Hernandez Herrera, Gabriel A

Abstract Objective To describe the presenting symptoms, treatment regimens, and outcomes associated with oropharyngeal adenoid cystic carcinoma. Data Sources Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and Scopus via Elsevier. Review Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses. A medical librarian conducted the literature search using controlled vocabulary and keywords, with investigator input. Eligible articles were clinical trials and observational studies reporting on clinical features, treatment, or outcomes for oropharyngeal adenoid cystic carcinoma. Results Our search identified 233 unique citations, with 44 articles included covering 195 patients. The female‐to‐male ratio was 1.7:1, and the base of the tongue was the most common subsite (73%). Presenting symptoms were mainly pain/discomfort (n = 31), followed by a palpable mass (n = 19) and dysphagia (n = 12). At diagnosis, 22.3% (29 patients) had positive lymph nodes. Treatment was primarily surgical (n = 102), with definitive radiation therapy used in 58 cases. Disease progression was noted in 86 patients, 36% (n = 31) of whom developed distant metastases—primarily to the lungs (n = 26). Long‐term outcomes (n = 76) showed 3‐ and 5‐year overall survival rates of 71.5% to 100% and 47.6% to 79.0%, and disease‐free survival rates of 54.7% to 70.0% and 21.9% to 44.0%, respectively. Conclusion Among patients with available data, oropharyngeal adenoid cystic carcinoma appeared more common in women and has a predilection for the base of the tongue. However, this finding should be interpreted with caution, given the high proportion of missing data. These tumors appear to carry a higher risk for nodal metastases and may lead to poor outcomes.

Abstract Cockayne Syndrome is an ultra-rare premature aging condition associated with UV sensitivity, neurocognitive decline, retinopathy, metronidazole-induced lethality, and sensorineural hearing loss. In 70% of affected patients, bi-allelic pathogenic variants in ERCC6 are identified. Although the role of ERCC6 in DNA damage repair has been studied, little is known about the mechanism for defective ERCC6 function in clinical findings, particularly hearing loss. To identify the mechanism of disease caused by pathogenic variants in ERCC6, we developed a zebrafish (Danio rerio) ercc6 loss of function model. We assessed survival after UV and metronidazole exposure, measured basal respiration rates, and evaluated mechanoelectrical transduction function and counts of lateral line hair cells. We found that UV exposure significantly reduces ercc6−/− larval viability. Metronidazole treatment results in complete lethality; wildtype controls show nearly complete survival. ercc6−/− embryos have significantly increased oxygen consumption, suggesting abnormal mitochondrial function. Phalloidin staining of lateral line hair cells with and without UV treatment shows no difference in hair cell counts per neuromast between treatment groups. Mechanoelectrical transduction function after UV exposure, measured by FM1–43 uptake, is reduced. Metronidazole lethality is reduced, oxygen consumption rates are restored, and mechanoelectrical transduction function is preserved by treatment with Mn(III)tetrakis(4-benzoic acid)porphyrin Chloride (MnTBAP), a superoxide dismutase mimetic. We propose that defective mitochondrial function and increased reactive oxygen species levels provide a mechanism for hair cell dysfunction in this model of Cockayne Syndrome. These results provide a foundation for further experiments to explore disease mechanisms and treatment modalities for this premature aging condition.

Importance Adverse events in otolaryngology–head and neck surgery (OHNS) are inconsistently reported. The Clavien-Dindo Classification has been modified and validated in several surgical subspecialties but has yet to be validated in OHNS. Objective To create and validate a modified Clavien-Dindo Classification for OHNS that reflects the severity and duration of harm for complications experienced by patients undergoing OHNS. Design, Setting, and Participants This is a multicenter survey study of subject matter experts (SMEs) from OHNS subspecialties from academic institutions within the US. A literature review identified publications reporting surgical complications in OHNS in the English language between January 2019 and April 2020. Complications were summarized and used to inform a modified Clavien-Dindo Classification. Feedback from internal SMEs was incorporated. Thirty-five clinical vignettes were created, and an electronic survey was sent to SMEs at outside institutions. Each SME was randomly assigned to 1 of 4 groups to evaluate 8 to 9 vignettes. The survey was conducted in September 2023, and data were analyzed from February to May 2024. Exposure Participation in the electronic survey. Main Outcomes and Measures Vignette scores were assessed and the Comprehensive Complication Index (CCI) calculator was used to assess cumulative morbidity. The scale is based on the grading by the Clavien-Dindo Classification and reflects overall morbidity on a scale from 0 (no complication) to 100 (death). Variability of the CCIs between reviewers, the primary outcome, was summarized with the SD. The percentage of reviewers with a high (≥26.2) or low (<26.2) CCI within a vignette was reported. Reliability was summarized using Krippendorff α. Results Of 106 SMEs, 43 (response rate, 40.6%) completed at least 1 vignette. Eighteen of 35 vignettes (51.4%; 95% CI, 34.9%-68.0%) had unanimous high CCI, and 8 of 35 vignettes (22.9%; 95% CI, 8.9%-36.8%) had unanimous low CCI (overall categorical agreement, 74.3%; 95% CI, 59.8%-88.8%). On average, the Krippendorff α was 0.74, indicating moderate reliability. A total of 21 850 OHNS complications were reviewed and categorized as surgical or medical with 12 including subcategorization for specificity. Each category was then assigned a modified OHNS Clavien Dindo classification grade. Conclusions and Relevance In this survey study of OHNS experts, a modified OHNS Clavien-Dindo Classification was developed and validated using case vignettes. The modified Clavien-Dindo Classification provided a granular subcategorization for each complication category and grade, duration of harm, and an overall summary complication score (CCI). Results suggest the modified OHNS Clavien-Dindo Classification reliably differentiated between high-grade and low-grade OHNS complications and could be utilized for assessing surgical outcomes.

Objective Computer-based auditory training (CBAT) has been shown to improve outcomes in adult cochlear implant (CI) users. This study evaluates in new CI users whether starting CBAT within 3 months of activation or later impacts CI outcomes. Study Design Prospective natural experiment. Setting Tertiary academic medical center. Patients Sixty-five new adult CI users. Interventions CBAT use over the first-year postactivation. Main Outcome Measures Speech recognition scores and CIQOL-35 Profile score improvements between CI recipients who started CBAT resources early (<3 mo) and late (3–12 mo) postactivation. Results A total of 43 CI recipients started using CBAT within 3 months postactivation (early) and 22 after 3 months (late). Patients who used CBAT within 3 months postactivation showed significantly greater improvement in consonant-nucleus-consonant words (CNCw) (48.3 ± 24.2% vs 27.8 ± 24.9%; d = 0.84), AzBio Sentences in quiet (55.1 ± 28.0% vs 35.7 ± 36.5%; d = 0.62), and CIQOL-35 listening domain scores (18.2 ± 16.3 vs 6.9 ± 12.9, d = 0.73 [0.023, 1.43]), at 3 months postactivation, compared to those who had not yet initiated CBAT. However, by 12 months postactivation, after which all CI recipients had started CBAT, there were no differences observed between patients who started CBAT early or late in speech recognition scores (CNCw: d = 0.26 [−0.35, 0.88]; AzBio: d = 0.37 [−0.23, 0.97]) or in any CIQOL global or domain score (d-range = 0.014–0.47). Conclusions Auditory training with self-directed computer software (CBAT) may yield speech recognition and quality-of-life benefits for new adult CI recipients. While early users showed greater improvement in outcomes at 3 months postactivation than users who started later, both groups achieved similar benefits by 12 months postactivation.