| 1. |
- 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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| 2. |
- 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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| 3. |
- Peccatori, J, et al.
(författare)
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Prognostic factors for survival in patients with advanced renal cell carcinoma undergoing nonmyeloablative allogeneic stem cell transplantation
- 2005
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 104:10, s. 2099-2103
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. The objective of this study was to identify prognostic factors for predicting survival in patients with advanced renal cell carcinoma (RCC) who had undergone an allogeneic stem cell transplantation after failure on immunotherapy. METHODS. The authors Studied 70 patients with advanced RCC Who underwent allogeneic transplantation with a fludarabine-based, reduced-intensity regimen. Ten parameters were analyzed at the time of transplantation for their power to predict Survival. Clinical features were examined first univariately; then, variables that were correlated significantly with Survival in the univariate analysis were included in a multivariate Cox regression model. RESULTS. Factors that were found to be associated significantly with limited survival were performance Status, the number of metastatic sites, the presence of mediastinal metastasis, hemoglobin level, C-reactive protein (CRP) level, lactate dehydrogenase (LDH) level, and neutrophil counts. All these variables were included in a multivariate Cox regression model, and three were retained in the final model. Patients were classified according to the score estimated by the final Cox model in two groups (above or below the median Value): The median Survival was 3.5 months for patients who had a poor prognosis patients versus 23 months for patients who had a good prognosis. CONCLUSIONS. The Current findings suggested that three easily available parameters (performance status, CRP level, and LDH level) could be used to stratify patients with advanced RCC who are candidates for allografting and to assist clinicians in decision-making and selection of an appropriate treatment program.
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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. |
- 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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| 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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