Rare Case of Tularemia With Preauricular Lymphadenopathy and Conjunctivitis in a 27-Year-Old Male Patient in Germany.

Tularemia is a rare disease but shows an approximately 10-fold increase in reported cases over the last 15 years in Germany. Clinical symptoms of acute tularemia infection are various, which often delays diagnosis. This case report gives an overview of the clinical manifestations of acute tularemia and shows the importance of interdisciplinary work to shorten the time from the onset of symptoms to effective treatment in infection with Francisella tularensis. Since some cases of tularemia are life-threatening, early diagnosis is vital. This case report serves as a reminder that rare diseases need to be considered in cervical lymphadenopathy.

Vestibular testing in children - The suppression head impulse (SHIMP) test.

INTRODUCTION: The incidence of vestibular disorders and vertigo during childhood is increasing and pediatric clinicians have become more sensitive to children's balance disorders; thus, there is a need for appropriate detection test procedures for peripheral vestibular hypofunction. In order to ensure a reliable diagnosis and minimize misdiagnosis, a standardized clinical procedure via careful history and clinical examination is recommended. However, children, especially, are often unable to verbalize "vertigo" in a concrete manner, which often necessitates a consultation with a pediatrician holding nonspecific symptoms. The so-called suppression of the head impulse test (SHIMPs) represents a modification of the video head impulse test (HIMP) and is used for a more sensitive assessment of residual vestibular functions. In adults, SHIMPs are already an established diagnostic method. Nevertheless, to date, nothing is known about the applicability and standard values in childhood. MATERIAL AND METHODS: In this monocentric, prospective study, we investigated whether SHIMPs enable a sensitive functional analysis of the vestibular system in healthy children of different ages. For this purpose, SHIMPs were performed in 40 children aged 3-18 years. RESULTS: In this study, we demonstrated that SHIMPs can be easily performed in children (3-18 years). It is vital that the test be appropriately explained for children to ensure sufficient test tolerance and compliance. CONCLUSION: SHIMPs are a helpful supplement to clinically established vestibular tests such as the HIMP in pediatric vestibular balance disorder diagnostics and can be integrated into the clinical routine, especially in children who have minimal verbal abilities or understanding of the instructions for HIMP. Similar to the HIMP, SHIMPs are characterized by a short test duration and a high tolerance.

[Effects of the SARS-CoV­2 pandemic on the otolaryngology university hospitals in the field of research, student teaching and specialist training]. / Auswirkungen der SARS-CoV­2-Pandemie auf die universitäre Hals-Nasen-Ohren-Heilkunde im Bereich der Forschung, Lehre und Weiterbildung.

BACKGROUND: From spring 2020, SARS-CoV­2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.

[Effects of the SARS-CoV-2 pandemic on the otorhinolaryngology university hospitals in the field of medical care]. / Auswirkungen der SARS-CoV-2-Pandemie auf die universitäre Hals-Nasen-Ohrenheilkunde im Bereich der Krankenversorgung.

INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8 % to 26.2 ±â€Š14.2 % and in surgical treatments by 65.9 % to 34.1 ±â€Š13.9 %. In contrast, emergency treatment remained unchanged or even increased in 80 % of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90 %. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35 000 outpatients and about 12 000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.

[Necrotizing fasciitis in the head and neck region-three case reports and a review of the literature]. / Nekrotisierende Fasziitis der Kopf-Hals-Region ­ 3 Fallberichte und Literaturübersicht.

Necrotizing fasciitis (NF) is a life-threatening, usually bacterial, soft tissue infection that rarely affects the head and neck region. Rapid progression and systemic illness are typical for the disease and complicate diagnosis. Immediate surgical and antimicrobial therapy is required. Three cases of cervicofacial NF are presented in this case report. All patients showed a rapidly progressing, painful swelling and redness in the cervicofacial region. After diagnosing NF based on clinical symptoms, laboratory parameters, and CT, the patients were treated with systemic antibiotics and multiple extensive debridements. Two of the three patients died within 48 h from systemic illness with septic organ failure; one patient was discharged after intensive care treatment and reconstruction of the tissue defects caused by debridement. NF is a fast-developing soft tissue infection associated with high mortality and morbidity, and is often recognized too late. Diagnosis is based on clinical signs such as progressive diffuse swelling, pain, erythema, and early systemic illness. Laboratory parameters (Laboratory Risk Indicator for Necrotizing Fasciitis [LRINEC] score) and imaging via CT or MRT are helpful. CT/MRT images can show soft tissue swelling with pathognomonic gas formation. Immediate surgical debridement and antimicrobial therapy are critical for survival. Intravenously administered immunoglobulins and hyperbaric pressure therapy should only be used as supplementary treatments.

[Exosomes as immune regulators in head and neck cancer]. / Exosomen als Immunregulatoren in Kopf-Hals-Karzinomen.

Exosomes, virus-sized nanovesicles, are utilized as messenger systems of our body to communicate with other body cells and regulate immune functions. Almost all cells produce exosomes and are able to interact with immune cells in the blood stream and peripheral body areas. Different markers on the surface of exosomes are necessary for immune cell adhesion and interaction. Furthermore, many types of exosome-immune cell interaction, such as surface receptor contact and phagocytosis, are known. As carriers of different cargos, exosomes affect different immune cell types in head and neck cancers: So far, T cells, natural killer cells, macrophages, and dendritic cells have been described in this context. For diagnostic purposes, a combined analysis of different parameters including protein amount, nucleic acid/protein expression, and the immunosuppressive impact of exosomes could empower exosomes as useful tools for evaluation of tumor promotion and progression in the future.

Adenosine production in mesenchymal stromal cells in relation to their developmental status.

BACKGROUND: Mesenchymal stromal cells (MSC) are multipotent progenitor cells found in the tumor microenvironment. They have an innate and regulatory immune activity, and they are able to produce immunosuppressive adenosine (ADO) via their ectonucleotidases CD39 and CD73. The present study explores ADO metabolism of MSC in relation to their developmental status. METHODS: We analyzed MSC (n = 6), chondrogenic progenitor cells (CPC, n = 8), and chondrocytes (n = 8) for surface markers by flow cytometry. The ability to hydrolyze ATP and to produce ADO was tested by luminescence assays and mass spectrometry. RESULTS: Significant differences in the surface marker expression of MSC, CPC, and chondrocytes were seen. While the expression of CD73 was observed to be the same on all cell types, the expression of the ectonucleotidase CD39 was significantly increased on MSC. Consequently, production of ADO was most abundant in MSC as compared with chondrocytes and CPC. CONCLUSION: Mesenchymal stromal cells are potent producers of ADO and are, therefore, able to increase immunosuppression. As MSC differentiate into chondrocytes, they lose this ability and may take on other functions.

[Prevalence of peripheral vestibular diseases in children in Germany]. / Prävalenz peripher-vestibulärer Erkrankungen bei Kindern in Deutschland.

INTRODUCTION: Dizziness is a common complaint among patients; however, a lack of valid data concerning age and gender distribution of dizziness disorders among children under the age of 15 years can preclude effective diagnosis and treatment. The goal of this study was to describe the prevalence and gender distribution of three classical peripheral vestibular disorders; benign paroxysmal positional vertigo (BPPV), vestibular neuritis (VN), and Menière's disease (MD) as well as unspecific dizziness (UV) in children between 0 and 15 years of age, using state sponsored health insurance data. METHODS: A population-based epidemiological survey based on confirmed International Classification of Diseases (ICD) 10 codes of all persons aged 0-15 years in a national population was performed. Outcome measures were age and gender distribution and prevalence of BPPV, VN, and MD in this population. RESULTS: Dizziness diagnosed as being of peripheral vestibular origin was found in 1414 patients. The prevalence of peripheral vestibular disorders was found to be 15.16 per 100,000 individuals. The BPPV was coded most frequently with a prevalence of 10.21 per 100,000 individuals, followed by VN with a prevalence of 3.5 per 100,000 and MD at 1.54 per 100,000. CONCLUSION: Peripheral vestibular disorders can occur in childhood and the prevalence increases with age. In childhood, girls and boys are similarly affected. Peripheral vestibular disorders should be taken into consideration when a young child presents with vertigo or dizziness and are even more important when a child presents with unclear symptoms, as very young children might not be able to adequately verbalize dizziness and vertigo. For that reason peripheral vestibular disorders in childhood are probably underdiagnosed.

Addition of decellularized extracellular matrix of porcine nasal cartilage improves cartilage regenerative capacities of PCL-based scaffolds in vitro.

Composite scaffolds can improve regenerative capacities of scaffolds in various tissue-engineering approaches. In order to generate a 3D printable scaffold that is capable of cartilage regeneration, decellularized extracellular matrix (DECM) of porcine nasal cartilage was added to 3D printed polycaprolactone (PCL) scaffolds. Subsequently, scaffolds (PCL, PCL/DECM and DECM) were seeded with human primary nasoseptal chondrocytes and differentiated with cartilage inductive medium for up to 42 days in vitro. Afterwards samples were analyzed with scanning electron microscopy, histology, biochemical assays and gene expression analysis. In short, results showed cell attachment and proliferation on all scaffolds. There was a trend towards ossification on pure PCL scaffolds, whereas we found evidence for cartilage tissue formation on DECM scaffolds as well as on PCL/DECM scaffolds. Moreover, biochemical analysis indicated an enhanced differentiation on novel PCL/DECM scaffolds. In conclusion, the addition of DECM to 3D printable PCL scaffolds may yield a new composite material for regenerative approaches in cartilage for facial reconstructive surgery. Further research will be necessary to evaluate these findings in vivo.

Treatment of ear keloids: algorithm for a multimodal therapy regimen.

Keloids are benign cutaneous lesions, arising from proliferating fibroblasts. Keloids of the ear may occur after trauma, surgery or helix piercings and are difficult to treat, since they tend to form recurrences. Guidelines suggest multimodal therapy; however, recurrence rates remain high and distinct algorithms for the combination of different modalities are missing. To unravel the most effective combination of therapeutic options for keloids of the ear, 38 patients with the diagnosis of an ear keloid were included in our cohort. In a prospective subgroup (B) of this cohort (n = 17), patients either underwent surgery using the "fillet technique" (a meticulous peeling of the keloid skin) and intra-lesional injections of triamcinolone 10 mg/ml every 4-6 weeks for 6 months, or they were additionally treated with a non-customized pressure device which was recommended for at least 16/24 h per day over 6 months. To further compare our results, the remaining 21 patients of our cohort, who were treated at our clinic before, were retrospectively evaluated concerning their recurrence rates. The mean follow-up was 48 months. The mean count of adjuvant steroid injections was two in all patients, four in subgroup B. The recurrence rate was 30% (13/38) in all patients (subgroup B 0/17). Aesthetic results were good to excellent in all non-recurrent cases. No patient treated with fillet technique showed recurrence (p < 0.001). However, we could not confirm a significant effect but a trend of repeated steroid injections for preventing recurrences (p = 0.099). The application of pressure using our non-customized clip also showed a clear trend towards preventing recurrences in cross-table analysis (p = 0.057). Although several studies on different treatment regimens for keloids of the ear exist, the effectiveness of a multimodal treatment regimen needs to be elucidated. Overall, the best results in preventing recurrences were achieved by combining three different treatments. However, the fillet technique was the only modality preventing recurrences of keloids in uni- and multivariate analysis. The application of pressure with a non-customized clip and repeated steroid injections also showed a positive trend but failed level of significance. Based on our data and the literature we recommend, when feasible, the combination of more than one therapeutic regimen, since relapse risk went down from single to dual and triple therapy from 40% (8/20) to 14.3% (2/14) to 0% (0/4), respectively in our cohort. The use of "fillet technique" was especially beneficial.

A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1).

BACKGROUND: Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for locally advanced head and neck cancer. This phase II study investigated the effectivity of a split-dose TPF ICT before surgery for locally advanced resectable (stage III/IVA) oral and oropharyngeal cancer. PATIENTS AND METHODS: Patients received TPF split on two dosages on days 1 and 8 per cycle (30 mg/m2 docetaxel, 40 mg/m2 cisplatin, 2000 mg/m2 fluorouracil per week). Responders (reduction tumor volume ≥30% after first cycle) received three 3-week cycles and non-responders only one cycle before surgery and postoperative radio(chemo)therapy (RCT). The primary endpoint was progression-free survival rate after 24 months. Secondary endpoints were amongst others overall survival, histopathological response to ICT, toxicity, quality of life and swallowing function. RESULTS: Fifty-four patients (91% stage IVA, 87% male, 72% oropharyngeal cancer, 70% responders) were eligible for a per-protocol analysis. The progression-free survival rate after 24 months was 88.5% for responders and 60.6% for non-responders (P = 0.005). The overall survival rate after 24 months was 97.3% for responders and 73.7% for non-responders (P = 0.032). The rate of histopathological complete remission of the primary tumor was higher in responders (P = 0.015). High-risk classification for postoperative RCT was lower in responders (P < 0.0001). The most common grade 3+ adverse event was neutropenia in 26% of patients during ICT and mucositis in 13% during postoperative RCT. During treatment and follow-up quality of life and swallowing function was not different between responders and non-responders. CONCLUSION: Patients with oral and oropharyngeal cancer responding to split-dose TPF before surgery and postoperative RCT show good oncological results. The tri-modal treatment regime was well tolerated. ICT using tumor response as criterion for duration of ICT before surgery of oral and oropharyngeal cancer merits additional investigation in a phase III study. CLINICAL TRIAL NUMBER: NCT01108042.

Application of a computer-assisted flexible endoscope system for transoral surgery of the hypopharynx and upper esophagus.

Zenker's diverticulum is a common pathology in the transition zone of the posterior hypopharynx and esophagus. Surgical treatment is routinely performed by ENT and general surgeons. Besides the traditional open transcervical diverticulectomy, the introduction of transoral rigid treatment led to a paradigm change and is now the preferred treatment option for patients who are fit for general anesthesia. The implementation of interventional flexible endoscopy has opened another new micro-invasive approach for patients with high morbidity. Here, we present the potential utilization of a flexible, single port, robot-assisted, and physician-controlled endoscope system to facilitate transoral surgical access to the hypopharynx and upper esophagus. Transoral surgery of the hypopharynx and upper esophagus was performed in human cadavers (n = 5) using the Flex System (Medrobotics, Raynham, USA). Anatomical landmarks were identified, and posterior cricothyroid myotomy was performed with compatible flexible instruments in all cases. The approach to the hypopharynx and upper esophagus using the Flex system is feasible in a cadaveric model. Myotomy with a flexible tool and needle knife (from the perspective of treatment of Zenker´s diverticulum) was successful in all cases. Visualization of the surgical site with the system's HD camera is suitable and the flexible instruments meet the special needs of a micro-invasive transoral approach. Zenker´s diverticulum can be potentially treated with a transoral minimally invasive approach using a computer-assisted flexible endoscope system. This setup could be of advantage in patients with reduced mobility of the cervical spine to prevent open transcervical surgery. In our study, the Flex system enabled advanced visualization of the surgical site and extended intervention options, compared to standard flexible endoscopic treatment. However, general anesthesia is mandatory for the presented approach. Application in live patients with actual pathologies of the hypopharynx and upper esophagus will have to prove suitability for the treatment of Zenker's diverticulum. Further development of the system could include improved instrumentation and an adoption by other disciplines with challenging anatomy such as colorectal surgery.

First use of flat-panel computed tomography during cochlear implant surgery : Perspectives for the use of advanced therapies in cochlear implantation.

BACKGROUND: Cochlear implantation in routine cases with normal anatomy is commonly performed without intraoperative image guidance. Revision cochlear implantation as well as surgery in malformations require not only a precise understanding of the underlying complex anatomy, but surgeons need to transform two-dimensional computed tomography (2D CT) scans into the surgical field and use this information for intraoperative surgical navigation. So far, information about the exact position of the electrode during insertion cannot be provided to the surgeon. Here, we present our first operative experience with cochlear implant surgery supported by intraoperative Dyna-CT technology, providing the surgeon with detailed views of the electrode location. METHODS: To prove the feasibility of the procedure, two cases of cochlear implantation were performed with intraoperative application of cone-beam CT acquired by a C-arm Dyna-CT system (Artis Zeego, Siemens Healthcare, Erlangen, Germany). Image reconstruction was performed intraoperatively in order to assess the correct positioning of the electrodes. RESULTS: Intraoperative Dyna-CT enabled clear visualization of the surgical anatomy and intracochlear electrode position. Dyna-CT technology can be applied with acceptable additional time requirements without adding too much complexity to the surgical procedure. CONCLUSION: Intraoperative data acquisition by Dyna-CT represents a suitable option for online surgical navigation during cochlear implant surgery. This imaging technology will push further advances in cochlear implant surgery and lateral skull base surgery, particularly if linked to intraoperative navigation.

[Evidence-Based and Evidence-lacking Therapies of Nasal Obstruction and Rhinosinusitis]. / Evidenz und Evidenzlücken bei der Behandlung der behinderten Nasenatmung und der Rhinosinusitis.

Therapeutic decisions in otorhinolaryngology are based on clinical experience, surgical skills and scientific evidence. Lately, evidence-based therapies have gained increased attention and importance due to their potential to improve individual patients treatments and their potential to at the same time reduce treatment costs. In clinical practice it is almost impossible to stay ahead of the increasing masses of literature and on the other hand to critically assess the presented data. A solid scientific and statistical knowledge as well as a significant amount of spare time are required to detect systematic bias and other errors in study designs, also with respect to assessing whether a study should be part of an individual therapeutic decision or not. Meta-analyses, reviews and clinical guidelines are therefore of increasing importance for evidence-based therapy in clinical practice.This review is an update of the availability of external evidence for the treatment of nasal obstruction and rhinosinusitis. It becomes evident that both groups of diseases differ significantly in the availability of external evidence. Furthermore, it becomes obvious that surgical treatment options are usually based on evidence of significantly lower quality than medical treatment options.

[Autologous composite grafts from the cavum conchae for reconstruction of multilayer nasal defects]. / Das autologe Haut-Knorpel-Transplantat aus dem Cavum conchae zur Rekonstruktion mehrschichtiger nasaler Defekte.

BACKGROUND: Autologous transplants comprising skin and cartilage, so-called composite grafts (cgs), are an important reconstructive tool for multilayered defects of the nose. A cg from the auricular cavum conchae needs to fulfill both functional and esthetic demands. OBJECTIVE: This article illustrates the indications for and requirements of cgs, and also investigates graft healing and functional-aesthetic results. The current publication is a review article; the original data were published with the award of the 2014 APKO prize under the title "The auricle's cavum conchae composite graft in nasal reconstruction". MATERIALS AND METHODS: At the ENT department of Ulm University Medical School, multilayered defects of different nasal esthetic subunits are reconstructed with cgs. Based on these experiences, the authors report on long-term functional and esthetic results in the areas of the donor and recipient sites. CONCLUSION: Auricular cgs are versatile and reliable autologous transplants. The ease of harvesting, minimal donor site morbidity, and stable convex shape of these grafts render them ideal for reconstruction of multilayered nasal defects. Septal splints and custom-made prosthesis promote healing and prevent stenotic scarring.

Characterization of a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features and their potential for in vivo cartilage regeneration strategies.

BACKGROUND: Progenitor cells display interesting features for tissue repair and reconstruction. In the last years, such cells have been identified in different cartilage types. In this study, we isolated a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features by outgrowth from human nasal septum cartilage. These putative progenitor cells were comparatively characterized with mesenchymal stem cells (MSC) and human nasal septum chondrocytes with respect to their cellular characteristics as well as surface marker profile using flow cytometric analyses. Differentiation capacity was evaluated on protein and gene expression levels. RESULTS: The migrative subpopulation differentiated into osteogenic and chondrogenic lineages with distinct differences to chondrocytes and MSC. Cells of the migrative subpopulation showed an intermediate surface marker profile positioned between MSC and chondrocytes. Significant differences were found for CD9, CD29, CD44, CD90, CD105 and CD106. The cells possessed a high migratory ability in a Boyden chamber assay and responded to chemotactic stimulation. To evaluate their potential use in tissue engineering applications, a decellularized septal cartilage matrix was either seeded with cells from the migrative subpopulation or chondrocytes. Matrix production was demonstrated immunohistochemically and verified on gene expression level. Along with secretion of matrix metalloproteinases, cells of the migrative subpopulation migrated faster into the collagen matrix than chondrocytes, while synthesis of cartilage specific matrix was comparable. CONCLUSIONS: Cells of the migrative subpopulation, due to their migratory characteristics, are a potential cell source for in vivo regeneration of nasal cartilage. The in vivo mobilization of nasal cartilage progenitor cells is envisioned to be the basis for in situ tissue engineering procedures, aiming at the use of unseeded biomaterials which are able to recruit local progenitor cells for cartilage regeneration.

A single-port operator-controlled flexible endoscope system for endoscopic skull base surgery.

OBJECTIVE: In a human cadaver study, a single-port operator-controlled flexible endoscope (Flex® System), facilitated with a high-definition camera and two accessory channels was tested for skull base surgery. DESIGN: Skull base surgery was performed on human cadavers (n=4) using the Flex® System. A modified surgical midfacial approach, performed by rigid standard tools, was used for access to the sinus system, the skull base, and the middle cranial fossa. RESULTS: Endoscopic skull base visualization with the Flex® System is feasible. Surgical procedures performed included extended sinus surgery, anterior skull base approach, and visualization of the brain stem in the posterior cranial fossa. Important landmarks of the anterior skull base were visualized and manipulated by flexible compatible tools. CONCLUSION: The Flex® System allows for manipulation of the anterior skull base and visualization of the posterior cranial fossa in a preclinical setting. Further studies as well as development of supplemental tools are in progress.

Immortalised human mesenchymal stem cells undergo chondrogenic differentiation in alginate and PGA/PLLA scaffolds.

Adult mesenchymal stem cells (MSCs) are a promising cell source in tissue engineering due to their availability, ease of isolation and high proliferative activity. This study was undertaken to investigate whether immortalised human MSC are able to undergo chondrogenic differentiation when cultured in alginate or in resorbable scaffolds. We directly compared chondrogenesis MSCs with that of human nasoseptal chondrocytes. Two previously established human stem cell lines L87/4 and V54-2 immortalised using the SV40 large T-antigen were either cultured in alginate or in polyglycolic acid/poly-L-lactic acid (PGA/PLLA) (90/10) copolymer scaffolds. TGF-ß1 was added for induction of chondrogenesis. Human nasoseptal chondrocytes and human fibroblasts were used as controls. Cultures were analysed for sulfated glycosaminoglycans (alcian blue staining) and for the presence of collagen type I, II and X (immunolabelling). SV40 large T-antigen immortalised human MSCs have the potential to undergo chondrogenic differentiation: After 21 days, cartilage-specific type II collagen was present in alginate and PGA/PLLA scaffolds, independent of the addition of TGF-ß1. Collagen type X was present in monolayer cultures as well as in alginate and PGA/PLLA scaffolds. Collagen type I was produced in marginal amounts only. Immortalised human MSCs are a suitable tool to study chondrogenesis in vitro and to screen biomaterials for cartilage tissue engineering applications.