Computertomographische Messung der Veränderungen von Knochendichte, Knochenstruktur und Knochenstärke amSchenkelhals unter 2jähriger Teriparatid (PTH-1,34) Therapie : Ergebnisse der EUROFORS Studie

Die Ergebnisse dieser Untersuchung zeigen, dass sich die hier zum ersten Mal in vivo erprobte QCT BIT Analyse, mit der Exzentrizitätsmethode zur VOI Findung, als sensitive Methode zur Darstellung von kleinsten Veränderungen der Knochendichte, Geometrie und Biomechanik am Schenkelhals erwiesen hat. Mit diesem Resultat wird eine wichtige Grundlage für die Weiterentwicklung der computertomographischen Osteoporose-Diagnostik an der Hüfte bereitgestellt. In Zukunft sollte es das Ziel sein, in vivo die Regio intertrochanterica sowie Segmente des Schenkelhalsquerschnittes separat zu untersuchen. Es konnte gezeigt werden, dass die Knochendichte mit der Buckling Ratio eng korreliert während die Knochendichtewerte keinen Zusammenhang mit der Biegesteifigkeit des Schenkelhalses zeigten. Somit kann die QCT im Gegensatz zur DXA insbesondere durch die genaue Berechnung von Widerstandsmomenten additive Information bereitstellen. QCT erwies sich hier als wertvolles Verfahren mit dem zeitliche Veränderungen in unterschiedlichen Knochenkompartimenten (trabekulär vs kortikal; endosteal vs. periosteal) analysiert werden können. Biomechanische Größen wie Widerstandsmoment und Knicklast können aus QCT Daten ermittelt werden und die biomechanische Kompetenz des Schenkelhalses unter verschiedenen Belastungsmodi umfassend beschreiben. Die Beobachtung von Veränderungen unter TPTD Behandlung erbrachten neue Erkenntnisse, indem gezeigt wurde, dass die 24 monatige Behandlung einer Gruppe von Frauen mit schwerer Osteoporose nicht nur einen BMD Anstieg verursacht, sondern ebenso eine Verbesserung der Strukturparameter für Biegesteifigkeit und unter Axialbelastung bewirkt. Erstmals konnte geklärt werden, dass diese gemessenen Veränderungen am Schenkelhals durch den Anstieg der trabekulären Dichte und endostealer Knochenapposition bewirkt wurden, und nicht durch periostealen Anbau, wie es durch Studien an Mäusen oder am Menschen bei Messungen an anderen Knochen suggeriert worden war. Zudem zeigte sich, dass eine Reduktion der Knochendichte, wie sie bei vorbehandelten Patienten nach 6 Monaten auftritt, nicht mit einer Schwächung der biomechanisch relevanten Parameter einhergeht, und somit die Veränderung der Dichte nicht mit der Veränderung der Bruchfestigkeit gleichgesetzt werden kann

Bone-GAN: Generation of virtual bone microstructure of high resolution peripheral quantitative computed tomography

Background:Data-driven development of medical biomarkers of bone requires a large amount of image data but physical measurements are generally too restricted in size and quality to perform a robust training. Purpose: This study aims to provide a reliable in silico method for the generation of realistic bone microstructure with defined microarchitectural properties. Synthetic bone samples may improve training of neural networks and serve for the development of new diagnostic parameters of bone architecture and mineralization. Methods: One hundred-fifty cadaveric lumbar vertebrae from 48 different male human spines were scanned with a high resolution peripheral quantitative CT. After prepocessing the scans, we extracted 10,795 purely spongeous bone patches, each with a side length of 32 voxels (5 mm) and isotropic voxel size of 164 m. We trained a volumetric generative adversarial network (GAN) in a progressive manner to create synthetic microstructural bone samples. We then added a style transfer technique to allow the generation of synthetic samples with defined microstructure and gestalt by simultaneously optimizing two entangled loss functions. Reliability testing was performed by comparing real and synthetic bone samples on 10 well-understood microstructural parameters. Results: The method was able to create synthetic bone samples with visual and quantitative properties that effectively matched with the real samples. The GAN contained a well-formed latent space allowing to smoothly morph bone samples by their microstructural parameters, visual appearance or both. Optimum performance has been obtained for bone samples with voxel size 32 × 32 × 32, but also samples of size 64 × 64 × 64 could be synthesized. Conclusions: Our two-step-approach combines a parameter-agnostic GAN with a parameter-specific style transfer technique. It allows to generate an unlimited anonymous database of microstructural bone samples with sufficient realism to be used for the development of new data-driven methods of bonebiomarkers. Particularly, the style transfer technique can generate datasets of bone samples with specific conditions to simulate certain bone pathologies.Este artículo se encuentra publicado en Medical Physics, (Junio 2023

Safety and efficacy of the Derivo Embolization Device for the treatment of unruptured intracranial aneurysms: a multicentric study

Background The Derivo Embolization Device (DED) is a novel flow diverter stent that provides increased x-ray visibility, an improved delivery system, and potentially reduced thrombogenicity. The objective of this study was to evaluate the early safety and efficacy of the second-generation DED. Methods We retrospectively analyzed all patients with unruptured intracranial aneurysms (UIAs) treated with the DED between November 2015 and December 2017 in three German tertiary care centers. Procedural details, complications, and morbidity within 30 days after treatment, as well as the aneurysm occlusion rates after 6 months (O'Kelly-Marotta scale, OKM), were evaluated. Results Implantation of the DED was attempted in 42 patients with 42 aneurysms. All procedures were technically successful. Multiple DEDs were used in three aneurysms (7.2%) and adjunctive coiling in 11 (26.2%). Procedure-related complications occurred in four cases (9.5%) including three thromboembolic events and one aneurysm perforation. The morbidity rate was 2.4% and there was no mortality. One patient suffered an ischemic stroke with persistent aphasia at 30-day follow-up due to a thromboembolic infarct (modified Rankin Scale score 1). Among 33 patients (78.6%) available for angiographic follow-up, complete (OKM D) and favorable (OKM C+D) aneurysm occlusion was obtained in 72.7% (24/33) and 87.9% (29/33), respectively. Conclusions Endovascular treatment of UIAs with the DED is associated with high procedural safety and adequate occlusion rates. Examinations at 1- and 2-year follow-up will provide data on the long-term safety and angiographic outcomes of this device

Targeted regeneration of bone in the osteoporotic human femur.

We have recently developed image processing techniques for measuring the cortical thicknesses of skeletal structures in vivo, with resolution surpassing that of the underlying computed tomography system. The resulting thickness maps can be analysed across cohorts by statistical parametric mapping. Applying these methods to the proximal femurs of osteoporotic women, we discover targeted and apparently synergistic effects of pharmaceutical osteoporosis therapy and habitual mechanical load in enhancing bone thickness

CIRSE Vascular Closure Device Registry

The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters

An International Multicenter Cohort Study on beta-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia

Background: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk, but studies comparing individual β-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of β-blocker in a large cohort of symptomatic children with CPVT.Methods: From 2 international registries of patients with CPVT, RYR2 variant–carrying symptomatic children (defined as syncope or sudden cardiac arrest before β-blocker initiation and age at start of β-blocker therapy &lt;18 years), treated with a β-blocker were included. Cox regression analyses with time-dependent covariates for β-blockers and potential confounders were used to assess the hazard ratio (HR). The primary outcome was the first occurrence of sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or syncope. The secondary outcome was the first occurrence of any of the primary outcomes except syncope.Results: We included 329 patients (median age at diagnosis, 12 [interquartile range, 7–15] years, 35% females). Ninety-nine (30.1%) patients experienced the primary outcome and 74 (22.5%) experienced the secondary outcome during a median follow-up of 6.7 (interquartile range, 2.8–12.5) years. Two-hundred sixteen patients (66.0%) used a nonselective β-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a β1-selective β-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial β-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for β1-selective compared with nonselective β-blockers (HR, 2.04 [95% CI, 1.31–3.17]; and HR, 1.99 [95% CI, 1.20–3.30], respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 [95% CI, 1.44–4.99]), bisoprolol (HR, 3.24 [95% CI, 1.47–7.18]), and metoprolol (HR, 2.18 [95% CI, 1.08–4.40]) compared with nadolol, but did not differ from propranolol. The HR of the secondary outcome was only higher in atenolol compared with nadolol (HR, 2.68 [95% CI, 1.30–5.55]).Conclusions: β1-selective β-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective β-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred β-blocker for treating symptomatic children with CPVT.</p

Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

With ageing, intrinsic haematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing also affects the HSC niche, and thereby impairs its capacity to support HSC function, is still widely debated. Here, by using in-vivo long-term label-retention assays we demonstrate that aged label-retaining HSCs, which are, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches are uniquely preserved in shape, morphology and number on ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches in the long term, which is linked to the lack of recovery of endothelial Jag2 at sinusoids. Overall, our data characterize the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and thereby protect HSCs from ageing

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Cardiac alterations are frequently observed after acute neurological disorders. Takotsubo syndrome (TTS) represents an acute heart failure syndrome and is increasingly recognized as part of the spectrum of cardiac complications observed after neurological disorders. A systematic investigation of TTS patients with neurological disorders has not been conducted yet. The aim of the study was to expand insights regarding neurological disease entities triggering TTS and to investigate the clinical profile and outcomes of TTS patients after primary neurological disorders. The International Takotsubo Registry is an observational multicenter collaborative effort of 45 centers in 14 countries (ClinicalTrials.gov, identifier NCT01947621). All patients in the registry fulfilled International Takotsubo Diagnostic Criteria. For the present study, patients were included if complete information on acute neurological disorders were available. 2402 patients in whom complete information on acute neurological status were available were analyzed. In 161 patients (6.7%) an acute neurological disorder was identified as the preceding triggering factor. The most common neurological disorders were seizures, intracranial hemorrhage, and ischemic stroke. Time from neurological symptoms to TTS diagnosis was ≤ 2 days in 87.3% of cases. TTS patients with neurological disorders were younger, had a lower female predominance, fewer cardiac symptoms, lower left ventricular ejection fraction, and higher levels of cardiac biomarkers. TTS patients with neurological disorders had a 3.2-fold increased odds of in-hospital mortality compared to TTS patients without neurological disorders. In this large-scale study, 1 out of 15 TTS patients had an acute neurological condition as the underlying triggering factor. Our data emphasize that a wide spectrum of neurological diseases ranging from benign to life-threatening encompass TTS. The high rates of adverse events highlight the need for clinical awareness.The International Takotsubo Registry was supported by the Biss Davies Charitable Trust. Dr. Scheitz has been supported by the Corona Foundation. Dr. Templin has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation.info:eu-repo/semantics/publishedVersio

Prognostic impact of acute pulmonary triggers in patients with Takotsubo syndrome : new insights from the International Takotsubo Registry

© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002). Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.C. T. has been supported by the H.H. Sheikh Khalifa binHamad Al-Thani Research Programme and the Swiss HeartFoundation. The InterTAK Registry is supported by the BissDavies Charitable Trust. L. S. M. has been supported by EUHORIZON 2020(SILICOFCM ID777204)info:eu-repo/semantics/publishedVersio