Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study.

Aims: The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). Methods and results: In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German population-based cohorts. Using log-binomial regression models, an increased risk for occurrence of arterial hypertension [relative risk (RR) 1.38, 95% confidence interval (95% CI 1.21-1.57)] and dyslipidaemia [RR 1.26 (95% CI 1.12-1.42)] was found. This indicates a premature occurrence compared to the general population of approximately 6 and 8 years, respectively [rate advancement period estimator, RAPhypertension 5.75 (95% CI 3.5-8.0) and RAPdyslipidaemia 8.16 (95% CI 4.4-11.9)]. Overall, no differences were observed for obesity and diabetes. Overt CVD was present in 4.5% (95% CI 3.0-6.6%) of CCS [RR 1.89 (95% CI 1.34-2.66), RAPCVD 7.9 (95% CI 4.1-11.7)], of which the most frequent entities were congestive heart failure and venous thromboembolism. Prevalences of CVRF and CVD increased with age without reaching a plateau over time. Conclusion: This large CCS screening examination revealed consistently in comparison to three population samples a considerably increased risk for premature CVD. The findings in these young adult CCS indicate a high burden of cardiovascular morbidity and mortality in the long term. Clinicaltrials. gov-Nr: NCT02181049.

Leukoaraiosis Attenuates Diagnostic Accuracy of Large-Vessel Occlusion Scales.

BACKGROUND AND PURPOSE: Prehospital stroke scales may help identify patients likely to have large-vessel occlusion to facilitate rapid triage to thrombectomy-capable stroke centers. Scale misclassification may result in inaccurate decisions and possible harm. Pre-existing leukoaraiosis has been shown to attenuate the association between deficit type and stroke severity. We sought to determine whether leukoaraiosis affects the predictive ability of 5 commonly used large-vessel occlusion scales. MATERIALS AND METHODS: We retrospectively analyzed 274 consecutive patients with stroke with available brain MR imaging and vessel imaging. We used the following large-vessel occlusion scales: the 3-Item Stroke Scale; Field Assessment Stroke Triage for Emergency Destination; Rapid Arterial Occlusion Evaluation; Vision, Aphasia, Neglect score; and Cincinnati Prehospital Stroke Severity Scale. For diagnostic scale accuracy, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and κ. Multivariable logistic regression was used to determine the predictive ability of the scales after adjustment for leukoaraiosis and potential confounders. RESULTS: In unadjusted analyses, all scales predicted the presence of large-vessel occlusion (n = 46, P < .01 each), though diagnostic accuracy was attenuated among patients with moderate-to-severe leukoaraiosis. After adjustment, the Field Assessment Stroke Triage for Emergency Destination (OR = 3.2; 95% CI, 1.1-9.5; P = .033) and Rapid Arterial Occlusion Evaluation (OR = 3.7; 95% CI, 1.3-10.8; P = .015), but not the 3-Item Stroke Scale (OR = 5.4; 95% CI, 0.86-33.9; P = .073), Vision, Aphasia, Neglect score (OR = 2.5; 95% CI, 0.8-7.2), and Cincinnati Prehospital Stroke Severity Scale (OR = 2.8; 95% CI, 1.0-8.0), predicted large-vessel occlusion. CONCLUSIONS: The diagnostic accuracy of the tested large-vessel occlusion scales was attenuated in the presence of moderate-to-severe leukoaraiosis. This information that may aid the design of future studies that require large-vessel occlusion scale screening of patients who are likely to have concomitant leukoaraiosis.

White matter hyperintensity lesion burden is associated with the infarct volume and 90-day outcome in small subcortical infarcts.

OBJECTIVES: Small subcortical infarcts (SSI) frequently coexist with brain white matter hyperintensity (WMH) lesions. We sought to determine whether preexisting WMH burden relates to SSI volume, SSI etiology, and 90-day functional outcome. MATERIALS AND METHODS: We retrospectively studied 80 consecutive patients with acute SSI. Infarct volume was determined on diffusion weighted imaging, and WMH burden was graded on fluid-attenuated inversion recovery sequences according to the Fazekas scale. SSI etiology was categorized as small vessel disease (SVD) vs non-SVD related. Multivariable linear and logistic regression models were constructed to determine whether WMH burden was independently associated with the SSI volume and a poor 90-day outcome (modified Rankin scale [mRS] score >2), respectively. RESULTS: In unadjusted analyses, patients with non-SVD-related SSI were older (P=.002) and more frequently had multiple infarcts (P<.001) than patients with SVD-related SSI. In the fully adjusted model, WMH severity (Coefficient 0.07; 95%-CI 0.029-0.117; P=.002) but not SSI etiology (P>.1) was independently associated with the SSI volume. On multivariable logistic regression, worse WMH (OR 2.28; 95%-CI 1.04-4.99; P=.040), SSI etiology (OR 9.20; 95%-CI 1.04-81.39; P=.046), preadmission mRS (OR 8.96; 95%-CI 2.65-30.27; P<.001), and SSI volume (OR 1.98; 95%-CI 1.14-3.44; P=.016) were associated with a poor 90-day outcome. CONCLUSIONS: Greater WMH burden is independently associated with a larger SSI volume and a worse 90-day outcome.

Leukoaraiosis predicts a poor 90-day outcome after endovascular stroke therapy.

BACKGROUND AND PURPOSE: Leukoaraiosis is a common finding among patients with ischemic stroke and has been associated with poor stroke outcomes. Our aim was to ascertain whether the severity of pre-existing leukoaraiosis is associated with outcome in patients with acute ischemic stroke who are treated with endovascular stroke therapy. MATERIALS AND METHODS: We retrospectively analyzed data from 129 consecutive, prospectively enrolled patients with stroke undergoing endovascular stroke therapy at a single tertiary care center between January 2006 and August 2013. Leukoaraiosis was assessed as supratentorial white matter hypoattenuation on admission head CT and graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. We dichotomized the 90-day mRS into good (0-2 or return to baseline) versus poor (3-6) as the primary study outcome. Incremental multivariable logistic regression analyses were performed to identify independent predictors of a poor 90-day outcome. RESULTS: In all multivariable models, severe leukoaraiosis was independently (P < .05) associated with a poor outcome at 90 days (fully adjusted model: OR, 6.37; 95% CI, 1.83-12.18; P = .004). The independent association between leukoaraiosis and a poor outcome remained when the analysis was restricted to patients who were alive at discharge (n = 87, P < .05). Last, among patients who were alive at discharge, those with severe leukoaraiosis had significantly less frequent improvement on the mRS from discharge to 90 days compared with patients with absent-to-moderate leukoaraiosis (P = .034). CONCLUSIONS: The severity of pre-existing leukoaraiosis is independently associated with 90-day functional outcome in patients with stroke who underwent endovascular stroke therapy. These results highlight the need to further explore leukoaraiosis as a promising surrogate marker for poor outcome after endovascular stroke therapy to improve risk assessment, patient selection, and early prognostic accuracy.

Spatial learning induces predominant downregulation of cytosolic proteins in the rat hippocampus.

Spatial learning is known to depend on protein synthesis in the hippocampus. Whereas the role of the hippocampus in spatial memory is established, the biochemical and molecular mechanisms underlying this process are poorly understood. To comprehend the complex pattern of protein expression induced by spatial learning, we analyzed alterations in the rat hippocampus proteome after 7 days of spatial learning in the Morris water maze. Forty Wistar rats were randomized into two groups. Animals of group A learned to localize a hidden platform in the water maze. Animals of group B served as controls and spent exactly the same time in the water maze as animals of group A. However, no platform was used in this test and the rats could not learn to localize the target. After the last trial, hydrophilic proteins from the hippocampus were isolated. A proteome-wide study was performed, based on two-dimensional gel electrophoresis and mass spectrometry. Compared with non-learning animals, 53 (70%) proteins were downregulated and 23 (30%) proteins were upregulated after 7 days in rats with spatial learning. The overall changes in protein expression, as quantified by the induction factor, ranged from -1.62 (downregulation to 62%) to 2.10 (upregulation by 110%) compared with controls (100%). Most identified proteins exhibit known functions in vesicle transport, cytoskeletal architecture, and metabolism as well as neurogenesis. These findings indicate that learning in the Morris water maze has a morphological correlate on the proteome level in the hippocampus.

The utility of the Fear Survey Schedule-III: an extended replication.

This investigation examined the factor structure of the Fear Survey Schedule-III in patients with specific anxiety disorders, including patients with panic disorder, agoraphobia without panic, generalized anxiety disorder, social phobia, specific phobia, obsessive compulsive disorder, post traumatic stress disorder, and anxiety disorder NOS. Four factors were obtained, reflecting a similar structure as has been noted in other studies. However, the ability of the obtained factors to discriminate among patients with panic disorder, social phobia, and specific phobia was not high. Future directions are highlighted.