Annekatrin Coordes

Inhibition of pan-class I phosphatidyl-inositol-3-kinase by NVP-BKM120 effectively blocks proliferation and induces cell death in diffuse large B-cell lymphoma.

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most frequent aggressive lymphoma, with a great demand for novel treatments for relapsing and refractory disease. Constitutive activation of the phosphatidyl-inositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is often detected in this lymphoma. Inhibition of this signaling cascade with the pan-class I PI3K inhibitor NVP-BKM120 decreased cell proliferation and increased apoptotic cell death. DLBCL proliferation was further decreased if NVP-BKM120-induced autophagy was blocked. Treatment with NVP-BKM120 was associated with an increase of the pro-apoptotic BH3-only proteins Puma and Bim and down-regulation of the anti-apoptotic Bcl-xL and Mcl-1. Translation of Bcl-xL and Mcl-1 is facilitated by cap-dependent mRNA translation, a process that was partially inhibited by NVP-BKM120. Overall, we demonstrated here the potential of NVP-BKM120 for the treatment of DLBCL.

Apoptotic Cascades in the Central Auditory Pathway after Noise Exposure

Noise exposure leads to dramatic physiological and anatomical changes within the central auditory pathway in addition to the well-known cochlear damage. Our group previously described a significant loss of neurons in different central auditory structures upon acoustic overstimulation. The aim of the present study was to investigate if declined neuronal cell density is caused by apoptotic mechanisms. Mice were noise-exposed (3 h, 5-20 kHz) at 115 dB SPL under anesthesia and investigated immediately after, and at 6 h, 24 h, or 7 days after the exposure (n=16). Unexposed animals were used as controls (n=5). Apoptotic cells were detected by fluorescence microscopy after terminal deoxynucleotidyl transferase dUTP nick-end labeling assay (TUNEL). TUNEL-positive cells were compared to cell density (diamidino phenylindole, DAPI) within the dorsal and ventral cochlear nucleus (VCN), and the central nucleus of the inferior colliculus (ICC). In all investigated auditory areas, TUNEL-positive cells were significantly increased after acoustic overstimulation. In the acute, 6-h, and 24-h groups, their numbers were significantly increased in the VCN, as well as in the 6-h, 24-h, and 7-day groups in the dorsal cochlear nucleus (DCN). In the ICC, TUNEL-positive cells were significantly increased in all exposed mice. In the VCN, the number of TUNEL-positive cells of the same grid size was three times the numbers in the ICC. Our results show that noise exposure induces apoptosis-related pathophysiological changes within the central auditory pathway in a time-dependent manner. This may represent potential therapeutic targets, and helps clarify the complex psychoacoustic phenomena of noise-induced hearing loss.

Round window membrane insertion with perimodiolar cochlear implant electrodes.

Objective The round window membrane (RWM) approach is designed to provide an atraumatic approach to scala tympani implantation with the goal of enhanced preservation of hearing and vestibular receptor function. Perimodiolar electrode designs offer advantages in electrophysiologic testing. However, perimodiolar arrays have only been investigated in insertion trials using temporal bone material. The aim of the present study was to evaluate perimodiolar electrode placement in a clinical trial. Materials and Methods The prospective nonrandomized study included 27 patients (October 2010 to February 2011). Due to the RWM approach, cochlear implantation electrode insertion was performed using a perimodiolar electrode array fitted with a stylet that enables movement through the first cochlear turn by withdrawing the stylet. We judged the feasibility of RWM approaches with perimodiolar electrodes and the electrode placement using flat panel detector radiography. Hearing preservation, vestibular receptor function (vestibular evoked myogenic potentials, subjective haptic vertical, and caloric irrigation), and subjective vertigo were evaluated in all RWM approaches. Results For anatomic reasons, RWM insertions were possible in 21 cases (78%). The basilar membrane disruption rate was 19% in RWM insertions using perimodiolar electrodes. In those patients with the electrode position within the scala tympani, vestibular receptor functions and subjective vertigo remained unchanged. The residual hearing preservation was unsatisfactory. The mean pure-tone average loss was 21 dB. Conclusion We believe that if performed regularly, the RWM insertion technique has almost no negative effects on vestibular receptor function and produces no vertigo. However, cochlear hair cells may be more sensitive to electrode insertion traumas than vestibular receptor cells. The use of perimodiolar electrodes may require more atraumatic electrodes to achieve hearing preservation.

Sound-induced vertigo after cochlear implantation.

Aim Postoperative vertigo is a well-known complication after cochlear implantation. The aim of the study was to investigate whether the electrical stimulation of the auditory structures via cochlear implant electrodes can affect the vestibular system and induce vertigo. Materials and Methods In the first group, 114 patients were surveyed retrospectively via questionnaires to evaluate the occurrence and frequency of sound-induced vertigo after cochlear implantation. In the second group of 26 patients, the effects of electrical stimulation on the vestibular system were studied prospectively. Results In the first group of patients without any preoperative sound-induced vertigo (n = 104), 20 patients (18%) reported sound-induced vertigo, which occurred after cochlear implantation. In the second group, an acoustic stimulus delivered via the speech processor of the cochlear implant elicited a vestibular evoked myogenic potential response in 4 of the 26 patients as a sign of vestibular costimulation (of the macula sacculi as part of the otolith organs). Horizontal and vertical nystagmus was triggered, whereas utricular function and postural stability remained unchanged. No correlation was found between C/M levels and the vestibular evoked myogenic potentials and nystagmus responses. Conclusion Sound-induced vertigo can occur in cochlear implantees. This seems to be primarily caused by electrical costimulation of the sacculus as part of the otolith organs.

Selection and Placement of Oral Ventilation Tubes Based on Tracheal Morphometry

Evidence‐based guidelines for the selection of appropriately sized ventilation tubes as well as their placement do not exist, although iatrogenic injuries to the trachea and larynx following endotracheal intubation are not infrequent. Our objective was to provide selection recommendations for ventilation tubes based on anatomic criteria.

Incidence and long‐term survival of patients with de novo head and neck carcinoma after liver transplantation

Liver transplant recipients have an increased risk of developing de novo malignancies.

Etiologic and differential diagnostic significance of tumor location in the supraclavicular fossa: Tumor Location in the Supraclavicular Fossa

Patients presenting with a cervical mass are common for head and neck specialists and present a diagnostic challenge against the backdrop of a wide variety of etiologies. The objective of the present study was to evaluate the significance of a mass in the supraclavicular fossa for etiology, diagnostic procedure, and therapy.

Active middle ear implant coupled bilaterally to the round window despite bilateral implanted stapes prostheses.

After stapes surgery, patients with mixed or moderate hearing loss have limited possibilities for hearing improvement. We are reporting on a patient who underwent stapedotomy bilaterally 20 years ago and had sensorineural and mixed hearing loss. Recurrent otitis externa prevented the use of hearing aids. This patient was treated bilaterally with the Vibrant Soundbridge (Med‐El, Innsbruck, Austria) successively. The Schuknecht piston stapes prostheses remained in situ. The Floating Mass Transducer (FMT; Med‐El) was coupled to the round window (RW) and provided good acoustic reinforcement bilaterally. In conclusion, for patients with otosclerosis and stapes surgery, the FMT–RW coupling (Bess AG, Berlin, DE) is a safe procedure with good acoustic amplification. Laryngoscope, 2016 127:500–503, 2017

Association of Oversized Tracheal Tubes and Cuff Overinsufflation With Postintubation Tracheal Ruptures

Objectives Postintubation tracheal ruptures (PTR) are rare but cause severe complications. Our objective was to investigate the tracheal pattern of injury resulting from cuff inflation of the tracheal tube, to study the two main factors responsible for PTR (cuff overinsufflation and inapplicable tube sizes), and to explain the context, why small women are particularly susceptible to PTR. Methods Experimental study performed on 28 fresh human laryngotracheal specimens (16 males, 12 females) within 24 hours post autopsy. Artificial ventilation was simulated by using an underwater construction and a standard tracheal tube. Tube sizes were selected according to our previously published nomogram. Tracheal lesions were detected visually and tracheal diameters measured. The influence of body size, sex difference and appropriate tube size were investigated according to patient height. Results In all 28 cases, the typical tracheal lesion pattern was a longitudinal median rupture of the posterior trachea. Appropriate tube sizes according to body size caused PTR with significantly higher cuff pressure when compared with oversized tubes. An increased risk of PTR was found in shorter patients, when oversized tubes were used. Sex difference did not have any significant influence. Conclusion This experimental model provides information about tracheal patterns in PTR for the first time. The model confirms by experiment the observations of case series in PTR patients, and therefore emphasizes the importance of correct tube size selection according to patient height. This minimizes the risk of PTR, especially in shorter patients, who have an increased risk of PTR when oversized tubes are used.

Ohnmachtsanfälle bei der Nahrungsaufnahme

MEDICAL HISTORY A 49-year-old woman was referred to the ENT department with a 1.5-year history of dysphagia accompanied by globus sensation and regurgitation as well as recurrent syncopal attacks associated with swallowing solid foods. CLINICAL FINDINGS Endoscopic examination revealed hyperplasia of the tongue base and redness of the aryepiglottic region. An axial hiatal hernia (> 3 cm) was seen on esophago-gastro-duodenoscopy. Esophageal manometry showed a diffuse esophageal spasm. Holter monitoring (24 h) revealed a third-degree atrioventricular block. THERAPY The patient’s symptoms resolved following placement of a permanent cardiac pacemaker. Globus sensation and regurgitation persisted. Treatment with proton pump inhibitors was successful. The final functional endoscopic evaluation of swallowing revealed no relevant findings. CONCLUSION We describe a case of a rare and extreme form of a vagal reflex. Deglutition syncope can be successfully treated by a multidisciplinary team consisting of otorhinolaryngologists, neurologists and cardiologists.