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Background: To improve the biocompatibility of porous polyethylene (PPE) implants and expand their application range for reconstructive surgery in poorly vascularized environments, implants were coated with tumor necrosis factor α (TNFα) inhibitor Etanercept. While approved for systemic application, local application of the drug is a novel experimental approach. Microvascular and mechanical integration as well as parameters of inflammation were analyzed in vivo. Methods: PPE implants were coated with Etanercept and extracellular matrix (ECM) components prior to implantation into dorsal skinfold chambers of C57BL/6 mice. Fluorescence microscopy analyses of angiogenesis and local inflammatory response were thrice performed in vivo over a period of 14 days to assess tissue integration and biocompatibility. Uncoated implants and ECM-coated implants served as controls. Results: TNFα inhibition with Etanercept led to a reduced local inflammatory response: leukocyte-endothelial cell adherence was significantly lowered compared to both control groups (n = 6/group) on days 3 and 14, where the lowest values were reached: 3573.88 leukocytes/mm-2 ± 880.16 (uncoated implants) vs. 3939.09 mm-2 ± 623.34 (Matrigel only) vs. 637.98 mm-2 + 176.85 (Matrigel and Etanercept). Implant-coating with Matrigel alone and Matrigel and Etanercept led to significantly higher vessel densities 7 and 14 days vs. 3 days after implantation and compared to uncoated implants. Mechanical implant integration as measured by dynamic breaking strength did not differ after 14 days. Conclusion: Our data show a reduced local inflammatory response to PPE implants after immunomodulatory coating with Etanercept in vivo, suggesting improved biocompatibility. Application of this tissue engineering approach is therefore warranted in models of a compromised host environment.

Regulatory and economic conditions drive the application of the concept of homologous groups on therapeutic and diagnostic formulations. In this context, a possible reduction of allergens in the skin prick test panel in the clinical routine should be investigated for the grass, birch and Dermatophagoides homologous group. Grass and cultivated rye skin prick test results of 1101 patients, birch/hazel/alder skin prick test results of 1131 patients and 1068 Dermatophagoides pteronyssinus and farinae skin prick tests were retrospectively evaluated with regard to sensitivity and false-negative rate detecting sensitization against cultivated rye with grass skin prick test, sensitization against hazel and/or alder with birch skin prick test and sensitization towards Dermatophagoides farinae with Dermatophagoides pteronyssinus skin prick test. Skin prick test results in all groups highly correlated in Spearman Rank Order correlation. Sensitivity of grass skin prick test detecting sensitization against cultivated rye was highest with 98.9%, sensitivity of birch skin prick test detecting sensitization toward hazel and alder was 95.6 and 90.0%, respectively. Sensitivity of skin prick test with Dermatophagoides pteronyssinus detecting sensitization towards Dermatophagoides farinae was 93.6%. Only 26 patients with positive rye, hazel, alder or Dermatophagoides farinae skin prick test that were overlooked by grass, birch or Dermatophagoides pteronyssinus skin prick test reported allergic symptoms. In routine clinical practice, sensitization against cultivated rye can safely be detected by skin prick test with grass allergen. In addition, the sensitivity of birch skin prick test is high in terms of sensitization towards hazel, but lower for alder. Sensitivity of Dermatophagoides pteronyssinus skin prick test also is high to detect sensitization towards Dermatophagoides farinae. Further research will indicate if several skin prick test allergens will disappear and be completely replaced by a single skin prick test based on the principle of homologous groups.

In current voice research, there is a growing interest in semi-occluded vocal tract exercises and their contribution to an increased vocal efficiency. However, there are only few studies on the lasting effects.Eight vocally healthy subjects were asked to sustain a phonation at a comfortable loudness on the vowel /i/, with a Fundamental Frequency of 250 Hz (females) or 125 Hz (males). During phonation the subjects were simultaneously recorded with transnasal High Speed Videoendoscopy (HSV, 20,000fps), electroglottography, and audio signals. The subjects then performed a water resistance therapy (WRT) for 10 min (tube: 30 cm length, 5 cm below water surface, diameter 9 mm). Repeated measurements of sustained phonation were performed 0, 5, 10, 20, and 30 min after exercising. From the HSV material the Glottal Area Waveform (GAW) was segmented and GAW parameters were computed.There were strong inter-individual differences concerning the changes of different measures over time after WRT. In general, directly after WRT there was a lowering of the GAW derived Period Perturbation Quotient, a lowering of the Closing Quotient and an increase of the Sound Pressure Level (SPL) in comparison to the pre-intervention measurement. However, only 5 min post WRT there was no longer a clear difference compared to baseline results before WRT. Other values such as Open Quotients exhibited no evident changes by WRT at any timepoint.WRT showed strong inter-individual effects concerning the changes in the evaluated measures post-intervention. General tendencies of some measures directly after the intervention showed a brief effect of only a few minutes.

Aspirin-exacerbated respiratory disease (AERD) is a severe form of chronic rhinosinusitis with nasal polyps (CRSwNP) accompanied by asthma and an aspirin intolerance. The underlying pathomechanism of AERD still remains unclear, recent data suggest a complex inflammatory imbalance. In the present study, we investigated the cytokine patterns in AERD, CRSwNP and healthy control patients. Furthermore, we describe the change in cytokine level in the course of aspirin desensitization (AD) with continuous intake of aspirin. The study included a total of 104 participants, 48 healthy controls, 45 patients with nasal polyps and 11 patients with AERD undergoing AD. Nasal secretions were analyzed for IL-1β, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, THF-α, IFN-γ, eotaxin and ECP using Bio-Plex Human Cytokine Assay and Uni-CAP FEIA. Baseline measurements of cytokine levels were performed in all 104 patients; in patients with AERD, follow-up was performed 1–6 and 6–24 months after the initiation of AD. Our preliminary results show a TH2 dominated, eosinophilic milieu in AERD patients, which decreased in the first weeks of AD. However, after 6 months of AD, proinflammatory cytokines show a tendency to increase again. Also, TH1 as well as Treg associated cytokine seem to increase over time. For the first time, the present work shows the cytokine pattern in nasal secretions of AERD patients before and during AD. Further investigation of the complex interaction of inflammatory cytokines during AD might reveal important insights into the disease entity of AERD and open up new horizons for a targeted therapy.

Der Schluckakt ist ein hochkomplexer Vorgang, der auf vielen Ebenen storanfallig ist. Schluckstorungen kommen besonders haufig im hoheren Lebensalter vor. Zum einen nimmt die Inzidenz von Erkrankungen, die mit Dysphagie einhergehen, zu. Zum anderen ist das Schlucken aufgrund von altersphysiologischen Veranderungen weniger effizient.

Purpose For perennial inhalant allergens such as house dust mite (HDM), the German guideline on allergen-specific immunotherapy explicitly recommends provocation testing. This procedure is time-consuming, expensive, and potentially dangerous for the patient. Recently it has been discussed whether provocation tests are really necessary for diagnosing allergy to Dermatophagoides species. Thus, our study aimed to analyze the concordance between nasal provocation tests with Dermatophagoides species and anamnestic data. Methods We retrospectively analyzed the concordance between patients’ histories including self-reported symptom scores and the results of provocation testing in 471 individuals with proven sensitization to Dermatophagoides species. Results 248 patients had a positive nasal provocation test (NPT) result to Dermatophagoides species and 223 individuals a negative NPT result. Patients allergic to HSM suffered significantly more often from atopic dermatitis (14% vs. 7%, p = 0.046) and more from asthma (20% vs. 19%, p = 0.851). Moreover, individuals with clinically silent sensitization complained less about nasal secretion (37% vs. 45%, p = 0.244) but significantly more about nasal dryness (46% vs. 34%, p = 0.046) whereas rates of nasal airway obstruction, ocular complaints and sleep quality were comparable in both groups. Allergic patients reported more often perennial (34% vs. 30%, p = 0.374) and location-dependent (39% vs. 31%, p = 0.090) symptoms. However, the discrepant prevalence of atopic dermatitis was the only statistically significant difference between both groups. Conclusion Despite slight differences between both patient groups, clinical data are not sufficient to distinguish between silent sensitization and clinically relevant allergic rhinitis to HDM. Therefore, nasal provocation testing remains the gold standard for assessing clinical relevance in patients sensitized to Dermatophagoides species.

Introduction Diseases of the salivary glands are rare in children and adolescents, with the exception of viral-induced infections. Objective To determine the clinical course of the disease, the diagnostic procedures, the treatment and the outcome of all children and adolescents affected with salivary gland diseases at our clinic over a period of 15 years. Methods A retrospective chart review including a long-term follow-up was conducted among 146 children and adolescents treated for salivary gland disorders from 2002 to 2016. Results Diagnosing acute sialadenitis was easily managed by all doctors regardless of their specialty. The diagnosis of sialolithiasis was rapidly made only by otorhinolaryngologists, whereas diagnosing juvenile recurrent parotitis imposed difficulties to doctors of all specialties – resulting in a significant delay between the first occurrence of symptoms and the correct diagnosis. The severity-adjusted treatment yielded improvements in all cases, and a full recovery of 75% of the cases of sialolithiasis, 73% of the cases of juvenile recurrent parotitis, and 100% of the cases of acute sialadenitis. Conclusions Due to their low prevalence and the lack of pathognomonic symptoms, salivary gland diseases in children and adolescents are often misdiagnosed, resulting in an unnecessarily long period of suffering despite a favorable outcome following the correct treatment.

Introduction: House dust mite contains several allergen components and causes perennial allergy. Lately, a new major allergen, Der p 23, was described with relatively high sensitization rates in different European Countries. In addition, Der p 23 is supposed to cause asthmatic disease. Objective: We would like to question the prevalence and clinical impact of specific immunoglobulin E to Der p 23 in a large patient sample in southern Bavaria, Germany. Methods: 474 patients from southern Bavaria, who visited the allergy department within the Department of Oto-Rhino-Laryngology of a university hospital, with sensitization to Dermatophagoides pteronyssinus were retrospectively compared regarding their sensitization profile to Der p 1, Der p 2, and Der p 23 and their clinical characteristics. Results: Among D. pteronyssinus-sensitized patients, the overall sensitization rate to Der p 23 was 42% in southern Bavaria. Most likely, patients were simultaneously sensitized to Der p 1, Der p 2, and Der p 23. Der p 23-sensitized patients reported more frequently asthma and showed higher prevalence of poly-sensitization towards 3 additional allergen groups and higher prevalence of double-sensitization to Der p 1 and Der p 2 compared to patients with missing sensitization to Der p 23. Considering the results of allergen provocation tests, neither IgE sensitization against Der p 23 nor levels of specific immunoglobulin E to Der p 23 allow a clear prediction of the clinical relevance of the sensitization. Conclusion: With a sensitization rate of 42%, Der p 23 closely misses the criterion of a major allergen in our southern Bavarian patient collective. A higher prevalence of polysensitization and self-reported asthma was the only clinical feature found in Der p 23-sensitized patients.

Background Static magnetic fields (SMF) exhibit antitumoral activity and enhance the efficacy of chemotherapy by opening the tumor-blood barrier. This study aimed to analyze different SMF-exposure protocols on epidermal growth factor receptor (EGFR)-overexpressing tumors, as well as their combination with cetuximab. Materials and methods Experiments were performed in skinfold chamber preparations of C57Bl/6-and CD-1nu/nu mice bearing LLC-1 tumors. Animals were exposed to 587 mT magnetic field following different exposure protocols. A subgroup received additional cetuximab injections. Using in vivo-fluorescence microscopy and planimetry, tumor angiogenesis, growth and microcirculation were repeatedly analyzed for 13 days. Results In contrast to daily short SMF exposure, three-fold SMF exposure for 2 h led to a significant 46% reduction of tumor growth. Adding cetuximab to SMF exposure did not yield any benefit, although cetuximab monotherapy was highly effective (53% reduction of tumor growth), indicating a potential interference of SMF and EGFR signaling. No effects on microcirculation, angiogenesis or leukocyte-endothelium interactions were documented. Conclusion The use of SMF is promising in the treatment of solid tumors; however, it appears to interfere with EGFR-targeted therapy.

Background: Bet v 6, a minor birch pollen allergen, is commercially available for allergen-specific IgE antibody testing. However, there is hardly any literature on the clinical impact of Bet v 6. The aim of the present study was to analyze if testing specific IgE against Bet v 6 can add valuable benefit to the standard diagnostics of birch pollen-sensitized patients, especially in patients with unknown sensitization-eliciting allergens. Methods: Birch pollen-sensitized patients with missing IgE reactivity against Bet v 1, 2, and 4 were tested for specific IgE antibodies against Bet v 6. For comparison, an equal number of randomly selected patients with birch pollen sensitization, regardless of their individual sensitization patterns, were tested for specific anti-Bet v 6. Results: Of 57 cases with missing reactivity against the standard birch pollen allergens, 2 patients were positive for Bet v 6. In the representative sample, 3 patients showed specific IgE against Bet v 6 - resulting in a total prevalence of 5%. None of the Bet v 6-positive patients showed allergic symptoms after exposure to birch pollen or an oral allergy syndrome. An increased prevalence of asthma and a higher degree of sensitization were the only distinctive clinical features in Bet v 6-positive patients. Conclusions: Among birch pollen-sensitized patients, the prevalence of specific IgE against Bet v 6 is low. Further, sensitization to Bet v 6, which shows characteristics of a panallergen, remains clinically silent. Therefore, determination of anti-Bet v 6 is not considered useful in the clinical routine.

Since the beneficial implementation of allergen specific subcutaneous immunotherapy (SCIT), there are only a few studies on the risk of SCIT-induced neosensitizations. In 51 patients, we retrospectively analyzed sIgE and sIgG patterns by a multiplex ELISA as well as demographic and clinical features before and after SCIT. 33 allergic patients, who only received symptomatic treatment, served as controls. In 12 of 51 SCIT-treated patients (24%), we found new sIgE against allergen components of the allergen source treated by SCIT; eight of them were adults. Among controls, no adult patient showed neosensitization to components of the primarily affected allergen source. Only two children of the control group were affected by neosensitization, which was limited to major allergen components and rarely accompanied by sIgG. In the SCIT-treated group, neosensitization affected major and minor allergen components, and was accompanied by a strong induction of sIgG against major components. A clear clinical predictor of neosensitization during SCIT was not found. Comparing symptom scores, patients seem to profit more from SCIT, if neosensitization remained absent. Patients undergoing SCIT might carry an enhanced risk of neosensitization towards formerly unrecognized allergen components. According to anamnestic data, these neosensitizations might be of clinical relevance - supporting attempts towards personalized recombinant vaccines.

OBJECTIVES: This study aims to answer whether acoustic radiation force impulse imaging (ARFI) can reasonably be employed in initial examination and follow-up during therapy in patients with sialolithiasis, one of the most common non-malignant disorders of the salivary glands. METHODS: Mechanical tissue properties of affected and contralateral healthy salivary glands were analyzed by ARFI in 129 patients with sialolithiasis. In different subgroup analyses, ARFI shear wave velocity values were compared between healthy and diseased submandibular or parotid glands, salivary glands with calculi exhibiting different sizes, as well as before and after therapy. The patients’ symptoms were evaluated by a standardized questionnaire. The t-test (2 groups) or the One-way ANOVA test (>2 groups) was used for the estimation of stochastic probability in intergroup comparisons. RESULTS: Submandibular or parotid glands affected by sialolithiasis were found to exhibit significant lower ARFI values as compared to the healthy contralateral glands in the same individuals. ARFI values in submandibular glands with a single calculus of more than 5 mm in diameter or with multiple calculi as well as in parotid glands with calculi exhibiting diameters of more than 5 mm were significantly higher as compared to the respective healthy contralateral glands. No significant differences in ARFI values of affected salivary glands were detected between patients with low or high symptom perception. CONCLUSIONS: ARFI provides an easy, quick and reliable diagnostic tool for the objective assessment of disease severity and progression in patients with sialolithiasis that can simply be implemented in pre-existing ultrasound protocols.