Publications by authors named "Karthik Balakrishnan"

85 Publications

Opioid-Free Tonsillectomy With and Without Adenoidectomy: The Role of Regional Anesthesia in the "New Era".

Anesth Analg 2021 07;133(1):e7-e9

Department of Otolaryngology-Head & Neck, Lucile Packard Children's Hospital at Stanford, Stanford, California.

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http://dx.doi.org/10.1213/ANE.0000000000005567DOI Listing
July 2021

Sinonasal adenocarcinoma: A population-based analysis of demographic and socioeconomic disparities.

Head Neck 2021 Jun 12. Epub 2021 Jun 12.

Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Background: Sinonasal adenocarcinoma (SNAC) is a rare tumor. The impact of health disparities on survival, stage at presentation, and utilization of surgery is not well understood in patients with SNAC.

Methods: The Surveillance, Epidemiology, and End Results database was queried for cases of SNAC from 1973 to 2015. Cases were analyzed to assess for disparities in presentation, treatment, and survival.

Results: SNAC was identified in 630 patients. In a multivariate model of overall survival, an age increase of 10 years (Hazard Ratio (HR) = 1.37, p < 0.001), male sex (HR = 1.26, p = 0.045), and more recent decade of diagnosis (HR = 0.74, p < 0.001) were significantly related to time-to-death. There is a higher rate of SNAC-related death in counties with more rural populations (p = 0.027).

Conclusion: Future interventions targeting rural and less well-educated populations may improve care with the goal of increasing the span of healthy life and reducing survival disparities related to SNAC.
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http://dx.doi.org/10.1002/hed.26783DOI Listing
June 2021

Suprazygomatic maxillary (SZM) nerve blocks for perioperative pain control in pediatric tonsillectomy and adenoidectomy.

J Clin Anesth 2021 Aug 20;71:110240. Epub 2021 Mar 20.

Department of Anesthesiology, Perioperative, and Pain Medicine, Lucile Packard Children's Hospital at Stanford, Stanford, CA, United States. Electronic address:

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http://dx.doi.org/10.1016/j.jclinane.2021.110240DOI Listing
August 2021

Laryngeal and Tracheal Pressure Injuries in Patients With COVID-19.

JAMA Otolaryngol Head Neck Surg 2021 05;147(5):484-485

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland.

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http://dx.doi.org/10.1001/jamaoto.2021.0001DOI Listing
May 2021

YY1 regulated transcription-based stratification of gastric tumors and identification of potential therapeutic candidates.

J Cell Commun Signal 2021 Jun 23;15(2):251-267. Epub 2021 Feb 23.

Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India.

Gastric cancer is one of the leading causes of cancer-related death worldwide. The transcription factor YY1 regulates diverse biological processes, including cell proliferation, development, DNA damage responses, and carcinogenesis. This study was designed to explore the role of YY1 regulated transcription in gastric cancer. YY1 silencing in gastric cancer cells has resulted in the inhibition of Wnt/β-catenin, JNK/MAPK, ERK/MAPK, ER, and HIF-1α signaling pathways. Genome-wide mRNA profiling upon silencing the expression YY1 gene in gastric cancer cells and comparison with the previously identified YY1 regulated genes from other lineages revealed a moderate overlap among the YY1 regulated genes. Despite the differing genes, all the YY1 regulated gene sets were expressed in most of the intestinal subtype gastric tumors and a subset of diffuse subtype gastric tumors. Integrative functional genomic analysis of the YY1 gene sets revealed an association among the pathways Wnt/β-catenin, Rapamycin, Cyclin-D1, Myc, E2F, PDGF, and AKT. Further, the drugs capable of inhibiting YY1 mediated transcription were identified as suitable targeted therapeutic candidates for gastric tumors with activated YY1. The data emerging from the investigation would pave the way for the development of YY1-based targeted therapeutics for gastric cancer.
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http://dx.doi.org/10.1007/s12079-021-00608-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991048PMC
June 2021

Postoperative dysphagia immediately following pediatric endoscopic laryngeal cleft repair.

Int J Pediatr Otorhinolaryngol 2021 Mar 12;142:110625. Epub 2021 Jan 12.

Department of Otolaryngology,Head and Neck Surgery, Stanford University, Palo Alto, CA, USA; Lucile Packard Children's Hospital Stanford, Palo Alto, CA, USA. Electronic address:

Objectives: In pediatric patients undergoing endoscopic laryngeal cleft repair, immediate postoperative dysphagia is not well-characterized. This study examined whether worsened dysphagia is present in the immediate postoperative period as detected by clinical swallow evaluation, and evaluated how this relates to postoperative change in presenting symptoms and findings on swallow studies.

Methods: A retrospective cohort was conducted at a tertiary academic medical center, evaluating all pediatric patients who underwent endoscopic laryngeal cleft repair by a single surgeon from October 2014 through December 2018. All patients underwent instrumental swallow evaluation preoperatively and clinical swallow evaluation within 24 h following surgery.

Results: Thirty-nine patients met inclusion criteria. Based on clinical swallow evaluation performed within 24 h after surgery, 4 patients (10%) were recommended to thicken their diet from preoperative baseline; all others were unchanged. All patients were admitted to the PICU for observation; 34 (87%) discharged on postoperative day 1. Thirty-seven patients attended 6-week follow-up, with 2 (5%) requiring thicker diet since discharge; all others were stable or improved. Prevalence of recurrent respiratory infections, subjective dysphagia, chronic cough, and wheezing significantly decreased after surgery. No statistically significant change occurred in prevalence of aspiration or penetration on instrumental swallow studies postoperatively.

Conclusion: Endoscopic laryngeal cleft repair is well-tolerated in pediatric patients, and most do not have obviously worsened dysphagia at immediate postoperative evaluation. Improvement in symptoms postoperatively may be a more useful indicator of surgical outcomes beyond instrumental swallow studies alone. The relative stability of these patients provides further evidence that they can likely be managed on the floor or as outpatients rather than in the ICU postoperatively.
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http://dx.doi.org/10.1016/j.ijporl.2021.110625DOI Listing
March 2021

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

Laryngoscope 2021 06 6;131(6):E1941-E1949. Epub 2021 Jan 6.

Department of Otolaryngology-Head and Neck Surgery, University of Texas (UT) Southwestern Medical Center, Dallas, Texas, U.S.A.

Objectives/hypothesis: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality.

Study Design: Delphi method-based survey series.

Methods: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up.

Results: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18).

Conclusion: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes.

Level Of Evidence: 5 Laryngoscope, 131:E1941-E1949, 2021.
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http://dx.doi.org/10.1002/lary.29343DOI Listing
June 2021

International Pediatric Otolaryngology Group (IPOG) survey: Efforts to avoid complications in home tracheostomy care.

Int J Pediatr Otorhinolaryngol 2021 Feb 18;141:110563. Epub 2020 Dec 18.

Department of Otolaryngology - Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Boston, MA, USA. Electronic address:

Objective: To provide guidance for home care tracheostomy management in the pediatric population. The mission of the IPOG is to develop expertise-based recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care.

Methods: Survey of expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG).

Results: Survey results provide guidance for caregiver teaching, the reuse of tracheostomies and suction catheters while inpatient and following discharge, acceptable sterilization practices for tracheostomies, tracheitis workup and management, and outpatient follow-up practices.

Conclusion: This presentation of common home tracheostomy care practices are aimed at improving patient-centered care in the pediatric population.
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http://dx.doi.org/10.1016/j.ijporl.2020.110563DOI Listing
February 2021

Intraoperative Sentinel Events in the Era of Surgical Safety Checklists: Results of a National Survey.

OTO Open 2020 Oct-Dec;4(4):2473974X20975731. Epub 2020 Dec 9.

University of Michigan Medical School, Ann Arbor, Michigan, USA.

Objective: Despite the implementation of advanced health care safety systems including checklists, preventable perioperative sentinel events continue to occur and cause patient harm, disability, and death. We report on findings relating to otolaryngology practices with surgical safety checklists, the scope of intraoperative sentinel events, and institutional and personal response to these events.

Study Design: Survey study.

Setting: Anonymous online survey of otolaryngologists.

Methods: Members of the American Academy of Otolaryngology-Head and Neck Surgery were asked about intraoperative sentinel events, surgical safety checklist practices, fire safety, and the response to patient safety events.

Results: In total, 543 otolaryngologists responded to the survey (response rate 4.9% = 543/11,188). The use of surgical safety checklists was reported by 511 (98.6%) respondents. At least 1 patient safety event in the past 10 years was reported by 131 (25.2%) respondents; medication errors were the most commonly reported (66 [12.7%] respondents). Wrong site/patient/procedure events were reported by 38 (7.3%) respondents, retained surgical items by 33 (6.4%), and operating room fire by 18 (3.5%). Although 414 (79.9%) respondents felt that time-outs before the case have been the single most impactful checklist component to prevent serious patient safety events, several respondents also voiced frustrations with the administrative burden.

Conclusion: Surgical safety checklists are widely used in otolaryngology and are generally acknowledged as the most effective intervention to reduce patient safety events; nonetheless, intraoperative sentinel events do continue to occur. Understanding the scope, causes, and response to these events may help to prioritize resources to guide quality improvement initiatives in surgical safety practices.
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http://dx.doi.org/10.1177/2473974X20975731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731722PMC
December 2020

International Pediatric Otolaryngology Group (IPOG) management recommendations: Pediatric tracheostomy decannulation.

Int J Pediatr Otorhinolaryngol 2021 Feb 15;141:110565. Epub 2020 Dec 15.

Division of Otolaryngology, Children's National Medical Center, George Washington University, Washington DC, USA.

Objectives: To provide recommendations to otolaryngologists, pulmonologists, and allied clinicians for tracheostomy decannulation in pediatric patients.

Methods: An iterative questionnaire was used to establish expert recommendations by the members of the International Pediatric Otolaryngology Group.

Results: Twenty-six members completed the survey. Recommendations address patient criteria for decannulation readiness, airway evaluation prior to decannulation, decannulation protocol, and follow-up after both successful and failed decannulation.

Conclusion: Tracheostomy decannulation recommendations are aimed at improving patient-centered care, quality and safety in children with tracheostomies.
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http://dx.doi.org/10.1016/j.ijporl.2020.110565DOI Listing
February 2021

Endotracheal metallic stent removal: A novel ABC (airway balloon collapse) technique.

Int J Pediatr Otorhinolaryngol 2021 Jan 10;140:110490. Epub 2020 Nov 10.

Department of Otorhinolaryngology, Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA.

To illustrate a previously unreported method of tracheal stent removal that appears to cause less mucosal injury we present a case of a 9-year-old Down syndrome patient with a history of tracheoesophageal fistula, brought to our attention after recurrent bouts of exacerbating cough and tracheo-bronchitis. Endoscopic examination under general anesthesia noted the presence of severe tracheomalacia with inspiratory collapse, and a 10-mm balloon expandable metallic stent (BEMS) was deployed and symptomatic improvement was noted. The initial stent was then removed to consider a definitive procedure using the typical grasping fashion with an alligator forceps and expected mucosal excoriation was noted. Due to symptom recurrence, the patient underwent placement of a second BEMS stent. Initial improvement was noted followed by recurrent episodes of respiratory distress due to granulation tissue formation and stent compression and a decision to remove the stent was made. A new method of stent removal deemed ABC (airway balloon collapse) method was utilized where an expandable airway balloon is placed outside the stent between the stent and tracheal wall and then inflated to collapse the stent, facilitating easy removal.
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http://dx.doi.org/10.1016/j.ijporl.2020.110490DOI Listing
January 2021

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Management of suprastomal collapse in the pediatric population.

Int J Pediatr Otorhinolaryngol 2020 Dec 13;139:110427. Epub 2020 Oct 13.

Section of Pediatric ORL, Department of ORL, University Hospital Center S. Joao, University of Porto Faculty of Medicine and CINTESIS, Porto, Portugal.

Introduction: Suprastomal Collapse (SuStCo) is a common complication of prolonged tracheostomy in children. There is a paucity of literature on this subject, especially regarding how to manage significant suprastomal collapse that prevents safe decannulation.

Objective: Provide a definition, classification system, and recommend management options for significant suprastomal collapse in children with tracheostomy.

Methods: Members of the International Pediatric Otolaryngology Group (IPOG) who are experts in pediatric airway conditions were surveyed and results were refined using a modified Delphi method.

Results: Consensus was defined as > 70% agreement on a subject. The experts achieved consensus: CONCLUSION: This consensus statement provides recommendations for medical specialists who manage infants and children with tracheostomies with significant Suprastomal Collapse. It provides a classification system to facilitate diagnosis and treatment options for this condition.
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http://dx.doi.org/10.1016/j.ijporl.2020.110427DOI Listing
December 2020

Sequential Minimally Invasive Fetal Interventions for Two Life-Threatening Conditions: A Novel Approach.

Fetal Diagn Ther 2021 20;48(1):70-77. Epub 2020 Oct 20.

Division of Pediatric Surgery, Department of Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

Introduction: In utero interventions are performed in fetuses with "isolated" major congenital anomalies to improve neonatal outcomes and quality of life. Sequential in utero interventions to treat 2 anomalies in 1 fetus have not yet been described.

Case Presentation: Here, we report a fetus with a large left-sided intralobar bronchopulmonary sequestration (BPS) causing mediastinal shift, a small extralobar BPS, and concomitant severe left-sided congenital diaphragmatic hernia (CDH). At 26-week gestation, the BPS was noted to be increasing in size with a significant reduction in right lung volume and progression to fetal hydrops. The fetus underwent ultrasound-guided ablation of the BPS feeding vessel leading to complete tumor regression. However, lung development remained poor (O/E-LHR: 0.22) due to the left-sided CDH, prompting fetal endoscopic tracheal occlusion therapy at 28-week gestation to allow increased lung growth. After vaginal delivery, the newborn underwent diaphragmatic repair with resection of the extralobar sequestration. He was discharged home with tracheostomy on room air at 9 months.

Discussion/conclusion: Sequential in utero interventions to treat 2 severe major anomalies in the same fetus have not been previously described. This approach may be a useful alternative in select cases with otherwise high morbidity/mortality. Further studies are required to confirm our hypothesis.
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http://dx.doi.org/10.1159/000510635DOI Listing
October 2020

Oral Intubation Attempts in Patients With a Laryngectomy: A Significant Safety Threat.

Otolaryngol Head Neck Surg 2021 05 13;164(5):1040-1043. Epub 2020 Oct 13.

American Board of Otolaryngology-Head and Neck Surgery, Houston, Texas, USA.

It is impossible to secure the airway of a patient with "neck-only" breathing transorally or transnasally. Surgical removal of the larynx (laryngectomy) or tracheal rerouting (tracheoesophageal diversion or laryngotracheal separation) creates anatomic discontinuity. Misguided attempts at oral intubation of neck breathers may cause hypoxic brain injury or death. We present national data from the American Academy of Otolaryngology-Head and Neck Surgery, the American Head and Neck Society, and the United Kingdom's National Reporting and Learning Service. Over half of US otolaryngologist respondents reported instances of attempted oral intubations among patients with laryngectomy, with a mortality rate of 26%. UK audits similarly revealed numerous resuscitation efforts where misunderstanding of neck breather status led to harm or death. Such data underscore the critical importance of staff education, patient engagement, effective signage, and systems-based best practices to reliably clarify neck breather status and provide necessary resources for safe patient airway management.
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http://dx.doi.org/10.1177/0194599820960728DOI Listing
May 2021

Competency-Based Assessment Tool for Pediatric Esophagoscopy: International Modified Delphi Consensus.

Laryngoscope 2021 05 9;131(5):1168-1174. Epub 2020 Oct 9.

Department of Otolaryngology, Head and Neck Surgery, Stanford University, Lucile Salter Packard Children's Hospital, Palo Alto, California, U.S.A.

Objectives/hypothesis: Create a competency-based assessment tool for pediatric esophagoscopy with foreign body removal.

Study Design: Blinded modified Delphi consensus process.

Setting: Tertiary care center.

Methods: A list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as "keep" or "remove" and comments were incorporated. In the second round, experts rated the importance of each item on a seven-point Likert scale. Consensus was determined with a goal of 7 to 25 final items.

Results: The response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to "keep" all items and 172 comments were incorporated. Twenty-four task-specific and 7 previously-validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task-specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus.

Conclusions: It is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated.

Level Of Evidence: 5. Laryngoscope, 131:1168-1174, 2021.
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http://dx.doi.org/10.1002/lary.29126DOI Listing
May 2021

Opioid Prescribing Patterns Following Pediatric Tonsillectomy in the United States, 2009-2017.

Laryngoscope 2021 05 7;131(5):E1722-E1729. Epub 2020 Oct 7.

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

Objectives: Assess national trends in opioid prescription following pediatric tonsillectomy: 1) overall percentage receiving opioids and mean quantity, 2) changes during 2009-2017, and 3) determinants of prescription patterns.

Methods: Cross-sectional analysis using 2009-2017 Optum claims data to identify opioid-naïve children aged 1-18 with claims codes for tonsillectomy (n = 82,842). Quantities of opioids filled in outpatient pharmacies during the perioperative period were extracted and converted into milligram morphine equivalents (MMEs) for statistical comparison. Demographic, clinical, and socioeconomic predictors of opioid fill rate and quantity were determined using regression analyses.

Results: In 2009, 83.3% of children received opioids, decreasing to 58.3% by 2017. Rates of all-cause readmissions and post-tonsillectomy hemorrhages were similar over time. Mean quantity received was 153.47MME (95% confidence intervals [95%CI]: 151.19, 155.76) and did not significantly change during 2009-2017. Opioids were more likely in older children and those with higher household income, but less likely in children with obstructive sleep apnea, other comorbidities, and Hispanic race. Higher quantities of opioids were more likely in older children, while lower quantities were associated with female sex, Hispanic race, and higher household income. Outpatient steroids were prescribed to 8.04% of patients, who were less likely to receive opioids.

Conclusion: While the percentage of children receiving post-tonsillectomy opioids decreased during 2009-2017, prescribed quantities remain high and have not decreased over time. Prescription practices were also influenced by clinical and sociodemographic factors. These results highlight the need for guidance, particularly with regard to opioid quantity, in children after tonsillectomy.

Level Of Evidence: N/A Laryngoscope, 131:E1722-E1729, 2021.
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http://dx.doi.org/10.1002/lary.29159DOI Listing
May 2021

Multidisciplinary Safety Recommendations After Tracheostomy During COVID-19 Pandemic: State of the Art Review.

Otolaryngol Head Neck Surg 2021 05 22;164(5):984-1000. Epub 2020 Sep 22.

Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA; Global Tracheostomy Collaborative, Raleigh, North Carolina, USA.

Objective: In the chronic phase of the COVID-19 pandemic, questions have arisen regarding the care of patients with a tracheostomy and downstream management. This review addresses gaps in the literature regarding posttracheostomy care, emphasizing safety of multidisciplinary teams, coordinating complex care needs, and identifying and managing late complications of prolonged intubation and tracheostomy.

Data Sources: PubMed, Cochrane Library, Scopus, Google Scholar, institutional guidance documents.

Review Methods: Literature through June 2020 on the care of patients with a tracheostomy was reviewed, including consensus statements, clinical practice guidelines, institutional guidance, and scientific literature on COVID-19 and SARS-CoV-2 virology and immunology. Where data were lacking, expert opinions were aggregated and adjudicated to arrive at consensus recommendations.

Conclusions: Best practices in caring for patients after a tracheostomy during the COVID-19 pandemic are multifaceted, encompassing precautions during aerosol-generating procedures; minimizing exposure risks to health care workers, caregivers, and patients; ensuring safe, timely tracheostomy care; and identifying and managing laryngotracheal injury, such as vocal fold injury, posterior glottic stenosis, and subglottic stenosis that may affect speech, swallowing, and airway protection. We present recommended approaches to tracheostomy care, outlining modifications to conventional algorithms, raising vigilance for heightened risks of bleeding or other complications, and offering recommendations for personal protective equipment, equipment, care protocols, and personnel.

Implications For Practice: Treatment of patients with a tracheostomy in the COVID-19 pandemic requires foresight and may rival procedural considerations in tracheostomy in their complexity. By considering patient-specific factors, mitigating transmission risks, optimizing the clinical environment, and detecting late manifestations of severe COVID-19, clinicians can ensure due vigilance and quality care.
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http://dx.doi.org/10.1177/0194599820961990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198753PMC
May 2021

Occurrence of differing metabolic dysregulations, a glucose driven and another fatty acid centric in gastric cancer subtypes.

Funct Integr Genomics 2020 Nov 19;20(6):813-824. Epub 2020 Sep 19.

Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India.

Gastric cancer is one of the most common cancers and ranks third in cancer-related deaths across globe. Cancer cells are known to take advantage of the altered metabolic processes to sustain their survival, proliferation, and cancer progression. In this investigation, we explored the available genome-wide expression profiles of few hundreds of gastric tumors and non-cancerous gastric tissues and analyzed in the context of metabolic pathways. Gastric tumors were investigated for the metabolic processes related to glucose metabolism, glucose transport, glutamine metabolism, and fatty acid metabolism, by metabolic pathway-focused gene set enrichment analysis. Notably, all glucose metabolism and glutamine metabolism-related gene sets were found enriched in intestinal subtype gastric tumors. On the other hand, the gene sets related to glucose transport and glucan (glycan) metabolisms are enriched in diffuse subtype gastric tumors. Strikingly, fatty acid metabolisms, fatty acid transport, and fat differentiation-related signatures are also highly activated in diffuse subtype gastric tumors. Exploration of the recently established metabolome profile of the massive panel of cell lines also revealed the metabolites of glucose and fatty acid metabolic pathways to show the differing abundance across gastric cancer subtypes. The subtype-specific metabolic rewiring and the existence of two distinct metabolic dysregulations involving glucose and fatty acid metabolism in gastric cancer subtypes have been identified. The identified differing metabolic dysregulations would pave way for the development of targeted therapeutic strategies for the gastric cancer subtypes.
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http://dx.doi.org/10.1007/s10142-020-00753-wDOI Listing
November 2020

Laryngotracheal Reconstruction in a Patient With a Central Conducting Lymphatic Anomaly.

Laryngoscope 2021 04 9;131(4):E1339-E1341. Epub 2020 Sep 9.

Department of Otolaryngology-Head and Neck Surgery, Stanford University; Aerodigestive and Airway Reconstruction Program, Lucile Packard Children's Hospital, Palo Alto, California, U.S.A.

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http://dx.doi.org/10.1002/lary.29071DOI Listing
April 2021

International Pediatric Otolaryngology Group (IPOG): Consensus recommendations on the prenatal and perinatal management of anticipated airway obstruction.

Int J Pediatr Otorhinolaryngol 2020 Nov 8;138:110281. Epub 2020 Aug 8.

Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

Objective: To make recommendations on the identification, routine evaluation, and management of fetuses at risk for airway compromise at delivery.

Methods: Recommendations are based on expert opinion by members of the International Pediatric Otolaryngology Group (IPOG). A two-iterative Delphi method questionnaire was distributed to all members of the IPOG and responses recorded. The respondents were given the opportunity to comment on the content and format of the survey, which was modified for the second round. "Consensus" was defined by >80% respondent affirmative responses, "agreement" by 51-80% affirmative responses, and "no agreement" by 50% or less affirmative responses.

Results: Recommendations are provided regarding etiologies of perinatal airway obstruction, imaging evaluation, adjunct evaluation, multidisciplinary team and decision factors, micrognathia management, congenital high airway obstruction syndrome management, head and neck mass management, attended delivery procedure, and delivery on placental support procedure.

Conclusions: Thorough evaluation and thoughtful decision making are required to optimally balance fetal and maternal risks/benefits.
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http://dx.doi.org/10.1016/j.ijporl.2020.110281DOI Listing
November 2020

International Pediatric Otolaryngology group (IPOG) consensus on the diagnosis and management of pediatric obstructive sleep apnea (OSA).

Int J Pediatr Otorhinolaryngol 2020 Nov 5;138:110276. Epub 2020 Aug 5.

Antwerp University of Antwerp, Department of Otolaryngology Head and Neck Surgery, University of Antwerp, Antwerp, Belgium. Electronic address:

Objective: To develop an expert-based consensus of recommendations for the diagnosis and management of pediatric obstructive sleep apnea.

Methods: A two-iterative Delphi method questionnaire was used to formulate expert recommendations by the members of the International Pediatric Otolaryngology Group (IPOG).

Results: Twenty-six members completed the survey. Consensus recommendations (>90% agreement) are formulated for 15 different items related to the clinical evaluation, diagnosis, treatment, postoperative management and follow-up of children with OSA.

Conclusion: The recommendations formulated in this IPOG consensus statement may be used along with existing clinical practice guidelines to improve the quality of care and to reduce variation in care for children with OSA.
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http://dx.doi.org/10.1016/j.ijporl.2020.110276DOI Listing
November 2020

Speech Pathology Utilization and Stroboscopy Before and After Adult Medialization Laryngoplasty.

J Voice 2020 Jul 18. Epub 2020 Jul 18.

Department of Otolaryngology - Head & Neck Surgery, Stanford University, Palo Alto, California.

Objectives: Evaluation of trends and utilization of speech-language-pathology (SLP) services, including stroboscopy, before and after medialization laryngoplasty (ML) over 11 years.

Methods: Retrospective national US database study conducted using OptumLabs Data Warehouse. Study cohort included patients (age ≥18 years) who underwent ML between January 2007 and December 2016. Primary outcomes were rates of SLP visits in the 12 months before and 12 months after ML. Linear regression analysis was performed assessing for trends utilization across years. Secondary outcomes were predictors of utilization After-ML using multivariable logistic regression.

Results: 1114 patients met criteria. Services, including stroboscopy, were utilized by 774 (69%) Before-ML and 697 (63%) After-ML. SLP services, excluding stroboscopy, were utilized by 512 (46%) Before-ML and 478 (43%) After-ML. Vocal cord paralysis was the most common diagnosis, 945 (84.8%) patients. Other service billed were stroboscopy, [Before-ML 676 (60.7%); After-ML 567 (50.9%)], voice evaluation [Before-ML 431(38.7%); After-ML 366 (32.9%)], voice therapy [Before-ML 309 (27.7%); After-ML 339 (30.4%)], laryngeal function studies, [Before-ML 175 (15.7%); After-ML 164 (14.7%)], swallow evaluations [Before-ML 150 (13.5%); After-ML 90 (8.1%)], and swallow therapy [Before-ML 53 (4.8%); After-ML 47 (4.2%)]. SLP utilization Before-ML predicted SLP utilization After-ML [Odds Ratio (95% Confidence Interval): 9.31 (6.78, 12.77)]. Nearly half (49%) of visits occurred in the 6 months around ML. Of those who had voice therapy, the majority (73.7%) had a total of 1 to 5 sessions.

Conclusion: Based on this retrospective US national database study, SLP services and stroboscopy are a complementary component of assessment and treatment of patients who undergo ML with the majority of services occurring in the 3 months before and after ML. Future work would benefit from outcome data.
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http://dx.doi.org/10.1016/j.jvoice.2020.06.024DOI Listing
July 2020

The Difficult Airway and Aerosol-Generating Procedures in COVID-19: Timeless Principles for Uncertain Times.

Otolaryngol Head Neck Surg 2020 11 23;163(5):934-937. Epub 2020 Jun 23.

Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.

The impact of the COVID-19 pandemic on otolaryngology practice is nowhere more evident than in acute airway management. Considerations of preventing SARS-CoV-2 transmission, conserving personal protective equipment, and prioritizing care delivery based on acuity have dictated clinical decision making in the acute phase of the pandemic. With transition to a more chronic state of pandemic, heightened vigilance is necessary to recognize how deferral of care in patients with tenuous airways and COVID-19 infection may lead to acute airway compromise. Furthermore, it is critical to respect the continuing importance of flexible laryngoscopy in diagnosis. Safely managing airways during the pandemic requires thoughtful multidisciplinary planning. Teams should consider trade-offs among aerosol-generating procedures involving direct laryngoscopy, supraglottic airway use, fiberoptic intubation, and tracheostomy. We share clinical cases that illustrate enduring principles of acute airway management. As algorithms evolve, time-honored approaches for diagnosis and management of acute airway pathology remain essential in ensuring patient safety.
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http://dx.doi.org/10.1177/0194599820936615DOI Listing
November 2020

COVID-19 pandemic and health care disparities in head and neck cancer: Scanning the horizon.

Head Neck 2020 Jul 20;42(7):1555-1559. Epub 2020 Jun 20.

Department of Otolaryngology-Head & Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.

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.
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http://dx.doi.org/10.1002/hed.26345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323088PMC
July 2020

COVID-19 Pandemic: What Every Otolaryngologist-Head and Neck Surgeon Needs to Know for Safe Airway Management.

Otolaryngol Head Neck Surg 2020 06 14;162(6):804-808. Epub 2020 Apr 14.

Department of Otolaryngology-Head & Neck Surgery and Center for Bioethics & Social Sciences in Medicine, University of Michigan, Ann Arbor, Michigan, USA.

The novel coronavirus disease 2019 (COVID-19) pandemic has unfolded with remarkable speed, posing unprecedented challenges for health care systems and society. Otolaryngologists have a special role in responding to this crisis by virtue of expertise in airway management. Against the backdrop of nations struggling to contain the virus's spread and to manage hospital strain, otolaryngologists must partner with anesthesiologists and front-line health care teams to provide expert services in high-risk situations while reducing transmission. Airway management and airway endoscopy, whether awake or sedated, expose operators to infectious aerosols, posing risks to staff. This commentary provides background on the outbreak, highlights critical considerations around mitigating infectious aerosol contact, and outlines best practices for airway-related clinical decision making during the COVID-19 pandemic. What otolaryngologists need to know and what actions are required are considered alongside the implications of increasing demand for tracheostomy. Approaches to managing the airway are presented, emphasizing safety of patients and the health care team.
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http://dx.doi.org/10.1177/0194599820919751DOI Listing
June 2020

Pediatric tracheostomy practice patterns.

Int J Pediatr Otorhinolaryngol 2020 Jun 4;133:109982. Epub 2020 Mar 4.

Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA; Pediatric Aerodigestive and Airway Reconstruction Center, Lucile Packard Children's Hospital, Stanford, Stanford, CA, USA. Electronic address:

Objective: Despite recent guidelines and the frequency of pediatric tracheostomy, surgical techniques and perioperative management are variable. We aim to describe the post-operative practice patterns following tracheostomy in children.

Methods: An electronic cross-sectional survey was distributed to American Society of Pediatric Otolaryngologists (ASPO) members in academic and private practice settings. Responses were collected anonymously and analyzed by percentages of respondents who employ specific management strategies. Statistical analysis of response distributions performed using the Z test of proportions for binary questions and the Mantel-Haenszel chi-square test for questions with more than two options. For questions with ordered categorical responses, Cuzick's nonparametric test of trend was used.

Results: One-hundred twenty-four responses were received (22.3%). Most respondents were fellowship trained and practiced in academic medical centers. A greater number of tracheostomies were performed by respondents practicing in the Midwest region (p = 0.042). There was no variability in the number of tracheostomies performed based on practitioner age, hospital setting, or fellowship training. The majority perform stoma maturation and/or stay suture techniques intraoperatively and send patients to the intensive care unit postoperatively. The routine use of postoperative paralysis was reported by a minority of respondents and 50% reported the use of sedation. There was a roughly-even distribution of respondents who reported postoperative immobilization, mobilization to a chair, and ambulation respectively. Routine; postoperative airway evaluations were reported by 35% of respondents. Clinic follow-up was; variable.

Conclusion: These results demonstrate ongoing variability in the postoperative management strategies following tracheostomy in children and highlight areas for further study.
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http://dx.doi.org/10.1016/j.ijporl.2020.109982DOI Listing
June 2020

The Relationship between Croup and Gastroesophageal Reflux: A Systematic Review and Meta-Analysis.

Laryngoscope 2021 01 10;131(1):209-217. Epub 2020 Feb 10.

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

Objective: The mechanism by which recurrent croup occurs is unknown. Gastroesophageal reflux is commonly implicated, although this relationship is only loosely documented. We conducted a systematic review with a meta-analysis component to evaluate the relationship between recurrent croup and gastroesophageal reflux disease (GERD), and to assess for evidence of improvement in croup symptoms when treated.

Style Design: Systematic Review and Meta Analysis.

Methods: We searched five separate databases. Studies were included if they discussed the relationship between croup and GERD in children, >5 subjects, and available in English. Literature retrieved was assessed according to pre-specified criteria. Retrieved articles were reviewed by two independent authors and decisions mediated by a third author. If there was a difference of opinion after first review, a second review was performed to obtain consensus. Heterogeneity was calculated and summarized in forest plots.

Results: Of 346 initial records, 15 met inclusion criteria. These were two retrospective cohort and 13 cross-sectional studies. Thirteen of 15 articles support an association between recurrent croup and GERD. Although heterogeneity is high among studies that reported prevalence of GERD, there is less uncertainty in results for improvement to recurrent croup after GERD treatment. Most studies lacked a control group and all carry a moderate-to-high risk of bias.

Conclusion: There is limited evidence linking GERD to recurrent croup; Further research is needed to assess for causality as most studies are retrospective, lack a control group, and have a study design exposing them to bias. Patients treated with reflux medication appear to demonstrate a reduced incidence of croup symptoms.

Level Of Evidence: 1 Laryngoscope, 131:209-217, 2021.
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http://dx.doi.org/10.1002/lary.28544DOI Listing
January 2021

Identification of the targeted therapeutic potential of doxycycline for a subset of gastric cancer patients.

Ann N Y Acad Sci 2020 05 15;1467(1):94-111. Epub 2020 Jan 15.

Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.

The identification of new drugs for the targeted therapy of gastric cancer remains an important need. The RAS/RAF/MEK/ERK/ELK1 signaling cascade is activated in many cancers, including gastric cancer. To identify the targetable inhibitors of the ERK/MAPK pathway, we performed a repurposing screening of a panel of antimicrobial agents in gastric cancer cells using an ERK/MAPK-driven firefly luciferase reporter assay. Multiple antibiotics were identified to inhibit ERK-mediated transcriptional activity. Among them, doxycycline showed high inhibition of ERK/MAPK-regulated transcriptional activity and the levels of ERK proteins. Doxycycline was further identified to inhibit the proliferation and the colony- and spheroid-forming potential of gastric cancer cells. By in vitro signaling pathway and genome-wide expression profiling analyses, doxycycline was identified to inhibit signaling pathways and transcriptional activities regulated by ER, Myc, E2F1, Wnt, SMAD2/3/4, Notch, and OCT4. Doxycycline was also found to activate p53-, ATF6-, NRF1/2-, and MTF1-mediated transcription and inhibit the transcription of histones, proteasomal genes, fibroblast growth factor, and other oncogenic factors. These observations show the multitargeting and targeted therapeutic features of doxycycline for a subset of gastric tumors.
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http://dx.doi.org/10.1111/nyas.14288DOI Listing
May 2020

Sclerotherapy for Venous Malformations of Head and Neck: Systematic Review and Meta-Analysis.

Neurointervention 2020 Mar 16;15(1):4-17. Epub 2020 Jan 16.

Department of Radiology and Vascular Centers, Mayo Clinic, Rochester, MN, USA.

We performed a systematic review and meta-analysis of studies performing sclerotherapy for treatment of venous malformations (VMs) of the face, head and neck. It is our hope that data from this study could be used to better inform providers and patients regarding the benefits and risks of percutaneous sclerotherapy for treatment of face, head and neck VMs. We searched PubMed, MEDLINE, and EMBASE from 2000-2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy of neck, face and head VMs. Two independent reviewers selected studies and abstracted data. The primary outcomes were complete and partial resolution of the VM. Data were analyzed using random-effects meta-analysis. Thirty-seven studies reporting on 2,067 patients were included. The overall rate of complete cure following percutaneous sclerotherapy with any agent was 64.7% (95% confidence interval [CI], 57.4-72.0%). Sodium tetradecyl sulfate had the lowest complete cure rate at 55.5% (95% CI, 36.1-74.9%) while pingyangmycin had the highest cure rate at 82.9% (95% CI, 71.1-94.7%). Overall patient satisfaction rates were 91.0% (95% CI, 86.1-95.9%). Overall quality of life improvement was 78.9% (95% CI, 67.0-90.8%). Overall permanent morbidity/mortality was 0.8% (95% CI, 0.3-1.3%) with no cases of mortality. Our systematic review and meta-analysis of 37 studies and over 2,000 patients found that percutaneous sclerotherapy is a very safe and effective treatment modality for treatment of VMs of the head, neck and face.
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http://dx.doi.org/10.5469/neuroint.2019.00213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105094PMC
March 2020

International Pediatric ORL Group (IPOG) Robin Sequence consensus recommendations.

Int J Pediatr Otorhinolaryngol 2020 Mar 28;130:109855. Epub 2019 Dec 28.

Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA, USA.

Objective: To provide recommendations for the comprehensive management of airway obstruction in patients with Robin Sequence.

Methods: Expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG).

Results: The consensus statement provides recommendations for medical specialists who manage infants with Robin Sequence including: evaluation and treatment considerations for commonly debated issues in post-natal airway obstruction, assessment of antenatal obstruction and perinatal airway management.

Conclusion: Consensus recommendations are aimed at improving management of airway obstruction in patients with Robin Sequence.
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http://dx.doi.org/10.1016/j.ijporl.2019.109855DOI Listing
March 2020