Loss or absence of hearing is common at both extremes of human lifespan, in the forms of congenital deafness and age-related hearing loss. While these are often studied separately, there is ...increasing evidence that their genetic basis is at least partially overlapping. In particular, both common and rare variants in genes associated with monogenic forms of hearing loss also contribute to the more polygenic basis of age-related hearing loss. Here, we directly test this model in the Penn Medicine BioBank-a healthcare system cohort of around 40,000 individuals with linked genetic and electronic health record data. We show that increased burden of predicted deleterious variants in Mendelian hearing loss genes is associated with increased risk and severity of adult-onset hearing loss. As a specific example, we identify one gene-TCOF1, responsible for a syndromic form of congenital hearing loss-in which deleterious variants are also associated with adult-onset hearing loss. We also identify four additional novel candidate genes (COL5A1, HMMR, RAPGEF3, and NNT) in which rare variant burden may be associated with hearing loss. Our results confirm that rare variants in Mendelian hearing loss genes contribute to polygenic risk of hearing loss, and emphasize the utility of healthcare system cohorts to study common complex traits and diseases.
This article represents the first reported case in the external auditory canal of epithelioid fibrous histiocytoma (EFH), a rare benign cutaneous epithelioid neoplasm. Immunostaining revealed ...uncommon negative staining for anaplastic lymphoma kinase (ALK) expression. This case and literature review outline the diagnostic strategy for this highly unusual neoplasm. Laryngoscope, 134:3371–3373, 2024
This article represents the first reported case in the external auditory canal of epithelioid fibrous histiocytoma (EFH), a rare benign cutaneous epithelioid neoplasm. Immunostaining revealed uncommon negative staining for anaplastic lymphoma kinase (ALK) expression. This case and literature review outline the diagnostic strategy for this highly unusual neoplasm.
Cochlear implantation has become the standard of care for hearing loss not amenable to amplification by bypassing the structures of the cochlea and stimulating the spiral ganglion neurons directly. ...Since the first single channel electrodes were implanted, significant advancements have been made: multi-channel arrays are now standard, they are softer to avoid damage to the cochlea and pre-curved to better position the electrode array adjacent to the nerve, and surgical and stimulation techniques have helped to conform to the anatomy and physiology of the cochlea. However, even with these advances the experience does not approach that of normal hearing. In order to make significant advances in performance, the next generation of implants will require novel interface technology. Advances in regenerative techniques, optogenetics, piezoelectric materials, and bioengineered living scaffolds hold the promise for the next generation of implantable hearing devices, and hope for the restoration of natural hearing.
Objectives
Determine if intensive local therapy (i.e., local surgery or radiation) has a survival benefit for patients presenting with distantly metastatic oropharyngeal squamous cell carcinoma ...(OPSCC).
Methods
Retrospective population‐based cohort study of patients in the National Cancer Database presenting with distantly metastatic OPSCC. Overall survival (OS) was compared for patients receiving systemic therapy alone or in combination with local surgery or curative dose radiation, controlling for various clinicodemographic factors.
Results
Between 2010 and 2015, 627 patients presented with newly diagnosed, metastatic OPSCC and an initial treatment course including systemic chemotherapy. Multivariable analysis demonstrated that local radiation therapy was independently associated with improved OS (OR 0.64, CI 0.51–0.81); local surgery was not independently associated with improved OS (OR 0.99, CI 0.65–1.53). Higher T stages were associated with worse OS (OR 1.69, CI 1.14–2.50 for T3 and OR 1.77, CI 1.22–2.58 for T4 compared to T1). HPV‐positive (HPV+) tumors were associated with improved OS compared to HPV‐ (OR 0.79, CI 0.64–0.97). Multiagent chemotherapy was associated with improved OS compared to single‐agent (OR 0.78, CI 0.62–1.00). The best survival for the entire cohort and for HPV+ patients was for radiation with systemic therapy and the worst survival for systemic therapy alone.
Conclusions
Curative dose local radiotherapy in addition to systemic therapy is associated with improved OS compared to systemic therapy alone in patients presenting with distantly metastatic OPSCC. There is not a significant survival benefit for local surgery in addition to systemic therapy in this patient population, regardless of HPV status.
Level of Evidence
3 Laryngoscope, 134:2243–2251, 2024
Retrospective population‐based cohort study of patients presenting with metastatic oropharyngeal squamous cell carcinoma comparing survival for treatment with systemic therapy alone or in combination with local surgery or curative dose radiation. Curative dose local radiation is associated with improved overall survival when added to systemic therapy, but there is not a significant survival benefit for including local surgery in the treatment algorithm.
To design and validate a disease-specific quality of life instrument for Meniere's disease.
We used a sequential process of expert input, patient focus groups, and analyses of responses to draft ...questionnaires to create a 24-item Meniere's disease quality of life (MenQOL) instrument. The MenQOL and the SF-36v2 were administered to a cohort of 50 patients with Meniere's disease and 60 comparison patients with tinnitus, vertigo, or hearing loss from other causes identified at a tertiary academic center. We performed exploratory factor analysis, Cronbach's α, between group comparisons of total MenQOL scores, and regression analyses between the MenQOL and SF-36v2 to evaluate the instrument's factor structure, internal consistency, face validity, and external validity. Segregation of the instrument into domains was assessed by exploratory factor analysis.
Exploratory factor analysis revealed that the MenQOL has a single domain. Cronbach's α = 0.914 indicated high internal consistency for the instrument as a whole. Mean MenQOL scores showing significantly worse quality of life among patients with Meniere's disease than comparison participants (52.5 ± 15.8 vs. 43.2 ± 12.6; p = 0.0051), indicating good construct validity. Significant inverse relationships in bivariate linear regressions between total MenQOL scores and SF-36v2 physical (slope = -0.94, p < 0.0001) and mental (slope = -1.16, p < 0.0001) composite scores showed acceptable concurrent validity.
We have described the initial development of the MenQOL, a simple, valid patient-reported outcome measure that, subject to further study, may be used to assess the effects of treatment on disease-specific quality of life in patients with Meniere's disease.
3 Laryngoscope, 2024.
To examine long-term (>5 yr) low-frequency hearing preservation after hybrid cochlear implantation.
Retrospective cross-sectional study.
Tertiary care center outpatient clinic.
All patients older ...than 21 years implanted with a Cochlear Hybrid L24 device from 2014 to 2021.
Changes in low-frequency pure-tone average (LFPTA) were calculated at each of several time points relative to the date of implantation. The proportion of patients with preserved LFPTA at last follow-up and Kaplan-Meier estimates for loss of residual hearing were calculated in addition to hazard ratios for hearing loss according to patient- and surgery-specific factors.
Thirty ears in 29 patients underwent hybrid cochlear implantation and were eligible for inclusion (mean age, 59 yr; 65% female). Mean preoperative LFPTA was 31.7 dB. Mean LFPTA across all implanted ears at first follow-up was 45.1 dB; no patient had experienced loss of residual hearing at first follow-up. Six patients had loss of residual hearing during the follow-up period, with Kaplan-Meier probability estimates of preserved hearing of 100% at 1 month, 90% at 12 months, 87% at 24 months, and 80% at 48 months. There was no association between loss of residual hearing and patient age, preoperative LFPTA, surgeon, or use of topical steroids intraoperatively (hazard ratios, 1.05 0.96-1.15, 0.97 0.88-1.05, 1.39 0.20-9.46, 0.93 0.09-9.74, respectively).
Long-term (>5 yr) outcomes after hybrid cochlear implantation demonstrate good preservation of low-frequency hearing, with only modest decline in the long-term postimplantation, and a low proportion of loss of residual low-frequency hearing.
Objective:
To review the literature and our institutional experience regarding the risk of meningitis in patients with spontaneous lateral skull base cerebrospinal fluid (sCSF) leaks awaiting ...surgical repair, and the roles of antibiotic prophylaxis and pneumococcal vaccination, if known.
Methods:
A retrospective chart review and systematic review of the literature was undertaken to identify the incidence of meningitis in patients with sCSF leaks awaiting surgical repair. Adults managed surgically for sCSF leaks at an academic tertiary care center over a 10-year period were included. Data was collected on receipt of prophylactic antibiotics and/or pneumococcal vaccines during the timeframe between diagnosis and surgical repair.
Results:
Institutional review identified 87 patients who underwent surgical repair of spontaneous leaks, with a 0% incidence of meningitis over a median duration of 2 months while awaiting surgery (mean 5.5 months, range 0.5-118 months). Eighty-eight percent of patients did not receive prophylactic antibiotics. No studies in the published literature demonstrated the impact of prophylactic antibiotics or pneumococcal vaccine on meningitis risk.
Conclusions:
There appears to be a low risk of meningitis among patients with lateral skull base sCSF leaks awaiting surgery for short durations (≤2 months), even in the absence of prophylactic antibiotics. There is a substantial gap in the published literature assessing the risk of meningitis and roles of antibiotics and vaccination in this patient population, indicating the need for large-scale study to conclusively elucidate the nature of this risk.
Unilateral cochlear nerve deficiency in children Clemmens, Clarice S; Guidi, Jessica; Caroff, Aviva ...
Otolaryngology-head and neck surgery,
August 2013, Letnik:
149, Številka:
2
Journal Article
Recenzirano
Cochlear nerve deficiency (CND) is increasingly diagnosed in children with sensorineural hearing loss (SNHL). We sought to determine the prevalence of CND, its imaging characteristics, and ...correlations with audiologic phenotype in children with unilateral SNHL.
Case series with chart review.
Tertiary pediatric hospital.
In 128 consecutive children with unilateral SNHL who underwent high-resolution magnetic resonance imaging, the diameters, area, and signal intensity of the cochlear nerve (CN) were measured and normalized to the ipsilateral facial nerve. Presence of CND was determined by comparison to normative data. Relationships among hearing loss severity, progression, and nerve size were investigated.
Cochlear nerve deficiency was present in 26% of children with unilateral SNHL. Its prevalence was higher (48%) in severe to profound SNHL, especially when in infants (100%). Width of the bony cochlear nerve canal (BCNC) correlated strongly with relative CN diameter, density, and area (R = 0.5); furthermore, a narrow BCNC (<1.7 mm) strongly predicted CND. Severity of hearing loss modestly correlated with nerve size, although significant variability was observed. Progression never occurred unless there were other inner ear malformations, whereas in the non-CND group, it occurred in 22%. Ophthalmologic abnormalities were very common (67%) in CND children, particularly oculomotor disturbances.
Cochlear nerve deficiency is a common cause of unilateral SNHL, particularly in congenital unilateral deafness. Width of the BCNC effectively predicts CND, a finding useful when only computed tomography imaging is available. In an ear with CND, hearing can be expected to remain stable over time. Diagnosis should prompt evaluation by an ophthalmologist.
Background
Management of the neck in laryngeal squamous cell carcinoma (LSCC) is essential to oncologic control and survival. We aim to describe patterns and rates of clinical/pathologic lymph node ...disease, elective neck dissection (END), and occult lymph node metastasis (LNM) in patients with surgically‐managed LSCC.
Methods
Retrospective cohort study of patients in the National Cancer Database (NCDB) diagnosed with LSCC between January 2004 and December 2016 who underwent primary surgery.
Results
Seven thousand eight hundred and seventy‐six patients met inclusion criteria. For cN0 patients, the rates of END and occult LNM both increased with tumor stage and were highest for supraglottic tumors. Predictors of occult LNM included supraglottic site, pathologic T3 and T4 stage, positive margins, and presence of lymphovascular invasion (p < 0.05).
Conclusions
The propensity for cervical LNM in surgically‐managed LSCC varies based on primary tumor site and stage, and a variety of disease factors increase risk of occult LNM.
Objectives/Hypothesis
To identify relevant patient and surgical risk factors associated with prolonged length of stay, return to the operating room, and readmission within 30 days following total ...laryngectomy using the American College of Surgeons National Quality Improvement Program (ACS‐NSQIP)
Study Design
Retrospective database study. Patients undergoing total laryngectomy alone for laryngeal cancer were identified from the ACS‐NSQIP database from 2005 to 2014.
Methods
Multivariate logistic regression was used to identify independent predictors for prolonged length of stay, readmissions, and unplanned reoperations within 30 days.
Results
Among 871 patients meeting inclusion and exclusion criteria, the median length of stay was 8.0 days (range, 0–130 days). Totally dependent functional status (P < .01; odds ratio OR: 32.62), Black or African American race (P = .029; OR: 1.75), and operative time (P < .0001; OR: 1.15) were associated with prolonged length of stay. The overall rate of return to the operating room within 30 days was 12.4%. Contaminated wound status (P = .025; OR: 3.53), operative time (P = .015; OR: 1.10), steroid use (P < .01; OR: 2.92), and smoking (P = .05; OR: 1.60) were significantly associated with return to the operating room. Unplanned readmission rate was 11.9%, and 47.37% of readmissions were due to wound infection/pharyngocutaneous fistula. Dirty/contaminated wound classification (P = .05; OR: 22.5) was associated with readmission on multivariate analysis.
Conclusions
This is the first population‐level analysis to be performed on length of stay, readmission, and reoperation for total laryngectomy. Assessing and identifying modifiable risk factors on quality metrics may reduce overall cost and the burden on limited hospital resources.
Level of Evidence
4. Laryngoscope, 127:1339–1344, 2017
