Platelet glycoprotein IIb/IIIa inhibitor tirofiban in clopidogrel-naïve patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The safety of administration of tirofiban, a platelet glycoprotein IIb/IIIa inhibitor, followed by a clopidogrel loading dose in clopidogrel-naïve patients undergoing ad-hoc percutaneous coronary intervention (PCI) is not yet clear. METHODS: In a retrospective observational cohort analysis, clopidogrel-naïve patients undergoing ad-hoc PCI who received a high-dose bolus of tirofiban (25 µg/kg) followed by a 600-mg clopidogrel loading dose (group 1) were compared with patients undergoing elective PCI who were pretreated with clopidogrel (group 2), between September 2014 and October 2021. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of death, myocardial infarction, stroke, target-lesion revascularisation and bleeding at 30 days. Secondary outcomes were MACE at 7 days and individual components of the primary outcome at 7 and 30 days. RESULTS: A total of 1404 patients were included: 432 (31%) in group 1 and 972 (69%) in group 2. Median age was 69 years, and 28% were female. At 7­day follow-up, MACE occurred in 1.4% in group 1 versus 3.0% in group 2 (p = 0.08). 30-day MACE were observed in 1.9% in group 1 and 4.2% in group 2 (p = 0.03). Secondary outcomes were comparable between the groups. Cox regression analysis, corrected for baseline differences, revealed no significant difference in the primary outcome (hazard ratio: 1.8; 95% confidence interval: 0.8-3.9). CONCLUSION: Ad-hoc PCI in clopidogrel-naïve patients who were treated with high-dose bolus of tirofiban followed by a clopidogrel loading dose immediately after the procedure appeared to be safe.

Long-term outcome after deferred revascularization due to negative fractional flow reserve in intermediate coronary lesions.

OBJECTIVES: The aim was to assess long-term outcome after deferring intervention of coronary lesions with a fractional flow reserve (FFR) value of >0.80 in a real-world patient population and then to identify factors associated with deferred target lesion failure (DTLF). BACKGROUND: Deferring coronary interventions of intermediate lesions based on FFR measurement is safe, irrespective of the extent of coronary artery disease. However, FFR values near the cut-off of >0.80 may have less favorable outcome. METHODS: A retrospective analysis was performed in patients with deferred coronary intervention based on FFR value >0.80. The primary endpoint was DTLF, a composite of acute coronary syndrome (ACS) and any coronary revascularization, related to the initially deferred stenosis. RESULTS: A total of 600 patients, mean age of 66 ± 10 years, and 751 coronary lesions with negative FFR values (mean 0.88 ± 0.04) were included. The mean follow-up was 27 ± 15 months. DTLF occurred in 44 patients (7.3%), revascularization in 42 (7%), and ACS without revascularization in 2 patients (0.3%). Patients with DTLF more often had diabetes mellitus, previous coronary artery bypass grafting, multivessel disease (MVD), and lower FFR at inclusion. Multivariable regression analysis showed that lower deferred FFR values [FFR 0.81-0.85: hazard ratio (HR) 2.79 (95% CI [confidence interval]; 1.46-5.32), p .002], MVD [HR 1.98 (95% CI; 1.05-3.75), p .036], distal lesions [HR 2.43 (95% CI; 1.29-4.57), p .006], and lesions located in a saphenous vein graft (SVG) [HR 6.35 (95% CI; 1.81-22.28), p .004] were independent predictors for DTLF. CONCLUSIONS: The long-term rate of DTLF of initially deferred coronary lesions was 7.3%. Independent predictors for DTLF are lower deferred FFR value, the presence of MVD, distal lesions, and lesions in SVG.

Longitudinal alteration of cortical thickness and volume in high-impact sports.

Collegiate football athletes are subject to repeated head impacts. The purpose of this study was to determine whether this exposure can lead to changes in brain structure. This prospective cohort study was conducted with up to 4 years of follow-up on 63 football (high-impact) and 34 volleyball (control) male collegiate athletes with a total of 315 MRI scans (after exclusions: football n â€‹= â€‹50, volleyball n â€‹= â€‹24, total scans â€‹= â€‹273) using high-resolution structural imaging. Volumetric and cortical thickness estimates were derived using FreeSurfer 5.3's longitudinal pipeline. A linear mixed-effects model assessed the effect of group (football vs. volleyball), time from baseline MRI, and the interaction between group and time. We confirmed an expected developmental decrement in cortical thickness and volume in our cohort (p â€‹< â€‹.001). Superimposed on this, total cortical gray matter volume (p â€‹= â€‹.03) and cortical thickness within the left hemisphere (p â€‹= â€‹.04) showed a group by time interaction, indicating less age-related volume reduction and thinning in football compared to volleyball athletes. At the regional level, sport by time interactions on thickness and volume were identified in the left orbitofrontal (p â€‹= â€‹.001), superior temporal (p â€‹= â€‹.001), and postcentral regions (p â€‹< â€‹.001). Additional cortical thickness interactions were found in the left temporal pole (p â€‹= â€‹.003) and cuneus (p â€‹= â€‹.005). At the regional level, we also found main effects of sport in football athletes characterized by reduced volume in the right hippocampus (p â€‹= â€‹.003), right superior parietal cortical gray (p â€‹< â€‹.001) and white matter (p â€‹< â€‹.001), and increased volume of the left pallidum (p â€‹= â€‹.002). Within football, cortical thickness was higher with greater years of prior play (left hemisphere p â€‹= â€‹.013, right hemisphere p â€‹= â€‹.005), and any history of concussion was associated with less cortical thinning (left hemisphere p â€‹= â€‹.010, right hemisphere p â€‹= â€‹.011). Additionally, both position-associated concussion risk (p â€‹= â€‹.002) and SCAT scores (p â€‹= â€‹.023) were associated with less of the expected volume decrement of deep gray structures. This prospective longitudinal study comparing football and volleyball athletes shows divergent age-related trajectories of cortical thinning, possibly reflecting an impact-related alteration of normal cortical development. This warrants future research into the underlying mechanisms of impacts to the head on cortical maturation.

Baseline MDCT findings after prosthetic heart valve implantation provide important complementary information to echocardiography for follow-up purposes.

OBJECTIVES: Recent studies have proposed additional multidetector-row CT (MDCT) for prosthetic heart valve (PHV) dysfunction. References to discriminate physiological from pathological conditions early after implantation are lacking. We present baseline MDCT findings of PHVs 6 weeks post implantation. METHODS: Patients were prospectively enrolled and TTE was performed according to clinical guidelines. 256-MDCT images were systematically assessed for leaflet excursions, image quality, valve-related artefacts, and pathological and additional findings. RESULTS: Forty-six patients were included comprising 33 mechanical and 16 biological PHVs. Overall, MDCT image quality was good and relevant regions remained reliably assessable despite mild-moderate PHV-artefacts. MDCT detected three unexpected valve-related pathology cases: (1) prominent subprosthetic tissue, (2) pseudoaneurysm and (3) extensive pseudoaneurysms and valve dehiscence. The latter patient required valve surgery to be redone. TTE only showed trace periprosthetic regurgitation, and no abnormalities in the other cases. Additional findings were: tilted aortic PHV position (n = 3), pericardial haematoma (n = 3) and pericardial effusion (n = 3). Periaortic induration was present in 33/40 (83 %) aortic valve patients. CONCLUSIONS: MDCT allowed evaluation of relevant PHV regions in all valves, revealed baseline postsurgical findings and, despite normal TTE findings, detected three cases of unexpected, clinically relevant pathology. KEY POINTS: • Postoperative MDCT presents baseline morphology relevant for prosthetic valve follow-up. • 83 % of patients show periaortic induration 6 weeks after aortic valve replacement. • MDCT detected three cases of clinically relevant pathology not found with TTE. • Valve dehiscence detection by MDCT required redo valve surgery in one patient. • MDCT is a suitable and complementary imaging tool for follow-up purposes.

Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma.

OBJECTIVES: Human leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial. METHODS: The pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas. RESULTS: In squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P < 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months; P = 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months; P = 0.002). CONCLUSIONS: Upregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.

Multidetector-row computed tomography for prosthetic heart valve dysfunction: is concomitant non-invasive coronary angiography possible before redo-surgery?

OBJECTIVES: Retrospective ECG-gated multidetector-row computed tomography (MDCT) is increasingly used for the assessment of prosthetic heart valve (PHV) dysfunction, but is also hampered by PHV-related artefacts/cardiac arrhythmias. Furthermore, it is performed without nitroglycerine or heart rate correction. The purpose was to determine whether MDCT performed before potential redo-PHV surgery is feasible for concomitant coronary artery stenosis assessment and can replace invasive coronary angiography (CAG). METHODS: PHV patients with CAG and MDCT were identified. Based on medical history, two groups were created: (I) patients with no known coronary artery disease (CAD), (II) patients with known CAD. All images were scored for the presence of significant (>50 %) stenosis. CAG was the reference test. RESULTS: Fifty-one patients were included. In group I (n = 38), MDCT accurately ruled out significant stenosis in 19/38 (50 %) patients, but could not replace CAG in the remaining 19/38 (50 %) patients due to non-diagnostic image quality (n = 16) or significant stenosis (n = 3) detection. In group II (n = 13), MDCT correctly found no patients without significant stenosis, requiring CAG imaging in all. MDCT assessed patency in 16/19 (84 %) grafts and detected a hostile anatomy in two. CONCLUSION: MDCT performed for PHV dysfunction assessment can replace CAG (100 % accurate) in approximately half of patients without previously known CAD. KEY POINTS: • Retrospective MDCT is increasingly used for prosthetic heart valve dysfunction assessment • In case of PHV reoperation, invasive coronary angiography is also required • MDCT can replace CAG in 50 % of patients without coronary artery disease • When conclusive for coronary assessment, MDCT stenosis rule out is highly accurate • Replacing CAG saves associated risks of distant embolization of thrombi or vegetations.

The additional value of three-dimensional transesophageal echocardiography in complex aortic prosthetic heart valve endocarditis.

BACKGROUND: Two-dimensional transthoracic and transesophageal echocardiography (2DTTE and 2DTEE) may fail to detect signs of prosthetic heart valve (PHV) endocarditis due to acoustic shadowing. Three-dimensional (3D) TEE may have additional value; however, data are scarce. This study was performed to investigate the additional value of 3DTEE for the detection of aortic PHV endocarditis and the extent of the disease process. METHODS: Retrospective analysis of complex aortic PHV endocarditis cases that underwent 2DTTE, 2DTEE, and 3DTEE before surgery. Echocardiograms were individually assessed by 2 cardiologists blinded for the outcome. Surgical and pathological inspection served as the reference standard for vegetations and peri-annular extensions (abscesses/mycotic aneurysms). To determine if the proximal coronary arteries were involved in the inflammatory process as well, computed tomography angiography findings were added to reference standard. RESULTS: Fifteen aortic PHV endocarditis cases were identified. According to the reference standard, all 15 cases had peri-annular extensions, 13 of which had a close relationship with the proximal right and/or left coronary artery. In 6 of 15 patients, a vegetation was present. Combined 2DTTE/TEE missed 1/6 vegetations and 1/15 peri-annular extensions. After addition of 3DTEE, all vegetations (6/6) and peri-annular extensions (15/15) were detected, without adding false positives. Compared to 2DTEE, in 3/15 cases, 3DTEE resulted in better delineation of the anatomical relationship of the proximal coronary arteries to the peri-annular extensions. As a result, 3DTEE had an additional value in 5/15 cases. CONCLUSION: In complex aortic, PHV endocarditis 3DTEE may have additional value compared to 2D echocardiography.

Low incidence of early postoperative cerebral edema after coronary artery bypass grafting.

OBJECTIVE: Using magnetic resonance imaging, the authors studied the influence of a single high dose of intraoperative dexamethasone on the severity of cerebral edema that can occur early after coronary artery bypass grafting (CABG). It was hypothesized that high-dose intraoperative dexamethasone reduces cerebral edema after CABG. DESIGN: Secondary analysis in a subset of participants of the Dexamethasone for Cardiac Surgery (DECS) trial. The DECS trial was a multicenter, randomized, double-blind, placebo-controlled trial in 4,494 cardiac surgery patients, which studied the effect of high-dose dexamethasone on mortality and major complications after cardiac surgery. SETTING: A large university hospital in The Netherlands. PARTICIPANTS: Twenty adult patients who underwent CABG with cardiopulmonary bypass (CPB) between March and November 2011. INTERVENTIONS: Participants received a single intravenous dose of dexamethasone, 1 mg/kg, or placebo, at induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Patients underwent magnetic resonance imaging scanning immediately after surgery. The primary outcome was the severity of cerebral edema. Data from 18 patients (9 in each group, median age 69 years in both groups) could be analyzed. Patients in the dexamethasone group were (median, interquartile range 66 (53-99) minutes on cardiopulmonary bypass v 95 (81-105) minutes in the placebo group (p = 0.11). Only 1 patient in the dexamethasone group had slight cerebral edema (0% v 11%, p = 1.00), and edema severity did not differ between groups (p = 1.00). CONCLUSIONS: Relevant degrees of early postoperative cerebral edema were not observed. The present study findings strongly contrasted with older studies showing cerebral edema early after CABG in most patients.

Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features.

PURPOSE: To derive quantitative image features from magnetic resonance (MR) images that characterize the radiographic phenotype of glioblastoma multiforme (GBM) lesions and to create radiogenomic maps associating these features with various molecular data. MATERIALS AND METHODS: Clinical, molecular, and MR imaging data for GBMs in 55 patients were obtained from the Cancer Genome Atlas and the Cancer Imaging Archive after local ethics committee and institutional review board approval. Regions of interest (ROIs) corresponding to enhancing necrotic portions of tumor and peritumoral edema were drawn, and quantitative image features were derived from these ROIs. Robust quantitative image features were defined on the basis of an intraclass correlation coefficient of 0.6 for a digital algorithmic modification and a test-retest analysis. The robust features were visualized by using hierarchic clustering and were correlated with survival by using Cox proportional hazards modeling. Next, these robust image features were correlated with manual radiologist annotations from the Visually Accessible Rembrandt Images (VASARI) feature set and GBM molecular subgroups by using nonparametric statistical tests. A bioinformatic algorithm was used to create gene expression modules, defined as a set of coexpressed genes together with a multivariate model of cancer driver genes predictive of the module's expression pattern. Modules were correlated with robust image features by using the Spearman correlation test to create radiogenomic maps and to link robust image features with molecular pathways. RESULTS: Eighteen image features passed the robustness analysis and were further analyzed for the three types of ROIs, for a total of 54 image features. Three enhancement features were significantly correlated with survival, 77 significant correlations were found between robust quantitative features and the VASARI feature set, and seven image features were correlated with molecular subgroups (P < .05 for all). A radiogenomics map was created to link image features with gene expression modules and allowed linkage of 56% (30 of 54) of the image features with biologic processes. CONCLUSION: Radiogenomic approaches in GBM have the potential to predict clinical and molecular characteristics of tumors noninvasively. Online supplemental material is available for this article.

The development of a web-based brief alcohol intervention in reducing heavy drinking among college students: an Intervention Mapping approach.

In the Netherlands, young adults' drinking practices have become an issue of public concern since their drinking levels are high. Heavy drinking can place young adults at an increased risk for developing short- and long-term health-related problems. Current national alcohol prevention programmes focus mainly on adolescents and their parents and paying less systematic attention to young adults. The present study describes the theory and evidence-based development of a web-based brief alcohol intervention entitled What Do You Drink (WDYD). We applied the Intervention Mapping (IM) protocol to combine theory and evidence in the development and implementation of WDYD. The WDYD intervention aims to detect and reduce heavy drinking of young adults who are willing to decrease their alcohol consumption, preferably below the Dutch guidelines of low-risk drinking. According to the IM protocol, the development of WDYD resulted in a structured intervention. Reducing heavy drinking to low-risk drinking was proposed as the behavioural outcome. Motivational interviewing principles and parts of the I-Change Model were used as methods in the development of WDYD, whereas computer tailoring was selected as main strategy. An effect and a process evaluation of the intervention will be conducted. IM was found to be a practical instrument for developing the WDYD intervention tailored to a specific target population in the area of alcohol prevention.

Storage time of red blood cell concentrates and adverse outcomes after cardiac surgery: a cohort study.

Stored red blood cells undergo progressive structural and functional changes over time. Recently, concerns have been raised about the transfusion of older red blood cell (RBC) concentrates after cardiac surgery. The objective of the study was to test the hypothesis that longer storage time of RBCs increases the risk of adverse outcome after cardiac surgery. This is a retrospective cohort study which includes patients who underwent coronary artery bypass surgery and/or valve surgery. All patients were operated in the period from September 2006 to December 2010 and received 1 to 6 units of RBCs intraoperative or after surgery. Patients were divided into two groups according to the storage time of the RBCs. The "younger" group comprised patients who received RBCs ≤14 days old (n = 111) and the "any older" group comprised patients who received RBCs >14 days old (n = 710). Using univariable and multivariable regression analysis, we examined the effect of storage time on the primary composite endpoint of death, myocardial infarction, and stroke (major adverse cardiovascular events). Secondary outcomes were prolonged ICU and hospital stay. Data of 821 patients who received a total of 2,004 RBCs were analyzed. The median storage time for the younger group was 13 ± 2 days, the median storage time for the "any older" group was 21 ± 5 days. The incidence of the primary outcome was 8.6 % in the "any older" group and 4.5 % in the younger group (adjusted odds ratio (OR) 1.68; 95 % confidence interval (CI), 0.65-4.34). Prolonged ICU stay was 12.3 % in the "any older" group and 6.3 % in the younger group (adjusted OR 1.58; 95 % CI, 0.69-3.66). In patients undergoing cardiac surgery, transfusion of RBCs stored for more than 2 weeks was not associated with adverse outcomes.

The effectiveness of the 'what do you drink' web-based brief alcohol intervention in reducing heavy drinking among students: a two-arm parallel group randomized controlled trial.

AIMS: To evaluate the effectiveness of a web-based brief alcohol intervention 'What Do You Drink' (WDYD) among heavy drinking students at 1- and 6-month post-intervention. Additionally, it was investigated whether certain subgroups would benefit more than others from the WDYD intervention. METHODS: A two-arm parallel group randomized controlled trial was conducted online in the Netherlands in 2010-2011. Inclusion criteria were: (1) being between 18- and 24-year old, (2) reporting heavy drinking in the past 6 months, (3) being motivated to change alcohol consumption, (4) having access to the Internet and (5) giving informed consent. Participants (n = 913) were randomized to the experimental (WDYD intervention) or control condition (no intervention). Measures were heavy drinking, frequency of binge drinking and weekly alcohol consumption. RESULTS: Analyses according to the intention-to-treat principle revealed no significant main intervention effects in reducing the alcohol measures at the follow-up assessments. Secondary analyses revealed that gender, freshmen and fraternity or sorority membership did not moderate the effect of the WDYD intervention at both follow-ups. Readiness to change, problem drinking and carnival participation moderated intervention effects such that contemplators, those with severe symptoms of alcohol abuse or dependence, and those who participated in carnival benefited more than others from the WDYD intervention regarding weekly alcohol consumption at 1-month follow-up. CONCLUSIONS: The WDYD intervention was not effective in reducing the alcohol measures among heavy drinking students at 1- and 6-month post-intervention. However, there is preliminary evidence that the WDYD intervention is effective in lowering drinking levels for subgroups of heavy drinking students in the short term.

The effectiveness of a web-based brief alcohol intervention in reducing heavy drinking among adolescents aged 15-20 years with a low educational background: a two-arm parallel group cluster randomized controlled trial.

BACKGROUND: To evaluate the slightly modified version of the web-based brief alcohol intervention "What Do You Drink" (WDYD) among heavy drinking adolescents and young adults aged 15-20 years with a low educational background at one and six months follow-up. METHODS: A two-arm parallel group cluster randomized controlled trial was conducted online in the Netherlands in 2011-2012. Participants included in the trial were recruited from preparatory and secondary vocational education institutions and had to be between 15 and 20 years of age and report heavy drinking in the past six months. In total, 73 classes representing 609 (59.9% male) participants were allocated to the experimental condition (37 classes, 318 participants: WDYD intervention) or control condition (36 classes, 291 participants: no intervention). Outcomes were heavy drinking, weekly alcohol consumption, and frequency of binge drinking. RESULTS: Regressions analyses revealed no significant main intervention effects on any of the alcohol outcomes at one and six month's follow-up according to the intention-to-treat principle. Additionally, there were no moderating effects of gender, age, educational level, and readiness to change on the relation between the WDYD intervention and the alcohol outcomes at follow-up. CONCLUSIONS: The WDYD intervention was not effective in reducing alcohol consumption among heavy drinking adolescents and young adults aged 15-20 years with a low educational background at one and six months follow-up. However, the absence of intervention effectiveness cannot be used as an argument for not conducting these types of interventions with low educated individuals, since our study was the first to target this population. TRIAL REGISTRATION: Netherlands Trial Register NTR2971.

Sequential use of human-derived medium supplements favours cardiovascular tissue engineering.

For clinical application of tissue engineering strategies, the use of animal-derived serum in culture medium is not recommended, because it can evoke immune responses in patients. We previously observed that human platelet-lysate (PL) is favourable for cell expansion, but generates weaker tissue as compared to culture in foetal bovine serum (FBS). We investigated if human serum (HS) is a better human supplement to increase tissue strength. Cells were isolated from venous grafts of 10 patients and expanded in media supplemented with PL or HS, to determine proliferation rates and expression of genes related to collagen production and maturation. Zymography was used to assess protease expression. Collagen contraction assays were used as a two-dimensional (2D) model for matrix contraction. As a prove of principle, 3D tissue culture and tensile testing was performed for two patients, to determine tissue strength. Cell proliferation was lower in HS-supplemented medium than in PL medium. The HS cells produced less active matrix metallo-proteinase 2 (MMP2) and showed increased matrix contraction as indicated by gel contraction assays and 3D-tissue culture. Tensile testing showed increased strength for tissues cultured in HS when compared to PL. This effect was more pronounced if cells were sequentially cultured in PL, followed by tissue culture in HS. These data suggest that sequential use of PL and HS as substitutes for FBS in culture medium for cardiovascular tissue engineering results in improved cell proliferation and tissue mechanical properties, as compared to use of PL or HS apart.

Trans-apical versus surgical implantation of autologous ovine tissue-engineered heart valves.

BACKGROUND AND AIM OF THE STUDY: Living tissue-engineered heart valves (TEHVs) based on rapidly degrading scaffolds and autologous cells might overcome the limitations of today's valve substitutes. Following minimally invasive trans-apical implantation into an ovine model, TEHVs showed adequate in-vivo functionality, but a thickening of the leaflets was observed. In order to evaluate the impact of the substantial tissue deformations of TEHVs associated with the crimping procedure during minimally invasive delivery, trans-apical and conventional implantation technologies were compared in an ovine model. METHODS: Trileaflet heart valves (n=11) based on PGA/P4HB-scaffolds, integrated into self-expandable stents, were engineered from autologous ovine vascular-derived cells. After in-vitro culture, the TEHVs were either implanted surgically (n=5), replacing the native pulmonary valve, or delivered trans-apically (n=6) into the orthotopic pulmonary valve position. In-vivo functionality was assessed by echocardiography and by angiography for up to eight weeks. The tissue compositions of the explanted TEHVs and corresponding control valves were analyzed. RESULTS: TEHV implantations were successful in all cases. Independent of the implantation method, the explants demonstrated a comparable layered tissue formation with thickening and deposited fibrous layers. Active remodeling of these layers was evident in the explants, as indicated by vascularization of the walls, invasion of the host cells, and the formation of a luminal endothelial layer on the TEHV leaflets. CONCLUSION: This direct comparison of trans-apical and conventional surgical implantation techniques showed that crimping had no adverse effect on the integrity or functional outcome of TEHVs. This suggests that a thickening of TEHVs in vivo is neither caused by nor enhanced by the crimping procedure, but represents a functional tissue remodeling process.

Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial.

CONTEXT: Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking. OBJECTIVE: To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, 2011. INTERVENTION: Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255). MAIN OUTCOME MEASURES: A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. RESULTS: Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexamethasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels. CONCLUSION: In our trial of adults undergoing cardiac surgery, the use of intraoperative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00293592.

Frequently occurring polar symptoms assessed by successful cases.

BACKGROUND: Frequently occurring symptoms with opposite poles like 'Cold ameliorates/aggravates' are regarded valuable for homeopathic practice, but are insufficiently assessed and impossible to handle with conventional repertorisation. METHOD: In a pilot study 30 questions out of a standard questionnaire in 102 cases responding well to five medicines were analysed and compared with a control group of 100 consecutive new cases. Outcomes of a pivot table, Likelihood Ratio (LR) calculations and Multivariate Analysis (MVA) were compared. RESULTS: Some questions were less useful than expected. With an average of 4.8 useful answers per patient and moderate LRs this questionnaire provided substantial information. MVA was useful in emphasising differences between medicines and for differential diagnosis. CONCLUSION: The value of frequently occurring symptoms could be much enhanced by scientific assessment. We propose further research with an improved questionnaire.

Prosthetic heart valve assessment with multidetector-row CT: imaging characteristics of 91 valves in 83 patients.

OBJECTIVES: Multidetector CT (MDCT) has shown potential for prosthetic heart valve (PHV) assessment. We assessed the image quality of different PHV types to determine which valves are suitable for MDCT evaluation. METHODS: All ECG-gated CTs performed in our institutions since 2003 were reviewed for the presence of PHVs. After reconstruction in 3 specific PHV planes, image quality of the supravalvular, perivalvular, subvalvular and valvular regions was scored on a four-point scale (1 = non-diagnostic, 2 = moderate, 3 = good and 4 = excellent) by two independent observers. RESULTS: Eighty-four CT examinations (66 cardiac, 18 limited-dose aortic protocols) of 83 patients with a total of 91 PHVs in the aortic (n = 71), mitral (n = 17), pulmonary (n = 1) and tricuspid (n = 2) position were included. CT was performed on a 16-slice (n = 4), 64-slice (n = 28) or 256-slice (n = 52) MDCT system. Median image quality scores for the supra-, peri- and subvalvular regions and valvular detail were (3.5, 3.3, 3.5 and 3.5, respectively) for bileaflet PHV; (3.0, 3.0, 3.5 and 3.0, respectively) for Medtronic Hall PHV; (1.0, 1.0, 1.0 and 1.0, respectively) for Björk-Shiley and Sorin monoleaflet PHV and (3.5, 3.5, 4.0 and 2.0 respectively) for biological PHV. CONCLUSION: Currently implanted PHVs have good image quality on MDCT and are suitable for MDCT evaluation.

Targeting young drinkers online: the effectiveness of a web-based brief alcohol intervention in reducing heavy drinking among college students: study protocol of a two-arm parallel group randomized controlled trial.

BACKGROUND: The prevalence of heavy drinking among college students and its associated health related consequences highlights an urgent need for alcohol prevention programs targeting 18 to 24 year olds. Nevertheless, current alcohol prevention programs in the Netherlands pay surprisingly little attention to the drinking patterns of this specific age group. The study described in this protocol will test the effectiveness of a web-based brief alcohol intervention that is aimed at reducing alcohol use among heavy drinking college students aged 18 to 24 years old. METHODS/DESIGN: The effectiveness of the What Do You Drink web-based brief alcohol intervention will be tested among 908 heavy drinking college students in a two-arm parallel group randomized controlled trial. Participants will be allocated at random to either the experimental (N=454: web-based brief alcohol intervention) or control condition (N=454: no intervention). The primary outcome measure will be the percentage of participants who drink within the normative limits of the Dutch National Health Council for low-risk drinking. These limits specify that, for heavy alcohol use, the mean consumption cannot exceed 14 or 21 glasses of standard alcohol units per week for females and males, respectively, while for binge drinking, the consumption cannot exceed five or more glasses of standard alcohol units on one drinking occasion at least once per week within one month and six months after the intervention. Reductions in mean weekly alcohol consumption and frequency of binge drinking are also primary outcome measures. Weekly Ecological Momentary Assessment will measure alcohol-related cognitions, that is, attitudes, self-efficacy, subjective norms and alcohol expectancies, which will be included as the secondary outcome measures. DISCUSSION: This study protocol describes the two-arm parallel group randomized controlled trial developed to evaluate the effectiveness of a web-based brief alcohol intervention. We expect a reduction of mean weekly alcohol consumption and frequency of binge drinking in the experimental condition compared to the control condition as a direct result of the intervention. If the website is effective, it will be implemented in alcohol prevention initiatives, which will facilitate the implementation of the protocol. TRIAL REGISTRATION: Netherlands Trial Register NTR2665.

Neuroradiologic Evaluation of MRI in High-Contact Sports.

Background and Purpose: Athletes participating in high-contact sports experience repeated head trauma. Anatomical findings, such as a cavum septum pellucidum, prominent CSF spaces, and hippocampal volume reductions, have been observed in cases of mild traumatic brain injury. The extent to which these neuroanatomical findings are associated with high-contact sports is unknown. The purpose of this study was to determine whether there are subtle neuroanatomic differences between athletes participating in high-contact sports compared to low-contact athletic controls. Materials and Methods: We performed longitudinal structural brain MRI scans in 63 football (high-contact) and 34 volleyball (low-contact control) male collegiate athletes with up to 4 years of follow-up, evaluating a total of 315 MRI scans. Board-certified neuroradiologists performed semi-quantitative visual analysis of neuroanatomic findings, including: cavum septum pellucidum type and size, extent of perivascular spaces, prominence of CSF spaces, white matter hyperintensities, arterial spin labeling perfusion asymmetries, fractional anisotropy holes, and hippocampal size. Results: At baseline, cavum septum pellucidum length was greater in football compared to volleyball controls (p = 0.02). All other comparisons were statistically equivalent after multiple comparison correction. Within football at baseline, the following trends that did not survive multiple comparison correction were observed: more years of prior football exposure exhibited a trend toward more perivascular spaces (p = 0.03 uncorrected), and lower baseline Standardized Concussion Assessment Tool scores toward more perivascular spaces (p = 0.02 uncorrected) and a smaller right hippocampal size (p = 0.02 uncorrected). Conclusion: Head impacts in high-contact sport (football) athletes may be associated with increased cavum septum pellucidum length compared to low-contact sport (volleyball) athletic controls. Other investigated neuroradiology metrics were generally equivalent between sports.