| 1. |
- Mishra, A., et al.
(författare)
-
Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
-
Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
|
|
| 2. |
- Guisado-Clavero, M., et al.
(författare)
-
The role of primary health care in long-term care facilities during the COVID-19 pandemic in 30 European countries: a retrospective descriptive study (Eurodata study)
- 2023
-
Ingår i: Primary Health Care Research and Development. - 1463-4236. ; 24
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aim:Primary health care (PHC) supported long-term care facilities (LTCFs) in attending COVID-19 patients. The aim of this study is to describe the role of PHC in LTCFs in Europe during the early phase of the pandemic.Methods:Retrospective descriptive study from 30 European countries using data from September 2020 collected with an ad hoc semi-structured questionnaire. Related variables are SARS-CoV-2 testing, contact tracing, follow-up, additional testing, and patient care.Results:Twenty-six out of the 30 European countries had PHC involvement in LTCFs during the COVID-19 pandemic. PHC participated in initial medical care in 22 countries, while, in 15, PHC was responsible for SARS-CoV-2 test along with other institutions. Supervision of individuals in isolation was carried out mostly by LTCF staff, but physical examination or symptom's follow-up was performed mainly by PHC.Conclusion:PHC has participated in COVID-19 pandemic assistance in LTCFs in coordination with LTCF staff, public health officers, and hospitals.
|
|
| 3. |
- Ares-Blanco, S., et al.
(författare)
-
Clinical pathway of COVID-19 patients in primary health care in 30 European countries: Eurodata study
- 2023
-
Ingår i: European Journal of General Practice. - : Informa UK Limited. - 1381-4788 .- 1751-1402. ; 29:2
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundMost COVID-19 patients were treated in primary health care (PHC) in Europe.ObjectivesTo demonstrate the scope of PHC workflow during the COVID-19 pandemic emphasising similarities and differences of patient's clinical pathways in Europe.MethodsDescriptive, cross-sectional study with data acquired through a semi-structured questionnaire in PHC in 30 European countries, created ad hoc and agreed upon among all researchers who participated in the study. GPs from each country answered the approved questionnaire. Main variable: PHC COVID-19 acute clinical pathway. All variables were collected from each country as of September 2020.ResultsCOVID-19 clinics in PHC facilities were organised in 8/30. Case detection and testing were performed in PHC in 27/30 countries. RT-PCR and lateral flow tests were performed in PHC in 23/30, free of charge with a medical prescription. Contact tracing was performed mainly by public health authorities. Mandatory isolation ranged from 5 to 14 days. Sick leave certification was given exclusively by GPs in 21/30 countries. Patient hotels or other resources to isolate patients were available in 12/30. Follow-up to monitor the symptoms and/or new complementary tests was made mainly by phone call (27/30). Chest X-ray and phlebotomy were performed in PHC in 18/30 and 23/30 countries, respectively. Oxygen and low-molecular-weight heparin were available in PHC (21/30).ConclusionIn Europe PHC participated in many steps to diagnose, treat and monitor COVID-19 patients. Differences among countries might be addressed at European level for the management of future pandemics.
|
|
| 4. |
- Dias, N., et al.
(författare)
-
Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms
- 2023
-
Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 278:4, s. 568-577, s. 568-577
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs).Background: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described.Methods: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair.Results: A total of 2603 patients (69% males; mean age 72 +/- 10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P < 0.001) and rates of MAEs (34% vs 20%, P < 0.001). Median follow-up was 15 months ( interquartile range, 7-37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50 +/- 4% vs 70 +/- 1% and 21 +/- 3% vs 7 +/- 1%, P < 0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality ( hazard ratio, 1.92; 95% CI] 1.50-2.44; P < 0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63-3.62; P < 0.001).Conclusions: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.
|
|
| 5. |
- Niborski, Leticia L., et al.
(författare)
-
Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system
- 2021
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 63
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To deeply understand the role of antibodies in the context of Trypanosoma cruzi infection, we decided to characterize A2R1, a parasite antibody selected from single-chain variable fragment (scFv) phage display libraries constructed from B cells of chronic Chagas heart disease patients. Methods: Immunoblot, ELISA, cytometry, immunofluorescence and immunohistochemical assays were used to characterize A2R1 reactivity. To identify the antibody target, we performed an immunoprecipitation and two-dimensional electrophoresis coupled to mass spectrometry and confirmed A2R1 specific interaction by producing the antigen in different expression systems. Based on these data, we carried out a comparative in silico analysis of the protein targets orthologues, focusing mainly on post-translational modifications. Findings: A2R1 recognizes a parasite protein of similar to 50 kDa present in all life cycle stages of T. cruzi, as well as in other members of the kinetoplastid family, showing a defined immunofluorescence labeling pattern consistent with the cytoskeleton. A2R1 binds to tubulin, but this interaction relies on its post-translational modifications. Interestingly, this antibody also targets mammalian tubulin only present in brain, staining in and around cell bodies of the human peripheral and central nervous system. Interpretation: Our findings demonstrate for the first time the existence of a human antibody against T. cruzi tubulin capable of cross-reacting with a human neural protein. This work re-emphasizes the role of molecular mimicry between host and parasitic antigens in the development of pathological manifestations of T. cruzi infection.
|
|
| 6. |
- Omerovic, Elmir, 1968, et al.
(författare)
-
Pathophysiology of Takotsubo syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 1: overview and the central role for catecholamines and sympathetic nervous system
- 2022
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:2, s. 257-273
-
Tidskriftsartikel (refereegranskat)abstract
- This is the first part of a scientific statement from the Heart Failure Association (HFA) of the European Society of Cardiology focused upon the pathophysiology of Takotsubo syndrome and is complimentary to the previous HFA position statement on Takotsubo syndrome which focused upon clinical management. In part 1 we provide an overview of the pathophysiology of Takotsubo syndrome and fundamental questions to consider. We then review and discuss the central role of catecholamines and the sympathetic nervous system in the pathophysiology, and the direct effects of high surges in catecholamines upon myocardial biology including beta-adrenergic receptor signalling, G-protein coupled receptor kinases, cardiomyocyte calcium physiology, myofilament physiology, cardiomyocyte gene expression, myocardial electrophysiology and arrhythmogenicity, myocardial inflammation, metabolism and energetics. The integrated effects upon ventricular haemodynamics are discussed and integrated into the pathophysiological model.
|
|
| 7. |
- Dias-Neto, Marina, et al.
(författare)
-
Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms
- 2023
-
Ingår i: Journal of Vascular Surgery. - : MOSBY-ELSEVIER. - 0741-5214 .- 1097-6809. ; 77:6, s. 1588-1597
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs).Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single-or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality.Results: A total of 1947 patients (65% male; mean age, 71 +/- 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9 +/- 1.3% vs 79.6 +/- 1.7%) and 3 years (72.7 +/- 2.1% vs 64.2 +/- 2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach.Conclusions: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years.
|
|
| 8. |
|
|
| 9. |
- Fumagalli, M, et al.
(författare)
-
Ultrasound of acquired posterior fossa abnormalities in the newborn
- 2020
-
Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 87:SUPPL 1Suppl 1, s. 25-36
-
Tidskriftsartikel (refereegranskat)abstract
- Neonatal brain sonography is part of routine clinical practice in neonatal intensive care units, but ultrasound imaging of the posterior fossa has gained increasing attention since the burden of perinatal acquired posterior fossa abnormalities and their impact on motor and cognitive neurodevelopmental outcome have been recognized. Although magnetic resonance imaging (MRI) is often superior, posterior fossa abnormalities can be suspected or detected by optimized cranial ultrasound (CUS) scans, which allow an early and bed-side diagnosis and monitoring through sequential scans over a long period of time. Different ultrasound appearances and injury patterns of posterior fossa abnormalities are described according to gestational age at birth and characteristics of the pathogenetic insult. The aim of this review article is to describe options to improve posterior fossa sequential CUS image quality, including the use of supplemental acoustic windows, to show standard views and normal ultrasound anatomy of the posterior fossa, and to describe the ultrasound characteristics of acquired posterior fossa lesions in preterm and term infants with effect on long-term outcome. The limitations and pitfalls of CUS and the role of MRI are discussed.
|
|
| 10. |
- Horsch, S., et al.
(författare)
-
Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury
- 2020
-
Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this post-hoc analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants. Methods: This report is an exploratory post-hoc analysis of a phase II trial in which infants <28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers. Results: The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II-III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (n = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed. Conclusion: The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start.
|
|
| 11. |
- Mereaux, JL, et al.
(författare)
-
Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations
- 2021
-
Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6753 .- 1364-6745. ; 22:1, s. 71-79
-
Tidskriftsartikel (refereegranskat)abstract
- Spastic ataxias are rare neurogenetic disorders involving spinocerebellar and pyramidal tracts. Many genes are involved. Among them, CAPN1, when mutated, is responsible for a complex inherited form of spastic paraplegia (SPG76). We report the largest published series of 21 novel patients with nine new CAPN1 disease-causing variants and their clinical characteristics from two European university hospitals (Paris and Stockholm). After a formal clinical examination, causative variants were identified by next-generation sequencing and confirmed by Sanger sequencing. CAPN1 variants are a rare cause (~ 1.4%) of young-adult-onset spastic ataxia; however, together with all published cases, they allowed us to better describe the clinical and genetic spectra of this form. Truncating variants are the most frequent, and missense variants lead to earlier age at onset in favor of an additional deleterious effect. Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity. We also suggest that cognitive impairment and depression should be assessed specifically in the follow-up of SPG76 cases.
|
|
| 12. |
- Omerovic, Elmir, 1968, et al.
(författare)
-
Pathophysiology of Takotsubo Syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 2: vascular pathophysiology, gender and sex hormones, genetics, chronic cardiovascular problems and clinical implications.
- 2022
-
Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 24:2, s. 274-286
-
Tidskriftsartikel (refereegranskat)abstract
- While the first part of the scientific statement on the pathophysiology of Takotsubo syndrome was focused the catecholamines and sympathetic nervous system, in the second part we focus on the vascular pathophysiology including coronary and systemic vascular responses, the role of the central and peripheral nervous systems during the acute phase and abnormalities in the subacute phase, the gender differences and integrated effects of sex hormones, genetics of Takotsubo syndrome including insights from microRNA studies and inducible pluripotent stem cell models of Takotsubo syndrome. We then discuss the chronic abnormalities of cardiovascular physiology in survivors, the limitations of current clinical and preclinical studies, the implications of the knowledge of pathophysiology for clinical management and future perspectives and directions of research. This article is protected by copyright. All rights reserved.
|
|
| 13. |
- Parodi, A, et al.
(författare)
-
Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome
- 2020
-
Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 87:SUPPL 1Suppl 1, s. 13-24
-
Tidskriftsartikel (refereegranskat)abstract
- Germinal matrix-intraventricular haemorrhage (GMH-IVH), periventricular haemorrhagic infarction (PHI) and its complication, post-haemorrhagic ventricular dilatation (PHVD), are still common neonatal morbidities in preterm infants that are highly associated with adverse neurodevelopmental outcome. Typical cranial ultrasound (CUS) findings of GMH-IVH, PHI and PHVD, their anatomical substrates and underlying mechanisms are discussed in this paper. Furthermore, we propose a detailed descriptive classification of GMH-IVH and PHI that may improve quality of CUS reporting and prediction of outcome in infants suffering from GMH-IVH/PHI.
|
|
| 14. |
- Tenorio, Emanuel R, et al.
(författare)
-
Multicenter global early feasibility study to evaluate total endovascular arch repair using three-vessel inner branch stent-grafts for aneurysms and dissections
- 2021
-
Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 1097-6809 .- 0741-5214. ; 74:4, s. 4-1065
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the outcomes of total endovascular aortic arch repair using three-vessel inner branch stent-grafts for aneurysms and chronic dissections.METHODS: We reviewed the clinical data and outcomes of consecutive patients treated by total endovascular aortic arch repair at eight academic centers using three-vessel inner branch stent-grafts (William Cook Europe, Bjaeverskov, Denmark) between 2016 to 2019. All patients received three vessel designs with two antegrade and one retrograde inner branch, which was used to incorporate the innominate (IA), left common carotid (LCCA) and left subclavian arteries (LSA). The antegrade inner branches were accessed via carotid or upper extremity access. A preloaded catheter was used for access to the retrograde LSA branch via trans-femoral approach. End-points were technical success, mortality, major adverse events (MAEs), any stroke (minor or major) or transient ischemia attack (TIA), secondary interventions, target vessel patency, target vessel instability, aneurysm-related mortality and patient survival.RESULTS: There were 39 patients (31 male patients [79%], mean age 70±7) treated for 14 (36%) degenerative and 25 (64%) chronic post-dissection arch aneurysms. Clinical characteristics included American Society of Anesthesiologist (ASA) classification > 3 in 28 patients (95%) and prior median sternotomy for ascending aortic repair in 28 patients (72%). Technical success rate was 100%. There were two in-hospital or 30-day deaths (5%) and two strokes (one minor). Combined mortality/any stroke rate was 8% (n=3). MAEs occurred in 10 patients (26%), including respiratory failure in four patients (10%) and estimated blood loss >1L, myocardial infarction and acute kidney injury in two patients each (5%). Median follow up was 3.2 months (IQR, 1 to 14). Twelve patients (31%) required secondary interventions to treat vascular access complications in five patients, endoleak in six patients (three type II, one type IC, one type IA/IB, one type IIIA) and target vessel stenosis in one patient. At 1-year, primary and secondary patency rates and freedom from target vessel instability were 95%±5%, 100% and 91%±5%. Freedom from aortic-related mortality and patient survival were 94%±4% and 90%±6%, respectively.CONCLUSION: This multicenter global experience demonstrates the technical feasibility and safety of total endovascular aortic arch repair for aneurysms and chronic dissections using three-vessel inner branch stent-grafts. Mortality and stroke rates compare favorably to open surgical repair in a higher risk group of patients. Rate of secondary interventions was high (31%), emphasizing need for larger experience and longer follow-up.
|
|
