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Kortikosteroide bei Patienten mit Neuritis vestibularis: Eine aktualisierte Metaanalyse
Get PDFHintergrund und Ziele:
Die Neuritis vestibularis ist ein häufig auftretendes Krankheitsbild im Fachbereich der Neurologie und der Hals-Nasen-Ohren-Heilkunde. Seit vielen Jahren wird zur Behandlung eine kortisonbasierte Therapie angewendet, obwohl die evidenzbasierte Datenlage bisher sehr gering ist. Ziel dieser Meta-Analyse ist eine aktuelle Zusammenfassung der bisherigen Datenlage anhand des Vergleichs bisheriger klinischer Studien. Dabei wird die Fragestellung bearbeitet, ob eine Kortisontherapie bei Neuritis vestibularis im Vergleich zu Kontrollgruppen mit Plazebotherapie zur besseren Genesung führt.
Methoden:
Als Datenbanken für klinische Studien zu der o.g. Fragestellung wurden Medline, Scopus und Cochrane für den Zeitraum von 1970 bis 2020 verwendet. Dabei wurden Studien eingeschlossen, die randomisiert und kontrolliert waren (RCT), eine Therapiegruppe und eine Kontrollgruppe hatten und das Patientenalter über 18 Jahre lag. Insgesamt konnten 15 Studien mit 363 Teilnehmern in der Therapiegruppe mit Kortison und 489 Teilnehmern in der Kontrollgruppe mit Plazebotherapie erfasst und eingeschlossen werden. 8 Studien wiesen dabei ein hohes Risiko an Bias auf. Verglichen wurde dabei die bessere Genesung anhand klinischer Besserung in der akuten Phase innerhalb eines Monats und Verbesserung der Testergebnisse in klinischen Tests des Gleichgewichts nach sechs Monaten bis zu zwei Jahren. Zudem wurden die Nebenwirkungen einer Kortisontherapie evaluiert.
Ergebnisse und Beobachtungen:
In der akuten Phase zeigte sich bei einer Odds Ratio (OR) von 3.1 (95% CI 1.2-7.8; p=.015) ein statistisch signifikant besseres Ergebnis in der Verbesserung des klinischen Zustandes in der Steroidtherapiegruppe. Dabei müssen sechs Patienten behandelt werden (= Number needed to treat (NNT)), damit ein Patient von der Kortisontherapie profitiert (95% CI 4-23). Auch bei der Wiederherstellung der Gleichgewichtsfunktion nach sechs Monaten bis zu zwei Jahren zeigten sich statistisch signifikant bessere Erfolge in der Steroidtherapiegruppe, OR von 2.4 (95% CI 1.3-4.4; p=.004), bei einer NNT von sieben Patienten, damit ein Patient von der Kortisontherapie profitiert (95% CI 5-18). Der statistisch signifikante Vorteil einer Kortisontherapie blieb dabei unabhängig von der Betrachtung von randomisierten oder nicht randomisierten Studien. Das Risiko von Nebenwirkungen war in der Steroidtherapiegruppe größer. Dabei traten durchschnittlich bei jedem vierten Patienten Nebenwirkungen auf (Number needed to harm (NNH) =4; 95% CI 3-19). Zusammenfassend lässt sich ein statistisch signifikanter Vorteil in der Kortisontherapie bei Neuritis vestibularis sowohl in der akuten Phase als auch langfristig zeigen.
Schlussfolgerungen:
Die durchgeführte Metaanalyse lässt auf einen Vorteil der Kortisontherapie bei Neuritis vestibularis sowohl im kurz- als auch im langfristigen Verlauf schließen. Die verglichenen Studien weisen allerdings ein weites Spektrum an Qualität, Studienaufbau und Verzerrungsrisiko auf
Osteointegration of functionalised high-performance oxide ceramics: imaging from micro-computed tomography
Get PDFBackground This study evaluated the osseointegration potential of functionalised high-performance oxide ceramics (HPOC) in isolation or coated with BMP-2 or RGD peptides in 36 New Zeeland female rabbits using micro-computed tomography (micro CT). The primary outcomes of interest were to assess the amount of ossification evaluating the improvement in the bone volume/ total volume (BV/TV) ratio and trabecular thickness at 6 and 12 weeks. The second outcome of interest was to investigate possible differences in osteointegration between the functionalised silanised HPOC in isolation or coated with Bone Morphogenetic Protein 2 (BMP-2) or RGD peptides. Methods 36 adult female New Zealand white rabbits with a minimum weight of three kg were used. One-third of HPOCs were functionalised with silicon suboxide (SiOx), a third with BMP-2 (sHPOC-BMP2), and another third with RGD (sHPOC-RGD). All samples were scanned with a high-resolution micro CT (U-CTHR, MILabs B.V., Houten, The Netherlands) with a reconstructed voxel resolution of 10 µm. MicroCT scans were reconstructed in three planes and processed using Imalytics Preclinical version 2.1 (Gremse-IT GmbH, Aachen, Germany) software. The total volume (TV), bone volume (BV) and ratio BV/TV were calculated within the coating area. Results BV/TV increased significantly from 6 to 12 weeks in all HPOCs: silanised (P = 0.01), BMP-2 (P < 0.0001), and RGD (P < 0.0001) groups. At 12 weeks, the BMP-2 groups demonstrated greater ossification in the RGD (P < 0.0001) and silanised (P = 0.008) groups. Trabecular thickness increased significantly from 6 to 12 weeks (P < 0.0001). At 12 weeks, BMP-2 promoted greater trabecular thickness compared to the silanised group (P = 0.07), although no difference was found with the RGD (P = 0.1) group. Conclusion Sinalised HPOC in isolation or functionalised with BMP-2 or RGD promotes in vivo osteointegration. The sinalised HOPC functionalised with BMP-2 demonstrated the greatest osseointegration.German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) as part of the Validation of the Technological and Social Innovation Potential of Scientific Research (Validierung des Technologischen und Gesellschaftlichen Innovationspotenzials wissenschaftlicher Forschung) Fundin
Enhanced interlocking in granular jamming grippers through hard and soft particle mixtures
Get PDFWe investigate the influence of particle stiffness on the grasping performance of granular grippers, a class of soft robotic effectors that utilize granular jamming for object manipulation. Through experimental analyses and X-ray imaging, we show that grippers with soft particles exhibit improved wrapping of the object after jamming, in contrast to grippers with rigid particles. This results in significantly increased holding force through the interlocking. The addition of a small proportion of rigid particles into a predominantly soft particle mixture maintains the improved wrapping but also significantly increases the maximum holding force. These results suggest a tunable approach to optimizing the design of granular grippers for improved performance in soft robotics applications. Graphic abstractOpen Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Epidemiological Characteristics and Prognostic Scoring in Toxic Epidermal Necrolysis and Stevens–Johnson Syndrome: Insights from a 17-Year Burn Center Experience
Get PDFBackground and Objectives : Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are rare yet life-threatening dermatologic conditions characterized by severe skin and mucous membrane involvement. Accurate prognostic systems are crucial for clinical management to assess disease severity and predict outcomes. The primary objective of this study was to assess the epidemiological characteristics and clinical outcomes of patients with Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap over a 17-year period at a specialized burn center. The secondary objectives were to evaluate the performance of existing prognostic scoring systems (SCORTEN, Re-SCORTEN, and ABCD-10) in predicting mortality and to propose a novel classification tree model to improve mortality prediction. Materials and Methods : A 17-year retrospective study at a burn center included 68 patients with SJS, SJS/TEN overlap, or TEN. Demographic, clinical, laboratory data, and prognostic scores (SCORTEN, Re-SCORTEN, ABCD-10) were collected and analyzed for associations with mortality. A classification tree was created to detect unknown determinants of SJS/TEN mortality. Results : The drug most frequently associated with the occurrence of SJS/TEN was metamizole. The mortality rate was 51%. Affected body surface area, platelet count, and serum blood urea nitrogen differed significantly between survivors and non-survivors. Regarding the scoring systems, only the Re-SCORTEN showed reliable differentiation for these groups. A classification tree model achieved an accuracy of 89% in predicting the mortality risk. In the ROC curve analysis, the AUC values were 0.88 for the classification tree, 0.66 for Re-SCORTEN, 0.61 for SCORTEN, and 0.56 for ABCD-10. Conclusions : This study explores mortality predictors in SJS/TEN via a classification tree model, highlighting potential factors for further investigation. While cautioning against immediate clinical application due to data constraints, the findings underscore the need for larger studies to validate and refine prediction models in this context.This research received no external funding
Progress in electron beam additive manufacturing
Get PDFOpen Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Mutational analysis differentiating sporadic carcinomas from colitis-associated colorectal carcinomas
Get PDFBackground Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that is associated with increased risk of developing colitis-associated carcinoma (CAC). The genetic profile of CACs is fairly similar to the sporadic colorectal carcinomas (sCRCs), although showing certain differences in the timing and sequence of alterations that contribute to carcinogenesis. Also, both cancer types typically show a strong histological resemblance, which complicates the pathologists’ diagnosis. Due to the different clinical consequences, it is of utmost importance to categorize the corresponding cancer type correctly. Methods In this study, we determined the mutation profiles of 64 CACs and sCRCs in the hotspot regions of 50 cancer-associated genes and compared them to 29 controls to identify genetic gene variants that can facilitate the pathologists’ diagnosis. Pearson Chi-Square or Fisher’s exact tests were used for statistical analyses. Results We found that sCRCs tend to mutate more frequently in APC and PIK3CA genes than CACs and that mainly males were affected. Our CAC cohort identified the KRAS G12D mutation as group-specific variant that was not detected in the sCRCs. When separating conventional from non-conventional CACs, it was discovered that the conventional type shows significantly more mutations for ATM. Conclusions Taken together, our data highlights genetic differences between sCRC and CAC and enables the possibility to utilize specific gene alterations to support the pathologist’s diagnosis.Open Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Elevated Insulin Levels Engage the Salience Network during Multisensory Perception
Get PDFIntroduction: Brain insulin reactivity has been reported in connection with systematic energy metabolism, enhancement in cognition, olfactory sensitivity, and neuroendocrine circuits. High receptor densities exist in regions important for sensory processing. The main aim of the study was to examine whether intranasal insulin would modulate the activity of areas in charge of olfactory-visual integration. Methods: As approach, a placebo-controlled double-blind within crossover design was chosen. The experiments were conducted in a research unit of a university hospital. On separate mornings, twenty-six healthy normal-weight males aged between 19 and 31 years received either 40 IU intranasal insulin or placebo vehicle. Subsequently, they underwent 65 min of functional magnetic resonance imaging whilst performing an odor identification task. Functional brain activations of olfactory, visual, and multisensory integration as well as insulin versus placebo were assessed. Regarding the odor identification task, reaction time, accuracy, pleasantness, and intensity measurements were taken to examine the role of integration and treatment. Blood samples were drawn to control for peripheral hormone concentrations. Results: Intranasal insulin administration during olfactory-visual stimulation revealed strong bilateral engagement of frontoinsular cortices, anterior cingulate, prefrontal cortex, mediodorsal thalamus, striatal, and hippocampal regions ( p ≤ 0.001 familywise error [FWE] corrected). In addition, the integration contrast showed increased activity in left intraparietal sulcus, left inferior frontal gyrus, left superior frontal gyrus, and left middle frontal gyrus ( p ≤ 0.013 FWE corrected). Conclusions: Intranasal insulin application in lean men led to enhanced activation in multisensory olfactory-visual integration sites and salience hubs which indicates stimuli valuation modulation. This effect can serve as a basis for understanding the connection of intracerebral insulin and olfactory-visual processing.Funding of this study was provided by a grant from the German Research Foundation to JF (DFG, FR 3114/6-1)
Anti-CGRP antibody galcanezumab modifies the function of the trigeminovascular nocisensor complex in the rat
Get PDFBackground Monoclonal antibodies directed against the neuropeptide calcitonin gene-related peptide (CGRP) are effective in the prevention of chronic and frequent episodic migraine. Since the antibodies do not cross the blood brain barrier, their antinociceptive effect is attributed to effects in meningeal tissues. We aimed to probe if such an antibody can be visualized within the dura mater and the trigeminal ganglia following its administration to rats and to examine if the activity of the trigeminovascular nocisensor complex is influenced by this treatment. Methods Effects of the anti-CGRP antibody galcanezumab on the trigeminovascular nocisensor complex was examined by measuring release of sensory neuropeptides and histamine from the rat dura mater. Deposits of galcanezumab were visualized by fluorescence microscopy in the trigeminal ganglion and the dura mater. Results Fluorophore-labelled galcanezumab was detected in the dura mater and the trigeminal ganglion up to 30 days after treatment affirming the long-lasting modulatory effect of this antibody. In female rats, seven days after systemic treatment with galcanezumab the capsaicin-induced release of CGRP was decreased, while that of substance P (SP) was increased in the dura mater. In control rats, release of the inhibitory neuropeptide somatostatin (SOM) was higher in females than in males. Stimulation with high concentration of KCl did not significantly change the release of SOM in control animals, while in rats treated with galcanezumab SOM release was slightly reduced. Galcanezumab treatment also reduced the amount of histamine released from dural mast cells upon stimulation with CGRP, while the effect of compound 48/80 on histamine release was not changed. Conclusions Galcanezumab treatment is followed by multiple changes in the release of neuropeptides and histamine in the trigeminal nocisensor complex, which may contribute to the migraine preventing effect of anti-CGRP antibodies. These changes affecting the communication between the components of the trigeminal nocisensor complex may reduce pain susceptibility in migraine patients treated with CGRP targeting monoclonal antibodies.Open access funding provided by University of Szeged.University of SzegedAlexander von Humboldt FoundationHungarian National Research, Development and Innovation OfficeUniversity of Szege
Thermal Conductivity of Glycerol at Atmospheric Pressure Between 268 K and 363 K by Using a Steady-State Parallel-Plate Instrument
Get PDFThe present work reports experimental data for the thermal conductivity of glycerol which is an important fluid in many technical applications. Measurements were performed in an absolute way at ambient pressure using a steady-state guarded parallel-plate instrument (GPPI) with an average expanded ( k = 2) measurement uncertainty of 2.3%. For data representation over a temperature range from (268.15 to 363.15) K in steps of 5 K, the thermal conductivities are averaged from measurements at three different temperature gradients for each temperature. The present results indicate an almost constant thermal conductivity of glycerol over the studied temperature range and agree with the sparse experimental data available in the literature. Based on the experimental database including the results from this work, a simple correlation for the thermal conductivity of glycerol at 0.1 MPa as a function of temperature between (268 and 413) K is suggested. The additional study on the influence of water as possible contamination up to water mass fractions of 0.02 on the thermal conductivity of glycerol reveals negligible changes. Overall, the experimental results from this work contribute to an improved data situation for the thermal conductivity of glycerol, particularly in the subcooled liquid region at temperatures below 283 K.Open Access funding enabled and organized by Projekt DEAL.Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells
Get PDFColorectal cancer (CRC) tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is poorly understood. Using CRC patient derived organoids (PDOs), we find that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing single cell RNA-sequencing (scRNA-seq) expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.The mechanical properties of heterogeneous cell populations in colorectal tumors and the relevance to cancer metastasis remain not fully understood. Here, the authors suggest that the variations in malignant phenotypes between LGR5-positive cancer stem cells and LGR5-negative cells could be due to their distinct mechanical phenotypes observed in vitro, determined by the membrane to cortex attachment proteins Ezrin/Radixin/Moesin.EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)https://doi.org/10.13039/10001066