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BackgroundSimultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) is a novel hybrid imaging method integrating the advances of morphological tissue characterization of MRI with the pathophysiological insights of PET applications.AimThis study evaluated the use of simultaneous 18-FDG PET/MR imaging for characterizing atherosclerotic lesions in lower extremity arterial disease (LEAD).MethodsEight patients with symptomatic stenoses of the superficial femoral artery (SFA) under simultaneous acquisition of 18-FDG PET and contrast-enhanced MRI using an integrated whole-body PET/MRI scanner. Invasive plaque characterization of the SFA was performed by intravascular imaging using optical coherence tomography. Histological analysis of plaque specimens was performed after directional atherectomy.ResultsMRI showed contrast enhancement at the site of arterial stenosis, as assessed on T2-w and T1-w images, compared to a control area of the contralateral SFA (0.38 ± 0.15 cm vs. 0.23 ± 0.11 cm; 1.77 ± 0.19 vs. 1.57 ± 0.15; p-value 1) at the level of symptomatic stenosis was observed in all but one patient. Contrast medium-induced MR signal enhancement was detected in all plaques, whereas FDG uptake in PET imaging was increased in lesions with active fibroatheroma and reduced in fibrocalcified lesions.ConclusionIn this multimodal imaging study, we report the feasibility and challenges of simultaneous PET/MR imaging of LEAD, which might offer new perspectives for risk estimation.

Background Stent underexpansion has been known to be associated with worse outcomes. We sought to define optical coherence tomography assessed optimal stent expansion index (SEI), which associates with lower incidence of follow‐up major adverse cardiac events (MACEs). Methods and Results A total of 315 patients (involving 370 lesions) who underwent optical coherence tomography–aided coronary stenting were retrospectively included. SEI was calculated separately for equal halves of each stented segment using minimum stent area/mean reference lumen area ([proximal reference area+distal reference area]/2). The smaller of the 2 was considered to be the SEI of that case. Follow‐up MACE was defined as a composite of all‐cause death, myocardial infarction, stent thrombosis, and target lesion revascularization. Average minimum stent area was 6.02 (interquartile range, 4.65–7.92) mm2, while SEI was 0.79 (interquartile range, 0.71–0.86). Forty‐seven (12.7%) incidences of MACE were recorded for 370 included lesions during a median follow‐up duration of 557 (interquartile range, 323–1103) days. Receiver operating characteristic curve analysis identified 0.85 as the best SEI cutoff (

Abstract Adeno‐associated viruses (AAVs) are frequently used for gene transfer and gene editing in vivo, except for endothelial cells, which are remarkably resistant to unmodified AAV‐transduction. AAVs are retargeted here toward endothelial cells by coating with second‐generation polyamidoamine dendrimers (G2) linked to endothelial‐affine peptides (CNN). G2CNN AAV9‐Cre (encoding Cre recombinase) are injected into mTmG‐mice or mTmG‐pigs, cell‐specifically converting red to green fluorescence upon Cre‐activity. Three endothelial‐specific functions are assessed: in vivo quantification of adherent leukocytes after systemic injection of ‐ G2CNN AAV9 encoding 1) an artificial adhesion molecule (S1FG) in wildtype mice (day 10) or 2) anti‐inflammatory Annexin A1 (Anxa1) in ApoE−/− mice (day 28). Moreover, 3) in Cas9‐transgenic mice, blood pressure is monitored till day 56 after systemic application of G2CNN AAV9‐gRNAs, targeting exons 6–10 of endothelial nitric oxide synthase (eNOS), a vasodilatory enzyme. G2CNN AAV9‐Cre transduces microvascular endothelial cells in mTmG‐mice or mTmG‐pigs. Functionally, G2CNN AAV9‐S1FG mediates S1FG‐leukocyte adhesion, whereas G2CNN AAV9‐Anxa1‐application reduces long‐term leukocyte recruitment. Moreover, blood pressure increases in Cas9‐expressing mice subjected to G2CNN AAV9‐gRNAeNOS. Therefore, G2CNN AAV9 may enable gene transfer in vascular and atherosclerosis models.

Subjective cognitive decline (SCD) patients are considered as a risk population for preclinical Alzheimer's Disease (AD). Supporting this idea, previous studies in SCD populations report subtle alterations in various cognitive and neuroimaging biomarkers that are typically affected during AD progression. To extend these observations, the present study examined whether SCD patients show atrophy of cholinergic basal forebrain nuclei (chBFN), analogous with recent findings in prodromal and clinical AD patients. We assessed volume reductions of the chBFN in 24 SCD subjects compared to 49 matched controls on 3D-T1-weighted MR images based on a postmortem derived atlas. Furthermore, we assessed whether chBFN atrophy was linked with cognitive, structural and metabolic biomarker alterations we previously reported in this SCD cohort: Using correlation analyses we tested for associations between the volumes of the chBFN with the hippocampal gray matter volume, and posterior medial glucose consumption, and the trajectory of verbal memory performance. The SCD cases showed a significant total volume reduction of the chBFN, with largest effect sizes in the Ch1/2 and Ch4p subdivisions of the chBFN. The latter was associated with a reduced glucose metabolism in the precuneus for the SCD group only. These data show an early involvement of the cholinergic basal forebrain nuclei in SCD predominantly in Ch1/2 and Ch4p which supports the conceptual link between SCD and preclinical AD. Keywords: Basal forebrain, Subjective cognitive decline, Nucleus basalis Meynert, Glucose metabolism, Precuneus, Alzheimer

Background: Oxidative stress, inflammation, and endothelial dysfunction represent a key triad for the development and progression of atherosclerosis. Due to chronic low-grade inflammation in chronic kidney disease (CKD), concentrations of various inflammatory, endothelial, and oxidative stress markers are elevated, increasing the risk of atherosclerosis. The present study was undertaken to compare oxidative stress, inflammation, and endothelial dysfunction in diabetic and nondiabetic CKD pre-dialysis patients. Materials and Methods: This was an observational study on 120 CKD pre-dialysis patients: 60 with diabetes and 60 without diabetes. Markers of oxidative stress were measured in blood -- malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), paroxonase-1 (PON-1), ischemia-modified albumin (IMA); inflammation -- interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP); and endothelial dysfunction -- nitric oxide (NO), carotid wall intima--media thickness (CIMT). Comparisons between the two groups for continuous variables were made with the Student's unpaired t-test or Mann--Whitney test and for categorical values with χ²-test, as appropriate. Results: MDA, IMA, IL-6, hsCRP, NO, and CIMT were significantly higher, while FRAP and PON-1 were significantly lower in the diabetic group when compared to nondiabetic group (P < 0.001). The number of atherosclerotic plaques was also significantly higher in the diabetic group compared to nondiabetic group. Conclusion: Our study showed increased oxidative stress, inflammation, endothelial dysfunction, and atherosclerosis in diabetic CKD pre-dialysis patients when compared to nondiabetic CKD pre-dialysis patients and in late stages when compared to early stages of CKD in both groups, indicating increased cardiovascular risk in late stages and diabetic CKD pre-dialysis patients. [ABSTRACT FROM AUTHOR]

Abstract Background Our objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. Methods Cognitively normal elderly participants of the German Study on Ageing, Cognition, and Dementia study (N = 2330) with SCD (subjective decline in memory with and without associated concerns) and without SCD at baseline were assessed over 8 years with regard to immediate and delayed verbal recall, verbal fluency, working memory, and global cognition. Baseline performance and cognitive trajectories were compared between groups. In addition, cognitive trajectories before and after the initial report of SCD (incident SCD) were modelled in those without SCD at baseline. Results Baseline performance in the SCD group was lower and declined more steeply in immediate and delayed verbal recall than in the control group (no SCD at baseline). This effect was more pronounced in the SCD group with concerns. Incident SCD was preceded by decline in immediate and delayed memory and word fluency. Conclusions SCD predicts future memory decline. Incident SCD is related to previous cognitive decline. The latter finding supports the concept of SCD indicating first subtle decline in cognitive performance that characterizes preclinical Alzheimer's disease.

Oscar D Sanchez, Kazuyuki Yahagi, Tobias Koppara, Renu Virmani, Michael Joner CVPath Institute, Inc., Gaithersburg, MD, USA Abstract: Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. The pathogenesis of CAD relates to the presence of atherosclerotic plaques in the coronary arteries, which are most frequently treated today by percutaneous coronary intervention. Small vessel disease treatment represents one-third of all percutaneous coronary interventions with higher rates of restenosis and major adverse cardiac events. Initially, drug-eluting stents (DES) were developed to reduce in-stent restenosis, improving clinical outcomes and reducing the need for target vessel revascularization. However, late and very late stent thrombosis emerged as a new problem compromising DES's long-term results. The cobalt–chromium everolimus-eluting stent (CoCr-EES) represents the results of an evolutionary process in DES technology aimed at improving the shortcomings of first-generation DES. Small vessel CAD has historically been an obstacle to long-term patency following implantation of DES. Antirestenotic efficacy has been shown to be of high relevance in small vessels. Therefore, stent selection may play an important role in determining outcomes in this subgroup of patients. This article will review the performance of CoCr-EES in the treatment of small vessel CAD from preclinical, clinical, and pathology perspectives, and it will highlight the most important findings in this regard. Keywords: small vessel, cobalt–chromiun everolimus-eluting stent, Xience V, pathology

OBJECTIVE:Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. METHODS:Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. RESULTS:Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. CONCLUSION:Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.