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- Schiava, M., et al.
(författare)
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Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study
- 2022
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 93:10, s. 1099-1111
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Tidskriftsartikel (refereegranskat)abstract
- Background Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype-phenotype correlations. Methods Descriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene. Results Two hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8 +/- 9.6 years and mean age of onset 45.6 +/- 9.3 years. Mean diagnostic delay was 7.7 +/- 6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8 +/- 7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC Conclusion This study expands the knowledge on the phenotypic presentation, natural history, genotype-phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease.
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- Claeys, M. J., et al.
(författare)
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Organization of intensive cardiac care units in Europe : Results of a multinational survey
- 2020
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 9:8, s. 993-1001
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Tidskriftsartikel (refereegranskat)abstract
- Background: The present survey aims to describe the intensive cardiac care unit organization and admission policies in Europe. Methods: A total of 228 hospitals (61% academic) from 27 countries participated in this survey. In addition to the organizational aspects of the intensive cardiac care units, including classification of the intensive cardiac care unit levels, data on the admission diagnoses were gathered from consecutive patients who were admitted during a two-day period. Admission policies were evaluated by comparing illness severity with the intensive cardiac care unit level. Gross national income was used to differentiate high-income countries (n=13) from middle-income countries (n=14). Results: A total of 98% of the hospitals had an intensive cardiac care unit: 70% had a level 1 intensive cardiac care unit, 76% had a level 2 intensive cardiac care unit, 51% had a level 3 intensive cardiac care unit, and 60% of the hospitals had more than one intensive cardiac care unit level. High-income countries tended to have more level 3 intensive cardiac care units than middle-income countries (55% versus 41%, p=0.07). A total of 5159 admissions were scored on illness severity: 63% were low severity, 24% were intermediate severity, and 12% were high severity. Patients with low illness severity were predominantly admitted to level 1 intensive cardiac care units, whereas patients with high illness severity were predominantly admitted to level 2 and 3 intensive cardiac care units. A policy mismatch was observed in 12% of the patients; some patients with high illness severity were admitted to level 1 intensive cardiac care units, which occurred more often in middle-income countries, whereas some patients with low illness severity were admitted to level 3 intensive cardiac care units, which occurred more frequently in high-income countries. Conclusion: More than one-third of the admitted patients were considered intermediate or high risk. Although patients with higher illness severity were mostly admitted to high-level intensive cardiac care units, an admission policy mismatch was observed in 12% of the patients; this mismatch was partly related to insufficient logistic intensive cardiac care unit capacity.
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- Goderis, Steven, et al.
(författare)
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Globally distributed iridium layer preserved within the Chicxulub impact structure
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- The Cretaceous-Paleogene (K-Pg) mass extinction is marked globally by elevated concentrations of iridium, emplaced by a hypervelocity impact event 66 million years ago. Here, we report new data from four independent laboratories that reveal a positive iridium anomaly within the peak-ring sequence of the Chicxulub impact structure, in drill core recovered by IODP-ICDP Expedition 364. The highest concentration of ultrafine meteoritic matter occurs in the post-impact sediments that cover the crater peak ring, just below the lowermost Danian pelagic limestone. Within years to decades after the impact event, this part of the Chicxulub impact basin returned to a relatively low-energy depositional environment, recording in unprecedented detail the recovery of life during the succeeding millennia. The iridium layer provides a key temporal horizon precisely linking Chicxulub to K-Pg boundary sections worldwide.
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- Mus, Liselot M., et al.
(författare)
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The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is an aggressive childhood cancer arising from sympatho-adrenergic neuronal progenitors. The low survival rates for high-risk disease point to an urgent need for novel targeted therapeutic approaches. Detailed molecular characterization of the neuroblastoma genomic landscape indicates that ALK-activating mutations are present in 10% of primary tumours. Together with other mutations causing RAS/MAPK pathway activation, ALK mutations are also enriched in relapsed cases and ALK activation was shown to accelerate MYCN-driven tumour formation through hitherto unknown ALK-driven target genes. To gain further insight into how ALK contributes to neuroblastoma aggressiveness, we searched for known oncogenes in our previously reported ALK-driven gene signature. We identified ETV5, a bona fide oncogene in prostate cancer, as robustly upregulated in neuroblastoma cells harbouring ALK mutations, and show high ETV5 levels downstream of the RAS/MAPK axis. Increased ETV5 expression significantly impacted migration, invasion and colony formation in vitro, and ETV5 knockdown reduced proliferation in a murine xenograft model. We also established a gene signature associated with ETV5 knockdown that correlates with poor patient survival. Taken together, our data highlight ETV5 as an intrinsic component of oncogenic ALK-driven signalling through the MAPK axis and propose that ETV5 upregulation in neuroblastoma may contribute to tumour aggressiveness.
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- Schiele, Francois, et al.
(författare)
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2020 Update of the quality indicators for acute myocardial infarction: a position paper of the Association for Acute Cardiovascular Care: the study group for quality indicators from the ACVC and the NSTE-ACS guideline group
- 2021
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 2048-8726 .- 2048-8734. ; 10:2, s. 224-233
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Tidskriftsartikel (refereegranskat)abstract
- Aims Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. However, an update of these QIs is needed in light of the accumulated experience and the changes in the supporting evidence. Methods and results The ESC methodology for the QI development was used to update the 2017 ACVC QIs. We identified key domains of AMI care, conducted a literature review, developed a list of candidate QIs, and used a modified Delphi method to select the final set of indicators. The same seven domains of AMI care identified by the 2017 Study Group were retained for this update. For each domain, main and secondary QIs were developed reflecting the essential and complementary aspects of care, respectively. Overall, 26 QIs are proposed in this document, compared to 20 in the 2017 set. New QIs are proposed in this document (e.g. the centre use of high-sensitivity troponin), some were retained or modified (e.g. the in-hospital risk assessment), and others were retired in accordance with the changes in evidence [e.g. the proportion of patients with non-ST segment elevation myocardial infarction (NSTEMI) treated with fondaparinux] and the feasibility assessments (e.g. the proportion of patients with NSTEMI whom risk assessment is performed using the GRACE and CRUSADE risk scores). Conclusion Updated QIs for the management of AMI were developed according to contemporary knowledge and accumulated experience. These QIs may be applied to evaluate and improve the quality of AMI care.
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