Search

IntroductionThe understanding of the pathophysiology of multiple sclerosis (MS) has evolved alongside the characterization of cytokines and chemokines in cerebrospinal fluid (CSF) and serum. However, the complex interplay of pro- and anti-inflammatory cytokines and chemokines in different body fluids in people with MS (pwMS) and their association with disease progression is still not well understood and needs further investigation. Therefore, the aim of this study was to profile a total of 65 cytokines, chemokines, and related molecules in paired serum and CSF samples of pwMS at disease onset.MethodsMultiplex bead-based assays were performed and baseline routine laboratory diagnostics, magnetic resonance imaging (MRI), and clinical characteristics were assessed. Of 44 participants included, 40 had a relapsing–remitting disease course and four a primary progressive MS.ResultsThere were 29 cytokines and chemokines that were significantly higher in CSF and 15 in serum. Statistically significant associations with moderate effect sizes were found for 34 of 65 analytes with sex, age, CSF, and MRI parameters and disease progression.DiscussionIn conclusion, this study provides data on the distribution of 65 different cytokines, chemokines, and related molecules in CSF and serum in newly diagnosed pwMS.

Summary: Background: Inter-individual courses of multiple sclerosis (MS) are extremely variable. The objective of this study was to investigate whether κ-free light chain (κ-FLC) index and serum neurofilament light (sNfL) have an additive predictive value for MS disease activity. Methods: Patients with early MS who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for four years. At baseline, age, sex, disease duration, number of T2-hyperintense (T2L), and contrast-enhancing T1 lesions (CEL) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying treatment (DMT) were registered. κ-FLC was measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. sNfL was determined by single-molecule array, and age- and body-mass-index adjusted Z scores were calculated. Findings: A total of 86 patients at a mean age of 33 ± 10 years and with a female predominance of 67% were included; 36 (42%) patients experienced a second clinical attack during follow-up. Cox regression analysis adjusted for age, sex, T2L, CEL, disease and follow-up duration, and DMT use during follow-up revealed that both κ-FLC index as well as sNfL Z score independently predict time to second clinical attack. The chance for freedom of relapse within 12 months was 2% in patients with high levels of κ-FLC index (>100) and high sNfL Z score (>3), 30% in patients with high κ-FLC index (>100) and lower sNfL Z score (≤3), 70% in patients with lower κ-FLC index (≤100) but high sNfL Z score (>3), and 90% in patients with lower levels of κ-FLC index (≤100) and sNfL Z score (≤3). Interpretation: κ-FLC index and sNfL Z score have an additive predictive value for early MS disease activity that is independent of known predictors. Funding: This study was funded by a grant of the charitable foundation of the Austrian Multiple Sclerosis Society.

As electrolyte materials for proton conductive fuel cells, perovskite-type materials such as barium cerates and barium zirconates have received a lot of attention due to their high protonic conduction at intermediate temperatures. Yet, the crystalline structure and the microstructure of the electrolyte layers are of the utmost importance that define the resulting protonic conductivity. The aim of this research was to investigate the formation of doped/undoped BCO and BZO thin films using e-beam vapor deposition and to analyze the influence of the formation parameters on the microstructural and crystallographic properties. Crystalline structure and microstructure were investigated by X-ray diffractometer and scanning electron microscope, while the elemental composition of the resulting thin films was analyzed by an energy-dispersive X-ray spectroscope. It was found that the formed thin films were highly dense and consisted of the oriented columnar grains. The crystallinity of the thin films was strongly expressed with the predominant crystallographic orientations for undoped/doped barium cerates. Yttrium dopant had an influence on the lattice parameters and crystallite sizes. With the chosen technological parameters allowed to both, barium cerates and barium zirconates did not form carbonates and did not experience the degradation process.

Mitral annular disjunction (MAD) represents the detachment of the mitral leaflet hinge-point from the ventricular myocardium. Its role in patients with ST-segment-elevation myocardial infarction (STEMI) is unknown. This study aims to investigate the prevalence of MAD by cardiac magnetic resonance imaging (CMR) in STEMI-patients and its association with serious adverse events. STEMI-patients (n = 621) underwent CMR 4 days [interquartile range (IQR) 2–5] after percutaneous coronary intervention. Presence and longitudinal extent of MAD were obtained in long-axis cine-images, infarct characteristics in late gadolinium enhancement-images. During a median follow-up time of 366 days (IQR 136–454), patients were observed for the occurrence of major adverse cardiac events (MACE), comprising death, myocardial reinfarction, and congestive heart failure. Overall, 307 patients (49 %) had MAD. Longitudinal MAD-distance was 4.6 ± 1.7 mm and the P3-segment was affected most frequently (n = 262, 85 % of MAD-patients). MAD-patients had a significantly smaller infarct size, lower prevalence of microvascular obstruction, and intramyocardial hemorrhage as well as a higher ejection fraction (all p < 0.03). During follow-up period, MACE occurred in 52 patients (8 %) and did not show significant difference between patients with and without MAD (7 % vs. 9 %, p = 0.424). Cardiovascular death occurred significantly more often in patients without MAD (n = 10, 3.2 % vs. n = 2, 0.7 %, p = 0.021). MAD is a rather common finding in patients presenting with STEMI. Patients with MAD had less severe infarct characteristics, however, they were not more commonly affected by MACE. Further confirmation and longer follow-up intervals are necessary to define the exact role of MAD in STEMI patients. MAD occurred in 51 % of patients suffering ST-segment elevation myocardial infarction. Infarct parameters such as infarct size, ejection fraction, and prevalence of IMH were significantly different between these two groups, in favor of patients with disjunction. IMH, intramyocardial hemorrhage; LVMM, left ventricular myocardial mass; MAD, mitral annular disjunction; STEMI, ST-segment elevation myocardial infarction. [Display omitted] • Mitral annular disjunction (MAD) is a common finding in ST-segment-elevation myocardial infarction patients. • The P3-segment was the most frequently affected part of the mitral valve. • In our study, MAD-patients presented with less severe infarctions. • Major adverse cardiac events did not occur significantly more often in MAD-patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Isolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome., Methods: Combining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon β, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for ≥12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for ≥2 years after the second MRI. The primary endpoint was occurrence of relapse during follow-up. The number of new T2 lesions (T2L) and DMT strategy (continuing low-/moderate-efficacy DMT vs escalating DMT) were used as covariates in regression analyses., Results: A total of 131 patients with RMS, median age of 36 (25th-75th percentiles: 29-43) years, 73% women, were included and observed over a median period of 6 (5-9) years after second MRI. Sixty-two (47%) patients had relapse. Patients who continued first-line DMT had a 3-fold increased risk of relapse given 2 new T2L (hazard ratio [HR] 3.2, lower limit [LL] of 95% CI: 1.5) and a 4-fold increased risk given ≥3 new T2L (HR 4.0, LL-CI: 2.1). Escalation of DMT lowered the risk of relapse in patients with 2 new T2L by approximately 80% (HR 0.2, upper limit [UL] of 95% CI: 1.3) and with ≥3 new T2L by 70% (HR 0.3, UL-CI: 0.8). In case of only 1 new T2L, the increased risk of relapse and the treatment effect did not reach statistical significance of 5%., Discussion: In our real-world cohort of patients clinically stable under low-to-moderate-efficacy DMT, escalation of DMT based on isolated MRI activity decreased risk of further relapse when at least 2 new T2L had occurred., Classification of Evidence: This study provides Class III evidence that clinically stable patients with MS on low-/moderate-efficacy DMT with ≥3 new T2L on MRI who escalate DMT have a reduced risk of relapse and Expanded Disability Status Scale progression.

Introduction: The understanding of the pathophysiology of multiple sclerosis (MS) has evolved alongside the characterization of cytokines and chemokines in cerebrospinal fluid (CSF) and serum. However, the complex interplay of pro- and anti-inflammatory cytokines and chemokines in different body fluids in people with MS (pwMS) and their association with disease progression is still not well understood and needs further investigation. Therefore, the aim of this study was to profile a total of 65 cytokines, chemokines, and related molecules in paired serum and CSF samples of pwMS at disease onset., Methods: Multiplex bead-based assays were performed and baseline routine laboratory diagnostics, magnetic resonance imaging (MRI), and clinical characteristics were assessed. Of 44 participants included, 40 had a relapsing-remitting disease course and four a primary progressive MS., Results: There were 29 cytokines and chemokines that were significantly higher in CSF and 15 in serum. Statistically significant associations with moderate effect sizes were found for 34 of 65 analytes with sex, age, CSF, and MRI parameters and disease progression., Discussion: In conclusion, this study provides data on the distribution of 65 different cytokines, chemokines, and related molecules in CSF and serum in newly diagnosed pwMS., Competing Interests: KB has participated in meetings sponsored by, received travel funding from, or received honoraria for acting as an advisor/speaker for Roche, Biogen, TEVA, Sanofi-Genzyme, Merck, and Novartis. AB was an employee of VASCage – Research Centre on Vascular Ageing and Stroke and has participated in meetings sponsored by or received travel funding from Novartis, Sanofi-Genzyme, Merck, Almirall, and Biogen. DR was an employee of VASCage – Research Centre on Vascular Ageing and Stroke. MA received speaker honoraria and/or travel grants from Biogen, Merck, Novartis, and Sanofi. RB has participated in meetings sponsored by and received travel grants from Biogen, Novartis, and Sanofi. AZ has participated in meetings sponsored by and received speaking honoraria or travel funding from Biogen, Merck, Sanofi-Genzyme and Teva. SW has participated in meetings sponsored by and received honoraria or travel funding from Allergan, Biogen, Ipsen Pharma, Merck, Novartis, Roche, Sanofi Genzyme, Teva, and Bristol Myers Squibb. TB has participated in meetings sponsored by and received honoraria lectures, advisory boards, and consultations from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, BMS/Celgene, GSK, GW/Jazz Pharma, Horizon, Janssen-Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi-Genzyme, Teva, and UCB. FP has participated in meetings sponsored by and received honoraria lectures, advisory boards, consultations or travel funding from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Teva, Celgene, and Roche. Her institution has received research grants from Roche. FD has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Almirall, Alexion, Biogen, Celgene, Genzyme-Sanofi, Horizon, Janssen, Merck, Novartis Pharma, Roche, and TEVA ratiopharm. His institution has received research grants from Biogen and Genzyme Sanofi. He is a section editor of the MSARD Journal Multiple Sclerosis and Related Disorders and a review editor of Frontiers Neurology. HH has participated in meetings sponsored by and received speaker honoraria or travel funding from Bayer, Biogen, Celgene, Merck, Novartis, Sanofi-Genzyme, Siemens, and Teva, and received honoraria for acting as consultant for Biogen, Celgene, Novartis, and Teva. MR was supported by a research support from Euroimmun and Roche. The University Hospital and Medical University of Innsbruck Austria, employer of Dr. Reindl receives payments for antibody assays MOG, AQP4, and other autoantibodies and for MOG and AQP4 antibody validation experiments organized by Euroimmun Lübeck, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Berek, Bauer, Rudzki, Auer, Barket, Zinganell, Lerch, Hofer, Grams, Poskaite, Wurth, Berger, Di Pauli, Deisenhammer, Hegen and Reindl.)

Background: Inter-individual courses of multiple sclerosis (MS) are extremely variable. The objective of this study was to investigate whether κ-free light chain (κ-FLC) index and serum neurofilament light (sNfL) have an additive predictive value for MS disease activity., Methods: Patients with early MS who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for four years. At baseline, age, sex, disease duration, number of T2-hyperintense (T2L), and contrast-enhancing T1 lesions (CEL) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying treatment (DMT) were registered. κ-FLC was measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. sNfL was determined by single-molecule array, and age- and body-mass-index adjusted Z scores were calculated., Findings: A total of 86 patients at a mean age of 33 ± 10 years and with a female predominance of 67% were included; 36 (42%) patients experienced a second clinical attack during follow-up. Cox regression analysis adjusted for age, sex, T2L, CEL, disease and follow-up duration, and DMT use during follow-up revealed that both κ-FLC index as well as sNfL Z score independently predict time to second clinical attack. The chance for freedom of relapse within 12 months was 2% in patients with high levels of κ-FLC index (>100) and high sNfL Z score (>3), 30% in patients with high κ-FLC index (>100) and lower sNfL Z score (≤3), 70% in patients with lower κ-FLC index (≤100) but high sNfL Z score (>3), and 90% in patients with lower levels of κ-FLC index (≤100) and sNfL Z score (≤3)., Interpretation: κ-FLC index and sNfL Z score have an additive predictive value for early MS disease activity that is independent of known predictors., Funding: This study was funded by a grant of the charitable foundation of the Austrian Multiple Sclerosis Society., Competing Interests: Declaration of interests HH has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Celgene, Merck, Novartis, Sanofi-Genzyme, Siemens, Teva, and received honoraria for acting as consultant for Biogen, Celgene, Novartis and Teva. He is associate editor of Frontiers in Neurology. KB has participated in meetings sponsored by and received travel funding or speaker honoraria from Roche, Teva, Merck, Biogen, Sanofi. GB has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene, Lilly, Merck, Novartis, Sanofi-Genzyme and Teva, and received honoraria for consulting Biogen, Celgene, Merck, Novartis, Roche and Teva. MA received speaker honoraria and/or travel grants from Biogen, Novartis, Merck and Sanofi. PA has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Merck, Roche, Sanofi-Genzyme and Teva, and received honoraria for consulting from Biogen. He received a research grant from Quanterix International and was awarded a combined sponsorship from Biogen, Merck, Sanofi-Genzyme, Roche, and Teva for a clinical study. FDP has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Celgene, Merck, Novartis, Sanofi-Genzyme, Roche and Teva. AG has nothing to disclose. DM has participated in meetings sponsored by Siemens. MP has participated in meetings sponsored by, received speaker or consulting honoraria or travel funding from Amicus, Merck, Novartis and Sanofi-Genzyme. PP has nothing to disclose. CS has participated in meetings sponsored by Siemens. SW has participated in meetings sponsored by, received honoraria or travel funding from Allergan, Biogen, Ipsen Pharma, Merck, Novartis, Roche, Sanofi Genzyme, Teva and Bristol Myers Squibb. AZ has participated in meetings sponsored by, received speaking honoraria or travel funding from Biogen, Merck, Novartis, Sanofi-Genzyme and Teva. TB has participated in the last 2 years in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for multiple sclerosis: Almirall, Biogen, Bionorica, BMS/Celgene, Eisai, Horizon, Jazz Pharmaceuticals, Janssen-Cilag, MedDay, Merck, Novartis, Roche, Sanofi Aventis/Genzyme, Sandoz, TG Therapeutics, TEVA and UCB. His institution has received financial support in the last 2 years by unrestricted research grants (Biogen, BMS/Celgene, Novartis, Sanofi Aventis/Genzyme, Roche, TEVA) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, BMS/Celegen, Merck, Novartis, Roche, Sanofi Aventis/Genzyme, TEVA. JW has nothing to disclose. FD has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Almirall, Biogen, Celgene-BMS, Genzyme-Sanofi, Horizon, Merck, Novartis Pharma, Roche, and Teva. His institution has received research grants from Biogen and Genzyme Sanofi. He is section editor of the MSARD Journal (Multiple Sclerosis and Related Disorders) and review editor of Frontiers Neurology., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: To determine the phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) slice-position above aortic leaflet-attachment-plane (LAP) that provides flow-velocity, -volume and aortic valve area (AVA) measurements with best agreement to invasive and echocardiographic measurements in aortic stenosis (AS)., Methods and Results: Fifty-five patients with moderate/severe AS underwent cardiac catheterization, transthoracic echocardiography (TTE) and CMR. Overall, 171 image-planes parallel to LAP were measured via PC-CMR between 22 mm below and 24 mm above LAP. AVA via PC-CMR was calculated as flow-volume divided by peak-velocity during systole. Stroke volume (SV) and AVA were compared to volumetric SV and invasive AVA via the Gorlin-formula, respectively. Above LAP, SV by PC-CMR showed no significant dependence on image-plane-position and correlated strongly with volumetry (rho: 0.633, p < 0.001, marginal-mean-difference (MMD): 1 ml, 95 % confidence-interval (CI): -4 to 6). AVA assessed in image-planes 0-10 mm above LAP differed significantly from invasive measurement (MMD: -0.14 cm 2 , 95 %CI: 0.08-0.21). In contrast, AVA-values by PC-CMR measured 10-20 mm above LAP showed good agreement with invasive determination without significant MMD (0.003 cm 2 , 95 %CI: -0.09 to 0.09). Within these measurements, a plane 15 mm above LAP resulted in the lowest bias (MMD: 0.02 cm 2 , 95 %CI:-0.29 to 0.33). SV and AVA via TTE correlated moderately with volumetry (rho: 0.461, p < 0.001; bias: 15 ml, p < 0.001) and cardiac catheterization (rho: 0.486, p < 0.001, bias: -0.13 cm 2 , p < 0.001), respectively., Conclusion: PC-CMR measurements at 0-10 mm above LAP should be avoided due to significant AVA-overestimation compared to invasive determination. AVA-assessment by PC-CMR between 10 and 20 mm above LAP did not differ from invasive measurements, with the lowest intermethodical bias measured 15 mm above LAP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To investigate whether κ-free light chain (κ-FLC) index predicts multiple sclerosis (MS) disease activity independent of demographics, clinical characteristics, and MRI findings., Methods: Patients with early MS who had CSF and serum sampling at disease onset were followed for 4 years. At baseline, age, sex, type of symptoms, corticosteroid treatment, and number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CELs) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying therapy (DMT) were registered. κ-FLCs were measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient., Results: A total of 88 patients at a mean age of 33 ± 10 years and female predominance of 68% were included; 38 (43%) patients experienced a second clinical attack during follow-up. In multivariate Cox regression analysis adjusting for age, sex, T2L, CEL, disease and follow-up duration, administration of corticosteroids at baseline and DMT during follow-up revealed that κ-FLC index predicts time to second clinical attack. Patients with κ-FLC index >100 (median value 147) at baseline had a twice as high probability for a second clinical attack within 12 months than patients with low κ-FLC index (median 28); within 24 months, the chance in patients with high κ-FLC index was 4 times as high as in patients with low κ-FLC index. The median time to second attack was 11 months in patients with high κ-FLC index whereas 36 months in those with low κ-FLC index., Conclusion: High κ-FLC index predicts early MS disease activity., Classification of Evidence: This study provides Class II evidence that in patients with early MS, high κ-FLC index is an independent risk factor for early second clinical attack., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: To prospectively compare image quality and reliability of a non-contrast, self-navigated 3D whole-heart magnetic resonance angiography (MRA) sequence with contrast-enhanced computed tomography angiography (CTA) for sizing of thoracic aortic aneurysm (TAA)., Methods: Self-navigated 3D whole-heart 1.5 T MRA was performed in 20 patients (aged 67 ± 9 years, 75% male) for sizing of TAA; a subgroup of 18 (90%) patients underwent additional contrast-enhanced CTA on the same day. Subjective image quality was scored according to a 4-point Likert scale and ratings between observers were compared by Cohen's Kappa statistics. For MRA, subjective motion blurring and signal inhomogeneity was rated according to a 3-point scale, respectively. Objective signal inhomogeneity of MRA was quantified as standard deviation of the voxel intensities in a circular region of interest (ROI) placed in the ascending aorta divided by their mean value. Continuous MRA and CTA measurements were analyzed with regression and Bland-Altman analysis., Results: Overall subjective image quality as rated by two observers was 1 [interquartile range (IQR) 1-2] for self-navigated MRA and 1.5 [IQR 1-2] for CTA (p = 0.717). For MRA, perfect inter-observer agreement was found regarding presence of artefacts and subjective image sharpness (κ = 1). Subjective signal inhomogeneity agreed moderately between the observers (κ = 0.58, p = 0.007), however, it correlated strongly with objectively quantified inhomogeneity of the blood pool signal (r = 0.78, p < 0.0001). Maximum diameters of TAA as measured by self-navigated MRA and CTA showed very strong correlation (r = 0.99, p < 0.0001) without significant inter-method bias (bias -0.03 mm, lower and upper limit of agreement -0.74 and 0.68 mm, p = 0.749). Inter-observer correlation of aortic aneurysm as measured by MRA was very strong (r = 0.96) without significant bias (p = 0.695)., Conclusion: Self-navigated 3D whole-heart MRA enables reliable contrast- and radiation free aortic dilation surveillance without significant difference to standardized CTA while providing predictable acquisition time and offering excellent image quality., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)