Characteristics of Idiopathic Subglottic Stenosis in the Elderly.

OBJECTIVE: To compare characteristics of patients ≥65 years presenting with idiopathic subglottic stenosis (iSGS) to patients diagnosed at <65 years. We hypothesize that the groups have similar comorbidities and disease courses. DATA SOURCES: Medical records of patients treated for iSGS at a tertiary care institution from January 2005-September 2022. REVIEW METHODS: Patient demographics, time from symptom onset to diagnosis, medical history and comorbidities, and treatment modalities/intervals were recorded and analyzed. Characteristics of patients ≥65 and <65 years at presentation were compared using Chi-square analysis for non-numeric values and the Mann-Whitney U-test for numeric values. RESULTS: One hundred seven patients with iSGS were identified and 16 (15%) were aged ≥65 years (mean age 72.6, 15 female) at presentation. These patients were compared to 91 patients aged <65 years (mean age = 47.6, 90 female). Patients ≥65 years had higher rates of type 2 diabetes mellitus (T2DM) (p = 0.004) and tobacco use (p = 0.004). There were no significant differences in body mass index, gastroesophageal reflux disease, hormone replacement therapy, time from symptom onset to presentation, or length of operative treatment intervals. CONCLUSION: Patients ≥65 years with iSGS have higher rates of tobacco use, suggesting that alterations in wound healing may play a role in the development of iSGS in this age group. Although rates of T2DM were higher in the elderly group, clinical significance may be limited given the overall higher rate of diabetes mellitus in the elderly population. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3075-3079, 2023.

Association of Genre of Singing and Phonotraumatic Vocal Fold Lesions in Singers.

OBJECTIVES/HYPOTHESIS: To determine if (1) the likelihood of presenting with phonotraumatic lesions differs by singing genre in treatment-seeking singers and (2) if the distribution of phonotraumatic lesion types differs by singing genre. STUDY TYPE: Retrospective. METHODS: Records of singers who presented with a voice complaint over the course of 2.5 years (June 2017-December 2019) were reviewed to determine the proportion of those with phonotraumatic lesions as a function of genre (Study 1). Separately, the lesion types and genres of singers diagnosed with phonotraumatic lesions over a 9-year period (July 2011-March 2020) were determined (Study 2). RESULTS: In Study 1, 191 of 712 (26.8%) dysphonic singers were diagnosed with phonotraumatic lesions. Country/folk, gospel/jazz, and musical theater singers were more likely to present with phonotraumatic lesions. In Study 2, in 443 singers with phonotraumatic lesions, polyps and pseudocysts, but not nodules, were found to be distributed unequally across genres (χ2 p = 0.006, p < 0.0001, p = 0.064, respectively). Praise/worship singers had significantly higher proportions of polyps compared to choral singers (OR 4.8 [95% CI 1.9-12.5]) or compared to musical theater singers (OR 7.2 [95% CI 2.5-20.8]). Opera singers had significantly higher proportions of pseudocysts than choral singers (OR 3.1 [95% CI 1.5-6.1]) or musical theater singers (OR 3.7 [95% CI 1.8-7.6]). CONCLUSIONS: The higher incidence of polyps in praise/worship singers likely reflects the more emphatic nature of singing and the tendency for acute injury. The higher incidence of pseudocysts in opera singers may reflect a more chronic nature of injury. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1683-1689, 2023.

Voice Therapy Expectations for Injured Singers.

OBJECTIVES/HYPOTHESIS: Voice therapy is a mainstay treatment modality in the management of phonotrauma in singers. However, the typical duration of therapy an injured singer undergoes is unknown. The primary aims of the study were to determine (1) the number of therapy sessions preceding a decision for surgery and (2) the number of sessions and length of time to achieve improvement in singers who did not undergo surgery. Whether specific singer factors were associated with the length of therapy was also investigated. STUDY DESIGN: Retrospective. METHODS: Records of singers with phonotraumatic vocal fold lesions seen over a 9-year period at a tertiary care voice center were reviewed. RESULTS: Sixty singers who underwent surgery and 183 singers who did not undergo surgery were included in the final analysis. In nearly ¾ of the surgical patients, five or fewer voice therapy sessions were completed prior to the decision for surgery. Singers who did not undergo surgery required on average 3-4 sessions before noting improvement. Over 60% of the non-surgical singers improved within 3 months and 84% were judged to be improved by 6 months. Lesion type, professional/amateur status, formal voice training, and having a current voice teacher/coach were not associated with the length of voice therapy. CONCLUSIONS: The length of voice therapy prior to decision for surgery was limited, and so was the length of therapy leading to initial improvement in singers who did not require surgery. These findings provide a framework for voice therapy expectations and could be reassuring for this unique population.

KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma.

The H3K27me2/me3 histone demethylase KDM6B is essential to neuroblastoma cell survival. However, the mechanism of KDM6B action remains poorly defined. We demonstrate that inhibition of KDM6B activity 1) reduces the chromatin accessibility of E2F target genes and MYCN, 2) selectively leads to an increase of H3K27me3 but a decrease of the enhancer mark H3K4me1 at the CTCF and BORIS binding sites, which may, consequently, disrupt the long-range chromatin interaction of MYCN and E2F target genes, and 3) phenocopies the transcriptome induced by the specific CDK4/6 inhibitor palbociclib. Overexpression of CDK4/6 or Rb1 knockout confers neuroblastoma cell resistance to both palbociclib and the KDM6 inhibitor GSK-J4. These data indicate that KDM6B promotes an oncogenic CDK4/6-pRB-E2F pathway in neuroblastoma cells via H3K27me3-dependent enhancer-promoter interactions, providing a rationale to target KDM6B for high-risk neuroblastoma.

Safety and efficacy of sphenopalatine artery ligation in recalcitrant pediatric epistaxis.

BACKGROUND: Epistaxis is a common cause for emergency department visits for both children and adults. In particular, posterior bleeds can be difficult to identify and treat. In adults, endoscopic sphenopalatine artery (SPA) ligation has been shown to be safe, cost-effective, and curative. Conversely, very few studies have delved into the safety and efficacy of SPA ligation in children. This study aims to evaluate the feasibility of SPA ligation for treatment of recalcitrant epistaxis in children. METHODS: A retrospective analysis of outcomes in pediatric patients who underwent SPA ligation at a tertiary academic center was performed. Patients with coagulopathies or other underlying conditions were excluded from the study. RESULTS: Data obtained from 5 patients demonstrated 60% of the population were female, with ages ranging from 2 to 13 years. 7 SPA ligations were performed among the 5 patients, with 3 undergoing unilateral SPA ligation only. The remaining 4 underwent contralateral SPA ligation subsequently. No postoperative complications were observed, and all patients experienced resolution of significant epistaxis. CONCLUSION: Although additional studies are necessary to further support our findings, SPA ligation in the pediatric population appears to be a safe and effective treatment to control persistent posterior bleeds.

Histone demethylases and their roles in cancer epigenetics.

The genetic abnormalities that drive tumorigenesis are usually coupled with epigenetic alterations, such as DNA methylation and aberrant histone modifications, which may help oncogenic drivers accelerate cancer progression, metastasis, and therapy resistance. The discovery of histone demethylases has provided us new insight for understanding the epigenetic landscape of the chromatin environment of cancer cells. This review aims to summarize the current knowledge on the human histone lysine demethylases and their functions in cancers, and recent advances in development of small molecule inhibitors to target histone demethylases in cancer treatment.