Background Procalcitonin (PCT)-guided antibiotic stewardship (ABS) has been shown to reduce antibiotics (ABxs), with lower side-effects and an improvement in clinical outcomes. The aim of this ...experts workshop was to derive a PCT algorithm ABS for easier implementation into clinical routine across different clinical settings. Methods Clinical evidence and practical experience with PCT-guided ABS was analyzed and discussed, with a focus on optimal PCT use in the clinical context and increased adherence to PCT protocols. Using a Delphi process, the experts group reached consensus on different PCT algorithms based on clinical severity of the patient and probability of bacterial infection. Results The group agreed that there is strong evidence that PCT-guided ABS supports individual decisions on initiation and duration of ABx treatment in patients with acute respiratory infections and sepsis from any source, thereby reducing overall ABx exposure and associated side effects, and improving clinical outcomes. To simplify practical application, the expert group refined the established PCT algorithms by incorporating severity of illness and probability of bacterial infection and reducing the fixed cut-offs to only one for mild to moderate and one for severe disease (0.25 μg/L and 0.5 μg/L, respectively). Further, guidance on interpretation of PCT results to initiate, withhold or discontinue ABx treatment was included. Conclusions A combination of clinical patient assessment with PCT levels in well-defined ABS algorithms, in context with continuous education and regular feedback to all ABS stakeholders, has the potential to improve the diagnostic and therapeutic management of patients suspected of bacterial infection, thereby improving ABS effectiveness.
The first FDA-approved test to assess risk for acute kidney injury (AKI), TIMP-2•IGFBP7, is clinically available in many parts of the world, including the USA and Europe. We sought to understand how ...the test is currently being used clinically.
We invited a group of experts knowledgeable on the utility of this test for kidney injury to a panel discussion regarding the appropriate use of the test. Specifically, we wanted to identify which patients would be appropriate for testing, how the results are interpreted, and what actions would be taken based on the results of the test. We used a modified Delphi method to prioritize specific populations for testing and actions based on biomarker test results. No attempt was made to evaluate the evidence in support of various actions however.
Our results indicate that clinical experts have developed similar practice patterns for use of the TIMP-2•IGFBP7 test in Europe and North America. Patients undergoing major surgery (both cardiac and non-cardiac), those who were hemodynamically unstable, or those with sepsis appear to be priority patient populations for testing kidney stress. It was agreed that, in patients who tested positive, management of potentially nephrotoxic drugs and fluids would be a priority. Patients who tested negative may be candidates for "fast-track" protocols.
In the experience of our expert panel, biomarker testing has been a priority after major surgery, hemodynamic instability, or sepsis. Our panel members reported that a positive test prompts management of nephrotoxic drugs as well as fluids, while patients with negative results are considered to be excellent candidates for "fast-track" protocols.
DNA microarray technology has already revolutionized basic research in infectious diseases, and whole-genome sequencing efforts have allowed for the fabrication of tailor-made spotted microarrays for ...an increasing number of bacterial pathogens. However, the application of microarrays in diagnostic microbiology is currently hampered by the high costs associated with microarray experiments and the specialized equipment needed. Here, we show that a thorough bioinformatic postprocessing of the microarray design to reduce the amount of unspecific noise also allows the reliable use of spotted gene expression microarrays for gene content analyses. We further demonstrate that the use of only single-color labeling to halve the costs for dye-labeled nucleotides results in only a moderate decrease in overall specificity and sensitivity. Therefore, gene expression microarrays using only single-color labeling can also reliably be used for gene content analyses, thus reducing the costs for potential routine applications such as genome-based pathogen detection or strain typing.
The paracaspase Malt1 is a key regulator of canonical NF-κB activation downstream of multiple receptors in both immune and nonimmune cells. Genetic disruption of Malt1 protease function in mice and
...mutations in humans results in reduced regulatory T cells and a progressive multiorgan inflammatory pathology. In this study, we evaluated the altered immune homeostasis and autoimmune disease in Malt1 protease-deficient (Malt1PD) mice and the Ags driving disease manifestations. Our data indicate that B cell activation and IgG1/IgE production is triggered by microbial and dietary Ags preferentially in lymphoid organs draining mucosal barriers, likely as a result of dysregulated mucosal immune homeostasis. Conversely, the disease was driven by a polyclonal T cell population directed against self-antigens. Characterization of the Malt1PD T cell compartment revealed expansion of T effector memory cells and concomitant loss of a CD4
T cell population that phenotypically resembles anergic T cells. Therefore, we propose that the compromised regulatory T cell compartment in Malt1PD animals prevents the efficient maintenance of anergy and supports the progressive expansion of pathogenic, IFN-γ-producing T cells. Overall, our data revealed a crucial role of the Malt1 protease for the maintenance of intestinal and systemic immune homeostasis, which might provide insights into the mechanisms underlying IPEX-related diseases associated with mutations in
.
Activated protein C (APC) is a plasma serine protease with antithrombotic and cytoprotective functions. Based on the hypothesis that specific inhibition of APC's anticoagulant but not its ...cytoprotective activity can be beneficial for hemophilia therapy, 2 types of inhibitory monoclonal antibodies (mAbs) are tested: A type I active-site binding mAb and a type II mAb binding to an exosite on APC (required for anticoagulant activity) as shown by X-ray crystallography. Both mAbs increase thrombin generation and promote plasma clotting. Type I blocks all APC activities, whereas type II preserves APC's cytoprotective function. In normal monkeys, type I causes many adverse effects including animal death. In contrast, type II is well-tolerated in normal monkeys and shows both acute and prophylactic dose-dependent efficacy in hemophilic monkeys. Our data show that the type II mAb can specifically inhibit APC's anticoagulant function without compromising its cytoprotective function and offers superior therapeutic opportunities for hemophilia.
Context. With an orbital distance comparable to that of Saturn in the solar system, β Pictoris b is the closest (semi-major axis ≃9 au) exoplanet that has been imaged to orbit a star. Thus it offers ...unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to β Pictoris have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet’s orbital parameters. Aims. We aimed at further constraining β Pictoris b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit. Methods. We used SPHERE at the VLT to precisely monitor the orbital motion of beta β Pictoris b since first light of the instrument in 2014. Results. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6 au) and prevented further detection. We redetected β Pictoris b on the northeast side of the disk at a separation of 139 mas and a PA of 30° in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of a = 9.0 ± 0.5 au (1σ), it definitely excludes previously reported possible long orbital periods, and excludes β Pictoris b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.
We report the discovery of a bright, brown dwarf companion to the star HIP 64892, imaged with VLT/SPHERE during the SHINE exoplanet survey. The host is a B9.5V member of the Lower-Centaurus-Crux ...subgroup of the Scorpius Centaurus OB association. The measured angular separation of the companion (1.2705 ± 0.0023”) corresponds to a projected distance of 159 ± 12 AU. We observed the target with the dual-band imaging and long-slit spectroscopy modes of the IRDIS imager to obtain its spectral energy distribution (SED) and astrometry. In addition, we reprocessed archival NACO L-band data, from which we also recover the companion. Its SED is consistent with a young (<30 Myr), low surface gravity object with a spectral type of M9γ ± 1. From comparison with the BT-Settl atmospheric models we estimate an effective temperature of Teff = 2600 ± 100 K, and comparison of the companion photometry to the COND evolutionary models yields a mass of ~29−37 MJ at the estimated age of 16−7+15 $16^{+15}_{-7}$16−7+15 Myr for the system. The star HIP 64892 is a rare example of an extreme-mass ratio system (q ~ 0.01) and will be useful for testing models relating to the formation and evolution of such low-mass objects.
To investigate adrenocorticotropin, androstenedione (ASD), cortisol, or dehydroepiandrosterone sulfate (DHEAS) before and during a corticotropin releasing hormone (hCRH) test in patients with ...moderately active systemic lupus erythematosus (SLE) undergoing low dose longterm glucocorticoid therapy, and to examine these hormones in relation to interleukin 6 (IL-6) or tumor necrosis factor (TNF).
Serum levels of hormones and cytokines were measured before and during an hCRH test. The results of 12 patients with SLE were compared to 12 healthy subjects (HS) and 12 healthy subjects given prior short term prednisolone (HS+P).
Baseline and stimulated serum ASD, cortisol, and DHEAS were lower in patients with SLE vs. HS (p<0.005), but baseline and stimulated plasma adrenocorticotropin was normal in SLE. In SLE, but not in HS+P or HS, baseline and stimulated DHEAS was low in relation to cortisol or ASD (i.e., shift from DHEAS to cortisol or ASD). In patients with SLE, baseline and stimulated serum levels of adrenal hormones were lower in relation to IL-6 or TNF compared to HS or HS+P (p< 0.001). In contrast, in SLE patients, the baseline and stimulated pituitary hormone adrenocorticotropin was normal in relation to these cytokines.
We found marked adrenal insufficiency and a shift in steroidogenesis to cortisol in patients with SLE, but a completely normal pituitary function (in absolute values and in relation to IL-6 or TNF). This may depend in part on prior longterm glucocorticoid therapy and changes of steroidogenesis due to cytokines. The situation in patients with SLE was not mimicked by high dose short term prednisolone in healthy subjects. Further longitudinal studies in untreated patients are needed to investigate the endocrine-immune interplay and its consequences during the course of SLE.
Road construction sites often are the reason for traffic jams and accidents due to the reduced road width. Driver assistance systems for these demanding environments highly benefit from a digital ...representation of the road layout. This digital map includes all important infrastructure elements, such as barriers, temporary road markings and guiding reflector posts. The paper describes the automatic generation of a detailed and highly accurate "Road Work Map" using video camera and laser scanners.
PDF
![Clinical use of [TIMP-2]•[I...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1364-8535_1466-609X/small "Clinical use of [TIMP-2]•[IGFBP7] biomarker testing to assess risk of acute kidney injury in critical care: guidance from an expert panel")
