, metabolic flux and gene expression data we characterized the interaction between cisplatin resistance and metabolic reprogramming. Results: Cisplatin toxicity in HNSCC was driven by generation of intra-cellular oxidative stress. This was validated by demonstrating that acquisition of cisplatin resistance generates cross-resistance to ferroptosis agonists despite the fact that cisplatin itself does not trigger ferroptosis. Acquisition of cisplatin resistance dysregulated the expression of genes involved in amino acid, fatty acid metabolism and central carbon catabolic pathways, enhanced glucose catabolism and serine synthesis. Acute cisplatin exposure increased intra-tumoral levels of S-methyl-5-thiadenosine (MTA) precursors and metabotoxins indicative of generalized oxidative stress. Conclusions: Acquisition of cisplatin resistance is linked to metabolic recovery from oxidative stress. Although this portends poor effectiveness for directed metabolic targeting, it supports the potential for biomarker development of cisplatin effectiveness using an integrated approach.
Keywords: amino acid; cisplatin; fatty acid; ferroptosis; head and neck cancer; oxidative stress.
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9
Appl Ergon
. 2020 Feb;83:102679. doi: 10.1016/j.apergo.2018.04.013. Epub 2018 May 4.
The Ipswich Microbreak Technique to Alleviate Neck and Shoulder Discomfort During Microscopic Procedures
Ananth Vijendren 1, Gavin Devereux 2, Aaron Tietjen 2, Kathy Duffield 3, Vincent Van Rompaey 4, Paul Van de Heyning 4, Matthew Yung 3
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PMID: 29735161 DOI: 10.1016/j.apergo.2018.04.013
Abstract
Neck and shoulder disorders are a considerable health problem amongst frequent microscope users. We aimed to investigate the neck and shoulder discomfort experienced during prolonged microscopic activity and to assess the benefits of minibreaks. A prospective crossover study was performed on 17 healthy volunteers sitting still while looking down a bench with and without the Ipswich Microbreak Technique (IMT). We used a subjective measure of time to fatigue and pain in the neck and shoulder regions as well as objective readings from a surface electromyogram (sEMG). The IMT delayed the sensation of pain in the neck and shoulder region while reducing the overall sEMG muscle activation. In conclusion, IMT is a useful strategy in reducing and delaying the pain in neck and shoulder from prolonged working under the microscope. This technique can be incorporated in other activities that involve a sustained stationary position.
Keywords: Micropauses; Microscope; Mini-breaks; Neck pain; Work-related musculoskeletal disorders.
Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.
Cited by 1 article
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10
World J Surg Oncol
. 2020 Jun 27;18(1):145. doi: 10.1186/s12957-020-01923-7.
BRAF V600E Mutation, BRAF-activated Long Non-Coding RNA and miR-9 Expression in Papillary Thyroid Carcinoma, and Their Association With Clinicopathological Features
Chenlei Shi 1, Jia Cao 2, Tiefeng Shi 3, Meihua Liang 1, Chao Ding 1, Yichen Lv 1, Weifeng Zhang 1, Chuanle Li 1, Wenchao Gao 4, Gang Wu 1, Jianting Man 1
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PMID: 32593310 DOI: 10.1186/s12957-020-01923-7
Free article
Abstract
Background: The incidence of thyroid cancer is increasing worldwide. This study investigated the association of B-type RAF kinase (BRAF)V600E mutation status, the expression of BRAF-activated long non-coding RNA (BANCR) and microRNA miR-9, and the clinicopathological features of papillary thyroid carcinoma (PTC).
Methods: Clinicopathological data for PTC patients (n = 51) diagnosed and treated between 2018 and 2019 were collected. Carcinoma and adjacent normal tissue samples were analyzed for the presence of the BRAFV600E mutation and/or expression of BANCR and miR-9.
Results: Larger tumor, higher rate of bilateral tumors and multifocality, extracapsular invasion, and lateral lymph node metastasis (LNM) were observed in PTC patients with BRAF V600E mutation. Patients with higher BANCR expression had a higher rate of extracapsular invasion and lateral LNM in carcinoma tissue and a lower frequency of bilateral tumors and multifocality in normal adjacent tissue. Patients with higher miR-9 expression had a lower rate of central and lateral LNM in carcinoma tissue and higher rates of bilateral tumor location and multifocality in normal adjacent tissue. Patients with BRAFV600E mutation have a higher rate of BANCR overexpression and tended to have a lower rate of miR-9 overexpression (P = 0.057), and a negative association was observed between BANCR and miR-9 expression in carcinoma tissue.
Conclusions: BRAFV600E mutation and the BANCR and miR-9 expression were closely associated with the tumor size, bilateral tumor location, multifocality, extracapsular invasion, and lateral LNM. PTC patients with these clinicopathological characteristics, BRAFV600E mutation, and high BANCR expression and low miR-9 expression needed earlier surgical treatment and are recommended for total thyroidectomy in primary surgery for reducing the risk of recurrence. These findings provide new insight into the molecular basis for PTC and can inform strategies for the management of PTC.
Keywords: BRAF V600E mutation; BRAF-activated long non-coding RNA; Papillary thyroid carcinoma; miR-9.
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11
Otolaryngol Head Neck Surg
. 2020 Mar;162(3):367-374. doi: 10.1177/0194599819900762. Epub 2020 Jan 21.
Otitis Media Middle Ear Effusion Identification and Characterization Using an Optical Coherence Tomography Otoscope
Diego Preciado 1 2, Ryan M Nolan 3, Radhika Joshi 1 2, Gina M Krakovsky 1, Anqi Zhang 3, Nickolas A Pudik 3, Nankee K Kumar 2, Ryan L Shelton 3, Stephen A Boppart 3, Nancy M Bauman 1
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PMID: 31959053 PMCID: PMC7289273 (available on 2021-03-01) DOI: 10.1177/0194599819900762
Free PMC article
Abstract
Objective: To determine the feasibility of detecting and differentiating middle ear effusions (MEEs) using an optical coherence tomography (OCT) otoscope.
Study design: Cross-sectional study.
Setting: US tertiary care children's hospital.
Subjects and methods: Seventy pediatric patients undergoing tympanostomy tube placement were preoperatively imaged using an OCT otoscope. A blinded reader quiz was conducted using 24 readers from 4 groups of tiered medical expertise. The primary outcome assessed was reader ability to detect presence/absence of MEE. A secondary outcome assessed was reader ability to differentiate serous vs nonserous MEE.
Results: OCT image data sets were analyzed from 45 of 70 total subjects. Blinded reader analysis of an OCT data subset for detection of MEE resulted in 90.6% accuracy, 90.9% sensitivity, 90.2% specificity, and intra/interreader agreement of 92.9% and 87.1%, respectively. Differentiating MEE type, reader identification of nonserous MEE had 70.8% accuracy, 53.6% sensitivity, 80.1% specificity, and intra/interreader agreement of 82.9% and 75.1%, respectively. Multivariate analysis revealed that age was the strongest predictor of OCT quality. The mean age of subjects with quality OCT was 5.01 years (n = 45), compared to 2.54 years (n = 25) in the remaining subjects imaged (P = .0028). The ability to capture quality images improved over time, from 50% to 69.4% over the study period.
Conclusion: OCT otoscopy shows promise for facilitating accurate MEE detection. The imageability with the prototype device was affected by age, with older children being easier to image, similar to current ear diagnostic technologies.
Keywords: acute otitis media; imaging; middle ear effusion; optical coherence tomography; otitis media; otitis media with effusion; otoscopy; pediatric.
Cited by 2 articles
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12
J Int Med Res
. 2020 Jun;48(6):300060520927918. doi: 10.1177/0300060520927918.
Histological Transformation of Lung Adenocarcinoma to Small Cell Lung Cancer With Mutant C797S Conferring Acquired Resistance to Osimertinib
Xiaohui Ren 1, Xinfeng Cai 2, Jing Li 1, Xia Zhang 1, Jianfei Yu 3, Xin Song 4, Henghui Zhang 5, Xia Song 1
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PMID: 32600081 DOI: 10.1177/0300060520927918
Abstract
Epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer may initially respond to EGFR tyrosine kinase inhibitors (TKIs), but may subsequently become resistant; however, the resistance mechanisms remain unclear. We report a rare case of acquired resistance to osimertinib associated with transformation to small cell lung cancer (SCLC) with cis-C797S mutation. A man with recurrent lung adenocarcinoma harboring an EGFR exon 19 deletion received erlotinib for 10 months following curative surgery and adjuvant chemotherapy. However, he switched to osimertinib after repeat biopsy showed EGFR exon 19 deletion and T790M mutation leading to erlotinib resistance. His disease progressed after 15 months and repeat biopsy showed SCLC. Next-generation sequencing of peripheral blood detected EGFR exon 19 deletion, T790M mutation, cis-C797S mutation, and RB1 inactivation. The tumor was reduced after four cycles of etoposide and cisplatin and his respiratory symptoms improved. However, computed tomography after six cycles of chemotherapy showed multiple bilateral lung lesions, and single-photon emission computed tomography showed bone metastasis. The patient received paclitaxel plus cisplatin for two cycles with partial response. Because heterogeneous genetic and phenotypic mechanisms of TKI-resistance may occur at different times and locations, histopathological and molecular testing both provide evidence to support appropriate treatment.
Keywords: C797S; Osimertinib; acquired resistance; epidermal growth factor receptor tyrosine kinase inhibitor; histological transformation; lung adenocarcinoma; small cell lung carcinoma.
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13
Clinical Trial Eur J Cancer
. 2020 Jan;124:178-185. doi: 10.1016/j.ejca.2019.10.025. Epub 2019 Nov 30.
Concurrent Cisplatin or Cetuximab With Radiotherapy for HPV-positive Oropharyngeal Cancer: Medical Resource Use, Costs, and Quality-Adjusted Survival From the De-ESCALaTE HPV Trial
David A Jones 1, Pankaj Mistry 2, Matthew Dalby 2, Tessa Fulton-Lieuw 3, Anthony H Kong 3, Janet Dunn 2, Hisham M Mehanna 3, Alastair M Gray 4
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PMID: 31794928 PMCID: PMC6947474 DOI: 10.1016/j.ejca.2019.10.025
Free PMC article
Abstract
Background: The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence.
Materials and methods: Resource use and HRQoL data were collected at intervals from the baseline to 24 months post treatment (PT). Health care costs were estimated using UK-based unit costs. Missing data were imputed. Differences in mean EQ-5D-5L utility index and adjusted cumulative quality-adjusted life years (QALYs) were compared using the Wilcoxon signed-rank test and linear regression, respectively. Mean resource usage and costs were compared through two-sample t-tests.
Results: 334 patients were randomised to cisplatin (n = 166) or cetuximab (n = 168). Two-year overall survival (97·5% vs 90·0%, HR: 3.268 [95% CI 1·451 to 7·359], p = 0·0251) and recurrence rates (6·4% vs 16·0%, HR: 2·67 [1·38 to 5·15]; p = 0·0024) favoured cisplatin. No significant differences in EQ-5D-5L utility scores were detected at any time point. At 24 months PT, mean difference was 0·107 QALYs in favour of cisplatin (95% CI: 0·186 to 0·029, p = 0·007) driven by the mortality difference. Health care costs were similar across all categories except the procurement cost and delivery of the systemic agent, with cetuximab significantly more expensive than cisplatin (£7779 [P < 0.001]). Consequently, total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab (mean difference £7547 [95% CI: £6512 to £8582]).
Conclusions: Cisplatin chemoradiotherapy provided more QALYs and was less costly than cetuximab bioradiotherapy, remaining standard of care for nonsurgical treatment of HPV-positive OPSCC.
Keywords: Cetuximab; Chemoradiotherapy; Cisplatin; Costs; Human papillomavirus; Oropharyngeal squamous cell carcinoma; Overall survival; Quality of life; Recurrence; Resource use.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Hisham Mehanna reports personal fees from Warwickshire Head Neck Clinic Ltd, AstraZeneca, MSD, Sanofi Pasteur, and Merck; grants from GlaxoSmithKline Biologicals, MSD, Sanofi Pasteur, Silence Therapeutics, GlaxoSmithKline, AstraZeneca, and several academic funders including the National Institute for Health Research (NIHR) Health Technology Assessment Unit, Cancer Research UK, and the Medical Research Council; and travel expenses from Sanofi Pasteur, MSD, and Merck, outside the submitted work.
All other authors declare no conflict of interests.
Cited by 1 article26 references3 figures
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14
Br J Cancer
. 2020 Jun 30. doi: 10.1038/s41416-020-0943-2. Online ahead of print.
EGFR/Ras-induced CCL20 Production Modulates the Tumour Microenvironment
Andreas Hippe 1, Stephan Alexander Braun 1 2, Péter Oláh 1 3, Peter Arne Gerber 1, Anne Schorr 1, Stephan Seeliger 4, Stephanie Holtz 1, Katharina Jannasch 5, Andor Pivarcsi 6, Bettina Buhren 1, Holger Schrumpf 1, Andreas Kislat 1, Erich Bünemann 1, Martin Steinhoff 7, Jens Fischer 8, Sérgio A Lira 9, Petra Boukamp 10, Peter Hevezi 11, Nikolas Hendrik Stoecklein 12, Thomas Hoffmann 13, Frauke Alves 5, Jonathan Sleeman 14 15, Thomas Bauer 16, Jörg Klufa 16, Nicole Amberg 16 17, Maria Sibilia 16, Albert Zlotnik 18, Anja Müller-Homey 19, Bernhard Homey 20
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PMID: 32601464 DOI: 10.1038/s41416-020-0943-2
Abstract
Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.
Methods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.
Results: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.
Conclusion: We propose that the chemokine axis CCL20-CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.
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15
Eur Ann Otorhinolaryngol Head Neck Dis
. 2020 Jun 26;S1879-7296(20)30147-2. doi: 10.1016/j.anorl.2020.06.008. Online ahead of print.
Pasteurella Multocida Acute Epiglottitis
L Jan 1, P Boute 2, F Mouawad 3
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PMID: 32600824 DOI: 10.1016/j.anorl.2020.06.008
Abstract
Introduction: Apart from cases related to direct inoculation, pasteurellosis is a rare opportunistic infection occurring in predisposed subjects. Close contact with domestic animals, usually cats, is generally reported. Localized ENT forms are possible and are due to oropharyngeal carriage.
Case report: We present the case of a patient with no notable history, who presented with laryngeal dyspnea and hyperthermia leading to a diagnosis of acute epiglottitis. Bacteremia was detected and blood cultures were positive for Pasteurella multocida. Treatment consisted of the standard treatment for acute epiglottitis with hospitalisation and intravenous antibiotics.
Discussion: This patient presented a history of animal exposure, but no other known risk factors. The activity spectrum of antibiotic therapy for epiglottitis should include H. influenzae and this case illustrates the diversity of the micro-organisms potentially involved. Immunosuppression or another chronic disease does not appear to be a prerequisite for ENT infection.
Keywords: Epiglottitis; Pasteurella multocida; Septicemia; Zoonosis.
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
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16
Otolaryngol Head Neck Surg
. 2020 Mar;162(3):392-399. doi: 10.1177/0194599819900014. Epub 2020 Feb 4.
Prediction of Apnea-Hypopnea Index Using Sound Data Collected by a Noncontact Device
Jeong-Whun Kim 1, Taehoon Kim 2, Jaeyoung Shin 3, Kyogu Lee 3, Sunkyu Choi 4, Sung-Woo Cho 1
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PMID: 32013710 DOI: 10.1177/0194599819900014
Abstract
Objective: To predict the apnea-hypopnea index (AHI) in patients with obstructive sleep apnea (OSA) using data from breathing sounds recorded using a noncontact device during sleep.
Study design: Prospective cohort study.
Setting: Tertiary referral hospital.
Subject and methods: Audio recordings during sleep were performed using an air-conduction microphone during polysomnography. Breathing sounds recorded from all sleep stages were analyzed. After noise reduction preprocessing, the audio data were segmented into 5-second windows and sound features were extracted. Estimation of AHI by regression analysis was performed using a Gaussian process, support vector machine, random forest, and simple linear regression, along with 10-fold cross-validation.
Results: In total, 116 patients who underwent attended, in-laboratory, full-night polysomnography were included. Overall, random forest resulted in the highest performance with the highest correlation coefficient (0.83) and least mean absolute error (9.64 events/h) and root mean squared error (13.72 events/h). Other models resulted in somewhat lower but similar performances, with correlation coefficients ranging from 0.74 to 0.79. The estimated AHI tended to be underestimated as the severity of OSA increased. Regarding bias and precision, estimation performances in the severe OSA subgroup were the lowest, regardless of the model used. Among sound features, derivative of the area methods of moments of overall standard deviation demonstrated the highest correlation with AHI.
Conclusion: AHI was fairly predictable by using data from breathing sounds generated during sleep. The prediction model may be useful not only for prescreening but also for follow-up after treatment in patients with OSA.
Keywords: machine learning; obstructive sleep apnea; respiratory sound.
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17
Elife
. 2020 Jun 30;9:e55249. doi: 10.7554/eLife.55249.
Generation of Inner Ear Hair Cells by Direct Lineage Conversion of Primary Somatic Cells
Louise Menendez 1 2 3, Talon Trecek 1 2, Suhasni Gopalakrishnan 1 2 3, Litao Tao 1 2, Alexander L Markowitz 3 4, Haoze V Yu 1 2, Xizi Wang 1 2, Juan Llamas 1 2, Chichou Huang 5, James Lee 5, Radha Kalluri 3 4, Justin Ichida 1 2 3, Neil Segil 1 2 4
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PMID: 32602462 DOI: 10.7554/eLife.55249
Free article
Abstract
The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular dysfunction. Their paucity and inaccessibility has limited the search for otoprotective and regenerative strategies. Growing hair cells in vitro would provide a route to overcome this experimental bottleneck. We report a combination of four transcription factors (Six1, Atoh1, Pou4f3, and Gfi1) that can convert mouse embryonic fibroblasts, adult tail-tip fibroblasts and postnatal supporting cells into induced hair cell-like cells (iHCs). iHCs exhibit hair cell-like morphology, transcriptomic and epigenetic profiles, electrophysiological properties, mechanosensory channel expression, and vulnerability to ototoxin in a high-content phenotypic screening system. Thus, direct reprogramming provides a platform to identify causes and treatments for hair cell loss, and may help identify future gene therapy approaches for restoring hearing.
Keywords: developmental biology; inner ear; mouse; ototoxin; regeneration; regenerative medicine; reprogramming; screening; sensory hair cell; stem cells.
Plain Language Summary
Worldwide, hearing loss is the most common loss of sensation. Most cases of hearing loss are due to the death of specialized hair cells found deep inside the ear. These hair cells convert sounds into nerve impulses which can be understood by the brain. Hair cells naturally degrade as part of aging and can be damaged by other factors including loud noises, and otherwise therapeutic drugs, such as those used in chemotherapy for cancer. In humans and other mammals, once hair cells are lost they cannot be replaced. Hair cells have often been studied using mice, but the small number of hair cells in their ears, and their location deep inside the skull, makes it particularly difficult to study them in this way. Scientists are seeking ways to grow hair cells in the laboratory to make it easier to understand how they work and the factors that contribute to their damage and loss. Different cell types in the body are formed in response to specific combinations of biological signals. Currently, scientists do not have an efficient way to grow hair cells in the laboratory, because the correct signals needed to create them are not known. Menendez et al. have now identified four proteins which, when activated, convert fibroblasts, a common type of cell, into hair cells similar to those in the ear. These proteins are called Six1, Atoh1, Pou4f3 and Gfi1. Menendez et al. termed the resulting cells induced hair cells, or iHCs for short, and analyzed these cells to identify those characteristics that are similar to normal hair cells, as well as their differences. Importantly, the iHCs were found to be damaged by the same chemicals that specifically harm normal hair cells, suggesting they are useful test subjects. The ability to create hair cells in the laboratory using more easily available cells has many uses. These cells can help to understand the normal function of hair cells and how they become damaged. They can also be used to test new drugs to assess their success in preventing or reversing hearing loss. These findings may also lead to genetic solutions to curing hearing loss.
© 2020, Menendez et al.
Conflict of interest statement
LM, TT, LT, AM, HY, XW, JL, RK, JI, NS No competing interests declared, SG Currently employed at a for-profit corporation, Allogene. This company has no competing technology, nor is it involved in this research. CH, JL Employed by a for-profit company that will benefit from the software development that they contributed to this project.
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18
Otolaryngol Head Neck Surg
. 2020 Mar;162(3):343-345. doi: 10.1177/0194599820901684. Epub 2020 Jan 21.
A Surgical Simulator for Tympanostomy Tube Insertion Incorporating Capacitive Sensing Technology to Track Instrument Placement
Vilija J Vaitaitis 1, Michael E Dunham 1, Yong-Chan Kwon 2, Wyatt C Mayer 1, Adele K Evans 1, Amari J Baker 2, Kyla D Walker 2, Gabriel D Cespedes 2, Abishek Stanley 2, Michelle Opiri 2
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PMID: 31961771 DOI: 10.1177/0194599820901684
Abstract
We describe a device engineered for realistic simulation of myringotomy and tympanostomy tube insertion that tracks instrument placement and objectively measures operator proficiency. A 3-dimensional computer model of the external ear and cartilaginous external auditory canal was created from a normal maxillofacial computed tomography scan, and models for the bony external auditory canal and tympanic cavity were created with computer-aided design software. Physical models were 3-dimensionally printed from the computer reconstructions. The external auditory canal and tympanic cavity surfaces were coated with conductive material and wired to a capacitive sensor interface. A programmable microcontroller with custom embedded software completed the system. Construct validation was completed by comparing the run times and total sensor contact times of otolaryngology faculty and residents.
Keywords: 3D printing; capacitive sensing; surgical simulator; surgical training; tympanostomy tube.
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19
Review Otolaryngol Head Neck Surg
. 2020 Feb;162(2):177-180. doi: 10.1177/0194599819897067. Epub 2019 Dec 24.
Navigating the Informed Consent Process When Using Innovative Surgery
Daniel Wehrmann 1, Glenn E Green 1, Kevin J Weatherwax 2, Andrew G Shuman 1 3
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PMID: 31874066 DOI: 10.1177/0194599819897067
Abstract
No abstract available
Keywords: expanded access; research ethics; surgical innovation.
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20
Allergy
. 2020 Jun 26. doi: 10.1111/all.14471. Online ahead of print.
ARIA-EAACI Statement on Asthma and COVID-19 (June 2, 2020)
Jean Bousquet 1 2 3, Marek Jutel 4, Cezmi A Akdis 5, Ludger Klimek 6, Oliver Pfaar 7, Kari C Nadeau 8, Thomas Eiwegger 9, Anna Bedbrook 3, Ignacio J Ansotegui 10, Josep M Anto 11 12 13 14, Claus Bachert 15 16 17 18, Eric D Bateman 19, Kazi S Bennoor 20, Emilia Camelia Berghea 21, Karl-Christian Bergmann 1, Hubert Blain 22 23, Mateo Bonini 24 25, Sinthia Bosnic-Anticevich 26, Louis-Philippe Boulet 27, Luisa Brussino 28, Roland Buhl 29, Paulo Camargos 30, G Walter Canonica 31, Victoria Cardona 32, Thomas Casale 33, Sharon Chinthrajah 8, Mübeccel Akdis 5, Tomas Chivato 34, George Christoff 35, Alvaro A Cruz 36, Wienczyslawa Czarlewski 37, Stefano Del Giacco 38, Hui Du 39, Yehia El-Gamal 40, Wytske J Fokkens 41, Joao A Fonseca 42 43 44 45, Yadong Gao 39, Mina Gaga 46, Bilun Gemicioglu 47, Maia Gotua 48, Tari Haahtela 49, David Halpin 50, Eckard Hamelmann 51, Karin Hoffmann-Sommergruber 52, Marc Humbert 53, Nataliya Ilina 54, Juan-Carlos Ivancevich 55, Guy Joos 56, Musa Khaitov 54, Bruce Kirenga 57, Edward F Knol 58, Fanny W Ko 59, Seppo Koskinen 60, Marek L Kowalski 61, Helga Kraxner 62, Dmitri Kudlay 54, Piotr Kuna 63, Maciej Kupczyk 63, Violeta Kvedariene 64, Amir H Abdul Latiff 65, Lan T Le 66, Michael Levin 67, Desiree Larenas-Linnemann 68, Renaud Louis 69, Mohammad R Masjedi 70, Erik Melén 71, Florin Mihaltan 72, Branislava Milenkovic 73, Yousser Mohammad 74, Mario Morais-Almeida 75, Joaquim Mullol 76, Leyla Namazova 77, Hugo Neffen 78, Elisabete Nunes 79, Paul O'Byrne 80, Robyn O'Hehir 81, Liam O'Mahony 82, Ken Ohta 83, Yoshitaka Okamoto 84, Gabrielle L Onorato 3, Petr Panzner 85, Nikos G Papadopoulos 86, Gianni Passalacqua 87, Vincenzo Patella 88, Ruby Pawankar 89, Nhân Pham-Thi 90, Bernard Pigearias 91, Todor A Popov 92, Francesca Puggioni 31, Frederico S Regateiro 93, Giovanni Rolla 28, Menachem Rottem 94, Boleslaw Samolinski 95, Joaquin Sastre 96, Jurgen Schwarze 97, Aziz Sheikh 98, Nicola Scichilone 99, Manuel Soto-Quiros 100, Milan Sova 101, Stefania Nicola 28, Rafael Stelmach 102, Charlotte Suppli-Ulrik 103, Luis Taborda-Barata 104 105, Teresa To 106, Peter-Valentin Tomazic 107, Sanna Toppila-Salmi 49, Ioanna Tsiligianni 108 109, Omar Usmani 110, Arunas Valiulis 111 112, Maria Teresa Ventura 113, Giovanni Viegi 114, Theodor Vontetsianos 115, De Yun Wang 116, Sian Williams 117, Gary Wk Wong 118, Arzu Yorgancioglu 119, Mario Zernotti 120, Mihaela Zidarn 121, Torsten Zuberbier 1, Ioana Agache 122
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PMID: 32588922 DOI: 10.1111/all.14471
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