EAONO/JOS classification for acquired cholesteatoma: evaluating the impact of the number of affected sites on treatment and outcomes.

PURPOSE: The European and Japanese system for cholesteatoma classification proposed an anatomical differentiation in five sites. In stage I disease, one site would be affected and in stage II, two to five. We tested the significance of this differentiation by analyzing the influence of the number of affected sites on residual disease, hearing ability and surgical complexity. METHODS: Cases of acquired cholesteatoma treated at a single tertiary referral center between 2010-01-01 and 2019-07-31 were retrospectively analyzed. Residual disease was determined according to the system. The air-bone gap mean of 0.5, 1, 2, 3 kHz (ABG) and its change with surgery served as hearing outcome. The surgical complexity was estimated regarding the Wullstein's tympanoplasty classification and the procedure approach (transcanal, canal up/down). RESULTS: 513 ears (431 patients) were followed-up during 21.6 ± 21.5 months. 107 (20.9%) ears had one site affected, 130 (25.3%) two, 157 (30.6%) three, 72 (14.0%) four and 47 (9.2%) five. An increasing number of affected sites resulted in higher residual rates (9.4-21.3%, p = 0.008) and surgical complexity, as well poorer ABG (preoperative 14.1 to 25.3 dB, postoperative 11.3-16.8 dB, p < 0.001). These differences existed between the means of cases of stage I and II, but also when only considering ears with stage II classification. CONCLUSION: The data showed statistically significant differences when comparing the averages of ears with two to five affected sites, questioning the pertinence of the differentiation between stages I and II.

Robust Fermi-Surface Morphology of CeRhIn_{5} across the Putative Field-Induced Quantum Critical Point.

We report a comprehensive de Haas-van Alphen (dHvA) study of the heavy-fermion material CeRhIn_{5} in magnetic fields up to 70 T. Several dHvA frequencies gradually emerge at high fields as a result of magnetic breakdown. Among them is the thermodynamically important ß_{1} branch, which has not been observed so far. Comparison of our angle-dependent dHvA spectra with those of the non-4f compound LaRhIn_{5} and with band-structure calculations evidences that the Ce 4f electrons in CeRhIn_{5} remain localized over the whole field range. This rules out any significant Fermi-surface reconstruction, either at the suggested nematic phase transition at B^{*}≈30 T or at the putative quantum critical point at B_{c}≃50 T. Our results rather demonstrate the robustness of the Fermi surface and the localized nature of the 4f electrons inside and outside of the antiferromagnetic phase.

Studying the Dynamics of Relativistic Laser-Plasma Interaction on Thin Foils by Means of Fourier-Transform Spectral Interferometry.

We apply Fourier-transform spectral interferometry (FTSI) to study the interaction of intense laser pulses with ultrathin targets. Ultrathin submicrometer-thick solid CH targets were shot at the PHELIX laser facility with an intensity in the mid to upper 10^{19} W/cm^{2} range using an innovative double-pulse structure. The transmitted pulse structure was analyzed by FTSI and shows a transition from a relativistic transparency-dominated regime for targets thinner than 500 nm to a hole-boring-dominated laser-plasma interaction for thicker targets. The results also confirm that the inevitable preplasma expansion happening during the rising slope of the pulse, a few picoseconds before the maximum of the pulse is reached, cannot be neglected and plays a dominant role in laser-plasma interaction with ultrathin solid targets.

[Cochlear implant fitting strategies]. / Anpassung von Cochleaimplantatsystemen.

Cochlear implant (CI) fitting is the technical adjustment of a CI processor to the individual needs of a subject. Fitting comprises the choice of stimulation strategy and determination of the lower and upper stimulation levels for the individual. This electrical dynamic range defines the stimulation range for the real-time functioning of the CI system. All of the CI manufacturers provide a large set of parameters which have to be optimized for proper hearing and speech comprehension. As a consequence of the widening of indication criteria for CIs and lowering the age of implantation for children, the fitting process has changed dramatically over the years. This includes replacement of behavioral responses by other data from objective electrophysiologic measures and from expert knowledge. Recent developments aim to structure and automatize the CI fitting process. This reduces the time requirement for CI fitting and leads to fast settings which can be tested in the real-time situation. This review provides an overview of state-of-the-art fitting procedures and recent developments for fitting strategies. These will be discussed with respect to practicability and quality assurance.

[Hearing restoration with cochlear implants after translabyrinthine vestibular schwannoma resection]. / Hörrehabilitation mit Cochleaimplantaten nach translabyrinthärer Vestibularisschwannomresektion.

BACKGROUND: Hearing restoration after translabyrinthine vestibular schwannoma resection is a challenge. Because the cochlea can begin to ossify a few months after cochlear or labyrinthine injury, the time interval for cochlear implant surgery is limited. To avoid complete ossification and to prolong the time interval until cochlear implantation, it is possible to insert a placeholder (depth gauge) into the cochlea and perform the cochlear implant surgery at a later time point (two-stage approach). OBJECTIVE: The aim of this retrospective case series was to present the outcomes after restoration of hearing with cochlea implants in six patients and to evaluate the use of the depth gauge in practice. METHODS: The hearing outcome of all patients with (n = 3) and without (n = 3) insertion of a depth gauge was measured with the Freiburg monosyllabic test without background noise at 65 dB. The first measurement was performed prior to the translabyrinthine vestibular schwannoma resection, the last measurement was performed up to 48 months after cochlear implantation. RESULTS: All 6 patients reached 22.5 ± 36.57% prior to vestibular schwannoma resection and 41.3 ± 26% 12 months after cochlear implantation. The understanding values of the patients with a depth gauge were 25.8 ± 16% after 12 months which is below the values of the other patients with 56.6 ± 25.0%. No severe intraoperative or postoperative complications occurred in any patient. CONCLUSION: The two-stage approach for cochlear implantation with depth gauge insertion following labrynthine incision and intact nerve appears to represent a very promising and safe variation for hearing restoration. Intensified research on this approach seems to be justified and necessary.

[NiTiBOND an optimized self-crimping stapes prosthesis for treatment of otosclerosis]. / NiTiBOND, eine optimierte Steigbügelprothese zur chirurgischen Behandlung der Otosklerose.

BACKGROUND: Compared to traditional stapes prostheses, self-crimping prostheses have been shown to result in similar, if not better, closure of the air bone gap in patients undergoing stapedotomy for otosclerosis. To achieve self-crimping, nitinol, a shape memory alloy, has been used for several years but concerns have been raised regarding possible damage to the incus and its muco-periosteum. We investigate these concerns with regard to the newer NiTiBOND stapes prosthesis in an observational multi-centre study. MATERIAL AND METHODS: In a multicentre, prospective observational study, 76 patients undergoing stapedotomy with the NiTiBond prosthesis across 4 centres were compared to 75 -retrospectively selected control SMart patients. Complications, intra-operative user-friendliness and audiological results at 3 months were documented. RESULTS: Audiological improvement and the rate of complications were similar in both groups. Non inferiority was shown at all frequencies and in the pure-tone average. The NiTiBOND prosthesis was described as very user-friendly. CONCLUSIONS: By eliminating manual crimping, stapedotomy using the NiTiBOND prosthesis can be facilitated and standardized. Furthermore, intraoperative handling characteristics of the prosthesis are very good which may further reduce operative risk. Importantly, we show that these benefits are not to the detriment of audiological outcome. Larger and longer-term studies are required to further evaluate results.

[Helping medical students to approach death]. / Aider les étudiants en médecine à approcher la mort.

A project recently launched by the Faculty of biology and medicine of Lausanne introduces the approach of facing death during both the dissection and the course of clinical activities. Existential questions relating to mortality are bound to arise sooner or later during the course of the study. For the sake of humanized clinical practice, these questions must be confronted. In response to a request by a student association, an accompanying curriculum with active student's contribution through encounters with death in anatomy and clinical situations was created in Lausanne. Students will benefit from this new program throughout their curriculum. This program is the first of its kind in Switzerland.

[A young patient with paraganglioma syndrome type I. An interdisciplinary challenge]. / Junger Patient mit Paragangliomsyndrom Typ 1. Eine interdisziplinäre Herausforderung.

A 33-year old patient presented at our outpatient department with pulse-synchronous tinnitus in the left ear of several years' standing. Examination of the left ear showed a neoplasm at the base of the meatus in front of the ear drum. In addition, there was paresis of the right hypoglossal nerve and right vocal cord. CT scan showed multiple paraganglioma in the head and neck region. Molecular genetic screening analysis showed a mutation of the SDHD gene and thus the diagnosis of paraganglioma syndrome type 1 was made. In the treatment concept presented here the main goal was preservation of function of the left cranial nerves due to the functional loss of the right cranial nerves X and XII. This goal could be achieved by means of a staged procedure in collaboration with radiotherapists.

Fermi surface of the chiral topological semimetal PtGa.

PtGa is a topological semimetal with giant spin-split Fermi arcs. Here, we report on angular-dependent de Haas-van Alphen (dHvA) measurements combined with band-structure calculations to elucidate the details of the bulk Fermi surface of PtGa. The strong spin-orbit coupling leads to eight bands crossing the Fermi energy that form a multitude of Fermi surfaces with closed extremal orbits and results in very rich dHvA spectra. The large number of experimentally observed dHvA frequencies make the assignment to the equally large number of calculated dHvA orbits challenging. Nevertheless, we find consistency between experiment and calculations verifying the topological character with maximal Chern number of the spin-split Fermi surface.

Early activation of sperm by HCO(3) (-) is regulated hormonally in the murine uterus.

Sperm deposited in the female genital tract receive signals for capacitation. Past work indicates that HCO(3) (-) is the initiating signal that the female reproductive tract contains the HCO(3) (-) -permeant anion channel cystic fibrosis transmembrane conductance regulator (CFTR) and that mutations in CFTR cause subfertility in both sexes. In this study, we examined whether CFTR controls uterine HCO(3) (-) content and sperm responses to it. Both CFTR protein and mRNA were absent in prepubertal murine uterus, but appeared in pubertal and adult tissues. Thus, CFTR is upregulated during development. Uterine CFTR mRNA additionally increased upon induced oestrus, most abundantly in uterus body and distal horns. Uterine fluid of oestrous females contained two-, and nearly fourfold more HCO(3) (-) than that of dioestrous and prepubertal animals, correlating with increased CFTR expression. For sperm incubated in and recovered from prepubertal uteri, flagellar beat frequency was no different from that before incubation. However, for sperm recovered from dioestrous and oestrous uteri, beat frequency was two- and fourfold higher, respectively. Thus, uterine HCO(3) (-) content may have physiological consequences for sperm motility. The male reproductive tract showed no regional distributions or developmental dependence of CFTR expression. Although the sperm flagellum showed CFTR immunoreactivity, CFTR blockers GlyH-101 or CFTR(inh) -172 did neither diminish HCO(3) (-) -evoked increases in sperm motility nor protein tyrosine phosphorylation. Our results indicate that in the uterus, both CFTR expression and the supply of HCO(3) (-) are upregulated hormonally. We propose that these changes coordinate ovulation with increases in sperm motility and promote other components of capacitation by pathways that do not require CFTR in sperm.

Time-resolved study of holeboring in realistic experimental conditions.

The evolution of dense plasmas prior to the arrival of the peak of the laser irradiation is critical to understanding relativistic laser plasma interactions. The spectral properties of a reflected laser pulse after the interaction with a plasma can be used to gain insights about the interaction itself, whereas the effect of holeboring has a predominant role. Here we developed an analytical model, describing the non-relativistic temporal evolution of the holeboring velocity in the presence of an arbitrary overdense plasma density and laser intensity profile. We verify this using two-dimensional particle-in-cell simulations, showing a major influence on the holeboring dynamic depending on the density profile. The influence on the reflected laser pulse has been verified during an experiment at the PHELIX laser. We show that this enables the possibility to determine the sub-micrometer scale length of the preplasma by measuring the maximum holeboring velocity and acceleration during the laser-plasma interaction.

Analysis of laser-proton acceleration experiments for development of empirical scaling laws.

Numerous experiments on laser-driven proton acceleration in the MeV range have been performed with a large variety of laser parameters since its discovery around the year 2000. Both experiments and simulations have revealed that protons are accelerated up to a maximum cut-off energy during this process. Several attempts have been made to find a universal model for laser proton acceleration in the target normal sheath acceleration regime. While these models can qualitatively explain most experimental findings, they can hardly be used as predictive models, for example, for the energy cut-off of accelerated protons, as many of the underlying parameters are often unknown. Here we analyze experiments on laser proton acceleration in which scans of laser and target parameters were performed. We derive empirical scaling laws from these parameter scans and combine them in a scaling law for the proton energy cut-off that incorporates the laser pulse energy, the laser pulse duration, the focal spot radius, and the target thickness. Using these scaling laws, we give examples for predicting the proton energy cut-off and conversion efficiency for state-of-the-art laser systems.

[Radiofrequency ablation as a palliative therapy option in ENT tumors: in vivo and in vitro testing]. / Radiofrequenzablation als palliative Therapieoption bei HNO-Tumoren : In-vivo- und In-vitro-Versuche.

BACKGROUND: High frequency thermotherapy (HFTT) is an established palliative therapy for hepatic malignancies. An in vivo and in vitro trial examined the preconditions for the application of HFTT with liquid-cooled wet electrodes for minimally invasive palliation of head and neck tumors. MATERIAL AND METHOD: HFTT was applied with needle electrodes, cooled with isotonic saline solution, and a high-frequency generator (Elektrotom HiTT 106, Berchtold, Tuttlingen) to porcine tongue and narcotized, juvenile domestic pigs to the tongue and neck, and monitored in realtime by B-mode ultrasound. RESULTS: The direction of spread of the hyperthermic zone is well observed using ultrasound. Determining the direction of spread is not possible with cooled-tip electrode needles. Severe complications were not observed during the application. CONCLUSION: RFA with liquid-cooled needle applicators is not safely applicable for the therapy of head and neck tumors.

Splitting of the magnetic monopole pair-creation energy in spin ice.

The thermodynamics in spin-ice systems are governed by emergent magnetic monopole excitations and, until now, the creation of a pair of these topological defects was associated with one specific pair-creation energy. Here, we show that the electric dipole moments inherent to the magnetic monopoles lift the degeneracy of their creation process and lead to a splitting of the pair-creation energy. We consider this finding to extend the model of magnetic relaxation in spin-ice systems and show that an electric dipole interaction in the theoretically estimated order of magnitude leads to a splitting which can explain the controversially discussed discrepancies between the measured temperature dependence of the magnetic relaxation times and previous theory. By applying our extended model to experimental data of, various spin-ice systems, we show its universal applicability and determine a dependence of the electric dipole interaction on the system parameters, which is in accordance with the theoretical model of electric dipole formation.

Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line.

In contrast to mouse epidermal cells, human skin keratinocytes are rather resistant to transformation in vitro. Immortalization has been achieved by SV40 but has resulted in cell lines with altered differentiation. We have established a spontaneously transformed human epithelial cell line from adult skin, which maintains full epidermal differentiation capacity. This HaCaT cell line is obviously immortal (greater than 140 passages), has a transformed phenotype in vitro (clonogenic on plastic and in agar) but remains nontumorigenic. Despite the altered and unlimited growth potential, HaCaT cells, similar to normal keratinocytes, reform an orderly structured and differentiated epidermal tissue when transplanted onto nude mice. Differentiation-specific keratins (Nos. 1 and 10) and other markers (involucrin and filaggrin) are expressed and regularly located. Thus, HaCaT is the first permanent epithelial cell line from adult human skin that exhibits normal differentiation and provides a promising tool for studying regulation of keratinization in human cells. On karyotyping this line is aneuploid (initially hypodiploid) with unique stable marker chromosomes indicating monoclonal origin. The identity of the HaCaT line with the tissue of origin was proven by DNA fingerprinting using hypervariable minisatellite probes. This is the first demonstration that the DNA fingerprint pattern is unaffected by long-term cultivation, transformation, and multiple chromosomal alterations, thereby offering a unique possibility for unequivocal identification of human cell lines. The characteristics of the HaCaT cell line clearly document that spontaneous transformation of human adult keratinocytes can occur in vitro and is associated with sequential chromosomal alterations, though not obligatorily linked to major defects in differentiation.

[Stapes surgery : first experiences with the new Soft-CliP piston]. / Steigbügelchirurgie : Erste Erfahrungen mit dem Einsatz des neuen Soft-CliP(R)-Pistons.

BACKGROUND: The first hearing results with a new stapes prosthesis with clip function (Soft-CliP(R) piston) are presented. PATIENTS AND METHODS: This new prosthesis was used in 15 patients (mean age 45.2 years; range 21-63 years) undergoing routine stapes surgery. Soft-CliP(R) piston prostheses with a shaft diameter of 0.4 mm and a length ranging from 4.25 mm to 5.5 mm were used. Postoperative audiological testing and measurement of the air-bone gap were performed after an average of 47.3 days and compared with the preoperative values. RESULTS: The median observed postoperative air-bone gap (ABG) was 8.33 dB +/-4.16 dB. All patients had less than 20 dB ABG and in 53.3% of cases was less than 10 dB. The operating time showed a clear difference between the left (66.5 min +/-37.79 min) and right ears (47.2 min +/-11.08 min). DISCUSSION: This new prosthesis design greatly facilitates a very difficult step in stapes surgery, the prosthesis fixation to the incus. The first postoperative hearing results are very promising but long-term results in a larger group of patients are still pending.

Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants.

Ketamine is a drug that reduces depressive and elicits schizophrenia-like symptoms in humans. However, it is largely unexplored whether women and men differ with respect to ketamine-action and whether age contributes to drug-effects. In this study we assessed dissociative symptoms via the Clinician Administered Dissociative States Scale (CADSS) in a total of 69 healthy subjects aged between 18 and 30 years (early adulthood) after ketamine or placebo infusion. Dissociative symptoms were generally increased only in the ketamine group post-infusion. Specifically, within the ketamine group, men reported significantly more depersonalization and amnestic symptoms than women. Furthermore, with rising age only men were less affected overall with respect to dissociative symptoms. This suggests a sex-specific protective effect of higher age which may be due to delayed brain maturation in men compared to women. We conclude that it is crucial to include sex and age in studies of drug effects in general and of ketamine-action in specific to tailor more efficient psychiatric treatments. Clinical Trial Registration: EU Clinical Trials Register (EudraCT), trial number: 2010-023414-31.

Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor.

In order to determine the distribution and function of the 5-HT5A serotonin receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT5A receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT5A receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT5A receptors.

Equipment-independent reference values for dopamine transporter imaging with 123I-FP-CIT.

AIM: Reliable reference values are helpful to interpret and compare the results of dopamine transporter imaging with SPECT. Since semi-quantitative reference values cannot be easily transferred between imaging equipments, this study aimed to establish equipment independent normal values for the true striatal binding of 123I-FP-CIT. PATIENTS, METHODS: Specific striatal FP-CIT binding of 6 healthy volunteers and 26 patients with essential tremor were used to generate a reference range by applying an equipment specific resolution dependent factor to compensate for recovery effects. This factor has been determined previously by a series of standardized phantom measurements of an anthropomorphic basal ganglia phantom. Herewith, the resulting DAT binding values represent the expected true specific binding in the striatum. RESULTS: On average, true specific striatal binding was 5.83 +/- 0.96 in healthy controls, 5.25 +/- 0.67 in patients with essential tremor and 5.36 +/- 0.75 in the entire study cohort. CONCLUSION: These preliminary results may serve as a basis for the generation of a generally accepted equipment independent reference range for dopamine transporter imaging with 123I-FP-CIT. By a simple phantom measurement that can be accomplished within one day factors related to specific imaging equipment and processing can be corrected for, resulting in specific binding values which may enable a more standardized interpretation of dopamine transporter scans.

[First experiences with a new nickel-titanium piston with a shape memory feature]. / Einsatz eines Nickel-Titan-Piston mit Memory-Eigenschaften: Erster Erfahrungsbericht.

BACKGROUND: The aim of this study was to describe a new stapes prosthesis with memory characteristics for wire crimping (SMart-Piston). PATIENTS AND METHODS: This technique was used in 15 patients (mean age 43.4 years; range 28-71) undergoing routine stapes surgery. SMart-Piston prostheses with a shaft diameter of 0.5 mm and length ranging from 4.25-4.5 mm were used. Heat induced wire crimping was performed by CO2 laser in five patients, and by bipolar diathermy forceps in ten patients. In 15 patients, postoperative audiological testing was performed at an average 21.9 days and in another 10 again after 435 days following surgery. RESULTS: The median observed air-bone-gap (ABG) postoperatively was 8.7 dB+/-7.7 dB. A total of 73% of all patients had an ABG of 10 dB or less, and all patients had less than 20 dB. In the ten patients controlled after 435 days, the ABG was 4.4 dB+/-2.4 dB. It was lower than 10 dB in all individuals. DISCUSSION: A critical point in every stapes surgery, the prosthesis fixation to the incus, is greatly facilitated by this novel technique. Long-term results in a larger group of patients are pending.