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Objective: To perform a qualitative evaluation of the Thyroid Network, with a quantitative analysis of second opinion referrals for patients in the southwestern part of the Netherlands who have thyroid nodules and cancer. Methods: This prospective observational study registered all patients with thyroid nodules and cancer who were referred to the academic hospital from 2 years before and 4 years after the foundation of the Thyroid Network. We implemented biweekly regional multidisciplinary tumor boards using video conference and a regional patient care pathway for patients with thyroid nodules and cancer. For qualitative evaluation, interviews were conducted with a broad selection of stakeholders via maximum variation sampling. The primary outcome was the change in second opinions after the foundation of the Thyroid Network. Results: Second opinions from Thyroid Network hospitals to the academic hospital decreased from 10 (30%) to 2 (7%) two years after the start of the Thyroid Network (P =.001), while patient referrals remained stable (n = 108 to 106). Qualitative evaluation indicated that the uniform care pathway and the regional multidisciplinary tumor board were valued high. Discussion: Establishing a regional network, including multidisciplinary tumor boards and a care pathway for patients with thyroid nodules and cancer, resulted in a decrease in second opinions of in‐network hospitals and high satisfaction of participating specialists. Implications for Practice: The concept of the Thyroid Network could spread to other regions as well as to other specialties in health care. Future steps would be to assess the effect of regional collaboration on quality of care and patient satisfaction. [ABSTRACT FROM AUTHOR]

Summary: The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high‐risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality—in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma—it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood‐ and imaging‐based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity. [ABSTRACT FROM AUTHOR]

Aims: Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification. The aim of this study was first to estimate the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology. Methods and results: The CARDIOBESE study is a cross‐sectional multicentre study of 100 obesity patients [body mass index (BMI) ≥ 35 kg/m2] without known cardiovascular disease and 50 age‐matched and gender‐matched non‐obese controls (BMI ≤ 30 kg/m2). Echocardiography was performed, blood samples were collected, and a Holter monitor was affixed. Fifty‐nine obesity patients [48 (42–50) years, 70% female] showed subclinical cardiac dysfunction: 57 patients had decreased global longitudinal strain (GLS), and two patients with normal GLS had either diastolic dysfunction or increased brain natriuretic peptide (BNP). Only one non‐obese control had diastolic dysfunction, and none had another sign of cardiac dysfunction. Multivariable logistic analysis identified male gender and standard deviation of all NN intervals (SDNN) index, which is a measure of autonomic dysfunction, as independent significant risk factors for subclinical cardiac dysfunction in obesity patients. Conclusions: There was a high prevalence (61%) of subclinical cardiac dysfunction in obesity patients without known cardiovascular disease, which appeared to be best identified by GLS. Subclinical cardiac dysfunction in obesity was linked to autonomic dysfunction and male gender, and not to the presence of traditional cardiac risk factors, increased C‐reactive protein, increased BNP, increased high‐sensitivity troponin I, or increased left ventricular mass. [ABSTRACT FROM AUTHOR]

Abstract: Background: Levels of apolipoprotein (apo) B48 may be increased in conditions associated with systemic inflammation and increased cardiovascular disease (CVD) risk such as rheumatoid arthritis (RA). We aimed to evaluate apo B48 levels in patients with RA in relation to subclinical atherosclerosis. Methods: Patients with RA (without CVD) and controls without RA but with high CVD risk (based on the presence of diabetes mellitus or a history of CVD) and healthy controls were included in this cross‐sectional study. Carotid intima‐media thickness (cIMT) was measured as a surrogate for vascular damage. Results: In total, 312 patients with RA, 65 controls with high CVD risk and 36 healthy controls were included. Patients with RA had the highest mean apo B48 (10.00 ± 6.65 mg/L) compared to controls with high CVD risk and healthy controls (8.37 ± 5.16 and 5.22 ± 2.46, P < .001). Triglycerides levels were comparable with controls. In RA, apo B48 correlated positively with triglycerides (r = .645; P < .001) but not with cIMT. However, in RA subjects not using lipid or blood pressure lowering medication, a weak correlation was found with cIMT (r = .157; P = .014). RA patients in the highest apo B48 tertile were more often rheumatoid factor positive and anti‐CCP positive compared to the lowest tertile. Conclusion: Rheumatoid arthritis patients have higher levels of apo B48 compared to controls with high CVD risk and healthy controls, with normal levels of triglycerides. This accumulation of atherogenic chylomicron remnants may contribute to the elevated CVD risk in RA patients. [ABSTRACT FROM AUTHOR]

Background Leucocyte activation is an obligatory factor in the development of atherosclerosis. The postprandial situation has been associated to increased leucocyte activation in several disorders, such as type 2 diabetes mellitus and familial combined hyperlipidaemia. Our study aim was to evaluate the effect of post- OGTT hyperglycaemia on leucocyte activation in patients with familial hypercholesterolemia ( FH). Materials and methods Patients who met the diagnostic criteria for heterozygous FH and healthy volunteers were asked to undergo an oral glucose tolerance test. Leucocyte activation markers CD11b and CD66b were determined by flow cytometry. Post- OGTT changes were calculated as area under the curve ( AUC) and the incremental area under the curve corrected for baseline values ( dAUC). The impact of being an FH patient and using statins on the time-dependent profile of the leucocyte activation markers was studied with repeated measurements analysis. Results Thirteen FH patients using statins, nine FH patients without statins and 14 healthy volunteers were included. FH subjects on statins had a slightly higher HbA1c than those not using these drugs or controls. Post- OGTT glucose levels were significantly higher in patients with FH when compared to healthy controls ( P = 0·001). These effects were independent from the use of statins. Conclusions Surprisingly, our study shows impaired post- OGTT glucose excursions in patients with FH compared to healthy volunteers. Post- OGTT hyperglycaemia may be related to persistent post- OGTT activation of monocytes in FH patients compared to healthy controls, and therefore, it may contribute to the development of cardiovascular disease in patients with FH. [ABSTRACT FROM AUTHOR]

Introduction: No data are available for normative values of cutaneous threshold and spatial discrimination in the feet. We developed clinically applicable reference values in relation to the nerve distributions of the feet.Methods: We determined foot sensation in 196 healthy individuals. Cutaneous threshold (1-point static discrimination, S1PD) was tested with monofilaments (0.008 to 300 gram) and spatial discrimination (2-point static [S2PD] and moving [M2PD] discrimination) on five locations per foot.Results: There was a significant age-dependent increase in S1PD, S2PD, and M2PD values (P < 0.05). No significant differences were found between both feet. S1PD values differed up to 0.8 g between genders. There were no significant differences between genders for S2PD and M2PD measurements. M2PD values were generally lower than S2PD values.Conclusions: This study provides age-related normative values for foot sensation to help clinicians assess sensory deficits in relation to aging and identify patients with underlying nerve problems. Muscle Nerve 56: 399-407, 2017. [ABSTRACT FROM AUTHOR]

Background The binding of apolipoprotein (apo) B-containing lipoproteins to circulating erythrocytes (ery-apoB) is associated with a decreased prevalence of atherosclerosis. In this study, we evaluated ery-apoB as a possible prognostic factor in cardiovascular events and all-cause mortality, in a prospective cohort study. Materials and methods Ery-apoB was measured by flow cytometry in subjects with and without cardiovascular disease ( CVD). The primary endpoint was the cardiovascular event rate. Secondary endpoints were all-cause mortality and the combined endpoint of all-cause mortality and cardiovascular events (any event rate). A Cox regression analysis with univariate and multivariate analyses and Kaplan-Meier survival analysis was performed. Results Follow-up data were available of 384 subjects. Subjects were divided according to high (> 2·0 au, n = 60), intermediate (0·2-2·0 au, n = 274) or low (< 0·2 au, n = 50) ery-apoB. Median follow-up was 1767 days ( IQR 1564-2001). In univariate analysis, low ery-apoB was associated with increased all-cause mortality [ HR 9·9 (1·2-79·0), P = 0·031] and any event rate [ HR 3·4 (95% CI 1·3-8·7), P = 0·012]. In a Cox regression analysis, only a history of CVD was significantly associated with any event rate [ HR 3·6 (1·6-8·0), P = 0·002], while low ery-apoB showed a trend [ HR 2·4 (0·9-6·4), P = 0·07]. In a subgroup analysis, in subjects with a history of CVD, ery-apoB was significantly associated with all-cause mortality (log rank P = 0·021) and any event rate (log rank P = 0·009). Conclusions Low ery-apoB is associated with increased mortality and cardiovascular risk, especially in patients with a prior history of CVD. These subjects may benefit from more aggressive secondary prevention treatment. [ABSTRACT FROM AUTHOR]

Background Atherosclerosis is a pro-inflammatory condition, in which leucocyte activation plays an important role. The interaction between circulating leucocytes and apolipoprotein (apo) B-containing lipoproteins results in pro-inflammatory changes of these cells. We aimed to evaluate the relationship between apo B bound to circulating leucocytes and atherosclerosis. Methods Apo B on circulating leucocytes was measured by flow cytometry in subjects with and without cardiovascular disease ( CVD), expressed as mean fluorescent intensity in arbitrary units (au). Carotid intima-media thickness ( cIMT) was measured using B-mode ultrasound. Data are given as median (interquartile range). Results A total of 396 subjects were included, of whom 183 had a history of CVD. Compared to subjects without CVD, patients with CVD had lower apo B bound to neutrophils (12·7 au (9·8-16·2) and 14·2 au (10·1-17·5), respectively, P = 0·038) and to monocytes (2·5 au (1·7-3·1) and 2·7 (1·9-3·6) au, respectively, P = 0·025). No differences were found for lymphocyte-bound apo B. Neutrophil- and monocyte-bound apo B were inversely correlated with cIMT (Spearman's rho: −0·123, P = 0·017 and −0·108, P = 0·035, respectively). Both monocyte- and neutrophil-bound apo B were inversely associated with different factors related to the metabolic syndrome, such as body mass index, triglycerides and complement C3. There was a positive association between erythrocyte-bound apo B and apo B bound to each of the leucocyte classes, possibly reflecting a similar mechanism. Discontinuation of statins in 54 subjects did not influence leucocyte-bound apo B. Conclusion Unexpectedly, the presence of noninternalized apo B-containing lipoproteins on circulating neutrophil and monocyte membranes may represent a protective mechanism against atherosclerosis. [ABSTRACT FROM AUTHOR]

Background Coronary artery disease ( CAD) may reflect generalized inflammation. We evaluated leucocyte activation in subjects with and without CAD in different vascular compartments. Materials and Methods Patients were divided in two groups; subjects without CAD (controls; n = 25) and with stable CAD ( n = 52) based on coronary angiography. After blood sampling from vessels, cardiovascular risk factors and leucocyte activation markers CD11b, CD66b and cytoplasmatic myeloperoxidase ( MPO) were determined by flow cytometry. Results Myeloperoxidase ( MPO) was higher in patients with CAD at all sites compared with controls (188 ± 7 vs. 210 ± 12 au for venous ( P < 0·05), 178 ± 7 vs. 212 ± 12 au for femoral artery ( P = 0·08), 166 ± 7 vs. 195 ± 12 au for abdominal artery ( P < 0·05), 166 ± 6 vs. 189 ± 14 au for left coronary ( P = 0·08) and 163 ± 6 vs. 193 ± 12 au for the right coronary artery ( P < 0·05)). Other markers did not differ between the groups. A gradient of inflammation from peripheral vessels to the coronaries was found by differences in MPO in both groups; from 210 ± 12 au in the venous compartments towards 189 ± 14 and 193 ± 12 au, in the left and right coronaries, respectively, for the controls ( P = 0·001), and from 188 ± 7 au in the venous compartment towards 166 ± 6 and 163 ± 6 au in the left and right coronaries, respectively, for the patients ( P = 0·007). Other leucocyte activation markers did not show such a gradient. Conclusions There is a generalized inflammatory neutrophil gradient for MPO from peripheral vessels towards the coronaries in both patients with CAD and controls. However, patients with CAD show a higher degree of inflammation, mostly in the coronaries. These data strengthen the role of activated neutrophils in CAD. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012; 42 (4): 365-370 Abstract Background Apolipoprotein (apo) B-containing lipoproteins are closely linked to atherogenesis. These lipoproteins are transported in plasma and are also associated with blood leucocytes. Our aim was to investigate whether apoB-containing lipoproteins are also present on the surface of erythrocytes and investigate the relationship with the presence of atherosclerosis in a cross-sectional study. Materials and methods Erythrocyte-bound apoB (ery-apoB) was measured by flowcytometry in subjects with (CAD+) and without coronary artery disease (CAD−), based on coronary angiography or on a history of cardiovascular disease. Intima media thickness (IMT) measurements were carried out using B-mode ultrasound. The relationship between ery-apoB and clinical and subclinical atherosclerosis was evaluated with binary logistic regression. Results A total of 166 subjects were included (40 CAD+ and 126 CAD−). ApoB was detected on freshly isolated erythrocytes (range: 0·1-5·5 au; mean ± SEM 0·86 ± 0·09 au) in all but nine subjects (four CAD+ and five CAD−). Ery-apoB was lower in CAD+ (0·62 ± 0·09 au) compared to CAD− (1·18 ± 0·10 au; P < 0·001). Higher ery-apoB was associated with a lower risk of CAD (adjusted OR: 0·003 (95% CI: 0·001-0·08; P < 0·001), but the protective effect was diminished with increasing age (adjusted OR: 1·10 (95% CI: 1·04-1·16; P < 0·001). IMT was increased in CAD+ subjects (0·77 ± 0·13 mm) compared to CAD− (0·57 ± 0·14 mm; P < 0·001). A significant negative association was found between ery-apoB and IMT (β = −0·214: 95% CI −0·284 to −0·145; P < 0·001). There was no association between ery-apoB and plasma apoB (Pearson's r = −0·45; P = 0·57). Conclusions Human erythrocytes carry apoB-containing lipoproteins. Subjects with atherosclerosis have lower ery-apoB. High ery-apoB may be protective against atherosclerosis and may reflect an alternative blood cell-mediated lipoprotein transport system in the circulation, in which these lipoproteins less likely interact with the endothelium. [ABSTRACT FROM AUTHOR]

Background: Women are relatively protected from cardiovascular disease compared with men. Since morbid obesity is an independent risk factor for cardiovascular disease, the current study investigated whether the association between sex and cardiovascular risk factors and outcomes can be demonstrated in subjects suffering from morbid obesity. Materials and methods: Two hundred subjects enrolled in a study on cardiovascular risk factors in morbid obesity underwent extensive laboratory screening, carotid intima‐media thickness (cIMT) and pulse wave velocity (PWV) measurements. Gender differences were analysed using univariate and multivariable linear regression models. In addition, the effect of menopause on cIMT and PWV was analysed. Results of these models were reported as B coefficients with 95% confidence intervals. Results: The group consisted of 52 men and 148 women, with a mean age of 41 (±11.8) years and a mean body mass index (BMI) of 42.7 (±5.2) kg/m2. Both, cIMT and PWV were significantly higher in men than in women, although the difference in cIMT disappeared after adjustment for covariables such as waist circumference, age, high‐density lipoprotein cholesterol and mean arterial pressure. PWV was associated with sex after adjustments for covariables in morbidly obese patients. Postmenopausal women had significantly increased cIMT and PWV when compared with premenopausal women. Conclusion: Sex differences in PWV persist in subjects suffering from morbid obesity. However, no difference was found in cIMT between morbidly obese men and women after adjustment for classic cardiovascular risk factors. Premenopausal morbidly obese women are protected for cardiovascular disease when compared with postmenopausal morbidly obese women. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend screening the feet of diabetic subjects with a 10-g monofilament or tuning fork. We investigated which tests and locations on the feet have the best predictive value regarding 1-year ulcer-free survival in diabetic subjects participating in the prospective Rotterdam Diabetic Foot Study.Methods: Decision tree analysis was used to predict ulcer-free survival based on responses from individual test locations (monofilaments on 10 sites, vibration sense was tested on both halluces and medial malleoli). Separate trees for patients with and without a history of diabetic foot ulcer (DFU) were developed.Results: Four hundred sixteen subjects (mean [SD] age, 61.8 years [12.4]; range, 21.6-90.2) were measured, of whom 24 developed new DFUs. Three tests exhibited discriminative and predictive properties: testing vibration sense on the medial malleolus and monofilament testing on heel and hallux. The decision tree to predict ulcer-free survival in patients with a history of DFU yielded a sensitivity of 87.0%, which was 99.6% for the tree of patients without a history of DFU.Conclusion: The findings of this study aids medical decision making by discriminating between high- and low-risk patients of developing DFU using selective testing on sites with predictive properties. [ABSTRACT FROM AUTHOR]