Erdem Yildiz

Objective: Excessively prescribed opioids promote chronic drug abuse and worsen a highly prevalent public health problem in the era of the opioid epidemic. This study aimed to (a) determine general analgesic prescription patterns after surgery for vestibular schwannoma (VS) with a focus on opioid prescription rates, (b) identify risk factors for receiving narcotics for postoperative pain management, and (c) highlight the feasibility of opioid-free analgesic treatment strategies. Study Design: Retrospective chart review. Setting: Tertiary referral center. Patients: A total of 105 adult inpatients who underwent VS surgery. Interventions: Analgesic prescription patterns were evaluated, and factors associated with opioid prescriptions were identified. Main outcome measure: Number of prescribed analgesics. Results: Metamizole (=dipyrone) and acetaminophen (=paracetamol) were the most frequently prescribed non-opioid drugs. Sixty-three (60%) patients received an opioid with a median intake of 23.2 ± 24 mg of oral morphine equivalents. Only 10 (9.5%) individuals received opioids for longer than postoperative day 1. Subjects with small tumors undergoing middle cranial fossa tumor removal (p = 0.007) were more likely to receive opioid drugs. In contrast, patients undergoing retrosigmoid craniotomy required fewer opioids for pain control (p = 0.004). Furthermore, individuals receiving opioids were prone to obtain higher dosages of acetaminophen (odds ratio 1.054, 95% confidence interval 1.01–1.10, p = 0.022). Conclusions: Opioids for acute postoperative analgesia after VS surgery may be necessary in many patients. However, middle- and long-term pain control can be accomplished using non-opioid treatment regimens, resulting in a reduction in opioid prescriptions and the accompanying negative effects on individual and public health.

Background/Objectives: Cancer-associated cachexia in head and neck squamous cell carcinoma (HNSCC) is challenging to diagnose due to its complex pathophysiology. This study aimed to identify metabolic biomarkers linked to cachexia and survival in HNSCC patients using [¹⁸F]FDG-PET/CT imaging and machine learning (ML) techniques. Methods: We retrospectively analyzed 253 HNSCC patients from Vienna General Hospital and the MD Anderson Cancer Center. Automated organ segmentation was employed to quantify metabolic and volumetric data from [¹⁸F]FDG-PET/CT scans across 29 tissues and organs. Patients were categorized into low weight loss (LoWL; grades 0–2) and high weight loss (HiWL; grades 3–4) groups, according to the weight loss grading system (WLGS). Machine learning models, combined with Cox regression, were used to identify survival predictors. Shapley additive explanation (SHAP) analysis was conducted to determine the significance of individual features. Results: The HiWL group exhibited increased glucose metabolism in skeletal muscle and adipose tissue (p = 0.01), while the LoWL group showed higher lung metabolism. The one-year survival rate was 84.1% in the LoWL group compared to 69.2% in the HiWL group (p < 0.01). Pancreatic volume emerged as a key biomarker associated with cachexia, with the ML model achieving an AUC of 0.79 (95% CI: 0.77–0.80) and an accuracy of 0.82 (95% CI: 0.81–0.83). Multivariate Cox regression confirmed pancreatic volume as an independent prognostic factor (HR: 0.66, 95% CI: 0.46–0.95; p < 0.05). Conclusions: The integration of metabolic and volumetric data provided a strong predictive model, highlighting pancreatic volume as a key imaging biomarker in the metabolic assessment of cachexia in HNSCC. This finding enhances our understanding and may improve prognostic evaluations and therapeutic strategies.

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Due to the heterogeneity of causes for SNHL, effective treatment options remain scarce, creating an unmet need for novel drugs in the field of otology. Cochlear implantation (CI) currently is the only established method to restore hearing function in profound SNHL and deaf patients. The cochlear implant bypasses the non-functioning sensory hair cells (HCs) and electrically stimulates the neurons of the cochlear nerve. CI also benefits patients with residual hearing by combined electrical and auditory stimulation. However, the insertion of an electrode array into the cochlea induces an inflammatory response, characterized by the expression of pro-inflammatory cytokines, upregulation of reactive oxygen species, and apoptosis and necrosis of HCs, putting residual hearing at risk. Here, we characterize the small molecule AC102, a pyridoindole, for its protective effects on residual hearing in CI. In a gerbil animal model of CI, AC102 significantly improves the recovery of hearing thresholds across multiple frequencies and confines the cochlear trauma to the directly mechanically injured area. In addition, AC102 significantly preserves auditory nerve fibers and inner HC synapses throughout the whole cochlea. In vitro experiments in an ethanol challenged HT22 cell-line revealed significant and dose-responsive anti-apoptotic effects following the treatment of with AC102. Further, AC102 treatment resulted in significant downregulation of the expression of pro-inflammatory cytokines in an organotypic ex vivo model of electrode insertion trauma (EIT). These results suggest that AC102’s effects are likely elicited during the inflammatory phase of EIT and mediated by anti-apoptotic and anti-inflammatory properties, highlighting AC102 as a promising compound for hearing preservation during CI. Moreover, since the inflammatory response in CI shares similarities to that in other etiologies of SNHL, AC102 may be inferred as a potential general treatment option for various inner ear conditions.

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5–15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Due to the heterogeneity of causes for SNHL, effective treatment options remain scarce, creating an unmet need for novel drugs in the field of otology. Cochlear implantation (CI) currently is the only established method to restore hearing function in profound SNHL and deaf patients. The cochlear implant bypasses the non-functioning sensory hair cells (HCs) and electrically stimulates the neurons of the cochlear nerve. CI also benefits patients with residual hearing by combined electrical and auditory stimulation. However, the insertion of an electrode array into the cochlea induces an inflammatory response, characterized by the expression of pro-inflammatory cytokines, upregulation of reactive oxygen species, and apoptosis and necrosis of HCs, putting residual hearing at risk. Here, we characterize the effects of the small molecule AC102, a pyridoindole, for its protective effects on residual hearing in CI. We show that AC102 significantly preserves hearing thresholds across the whole cochlea and confines the cochlear trauma to the directly mechanically injured area. In addition, AC102 significantly preserves auditory nerve fibers and inner HC synapses throughout the whole cochlea. AC102s effects are likely elicited during the inflammatory phase of electrode insertion trauma (EIT) and mediated by anti-apoptotic and anti-inflammatory properties, as uncovered by anin vitroassay of ethanol induced apoptosis and evaluation of mRNA expression of pro-inflammatory cytokines in an organotypicex vivomodel of EIT. The results in this study highlight AC102 as a promising compound for the attenuation of EIT during CI. Moreover, as the inflammatory response in cochlear implantation shares similarities to other etiologies of SNHL, a beneficial effect of AC102 can be inferred for other inner ear conditions as well.

Background The temporalis muscle flap transfer with fascia lata augmentation (FLA) is a promising method for smile reconstruction after facial palsy. International literature lacks a detailed anatomical analysis of the temporalis muscle (TPM) combined with fascia lata (FL) augmentation. This study aims to describe the muscle's properties and calculate the length of FL needed to perform the temporalis muscle flap transfer with FLA. Methods Twenty nonembalmed male (m) and female (f) hemifacial cadavers were dissected to investigate the temporalis muscle's anatomy. Results The calculated minimum length of FL needed is 7.03cm (f) and 5.99cm (m). The length of the harvested tendon is 3.16cm/± 1.32cm (f) and 3.18/± 0.73cm (m). The length of the anterior part of the temporalis muscle (aTPM) is 4.16/± 0.80cm (f) and 5.30/± 0.85cm (m). The length of the posterior part (pTPM) is 5.24/± 1.51cm (f) and 6.62/± 1.03cm (m). The length from the most anterior to the most posterior point (aTPMpTPM) is 8.60/± 0.98cm (f) and 10.18/± 0.79cm (m). The length from the most cranial point to the distal tendon (cTPMdT) is 7.90/± 0.43cm (f) and 9.79/± 1.11cm (m). Conclusions This study gives basic information about the temporalis muscle and its anatomy to support existing and future surgical procedures in their performance. The recommended minimum length of FL to perform a temporalis muscle transfer with FLA is 7.03cm for female and 5.99cm for male, and minimum width of 3 cm. We recommend harvesting some extra centimeters to allow adjusting afterward. In this study, we investigated the surgical anatomy of cadaver donors. The cadaver donors provided their consent in their lifetime that their bodies may be used for scientific purposes. This study has been ethical approved by the ethical committee (IRB) of the Medical University of Vienna with the EK Nr. 1463/2018. Y.Z. was involved in conceptualization, data curation, formal analysis, investigation, methodology, visualization, and writing --original draft. J.S. contributed to conceptualization, investigation, methodology, and writing –review and editing. W.J.W., U.M.H., and L.R. helped in providing resources. ErdemYildiz helped in investigation. C.H.J.T. contributed to conceptualization, investigation, methodology, project administration, supervision, and writing –review and editing. WRSM 2019 50^th Annual meeting of the German Society of Plastic, Reconstructive and Aesthetic Surgery 58^th Annual Meeting of the Austrian Society of Plastic, Aesthetic and Reconstructive Surgery DAM 2021 (German speaking-group for Microsurgery) Received: 03 April 2022 Accepted: 12 August 2022 Article published online: 06 February 2023 © 2023. The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Objective: To evaluate the impact of radiotherapy (RT) on dysphagia and long-term swallowing outcome in patients with stage III and IV head and neck squamous cell carcinomas (HNSCCs). Material and Methods: Between 2005 and 2008, 189 patients with HNSCCs underwent primary or adjuvant RT in a curative setting. Long-term swallowing outcome was evaluated in 50 patients. Among them, 26 were further eligible for prospective analysis of long-term swallowing and dysphagia outcome. Medical charts were retrospectively reviewed regarding pre- and post-treatment dysphagia (3 months after last irradiation setting) as well as persisting long-term dysphagia (2019–2021). Results: Pre-treatment dysphagia was observed in 24 (48%) of 50 patients, particularly in oropharyngeal or hypopharyngeal stage III–IV tumors (OR 9.3; p = 0.003). Conversely, 46 patients (92%) complained about post-treatment dysphagic symptoms, which were more commonly seen in patients with positive neck nodes (OR 10.5; p = 0.037). The post-treatment dysphagia rate dropped from 92% to 24% (p < 0.001) during surveillance, which was significantly linked to xerostomia (OR 5.77; p = 0.019), dysgeusia (OR 9.9; p = 0.036) and free flap reconstruction (OR 6.1; p = 0.022). Conclusion: Pretreatment dysphagia is common in advanced stage HNSCCs and almost all patients complain about dysphagia at the end of RT. Importantly, applied RT protocols did not affect long-term dysphagia, which improves significantly in the majority of patients over time. Meeting Information: Preliminary results have been presented at the 65th Annual Meeting of the Austrian Society of Otorhinolaryngology, 22–26 September 2021, Austria.

Introduction: Temporal bone paragangliomas are rare tumors with high vascularization and usually benign entity. A variety of modalities, including gross total resection, subtotal resection, conventional or stereotactic radiotherapy including gamma-knife, embolization, and wait-and-scan strategy can be considered. The aim of this study was to compare long-term outcomes of different primary treatment modalities in temporal bone paragangliomas. Materials and Methods: Patients with temporal bone paragangliomas treated between 1976 and 2018 at a tertiary referral center were retrospectively analyzed in this study. Collected patient data of 42 years were analyzed and long-term results including interdisciplinary management were assessed. Patient outcomes were compared within the different therapy modalities according to tumor control rate and complications. Clinical characteristics, radiological imaging, tumor extent and location (according to Fisch classification), symptoms, and follow-up were evaluated and a descriptive analysis for each treatment modality was performed. Tumor recurrence or growth progression and respective cranial nerve function before and after therapy were described. Results: A total of 59 patients were treated with a single or combined treatment modality and clinical follow-up was 7 (13) years (median, interquartile range). Of the included patients 45 (76%) were female and 14 (24%) male (ratio 3:1) with a patient age range from 18 to 83 years. Total resection was performed on 31 patients, while 14 patients underwent subtotal resection. Eleven patients were treated with conventional primary radiotherapy or gamma-knife radiosurgery. Pulsatile tinnitus (n = 17, 29%) and hearing impairment (n = 16, 27%) were the most common symptoms in our patient group. Permanent lower cranial nerve deficits were observed only in patients with large tumors (Fisch C and D, n = 14, 24%). Among the 45 patients who were treated surgically, 88% of patients with Fisch A and B paragangliomas had no recurrent disease, while no tumor growth was perceived in 83% of patients with Fisch C and D paragangliomas. Conclusion: In conclusion, we propose surgery as a treatment option for patients with small tumors, due to a high control rate and less cranial nerve deficits compared to larger tumors. Although patients with Fisch C and D temporal bone paraganglioma can be treated surgically, only subtotal resections are possible in many cases. Additionally, frequent occurrence of cranial nerve deficits in those patients and tumor growth progression in long-term follow-up examinations make a combination of the therapy modalities or a primary radiotherapy more suitable in larger tumors.