Digital live imaging of intraoperative electrocochleography during cochlear implantation: the first 50 patients.

INTRODUCTION: Real-time visualization of intraoperative electrocochleography (ECochG) potentials via a digital microscope during cochlear implantation can provide direct feedback during electrode insertion. The aim of this prospective, randomized study of 50 patients was to obtain long-term data with a focus on residual hearing preservation and speech understanding. MATERIAL AND METHODS: Cochlear implantations were performed in 50 patients (26 female, 24 male) with residual hearing using a digital microscope. Patients were randomized into two groups. Intraoperative ECochG potentials were either displayed directly in the surgeon's field of view (picture-in-picture display, PiP) or not directly in the field of view (without picture-in-picture display, without PiP). Residual hearing preservation and speech comprehension were recorded within a 1-year follow-up period, compared between groups (PiP versus without PiP) and to a control group of 26 patients implanted without ECochG. RESULTS: Mean insertion time was significantly longer in the picture-in-picture group (p = 0.025). Residual hearing preservation after 6 weeks at 250 Hz was significantly better in the picture-in-picture group (p = 0.017). After one year, 76% of patients showed residual hearing in the picture-in-picture group (62% without picture-in-picture technique, p = n.s.). Use of the picture-in-picture technique resulted in better long-term pure tone residual hearing preservation at 250, 500, and 1000 Hz. Speech intelligibility improved by 46% in the picture-in-picture group (38% without picture-in-picture). DISCUSSION: This study is the first to describe long-term results in a large cohort of cochlear implant patients in whom digital visualization of intraoperative ECochG was used. Our results show that visualization of intraoperative ECochG has a positive effect on residual hearing preservation.

Muscular tension in ear surgeons during cochlear implantations: does a new microscope improve musculoskeletal complaints?

PURPOSE: Musculoskeletal complaints and fatigue are commonly described symptoms in daily work of ear nose and throat surgeons using a microscope. Long ear surgical procedures are associated with prolonged microscope use, which can lead to unconsciously tense and uncomfortable body posture. The digital microscope RoboticScope® allows visualization of surgical site through a Head-Mounted Display, independent from camera head and is therefore much easier on the back, as the sitting position can be adjusted flexibly. Aim of the prospective study was to investigate to what extent the use of a RoboticScope® changes the tension of neck and shoulder muscles of the surgeons in comparison to a conventional tripod microscope. METHODS: For this purpose, the electric activity of neck and shoulder muscles of surgeons was recorded using surface electromyography during cochlear implantations. Electrical potentials were derived via electrodes on neck and shoulder muscles. The basic tension of those muscles was measured in relaxed position before and after surgery. During microscope use the tension was continued to be measured. A questionnaire recorded parameters such as level of difficulty of operation as well as patient data. RESULTS: Results from 58 operations, 33 of which were performed using a conventional microscope and 25 using a Head-Mounted Display, show a significant reduction in muscular tension during surgery by 40% (p < 0.001) in experienced ear surgeons when using a RoboticScope®, regardless of the surgeon. CONCLUSION: Our results are in line with the relevance of preventive measures to avoid acute and chronic work-related illnesses/symptoms described in literature.

Two different methods to digitally visualize continuous electrocochleography potentials during cochlear implantation: a first description of feasibility.

PURPOSE: The study explores the potential of real-time electrocochleographic potentials (ECochG) visualization during electrode insertion using digital microscopes such as RoboticScope (BHS®). Collaborative software development of the MAESTRO Software (MED-EL®) offers continuous ECochG monitoring during implantation and postoperative hearing evaluation, addressing previous time constraints. The study aims to assess software applicability and the impact of real-time visualization on long-term residual hearing preservation. METHODS: Eight patients with residual hearing underwent cochlear implantation with Flex26 or Flex28 electrode according to the Otoplan evaluation. ECochG responses were measured and visualized during electrode insertion, with insertion times recorded. Two randomized display methods (graph and arrows) tracked ECochG potentials. Postoperative behavioral thresholds determined hearing preservation. Successful real-time intraoperative ECochG visualization was achieved in all cases, enabling surgeon adaptation. Mean electrode insertion time was 114 s, with postoperative thresholds comparable to preoperative values. Visualization did not affect surgeon workload. ECochG amplitudes differed between patients with and without residual hearing. CONCLUSION: The study demonstrates effective implementation of advanced ECochG software combined with real-time visualization, enabling residual hearing preservation during CI. Visualization had no apparent effect on surgeon performance or workload. Future investigation involving a larger population will assess the long-term impact of ECochG on hearing threshold and structure preservation.

Bacterial biofilm formation on headpieces of Cochlear implants.

INTRODUCTION: Bacterial biofilm formation on medical devices, such as Cochlear implants (CI), can lead to chronic infections. Not only the inner parts of the implant but also the externally located headpiece might be associated with prolonged superficial skin eczema resulting in the inability of wearing the headpiece. In this study, the surface of three CI headpieces from different manufacturers were examined for bacterial biofilm formation. MATERIALS AND METHODS: Two bacterial species associated with implant-related infections were tested: Pseudomonas aeruginosa (ATCC9027) and Staphylococcus aureus (ATCC6538). Biofilms were formed over 24 h in tryptic soy broth at 36 °C. Biofilm formation was detected in form of biomass measurement by crystal violet staining. CI headpiece dummies of three manufacturers were used. RESULTS: Both tested bacterial species formed biofilms on the examined CI headpiece-surfaces in a species-dependent manner with higher biofilm formation of P. aeruginosa. For both, S. aureus and P. aeruginosa, biofilm formation on the CI components was comparable to a polystyrene control surface. Between the three manufacturers, no significant difference in biofilm formation was found. DISCUSSION: The tested bacteria displayed biofilm formation on the CI headpieces in a species-specific manner with higher amount of biofilm formed by P. aeruginosa. The biofilm formation was comparable between the manufacturers. In this study, an enhanced biofilm formation on CI headpieces could not be demonstrated. These in vitro tests suggest a minor role of bacterial biofilm on the CI headpiece in skin infections under the CI headpiece.

Comparative Analysis of Fistula Development After Parotid Gland Surgery: Lateral Parotidectomy Versus Extracapsular Dissection Technique.

PURPOSE: The primary objective of this study was to explore the potential disparity in postoperative fistula occurrence rates between patients who undergo (partial) lateral parotidectomy and those who undergo the extracapsular dissection technique for the management of benign parotid gland tumours. METHODS: A consecutive series of 363 patients treated with (partial) lateral parotidectomy and extracapsular dissection technique for benign parotid gland tumours at one tertiary centre between 2018 and 2022 were included. To evaluate the impact of the surgical technique and possible other risk factors (tumour location, tumour size, Body Mass Index, age, smoking, diabetes mellitus, arterial hypertension) for the development of fistulas, multivariate logistic regression analyses using backward lection were applied to estimate odds ratios (ORs) and 95%-confidence intervals (CIs). RESULTS: In 363 patients, 21 patients (5.8%) developed a fistula. Patients who underwent (partial) lateral parotidectomy had three times higher chance of developing a fistula compared to patients who were operated using the extracapsular dissection technique (ORadjusted = 2.6, 4.1% vs. 12.5%, p = 0.044). In the multivariate analyses, no other risk factors for the development of fistulas were statistically significant in this cohort. The incidence of facial nerve paralysis was not significantly different between the extracapsular dissection and lateral parotidectomy group (5/73 = 6.8% vs. 11/290 = 3.8%, p = 0.333). CONCLUSION: Fistulas occur more often in patients treated by means of a (partial) lateral parotidectomy approach compared to patients treated using the extracapsular dissection technique. Therefore, surgeons should be vigilant about postoperative fistula risks in lateral parotidectomy and consider preventive measures.

[Increased rate of complications of pediatric acute otitis media and sinusitis in 2022/2023]. / Häufung von Komplikationen der akuten Otitis media und Sinusitis bei Kindern 2022/2023.

BACKGROUND: Acute mastoiditis and orbital complications of acute rhinosinusitis are among the most common complications of pediatric infections in otolaryngology. OBJECTIVE: The aim of this study was to investigate the frequency of pediatric acute mastoiditis in the setting of acute otitis media as well as pediatric orbital complications in the setting of acute rhinosinusitis. Data from before the pandemic were compared to data after the end of the COVID-19 restrictions. MATERIALS AND METHODS: Included were hospitalized children who presented with acute mastoiditis from acute otitis media or with orbital complications from acute rhinosinusitis during the period from April 2017 to March 2023. Compared were three periods using descriptive statistics: April 2017 to March 2020 (before the pandemic in Germany), April 2020 to March 2022 (during the contact restrictions of the pandemic), and April 2022 to March 2023 (after the contact restrictions were lifted). RESULTS: A total of 102 children (43 with acute mastoiditis, 42%, and 59 with orbital complications of acute sinusitis, 58%) were included. During the 2022/2023 period, more than twice as many children with acute mastoiditis and approximately three times as many children with orbital complications of acute rhinosinusitis were hospitalized compared to the average of the periods 2017/2018, 2018/2019, and 2019/2020. In the 2021/2022 period, the number of these patients was below the average of previous years. CONCLUSION: This year's seasonal cluster of upper respiratory tract infections is associated with a higher-than-average incidence of orbital complications and mastoiditis.

Crossing Borders: 95. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie vom 8. bis 11. Mai 2024 in Essen. / Crossing Borders: 95. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie vom 8. bis 11. Mai 2024 in Essen.

Dear colleagues,Dear readers,We are constantly developing innovative solutions and treatment concepts for our patients in our discipline. In this context, interdisciplinary collaboration is essential. The conference motto "Crossing Borders: interdisciplinary, international, interactive" of the 95th Annual Meeting of the German Society of Otorhinolaryngology, Head and Neck Surgery emphasizes the relevance of interdisciplinary cooperation and global exchange. This year, joint meetings with the European Laryngological Society (ELS) and the Rhinoplasty Society of Europe (RSE) will take place for the first time. The American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) and the Confederation of European Otorhinolaryngology - Head and Neck Surgery (CEORL-HNS) are also involved in the scientific program. The interdisciplinary presentations offer insights into the most recent developments in the fields of head and neck oncology, skull base and orbital surgery, among others. They are a great opportunity to expand your own knowledge and exchange the latest research findings.

[Results of a survey on the current management of chronic rhinosinusitis with nasal polyps in Germany]. / Ergebnisse einer Umfrage zur aktuellen Behandlung der chronischen Rhinosinusitis mit nasalen Polypen.

INTRODUCTION: With a prevalence of 0.55% to 4%, chronic rhinosinusitis with nasal polyps (CRSwNP) is a relevant part of the daily work of German otolaryngologists. The aim of the questionnaire-based data collection was to assess the current treatment status of CRSwNP in Germany. MATERIAL AND METHODS: For this purpose, 24 questions within an anonymized online questionnaire were sent to all German ENT departments. RESULTS: Of 160 contacted ENT departments, 50 participated in the survey (31.3%). Among these, 76% performed more than 100 sinus surgeries annually and 38% treated more than 50 patients with biologics. Saline irrigations (80%) and intranasal glucocorticoids (GCS, 96%) were the most common conservative therapies. Systemic GCSs (52%) and intranasal GCS irrigation (20%) were less common. 80% of departments used biologics in the therapy of CRSwNP with an overall preference for dupilumab (70%). For therapy of aspirin intolerance, biologics (52%) were preferred to aspirin desensitization (26%). Prior to treatment with biologics clinical workup included the nasal polyp score (90%), the SNOT-22 questionnaire (84%), surrogate markers of type 2 inflammation (60%-72%), and computer tomography (50%). Final treatment success was assessed after 24 weeks (50%). CONCLUSION: Mostly, the responding departments followed German and European recommendations for diagnosis and therapy of CRSwNP. Therapy with biologics is widely used. The value of preoperative systemic GCS and the frequent performance of CT before initiation of therapy with a biologic should be debated in regard to its currently widespread use.

[Nodal metastasis and value of neck dissection in T1/2 oropharyngeal and hypopharyngeal carcinomas]. / Nodale Metastasierung und Stellenwert der Neck Dissection bei T1/2-Oro- und Hypopharynxkarzinomen.

BACKGROUND: Due to heterogeneous data, the indication for elective neck dissection (END) in patients with squamous cell carcinoma of the hypopharynx and oropharynx (HPSCC and OPSCC) in stages T1/2N0 is somewhat unclear. Therefore, in this multicenter study, we performed detailed analysis of the metastatic behavior of HPSCC and OPSCC. MATERIAL AND METHODS: The nodal metastatic patterns of 262 HPSCC and OPSCC patients who had undergone surgery was retrospectively investigated. In addition, recurrence-free and overall survival were recorded. Furthermore, a systematic literature review on the topic was completed. RESULTS: In patients with HPSCC, a discrepancy between clinical and pathologic N status was recorded in 62.1% of patients vs. 52.4% for p16- OPSCC, and 43.6% for p16+ OPSCC. The occult metastasis rate in cT1/2cN0 primary tumors was 38.9% for HPSCC vs. 17.8% (p16- OPSCC) and 11.1% (p16+ OPSCC). Contralateral metastases occurred in 22.2% of cases for HPSCC at stages cT1/2cN0, compared to only 9.1% for p16- OPSCC, and 0% for p16+ OPSCC patients.Patients with p16+ OPSCC had better recurrence-free and overall survival than p16- OPSCC and HPSCC patients. A direct association between patient survival and the extent of neck surgical therapy could not be demonstrated in our patients. CONCLUSION: Patients with HPSCC are at risk for bilateral neck metastases from stage cT1/2cN0, justifying bilateral END. Patients with T1/2 OPSCC present with occult metastases ipsilaterally in >20% of cases; however, the risk for contralateral occult metastasis is <10%. Hence, in strictly lateralized cT1/2CN0 tumors, omission of contralateral END may be considered.

HPV-associated head and neck cancer is characterized by distinct profiles of CD8+ T cells and myeloid-derived suppressor cells.

Patients with HPV--localized head and neck cancer (HNC) show inferior outcomes after surgery and radiochemotherapy compared to HPV-associated cancers. The underlying mechanisms remain elusive, but differences in immune status and immune activity may be implicated. In this study, we analyzed immune profiles of CD8+ T cells and myeloid-derived suppressor cells (MDSC) in HPV+ versus HPV- disease.The overall frequency of CD8+ T cells was reduced in HNC versus healthy donors but substantially increased after curative therapy (surgery and/or radiochemotherapy). In HPV+ patients, this increase was associated with significant induction of peripheral blood CD8+/CD45RA-/CD62L- effector memory cells. The frequency of HPV-antigen-specific CD8+ cells was low even in patients with virally associated tumors and dropped to background levels after curative therapy. Pre-therapeutic counts of circulating monocytic MDSC, but not PMN-MDSC, were increased in patients with HPV- disease. This increase was accompanied by reduced fractions of terminally differentiated CD8+ effector cells. HPV- tumors showed reduced infiltrates of CD8+ and CD45RO+ immune cells compared with HPV+ tumors. Importantly, frequencies of tumor tissue-infiltrating PMN-MDSC were increased, while percentages of Granzyme B+ and Ki-67+ CD8 T cells were reduced in patients with HPV- disease.We report differences in frequencies and relative ratios of MDSC and effector T cells in HPV- HNC compared with more immunogenic HPV-associated disease. Our data provide new insight into the immunological profiles of these two tumor entities and may be utilized for more tailored immunotherapeutic approaches in the future.

Cognitive deficits in patients with peripheral vestibular dysfunction.

BACKGROUND AND PURPOSE: Previous studies demonstrated cognitive deficits in patients with peripheral vestibulopathy (PVP) with dysfunction of spatial navigation and orientation, but also documented cognitive decline in nonspatial abilities. This study evaluates cognitive deficits in patients with unilateral vestibulopathy (UVP) as well as bilateral vestibulopathy (BVP) in multiple cognitive domains using common screening tests to reliably detect these deficits in clinical practice. METHODS: This prospective study compared patients with UVP and BVP to age- and sex-matched healthy controls (HC). Tests included the Alzheimer's Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Trail Making Test Part A and B, Clock Drawing Task, Executive Interview-25 (EXIT25), Dementia Detection (DemTect), and the Judgment of Line Orientation (JLO). The Montgomery-Åsberg Depression Rating Scale was used to control for depression. Videonystagmography objectively reconfirmed PVP. The Vertigo Symptoms Scale and the Dizziness Handicap Inventory were used to assess for symptom severity and restrictions of activities of daily living. RESULTS: Eighty-one patients (65 UVP, 16 BVP) were compared to 55 HC. Patients showed impairment in ADAS, MMSE, DemTect, EXIT25, and JLO. No differences between UVP and BVP were detected. The relative risk (RR) estimates of developing cognitive deficits following PVP were increased. The RR for the ADAS was higher in BVP (RR = 4.91, 95% confidence interval [CI] = 1.87-12.9, p = 0.001) than in UVP (RR = 3.75, 95% CI = 1.65-8.51, p = 0.002), but was similar for the MMSE and DemTect between groups. CONCLUSIONS: Patients with PVP showed deficits in multiple cognitive domains including nonspatial cognitive abilities. Vestibulopathy could be a risk factor for the development of cognitive impairment.

Visualizing Contralateral Suppression of Hearing Sensitivity via Acoustic and Electric Brainstem Audiometry in Bimodal Cochlear Implant Patients: A Feasibility Study.

INTRODUCTION: The medial olivocochlear reflex (MOCR) is a part of the binaural processing strategies and influences the efferent auditory pathway in normal-hearing individuals. Patients with asymmetric hearing loss often benefit from a bimodal hearing solution with a cochlear implant (CI) and a hearing aid (HA). However, hearing performances may vary with some surprisingly high- or low-performing CI/HA users. A potential role of the MOCR among these patients warrants further investigation. Otoacustics emissions are an established method to visualize the reflex; however, this technique implies some disadvantages. To visualize the MOCR via auditory brainstem response (ABR) could be a promising alternative. METHODS: Twenty-three bimodal CI/HA users were enrolled. Experimental setup was as follows: I. electrical ABR on the CI side was recorded with and without simultaneous contralateral noise signal at the HA side, II. acoustic ABR was recorded on the HA side with and without simultaneous contralateral noise at the CI side. Brainstem thresholds and amplitudes of waveforms I-V with and without contralateral noise were compared. Potential correlations of patient-related factors and hearing performances were analysed. RESULTS: In four individuals, a reduction of brainstem audiometry thresholds could be observed at the acoustic brainstem audiometry. In these cases, results could be reproduced. Summarizing ABR measurements at the HA side of all individuals, no relevant changes of ABR thresholds (dB nHL) or waveform amplitude reductions (nV) could be observed irrespective of the presence or absence of a contralateral suppression signal. CONCLUSION: Threshold changes of acoustic ABR upon presentation of a contralateral suppression signal could not generally be measured in bimodal CI users. However, in a subgroup, a highly reproducible effect was demonstrated if a contralateral suppression signal was applied. A reactivated rather than rehabilitated MOCR may have accounted for this effect in this subgroup. One could speculate that in these patients, bimodal fitting could be affected by the MOCR efferents.

S2k Guideline - Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - Update 2022.

Merkel cell carcinoma (MCC, ICD-O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear. MCC appears clinically as a reddish to purple spherical tumor with a smooth, shiny surface and a soft to turgid, elastic consistency, usually showing rapid growth. Spontaneous and often complete regressions of the tumor are observed. These likely immunologically-mediated regressions explain the cases in which only lymph node or distant metastases are found at the time of initial diagnosis and why the tumor responds very well to immunomodulatory therapies even at advanced stages. Due to its aggressiveness, the usually given indication for sentinel lymph node biopsy, the indication of adjuvant therapies to be evaluated, as well as the complexity of the necessary diagnostics, clinical management should already be determined by an interdisciplinary tumor board at the time of initial diagnosis.

[Results of a nationwide survey on the treatment of salivary gland diseases in German hospitals]. / Ergebnisse einer deutschlandweiten Umfrage zur Behandlung von Speicheldrüsenerkrankungen im Krankenhaus.

BACKGROUND: Salivary gland diseases are an important part of the work of ENT physicians in hospitals. The treatment strategies depend, among other things, on the doctrine at the respective location. OBJECTIVE: The aim of this questionnaire-based study was to assess the current diagnostic workup and therapeutic strategies for salivary gland diseases in German otorhinolaryngology departments. MATERIALS AND METHODS: A survey was performed using a 25-question online questionnaire sent to all German otorhinolaryngology department directors. RESULTS: The questionnaire was answered by 92 of 175 otorhinolaryngology departments (52.6%). In the diagnosis of salivary gland tumors, a dominance of sonography and MRI was shown. Fine- and core-needle aspiration were not performed by more than 50% of the clinics. The dominant technique for parotidectomy was under microscopic control (82%). In 99% of clinics, EMG was used during resection of the parotid gland for intraoperative monitoring of the facial nerve. There was a trend towards performing partial parotidectomies (85%), lateral parotidectomies (70%), and extracapsular dissections (57%) for benign tumors of the parotid gland. The treatment concepts for malignant tumors were inconsistent. CONCLUSION: In particular, the treatment strategy and extent of surgery for benign and malignant salivary gland tumors differed depending on location. The choice of palliative (drug) therapy was also diverse. Prospective multicenter studies could help to develop evidence-based treatment strategies.

[Recommendations of the German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) for the granting of resident training program authorizations]. / Empfehlungen der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC) für die Erteilung der fachspezifischen Weiterbildungsbefugnis.

The 2018 template for otorhinolaryngology specialist training of the German Medical Association is increasingly implemented by the federal associations. In this regard, the German Society recommended an otorhinolaryngology resident training plan for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) together with the Professional Association of German Otorhinolaryngologists as a suggested guideline for the federal medical associations. In this context, the state medical associations currently work on criteria on the basis of which otorhinolaryngologists and their training institutions can be granted authority for such a certified otorhinolaryngology resident training program.The DGHNO-KHC last made recommendations for the granting of authorizations for specialist training in otorhinolaryngology in 1999. Many contents have changed as a result of the 2018 model specialist training regulations. Therefore, a scientifically formulated proposal for the granting of continuing education authorizations is herewith provided as recommendation to the federal state medical associations.

SIRT1-mediated deacetylation of FOXO3a transcription factor supports pro-angiogenic activity of interferon-deficient tumor-associated neutrophils.

Angiogenesis plays an important role during tumor growth and metastasis. We could previously show that Type I interferon (IFN)-deficient tumor-associated neutrophils (TANs) show strong pro-angiogenic activity, and stimulate tumor angiogenesis and growth. However, the exact mechanism responsible for their pro-angiogenic shift is not clear. Here, we set out to delineate the molecular mechanism and factors regulating pro-angiogenic properties of neutrophils in the context of Type I IFN availability. We demonstrate that neutrophils from IFN-deficient (Ifnar1-/- ) mice efficiently release pro-angiogenic factors, such as VEGF, MMP9 or BV8, and thus significantly support the vascular normalization of tumors by increasing the maturation of perivascular cells. Mechanistically, we could show here that the expression of pro-angiogenic factors in neutrophils is controlled by the transcription factor forkhead box protein O3a (FOXO3a), which activity depends on its post-translational modifications, such as deacetylation or phosphorylation. In TANs isolated from Ifnar1-/- mice, we observe significantly elevated SIRT1, resulting in SIRT1-mediated deacetylation of FOXO3a, its nuclear retention and activation. Activated FOXO3a supports in turn the transcription of pro-angiogenic genes in TANs. In the absence of SIRT1, or after its inhibition in neutrophils, elevated kinase MEK/ERK and PI3K/AKT activity is observed, leading to FOXO3a phosphorylation, cytoplasmic transfer and inactivation. In summary, we have found that FOXO3a is a key transcription factor controlling the angiogenic switch of neutrophils. Post-translational FOXO3a modifications regulate its transcriptional activity and, as a result, the expression of pro-angiogenic factors supporting development of vascular network in growing tumors. Therefore, targeting FOXO3a activity could provide a novel strategy of antiangiogenic targeted therapy for cancer.

TNF-α and IL-1ß sensitize human MSC for IFN-γ signaling and enhance neutrophil recruitment.

During inflammatory processes, tissue environmental cues are influencing the immunoregulatory properties of tissue-resident mesenchymal stem/stromal cells (MSC). In this study, we elucidated one of the molecular and cellular responses of human MSC exposed to combinations of inflammatory cytokines. We showed that during multi-cytokine priming by TNF-α, IL-1ß, and IFN-γ, IL-1ß further augmented the well-established immunoregulatory activity induced by TNF-α/IFN-γ. On the molecular level, TNF-α and IL-1ß enhanced the expression of IFN-γ receptor (IFN-γR) via NF 'kappa-light-chain-enhancer' of activated B-cells (NF-κΒ) signaling. In turn, enhanced responsiveness to IFN-γ stimulation activated STAT5 and p38-MAPK signaling. This molecular feedback resulted in an increased IL-8 release and augmented recruitment of polymorphonuclear granulocytes (PMN). Our study suggests the possibility that responses of MSC to multi-cytokine priming regimens may be exploited therapeutically to fine-tune inflammatory activity in tissues. This study elucidates molecular mechanisms underlying the immunological priming of mesenchymal stromal cells (MSC) and their interaction with neutrophils.

Tracheal Resection after Previous Treatment Provides Comparable Outcome to Primary Surgery.

BACKGROUND: Tracheal and laryngotracheal surgery provides both excellent functional results and long-term outcomes in the treatment of tracheal stenosis. Consequently, challenging re-resections are rarely necessary. The purpose of this study was to compare the outcome of (laryngo-)tracheal re-resection and surgery after bronchoscopic interventions with that of primary surgery. METHODS: Patients undergoing resection for benign tracheal stenosis at our center between 1/2016 and 4/2020 were included. Perioperative characteristics and functional outcomes of patients were used for statistical analysis. RESULTS: Sixty-six patients who underwent (laryngo-)tracheal resection were included (previous resection [A = 6], previous stent [B = 6], previous bronchoscopic intervention w/o stenting [C = 19], untreated [D = 35]). Baseline parameters were largely comparable between groups with exception from group B that had significantly worse lung function. Group A necessitated more complex reconstructions (end-to-end: n = 1: 17%| cricotracheal n = 2: 33%| cricotracheal with mucosectomy n = 2: 33%| laryngoplasty: n = 1: 17%) than patients in group D (end-to-end n = 21: 60%| cricotracheal n = 14: 40%). Postoperative outcomes were comparable throughout groups (intensive care unit: 1[1-18] days; hospital stay: 8[5-71] days). Anastomotic complications were higher after previous stenting (A: 0%; B: 33.3%; C: 10.5%; D: 2.9%; B/D p = 0.008| surgical revisions: A: 16.7%; B: 33.3%; C: 0%; D: 5.7%; B/D, p = 0.035). Overall, postoperative lung function was significantly better (forced expiratory volume in 1 second: 63% ± 24 vs. 75% ± 20; p = 0.001 | PeakEF 3.3 ± 1.9 vs. 5.0 ± 2.2L; p = 0.001). No 90-day mortality was observed in any group. Median follow-up was 12(1-47) months. CONCLUSION: In carefully selected patients treated in a specialized center, tracheal or laryngotracheal resection after previous tracheal interventions provides comparable outcome to primary surgery.

Proposing a surgical algorithm for graduated orbital decompression in patients with Graves' orbitopathy.

PURPOSE: To determine the outcome after orbital decompression using a graduated technique, adapting the surgical technique according to individual patients' disease characteristics. METHODS: We retrospectively examined the postoperative outcome in patients treated with a graduated balanced orbital decompression regarding reduction of proptosis, new onset diplopia and improvement in visual function. 542 patients (1018 orbits) were treated between 2012 and 2020 and included in the study. Clinical examinations including visual acuity, exophthalmometry (Hertel) and orthoptic evaluation were performed preoperatively and at minimum 6 weeks postoperatively. Mean follow-up was 22.9 weeks. RESULTS: Mean proptosis values have significantly decreased after surgery (p < 0.01). In 83.3% of the patients Hertel measurement normalized (≤ 18 mm) after surgery, New onset diplopia within 20° of primary position occurred in 33.0% of patients, of whom 16.0% had preoperative double vision in secondary gaze. Patients suffering from dysthyroid optic neuropathy (DON) had a significant increase in visual acuity (p < 0.01). CONCLUSION: We demonstrated that individually adapted graduated orbital decompression successfully improves key disease parameters of Graves' orbitopathy with low morbidity.

The accuracy of clinical neck staging for p16-positive and negative oropharyngeal cancer and its therapeutic implications.

PURPOSE: Oropharyngeal squamous cell carcinoma (OPSCC) may be treated with primary surgery or primary (chemo)radiation. While surgery with concurrent neck dissection provides definitive pathological staging of the neck, non-surgical treatment relies on clinical staging for treatment planning. To assess the accuracy of clinical neck staging, we compared clinical to surgical staging after primary surgery in patients with p16-negative and p16-positive OPSCC. METHODS: Retrospective analysis of clinical, pathological, and oncologic outcome data of patients with OPSCC treated with primary surgery and bilateral neck dissection. Clinical and pathological nodal status were compared for p16-negative and p16-positive patients. Patients with occult metastatic disease were analyzed in detail. RESULTS: 95 patients were included. 60.5% of p16-negative patients and 66.6% of p16-positive patients had pathologically confirmed metastatic neck disease. p16-positive patients had improved 24-month recurrence-free survival compared to p16-negative patients at 93.3% vs. 69.6%. Pathological N-status differed from clinical N-status in 36.8% of p16-negative patients vs. 31.6% of p16-positive patients. Occult metastatic disease was more common in p16-negative patients at 18.4% vs. 8.8% for p16-positive patients. Clinical detection sensitivity for extranodal extension was low overall; sensitivity was 27.3% and specificity was 91.6% for p16-negative patients vs. 61.5% and 80.0% for p16-positive patients, respectively. CONCLUSION: Our data show a considerable degree of inaccuracy of clinical neck staging results in all OPSCC patients which needs to be taken into consideration during therapy planning. For p16-positive patients, these findings warrant attention in the context of therapy deintensification to avoid undertreatment.