Effects of percutaneous transluminal angioplasty on muscle BOLD-MRI in patients with peripheral arterial occlusive disease: preliminary results

The purpose was to evaluate the effect of percutaneous transluminal angioplasty (PTA) of the superficial femoral artery (SFA) on the blood oxygenation level-dependent (BOLD) signal change in the calf musculature of patients with intermittent claudication. Ten patients (mean age, 63.4 ± 11.6years) with symptomatic peripheral arterial occlusive disease (PAOD) caused by SFA stenoses were investigated before and after PTA. Patients underwent BOLD-MRI 1 day before and 6 weeks after PTA. A T2*-weighted single-shot multi-echo echo-planar MR-imaging technique was applied. The BOLD measurements were acquired at mid-calf level during reactive hyperaemia at 1.5 T. This transient hyperperfusion of the muscle tissue was provoked by suprasystolic cuff compression. Key parameters describing the BOLD signal curve included maximum T2* (T2*max), time-to-peak to reach T2*max (TTP) and T2* end value (EV) after 600 s of hyperemia. Paired t-tests were applied for statistic comparison. Between baseline and post-PTA, T2*max increased from 11.1 ± 3.6% to 12.3 ± 3.8% (p = 0.51), TTP decreased from 48.5 ± 20.8 s to 35.3 ± 11.6s (p = 0.11) and EV decreased from 6.1 ± 6.4% to 5.0 ± 4.2% (p = 0.69). In conclusion, BOLD-MRI reveals changes of the key parameters T2*max, TTP, and EV after successful PTA of the calf muscles during reactive hyperaemi

Sinusoidal Obstruction Syndrome Following Myeloablative Therapy and Tranexamic Acid Treatment for Hemorrhage in Two Patients with Neuroblastoma

Adverse thromboembolic events following administration of the anti-fibrinolytic agent tranexamic acid (TA), used to prevent/treat excessive blood loss, are rare. We present the clinical course of two young patients (22 and 56 months) receiving busulfan/melphalan (Bu/Mel) high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) to treat high-risk neuroblastoma, who developed hepatic sinusoidal obstruction syndrome (SOS) within 48 h after systemic TA treatment for a hemodynamically relevant hemorrhage. Defibrotide treatment resolved hepatic SOS, but the short time between TA administration and SOS onset suggests a causal association

CD171- and GD2-specific CAR-T cells potently target retinoblastoma cells in preclinical in vitro testing

BACKGROUND: Chimeric antigen receptor (CAR)-based T cell therapy is in early clinical trials to target the neuroectodermal tumor, neuroblastoma. No preclinical or clinical efficacy data are available for retinoblastoma to date. Whereas unilateral intraocular retinoblastoma is cured by enucleation of the eye, infiltration of the optic nerve indicates potential diffuse scattering and tumor spread leading to a major therapeutic challenge. CAR-T cell therapy could improve the currently limited therapeutic strategies for metastasized retinoblastoma by simultaneously killing both primary tumor and metastasizing malignant cells and by reducing chemotherapy-related late effects. METHODS: CD171 and GD2 expression was flow cytometrically analyzed in 11 retinoblastoma cell lines. CD171 expression and T cell infiltration (CD3+) was immunohistochemically assessed in retrospectively collected primary retinoblastomas. The efficacy of CAR-T cells targeting the CD171 and GD2 tumor-associated antigens was preclinically tested against three antigen-expressing retinoblastoma cell lines. CAR-T cell activation and exhaustion were assessed by cytokine release assays and flow cytometric detection of cell surface markers, and killing ability was assessed in cytotoxic assays. CAR constructs harboring different extracellular spacer lengths (short/long) and intracellular co-stimulatory domains (CD28/4-1BB) were compared to select the most potent constructs. RESULTS: All retinoblastoma cell lines investigated expressed CD171 and GD2. CD171 was expressed in 15/30 primary retinoblastomas. Retinoblastoma cell encounter strongly activated both CD171-specific and GD2-specific CAR-T cells. Targeting either CD171 or GD2 effectively killed all retinoblastoma cell lines examined. Similar activation and killing ability for either target was achieved by all CAR constructs irrespective of the length of the extracellular spacers and the co-stimulatory domain. Cell lines differentially lost tumor antigen expression upon CAR-T cell encounter, with CD171 being completely lost by all tested cell lines and GD2 further down-regulated in cell lines expressing low GD2 levels before CAR-T cell challenge. Alternating the CAR-T cell target in sequential challenges enhanced retinoblastoma cell killing. CONCLUSION: Both CD171 and GD2 are effective targets on human retinoblastoma cell lines, and CAR-T cell therapy is highly effective against retinoblastoma in vitro. Targeting of two different antigens by sequential CAR-T cell applications enhanced tumor cell killing and preempted tumor antigen loss in preclinical testing

ECG-triggered non-enhanced MR angiography of peripheral arteries in comparison to DSA in patients with peripheral artery occlusive disease

Object: The purpose of this study was to evaluate peripheral non-enhanced-MRA (NE-MRA) acquired with a 3D Turbo Spin Echo sequence with electrocardiographt (ECG) triggering in comparison to Digital Subtraction Angiography (DSA) as the gold standard in symptomatic peripheral artery occlusive disease (PAOD) patients. Materials and methods: This IRB approved prospective study included 23 PAOD patients from whom three patients had to be excluded. The remaining 20 subjects were included in the analysis (15 male; mean age 62.4±15.3years). The patients first underwent DSA followed by NE-MRA on a 1.5-T whole body scanner within 24h after the DSA study. A NATIVE (Non-contrast Angiography of the Arteries and Veins) SPACE (Sampling Perfection with Application Optimized Contrast by using different flip angle Evolution) sequence at four levels (pelvis, upper leg, knee region and lower leg) was acquired. For evaluation purposes, subtracted standardized MIP (maximum intensity projection) images were generated from the NE-MRA data sets. Qualitative assessment of NE-MRA images in reference to the corresponding DSA images, as well as blinded stenosis grading of preselected segments in NE-MRA images were performed by two experienced readers. Image quality in 95 corresponding arterial segments was rated from 1 (good) to 4 (inadequate) directly comparing the NE-MRA with the corresponding DSA segment as the gold standard. Blinded stenosis grading consisted of 66 preselected stenoses rated from 1 (90%) in NE-MRA which were compared to the grade in the corresponding DSA. Results: The mean image quality of NE-MRA in comparison to DSA was 2.7±1.1 (reader 1) and 3.0±1.0 (reader 2). The kappa value indicating interobserver agreement was 0.34; readers 1 and 2 rated the image quality as good in 21% and 3%, sufficient in 19% and 41%, limited in 29% and 14% and inadequate in 31% and 42%, respectively. Stenosis graduation revealed significantly higher grades in NE-MRA (reader 1: 3.0±0.7, p<0.001 and reader 2: 3.1+0.8, p<0.001) compared to DSA (mean value DSA 2.7±0.8). The kappa value indicating interobserver agreement concerning stenosis grading was 0.59. Conclusion: NE-MRA revealed a relatively high number of inadequate quality segments. This is in line with recently published comparable studies of the similar SPACE NE-MRA techniques. Further advance of NE-MRA techniques remains desirable for patients with PAO

Clinical implications of skeletal muscle blood-oxygenation-level-dependent (BOLD) MRI

Blood-oxygenation-level-dependent (BOLD) contrast in magnetic resonance (MR) imaging of skeletal muscle mainly depends on changes of oxygen saturation in the microcirculation. In recent years, an increasing number of studies have evaluated the clinical relevance of skeletal muscle BOLD MR imaging in vascular diseases, such as peripheral arterial occlusive disease, diabetes mellitus, and chronic compartment syndrome. BOLD imaging combines the advantages of MR imaging, i.e., high spatial resolution, no exposure to ionizing radiation, with functional information of local microvascular perfusion. Due to intrinsic contrast provoked via changes in hemoglobin oxygen saturation, it is a safe and easy applicable procedure on standard whole-body MR devices. Therefore, BOLD MR imaging of skeletal muscle is a potential new diagnostic tool in the clinical evaluation of vascular, inflammatory, and muscular pathologies. Our review focuses on the current evidence concerning the use of BOLD MR imaging of skeletal muscle under pathological conditions and highlights ways for future clinical and scientific application

Anxiety in response to the climate and environmental crises: validation of the Hogg Eco-Anxiety Scale in Germany

Background: As the climate and environmental crises unfold, eco-anxiety, defined as anxiety about the crises’ devastating consequences for life on earth, affects mental health worldwide. Despite its importance, research on eco-anxiety is currently limited by a lack of validated assessment instruments available in different languages. Recently, Hogg and colleagues proposed a multidimensional approach to assess eco-anxiety. Here, we aim to translate the original English Hogg Eco-Anxiety Scale (HEAS) into German and to assess its reliability and validity in a German sample. Methods: Following the TRAPD (translation, review, adjudication, pre-test, documentation) approach, we translated the original English scale into German. In total, 486 participants completed the German HEAS. We used Bayesian confirmatory factor analysis (CFA) to assess whether the four-factorial model of the original English version could be replicated in the German sample. Furthermore, associations with a variety of emotional reactions towards the climate crisis, general depression, anxiety, and stress were investigated. Results: The German HEAS was internally consistent (Cronbach’s alphas 0.71–0.86) and the Bayesian CFA showed that model fit was best for the four-factorial model, comparable to the factorial structure of the original English scale (affective symptoms, rumination, behavioral symptoms, anxiety about personal impact). Weak to moderate associations were found with negative emotional reactions towards the climate crisis and with general depression, anxiety, and stress. Discussion: Our results support the original four-factorial model of the scale and indicate that the German HEAS is a reliable and valid scale to assess eco-anxiety in German speaking populations

Studie über die Nutzung von Newsfeed-Reader-Apps als Grundlage für Verhaltensdesign

Das Lesen von Newsfeeds wird immer populärer, obwohl digitale Medien zunehmend für Nutzer_innen verborgene Risiken, wie z.B. die Anwendung von verhaltensbeeinflussenden Designelementen, beinhalten. Um den Einfluss solcher Designelemente zu erforschen, widmet sich diese Studie, als Vorstudie für eine weitere Fallstudie mit einer Newsfeed-Reader-App, der Untersuchung des Leseverhaltens. Dabei wird den Fragen nachgegangen, wie sich das Leseverhalten von potenziellen Nutzer_innen einer Newsfeed-Reader-App gestaltet und welche Bedarfe Nutzer_innen haben. Zudem wurden die Teilnehmenden zur Untersuchung des Risikobewusstseins in Bezug auf digitale Medien zu ihrer Einschätzung der YouTube- und Facebook-App befragt. Die insgesamt 77 Teilnehmenden der Studie wurden an der Ruhr-Universität Bochum befragt. Zur Erhebung der Daten wurde ein Online-Fragebogen genutzt. Die Analyse der deskriptiven Daten erfolgte anhand von Abbildungen und Tabellen. Die Teilnehmenden bilden eine anspruchsvolle und bewusste Leserschaft, die zumeist mehrmals am Tag und oft zwischendurch liest und sich der Risiken der digitalen und sozialen Medien bewusst ist. Ein App-Design, welches darauf abzielt, Leser_innen dazu zu bewegen, häufiger zu lesen, z.B. mit nicht mehr als ein oder zwei Push-Nachrichten täglich, hat gute Chancen, die Lesehäufigkeit und dadurch auch die gesamte Lesezeit zu erhöhen. Der Einbau von sozialen Aspekten, wie z.B. der Vergleich der Leseleistung mit anderen Leser_innen sowie eine Diskussionsmöglichkeit oder Bewertung von Artikeln durch Mitleser_innen wird ebenfalls empfohlen. Möglichst vielseitige, aber transparente Filteroptionen, die Möglichkeit zur selbstbestimmten Auswahl an Nachrichteninhalten, Schnelllese- und Vorlesefunktionen bzw. eine Lesehilfe sind auch erwünscht. Ablenkende Elemente wie Gamification, Werbung, Boulevardjournalismus und Meinungs-Bubbles sollten vermieden werden. Reading newsfeeds gets more and more popular, although digital media contain an increasing number of hidden risks for users, such as the application of design elements that influence behaviour. In order to study the influence of such design elements, we investigate reading behaviour in the present study, which is a scoping study for a follow-up case study implementing a newsfeed reader app. Using a survey, we ask potential users of a newsfeed reader app about their reading habits and needs. Moreover, we ask participants to assess their risk perception of digital media with regard to the YouTube and Facebook apps. The overall 77 participants of the study were recruited at the Ruhr-University Bochum. We used an online survey to collect data. For the analysis of the descriptive data, we used figures and tables. The participants make up a demanding and conscious readership. Most of them read several times a day and often in between. They are conscious about the risks of digital and social media. An app design that aims to make readers reading more often has good chances to succeed in increasing reading frequency and thus also total reading time unless it contains more than one or two push notifications a day. We also recommend to build in social aspects, such as comparison of reading performance, and possibilities to discuss or rate articles. All-round but still transparent filtering options, a possibility to self-select news content, speed reading, text-to-speech, and reading aid functionalities are desirable. Distracting elements, such as gamification, ads, tabloid press and opinion bubbles should be avoided

BMI, Alcohol Consumption and Gut Microbiome Species Richness Are Related to Structural and Functional Neurological Abnormalities

The incidence of neurological diseases is increasing throughout the world. The aim of the present study was to identify nutrition and microbiome factors related to structural and functional neurological abnormalities to optimize future preventive strategies. Methods: Two hundred thirty-eight patients suffering from (1) structural (neurodegeneration) or (2) functional (epilepsy) neurological abnormalities or (3) chronic pain (migraine) and 612 healthy control subjects were analyzed by validated 12-month food frequency questionnaire (FFQ) and 16S rRNA micro- biome sequencing (from stool samples). A binomial logistic regression model was applied for risk calculation and functional pathway analysis to show which functional pathway could discriminate cases and healthy controls. Results: Detailed analysis of more than 60 macro- and micronutrients revealed no distinct significant difference between cases and controls, whereas BMI, insulin resistance and metabolic inflammation in addition to alcohol consumption were major drivers of an overall neurological disease risk. The gut microbiome analysis showed decreased alpha diversity (Shannon index: p = 9.1× 10 −7 ) and species richness (p = 1.2 × 10 −8 ) in the case group as well as signifi- cant differences in beta diversity between cases and controls (Bray–Curtis: p = 9.99 × 10 −4 ; Jaccard: p = 9.99 × 10 −4 ). The Shannon index showed a beneficial effect (OR = 0.59 (95%-CI (0.40, 0.87); p = 8 × 10 −3 ). Cases were clearly discriminated from healthy controls by environmental information processing, signal transduction, two component system and membrane transport as significantly different functional pathways. Conclusions: In conclusion, our data indicate that an overall healthy lifestyle, in contrast to supplementation of single micro- or macronutrients, is most likely to reduce overall neurological abnormality risk and that the gut microbiome is an interesting target to develop novel preventive strategies

Precision Nutrition in Chronic Inflammation

The molecular foundation of chronic in fl ammatory diseases (CIDs) can differ markedly between individuals. As our understanding of the biochemical mechanisms underlying individual disease manifestations and progressions expands, new strategies to adjust treatments to the patient ’ s characteristics will continue to profoundly transform clinical practice. Nutrition has long been recognized as an important determinant of in fl ammatory disease phenotypes and treatment response. Yet empirical work demonstrating the therapeutic effectiveness of patient-tailored nutrition remains scarce. This is mainly due to the challenges presented by long-term effects of nutrition, variations in inter-individual gastrointestinal microbiota, the multiplicity of human metabolic pathways potentially affected by food ingredients, nutrition behavior, and the complexity of food composition. Historically, these challenges have been addressed in both human studies and experimental model laboratory studies primarily by using individual nutrition data collection in tandem with large- scale biomolecular data acquisition (e.g. genomics, metabolomics, etc.). This review highlights recent fi ndings in the fi eld of precision nutrition and their potential implications for the development of personalized treatment strategies for CIDs. It emphasizes the importance of computational approaches to integrate nutritional information into multi- omics data analysis and to predict which molecular mechanisms may explain how nutrients intersect with disease pathways. We conclude that recent fi ndings point towards the unexhausted potential of nutrition as part of personalized medicine in chronic in fl ammation