Assessing the feasibility of a multimodal liquid biopsy for the diagnosis of HPV-associated oropharyngeal squamous cell carcinoma.

OBJECTIVES: In this feasibility study, we explored the combined use of circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) and HPV serology as diagnostic tests for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Among patients with research-banked serum or plasma at diagnosis, IgG antibodies to oncoproteins from HPV types 16, 18, 31, 33, 35, 45, 52, and 58 were detected with multiplex serology. Positivity for HPV 16 was defined based on detection of combinations of anti-E6, E1, E2, and E7 and for other high-risk types on detection of anti-E6 and anti-E7. Circulating tumor HPV DNA was detected by custom digital droplet polymerase chain reaction (ddPCR) assays for HPV types 16, 18, 33, 35, and 45. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization (ISH) using a cocktail of 18 high-risk HPV types were performed on tissue. RESULTS: Of 75 patients, 67 (89.3%) were HPV-associated (p16 and HPV RNA ISH positive) and 8 (10.7%) were HPV-independent. All 8 HPV-independent patients were seronegative and negative for ctHPVDNA (100% specificity). Serology was positive in 53 (79.1%) of 67 HPV-associated patients, while ddPCR was positive for ctHPVDNA in 59 (88.6%) of 67 HPV-associated patients. Requiring both tests to be positive resulted in a sensitivity of 50 (74.6%) of 67 while combining assays (either positive) improved sensitivity to 62 (92.6%) of 67. CONCLUSIONS: Compared to HPV RNA ISH, HPV serology and ctHPVDNA are sensitive and highly specific biomarkers for HPV-associated OPSCC at the time of presentation.

A Single Center Description of Adult and Pediatric Endoscopic Posterior Costal Cartilage Grafting.

OBJECTIVE: Posterior glottis impairment alters breathing, voicing, and swallowing. Bilateral vocal fold movement impairment (BVFMI) occurs when the vocal cords are fixed/remain midline. Studies inadequately assessed endoscopic posterior costal cartilage grafting (enPCCG) for BVFMI across broad ages. We aim to assess decannulation and prosthesis free airway in children and adults who have undergone enPCCG. STUDY DESIGN: Retrospective cohort. SETTING: Referral center. METHODS: This study included adults and children who received enPCCG for BVFMI (2010-2018) and were followed for 35 months on average. The main outcome was successful decannulation of patients, or airway improvement in those without tracheostomy. Data on comorbidities, surgical complications, and interventions following surgery were collected. RESULTS: Ten children and 11 adults underwent enPCCG for BVFMI. Eighty-one percent of patients had a tracheostomy at surgery; adults were more likely to have a tracheostomy at surgery (P = 0.035), and to undergo double-staged procedure (P = 0.035) and stent (P = 0.008). Average stent duration was 29.7 days. Overall decannulation rate was 76% (90% for children; 70% for adults). Children were more likely to receive postoperative intensive care unit care (P = 0.004). Adults had mean 4.4 post-enPCCG interventions per patient compared to children's mean 3.91 interventions. The most common interventions were steroid injection (17.6%) and balloon dilation (16%). Preliminary analysis suggests postoperative dysphonia was reported in 66.7% of patients; postoperative dysphagia was rare. CONCLUSION: EnPCCG was more successful at achieving decannulation in children. Adults required additional interventions. A double-staged operation with prolonged stenting is recommended for adult patients. A majority of patients were decannulated at last follow-up.

Pediatric Otolaryngology Short-Term Mission Outcomes at a Surgical Mission Hospital in Guatemala.

OBJECTIVE: The frequency of humanitarian surgical mission trips has grown over recent decades. Unfortunately, research on patient outcomes from these trips has not increased proportionately. We aim to analyze the safety and efficacy of surgeries in a low- and middle-income country missions-based surgery center in Guatemala City, Guatemala, and identify factors that influence surgical outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Guatemalan surgery center is called the Moore Center. METHODS: Pediatric patients underwent otolaryngology surgery between 2017 and 2019. All patients required follow up. We analyzed the effect of patient, surgical, and geographic factors on follow up and complications with univariate and multivariate analyses. RESULTS:  A total of 1094 otolaryngologic surgeries were performed between 2017 to 2019, which comprised 37.4% adenotonsillectomies, 26.8% cleft lip (CL)/cleft palate (CP) repairs, 13.6% otologic, and 20% "other" surgeries. Patients traveled on average 88 km to the center (±164 km). Eighty-nine percent attended their first follow up and 55% attended their second. The 11% who missed their first follow up lived farther from the center (p < .001) and had a higher ASA classification (p < .001) than the 89% who did attend. Sixty-nine (6.3%) patients had 1 or more complications. CL/CP surgery was associated with more complications than other procedures (p < .001). Of 416 tonsillectomies, 4 patients (1%) had a bleeding episode with 2 requiring reoperation. CONCLUSION: This surgical center models effective surgical care in low-resource areas. Complications and follow-up length vary by diagnosis. Areas to improve include retaining complex patients for follow up and reducing complications for CL/CP repair.

Clinical and molecular features of disseminated pediatric low-grade glioma and glioneuronal tumors: a systematic review and survival analysis.

Background: Disseminated pediatric low-grade gliomas and glioneuronal tumors (dpLGG/GNTs) are associated with a poorer prognosis than nondisseminated pLGG/GNTs. To date there is no comprehensive report characterizing the genome profile of dpLGG/GNTs and their relative survival. This systematic review aims to identify the pattern of genetic alterations and long-term outcomes described for dpLGG/GNT. Methods: A systematic review of the literature was performed to identify relevant articles. A quality and risk of bias assessment of articles was done using the GRADE framework and ROBINS-I tool, respectively. Results: Fifty studies published from 1994 to 2020 were included in this review with 366 cases reported. There was sporadic reporting of genetic alterations. The most common molecular alterations observed among subjects were 1p deletion (75%) and BRAF-KIAA1549 fusion (55%). BRAF p.V600E mutation was found in 7% of subjects. A higher proportion of subjects demonstrated primary dissemination compared to secondary dissemination (65% vs 25%). First-line chemotherapy consisted of an alkylation-based regimen and vinca alkaloids. Surgical intervention ranged from biopsy alone (59%) to surgical resection (41%) and CSF diversion (28%). Overall, 73% of cases were alive at last follow-up. Survival did not vary by tumor type or timing of dissemination. All studies reviewed either ranked low or moderate for both quality and risk of bias assessments. Conclusions: Chromosome 1p deletion and BRAF-KIAA1549 fusion were the most common alterations identified in dpLGG/GNT cases reviewed. The relative molecular heterogeneity between DLGG and DLGNT, however, deserves further exploration and ultimately correlation with their biologic behavior to better understand the pathogenesis of dpLGG/GNT.

Bilateral sensorineural hearing loss after opioid overdose in an adolescent male.

Opioid-induced hearing loss has been described as a form of sudden sensorineural hearing loss that can occur with chronic or acute opioid use. Here, we report a case of a 16-year-old patient with sudden onset hearing loss after opioid overdose requiring prolonged intubation with fentanyl sedation.

Cross-talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossification.

BACKGROUND: Progressive maturation of growth plate chondrocytes drives long bone growth during endochondral ossification. Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein-2 (BMP2), are required for normal chondrocyte maturation. Here, we investigated cross-talk between EGFR and BMP2 signals in developing and adult growth plates. RESULTS: Using in vivo mouse models of conditional cartilage-targeted EGFR or BMP2 loss, we show that canonical BMP signal activation is increased in the hypertrophic chondrocytes of EGFR-deficient growth plates; whereas EGFR signal activation is increased in the reserve, prehypertrophic and hypertrophic chondrocytes of BMP2-deficient growth plates. EGFR-deficient chondrocytes displayed increased BMP signal activation in vitro, accompanied by increased expression of IHH, COL10A1, and RUNX2. Hypertrophic differentiation and BMP signal activation were suppressed in normal chondrocyte cultures treated with the EGFR ligand betacellulin, effects that were partially blocked by simultaneous treatment with BMP2 or a chemical EGFR antagonist. CONCLUSIONS: Cross-talk between EGFR and BMP2 signals occurs during chondrocyte maturation. In the reserve and prehypertrophic zones, BMP2 signals unilaterally suppress EGFR activity; in the hypertrophic zone, EGFR and BMP2 signals repress each other. This cross-talk may play a role in regulating chondrocyte maturation in developing and adult growth plates.

Chondrocytes respond both anabolically and catabolically to impact loading generally considered non-injurious.

We aimed to determine the longitudinal effects of low-energy (generally considered non-injurious) impact loading on (1) chondrocyte proliferation, (2) chondroprogenitor cell activity, and (3) EGFR signaling. In an in vitro study, we assessed 127 full-thickness, cylindrical osteochondral plugs of bovine cartilage undergoing either single, uniaxial unconfined impact loads with energy densities in the range of 1.5-3.2mJ/mm3 or no impact (controls). We quantified cell responses at two, 24, 48, and 72 h via immunohistochemical labeling of Ki67, Sox9, and pEGFR antibodies. We compared strain, stress, and impact energy density as predictors for mechanotransductive responses from cells, and fit significant correlations using linear regressions. Our study demonstrates that low-energy mechanical impacts (1.5-3.2mJ/mm3) generally stimulate time-dependent anabolic responses in the superficial zone of articular cartilage and catabolic responses in the middle and deep zones. We also found that impact energy density is the most consistent predictor of cell responses to low-energy impact loading. These spatial and temporal changes in chondrocyte behavior result directly from low-energy mechanical impacts, revealing a new level of mechanotransductive sensitivity in chondrocytes not previously appreciated.

The behavioral, psychological, and social impacts of team sports: a systematic review and meta-analysis.

Objectives: To assess the association between team sport participation and behavioral, psychological, and social health outcomes in young athletes.Methods: A systematic review and meta-analysis were undertaken to identify studies published between 01/01/1950-05/01/2020 investigating the association between team sport participation and health outcomes in young athletes (<25 years). Included studies compared team sport participants to controls or themselves, assessed health outcomes, and had a sample size >50. Prospective and retrospective studies were included; non-primary literature was excluded. Health outcomes were categorized as: 1) behavioral, 2) psychological, or 3) social. Data were extracted to form 2 × 2 tables for each study to calculate odds ratios (OR) and 95% confidence intervals (CI).Results: Of 371 queried articles, 34 studies from 10 countries across 4 continents were included, with 9 reporting homogenous outcomes for meta-analysis.Behavioral: Fifteen studies evaluated behavioral health outcomes of alcohol and/or drug use, fitness, and diet. Quantitatively, team sport participation was found to decrease rates of cigarette/tobacco use across 5 studies (OR 0.72, 95% CI 0.69-0.76) and alcohol/drug use across 7 studies (OR 0.73, 95% CI 0.69-0.77). Qualitatively, 12/15 (80%) of studies confirmed improved behavioral health outcomes with team sport participation.Psychological: Nineteen studies evaluated psychological health outcomes including anorexia, anxiety, depression, self-esteem, and suicidal ideation. Quantitatively, team sport participation was associated with decreased depression/anxiety rates across 5 studies (OR 0.59, 95%CI 0.54-0.64). Qualitatively, 14/19 (74%) of studies confirmed improved psychological health.Social: Ten studies evaluated social health outcomes including academic performance, commitment, psychosocial health, social behavior/identity, and delinquency/high-risk activity. Qualitatively, 7/10 (70%) of studies confirmed improved social health outcomes with team sport participation.Conclusion: Team sport participation was associated with decreased odds of smoking/tobacco use, alcohol/drug use, and depression/anxiety. Though few studies mentioned potential negative effects of team sport participation, the majority reported improved behavioral, psychological, and social health outcomes in youth athletes worldwide.