fMRI BOLD and MEG theta power reflect complementary aspects of activity during lexicosemantic decision in adolescents with ASD.

Neuroimaging studies of autism spectrum disorder (ASD) have been predominantly unimodal. While many fMRI studies have reported atypical activity patterns for diverse tasks, the MEG literature in ASD remains comparatively small. Our group recently reported atypically increased event-related theta power in individuals with ASD during lexicosemantic processing. The current multimodal study examined the relationship between fMRI BOLD signal and anatomically-constrained MEG (aMEG) theta power. Thirty-three adolescents with ASD and 23 typically developing (TD) peers took part in both fMRI and MEG scans, during which they distinguished between standard words (SW), animal words (AW), and pseudowords (PW). Regions-of-interest (ROIs) were derived based on task effects detected in BOLD signal and aMEG theta power. BOLD signal and theta power were extracted for each ROI and word condition. Compared to TD participants, increased theta power in the ASD group was found across several time windows and regions including left fusiform and inferior frontal, as well as right angular and anterior cingulate gyri, whereas BOLD signal was significantly increased in the ASD group only in right anterior cingulate gyrus. No significant correlations were observed between BOLD signal and theta power. Findings suggest that the common interpretation of increases in BOLD signal and theta power as 'activation' require careful differentiation, as these reflect largely distinct aspects of regional brain activity. Some group differences in dynamic neural processing detected with aMEG that are likely relevant for lexical processing may be obscured by the hemodynamic signal source and low temporal resolution of fMRI.

Dynamic time warping outperforms Pearson correlation in detecting atypical functional connectivity in autism spectrum disorders.

Resting state fMRI (rsfMRI) is frequently used to study brain function, including in clinical populations. Similarity of blood-oxygen-level-dependent (BOLD) fluctuations during rsfMRI between brain regions is thought to reflect intrinsic functional connectivity (FC), potentially due to history of coactivation. To quantify similarity, studies have almost exclusively relied on Pearson correlation, which assumes linearity and can therefore underestimate FC if the hemodynamic response function differs regionally or there is BOLD signal lag between timeseries. Here we show in three cohorts of children, adolescents and adults, with and without autism spectrum disorders (ASDs), that measuring the similarity of BOLD signal fluctuations using non-linear dynamic time warping (DTW) is more robust to global signal regression (GSR), has higher test-retest reliability and is more sensitive to task-related changes in FC. Additionally, when comparing FC between individuals with ASDs and typical controls, more group differences are detected using DTW. DTW estimates are also more related to ASD symptom severity and executive function, while Pearson correlation estimates of FC are more strongly associated with respiration during rsfMRI. Together these findings suggest that non-linear methods such as DTW improve estimation of resting state FC, particularly when studying clinical populations whose hemodynamics or neurovascular coupling may be altered compared to typical controls.

CD11b expression on monocytes and data of inflammatory parameters after Transcatheter Aortic Valve Implantation in dependence of early mortality.

An inflammatory systemic reaction is common after Transcatheter Aortic Valve Implantation (TAVI). We recently reported about an involvement of Mon2-monocytes, the CD11b expression on monocytes and parameters of systemic inflammation before TAVI correlating with early mortality after TAVI. Here, we provide data of monocyte subpopulations, CD11b expression and parameters of a systemic inflammation in dependence of three-month mortality after TAVI. With this, we provide further insights into inflammatory mechanism after TAVI. The data were collected by flow-cytometric quantification analyses of peripheral blood in 120 consecutive patients who underwent TAVI (on day 1 and 7 after TAVI). Monocyte-subsets were identified by their CD14 and CD16 expression and monocyte-platelet-aggregates (MPA) by CD14/CD41 co-expression. The extent of monocyte activation was determined by quantification of CD11b-expression (activate epitope). Additionally, pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, C-reactive protein, procalcitonin were measured using the cytometric bead array method or standard laboratory tests. Additionally, we report procedural outcomes in dependence of three-month mortality. Furthermore, correlations of CD11b-expression on monocytes with parameters of platelet activation or further inflammatory parameters are presented. For further interpretation of the presented data, please see the research article "Mon2-Monocytes and Increased CD-11b Expression Before Transcatheter Aortic Valve Implantation are Associated with Earlier Death" by Pfluecke et al.[1].

Mon2-monocytes and increased CD-11b expression before transcatheter aortic valve implantation are associated with earlier death.

BACKGROUND: In the first three months after Transcatheter aortic valve implantation (TAVI), a remarkable number of patients have an unfavorable outcome. An inflammatory response after TAVI is suspected to have negative effects. The exact mechanisms remain unclear. We examined the influence of monocyte subpopulations on the clinical outcome, along with the degree of monocyte activation and further parameters of inflammation and platelet activation. METHODS: Flow-cytometric quantification analyses of peripheral blood were done in 120 consecutive patients who underwent TAVI (one day before TAVI and on day 1 and 7 after TAVI). Monocyte-subsets were defined by their CD14 and CD16 expression, monocyte-platelet-aggregates (MPA) by CD14/CD41 co-expression. The extent of monocyte activation was determined by quantification of CD11b-expression (activation epitope). Additionally, pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, C-reactive protein were measured with the cytometric bead array method or standard laboratory tests. RESULTS: Elevated Mon2 (CD14++CD16+) - monocytes (38 vs. 62 cells/µl, p < 0.001) and a high expression of CD11b prior to TAVI (MFI 50.1 vs. 84.6, p < 0.05) were independently associated with death 3 months after TAVI. Mon2 showed the highest CD11b-expression and CD11b correlated with platelet activation and markers of systemic inflammation. Even CRP and IL-8 before TAVI were associated with death after TAVI. In contrast, a systemic inflammation response shortly after TAVI was not associated with early death. CONCLUSIONS: Elevated Mon2-monocytes and a high level of monocyte activation before TAVI are associated with early mortality after TAVI. Chronic inflammation in aging patients seems to be an important risk factor after TAVI.

Sex-based differences in outcomes with bivalirudin or unfractionated heparin for transcatheter aortic valve replacement: Results from the BRAVO-3 randomized trial.

BACKGROUND: Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. RESULTS: The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. CONCLUSIONS: There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Effective diameter of the aortic annulus prior to transcatheter aortic valve implantation: influence of area-based versus perimeter-based calculation.

In computed tomography (CT) evaluation prior to transcatheter aortic valve implantation area- and perimeter-based calculation of the aortic annulus diameter, the so-called effective annulus diameter (ED), is the preferred parameter for decision making regarding prosthesis sizes. Currently, it is unclear how relevant the differences between the two methods of measurement are and how they are influenced by the cardiac cycle. The aim of this study was to compare area- and perimeter-based measurements in computed tomography derived aortic annulus sizing. A total of 60 patients who underwent evaluation for transcatheter aortic valve implantation were included in this study. All patients received pre-procedural ECG gated CT. The aortic annulus area and perimeter were measured and the derived ED compared using parametric statistics and Bland and Altman analysis. The mean patient age was 80.2 ± 4 years. Systolic aortic annulus area and perimeter were higher compared to diastolic results (mean difference area 12.8 ± 24 mm(2) and perimeter 0.72 ± 1 mm; p = 0.009-0.068). Both the area- and perimeter-based ED had a good agreement within two standard deviations for systolic and diastolic measurements. Effective diameter measurements derived from the area were significantly smaller compared to perimeter-based measurements (mean difference: systolic 0.72 ± 0.3 mm and diastolic 0.81 ± 0.4 mm; p < 0.001). While the area-based ED was significantly influenced by the cardiac cycle with a mean difference of 0.4 ± 0.6 mm (p = 0.009), no significant difference was found for the perimeter-based ED (mean difference: 0.2 ± 0.4; p = 0.07). For patients undergoing CT evaluation prior to transcatheter aortic valve implantation, the perimeter-based effective annulus diameter provides a reliable parameter for annulus sizing without significant affection by the cardiac cycle and therefore facilitates annulus measurements with a single heart phase. However, perimeter-based diameters of the annulus are significantly larger than area-based diameters.

[Imaging prior to transcatheter aortic valve implantation]. / Bildgebung vor Transkatheteraortenklappenersatz.

Percutaneous transcatheter aortic valve implantation (TAVI) is an established alternative to open heart surgery in patients with severe aortic stenosis (AS) unsuitable for conventional aortic valve replacement due to comorbidities with a high perioperative risk or contraindications. Preprocedural imaging plays a major role for adequate determination of indications and prosthesis selection, prosthesis sizing and therefore for a reduction of periprocedural complications. Besides Doppler echocardiography which is mainly used for grading of the severity of aortic valve stenosis and peri-interventional imaging, cardiac computed tomography (CCT) is the imaging modality of choice. The CCT procedure not only allows for reliably assessment and measuring of the complex 3-dimensional geometry of the aortic root but also for the aorta and the peripheral vessels used as potential access paths.

Role of preprocedural computed tomography in transcatheter aortic valve implantation.

UNLABELLED: Transcatheter aortic valve implantation (TAVI) is currently considered an acceptable alternative for the treatment of patients with severe aortic stenosis and a high perioperative risk or a contraindication for open surgery. The benefit of TAVI significantly outweighs the risk of the procedure in patients requiring treatment that are not suitable for open surgery, and leads to a lower mortality in the one-year follow-up. The absence of a direct view of the aortic root and valve remains a challenge for the transcatheter approach. While direct inspection of the aortic valve during open surgery allows an adequate prosthesis choice, it is crucial for TAVI to know the individual anatomical details prior to the procedure in order to assure adequate planning of the procedure and proper prosthesis choice and patient selection. Among the imaging modalities available for the evaluation of patients prior to TAVI, computed tomography (CT) plays a central role in patient selection. CT reliably visualizes the dimensions of the aortic root and allows a proper choice of the prosthesis size. The morphology of the access path and relevant comorbidities can be assessed. The present review summarizes the current state of knowledge regarding the value of CT in the evaluation of patients prior to TAVI. KEY POINTS: CT plays a central role in patient selection and planning prior to TAVI. ▶ CT reliably detects the dimensions of the aortic root including the size of the aortic annulus, the degree of valve calcification and the morphology of the access routes. ▶ CT provides a more accurate measurement of the aortic annulus than 2D TEE and CT is the only imaging modality that allows a risk assessment for paravalvular leakages based on the calcification of the aortic valve.

Echocardiography in transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) has become a feasible and effective therapeutic option for patients with severe aortic stenosis and high operative risk or relative contraindications for surgical aortic valve replacement (SAVR). Patient selection plays a crucial role in the success of TAVI. Echocardiography is a mainstay during the whole process starting with the very important morphological evaluation and accurate measurement of the aortic root, followed by guiding the procedure and detecting possible complications, and ending with serial assessment of the patient's heart and the implanted prosthesis. This present article reviews the role of echocardiography before, during, and after transcatheter aortic valve implantation.

Experience with anatomically orientated devices for transapical aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is a new technology, which is rapidly growing to a routine procedure amenable for patients with symptomatic aortic valve stenosis and higher than average risk for conventional aortic valve surgery. The crucial disadvantage of TAVI remains the not well foreseeable risk of more than trivial degree of paravalvular leakage and a high rate of atrioventricular block and consecutive pacemaker implantation. In addition, current implantation techniques do not allow controlling the rotation of first-generation devices that might be beneficial regarding optimal physiological valve performance, optimal coronary flow and avoidance of placement of covered commissures in front of the coronary ostia. These shortcomings had pushed the development of second-generation self-expandable nitinol-based devices for subcoronary implantation that aim a reduction of paravalvular leak and AV-block by anatomical orientated positioning into the aortic root. This review focuses on the description of three different TAVI concepts, which are presently under early clinical evaluation, or have recently received commercial approval, using the transapical approach.

Impact of coronary artery disease on in-hospital mortality in patients with aortic valve disease. Results from the German ALKK registry.

OBJECTIVE: Although aortic valve disease (AVD) is frequently associated with coronary artery disease (CAD), little is known about the impact of significant coronary artery disease on mortality after diagnostic cardiac catheterization in patients with AVD. METHODS: We analyzed data of the coronary angiography registry of the "Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte" (ALKK) in Germany. The primary endpoint was in-hospital mortality. RESULTS: A total of 1427 consecutive patients with AVD (438 patients with CAD versus 989 patients without CAD) underwent diagnostic catheterization in 2006 in 42 hospitals. All cause in-hospital mortality was more than threefold higher in patients with CAD (16/438; 3.7%) as compared to patients without CAD (12/989; 1.2%; p < 0.01; OR 3.09, 95% CI 1.45-6.58). Even after adjustment for age, sex, presence of diabetes mellitus and renal insufficiency, in-hospital all cause mortality remained statistically significant different between the two groups (OR 2.4; 95% CI 1.09-5.28; p < 0.01). Several factors, such as transient ischemic attack/stroke, volume of contrast agent, and left heart catheter-associated complications could not be identified as possible causes for the increase in mortality. CONCLUSION: This analysis in patients with the leading diagnosis of AVD shows a significantly higher in-hospital mortality after diagnostic cardiac catheterization in case of an accompanying CAD. However, further studies are necessary to identify the driving force for the increase in mortality.

Role of preprocedural computed tomography in transcatheter aortic valve implantation.

UNLABELLED: Transcatheter aortic valve implantation (TAVI) is currently considered an acceptable alternative for the treatment of patients with severe aortic stenosis and a high perioperative risk or a contraindication for open surgery. The benefit of TAVI significantly outweighs the risk of the procedure in patients requiring treatment that are not suitable for open surgery, and leads to a lower mortality in the one-year follow-up. The absence of a direct view of the aortic root and valve remains a challenge for the transcatheter approach. While direct inspection of the aortic valve during open surgery allows an adequate prosthesis choice, it is crucial for TAVI to know the individual anatomical details prior to the procedure in order to assure adequate planning of the procedure and proper prosthesis choice and patient selection. Among the imaging modalities available for the evaluation of patients prior to TAVI, computed tomography (CT) plays a central role in patient selection. CT reliably visualizes the dimensions of the aortic root and allows a proper choice of the prosthesis size. The morphology of the access path and relevant comorbidities can be assessed. The present review summarizes the current state of knowledge regarding the value of CT in the evaluation of patients prior to TAVI. CT plays a central role in patient selection and planning prior to TAVI. CT reliably detects the dimensions of the aortic root including the size of the aortic annulus, the degree of valve calcification and the morphology of the access routes. KEY POINTS: CT plays a central role in patient selection and planning prior to TAVI. CT reliably detects the dimensions of the aortic root including the size of the aortic annulus, the degree of valve calcification and the morphology of the access routes. CT provides a more accurate measurement of the aortic annulus than 2D TEE and CT is the only imaging modality that allows a risk assessment for paravalvular leakages based on the calcification of the aortic valve.

A portable Compton spectrometer for clinical X-ray beams in the energy range 20-150 keV.

Primary beam spectra were obtained for an X-ray industrial equipment (40-150 kV), and for a clinical mammography apparatus (25-35 kV) from beams scattered at angles close to 90°, measured with a CdTe Compton spectrometer. Actual scattering angles were determined from the Compton energy shift of characteristic X-rays or spectra end-point energy. Evaluated contribution of coherent scattering amounts to more than 15% of fluence in mammographic beams. This technique can be used in clinical environments.

Encoding strategy accounts for individual differences in change detection measures of VSTM.

Visual short-term memory (VSTM) capacity is often assessed using change detection tasks, and individual differences in performance have been shown to predict cognitive aptitudes across a range of domains in children and adults. We recently showed that intelligence correlates with an attentional component necessary for change detection rather than with memory capacity per se (Cusack, Lehmann, Veldsman, & Mitchell, 2009). It remained unclear, however, whether different attentional strategies during change detection have most impact during the encoding or maintenance of information. Here we present recent findings from our laboratory supporting the hypothesis that attentional selection during encoding dominates individual differences in change detection measures of visual short-term memory. In a first study, we unpredictably varied whether short-term memory was probed using change detection or whole report, encouraging participants to adopt the same encoding strategy throughout the tasks. Change detection performance of lower-IQ individuals improved. In a second study, we found that deficits in top-down attentional selectivity can be alleviated in participants with low change detection performance by providing helpful grouping information during encoding. Finally, a meta-analysis of neuroimaging data from 112 participants performing a variety of VSTM tasks showed that performance correlates with activity in several parietal and frontal regions during the encoding but not the maintenance phase. Taken together, these results support the notion that encoding strategy and not short-term memory capacity itself largely determines individual differences in visual change detection performance.

Metabolic profile and nitric oxide synthase expression of skeletal muscle fibers are altered in patients with type 1 diabetes.

We investigate muscle fiber composition, fiber-specific glycolytic and oxidative enzyme capacity and nitric oxide synthase (NOS) expression in skeletal muscle of patients with type 1 diabetes (T1D) compared to individuals with normal glucose tolerance (NGT). Vastus lateralis muscle was obtained by percutaneous biopsy from 7 T1D patients and 10 healthy controls with similar characteristics. Using cytophotometry, muscle fiber composition and fiber type-specific glycolytic and oxidative enzyme activities were measured in slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers. In addition, NOS 1-3 protein expression was mea-sured. The glycolytic fiber fraction was 1.4 fold higher, whereas FOG and SO fiber fractions were significantly reduced by 13.5% and 6.2% in skeletal muscle from T1D patients. Glycolytic enzyme activities and fiber-specific ratio of glycolytic relative to oxidative enzyme activity were significantly higher in all fiber types of T1D patients and correlated with HbA (1c). Expression of NOS1-3 isoforms was reduced in skeletal muscle of T1D subjects. Increased glycolytic enzyme activity in muscle of T1D patients is most likely due to both a higher number of fast glycolytic fibers and a shift towards increased glycolytic metabolism in all fiber types. Alterations in muscle fiber distribution and enzyme activities seem to be due to impaired long-term glycemic control.

Adipokines in diabetes and cardiovascular diseases.

Recent studies suggest that adipocyte-secreted factors called adipokines are involved in obesity-associated complications including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Among those, adiponectin is an antidiabetic and antiatherogenic protein, concentrations of which are decreased in obesity-associated metabolic and vascular disorders. In contrast, leptin, tumor necrosis factor a, interleukin-6, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1 are upregulated in obesity and contribute to the development of diabetes and vascular disease. In this review, the relevance of adipokines in obesity, insulin resistance, diabetes mellitus, atherosclerosis, and cardiovascular diseases is discussed.

Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia.

AIMS: Despite considerable advances in the therapy of patients with peripheral arterial occlusive disease (PAOD) and critical limb ischaemia (CLI), a substantial number remain, in whom amputation has to be considered the only and final option. Recent evidence from animal models of hind limb ischaemia suggests that neovascularization induced by circulating blood-derived progenitor cells (CPCs) may permit limb salvage. It remains unclear, however, whether an intra-arterial application of autologous CPCs in patients with infrapopliteal PAOD and CLI is safe, feasible, and of potentially beneficial effects. METHODS AND RESULTS: Seven patients with critical PAOD were treated with an intra-arterial infusion of autologous CPCs (39+/-24 x 10(6)) isolated from peripheral blood. Pre-interventional stimulation with G-CSF and CPC application was well tolerated. Twelve weeks after CPC administration, the pain-free walking distance increased from 6+/-13 to 195+/-196 m. A significant increase in the ankle-brachial index, transcutaneous O(2), flow-dependent vasodilation, flow reserve in response to adenosine, and endothelium-dependent vasodilation was observed. CONCLUSION: These preliminary data in a small series of patients with CLI without surgical or interventional options indicate that CPC application is safe, feasible, and may improve both functional and clinical indices.

[Physical exercise in older patients with chronic heart failure]. / Körperliche Aktivität bei älteren Patienten mit chronischer Herzinsuffizienz.

Maximal exercise capacity undergoes a steady decline after the age of 30 by approximately 10 % per decade. As a consequence of this development older people > 65 years of age suffer from the exercise limitation caused by age-associated cardiac, vascular and skeletal muscle changes. These physiologic alterations make older people especially vulnerable for the cardiovascular and peripheral alterations associated with chronic heart failure (CHF). These changes are not phenomenologically different from age-associated changes. Physical activity plays an important role for regaining a considerable part of vasomotor function, skeletal muscle contractility, and cardiac reserve. Up to now there are no prospective trials comparing the effects of physical training between older and younger patients with CHF. However, smaller observational studies indicate that elderly patients benefit equally well from training interventions with regard to functional improvements in proportion to their lower baseline values. In an aging population training aims at maintaining skeletal muscle force and muscle mass as well as locomotor coordination. Ultimately, the goal is to reduce the substantial morbidity among elderly CHF patients which constitute 79 % of all hospital admissions for heart failure.