Audiometric outcomes following surgery for spontaneous temporal bone cerebrospinal fluid leaks - A single institution study.

PURPOSE: To assess the audiometric outcomes following surgical repair of spontaneous temporal bone cerebrospinal fluid otorrhea and compare different surgical approaches. MATERIALS AND METHODS: Retrospective review of adults (≥18 years old) who underwent repair of spontaneous CSF leak between 2011 and 2022. Audiometric outcomes were compared across the three surgical groups: transmastoid, middle cranial fossa and combined. RESULTS: Thirty-nine patients (40 ears) met the inclusion criteria (71.8 % females; mean age 59.77 +/- 12.4). Forty-two percent underwent transmastoid, 12.5 % middle cranial fossa and 45 % transmastoid-middle cranial fossa. Four patients (10 %) had recurrence, 3 in the transmastoid group and 1 in the combined approach. The mean change in air-bone gap (ABG) for all patients (postoperative-preoperative) was -7.4 (paired t-test, p-value = 0.0003). The postoperative ABG was closed in 28 (70 %) ears (postoperative ABG ≤ 15). The mean change in pure tone average (PTA) for all patients (postoperative-preoperative) was -4.1 (paired t-test, p-value = 0.13). The mean change in word recognition scores (WRS) for all patients (postoperative-preoperative) was -3 (paired t-test, p-value = 0.35). On multivariable analysis (controlling for site and reconstruction material), there was no significant difference in ABG, PTA and WRS change between surgical groups. CONCLUSIONS: Transmastoid, middle cranial fossa and combined approaches are all effective in treatment of spontaneous CSF leaks and all showed mean decrease in post-operative ABG. Transmastoid approach showed the greatest decrease in ABG and PTA (although middle cranial fossa approach shows the greatest decrease, when excluding profound hearing loss in a patient with superior canal dehiscence). Further studies comparing audiometric outcomes are needed.

Using the sino-nasal outcome test (SNOT-22) to study outcome of treatment of nasal obstruction.

OBJECTIVE: To validate the sino-nasal outcome test (SNOT-22) as an outcome measure for nasal obstruction, and to determine if it correlates with the nasal obstruction and septoplasty effectiveness (NOSE) scale. STUDY DESIGN: Prospective cohort study. METHODS: All patients presenting to our otolaryngology clinic for nasal obstruction secondary to nasal septal deviation and/or inferior turbinate hypertrophy between August 2020 and June 2022 were asked to fill both the SNOT-22 and the NOSE questionnaires. Demographics and comorbidities were reviewed. Patients with chronic rhinosinusitis (CRS) were excluded. SNOT-22 total and subdomain scores were then compared to NOSE scores. RESULTS: 126 patients completed both surveys. Average age was 42.6 years (range 13.8-78.3 years), and 40.5 % were female. 35 patients had septoplasty and inferior turbinoplasty (IT), 34 had functional septorhinoplasty and IT, 6 patients had IT, 7 had nasal septal perforation repair and 44 patients had medical treatment. Overall, SNOT-22 and NOSE scores correlated well preoperatively and postoperatively (r = 0.54, p < 0.0001; r = 0.68, p < 0.0001 respectively). The rhinologic and sleep SNOT-22 subdomains scores had the strongest correlation to NOSE score (r = 0.56, p < 0.0001; r = 0.64, p < 0.0001 respectively). Both NOSE and SNOT-22 scores showed improvement postoperatively [NOSE: 67.4 vs 25.1 (p < 0.0001) at 3 months, 69.5 vs 34 (p < 0.0001) at 6 months; SNOT-22: 37.1 vs 25.2 (p = 0.002) at 3 months, 38.1 vs 22.6 (p = 0.002) at 6 months]. No significant improvement in NOSE or SNOT scores was seen in the medical treatment group. CONCLUSION: SNOT-22 instrument can be used to study the outcome of treatment for nasal obstruction secondary to nasal septal deviation and/or inferior turbinate hypertrophy.

Effects of Soft Tissue Sleep Surgery on Morbidly Obese Patients.

INTRODUCTION: Morbidly obese patients with obstructive sleep apnea (OSA) are often intolerant of continuous positive airway pressure (CPAP). The effects of sleep surgery in this population is not well documented, and sleep surgery is generally avoided due to the expectation of poor outcomes, leaving these patients untreated. METHODS: This retrospective study included 42 patients with a body mass index (BMI) ≥40.0 and OSA with a preoperative apnea hypopnea index (AHI) ≥5. Preoperative BMI ranged from 40.0 to 69.0 kg/m2. Preoperative AHI ranged from 7.2 to 130.0. Of 42 patients, 12 (28.6%) underwent concurrent pharyngeal and retrolingual surgery. Subgroup analysis of change in AHI was measured with respect to preoperative OSA severity, change in preoperative BMI, and BMI severity. Univariate linear and logistic regression was performed assessing change in AHI and surgical success with respect to age, sex, preoperative AHI, preoperative BMI, change in BMI, total procedures, palatal procedure, retrolingual procedure, nasal procedure, and multilevel procedures. RESULTS: The mean AHI improved from 45.9 ± 31.8 to 31.9 ± 31.6 (P = .007). Epworth sleepiness score (ESS) improved from 13.2 ± 5.5 to 9.6 ± 5.4 (P = .00006). Lowest oxygen saturation (LSAT) improved from 74.4 ± 10.7 to 79.9 ± 10.4 (P = .002). About 33.3% of patients had surgical success (AHI < 20 with at least 50% reduction in AHI). Preoperative AHI was the most significant factor for change in AHI in univariate and multivariate models (P = .015). CONCLUSION: Sleep surgery is effective in reducing OSA burden in most morbidly obese patients and can result in surgical cure for a third of patients.

Assessing Prognostic Value of Quantitative Neck Dissection Quality Measures in Patients With Clinically Node-Negative Oral Cavity Squamous Cell Carcinoma.

Importance: In clinically localized (T1-2) oral cavity squamous cell carcinoma (OCSCC), regional lymph node metastasis is associated with a poor prognosis. Given the high propensity of subclinical nodal disease in these patients, upfront elective neck dissections (END) for patients with clinically node-negative disease are common and associated with better outcomes. Unfortunately, even with this risk-adverse treatment paradigm, disease recurrence still occurs, and our understanding of the factors that modulate this risk and alter survival have yet to be fully elucidated. Objective: To investigate the prognostic value of lymph node yield (LNY), lymph node ratio (LNR), and weighted LNR (wLNR) in patients with clinically node-negative T1-2 OCSCC. Design, Setting, and Participants: In this cohort study, data were collected retrospectively from 7 tertiary care academic medical centers. Overall, 523 patients with cT1-2N0 OCSCC who underwent elective neck dissections after primary surgical extirpation were identified. Exposures: Lymph node yield was defined as the number of lymph nodes recovered from elective neck dissection. Lymph node ratio was defined as the ratio of positive nodes against total LNY. Weighted LNR incorporated information from both LNY and LNR into a single continuous metric. Main Outcomes and Measures: Locoregional control (LRC) and disease-free survival (DFS) were both evaluated using nonparametric Kaplan-Meier estimators and semiparametric Cox regression. Results: On multivariable analysis, LNY less than or equal to 18 lymph nodes was found to be significantly associated with decreased LRC (aHR, 1.53; 95% CI, 1.04-2.24) and DFS (aHR, 1.46; 95% CI, 1.12-1.92) in patients with pN0 disease, but not those with pN-positive disease. Importantly, patients with pN0 disease with LNY less than or equal to 18 and those with pN1 diseasehad nearly identical 5-year LRC (69.7% vs 71.4%) and DFS (58.2% vs 55.7%). For patients with pN-positive disease, LNR greater than 0.06 was significantly associated with decreased LRC (aHR, 2.66; 95% CI, 1.28-5.55) and DFS (aHR, 1.65; 95% CI, 1.07-2.53). Overall, wLNR was a robust prognostic variable across all patients with cN0 disease, regardless of pathologic nodal status. Risk stratification via wLNR thresholds demonstrated greater optimism-corrected concordance compared with American Joint Committee on Cancer (AJCC) 8th edition nodal staging for both LRC (0.61 vs 0.57) and DFS (0.61 vs 0.58). Conclusions and Relevance: Movement toward more robust metrics that incorporate quantitative measures of neck dissection quality and regional disease burden, such as wLNR, could greatly augment prognostication in cT1-2N0 OCSCC by providing more reliable and accurate risk estimations.

Complications of primary pediatric endoscopic sinus surgery for chronic rhinosinusitis: A 25-year single surgeon experience.

Objective: To report our experience on the complications of primary pediatric endoscopic sinus surgery (ESS). Methods: Case series of pediatric ESS performed from 1991 to 2016 on children who failed maximal medical therapy and/or adenoidectomy. Inclusion criteria were children (age <12 years old) who underwent primary ESS with or without adenoidectomy for chronic rhinosinusitis (CRS) after failed maximal medical therapy and/or adenoidectomy. All patients underwent maxillary antrostomy ± partial or total ethmoidectomy. Patients with complicated acute rhinosinusitis were excluded. Complications reviewed included: skull base injury and CSF leak, orbital injuries (blindness, orbital hemorrhage, emphysema, periorbital swelling and bruising, fat exposure), and bleeding requiring intervention. Results: A total of 352 patients underwent ESS between 1991 and 2016. There were no blindness or orbital hematoma reported, and no major nasal bleeding requiring intervention. The total number of complications was 31 (8.8%): 1 (0.3%) CSF leak, 3 (0.85%) orbital emphysema, 5 (1.4%) periorbital ecchymosis, and 22 (6.3%) lamina papyracea violation with orbital fat exposure. Conclusions: Complications of primary pediatric ESS can be rare dependent on surgeon's experience, the most common being orbital injury.Level of evidence: 4.

Development and Validation of Machine Learning Models for Predicting Occult Nodal Metastasis in Early-Stage Oral Cavity Squamous Cell Carcinoma.

Importance: Given that early-stage oral cavity squamous cell carcinoma (OCSCC) has a high propensity for subclinical nodal metastasis, elective neck dissection has become standard practice for many patients with clinically negative nodes. Unfortunately, for most patients without regional metastasis, this risk-averse treatment paradigm results in unnecessary morbidity. Objectives: To develop and validate predictive models of occult nodal metastasis from clinicopathological variables that were available after surgical extirpation of the primary tumor and to compare predictive performance against depth of invasion (DOI), the currently accepted standard. Design, Setting, and Participants: This diagnostic modeling study collected clinicopathological variables retrospectively from 7 tertiary care academic medical centers across the US. Participants included adult patients with early-stage OCSCC without nodal involvement who underwent primary surgical extirpation with or without upfront elective neck dissection. These patients were initially evaluated between January 1, 2000, and December 31, 2019. Exposures: Largest tumor dimension, tumor thickness, DOI, margin status, lymphovascular invasion, perineural invasion, muscle invasion, submucosal invasion, dysplasia, histological grade, anatomical subsite, age, sex, smoking history, race and ethnicity, and body mass index (calculated as weight in kilograms divided by height in meters squared). Main Outcomes and Measures: Occult nodal metastasis identified either at the time of elective neck dissection or regional recurrence within 2 years of initial surgery. Results: Of the 634 included patients (mean [SD] age, 61.2 [13.6] years; 344 men [54.3%]), 114 (18.0%) had occult nodal metastasis. Patients with occult nodal metastasis had a higher frequency of lymphovascular invasion (26.3% vs 8.1%; P < .001), perineural invasion (40.4% vs 18.5%; P < .001), and margin involvement by invasive tumor (12.3% vs 6.3%; P = .046) compared with those without pathological lymph node metastasis. In addition, patients with vs those without occult nodal metastasis had a higher frequency of poorly differentiated primary tumor (20.2% vs 6.2%; P < .001) and greater DOI (7.0 vs 5.4 mm; P < .001). A predictive model that was built with XGBoost architecture outperformed the commonly used DOI threshold of 4 mm, achieving an area under the curve of 0.84 (95% CI, 0.80-0.88) vs 0.62 (95% CI, 0.57-0.67) with DOI. This model had a sensitivity of 91.7%, specificity of 72.6%, positive predictive value of 39.3%, and negative predictive value of 97.8%. Conclusions and Relevance: Results of this study showed that machine learning models that were developed from multi-institutional clinicopathological data have the potential to not only reduce the number of pathologically node-negative neck dissections but also accurately identify patients with early OCSCC who are at highest risk for nodal metastases.

Does length of time between cases affect resident operative time for tonsillectomy and adenoidectomy?

OBJECTIVE: To evaluate the effect of prolonged time intervals between tonsillectomy and adenoidectomy (TA) on resident operative time and complications. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary academic hospital. METHODS: This retrospective study covers a five-year period from 2015 to 2020. Time intervals between isolated pediatric TA cases performed by eight otolaryngology residents were reviewed to assess effect on operative time (defined as prolonged if ≥ 30 min and non-prolonged if < 30 min). Intervals including a procedure involving either a tonsillectomy or adenoidectomy that was a non-isolated TA were excluded. RESULTS: A total of 309 isolated TAs were identified with 67.3% of procedures performed under 30 min. The mean surgical time interval between procedures was 5.83 ± 10.02 days (range 0.02-69.82). Most TAs were performed on patients aged 7 years or younger. Surgical time interval between TA was not a significant factor in determining prolonged operative time on univariable logistic regression, OR 1.01 (CI: 0.98 to 1.03) (p = 0.63). Patient age at surgery, adenoid grade, tonsil size and total number of TAs performed to date were significant factors in determining prolonged operative time in both univariable and multivariable logistic regression models. Prolonged operative time did not have a significant effect on readmission, reoperation, or post-operative bleeding. CONCLUSION: Extended time interval (up to 3 months) between routine TA does not affect operative time. Expansion of our methodology to more complex cases would be beneficial in designing resident training curriculum.

Variables predictive of surgical outcomes after hyoid myotomy with suspension to thyroid cartilage.

OBJECTIVES: To evaluate variables predicting improvement in obstructive sleep apnea (OSA) with hyoid suspension to thyroid cartilage 4-suture technique. METHODS: Sixty adult patients (age range 23-78 years) with OSA underwent hyoid suspension to thyroid cartilage with or without concurrent multi-level surgery over an eight-year period from 2011 to 2019 at a tertiary academic center. All patients had a preoperative apnea hypopnea index (AHI) ≥ 5. Changes in mean AHI, Epworth Sleepiness Scale (ESS), and lowest oxygen saturation (LSAT) were measured with paired Student t-test. Linear and logistic regression models were used to predict change in AHI and surgical success respectively with respect to body mass index (BMI), age, sex, previous sleep surgery, concurrent retrolingual surgery, concurrent palatopharyngoplasty, and preoperative AHI. RESULTS: The mean AHI demonstrated a significant improvement from a preoperative AHI of 39.0 ± 25.5 to a postoperative AHI of 31.2 ± 23.4 (p = 0.005). The mean Epworth Sleepiness Score (ESS) significantly improved from 13.1 ± 6.0 to 9.2 ± 5.7 (p = 0.000012). Surgical success, defined as a 50% reduction in preoperative AHI to a postoperative AHI ≤ 20, was obtained in 18/60 (30.0%) patients. Preoperative BMI significantly correlates with variation of change in AHI in multivariable linear regression model (p = 0.003). Preoperative AHI was significant predictor of surgical success in multivariable logistic regression model. CONCLUSION: The magnitude of improvement in polysomnographic parameters after hyoid suspension to thyroid appears to be more significant in patients with lower BMI. Even patients with an obese BMI and severe OSA achieve significant improvement from this procedure.

Salvage surgery for recurrent squamous cell carcinoma of the head and neck: Systematic review and meta-analysis.

The present study aims to estimate a pooled hazard ratio (HR) comparing overall survival (OS) for salvage surgery compared to nonsurgical management of recurrent head and neck squamous cell carcinoma (HNSCC). PubMed/MEDLINE and Embase-Ovid were searched on March 5, 2020, for English-language articles reporting survival for salvage surgery and nonsurgical management of recurrent HNSCC. Meta-analysis of HR estimates using random effects model was performed. Fifteen studies reported survival for salvage surgery and nonsurgical management of recurrence. Five-year OS ranged from 26% to 67% for the salvage surgery groups, compared to 0% to 32% for the nonsurgical management groups. Six studies reported HRs comparing salvage surgery to nonsurgical management; the pooled HR was 0.25 (95% CI [0.16, 0.38]; p < 0.0001). Selection for salvage surgery was associated with one quarter of the mortality rate associated with nonsurgical management in light of confounding factors including subsite and treatment intent.

Differential Outcomes Among Survivors of Head and Neck Cancer Belonging to Racial and Ethnic Minority Groups.

Importance: Approximately 1 in 5 new patients with head and neck cancer (HNC) in the US belong to racial and ethnic minority groups, but their survival rates are worse than White individuals. However, because most studies compare Black vs White patients, little is known about survival differences among members of racial and ethnic minority groups. Objective: To describe differential survival and identify nonclinical factors associated with stage of presentation among patients with HNC belonging to racial and ethnic minority groups. Design, Setting, and Participants: This population-based retrospective cohort study used data from the 2007 to 2016 Surveillance, Epidemiology, and End Results (SEER) database and included non-Hispanic Black, Asian Pacific Islander, American Indian/Alaska Native, and Hispanic patients with HNC. The data were analyzed from December 2020 to May 2021. Main Outcomes and Measures: Outcomes were time to event measures: (HNC-specific and all-cause mortality) and stage of presentation. Covariates included nonclinical (age at diagnosis, sex, race and ethnicity, insurance status, marital status, and a composite socioeconomic status [SES]) and clinical factors (stage, cancer site, chemotherapy, radiation, and surgery). A Cox regression model was used to adjust associations of covariates with the hazard of all-cause death, and a Fine and Gray competing risks proportional hazards model was used to estimate associations of covariates with the hazard of HNC-specific death. A proportional log odds ordinal logistic regression identified which nonclinical factors were associated with stage of presentation. Results: There were 21 966 patients with HNC included in the study (mean [SD] age, 56.02 [11.16] years; 6072 women [27.6%]; 9229 [42.0%] non-Hispanic Black, 6893 [31.4%] Hispanic, 5342 [24.3%] Asian/Pacific Islander, and 502 [2.3%] American Indian/Alaska Native individuals). Black patients had highest proportion with very low SES (3482 [37.7%]) and the lowest crude 5-year overall survival (46%). After adjusting for covariates, Hispanic individuals had an 11% lower subdistribution hazard ratio (sdHR) of HNC-specific mortality (sdHR, 0.89; 95% CI, 0.83-0.95), 15% lower risk for Asian/Pacific Islander individuals (sdHR, 0.85; 95% CI, 0.78-0.93), and a trending lower risk for American Indian/Alaska Native individuals (sdHR, 0.85; 95% CI, 0.71-1.01), compared with non-Hispanic Black individuals. Race, sex, insurance, marital status, and SES were consistently associated with all-cause mortality, HNC-specific mortality, and stage of presentation, with non-Hispanic Black individuals faring worse compared with individuals of other racial and ethnic minority groups. Conclusions and Relevance: In this cohort study that included only patients with HNC who were members of racial and ethnic minority groups, Black patients had significantly worse outcomes that were not completely explained by stage of presentation. There may be unexplored multilevel factors that are associated with social determinants of health and disparities in HNC outcomes.

The utility of intra-oral ultrasound in improving deep margin clearance of oral tongue cancer resections.

OBJECTIVES: To investigate the potential utility of intra-oral ultrasound (IOUS) in guiding deep margin clearance and measuring depth of invasion (DOI) of oral tongue carcinomas (OTC). MATERIALS AND METHODS: Retrospective chart review of consecutive patients with T1-T3 OTC who underwent intraoperative ultrasound-guided resection and a comparator group that had undergone resection without the use of IOUS both by a single surgeon. Data was extracted from operative, pathology and radiology reports. Deep margins and DOI were reviewed by a dedicated head and neck pathologist. Correlation between histologic and ultrasound DOI was assessed using Pearson correlation. RESULTS: A total of 23 patients were included in the study cohort with a comparator group of 21 patients in the control group. None of the patients in the study cohort had a positive (cut-through) deep margin and the mean deep margin clearance was 8.5 ± 4.9 and 6.7 ± 3.8 for the IOUS and non-IOUS groups respectively (p-value 0.18) showing a non-significant improvement in the IOUS group. As a secondary outcome, there was a strong correlation between histologic and ultrasound DOI (0.9449). CONCLUSION: Ultrasound appears to be a potentially effective tool in guiding OTC resections. In this small series, IOUS facilitated deep margin clearance and resulted in a non-statistically significant increase in deep margin clearance. Intraoral ultrasound can accurately measure lesional DOI.

Coronary artery bypass grafting versus percutaneous coronary intervention in end-stage kidney disease: A systematic review and meta-analysis of clinical studies.

The most significant complication of end-stage kidney disease (ESKD) is cardiovascular disease, mainly coronary artery disease (CAD). Although the effective treatment of CAD is an important prognostic factor, whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is better for treating CAD in this group of patients is still controversial. We searched Pubmed/Medline, Web of Science, Embase, the Cochrane Central Register of Controlled Trials articles that compared the outcomes of CABG versus PCI in patients with ESKD requiring dialysis. A total of 10 observational studies with 39,666 patients were included. Our analysis showed that when compared to PCI, CABG had lower risk of need for repeat revascularization (relative risk [RR] = 2.25, 95% confidence interval [CI] 2.1-2.42, p < 0.00001) and cardiovascular death (RR = 1.19, 95% CI 1.14-1.23, p < 0.00001) and higher risk for short-term mortality (RR = 0.43, 95% CI 0.38-0.48, p < 0.00001). There was no statistically significant difference between the PCI and CABG groups in the risk for late mortality (RR = 1.05, 95% CI 0.97-1.14, p = 0.25), myocardial infarction (RR = 1.05, 95% CI 0.46-2.36, p = 0.91) or stroke (RR = 1.02, 95% CI 0.64-1.61, p = 0.95). This meta-analysis showed that in ESKD patients requiring dialysis, CABG was superior to PCI in regard to cardiovascular death and need for repeat revascularization and inferior to PCI in regard to short term mortality. However, this meta-analysis has limitations and needs confirmation with large randomized controlled trials.

Prediction of Speech, Swallowing, and Quality of Life in Oral Cavity Cancer Patients: A Pilot Study.

OBJECTIVES/HYPOTHESIS: To investigate the impact of specific treatment-related variables on functional and quality of life outcomes in oral cavity cancer (OCC) patients. STUDY DESIGN: Retrospective Cohort. METHODS: Patients with primary OCC at least 6 months after resection and adjuvant therapy were included. Patients completed surveys including the Speech Handicap Index (SHI), M.D. Anderson Dysphagia Inventory (MDADI), and Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN). Performance Status Scale (PSS) and tongue mobility scale were completed to allow provider-rated assessment of speech and tongue mobility, respectively. Additional details regarding treatment were also collected. These data were used to generate a predictive model using linear regression. RESULTS: Fifty-three patients with oral tongue and/or floor of mouth (FOM) resection were included in our study. In multivariable analysis, greater postoperative tongue range of motion (ROM) and time since treatment improved SHI. Flap reconstruction and greater postoperative tongue ROM increased MDADI and PSS (eating and speech). A larger volume of resected tissue was inversely correlated with PSS (diet and speech). Tumor site was an important predictor of PSS (all sections). There were no statistically significant predictors of FACT-HN. CONCLUSIONS: In this pilot study, we propose a battery of tools to assess function in OCC patients treated with surgery. Using the battery of tools we propose, our results show that a surgical endpoint that preserves tongue mobility and employs flap reconstruction resulted in better outcomes, whereas those with greater volume of tissue resected and FOM involvement resulted in poorer outcomes. Larger prospective studies are needed to validate our findings. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2497-2504, 2021.

Margin Practices in Oral Cavity Cancer Resections: Survey of American Head and Neck Society Members.

OBJECTIVES/HYPOTHESIS: To investigate the definition of a clear margin and the use of frozen section (FS) among practicing head and neck surgeons in oral cancer management. STUDY DESIGN: Cross-sectional survey. METHODS: We designed a survey that was sent to American Head and Neck Society (AHNS) members via an email link. RESULTS: A total of 185 (13% of 1,392) AHNS members completed our survey. Most surgeons surveyed (96.8%) use FS to supplement oral cavity squamous cell carcinoma resections. Fifty-five percent prefer a specimen-based approach. The majority of respondents believe FS is efficacious in guiding re-resection of positive margins, with 81% considering the new margin to be negative. More than half of respondents defined a distance of >5 mm on microscopic examination as a negative margin. CONCLUSIONS: To avoid oral cancer resections that result in positive margins on final analysis, and thus the need for additional therapy, most surgeons surveyed use FS. A majority of surveyed surgeons now prefer a specimen-based approach to margin assessment. Although there is a debate on what constitutes a negative margin, most surgeons surveyed believe it to be >5 mm on microscopic examination. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:782-787, 2021.

Therapeutic implications of shared mechanisms in non-alcoholic fatty liver disease and chronic kidney disease.

The most common cause of liver disease worldwide is now non-alcoholic fatty liver disease (NAFLD). NAFLD refers to a spectrum of disease ranging from steatosis to non-alcoholic steatohepatitis, causing cirrhosis, and ultimately hepatocellular carcinoma. However, the impact of NAFLD is not limited to the liver. NAFLD has extra-hepatic consequences, most notably, cardiovascular and renal disease. NAFLD and chronic kidney disease share pathogenic mechanisms including insulin resistance, lipotoxicity, inflammation and oxidative stress. Not surprisingly, there has been a recent surge in efforts to manage NAFLD in an integrated way that not only protects the liver but also delays comorbidities such as chronic kidney disease. This concept of simultaneously addressing the main disease target and comorbidities is key to improve outcomes, as recently demonstrated by clinical trials of SGLT2 inhibitors and GLP1 receptor agonists in diabetes. HIF activators, already marketed in China, also have the potential to protect both liver and kidney, as suggested by preclinical data. This review concisely discusses efforts at identifying common pathogenic pathways between NAFLD and chronic kidney disease with an emphasis on potential paradigm shifts in diagnostic workup and therapeutic management.

Rett Syndrome, a Neurodevelopmental Disorder, Whole-Transcriptome, and Mitochondrial Genome Multiomics Analyses Identify Novel Variations and Disease Pathways.

Rett syndrome (RTT) is a severe neurodevelopmental disorder reported worldwide in diverse populations. RTT is diagnosed primarily in females, with clinical findings manifesting early in life. Despite the variable rates across populations, RTT has an estimated prevalence of ∼1 in 10,000 live female births. Among 215 Saudi Arabian patients with neurodevelopmental and autism spectrum disorders, we identified 33 patients with RTT who were subsequently examined by genome-wide transcriptome and mitochondrial genome variations. To the best of our knowledge, this is the first in-depth molecular and multiomics analyses of a large cohort of Saudi RTT cases with a view to informing the underlying mechanisms of this disease that impact many patients and families worldwide. The patients were unrelated, except for 2 affected sisters, and comprised of 25 classic and eight atypical RTT cases. The cases were screened for methyl-CpG binding protein 2 (MECP2), CDKL5, FOXG1, NTNG1, and mitochondrial DNA (mtDNA) variants, as well as copy number variations (CNVs) using a genome-wide experimental strategy. We found that 15 patients (13 classic and two atypical RTT) have MECP2 mutations, 2 of which were novel variants. Two patients had novel FOXG1 and CDKL5 variants (both atypical RTT). Whole mtDNA sequencing of the patients who were MECP2 negative revealed two novel mtDNA variants in two classic RTT patients. Importantly, the whole-transcriptome analysis of our RTT patients' blood and further comparison with previous expression profiling of brain tissue from patients with RTT revealed 77 significantly dysregulated genes. The gene ontology and interaction network analysis indicated potentially critical roles of MAPK9, NDUFA5, ATR, SMARCA5, RPL23, SRSF3, and mitochondrial dysfunction, oxidative stress response and MAPK signaling pathways in the pathogenesis of RTT genes. This study expands our knowledge on RTT disease networks and pathways as well as presents novel mutations and mtDNA alterations in RTT in a population sample that was not previously studied.

Understanding approaches to measurement and impact of depth of invasion of oral cavity cancers: A survey of American Head and Neck Society Membership.

OBJECTIVES: To investigate methods used by head and neck surgeons to pre-operatively measure depth of invasion (DOI) in light of the new staging for oral cavity squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: A survey was designed and sent to all American Head and Neck Society (AHNS) members via an email link. The last response was recorded on January 16, 2019. RESULTS: We received 185 (13.3%) responses from 184 surgeons and 1 radiation oncologist. The majority of surgeons correctly identified DOI (78.9%) and indicated measuring DOI pre-operatively (86%). The most common methods for measuring DOI were manual palpation (32.5%) and full thickness biopsy (25.2%). In addition, most surgeons (84.7%) reported using a DOI threshold (in mm) as their primary criterion in their decision to pursue a neck dissection in the N0 neck. The most common reported threshold was 4 mm (37.4% of those that reported using DOI), however, the range varied from 2 to >10 mm. Two-thirds of surgeons considered DOI an important indicator for adjuvant therapy. CONCLUSION: DOI is believed to be an important prognostic indicator guiding neck dissection and the need for adjuvant therapy. While most surgeons currently measure DOI pre-operatively, most use subjective methods. Future studies are needed to establish objective pre-operative DOI measurement techniques and to better inform the decision to perform prophylactic neck dissection, given the current majority practice of prophylactic neck dissection for DOI of 4 mm or greater.