COVID-19 Research

COVID-19 Research

OHNS scientists have launched research projects and published several papers as part of the Stanford Medicine and global response to COVID-19. Some aim to prevent, diagnose and treat the disease; others aim to understand how it spreads and how people’s immune systems respond to it.

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Trials

COVID Catalyst Award

“Prospective, double blind, randomized control trial of the virucidal activity of povidone-iodine (PVP-I) spray in patients infected with COVID-19”

5/15/20 – 12/31/20
Center for Emerging and Neglected Diseases (CEND)

PI: JV Nayak, MD, PhD, Associate Professor of Otolaryngology, Head & Neck Surgery (Rhinology)
Katie Phillips, MD; Neelaysh Vukkadala, MD

Arresting SARS-CoV-2 (COVID-19) replication after infection of the nasal tissues specifically may decrease the severity of infection in COVID-19-exposed patients, and may impact COVID transmission. Given the promising properties and early data on efficacy of PVP-I for inactivation of SARS and MERS virus,  Dr. Nayak’s team is conducting a grant funded, clinical trial of dilute povidone-iodine (PVP-I; Betadine), a well-known anti-septic that has been used to clean surgical sites and wounds. In vitro data shows that PVP-I is highly virucidal against SARS and MERS. Prior research data has shown dilute PVP-I to be well tolerated in human subjects. The team is performing a randomized control trial of PVP-I to determine whether it reduces the viral load in the nasopharynx.

Studies & Projects

Assessment of NK Cell Response to SARS-CoV-2

PI: John B. Sunwoo

In this study, we will assess the ability of NK cells to produce a robust response to SARS-CoV-2. NK cells can be activated by IgG antibodies bound to target cells. Importantly, IgG antibodies against coronavirus are highest in patients with severe disease, peak around 2 weeks after onset of illness, and stay elevated until at least 60 days post-onset. We hypothesize that the presence of large numbers of NK cells and antibodies that recognize SARS-CoV2 infected cells would result in the efficient elimination of the virus. 

Consensus Statement on Clinic Operations in the Era of COVID-19

PI: Peter Hwang, Jennifer Y. Lee, Arifeen Rahman

We are doing a consensus statement on clinic operations in the era of COVID 19. It involves UW, OhSU, UCD, UCSF, Kaiser Oakland, UCLA, UCSD, and USC.

Data Collection Regarding Otolaryngologists Affected by COVID-19

PI: Zara M. Patel, Zoukaa Sargi, Steven Sobol

Spearheading the US portion, covered under Stanford IRB, of an international effort on data collection regarding Otolaryngologists affected by COVID-19, organized by the International Federation of Otolaryngologic Surgeons. The purpose of this study is to gather real time prevalence within our specialty and potentially identify high or low risk procedures and settings in order to better direct use of PPE and other precautions.

Evaluation and Mitigation of Potential Aerosol Generating Procedures in Otolaryngology

PI: Zara M. Patel, Katie Phillips, Tulio Valdez, Raana Sadabad

This is a basic science study utilizing spectroscopy to evaluate potential aerosol generation during common clinic and OR procedures. This project hopes to fill gaps in our current knowledge regarding these procedures and potentially confirm other recently published data on this topic.

MyMask: Facial Scanning App with Digital Manufacture of Custom Masks

PI: Stanley Yung-Chuan Liu, MD, DDS, Assistant Professor of Otolaryngology/Head & Neck Surgery, Jesse Chang

Mission: To address the shortage of surgical masks in the fight against COVID-19, collaborators with Stanford roots launched a free iPhone app, called MyMask, available soon in the Apple App store. The app creates a 3D printable model of a mask engineered to fit individual’s unique face using the same depth-sensing technology that powers Apple's Face ID. Loose-fitting protection, such as surgical masks and bandanas, lack proper fit. As such, the CDC and NIOSH do not consider or approve them as respiratory protection. The MyMask app addresses this challenge by harnessing facial scanning technology to design a custom-fit mask with a tight but comfortable seal. After a quick scan, the personalized file is sent to a digital manufacturer, fabricated, and paired with off-the-shelf filter and straps. The masks, intended to withstand repeated sterilization between wears, are based on an NIH reviewed model and have undergone rigorous testing.

 

Milestones:

  • 1. Stanford’s office of technology and licensing (OTL) started a Covid platform with Harvard and MIT at the beginning of the pandemic (since extended to other institutions). We are now one of the 18 projects that Stanford is licensing.
  • 2. Our Non profit website
  • 3. Provisional IP filed 4/24/2020 (serial # 63/015,176)
  • 4. Stanford OTL began pitching the project to over 100 companies today, also to launch social medial campaign next week. We already have 2 inquiries from Envisiontec, MedMasks. Scheduled discussions with NYU and Mass Gen for trials of the app and mask
  • 5. We are currently working on getting both the App and the mask (surgical and respirator) through FDA approval

Prevalence of Pre-operative COVID-19 Positivity in Head and Neck Surgery Patients

PI: Dr. K. Dewan, MD, Assistant Professor of Otolaryngology, OHNS

The recent outbreak of coronavirus disease of 2019 (COVID-19) had a tremendous impact on scheduling and surgical cases. For all surgical head and neck surgery cases, pre-operative COVID-19 testing is done to minimize exposure risk of surgeons and operating room staff. The goal of this study is to assess the general utility and prevalence of COVID-19 positivity among patients who received pre-operative COVID-19. The findings of this study will allow us to understand the true exposure risk and thereby critically appraise the role of pre-op COVID-19 testing.

Steroid Use in COVID-19 Patients with Anosmia

PI: Zara M. Patel, Puya Deghani-Mobaraki

International, multi-center observational study evaluating steroid use in COVID-19 patients with anosmia. Evaluating the potential risks of oral versus topical use in this patient population.

The Digital Divide and COVID-19: Access to Technology As an Emerging Health-Care Disparity in Children

PI: Meister K

We are examining the differential access to technology-based healthcare, such as patient portals and telemedicine appointments, experienced by some families.  This disparity in access has been exacerbated during a the COVID-19 pandemic because traditional access to healthcare has become more difficult and limited.

The Surgical Kit: a Novel Training Concept for the Sidelined COVID-19 Surgical Resident

PI: Okland TS, Arbouin Vargas JF, Yang SM, Pepper JP, Valdez TA

This is a prospective study outlining our experience with the novel surgical kit. This concept refers to a 3D designed and printed model, packaged in a kit with all instruments necessary to perform the related procedure. These kits were distributed to our OHNS junior residents. We recently distributed kit#3, and plan to collect the final data and submit to either the journal of surgical education or JAMA otolaryngology by June.

Publications

Balakrishnan, Karthik, Samuel Schechtman, Norman D. Hogikyan, Anthony Y. B. Teoh, Brendan McGrath, and Michael J. Brenner. 2020. “COVID-19 Pandemic: What Every Otolaryngologist–Head and Neck Surgeon Needs to Know for Safe Airway Management.” Otolaryngology–Head and Neck Surgery, April, 019459982091975. https://doi.org/10.1177/0194599820919751.

SUMMARY: This manuscript was one of the first multicenter efforts to describe safe airway management and safe airway surgery in adults and children. It provided fundamental guidance on provider and clinical staff safety during a period of great uncertainty at the early stages of the pandemic in the US and Europe. The authors, including otolaryngologists and anesthesiologists, represented institutions in the US, Europe, and Asia, providing a global perspective from varying stages of the pandemic.


Givi, Babak, Bradley A. Schiff, Steven B. Chinn, Daniel Clayburgh, N. Gopalakrishna Iyer, Scharukh Jalisi, Michael G. Moore, et al. 2020. “Safety Recommendations for Evaluation and Surgery of the Head and Neck During the COVID-19 Pandemic.” JAMA Otolaryngology–Head & Neck Surgery, March. https://doi.org/10.1001/jamaoto.2020.0780.

SUMMARY:  These are some of the earliest published guidelines for safely performing the head and neck physical examination and associated procedures during the coronavirus disease 2019 (COVID-19) pandemic, by otolaryngologist-head and neck surgeons from within and beyond the American Head and Neck Society (AHNS).


Graboyes E, Cramer J, Balakrishnan K, et al. "COVID-19 pandemic and health care disparities in head and neck cancer: Scanning the horizon." Head Neck. 2020;42(7):1555-1559. https://doi:10.1002/hed.26345.

SUMMARY: The COVID‐19 pandemic has profoundly disrupted head and neck cancer (HNC) care delivery in ways that will likely persist long term. As we scan the horizon, this crisis has the potential to amplify preexisting racial/ethnic disparities for patients with HNC. Potential drivers of disparate HNC survival resulting from the pandemic include (a) differential access to telemedicine, timely diagnosis, and treatment; (b) implicit bias in initiatives to triage, prioritize, and schedule HNC‐directed therapy; and (c) the marked changes in employment, health insurance, and dependent care. We present four strategies to mitigate these disparities: (a) collect detailed data on access to care by race/ethnicity, income, education, and community; (b) raise awareness of HNC disparities; (c) engage stakeholders in developing culturally appropriate solutions; and (d) ensure that surgical prioritization protocols minimize risk of racial/ethnic bias. Collectively, these measures address social determinants of health and the moral imperative to provide equitable, high‐quality HNC care.


Kligerman, Maxwell P., Neelaysh Vukkadala, Raymond K. Y. Tsang, John B. Sunwoo, F. Christopher Holsinger, Jason Y. K. Chan, Edward J. Damrose, Ann Kearney, and Heather M. Starmer. 2020. “Managing Head and Neck Cancer Patients with Tracheostomy or Laryngectomy during the COVID ‐19 Pandemic.” Head & Neck, April, hed.26171. https://doi.org/10.1002/hed.26171.

SUMMARY: This manuscript provides evidence based guidance for provision of care to patients with trachestomy or laryngectomy during the COVID outbreak. 


Ku, Peter K. M., Floyd Christopher Holsinger, Jason Y. K. Chan, Zenon W. C. Yeung, Becky Y. T. Chan, Michael C. F. Tong, and Heather M. Starmer. 2020. “Management of Dysphagia in the Patient with Head and Neck Cancer during COVID ‐19 Pandemic: Practical Strategy.” Head & Neck, May, hed.26224. https://doi.org/10.1002/hed.26224.

SUMMARY: The global pandemic of 2019 novel coronavirus disease (COVID‐19) has tremendously altered routine medical service provision and imposed unprecedented challenges to the health care system. This impacts patients with dysphagia complications caused by head and neck cancers. As this pandemic of COVID‐19 may last longer than severe acute respiratory syndrome (SARS) in 2003, a practical workflow for managing dysphagia is crucial to ensure a safe and efficient practice to patients and health care personnel. This document provides clinical practice guidelines based on available evidence to date to balance the risks of SARS‐CoV‐2 exposure with the risks associated with dysphagia. Critical considerations include reserving instrumental assessments for urgent cases only, optimizing the noninstrumental swallowing evaluation, appropriate use of personal protective equipment (PPE), and use of telehealth when appropriate. Despite significant limitations in clinical service provision during the pandemic of COVID‐19, a safe and reasonable dysphagia care pathway can still be implemented with modifications of setup and application of newer technologies.

 


Mehanna H.*, Hardman JC*, Shenson JA*, Topf MC*, ... Holsinger FC. 2020."Recommendations for Head and Neck Surgical Oncology Practice in a setting of acute severe resource constraint: A consensus statement." Lancet Oncology. (In press.2020) *Co-first authors

SUMMARY: This international consensus statement on modifications in head and neck surgical oncology practice as result of the COVID-19 pandemic offers guidance to surgeons around the world in navigating this tumultuous period. Recommendations were reached through a Delphi process involving 40 head and neck oncologists representing 35 international professional societies and clinical trials groups.


Munjal, Tina, Katherine R. Kavanagh, Rami M. Ezzibdeh, and Tulio A. Valdez. 2020. “The Impact of COVID-19 on Global Disparities in Surgical Training in Pediatric Otolaryngology.” International Journal of Pediatric Otorhinolaryngology 138 (November): 110267. https://doi.org/10.1016/j.ijporl.2020.110267.

SUMMARY:

Objective: To assess global trends in otolaryngologic and non-otolaryngologic education in response to COVID-19, specifically with regard to surgical simulation and personnel reallocation needs in case of patient demand.

Study design: Online survey.

Methods: A multiple-choice survey regarding operative caseload and impact on resident education was sent to Otolaryngology residents and Pediatric Otolaryngology faculty globally. The survey was open for responses for ten days in March 2020. 

Results: A total of 96 completed surveys were received across 22 countries. 87.5% of respondents reported that no supplementary operative education is being provided. Despite 71.43% of responses indicating that simulation was useful for all levels of residents, 20.95% of responses indicated that simulation is not possible at their institution, with the majority of these being skewed toward responses from South America. 

Conclusion: Despite the majority of respondents stating that simulation was helpful, there were disparities in access to simulation seen across countries. The results inform the need for a coordinated effort to expand educational efforts outside of the operating room and clinical environment. A major limitation of this study is the low domestic response rate.


Noel, Julia E., Lisa A. Orloff, and Kwang Sung. 2020. “Laryngeal Evaluation during the COVID-19 Pandemic: Transcervical Laryngeal Ultrasonography.” Otolaryngology–Head and Neck Surgery, April, 019459982092298. https://doi.org/10.1177/0194599820922984.

SUMMARY: This article discusses the indications and technique of noninvasive transcervical laryngeal ultrasound for the evaluation of vocal fold motion, during and even independent of the COVID-19 pandemic. Laryngeal ultrasound provides a non-aerosol-generating alternative to the procedure of fiberoptic laryngoscopy, to inform decisions about safety of feeding, airway, and progression of care.


Parma, Valentina, Kathrin Ohla, Maria G. Veldhuizen, Masha Y. Niv, Christine E. Kelly, Alyssa J. Bakke, Keiland W. Cooper, et al. 2020. “More than Just Smell - COVID-19 Is Associated with Severe Impairment of Smell, Taste, and Chemesthesis.” Preprint. Infectious Diseases (except HIV/AIDS). https://doi.org/10.1101/2020.05.04.20090902.

SUMMARY: This is the first manuscript published by the Global Consortium on Chemosensory Research (GCCR). The data is compiled from a global, crowd-sourced, multi-lingual survey which over 4000 participants around the world responded to. Covid-19 is associated not only with smell loss, but also dysfunction of taste and chemesthesis, suggesting a multi-faceted neurologic impact.


Patel, Zara M, Juan Fernandez-Miranda, Peter H Hwang, Jayakar V Nayak, Robert L Dodd, Hamed Sajjadi, and Robert K Jackler. 2020. “In Reply: Precautions for Endoscopic Transnasal Skull Base Surgery During the COVID-19 Pandemic.” Neurosurgery, April, nyaa156. https://doi.org/10.1093/neuros/nyaa156.

SUMMARY: Invited commentary responding to a letter from Wuhan regarding an anecdotal case report we reported on in our initial statement. Due diligence and further investigation confirmed our stance on increased need for precaution and PPE in our specialty.


Patel, Zara M, Juan Fernandez-Miranda, Peter H Hwang, Jayakar V Nayak, Robert Dodd, Hamed Sajjadi, and Robert K Jackler. 2020. “Letter: Precautions for Endoscopic Transnasal Skull Base Surgery During the COVID-19 Pandemic.” Neurosurgery, April, nyaa125. https://doi.org/10.1093/neuros/nyaa125.

SUMMARY: Our initial statement that circulated widely to warn the otolaryngology community of the possibility of increased exposure and impact of COVID-19 within our specialty, based on communications received from our colleagues around the world.


Patel, Zara M. 2020. “Reflections and New Developments within the COVID‐19 Pandemic.” International Forum of Allergy & Rhinology 10 (5): 587–88. https://doi.org/10.1002/alr.22582.

SUMMARY: Invited correspondence to comment on the ever-evolving impact of COVID-19 on our specialty.


Ramamurthi, Divya, Cindy Chau, and Robert K Jackler. 2020. “Exploitation of the COVID-19 Pandemic by e-Cigarette Marketers.” Tobacco Control, August, tobaccocontrol-2020-055855. https://doi.org/10.1136/tobaccocontrol-2020-055855.

INTRODUCTION: Over the last decade, a wide variety of e-cigarette advertisements have claimed superior healthfulness compared with cigarettes.1 Recently, we recognised a novel form of health reassurance advertising, promotion of e-cigarettes via COVID-19 pandemic themes. This led us to systematically explore COVID-19 marketing of e-cigarette brands and vape stores on their websites and Instagram accounts. We have collected over 300 COVID-19 themed e-cigarette promotional images and posted them to our online repository (tobacco.stanford.edu/COVID-19).2 These images represent 21 e-cigarette brands and 41 online vaping stores that vend multiple brands. The COVID-19 messaging in these advertisements took several forms.

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Soler, Zachary M., Zara M. Patel, Justin H. Turner, and Eric H. Holbrook. 2020. “A Primer on Viral-Associated Olfactory Loss in the Era of COVID-19.” International Forum of Allergy & Rhinology, April. https://doi.org/10.1002/alr.22578.

SUMMARY: This is a short primer on workup, diagnosis and treatment of post-viral olfactory loss, as this is now a widely recognized possible symptom of COVID-19 and the prevalence of smell and taste loss will be increasing accordingly in our country and around the world. It includes specific instructions on olfactory training and a patient education handout.


Topf, Michael C., Jared A. Shenson, F. Christopher Holsinger, Samuel H. Wald, Lisa J. Cianfichi, Eben L. Rosenthal, and John B. Sunwoo. 2020. “Framework for Prioritizing Head and Neck Surgery during the COVID ‐19 Pandemic.” Head & Neck, May, hed.26184. https://doi.org/10.1002/hed.26184.

SUMMARY: Details of the Stanford Otolaryngology–Head & Neck Surgery evidence-based approach to prioritizing head and neck oncologic surgery during the COVID-19 pandemic. This includes criteria to establish the level of procedural urgency, our internal review process for indeterminate cases, and our clinical pathway for preoperative evaluation and transmission mitigation.


Vukkadala, Neelaysh, Z. Jason Qian, F. Christopher Holsinger, Zara M. Patel, and Eben Rosenthal. 2020. “COVID‐19 and the Otolaryngologist: Preliminary Evidence‐Based Review.” The Laryngoscope, April, lary.28672. https://doi.org/10.1002/lary.28672.


Zaga CJ, Pandian V, Wallace S, Cameron TS, Chao C, Orloff LA, Atkins NE, McGrath BA, Lazarus CL, Brodsky MB, Vogel AP, Brenner MJ. 2020."Speech-Language Pathology Guidance for Tracheostomy during the COVID-19 Pandemic: An International Multidisciplinary Perspective." Am J Speech Lang Pathol. (In press. 2020)

SUMMARY: This international multidisciplinary panel offers guidance for healthcare workers caring for patients with tracheostomy during the COVID-19 pandemic.  The information is aimed at improving safety for speech language pathologists, nurses, doctors, & respiratory therapists.


Zhao, Chen, Alonço Viana, Yan Wang, Hong-quan Wei, Ai-hui Yan, and Robson Capasso. 2020. “Otolaryngology during COVID-19: Preventive Care and Precautionary Measures.” American Journal of Otolaryngology, April, 102508. https://doi.org/10.1016/j.amjoto.2020.102508.

SUMMARY: The article provides a high level review for otolaryngologists detailing the early experience in three countries, particularly in Wuhan, with a literature overview, and description of clinical characteristics and infection control measures for COVID-19, as well as practical knowledge from first-line otolaryngologists in China, the United States, and Brazil.

Submitted for Publication

How do we teach surgical residents in the COVID-19 era?

Okland TS, Pepper JP, Valdez TA.

This is a perspective article outlining the challenges of training residents to operate when caseloads are diminished. Submitted to the Journal of Surgical Education in April.

 

Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract and is not increased by ACE inhibitors or angiotensin receptor blockers

Ivan T. Lee1,2,3,14, Tsuguhisa Nakayama2,14, Chien-Ting Wu4,14, Yury Goltsev1,14, Sizun Jiang1, Phillip A. Gall2, Chun-Kang Liao5, Liang-Chun Shih6,7,8, Christian M. Schürch1, David R. McIlwain1, Pauline Chu1, Nicole A. Borchard2, David Zarabanda2, Sachi S. Dholakia2, Angela Yang2, Dayoung Kim2, Tomoharu Kanie4, Chia-Der Lin 6,7,9, Ming-Hsui Tsai6,7,9, Katie M. Phillips2, Raymond Kim2, Jonathan B. Overdevest2,10, Matthew A. Tyler2,11, Carol H. Yan2,12, Chih-Feng Lin5, Yi-Tsen Lin5, Da-Tian Bau7,8, Gregory J. Tsay9,13, Zara M. Patel2, Yung-An Tsou6,9, Chih-Jaan Tai6,9, Te-Huei Yeh5, Peter H. Hwang2, Garry P. Nolan1,15,*, Jayakar V. Nayak2,15, Peter K. Jackson1,4,15

1Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
2Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA
3Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
4Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, California, USA
5Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
6Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan
7Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
8Terry Fox Cancer Research Laboratory, Translational Medicine Center, China Medical University Hospital, Taichung, Taiwan
9School of Medicine, China Medical University, Taichung, Taiwan
10Department of Otolaryngology–Head and Neck Surgery, Columbia University School of Medicine, New York City, NY.
11Department of Otolaryngology–Head and Neck Surgery, University of Minnesota School of Medicine, Minneapolis, MN.
12Department of Otolaryngology–Head and Neck Surgery, University of California San Diego School of Medicine, San Diego, CA.
13Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
14These authors contributed equally: Ivan T. Lee, Tsuguhisa Nakayama, Chien-Ting Wu, Yury Goltsev
15These authors jointly supervised this work: Garry P. Nolan, Jayakar V. Nayak, Peter K. Jackson.

*Corresponding author: Garry P. Nolan (gnolan@stanford.edu)

Speech-Language Pathology Guidance for Tracheostomy during the COVID-19 Pandemic: An International Multidisciplinary Perspective

Charissa Joy Zaga, Austin Health
Heidelberg, Victoria AUSTRALIA
Vinciya Pandian, Martin B. Brodsky, Sarah Wallace, Tanis S. Cameron, Caroline Chao, Lisa Ann Orloff, Naomi E Atkins, Brendan A McGrath, Cathy L Lazarus, Adam P Vogel, Michael J Brenner

Purpose:  As the COVID-19 pandemic has unfolded, there has been growing recognition of risks to frontline healthcare workers. When caring for patients with tracheostomy, speech- language pathologists have significant exposure to mucosal surfaces, secretions, and aerosols that may harbor the SARS-CoV-2 virus. This tutorial provides guidance on practices for safely performing patient evaluation and procedures, thereby reducing risk of infection.

Methods:  Data were collated through review of literature, guidelines, and consensus statements relating to COVID-19 and similar high-consequent infections, with a focus on mitigating risk of transmission to healthcare workers. Particular emphasis was placed on speech language pathologists, nurses, and other allied health professionals. A multinational interdisciplinary team then analyzed findings, arriving at recommendations through consensus via electronic communications and video conference.

Results:  Reports of transmission of infection to healthcare workers in the current COVID-19 pandemic and previous outbreaks substantiate the need for safe practices. Many procedures routinely performed by speech language pathologists have significant risk of infection due to aerosol generation. COVID-19 testing can inform level of protective equipment, and meticulous hygiene can stem spread of nosocomial infection. Modifications to standard clinical practice in tracheostomy are often required. Personal protective equipment including N95 mask, gloves, goggles, and gown are needed when performing aerosol-generating procedures in patients with known or suspected COVID-19 infection.

Conclusions:  Speech language pathologists are often called on to assist in the care of patients with tracheostomy and known or suspected COVID-19 infection. Appropriate care of these patients is predicated on maintaining the health and safety of the healthcare team. Careful adherence to best practices can greatly reduce risk of infectious transmission.

Submitted to American Journal of Speech-Language Pathology.

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