[Emphysema after cochlear implantation - risk factors and therapeutic options]. / Emphyseme nach Cochlea-Implantation ­ Risikofaktoren und Therapieoptionen.

OBJECTIVE: In case of cochlear implantation seroma, hematoma, local wound infections or vertigo are rare but typical complications. In contrast, emphysema is seldom reported. They can occur after cochlear implantation both in the postoperative healing phase and years later. A therapeutic algorithm does not yet exist. METHODS: We report on 3 patients with subcutaneous emphysema in the area of the receiver-stimulator. An unsystematic review of the literature of cases with emphysema after cochlear implantation highlights possible risk factors and the therapeutic options. RESULTS: The 3 cases developed subcutaneous emphysema 2-11 month after cochlear implantation due to nose blowing or CPAP therapy in obstructive sleep apnea. The current literature reports another 35 cases of emphysema after cochlear implantation. Air insufflation via the Eustachian tube is the most frequently described cause. Diseases of the nose and sinuses, tube dysfunction and obstructive sleep apnea are potential risk factors. Pressure bandage, puncture, tympanic tubes, and surgical revision are common treatments. CONCLUSIONS: Most emphysema can be controlled by conservative methods such as pressure bandaging and behavioral instruction. Punctures should be avoided due to the risk of upcoming infections. The prophylactic use of antibiotics seems dispensable. Surgical revision should be considered especially in cases of pneumocephalus with suspected leakage in the dura. The coverage of the mastoidectomy by a bony cap can be precautious and beneficial in cases with risk factors.

[Closure of Nasal Septal Perforation]. / Der chirurgische Septumperforationsverschluss.

Symptomatic nasal septal perforations can lead to a substantial restriction in the quality of life of patients and present a distinct surgical challenge for the otolaryngologist/head and neck surgeon. Symptomatic patients complain about nasal crusting, recurrent nosebleeds and nasal obstruction. The so called 4 bridge-flap technique including the interposition of autologous ear cartilage presents an established surgical method for closure of a septal perforation. In the present article, the surgical procedure is described in detail.

Prospective Analysis in Patients With HAE Under Prophylaxis With Lanadelumab: A Real-life Experience.

BACKGROUND AND OBJECTIVES: Patients with the rare disease hereditary angioedema (HAE) suffer from recurrent acute attacks of edema. There is no curative therapy, but the frequency of attacks and quality of life of severely affected patients can be improved by prophylactic therapy. The monoclonal antibody lanadelumab has been approved for routine prophylaxis in patients with HAE since November 2018. PATIENTS AND METHODS: In this prospective assessment, a long-term therapy with lanadelumab was initiated in 12 adult patients with HAE. We analyzed their course of disease 6 months after the start of long-term prophylactic therapy using a validated quality-of-life questionnaire and evaluated the frequency and severity of attacks as well as side effects. Furthermore, the therapy with lanadelumab was compared with the previous medication. RESULTS: To date, our study is the first prospective quality of life analysis in HAE patients under treatment with lanadelumab in real life conditions. Mean attack frequencies were reduced from 6.4 to 0.3 attacks per month and patient in our cohort (P<0.0001). No severe attacks occurred under lanadelumab prophylaxis. In all patients, quality of life increased significantly. CONCLUSIONS: Lanadelumab is an effective but expensive long-term prophylaxis for HAE patients. A favorable side-effect profile has been shown. J Drugs Dermatol. 2020;19(10):978-983. doi:10.36849/JDD.2020.5269.

[Surgery of the Nasal Septum]. / Chirurgie des Nasenseptums.

Dimension, position and stability of the cartilaginous nasal septum are crucial for successful surgery of the nasal septum. The objective of septoplasty is to create sufficient space in the anterior parts of the nose, particularly in the region of the nasal valves. Therefore, the cartilaginous nasal septum should obtain a state of "balanced tension". Essential steps of septoplasty include the hemitransfixion incision, the dissection of subperichondrial/subperiosteal tunnels, the mobilization via chondrotomy/osteotomy, the resection of cartilage/bone, the replantation of extracorporeally straightened material/reconstruction of the caudal nasal septum, closure by suture and fixation with nasal splints. Firmness of the caudal nasal septum is essential for sustainable septal surgery. It ensures the stability of the entire cartilaginous nose over decades.

Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status.

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens and 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive and 209 HPV-negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c-myc, LAGE-1, MAGE-A1, -A3, -A4, NY-ESO-1, SpanX-a1 and p53. AR to MAGE-A3, MAGE-A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue-sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV-positive and HPV-negative HNSCC.

Radial diffusivity in the cerebellar peduncles correlates with clinical severity in Friedreich ataxia.

Friedreich ataxia (FRDA) is a common inherited ataxia, caused by an expanded GAA repeat sequence in the Frataxin (FXN) gene. The proprioceptive system, which enters the cerebellum through the cerebellar peduncles, is a primary focus of pathology. In this study, we investigate the relationship of clinical and genetic data with diffusion-tensor imaging (DTI) indices reflecting white matter integrity of the cerebellar peduncles. Nine FRDA patients underwent DTI. After between-subject registration using tract-based spatial statistics, a white matter atlas was used for computing average values of DTI indices in the regions of interest. These were the inferior, middle and superior cerebellar peduncles (ICP, MCP, SCP). For Bonferroni correction, significance threshold was set to p < 0.0056. We found that radial diffusivity (D(⊥)) within the ICP significantly correlated with scores on the Friedreich Ataxia Rating Scale (FARS, Spearman's ρ = 0.883, p = 0.0016, all two-sided) and, at trend level, with number of trinucleotide repeats (ρ = 0.812, p = 0.008). D(⊥) in the SCP correlated with scores on the Scale for the Assessment and Rating of Ataxia (SARA, ρ = 0.867, p = 0.0025). These findings support the role of DTI, and especially D(⊥), as an informative biomarker in FRDA.

Enhanced cellular migration and prolonged chondrogenic differentiation in decellularized cartilage scaffolds under dynamic culture conditions.

Lesions of aural, nasal and tracheal cartilage are frequently reconstructed by complex surgeries which are based on harvesting autologous cartilage from other locations such as the rib. Cartilage tissue engineering (CTE) is regarded as a promising alternative to attain vital cartilage. Nevertheless, CTE with nearly natural properties poses a significant challenge to research due to the complex reciprocal interactions between cells and extracellular matrix which have to be imitated and which are still not fully understood. Thus, we used a custom-made glass bioreactor to enhance cell migration into decellularized porcine cartilage scaffolds (DECM) and mimic physiological conditions. The DECM seeded with human nasal chondrocytes (HPCH) were cultured in the glass reactor for 6 weeks and examined by histological and immunohistochemical staining, biochemical analyses and real time-PCR at 14, 28 and 42 days. The migration depth and the number of migrated cells were quantified by computational analysis. Compared to the static cultivation, the dynamic culture (DC) fostered migration of HPCH into deeper tissue layers. Furthermore, cultivation in the bioreactor enhanced differentiation of the cells during the first 14 days, but differentiation diminished in the course of further cultivation. We consider the DC in the presented bioreactor as a promising tool to facilitate CTE and to help to better understand the complex physiological processes during cartilage regeneration. Maintaining differentiation of chondrocytes and improving cellular migration by further optimizing culture conditions is an important prerequisite for future clinical application.

The Surgical Treatment of Peritonsillar Abscess: A Retrospective Analysis in 584 Patients.

OBJECTIVES: There are three surgical treatment options for patients with peritonsillar abscess (PTA): needle aspiration, incision and drainage (ID), and abscess tonsillectomy (ATE). The updated German national guideline (2015) included changes in the treatment of PTA. The indication for tonsillectomy (TE) in patients became more stringent and preference was given to ID in certain cases. STUDY DESIGN: Retrospective analysis. METHODS: We performed a retrospective systematic analysis of patient data using the in-house electronic patient records and considered a 4-year period from 2014 to 2017. About 584 patients were identified. Our aim was to analyze the influence of the updated guideline on clinical practice. RESULTS: 236 of 584 patients (40.4%) underwent ATE with contralateral TE. In 225 patients (38.5%), unilateral ATE was performed. Mean surgery time was significantly shortened when only unilateral ATE was performed. Concerning postoperative bleeding, we noted a tendency toward a lower incidence after ATE in comparison to ATE with contralateral TE. Less than 1% of patients who underwent ATE had to be revised surgically due to postoperative hemorrhage. After the revision of the guideline, unilateral ATE and ID were conducted more frequently. CONCLUSION: These results support that ATE in an inpatient setting is a considerably safe and effective primary therapeutic option. ID represents a favorable treatment option for patients with PTA and comorbidities, nevertheless, patient compliance is required and insufficient drainage or recurrence of PTA may occur. The revision of the guideline had a significant impact on the choice of interventions (P < .001), which is reflected by the increased number of unilateral ATE. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2706-2712, 2021.

Increasing Mean Age of Head and Neck Cancer Patients at a German Tertiary Referral Center.

BACKGROUND: The impact of demographic change on the age at diagnosis in German head and neck cancer (HNC) patients is unclear. Here we present an evaluation of aging trends in HNC at a tertiary referral center. METHODS: Retrospective cohort study on aging trends at the initial diagnosis of newly diagnosed patients with HNC between 2004 and 2018 at the head and neck cancer center Ulm in relation to demographic data of the catchment area. RESULTS: The study population consisted of 2450 individuals diagnosed with HNC with a mean age of 62.84 (±11.67) years. We observed a significant increase in annual incidence rates and mean age over time. Mean age among HNC patients increased significantly more than among the population in the catchment area. Whereas the incidence rate of patients <50 years did not change, the incidence of HNC patients aged ≥70 years increased the most. The mean patient age in the main tumor sites increased significantly. Surprisingly, HPV-positive patients were not younger than HPV-negative patients, but showed a non-significant trend towards a higher mean age (63.0 vs. 60.7 years). CONCLUSIONS: Increasing incidence rates in older patients pose a challenge for health care systems. A nationwide study is needed to assess the dynamics and impact of aging on the incidence of HNC.

Antibody Responses to Cancer Antigens Identify Patients with a Poor Prognosis among HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma Patients.

PURPOSE: The identification of high-risk patients within human papillomavirus (HPV)-positive and -negative head and neck squamous cell carcinoma (HNSCC) is needed for improved treatment and surveillance strategies. In this study, we set out to discover antibody responses (AR) with prognostic impact in HNSCC stratified by HPV status. EXPERIMENTAL DESIGN: A fluorescent bead-based multiplex serology assay on 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens, and 8 oncogenes) and 29 HPV antigens was performed in samples of 362 patients with HNSCC from five independent cohorts (153 HPV positive, 209 HPV negative). A multivariable Cox proportional hazard model with bootstrapping (M = 1000) was used for validation of prognostic antibody responses. RESULTS: Antibody response to any of the cancer antigens was found in 257 of 362 patients (71%). In HPV-negative patients, antibody responses to c-myc, MAGE-A1, -A4, and Rhodopsin E2 (combined as ARhigh risk) were significantly associated with shorter overall survival. In HPV-positive patients, antibody responses to IMP-1 were discovered as a negative prognostic factor. ARhigh risk (HR = 1.76) and antibody responses to IMP-1 (HR = 3.28) were confirmed as independent markers for a poor prognosis in a multivariable Cox proportional hazard model with bootstrapping (M = 1000). CONCLUSIONS: We identified antibody responses to cancer antigens that associate with a dismal prognosis in patients with HNSCC beyond HPV-positive status. ARhigh risk may be used to detect HPV-negative patients with an extraordinarily bad prognosis. Most importantly, antibody response to IMP-1 may serve as a marker for a subgroup of HPV-positive patients who present with a poor prognosis similar to that in HPV-negative patients.

Biphasic synovial sarcoma of the epiglottis: Case report and literature review.

Synovial sarcomas are rare malignant tumors supposed to arise from pluripotent mesenchymal stem cells predominantly affecting the deep soft tissue of the lower and upper extremities in young adults. The occurrence of this tumor entity in the head and neck is very uncommon and hence, timely diagnosis and treatment of synovial sarcoma in this region remain a challenge. We describe the clinical and molecular pathological features of a biphasic synovial sarcoma of the epiglottis, a site where the primary manifestation of this tumor entity has not been documented to date. With this background the existing literature is being reviewed. Whilst wide excision of synovial sarcoma is considered as the primary mainstay of therapy, (neo)adjuvant treatment strategies have been proposed to increase local control and prolong disease-free survival.

Auditory verbal hallucinations and the interhemispheric auditory pathway in chronic schizophrenia.

OBJECTIVES: The interhemispheric auditory pathway has been shown to play a crucial role in the processing of acoustic stimuli, and alterations of structural and functional connectivity between bilateral auditory areas are likely relevant to the pathogenesis of auditory verbal hallucinations (AVHs). The aim of this study was to examine this pathway in patients with chronic schizophrenia regarding their lifetime history of AVHs. METHODS: DTI scans were acquired from 33 healthy controls (HC), 24 schizophrenia patients with a history of AVHs (LT-AVH) and nine schizophrenia patients without any lifetime hallucinations (N-LT-AVH). The interhemispheric auditory fibre bundles were extracted using streamline tractography. Subsequently, diffusivity indices, namely Fractional Anisotropy (FA), Trace, Mode, Axial and Radial diffusivity, were calculated. RESULTS: FA was decreased over the entire pathway in LT-AVH compared with N-LT-AVH. Moreover, LT-AVH displayed decreased FA and Mode as well as increased radial diffusivity in the midsagittal section of the fibre tract. CONCLUSIONS: These findings indicate complex microstructural changes in the interhemispheric auditory pathway of schizophrenia patients with a history of AVHs. Alterations appear to be absent in patients who have never hallucinated.

White matter changes in patients with friedreich ataxia after treatment with erythropoietin.

BACKGROUND AND PURPOSE: Erythropoietin (EPO) has received growing attention because of its neuroregenerative properties. Preclinical and clinical evidence supports its therapeutic potential in brain conditions like stroke, multiple sclerosis, and schizophrenia. Also, in Friedreich ataxia, clinical improvement after EPO therapy was shown. The aim of this study was to assess possible therapy-associated brain white matter changes in these patients. METHODS: Nine patients with Friedreich ataxia underwent Diffusion Tensor Imaging (DTI) before and after EPO treatment. Tract-based spatial statistics was used for longitudinal comparison. RESULTS: We detected widespread longitudinal increase in fractional anisotropy and axial diffusivity (D||) in cerebral hemispheres bilaterally (P < .05, corrected), while no changes were observed within the cerebellum, medulla oblongata, and pons. CONCLUSIONS: To the best of our knowledge, this is the first DTI study to investigate the effects of EPO in a neurodegenerative disease. Anatomically, the diffusivity changes appear disease unspecific, and their biological underpinnings deserve further study.

CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.

CNTNAP2 is a gene on chromosome 7 that has shown associations with autism and schizophrenia, and there is evidence that it plays an important role for neuronal synchronization and brain connectivity. In this study, we assessed the relationship between Diffusion Tensor Imaging (DTI), a putative marker of anatomical brain connectivity, and multiple single nucleotide polymorphisms (SNPs) spread out over this large gene. 81 healthy controls and 44 patients with schizophrenia (all Caucasian) underwent DTI and genotyping of 31 SNPs within CNTNAP2. We employed Tract-based Spatial Statistics (TBSS) for inter-subject brain registration and computed average diffusivity values for six major white matter tracts. Analyses of Covariance (ANCOVAs) were computed to test for possible associations with genotypes. The strongest association, which survived rigorous Bonferroni correction, was between rs2710126 genotype and Fractional Anisotropy (FA) in the uncinate fasciculus (p = .00003). This anatomical location is particularly interesting given the enriched fronto-temporal expression of CNTNAP2 in the developing brain. For this SNP, no phenotype association has been reported before. There were several further genotype-DTI associations that were nominally significant but did not survive Bonferroni correction, including an association between axial diffusivity in the dorsal cingulum bundle and a region in intron 13 (represented by rs2710102, rs759178, rs2538991), which has previously been reported to be associated with anterior-posterior functional connectivity. We present new evidence about the effects of CNTNAP2 on brain connectivity, whose disruption has been hypothesized to be central to schizophrenia pathophysiology.