Lifetime ADHD symptoms highly prevalent in women with cardiovascular complaints. A cross-sectional study.

Patients with Attention Deficit Hyperactivity Disorder (ADHD) are at greater cardiovascular risk. We investigated the association between ADHD symptoms and cardiovascular disease in women at a specialized Dutch cardiological clinic. Lifetime ADHD symptoms were found in 35% of women (n = 300) with cardiac complaints. Women with ADHD symptoms compared to those without were significantly younger but had no different cardiological profile. To protect women's health, further research and multidisciplinary cooperation is required to better understand the relationship between ADHD and cardiovascular disease.

Coexistence of malnutrition, frailty, physical frailty and disability in patients with COPD starting a pulmonary rehabilitation program.

BACKGROUND & AIMS: Malnutrition, frailty, physical frailty, and disability are common conditions in patients with chronic obstructive pulmonary disease (COPD). Insight in the coexistence and relations between these conditions may provide information on the nature of the relationship between malnutrition and frailty. Such information may help to identify required interventions to improve the patient's health status. We therefore aimed to explore whether malnutrition, frailty, physical frailty, and disability coexist in patients with COPD at the start of pulmonary rehabilitation. METHODS: For this cross-sectional study, from March 2015 to May 2017, patients with COPD were assessed at the start of a pulmonary rehabilitation program. Nutritional status was assessed with the Scored Patient-Generated Subjective Global Assessment (PG-SGA) based Pt-Global app. Frailty was assessed by the Evaluative Frailty Index for Physical activity (EFIP), physical frailty by Fried's criteria, and disability by the Dutch version of World Health Organization Disability Assessment Schedule 2.0 (WHODAS). These variables were dichotomized to determine coexistence of malnutrition, frailty, physical frailty, and disability. Associations between PG-SGA score and respectively EFIP score, Fried's criteria, and WHODAS score were analyzed by Pearson's correlation coefficient. Two tailed P-values were used, and significance was set at P < 0.05. RESULTS: Of the 57 participants included (age 61.2 ± 8.7 years), malnutrition and frailty coexisted in 40%. Malnutrition and physical frailty coexisted in 18%, and malnutrition and disability in 21%. EFIP score and PG-SGA score were significantly correlated (r = 0.43, P = 0.001), as well as Fried's criteria and PG-SGA score (r = 0.37, P = 0.005). CONCLUSIONS: In this population, malnutrition substantially (40%) coexists with frailty. Although the prevalence of each of the four conditions is quite high, the coexistence of all four conditions is limited (11%). The results of our study indicate that nutritional interventions should be delivered by health care professionals across multiple disciplines.

Diagnostic performance of MRI for assessment of response to neoadjuvant chemoradiotherapy in oesophageal cancer.

BACKGROUND: Patients with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer may benefit from non-surgical management. The aim of this study was to determine the diagnostic performance of visual response assessment of the primary tumour after nCRT on T2-weighted (T2W) and diffusion-weighted (DW) MRI. METHODS: Patients with locally advanced oesophageal cancer who underwent T2W- and DW-MRI (1·5 T) before and after nCRT in two hospitals, between July 2013 and September 2017, were included in this prospective study. Three radiologists evaluated T2W images retrospectively using a five-point score for the assessment of residual tumour in a blinded manner and immediately rescored after adding DW-MRI. Histopathology of the resection specimen was used as the reference standard; ypT0 represented a pCR. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and interobserver agreement were calculated. RESULTS: Twelve of 51 patients (24 per cent) had a pCR. The sensitivity and specificity of T2W-MRI for detection of residual tumour ranged from 90 to 100 and 8 to 25 per cent respectively. Respective values for T2W + DW-MRI were 90-97 and 42-50 per cent. AUCs for the three readers were 0·65, 0·66 and 0·68 on T2W-MRI, and 0·71, 0·70 and 0·70 on T2W + DW-MRI (P = 0·441, P = 0·611 and P = 0·828 for readers 1, 2 and 3 respectively). The κ value for interobserver agreement improved from 0·24-0·55 on T2W-MRI to 0·55-0·71 with DW-MRI. CONCLUSION: Preoperative assessment of residual tumour on MRI after nCRT for oesophageal cancer is feasible with high sensitivity, reflecting a low chance of missing residual tumour. However, the specificity was low; this results in overstaging of complete responders as having residual tumour and, consequently, overtreatment.

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study.

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .

Evaluation of peri-tumoral vessels surrounding colorectal liver metastases after intravenous injection of extruded magnetoliposomes in rats: correlation with 3T MRI and histopathology.

BACKGROUND: Magnetoliposomes have pronounced signal-enhancing effect on T1-weighted (T1w) images of the liver using qualitative analysis which may be benefical for demonstrating peritumoral vasculature. PURPOSE: To correlate peri-tumoral vasculature (ring-enhancement) surrounding colorectal liver metastases after injection of magnetoliposomes using T1-weighted (T1w) imaging with histopathology in a rat model. MATERIAL AND METHODS: All experiments were approved by the responsible Animal Care Committee. Three rats injected with CC531 coloncarcinoma cells in the portal vein were imaged at 3T using a small diameter four channel coil. The presence of liver metastases, signal intensity changes within intrahepatic vessels, peri-tumoral vasculature (ring-enhancement) surrounding liver metastases on T1w imaging and histopathology, and the histopathological distribution of iron particles were evaluated. SS SE-EPI and T1w GE sequences were used. Images were evaluated qualitatively and MRI findings were correlated with histopathology. RESULTS: Fifteen liver metastases were present which were all detected at MRI (mean diameter 2.4 mm (SD 0.8 mm, range 1.5-4.7 mm)). Ring-enhancement surrounding liver metastases at contrast-enhanced T1w GE sequences was present in all liver metastases. Correlation with histopathology showed the corresponding presence of dilated sinusoids filled with iron particles surrounding the liver metastases. CONCLUSION: Blood-pooling of iron oxide particles within magnetoliposomes was demonstrated with increased and hyperintensity of vessels after injection of magnetoliposomes. Qualitatively, ring-enhancement surrounding the liver metastases was seen on T1w imaging and corresponded histopathologically with the presence of iron particles (magnetoliposomes) within the dilated sinusoids surrounding the liver metastases.

MRS-lateralisation index in patients with epilepsy and focal cortical dysplasia or a MEG-focus using bilateral single voxels.

PURPOSE: To evaluate if single voxel proton magnetic resonance spectroscopy (SV-MRS) can help in lateralising and sometimes in localizing an epileptogenic focus. The assumption is that in MRI negative patients the underlying pathology most often is focal cortical dysplasia (FCD). Several studies have shown that in the presence of FCD there are also (1)H-MRS abnormalities on the contralateral side. However, in most cases the studied group was not homogeneous and included different forms of dysplasias, including band heterotopias and polymicrogyria, and the studies used different spectroscopy protocols. In the present study, using bilateral SV-MRS we investigated the presence of a lateralisation index in two groups of patients with localisation related epilepsy: patients with focal cortical dysplasia on MRI and patients without MRI abnormalities with a focus identified by MEG. Aim of the study was to show that in both groups the expected epileptogenic side shows more pronounced metabolic alterations, making MRS a possible screening tool for clarifying lateralisation questions in patients with cryptogenic localisation related epilepsy. METHODS: In ten patients a single voxel was placed over the FCD and in nine patients over the region of interest (ROI) as indicated by MEG. In all patients a voxel was also placed in the contralateral homologus location. We used metabolite concentrations as peak ratios relative to the creatine (Cr) peak to calculate a lateralisation index. RESULTS: In both groups NAA/Cr was significantly lower on the affected side whereas the results for Cho/Cr were more diverse. There were no significant differences between the two groups. The limitations of the used methods and the implications of the findings are discussed.

Comparison of respiratory-triggered T2-weighted turbo spin-echo imaging versus breath-hold T2-weighted turbo spin-echo imaging: distinguishing benign from malignant liver lesions in patients with colorectal cancer.

T2-weighted turbo spin echo sequences are being used as a first sequence for abdominal magnetic resonance imaging in many cases. For oncological patients breath-hold imaging can be difficult. T2-weighted turbo spin echo sequences can be used during breath-hold or during respiratory-triggering. The purpose of our study is to compare a respiratory-triggered fat-suppressed and breath-hold T2-weighted Turbo Spin Echo (RT and BH FS T2w TSE) sequence for focal liver lesions. Prospectively, both T2w TSE sequences were acquired in 40 patients using 1.5T MRI. Qualitatively analysis was performed for image quality, lesion conspicuity, diagnostic confidence, artifacts using two-tailed Wilcoxon signed-ranks test. Quantitative analysis was performed for lesion-to-liver Contrast-to-Noise Ratio (CNR) using two-tailed Student's t-test. Qualitatively, RT FST2wTSE performed significantly (p < 0.05) better than BH FST2wTSE concerning image quality, lesion conspicuity, diagnostic confidence and artifacts. Seventy-eight metastases and 47 hemangiomas were detected on both FST2wTSE sequences. Seven liver metastases and 2 hemangiomas < 10 mm and 3 metastases between 10-20 mm detected on RT FS T2wTSE were only retrospectively detected on BH FS T2wTSE. Diagnostic confidence scores were best using RT FS T2w TSE compared with BH FS T2w TSE. Mean CNR of all lesions, mean CNR of all lesions < 10 mm and mean CNR between hemangiomas and metastases was significantly better using the RT sequence compared with the BH sequence. RT FST2wTSE might perform better than BH FST2wTSE for lesion detection and characterization in this study.

Improved focal liver lesion detection: comparison of single-shot diffusion-weighted echoplanar and single-shot T2 weighted turbo spin echo techniques.

The purpose of this study was to compare diffusion-weighted respiratory-triggered single-shot spin echo echoplanar imaging (SS SE-EPI) sequence using four b-values (b = 0, b = 20, b = 300, b = 800 s mm(-2)) and single-shot T2 weighted turbo spin echo (T2W SS TSE) in patients with focal liver lesions, with special interest in small (<10 mm) lesions. Twenty-four patients underwent routine MRI. The five sequences were compared qualitatively for image quality, lesion conspicuity and artefacts. Quantitative analysis was performed for lesion identification and lesion-to-liver contrast-to-noise ratio (CNR). Subgroup analyses were performed for different types of lesions with different sizes. Sequences were compared by rank order statistic (RIDIT) and Kruskal-Wallis test. The best image quality (p<0.05) was achieved with T2W TSE and the best lesion conspicuity (p<0.05) with T2W TSE for biliary cysts and SE-EPI diffusion-weighted imaging (DWI) (b = 20 s mm(-2)) for haemangiomas and metastases. Image artefacts were lowest (p<0.05) with T2W TSE. T2W TSE was found to be the best protocol (p<0.05) for the identification of biliary cysts and SE-EPI DWI (b = 20 s mm(-2)) for haemangiomas and metastases. The lesion-to-liver CNRs were highest on T2W TSE for biliary cysts and on SE-EPI diffusion-weighted imaging (DWI) for haemangiomas and metastases (p<0.05). This study shows the potential of SS SE-EPI DWI (especially with a b-value of 20 s mm(-2)) as a promising technique for detecting small (<10 mm) focal liver lesions.

Nuclear magnetic resonance study of the conformation and dynamics of beta-casein at the oil/water interface in emulsions.

A (13)C and (31)P nuclear magnetic resonance (NMR) study has been carried out on beta-casein adsorbed at the interface of a tetradecane/water emulsion. (13)C NMR spectra show signals from the carbonyl, carboxyl, aromatic, and C alpha carbons in beta-casein, well resolved from solvent resonances. Only a small fraction of all carbon atoms in beta-casein contribute to detectable signals; intensity measurements show that the observable spectrum is derived from about 30 to 40 amino acid residues.(31)P NMR spectra show signals from the five phosphoserines on the hydrophilic N-terminal part of the protein. Analysis of T(1) relaxation times of these nuclei, using the model free approach for the spectral density function and the line shape of the alpha-carbon region, indicates that a large part of the protein is in a random coil conformation with restricted motion and a relatively long internal correlation time. The NMR results show that the conformation and dynamics of the N-terminal part of beta-casein are not strongly altered at the oil/water interface, as compared to beta-casein in micelle-like aggregates in aqueous solution.