Comparison of two different intratympanic corticosteroid injection protocols as salvage treatments for idiopathic sudden sensorineural hearing loss.

PURPOSE: We aimed to investigate the effect of interval length and total count of intratympanic steroid (ITS) injections in salvage treatment of patients with idiopathic sudden sensorineural hearing loss (ISSNHL). METHODS: This retrospective case-control study included 64 patients with ISSNHL, who were treated with ITS injections as salvage therapy at a tertiary referral centre. From September 2019 to December 2020, 32 patients received up to four injections every 2-4 days (revised-protocol group). These patients were 1:1 matched to patients, who received up to three injections at 1-week intervals between January 2014 and August 2019 (initial-protocol group). Hearing outcomes of the two groups were compared. RESULTS: Both ITS salvage treatment protocols resulted in a statistically significant hearing improvement (p < 0.05). The initial-protocol declined hearing thresholds by 12 ± 11.7 dB (p < 0.001, d = 1, P = 99%). Mean hearing function was improved by 13.4 ± 19.1 dB in the revised-protocol group [p < 0.001, d = 0.7, P = 98%]. A clinically significant hearing improvement (> 10 dB) was seen in 18 patients (58.1%) in the initial-protocol group and in 14 patients (41.9%) in the revised-protocol group. A comparison of the hearing outcomes between protocol groups revealed no statistically significant differences (p > 0.05). CONCLUSION: These results indicate that a shorter injection interval does not lead to better hearing outcomes in ITS salvage treatment for ISSNHL. Moreover, fewer ITS injections may reduce costs, physical/mental stress of the patients and lower the risk of persistent tympanic perforations.

Scala vestibuli cochlear implant supported by 3D modeling of the inner ear.

Patients with scala tympani (ST) ossification present a distinct surgical challenge. Three-dimensional (3D) segmentation of the inner ear offers accurate identification of ossification and surgical planning of the cochleostomy to access the scala vestibuli. The scala vestibuli placement of cochlear implantation electrode is an alternate solution in these patients and is well supported by the literature.The present report describes a case of cochlear implantation in the scala vestibuli assisted by 3D segmentation of the cochlea for a patient with ossification in the ST and reviews the relevant literature. Clinical presentation of a 45-year-old Austrian female who was referred with a history of sudden sensorineural hearing loss 2 years ago in the right ear, confirmed by pure tone audiometry (PTA) and acoustically evoked auditory brainstem response (ABR). 3D segmentation of the inner ear identified the extent of ossification in the ST and assisted in the surgical planning of cochleostomy drilling anterior-superior to the round window to access the scala vestibuli for the electrode placement. Postoperative computed tomography (CT) to confirm the electrode placement in the scala vestibuli and PTA was performed to assess the hearing threshold following the cochlear implantation. Postoperative CT confirmed the full insertion of a flexible electrode. The hearing threshold measured by PTA was ≤ 40 dB across all frequencies tested. Review of the literature identified a total of 13 published reports on cochlear implantation electrode placement in scala vestibuli in cases with ossification in the ST.

Intratympanic Triamcinolone Acetonide as a Salvage Treatment for Idiopathic Sudden Sensorineural Hearing Loss.

INTRODUCTION: Intratympanic steroid (ITS) injections represent an increasingly used salvage treatment option for patients with idiopathic sudden sensorineural hearing loss -(ISSHL) after systemic treatment. The most effective corticosteroid for this treatment modality still remains unclear. Triamcinolone acetonide has been used for ITS treatment in various clinical settings. However, there are limited clinical data of its usage in the therapeutic management of ISSHL. The aim of this study was to determine the efficacy of intratympanic triamcinolone acetonide injections as a salvage treatment for ISSHL. METHODS: We conducted a retrospective chart review on patients affected by ISSHL with insufficient hearing recovery after primary systemic corticosteroid therapy and who were treated with intratympanic triamcinolone acetonide as a salvage therapy between January 2014 and August 2019. The patients were divided into groups according to their degree of hearing recovery, and we evaluated potential predictors of hearing recovery. Audiometric results were then compared to historic studies using dexamethasone or methylprednisolone. RESULTS: One-hundred and fifty-two patients received up to 3 intratympanic injections with triamcinolone acetonide at 1-week intervals. The mean hearing improvement due to ITS salvage treatment was 15.9 ± 18.9 dB. Complete hearing recovery was noted in 15 patients (9.9%), while 73 patients (48%) obtained partial recovery, and 64 patients (42.1%) had no recovery. Primary systemic treatment delay, hearing improvement by primary systemic treatment, and severity of initial hearing loss were identified as significant predictors of hearing improvement. The first of the 3 injections resulted in the greatest hearing improvement. CONCLUSION: The use of triamcinolone acetonide in ITS salvage treatment resulted in similar hearing improvements as the use of the commonly used corticosteroids, namely, dexamethasone and methylprednisolone. Longer treatment delays, lower hearing improvement by primary systemic treatment, and higher initial hearing loss are associated with poorer prognoses of hearing recovery.

DRH1 - a novel blood-based HPV tumour marker.

BACKGROUND: To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay. METHODS: In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies. Analytical specificity was determined using WHO reference-sera for HPV16/18 and 29 pre- and post-immune sera of Gardasil-9-vaccinees. Tumour-tissue was immunochemically stained for HPV-L1-capsidprotein-expression. FINDINGS: The DRH1-competitive-serological-assay showed a sensitivity of 95% (95% CI, 77.2-99.9%) for HPV16-driven HNSCC, and 90% (95% CI, 55.5-99.7%) for HPV16-induced anal cancer in HIV-positives. Overall diagnostic specificity was 99.46% for men and 99.29% for women ≥ 30 years. After vaccination, antibody level increased from average 364 ng/ml to 37,500 ng/ml. During post-therapy-monitoring, HNSCC patients showing an antibody decrease in the range of 30-100% lived disease free over a period of up to 26 months. The increase of antibodies from 2750 to 12,000 ng/ml mirrored recurrent disease. We can also show that the L1-capsidprotein is expressed in HPV16-DNA positive tumour-tissue. INTERPRETATION: HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease. As post-treatment biomarker, the assay allows independent post-therapy monitoring as well as early diagnosis of tumour recurrence. An AUC of 0.96 indicates high sensitivity and specificity for early detection of HPV16-induced disease. FUNDING: The manufacturer provided assays free of charge.

Sex-specific differences in patients with nonmelanoma skin cancer of the pinna.

BACKGROUND: Generally, it is known that men are affected more frequently by nonmelanoma skin cancer (NMSC) than women. The aim of our study was to investigate the effect of sex on the characteristics of NMSCs of the pinna at the population that our center serves and to compare it with the international data. METHODS: We analyzed retrospectively the data of 225 patients with NMSC of the pinna. Sex-specific differences were investigated for basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) subgroups. RESULTS: The ratio of BCC to cSCC was determined in male patients at 1:1.3, in contrast in females it was identified at 4:1 (P = .001). CONCLUSION: In our study, a new aspect of the sex-dependent distribution of cSCC and BCC of the pinna was demonstrated. Women are affected four times more frequently by BCC than by cSCC, whereas in men this ratio is approximately equal.

Head and neck cancer in Styria : An epidemiologic and clinical audit.

BACKGROUND: The outcome of patients with cancer of the head and neck is significantly improved by increased interdisciplinary cooperation. The main focus of this study was a comparison of epidemiologic factors (age, sex, origin, staging) of patients with head and neck cancer in Styria, with those for patients throughout Austria. METHODS: A retrospective data analysis of collected archived tumor board protocols of the Comprehensive Cancer Center (CCC) Graz included the patient's age, sex, area of residence, TNM stage, reasons for inoperability, comorbidities and performance status by ECOG (Eastern Cooperative Oncology Group), was performed. This study focuses on 340 patients who presented with a head and neck malignancy for the first time. RESULTS: In the period from January 2014 to December 2015 a total of 252 men (74.1%) and 88 women (25.9%) with malignant head and neck tumors, were presented in the tumor board for the first time. The mean age at diagnosis was 63.4 years. In 45.5% the patients already demonstrated advanced tumor stages (T4 = 27.9%, T3 = 17.6%). Most newly diagnosed neoplasms were cancers of the oropharynx (24.1%), larynx (19.4%) and oral cavity (18.8%) and 36.5% were considered to be inoperable. Curative and palliative treatments were initiated in 83.2% and 16.9%, respectively. CONCLUSION: The region of south Styria showed a higher incidence of T3 and T4 tumors of the oropharynx than the average Austrian population. Measures to increase awareness of this problem should be initiated to support general otorhinolaryngologists and general practitioners in detecting oropharyngeal cancers at an earlier stage.

Carotid endarterectomy significantly improves postoperative laryngeal sensitivity.

OBJECTIVE: Iatrogenic injury of the vagus nerve or its branches during carotid endarterectomy (CEA) can result in globus sensation, dysphagia, and even vocal fold immobility. Knowledge of morphologic and functional laryngopharyngeal outcomes after CEA is poor. The present study was performed to determine potential iatrogenic damage to the laryngeal innervation after CEA. An area of particular interest was the supraglottic sensory threshold, which was examined by Fiberoptic Endoscopic Evaluation of Swallowing With Sensory Testing (FEESST; Pentax Medical Company, Montvale, NJ), a validated and safe method for the determination of the motor and sensory components of swallowing. METHODS: FEESST was used preoperatively in 32 patients scheduled to undergo CEA and twice postoperatively to examine the motor and sensory components of swallowing. In this endolaryngeal examination, laryngopharyngeal sensory thresholds (in mm Hg) were defined as normal at <4.0 mm Hg air pulse pressure (APP), moderate deficit at 4.0 to 6.0 mm Hg APP, or severe deficit at >6.0 mm Hg APP, with a value >10.0 mm Hg APP indicating abolished laryngeal adductor reflex. Acoustic voice parameters were also analyzed for further functional changes of the larynx. RESULTS: The mean ± standard deviation preoperative FEESST measures showed no significant differences (P = .065) between the operated-on side (6.73 ± 1.73 mm Hg) and the opposite side (5.83 ± 1.68 mm Hg). At 2 days postoperatively, the threshold increased (P = .001) to 7.62 ± 1.98 mm Hg on the operated-on side. A laryngopharyngeal mucosal hematoma on the operated side was endoscopically detectable in eight patients (30.8%); in these patients, we found a markedly elevated (P = .021) measure of 9.50 ± 0.93 mm Hg. On the opposite (nonoperated-on) side of the laryngopharynx, the thresholds remained at the same level as preoperatively over all assessments (P >.05), whereas the differences between the operated and nonoperated-on sides and the hematoma and nonhematoma groups were highly significant (P = .004 and P = .001, respectively). Surprisingly, the sensory threshold on the operated-on side (6.08 ± 2.02 mm Hg) decreased significantly at the 6-week follow-up, even in relation to the preoperative measure (P = .022). With the exception of one patient with permanent unilateral vocal fold immobility, no signs of nerve injury were detected. CONCLUSIONS: In accordance with previous reports, injuries to the recurrent laryngeal nerve during CEA seem to be rare. In most patients, postoperative symptoms (globus, dysphagia, dysphonia) and signs fade within a few weeks without any specific therapeutic intervention. This study shows an improved long-term postoperative superior laryngeal nerve function with regard to laryngopharyngeal sensitivity.

Unknown primary of the head and neck: A long-term follow-up.

BACKGROUND: A diagnosis of squamous cell carcinoma of an unknown primary (CUP) is a major burden for patients. Because the location of the primary tumor is unclear, patients remain fearful of recurrence, which aggravates the uncertain prognosis of the disease. This study evaluates factors associated with long-term recurrence-free and overall survival of patients with CUP of the head and neck. Additionally, patient survival rates are compared with those of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 293 consecutive patients operated on between January 1999 and December 2009 with at least a 5-year follow-up (survival permitting), were evaluated retrospectively. RESULTS: Twenty-six patients with a CUP of the head and neck were identified. Patients with CUP had a low overall survival rate, comparable with that of patients with pN + HNSCC, and recurrent disease occurred with a similar likelihood as in patients with pN + HNSCC. The median recurrence-free survival in the CUP group was 28.5 months compared with 48 months in the whole of the HNSCC group. The median overall survival of the CUP group was 56 months versus 65 months for the HNSCC group. Extracapsular spread was the only independent prognostic factor for overall survival for CUP patients. CONCLUSION: Patients diagnosed with CUP syndrome have a poorer prognosis for overall survival compared with other HNSCC patients. Postoperative radiotherapy diminished disease recurrence and improved overall survival. Omission of postoperative radiotherapy resulted in a very high recurrence rate (75%) for CUP patients. Based on these results we suggest postoperative radiotherapy including the oral mucosa for all patients, regardless of histopathological results, possible favorable nodal disease, or favorable lymph node ratios.

Establishing principles of macromolecular crowding for in vitro fibrosis research of the vocal fold lamina propria.

OBJECTIVES/HYPOTHESIS: Vocal fold fibrosis represents a major disease burden. Screening of antifibrotic compounds could be facilitated by an in vitro fibrogenesis system. Limitations of existing models might be overcome by implication of the excluded volume effect. STUDY DESIGN: In-vitro study. METHODS: Vocal fold fibroblasts obtained from rats' lamina propria were cultured in four different settings: in standard medium, under "crowded" conditions by adding inert macromolecules, under external administration of transforming growth factor (TGF)ß-1, and under a combination of both. After 5 days, supernatant and cell layer were collected and analyzed by enzyme-linked immunosorbent assay. Immunofluorescence was additionally performed. RESULTS: Collagen-alpha1(I) deposition increased significantly under crowded conditions and after administration of TGFß-1. Amounts of collagen in the cell layer were significantly higher under crowding conditions with TGFß-1 compared to administration of TGFß-1 alone. CONCLUSION: Crowding enhanced collagen deposition, resulting in more favorable conditions for studying fibrogenesis. This can be the first step toward developing a robust in vitro model for testing antifibrotic compounds. LEVEL OF EVIDENCE: NA.

Vocal fold fibroblast response to growth factor treatment is age dependent: results from an in vitro study.

INTRODUCTION: Vocal fold (VF) fibroblasts (VFFs) are the central target in developing new strategies for treatment of VF injury and scarring. Nevertheless, only little is known about the basic biological characteristics of these cells. The aim of this study was to explore the impact of age of VFFs on the response to external growth factor stimulation. STUDY DESIGN: In vitro cell study using a rat model. METHODS: VFFs were extracted from young and aged rat VF 3 months after establishing unilateral injury. Resulting scar fibroblasts (SFs) and normal fibroblasts (NFs) were subsequently cultured separately with or without the addition of hepatocyte growth factor (HGF). After 24 and 72 hours, the production of hyaluronic acid (HA) was examined in the supernatant culture media using enzyme-linked immunosorbent assay. RESULTS: Only cultured SF and NF from young animals could be stimulated significantly in the production of HA by HGF. Within these, average percentage increase was higher in NF compared with SF. CONCLUSION: The response of VFFs in cell culture to growth factors stimulation is highly depending on the age of the animals. This is another step in a nearer characterization of scar VFF and could furthermore be an important point when estimating the success of an intervention. Age-depending effects must be considered as an important factor in developing possible therapeutic agents for VF scarring.

Age effects on extracellular matrix production of vocal fold scar fibroblasts in rats.

Vocal fold (VF) fibroblasts are the central subject of interest in fibrogenesis and wound healing after VF injury. Scar fibroblasts (SF) exhibit an aberrant production of several extracellular matrix (ECM) components which lead either to VF fibrosis or scarless wound healing. This study aimed to investigate the role of age at the time of injury on ECM production of SF. This is designed as an animal study. VF injury was established unilaterally in eight male Sprague-Dawley rats [3 months of age (n = 4), 11 months of age (n = 4)], while the other side was left intact. Three months after injury the larynges were excised and fibroblasts were extracted from VF [normal fibroblasts (NF)­scar fibroblasts (SF)] and cultured in vitro. After first passage, VF fibroblasts were plated in 24-well plates and levels of hyaluronic acid (HA) and collagen type I were determined enzymatically from supernatant after 24 and 72 h. Cultured SF from younger animals produced significantly higher levels of HA compared to NF fibroblasts from the same animals. HA concentrations of the older animals did not differ significantly between the NF and SF cultures, but the range in SF cultures was large. In contrast to previous studies, we found that even 3 months after VF injury cultured SF from young animals expressed higher levels of HA in comparison to SF from older animals. No difference in collagen levels were observed between the younger and older animals. Age of animals is an essential factor during VF healing and has to be considered for study design.

Subjective and objective vocal parameters in women with polycystic ovary syndrome.

INTRODUCTION: Despite the relatively high prevalence of the polycystic ovary syndrome (PCOS) affecting up to 15% of all women of reproductive age, only little is known about vocal changes related to this endocrinologic disorder that is characterized by biochemical or clinical hyperandrogenism, impaired cycles, and/or polycystic ovaries. The aim of our study was to describe objective and subjective vocal changes in women with a diagnosed PCOS compared with a control group. MATERIALS AND METHODS: Our study group comprised 34 women-24 cases with confirmed PCOS and 10 controls in whom PCOS was excluded. A complete endocrinologic laboratory status was obtained by all participants; study procedures included a videolaryngostroboscopy, voice recording, and completion of the German version of the Voice Handicap Index. RESULTS: A trend toward lower mean fundamental frequency was detectable, but this failed statistical significance. No differences were found in the objective and subjective voice parameters. CONCLUSION: Elevated serum levels of androgens, as found in women with PCOS, were shown not to have an impact on the subjective and objective voice parameters.