Igor Stenin

Comparison of the nasal release of IL-4, IL-10, IL-17, CCL13/MCP-4, and CCL26/eotaxin-3 in allergic rhinitis during season and after allergen challenge.

Background Allergic rhinitis is an inflammatory disease characterized by local overproduction of type 2 cytokines and tissue eosinophilia. Recent research suggests the involvement of additional cytokines such as IL-17, chemokine (C-C motif) ligand (CCL) 26/eotaxin-3, and CCL13/monocyte chemoattractant protein-4 (MCP-4) in its pathophysiology. Furthermore, bronchial epithelial cells treated with IL-17 and type 2 cytokines distinctively up-regulated eotaxin-3 gene expression. In this study we investigated the kinetics of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in seasonal allergic rhinitis volunteers after nasal allergen challenge (NAC) and their release during natural pollen exposure. Methods The nasal lavages of 15 symptomatic allergic and 14 nonallergic subjects were collected during the pollination season. Additionally, six allergic subjects underwent a single unilateral nasal allergen and control challenge out of season, and nasal secretions were collected. Levels of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in nasal lavages and secretions were measured using an electrochemiluminescent assay. Results After NAC, allergic subjects had a significant immediate response of nasal symptoms as well as a significant increase at 5 hours of IL-4, IL-10, and IL-17 and at 2, 5, and 24 hours significantly raising levels of eotaxin-3. IL-17 and eotaxin-3 concentrations at 5 hours were correlated (r = 0.94; p = 0.005). During natural pollen exposure, barely detectable levels of IL-17 in allergic subjects were also correlated with eotaxin-3 (r = 0.62; p = 0.01). Eotaxin-3 and MCP-4 levels were significantly elevated 9- or 3.7-fold, respectively, and IL-10 and, unexpectedly, IL-4 were significantly lower in allergic subjects compared with nonallergic subjects. Conclusion Nasal IL-17, MCP-4, and, possibly, eotaxin-3 may aggravate and IL-10 may alleviate nasal mucosal allergy.

The release of IL-31 and IL-13 after nasal allergen challenge and their relation to nasal symptoms

BackgroundIL-31, a recently discovered member of the gp130/IL-6 cytokine family, is mainly expressed by human mast cells and T helper type 2 cells. IL-31 is a key trigger of atopic dermatitis. Recent studies also suggest a role of IL-31 in the pathogenesis of other allergic diseases including allergic rhinitis. In the present study we studied the release of IL-31 and IL-13 in allergen-challenged allergic rhinitis patients.MethodsSeven seasonal allergic volunteers underwent unilateral nasal provocation with allergen (and a control challenge) with the disc method out of the allergy season. Nasal symptom scores (rhinorrhea, itching, sneezing, obstruction) and bilateral nasal secretions were quantified before and after allergen provocation. IL-13 and IL-31 in nasal secretions and serum were measured by electrochemiluminescent immunoassay or ELISA, respectively.ResultsNasal allergen challenge induced the typical clinical symptoms and physiological changes. IL-31 and IL-13 in nasal secretions increased in four and five, respectively, volunteers at 5 h after allergen but not after control challenge. We observed correlation trends between nasal IL-31 concentrations and IL-13 concentrations (r = 0.9, p = 0.002), and IL-31 contents and symptom scores (r = 0.9, p = 0.013) 5 h after allergen provocation. No IL-31 could be detected contralaterally or systemically in the sera.ConclusionsThe observed local upregulation of IL-31 mainly during the late phase reaction after nasal allergen challenge suggests a role of IL-31 in allergic rhinitis. In which way IL-31 modulates the inflammatory reaction and type 2 responses in allergic rhinitis remains to be investigated.

Nasal levels of soluble IL‐33R ST2 and IL‐16 in allergic rhinitis: inverse correlation trends with disease severity

Serum levels of IL‐16, IL‐33 and the decoy receptor of IL‐33, soluble ST2, are elevated in allergic rhinitis. Recent studies show that IL‐16, soluble ST2 or anti‐IL‐33 reduce type 2 cytokines (such as IL‐5) and eosinophilia in murine models of allergic asthma or allergic rhinitis respectively.

Minimally Invasive Multiport Surgery of the Lateral Skull Base

Objective. Minimally invasive procedures minimize iatrogenic tissue damage and lead to a lower complication rate and high patient satisfaction. To date only experimental minimally invasive single-port approaches to the lateral skull base have been attempted. The aim of this study was to verify the feasibility of a minimally invasive multiport approach for advanced manipulation capability and visual control and develop a software tool for preoperative planning. Methods. Anatomical 3D models were extracted from twenty regular temporal bone CT scans. Collision-free trajectories, targeting the internal auditory canal, round window, and petrous apex, were simulated with a specially designed planning software tool. A set of three collision-free trajectories was selected by skull base surgeons concerning the maximization of the distance to critical structures and the angles between the trajectories. Results. A set of three collision-free trajectories could be successfully simulated to the three targets in each temporal bone model without violating critical anatomical structures. Conclusion. A minimally invasive multiport approach to the lateral skull base is feasible. The developed software is the first step for preoperative planning. Further studies will focus on cadaveric and clinical translation.

Towards Automatic Path Planning for Multi-port Minimally-Traumatic Lateral Skull Base Surgery

We investigate a multi-port minimally-traumatic approach for lateral skull base surgery. Our long-term goal is to automatically determine the best combination of three paths from the skull surface to the surgical target. Since this multi-port approach is not yet in clinical use, it is difficult to define what the best combination of paths is. Therefore, we present a planning tool which allows to manually select a combination of three paths. A clinician used this planning tool to select the best combination of three paths for three target structures in computed tomography data sets of 20 patients. From this choice we derived initial constraints for an automatic planning of the best combination of paths.

Generalized Trajectory Planning for Nonlinear Interventions

Minimally invasive procedures with flexible instruments such as endoscopes, needles or drilling units are becoming more and more common. Their automated insertion will be standard across several applications in operation rooms of the future. In such scenarios regular re-planning for feasible nonlinear trajectories is a mandatory step toward automation. However, state of the art methods focus on isolated solutions only. In this paper we introduce a generalized motion planning formulation in SE(3), regarding both position and orientation, that is suitable for these approaches. To emphasize the generalization of this formulation we evaluate the performance of proposed Bidirectional Rapidly-exploring Random Trees (Bi-RRT) on four different clinical applications: Drilling in temporal bone surgery, trajectory planning for cardiopulmonary endoscopy, automatic needle insertion for spine biopsy and liver tumor removal. Experiments show that for all four scenarios the formulation is suitable and feasible trajectories can be planned successfully.

Genauigkeit und Machbarkeit robotische Multi-Port Cochleaimplantation – Evaluierung am Phantom

Untersuchungsziel Der Multi-Port Ansatz fur die robotische Cochleaimplantation bietet Vorteile bezuglich Instru-mentenmanipulation und Visualisierung und eine Beruhrung von Trommelfell und Gehorkno-chelchen kann vermieden werden. In dieser Studie wurde die Machbarkeit einer minimal-invasiven Cochleaimplantation uber einen Multi-Port Zugang untersucht. Methodik In Bilddaten (CT, 0.15 x 0.15 x 0.2 mm) eines Schlafenbeinmodels (Phacon) wurden vier Trajektorien (∅ 1.8 mm, l = 21.5 bis 31.8 mm) von der Oberflache des Felsenbeins kollisions-frei zu anatomischen Strukturen zum runden Fenster geplant: retro-facial (RF), suprameatal (SM), sub-facial (SF) und durch den Rezessus Facialis (FR) und mittels eines CI-Robotersystems (Universitat Bern) realisiert. Es wurden sechs Insertionsversuche durchge-fuhrt (Visualisierung mittels EndoGnost, 0.55 mm Durchmesser, 0° Winkel, PolyDiagnost und Manipulation mit einer geraden Nadel, Medicon). Jeder Zugang bestand aus je einer Trajek-torie fur Elektrodeninsertion (immer FR), Visualisierung und Instrumentenmanipulation (Kom-bination aus RF, SM und SF). Pro Kombination wurden die endoskopisch darstellbaren sowie fur die Instrumente erreichbaren anatomischen Strukturen, die erreichte Elektrodeninserti-onstiefe und die dafur benotigte Zeit bestimmt. Anhand eines postoperativen CT wurden die Trajektorien geometrisch vermessen. Ergebnisse Der mittlere Bohrfehler betrug 0.15 mm. (SM 0.12 mm; FR 0.2 mm; RF 0.07 mm; SF 0.2 mm). Fur eine volle Insertion des Elektrodenarrays war ein Zugang bestehend aus den Trajektorien FR, RF und SF am geeignetsten (12 von 12 Elektroden innerhalb von 4:30 Minu-ten). Visualisierung und Instrumentenmanipulation via Trajektorien RF respektive SF ermog-lichten freie Sicht auf bzw. Erreichbarkeit des runden Fensters und erlaubten die zusatzliche manuelle Unterstutzung bei der Einfuhrung des Elektrodenarrays. Ein Multi-Port Zugang be-stehend aus den Trajektorien SF fur Visualisierung und RF fur Instrumentenmanipulation er-moglichte Visualisierung vieler anatomischer Strukturen, jedoch war die Trajektorie RF we-gen dem Winkel zum runden Fenster als Hilfestellung zur Elektrodeninsertion mittels eines ri-giden Instrumentes nutzlos. Die ubrigen Zugange waren mangels Visualisierung oder Er-reichbarkeit des runden Fensters ungeeignet fur eine verlassliche Insertion. Schlussfolgerung Die Moglichkeit eines Multi-Port Zugang zum runden Fenster bestehend aus drei Trajektorien ohne Beeinflussung anatomischer Strukturen konnte initial im Phantom bestatigt werden. Verschiedene Kombinationen von Zugangen wurden miteinander verglichen. Visualisierung und Manipulation durch die RF und SF verlaufenden Trajektorien ermoglichte die Darstellung und Erreichbarkeit aller zur Cochleaimplantation notigen Strukturen.

Multistep translation and cultural adaptation of the Penn acoustic neuroma quality-of-life scale for German-speaking patients

BackgroundMonitoring the health-related quality of life (HRQOL) for patients with vestibular schwannoma (VS) has garnered increasing interest. In German-speaking countries, there is no disease-specific questionnaire available similar to the “Penn Acoustic Neuroma Quality-of-life Scale” (PANQOL).MethodWe translated the PANQOL for German-speaking patients based on a multistep protocol that included not only a forward-backward translation but also linguistic and sociocultural adaptations. The process consists of translation, synthesis, back translation, review by an expert committee, administration of the prefinal version to our patients, submission and appraisal of all written documents by our research team. The required multidisciplinary team for translation comprised head and neck surgeons, language professionals (German and English), a professional translator, and bilingual participants. A total of 123 patients with VS underwent microsurgical procedures via different approaches at our clinic between January 2007 and January 2017. Among these, 72 patients who underwent the translabyrinthine approach participated in the testing of the German-translated PANQOL.ResultThe first German version of the PANQOL questionnaire was created by a multistep translation process. The responses indicate that the questionnaire is simple to administer and applicable to our patients.ConclusionThe use of a multistep process to translate quality-of-life questionnaires is complex and time-consuming. However, this process was performed properly and resulted in a version of the PANQOL for assessing the quality of life of German-speaking patients with VS.