University Hospital Maastricht Research Articles

Frontiers of ankylosing spondylitis research: an analysis from the top 100 most influential articles in the field.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that frequently results in disability. It has a negative impact on patients' quality of life and puts an enormous budgetary and societal burden on society. The most effective treatment for AS has grown to be a significant issue worldwide. In order to pinpoint research focus and trends in this region, we performed a bibliometric analysis of the top 100 cited papers in this study. We searched the Science Citation Index Expanded (SCI-Expanded) on the Web of Science (WOS) and selected the top 100 cited papers based on AS. The pertinent literature from various years, journals, nations/regions, institutions, authors, keywords, and references were then examined. To construct knowledge maps, we used the VOSviewer, CiteSpace, and Scimago Graphica programs. Excel was then used to compile the information from the pertinent literature that we had retrieved, and we were able to make predictions about the focus and trends that were currently occurring in the field. Between 1999 and 2019, the top 100 cited papers appeared in 23 journals from 36 different nations and regions. Annals of the rheumatic diseases published the majority of the articles, while Lancet had the highest average number of citations per paper. Germany contributed the most publications, followed by the Netherlands and the USA. In terms of the total number of publications, Rheumazentrum Ruhrgebiet contributed the most papers, followed by University Hospital Maastricht and Leiden University. The three major categories are Rheumatology, Medicine, General & Internal, and Genetics & Heredity, whereas the top 5 co-occurrence of keywords included rheumatoid arthritis, double-blind, disease activity, efficacy, and infliximab. The cluster analysis results indicate that inflammation and immunology, safe and effective therapies, and placebo-controlled trials may be focus and trends for future AS research. Bibliometric analysis can swiftly and visually identify the focus and boundaries of AS research. Our findings imply that inflammation and immunology, safe and effective therapies, and placebo-controlled trials may be focus and trends for future AS research.

Protocol for a multicentre, parallel, randomised, controlled trial on the effect of sweeteners and sweetness enhancers on health, obesity and safety in overweight adults and children: the SWEET project

IntroductionThe aim of this randomised controlled trial (RCT) is to investigate whether prolonged consumption of sweeteners and sweetness enhancers (S&SEs) within a healthy diet will improve weight loss maintenance and...

The Role of Vascular Risk Factors in Biomarker-Based AT(N) Groups: A German-Dutch Memory Clinic Study.

The relation between vascular risk factors (VRFs) and Alzheimer's disease (AD) is important due to possible pathophysiological association. To assess the prevalence of VRFs in biomarker-based AT(N) groups and the associations between VRFs, AD cerebrospinal fluid (CSF) biomarkers, brain magnetic resonance imaging (MRI), and cognition in clinical context. We included patients from two memory clinics in University Hospital Aachen (Germany) and Maastricht University Medical Centre (The Netherlands). Subjects were older than 45 years and had available data on demographics, VRFs, CSF AD biomarkers, and MRI. We categorized individuals in normal AD biomarkers, non-AD change, and AD-continuum groups based on amyloid (A), tau (T), and neurodegeneration (N) status in CSF and MRI. Regression models were corrected for age, sex, and site. We included 838 participants (mean age 68.7, 53.2% male, mean MMSE 24.9). The most common VRFs were smoking (60.9%), hypertension (54.6%), and dyslipidemia (37.8%). Alcohol abuse and smoking were most frequent in the non-AD-change group, and coronary heart disease and carotid artery stenosis in the AD continuum group. Higher rates of depression were found in the normal AD biomarkers group. Parietal atrophy and cortical microbleeds were specific for the AD continuum group. Carotid artery stenosis was associated with pathological Aβ42 and T-tau values, and diabetes and alcohol abuse were associated with worse medial temporal atrophy and atrial fibrillation, with worse cognition. VRFs are common in memory clinic patients, showing differences across the AT(N) biomarker groups. This is important for prevention and individualized treatment of dementia.

Effectiveness and cost-effectiveness of dynamic bracing versus standard care alone in patients suffering from osteoporotic vertebral compression fractures: protocol for a multicentre, two-armed, parallel-group randomised controlled trial with 12 months of follow-up

IntroductionPatients with osteoporosis may suffer from a fracture after minimal trauma. Osteoporotic vertebral compression fractures (OVCFs) are among the most common fractures, often leading to substantial pain. There is a...

Renal Clearance of FGF23 and its Fragments in Humans

Background: Relative abundance of fibroblast growth factor-23 (FGF23) measured by the C-terminal (cFGF23, which measures both intact FGF23 & c-terminal fragments) vs intact (iFGF23, measures only intact hormone) assays varies by kidney function in humans. Differential kidney clearance may explain this. Methods: We measured cFGF23 and iFGF23 in the aorta and bilateral renal veins of 162 patients with essential hypertension undergoing renal angiography. Using multivariable linear regression models, we examined factors associated with aorta to renal vein reduction of FGF23 using both assays. Similar, parameters and urine concentrations were measured in 6 Wistar rats. Results: Mean age was 54±12 years, 54% percent were women, and mean creatinine clearance was 72±48 ml/min/100g. The human kidney reduces the concentrations of both cFGF23 (16±12%) and iFGF23 (21±16%) compared to aorta, but reduction was higher for iFGF23. Greater kidney creatinine and PTH reduction were each independently associated with greater reductions of both cFGF23 and iFGF23. The relative kidney reduction of iFGF23 and cFGF23 appeared stable and consistent across the range of creatinine clearance. Kidney clearance was similar, and urine concentrations of both assays were low in the rat models, suggesting kidney metabolism of both cFGF23 and iFGF23. Conclusions: Renal reduction of iFGF23 is higher than that of creatinine and cFGF23.FGF23 is likely metabolized and cleared through the human kidney tubules, above and beyond glomerular filtration. Kidney clearance of FGF23 does not explain differences in C-terminal and intact moieties across the range of kidney function. Funding: This work was supported by National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) Grants R01DK119528 and K24DK110427 (J.H.I). P30 DK079328, R01 DK091392, R01 DK092461 and R01 DK119528 (O.W.M). Veterans Health Administration IK2-CX002195 (SS). Declaration of Interest: Dr. Ix is principal investigator of an investigator-initiated research grant from Baxter International, serves as a data safety monitoring board member for Sanifit International, and has served on advisory boards for Alpha Young, AstraZeneca, Ardelyx Inc., and Jnana Inc. Dr. Moe has served on advisory boards and received compensations in the last 5 years for Allena, Alnylam, Ardelyx, Applied Therapeutics, Dicerna, Janssen, Genzyme-Sanofi, and Tricida. Remaining authors have declared no conflicts of interest. Ethical Approval: The human renal angiography studies were approved by the medical ethical committee of the Maastricht University Hospital. Animal studies were performed in accordance with the National Institutes for Health’s Guide for Care and Use of Laboratory Animals, and the experimental protocols had gained approval by the VA San Diego Health Care Systems and conducted under their guidelines.

Epilepsy and TSC-Associated Neuropsychiatric Disorders.

Investigators from multiple institutions (Cleveland Clinic, University Hospital Leuven, ZOL Genk, Kempenhaeghe and Maastricht UMC+, and Children's Hospitals and Clinics of Minnesota) used the Tuberous Sclerosis Complex Natural History Database (TSCNHD) to evaluate the relationship between epilepsy and neuropsychiatric disorders in individuals with TSC, along with any potential influence of genotype.

Wednesday, September 26, 2018 1:00 PM – 2:00 PM Spinal Trauma: 56. Two nation comparison of surgical treatment of traumatic thoracolumbar spinal fractures: posterior only versus circumferential stabilization

BACKGROUND CONTEXT For many traumatic thoracolumbar spinal fractures the best choice of treatment is uncertain, and if surgery is indicated, which type of surgery is also under debate. In literature, there is only poor evidence about the comparison of posterior versus circumferential stabilization. PURPOSE To compare the functional, radiological and clinical outcome of posterior-only versus circumferential stabilization in traumatic thoracolumbar fractures. STUDY DESIGN/SETTING Comparative retrospective cohort study, surgical equipoise. PATIENT SAMPLE Multicenter analysis of patients who were surgically treated for a traumatic thoracolumbar fracture between 2009 and 2015 in University Hospital Aachen (Germany), Maastricht University Hospital (Netherlands) or Zuyderland Heerlen (Netherlands). Patients in Germany were treated by circumferential stabilization and in the Netherlands by posterior only surgery. OUTCOME MEASURES Clinical outcome parameters: number of segments, length of hospital stay, surgery times, complications. Radiological parameter: regional sagittal angle (RSA). Functional outcome parameters: VAS pain and Oswestry Disability Index (ODI). METHODS Patients were included by surgical equipoise in the circumferential group (CG) or the posterior only group (PG). Data about patient characteristics, fracture type and surgery type were distracted from patient files. RESULTS Seventy-nine patients were included for analysis (40 PG, 39 CG). Seventy-one percent completed two-year follow-up. Baseline characteristics were equal except for BMI (26.8 kg/m2 in the CG and 24.5 kg/m2 in the PG; p=.02). In the CG 77% of the fractures were classified as burst fractures, and in the PG there were 45% burst and 45% B-type fractures. Clinical outcome: the length of segment fixation was longer in the PG, with a mean of 4.3 levels compared to 3.3 levels in the CG (p CONCLUSIONS This two-nation study shows similar radiological and functional outcome in surgically treated thoracolumbar spinal fractures by posterior only compared to circumferential stabilization. Surgical time, low complication rate and shorter length of stay were all in benefit of the posterior only group, while the circumferential group had the advantage of shorter segment fixation. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Chordoma and its embryonic determinants

Background. Chordomas are rare malignant tumors occurring along the axial skeleton that originate from notochordal remnants. It is hypothesized that embryonic factors are involved in their aetiology. In the present study, four such factors are of interest: EVX1, which mediates posterior patterning of the embryo and is found in prostate. Wnt3a, localized to the placenta, is involved in different proliferation signaling pathways. Twist is a mediator of the epithelial-mesenchymal transition (EMT) and is expressed in the neuroblastoma cell line SHSY 5Y. Finally, brachyury is a crucial EMT mediator and involved in cell cycle regulation. Research question. The research question is tripartite. (I) It is the aim to obtain positive control tissue for validation of embryonic primers for the EVX1, Wnt3a and Twist genes. (II) Second, expression of brachyury mRNA in cultured chordoma cells will be assessed in order to validate the cell line. (III) Last, it will be investigated whether fibroblast conditioned cell culturing medium exerts a positive effect on chordoma proliferation in vitro. Materials and methods. (I) Placenta and prostate samples were obtained from patients in the Maastricht University Hospital. mRNA was isolated from prostate, placenta and SHSY 5Y cells and cDNA of the genes of interest was generated after which PCR and gel electrophoresis was employed to yield amplicon bands. (II) Chordoma cells were cultured and brachyury mRNA expression was assessed by PCR assay. (III) Cultured chordoma cells were grown in enriched DMEM or in enriched DMEM containing 33% fibroblast conditioned medium and proliferation was assessed. Results. (I) Both EVX1 and Twist are positive in prostate and SHSY 5Y respectively. Wnt3a is not positive in placenta. (II) Brachyury expression is either strongly downregulated or not expressed in two slowly growing chordoma cell cultures. (III) First data indicate enriched DMEM containing 33% fibroblast conditioned medium does not stimulate chordoma proliferation in vitro as compared to enriched DMEM without fibroblast conditioned medium.

Biomarkers for Prediction of Central Venous Catheter Related-Thrombosis in Patients With Hematological Malignancies.

In a prospective setting, we aimed to find associations between biomarkers of the hemostatic system and the occurrence of central venous catheter (CVC)-related thrombosis in patients with hematological malignancies undergoing intensive chemotherapy. The study was conducted between July 2006 and August 2010 at the University Hospital Maastricht, the Netherlands. Consecutive adult patients with hematological malignancies who were going to receive a CVC for intensive chemotherapy were included. The primary end points were (a) symptomatic CVC-related thrombosis and (b) CVC-related infections. Blood samples were taken directly after catheterization, and easy to determine biomarkers (platelet count, leukocyte count, and hemoglobin level) in combination with blood group, factor VIII (FVIII), plasminogen activator inhibitor 1 (PAI-1), activated protein C (APC) resistance, and free protein S antigen were determined. Blood was collected and analyzed from 168 patients. The incidence of symptomatic CVC-related thrombosis was 9%. In univariate analysis, white blood cell count >10.6 × 109/L, mean FVIII activity, and PAI-1 >12.2 IU/mL were found to be associated with the development of symptomatic CVC-related thrombosis. Elevated leukocyte count, high PAI-1, and high FVIII were associated with an increased incidence of symptomatic CVC-related thrombosis. We hope in future that simple, easy to determine laboratory tests that reflect the hemostatic and fibrinolytic activity in combination with clinical parameters may help to identify hematological patients at highest risk of CVC-related thrombosis and help to tailor the management of thromboprophylaxis in hematological patients undergoing CVC placement.

Liver resection in the elderly: A retrospective cohort study of 460 patients – Feasible and safe

IntroductionThe aim of this study was to determine the influence of age on the early postoperative outcome after liver surgery. Material and methodsBetween January 2005 and July 2012 460 hepatic resections were performed in patients aged 60 years or younger and 70 years or older at the University Hospital Aachen and University Hospital Maastricht. The postoperative outcome of hepatic resection was evaluated by the time of intensive care unit (ICU) stay, length of hospital stay, appearance of postoperative complications and in-hospital mortality. ResultsThe median postoperative hospital stay was 7 days in group ≤60 and 8 days in group ≥70 (p = 0.007). The median time of ICU stay was 1 day in both groups. There were no statistically significant differences according to liver related complications. In group ≥70, significantly more patients suffered from pneumonia (8% vs. 2% in group ≤60, p = 0.015). The overall mortality rate was 3.5%. ConclusionAge alone should not be a contraindication for liver resection. However, elderly patients who develop pneumonia are at high risk for postoperative mortality. Therefore, factors such as short time of invasive ventilation, direct and intensive respiratory therapy and mobilization are of particular importance and should be focused on even more.

TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC trial): study protocol for a randomized controlled trial.

BackgroundCervical intraepithelial neoplasia (CIN) is the premalignant condition of cervical cancer. Whereas not all high grade CIN lesions progress to cervical cancer, the natural history and risk of progression of individual lesions remain unpredictable. Therefore, high-grade CIN is currently treated by surgical excision: large loop excision of the transformation zone (LLETZ). This procedure has potential complications, such as acute haemorrhage, prolonged bleeding, infection and preterm birth in subsequent pregnancies. These complications could be prevented by development of a non-invasive treatment modality, such as topical imiquimod treatment.The primary study objective is to investigate the efficacy of topical imiquimod 5 % cream for the treatment of high-grade CIN and to develop a biomarker profile to predict clinical response to imiquimod treatment. Secondary study objectives are to assess treatment side-effects, disease recurrence and quality of life during and after different treatment modalities.Methods/designThe study design is a randomized controlled trial. One hundred forty women with a histological diagnosis of high-grade CIN (CIN 2–3) will be randomized into two arms: imiquimod treatment during 16 weeks (experimental arm) or immediate LLETZ (standard care arm). Treatment efficacy will be evaluated by colposcopy with diagnostic biopsies at 20 weeks for the experimental arm. Successful imiquimod treatment is defined as regression to CIN 1 or less, successful LLETZ treatment is defined as PAP 1 after 6 months. Disease recurrence will be evaluated by cytology at 6, 12 and 24 months after treatment. Side-effects will be evaluated using a standardized report form. Quality of life will be evaluated using validated questionnaires at baseline, 20 weeks and 1 year after treatment. Biomarkers, reflecting both host and viral factors in the pathophysiology of CIN, will be tested at baseline with the aim of developing a predictive biomarker profile for the clinical response to imiquimod treatment.DiscussionTreatment of high-grade CIN lesions with imiquimod in a selected patient population may diminish complications as a result of surgical intervention. More knowledge on treatment efficacy, side effects and long-term recurrence rates after treatment is necessary.Trial registrationEU Clinical Trials Register EU-CTR2013-001260-34. Registered 18 March 2013.Medical Ethical Committee approval number: NL44336.068.13 (Medical Ethical Committee Maastricht University Hospital, University of Maastricht).Affiliation: Maastricht University Hospital.Registration number ClinicalTrials.gov: NCT02329171.

Expression of Hedgehog signaling molecules in human atherosclerotic lesions: An autopsy study

Article history: Received 21 June 2015 Accepted 29 July 2015 Available online 31 July 2015 8 femoral artery (FA) segments and 10 carotid artery (CA) segments) were harvested at autopsy at the University Hospital Maastricht. The collection, storage and use of tissue and patient data were performed in accordancewith the “Code for Proper Use of SecondaryHumanTissue in The Netherlands”. The atherosclerotic lesion samples were classified to six categories according AHA classification [6]. Patient characteristics are presented in Table 1. The samples were stained with Shh, Ihh, and

The COgnitive-Pulmonary Disease (COgnitive-PD) study: protocol of a longitudinal observational comparative study on neuropsychological functioning of patients with COPD

IntroductionIntact cognitive functioning is necessary for patients with chronic obstructive pulmonary disease (COPD) to understand the value of healthy lifestyle guidelines, to make informed decisions and subsequently act on it....

The use of a proactive dissemination strategy to optimize reach of an internet-delivered computer tailored lifestyle intervention

BackgroundThe use of reactive strategies to disseminate effective Internet-delivered lifestyle interventions restricts their level of reach within the target population. This stresses the need to invest in proactive strategies to offer these interventions to the target population. The present study used a proactive strategy to increase reach of an Internet-delivered multi component computer tailored intervention, by embedding the intervention in an existing online health monitoring system of the Regional Public Health Services in the Netherlands.MethodsThe research population consisted of Dutch adults who were invited to participate in the Adult Health Monitor (N = 96,388) offered by the Regional Public Health Services. This Monitor consisted of an online or a written questionnaire. A prospective design was used to determine levels of reach, by focusing on actual participation in the lifestyle intervention. Furthermore, adequacy of reach among the target group was assessed by composing detailed profiles of intervention users. Participants’ characteristics, like demographics, behavioral and mental health status and quality of life, were included in the model as predictors.ResultsA total of 41,155 (43%) people participated in the Adult Health Monitor, of which 41% (n = 16,940) filled out the online version. More than half of the online participants indicated their interest (n = 9169; 54%) in the computer tailored intervention and 5168 participants (31%) actually participated in the Internet-delivered computer tailored intervention. Males, older respondents and individuals with a higher educational degree were significantly more likely to participate in the intervention. Furthermore, results indicated that especially participants with a relatively healthier lifestyle and a healthy BMI were likely to participate.ConclusionsWith one out of three online Adult Health Monitor participants actually participating in the computer tailored lifestyle intervention, the employed proactive dissemination strategy succeeded in ensuring relatively high levels of reach. Reach among at-risk individuals (e.g. low socioeconomic status and unhealthy lifestyle) was modest. It is therefore essential to further optimize reach by putting additional effort into increasing interest in the lifestyle intervention among at-risk individuals and to encourage them to actually use the intervention.Trial registrationDutch Trial Register (NTR1786) and Medical Ethics Committee of Maastricht University and the University Hospital Maastricht (NL2723506809/MEC0903016).

Perception of Bronchoconstriction: A Complementary Disease Marker in Children with Asthma

Introduction. Asthma guidelines use symptoms as the most important aspect of asthma control. Symptom perception varies widely between individuals. Over-perception as well as underperception of bronchoconstriction could have a negative effect on asthma management. We hypothesized that perception of bronchoconstriction in childhood asthma is not related to common measures of disease control. For that reason, we examined the clinical determinants of the perception of bronchoconstriction and the repeatability of perception measurements. Patients and methods. In school-age children with moderately severe atopic asthma, we measured the perception of bronchoconstriction (decrease in forced expiratory volume in 1 second (FEV1)) during methacholine bronchoprovocation challenges. The perception of bronchoconstriction was assessed as the slope of the relation between FEV1 and Borg score, and as the Borg score at a 20% decrease in FEV1 from baseline during the provocation test (PS20). Data from subjects who had a 20% or more decrease in FEV1 (n = 112) were used for the analysis. Fifty-four children repeated the test after 3 months. Symptoms, use of rescue medication, and peak expiratory flows were scored in diaries during the 2 weeks before testing. Results. Symptom perception was significantly better in children without (PD20 > 1570 μg, n = 28) than in children with airway hyperresponsiveness (PD20 ≤ 1570 μg, n = 112), slope 0.22 versus 0.13 respectively (p < .001). Borg scores correlated with PD20 (p = .01), baseline FEV1 (only for slope, p = .04), and use of rescue beta agonist (p = .01), but not with other aspects of asthma control. Repeatability of Borg scores was good (slope: R = 0.59, PS20: R = 0.52). Conclusion. Poorer symptom perception in asthmatic children correlated with hyperresponsiveness, and was associated with lower baseline FEV1 and less use of rescue bronchodilators. This suggests that the measurement of symptom perception should be taken into account in individual management plans for children with asthma.CATO Study Group Members: Department of Pediatric Respiratory Medicine, Haga Hospital/Juliana Children’s Hospital, The Hague (M. Nuijsink, M.D., J. M. Kouwenberg, M.D.). Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Rotterdam (W. C. J. Hop, Ph.D.). Department of Respiratory Medicine, Academic Medical Centre, University, Amsterdam (Prof. P. J. Sterk, Ph.D.). Leiden University Medical Center, Leiden (E. R. V. M. Rikkers-Mutsaerts, M.D.). Department of Pediatric Respiratory Diseases, University Medical Center Groningen (Prof. E. J. Duiverman, M.D., Ph.D.). Department of Pediatric Respiratory Medicine, Erasmus University Medical Center/Sophia Children’s Hospital, Rotterdam (Prof. J. C. de Jongste, M.D., Ph.D.). Asthma Center Heideheuvel, Hilversum (O. H. van der Baan-Slootweg, M.D., E. E. M. van Essen-Zandvliet, M.D., Ph.D.). Flevo Hospital, Almere (N. J. van den Berg, M.D., Ph.D.). Prof. Dr. J. M. Boogaard, Ph.D. Isala Klinieken, Zwolle (P. L. P. Brand, M.D. Ph.D., Ph.D., A. W. A. Kamps, M.D., Ph.D.). Medical Center, Alkmaar (G. Brinkhorst, M.D.). VU Medical Center, Amsterdam (J. E. Dankert-Roelse, M.D. Ph.D., A. F. Nagelkerke M.D.). Maxima Medical Center, Veldhoven (R. van Gent, M.D., Ph.D.). Maasland Hospital, Sittard (J. W. C. M. Heijnens, M.D.). University Hospital Maastricht (J. J. E. Hendriks, M.D., Ph.D., Q. Jöbsis, M.D., Ph.D.). University Medical Center/Wilhelmina Children’s Hospital, Utrecht (J. van der Laag, M.D., H. J. L. Brackel, M.D., Ph.D.). Academic Medical Center, Amsterdam (J. C. van Nierop, M.D.). Amphia Hospital, Breda (A. A. P. H. Vaessen-Verberne, M.D., Ph.D.) all from The Netherlands.

Sentinel node in ovarian cancer: study protocol for a phase 1 study

BackgroundThe concept of sentinel lymph node surgery is to determine whether the cancer has spread to the very first lymph node or sentinel node. If the sentinel node does not contain cancer, then there is a high likelihood that the cancer has not spread to other lymph nodes. The sentinel node technique has been proven to be effective in different types of cancer. In this study we want to determine whether a sentinel node procedure in patients with ovarian cancer is feasible when the tracers are injected into the ovarian ligaments.Methods/DesignPatients with a high likelihood of having an ovarian malignancy in whom a median laparotomy and a frozen section analysis is planned and patients with endometrial cancer in whom a staging laparotomy is planned will be included.Before starting the surgical staging procedure, blue dye and radioactive colloid will be injected into the ligamentum ovarii proprium and the ligamentum infundibulo-pelvicum. In the analysis we calculate the percentage of patients in whom it is feasible to identify sentinel nodes. Other study parameters are the anatomical localization of the sentinel node(s) and the incidence of false negative lymph nodes.Trial registrationApproval number: NL40323.068.12Name: Medical Ethical Committee Maastricht University Hospital, University of MaastrichtAffiliation: Maastricht University HospitalBoard Chair Name: Medisch Ethische Commissie azM/UM

Is s-ketamine with or without magnesium sulphate an alternative for postoperative pain treatment? Randomised study

Is s-ketamine with or without magnesium sulphate an alternative for postoperative pain treatment? Randomised study

Improvement of left atrial function and left atrial reverse remodeling after minimally invasive radiofrequency ablation evaluated by 2-dimensional speckle tracking echocardiography

The present study was aimed at demonstrating the beneficial effect of minimally invasive radiofrequency surgical ablation on left atrial remodeling using 2-dimensional speckle-tracking echocardiography. The study population consisted of 33 patients (mean age, 64.6 ± 6.9 years; 84.8% men) with paroxysmal lone atrial fibrillation undergoing minimally invasive radiofrequency surgical ablation at our institution (University Hospital Maastricht, Maastricht, The Netherlands) from 2007 to 2011. The control group included 20 age- and gender-matched healthy adults. The left atrial peak systolic strain, peak strain rate, peak early diastolic strain rate, and peak negative strain rate were measured. Left atrial reverse remodeling was defined as a reduction in the left atrial volume index of 15% or greater. The peak systolic strain was lower in patients with atrial fibrillation than in the controls (P<.001). It had increased significantly at 3 months (P<.001) and 12 months (P=.01) after surgery. Similarly, the peak strain rate (P<.001) was lower in patients with atrial fibrillation but had increased 3 months (P=.004) and 12 months (P=.001) after surgery. Finally, the peak early diastolic strain rate (P<.001) and peak negative strain rate (P<.001) were less negative at baseline compared with the rates in the controls. Both indexes had improved significantly at the follow-up examinations (3 months, P=.008 and P=.02; 12 months, both P=.01). Left atrial reverse remodeling occurred in 60.6% of patients at 3 months and 72.7% at 12 months postoperatively. Minimally invasive radiofrequency ablation resulted in significant left atrial reverse remodeling and significant improvement in left atrial compliance and function after restoration of sinus rhythm, as demonstrated by 2-dimensional speckle-tracking echocardiography analysis. Our findings need to be confirmed by additional and larger prospective studies.

Flavanols exert cardiovascular health benefits in humans by altering gene transcription levels in white blood cells

Epidemiological evidence highlights that a diet rich in flavanols reduces the risk of cardiovascular disease. The molecular mechanisms by which flavanols establish their vascular health effects in humans are still not fully clear.In a randomized, double‐blind, placebo controlled study gene transcription levels were determined in white blood cells of male smokers before and at the end of the 8‐weeks supplementation of daily 200 mg of monomeric and oligomeric grape‐seed flavanols. Upon approval by the Medical Ethical Committee of the Maastricht University and Academic Hospital Maastricht, The Netherlands, the study was conducted in accordance with the World Medical Association Declaration of Helsinki of 1975 as revised in 2008.Flavanols significantly altered expression of genes mediating inflammation, redox processes, lipid metabolism and endothelial homeostasis. The beneficial regulation of transcriptional pathways involved in the pathology of cardiovascular diseases is suggested a major subcellular mechanism by which flavanols sustain vascular health in humans.

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial

To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI). In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months. Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the only independent risk factors for MI. In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug-drug interaction.