Entwicklung von Methoden zum Nachweis von ökologisch erzeugten Produkten am Beispiel der Lachszucht

Zur Zeit stehen der Lebensmittelüberwachung keine analytischen Methoden zur Verfügung mit denen Deklarationen wie „Bio-Fisch“, „Bio-Lachs“ oder „Organic Salmon“ am Erzeugnis überprüft werden können. Das Ziel dieses Projektes bestand in der Entwicklung von objektiven, praxistauglichen Analysenverfahren zur Identifizierung von Lachserzeugnissen aus der ökologischen Aquakultur. Die Verfügbarkeit solcher Verfahren ermöglicht einen verbesserten Verbraucherschutz und eine Stärkung des redlichen Handels. Es kann aber auch der Tierschutz von den Ergebnissen des Projektes profitieren, wenn man berücksichtigt, dass die ökologische Aquakultur eine artgerechte Haltung der Fische besonders fördern soll. In einem umfangreichen Untersuchungsprogramm wurden biologische und chemische Methoden, sowie ganzheitliche Verfahren eingesetzt. Zum Vergleich wurden auch Wildlachse und einige Lachsfutter analysiert. Probenziehungen fanden in den Jahren 2002 und 2003 statt; der Ökolachs und Wildlachs stammte aus Irland, Farmlachse hoher Qualität wurden aus Irland und Norwegen bezogen. Insgesamt wurden 100 Lachsproben analysiert. Folgende Methoden kamen u.a. zum Einsatz: Beurteilung des Ausgangsmaterials (Aussehen, Kondition der Lachse), DNA Analyse, Bildverarbeitung (Muskelstruktur), Aromaprofil Bestimmung, Messung der Gehalte an Eiweiß und Fett, Bestimmung von Stoffwechselprodukten und Stressparametern, Stabil-Isotopen-Analyse (15-N, 13-C), Bestimmung der Astaxanthin-Isomere und Canthaxanthingehalte, Bestimmung von organischen und anorganischen Rückständen. Aus den vielfältigen Ergebnissen ist zu schließen, dass Öko- und Farmlachs sich in Aussehen, Zusammensetzung (z.B. im Fettgehalt) und Schadstoffgehalten generell nicht unterscheiden. Nur mit Hilfe einer Methode, der Bestimmung der Astaxanthin-Isomere, konnte der Ökolachs aus Irland sicher identifiziert werden

Comparison of Chimerism and Minimal Residual Disease Monitoring for Relapse Prediction after Allogeneic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia

AbstractLittle data are available on the relative merits of chimerism and minimal residual disease (MRD) monitoring for relapse prediction after allogeneic hematopoietic stem cell transplantation (HCT). We performed a retrospective analysis of serial chimerism assessments in 101 adult HCT recipients with acute lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22 patients. All patients had received myeloablative conditioning. The cumulative incidence of relapse was significantly higher in the patients with increasing mixed chimerism (in-MC) compared with those with complete chimerism, low-level MC, and decreasing MC, but the sensitivity of in-MC detection with regard to relapse prediction was only modest. In contrast, MRD assessment was highly sensitive and specific. Patients with MRD positivity after HCT had the highest incidence of relapse among all prognostic groups analyzed. The median time from MRD positivity to relapse was longer than the median time from detection of in-MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD assessment is a powerful prognostic tool that should be included in the routine post-transplantation monitoring of patients with ALL, but chimerism analysis may provide additional information in some cases. Integration of these tools and clinical judgment should allow optimal decision making with regard to post-transplantation therapeutic interventions

Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals

Aims: For vancomycin treatment in obese patients, there is no consensus on the optimal dose that will lead to the pharmacodynamic target (area under the curve 400–700 mg h L−1). This prospective study quantifies vancomycin pharmacokinetics in morbidly obese and nonobese individuals, in order to guide vancomycin dosing in the obese. Methods: Morbidly obese individuals (n = 20) undergoing bariatric surgery and nonobese healthy volunteers (n = 8; total body weight [TBW] 60.0–234.6 kg) received a single vancomycin dose (obese: 12.5 mg kg−1, maximum 2500 mg; nonobese: 1000 mg) with plasma concentrations measured over 48 h (11–13 samples per individual). Modelling, internal validation, external validation using previously published data and simulations (n = 10.000 individuals, TBW 60–230 kg) were performed using NONMEM. Results: In a 3-compartment model, peripheral volume of distribution and clearance increased with TBW (both p  90% target attainment (area under the curve > 400 mg h L−1) in individuals up to 200 kg, with corresponding trough concentrations of 5.7–14.6 mg L−1 (twice daily dosing). For continuous infusion, a loading dose of 1500 mg is required for s

Critical implications of IVDR for innovation in diagnostics: input from the BioMed alliance diagnostics task force

With the implementation of Regulation (European Union [EU]) 2017/746 on in vitro diagnostic medical devices (IVDR), from May 26, 2022, onwards, the development and use of diagnostic tests will be governed by a vastly expanded and upgraded EU regulatory framework. We provide here an overview of the amended transition timelines, the role of notified bodies, EU reference laboratories, expert panels, and the Medical Device Coordination Group (MDCG). We also describe the implications of the IVDR for innovative laboratory medicine by explaining the exemption for in-house devices (IH-IVDs). Two key challenges faced by the academic diagnostic sector are: (1) the stipulation on equivalence of tests (article 5.5d), which poses a new condition for the use of IH-IVDs and (2) the gray area between CE marked in vitro diagnostics (CE-IVDs), modified CE-IVDs, Research Use Only (RUO) tests, and IH-IVDs. Furthermore, the results of a questionnaire on current diagnostic practice conducted by European medical societies collaborating in the BioMed Alliance indicate widespread use of IH-IVDs in diagnostic laboratories across Europe and emphasize the need for support and guidance to comply with the IVDR. Diagnostic equivalents of the European Reference Networks (ERNs) for rare diseases could help ensure affordable and equal access to specialized diagnostics across the EU. Concerted action by clinical and laboratory disciplines, regulators, industry, and patient organizations is needed to support the efficient and effective implementation of the IVDR in a way that preserves innovation and safeguards the quality, safety, and accessibility of innovative diagnostics.Peer reviewe

High-dose posaconazole for azole-resistant aspergillosis and other difficult-to-treat mould infections

Background: Oral follow-up therapy is problematic in moulds with reduced azole-susceptibility, such as azole-resistant Aspergillus fumigatus infection. Currently, only intravenous liposomal amphotericin B (L-AmB) is advocated by guidelines for the treatment of azole-resistant aspergillosis infections. Preclinical research indicates that high-dose posaconazole (HD-POS) might be a feasible option provided that high drug exposure (ie POS serum through levels >3 mg/L) can be achieved and is safe. Objectives: To describe our experience with the use of oral HD-POS as treatment strategies for patients infected with pathogens with a POS MIC close to the clinical breakpoint. Patients/Methods: We review evidence supporting the use of HD-POS and describe our experience on safety and efficacy in 16 patients. In addition, we describe the adverse events (AE) observed in 25 patients with POS concentrations at the higher end of the population distribution during treatment with the licensed dose. Results: Sixteen patients were treated intentionally with HD-POS for voriconazole-resistant invasive aspergillosis (7/16), mucormycosis (4/16), salvage therapy for IA (4/16) and IA at a sanctuary site (spondylodiscitis) in 1. Grade 3-4 AEs were observed in 6, and all of them were considered at least possibly related. Grade 3-4 AEs were observed in 5 of the 25 patients with spontaneous high POS serum through levels considered at least possibly related using Naranjo scale. Conclusions: High-dose posaconazole is a treatment option if strict monitoring for both exposure and for AE is possible

Insufficient serum caspofungin levels in a paediatric patient on ECMO

Caspofungin, aechinocandin, is a relatively new lipophilic antifungal drug. Little is known concerning the pharmacokinetics of caspofungin in children. Extracorporeal membrane oxygenation (ECMO) allows prolonged cardiopulmonary support in patients with life-threatening respiratory or cardiac failure. Pharmacokinetics may be altered by ECMO. We describe the case of a paediatric patient on ECMO with severe pneumonia and sepsis, who had subtherapeutic exposure of caspofungin despite normal to high dosages of caspofungin. Therapeutic drug monitoring is warranted

Tobramycin Clearance Is Best Described by Renal Function Estimates in Obese and Non-obese Individuals: Results of a Prospective Rich Sampling Pharmacokinetic Study

Purpose Tobramycin is an aminoglycoside antibiotic of which the 24 h exposure correlates with efficacy. Recently, we found that clearance of the aminoglycoside gentamicin correlates with total body weight (TBW). In this study, we investigate the full pharmacokinetic profile of tobramycin in obese and non-obese individuals with normal renal function. Methods Morbidly obese individuals (n = 20) undergoing bariatric surgery and non-obese healthy volunteers (n = 8), with TBW ranging 57–194 kg, received an IV dose of tobramycin with plasma concentrations measured over 24 h (n = 10 per individual). Statistical analysis, modelling and simulations were performed using NONMEM. Results In a two-compartment model, TBW was the best predictor for central volume of distribution (p< 0.001). For clearance, MDRD (de-indexed for body surface area) was identified as best covariate (p < 0.001), and was superior over TBW ((p < 0.05). Other renal function estimates (24 h urine GFR and de-indexed CKD-EPI) led to similar results as MDRD (all p < 0.001)). Conclusions In obese and non-obese individuals with normal renal function, renal function estimates such as MDRD were identified as best predictors f

Population Pharmacokinetic Model and Pharmacokinetic Target Attainment of Micafungin in Intensive Care Unit Patients

_Objective:_ To study the pharmacokinetics of micafungin in intensive care patients and assess pharmacokinetic (PK) target attainment for various dosing strateg