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Nut consumption may reduce age-related cognitive decline, but underlying mechanisms are unclear. To investigate in older adults longer-term effects of mixed nut consumption on brain vascular function, which may underlie improvements in cognitive performance. Twenty-eight healthy individuals (age [mean ± SD]: 65 ± 3 years; BMI: 27.9 ± 2.3 kg/m2) were included in a randomized, single-blinded, cross-over trial with a 16-week intervention (60 g/d mixed nuts: walnuts, pistachio, cashew, and hazelnuts) and control period (no nuts), separated by 8 weeks of washout. Participants followed the Dutch food-based dietary guidelines. At the end of each period, cerebral blood flow (CBF), a marker of brain vascular function, was quantified using arterial spin labeling magnetic resonance imaging. Effects on endothelial function, arterial stiffness, and the retinal microvasculature were also assessed. Cognitive performance was measured using the Cambridge Neuropsychological Test Automated Battery. Body weight remained stable during the study. As compared to the control period, the mixed nut intervention resulted in a higher regional CBF in the right frontal and parietal lobes (treatment effect: 5.0 ± 6.5 mL/100 g/min; P < 0.001), left frontal lobe (5.4 ± 7.1 mL/100 g/min; P < 0.001), and bilateral prefrontal cortex (5.6 ± 6.6 mL/100 g/min; P < 0.001). Carotid artery reactivity (0.7 PP; 95%CI: 0.2 to 1.2; P = 0.007), brachial flow-mediated vasodilation (1.6 PP; 95%CI: 1.0 to 2.2; P < 0.001) and retinal arteriolar calibers were higher (2 μm; 95%CI: 0 to 3; P = 0.037), and carotid-to-femoral pulse wave velocity lower (−0.6 m/s; 95%CI: −1.1 to −0.1; P = 0.032). Further, visuospatial memory (−4 errors [16%]; 95%CI: −8 to 0; P = 0.045) and verbal memory (+1 correct [16%]; 0 to 2; P = 0.035) improved, but executive function and psychomotor speed did not change. Longer-term mixed nut consumption as part of a healthy diet beneficially affected brain vascular function, which may relate to the observed beneficial effects on memory in older adults. Moreover, different characteristics of the peripheral vascular tree also improved. [ABSTRACT FROM AUTHOR]

Implant loss following breast reconstruction is a devastating complication, which should be prevented as much as possible. This study aimed to validate a previously developed multicenter risk model for implant loss after implant-based breast reconstructions, using national data from the Dutch Breast Implant Registry (DBIR). The validation cohort consisted of patients who underwent a mastectomy followed by either a direct-to-implant (DTI) or two-stage breast reconstruction between September 2017 and January 2021 registered in the DBIR. Reconstructions with an autologous adjunctive and patients with missing data on the risk factors extracted from the multicenter risk model (obesity, smoking, nipple preserving procedure, DTI reconstruction) were excluded. The primary outcome was implant loss. The predicted probability of implant loss was calculated using beta regression coefficients extracted from the multicenter risk model and compared to the observed probability. The validation cohort consisted of 3769 reconstructions and implant loss occurred after 307 reconstructions (8.1%). Although the observed implant loss rate increased when the risk factors accumulated, the predicted and observed probabilities of implant loss did not match. Of the four risk factors in the multicenter risk model, only obesity and smoking were significantly associated to implant loss. The multicenter risk model could not be validated using nationwide data of the DBIR and is therefore not accurate in Dutch practice. In the future, the risk model should be improved by including other factors to provide a validated tool for the preoperative risk assessment of implant loss. [ABSTRACT FROM AUTHOR]

Presently, acute pharmacological termination of paroxysmal supraventricular tachycardia (PSVT) unresponsive to patient-initiated vagal maneuvers requires in-hospital intervention. Etripamil, a fast-acting, nondihydropyridine, L-type calcium channel blocker, is formulated as an intranasal spray to rapidly terminate atrioventricular (AV) nodal-dependent PSVT in a medically unsupervised setting. The NODE-301 study did not meet its prespecified primary end point of PSVT conversion over 5 hours following a single dose of etripamil 70 mg. However, analysis at earlier time points demonstrated etripamil treatment effect during the first 30 minutes, consistent with its expected rapid onset and short duration of action. This led to the design of the RAPID study, which includes a new dosing regimen (up to 2 etripamil 70 mg doses separated by 10 minutes) to increase the exposure and pharmacodynamic effect of etripamil. The primary objective of RAPID (NCT03464019) is to determine if etripamil self-administered by patients is superior to placebo in terminating PSVT in an at-home setting. The secondary objective is to evaluate the safety of etripamil when self-administered by patients without medical supervision. Additional efficacy end points include the proportion of patients requiring additional medical intervention in an emergency department to terminate PSVT and patient-reported outcomes. After successfully completing a test dose to assess the safety of 2 70 mg doses of etripamil during sinus rhythm, approximately 500 patients will be randomized 1:1 to etripamil or placebo to accrue 180 positively adjudicated AV nodal-dependent PSVT events for treatment with the study drug. Etripamil may offer a new alternative to the current in-hospital treatment modality, providing for safe and effective at-home termination of PSVT. [ABSTRACT FROM AUTHOR]

Background and Aims: Elevated circulating levels of CathepsinD (CatD) have been linked to metabolic deviations including liver inflammation. We investigated 1) whether supplementation with probiotics and/or fish oil affects CatD and 2) whether the CatD concentration would associate with gestational diabetes (GDM), low-grade inflammation, lipid metabolism, body fat % and dietary composition.Methods and Results: Overweight/obese pregnant women (n = 438) were randomized into fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo groups. Fish oil contained 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid and probiotics were Lacticaseibacillusrhamnosus HN001 (formerly Lactobacillusrhamnosus HN001) and Bifidobacteriumanimalis ssp. lactis 420, 1010 colony-forming units each). Serum CatD levels were analysed by ELISA, GlycA and lipid metabolites by NMR, high sensitive C-reactive protein (hsCRP) by immunoassay, and intakes of energy yielding nutrients and n-3 and n-6 fatty acids from food diaries at both early and late pregnancy. GDM was diagnosed by OGTT. CatD concentrations did not differ between the intervention groups or by GDM status. Multivariable linear models revealed that body fat % and GlycA affected CatD differently in healthy women and those with GDM.Conclusion: The serum CatD concentration of pregnant women was not modified by this dietary intervention. Serum CatD was influenced by two parameters, body fat and low grade inflammation, which were dependent on the woman's GDM status. CLINICAL TRIAL REG. NO: NCT01922791, clinicaltrials.gov (secondary analysis). [ABSTRACT FROM AUTHOR]

Infectious complications are frequently encountered after abdominal surgery. Early recognition, diagnosis, and subsequent timely treatment is the single most important denominator of postoperative outcome. This study prospectively addressed the predictive value of routine assessment of C-reactive protein levels as an early marker for infectious complications after major abdominal surgery. Consecutive patients undergoing major abdominal surgery between November 2015 and November 2019 were prospectively enrolled. Routine C-reactive protein measurements were implemented on postoperative days 3, 4, and 5, and additional computed tomography examinations were performed on demand. The primary endpoint was the occurrence of Clavien-Dindo grade III or higher infectious complications. Of 350 patients, 71 (20.3%) experienced a major infectious complication, and median time to diagnosis was 7 days. C-reactive protein levels were significantly higher in patients with major infectious complications compared to minor or no infectious complications. The optimal cut-off was calculated for each postoperative day, being 175 mg/L on day 3, 130 mg/L on day 4, and 144 mg/L on day 5, and corresponding sensitivities, specificities, and positive and negative predictive values were over 80%, 65%, 40%, and 92% respectively. Alternative safe discharge cut-offs were calculated at 105 mg/L, 71 mg/L and 63 mg/L on days 3, 4, and 5, respectively, each having a negative predictive value of over 97%. The C-reactive protein cut-offs provided in this study can be used as a discharge criterion or to select patients that might require an invasive intervention due to infectious complications. These diagnostic criteria can easily be implemented in daily surgical practice. [ABSTRACT FROM AUTHOR]

La prise en charge du syndrome de sevrage d'alcool est une pratique clinique courante aussi bien en médecine de ville qu'en service hospitalier. Le Delirium Tremens (DT) est une des complications les plus sévères du sevrage. Cette mise au point a pour objet de mettre à jour les connaissances sur cette complication en terme de diagnostic, d'évaluation et d'approches thérapeutiques. Elle propose aussi une réflexion sur la trajectoire de soins des patients pendant le DT mais aussi au décours. The management of alcohol withdrawal syndrome is a frequent work in both community medicine and hospital wards. One of the most severe complications of alcohol withdrawal is Delirium Tremens (DT). The purpose of this development is to update knowledge on this complication in terms of diagnosis, evaluation and therapeutic approaches. It also proposes a reflection on the trajectory of care during and after DT. [ABSTRACT FROM AUTHOR]

Dicarbonyl compounds contribute to the formation of advanced glycation endproducts (AGEs) and the development of insulin resistance and vascular complications. Dicarbonyl stress may already be detrimental in obesity. We evaluated whether diet-induced weight loss can effectively reverse dicarbonyl stress in abdominally obese men. Plasma samples were collected from lean (n = 25) and abdominally obese men (n = 52) in the fasting state, and during a mixed meal test (MMT). Abdominally obese men were randomized to 8 weeks of dietary weight loss or habitual diet, followed by a second MMT. The α-dicarbonyls methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG) and AGEs were measured by UPLC-MS/MS. Skin autofluorescence (SAF) was measured using the AGE reader. T-tests were used for the cross-sectional analysis and ANCOVA to assess the treatment effect. Postprandial glucose, MGO and 3-DG concentrations were higher in obese men as compared to lean men (p < 0.05 for all). Fasting dicarbonyls, AGEs, and SAF were not different between lean and obese men. After the weight loss intervention, fasting MGO levels tended to decrease by 25 nmol/L (95%-CI: -51-0.5; p = 0.054). Postprandial dicarbonyls were decreased after weight loss as compared to the control group: iAUC of MGO decreased by 57% (5280 nmol/L∙min; 95%-CI: 33–10526; p = 0.049), of GO by 66% (11,329 nmol/L∙min; 95%-CI: 495–22162; p = 0.041), and of 3-DG by 45% (20,175 nmol/L∙min; 95%-CI: 5351–35000; p = 0.009). AGEs and SAF did not change significantly after weight loss. Abdominal obesity is characterized by increased postprandial dicarbonyl stress, which can be reduced by a weight loss intervention. Registered under ClinicalTrials.gov Identifier no. NCT01675401. [ABSTRACT FROM AUTHOR]

The saturated fatty acid stearic acid (C18:0) lowers HDL cholesterol compared with palmitic acid (C16:0). However, the ability of HDL particles to promote cholesterol efflux from macrophages (cholesterol efflux capacity; CEC) may better predict coronary heart disease (CHD) risk than HDL cholesterol concentrations. We examined effects of exchanging dietary palmitic acid for stearic acid on ATP-binding cassette transporter A1 (ABCA1)-mediated CEC, and other conventional and emerging cardiometabolic risk makers. In a double-blind, randomized, crossover study with two 4-week isocaloric intervention periods, 34 healthy men and postmenopausal women (61.5 ± 5.7 years, BMI: 25.4 ± 2.5 kg/m2) followed diets rich in palmitic acids or stearic acids. Difference in intakes was 6% of daily energy. ABCA1-mediated CEC was measured from J774 macrophages to apolipoprotein (apo)B-depleted serum. Compared with the palmitic-acid diet, the stearic-acid diet lowered serum LDL cholesterol (−0.14 mmol/L; p = 0.010), HDL cholesterol (−0.09 mmol/L; p=<0.001), and apoA1 (−0.05 g/L; p < 0.001). ABCA1-mediated CEC did not differ between diets (p = 0.280). Cholesteryl ester transfer protein (CETP) mass was higher on stearic acid (0.11 mg/L; p = 0.003), but CETP activity was comparable. ApoB100 did not differ, but triacylglycerol concentrations tended to be higher on stearic acid (p = 0.100). Glucose concentrations were comparable. Effects on insulin and C-peptide were sex-dependent. In women, the stearic-acid diet increased insulin concentrations (1.57 μU/mL; p = 0.002), while in men, C-peptide concentrations were lower (−0.15 ng/mL; p = 0.037). Interleukin 6 (0.15 pg/mL; p = 0.039) and tumor necrosis factor alpha (0.18 pg/mL; p = 0.005), but not high-sensitivity C-reactive protein, were higher on stearic acid. Soluble intracellular adhesion molecule (9 ng/mL; p = 0.033), but not soluble vascular cell adhesion molecule and endothelial-selectin concentrations decreased after stearic-acid consumption. As expected, stearic-acid intake lowered LDL cholesterol, HDL cholesterol, and apoA1. Insulin sensitivity in women and low-grade inflammation might be unfavorably affected by stearic-acid intake. However, palmitic-acid and stearic-acid intakes did not differently affect ABCA1-mediated CEC. This trial was registered at clinicaltrials.gov as NCT02835651. [ABSTRACT FROM AUTHOR]

Effects of weight loss on postprandial vascular function have not been studied so far. We therefore examined (i) effects of diet-induced weight loss on postprandial changes in various vascular function markers after consumption of a mixed meal and (ii) differences between normal-weight and abdominally obese men of comparable age at baseline and after weight loss. Fifty-four apparently healthy abdominally obese (waist circumference: 102–110 cm) and 25 normal-weight men (waist circumference: <94 cm) participated. The abdominally obese men were randomly allocated to a diet-induced weight-loss program or a no-weight loss control group. Men assigned to the weight-loss program followed a calorie-restricted diet for six weeks targeting a waist circumference of less than 102 cm, followed by a weight-maintenance period for two weeks. The control group maintained their habitual diet and physical activity levels. Measurements were performed before and two hours after consumption of the test meal consisting of two muffins (containing 56.6 g fat) and 300 mL low-fat milk. The mean weight loss was 10.3 kg in the weight-loss compared with the control group. The postprandial change in flow-mediated vasodilation of the brachial artery (FMD) was significantly higher at baseline in normal-weight as compared with the postprandial change in abdominally obese men (1.89 ± 2.52 versus 0.48 ± 2.50 percentage points; P = 0.027). However, no differences in postprandial changes were observed in the abdominally obese men after weight loss compared with the control treatment. Also, weight reduction did not affect postprandial changes in carotid-to-femoral pulse wave velocity, retinal microvascular caliber properties, or plasma markers of microvascular endothelial function. Even though postprandial increases in triacylglycerol (P = 0.028), insulin (P = 0.029) and C-peptide concentrations (P < 0.001) were reduced in the abdominally obese men following weight loss, postprandial changes in FMD at the end of the weight-loss treatment were still more unfavorable as compared with those observed in normal-weight individuals. In this trial with abdominally obese men, we did not find effects of diet-induced weight loss on postprandial changes in vascular endothelial function, arterial stiffness and markers of microvascular function. This trial was registered on ClinicalTrials.gov under study number NCT01675401. [ABSTRACT FROM AUTHOR]

Background: Optimal health is demanded for service members in military operations. However, the strains of deployment can result in a deterioration, moreover when combat-related injuries are sustained, affecting level of participation and health related quality of life (HRQOL). Secondary health conditions may occur in time, however existing studies measure coping, level of activity and participation and HRQOL at one point in time.Aim: To assess the change over time concerning coping, mobility, level of participation and HRQOL in Dutch service members with combat-related injuries sustained during operation Task Force Uruzgan (TFU).Methods: The lower extremity functional scale (LEFS), the cognitive emotion regulation questionnaire (CERQ), the assessment of life habits short version (LIFE-H) and the EuroQol-5D (EQ-5D), measuring HRQOL, were administered in 2010 and 2014. Change of scores between the two time points was tested with the Wilcoxon signed rank test.Results: The response rate was 53% (28/53). The score on the coping strategy self-blame showed a significant increase over time with low scores on both occasions. The coping strategies positive reappraisal and acceptance showed the highest scores. No significant change is shown in mobility, the level of participation or HRQOL.Conclusion: service members with combat-related injuries remain stable in level of activity and participation and HRQOL in time and they use adaptive coping strategies. [ABSTRACT FROM AUTHOR]

Dietary plant sterols and stanols as present in our diet and in functional foods are well-known for their inhibitory effects on intestinal cholesterol absorption, which translates into lower low-density lipoprotein cholesterol concentrations. However, emerging evidence suggests that plant sterols and stanols have numerous additional health effects, which are largely unnoticed in the current scientific literature. Therefore, in this review we pose the intriguing question "What would have occurred if plant sterols and stanols had been discovered and embraced by disciplines such as immunology, hepatology, pulmonology or gastroenterology before being positioned as cholesterol-lowering molecules?" What would then have been the main benefits and fields of application of plant sterols and stanols today? We here discuss potential effects ranging from its presence and function intrauterine and in breast milk towards a potential role in the development of non-alcoholic steatohepatitis (NASH), cardiovascular disease (CVD), inflammatory bowel diseases (IBD) and allergic asthma. Interestingly, effects clearly depend on the route of entrance as observed in intestinal-failure associated liver disease (IFALD) during parenteral nutrition regimens. It is only until recently that effects beyond lowering of cholesterol concentrations are being explored systematically. Thus, there is a clear need to understand the full health effects of plant sterols and stanols. • Dietary plant sterols and stanols lower low density lipoprotein cholesterol, a causal risk factor for cardiovascular diseases • Although plant sterols and stanols are poorly absorbed they are taken up by various organs, which may affect health and disease. • Plant sterols and stanols may play a crucial role in functioning of immune cells and have beneficial effects beyond lowering low density lipoprotein cholesterol • Effects of plant sterols on liver health depend on the route of administration as observed during parenteral nutrition regimens • Intracellular oxidation of plant sterols might be a protective response avoiding accumulation of plant sterols within the cell. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • NWT-03 (5 g/d) improved carotid-radial PWV (cr-PWV) in subjects with IGT or T2DM. • NWT-03 (5 g/d) improved various metabolic parameters in subjects with IGT or T2DM. • No side effects were reported. • Whether these beneficial effects maintain on the longer term warrants further study. Abstract It was shown in animals that the egg protein-hydrolysate NWT-03 improves endothelial function. We designed a human crossover study to assess acute (2 h) and short-term (2 days) effects of 5 g/d NWT-03 in 40 overweight and obese subjects with impaired glucose-tolerance or type-2 diabetes. At day 1, both fasting (time point 0;t0) and 120 min after intake (t120), and day 3 (t120), pulse-wave velocity, augmentation index, heart rate and blood pressure were measured and blood was sampled for analysis of metabolic parameters (serum lipids, glucose and insulin). Acute and short-term effects were calculated. Carotid-radial PWV (short-term), AIx (acute), triacylglycerol (short-term), glucose (acute), and insulin (acute) decreased, while HDL cholesterol (short-term) increased significantly during NWT-03 consumption. The egg protein-hydrolysate NWT-03 is a potential functional food ingredient in IGT and T2DM. Whether the improvement in cr-PWV is mediated through effects on metabolism as well as long-term benefits warrants further study. [ABSTRACT FROM AUTHOR]

Endobronchial localizations of inflammatory myofibroblastic tumors are very unusual. We report the multimodal, bronchoscopic management of 3 cases, offering durable local control in all cases (including 2 patients who were definitively cured). Although surgery is usually considered the gold standard, therapeutic bronchoscopy should probably be considered as a frontline option for proximal lesions with limited base (< 10 mm2) because of uncommon metastatic spread and delayed local recurrence. Of note, 1 of our cases is a rare airway case after allograft hematopoietic stem cell transplant. [ABSTRACT FROM AUTHOR]

Recurrence is frequently observed after esophageal cancer surgery, with dismal post-recurrence survival. Neoadjuvant chemoradiotherapy followed by esophagectomy is the gold standard for resectable esophageal tumors in the Netherlands. This study investigated the recurrence patterns and survival after multimodal therapy. This retrospective cohort study included patients with recurrent disease after neoadjuvant chemoradiotherapy followed by esophagectomy for an esophageal adenocarcinoma in the Amsterdam UMC between 01 and 01–2010 and 31-12-2018. Post-recurrence treatment and survival of patients were investigated and grouped by recurrence site (loco-regional, distant, or combined loco-regional and distant). In total, 278 of 618 patients (45.0%) developed recurrent disease after a median of 49 weeks. Thirty-one patients had loco-regional (11.2%), 145 distant (52.2%), and 101 combined loco-regional and distant recurrences (36.3%). Post-recurrence survival was superior for patients with loco-regional recurrences (33 weeks, 95%CI 7.3–58.7) compared to distant (12 weeks, 95%CI 6.9–17.1) or combined loco-regional and distant recurrent disease (18 weeks, 95%CI 9.3–26.7). Patients with loco-regional recurrences treated with curative intent had the longest survival (87 weeks, 95%CI 6.9–167.4). Recurrent disease after potentially curative treatment for esophageal cancer was most frequently located distantly, with dismal prognosis. A subgroup of patients with loco-regional recurrence was treated with curative intent and had prolonged survival. These patients may benefit from intensive surveillance protocols, and more research is needed to identify these patients. Recurrence is frequently observed after esophageal cancer surgery. This study investigated the recurrence patterns and survival after neoadjuvant chemoradiotherapy and esophagectomy. It showed that recurrent disease was most frequently located distantly, outside of the initial radiation field, with dismal prognosis. [ABSTRACT FROM AUTHOR]