Further Validity Evidence for Patient-Specific Virtual Reality Temporal Bone Surgical Simulation.

OBJECTIVE: Patient-specific virtual reality (VR) simulation of cochlear implant (CI) surgery potentially enables preoperative rehearsal and planning. We aim to gather supporting validity evidence for patient-specific simulation through the analysis of virtual performance and comparison with postoperative imaging. METHODS: Prospective, multi-institutional study. Pre- and postoperative cone-beam CT scans of CI surgical patients were obtained and processed for patient-specific VR simulation. The virtual performances of five trainees and four attendings were recorded and (1) compared with volumes removed during actual surgery as determined in postoperative imaging, and (2) assessed using the Copenhagen Cochlear Implant Surgery Assessment Tool (CISAT) by two blinded raters. The volumes compared were cortical mastoidectomy, facial recess, and round window (RW) cochleostomy as well as violation of the facial nerve and chorda. RESULTS: Trainees drilled more volume in the cortical mastoidectomy and facial recess, whereas attendings drilled more volume for the RW cochleostomy and made more violations. Except for the cochleostomy, attendings removed volumes closer to that determined in postoperative imaging. Trainees achieved a higher CISAT performance score compared with attendings (22.0 vs. 18.4 points) most likely due to lack of certain visual cues. CONCLUSION: We found that there were differences in performance of trainees and attendings in patient-specific VR simulation of CI surgery as assessed by raters and in comparison with actual drilled volumes. The presented approach of volume comparison is novel and might be used for further validation of patient-specific VR simulation before clinical implementation for preoperative rehearsal in temporal bone surgery. LEVEL OF EVIDENCE: n/a Laryngoscope, 134:1403-1409, 2024.

Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease.

In this retrospective cohort study of 193 consecutive subjects with primary mitochondrial disease (PMD) seen at the Children's Hospital of Philadelphia Mitochondrial Medicine Frontier Program, we assessed prevalence, severity, and time of onset of sensorineural hearing loss (SNHL) for PMD cases with different genetic etiologies. Subjects were grouped by genetic diagnosis: mitochondrial DNA (mtDNA) pathogenic variants, single large-scale mtDNA deletions (SLSMD), or nuclear DNA (nDNA) pathogenic variants. SNHL was audiometrically confirmed in 27% of PMD subjects (20% in mtDNA pathogenic variants, 58% in SLSMD and 25% in nDNA pathogenic variants). SLSMD had the highest odds ratio for SNHL. SNHL onset was post-lingual in 79% of PMD cases, interestingly including all cases with mtDNA pathogenic variants and SLSMD, which was significantly different from PMD cases caused by nDNA pathogenic variants. SNHL onset during school age was predominant in this patient population. Regular audiologic assessment is important for PMD patients, and PMD of mtDNA etiology should be considered as a differential diagnosis in pediatric patients and young adults with post-lingual SNHL onset, particularly in the setting of multi-system clinical involvement. Pathogenic mtDNA variants and SLSMD are less likely etiologies in subjects with congenital, pre-lingual onset SNHL.

Extended genetic diagnostics for children with profound sensorineural hearing loss by implementing massive parallel sequencing. Diagnostic outcome, family experience and clinical implementation.

OBJECTIVES: The aim of this study was to investigate genetic outcomes, analyze the family experience, and describe the process of implementing genetic sequencing for children with profound sensorineural hearing loss (SNHL) at a tertial audiological center in southern Sweden. DESIGN: This is a prospective pilot study including eleven children with profound bilateral SNHL who underwent cochlear implant surgery. Genetic diagnostic investigation was performed with whole exome sequencing (WES) complemented with XON-array to identify copy number variants, using a manually curated gene panel incorporating 179 genes associated with non-syndromic and syndromic SNHL. Mitochondrial DNA (mtDNA) from blood was examined separately. A patient reported experience measures (PREM) questionnaire was used to evaluate parental experience. We also describe here the process of implementing WES in an audiology department. RESULTS: Six female and five male children (mean 3.4 years, SD 3.5 years), with profound bilateral SNHL were included. Genetic variants of interest were found in six subjects (55%), where three (27%) could be classified as pathogenic or likely pathogenic. Among the six cases, one child was found to have a homozygous pathogenic variant in MYO7A and two children had homozygous likely pathogenic variants in SLC26A4 and PCDH15, respectively. One was carrying a compound heterozygote frameshift variant of uncertain significance (VUS) on one allele and in trans, a likely pathogenic deletion on the other allele in PCDH15. Two subjects had homozygous VUS in PCDH15 and ADGRV1, respectively. In five of the cases the variants were in genes associated with Usher syndrome. For one of the likely pathogenic variants, the finding was related to Pendred syndrome. No mtDNA variants related to SNHL were found. The PREM questionnaire revealed that the families had difficulty in fully understanding the results of the genetic analysis. However, the parents of all eleven (100%) subjects still recommended that other families with children with SNHL should undergo genetic testing. Specifically addressed referrals for prompt complementary clinical examination and more individualized care were possible, based on the genetic results. Close clinical collaboration between different specialists, including physicians of audiology, audiologists, clinical geneticists, ophthalmologists, pediatricians, otoneurologists, physiotherapists and hearing habilitation teams was initiated during the implementation of the new regime. For all professionals involved, a better knowledge of the diversity of the genetic background of hearing loss was achieved. CONCLUSIONS: Whole exome sequencing and XON-array using a panel of genes associated with SNHL had a high diagnostic yield, added value to the families, and provided guidance for further examinations and habilitation for the child. Great care should be taken to thoroughly inform parents about the genetic test result. Collaborations between departments were intensified and knowledge of hearing genomics was increased among the staff.

Inter-rater reliability of the diagnosis of otitis media based on otoscopic images and wideband tympanometry measurements.

OBJECTIVES: This study aims to investigate the inter-rater reliability and agreement of the diagnosis of otitis media with effusion, acute otitis media, and no effusion cases based on an otoscopy image and in some cases an additional wideband tympanometry measurement of the patient. METHODS: 1409 cases were examined and diagnosed by an otolaryngologist in the clinic, and otoscopy examination and wideband tympanometry (WBT) measurement were conducted. Afterwards, four otolaryngologists (Ear, Nose, and Throat doctors, ENTs), who did not perform the acute examination of the patients, evaluated the otoscopy images and WBT measurements results for diagnosis (acute otitis media, otitis media with effusion, or no effusion). They also specified their diagnostic certainty for each case, and reported whether they used the image, wideband tympanometry, or both, for diagnosis. RESULTS: All four ENTs agreed on the diagnosis in 57% of the cases, with a pairwise agreement of 74%, and a Light's Kappa of 0.58. There are, however, large differences in agreement and certainty between the three diagnoses. Acute otitis media yields the highest agreement (77% between all four ENTs) and certainty (0.90), while no effusion shows much lower agreement and certainty (34% and 0.58, respectively). There is a positive correlation between certainty and agreement between the ENTs across all cases, and both certainty and agreement increase for cases where a WBT measurement is shown in addition to the otoscopy image. CONCLUSIONS: The inter-rater reliability between four ENTs was high when diagnosing acute otitis media and lower when diagnosing otitis media with effusion. However, WBT can add valuable information to get closer to the ground-truth diagnosis without myringotomy. Furthermore, the diagnostic certainty increases when the WBT is examined together with the otoscopy image.

Nasal symptoms increase the risk of snoring and snoring increases the risk of nasal symptoms. A longitudinal population study.

PURPOSE: Humans have a preference for nasal breathing during sleep. This 10-year prospective study aimed to determine if nasal symptoms can predict snoring and also if snoring can predict development of nasal symptoms. The hypothesis proposed is that nasal symptoms affect the risk of snoring 10 years later, whereas snoring does not increase the risk of developing nasal symptoms. METHODS: In the cohort study, Respiratory Health in Northern Europe (RHINE), a random population from Denmark, Estonia, Iceland, Norway, and Sweden, born between 1945 and 1973, was investigated by postal questionnaires in 1999-2001 (RHINE II, baseline) and in 2010-2012 (RHINE III, follow-up). The study population consisted of the participants who had answered questions on nasal symptoms such as nasal obstruction, discharge, and sneezing, and also snoring both at baseline and at follow-up (n = 10,112). RESULTS: Nasal symptoms were frequent, reported by 48% of the entire population at baseline, with snoring reported by 24%. Nasal symptoms at baseline increased the risk of snoring at follow-up (adj. OR 1.38; 95% CI 1.22-1.58) after adjusting for age, sex, BMI change between baseline and follow-up, and smoking status. Snoring at baseline was associated with an increased risk of developing nasal symptoms at follow-up (adj. OR 1.22; 95% CI 1.02-1.47). CONCLUSION: Nasal symptoms are independent risk factors for development of snoring 10 years later, and surprisingly, snoring is a risk factor for the development of nasal symptoms.

PAP treatment in patients with OSA does not induce long-term nasal obstruction.

We hypothesized that positive airway pressure treatment would induce nasal obstruction and decrease nasal cavity due to mucosal swelling. We further hypothesized that subjective and objective nasal obstruction at baseline would negatively affect positive airway pressure adherence. A total of 728 patients with sleep apnea were investigated in the Icelandic Sleep Apnea Cohort at baseline and 2 years after starting positive airway pressure. Patients underwent home sleep apnea testing at baseline. Questionnaires were answered and acoustic rhinometry was completed at baseline and follow-up. The proportion of patients reporting subjective nocturnal nasal obstruction was reduced (baseline: 35% versus follow-up: 24%; p < 0.001). Small interior nasal dimensions increased (p < 0.001) independent of adherence to treatment. Small nasal volume at baseline was a determinant for becoming a non-user of positive airway pressure treatment (odds ratio 2.22, confidence interval 95% 1.35-3.67, p = 0.002). Subjective nasal obstruction decreased 2 years after initiating positive airway treatment in sleep apnea, and objectively small nasal dimensions increased. Small nasal volume at baseline was a negative predictor for positive airway pressure treatment adherence. Maybe most importantly, positive airway pressure treatment did not cause long-term objective or subjective nasal obstruction.

Nocturnal nasal obstruction is frequent and reduces sleep quality in patients with obstructive sleep apnea.

The prevalence and consequences of nasal obstruction in untreated obstructive sleep apnea patients are not known. The study objectives were to investigate the frequency of subjective and objective nasal obstruction in untreated sleep apnea patients and the associations with sleep and quality of life. Patients in the Icelandic Sleep Apnea Cohort were subjected to a type 3 sleep study, answered questionnaires and had their nasal dimensions measured by acoustic rhinometry. In total, 810 patients participated (including 153 females), aged 54.5 ± 10.6 years [mean ± standard deviation (SD)] with an apnea/hypopnea index 44.7 ± 20.7 h-1 . Nocturnal nasal obstruction (greater than or equal to three times per week) was reported by 35% of the patients. These patients had smaller nasal dimensions measured by the minimum cross-sectional area within the smaller nasal valve (0.42 ± 0.17 versus 0.45 ± 0.16 cm2 , P = 0.013), reported more daytime sleepiness (Epworth Sleepiness Scale score 12.5 ± 4.9 versus 10.8 ± 5.0; P < 0.001) and slightly lower mental quality of life than patients without nocturnal nasal obstruction. Nocturnal nasal obstruction is reported in one-third of the sleep apnea patients and they are more likely to suffer from daytime sleepiness and slightly reduced quality of life than other sleep apnea patients.

Long-term follow-up of patients operated with Uvulopalatopharyngoplasty from 1985 to 1991.

OBJECTIVES: Short-term outcome and side effects after Uvulopalatopharyngoplasty (UPPP) are well recognized. However, there is a lack of knowledge of the long-term outcome and side effects after this surgery. This study was completed to investigate the outcome and side effects 20 years after UPPP for snoring and obstructive sleep apnoea. METHODS: Medical records of patients who underwent UPPP surgery for sleep apnoea and snoring between 1985 and 1991 were investigated retrospectively. A specific questionnaire focusing on the present health profile, side effects of previous UPPP surgery and present sleeping patterns of patients was mailed out. RESULTS: UPPP patients, 186 (including 11 females) were identified. Of these, 35 (19%) had passed away and 7 (4%) were not located. 129 patients (mean: age 68 years, range 43-83) of the possible 144 patients answered the questionnaire (response rate 90%). At follow-up, 41 patients (32%) used continuous positive airway pressure (CPAP). 66 of the patients (52%) were satisfied with the result of the operation, but 61 (47%) were not satisfied. 49 patients (38%) reported persistent side effects (problems with nasal regurgitation 18 (14%), swallowing 26 (20%), changed voice 15 (12%), and pain in the oral cavity 15 (12%). CONCLUSION: Almost 50% of patients operated with UPPP were not satisfied with the result of the operation after about 20 years, and one third used CPAP at follow-up. A large proportion of patients still experienced side effects, which, after this time, are likely to be permanent.