Publications by authors named "Michael T Chang"

16 Publications

  • Page 1 of 1

Oral Corticosteroids Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis Without Nasal Polyposis: A Randomized Clinical Trial.

JAMA Otolaryngol Head Neck Surg 2021 Mar 4. Epub 2021 Mar 4.

Stanford University School of Medicine, Department of Otolaryngology-Head & Neck Surgery, Stanford, California.

Importance: Although oral corticosteroids are commonly prescribed following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) without nasal polyposis, there are little data to suggest that this is a beneficial practice.

Objective: To assess the efficacy of oral corticosteroids following ESS in CRS without polyps.

Design, Setting, And Participants: This prospective double-blinded, placebo-controlled, randomized noninferiority clinical trial conducted in a single academic tertiary rhinology practice included adults with CRS without polyps undergoing ESS. Of 81 patients recruited, 72 completed the study.

Interventions: Patients were randomized into 2 treatment groups: a 12-day postoperative taper of oral prednisone vs matched placebo tablets. All study patients also received a uniform 2-week postoperative regimen of oral antibiotics, fluticasone nasal spray, and saline rinses.

Main Outcomes And Measures: The primary outcome measures were Sinonasal Outcome Test-22 (SNOT-22) scores and Lund-Kennedy endoscopy scores, collected preoperatively and postoperatively at 1 week, 1 month, 3 months, and 6 months. Scores were compared between treatment groups at each time point using longitudinal difference between treatment groups and analyzed using 2-way, repeated measures analysis of variance. Secondary outcome measures included treatment-related adverse effects.

Results: Overall, 72 patients (mean [SD] age, 49.4 [14.9] years; 36 men, 36 women) completed the study, with 33 in the prednisone arm and 39 in the placebo arm. When comparing longitudinal differences between treatment groups, there was no clinically meaningful difference observed in SNOT-22 total (F[4254] = 1.71, η2 = 0.01 [95% CI, 0.00-0.05]) or Lund-Kennedy scores (F[4247] = 1.23, η2 = 0.02 [95% CI, 0.00-0.50]). In SNOT-22 subdomain analyses, there was no clinically meaningful difference between treatment groups for rhinologic, extranasal rhinologic, ear/facial, or sleep subdomains. However, the prednisone group had worse longitudinal scores for psychological dysfunction compared with the placebo group (F[4254] = 3.18, η2 = 0.05 [95% CI, 0.02-0.09]). Reported adverse effects were similar between the 2 treatment groups.

Conclusions And Relevance: In this randomized clinical trial of patients with CRS without polyps, oral prednisone following ESS conferred no additional benefit over placebo in terms of SNOT-22 total scores, SNOT-22 rhinologic subscores, or Lund-Kennedy endoscopy scores up to 6 months after surgery. Patients receiving prednisone, however, did demonstrate worse SNOT-22 psychologic subdomain scores. These results suggest that the risks of oral corticosteroids may outweigh the benefits; thus use of oral corticosteroids after ESS for CRS without polyps should be carefully considered.

Trial Registration: ClinicalTrials.gov Identifier: NCT02748070.
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http://dx.doi.org/10.1001/jamaoto.2021.0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934078PMC
March 2021

A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

Authors:
Cory J Evans John M Olson Bama Charan Mondal Pratyush Kandimalla Ariano Abbasi Mai M Abdusamad Osvaldo Acosta Julia A Ainsworth Haris M Akram Ralph B Albert Elitzander Alegria-Leal Kai Y Alexander Angelica C Ayala Nataliya S Balashova Rebecca M Barber Harmanjit Bassi Sean P Bennion Miriam Beyder Kush V Bhatt Chinmay Bhoot Aaron W Bradshaw Tierney G Brannigan Boyu Cao Yancey Y Cashell Timothy Chai Alex W Chan Carissa Chan Inho Chang Jonathan Chang Michael T Chang Patrick W Chang Stephen Chang Neel Chari Alexander J Chassiakos Iris E Chen Vivian K Chen Zheying Chen Marsha R Cheng Mimi Chiang Vivian Chiu Sharon Choi Jun Ho Chung Liset Contreras Edgar Corona Courtney J Cruz Renae L Cruz Jefferson M Dang Suhas P Dasari Justin R O De La Fuente Oscar M A Del Rio Emily R Dennis Petros S Dertsakyan Ipsita Dey Rachel S Distler Zhiqiao Dong Leah C Dorman Mark A Douglass Allysen B Ehresman Ivy H Fu Andrea Fua Sean M Full Arash Ghaffari-Rafi Asmar Abdul Ghani Bosco Giap Sonia Gill Zafar S Gill Nicholas J Gills Sindhuja Godavarthi Talin Golnazarian Raghav Goyal Ricardo Gray Alexander M Grunfeld Kelly M Gu Natalia C Gutierrez An N Ha Iman Hamid Ashley Hanson Celesti Hao Chongbin He Mengshi He Joshua P Hedtke Ysrael K Hernandez Hnin Hlaing Faith A Hobby Karen Hoi Ashley C Hope Sahra M Hosseinian Alice Hsu Jennifer Hsueh Eileen Hu Spencer S Hu Stephanie Huang Wilson Huang Melanie Huynh Carmen Javier Na Eun Jeon Sunjong Ji Jasmin Johal Amala John Lauren Johnson Saurin Kadakia Namrata Kakade Sarah Kamel Ravinder Kaur Jagteshwar S Khatra Jeffrey A Kho Caleb Kim Emily Jin-Kyung Kim Hee Jong Kim Hyun Wook Kim Jin Hee Kim Seong Ah Kim Woo Kyeom Kim Brian Kit Cindy La Jonathan Lai Vivian Lam Nguyen Khoi Le Chi Ju Lee Dana Lee Dong Yeon Lee James Lee Jason Lee Jessica Lee Ju-Yeon Lee Sharon Lee Terrence C Lee Victoria Lee Amber J Li Jialing Li Alexandra M Libro Irvin C Lien Mia Lim Jeffrey M Lin Connie Y Liu Steven C Liu Irene Louie Shijia W Lu William Y Luo Tiffany Luu Josef T Madrigal Yishan Mai Darron I Miya Mina Mohammadi Sayonika Mohanta Tebogo Mokwena Tonatiuh Montoya Dallas L Mould Mark R Murata Janani Muthaiya Seethim Naicker Mallory R Neebe Amy Ngo Duy Q Ngo Jamie A Ngo Anh T Nguyen Huy C X Nguyen Rina H Nguyen Thao T T Nguyen Vincent T Nguyen Kevin Nishida Seo-Kyung Oh Kristen M Omi Mary C Onglatco Guadalupe Ortega Almazan Jahzeel Paguntalan Maharshi Panchal Stephanie Pang Harin B Parikh Purvi D Patel Trisha H Patel Julia E Petersen Steven Pham Tien M Phan-Everson Megha Pokhriyal Davis W Popovich Adam T Quaal Karl Querubin Anabel Resendiz Nadezhda Riabkova Fred Rong Sarah Salarkia Nateli Sama Elaine Sang David A Sanville Emily R Schoen Zhouyang Shen Ken Siangchin Gabrielle Sibal Garuem Sin Jasmine Sjarif Christopher J Smith Annisa N Soeboer Cristian Sosa Derek Spitters Bryan Stender Chloe C Su Jenny Summapund Beatrice J Sun Christine Sutanto Jaime S Tan Nguon L Tan Parich Tangmatitam Cindy K Trac Conny Tran Daniel Tran Duy Tran Vina Tran Patrick A Truong Brandon L Tsai Pei-Hua Tsai C Kimberly Tsui Jackson K Uriu Sanan Venkatesh Maique Vo Nhat-Thi Vo Phuong Vo Timothy C Voros Yuan Wan Eric Wang Jeffrey Wang Michael K Wang Yuxuan Wang Siman Wei Matthew N Wilson Daniel Wong Elliott Wu Hanning Xing Jason P Xu Sahar Yaftaly Kimberly Yan Evan Yang Rebecca Yang Tony Yao Patricia Yeo Vivian Yip Puja Yogi Gloria Chin Young Maggie M Yung Alexander Zai Christine Zhang Xiao X Zhang Zijun Zhao Raymond Zhou Ziqi Zhou Mona Abutouk Brian Aguirre Chon Ao Alexis Baranoff Angad Beniwal Zijie Cai Ryan Chan Kenneth Chang Chien Umar Chaudhary Patrick Chin Praptee Chowdhury Jamlah Dalie Eric Y Du Alec Estrada Erwin Feng Monica Ghaly Rose Graf Eduardo Hernandez Kevin Herrera Vivien W Ho Kaitlyn Honeychurch Yurianna Hou Jo M Huang Momoko Ishii Nicholas James Gah-Eun Jang Daphne Jin Jesse Juarez Ayse Elif Kesaf Sat Kartar Khalsa Hannah Kim Jenna Kovsky Chak Lon Kuang Shraddha Kumar Gloria Lam Ceejay Lee Grace Lee Li Li Joshua Lin Josephine Liu Janice Ly Austin Ma Hannah Markovic Cristian Medina Jonelle Mungcal Bilguudei Naranbaatar Kayla Patel Lauren Petersen Amanda Phan Malcolm Phung Nadiyah Priasti Nancy Ruano Tanveer Salim Kristen Schnell Paras Shah Jinhua Shen Nathan Stutzman Alisa Sukhina Rayna Tian Andrea Vega-Loza Joyce Wang Jun Wang Rina Watanabe Brandon Wei Lillian Xie Jessica Ye Jeffrey Zhao Jill Zimmerman Colton Bracken Jason Capili Andrew Char Michel Chen Pingdi Huang Sena Ji Emily Kim Kenneth Kim Julie Ko Sean Louise G Laput Sam Law Sang Kuk Lee Olivia Lee David Lim Eric Lin Kyle Marik Josh Mytych Andie O'Laughlin Jensen Pak Claire Park Ruth Ryu Ashwin Shinde Manny Sosa Nick Waite Mane Williams Richard Wong Jocelyn Woo Jonathan Woo Vishaal Yepuri Dorothy Yim Dan Huynh Dinali Wijiewarnasurya Casey Shapiro Marc Levis-Fitzgerald Leslie Jaworski David Lopatto Ira E Clark Tracy Johnson Utpal Banerjee

G3 (Bethesda) 2021 Jan;11(1)

Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.
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http://dx.doi.org/10.1093/g3journal/jkaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022729PMC
January 2021

The Effect of Endoscopic Sinus Surgery on Eustachian Tube Dysfunction Symptoms.

Otolaryngol Head Neck Surg 2020 09 28;163(3):603-610. Epub 2020 Apr 28.

Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, California, USA.

Objective: We assessed how eustachian tube dysfunction (ETD) changed with endoscopic sinus surgery (ESS) and identified factors associated with improvement.

Study Design: Retrospective chart review.

Setting: Academic center.

Subjects And Methods: Patients undergoing ESS for chronic rhinosinusitis with and without nasal polyposis (CRSwNP, CRSsNP) or recurrent acute rhinosinusitis (RARS) completed the Eustachian Tube Dysfunction Questionnaire 7 (ETDQ-7) preoperatively and postoperatively at 2 weeks, 6 weeks, 3 months, and 6 months. Included in analyses were demographics, comorbidities, Sinonasal Outcome Test 22 (SNOT-22), radiographic score, endoscopy score, procedure, and medication use. Regression analysis identified factors associated with improvement, defined as ΔETDQ-7 >3.5.

Results: In total, 302 patients were studied. ETD prevalence was 68% in CRSsNP, 48% in CRSwNP, and 88% in RARS. Patients with ETD had a mean baseline ETDQ-7 of 25.8 ± 8.0 and improved postoperatively at 2 weeks (19.9 ± 8.1, < .001), 6 weeks (17.8 ± 9.3, < .001), 3 months (16.8 ± 8.5, < .001), and 6 months (16.4 ± 7.9, < .001). At 6 months, ETD improved in 89% of patients with CRSsNP, 68% with CRSwNP, and 78% with RARS. On multivariate analysis, ETD improvement was associated with higher preoperative ETDQ-7 score (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.04-1.22; = .030), higher preoperative SNOT-22 score (aOR, 1.02; 95% CI, 1.02-1.08; = .001), higher preoperative SNOT-22 ear subscore (aOR, 1.27; 95% CI, 1.02-1.65; = .034), posterior ethmoidectomy (aOR, 1.59; 95% CI, 1.22-4.92; = .025), and postoperative corticosteroid spray use (aOR, 1.57; 95% CI, 1.17-1.66; = .008).

Conclusion: ETD symptoms often improve following ESS. Factors associated with improvement include higher preoperative disease burden, posterior ethmoidectomy, and postoperative corticosteroid spray.

Level Of Evidence: 4.
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http://dx.doi.org/10.1177/0194599820917396DOI Listing
September 2020

Hemodynamic changes in patients undergoing office-based sinus procedures under local anesthesia.

Int Forum Allergy Rhinol 2020 01 5;10(1):114-120. Epub 2019 Nov 5.

Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA.

Background: The objective of this study is to characterize changes in hemodynamics, pain, and anxiety during office-based endoscopic sinus procedures performed under local anesthesia.

Methods: We conducted a prospective study of adults undergoing in-office endoscopic sinus procedures under local anesthesia. Patients with American Society of Anesthesiologists (ASA) Physical Status Classification System class 1 or 2 were included. Anesthesia was administered by topical 4% lidocaine/oxymetazoline and submucosal injection of 1% lidocaine/1:200,000 epinephrine. Vital signs and pain were measured at baseline, postinjection, and 5-minute intervals throughout the procedure. Anxiety levels were scored using the State-Trait Anxiety Inventory (STAI). Univariate and multivariate regression analyses were performed to identify factors significantly associated with changes in each hemodynamic metric.

Results: Twenty-five patients were studied. This cohort was 52% male, mean age of 57.8 ± 14.4 years, and Charlson Comorbidity Index (CCI) median of 2. Mean procedure duration was 25.0 ± 10.3 minutes. Mean maximal increase in systolic blood pressure (SBP) was 24.6 ± 17.8 mmHg from baseline. Mean maximal heart rate increase was 22.8 ± 10.8 beats per minute (bpm) from baseline. In multivariate regression analysis, when accounting for patient age, cardiac comorbidity, CCI, and ASA, older age was significantly associated with an increase of >20 mmHg in SBP (p = 0.043). Mean pain score during procedures was 1.5 ± 1.3 with a mean maximum of 4.0 ± 2.6. STAI anxiety scores did not change significantly from preprocedure to postprocedure (32.8 ± 11.6 to 31.0 ± 12.6, p = 0.46). No medical complications occurred.

Conclusion: Although patients appear to tolerate office procedures well, providers should recognize the potential for significant fluctuations in blood pressure during the procedure, especially in older patients.
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http://dx.doi.org/10.1002/alr.22460DOI Listing
January 2020

Update on long-term outcomes for chronic rhinosinusitis in cystic fibrosis.

Curr Opin Otolaryngol Head Neck Surg 2020 Feb;28(1):46-51

Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, USA.

Purpose Of Review: This article reviews the existing body of literature regarding long-term outcomes of various treatments for chronic rhinosinusitis (CRS) in the cystic fibrosis population.

Recent Findings: The management of CRS in cystic fibrosis involves a multitude of medical and surgical therapies. Despite their high usage amongst clinicians, corticosteroids and antibiotics currently have little outcome data supporting their use. There is emerging evidence demonstrating beneficial outcomes for DNAse mucolytics and molecular modulators of cystic fibrosis transmembrane conductor regulator (CFTR). Endoscopic sinus surgery (ESS) improves sinonasal outcomes in cystic fibrosis CRS; however, the benefit on pulmonary outcomes remains unclear.

Summary: Successful management of CRS in cystic fibrosis requires multimodal and multidisciplinary care. The long-term outcome data is variable for different treatment modalities. There is recent evidence supporting the role of DNAse mucolytics, CFTR-targeting therapies, and ESS in management of cystic fibrosis CRS.
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http://dx.doi.org/10.1097/MOO.0000000000000596DOI Listing
February 2020

Cryosurgical ablation for treatment of rhinitis: A prospective multicenter study.

Laryngoscope 2020 08 30;130(8):1877-1884. Epub 2019 Sep 30.

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, U.S.A.

Objective: To assess the efficacy and safety of cryoablation of the posterior nasal nerve (PNN) for treatment of chronic rhinitis.

Methods: This was a prospective single-arm trial of 98 adult patients at six U.S. centers with chronic allergic and nonallergic rhinitis. PNN cryoablation was performed in-office under local anesthesia using a handheld device. Patients discontinued use of intranasal ipratropium 3 days prior to treatment and throughout the study period. Reflective Total Nasal Symptom Score (rTNSS) was measured at pretreatment baseline and posttreatment at 1 month, 3 months, 6 months, and 9 months. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was completed at pretreatment and 3 months posttreatment. Adverse effects and postprocedure medication usage were recorded.

Results: Ninety-eight procedures (100%) were successfully completed. rTNSS significantly improved over pretreatment baseline (6.1 ± 1.9) at 1 month (2.9 ± 1.9, P < 0.001), 3 months (3.0 ± 2.3, P < 0.001), 6 months (3.0 ± 2.1, P < 0.001), and 9 months (3.0 ± 2.4, P < 0.001) postprocedure. Nasal congestion and rhinorrhea subscores improved significantly at all time points (P < 0.001). Both allergic and nonallergic rhinitis subcohorts showed improvement (P < 0.001), with a comparable degree of improvement between groups. RQLQ significantly improved over pretreatment baseline (3.0 ± 1.0) at 3 months (1.5 ± 1.0, P < 0.001), and all RQLQ subdomains demonstrated improvement. Of 54 patients using intranasal medication at baseline, 19 (35.2%) were able to discontinue use. Twenty-nine adverse effects were reported, including headache, epistaxis, and sinusitis.

Conclusion: Cryoablation of the PNN for chronic rhinitis is safe and can result in relief of nasal symptoms and improvements in quality of life.

Level Of Evidence: 4 Laryngoscope, 130: 1877-1884, 2020.
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http://dx.doi.org/10.1002/lary.28301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384004PMC
August 2020

Operative Management of Vocal Fold Avulsion Following Pediatric Laryngotracheal Separation.

Ear Nose Throat J 2019 Sep 26:145561319866821. Epub 2019 Sep 26.

Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA.

Laryngotracheal disruption in children is rare but life-threatening, and endolaryngeal injuries may go overlooked. We present the case of a 10-year-old boy who sustained near-complete laryngotracheal separation, multiple laryngeal fractures, and arytenoid and vocal fold avulsion following blunt cervical trauma. These injuries were not identified radiographically and only became apparent intraoperatively. Following surgical repair, the patient was successfully decannulated, eating a normal diet, and had a serviceable speaking voice within 2 months. In children, the diagnosis of severe endolaryngeal injuries may be elusive and therefore require high degree of clinical suspicion. Surgical success requires accurate diagnosis and prompt intervention.
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http://dx.doi.org/10.1177/0145561319866821DOI Listing
September 2019

Clinical and molecular insights into adenoid cystic carcinoma: Neural crest-like stemness as a target.

Laryngoscope Investig Otolaryngol 2016 08 4;1(4):60-77. Epub 2016 Aug 4.

Section of Otolaryngology, Department of Surgery, Yale School of Medicine New Haven Connecticut USA.

Objectives: This review surveys trialed therapies and molecular defects in adenoid cystic carcinoma (ACC), with an emphasis on neural crest-like stemness characteristics of newly discovered cancer stem cells (CSCs) and therapies that may target these CSCs.

Data Sources: Articles available on Pubmed or OVID MEDLINE databases and unpublished data.

Review Methods: Systematic review of articles pertaining to ACC and neural crest-like stem cells.

Results: Adenoid cystic carcinoma of the salivary gland is a slowly growing but relentless cancer that is prone to nerve invasion and metastases. A lack of understanding of molecular etiology and absence of targetable drivers has limited therapy for patients with ACC to surgery and radiation. Currently, no curative treatments are available for patients with metastatic disease, which highlights the need for effective new therapies. Research in this area has been inhibited by the lack of validated cell lines and a paucity of clinically useful markers. The ACC research environment has recently improved, thanks to the introduction of novel tools, technologies, approaches, and models. Improved understanding of ACC suggests that neural crest-like stemness is a major target in this rare tumor. New cell culture techniques and patient-derived xenografts provide tools for preclinical testing.

Conclusion: Preclinical research has not identified effective targets in ACC, as confirmed by the large number of failed clinical trials. New molecular data suggest that drivers of neural crest-like stemness may be required for maintenance of ACC; as such, CSCs are a target for therapy of ACC.
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http://dx.doi.org/10.1002/lio2.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510248PMC
August 2016

The 50 Most Cited Articles in Facial Plastic Surgery.

Aesthetic Plast Surg 2017 Oct 20;41(5):1202-1207. Epub 2017 Jun 20.

Section of Otolaryngology, Yale School of Medicine, New Haven, CT, USA.

Bibliometric analysis is a common method to determine the most influential articles in medical specialties, as it is an objective measure of peer recognition of scientific work. This study is the first bibliometric analysis of the literature in facial plastic surgery, to determine the most cited papers in the field. Bibliometric analysis was performed using the Science Citation Index from the Institute for Scientific Information, accessed through the Web of Science™. Filter terms relevant to the field of facial plastic surgery were used to identify the 50 most cited journal articles between 1900 and 2016. The median number of citations was 150 (range 116-1091). The articles spanned a wide range of topics in the field, with the most common topics being free flap reconstruction (n = 10), nasal surgery (n = 9), and rhytidectomy (n = 6). The majority of these articles (n = 29) presented findings supported by level IV or V evidence. This analysis provides an overview of the most cited articles in facial plastic surgery, many of which introduced some of the most fundamental principles and techniques in the field. These landmark articles represent important educational points that should be reviewed by all clinicians and trainees in this field. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-017-0908-xDOI Listing
October 2017

NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem-Like Cells in Adenoid Cystic Carcinoma.

Clin Cancer Res 2016 Apr;22(8):2083-95

Department of Surgery, Section of Otolaryngology, Yale School of Medicine, New Haven, Connecticut.

Purpose: Although the existence of cancer stem cells (CSC) in adenoid cystic carcinoma (ACC) has been proposed, lack of assays for their propagation and uncertainty about molecular markers prevented their characterization. Our objective was to isolate CSC from ACC and provide insight into signaling pathways that support their propagation.

Experimental Design: To isolate CSC from ACC and characterize them, we used ROCK inhibitor-supplemented cell culture, immunomagnetic cell sorting, andin vitro/in vivoassays for CSC viability and tumorigenicity.

Results: We identified in ACC CD133-positive CSC that expressed NOTCH1 and SOX10, formed spheroids, and initiated tumors in nude mice. CD133(+)ACC cells produced activated NOTCH1 (N1ICD) and generated CD133(-)cells that expressed JAG1 as well as neural differentiation factors NR2F1, NR2F2, and p27Kip1. Knockdowns ofNOTCH1, SOX10, and their common effectorFABP7had negative effects on each other, inhibited spheroidogenesis, and induced cell death pointing at their essential roles in CSC maintenance. Downstream effects ofFABP7knockdown included suppression of a broad spectrum of genes involved in proliferation, ribosome biogenesis, and metabolism. Among proliferation-linked NOTCH1/FABP7 targets, we identified SKP2 and its substrate p27Kip1. A γ-secretase inhibitor, DAPT, selectively depleted CD133(+)cells, suppressed N1ICD and SKP2, induced p27Kip1, inhibited ACC growthin vivo, and sensitized CD133(+)cells to radiation.

Conclusions: These results establish in the majority of ACC the presence of a previously uncharacterized population of CD133(+)cells with neural stem properties, which are driven by SOX10, NOTCH1, and FABP7. Sensitivity of these cells to Notch inhibition and their dependence on SKP2 offer new opportunities for targeted ACC therapies.
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http://dx.doi.org/10.1158/1078-0432.CCR-15-2208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834904PMC
April 2016

Applications of 3-Dimensional Printing in Facial Plastic Surgery.

J Oral Maxillofac Surg 2016 Mar 28;74(3):427-8. Epub 2015 Oct 28.

Chief Resident, Section of Otolaryngology, Department of Surgery, Yale University School of Medicine, New Haven, CT.

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http://dx.doi.org/10.1016/j.joms.2015.10.016DOI Listing
March 2016

High rate of bilaterality in internal auditory canal metastases.

Am J Otolaryngol 2015 Nov-Dec;36(6):798-804. Epub 2015 Jun 10.

Yale University School of Medicine, Section of Otolaryngology, 800 Howard Ave, 4th Fl, New Haven, CT. Electronic address:

Purpose: Presentation of three cases of metastatic carcinoma to the internal auditory canal bilaterally, as well as a systematic review of the literature regarding the characteristics of these lesions.

Materials And Methods: Using a MEDLINE Ovid search (1946-2015), we identified and reviewed 102 cases of metastatic carcinoma to the internal auditory canal. Metrics recorded include: patient age, sex, tumor type, laterality, past oncologic history, co-occurring metastatic sites, clinical findings, radiographic findings, therapy received, and outcome. Cases of unilateral versus bilateral IAC were compared.

Results: Remarkably, 52.9% reported cases of internal auditory canal metastases have bilateral occurrence. The most common primary tumor sites for internal auditory canal metastases were lung (21.2%), skin (18.6%), and breast (16.7%), with lung and skin cancers having the highest rates of bilateral metastasis. Meningeal metastasis occurred at a much higher rate in bilateral cases (47.2%) versus unilateral cases (8.5%). Brain parenchymal metastasis also occurred at a higher rate in bilateral cases (38.2%) versus unilateral cases (19.2%). Outcomes for cases of internal auditory canal metastases are generally poor, with 56.3% of unilateral cases and 86.1% of bilateral cases reporting patient death within 5 years from diagnosis.

Conclusions: In cases of internal auditory canal metastasis, clinicians should carefully assess for not only contralateral disease but also additional metastatic disease of the central nervous system. Rapid-onset hearing loss, tinnitus, vertigo, or facial palsy should raise suspicion for internal auditory canal metastasis, particularly in patients with a known oncologic history.
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http://dx.doi.org/10.1016/j.amjoto.2015.06.002DOI Listing
August 2016

Severe epistaxis due to aberrant vasculature in a patient with STAT-1 mutation.

Head Neck 2016 Mar 7;38(3):E68-70. Epub 2015 Oct 7.

Department of Surgery, Section of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut.

Background: Signal transducer and activator 1 (STAT-1) mutations are rare and have been implicated in combined immunodeficiency, enhanced tumorigenesis, and vascular defects.

Methods: A 60-year-old woman with a novel STAT-1 mutation and resulting immunodeficiency, squamous cell carcinoma, and vascular disease presented with profuse epistaxis secondary to rupture of an aberrant artery that she developed in part because of this mutation. After unsuccessful posterior packing, embolization was initiated but subsequently aborted because of a bovine origin carotid artery and a history of multiple carotid dissections.

Results: After repeat posterior packing, hemostasis was achieved. No additional episodes of epistaxis occurred in the subsequent 13 months.

Conclusion: Vascular anomalies can present challenges in epistaxis management. In patients with conditions known to cause vascular anomalies, it is critical to obtain vascular imaging before intervention.
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http://dx.doi.org/10.1002/hed.24165DOI Listing
March 2016

Effectiveness of a segmental approach to climate policy.

Environ Sci Technol 2014 16;48(1):27-35. Epub 2013 Dec 16.

Engineering Systems Division, §Department of Urban Studies and Planning, ⊥Department of Political Science, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

Resistance to adopting a cap on greenhouse gas emissions internationally, and across various national contexts, has encouraged alternative climate change mitigation proposals. These proposals include separately targeting clean energy uptake and demand-side efficiency in individual end-use sectors, an approach to climate change mitigation which we characterize as segmental and technology-centered. A debate has ensued on the detailed implementation of these policies in particular national contexts, but less attention has been paid to the general factors determining the effectiveness of a segmental approach to emissions reduction. We address this topic by probing the interdependencies of segmental policies and their collective ability to control emissions. First, we show for the case of U.S. electricity how the set of suitable energy technologies depends on demand-side efficiency, and changes with the stringency of climate targets. Under a high-efficiency scenario, carbon-free technologies must supply 60-80% of U.S. electricity demand to meet an emissions reduction target of 80% below 1990 levels by midcentury. Second, we quantify the enhanced propensity to exceed any intended emissions target with this approach, even if goals are set on both the supply and demand side, due to the multiplicative accumulation of emissions error. For example, a 10% error in complying with separate policies on the demand and supply side would combine to result in a 20% error in emissions. Third, we discuss why despite these risks, the enhanced planning capability of a segmental approach may help counteract growing infrastructural inertia. The emissions reduction impediment due to infrastructural inertia is significant in the electricity sectors of each of the greatest emitters: China, the U.S., and Europe. Commonly cited climate targets are still within reach but, as we show, would require more than a 50% reduction in the carbon intensity of new power plants built in these regions over the next decade.
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http://dx.doi.org/10.1021/es305093cDOI Listing
September 2015

Biomechanical effects of simulated resorption cavities in cancellous bone across a wide range of bone volume fractions.

J Bone Miner Res 2012 Sep;27(9):1927-35

Orthopaedic Biomechanics Laboratory, Department of Mechanical Engineering, University of California, Berkeley, CA 94720, USA.

Resorption cavities formed during bone remodeling may act as "stress risers" and impair cancellous bone strength, but biomechanical analyses of the effects of stress risers have been limited. To provide further insight, we assessed the theoretical biomechanical effects of virtually-added resorption cavities in cancellous bone specimens spanning a wide range of bone volume fraction (BV/TV = 0.05-0.36) and across different anatomic sites (hip and spine) and species (human and canine). Micro-CT scans of 40 cubes of cancellous bone were converted into nonlinear finite element models (voxel element size ∼ 20 µm) for strength assessment. In each model, uniform trench-like resorption cavities with nominal dimensions 500 µm (length) × 200 µm (width) × 40 µm (depth), were virtually added either at random locations throughout the specimen, or, preferentially at locations of high tissue-level strain. We found that cancellous bone strength (p < 0.0001) and its relation with BV/TV (p < 0.001) were both altered by the virtual addition of the resorption cavities. When the resorption cavities were added at random locations throughout the specimen, the reduction in strength did not depend on BV/TV or anatomic site or species. When the resorption cavities were instead added preferentially at locations of high tissue-level strain, the effect was accentuated and was greatest in low-BV/TV bone. We conclude that, in theory, uniform-sized resorption cavities can reduce cancellous bone strength over the full range of BV/TV and across species, and the effect is larger if the cavities occur at highly strained locations in low-BV/TV bone.
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http://dx.doi.org/10.1002/jbmr.1657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423528PMC
September 2012

Quantifying interhospital patient sharing as a mechanism for infectious disease spread.

Infect Control Hosp Epidemiol 2010 Nov;31(11):1160-9

Division of Infectious Diseases and Health Policy Research Institute, University of California Irvine, Irvine, California, USA.

Background: Assessments of infectious disease spread in hospitals seldom account for interfacility patient sharing. This is particularly important for pathogens with prolonged incubation periods or carrier states.

Methods: We quantified patient sharing among all 32 hospitals in Orange County (OC), California, using hospital discharge data. Same-day transfers between hospitals were considered "direct" transfers, and events in which patients were shared between hospitals after an intervening stay at home or elsewhere were considered "indirect" patient-sharing events. We assessed the frequency of readmissions to another OC hospital within various time points from discharge and examined interhospital sharing of patients with Clostridium difficile infection.

Results: In 2005, OC hospitals had 319,918 admissions. Twenty-nine percent of patients were admitted at least twice, with a median interval between discharge and readmission of 53 days. Of the patients with 2 or more admissions, 75% were admitted to more than 1 hospital. Ninety-four percent of interhospital patient sharing occurred indirectly. When we used 10 shared patients as a measure of potential interhospital exposure, 6 (19%) of 32 hospitals "exposed" more than 50% of all OC hospitals within 6 months, and 17 (53%) exposed more than 50% within 12 months. Hospitals shared 1 or more patient with a median of 28 other hospitals. When we evaluated patients with C. difficile infection, 25% were readmitted within 12 weeks; 41% were readmitted to different hospitals, and less than 30% of these readmissions were direct transfers.

Conclusions: In a large metropolitan county, interhospital patient sharing was a potential avenue for transmission of infectious agents. Indirect sharing with an intervening stay at home or elsewhere composed the bulk of potential exposures and occurred unbeknownst to hospitals.
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http://dx.doi.org/10.1086/656747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064463PMC
November 2010