Retrospektive Analyse zur notwendigen Dauer der medikamentösen VTE-Prophylaxe bei Patientinnen mit primärer Mammakarzinom-Operation

Venöse Thromboembolien stellen ein häufig vorkommendes Krankheitsbild dar und treten insbesondere bei KrebspatientInnen vermehrt auf. Dabei nehmen Brustkrebspatientinnen eine besondere Rolle ein, da sie trotz onkologischer Grunderkrankung ein eher geringes Thromboserisiko aufweisen (J. W. Blom et al., 2006). Da in bisherigen Untersuchungen meist eine gemischte Gruppe Mammakarzinom Patientinnen in verschiedenen Stadien der Erkrankung und unter verschiedenen Therapieformen untersucht wurde, fokussiert sich diese Arbeit auf das Auftreten von venösen Thromboembolien bei Patientinnen mit primärer Brustkrebsoperation. Im Rahmen einer retrospektiven Krankenblattauswertung wurden 198 Patientinnen mit primärer Mammakarzinom-Operation erfasst, die 2017 in der Klinik für Frauenheilkunde am Universitätsklinikum des Saarlandes behandelt wurden. Diese haben nach dem Eingriff eine Thromboseprophylaxe mit niedermolekularem Heparin erhalten, die jeweils die Dauer des stationären Aufenthalts umfasst. Die untersuchten Patientinnen befanden sich mehrheitlich in einem Frühstadium der Erkrankung. Drei Viertel waren von einem Carcinoma in situ oder einem T1-Tumor betroffen und 87 % hatten keine Lymphmetastasen. 128 Patientinnen konnten mindestens ein halbes Jahr anhand der Patientenakte auf das Auftreten von symptomatischen thrombotischen Komplikationen nachbeobachtet werden. In der beschriebenen Gruppe kam es zum Auftreten von drei thrombotischen Komplikationen innerhalb der ersten sechs Monate nach der Operation. Alle drei Patientinnen wiesen eine Infiltration von Lymphknoten auf und durchliefen eine adjuvante Chemotherapie. Die Thrombosen ereigneten sich während der Chemotherapie und betrafen den Portkatheter und/oder angrenzende tiefe Venen bis hin zu den tiefen Armvenen. Vor Einsetzen der Chemotherapie ereigneten sich innerhalb der Gruppe der Patientinnen mit adjuvanter Therapie keine Thrombosen. Für 173 Brustkrebspatientinnen konnte eine Thrombose innerhalb des ersten Monats nach der Operation ausgeschlossen werden. Für 124 Patientinnen konnte eine Thrombose innerhalb von sechs Monaten nach der Operation ausgeschlossen werden. Es sind keine Thrombosen bei Patientinnen ohne Chemotherapie Behandlung oder mit neoadjuvanter Chemotherapie bekannt. Keine Patientin erlitt Komplikationen durch die Behandlung mit niedermolekularem Heparin. Für Patientinnen in einem frühen Stadium der Erkrankung und ohne Chemotherapie, die einen Großteil der hier beobachteten Patientinnen ausmachen, gibt es keinen Anhaltspunkt dafür, dass anders als bisher bezüglich der verabreichten postoperativen Thromboseprophylaxe verfahren werden sollte. Brustkrebspatientinnen unter adjuvanter Chemotherapie und mit Operation sollten Thema weiterer Forschung sein, da alle vorkommenden Thrombosen diese Subgruppe betrafen und sie möglicherweise von einer intensivierten VTE-Prophylaxe profitieren können.Retrospective Analysis of required prophylaxis duration to prevent venous thromboembolism in patients undergoing primary breast cancer surgery Venous thromboembolism is a frequently observed complication especially in patients with malignant disease. Nevertheless, breast cancer patients have a lower risk for thromboses than other cancer patients (J. W. Blom et al., 2006). Different from previous research with heterogeneous groups of breast cancer patients in various stages of the disease and undergoing varying forms of therapy, this analysis is focused on the occurrence of venous thromboembolism in patients with primary breast cancer surgery. Medical sheets of 198 female patients, who underwent primary breast cancer surgery in 2017 in the Saarland University Medical Center were evaluated. All those patients had thrombosis prophylaxis with lowmolecular- weight heparin for the period of their postoperative stationary stay. Most Patients were in an early stage of breast cancer. Three-quarters of them had a carcinoma in situ or a carcinoma in stage T1 and 87 % had no lymph metastases. 128 patients could be followed up for at least six months after operation based on their medical records. There have been three thrombotic complications in the described group of breast cancer patients, which occurred in the period up to six months after the surgery. All three patients had lymph node metastases and underwent adjuvant chemotherapies. The thromboses occurred during chemotherapy. They affected the chemotherapy port and close-by deep veins up to the brachial vein. There are no known thromboses in patients with adjuvant chemotherapy before the chemotherapy treatment started. Thrombosis could be excluded for 173 breast cancer patients in the first postoperative month and for 124 patients in six months following the surgery. There are no known thromboses in women who underwent neoadjuvant chemotherapy or did not have chemotherapy treatments. Neither there were complications caused by the low molecular heparin. For the group of patients with early-stage breast cancer and no chemotherapy treatments, the majority of the here included patients, there is no evidence that the currently applied method to give medical thrombosis prophylaxis during hospitalization after breast cancer surgery should be changed. Patients with adjuvant chemotherapy after surgery should be the topic of further research because all thromboses concern this subgroup and they might profit from more intensive prophylaxis

Superfluid and dissipative dynamics of a Bose-Einstein condensate in a periodic optical potential

We create Bose-Einstein condensates of Rb-87 in a static magnetic trap with a superimposed blue-detuned 1D optical lattice. By displacing the magnetic trap center we are able to control the condensate evolution. We observe a change in the frequency of the center-of-mass oscillation in the harmonic trapping potential, in analogy with an increase in effective mass. For fluid velocities greater than a local speed of sound, we observe the onset of dissipative processes up to full removal of the superfluid component. A parallel simulation study visualizes the dynamics of the Bose-Einstein condensate and accounts for the main features of the observed behavior

Membranolytic Mechanism of Amphiphilic Antimicrobial β-Stranded [KL]n_n Peptides

Amphipathic peptides can act as antibiotics due to membrane permeabilization. KL peptides with the repetitive sequence [Lys-Leu]$_n$-NH$_2$ form amphipathic β-strands in the presence of lipid bilayers. As they are known to kill bacteria in a peculiar length-dependent manner, we suggest here several different functional models, all of which seem plausible, including a carpet mechanism, a β-barrel pore, a toroidal wormhole, and a β-helix. To resolve their genuine mechanism, the activity of KL peptides with lengths from 6–26 amino acids (plus some inverted LK analogues) was systematically tested against bacteria and erythrocytes. Vesicle leakage assays served to correlate bilayer thickness and peptide length and to examine the role of membrane curvature and putative pore diameter. KL peptides with 10–12 amino acids showed the best therapeutic potential, i.e., high antimicrobial activity and low hemolytic side effects. Mechanistically, this particular window of an optimum β-strand length around 4 nm (11 amino acids × 3.7 Å) would match the typical thickness of a lipid bilayer, implying the formation of a transmembrane pore. Solid-state $^{15}$N- and $^{19}$F-NMR structure analysis, however, showed that the KL backbone lies flat on the membrane surface under all conditions. We can thus refute any of the pore models and conclude that the KL peptides rather disrupt membranes by a carpet mechanism. The intriguing length-dependent optimum in activity can be fully explained by two counteracting effects, i.e., membrane binding versus amyloid formation. Very short KL peptides are inactive, because they are unable to bind to the lipid bilayer as flexible β-strands, whereas very long peptides are inactive due to vigorous pre-aggregation into β-sheets in solution

A Simple Nonviral Method to Generate Human Induced Pluripotent Stem Cells Using SMAR DNA Vectors

Induced pluripotent stem cells (iPSCs) are a powerful tool for biomedical research, but their production presents challenges and safety concerns. Yamanaka and Takahashi revolutionised the field by demonstrating that somatic cells could be reprogrammed into pluripotent cells by overexpressing four key factors for a sufficient time. iPSCs are typically generated using viruses or virus-based methods, which have drawbacks such as vector persistence, risk of insertional mutagenesis, and oncogenesis. The application of less harmful nonviral vectors is limited as conventional plasmids cannot deliver the levels or duration of the factors necessary from a single transfection. Hence, plasmids that are most often used for reprogramming employ the potentially oncogenic Epstein–Barr nuclear antigen 1 (EBNA-1) system to ensure adequate levels and persistence of expression. In this study, we explored the use of nonviral SMAR DNA vectors to reprogram human fibroblasts into iPSCs. We show for the first time that iPSCs can be generated using nonviral plasmids without the use of EBNA-1 and that these DNA vectors can provide sufficient expression to induce pluripotency. We describe an optimised reprogramming protocol using these vectors that can produce high-quality iPSCs with comparable pluripotency and cellular function to those generated with viruses or EBNA-1 vectors.</p

Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis

PURPOSE: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy. METHODS: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected. RESULTS: 413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI. CONCLUSION: A broad range of actionable alterations was targeted with available molecular therapeutics. However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-022-04049-w

Study of Spin and Decay-Plane Correlations of W Bosons in the e+e- -> W+W- Process at LEP

Data collected at LEP at centre-of-mass energies \sqrt(s) = 189 - 209 GeV are used to study correlations of the spin of W bosons using e+e- -> W+W- -> lnqq~ events. Spin correlations are favoured by data, and found to agree with the Standard Model predictions. In addition, correlations between the W-boson decay planes are studied in e+e- -> W+W- -> lnqq~ and e+e- -> W+W- -> qq~qq~ events. Decay-plane correlations, consistent with zero and with the Standard Model predictions, are measured

Ultrarelativistic sources in nonlinear electrodynamics

The fields of rapidly moving sources are studied within nonlinear electrodynamics by boosting the fields of sources at rest. As a consequence of the ultrarelativistic limit the delta-like electromagnetic shock waves are found. The character of the field within the shock depends on the theory of nonlinear electrodynamics considered. In particular, we obtain the field of an ultrarelativistic charge in the Born-Infeld theory.Comment: 10 pages, 3 figure

Measurement of the Cross Section for Open-Beauty Production in Photon-Photon Collisions at LEP

The cross section for open-beauty production in photon-photon collisions is measured using the whole high-energy and high-luminosity data sample collected by the L3 detector at LEP. This corresponds to 627/pb of integrated luminosity for electron-positron centre-of-mass energies from 189GeV to 209GeV. Events containing b quarks are identified through their semi-leptonic decay into electrons or muons. The e+e- -> e+e-b b~X cross section is measured within our fiducial volume and then extrapolated to the full phase space. These results are found to be in significant excess with respect to Monte Carlo predictions and next-to-leading order QCD calculations

FAIR Metadata Standards for Low Carbon Energy Research—A Review of Practices and How to Advance

The principles of Findability, Accessibility, Interoperability, and Reusability (FAIR) have been put forward to guide optimal sharing of data. The potential for industrial and social innovation is vast. Domain-specific metadata standards are crucial in this context, but are widely missing in the energy sector. This report provides a collaborative response from the low carbon energy research community for addressing the necessity of advancing FAIR metadata standards. We review and test existing metadata practices in the domain based on a series of community workshops. We reflect the perspectives of energy data stakeholders. The outcome is reported in terms of challenges and elicits recommendations for advancing FAIR metadata standards in the energy domain across a broad spectrum of stakeholders

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London