1
Clin Epigenetics
. 2019 Nov 20;11(1):161. doi: 10.1186/s13148-019-0752-8.
Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma
Tobias A W Holderried 1, Luka de Vos 2, Emma Grace Bawden 3 4 5, Timo J Vogt 2, Joern Dietrich 2, Romina Zarbl 2, Friedrich Bootz 2, Glen Kristiansen 6, Peter Brossart 1, Jennifer Landsberg 7, Dimo Dietrich 8
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PMID: 31747929 PMCID: PMC6868848 DOI: 10.1186/s13148-019-0752-8
Free PMC article
Abstract
Background: The T cell immunoglobulin and mucin-domain containing-3 receptor TIM-3 (also known as hepatitis A virus cellular receptor 2, encoded by HAVCR2) and its ligand galectin 9 (LGALS9) are promising targets for immune checkpoint inhibition immunotherapies. However, little is known about epigenetic regulation of the encoding genes. This study aimed to investigate the association of TIM-3 and LGALS9 DNA methylation with gene expression, patients' survival, as well as molecular and immune correlates in malignant melanoma.

Results: Methylation of all six TIM-3 CpGs correlated significantly with TIM-3 mRNA levels (P ≤ 0.05). A strong inverse correlation (Spearman's ρ = - 0.49) was found in promoter regions, while a strong positive correlation (ρ = 0.63) was present in the gene body of TIM-3. High TIM-3 mRNA expression (hazard ratio (HR) = 0.88, 95% confidence interval (CI) [0.81-0.97], P = 0.007) was significantly associated with better overall survival. Seven of the eight LGALS9 CpG sites correlated significantly with LGALS9 mRNA levels (P ≤ 0.003). Methylation at five CpG sites showed a strong inverse correlation (Spearman's ρ = - 0.67) and at two sites a weak positive correlation (Spearman's ρ = 0.15). High LGALS9 mRNA expression was significantly associated with increased overall survival (HR = 0.83, 95%CI [0.75-0.93], P = 0.001). In addition, we found significant correlations between TIM-3 and LGALS9 methylation and mRNA expression with immune cell infiltrates and significant differences among distinct immune cell subsets.

Conclusions: Our study points toward an epigenetic regulation of TIM-3 and LGALS9 via DNA methylation and might provide an avenue for the development of a predictive biomarker for response to immune checkpoint blockade.

Keywords: Biomarker; DNA methylation; Galectin 9; HAVCR2; Immunotherapy; LGALS9; Melanoma; Prediction; Prognosis; TIM-3.

Conflict of interest statement
Dimo Dietrich owns patents and patent applications on biomarker technologies and methylation of immune checkpoint genes as predictive and prognostic biomarkers (DE 10 2016 005 947.8, DE 10 2015 009 187.5, DE 10 2017 125 780.2, PCT/EP2016/001237). The patents are licensed to Qiagen GmbH (Hilden, Germany). Dimo Dietrich is a consultant of Qiagen. The University Hospital Bonn (PI Dimo Dietrich) receives research funding from Qiagen. The other authors have declared that no conflict of interest exists.

70 references6 figures
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2
Review Curr Treat Options Oncol
. 2019 Mar 14;20(4):32. doi: 10.1007/s11864-019-0631-8.
Contemporary Treatment of Locally Advanced Oral Cancer
David Kim 1, Ryan Li 2
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PMID: 30874958 DOI: 10.1007/s11864-019-0631-8
Abstract
At our institution, locally advanced oral cancer is most commonly treated with surgical resection, immediate reconstruction, and adjuvant radiotherapy with or without concurrent systemic therapy depending on final surgical pathologic analysis. There are patients with markedly advanced local or regional disease who unfortunately will have a low probability of cure. We counsel these patients on induction chemotherapy, emphasizing that this is unlikely to result in a smaller volume of surgical resection. In these patients, a good response to induction chemotherapy is more frequently followed by concurrent chemoradiotherapy. We have not been in the practice of commonly recommending definitive chemoradiotherapy for locally advanced oral cancer when upfront surgery is an option. However, as reviewed below, there is a significant rationale for definitive chemoradiotherapy in patients who are surgical candidates, with the hope of good oncologic outcomes, and potential functional organ preservation. The experts who report their experiences in the studies reviewed below provide a strong argument for considering this approach.

Keywords: Immunotherapy; Neoadjuvant therapy; Oral cavity squamous cell carcinoma; Outcome; Primary chemoradiotherapy; Treatment.

Cited by 1 article29 references
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3
Review Expert Rev Neurother
. 2019 Feb;19(2):145-157. doi: 10.1080/14737175.2019.1561285. Epub 2019 Jan 9.
Multidisciplinary care for people with Parkinson's disease: the new kids on the block!
Danique L M Radder 1, Nienke M de Vries 1, Niels P Riksen 2, Sarah J Diamond 3, Ditza Gross 4, Daniel R Gold 5, John Heesakkers 6, Emily Henderson 7 8, Adrianus L A J Hommel 1 9, Herma H Lennaerts 2 10, Jane Busch 11 12, Ray E Dorsey 13, John Andrejack 14, Bastiaan R Bloem 1
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PMID: 30570362 DOI: 10.1080/14737175.2019.1561285
Abstract
Parkinson's disease (PD) is a chronic multisystem disorder that causes a wide variety of motor and non-motor symptoms. Over time, the progressive nature of the disease increases the risk of complications such as falls and loss of independence, having a profound impact on quality of life. The complexity and heterogeneity of symptoms therefore warrant a holistic, multidisciplinary approach. Specific healthcare professionals, e.g. the movement disorders neurologist and the PD nurse specialist, are considered essential members of this multidisciplinary team. However, with our increasing knowledge about different aspects of the disease, other disciplines are also being recognized as important contributors to the healthcare team. Areas covered: The authors describe a selection of these relatively newly-recognized disciplines, including the specialist in vascular medicine, gastroenterologist, pulmonologist, neuro-ophthalmologist, urologist, geriatrician/elderly care physician, palliative care specialist and the dentist. Furthermore, they share the view of a person with PD on how patients and caregivers should be involved in the multidisciplinary team. Finally, they have included a perspective on the new role of the movement disorder neurologist, with care delivery via 'tele-neurology'. Expert commentary: Increased awareness about the potential role of these 'new' professionals will further improve disease management and quality of life of PD patients.

Keywords: Parkinson’s disease; multidisciplinary care; non-motor symptoms; professional disciplines; self-management; tele-neurology; telemedicine.

Cited by 3 articles
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4
Ann Oncol
. 2019 Dec 1;30(12):1856-1883. doi: 10.1093/annonc/mdz400.
Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†
S Filetti 1, C Durante 1, D Hartl 2, S Leboulleux 3, L D Locati 4, K Newbold 5, M G Papotti 6, A Berruti 7, ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org
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PMID: 31549998 DOI: 10.1093/annonc/mdz400
No abstract available
Cited by 8 articles
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5
Review J Allergy Clin Immunol
. 2020 Jan;145(1):70-80.e3. doi: 10.1016/j.jaci.2019.06.049. Epub 2019 Oct 15.
Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence
Jean Bousquet 1, Holger J Schünemann 2, Akdis Togias 3, Claus Bachert 4, Martina Erhola 5, Peter W Hellings 6, Ludger Klimek 7, Oliver Pfaar 8, Dana Wallace 9, Ignacio Ansotegui 10, Ioana Agache 11, Anna Bedbrook 12, Karl-Christian Bergmann 13, Mike Bewick 14, Philippe Bonniaud 15, Sinthia Bosnic-Anticevich 16, Isabelle Bossé 17, Jacques Bouchard 18, Louis-Philippe Boulet 19, Jan Brozek 2, Guy Brusselle 20, Moises A Calderon 21, Walter G Canonica 22, Luis Caraballo 23, Vicky Cardona 24, Thomas Casale 25, Lorenzo Cecchi 26, Derek K Chu 2, Elisio M Costa 27, Alvaro A Cruz 28, Wienczyslawa Czarlewski 29, Gennaro D'Amato 30, Philippe Devillier 31, Mark Dykewicz 32, Motohiro Ebisawa 33, Jean-Louis Fauquert 34, Wytske J Fokkens 35, Joao A Fonseca 36, Jean-François Fontaine 37, Bilun Gemicioglu 38, Roy Gerth van Wijk 39, Tari Haahtela 40, Susanne Halken 41, Despo Ierodiakonou 42, Tomohisa Iinuma 43, Juan-Carlos Ivancevich 44, Marek Jutel 45, Igor Kaidashev 46, Musa Khaitov 47, Omer Kalayci 48, Jorg Kleine Tebbe 49, Marek L Kowalski 50, Piotr Kuna 51, Violeta Kvedariene 52, Stefania La Grutta 53, Désirée Larenas-Linnemann 54, Susanne Lau 55, Daniel Laune 56, Lan Le 57, Philipp Lieberman 58, Karin C Lodrup Carlsen 59, Olga Lourenço 60, Gert Marien 61, Pedro Carreiro-Martins 62, Erik Melén 63, Enrica Menditto 64, Hugo Neffen 65, Gregoire Mercier 66, Ralph Mosgues 67, Joaquim Mullol 68, Antonella Muraro 69, Leyla Namazova 70, Ettore Novellino 71, Robyn O'Hehir 72, Yoshitaka Okamoto 43, Ken Ohta 73, Hae Sim Park 74, Petr Panzner 75, Giovanni Passalacqua 76, Nhan Pham-Thi 77, David Price 78, Graham Roberts 79, Nicolas Roche 80, Christine Rolland 81, Nelson Rosario 82, Dermot Ryan 83, Boleslaw Samolinski 84, Mario Sanchez-Borges 85, Glenis K Scadding 86, Mohamed H Shamji 87, Aziz Sheikh 88, Ana-Maria Todo Bom 89, Sanna Toppila-Salmi 90, Ioana Tsiligianni 42, Marylin Valentin-Rostan 91, Arunas Valiulis 92, Erkka Valovirta 93, Maria-Teresa Ventura 94, Samantha Walker 95, Susan Waserman 96, Arzu Yorgancioglu 97, Torsten Zuberbier 13, Allergic Rhinitis and Its Impact on Asthma Working Group
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PMID: 31627910 DOI: 10.1016/j.jaci.2019.06.049
Abstract
The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.

Keywords: Allergic Rhinitis and Its Impact on Asthma; Allergic rhinitis; Development and Evaluation; Grading of Recommendations Assessment; guidelines; real-world evidence.

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Cited by 5 articles
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6
Review Pediatr Radiol
. 2019 Oct;49(11):1391-1403. doi: 10.1007/s00247-019-04457-7. Epub 2019 Oct 16.
Initial treatment of pediatric differentiated thyroid cancer: a review of the current risk-adaptive approach
Marguerite T Parisi 1 2, Hedieh Khalatbari 3, Sanjay R Parikh 4, Adina Alazraki 5
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PMID: 31620841 DOI: 10.1007/s00247-019-04457-7
Abstract
Differentiated thyroid cancer in children is a rare disease, accounting for only 1.4% of all pediatric malignancies. The diagnosis, biological behavior and treatment of differentiated thyroid cancer in children is different from that in adults. While there are many unresolved issues regarding approaches to management of differentiated thyroid cancer in the pediatric population, there is near universal consensus that treatment of this disease, which includes total thyroidectomy, central lymph node dissection at the time of initial surgery in those with nodal metastases, and the possible use of iodine-131 radiotherapy, is best performed by specialists including high-volume endocrine surgeons and experts with experience in calculating and administering radioactive iodine in children, when deemed appropriate.

Keywords: Carcinoma; Children; Complications; Iodine-131 therapy; Long-term follow-up; Nuclear medicine; Thyroid; Thyroidectomy; Ultrasound.

63 references
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7
Laryngoscope
. 2020 Feb;130(2):442-447. doi: 10.1002/lary.27993. Epub 2019 Apr 8.
Multi-Year Effect of Human Papillomavirus Vaccination on Recurrent Respiratory Papillomatosis
Hiroumi Matsuzaki 1, Kiyoshi Makiyama 1, Ryoji Hirai 1, Hirotaka Suzuki 1, Ryohei Asai 1, Takeshi Oshima 1
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PMID: 30963598 DOI: 10.1002/lary.27993
Abstract
Objective: To examine whether human papilloma virus (HPV) vaccination in combination with surgical resection could suppress recurrence for an extended period of time in patients with recurrent respiratory papillomatosis (RRP).

Methods: In a prospective case series, data of patients who received combination therapy comprising surgery and quadrivalent HPV vaccination (Gardasil; Merck & Co., West Point, PA) were collected. Patients were followed up for RRP from March 2012 to July 2018 in an academic tertiary care center. The patients comprised 16 adults with RRP who were observed for >12 months after HPV vaccination, and whose HPV-DNA status was tested before and for >12 months after completion of combination therapy. The outcomes of this study were the severity score of larynx disease, tumor incidence rate, and relationship between this rate and HPV-DNA negative conversion after therapy.

Results: The severity score of laryngeal disease significantly decreased from before combination therapy to the time of final examination (P = 0.00045). The tumor incidence rate decreased to approximately 20% during the period from 12 to 47 months after HPV vaccination. Regarding HPV-DNA status in the final test results of each patient, 12 of 16 (75%) patients showed negative conversion; these 12 were significantly less likely to experience recurrence than patients who persistently tested positive for HPV-DNA during the period between 12 and 47 months after vaccination.

Conclusion: HPV vaccination prevented recurrence associated with RRP surgery for 4 years in 80% of patients. This may be an effective adjuvant therapy, and HPV-DNA negative conversion after HPV vaccination might predict prevention of recurrence.

Level of evidence: 2 Laryngoscope, 130:442-447, 2020.

Keywords: Adjuvant therapy; HPV-DNA; human papillomavirus; recurrent respiratory papillomatosis (RRP); vaccine.

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

Cited by 1 article23 references
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8
Sci Rep
. 2019 Jan 24;9(1):472. doi: 10.1038/s41598-018-36778-2.
Combination of polyetherketoneketone scaffold and human mesenchymal stem cells from temporomandibular joint synovial fluid enhances bone regeneration
Yi Lin 1 2, Mayumi Umebayashi 2, Mohamed-Nur Abdallah 3, Guoying Dong 4, Michael G Roskies 2 5, Yaoyao Fiona Zhao 4, Monzur Murshed 6 7 8, Zhiguang Zhang 9, Simon D Tran 10
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PMID: 30679553 PMCID: PMC6345789 DOI: 10.1038/s41598-018-36778-2
Free PMC article
Abstract
Therapies using human mesenchymal stem cells (MSCs) combined with three-dimensional (3D) printed scaffolds are a promising strategy for bone grafting. But the harvest of MSCs still remains invasive for patients. Human synovial fluid MSCs (hSF-MSCs), which can be obtained by a minimally invasive needle-aspiration procedure, have been used for cartilage repair. However, little is known of hSF-MSCs in bone regeneration. Polyetherketoneketone (PEKK) is an attractive bone scaffold due to its mechanical properties comparable to bone. In this study, 3D-printed PEKK scaffolds were fabricated using laser sintering technique. hSF-MSCs were characterized and cultured on PEKK to evaluate their cell attachment, proliferation, and osteogenic potential. Rabbit calvarial critical-sized bone defects were created to test the bone regenerative effect of PEKK with hSF-MSCs. In vitro results showed that hSF-MSCs attached, proliferated, and were osteogenic on PEKK. In vivo results indicated that PEKK seeded with hSF-MSCs regenerated twice the amount of newly formed bone when compared to PEKK seeded with osteogenically-induced hSF-MSCs or PEKK scaffolds alone. These results suggested that there was no need to induce hSF-MSCs into osteoblasts prior to their transplantations in vivo. In conclusion, the combined use of PEKK and hSF-MSCs was effective in regenerating critical-sized bone defects.

Conflict of interest statement
The authors declare no competing interests.

Cited by 3 articles72 references7 figures
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9
Laryngoscope
. 2020 Feb;130(2):482-486. doi: 10.1002/lary.27950. Epub 2019 Apr 5.
The changing landscape of vestibular schwannoma diagnosis and management: A cross-sectional study
Khodayar Goshtasbi 1, Mehdi Abouzari 1, Omid Moshtaghi 1, Ronald Sahyouni 1 2, Autefeh Sajjadi 1, Harrison W Lin 1, Hamid R Djalilian 1 2
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PMID: 30953401 DOI: 10.1002/lary.27950
Free article
Abstract
Objectives: To assess the current state of the diagnosis and management of vestibular schwannoma (VS) as well as treatment trends, and to evaluate the role of treatment setting and various specialists in treatment plan.

Methods: Patients diagnosed with VS completed a voluntary and anonymous survey. The questionnaires were distributed through Acoustic Neuroma Association website, Facebook page, and e-mail newsletters from January to March 2017.

Results: In total, 789 VS patients completed the survey. Of those, 414 (52%) underwent surgery; 224 (28%) underwent radiotherapy; and 121 (15%) were observed. General otolaryngologists diagnosed 62% of responders, followed by primary care (11%) and neurotologists (10%). Patients who underwent surgery were significantly younger and had larger tumors compared to those treated with radiation or observation. The ratio of patients having nonsurgical versus surgical resection changed from 1:2 to 1:1 for the periods of 1979 through 2006 versus 2007 through 2017, respectively. Neurosurgeons (40%) and neurotologists (38%) were the most influential in treatment discussion. Neurotologists (P < 0.001) and general otolaryngologists (P = 0.04) were more influential than neurosurgeons for the decision process in patients with smaller tumors. Patients treated at academic versus nonacademic private institutions reported similar tumor sizes (P = 0.27), treatment decisions (P = 0.09), and decision satisfaction (P = 0.78).

Conclusion: There is a continuing trend toward nonsurgical management, with approximately half of the patients opting for nonsurgical management. In this cohort, the patients commonly presented with otologic symptoms and otolaryngologists made the most diagnoses. Neurotologists and neurosurgeons were the most influential in treatment discussion.

Level of evidence: NA Laryngoscope, 130:482-486, 2020.

Keywords: Vestibular schwannoma; acoustic neuroma; decision satisfaction; influential specialist; treatment trend.

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

35 references
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10
Laryngoscope
. 2020 Feb;130(2):381-384. doi: 10.1002/lary.27918. Epub 2019 Mar 13.
Risks and complications of thyroglossal duct cyst removal
Jennifer L Anderson 1 2, Kimberly Vu 1, Yarah M Haidar 1, Edward C Kuan 1, Tjoson Tjoa 1
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PMID: 30865298 DOI: 10.1002/lary.27918
Abstract
Objectives/hypothesis: Thyroglossal duct cysts (TGDCs) are the most common congenital neck cyst and typically present in childhood or adolescence, although a subset remains asymptomatic until adulthood. Although treatment involves surgical excision, few large-scale studies exist regarding the risks of surgical treatment of TGDCs in adults. This study aims to describe the characteristics of adult patients undergoing TGDC excision and to analyze risk factors associated with reoperation or other postoperative complications.

Study design: Retrospective cohort study utilizing the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database.

Methods: Patients age ≥ 18 years in the NSQIP database who underwent TGDC removal from 2005 to 2014 were included. Covariates included patient demographics, comorbidities, preoperative variables, and intraoperative variables. Outcomes included reoperation, complications, and length of hospital stay.

Results: A total of 793 cases met inclusion criteria. Patients were predominantly female (57.0%) and white (64.3%), with a mean age of 44.3 years. Thirty-day mortality did not occur in this cohort, but 3.0% of patients experienced at least one complication. Forty-eight patients (6.1%) underwent reoperation. Wound infection rates were higher in revision operations compared with primary operations (8.3% and 0.9%, respectively; P = .003). Low preoperative sodium was associated with reoperation (P = .047). Additionally, length of hospital stay was associated with increased total operative time (P = .02).

Conclusions: TGDC excision is a safe and well-tolerated procedure in the adult population, with low complication rates. However, the risk of reoperation, surgical-site infections, and medical complications should be taken into consideration during preoperative planning.

Level of evidence: NA Laryngoscope, 130:381-384, 2020.

Keywords: NSQIP; Sistrunk procedure; Thyroglossal duct cyst; neck mass; thyroglossal duct.

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

28 references
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11
Laryngoscope
. 2020 Feb;130(2):358-366. doi: 10.1002/lary.27908. Epub 2019 Mar 12.
A 3D-printed polycaprolactone/β-tricalcium phosphate mandibular prosthesis: A pilot animal study
Jae Hong Park 1, Soo Yeon Jung 2, Chi-Kyou Lee 1, Myung Jin Ban 1, Sang Jin Lee 3, Ha Yeong Kim 2 4, Hyun Ju Oh, Byeong Kook Kim 5, Hae Sang Park 6, Si-Hyong Jang 7, Han Su Kim 3
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PMID: 30861134 DOI: 10.1002/lary.27908
Abstract
Objective: In this study, we assessed the effectiveness of a tonsil-derived mesenchymal stem cell (TMSC)-transplanted polycaprolactone/beta-tricalcium phosphate prosthesis (specifically designed for easier fixing and grafting with a single scaffold) on rabbit mandible osteogenesis.

Methods: The mandibles of 18 rabbits were exposed, and 10 × 8-mm bone defects were made. Two rabbits did not receive implants; four were reconstructed with the scaffold control (SC) (SC group); four were reconstructed with scaffolds soaked in peripheral blood (PB) (PB group); four were reconstructed with TMSC-transplanted scaffolds (TMSC group); and four were reconstructed with differentiated osteocyte-transplanted scaffolds (DOC) (DOC group). Each rabbit was sacrificed 12 weeks after surgery, and the area of new bone formation was investigated by mechanical testing, histology, and micro-computed tomography.

Results: More extended and denser new bone masses were observed in the TMSC and DOC groups, although fibrosis and vascular formation levels were similar in all groups, suggesting that the dual-structured scaffold alone provides a good environment for bone attachment and regeneration. The bone volumes of representative scaffolds from the SC, PB, TMSC, and DOC groups were 43.12, 48.35, 53.10, and 57.44% of the total volumes, respectively.

Conclusion: The design of the scaffold resulted in effective osteogenesis, and TMSCs showed osteogenic potency, indicating that their combination could enable effective bone regeneration.

Level of evidence: NA Laryngoscope, 130:358-366, 2020.

Keywords: 3D printing; Graft material; Osteogenesis; Stem cell.

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

Cited by 2 articles47 references
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12
J Allergy Clin Immunol
. 2020 Jan;145(1):160-172. doi: 10.1016/j.jaci.2019.07.009. Epub 2019 Jul 19.
The IL-37-Mex3B-Toll-like receptor 3 axis in epithelial cells in patients with eosinophilic chronic rhinosinusitis with nasal polyps
Jin-Xin Liu 1, Bo Liao 1, Qi-Hong Yu 2, Hai Wang 1, Yi-Bo Liu 1, Cui-Lian Guo 1, Zhi-Chao Wang 1, Zhi-Yong Li 1, Zhe-Zheng Wang 1, Jian-Wen Ruan 1, Li Pan 1, Yin Yao 1, Cai-Ling Chen 1, Heng Wang 1, Yuxia Liang 3, Guohua Zhen 3, Zheng Liu 4
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PMID: 31330219 DOI: 10.1016/j.jaci.2019.07.009
Abstract
Background: The role of IL-37, an immunosuppressive cytokine, in patients with inflammatory diseases is unclear.

Objective: We sought to explore the expression and pathogenic function of IL-37 in patients with chronic rhinosinusitis (CRS).

Methods: Expression levels of IL-37, IL-18 receptor α, IL-1 receptor 8, Mex3 RNA binding family member B (Mex3B), and thymic stromal lymphopoietin (TSLP) in nasal samples were studied by using quantitative RT-PCR, immunohistochemistry, Western blotting, and ELISA. Human nasal epithelial cells (HNECs) and the BEAS-2B cell line were stimulated with various cytokines and Toll-like receptor (TLR) agonists. In some experiments BEAS-2B cells were transfected with Mex3B small interfering RNA or overexpressing lentiviruses. Genes regulated by IL-37b in HNECs were studied by using RNA sequencing analysis. IL-37b function was confirmed in mice in vivo.

Results: Compared with control subjects, although mRNA and protein expression of IL-37 were upregulated in diseased tissues, especially in nasal epithelial cells, in patients with CRS without nasal polyps or in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), IL-37 levels in nasal secretions were reduced in patients with eosinophilic CRSwNP. Type 2 cytokines inhibited IL-37 secretion from HNECs. HNECs expressed IL-37 receptors, IL-18 receptor α, and IL-1 receptor 8. IL-37b downregulated the expression of Mex3B, a TLR3 coreceptor, in HNECs. IL-37b suppressed polyinosinic-polycytidylic acid-induced TSLP production in HNECs in vitro and in murine nasal epithelial cells in vivo. Knocking down or overexpressing Mex3B in BEAS-2B cells abolished the inhibitory effect of IL-37b. Secreted IL-37 levels negatively correlated with Mex3B and TSLP levels and eosinophil numbers in patients with eosinophilic CRSwNP.

Conclusions: The suppressed IL-37 secretion caused by a type 2 milieu can enhance Mex3B-mediated TLR3 activation and subsequent TSLP production in nasal epithelial cells and therefore promotes eosinophilic inflammation in patients with CRSwNP.

Keywords: Eosinophil; IL-37; Mex3 RNA binding family member B; Toll-like receptor 3; chronic rhinosinusitis; epithelial cell; nasal polyp.

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comment in
IL-37: A new player in the chronic rhinosinusitis arena.
Markov N, Simon HU.
J Allergy Clin Immunol. 2020 Jan;145(1):105-107. doi: 10.1016/j.jaci.2019.10.018. Epub 2019 Oct 28.
PMID: 31672607 No abstract available.
Cited by 1 article
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13
Laryngoscope
. 2020 Feb;130(2):500-506. doi: 10.1002/lary.28007. Epub 2019 Apr 22.
Multifactorial positive influence of cochlear implantation on patients with single-sided deafness
Sophia M Häußler 1, Vanessa Köpke 1, Steffen Knopke 1, Stefan Gräbel 1, Heidi Olze 1
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PMID: 31006873 DOI: 10.1002/lary.28007
Abstract
Objectives: Single-sided deafness (SSD) is an extreme case with profound unilateral hearing loss in the poorer ear and regular hearing in the other ear. The aim of this study is to investigate the impairment in the daily life of SSD patients and the influence of cochlear implants (CI) on their health-related quality of life (HRQoL), the impact on existing tinnitus distress and psychological comorbidities, and audiometric parameters.

Methods: In total, 21 patients (8 male and 13 female) were included, and the Charité Test Battery was applied for all patients. Data on HRQoL were collected with the Nijmegen Cochlear Implant Questionnaire and the Medical Outcome Study Short Form 36 (SF-36) Survey. Tinnitus distress was assessed with the Tinnitus Questionnaire (TQ). Data with regard to psychological comorbidities were collected using four validated questionnaires. Speech perception was assessed with the Freiburg Monosyllable Test (FMS), the Oldenburg Sentence Test (OLSA), and the Oldenburg Inventory (OI).

Results: HRQoL improved in the subdomain social interactions. Tinnitus distress dropped significantly 6 months postoperatively. SSD patients preoperatively showed elevated levels of stress, depressive symptoms, and anxiety. Postoperatively, these psychological symptoms improved with regard to stress, tension, and demands. The audiometry tools revealed a significant improvement in directional hearing (OI), speech perception in silence, and in the speech intelligibility threshold (OLSA).

Conclusion: There was an improvement in HRQoL and a reduction of tinnitus and cognitive distress. The preoperatively elevated stress level decreased significantly, and psychological comorbidities such as depressive symptoms and anxiety all improved postimplantation.

Level of evidence: II-2 Laryngoscope, 130:500-506, 2020.

Keywords: Cochlear implantation; quality of life; single-sided deafness; stress; tinnitus.

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

Cited by 1 article51 references
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14
Meta-Analysis Laryngoscope
. 2020 Feb;130(2):465-473. doi: 10.1002/lary.28076. Epub 2019 Jun 7.
A systematic review and meta-analysis of predictors of airway intervention in adult epiglottitis
Anders Sideris 1 2 3, Timothy R Holmes 1 2 3, Benjamin Cumming 1 2 3, Thomas Havas 1 2 3
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PMID: 31173373 DOI: 10.1002/lary.28076
Abstract
Objective: Epiglottitis is typically considered a pediatric disease; however, there is growing evidence that the incidence of adult epiglottitis has changed since the introduction of the Haemophilus influenzae vaccine. The literature is composed of multiple small series with differing findings. To date, there has been no attempt to collaborate evidence on predictors of airway intervention in this disease.

Methods: The population of interest was adults with a diagnosis of epiglottitis. The primary outcome in this review was incidence of airway intervention. A comprehensive literature search was conducted of the MEDLINE and Embase databases, and a separate random-effects model meta-analysis was undertaken for all outcome data. Moderator tests for comparison between prevaccine and postvaccine estimates were made, and absolute risk difference (RD) and relative risk (RR) calculations were made for all predictors of airway intervention.

Results: Thirty studies and a total of 10,148 patients were finally included for meta-analysis. A significant decrease in airway intervention was seen post vaccine introduction introduction from 18.8% to 10.9% (P = 0.01). The presence of an abscess (RD 0.27, P = 0.04; RR 2.45, P < 0.001), stridor (RD 0.64, P < 0.001; RR 7.15, P < 0.001), or a history of diabetes mellitus (RD 0.11, P = 0.02; RR 2.15, P = 0.01) were associated with need for airway intervention.

Conclusion: In the postvaccine era, clinicians should expect to have to secure airways in 10.9% of cases. The presence of an epiglottic abscess, stridor, or a history of diabetes mellitus are the most reliable clinical features associated with need for airway intervention.

Level of evidence: NA Laryngoscope, 130:465-473, 2020.

Keywords: Adult epiglottitis; airway intervention; epiglottic abscess; epiglottitis; intubation; microbiology; tracheostomy.

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

Cited by 1 article40 references
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15
Laryngoscope
. 2020 Feb;130(2):546-550. doi: 10.1002/lary.27951. Epub 2019 Apr 5.
Long-term results of sleep-related quality-of-life and behavioral problems after adenotonsillectomy
In Sik Song 1, Seung-No Hong 2, Jae Woo Joo 1, Mun Soo Han 1, Sun Jin Hwang 1, Min Young Seo 1, Seung Hoon Lee 1
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PMID: 30950515 DOI: 10.1002/lary.27951
Abstract
Objectives: Improvements in sleep-related quality of life (QOL) and behavioral problems have been observed in children with obstructive sleep apnea (OSA) during a short-term follow-up after adenotonsillectomy. Whether this trend continues beyond the short term remains unclear. Therefore, we aimed to evaluate the long-term effects of surgery in children with OSA.

Methods: The study participants comprised 20 children with OSA who underwent adenotonsillectomy. We used the scores from the Attention Deficit and Hyperactivity Disorder Rating Scale (ADHD-RS) and total scores from the Korean OSA-18 Survey (KOSA-18) before and after adenotonsillectomy to compare and analyze behavioral problems and OSA-specific health-related QOL, respectively, during a long-term follow-up. Respiratory disturbance parameters from standard polysomnography and subjective symptom scores for snoring and apnea were also investigated.

Results: The mean patient age was 6.6 ± 3.4 years (range, 3-13), and the male-to-female ratio was 15:5. The mean follow-up period was 54.5 months (range, 27-98). The total scores for both ADHD-RS (from 17.6 to 10.5; P = 0.006) and KOSA-18 (from 74.3 to 40.7; P = 0.001) decreased significantly from before to after surgery. Significant decreases were also observed in the subjective symptom scores for snoring (from 5.4 to 2.4; P = 0.000) and apnea (from 3.3 to 0.8; P = 0.002).

Conclusion: Significant improvement was observed in sleep-related QOL and behavioral problems in children with OSA during long-term follow-up after adenotonsillectomy.

Level of evidence: 4 Laryngoscope, 130:546-550, 2020.

Keywords: Pediatric obstructive sleep apnea; adenotonsillectomy; behavior problem; long-term effect; quality of life.

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

27 references
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16
Multicenter Study Trials
. 2019 Dec 9;20(1):683. doi: 10.1186/s13063-019-3830-5.
The effect of antibiotics on post-adenotonsillectomy morbidity in Tanzanian children: study protocol for a randomized, double-blind, placebo-controlled trial
Denis R Katundu 1 2, Peter S Shija 3, Baltazari Nyombi 4, Hadija Semvua 5, Fieke K Oussoren 6, Niels van Heerbeek 3 6
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PMID: 31815643 PMCID: PMC6902588 DOI: 10.1186/s13063-019-3830-5
Free PMC article
Abstract
Background: Adenotonsillectomy is the most frequently performed operation in children worldwide. For decades, prophylactic antibiotics have been prescribed to limit postoperative complications. The effect of this antibiotic use has been refuted in a Cochrane Review. However, all reviewed studies were carried out in developed countries. In Tanzania, like many other developing countries with limited resources and a high burden of infectious diseases, postoperative antibiotic prescription is still very common to decrease the supposed higher postoperative morbidity. However, as a consequence of this widespread use of postoperative antibiotics, cross-resistance and risk of allergic side effects rise. Well-designed randomized controlled trials are needed to limit unnecessary antibiotic prescription and secondary antibiotic resistance.

Aim: The aim of this study is to analyse the prophylactic role of postoperative antibiotics on morbidity following adenotonsillectomy in children in Tanzania.

Design: The double-blinded, randomized, placebo-controlled trial was set in northern Tanzania. Participating centres are the Department of Otolaryngology at Kilimanjaro Christian Medical Centre in Moshi and the Department of Paediatric Surgery at the Arusha Lutheran Medical Centre in Arusha.

Methods: Around 270 children aged 2-14 years, all scheduled for elective (adeno)tonsillectomy, will be included and assigned to receive either a standard regimen of 5 days of antibiotic prophylaxis or placebo after surgery. The primary outcomes are postoperative haemorrhage, fever and pain. Secondary outcomes are the time until normal diet is resumed, the time until normal activities are resumed and the occurrence of adverse events and microbial recolonization of the tonsillar beds.

Discussion: This study will enhance an increase of proper antimicrobial prescription in Tanzanian institutions as well as other resource-limited countries where prescription of antibiotics is still very common. In addition, it might augment current knowledge about surface and core tonsillar micro-organisms and sensitivity patterns.

Trial registration: Pan African Clinical Trials Registry, PACTR201905466349317. Retrospectively registered on 15 May 2019. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=8119.

Keywords: Adenotonsillectomy; Amoxicillin; Antimicrobial resistance; Postoperative morbidity; Randomized controlled trial; Tonsillectomy.

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

10 references2 figures
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17
Clinical Trial Laryngoscope
. 2020 Feb;130(2):551-555. doi: 10.1002/lary.27987. Epub 2019 Apr 17.
Does drug-induced sleep endoscopy affect surgical outcome? A multicenter study of 326 obstructive sleep apnea patients
Kenny P Pang 1, Peter M Baptista 2, Ewa Olszewska 3, Itzhak Braverman 4, Marina Carrasco-Llatas 5, Srivinas Kishore 6, Sudipta Chandra 7, Hyung Chae Yang 8, Cybil Mei Zhi Wang 1, Yiong Huak Chan 9, Kathleen A Pang 1, Edward B Pang 10, Brian Rotenberg 11
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PMID: 30993741 DOI: 10.1002/lary.27987
Abstract
Objectives/hypothesis: Our objective was to determine whether drug-induced sleep apnea (DISE) affects the successfulness of the surgical outcome.

Study design: Prospective, seven-country, nonrandomized trial.

Methods: There were 326 consecutive obstructive sleep apnea (OSA) patients who had nose, palate, and/or tongue surgery included in the study. DISE was performed in only one group.

Results: There were 170 patients in the DISE group and 156 patients in no-DISE group. The mean preoperative body mass index (BMI) for the DISE group was 27.6 ± 4.6, whereas in the no-DISE group it was 28.1 ± 3.9 (P = .23). The mean preoperative systolic blood pressure (SBP) for the DISE group was 130.4 ± 16.7, whereas in the no-DISE group it was 142.9 ± 15.5 (P < .001). The mean preoperative diastolic blood pressure (DBP) for the DISE group was 81.4 ± 9.7, whereas in the no-DISE group it was 89.1 ± 9.7 (P < .001). The mean preoperative apnea-hypopnea index (AHI) for the DISE group was 32.6 ± 18.8, whereas in the no-DISE group it was 33.7 ± 19.6 (P = .61). The mean postoperative AHI for the DISE group was 15.9 ± 12.6, whereas in the no-DISE group it was 13.2 ± 8.8 (P = .023). The age-, gender-, BMI-adjusted percentage change in AHI for the DISE group was -48.4 ± 31.9, whereas in the no-DISE group it was -59.8 ± 18.6 (P < .001). The age-, gender-, and BMI-adjusted success rate for the DISE group was 66.5%, whereas in the no-DISE group it was 80.8% (P = .004). The age-, gender-, and BMI-adjusted change in SBP for the DISE group was -6.1 ± 8.6, whereas in the no-DISE group it was -13.3 ± 11.1 (P < .001). The age-, gender-, and BMI-adjusted change in DBP in the DISE group was -5.2 ± 12.1, whereas in the no-DISE group it was -12.4 ± 11.7 (P < .001). The mean age- and gender-adjusted change in BMI for the DISE group was -4.6 ± 12.9, whereas in the no-DISE group it was -6.3 ± 18.5 (P = .34). The Cohen effect of BMI on the overall AHI, lowest oxygen saturation, and blood pressure changes was 0.08.

Conclusions: DISE may not significantly affect surgical success in OSA.

Level of evidence: 2c Laryngoscope, 130:551-555, 2020.

Keywords: Drug-induced sleep endoscopy; obstructive sleep apnea; success rate.

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

Cited by 3 articles11 references
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18
Cancer Biol Ther
. 2019;20(6):826-836. doi: 10.1080/15384047.2018.1564569. Epub 2019 Mar 25.
miR-506 is a YAP1-dependent tumor suppressor in laryngeal squamous cell carcinoma
Changhui Gao 1, Shousen Hu 1
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PMID: 30907227 PMCID: PMC6606012 DOI: 10.1080/15384047.2018.1564569
Free PMC article
Abstract
Laryngeal squamous cell carcinoma (LSCC) accounts for 95% of laryngeal cancer incidence. Tobacco use has been shown to have a linear association with the development of the disease. While early diagnosis and treatment of LSCC are critical in improving the 5-year survival rate and quality of life, diagnosis of early-stage LSCC remains challenging because of the unapparent symptoms. Here, we report that miR-506, a critical regulator in many types of cancers, is aberrantly suppressed in LSCC patient tissues and cultured cancer cells. This is likely responsible for the enhanced production of YAP1 protein, a transcriptional factor that is well known for its oncogenic roles in LSCC malignancy. Statistical analysis has confirmed that the expression levels of miR-506 and YAP1 are strongly correlated with the malignant statuses of patient tumors. Restoring the expression level of miR-506 in cultured LSCC cells significantly inhibited proliferation, migration and invasion of the cells. The miR-506 and YAP1 regulatory network seems to affect at least pathways involved in apoptosis. Our study, for the first time, has demonstrated a tumor suppressive role of miR-506 in LSCC. This opens new opportunities for further exploring the molecular details of the development of the disease and thus will facilitate the development of novel diagnosis and therapeutic strategies.

Keywords: Laryngeal squamous cell carcinoma; YAPI; apoptosis; invasion; miR-506; migration; proliferation.

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19
Laryngoscope
. 2020 Feb;130(2):487-495. doi: 10.1002/lary.27991. Epub 2019 Apr 8.
Assessing fractional hair cell survival in archival human temporal bones
Pei-Zhe Wu 1 2 3, Wei-Ping Wen 3, Jennifer T O'Malley 1, M Charles Liberman 1 2
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PMID: 30963586 PMCID: PMC6783317 (available on 2020-10-08) DOI: 10.1002/lary.27991
Free PMC article
Abstract
Objectives/hypothesis: Histopathological analysis of hair cell survival in human temporal bone sections has historically been binarized such that each hair cell row is rated as either present or absent, thereby greatly underestimating the amount of hair cell loss. Here, we describe and validate a technique to reliably assess fractional hair cell survival in archival sections stained with hematoxylin and eosin (H&E) using high-resolution light microscopy and optical sectioning.

Study design: Technique validation.

Methods: Hair cell counts in archival temporal bone slide sets were performed by several observers using either differential interference contrast (DIC) or confocal microscopy of the endogenous eosin fluorescence in hair cells. As a further cross-check, additional decelloidinized sections were immunostained with hair cell markers myosin VI and VIIa.

Results: Cuticular plates and stereocilia bundles are routinely resolvable in DIC imaging of archival H&E-stained human material using standard research-grade microscopes, allowing highly accurate counts of fractional hair cell survival that are reproducible across observer and can be verified by confocal microscopy.

Conclusions: Reanalysis of cases from the classic temporal bone literature on presbycusis suggests that, contrary to prior reports, differences in audiometric patterns may be well explained by the patterns of hair cell loss.

Level of evidence: NA Laryngoscope, 130:487-495, 2020.

Keywords: Presbycusis; audiometric pattern; hair cell loss.

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

Conflict of interest statement
Conflicts and Disclosures: The authors have no conflicts of interest or financial relationships to disclose

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20
Neural Plast
. 2019 Dec 13;2019:1712342. doi: 10.1155/2019/1712342. eCollection 2019.
Morphological Neuroimaging Biomarkers for Tinnitus: Evidence Obtained by Applying Machine Learning
Yawen Liu 1, Haijun Niu 1, Jianming Zhu 2, Pengfei Zhao 3, Hongxia Yin 3, Heyu Ding 3, Shusheng Gong 4, Zhenghan Yang 3, Han Lv 3, Zhenchang Wang 1 3
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PMID: 31915431 PMCID: PMC6930742 DOI: 10.1155/2019/1712342
Free PMC article
Abstract
According to previous studies, many neuroanatomical alterations have been detected in patients with tinnitus. However, the results of these studies have been inconsistent. The objective of this study was to explore the cortical/subcortical morphological neuroimaging biomarkers that may characterize idiopathic tinnitus using machine learning methods. Forty-six patients with idiopathic tinnitus and fifty-six healthy subjects were included in this study. For each subject, the gray matter volume of 61 brain regions was extracted as an original feature pool. From this feature pool, a hybrid feature selection algorithm combining the F-score and sequential forward floating selection (SFFS) methods was performed to select features. Then, the selected features were used to train a support vector machine (SVM) model. The area under the curve (AUC) and accuracy were used to assess the performance of the classification model. As a result, a combination of 13 cortical/subcortical brain regions was found to have the highest classification accuracy for effectively differentiating patients with tinnitus from healthy subjects. These brain regions include the bilateral hypothalamus, right insula, bilateral superior temporal gyrus, left rostral middle frontal gyrus, bilateral inferior temporal gyrus, right inferior parietal lobule, right transverse temporal gyrus, right middle temporal gyrus, right cingulate gyrus, and left superior frontal gyrus. The accuracy in the training and test datasets was 80.49% and 80.00%, respectively, and the AUC was 0.8586. To the best of our knowledge, this is the first study to elucidate brain morphological changes in patients with tinnitus by applying an SVM classifier. This study provides validated cortical/subcortical morphological neuroimaging biomarkers to differentiate patients with tinnitus from healthy subjects and contributes to the understanding of neuroanatomical alterations in patients with tinnitus.

Copyright © 2019 Yawen Liu et al.

Conflict of interest statement
The authors declare that there are no conflicts of interests regarding the publication of this paper.

42 references4 figures
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21
Multicenter Study Laryngoscope
. 2020 Feb;130(2):431-436. doi: 10.1002/lary.27959. Epub 2019 May 2.
Salvage open partial horizontal laryngectomy after failed radiotherapy: A multicentric study
Andy Bertolin 1, Marco Lionello 1, Marco Ghizzo 1, Isida Cena 1, Federico Leone 2, Sara Valerini 3, Francesco Mattioli 3, Erika Crosetti 4, Livio Presutti 3, Giovanni Succo 4 5, Giuseppe Rizzotto 1
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PMID: 31046149 DOI: 10.1002/lary.27959
Abstract
Objectives: The primary aim of the present study was to report our multi-institutional experience in surgical salvage with open partial horizontal laryngectomies (OPHL) after failed radiotherapy (RT) for laryngeal squamous cell carcinoma (LSCC). Secondary aims were to analyze the prognostic meaning of the main clinical and pathological parameters in relation to the oncologic outcome and to compare our results with the available literature.

Study design: A retrospective multicenter analysis of surgical oncological outcomes.

Methods: We retrospectively review the clinical charts of 70 recurrent LSCC patients after primary RT failure undergone salvage OPHL.

Results: At last follow-up, 46 patients (65%) were disease-free; six (9%) were alive with disease; nine (12%) died because of the disease; and nine (12%) died without evidence of disease. The final local control, overall survival, disease-specific survival, and laryngectomy-free survival were 87%, 75%, 87%, and 91%, respectively. Twelve patients (17%) experienced postoperative complications, whereas 18 patients (25%) experienced late sequelae. In five patients (7%), decannulation was not possible because of postoperative laryngeal stenosis.

Conclusion: In selected patients, when proper selection criteria for conservation laryngeal surgery are adopted, OPHL can be considered for salvage after RT failure.

Level of evidence: 4 Laryngoscope, 130:431-436, 2020.

Keywords: OPHL; RT; laryngeal carcinoma; recurrence; salvage.

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

49 references
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22
Resuscitation
. 2019 May;138:250-258. doi: 10.1016/j.resuscitation.2019.03.029. Epub 2019 Mar 26.
Cost-effectiveness of public automated external defibrillators
Lars W Andersen 1, Mathias J Holmberg 2, Asger Granfeldt 3, Lyndon P James 4, Lisa Caulley 5
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PMID: 30926453 DOI: 10.1016/j.resuscitation.2019.03.029
Abstract
Background: Despite a consistent association with improved outcomes, public automated external defibrillators (AEDs) are rarely used in out-of-hospital cardiac arrest. One of the barriers towards increased use might be cost-effectiveness.

Methods: We compared the cost-effectiveness of public AEDs to no AEDs for out-of-hospital cardiac arrest in the United States over a life-time horizon. The analysis assumed a societal perspective and results are presented as costs per quality-adjusted life year (QALY). Model inputs were based on reviews of the literature. For the base case, we modelled an annual cardiac arrest incidence per AED of 20%. A probabilistic sensitivity analysis was conducted to account for joint parameter uncertainty.

Results: The no AED strategy resulted in 1.63 QALYs at a cost of $28,964. The AED strategy yielded an additional 0.26 QALYs for an incremental increase in cost of $13,793 per individual. The AED strategy yielded an incremental cost-effectiveness ratio of $53,797 per QALY gained. The yearly incidence of cardiac arrests occurring in the presence of an AED had minimal effect on the incremental cost-effectiveness ratio except at very low incidences. In several sensitivity analyses across a plausible range of health care and societal estimates, the AED strategy remained cost-effective. In the probabilistic sensitivity analysis, the AED strategy was cost-effective in 43%, 85%, and 91% of the scenarios at a willingness-to-pay threshold of $50,000, $100,000, and $150,000 per QALY gained, respectively.

Conclusion: Public AEDs are a cost-effective public health intervention in the United States. These findings support widespread dissemination of public AEDs.

Keywords: Automated external defibrillators; Cardiac arrest; Cardiopulmonary resuscitation; Cost-effectiveness analysis; Public; Public health; United States.

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

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23
Allergy
. 2020 Jul 27. doi: 10.1111/all.14517. Online ahead of print.
Distinct effects of asthma and COPD comorbidity on disease expression and outcome in patients with COVID-19
Jia Song 1, Ming Zeng 1, Hai Wang 1, Chuan Qin 2, Hong-Yan Hou 3, Zi-Yong Sun 3, San-Peng Xu 4, Guo-Ping Wang 4, Cui-Lian Guo 1, Yi-Ke Deng 1, Zhi-Chao Wang 1, Jin Ma 1, Li Pan 1, Bo Liao 1, Zhi-Hui Du 1, Qi-Miao Feng 1, Yang Liu 1, Jun-Gang Xie 5 6, Zheng Liu 1 6
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PMID: 32716553 DOI: 10.1111/all.14517
Abstract
Background: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood.

Objective: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients.

Methods: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines.

Results: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < 0.01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = 0.025) than asthmatics. COPD patients, particular those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells, and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8 and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated but TNF-α, IL-12 and IL-17A upregulated ACE2 expression in BEAS-2B cells.

Conclusion: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.

Keywords: angiotensin-converting enzyme II; cytokine; immune cell; severe acute respiratory syndrome coronavirus 2.

This article is protected by copyright. All rights reserved.

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24
Review Int J Mol Sci
. 2020 Jul 21;21(14):E5156. doi: 10.3390/ijms21145156.
Clinical Role of Extraoral Bitter Taste Receptors
Joanna Jeruzal-Świątecka 1, Wojciech Fendler 2 3, Wioletta Pietruszewska 1
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PMID: 32708215 DOI: 10.3390/ijms21145156
Abstract
Humans can recognise five basic tastes: sweet, sour, salty, bitter and umami. Sour and salty substances are linked to ion channels, while sweet, bitter and umami flavours are transmitted through receptors linked to the G protein (G protein-coupled receptors; GPCRs). There are two main types of GPCRs that transmit information about sweet, umami and bitter tastes-the Tas1r and TAS2R families. There are about 25 functional TAS2R genes coding bitter taste receptor proteins. They are found not only in the mouth and throat, but also in the intestines, brain, bladder and lower and upper respiratory tract. The determination of their purpose in these locations has become an inspiration for much research. Their presence has also been confirmed in breast cancer cells, ovarian cancer cells and neuroblastoma, revealing a promising new oncological marker. Polymorphisms of TAS2R38 have been proven to have an influence on the course of chronic rhinosinusitis and upper airway defensive mechanisms. TAS2R receptors mediate the bronchodilatory effect in human airway smooth muscle, which may lead to the creation of another medicine group used in asthma or chronic obstructive pulmonary disease. The discovery that functionally compromised TAS2R receptors negatively impact glucose homeostasis has produced a new area of diabetes research. In this article, we would like to focus on what facts have been already established in the matter of extraoral TAS2R receptors in humans.

Keywords: TAS2R; asthma; biomarker; bitter taste receptors; cancer; chronic rhinosinusitis; diabetes; genetic background; human tissue; obesity; receptor signalling; taste.

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25
Nat Commun
. 2020 Mar 24;11(1):1533. doi: 10.1038/s41467-020-15219-7.
Subpopulation targeting of pyruvate dehydrogenase and GLUT1 decouples metabolic heterogeneity during collective cancer cell invasion
R Commander 1, C Wei 2, A Sharma 2 3, J K Mouw 2 3, L J Burton 2 3, E Summerbell 1, D Mahboubi 4, R J Peterson 5, J Konen 6, W Zhou 2 3, Y Du 2 7 8, H Fu 2 3 7 8, M Shanmugam 9 10, A I Marcus 11 12
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PMID: 32210228 PMCID: PMC7093428 DOI: 10.1038/s41467-020-15219-7
Free PMC article
Abstract
Phenotypic heterogeneity exists within collectively invading packs of tumor cells, suggesting that cellular subtypes cooperate to drive invasion and metastasis. Here, we take a chemical biology approach to probe cell:cell cooperation within the collective invasion pack. These data reveal metabolic heterogeneity within invasive chains, in which leader cells preferentially utilize mitochondrial respiration and trailing follower cells rely on elevated glucose uptake. We define a pyruvate dehydrogenase (PDH) dependency in leader cells that can be therapeutically exploited with the mitochondria-targeting compound alexidine dihydrochloride. In contrast, follower cells highly express glucose transporter 1 (GLUT1), which sustains an elevated level of glucose uptake required to maintain proliferation. Co-targeting of both leader and follower cells with PDH and GLUT1 inhibitors, respectively, inhibits cell growth and collective invasion. Taken together, our work reveals metabolic heterogeneity within the lung cancer collective invasion pack and provides rationale for co-targeting PDH and GLUT1 to inhibit collective invasion.

Conflict of interest statement
The authors declare no competing interests.

Cited by 1 article81 references8 figures
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26
Accid Anal Prev
. 2020 Apr;138:105443. doi: 10.1016/j.aap.2020.105443. Epub 2020 Feb 12.
Occupant injuries in light passenger vehicles-A NASS study to enable priorities for development of injury prediction capabilities of human body models
Bengt Pipkorn 1, Johan Iraeus 2, Mats Lindkvist 3, Pradeep Puthan 4, Olle Bunketorp 5
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PMID: 32059123 DOI: 10.1016/j.aap.2020.105443
Abstract
To prioritize how the development of mathematical human body models for injury prediction in crash safety analysis should be made, the most frequent injuries in the NASS CDS data from 2000 to 2015 were analyzed. The crashes were divided into seven types, from front to side. Non-minor injuries (AIS2+) were analyzed in two steps. In the first step, a grouping was made according to the AIS definition of body regions: head, face, neck, thorax, abdomen and pelvic contents, spine, upper extremities (including shoulder girdle) and lower extremities (including pelvis). In a second step, the body regions were divided in organs, parts of the spine, and parts of the extremities. The three most often injured anatomical structures of each body region were estimated for drivers and front seat passengers in each type of crash. For drivers, an injury risk greater than 2.4 % was found for the lower extremities (pelvis) and the head (concussion) in side oblique near side impacts, for the head in frontal oblique near side impacts (concussion) and for the lower extremities (ankle joint) in frontal impacts. For passengers, an injury risk greater than 2.4 % was found for the thorax (lungs) in side near side impacts, for the head (concussion) in front oblique near side impacts, and for the thorax (sternum) and the upper extremities (wrist, hand) in frontal impacts. Future development of human body models should focus on injuries to the head, thorax and the lower extremities. More specifically, it should focus on concussion in all impact directions and on rib and pelvic fractures in side near side impacts and in side oblique near side impacts.

Keywords: AIS2+; Body region; Frontal; Impact; Injuries; NASS; Oblique; Side.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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27
Laryngoscope
. 2020 Feb;130(2):561-565. doi: 10.1002/lary.28027. Epub 2019 Apr 25.
Safety and reliability of a handheld stimulator for neural monitoring during thyroid surgery
Bradley R Lawson 1 2 3, Dipti Kamani 1, Mohamed Shama 1, Natalia Kyriazidis 1, Gregory W Randolph 1 4
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PMID: 31022318 DOI: 10.1002/lary.28027
Abstract
Objective: The Checkpoint nerve stimulator (Checkpoint Surgical, Cleveland, OH) is a U.S. Food and Drug Administration-approved device for neural localization and monitoring during surgery. Its safety, efficacy, and reliability for neural monitoring during thyroid and parathyroid surgery have not been compared to more standard formats of neural monitoring.

Study design: Retrospective review.

Methods: Vagal, recurrent, and superior laryngeal nerve monitoring were performed using both the Checkpoint stimulator and Medtronic NIM 3.0 laryngeal electromyography endotracheal tube (Medtronic, Jacksonville, FL) during thyroid and parathyroid surgery. A total of 21 operated sides in 15 patients were included for analysis. Latency and amplitude data for the Checkpoint stimulator were recorded using the NIM monitor and compared to normative endotracheal tube surface electrode data.

Results: Mean amplitude using the Checkpoint stimulator was 574.6 microvolts (μV), 1060.6 μV, and 182.8 μV for the vagus, recurrent laryngeal, and superior laryngeal nerves, respectively. Mean amplitude using standard laryngeal electromyography was 709 μV, 1077.0 μV, and 183.7 μV for the same nerves. Mean latency was significantly shorter with stimulation of the recurrent laryngeal nerve compared to the vagus nerve with both stimulators (P < 0.001). No neural injuries occurred during the study.

Conclusion: The Checkpoint stimulator is a safe and reliable alternative to traditional laryngeal electromyography providing equivalent induced electromyography of the vocalis for neural monitoring during thyroid and parathyroid surgery.

Level of evidence: 4 Laryngoscope, 130:561-565, 2020.

Keywords: Checkpoint stimulator; Endotracheal tube surface electrodes; electromyography; nerve stimulator; neural monitoring; parathyroid surgery; thyroid surgery.

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

Cited by 1 article19 references
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28
Nat Commun
. 2020 Mar 12;11(1):1343. doi: 10.1038/s41467-020-15198-9.
Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome
Mengnan Li 1 2, Shin-Ya Nishio 3, Chie Naruse 4, Meghan Riddell 1, Sabrina Sapski 5, Tatsuya Katsuno 6, Takao Hikita 1, Fatemeh Mizapourshafiyi 1 2, Fiona M Smith 7, Leanne T Cooper 7, Min Goo Lee 8, Masahide Asano 4, Thomas Boettger 9, Marcus Krueger 10, Astrid Wietelmann 11, Johannes Graumann 12 13, Bryan W Day 7, Andrew W Boyd 7, Stefan Offermanns 5, Shin-Ichiro Kitajiri 3, Shin-Ichi Usami 3, Masanori Nakayama 14 15 16
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PMID: 32165640 PMCID: PMC7067772 DOI: 10.1038/s41467-020-15198-9
Free PMC article
Abstract
Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function.

Conflict of interest statement
The authors declare no competing interests.

63 references7 figures
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29
Laryngoscope
. 2020 Feb;130(2):474-481. doi: 10.1002/lary.27945. Epub 2019 Mar 27.
Pattern of cochlear obliteration after vestibular Schwannoma resection according to surgical approach
Yening Feng 1, John I Lane 2, Christine M Lohse 3, Matthew L Carlson 1
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PMID: 30919457 DOI: 10.1002/lary.27945
Abstract
Objectives/hypothesis: To investigate the prevalence and course of cochlear obliteration according to microsurgical approach to inform clinical decision making regarding optimal timing of cochlear implantation.

Study design: Retrospective radiologic review and chart review.

Methods: Patients who underwent microsurgical resection of vestibular schwannoma (VS) with a minimum of two available postoperative magnetic resonance imaging (MRI) scans were analyzed. The prevalence and timing of cochlear and labyrinthine obliteration was classified using relevant MRI sequences.

Results: MRI studies in 60 patients were analyzed: 20 translabyrinthine (TL), 20 retrosigmoid, and 20 middle fossa (MF) cases. The first and last postoperative MRI was obtained a median of 3.4 months (interquartile range (IQR), 3.0-3.7 months) and 35 months (IQR, 27-83 months) after surgery, respectively. At the time of the first postoperative MRI, 21 (35%) patients had partial basal turn obliteration, and none of the patients had complete basal turn obliteration. At the time of the last postoperative MRI, six (10%) patients had partial basal turn obliteration and 17 (28%) patients had complete basal turn obliteration. The pattern of partial or complete basal turn obliteration differed significantly among all three surgical approaches (P < .001). Specifically, the risk of partial or complete obliteration of the basal turn was highest in the TL cohort and lowest in the MF cohort.

Conclusions: The prevalence and timing of cochlear obliteration after VS microsurgery varies significantly according to surgical approach. The risk of early and complete obliteration is highest in the TL group and lowest in the MF cohort. These data may inform clinical decision making regarding optimal timing of cochlear implantation in patients with advanced hearing loss after microsurgical resection.

Level of evidence: 4 Laryngoscope, 130:474-481, 2020.

Keywords: Vestibular schwannoma; acoustic neuroma; cochlea; cochlear implantation; skull base.

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

34 references
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30
Facial Plast Surg Aesthet Med
. 2020 Jul 22. doi: 10.1089/fpsam.2020.0049. Online ahead of print.
Online Ratings of Facial Plastic Surgeons: Worthwhile Additions to Conventional Patient Experience Surveys
Cory D Bovenzi 1, Kirstin A Manges 2, Howard Krein 1, Ryan Heffelfinger 1
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PMID: 32716653 DOI: 10.1089/fpsam.2020.0049
Abstract
Background: Physician review websites are now commonly used by patients. However, in facial plastic surgery, the trends and content in these websites are not well studied. We examined online reviews for U.S. facial plastic surgeons, and compared comment content with the most commonly used patient experience survey, the Consumer Assessment of Healthcare Providers and Systems (CAHPS) administered by Press Ganey. Methods: A retrospective mixed method study was employed to quantitatively compare online ratings and comments of 100 randomly selected U.S. facial plastic surgeons on vitals.com, healthgrades.com, google.com and zocdoc.com. Qualitative content analysis was utilized to categorize themes present in 957 patient-generated (unverified) comments, and compare these with CAHPS survey questions and themes. Results: The physician review websites had favorable ratings of facial plastic surgeons with 84.55% five-star reviews on Healthgrades and 78.40% on Vitals. These ratings were similar across surgeon age (p = 0.44), gender (p = 0.85), and geographic region (p = 0.29). Of sites examined, Healthgrades and Vitals were most frequently used. Analysis of patient comments identified themes aligning with CAHPS content (e.g., physician interactions, efficiency, and recommendation likelihood), as well as additional themes such as patient's outcome perception (55.28% of comments) and finances (86% of negatively rated reviews). Conclusions: These exploratory results suggest that facial plastic surgeons are generally rated positively online, and the comments left on these websites provide additional feedback that is not currently included in CAHPS surveys. In evaluating the patient experience with facial plastic surgery practices, these websites may prove to be useful.

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31
Laryngoscope
. 2020 Feb;130(2):392-397. doi: 10.1002/lary.27946. Epub 2019 Apr 5.
From presumed benign neck masses to delayed recognition of human papillomavirus-positive oropharyngeal cancer
Ruth J Davis 1, Eleni Rettig 1, Nafi Aygun 2, Lisa Rooper 3, Gypsyamber D'Souza 1 4, David W Eisele 1, Carole Fakhry 1 4
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PMID: 30950517 PMCID: PMC6778483 (available on 2020-10-05) DOI: 10.1002/lary.27946
Free PMC article
Abstract
Objectives/hypothesis: To describe patients with delayed diagnosis of human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPC) after initial incorrect diagnosis of branchial cleft cyst or nondiagnostic workup of unilateral neck mass.

Study design: Retrospective case series.

Methods: Patients with delayed diagnosis of HPV-OPC after initial nondiagnostic workup for unilateral neck mass were eligible. Medical record abstraction was performed to describe clinical characteristics at initial presentation and later diagnosis of HPV-OPC. To estimate nodal growth rates, the short axis diameter of the lymph nodes was determined from imaging reports.

Results: Six patients met eligibility criteria. After a median interval of 42 months (range, 3 months-7 years) from initial presentation with unilateral neck mass, patients were diagnosed with HPV-OPC. At the time of HPV-OPC diagnosis, five were AJCC eighth edition overall stage I, and one was stage II. Primary tumors were T0 or T1 in the majority (83.3%, n = 5). Among five patients with available serial imaging, despite diagnostic delay, three of five still had a single lymph node without involvement of additional nodes, whereas the remaining two developed additional suspicious nodes (ipsilateral and contralateral). Two of five developed evidence of extranodal extension. Median lymph node growth was 9.5% per year (range, -6% to 32%).

Conclusions: Although the natural history of HPV-OPC is not well understood, this case series suggests that it can be slow growing and mimic benign processes, leading to diagnostic delays. Adults presenting with neck masses should undergo complete diagnostic evaluation.

Level of evidence: 4 Laryngoscope, 130:392-397, 2020.

Keywords: Neck mass; human papillomavirus; squamous cell carcinoma.

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

Conflict of interest statement
Conflicts of Interest: None

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32
Comparative Study Arch Pathol Lab Med
. 2020 Mar;144(3):344-349. doi: 10.5858/arpa.2019-0093-CP. Epub 2019 Sep 4.
Comparative Performance of High-Risk Human Papillomavirus RNA and DNA In Situ Hybridization on College of American Pathologists Proficiency Tests
Elaine S Keung 1, Rhona J Souers 1, Julia A Bridge 1, William C Faquin 1, Rondell P Graham 1, Meera R Hameed 1, James S Lewis Jr 1, Jason D Merker 1, Patricia Vasalos 1, Joel T Moncur 1
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PMID: 31483999 DOI: 10.5858/arpa.2019-0093-CP
Abstract
Context.—: Detection of high-risk human papillomavirus (HR-HPV) in squamous cell carcinoma is important for classification and prognostication. In situ hybridization (ISH) is a commonly used HR-HPV-specific test that targets viral RNA or DNA. The College of American Pathologists (CAP) provides proficiency testing for laboratories performing HR-HPV ISH.

Objective.—: To compare the analytical performance of RNA- and DNA-based ISH methods on CAP HR-HPV proficiency tests.

Design.—: Data from the 2016-2018 CAP HPV ISH proficiency testing surveys were reviewed. These surveys consist of well-characterized samples with known status for HR-HPV, including 1 to 2 copies, 50 to 100 copies, 300 to 500 copies, and no copies of HR-HPV per cell.

Results.—: Ninety-five participants submitted 1268 survey results from 20 cores. Overall, RNA ISH had a significantly higher percentage of correct responses than DNA ISH: 97.4% (450 of 462) versus 80.6% (650 of 806) (P < .001). This disparity appears to be the consequence of a superior sensitivity of RNA ISH compared to DNA ISH for samples with 1 to 2 and with 50 to 100 copies of HR-HPV per cell: 95.2% (120 of 126) versus 53.8% (129 of 240), P < .001, respectively, and 100% (89 of 89) versus 76.3% (119 of 156), P < .001, respectively.

Conclusions.—: An assessment of CAP HR-HPV proficiency test performance indicates that RNA ISH shows significantly higher accuracy than DNA ISH owing to higher analytical sensitivity of RNA ISH in tumors with low (1-2 copies per cell) to intermediate (50-100 copies per cell) HR-HPV viral copy numbers. These data support the use of RNA over DNA ISH in clinical laboratories that perform HR-HPV testing as part of their testing algorithms.

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33
Cureus
. 2020 Jun 21;12(6):e8751. doi: 10.7759/cureus.8751.
A Retrospective Cohort and Systematic Review of Non-Operative Management of Exposed Calvaria Post-Radiotherapy
Pinkal Patel 1, James Edward Massey Young 2, Mark McRae 3, Jenny Santos 4, Carolyn Levis 4, Michael K Gupta 2, Sophocles Voineskos 4, Lucas Gallo 3, Emily Dunn 4, Matthew C McRae 5
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PMID: 32714689 PMCID: PMC7377020 DOI: 10.7759/cureus.8751
Free PMC article
Abstract
Scalp defects with exposed calvaria that have previously been irradiated present a unique reconstructive challenge. Patients with previously radiated scalp defects often have few reconstructive options due to poor health or personal choice. The aim of this study was to evaluate the results of non-operative management for patients with prior radiotherapy to the scalp who developed exposed calvaria. The outcomes of interest were major and minor complications related to exposed calvaria with a time frame of follow-up of greater than one year or death from any cause. A retrospective chart review was performed to identify patients with prior radiotherapy and surgery for skin cancer to the scalp who subsequently developed exposed calvaria. Data from four surgeons from 2008 to 2019 was collected. Next, a systematic review of PubMed, EMBASE, Cochrane Library, and CINAHL was conducted to identify articles in which non-operative management was utilized for exposed calvaria post-radiotherapy. Nineteen patients were identified who received radiotherapy either before developing recurrent malignancy requiring operation or requiring radiation postoperatively because of close or involved margins and who subsequently developed exposed calvaria. Six of these patients had an additional attempt at local flap or skin grafting that failed. All patients had an American Society of Anesthesiologists score of three or four. All were managed with local wound care. Ten patients had near-complete healing with wound care alone. Eight patients are still alive from one to six years after the presentation. One patient, who remains alive, developed an intracranial abscess requiring long-term antibiotics but was medically compromised by concomitant myelodysplastic syndrome, mantle cell lymphoma on chemotherapy, atrial fibrillation on anticoagulation, and heart failure. Three patients developed new malignancies requiring re-operation with watchful waiting. Two of the three cases resulted in failure to control disease, but control of malignancy occurred in one case with resection of recurrent cancer and exposed bone. The systematic review of the literature yielded three studies that met the inclusion criteria. None of the studies encountered cases of meningitis, encephalitis, or death due to the non-operative treatment of exposed calvaria post radiation. Coverage of the calvaria with well-vascularized tissue is the reconstructive goal in the majority of circumstances. This case series and systematic review found that non-operative management of exposed calvaria post-radiotherapy can be an option for patients who are either not candidates for aggressive surgical treatment or who refuse surgery.

Keywords: exposed calvaria; non-operative management; osteoradionecrosis; radiation; radiotherapy.

Copyright © 2020, Patel et al.

Conflict of interest statement
The authors have declared that no competing interests exist.

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34
Laryngoscope
. 2020 Feb;130(2):514-520. doi: 10.1002/lary.27888. Epub 2019 Mar 5.
Aspiration in the otherwise healthy Infant-Is there a natural course for improvement?
Geoffrey C Casazza 1 2, M Elise Graham 1 2, Fadi Asfour 3 2, Molly O'Gorman 3 2, Jonathan Skirko 1 2, Jeremy D Meier 1 2
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PMID: 30835858 DOI: 10.1002/lary.27888
Abstract
Objectives/hypothesis: Timing and indication for surgical intervention is a major challenge in managing pediatric oropharyngeal dysphagia. No study has evaluated a natural course of swallowing dysfunction in otherwise healthy infants. Our objective was to review the outcomes and time to resolution of abnormal swallow in infants with aspiration.

Study design: Retrospective case series at a tertiary children's hospital.

Methods: Fifty patients under 1 year old with aspiration on a modified barium swallow study were included. Patients born <34 weeks, with medical or genetic comorbidities, or who underwent surgical intervention for aspiration were excluded. Patients were followed until aspiration resolved on a swallow study. Kaplan-Meier survival analysis was performed.

Results: Forty patients (25 patients [50%] by 6 months, 10 [20%] by 1 year, three [6%] by 2 years, and two [4%] at the end of the follow-up interval) were recommended a normal diet, and 10 patients (20%) were still aspirating by the end of the follow-up interval. Median time to resolution was 202 ± 7 days (range, 19-842 days), probability 48% (95% confidence interval [CI]: 0.34-0.62). The probability of resolution at 6 months was 46% (95% CI: 0.4-0.68), at 1 year was 64% (95% CI: 0.51-0.77), at 2 years was 76% (95% CI: 0.64-0.88), and at the end of the follow-up interval 81.3% (95% CI: 0.7-0.92).

Conclusions: The majority of infants with aspiration and without any other major comorbidities improved within 1 year. Future research should be directed toward better understanding swallowing dysfunction in neurologically normal infants.

Level of evidence: 4 Laryngoscope, 130:514-520, 2020.

Keywords: Oropharyngeal dysphagia; aspiration; laryngology; pediatric otolaryngology.

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

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35
J Clin Med
. 2020 Jul 18;9(7):E2282. doi: 10.3390/jcm9072282.
Clinical Course and Outcomes of Severe Covid-19: A National Scale Study
Moran Amit 1, Alex Sorkin 2 3, Jacob Chen 2 4, Barak Cohen 5 6, Dana Karol 5, Avishai M Tsur 2 7 8, Shaul Lev 8 9, Tal Rozenblat 8 10, Ayana Dvir 11, Geva Landau 2 3, Lidar Fridrich 12, Elon Glassberg 2 13 14, Shani Kesari 2 15, Sigal Sviri 16, Ram Gelman 2 17, Asaf Miller 18, Danny Epstein 2 19, Ronny Ben-Avi 20 21, Moshe Matan 14 21, Daniel J Jakobson 22 23, Tarif Bader 2 24, David Dahan 25, Daniel A King 25 26, Anat Ben-Ari 27, Arie Soroksky 8 28, Alon Bar 29 30, Noam Fink 2 24, Pierre Singer 8 31, Avi Benov 2 14
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PMID: 32708357 DOI: 10.3390/jcm9072282
Abstract
Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined.

Methods: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality.

Results: This study included 156 patients (median age = 72 years (range = 22-97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0-37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84-0.96) were independent prognostic factors.

Conclusions: In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.

Keywords: ARDS; ICU; comorbidities; covid-19; mortality; prognosis.

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Laryngoscope
. 2020 Feb;130(2):460-464. doi: 10.1002/lary.28004. Epub 2019 May 9.
Cortical-Basal Ganglia-Cerebellar Networks in Unilateral Vocal Fold Paralysis: A Pilot Study
Philip L Perez 1, Kristine L Cueva 1, Clark A Rosen 1, VyVy N Young 1, Molly L Naunheim 1, Katherine C Yung 2, Sarah L Schneider 1, Danielle Mizuiri 1 3, David J Klein 1, John F Houde 1, Leighton B Hinkley 3, Srikantan S Nagarajan 1 3, Steven W Cheung 1
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PMID: 31070785 DOI: 10.1002/lary.28004
Abstract
Objectives/hypothesis: To evaluate differences in cortical-basal ganglia-cerebellar functional connectivity between treated unilateral vocal fold paralysis (UVFP) and healthy control cohorts using resting-state functional magnetic resonance imaging (RS-fMRI).

Study design: Cross-sectional.

Methods: Ten UVFP study patients treated by type I thyroplasty and 12 control subjects underwent RS-fMRI on a 3-Tesla scanner to evaluate differences in functional connectivity of whole-brain networks. Spontaneous RS-fMRI data were collected using a gradient echo planar pulse sequence, preprocessed, and analyzed to compare seed-to-voxel maps between the two cohorts. Seeds were placed in the caudate, putamen, and globus pallidus divisions of the basal ganglia in both hemispheres. Group contrasts were tested for statistical significance using two-tailed unpaired t tests corrected for multiple comparisons with a cluster false discovery rate threshold of P < .05.

Results: UVFP patients demonstrated increased connectivity between both caudate nuclei and the precuneus, a node of the default mode network, compared to healthy controls. Both caudate nuclei also showed decreased connectivity with the left cerebellar hemisphere. The putamen and globus pallidus divisions of the basal ganglia were not abnormally connected to other brain structures.

Conclusions: UVFP patients treated by type I thyroplasty exhibited long-term alterations of cortical-basal ganglia-cerebellar networks thought to be important for self-referential voice quality awareness and learning processes that compensate for changes to the paralyzed hemilarynx. This pilot study on relatively small cohorts adds to growing evidence for persistent central nervous system changes in treated UVFP. Replication studies with larger numbers of subjects will be essential to validate and extend findings.

Level of evidence: 3b Laryngoscope, 130:460-464, 2020.

Keywords: Basal ganglia; cerebellum; functional connectivity; resting-state functional magnetic resonance imaging; unilateral vocal fold paralysis.

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

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37
Review Cancer Treat Rev
. 2020 Jul 15;89:102069. doi: 10.1016/j.ctrv.2020.102069. Online ahead of print.
Systemic therapy in the management of recurrent or metastatic salivary duct carcinoma: A systematic review
M J M Uijen 1, G Lassche 1, A C H van Engen-van Grunsven 2, Y Tada 3, G W Verhaegh 4, J A Schalken 4, C M L Driessen 1, C M L van Herpen 5
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PMID: 32717621 DOI: 10.1016/j.ctrv.2020.102069
Abstract
Background: Salivary duct carcinoma (SDC) is an aggressive subtype of salivary gland cancer. Approximately half of SDC patients will develop recurrences or metastases. Therapeutic palliative therapy is therefore often needed. The majority of SDC tumors expresses the androgen receptor (AR) and one-third expresses human epidermal growth factor receptor 2 (HER2), both are potential therapeutic targets. The aim of this paper is to systematically review and summarize the evidence on systemic palliative therapy for SDC and to provide treatment recommendations.

Materials and methods: Electronic libraries were systematically searched with a broad search strategy to identify studies where SDC patients received systemic therapy. Due to the rarity of SDC no restrictions were placed on study designs.

Results: The search resulted in 2014 articles of which 153 were full-text analyzed. Forty-five studies were included in the analysis, which included in total 256 SDC patients receiving systemic therapy. Two phase 2 trials primarily including SDC patients were identified. The majority of the studies were case series or case reports, resulting in an overall low quality of available evidence. Based on studies including ≥ 5 SDC patients, objective responses to HER2 targeting agents were observed in 60-70%, to AR pathway agents in 18-53% and to chemotherapy in 10-50%.

Conclusion: For AR or HER2 positive SDC, agents targeting these pathways are the cornerstone for palliative treatment. Regarding chemotherapy, the combination of carboplatin combined with a taxane is best studied. Regarding other targeted agents and immunotherapy evidence is anecdotal, limiting formulation of treatment recommendations for these antineoplastic agents.

Keywords: Palliative treatment; Salivary duct carcinoma; Salivary gland cancer; Systemic therapy.

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CvH: Advisory (institution): Bayer, Bristol-Myers Squibb, Ipsen, MSD, Regeneron. Research grant (institution): Astra Zeneca, Bristol-Myers Squibb, MSD, Merck, Ipsen, Novartis, Sanofi. MU: nothing to declare. GL: nothing to declare. AvE: nothing to declare. CD: nothing to declare. YT: nothing to declare. GV: nothing to declare. JS: nothing to declare.

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38
Pediatr Neurol
. 2020 May 20;S0887-8994(20)30168-5. doi: 10.1016/j.pediatrneurol.2020.05.006. Online ahead of print.
Brain Magnetic Resonance Imaging in Congenital Cytomegalovirus With Failed Newborn Hearing Screen
Jennifer A Hranilovich 1, Albert H Park 2, Elizabeth D Knackstedt 3, Betsy E Ostrander 2, Gary L Hedlund 4, Kevin Shi 2, James F Bale Jr 5
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PMID: 32713673 DOI: 10.1016/j.pediatrneurol.2020.05.006
Abstract
Background: In 2013, Utah enacted legislation requiring that infants failing newborn hearing screening be tested for cytomegalovirus infection. As a result, cytomegalovirus-infected infants are being identified because of hearing deficits. The neuroimaging findings in this population have not been characterized.

Methods: Retrospective medical record review was used to identify patients seen at the University of Utah and Primary Children's Hospitals in Salt Lake City, Utah, who failed newborn hearing screening. A cohort of patients with congenital cytomegalovirus infection, brain magnetic resonance imaging (MRI), and sedated auditory brainstem response testing was studied.

Results: Seventeen patients were identified; 11 (65%) were female. Confirmatory auditory brainstem response testing, performed at a median age 29 days, showed profound hearing loss in 8 (47%) subjects, severe loss in two (12%), moderate loss in two (12%), and mild loss in three (18%); two (12%) subjects had normal hearing. The diagnosis of cytomegalovirus infection was made at a median age 23 days. Brain imaging was performed at a median age 65 days. Ten (59%) subjects had one or more neuroimaging abnormality. White matter lesions were found in eight (47%) subjects, cysts in three (18%), and stroke in two (12%). Polymicrogyria was identified in two (12%) subjects. Seven (41%) subjects had normal brain MRIs.

Conclusions: These results indicate that most infants whose cytomegalovirus infections were identified after failing newborn hearing screening had abnormal brain MRIs. Our results suggest that brain MRIs should be considered in infants with congenital cytomegalovirus infections who are identified through hearing screening programs.

Keywords: Auditory brainstem response; Brain MRI; Brain magnetic resonance imaging; Congenital CMV; Congenital cytomegalovirus infection; Hearing loss; Newborn hearing screen; White matter lesions.

Copyright © 2020 Elsevier Inc. All rights reserved.

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39
J Pediatr Surg
. 2020 Jul 1;S0022-3468(20)30470-X. doi: 10.1016/j.jpedsurg.2020.06.039. Online ahead of print.
Pyriform sinus fistula in children: A comparison of endoscopic-assisted surgery and endoscopic radiofrequency ablation
Tong Chen 1, Jianglong Chen 1, Qingfeng Sheng 1, Linlin Zhu 1, Xiaoling Bai 1, Weijue Xu 1, Jiangbin Liu 1, Xiaoyan Li 2, Zhibao Lv 3
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PMID: 32709530 DOI: 10.1016/j.jpedsurg.2020.06.039
Abstract
Background: Pyriform sinus fistula (PSF) is a rare congenital anomaly, and the preferred definitive treatment is yet to be verified. In this study, we investigated the treatment outcomes of PSF specifically comparing endoscopic-assisted surgery and endoscopic radiofrequency ablation (RA).

Methods: The medical records of patients treated for PSF at the Shanghai Children's Hospital between October 2016 and September 2019 were retrospectively evaluated.

Results: There were 93 girls and 98 boys. The median age at onset and operation was 3 years and 5 years, respectively. Endoscopic-assisted surgery was performed in 143 patients. During the same period, RA was performed in 48 patients, and 10 of them concurrently underwent incision and drainage of neck abscesses. Longer hospital stay was found in the endoscopic-assisted surgery group than in the RA group (10.50 ± 3.93 vs. 5.02 ± 3.30 days, P < 0.001). Postoperative complications were not significantly different between the two groups, except for neck infection (0 vs. 8.3%, P = 0.004). After a median follow-up period of 21 months, no significant difference was found between the two groups in terms of recurrence (1.4% vs. 0, P = 0.560).

Conclusion: Patients treated with RA had a significantly shorter hospital stay than those treated with endoscopic-assisted surgery. Outcomes of endoscopic-assisted surgery and RA were not significantly different for the management of PSF and treatment method should be tailored to the patient.

Level of evidence: IV.

Keywords: Endoscopic-assisted surgery; Outcomes; Pyriform sinus fistula; Radiofrequency ablation.

Copyright © 2020. Published by Elsevier Inc.

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40
Front Oncol
. 2020 Jun 25;10:1026. doi: 10.3389/fonc.2020.01026. eCollection 2020.
Apoptin Regulates Apoptosis and Autophagy by Modulating Reactive Oxygen Species (ROS) Levels in Human Liver Cancer Cells
Yiquan Li 1, Yilong Zhu 1, Jinbo Fang 1, Wenjie Li 1 2, Shanzhi Li 1 2, Xing Liu 1 2, Zirui Liu 2, Gaojie Song 1 2, Chao Shang 1 2, Jianan Cong 1 2, Bing Bai 1, Lili Sun 3, Ningyi Jin 1 2 4, Xiao Li 1 2 4
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PMID: 32714864 PMCID: PMC7344208 DOI: 10.3389/fonc.2020.01026
Free PMC article
Abstract
Apoptin is a protein that specifically induces apoptosis in tumor cells. The anti-tumorigenic functions of Apoptin, including autophagy activation and its interaction with apoptosis, have not been precisely elucidated. Here we investigate the main pathways of apoptin-mediated killing of human liver cancer cells, as well as its putative role in autophagy and apoptosis. The anti-proliferative effect of apoptin in liver cancer cells was analyzed in vitro by crystal violet staining and MTS detection, and also in vivo using a tumor-based model. The main pathway related to apoptin-induced growth inhibition in vitro was evaluated by flow cytometry and fluorescence staining. The relationship between apoptosis and autophagy on apoptin-treating cells was analyzed using apoptosis and autophagy inhibitors, mitochondrial staining, Annexin V-FITC/PI flow detection, LC3 staining, and western blotting. The effect of ROS toward the apoptosis and autophagy of apoptin-treating cells was also evaluated by ROS detection, Annexin V-FITC/PI flow detection, LC3 staining, and western blotting. Inhibition of apoptosis in apoptin-treating liver cancer cells significantly reduced the autophagy levels in vitro. The overall inhibition increased from 12 h and the effect was most obvious at 48 h. Inhibition of autophagy could increase apoptin-induced apoptosis of cells in a time-dependent manner, reaching its peak at 24 h. Apoptin significantly alters ROS levels in liver cancer cells, and this effect is directly related to apoptosis and autophagy. ROS appears to be the key factor linking apoptin-induced autophagy and apoptosis through the mitochondria in liver cancer cells. Therefore, evaluating the interaction between apoptin-induced apoptosis and autophagy is a promising step for the development of alternate tumor therapies.

Keywords: ROS; apoptin; apoptosis; autophagy; human liver cancer.

Copyright © 2020 Li, Zhu, Fang, Li, Li, Liu, Liu, Song, Shang, Cong, Bai, Sun, Jin and Li.

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41
J Med Virol
. 2020 Jul 25. doi: 10.1002/jmv.26354. Online ahead of print.
A Structural Equation Model to Examine the Clinical Features of Mild-to-Moderate Covid-19: A Multicenter Italian Study
Maria Rosaria Barillari 1 2, Luca Bastiani 3, Jerome R Lechien 2 4, Giuditta Mannelli 2 5, Gabriele Molteni 2 6, Giovanna Cantarella 2 7, Nicola Coppola 1, Giuseppe Costa 1, Eleonora M C Trecca 8, Calogero Grillo 9, Ignazio La Mantia 9, Carlos M Chiesa-Estomba 2 10, Claudio Vicini 11, Sven Saussez 2 12, Andrea Nacci 2 13, Giovanni Cammaroto 2 11
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PMID: 32710639 DOI: 10.1002/jmv.26354
Abstract
Purpose: To evaluate the clinical features of mild-to-moderate COVID-19 in a sample of Italian patients and to investigate the occurrence of smell and taste disorders.

Methods: Infected individuals with suspected (clinical diagnosis) or laboratory-confirmed COVID-19 infection were recruited. Patients completed a survey-based questionnaire with the aim of assessing their epidemiological and clinical characteristics, general otorhinolaryngological symptoms and smell and taste disorders.

Results: A total of 294 mild-to-moderate COVID19 patients completed the survey (147 females). The most prevalent general symptoms included fever, myalgia, cough and headache. A total of 70.4% and 59.2% of patients reported smell and taste disorders, respectively. A significant association between the two above-mentioned disorders was found (rs: 0.412; p<0.001). Smell disorders occurred prior to the other symptoms in 11.6% of patients and was not significantly associated with nasal obstruction or rhinorrhea. Interestingly, our statistical analysis did not show any significant difference, either for general symptoms or otorhinolaryngological features, between the clinical diagnosis group and the laboratory confirmed diagnosis (PCR) group. The structural equation model confirmed significant standardized paths (p <0.05) between general symptoms, comorbidities and general otorhinolaryngological complaints in the absence of a significant correlation between these elements and smell and taste alterations.

Conclusion: The prevalence of smell and taste disorders in mild-to-moderate Italian COVID-19 patients is significant both in suspected and laboratory confirmed cases and reveals a strong correlation between these clinical signs regardless of the presence of general or otorhinolaryngological symptoms, such as nasal obstruction or rhinorrhea. This article is protected by copyright. All rights reserved.

Keywords: COVID-19; ENT; SARS-CoV-2; anosmia; coronavirus; smell and taste; structural equation model.

This article is protected by copyright. All rights reserved.

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42
Oper Neurosurg (Hagerstown)
. 2020 Jul 25;opaa212. doi: 10.1093/ons/opaa212. Online ahead of print.
Collagen Matrix With Mucoperiosteum Graft as an Effective Fatless Flapless Reconstruction After Endoscopic Pituitary Adenoma Resection
Mostafa Shahein 1 2, Alaa S Montaser 1 3, Juan M Revuelta Barbero 1, Guillermo Maza 4, Alexandre B Todeschini 1, Bradley A Otto 1 4, Ricardo L Carrau 1 4, Daniel M Prevedello 1 4
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PMID: 32710760 DOI: 10.1093/ons/opaa212
Abstract
Background: Proper skull base reconstruction after endoscopic endonasal pituitary surgery is of great importance to decrease the rate of complications.

Objective: To assess the safety and efficacy of reconstruction with materials other than fat graft and naso-septal flaps (NSF) to avoid their associated morbidities.

Methods: The authors' institutional database for patients who underwent endoscopic endonasal approach for pituitary adenoma was reviewed. Exclusion criteria included recurrence, postradiation therapy, and reconstruction by fat graft or NSF. They were divided into group A, where collagen matrix (CM) (DuraGen® Plus Matrix, Integra LifeSciences Corporation, Plainsboro, New Jersey) alone was used; group B, where CM and simple mucoperiosteum graft were used and group C, which included cases without CM utilization.

Results: The study included 252 patients. No age, gender, or body mass index statistically significant difference between groups. Group B included the largest tumor size (23.0 mm) in comparison to groups A (18.0 mm) and C (13.0 mm). Suprasellar extension was more frequently present (49.4%) in comparison to groups A (29.8%, P = .001) and C (21.2%, P < .001). Postoperative cerebrospinal fluid (CSF) leak rate was 0%, 2.9%, and 6% in groups A, B, and C, respectively. In group B, the CSF leak rate decreased from 45.9% intraoperatively to 2.9% postoperatively (P < .001). In group A, the CSF leak reduction rate was almost statistically significant (P = .06).

Conclusion: Utilization of CM and simple mucosperiosteal graft in skull base reconstruction following pituitary adenoma surgery is an effective method to avoid the morbidities associated with NSF or fat graft.

Keywords: Collagen matrix; Endoscopic endonasal approach; Mucoperiosteal graft; Neuroendoscopy; Pituitary; Pituitary surgery; Skull base surgery.

Copyright © 2020 by the Congress of Neurological Surgeons.

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43
Laryngoscope
. 2020 Feb;130(2):454-459. doi: 10.1002/lary.27999. Epub 2019 May 6.
Quantifying vocal fold wound-healing biomechanical property changes
Gregory R Dion 1 2 3, Teja Guda 2, Shigeyuki Mukudai 3, Renjie Bing 3, Jean-Francois Lavoie 4, Ryan C Branski 3
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PMID: 31059589 DOI: 10.1002/lary.27999
Abstract
Objectives: Development of novel vocal fold (VF) therapeutics is limited by a lack of standardized, meaningful outcomes. We hypothesize that automated microindentation-based VF biomechanical property mapping matched to histology permits quantitative assessment.

Study design: Ex vivo.

Methods: Twelve anesthetized New Zealand white rabbits underwent endoscopic right VF injury. Larynges were harvested/bisected day 7, 30, or 60 (n = 4/group), with four uninjured controls. Biomechanical measurements (normal force, structural stiffness, and displacement at 1.96 mN) were calculated using automated microindentation mapping (0.3 mm depth, 1.2 mm/s, 2 mm spherical indenter) with a grid overlay (>50 locations weighted toward VF edge, separated into 14 zones). Specimens were marked/fixed/sectioned, and slides matched to measurement points.

Results: In the injury zone, normal force/structural stiffness (mean, standard deviation [SD]/mean, SD) increased from uninjured (2.2 mN, 0.64/7.4 mN/mm, 2.14) and day 7 (2.7 mN, 0.75/9.0 mN/mm, 2.49) to day 30 (4.3 mN, 2.11/14.2 mN/mm, 7.05) and decreased at 60 days (2.7 mN, 0.77/9.1 mN/mm, 2.58). VF displacement decreased from control (0.28 mm, 0.05) and day 7 (0.26 mm, 0.05) to day 30 (0.20 mm, 0.05), increasing at day 60 (0.25 mm, 0.06). A one-way ANOVA was significant; Tukey's post hoc test confirmed day-30 samples differed from other groups (P < 0.05), consistent across adjacent zones. Zones far from injury remained similar across groups (P = 0.143 to 0.551). These measurements matched qualitative histologic variations.

Conclusion: Quantifiable VF biomechanical properties can be linked to histology. This technological approach is the first to simultaneously correlate functional biomechanics with histology and is ideal for future preclinical studies.

Level of evidence: NA Laryngoscope, 130:454-459, 2020.

Keywords: Voice; biomechanics; injury; microindentation; vocal fold; wound healing.

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

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44
J Neurol
. 2020 Jul 25. doi: 10.1007/s00415-020-10092-2. Online ahead of print.
Introducing the DizzyQuest: an app-based diary for vestibular disorders
E C Martin 1, C Leue 2, P Delespaul 2, F Peeters 3, A M L Janssen 4 5, R Lousberg 2, A Erdkamp 6, S van de Weijer 6, J Widdershoven 1, H Blom 7, T Bruintjes 8, A Zwergal 9, E Grill 10, N Guinand 11, A Perez-Fornos 11, M R van de Berg 1, J J A Stultiens 1, H Kingma 1 12, R van de Berg 13 14
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PMID: 32712867 DOI: 10.1007/s00415-020-10092-2
Abstract
Background: Most questionnaires currently used for assessing symptomatology of vestibular disorders are retrospective, inducing recall bias and lowering ecological validity. An app-based diary, administered multiple times in daily life, could increase the accuracy and ecological validity of symptom measurement. The objective of this study was to introduce a new experience sampling method (ESM) based vestibular diary app (DizzyQuest), evaluate response rates, and to provide examples of DizzyQuest outcome measures which can be used in future research.

Methods: Sixty-three patients diagnosed with a vestibular disorder were included. The DizzyQuest consisted of four questionnaires. The morning- and evening-questionnaires were administered once each day, the within-day-questionnaire 10 times a day using a semi-random time schedule, and the attack questionnaire could be completed after the occurrence of a vertigo or dizziness attack. Data were collected for 4 weeks. Response rates and loss-to-follow-up were determined. Reported symptoms in the within-day-questionnaire were compared within and between patients and subgroups of patients with different vestibular disorders.

Results: Fifty-one patients completed the study period. Average response rates were significantly higher than the desired response rate of > 50% (p < 0.001). The attack-questionnaire was used 159 times. A variety of neuro-otological symptoms and different disease profiles were demonstrated between patients and subgroups of patients with different vestibular disorders.

Conclusion: The DizzyQuest is able to capture vestibular symptoms within their psychosocial context in daily life, with little recall bias and high ecological validity. The DizzyQuest reached the desired response rates and showed different disease profiles between subgroups of patients with different vestibular disorders. This is the first time ESM was used to assess daily symptoms and quality of life in vestibular disorders, showing that it might be a useful tool in this population.

Keywords: DizzyQuest; Experience sampling; Vestibular disorders.

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45
J Voice
. 2020 Jul 22;S0892-1997(20)30240-X. doi: 10.1016/j.jvoice.2020.06.026. Online ahead of print.
Functional Outcomes of the Hyaluronic Acid Injections in Patients Who Underwent Partial Laryngectomy
Elvin Alaskarov 1, Özcan Öztürk 1, Ayşegül Batıoğlu-Karaaltın 1, Züleyha Dilek Gülmez 2, Zülküf Burak Erdur 3, Hakkı Caner İnan 1
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PMID: 32712078 DOI: 10.1016/j.jvoice.2020.06.026
Abstract
Objective: The purpose of this study was to investigate the effects of hyaluronic acid injection on dysphagia, aspiration, and voice problems in patients with persistent functional problems despite appropriate rehabilitation after partial laryngectomy.

Methods: Seventeen patients who underwent hyaluronic acid injection due to persistent swallowing, aspiration, and voice problems after partial laryngectomy surgery were included in the study. The hyaluronic acid injection was performed after 2 years of follow-up after partial laryngectomy surgery. Evaluation of swallowing was performed through a fiberoptic endoscopic evaluation of swallowing and was quantified using two scales: a dysphagia score and a modified penetration-aspiration scale. Voice Handicap Index-10 was used for the determination of the psychosocial handicapping effects of the voice. Jitter percent, shimmer percent, fundamental frequency, harmonics-to-noise ratio, and maximum phonation time were evaluated for the acoustic analysis of the voice. All measurements were performed at preoperative day and postoperative months 1, 6, and 24.

Results: A statistically significant improvement was observed for all of the evaluated parameters except the harmonics-to-noise ratio for postoperative months 1 and 6 (P < 0.05). There was no statistically significant difference between the postoperative sixth month and the preoperative value of the harmonics-to-noise ratio. A statistically significant improvement was observed between the postoperative 24th month and preoperatively for jitter percent, shimmer percent, fundamental frequency, maximum phonation time, dysphagia, and penetration aspiration score (P < 0.05).

Conclusion: Surgical rehabilitation should be considered along with conservative treatments to improve swallowing and voice function after partial laryngectomy. Hyaluronic acid injection may be an effective method both in the short and long term for the surgical rehabilitation of persisting functional problems that may occur following partial laryngectomies.

Keywords: Hyaluronic acid; Open partial laryngectomy; Quality of life; Swallowing; Voice.

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

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46
Cancer Med
. 2020 Jul 27. doi: 10.1002/cam4.3339. Online ahead of print.
Human papillomavirus (HPV) in Chinese oropharyngeal squamous cell carcinoma (OPSCC): A strong predilection for the tonsil
Tingting Xu 1 2, Chunying Shen 1 2, Ye Wei 1 2, Chaosu Hu 1 2, Yu Wang 2 3, Jun Xiang 2 3, Guo-Hua Sun 2 3, Fengtao Su 4, Qifeng Wang 2 5, Xueguan Lu 1 2
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PMID: 32717137 DOI: 10.1002/cam4.3339
Free article
Abstract
Objective: Compared with Occident's data, the incidence of Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) had been reported as relatively low in Mainland China. The objective of this study was to report the integrated prevalence of HPV and Epstein-Barr virus (EBV), and further evaluate the different behaviors of HPV-positive and -negative OPSCCs in eastern China.

Methods: In a cohort of 170 nonmetastatic OPSCCs treated from January 2007 to July 2019, p16 protein expression, HPV genotypes, and Epstein-Barr virus-encoded RNA (EBER) were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). The clinical and pathologic findings were further collected and analyzed to comprehensively reveal the behaviors of Chinese OPSCCs.

Results: Out of the 170 tumor tissues evaluated, 57.6% (98) samples had positive p16 expressions. A total of 65.1% (99/152) samples had positive HPV genotypes, besides HPV16 (92/152), HPV11, 18, 33, 53, and 58 were also detected. The positive rate of EBER was 7.2% (9/124), and the co-infection rate of EBV/HPV was 4.0%. Related to the unequal distributions of p16 expression, HPV-related tumors arisen from tonsillar and non-tonsillar accounted for 68.8% (75/109) and 37.7% (23/61) of their cases, respectively (P < .001). With a median follow-up time of 13.1 months, significant survival advantages of HPV-related OSPCC were observed; 1-year OS, PFS, RFS, and MFS were 83.2% vs 96.7% (P < .001), 71.6% vs 96.2% (P < .001), 77.7% vs 96.2% (P = .002), and 90.4% vs 100.0% (P = .024) in p16-negative and -positive cases, respectively.

Conclusions: The relative percent of HPV-positive OPSCCs in this study is close to the positive rate in many Western countries and a strong predilection was discovered for the tonsillar. The EBV infection and co-infection of HPV/EBV were largely low. The prognosis of HPV-positive OSPCCs was more favorable than its negative counterpart.

Keywords: EBV; HPV; oropharyngeal squamous cell carcinoma; prognosis; tonsillar.

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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47
Oral Oncol
. 2020 Jul 23;111:104894. doi: 10.1016/j.oraloncology.2020.104894. Online ahead of print.
T cell fraction impacts oncologic outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma
Kathryn M Van Abel 1, David M Routman 2, Eric J Moore 3, Daniel J Ma 2, Linda X Yin 3, Paul A Fields 4, Matt Schofield 4, Kathleen R Bartemes 3, Kyriakos Chatzopoulos 5, Daniel L Price 3, Jeffrey R Janus 3, Jan L Kasperbauer 3, Katharine A Price 6, Ashish V Chintakuntlawar 6, Michelle A Neben-Wittich 2, Robert L Foote 2, Joaquin J Garcia 5
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PMID: 32712575 DOI: 10.1016/j.oraloncology.2020.104894
Abstract
Background: We investigated T cell clonality (TCC) and T cell fraction (TCF) in human papilloma virus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) progressors [cases] vs. non-progressors [controls].

Methods: This nested case-control study included patients undergoing intent-to-cure surgery ± adjuvant therapy from 6/1/2007-10/3/2016. Patients experiencing local/regional/distant disease (progressors), and a consecutive sample of non-progressors were matched (2 controls: 1 case) on tumor subsite, T-stage and number of metastatic lymph nodes. We performed imunosequencing of the CDR3 regions of human TCRβ chains.

Results: 34 progressors and 65 non-progressors were included. There was no statistically significant difference in baseline TCF (range: 0.039-1.084) and TCC (range: 0.007-0.240) (p > 0.05). Female sex was associated with higher TCF (p = 0.03), while extranodal extension (ENE) was associated with lower TCF (p = 0.01). There was a positive correlation between tumor size and clonality (R = 0.34, p < 0.01). The strongest predictor of progression-free survival (PFS) was TCF (HR 0.80, 95%CI 0.66-0.96, p = 0.02). The strongest predictors of cancer specific survival (CSS) were TCF (HR0.69, 95%CI 0.47-1.00, p < 0.05) and Adult Comorbidity Evaluation-27 (ACE-27) score (p < 0.05). Similarly, the strongest predictors of overall survival (OS) were TCF (HR 0.62, 95%CI 0.43-0.91, p = 0.01) and ACE-27 score (p = 0.03). On multivariable modeling, TCF ≥ 0.4 was independently associated with PFS (HR 0.34, 95%CI 0.14-0.85, p = 0.02) while an ACE-27 score of ≥ 2 independently predicted CSS (HR 3.85, 95%CI 1.07-13.85, p = 0.04) and OS (HR 3.51, 95%CI 1.10-11.20, p = 0.03).

Conclusions: In patients with HPV(+)OPSCC, TCF was higher in female patients and those without ENE, suggesting differential immune responses. Lower TCF was significantly and independently associated with disease progression. Better ACE-27 scores appear to predict improved oncologic control.

Keywords: ACE-27; Comorbidities; HPV; Human papillomavirus; Immune; Immunoseq; Oropharyngeal; Oropharynx; Squamous cell carcinoma; T cell clonality; T cell repertoire; Tumor microenvironment.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Conflict of interest statement
Declaration of Competing Interest PAF and MS have a financial interest in Adaptive Biotechnologies. KMV has consulted for Intuitive Surgical within the last 24 months.

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48
Prog Mol Biol Transl Sci
. 2020;173:91-137. doi: 10.1016/bs.pmbts.2020.04.015. Epub 2020 May 8.
Autism spectrum disorder risk prediction: A systematic review of behavioral and neural investigations
Xiujuan Geng 1, Xin Kang 2, Patrick C M Wong 3
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PMID: 32711819 DOI: 10.1016/bs.pmbts.2020.04.015
Abstract
A reliable diagnosis of autism spectrum disorder (ASD) is difficult to make until after toddlerhood. Detection in an earlier age enables early intervention, which is typically more effective. Recent studies of the development of brain and behavior in infants and toddlers have provided important insights in the diagnosis of autism. This extensive review focuses on published studies of predicting the diagnosis of autism during infancy and toddlerhood younger than 3 years using behavioral and neuroimaging approaches. After screening a total of 782 papers, 17 neuroimaging and 43 behavioral studies were reviewed. The features for prediction consist of behavioral measures using screening tools, observational and experimental methods, brain volumetric measures, and neural functional activation and connectivity patterns. The classification approaches include logistic regression, linear discriminant function, decision trees, support vector machine, and deep learning based methods. Prediction performance has large variance across different studies. For behavioral studies, the sensitivity varies from 20% to 100%, and specificity ranges from 48% to 100%. The accuracy rates range from 61% to 94% in neuroimaging studies. Possible factors contributing to this inconsistency may be partially due to the heterogeneity of ASD, different targeted populations (i.e., high-risk group for ASD and general population), age when the features were collected, and validation procedures. The translation to clinical practice requires extensive further research including external validation with large sample size and optimized feature selection. The use of multi-modal features, e.g., combination of neuroimaging and behavior, is worth further investigation to improve the prediction accuracy.

Keywords: Autism spectrum disorder; EEG; Early prediction of diagnosis outcome; Eye movement; MRI; Screening tools.

© 2020 Elsevier Inc. All rights reserved.

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49
Facial Plast Surg
. 2020 Jul 27. doi: 10.1055/s-0040-1713792. Online ahead of print.
Effect of Nasal Skin Type on Skin Problems following Rhinoplasty
Zulkuf B Erdur 1, Fatih Öktem 1, Ender İnci 1, Haydar M Yener 1, Emine D Gözen 1, Aslıhan Ö Birben 2, Samet Bayazit 2, Burhan Engin 2
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PMID: 32717761 DOI: 10.1055/s-0040-1713792
Abstract
Skin problems following rhinoplasty may cause dissatisfaction concerning the esthetic expectations of the patients. This study was conducted to determine whether nasal skin type has an effect on skin problems after rhinoplasty. Thirty-five patients undergoing rhinoplasty in our tertiary referral center between May 2018 and August 2019 were included in the study. The nasal skin sebum level was measured with Sebumeter preoperatively and patients were divided into two groups according to the median sebum level. Among the 35 patients, half of them with higher nasal skin sebum were categorized as oily skin group (n = 17; 14 males, 3 females; mean sebum level: 200.3 ± 26.9), and the other half were categorized as dry skin group (n = 18; 10 males, 8 females; mean sebum level: 101.9 ± 38). Periorbital edema and ecchymosis were assessed at postoperative days 1, 3, and 7. Acne and seborrhea severity determined with Global Acne Grading System and Seborrheic Dermatitis Area Severity Index the day before operation and postoperative days 7 and 14 and months 1, 3, and 10. Compared with dry skin group, upper eyelid ecchymosis score at postoperative day 7 was statistically higher in oily skin group (p = 0.044). There was no significant difference in upper eyelid edema scores between postoperative days 1 and 3 for oily skin group (p = 0.020). No statistically significant differences were found for acne and seborrhea severity. Nasal skin sebum levels may affect periorbital edema and ecchymosis after the procedure but no significant effect has been observed for acne and seborrhea. Predicting the effect of nasal skin types on these problems may help the surgeon to inform patients more correctly.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Conflict of interest statement
None declared.

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50
Ir J Med Sci
. 2020 May;189(2):669-676. doi: 10.1007/s11845-019-02141-1. Epub 2019 Nov 22.
Highly expressed CCR7 predicts poor prognosis in locally advanced nasopharyngeal carcinoma
Min Shen 1, Lingling Yi 1, Yidao Jiang 2
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PMID: 31758524 DOI: 10.1007/s11845-019-02141-1
Abstract
Background: Nasopharyngeal carcinoma (NC) is a malignant human tumor with a high incidence that occurs on the top and lateral wall of the nasopharynx.

Aims: To investigate the clinical value of chemokine receptor 7 (CCR7) in locally advanced NC.

Methods: We enrolled 114 patients with locally advanced NC admitted to our hospital in the observation group (OBG) and 100 normal healthy subjects who underwent physical examination in the control group (COG). The serum CCR7 expression levels in each group were measured using enzyme-linked immunosorbent assay and were compared between the groups.

Results: None of the 114 patients or their family members were lost during follow-up. Thirty-five patients died within 3 years and 79 survived (survival rate: 69.29%). The serum CCR7 level was higher in the OBG than in the COG (P < 0.05). The receiver operating characteristic (ROC) curve showed that the area under the ROC curve (AUC) was 0.837 for diagnostic value for locally advanced NC and the AUC was 0.759 for predictive value for 3-year mortality. The CCR7 AUC for diagnosis of locally advanced NC was 0.837 and for prediction of mortality was 0.759. Univariate analysis revealed significant differences in smoking history, long-term consumption of pickled food, family history of NC, primary lesion staging, lymph node staging, distant metastasis, clinical pathological staging, and CCR7 between the two groups (P < 0.05).

Conclusions: CCR7 was valuable in the diagnosis of locally advanced NC, and highly expressed CCR7 was predictive of poor prognosis.

Keywords: Chemokine receptor 7; NC; Valuable.

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