Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS.MethodsThis is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (QAlb), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z).ResultsMOGAD patients with myelitis were more likely to have a pleocytosis, a QAlb elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, QAlb>10×10-3, as well as higher mean QAlb values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were QAlb>10×10-3 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00).ConclusionBasic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but QAlb>10×10-3 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study

Aims Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Methods and results Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F2t-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. Conclusion This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT0064175

Politische Verantwortung von Sportorganisationen

Vor dem Hintergrund neuerer und neuster ,Skandale‘ und ihrer Debatten widmet sich diese Arbeit der Frage nach der politischen Verantwortung von Sportorganisationen. Aus Mangel an hinreichenden, allgemeine Kriterien, konnte die Frage nach der politischen Verantwortung von Sportorganisationen (im Verhältnis zu anderen Institutionen oder politischen Akteuren) bis zum jetzigen Zeitpunkt nicht befriedigend beantwortet werden. Das Ziel dieser Arbeit besteht folglich darin, die Frage nach der politischen Verantwortung von Sportorganisationen auf der Basis einer ethisch-normativen Argumentation zu beantworten. Der erste, grundlegende Teil dieser Untersuchung legt eine begriffliche Analyse der Termini ‚Verantwortung’ und ‚Sportorganisation’ vor. Diese Auseinandersetzung zeigt erstens, dass die Komplexität des Verantwortungsbegriffs innerhalb eines sportwissenschaftlichen bzw. sportpolitischen Zusammenhangs eine von Fall zu Fall unterschiedlich anzuwendende konzeptuelle Matrix darstellt. Daran anschliessend werden drei Bedeutungsebenen des Begriffs ‚Sportorganisation’ hinsichtlich der Frage nach politischer Verantwortung unterschieden: Die Sportorganisation als moralische Instanz, als Veranstalterin von Sportmassenevents sowie als politisch-ökonomische Akteurin. Im zweiten Teil wird, auf der Basis dieser begrifflichen Differenzierung, die Frage nach der politischen Verantwortung von Sportorganisationen im Rahmen einer philosophischnormativen Diskussion reflektiert. Die systematische Auffaltung der Implikationen unterschiedlicher Auffassungen von Sportorganisationen und den daraus resultierenden Formen von Verantwortung erlaubt es, fundierte normative Richtlinien für deren Verhalten aufzustellen. Diese lassen sich als sieben Kernpunkte formulieren, aus denen sich ein ethischer Leitfaden für die Zuschreibung politischer Verantwortung an Sportorganisationen ergibt. Das in dieser Untersuchung erarbeitete philosophisch-theoretische Fundament versteht sich damit als Vorbereitung für die konkrete Implementierung normativer Forderungen

SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To determine whether intraocular treatment with vascular endothelial growth factor (VEGF) inhibitors change systemic endothelial function (EF) in patients with neovascular age-related macular degeneration (AMD). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In this prospective, randomized, 2-center, double-masked controlled interventional trial, patients with neovascular and dry AMD were enrolled. Eligible neovascular AMD patients received 2 intravitreal loading doses of either ranibizumab 0.5 mg or bevacizumab 1.25 mg at 4-week intervals and were subsequently followed every 4 weeks and treated according to a pro re nata regime for up to 1 year. Patients with dry AMD served as controls. The primary endpoint was the change in EF assessed by flow-mediated dilatation (FMD) after 2 months of treatment with VEGF inhibitors in patients with AMD compared to patients with dry AMD. FMD was assessed with B-mode high-resolution ultrasonography of the left brachial artery. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; 24 patients with neovascular AMD and 26 patients with dry ADM were included in the trial. Treatment with VEGF inhibitors did not significantly change FMD (from 4.7 ± 2.4 to 3.9 ± 1.9% after 8 weeks, &lt;i&gt;p&lt;/i&gt; = 0.07, and to 5.1 ± 2.0% after 1 year; &lt;i&gt;p&lt;/i&gt; = 0.93 vs. baseline, respectively). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; EF did not significantly differ between patients with neovascular AMD treated with intravitreal VEGF inhibition and patients with dry AMD.</jats:p

Correlation of intravascular ultrasound findings with histopathological analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis

BACKGROUND: Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST. METHODS AND RESULTS: The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls). Of 28 patients with very late DES ST, 10 patients (1020+/-283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2+/-2.4 mm(2) and evidence of vessel remodeling (index, 1.6+/-0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263+/-149 white blood cells per high-power field) and eosinophils (DES, 20+/-24 eosinophils per high-power field; sirolimus-eluting stents, 34+/-28; paclitaxel-eluting stents, 6+/-6; P for sirolimus-eluting stents versus paclitaxel-eluting stents=0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20+/-24) than in those from spontaneous acute myocardial infarction (7+/-10), early bare-metal stent ST (1+/-1), early DES ST (1+/-2), and late bare-metal stent ST (2+/-3; P from ANOVA=0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm(2) increase in ISA cross-sectional area. CONCLUSIONS: Very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis, particularly in sirolimus-eluting stents, and correlate with the extent of stent malapposition

AUTOtech.agil: architecture and technologies for orchestrating automotive agility

Future mobility will be electrified, connected and automated. This opens completely new possibilities for mobility concepts that have the chance to improve not only the quality of life but also road safety for everyone. To achieve this, a transformation of the transportation system as we know it today is necessary. The UNICARagil project, which ran from 2018 to 2023, has produced architectures for driverless vehicles that were demonstrated in four full-scale automated vehicle prototypes for different applications. The AUTOtech.agil project builds upon these results and extends the system boundaries from the vehicles to include the whole intelligent transport system (ITS) comprising, e.g., roadside units, coordinating instances and cloud backends. The consortium was extended mainly by industry partners, including OEMs and tier 1 suppliers with the goal to synchronize the concepts developed in the university-driven UNICARagil project with the automotive industry. Three significant use cases of future mobility motivate the consortium to develop a vision for a Cooperative Intelligent Transport System (C-ITS), in which entities are highly connected and continually learning. The proposed software ecosystem is the foundation for the complex software engineering task that is required to realize such a system. Embedded in this ecosystem, a modular kit of robust service-oriented modules along the effect chain of vehicle automation as well as cooperative and collective functions are developed. The modules shall be deployed in a service-oriented E/E platform. In AUTOtech.agil, standardized interfaces and development tools for such platforms are developed. Additionally, the project focuses on continuous uncertainty consideration expressed as quality vectors. A consistent safety and security concept shall pave the way for the homologation of the researched ITS

Prognostic value of end-of-induction PET response after first-line immunochemotherapy for follicular lymphoma (GALLIUM): secondary analysis of a randomised, phase 3 trial

International audienc