| 1. |
- Tur, C, et al.
(författare)
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The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021
- 2022
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 28:9, s. 1424-1456
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Tidskriftsartikel (refereegranskat)abstract
- Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.
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| 2. |
- Ammirati, Enrico, et al.
(författare)
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Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction
- 2019
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 74:3, s. 299-311
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. Objectives: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. Results: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). Conclusions: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.
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| 3. |
- Benkert, P., et al.
(författare)
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Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study
- 2022
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Ingår i: The Lancet Neurology. - 1474-4422 .- 1474-4465. ; 21:3, s. 246-257
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum neurofilament light chain (sNfL) is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs and to prognosticate disease course in people with multiple sclerosis on the group level. The absence of representative reference values to correct for physiological age-dependent increases in sNfL has limited the diagnostic use of this biomarker at an individual level. We aimed to assess the applicability of sNfL for identification of people at risk for future disease activity by establishing a reference database to derive reference values corrected for age and body-mass index (BMI). Furthermore, we used the reference database to test the suitability of sNfL as an endpoint for group-level comparison of effectiveness across disease-modifying therapies. Methods: For derivation of a reference database of sNfL values, a control group was created, comprising participants with no evidence of CNS disease taking part in four cohort studies in Europe and North America. We modelled the distribution of sNfL concentrations in function of physiological age-related increase and BMI-dependent modulation, to derive percentile and Z score values from this reference database, via a generalised additive model for location, scale, and shape. We tested the reference database in participants with multiple sclerosis in the Swiss Multiple Sclerosis Cohort (SMSC). We compared the association of sNfL Z scores with clinical and MRI characteristics recorded longitudinally to ascertain their respective disease prognostic capacity. We validated these findings in an independent sample of individuals with multiple sclerosis who were followed up in the Swedish Multiple Sclerosis registry. Findings: We obtained 10 133 blood samples from 5390 people (median samples per patient 1 [IQR 1–2] in the control group). In the control group, sNfL concentrations rose exponentially with age and at a steeper increased rate after approximately 50 years of age. We obtained 7769 samples from 1313 people (median samples per person 6·0 [IQR 3·0–8·0]). In people with multiple sclerosis from the SMSC, sNfL percentiles and Z scores indicated a gradually increased risk for future acute (eg, relapse and lesion formation) and chronic (disability worsening) disease activity. A sNfL Z score above 1·5 was associated with an increased risk of future clinical or MRI disease activity in all people with multiple sclerosis (odds ratio 3·15, 95% CI 2·35–4·23; p<0·0001) and in people considered stable with no evidence of disease activity (2·66, 1·08–6·55; p=0·034). Increased Z scores outperformed absolute raw sNfL cutoff values for diagnostic accuracy. At the group level, the longitudinal course of sNfL Z score values in people with multiple sclerosis from the SMSC decreased to those seen in the control group with use of monoclonal antibodies (ie, alemtuzumab, natalizumab, ocrelizumab, and rituximab) and, to a lesser extent, oral therapies (ie, dimethyl fumarate, fingolimod, siponimod, and teriflunomide). However, longitudinal sNfL Z scores remained elevated with platform compounds (interferons and glatiramer acetate; p<0·0001 for the interaction term between treatment category and treatment duration). Results were fully supported in the validation cohort (n=4341) from the Swedish Multiple Sclerosis registry. Interpretation: The use of sNfL percentiles and Z scores allows for identification of individual people with multiple sclerosis at risk for a detrimental disease course and suboptimal therapy response beyond clinical and MRI measures, specifically in people with disease activity-free status. Additionally, sNfL might be used as an endpoint for comparing effectiveness across drug classes in pragmatic trials. Funding: Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, Roche. © 2022 Elsevier Ltd
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| 4. |
- Khalil, M., et al.
(författare)
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Neurofilaments as biomarkers in neurological disorders
- 2018
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Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766. ; 14:10, s. 577-589
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Tidskriftsartikel (refereegranskat)abstract
- Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. Reliable quantification and longitudinal follow-up of such damage are important for assessing disease activity, monitoring treatment responses, facilitating treatment development and determining prognosis. The neurofilament proteins have promise in this context because their levels rise upon neuroaxonal damage not only in the cerebrospinal fluid (CSF) but also in blood, and they indicate neuroaxonal injury independent of causal pathways. First-generation (immunoblot) and second-generation (enzyme-linked immunosorbent assay) neurofilament assays had limited sensitivity. Third-generation (electrochemiluminescence) and particularly fourth-generation (single-molecule array) assays enable the reliable measurement of neurofilaments throughout the range of concentrations found in blood samples. This technological advancement has paved the way to investigate neurofilaments in a range of neurological disorders. Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease. We also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice.
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| 5. |
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| 6. |
- Rodríguez, M. Jimena, et al.
(författare)
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PHANGS–JWST First Results : Dust-embedded Star Clusters in NGC 7496 Selected via 3.3 μm PAH Emission
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- The earliest stages of star formation occur enshrouded in dust and are not observable in the optical. Here we leverage the extraordinary new high-resolution infrared imaging from JWST to begin the study of dust-embedded star clusters in nearby galaxies throughout the Local Volume. We present a technique for identifying dust-embedded clusters in NGC 7496 (18.7 Mpc), the first galaxy to be observed by the PHANGS–JWST Cycle 1 Treasury Survey. We select sources that have strong 3.3 μm PAH emission based on a F300M − F335M color excess and identify 67 candidate embedded clusters. Only eight of these are found in the PHANGS-HST optically selected cluster catalog, and all are young (six have SED fit ages of ∼1 Myr). We find that this sample of embedded cluster candidates may significantly increase the census of young clusters in NGC 7496 from the PHANGS-HST catalog; the number of clusters younger than ∼2 Myr could be increased by a factor of 2. Candidates are preferentially located in dust lanes and are coincident with the peaks in the PHANGS-ALMA CO (2–1) maps. We take a first look at concentration indices, luminosity functions, SEDs spanning from 2700 Å to 21 μm, and stellar masses (estimated to be between ∼104 and 105 M⊙). The methods tested here provide a basis for future work to derive accurate constraints on the physical properties of embedded clusters, characterize the completeness of cluster samples, and expand analysis to all 19 galaxies in the PHANGS–JWST sample, which will enable basic unsolved problems in star formation and cluster evolution to be addressed.
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| 7. |
- Signori, A, et al.
(författare)
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Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network
- 2023
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 94:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.MethodsAll patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3–4.ResultsA total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria.ConclusionsContrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.
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| 8. |
- Schultheis, M., et al.
(författare)
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The nuclear stellar disc of the Milky Way : A dynamically cool and metal-rich component possibly formed from the central molecular zone
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 650
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Tidskriftsartikel (refereegranskat)abstract
- Context. The nuclear stellar disc (NSD) is, together with the nuclear star cluster (NSC) and the central massive black hole, one of the main components in the central parts of our Milky Way. However, until recently, only a few studies of the stellar content of the NSD have been obtained owing to extreme extinction and stellar crowding. Aims. We study the kinematics and global metallicities of the NSD based on the observations of K/M giant stars via a dedicated KMOS (VLT, ESO) spectroscopic survey. Methods. We traced radial velocities and metallicities, which were derived based on spectral indices (Na I and CO) along the NSD, and compared those with a Galactic bulge sample of APOGEE (DR16) and data from the NSC. Results. We find that the metallicity distribution function and the fraction of metal-rich and metal-poor stars in the NSD are different from the corresponding distributions and ratios of the NSC and the Galactic bulge. By tracing the velocity dispersion as a function of metallicity, we clearly see that the NSD is kinematically cool and that the velocity dispersion decreases with increasing metallicity contrary to the inner bulge sample of APOGEE (|b|< 4°). Using molecular gas tracers (H2CO, CO(4-3)) of the central molecular zone (CMZ), we find an astonishing agreement between the gas rotation and the rotation of the metal-rich population. This agreement indicates that the metal-rich stars could have formed from gas in the CMZ. On the other hand, the metal-poor stars show a much slower rotation profile with signs of counter-rotation, thereby indicating that these stars have a different origin. Conclusions. Coupling kinematics with global metallicities, our results demonstrate that the NSD is chemically and kinematically distinct with respect to the inner bulge, which indicates a different formation scenario.
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| 9. |
- Liu, Daizhong, et al.
(författare)
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PHANGS–JWST First Results : Stellar-feedback-driven Excitation and Dissociation of Molecular Gas in the Starburst Ring of NGC 1365?
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
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Tidskriftsartikel (refereegranskat)abstract
- We compare embedded young massive star clusters (YMCs) to (sub-)millimeter line observations tracing the excitation and dissociation of molecular gas in the starburst ring of NGC 1365. This galaxy hosts one of the strongest nuclear starbursts and richest populations of YMCs within 20 Mpc. Here we combine near-/mid-IR PHANGS–JWST imaging with new Atacama Large Millimeter/submillimeter Array multi-J CO (1–0, 2–1 and 4–3) and [C ı] (1–0) mapping, which we use to trace CO excitation via R42 = ICO(4−3)/ICO(2−1) and R21 = ICO(2−1)/ICO(1−0) and dissociation via RCICO = I[CI](1−0)/ICO(2−1) at 330 pc resolution. We find that the gas flowing into the starburst ring from northeast to southwest appears strongly affected by stellar feedback, showing decreased excitation (lower R42) and increased signatures of dissociation (higher RCICO) in the downstream regions. There, radiative-transfer modeling suggests that the molecular gas density decreases and temperature and [CI/CO] abundance ratio increase. We compare R42 and RCICO with local conditions across the regions and find that both correlate with near-IR 2 μm emission tracing the YMCs and with both polycyclic aromatic hydrocarbon (11.3 μm) and dust continuum (21 μm) emission. In general, RCICO exhibits ∼0.1 dex tighter correlations than R42, suggesting C ı to be a more sensitive tracer of changing physical conditions in the NGC 1365 starburst than CO (4–3). Our results are consistent with a scenario where gas flows into the two arm regions along the bar, becomes condensed/shocked, forms YMCs, and then these YMCs heat and dissociate the gas.
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| 10. |
- Petkova, Maya, 1990, et al.
(författare)
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Kinematics of Galactic Centre clouds shaped by shear-seeded solenoidal turbulence
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 525:1, s. 962-968
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Tidskriftsartikel (refereegranskat)abstract
- The Central Molecular Zone (CMZ; the central ∼500 pc of the Galaxy) is a kinematically unusual environment relative to the Galactic disc, with high-velocity dispersions and a steep size-linewidth relation of the molecular clouds. In addition, the CMZ region has a significantly lower star formation rate (SFR) than expected by its large amount of dense gas. An important factor in explaining the low SFR is the turbulent state of the star-forming gas, which seems to be dominated by rotational modes. However, the turbulence driving mechanism remains unclear. In this work, we investigate how the Galactic gravitational potential affects the turbulence in CMZ clouds. We focus on the CMZ cloud G0.253+0.016 ('the Brick'), which is very quiescent and unlikely to be kinematically dominated by stellar feedback. We demonstrate that several kinematic properties of the Brick arise naturally in a cloud-scale hydrodynamics simulation, that takes into account the Galactic gravitational potential. These properties include the line-of-sight velocity distribution, the steepened size-linewidth relation, and the predominantly solenoidal nature of the turbulence. Within the simulation, these properties result from the Galactic shear in combination with the cloud's gravitational collapse. This is a strong indication that the Galactic gravitational potential plays a crucial role in shaping the CMZ gas kinematics, and is a major contributor to suppressing the SFR, by inducing predominantly solenoidal turbulent modes.
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