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Due to the widespread use of high-resolution sonography, numerous thyroid nodules are diagnosed, often as incidental findings. The challenge lies in evaluating various criteria such as size, shape, and echogenicity to assess the nodules' malignancy risk. Risk stratification systems have been developed to enable systematic assessment as well as to avoid unnecessary medical interventions and malignant findings being overlooked. This article provides an overview of the current diagnostic standards in primary assessment of thyroid nodules., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Treatment of patients with cancer of the head and neck region is in focus in a multitude of studies. Of these patients, one patient group, those aged 76 and more, is mostly underrepresented despite requiring thorough and well-reasoned treatment decisions to offer curative treatment. This study investigates real-world data on curative treatment of old (≥76 years) patients with newly diagnosed squamous cell carcinoma of the head and neck region (HNSCC)., Patients and Methods: Between January 2010 and December 2021, we identified 71 patients older than 76 years with newly diagnosed HNSCC and cM0 at the Department of Radiation Oncology of the University Hospital of Erlangen-Nuremberg. Using electronic medical records, we analyzed treatment patterns and outcomes in terms of overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rate. Additionally, we performed univariate risk analysis and Cox regression in order to identify predictive factors associated with the abovementioned treatment outcomes., Results: The median follow-up was 18 months. OS was 83%, 79%, and 72% after 1 year, 2 years, and 3 years, respectively. PFS was 69%, 54%, and 46% after 1 year, 2 years, and 3 years, respectively. A total of 34 (48%) patients were treated with standard therapy according to current guidelines. The reasons for deviation from standard therapy before or during treatment were as follows: unfitness for cisplatin-based chemotherapy (n = 37), reduction of chemotherapy (n = 3), and dose reduction/interruption of radiotherapy (n = 8). Carboplatin-based systemic therapy showed improved PFS compared to cisplatin or cetuximab (60 vs. 28 vs. 15 months, p = 0.037) but without impact on OS (83 vs. 52 vs. 38 months, p = 0.807). Oropharyngeal tumor localization (p = 0.026) and combined treatment (surgery and postoperative treatment) (p = 0.008) were significant predictors for a better OS. In multivariate analysis, oropharyngeal tumor localization (p = 0.011) and combined treatment (p = 0.041) showed significantly increased PFS. After 1 year, 2 years, and 3 years, the cumulative incidence of locoregional recurrences (LRRs) was 13%, 24%, and 27%, respectively, and was significantly decreased in patients with oropharyngeal tumor localization (p = 0.037)., Conclusions: Adherence to treatment protocols for radiotherapy alone in old patients with HNSCC is good, whereas the application of concurrent chemotherapy often deviates from guidelines in terms of de-escalation. An important risk factor for decreased OS, PFS, and a higher rate of LRR appears to be non-oropharyngeal tumor location in old patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Winkler, Haderlein, Semrau, Putz, Höfler, Müller, Iro, Kesting, Fietkau and Schubert.)

Face masks were recognized as one of the most effective ways to prevent the spread of the COVID-19 virus in adults. These benefits were extended to children and adolescents. However, the fear of negative consequences from wearing a face mask during physical exercise led to cancellations of physical education lessons. This further decreased the amount of physical activity available to children and adolescents during the pandemic. However, there is little published data on the potential adverse effects of wearing the most effective and partially mandatory FFP2/N95 face masks during PE or physical activity (PA) in this age. Even though the pandemic has been declared as passed by the WHO, the rise of a new pandemic and thus the use of face masks for limiting its spread is inevitable, so we need to be better prepared for alternative options to lockdown and limitation of PA in such a scenario. Twenty healthy children aged 8-10 years performed two identical cardiopulmonary exercise tests as an incremental step test on a treadmill within an interval of 2 weeks, one time without wearing a protective mask and one time wearing an FFP2 mask. The cardiopulmonary exercise parameter and especially the end-expiratory gas exchange for oxygen and carbon dioxide (petO 2 and petCO 2 ) were documented for each step, at rest and 1 min after reaching physical exhaustion. Twelve boys (mean age 8.5 ± 1.4 years) and 8 girls (mean age 8.8 ± 1.4 years) showed no adverse events until maximal exertion. The mean parameters measured at peak exercise did not differ significantly between both examinations (mean peak VO 2  = 42.7 ± 9.5 vs 47.8 ± 12.9 ml/min/kg, p = 0.097, mean O 2 pulse 7.84 ± 1.9 ml/min vs. 6.89 ± 1.8, p = 0.064, mean VE/VCO 2 slope 33.4 ± 5.9 vs. 34.0 ± 5.3, p = 0.689). The only significant difference was the respiratory exchange rate (RER, 1.01 ± 0.08 vs 0.95 ± 0.08, p = 0.004). The measured respiratory gases (end-tidal O 2 and CO 2 ) decreased and respectively increased significantly in almost every step when wearing an FFP2 mask. However, these levels were well below hypercapnia and above hypoxia., Conclusion:  In this study, no significant differences in the cardiorespiratory function at peak exercise could be discerned when wearing an FFP2/N95 face mask. While the end-tidal values for CO 2 increased significantly and the end-tidal values for O 2 decreased significantly, these values did never reach levels of hypercapnia or hypoxia. Furthermore, the children terminated the exercise at a lower RER and heart rate (HR) suggesting a subconscious awareness of the higher strain. Since the detrimental effects of limiting sports during the pandemic are well documented, stopping PE lessons altogether because of the minor physiological effects of wearing these masks instead of simply stopping pushing children to perform at their best seems premature and should be reconsidered in the future., What Is Known: • Wearing a face mask has an influence on psychological, social, and physiological functions in adults. • Because of the observed effects of wearing face masks in adults, physical activity in children was limited during the pandemic., What Is New: • Wearing an FFP2/N95 mask during physical activity did not lead to hypercapnia or hypoxia in children in this study. • Even though end-tidal CO2 values were significantly higher and end-tidal O2 values significantly lower when wearing an FFP2/N95 face mask, no pathological values were reached., (© 2023. The Author(s).)

Scope: Maillard reaction products (MRPs) are believed to interact with the receptor for advanced glycation endproducts (RAGE) and lead to a pro-inflammatory cellular response. The structural basis for this interaction is scarcely understood. This study investigates the effect of individual lysine modifications in free form or bound to casein on human colon cancer cells., Methods and Results: Selectively glycated casein containing either protein-bound N-ε-carboxymethyllysine (CML), N-ε-fructosyllysine (FL), or pyrraline is prepared and up to 94%, 97%, and 61% of lysine modification could be attributed to CML, FL, or pyrraline, respectively. HCT 116 cells are treated with free CML, pyrraline, FL, or modified casein for 24 h. Native casein is used as control. Intracellular MRP content is analyzed by UPLC-MS/MS. Microscopic analysis of the transcription factors shows no activation of NFκB by free or protein-bound FL or CML, whereas casein containing protein-bound pyrraline activates Nrf2. RAGE expression is not influenced by free or casein-bound MRPs. Activation of Nrf2 by pyrraline-modified casein is confirmed by analyzing Nrf2 target proteins NAD(P)H dehydrogenase (quinone 1) (NQO1) and heme oxygenase-1 (HO-1)., Conclusion: Studies on the biological effects of glycated proteins require an individual consideration of defined structures. General statements on the effect of "AGEs" in biological systems are scientifically unsound., (© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Objectives: The aims of our study were to investigate the clinical and audiometric outcome of the surgical treatment of postinflammatory medial meatal fibrosis (PIMMF) and to review the histopathologic changes in the specimens of the fibrotic plug, in order to try to shed light on the pathogenesis of the disease., Materials and Methods: The clinical records and the histopathologic specimens of all patients who underwent tympanomeatoplasty for PIMMF at the ENT Clinic of the University of Erlangen between 2006 and 2020 were evaluated retrospectively., Results: Thirty-four patients (41 primary surgical procedures) made up our study cohort. Of this, 28 cases were managed by means of meatoplasty and 13 cases with tympanomeatoplasty. The mean preoperative air-bone gap (ABG) was 27.8 dB (10-44 dB). Postoperative ABG was significantly improved compared to preoperative values at both short- and long-term follow-ups ( P < .001 for both). No significant difference was noted between short-term and long-term ABG ( P = .240). An ABG ≤20 dB was achieved in 65.8% of patients (short term) and 50% (long term). The overall rate of revision surgery for restenosis was 29.3% (12/41). Histopathologic reevaluation of the fibrotic plugs revealed a mosaic of patterns with frequent occurrence of secondary cholesteatoma-like lesions and keloid-like tissue changes. Lichenoid submucosal inflammation and increased ectopic ceruminous gland lobules were seen less frequently., Discussion: The moderate long-term outcome of surgical management and the identification of histologic changes with therapeutic implications might pave the way for alternative nonsurgical treatment options.

Several studies have demonstrated the de novo formation of lymphatic vessels or the reorganization of lymphatic sinus in tumor-draining lymph nodes, partly preceding the detection of lymphatic metastases. This "lymphovascular niche"is supposed to facilitate the survival of metastatic tumor cells. Few studies on nodal lymphangiogenesis in invasive breast cancer (BC) have been published, not considering tumor-free sentinel lymph nodes (SLN) and tumor types. Specimens of SLN and/ or non-SLN (NSLN) of 95 patients with BC were examined immunohistochemically for expression of the lymphatic endothelial marker D2-40 (podoplanin) on lymphatic vessels and the subcapsular sinus. The number of D2-40-positive lymph vessels in metastases was evaluated with two morphometric methods (Chalkley count and number per HPF). Data was explored with respect to TNM parameters, grading, tumor type, size of metastasis, lymph vessel number and hormone receptor/HER2 status with appropriate statistical tests. Lymphangiogenesis was detected exclusively in and around BC metastases with both methods for lymph vessel quantification being equivalent. Lymph vessel number correlated with the size of metastases, being significantly higher in larger metastases (p < 0.001). There was no significant statistical difference with respect to tumor types. Intranodal lymphangiogenesis could not be verified by D2-40 staining in any of the tumor-free lymph nodes examined. However, D2-40 was frequently detected in sinus endothelial/virgultar cells of the subcapsular sinus, partly with strong uniform positivity. Staining intensity and stained proportion of the subcapsular sinus were markedly heterogeneous, significantly correlating with each other both in SLN and NSLN (p < 0.001). A higher proportion of D2-40 stained subcapsular sinus in SLN was significantly associated with worse overall survival (p = 0.0036) and an independent prognostic parameter in multivariate analysis (p = 0.033, HR 2.87). Further studies are necessary to elucidate the biological and clinical significance of the observed immunophenotypic variations of nodal sinus endothelium., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Westhoff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sinonasal non-intestinal type adenocarcinoma (non-ITAC) is a heterogeneous category that may benefit from improved taxonomy. With the recognition that most non-ITAC are phenotypically seromucinous, stratification may be improved by applying salivary type morphologic criteria and molecular findings. We report two cases of papillary seromucinous adenocarcinoma with sinonasal papilloma-like surface components that show histologic and molecular features analogous to the salivary sialadenoma papilliferum family of tumors. Case 1 concerns a 50-year-old female who presented with a left anterior nasoethmoid polyp, while case 2 is that of a 74 year old female with nasal polyposis. Histologically, both cases demonstrated a surface transitional sinonasal papilloma-like component (more prominent in case 2) with a deeper bilayered glandular component showing papillary and tufted micropapillary growth of monomorphic columnar to cuboidal cells with eosinophilic cytoplasm. Case 1 also showed a deep cribriform/microcystic component. Immunostains showed a delimiting p63/p40 positive basal layer around the SOX-10 positive glandular elements, while the transitional sinonasal papilloma-like components were diffusely p63/p40 positive. Like sialadenoma papilliferum and related tumors, both cases demonstrated BRAF p.V600E mutations in both components and no other alterations. The patients remain disease free at 9 and 19 months respectively. Our cases illustrate a novel sinonasal lesion and suggest that improved morphologic and molecular categorization may refine and reduce the category of non-ITAC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Despite various solutions to the issue of ipsilateral vessel-depleted neck in microvascular head and neck reconstruction, concrete data on its safety and implementation are scarce. This paper focuses on the feasibility and success rates of contralateral anastomosis in free flap reconstruction in the head and neck region., Methods: This single-center retrospective study at a tertiary referral center includes all patients who underwent free flap reconstruction of the head and neck with contralateral anastomosis between January 1st, 2007 and February 28th, 2021. Primary objectives were frequency, success, and flap-associated complication rates. Secondary objectives were recipient vessels and flap type., Results: Of 318 patients who underwent microvascular reconstruction, anastomosis was performed on the contralateral side of the neck in 32 patients (10.0%). Recipient vessels involved mainly the superior thyroid artery (74.2%; n = 23) and the facial vein (51.1%; n = 23). Thirty patients (93.8%) received a radial forearm free flap. Flap-associated complications occurred in 12.5% of included cases (n = 4): one partial flap necrosis (3.1%), one anastomotic insufficiency (3.1%), one venous thrombosis of the microvascular pedicle (3.1%), and one wound dehiscence (3.1%). All of these complications were resolved without complete flap loss., Conclusion: This study demonstrates that contralateral anastomosis is a successful and safe option in microvascular head and neck reconstruction, especially using a radial forearm free flap. Thus, anastomosing to the contralateral side of the neck can be advocated as a valuable option in the ipsilateral vessel-depleted neck., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The aim of this study was to investigate and compare the histopathological findings in pleomorphic adenomas (PA) of the parotid and submandibular gland with emphasis on the histological subtype and capsular characteristics., Materials and Methods: The histopathological specimens of all patients with PAs of the parotid and submandibular gland between 2000 and 2020 were re-examined by an experienced head and neck pathologist. Patients without representative slides allowing evaluation of the whole periphery of the PA were excluded from our study sample., Results: Nine hundred and thirty-four patients formed our study sample (327 men, 607 women, male-to-female ratio: 0.53:1). Eight hundred and forty-four cases had a PA in the parotid gland and the remaining 90 in the submandibular gland. Our comparative analysis showed that submandibular PAs are characterized by the consistent presence of an intact anatomical capsule, infrequent occurrence of pseudopodia and satellite nodules, and a low proportion of the high-risk myxoid subtype., Conclusion: Our study highlights significant differences between PAs of the parotid and submandibular glands in their histopathological characteristics. Their differences likely underlie the favorable surgical outcome observed in PAs of the submandibular glands and may explain the propensity of PAs of the parotid glands for local recurrences., (© 2021 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Purpose: Salivary Gland cancer (SGC) is a rare and heterogenous group of tumors. Standard therapeutic options achieve high local but poor distant control rates, especially in high-grade SGC. The aim of this monocentric study was to evaluate patterns of recurrence and its treatment options (local ablative vs. systemic) in a homogenously treated patient population with high-grade SGC after surgery and radio(chemo)therapy., Methods: Monocentric, retrospective study of patients with newly diagnosed high-grade salivary gland cancer. We retrospectively reviewed clinical reports from 69 patients with high-grade salivary gland cancer in a single-center audit. Survival rates were calculated using the Kaplan-Meier method and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox regression analysis)., Results: The median time of follow-up was 31 months. After 5 years, the cumulative overall survival was 65.2%, cumulative incidence of local recurrence was 7.2%, whereas the cumulative incidence of distant metastases was 43.5% after 5 years. 30 of 69 patients developed distant metastases during the time of follow-up, especially patients with adenoid cystic carcinoma, salivary duct carcinoma, adenocarcinoma NOS and acinic cell carcinoma with high-grade transformation. The most common type of therapy therefore was chemotherapy (50%). 85.7% of patients with local ablative therapy of distant metastases show disease progression during follow-up afterwards., Conclusion: With surgery and radio-chemotherapy, a high rate of loco-regional control is reached, but over 40% of patients develop distant metastases in the further follow-up which usually present a diffuse pattern involving in a diffuse metastases. Therefore, in the future, intensified interdisciplinary combination therapies even in the first-line treatment in certain subtypes of high-grade SGC should be investigated., (© 2021. The Author(s).)

Introduction: The aim of this study was to evaluate the impact of subspecialised head and neck versus general surgical pathologists on the reliability of the histopathologic evaluation during intraoperative consultation. Materials and Methods: The medical records of all patients who underwent a parotidectomy with frozen section between 2006 and 2021 were retrospectively evaluated. The frozen section was evaluated for sensitivity, specificity, accuracy, and predictive value. Assessment by two groups of pathologists (subspecialised head and neck versus general surgical pathologists) was compared, and the nature or types of misdiagnoses compared with final diagnoses on paraffin sections were analysed for the two groups. Results: Our study sample was made up of 669 cases. The mean age of patients was 57.7 years (range: 10−94 years). Of these, 490 patients had a benign lesion (73.2%), whereas 179 patients had a malignant lesion (26.8%). Frozen section had an overall accuracy of 97.6%, sensitivity for malignancy was 91.1%, specificity was 100%, PPV was 100%, and the NPV was 96.8%. The exact histologic subtype in the group of malignant tumours was correctly identified in FS in 89.4% of cases. A comparison of head and neck pathologists versus general surgical pathologists revealed a highly statistically significant difference concerning both overall detection of malignancy (p < 0.001) as well as correct identification of the histologic subtype (p < 0.001). Conclusion: Involvement of subspecialised head and neck pathologists in the intraoperative consultation for salivary gland tumours results in a gain of 19.8% more sensitivity, underlining the importance of specialisation in salivary gland pathology for the optimisation of frozen section quality.

The aim of this study was to search for associations between an electrodiagnostically abnormal but clinically normal facial nerve before parotidectomy and the intraoperative findings, as well as the postoperative facial nerve function. The records of all patients treated for parotid tumors between 2002 and 2021 with a preoperative House-Brackmann score of grade I but an abnormal electrophysiologic finding were studied retrospectively. A total of 285 patients were included in this study, and 222 patients had a benign lesion (77.9%), whereas 63 cases had a malignant tumor (22.1%). Electroneurographic facial nerve involvement was associated with nerve displacement in 185 cases (64.9%) and infiltration in 17 cases (6%). In 83 cases (29.1%), no tumor-nerve interface could be detected intraoperatively. An electroneurographic signal was absent despite supramaximal stimulation in 6/17 cases with nerve infiltration and in 17/268 cases without nerve infiltration ( p < 0.001). The electrophysiologic involvement of a normal facial nerve is not pathognomonic for a malignancy (22%), but it presents a rather rare (~6%) sign of a "true" nerve infiltration and could also appear in tumors without any contact with the facial nerve (~29%). Of our cases, two thirds of those with an anatomic nerve preservation and facial palsy had already directly and postoperatively recovered to a major extent in the midterm.

Objectives/hypothesis: The aim of this study was to identify potential associations between epidemiologic, morphologic, and histopathologic features in pleomorphic adenomas (PAs) of the parotid gland in order to extract information about the natural course and biologic behavior of these lesions on the basis of a single-center series of 845 cases within a period of 15 years., Study Design: Retrospective study in a tertiary academic center., Methods: For this study, an experienced head and neck pathologist critically re-evaluated the histological slides of the pathological specimens of all patients who underwent a parotidectomy for PA of the parotid gland between 2006 and 2020., Results: A total of 845 cases made up our study sample. Our analysis showed a statistically significant association of the histologic subtype with younger age (P = .001) and maximal diameter (P = .044), with the hypocellular type being encountered more often in younger patients and in smaller lesions. The same subtype was significantly associated with an incomplete capsule (P = .001), pseudopodia (P = .006), and satellite nodules (P = .001). An incomplete capsule was associated with the presence of pseudopodia (P = .001) and satellite nodules (P = .001)., Conclusion: It seems that various histologic subtypes have different capsule-producing properties. Apparently, over the course of time, tumor material builds a finger-like projection still inside the capsule, separates itself from the parenchyma with fibrous tissue still remaining enclosed within the capsule (pseudopodium), slowly penetrates the capsule (incomplete capsule), and leaves the main lesion taking a part of the capsule with it (satellite nodules). Laryngoscope, 132:73-77, 2022., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The aim of this study was to investigate the histopathologic findings in parotid and parapharyngeal pleomorphic adenomas and draw conclusions concerning the surgical strategy., Methods: Retrospective study of medical charts of patients with resected pleomorphic adenomas (PA) between 2005 and 2020 at two tertiary medical referral centers. Histologic specimens were reexamined by an experienced head and neck pathologist. Patients with insufficient/incomplete data were excluded from our study sample., Results: A total of 844 patients formed our study sample (291 men, 553 women, average age 48.9 years); 786 cases had a PA in the parotid gland (PG) (93.1%), and the remaining 58 cases had a PA in the parapharyngeal space (PS) (6.9%). Recurrences were detected in 8/844 cases (7/786 in the PG, 1/58 in the PS, 0.94% in total) with a mean follow-up time of 86.7 months (10-189 months) with no statistically significant differences between the study groups ( p = 0.527). Our analysis showed that parapharyngeal pleomorphic adenomas are characterized by a lower incidence of an intact anatomical capsule (71.4% vs. 82.6%, p = 0.035) and a remarkably more frequent occurrence of satellite nodules (20.7% vs. 7.5%, p < 0.001)., Conclusions: The more challenging histopathologic profile of parapharyngeal pleomorphic adenomas points towards the fact that parapharyngeal surgery should remain in the hands of experienced surgeons at high-volume centers.

The aim of this study was to compare several surgical modalities with respect to the incidence of positive margins and focal capsular exposure of pleomorphic adenoma of the parotid gland. The clinical records and histopathological findings of all patients who underwent parotidectomy for pleomorphic adenoma between 2006 and 2020 were retrospectively evaluated (n = 845). The lesion was removed by extracapsular dissection in 577 cases (68%) and facial nerve dissection in 268 (32%). Our analysis did not reveal a statistically significant difference between the examined modalities regarding positive margins (p=0.648) or capsular exposure (p=0.112). Recurrences were detected in 7/845 cases (0.82%) with a mean (range) follow-up time of 82.3 (6-183) months. The choice of surgical method does not seem to have a significant effect on the incidence of positive margins, or on the capsular exposure of a pleomorphic adenoma., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Performing tympanoplasty for tympanic perforations in children and adolescents is often considered to be less successful than in adults., Objectives: The aim of our study was to evaluate the surgical outcome of tympanoplasty type I in patients under 15 years of age with chronic otitis media and to identify potential factors that influence the success rate., Materials Und Methods: The present study was based on a retrospective analysis of the medical records of all patients under the age of 15 who were treated for chronic otitis media by means of type I tympanoplasty between 2005 and 2020. The minimum follow-up period was 6 months. The data were analyzed with regard to epidemiological parameters, tube-related pathologies in the contralateral ear, the local condition and the extent of the eardrum perforation as well as the extent of the surgical intervention (tympanoplasty type I with or without adenotomy)., Results: 83 cases were included in our study. The mean age at the time of the surgery was 8.9 years. The mean follow-up time was 46 months (6-182 months). The anatomical closure rate was 88.0%. Children with "dry" tympanic perforations tended to perform better (p = 0.052). The average improvement in the air bone gap was 2.0 dB., Conclusion: Detailed preoperative counseling about the advantages and disadvantages as well as the expected success rate of an early myringoplasty in this age group is just as important as an individualized approach for a high level of patient satisfaction., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The aim of our study was to perform a comparative analysis in our cases with titanium partial clip ossiculoplasty in terms of audiometric outcome and extrusion rates as well as to review the literature for relevant information on this surgical issue., Materials and Methods: The records of all patients who had undergone primary partial ossiculoplasty with the implantation of a CliP® Partial Prosthesis Dresden Type (CPPDT, group A) or a CliP Partial FlexiBAL® (CPF, Group B, both Heinz Kurz GmbH, Dusslingen, Germany) between 2012 and 2020 were studied retrospectively., Results: 274 patients made up our study sample (148 men, 126 women, male to female ratio: 1.17). Their mean age at the time of first surgery was 39.6 years (range: 4-79 years). The mean preoperative air-bone gap (ABG) was 22.7dΒ ± 10.5 dB. Mean follow-up was approximately 4 months (1-12 months). The mean postoperative ABG was 15.7 ± 8.1 dB. In total, the postoperative ABG was significantly improved compared to preoperative values (P < 0.001). Surgical success, defined as an ABG ≤ 20 dB, was achieved in the majority of our study patients (210/274, 76.6%). Extrusion of the prosthesis was detected in 3/216 CPF and 5/58 CPPDT cases (p = 0.012). Comparison of both prosthesis groups revealed a significantly better audiological outcome for the patients with ossicular reconstruction using CPF. A significantly better audiological outcome was detected in the cases with a normal aeration of the middle ear., Discussion: Titanium clip partial ossiculoplasty is a reliable component of modern tympanoplasty, allowing a satisfying audiologic outcome. The higher adaptability of the CPF to the changing postoperative circumstances and the frequently defective aeration of the middle ear is reflected in the better audiologic outcome for this prosthesis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Erosion of the long process of the incus is the most common ossicular chain pathology occurring in the course of chronic middle ear disease. The aim of this study was to evaluate our experience in the reconstruction of short-length defects of the long process of the incus using hydroxyapatite bone cement over a period of 15 years., Methods: The medical records of all patients treated with hydroxyapatite bone cement for an isolated short-length erosion of the long process of the incus or the lenticular process at an academic tertiary referral center between 2005 and 2019 were studied retrospectively., Results: 48 patients made up our study sample (19 men, 29 women). The mean age at the time of surgery was 38.1 years. The mean preoperative air-bone gap (ABG) was 21.36 dB. The mean postoperative ABG was 15.89 dB within 8 weeks of surgery and 11.81 dB at least 6 months after surgery. The postoperative ABG had significantly improved compared to preoperative ABG values at both the short- and middle-term follow-up (p < 0.001 for both). An ABG ≤ 20 dB was achieved in 68% in the short term and 83% in the middle term. The mean ABG in the long term (< 12 months) was 11.1 dB., Conclusion: Restoration of the anatomic and functional continuity of the ossicular chain using hydroxyapatite cement in defects of the long process of the incus seems to warrant a satisfactory audiologic outcome in the majority of cases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction and Importance: Reports about laryngeal trauma and fractures of the hyoid bone are rare in the literature. Most cases are forensic cases and the results of postmortem analysis. Traumatic larynx and hyoid bone fractures represent a rare but important differential diagnosis of the common symptom hoarseness., Case Presentation: A 60-year-old female patient presented with unclear dysphonia and globus sensation following intubation for a surgical treatment for a lower leg fracture after a bicycle accident two months ago. Endoscopy and the computed tomography (CT) of the neck revealed a fixed and immobile fractured piece of the larynx, a hyoid bone fracture and a pseudarthrosis between the greater horn of the hyoid bone and the upper edge of the thyroid cartilage. The hyoid bone fracture led to a distortion of the supraglottis. After surgical removal of the fractured part of the hyoid bone and the pseudarthrosis separation, the supraglottis appeared symmetrical again. Four weeks after surgery the patient was symptom-free., Clinical Discussion: Though combined hyoid bone and larynx fractures after traumatic injuries are rare, they represent an important differential diagnosis in trauma patients with dysphagia or dysphonia. The clinical symptoms can vary and occur immediately or within a latent period taking weeks or months until the proper diagnosis. Depending on the symptoms, surgical management can be effective., Conclusion: An isolated partial resection of the hyoid bone with separation of the pseudarthrosis is a reasonable therapeutic option and can lead to completely resolving symptom. Preoperatively, a CT provides further valuable information., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Traditional surgical philosophy condemns extracapsular dissection for pleomorphic adenoma as a euphemism for the enucleation of this lesion., Objectives: The aims of the study were to trace the development of surgical treatment by pleomorphic adenomas of the parotid gland over the last 15 years and explore its effects on the histopathology specimen., Materials and Methods: The medical records of all cases with pleomorphic adenomas of the parotid gland between 2006 and 2020 were examined for information on age, gender, and type of surgery. An experienced head and neck pathologist re-evaluated the histology slides from all the cases., Results: The study included 844 patients. Our analysis showed an increase in the performance of extracapsular dissection from 52.8% (2006) to 63.3% (2020), and an increase in histopathology specimens with tumours completely covered by healthy tissue from 27.7% (2006) to 50% (2020)., Conclusions: Our decision-making process reached its peak in the last study years, in terms of reduced surgical invasiveness and quality of the pathology specimen., Significance: Extracapsular dissection has gained a firm hold as an indispensable tool for the experienced parotid surgeon. Proper indication is based on careful selection of cases and the correct interpretation of preoperative features on palpation and imaging.

Mucus consistency affects voice physiology and is connected to voice disorders. Nevertheless, the rheological characteristics of human laryngeal mucus from the vocal folds remain unknown. Knowledge about mucus viscoelasticity enables fabrication of artificial mucus with natural properties, more realistic ex-vivo experiments and promotes a better understanding and improved treatment of dysphonia with regard to mucus consistency. We studied human laryngeal mucus samples from the vocal folds with two complementary approaches: 19 samples were successfully applied to particle tracking microrheology (PTM) and five additional samples to oscillatory shear rheology (OSR). Mucus was collected by experienced laryngologists from patients together with demographic data. The analysis of the viscoelasticity revealed diversity among the investigated mucus samples according to their rigidity (absolute G' and G″). Moreover some samples revealed throughout solid-like character (G' > G″), whereas some underwent a change from solid-like to liquid-like (G' < G″). This led to a subdivision into three groups. We assume that the reason for the differences is a variation in the hydration level of the mucus, which affects the mucin concentration and network formation factors of the mucin mesh. The demographic data could not be correlated to the differences, except for the smoking behavior. Mucus of predominant liquid-like character was associated with current smokers., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Objectives: The aim of this study was to thoroughly investigate the incidence of satellite nodules (SN) and some of their characteristics (number, distance to main lesion) in a large series of pleomorphic adenomas (PA) and to compare several surgical modalities regarding their efficacy in addressing this critical morphological feature., Materials and Methods: The records of all patients treated for primary PA of the parotid gland between 2006 and 2020 were studied retrospectively. All the histological slides of all tumours were critically re-evaluated for this study by an experienced head and neck pathologist., Results: 845 cases made up our initial study sample. SNs were detected in 68/845 cases (8%). No statistically significant difference could be detected in the incidence of SNs in the surgical specimens between the patient groups managed by extracapsular dissection (46/577, 7.9%) and facial nerve dissecting surgery (22/268, 8.2%, p = 0.502). In the group of cases with SNs, no recurrences were detected (mean follow-up time: 71.4 months). The mean distance from the main lesion to the most distant SN was 1.1 mm (0.08-6.3 mm). The mean size of the SN was 1.9 mm (0.1-9.7 mm). Altogether, the mean distance from the main lesion to the outer periphery of the most distant SN was 3.1 mm (0.4-10.5 mm)., Conclusion: Our analysis could not award SNs the title of an "extracapsular dissection's nightmare". In the majority of cases, their favourable histological patterns offer the ideal circumstances for their surgical inclusion in a tumour specimen., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far., Methods: The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE., Results: Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were "weight change", "difficulty to grip things", "bloody or mucous stool" and "insomnia". Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire., Conclusion: Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on "weight change" and "insomnia" may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients., Trial Registration: ClinicalTrials.gov, NCT03453892 . Registered on 05 March 2018.

The aim of this study was to investigate sonographic findings of low-grade malignant tumors of the parotid gland. The sonographic findings of all patients treated for T1-T2 low-grade carcinomas of the parotid gland between 2003 and 2018 were retrospectively examined and compared with those of patients with pleomorphic adenomas for the following parameters: definition of tumor margins, echotexture, echogenicity, shape and vascularization. Statistical analysis was performed using the χ 2 test. A p value of <0.05 was considered statistically significant. A total of 310 patients (62 with T1-T2 low-grade malignant tumors, 248 with pleomorphic adenomas) were evaluated. Our analysis detected a statistically significant difference in the definition of margins, echotexture, echogenicity and shape. Furthermore, we could detect a specific pattern (anechoic islets in a small hypoechoic lesion with distal enhancement) appearing far more frequently in low-grade malignant lesions. It seems that there is still potential to reduce the incidence of the false working hypothesis "benign lesion" on imaging of low-grade malignant tumors., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The Radiative-Convective Equilibrium Model Intercomparison Project (RCEMIP) is an intercomparison of multiple types of numerical models configured in radiative-convective equilibrium (RCE). RCE is an idealization of the tropical atmosphere that has long been used to study basic questions in climate science. Here, we employ RCE to investigate the role that clouds and convective activity play in determining cloud feedbacks, climate sensitivity, the state of convective aggregation, and the equilibrium climate. RCEMIP is unique among intercomparisons in its inclusion of a wide range of model types, including atmospheric general circulation models (GCMs), single column models (SCMs), cloud-resolving models (CRMs), large eddy simulations (LES), and global cloud-resolving models (GCRMs). The first results are presented from the RCEMIP ensemble of more than 30 models. While there are large differences across the RCEMIP ensemble in the representation of mean profiles of temperature, humidity, and cloudiness, in a majority of models anvil clouds rise, warm, and decrease in area coverage in response to an increase in sea surface temperature (SST). Nearly all models exhibit self-aggregation in large domains and agree that self-aggregation acts to dry and warm the troposphere, reduce high cloudiness, and increase cooling to space. The degree of self-aggregation exhibits no clear tendency with warming. There is a wide range of climate sensitivities, but models with parameterized convection tend to have lower climate sensitivities than models with explicit convection. In models with parameterized convection, aggregated simulations have lower climate sensitivities than unaggregated simulations., (©2020. The Authors.)

The aim of the present study was to determine whether free thyroxine (FT4) and calculated thyroid parameters predict the incidence of ventricular arrhythmias in euthyroid heart failure patients with implantable cardioverter-defibrillators (ICD). In this open-label prospective cohort study, 115 consecutive euthyroid patients (mean age 62.9 ± 1.3 years; 87% male; ischemic cardiomyopathy 63%) scheduled for primary prevention ICD implantation or exchange were enrolled. Serum concentrations of thyrotropin (thyroid-stimulating hormone) and FT4 were measured 1 day before device operation. Primary and secondary end points were defined as occurrence of appropriate ICD therapy (AIT) and cardiovascular death, respectively. During a mean follow-up of 1,191 ± 35 days, 24 patients (21%) experienced AIT, and cardiovascular death was observed in 10 patients (9%). Patients with AIT had higher FT4 concentrations compared with those without AIT (18.9 ± 0.48 vs 16.2 ± 0.22 pmol/L, p <0.001). FT4 was an independent predictor of AIT in an adjusted Cox regression (hazard ratio = 1.47, p <0.001). Kaplan-Meier analysis demonstrated that Jostel's thyroid-stimulating hormone index, reflecting the central component of the hypothalamus-pituitary-thyroid loop, and SPINA-GT as surrogate markers for thyroid's secretory capacity predicted AIT incidences. None of the indices predicted cardiovascular death. In conclusion, FT4 concentration predicts an increased incidence of ventricular arrhythmias in euthyroid patients receiving ICDs for primary prevention. Our data suggest that both impending primary hyperthyroidism and an increased thyroid homeostasis set point may increase the rate of AIT in this patient population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: A critical factor for the efficacy of drugs is their availability at the site of interest. However, crossing endothelial and epithelial cell layers like the blood-brain barrier and the blood-intestinal barrier represents a major bottleneck for drug targeting. Coupling drugs to carriers that recognize endogenous receptors, which are then transported through cell layers by transcytosis, is a promising approach to overcome this bottleneck. Areas covered: This review focuses on the intracellular pathways of receptor-mediated transcytosis and their applicability for transcellular drug delivery. It gives an overview about transcytotic trafficking routes in epithelia and highlights the well-studied examples of immungobulin transcytosis and transferrin transcytosis. The current knowledge about the less understood transcytosis pathways in endothelia is also summarized and low-density lipoprotein transcytosis is described. In addition, transcytosis pathways that are based on glycosphingolipids and lectins as their receptors are presented. Expert opinion: Multiple transcellular drug delivery approaches based on proteinaceous receptors have been developed in recent years, whereas lectins that bind to glycosphingolipids emerge as promising alternative. Closer investigation of endogenous transcytosis mechanisms, especially in endothelia, will be a fruitful endeavor to devise more optimized carriers for transcytotic drug delivery.

Objectives: Epithelial cell layers as well as endothelia forming the blood-brain barrier can drastically reduce the efficiency of drug targeting. Our goal was to investigate lectins recognizing the glycosphingolipid globotriaosylceramide (Gb3) for their potential as carriers for transcytotic drug delivery., Methods: We utilized an in vitro model based on Madin-Darby canine kidney cells transfected with Gb3 synthase to characterize transcytosis of the Gb3-binding lectins LecA from Pseudomonas aeruginosa and the B-subunit of Shiga toxin (StxB)., Results: Both lectins were rapidly transcytosed from the apical to the basolateral plasma membrane and vice versa. Whereas StxB proceeded on retrograde and transcytotic routes, LecA avoided retrograde transport. This differential trafficking could be explained by our observation that LecA and StxB segregated into different domains during endocytosis. Furthermore, inhibiting the small GTPase Rab11a, which organizes trafficking through apical recycling endosomes, blocked basolateral to apical transcytosis of both lectins., Conclusions: Gb3-binding lectins are promising candidates for transcytotic drug delivery. Our findings highlight that LecA and StxB, which both bind Gb3 but exhibit dissimilar valence and molecular structures of their carbohydrate binding sites and can take divergent intracellular trafficking routes. This opens up the possibility of developing tailor-made glycosphingolipid-binding carrier lectins, which take optimized trafficking pathways.

Household sand filters are applied to treat arsenic- and iron-containing anoxic groundwater that is used as drinking water in rural areas of North Vietnam. These filters immobilize poisonous arsenic (As) via co-oxidation with Fe(II) and sorption to or co-precipitation with the formed Fe(III) (oxyhydr)oxides. However, information is lacking regarding the effect of the frequency and duration of filter use as well as of filter sand replacement on the residual As concentrations in the filtered water and on the presence of potentially pathogenic bacteria in the filtered and stored water. We therefore scrutinized a household sand filter with respect to As removal efficiency and the presence of fecal indicator bacteria in treated water as a function of filter operation before and after sand replacement. Quantification of As in the filtered water showed that periods of intense daily use followed by periods of non-use and even sand replacement did not significantly (p<0.05) affect As removal efficiency. The As concentration was reduced during filtration from 115.1 ± 3.4 μg L(-1) in the groundwater to 5.3 ± 0.7 μg L(-1) in the filtered water (95% removal). The first flush of water from the filter contained As concentrations below the drinking water limit and suggests that this water can be used without risk for human health. Colony forming units (CFUs) of coliform bacteria increased during filtration and storage from 5 ± 4 per 100mL in the groundwater to 5.1 ± 1.5 × 10(3) and 15 ± 1.4 × 10(3) per 100mL in the filtered water and in the water from the storage tank, respectively. After filter sand replacement, CFUs of Escherichia coli of <100 per 100mL were quantified. None of the samples contained CFUs of Enterococcus spp. No critical enrichment of fecal indicator bacteria belonging to E. coli or Enterococcus spp. was observed in the treated drinking water by qPCR targeting the 23S rRNA gene. The results demonstrate the efficient and reliable performance of household sand filters regarding As removal, but indicate a potential risk for human health arising from the enrichment of coliform bacteria during filtration and from E. coli cells that are introduced by sand replacement., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Mitochondrial dysfunction has been strongly implicated in the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD), but its relation to protein aggregation is unclear. PD is characterized by synuclein aggregation (i.e., Lewy body [LB] formation). In AD, the abnormal accumulation of tau protein forms neurofibrillary tangles. In this study, we laser-dissected LB-positive and -negative neurons from the substantia nigra of postmortem PD brains, and tau-positive and -negative hippocampal neurons from AD brains. We quantified mitochondrial DNA deletions in relation to the cellular phenotype and in comparison with age-matched controls. Deletion levels were highest in LB-positive neurons of PD brains (40.5 ± 16.8%), followed by LB-negative neurons of PD cases (31.8 ± 14.4%) and control subjects (25.6 ± 17.5%; analysis of variance p < 0.005). In hippocampal neurons, deletion levels were 25%-30%, independent of disease status and neurofibrillary tangles. The presented findings imply increased mitochondrial DNA damage in LB-positive midbrain neurons, but do not support a direct causative link of respiratory chain dysfunction and protein aggregation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Deletions of the mitochondrial DNA (mtDNA) accumulate to high levels in dopaminergic neurons of the substantia nigra pars compacta (SNc) in normal aging and in patients with Parkinson's disease (PD). Human nigral neurons characteristically contain the pigment neuromelanin (NM), which is believed to alter the cellular redox-status. The impact of neuronal pigmentation, neurotransmitter status and brainstem location on the susceptibility to mtDNA damage remains unclear. We quantified mtDNA deletions (ΔmtDNA) in single pigmented and non-pigmented catecholaminergic, as well as non-catecholaminergic neurons of the human SNc, the ventral tegmental area (VTA) and the locus coeruleus (LC), using laser capture microdissection and single-cell real-time PCR., Results: In healthy aged individuals, ΔmtDNA levels were highest in pigmented catecholaminergic neurons (25.2 ± 14.9%), followed by non-pigmented catecholamergic (18.0 ± 11.2%) and non-catecholaminergic neurons (12.3 ± 12.3%; p < 0.001). Within the catecholaminergic population, ΔmtDNA levels were highest in dopaminergic neurons of the SNc (33.9 ± 21.6%) followed by dopaminergic neurons of the VTA (21.9 ± 12.3%) and noradrenergic neurons of the LC (11.1 ± 11.4%; p < 0.001). In PD patients, there was a trend to an elevated mutation load in surviving non-pigmented nigral neurons (27.13 ± 16.73) compared to age-matched controls (19.15 ± 11.06; p = 0.052), but levels where similar in pigmented nigral neurons of PD patients (41.62 ± 19.61) and controls (41.80 ± 22.62)., Conclusions: Catecholaminergic brainstem neurons are differentially susceptible to mtDNA damage. Pigmented dopaminergic neurons of the SNc show the highest ΔmtDNA levels, possibly explaining the exceptional vulnerability of the nigro-striatal system in PD and aging. Although loss of pigmented noradrenergic LC neurons also is an early feature of PD pathology, mtDNA levels are not elevated in this nucleus in healthy controls. Thus, ΔmtDNA are neither an inevitable consequence of catecholamine metabolism nor a universal explanation for the regional vulnerability seen in PD.

Acupuncture is able to improve restriction of motion in general and in the smaller joints of the upper extremity, disturbances in circulation, posttraumatic swelling, reversible nerve lesions and ulcers following burns or pressure of a plaster. Localisation of the points for acupuncture in the different conditions and the possibilities of their combinations are described. Acupuncture is performed bilaterally at symmetrical points, unilaterally in pareses, contralaterally in amputees and in cases with dressings. During ear acupuncture the analgesic effect occurs more quickly, but has a shorter duration of action; in paralyses it was without success. The course of the treatment was controlled by clinical examination and measurement of the range of motion.