Intralymphatic Immunotherapy (ILIT) With Bee Venom Allergens: A Clinical Proof-of-Concept Study and the Very First ILIT in Humans

BackgroundSubcutaneous venom immunotherapy (VIT) represents an effective treatment against bee venom allergy. However, it involves long treatment times, high costs, and the risk of adverse events (AEs). Shorter, safer, and cheaper treatment options are therefore pursued.ObjectiveTo determine the safety, immunogenicity, and efficacy of bee venom intralymphatic immunotherapy (ILIT).MethodsIn an open pilot study, 12 patients received bee venom ILIT in three sessions with 14-day intervals: 0.1–5 μg/dose. Ultrasound imaging was applied to guide an injection and to document the lymph node structure. In a second study, 67 patients from 15 centers in Europe and Australia were randomized to receive four doses of either 10- or 20-μg bee venom ILIT with 28-day intervals. Clinical endpoints included specific IgE and IgG and protection after a bee sting challenge. These studies were performed in the years 2000–2003.ResultsIn a proof-of-concept study, no serious AEs were observed. An increase in allergen-specific IgG1 but no IgG4 and IgE was observed. ILIT induced the protection against a bee sting challenge in 7 out of 8 challenged patients. In a multicenter study, an increase in allergen-specific IgG and IgE was observed, with the highest increase in patients receiving a higher ILIT dose. The study was terminated due to several serious AEs upon the sting challenge provocation after the completion of treatment. However, out of 45 patients challenged, 15 (65%) and 18 (82%) patients in the 10- and 20-μg group, respectively, showed an improvement of two grades or more. No correlation was observed between antibody levels and sting protection.ConclusionsWhile a pilot study suggested the safety and efficacy of bee venom ILIT, a high number of AEs seen after the sting challenge following a randomized study indicate that the immunology protection offered by bee venom ILIT is insufficient. Of note, the bee venom allergen extract used in the two studies were from the two different providers. While the first study used a formulation approved for use in subcutaneous VIT, the second study used a nonapproved formulation never tested in humans. Further studies on approved formulations should be performed to generate conclusive results regarding the safety and efficacy of bee venom ILIT

Evaluation der FDM-Beratung: Am Beispiel der Kontaktstelle Forschungsdatenmanagement der FSU Jena

Die Kontaktstelle Forschungsdatenmanagement (KS FDM) an der Friedrich-Schiller-Universität Jena (FSU) wurde im März 2015 eingerichtet, um mit einer angemessen Organisations- und Kompetenzstruktur auf den sich schnell entwickelnden Bedeutungszuwachs von Forschungsdatenmanagement (FDM) zu antworten. Das Leistungsportfolio der KS umfasst Sensibilisierung, Information (Grundlagen, aktuelle Entwicklungen), Beratung, Qualifizierung, Vernetzung, Strategische Entwicklung sowie Forschung und Entwicklung im Bereich des FDM. Seit der Gründung der KS FDM ist die Anzahl der Anfragen von Forschenden, die Unterstützung suchen, jedes Jahr weiter angestiegen und zeigt somit den Bedarf an Beratungsangeboten zum Thema FDM. Um die bisherige Beratungsarbeit der Kontaktstelle zu evaluieren und Verbesserungsmöglichkeiten zu identifizieren, wurden 68 Ratsuchende kontaktiert und zu verschiedenen Aspekten der FDM Beratung befragt. Als Grundlage diente das Beratungsprotokoll der KS FDM (Strukturmerkmale der Ratsuchenden, wissenschaftlicher oder organisatorischer Kontext) sowie eine Online-Befragung der von der KS FDM beratenen Personen (Themen und ihre Relevanz, Bearbeitung und dabei erreichte Lösungen, Einschätzung der zukünftigen Bedeutung des FDM im wissenschaftlichen Umfeld, Bedarf an weiteren FDM-Services). 23 der Ratsuchenden nahmen an der Umfrage teil. Es zeigte sich, dass die Beratung der KS FDM einen reellen Bedarf zur Unterstützung von Forschenden abdeckt und Forschende eine zentrale Anlaufstelle für ihre Fragen zum Thema FDM begrüßen. Der Großteil der Befragten (ca. 73%) schätzte die eigenen Kenntnisse bezüglich FDM gering bis grundlegend ein. Die Anliegen wurden in den meisten Fällen zur Zufriedenheit der Ratsuchenden gelöst (ca. 79%). Zwei Drittel (ca. 67%) wünschen sich für ihr Arbeitsfeld mehr Angebote zum Thema FDM. Prinzipiell waren die Ratsuchenden mit der Unterstützung durch die KS FDM zufrieden bis sehr zufrieden und würden die KS Ihren Kollegen weiterempfehlen. Die Evaluation wurde durchgeführt im Rahmen des Projektes eeFDM „Aufbau und Erprobung von Bausteinen für ein effektives und effizientes Forschungsdatenmanagement“, das durch das Bundesministerium für Bildung und Forschung (BMBF) im Rahmen der Förderrichtlinie „Erforschung des Managements von Forschungsdaten in ihrem Lebenszyklus an Hochschulen und außeruniversitären Forschungseinrichtungen“ gefördert wurde. Ein ausführlicher Bericht ist unter https://doi.org/10.22032/dbt.40382 veröffentlicht

Variational Approach to Molecular Kinetics

The eigenvalues and eigenvectors of the molecular dynamics propagator (or transfer operator) contain the essential information about the molecular thermodynamics and kinetics. This includes the stationary distribution, the metastable states, and state-to-state transition rates. Here, we present a variational approach for computing these dominant eigenvalues and eigenvectors. This approach is analogous the variational approach used for computing stationary states in quantum mechanics. A corresponding method of linear variation is formulated. It is shown that the matrices needed for the linear variation method are correlation matrices that can be estimated from simple MD simulations for a given basis set. The method proposed here is thus to first define a basis set able to capture the relevant conformational transitions, then compute the respective correlation matrices, and then to compute their dominant eigenvalues and eigenvectors, thus obtaining the key ingredients of the slow kinetics

Topical photodynamic therapy in the treatment of actinic keratoses and Bowen's disease in transplant recipients

BACKGROUND: Transplant recipients (TR) have a dramatically increased risk for widespread epithelial neoplasms of the skin. Thus, there is a need to treat initial stages of these neoplasms such as actinic keratoses (AK) and Bowen's disease (BD) to prevent progression to invasive and potentially fatal squamous cell carcinoma. Topical photodynamic therapy (PDT) has been proven to be an effective treatment for AK and BD in immunocompetent patients, but no prospective trials in immunocompromised TR have been performed so far. METHODS: Twenty TR and 20 controls with histologically confirmed AK or BD underwent either a single or two consecutive treatments of topical PDT in an open trial. The application of 20% 5-aminolevulinic acid (ALA) for 5 hours was followed by illumination with 75 J/cm2 of visible light delivered at 80 mW/cm2 by an incoherent light source. RESULTS: The overall complete response rates in TR at 4, 12, and 48 weeks were 0.86, 0.68, and 0.48, respectively. The cure rates in both patient groups were comparable at 4 weeks but were significantly lower in TR than in controls at 12 and 48 weeks (P<0.05). Side effects included erythema, edema, and crust formation after illumination. Cosmetic results were excellent without scar formation or alterations in pigmentation. CONCLUSIONS: Topical PDT with 20% 5-ALA is an effective and safe treatment for AK and BD in immunosuppressed TR, with initial response rates comparable with those in immunocompetent patients. It is particularly useful in TR because of the possibility for repeated treatment of large lesional areas

Intralymphatic allergen administration renders specific immunotherapy faster and safer: A randomized controlled trial

The only causative treatment for IgE-mediated allergies is allergen-specific immunotherapy. However, fewer than 5% of allergy patients receive immunotherapy because of its long duration and risk of allergic side effects. We aimed at enhancing s.c. immunotherapy by direct administration of allergen into s.c. lymph nodes. The objective was to evaluate safety and efficacy compared with conventional s.c. immunotherapy. In a monocentric open-label trial, 165 patients with grass pollen-induced rhinoconjunctivitis were randomized to receive either 54 s.c. injections with pollen extract over 3 years [cumulative allergen dose 4,031,540 standardized quality units (SQ-U)] or 3 intralymphatic injections over 2 months (cumulative allergen dose 3,000 SQ-U). Patients were evaluated after 4 months, 1 year, and 3 years by nasal provocation, skin prick testing, IgE measurements, and symptom scores. Three low-dose intralymphatic allergen administrations increased tolerance to nasal provocation with pollen already within 4 months (P < 0.001). Tolerance was long lasting and equivalent to that achievable after standard s.c. immunotherapy (P = 0.291 after 3 years). Intralymphatic immunotherapy ameliorated hay fever symptoms (P < 0.001), reduced skin prick test reactivity (P < 0.001), decreased specific serum IgE (P < 0.001), caused fewer adverse events than s.c. immunotherapy (P = 0.001), enhanced compliance (P < 0.001), and was less painful than venous puncture (P = 0.018). In conclusion, intralymphatic allergen administration enhanced safety and efficacy of immunotherapy and reduced treatment time from 3 years to 8 weeks

Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort.

OBJECTIVES: Data on the frequency of extraintestinal manifestations (EIMs) in Crohn's disease (CD) and ulcerative colitis (UC) and analyses of their risk factors are scarce. We evaluated their prevalence and risk factors in a large nationwide cohort of inflammatory bowel disease (IBD) patients. METHODS: IBD patients from an adult clinical cohort in Switzerland (Swiss IBD cohort study) were prospectively included. Data from validated physician enrolment questionnaires were analyzed. RESULTS: A total of 950 patients were included, 580 (61%) with CD (mean age 41 years) and 370 (39%) with UC (mean age 42 years). Of these, 249 (43%) of CD and 113 (31%) of UC patients had one to five EIMs. The following EIMs were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD 10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD and UC each 2%), and primary sclerosing cholangitis (CD 1%, UC 4%). Multiple logistic regression identified the following risk factors for ongoing EIM in CD: active disease (odds ratio (OR)=1.95, 95% confidence interval (CI)=1.17-3.23, P=0.01), and positive IBD family history (OR=1.77, 95% CI=1.07-2.92, P=0.025). No risk factors were identified in UC patients. CONCLUSIONS: EIMs are a frequent problem in CD and UC patients. Active disease and positive IBD family history are associated with ongoing EIM in CD patients. Identification of EIM prevalence and associated risk factors may result in increased awareness for this problem and thereby facilitating their diagnosis and therapeutic management