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  • 1
    Online Resource
    Online Resource
    Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries
    Elsevier BV ; 2022
    In:  The Lancet Vol. 400, No. 10363 ( 2022-11), p. 1607-1617
    Details
    In: The Lancet, Elsevier BV, Vol. 400, No. 10363 ( 2022-11), p. 1607-1617
    Type of Medium: Online Resource
    ISSN: 0140-6736
    URL: Article
    DOI: 10.1016/S0140-6736(22)01846-3
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 2
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    Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism—the Find-AF 2 study—rationale and design
    Elsevier BV ; 2023
    In:  American Heart Journal Vol. 265 ( 2023-11), p. 66-76
    Details
    In: American Heart Journal, Elsevier BV, Vol. 265 ( 2023-11), p. 66-76
    Type of Medium: Online Resource
    ISSN: 0002-8703
    URL: Article
    DOI: 10.1016/j.ahj.2023.06.016
    RVK:
    XA 18100
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 3
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    Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions
    Elsevier BV ; 2016
    In:  Cell Vol. 166, No. 2 ( 2016-07), p. 492-505
    Details
    In: Cell, Elsevier BV, Vol. 166, No. 2 ( 2016-07), p. 492-505
    Type of Medium: Online Resource
    ISSN: 0092-8674
    URL: Article
    DOI: 10.1016/j.cell.2016.06.044
    RVK:
    XA 36269
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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    SSG: 12
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  • 4
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    Safety and efficacy of direct cardiac shockwave therapy in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (the CAST-HF trial): study protocol for a randomized controlled trial—an update
    Springer Science and Business Media LLC ; 2022
    In:  Trials Vol. 23, No. 1 ( 2022-12-09)
    Details
    In: Trials, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12-09)
    Abstract: Coronary artery disease (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in the progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodelling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function. Methods In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min walk test distance, improvement of symptoms and assessment of quality of life. Discussion This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure. Trial registration ClinicalTrials.gov NCT03859466. Registered on 1 March 2019.
    Type of Medium: Online Resource
    ISSN: 1745-6215
    URL: Article
    DOI: 10.1186/s13063-022-06931-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 5
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    Prevention of Oxidative Damage in Spinal Cord Ischemia Upon Aortic Surgery: First‐In‐Human Results of Shock Wave Therapy Prove Safety and Feasibility
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of the American Heart Association Vol. 11, No. 20 ( 2022-10-18)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 20 ( 2022-10-18)
    Abstract: Spinal cord ischemia (SCI) remains a devastating complication after aortic dissection or repair. A primary hypoxic damage is followed by a secondary damage resulting in further cellular loss via apoptosis. Affected patients have a poor prognosis and limited therapeutic options. Shock wave therapy (SWT) improves functional outcome, neuronal degeneration and survival in murine spinal cord injury. In this first‐in‐human study we treated 5 patients with spinal cord ischemia with SWT aiming to prove safety and feasibility. Methods and Results Human neurons were subjected to ischemic injury with subsequent SWT. Reactive oxygen species and cellular apoptosis were quantified using flow cytometry. Signaling of the antioxidative transcription factor NRF2 (nuclear factor erythroid 2‐related factor 2) and immune receptor Toll‐like receptor 3 (TLR3) were analyzed. To assess whether SWT act via a conserved mechanism, transgenic tlr3 −/− zebrafish created via CRISPR/Cas9 were subjected to spinal cord injury. To translate our findings into a clinical setting, 5 patients with SCI underwent SWT. Baseline analysis and follow‐up (6 months) included assessment of American Spinal Cord Injury Association (ASIA) impairment scale, evaluation of Spinal Cord Independence Measure score and World Health Organization Quality of Life questionnaire. SWT reduced the number of reactive oxygen species positive cells and apoptosis upon ischemia via induction of the antioxidative factor nuclear factor erythroid 2‐related factor 2. Inhibition or deletion of tlr3 impaired axonal growth after spinal cord lesion in zebrafish, whereas tlr3 stimulation enhanced spinal regeneration. In a first‐in‐human study, we treated 5 patients with SCI using SWT (mean age, 65.3 years). Four patients presented with acute aortic dissection (80%), 2 of them exhibited preoperative neurological symptoms (40%). Impairment was ASIA A in 1 patient (20%), ASIA B in 3 patients (60%), and ASIA D in 1 patient (20%) at baseline. At follow‐up, 2 patients were graded as ASIA A (40%) and 3 patients as ASIA B (60%). Spinal cord independence measure score showed significant improvement. Examination of World Health Organization Quality of Life questionnaires revealed increased scores at follow‐up. Conclusions SWT reduces oxidative damage upon SCI via immune receptor TLR3. The first‐in‐human application proved safety and feasibility in patients with SCI. SWT could therefore become a powerful regenerative treatment option for this devastating injury.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.122.026076
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 6
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    Langerhans cells in hypospadias: an analysis of Langerin (CD207) and HLA-DR on epidermal sheets and full thickness skin sections
    Springer Science and Business Media LLC ; 2019
    In:  BMC Urology Vol. 19, No. 1 ( 2019-12)
    Details
    In: BMC Urology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2019-12)
    Abstract: Hypospadias are among the most common genital malformations. Langerhans Cells (LCs) play a pivotal role in HIV and HPV infection. The migration of LC precursors to skin coincides with the embryonic period of hypospadias development and genetic alterations leading to the formation of hypospadias impact the development of ectodermally derived tissues. We hypothesized that this might be associated with a difference in frequency or morphology of epidermal and dermal LCs in hypospadias patients. Methods A total of 43 patients from two centers were prospectively included into this study after parental consent and ethics approval. Epidermal and dermal sheets were prepared from skin samples of 26 patients with hypospadias, 13 patients without penile malformations and 4 patients with penile malformations other than hypospadias. Immunofluorescence staining of sheets was performed with anti-HLA-DR-FITC and anti-CD207/Langerin-A594 antibodies. Skin sections from 11 patients without penile malformation and 11 patients with hypospadias were stained for Langerin. Frequencies as well as morphology and distribution of epidermal and dermal LCs on sheets and sections were microscopically evaluated. Cell counts were compared by unpaired t-tests. Results There was no difference in frequency of epidermal LCs, Neither on sheets (873 ± 61 vs. 940 ± 84LCs/mm 2 , p  = 0.522) nor on sections (32 ± 3 vs. 30 ± 2LCs/mm 2 , p  = 0.697). Likewise, the frequency of dermal LCs (5,9 ± 0,9 vs. 7.5 ± 1.3LCs/mm 2 , p  = 0.329) was comparable between patients with hypospadias and without penile malformation. No differences became apparent in subgroup analyses, comparing distal to proximal hypospadias ( p  = 0.949), younger and older boys ( p  = 0.818) or considering topical dihydrotestosterone treatment prior to surgery ( p  = 0.08). The morphology of the LCs was not different comparing hypospadias patients with boys without penile malformations. Conclusions LCs are present in similar frequencies and with a comparable morphology and distribution in patients with hypospadias as compared to children without penile malformations. This suggests that patients with hypospadias are not different from patients with normal penile development considering this particular compartment of their skin immunity.
    Type of Medium: Online Resource
    ISSN: 1471-2490
    URL: Article
    DOI: 10.1186/s12894-019-0551-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
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  • 7
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    Shared and distinct white matter abnormalities in adolescent-onset schizophrenia and adolescent-onset psychotic bipolar disorder
    Cambridge University Press (CUP) ; 2023
    In:  Psychological Medicine Vol. 53, No. 10 ( 2023-07), p. 4707-4719
    Details
    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 53, No. 10 ( 2023-07), p. 4707-4719
    Abstract: While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need. Methods Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FA T ) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FA T and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence. Results Individuals with adolescent-onset psychosis exhibited pronounced FW and FA T abnormalities compared to HCs. FA T reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FA T was positively related to age. Conclusions We observe evidence for cellular (FA T ) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S003329172200160X
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2023
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    SSG: 5,2
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  • 8
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    Basic principles of cardiothoracic surgery training: a position paper by the European Association for Cardiothoracic Surgery Residents Committee
    Oxford University Press (OUP) ; 2022
    In:  Interactive CardioVascular and Thoracic Surgery Vol. 35, No. 4 ( 2022-09-09)
    Details
    In: Interactive CardioVascular and Thoracic Surgery, Oxford University Press (OUP), Vol. 35, No. 4 ( 2022-09-09)
    Abstract: OBJECTIVES Across Europe there are significant variations in the fundamental structure and content of cardiothoracic surgery (CTS) training programmes. Previous efforts have been made to introduce a Unified European Training System, which outlined the fundamentals of the ideal programme and supported a paradigm shift from an apprenticeship to a competency-based model. This article’s goal was to define key structural, administrative and executive details of such a programme to lay the foundations for the standardization of cardiothoracic surgical training across Europe. METHODS The European Association for Cardiothoracic Surgery Residents Committee had previously conducted a residents’ training survey across Europe in 2020. Training curricula from the twelve most represented countries across Europe were either searched online or obtained from the countries’ national trainee representative and reviewed by the committee. Information was collated and placed into one of the following categories to develop the position paper: (i) selection of eligible candidates, (ii) guidance for an outcome-based syllabus, (iii) documentation and evaluation of training progress, (iv) mandatory rotations and training courses, (v) number of independent or assisted cases and (vi) requirements and quality assurance of teachers. RESULTS An independent professional body should promote an outcome-based syllabus and take responsibility for the training programme’s quality assurance. Trainees should be selected on merit by an open and transparent process. Training should be delivered within a defined period and supervised by an appointed training committee to ensure its implementation. This committee should review the trainees progression regularly, provide feedback and offer trainees the opportunity to experience various training environments and trainers. A common electronic portal be used by trainees to record their agreed objectives and to evidence their completion. Trainees should regularly attend specialty-relevant courses and conferences to promote professional and academic development. The end of training is reached when the formal requirements of the training programme are met and the trainee is able to perform at the level expected of a day-1 independent surgeon. CONCLUSIONS This article defines the key structural, administrative, and executive principles for CTS training. Programmes are encouraged to review and modify their training curricula, if necessary, to ensure the delivery of high-quality, standardized, outcome-orientated CTS training across Europe.
    Type of Medium: Online Resource
    ISSN: 1569-9285
    URL: Article
    DOI: 10.1093/icvts/ivac213
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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    detail.hit.zdb_id: 3167862-2
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  • 9
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    Different calcification patterns of tricuspid and bicuspid aortic valves and their clinical impact
    Oxford University Press (OUP) ; 2022
    In:  Interactive CardioVascular and Thoracic Surgery Vol. 35, No. 6 ( 2022-11-08)
    Details
    In: Interactive CardioVascular and Thoracic Surgery, Oxford University Press (OUP), Vol. 35, No. 6 ( 2022-11-08)
    Abstract: OBJECTIVES Mechanical strain plays a major role in the development of aortic calcification. We hypothesized that (i) valvular calcifications are most pronounced at the localizations subjected to the highest mechanical strain and (ii) calcification patterns are different in patients with bicuspid and tricuspid aortic valves. METHODS Multislice computed tomography scans of 101 patients with severe aortic stenosis were analysed using a 3-dimensional post-processing software to quantify calcification of tricuspid aortic valves (n = 51) and bicuspid aortic valves (n = 50) after matching. RESULTS Bicuspid aortic valves exhibited higher calcification volumes and increased calcification of the non-coronary cusp with significantly higher calcification of the free leaflet edge. The non-coronary cusp showed the highest calcium load compared to the other leaflets. Patients with annular calcification above the median had an impaired survival compared to patients with low annular calcification, whereas patients with calcification of the free leaflet edge above the median did not (P = 0.53). CONCLUSIONS Calcification patterns are different in patients with aortic stenosis with bicuspid and tricuspid aortic valves. Patients with high annular calcification might have an impaired prognosis.
    Type of Medium: Online Resource
    ISSN: 1569-9285
    URL: Article
    DOI: 10.1093/icvts/ivac274
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2096257-5
    detail.hit.zdb_id: 3167862-2
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  • 10
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    Correlation between structural heart disease and cardiac SARS-CoV-2 manifestations
    Springer Science and Business Media LLC ; 2022
    In:  Communications Medicine Vol. 2, No. 1 ( 2022-11-11)
    Details
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 2, No. 1 ( 2022-11-11)
    Abstract: The prognosis of COVID-19 patients with cardiac involvement is unfavorable and it remains unknown which patients are at risk. The virus enters cells via its receptor angiotensin-converting enzyme 2 (ACE2). Myocardial ACE2 expression is increased in structural heart disease (SHD). We, therefore, aimed to analyze correlations between structural heart disease and cardiac SARS-CoV-2 manifestation. Methods: The clinical course of COVID-19 in patients with structural heart disease was assessed in a prospective cohort of 152 patients. The primary endpoints consisted of hospitalization and survival. Cardiac tissue of 23 autopsy cases with lethal COVID-19 course was obtained and analyzed for (a) the presence of SHD, (b) myocardial presence of SARS-CoV-2 via RT,-PCR, and (c) levels of ACE2 expression using immunofluorescence staining. Results: Structural heart disease is found in 67 patients, of whom 56 (83.60%) are hospitalized. The myocardium is positive for SARS-CoV-2 in 15 patients (65%) in 23 autopsy cases of lethal COVID-19. Moreover, most hearts with evidence of myocardial SARS-CoV-2 have structural heart disease [11 (91,67%) vs. 1 (8,33%), p  = 0.029]. Myocardial presence of SARS-CoV-2 is correlated with a significant downregulation of ACE2 compared to negative control hearts (6.545 ± 1.1818 A.U. vs. 7.764 ± 2.411 A.U., p  = 0.003). The clinical course of patients with cardiac SARS-CoV-2 manifestation is unfavorable, resulting in impaired survival (median, 12 days and 4.5 days, respectively, HR 0.30, 95% CI, 0.13 to 0.73, p  = 0.0005) Conclusions: We provide evidence for a correlation between SHD, altered ACE2 receptor expression, and cardiac SARS-CoV-2 manifestation. Consequently, structural heart disease may be considered a distinct risk factor for a severe clinical course after infection with SARS-CoV-2. Registration number local IRB: Ethics Committee of Northwestern and Central Switzerland ID 2020-00629; Ethics Committee of the Medical University Innsbruck EK Nr: 1103/2020. ClinicalTrials.gov number: NCT04416100.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    URL: Article
    DOI: 10.1038/s43856-022-00204-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 3096949-9
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