Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin.

BACKGROUND: Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation. OBJECTIVES: To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota. METHODS: Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily. RESULTS: Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model. CONCLUSIONS: Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.

Intracerebral gadolinium deposition following blood-brain barrier disturbance in two different mouse models.

To evaluate the influence of the blood-brain barrier on neuronal gadolinium deposition in a mouse model after multiple intravenous applications of the linear contrast agent gadodiamide. The prospective study held 54 mice divided into three groups: healthy mice (A), mice with iatrogenic induced disturbance of the blood-brain barrier by glioblastoma (B) or cerebral infarction (C). In each group 9 animals received 10 iv-injections of gadodiamide (1.2 mmol/kg) every 48 h followed by plain T1-weighted brain MRI. A final MRI was performed 5 days after the last contrast injection. Remaining mice underwent MRI in the same time intervals without contrast application (control group). Signal intensities of thalamus, pallidum, pons, dentate nucleus, and globus pallidus-to-thalamus and dentate nucleus-to-pons ratios, were determined. Gadodiamide complex and total gadolinium amount were quantified after the last MR examination via LC-MS/MS and ICP-MS. Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios showed no significant increase over time within all mice groups receiving gadodiamide, as well as compared to the control groups at last MR examination. Comparing healthy mice with group B and C after repetitive contrast administration, a significant SI increase could only be detected for glioblastoma mice in globus pallidus-to-thalamus ratio (p = 0.033), infarction mice showed no significant SI alteration. Tissue analysis revealed significantly higher gadolinium levels in glioblastoma group compared to healthy (p = 0.013) and infarction mice (p = 0.029). Multiple application of the linear contrast agent gadodiamide leads to cerebral gadolinium deposition without imaging correlate in MRI.

TEMPus VoLA: The timed Epstein multi-pressure vessel at low accelerations.

The field of planetary system formation relies extensively on our understanding of the aerodynamic interaction between gas and dust in protoplanetary disks. Of particular importance are the mechanisms triggering fluid instabilities and clumping of dust particles into aggregates, and their subsequent inclusion into planetesimals. We introduce the timed Epstein multi-pressure vessel at low accelerations, which is an experimental apparatus for the study of particle dynamics and rarefied gas under micro-gravity conditions. This facility contains three experiments dedicated to studying aerodynamic processes: (i) the development of pressure gradients due to collective particle-gas interaction, (ii) the drag coefficients of dust aggregates with variable particle-gas velocity, and (iii) the effect of dust on the profile of a shear flow and resultant onset of turbulence. The approach is innovative with respect to previous experiments because we access an untouched parameter space in terms of dust particle packing fraction, and Knudsen, Stokes, and Reynolds numbers. The mechanisms investigated are also relevant for our understanding of the emission of dust from active surfaces, such as cometary nuclei, and new experimental data will help interpreting previous datasets (Rosetta) and prepare future spacecraft observations (Comet Interceptor). We report on the performance of the experiments, which has been tested over the course of multiple flight campaigns. The project is now ready to benefit from additional flight campaigns, to cover a wide parameter space. The outcome will be a comprehensive framework to test models and numerical recipes for studying collective dust particle aerodynamics under space-like conditions.

Raman microscopic spectroscopy as a diagnostic tool to detect Staphylococcus epidermidis in bone grafts.

INTRODUCTION: Raman microscopic spectroscopyis a new approach for further characterization and detection of molecular features in many pathological processes. This technique has been successfully applied to scrutinize the spatial distribution of small molecules and proteins within biological systems by in situ analysis. This study uses Raman microscopic spectroscopyto identify any in-depth benefits and drawbacks in diagnosing Staphylococcus epidermidis in human bone grafts. MATERIAL AND METHODS: 40 non-infected human bone samples and 10 human bone samples infected with Staphylococcus epidermidis were analyzed using Raman microscopic spectroscopy. Reflectance data were collected between 200 cm-1 and 3600 cm-1 with a spectral resolution of 4 cm-1 using a Senterra II microscope (Bruker, Ettlingen, Germany). The acquired spectral information was used for spectral and unsupervised classification, such as principal component analysis. RESULTS: Raman measurements produced distinct diagnostic spectra that were used to distinguish between non-infected human bone samples and Staphylococcus epidermidis infected human bone samples by spectral and principal component analyses. A substantial loss in bone quality and protein conformation was detected by human bone samples co-cultured with Staphylococcus epidermidis. The mineral-to-matrix ratio using the phosphate/Amide I ratio (p = 0.030) and carbonate/phosphate ratio (p = 0.001) indicates that the loss of relative mineral content in bones upon bacterial infection is higher than in non-infected human bones. Also, an increase of alterations in the collagen network (p = 0.048) and a decrease in the structural organization and relative collagen in infected human bone could be detected. Subsequent principal component analyses identified Staphylococcus epidermidis in different spectral regions, respectively, originating mainly from CH2 deformation (wagging) of protein (at 1450 cm-1) and bending and stretching modes of C-H groups (∼2800-3000 cm-1). CONCLUSION: Raman microscopic spectroscopyis presented as a promising diagnostic tool to detect Staphylococcus epidermidis in human bone grafts. Further studies in human tissues are warranted.

Reliability and accuracy of straightforward measurements for liver volume determination in ultrasound and computed tomography compared to real volumetry.

To evaluate the suitability of volume index measurement (VI) by either ultrasound (US) or computed tomography (CT) for the assessment of liver volume. Fifty-nine patients, 21 women, with a mean age of 66.8 ± 12.6 years underwent US of the liver followed immediately by abdominal CT. In US and CT imaging dorsoventral, mediolateral and craniocaudal liver diameters in their maximum extensions were assessed by two observers. VI was calculated by multiplication of the diameters divided by a constant (3.6). The liver volume determined by a manual segmentation in CT ("true liver volume") served as gold standard. True liver volume and calculated VI determined by US and CT were compared using Bland-Altman analysis. Mean differences of VI between observers were - 34.7% (- 90.1%; 20.7%) for the US-based and 1.1% (- 16.1%; 18.2%) for the CT-based technique, respectively. Liver volumes determined by semi-automated segmentation, US-based VI and CT-based VI, were as follows: 1.500 ± 347cm3; 863 ± 371cm3; 1.509 ± 432cm3. Results showed a great discrepancy between US-based VI and true liver volume with a mean bias of 58.3 ± 66.9%, and high agreement between CT-based VI and true liver volume with a low mean difference of 4.4 ± 28.3%. Volume index based on CT diameters is a reliable, fast and simple approach for estimating liver volume and can therefore be recommended for clinical practice. The usage of US-based volume index for assessment of liver volume should not be used due to its low accuracy of US in measurement of liver diameters.

Simple diameter measurement as predictor of liver volume and liver parenchymal disease.

To investigate the accuracy of liver diameters for estimation of liver size and to evaluate their application as tool for assessment of parenchymal liver disease. In the course of a population-based study, (SHIP) one thousand nine hundred thirty-nine volunteers underwent magnetic resonance imaging (MRI) of the liver including 3D gradient echo MRI sequences. Maximum liver diameters were measured in cranio-caudal (CC), anterior-posterior (AP), medial-lateral (ML) orientation. Diameters were compared with true liver volume assessed by liver segmentation. Additionally, age-dependent reference values for diameters were defined. Finally, accuracy of liver diameters was assessed to discriminate volunteers with healthy livers and participants with parenchymal changes, measured by MRI and laboratory. Reference values of liver diameters within the healthy population (n = 886) were defined as follows (mean ± standard deviation, confidence interval CI in cm): CC 17.2 ± 2, CI 13.6/21.2; AP 15.8 ± 1.9, CI 12.6/19.8; ML 19.7 ± 2.3, CI 15.8/24.6. There was a poor correlation using linear regression between liver diameter and true liver volume; CC 0.393, AP 0.359; ML 0.137. The AP direction shows the best correlation to discriminate between healthy and pathologic liver changes; AUC 0.78; p < 0.001, CC AUC 0.53; p < 0.001 and ML AUC 0.52; p = 0.008. Measurement of liver diameter, especially in the anterior-posterior direction is a simple option to detect chronic liver disease but less suitable for prediction of liver volume.

[Treatment of mentally ill parents-Strengthen awareness for children]. / Behandlung psychisch erkrankter Eltern ­ Awareness für Kinder stärken.

To raise awareness that families with a mentally ill parent face special challenges and the correct handling of it, need to be considered more in health care. The simple question "how are you as a parent and your children?" is often not asked but this question is important so as not to endanger the healing process, to identify the need for assistance and to break the potential vicious circle for children. Awareness of the problem in the psychiatry of adults can support the care of affected persons and their children.

Long-term outcome of incidental cystic liver tumors in the general population.

Aim of this study was to investigate frequency, incidence and risk factors of liver cysts in the general population in a longitudinal survey. Cyst frequency was investigated in 607 adult volunteers (288 women, 319 men, mean age 55 years) using strong T2-weighted magnetic resonance imaging. Risk factors were investigated for occurrence, frequency and size of cystic lesions at baseline. Incidence and physiological growing of the lesions were observed in a 5-years follow-up. At baseline, 431 volunteers had 1,479 cysts (71.0%). The mean number of cysts per person was 3.4 ± 9.0. The mean size of cysts was 13.1 ± 11.7 mm. Women had a higher number of cysts than men (p = 0.026). Older and male volunteers demonstrated a higher cyst frequency (p = 0.002 and p = 0.025). Per one-year increase in age the chance for a liver cyst increased by 2%. Four-hundred seventeen volunteers had cysts in the follow-up, in 24.6% new lesions had occurred. Lesion size significantly increased in follow-up (p < 0.001). Age and male sex were associated with the occurrence of at least one liver cyst. Women had a higher average number of cysts. Cystic lesion progression is a physiological phenomenon in the long-term follow-up.

Whole-body R2∗ mapping to quantify tissue iron in iron storage organs: reference values and a genotype.

AIM: To define reference values for the transverse relaxation rate (R2∗) in iron storage organs and to investigate the role of human haemochromatosis protein (HFE) genotype on iron storage. MATERIALS AND METHODS: Whole-body magnetic resonance imaging (MRI) including a five-echo gradient-echo sequence was performed in 483 volunteers (269 men, mean age 59.3 ± 12.2 years) without clinical evidence of an iron storage disease at 1.5 T. R2∗ values were assessed for liver, spleen, pancreas, heart, bones, and brain parenchyma. The HFE genotype was determined regarding the single nucleotide polymorphisms (SNPs) rs74315324, rs1799945, rs41303501, rs1800562, rs1800730. R2∗ values were compared among participants without and with at least one mutation. R2∗ reference values were defined using volunteers without any mutation. RESULTS: Three hundred and one participants had no mutations in any HFE SNP, 182 had at least one mutation. HFE gene mutations were distributed as (heterozygous/homozygous) rs1799945:132/9, rs1800562:33/1, and rs1800730:11/0. Mean R2∗ values ± SD (per second) in the group without mutation were: liver: 33.4 ± 12.7, spleen: 24.1 ± 13.8, pancreas: 27.2 ± 6.6, heart: 32.7 ± 11.8, bone: 69.3 ± 21.0, brain parenchyma: 13.9 ± 1.2. No significant difference in R2∗ values were found between participants with and without the HFE gene mutation for any examined iron storage organ (pliver=0.09, pspleen=0.36, ppancreas = 0.08, pheart = 0.36, pbone = 0.98, pbrain=0.74). CONCLUSION: Reference values of R2∗ in iron storage organs are feasible to support the diagnosis of iron storage diseases. Non-specific mutations in HFE SNPs appear not to affect the phenotype of tissue iron accumulation.

Reduction of respiratory motion artifacts in gadoxetate-enhanced MR with a deep learning-based filter using convolutional neural network.

OBJECTIVES: To reveal the utility of motion artifact reduction with convolutional neural network (MARC) in gadoxetate disodium-enhanced multi-arterial phase MRI of the liver. METHODS: This retrospective study included 192 patients (131 men, 68.7 ± 10.3 years) receiving gadoxetate disodium-enhanced liver MRI in 2017. Datasets were submitted to a newly developed filter (MARC), consisting of 7 convolutional layers, and trained on 14,190 cropped images generated from abdominal MR images. Motion artifact for training was simulated by adding periodic k-space domain noise to the images. Original and filtered images of pre-contrast and 6 arterial phases (7 image sets per patient resulting in 1344 sets in total) were evaluated regarding motion artifacts on a 4-point scale. Lesion conspicuity in original and filtered images was ranked by side-by-side comparison. RESULTS: Of the 1344 original image sets, motion artifact score was 2 in 597, 3 in 165, and 4 in 54 sets. MARC significantly improved image quality over all phases showing an average motion artifact score of 1.97 ± 0.72 compared to 2.53 ± 0.71 in original MR images (p < 0.001). MARC improved motion scores from 2 to 1 in 177/596 (29.65%), from 3 to 2 in 119/165 (72.12%), and from 4 to 3 in 34/54 sets (62.96%). Lesion conspicuity was significantly improved (p < 0.001) without removing anatomical details. CONCLUSIONS: Motion artifacts and lesion conspicuity of gadoxetate disodium-enhanced arterial phase liver MRI were significantly improved by the MARC filter, especially in cases with substantial artifacts. This method can be of high clinical value in subjects with failing breath-hold in the scan. KEY POINTS: • This study presents a newly developed deep learning-based filter for artifact reduction using convolutional neural network (motion artifact reduction with convolutional neural network, MARC). • MARC significantly improved MR image quality after gadoxetate disodium administration by reducing motion artifacts, especially in cases with severely degraded images. • Postprocessing with MARC led to better lesion conspicuity without removing anatomical details.

[Handling of COVID-19 in the emergency department : Field report of the emergency ward of the University Hospital Münster]. / Umgang mit COVID-19 in der Notaufnahme : Erfahrungsbericht der interdisziplinären Notaufnahme des Universitätsklinikums Münster.

With the COVID-19 pandemic, emergency rooms are faced with major challenges because they act as the interface between outpatient and inpatient care. The dynamics of the pandemic forced emergency care at the University Hospital Münster to extensively adjust their processes, which had to be carried out in the shortest time possible. This included the establishment of an outpatient coronavirus test center and a medical student-operated telephone hotline. Inside the hospital, new isolation capacities in the emergency room and a dedicated COVID-19 ward were set up. The patient flow was reorganized using flow diagrams for both the outpatient and inpatient areas. The general and special emergency management was optimized for the efficient treatment of COVID-19-positive patients and the staff were trained in the use of protective equipment. This report of our experience is intended to support other emergency departments in their preparation for the COVID-19 pandemic.

Heart Transplantation in Systemic Sclerosis: New Impulses for Conventional Scleroderma Transplantation Regimen and Scleroderma Diagnostic Monitoring: 2 Case Reports.

BACKGROUND: Although low (but increasing) rates of lung/lung-heart transplantations of scleroderma (systemic sclerosis [SSc]) patients have been reported, exclusive heart transplantation is a rare approach for treatment of heart failure due to SSc. CASES: We report on 2 cases of SSc patients receiving a heart transplantation (HTx) due to severe and progressive right heart failure without pulmonary artery hypertension. One patient received a hepatitis C virus (HCV)-positive donor heart and recovered excellently from viral transmission after administration of a direct-acting antiviral (DAA) regimen. This is the first published case of an SSc patient who underwent HTx using an HCV-positive donor heart. The clinical course of both patients was monitored by different serum SSc biomarkers. Only xylosyltransferase activity proved to be a promising biomarker for disease stage determination and therapeutic monitoring, precisely reflecting fibrotic remodeling and successful organ recovery. CONCLUSIONS: Successful implementation of the 2 cases described here demonstrates that HTx is a safe and effective therapeutic option for defined SSc sub-patient groups despite the progressive character of the underlying disease. In the future, xylosyltransferase activity might be conducive to simplify the identification of patients with low systemic involvement but a strong indication for single heart transplantation. Finally, we demonstrate that treatment of HCV viral transmission from HCV-positive donor to organ recipient using DAA gives us new opportunities to consider HCV-positive donor organs for HTx and might reveal new possibilities to ease the lack of donor organs.

Accuracy of ultrasonography in the assessment of liver fat compared with MRI.

AIM: To investigate the accuracy of ultrasonography in the assessment of hepatic steatosis using magnetic resonance imaging (MRI) as standard of reference and to explore the influence of additional hepatic iron overload. MATERIAL AND METHODS: A total of 2,783 volunteers (1,442 women, 1,341 men; mean age, 52.3±13.8 years) underwent confounder-corrected chemical-shift-encoded MRI of the liver at 1.5 T. Proton-density fat fraction (PDFF) and transverse relaxation rate (R2*) were calculated to estimate hepatic steatosis and liver iron overload, respectively. In addition, the presence of hepatic steatosis was assessed by B-mode ultrasonography. The sensitivity, specificity, and accuracy of hepatic ultrasonography were determined for different degrees of hepatic steatosis and different amounts of liver iron. RESULTS: MRI revealed hepatic steatosis in 40% of participants (n=1,112), which was mild in 68.9% (n=766), moderate in 26.7% (n=297), and severe in 4.4% (n=49) of patients. Ultrasonography detected hepatic steatosis in 37.8% (n=1,052), corresponding to 74.5% sensitivity and 86.6% specificity. The sensitivity of ultrasound increased with the amount of hepatic fat present and was 65.1%, 95%, and 96% for low, moderate, and high fat content; whereas the specificity was constantly high at 86.6%. The diagnostic accuracy of ultrasound for detection of hepatic steatosis did not vary significantly with the amount of liver iron present. CONCLUSION: Ultrasonography is an excellent tool to assess hepatic steatosis in the clinical setting with some limitations in patients with a low liver fat content. The detection of hepatic steatosis by ultrasonography is not influenced by liver iron.

Comparison of sequential and high-pitch-spiral coronary CT-angiography: image quality and radiation exposure.

New protocols for coronary computed tomography angiography (CCTA) could lower the radiation dose for patients but influence the image quality. To compare image quality and radiation exposure in step-and-shoot CCTA and high-pitch spiral CCTA. Fifty-nine pairs of patients matched for weight, height, sex and heart rate were included in this study (74 m, 44 f, average age 60 years, age range 29-94 years). Step-and-shoot CCTA and high-pitch spiral CCTA was performed on a third generation dual-source CT in equally sized patient groups. The signal-to-noise ratio (SNR) in the ascending aorta and the coronary arteries were determined for each dataset. Image quality was rated using a five-point scale. We used the t-test for paired samples to compare SNR and effective dose, and the Wilcoxon test to compare image quality scores. Mean effective dose for the step-and-shoot protocol (4.15 ± 3.07 mSv) was significantly higher in comparison to the high-pitch spiral protocol (1.2 ± 0.69 mSv; p < 0.0001). Mean SNR was higher with the step-and-shoot protocol compared to the high-pitch spiral protocol in the aorta, in the left main and peripheral coronary arteries (p < 0.01), in the proximal right coronary artery (p = 0.027). Image quality scores were significantly better for the step-and-shoot protocol (p = 0.0003). Step-and-shoot CCTA has significantly better SNR and overall image quality compared to high-pitch spiral CCTA, but with a mean effective dose more than thrice as high.

[Percutaneous biliary and gallbladder interventions]. / Perkutane Intervention der Gallenwege und der Gallenblase.

CLINICAL ISSUE: Percutaneous transhepatic biliary and gall bladder interventions play an important role in the diagnosis and therapy of biliary tract diseases. PERFORMANCE: With technical success rates up to 99% as well as complications rates up to a maximum of 26% they showed good results. Indications were opacification of the biliary tree as well as treatment of biliary system pathologies, such as drainage and stents. ACHIEVEMENTS: Interventions were used if endoscopic approaches are not possible or exploited. We describe the current state of knowledge and the range for percutaneous biliary/gall bladder interventions and give an overview of technical approaches for fundamental interventional procedures, including percutaneous transhepatic biliary drainage. PRACTICAL RECOMMENDATIONS: Percutaneous transhepatic biliary and gall bladder interventions are safe and effective treatments for benign and malignant stenosis, postoperative complications and risk patients with cholecystitis.

Vitamin D supplementation of 4000 IU daily and cardiac function in patients with advanced heart failure: The EVITA trial.

BACKGROUND: Data regarding the effects of vitamin D on cardiac function are inconclusive. METHODS: In a post-hoc analysis of the EVITA (Effect of vitamin D on mortality in heart failure) trial, we investigated whether a daily vitamin D3 supplement of 4000 IU for three years affects echocardiography parameters like left ventricular end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), and LV ejection fraction (LVEF) in patients with advanced heart failure (HF) and 25­hydroxyvitamin D levels <75 nmol/L. Of 400 patients enrolled, 199 were assigned to vitamin D and 201 to placebo. We assessed time × treatment interaction effects using linear mixed models and analyzed in subgroups vitamin D effects at 12 and 36 months post-randomization using analysis of covariance with adjustments for baseline values. RESULTS: At baseline, values of LVEDD, LVESD, and LVEF were 67.5 ±â€¯10.5 mm, 58.9 ±â€¯12.0 mm, and 30.47 ±â€¯10.2%, respectively. There were no time × treatment interaction effects on LV echocardiographic parameters in the entire study cohort, neither at 12 months nor at 36 months post-randomization (P-values > 0.05). However, in the subgroup of patients aged ≥50 years, vitamin D treatment was associated with an increase in LVEF of 2.73% (95%CI: 0.14 to 5.31%) at 12 months post-randomization (n = 311). The increase was slightly attenuated to 2.60% (95%CI: -2.47 to 7.67%) at 36 months post-randomization (n = 242). CONCLUSION: Our data indicate that vitamin D supplementation does not significantly improve cardiac function in all patients with advanced HF. However, vitamin D probably improves LV function in HF patients aged ≥50 years.

Reference values of liver volume in Caucasian population and factors influencing liver size.

PURPOSE: To investigate factors influencing liver size and to determine reference values of liver volume (LV) for healthy subjects. METHODS: 2773 volunteers underwent magnetic resonance imaging (MRI) of the liver in the setting of the population based Study of Health in Pomerania. Based on measurement of maximum diameters in three orientations, LVs were calculated and correlated with demographic factors such as age, gender, and body mass index. In addition, LVs of healthy volunteers and participants with parenchymal liver diseases such as fatty liver disease, iron overload, fibrosis/cirrhosis were compared. Adjusted reference values of liver volumes were defined for the group of healthy participants. RESULTS: In general, mean LV (mean ±â€¯standard deviation) was 1505 ±â€¯385 cm3. Age, gender and body mass index correlated significantly with the liver volume (p ≤ 0.001). Parenchymal liver diseases significantly influence LV (with: 1624 ±â€¯420 cm3, n = 1525 and without parenchymal liver diseases: 1360 ±â€¯273 cm3; n = 1.248, p ≤ 0.001). Compared to LV of participants without liver diseases, LV was increased in volunteers with hepatic steatosis (1717 ±â€¯419 cm3; n = 1111), liver iron overload (1558 ±â€¯367 cm3; n = 553; p ≤ 0.001) as well as in participants with fibrosis/cirrhosis (1494 ±â€¯459 cm3; n = 383). CONCLUSIONS: LV is influenced by age, body mass index and parenchymal liver diseases. Reference values were established to aid in the diagnosis of parenchymal liver diseases.

Interference of DOACs in different DRVVT assays for diagnosis of lupus anticoagulants.

OBJECTIVE: Determination of lupus anticoagulants (LA) is an important, but still challenging test in the diagnosis of antiphospholipid syndrome (APS). This is especially the case in patients using one of the direct oral anticoagulants (DOACs). The aim of our study was to examine the influence of these drugs on DRVVT assays from two companies (in each case: screening test, confirming test and calculated ratio) and on aPTT and lupus-sensitive aPTT. METHODS: We used plasma samples from healthy volunteers spiked with the DOACs dabigatran, rivaroxaban and apixaban (0, 10, 30, 50, 100 ng/mL) for testing. Furthermore, samples from patients receiving a DOAC were investigated. The plasma concentrations of the DOACs were determined using ultra-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Depending on type and concentration, all the DOACs resulted in pathological values in the DRVVT screening assays. In samples spiked with apixaban, no influence on the DRVVT normalized ratio of the two assays was observed, but 7 to 15% of samples from patients receiving apixaban displayed pathological values. In contrast, up to 71% of dabigatran-spiked samples showed normalized ratio values above the cut-off, whereas there was no influence in the patients' samples. In both spiked and patient samples containing rivaroxaban, the DRVVT assays were influenced. CONCLUSION: LA diagnostics should, under DOAC therapy, be limited to situations in which time-critical evaluation is warranted. It is crucial to take into account the finding that even samples containing DOAC concentrations below the limit of detection of the drugs may lead to false-positive DRVVT measurements.