Gerstel (Germany)

Abstract Background Heart failure (HF) is one of the leading public health issues worldwide. Current guidelines recommend HF treatment using different drug classes depending on ejection fraction (EF) and underlying cause of HF. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a drug class with a class IA recommendation in the current ESC-guidelines for HF treatment independent of EF. The SGLT2i dapagliflozin is approved for treatment of HF across the entire spectrum of EF in Germany. However, real-world data are limited. Purpose The aim of EVOLUTION-HF DEallEF is to generate data on real-world dapagliflozin use in HF patients independently of EF in Germany under the multinational umbrella EVOLUTION-HF study protocol. Methods EVOLUTION-HF DEallEF is a non-interventional, prospective, longitudinal cohort study. It is planned to enrol a total of 1000 patients with chronic HF in Germany, including 40% patients with preserved (HFpEF; EF ≥ 50%), 20% with mildly reduced (HFmrEF; EF 41-49%), and 40% with reduced EF (HFrEF; EF ≤ 40%). Patients willing to participate, aged ≥18 years, who started dapagliflozin treatment 14 to 90 days prior to enrolment according to the local product label, are eligible for participation. Among reasons for exclusion is previous SGLT2i treatment (including dapagliflozin). Data on medical history, clinical symptoms, previous and concomitant medication and patient-reported outcomes (PROs) are collected. EVOLUTION-HF DEallEF has included its first patient in 04/2024 and is currently open for enrolment. Interim analyses (IA) were planned at predefined timepoints (after 250, 500 enrolled patients and enrolment completion). The three different EF cohorts (HFpEF, HFmrEF, HFrEF) are analysed separately and as a total population. Only descriptive statistical methods are used. Results This 1st IA (data cutoff: 02/12/2024) included 249 patients in the safety set (all patients received at least one dose of dapagliflozin, one patient refused data usage) and 244 patients who fulfilled all eligibility criteria in the full analysis set (FAS). Patients were enrolled in 31 study sites, mainly in office-based cardiologic practices. In the FAS, distribution of patients to HF cohorts was 51% with HFpEF (n=125), 30% with HFmrEF (n=73), and 19% with HFrEF (n=46). Conclusions Patients’ and disease characteristics observed at the time of the first IA are in range with previously published data indicating that a representative cohort of patients newly treated with dapagliflozin for HF are enrolled in EVOLUTION-HF DEallEF. Dysbalance in expected enrolment proportion per EF cohort is mainly caused by exclusion of patients with SGLT2i-pretreatment. The study aims to provide further insights into real-world dapagliflozin treatment for HF in Germany, focussing on clinical and patients’ perspective.

The detection of Δ9 -tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in hair, for the purpose of identifying cannabis consumption, is conducted in many forensic laboratories. Since external contamination of hair with these cannabis components cannot be excluded, even after hair decontamination, only the detection of THC metabolites such as 11-nor-9-carboxy-Δ9 -tetrahydrocannabinol (THC-COOH) or 11-hydroxy-Δ9 -tetrahydrocannabinol (OH-THC), is considered to prove cannabis consumption. At present, testing for THC metabolites is not standard practice due to its analytical complexity. For these reasons, we developed a novel method for the detection of THC-COOH and OH-THC as well as THC, CBD, and CBN in one single analytical run using gas chromatography-tandem mass spectrometry (GC-MS/MS) with electron ionization. After manual hair washing and grinding, sample preparation was fully automated, by means of a robotic autosampler. The hair extraction took place by digestion with sodium hydroxide. A solid-phase extraction (SPE) was chosen for sample clean-up, using a mixed-mode anion exchange sorbent. Derivatization of all analytes was by silylation. The method has been fully validated according to guidelines of the Society of Toxicological and Forensic Chemistry (GTFCh), with a limit of detection (LOD) of 0.2pg/mg for THC-COOH and OH-THC and 2pg/mg for THC, CBD and CBN, respectively, thus fulfilling the Society of Hair Testing (SoHT) recommendations. The validated method has been successfully applied to our routine forensic case work and a summary of data from authentic hair samples is given, as well as data from proficiency tests.

Off-line microscale chamber measurements of spray polyurethane foam require settings to be changed manually and an analyst to start and stop sampling times. An automated dynamic headspace system was used for on-line, fully automated microscale chamber measurements of SPF. In this way, precise measurement and computerized control of sampling times, volumes, and temperature would be possible. After the system was qualified analytically, timed measurements were carried out automatically over a period of approximately 15 h to understand off-gassing mechanisms of the foams. In a separate experiment, the effect of sample temperature was probed using an automated sequence in which temperatures were changed at defined times to simulate the heating of a foam sample in an attic or ceiling. Both experiments provided unattended and precise control and measurement of the three principle variables in microscale chamber experiments: time, sampling volume, and temperature. The system should prove useful for mathematical modeling and for sharing procedures between researchers.

The results of gas chromatography/mass spectrometry (MS), with Ion Signature Technology, Inc. (North Smithfield, RI) quantitative deconvolution software, are discussed for pesticides identified both as target compounds by using retention and MS data and as unknowns by using only mass spectra. Target compound analysis of 32 pesticides, surrogates, and an internal standard added to lemon oil over a wide concentration range produced precision and accuracy that are well within the acceptable criteria of 25 and 50% for complex samples. When 112 pesticides were added to orange oil and searched as unknowns, 110 of the 112 compounds were correctly identified, with an average pesticide recovery of 101 +/- 19%. The injection volume of the orange oil fortified with pesticides was selected so that 4 ng per compound was injected on column. No false negatives were found, because ion signals for the 2 unidentified pesticides were not acquired by the instrument in either the standard mixture or the oil. No false positives were detected, although >750 widely different compounds were included in the library search.

A mass spectrometer based chemical sensor was used to model citrus peel oils. Seven samples and one duplicate were analyzed and subsequently modeled with multivariate analyses such as principal component analysis (PCA) and Soft Independent Modeling of Class Analogy (SIMCA). Discrimination between samples was excellent with clear distinctions between the samples and considerable overlap of the duplicate sample. Samples were also analyzed with a gas chromatograph/mass spectrometer (GC/MS) using similar multivariate models. GCMS results were similar to the ones obtained by sampling the static headspace, but with longer analysis times. Statistics obtained using SIMCA analysis allowed for the determination of which samples were most similar to a target sample.

Emissions of oxygenated volatile organic compounds (OVOC) from several plant species were measured in continuously stirred tank reactors (CSTR). High emission pulses of OVOCs were observed when plants were exposed to stress. Absolute emission rates were highly variable ranging up to 10−13 mol · cm−2 · s−1. The temporal shape of these emissions was described by a formalism similar to that of a consecutive reaction of pseudo first order kinetics. The main emitted OVOC was (Z)-3-hexenol together with other C6-aldehydes and alcohols, suggesting that lipoxygenase activity on linolenic acid was mainly responsible for OVOC production. Various stress factors induced lipoxygenase activity and subsequent emissions of OVOCs. These factors were exposure to high ozone concentrations, pathogen attack, and wounding. The pattern of OVOC emissions from tobacco was similar for different stress applications and the same products of lipoxygenase activity were emitted from all investigated plant species. Our results imply that these emissions occur as general response of the plants to stress. Since plants experience various abiotic or biotic stress factors in the environment, OVOC emissions as a response to stress are likely to be of significant importance for atmospheric chemistry.

Abstract The separation and analysis of furan fatty acids and other minor component fatty acids present at very low concentrations in complex sample matrices, such as fish oil or lipids derived from liver and testes, require several pre‐analytical separation steps if single column gas chromatography is to furnish sufficient resolution: after extraction and transesterification hydrogenation, urea complex precipitation and argentation TLC have been applied prior to GC analysis of furan fatty acids.By using multidimensional GC‐MSD with cooled injection and flow‐controlled column switching with intermediate cold trapping, it has been possible to identify directly the methyl esters of furan fatty acids without further pre‐analytical separation.The most common of the furan fatty acids can be subdivided into two groups depending on whether they bear a propyl or pentyl side group in the 5‐position of the furan ring. In addition to the eight furan fatty acids known to be present in fish oil, six new ones were identified, four with propyl substitution and two with pentyl substitution. Four have earlier been reported to be present in the hepatopancreas of crayfish and in fish tissue, whereas the propyl‐substituted 16,19‐epoxy‐17,18‐dimethyldocosa‐16,18‐dienoic acid and the pentyl‐substituted furan fatty acid 6,9‐epoxy‐7‐methyltetradeca‐6,8‐dienoic acid were hitherto unknown.