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Sökning: WFRF:(Thiele Holger)

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  • Chioncel, Ovidiu, et al. (författare)
  • Epidemiology, pathophysiology and contemporary management of cardiogenic shock - a position statement from the Heart Failure Association of the European Society of Cardiology
  • 2020
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:8, s. 1315-1341
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patients underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management.
  • Feng, Shaohong, et al. (författare)
  • Dense sampling of bird diversity increases power of comparative genomics
  • 2020
  • Ingår i: Nature. - : NATURE RESEARCH. - 0028-0836 .- 1476-4687. ; 587:7833, s. 252-257
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
  • Figtree, Gemma A, et al. (författare)
  • Clinical Outcomes in Patients With ST-Segment Elevation MI and No Standard Modifiable Cardiovascular Risk Factors.
  • 2022
  • Ingår i: JACC. Cardiovascular interventions. - 1876-7605. ; 15:11, s. 1167-1175
  • Tidskriftsartikel (refereegranskat)abstract
    • The author recently reported ∼50% excess early mortality in patients with first-presentation ST-segment elevation myocardial infarction (STEMI) without standard modifiable cardiovascular risk factors (SMuRFs); the cause of this is not clear.The aim of this study was to examine differences in infarct characteristics and clinical outcomes in patients with versus without SMuRFs (dyslipidemia, hypertension, diabetes mellitus, and smoking).Individual-level data were pooled from 10 randomized percutaneous intervention (PCI) trials in which infarct size was measured within 1 month by either cardiac magnetic resonance or technetium-99m sestamibi single-photon emission computed tomography imaging. First-presentation STEMI was classified into 2 groups according to the presence or absence of at least 1 SMuRF.Among 2,862 patients, 524 (18.3%) were SMuRF-less. After adjusting for study effect, SMuRF-less patients had more frequent poor pre-PCI flow Thrombolysis In Myocardial Infarction 0/1 compared with patients with at least 1 SMuRF (72.0% vs 64.1%; OR: 1.35; 95% CI: 1.08-1.70). There were no independent associations between the presence or absence of SMuRFs at baseline and infarct size (estimate = -0.35; 95% CI: -1.93 to 1.23), left ventricular ejection fraction (estimate = -0.06; 95% CI: -1.33 to 1.20), or mortality at 30 days (HR: 0.46; 95% CI: 0.19-1.07) and 1 year (HR: 0.74; 95% CI: 0.43-1.29).First-presentation STEMI patients with no identifiable baseline SMuRFs had a higher risk of Thrombolysis In Myocardial Infarction flow grade 0/1 pre-PCI. However, after adjustment, there were no significant associations between SMuRF-less status and infarct size, left ventricle ejection fraction, or mortality.
  • Kolte, Dhaval, et al. (författare)
  • Culprit Vessel-Only Versus Multivessel Percutaneous Coronary Intervention in Patients With Cardiogenic Shock Complicating ST-Segment-Elevation Myocardial Infarction : A Collaborative Meta-Analysis
  • 2017
  • Ingår i: Circulation. Cardiovascular Interventions. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-7640 .- 1941-7632. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The optimal revascularization strategy in patients with multivessel disease presenting with cardiogenic shock complicating ST-segment-elevation myocardial infarction remains unknown. Methods and Results Databases were searched from 1999 to October 2016. Studies comparing immediate/single-stage multivessel percutaneous coronary intervention (MV-PCI) versus culprit vessel-only PCI (CO-PCI) in patients with multivessel disease, ST-segment-elevation myocardial infarction, and cardiogenic shock were included. Primary end point was short-term (in-hospital or 30 days) mortality. Secondary end points included long-term mortality, cardiovascular death, reinfarction, and repeat revascularization. Safety end points were in-hospital stroke, renal failure, and major bleeding. The meta-analysis included 11 nonrandomized studies and 5850 patients (1157 MV-PCI and 4693 CO-PCI). There was no significant difference in short-term mortality with MV-PCI versus CO-PCI (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.81-1.43; P=0.61). Similarly, there were no significant differences in long-term mortality (OR, 0.84; 95% CI, 0.54-1.30; P=0.43), cardiovascular death (OR, 0.72; 95% CI, 0.42-1.23; P=0.23), reinfarction (OR, 1.65; 95% CI, 0.84-3.26; P=0.15), or repeat revascularization (OR, 1.13; 95% CI, 0.76-1.69; P=0.54) between the 2 groups. There was a nonsignificant trend toward higher in-hospital stroke (OR, 1.64; 95% CI, 0.98-2.72; P=0.06) and renal failure (OR, 1.30; 95% CI, 0.98-1.72; P=0.06), with no difference in major bleeding (OR, 1.47; 95% CI, 0.39-5.63; P=0.57) with MV-PCI when compared with CO-PCI. Conclusions This meta-analysis of nonrandomized studies suggests that in patients with cardiogenic shock complicating ST-segment-elevation myocardial infarction, there may be no significant benefit with single-stage MV-PCI compared with CO-PCI. Given the limitations of observational data, randomized trials are needed to determine the role of MV-PCI in this setting.
  • Lopes, Renato D., et al. (författare)
  • Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation
  • 2019
  • Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 380:16, s. 1509-1524
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. Methods In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y(12) inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. Results Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P=0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. Conclusions In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y(12) inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both.
  • Redfors, Björn, et al. (författare)
  • Ambient temperature and infarct size, microvascular obstruction, left ventricular function and clinical outcomes after ST-segment elevation myocardial infarction.
  • 2022
  • Ingår i: Coronary artery disease. - 1473-5830. ; 33:2, s. 81-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Incidence and prognosis of ST-segment elevation myocardial infarction (STEMI) vary according to ambient temperature and season. We sought to assess whether season and temperature on the day of STEMI are associated with infarct size, microvascular obstruction (MVO), left ventricular ejection fraction (LVEF) and clinical outcomes after primary percutaneous coronary intervention (PCI).Individual patient data from 1598 patients undergoing primary PCI in six randomized clinical trials were pooled. Infarct size was evaluated by cardiac magnetic resonance within 30 days in all trials. Patients were categorized either by whether they presented on a day of temperature extremes (minimum temperature <0 °C or maximum temperature >25 °C) or according to season.A total of 558/1598 (34.9%) patients presented with STEMI on a day of temperature extremes, and 395 (24.7%), 374 (23.4%), 481 (30.1%) and 348 (21.8%) presented in the spring, summer, fall and winter. After multivariable adjustment, temperature extremes were independently associated with larger infarct size (adjusted difference 2.8%; 95% CI, 1.3-4.3; P < 0.001) and smaller LVEF (adjusted difference -2.3%; 95% CI, -3.5 to -1.1; P = 0.0002) but not with MVO (adjusted P = 0.12). In contrast, infarct size, MVO and LVEF were unrelated to season (adjusted P = 0.67; P = 0.36 and P = 0.95, respectively). Neither temperature extremes nor season were independently associated with 1-year risk of death or heart failure hospitalization (adjusted P = 0.79 and P = 0.90, respectively).STEMI presentation during temperature extremes was independently associated with larger infarct size and lower LVEF but not with MVO after primary PCI, whereas season was unrelated to infarct severity.
  • Rieke, Johanna Magdalena, et al. (författare)
  • SLC20A1Is Involved in Urinary Tract and Urorectal Development
  • 2020
  • Ingår i: Frontiers in Cell and Developmental Biology. - : FRONTIERS MEDIA SA. - 2296-634X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
  • Saad, Mohammed, et al. (författare)
  • Bioresorbable Vascular Scaffolds in a Real-World Patient Population-Results From a Mid-Term Angiographic Follow-Up
  • 2016
  • Ingår i: Journal of interventional cardiology. - 0896-4327 .- 1540-8183. ; 29:4, s. 341-347
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: We aimed to investigate the safety and efficacy of bioresorbable vascular scaffolds (BVS) in daily use in a real-world patient population.METHODS AND RESULTS: Between March 2013 and September 2014, 224 patients (233 lesions) were treated with BVS at a tertiary care center. Patients underwent follow-up coronary angiography 3-6 months after implantation. Clinical presentations were stable angina in 101 patients (45.1%), unstable angina in 47 (21.0%), NSTEMI in 38 (17.0%), and STEMI in 38 (17.0%) patients. Twenty-two patients (27 lesions) had chronic total occlusion (CTO). Procedural success was achieved in all patients. Two patients died in the follow-up period due to BVS thrombosis (0.9%). In-hospital death occurred in further 3 patients (1.3%) due to other causes not related to the BVS implantation. Total BVS thrombosis was 3.1% (7 patients) and there was only 1 case of relevant restenosis on angiographic follow-up. The overall incidence of major adverse cardiac events was 11 (4.9%).CONCLUSIONS: Mid-term follow-up after implantation of BVS suggests a satisfactory safety profile and low restenosis rate in routine daily practice involving a large range of complex lesions.
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