Kris Bogaerts

Circulating Oxidized LDL Is a Useful Marker for Identifying Patients With Coronary Artery Disease

Abstract—Our aim was to determine the usefulness of circulating oxidized low density lipoprotein (LDL) in the identification of patients with coronary artery disease (CAD). A total of 304 subjects were studied: 178 patients with angiographically proven CAD and 126 age-matched subjects without clinical evidence of cardiovascular disease. The Global Risk Assessment Score (GRAS) was calculated on the basis of age, total and high density lipoprotein cholesterol, blood pressure, diabetes mellitus, and smoking. Levels of circulating oxidized LDL were measured in a monoclonal antibody 4E6-based competition ELISA. Compared with control subjects, CAD patients had higher levels of circulating oxidized LDL (P <0.001) and a higher GRAS (P <0.001). The sensitivity for CAD was 76% for circulating oxidized LDL (55% for men and 81% for women) compared with 20% (24% for men and 12% for women) for GRAS, with a specificity of 90%. Logistic regression analysis revealed that the predictive value of oxidized LDL was additive to that of GRAS (P <0.001). Ninety-four percent of the subjects with high (exceeding the 90th percentile of distribution in control subjects) circulating oxidized LDL and high GRAS had CAD (94% of the men and 100% of the women). Thus, circulating oxidized LDL is a sensitive marker of CAD. Addition of oxidized LDL to the established risk factors may improve cardiovascular risk prediction.

Efficacy and Safety of Tenecteplase in Combination With the Low-Molecular-Weight Heparin Enoxaparin or Unfractionated Heparin in the Prehospital Setting The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS Randomized Trial in Acute Myocardial Infarction

Background—The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial infarction. Methods and Results—In the prehospital setting, 1639 patients with ST-elevation myocardial infarction were randomly assigned to treatment with tenecteplase and either (1) intravenous bolus of 30 mg enoxaparin (ENOX) followed by 1 mg/kg subcutaneously BID for a maximum of 7 days or (2) weight-adjusted unfractionated heparin (UFH) for 48 hours. The median treatment delay was 115 minutes after symptom onset (53% within 2 hours). ENOX tended to reduce the composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia to 14.2% versus 17.4% for UFH (P =0.080), although there was no difference for this composite end point plus in-hospital intracranial hemorrhage or major bleeding (18.3% versus 20.3%, P =0.30). Correspondingly, there were reductions in in-hospital reinfarction (3.5% versus 5.8%, P =0.028) and refractory ischemia (4.4% versus 6.5%, P =0.067) but increases in total stroke (2.9% versus 1.3%, P =0.026) and intracranial hemorrhage (2.20% versus 0.97%, P =0.047). The increase in intracranial hemorrhage was seen in patients >75 years of age. Conclusions—Prehospital fibrinolysis allows 53% of patients to receive reperfusion treatment within 2 hours after symptom onset. The combination of tenecteplase with ENOX reduces early ischemic events, but lower doses of ENOX need to be tested in elderly patients. At present, therefore, tenecteplase and UFH are recommended as the routine pharmacological reperfusion treatment in the prehospital setting.

Fibrinolysis or Primary PCI in ST-Segment Elevation Myocardial Infarction

BACKGROUND It is not known whether prehospital fibrinolysis, coupled with timely coronary angiography, provides a clinical outcome similar to that with primary percutaneous coronary intervention (PCI) early after acute ST-segment elevation myocardial infarction (STEMI). METHODS Among 1892 patients with STEMI who presented within 3 hours after symptom onset and who were unable to undergo primary PCI within 1 hour, patients were randomly assigned to undergo either primary PCI or fibrinolytic therapy with bolus tenecteplase (amended to half dose in patients ≥75 years of age), clopidogrel, and enoxaparin before transport to a PCI-capable hospital. Emergency coronary angiography was performed if fibrinolysis failed; otherwise, angiography was performed 6 to 24 hours after randomization. The primary end point was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days. RESULTS The primary end point occurred in 116 of 939 patients (12.4%) in the fibrinolysis group and in 135 of 943 patients (14.3%) in the primary PCI group (relative risk in the fibrinolysis group, 0.86; 95% confidence interval, 0.68 to 1.09; P=0.21). Emergency angiography was required in 36.3% of patients in the fibrinolysis group, whereas the remainder of patients underwent angiography at a median of 17 hours after randomization. More intracranial hemorrhages occurred in the fibrinolysis group than in the primary PCI group (1.0% vs. 0.2%, P=0.04; after protocol amendment, 0.5% vs. 0.3%, P=0.45). The rates of nonintracranial bleeding were similar in the two groups. CONCLUSIONS Prehospital fibrinolysis with timely coronary angiography resulted in effective reperfusion in patients with early STEMI who could not undergo primary PCI within 1 hour after the first medical contact. However, fibrinolysis was associated with a slightly increased risk of intracranial bleeding. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00623623.).

Recurrence of Mitral Valve Regurgitation After Mitral Valve Repair in Degenerative Valve Disease

Background—Durability assessment of mitral valve repair for degenerative valve incompetence is actually limited to reoperation as the primary indicator, with valve-related risk factors for late death as a secondary indicator. We assessed serial echocardiographic follow-up of valve function as an indicator of the durability of mitral valve repair. Methods and Results—In 242 patients who had undergone mitral valve repair for degenerative valve incompetence, echocardiographic follow-up of valve function, rate of reoperation, survival, and clinical outcome was studied. At 8 years after repair, clinical outcome was excellent, survival was 90.9±3.2%, freedom from reoperation was 94.2±2.3%, and freedom from anticoagulation bleeding and thromboembolic events was 90.4±2.7%. However, freedom from non-trivial mitral regurgitation (>1/4) was 94.3±1.6% at 1 month, 58.6±4.9% at 5 years, and 27.2±8.6% at 7 years. Freedom from severe mitral regurgitation (>2/4) was 98.3±0.9% at 1 month, 82.8±3.8% at 5 years and 71.1±7.4% at 7 years. The linearized recurrence rate of non-trivial mitral regurgitation (>1/4) was 8.3% per year and of severe mitral regurgitation (>2/4) was 3.7% per year. Inadequate surgical techniques (chordal shortening, no use of annuloplasty ring or sliding plasty) could only partially explain recurrence of regurgitation. In selected patients who did not have these risk factors, linearized recurrence rates were 6.9% per year and 2.5% per year, respectively. Conclusion—The durability of a successful mitral reconstruction for degenerative mitral valve disease is not constant, and this should be taken into account when asymptomatic patients are offered early mitral valve repair.

Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE

STUDY QUESTION The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2009: are there any changes in the trends compared with previous years? SUMMARY ANSWER Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. WHAT IS KNOWN ALREADY Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis. PARTICIPANTS/MATERIALS SETTING, METHODS From 34 countries (-2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partners semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported. MAIN RESULTS AND THE ROLE OF CHANCE In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.

Mapping of Pelvic Lymph Node Metastases in Prostate Cancer

BACKGROUND Opinions about the optimal lymph node dissection (LND) template in prostate cancer differ. Drainage and dissemination patterns are not necessarily identical. OBJECTIVE To present a precise overview of the lymphatic drainage pattern and to correlate those findings with dissemination patterns. We also investigated the relationship between the number of positive lymph nodes (LN+) and resected lymph nodes (LNs) per region. DESIGN, SETTING, AND PARTICIPANTS Seventy-four patients with localized prostate adenocarcinoma were prospectively enrolled. Patients did not show suspect LNs on computed tomography scan and had an LN involvement risk of ≥ 10% but ≤ 35% (Partin tables) or a cT3 tumor. INTERVENTION After intraprostatic technetium-99m nanocolloid injection, patients underwent planar scintigraphy and single-photon emission computed tomography imaging. Then surgery was performed, starting with a sentinel node (SN) procedure and a superextended lymphadenectomy followed by radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Distribution of scintigraphically detected SNs and removed SNs per region were registered. The number of LN+, as well as the percentage LN+ of the total number of removed LNs per region, was demonstrated in combining data of all patients. The impact of the extent of LND on N-staging and on the number of LN+ removed was calculated. RESULTS AND LIMITATIONS A total of 470 SNs were scintigraphically detected (median: 6; interquartile range [IQR]: 3-9), of which 371 SNs were removed (median: 4; IQR: 2.25-6). In total, 91 LN+ (median: 2; IQR: 1-3) were found in 34 of 74 patients. The predominant site for LN+ was the internal iliac region. An extended LND (eLND) would have correctly staged 32 of 34 patients but would have adequately removed all LN+ in only 26 of 34 patients. When adding the presacral region, these numbers increased to 33 of 34 and 30 of 34 patients, respectively. CONCLUSIONS Standard eLND would have correctly staged the majority of LN+ patients, but 13% of the LN+ would have been missed. Adding the presacral LNs to the template should be considered to obtain a minimal template with maximal gain. NOTE: This manuscript was invited based on the 2011 European Association of Urology meeting in Vienna.

Use of Time by Stroke Patients. A Comparison of Four European Rehabilitation Centers

Background and Purpose— Differences exist between European countries in the proportion of patients who die or become dependent after stroke. The aim of the present study was to identify differences in the use of time by stroke patients in 4 rehabilitation centers in 4 European countries. Methods— In each of the 4 centers, 60 randomly selected stroke patients were observed at 10-minute intervals using behavioral mapping. Observations took place on 30 weekdays selected at random, on equal numbers of morning, afternoon, and evening sessions. A logistic generalized estimating equation model with correction for differences in case mix and multiple testing was used for the analysis. Results— Overall time available from different professions was the highest in the United Kingdom, but patients in the United Kingdom spent on average only 1 hour per day in therapy. This was significantly less than patients in Belgium and Germany, who spent ≈2 hours, and patients in Switzerland who spent ≈3 hours per day in therapy. In all centers, patients spent less than half their time in interactions and >72% of the time in nontherapeutic activities. Conclusions— Important differences in the use of time were established, which appeared dependent on management decisions rather than the number of staff available. Patients in the Swiss and German centers spent more time in therapy, possibly because of the structured organization of rehabilitation. Further studies will verify whether this has an effect on outcome.

Prospective Evaluation of 11C-Choline Positron Emission Tomography/Computed Tomography and Diffusion-Weighted Magnetic Resonance Imaging for the Nodal Staging of Prostate Cancer with a High Risk of Lymph Node Metastases

BACKGROUND Contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging for lymph node (LN) staging of prostate cancer (PCa) are largely inadequate. OBJECTIVE Our aim was to assess prospectively the sensitivity, specificity, and positive and negative predictive values for the LN staging by (11)C-choline positron emission tomography (PET)-CT and MR diffusion-weighted imaging (DWI) of the pelvis before retropubic radical prostatectomy (RRP) with extended pelvic LN dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS From February 2008 to August 2009, 36 patients with histologically proven PCa and no pelvic LN involvement on contrast-enhanced CT with a risk ≥ 10% but ≤ 35% at LN metastasis according to the Partin tables were enrolled in this study. INTERVENTION Patients preoperatively underwent (11)C-choline PET-CT and DWI. Subsequently all patients underwent a wide RRP and an extended PLND. MEASUREMENTS Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for LN status of (11)C-choline PET-CT and DWI were calculated with the final histopathology of the LNs as comparator. RESULTS AND LIMITATIONS Seventeen patients (47%) had a pN1 stage, and 38 positive LNs were identified. On a LN region-based analysis, sensitivity, specificity, PPV, NPV, and the number of correctly recognised cases at (11)C-choline PET-CT were 9.4%, 99.7%, 75.0%, 91.0%, and 7.9%, respectively, and at DWI these numbers were 18.8%, 97.6%, 46.2%, 91.7%, and 15.8%, respectively. Twelve LN regions containing macrometastases, of which 2 had capsular penetration, were not detected by (11)C-choline PET-CT; 11 LNs, of which 2 had capsular penetration, were not detected by DWI. This is a small study with 36 patients, but we intend to recruit more patients. CONCLUSIONS From this prospective histopathology-based evaluation of (11)C-choline PET-CT and DWI for LN staging in high-risk PCa patients, it is concluded that these techniques cannot be recommended at present to detect occult LN metastases before initial treatment.

Prosthesis-Patient Mismatch Predicts Structural Valve Degeneration in Bioprosthetic Heart Valves

Background— Prosthesis-patient mismatch (P-PtM) after aortic valve replacement results in disturbed valve performance associated with increased pressure gradients. However, it is unknown whether this can be related to future structural valve deterioration (SVD) of the bioprosthesis. Methods and Results— In 564 patients (mean age, 74±5 years) receiving an aortic valve bioprosthesis, clinical follow-up (median, 6.1 years; maximum, 16.4 years) was analyzed including echocardiography. SVD was diagnosed in 40 patients (7%) as substantially increased stenosis (n=24) or regurgitation (n=16) of the operated valve over time. When patients with P-PtM (effective orifice area index <0.85 cm2/m2; n=285) developed SVD, it was preferentially of the stenosis type, whereas when patients without P-PtM (n=279) developed SVD, the majority was of the incompetence type (P<0.05). Multivariable analysis including patient- and valve-related variables revealed that P-PtM and label size ≤21 were independent predictors of SVD (P=0.04 and P=0.02, respectively). A nonparametric Turnbull estimate analysis showed that SVD is virtually nonexistent for up to 9 years in patients without P-PtM. Thereafter, SVD starts to occur and is mainly of the incompetence-type SVD (79% of cases). In patients with P-PtM, SVD starts to occur after 2 to 3 years after implantation and is mainly of the stenosis-type SVD (81% of cases). Conclusions— These data suggest that stenosis-type SVD is an early, P-PtM–related, and thus preventable phenomenon. Incompetence-type SVD is a time-dependent, nonspecific wear damage to bioprosthetic valves, which is not related to P-PtM.

Motor and Functional Recovery After Stroke A Comparison of 4 European Rehabilitation Centers

Background and Purpose— Outcome after first stroke varies significantly across Europe. This study was designed to compare motor and functional recovery after stroke between four European rehabilitation centers. Methods— Consecutive stroke patients (532 patients) were recruited. They were assessed on admission and at 2, 4, and 6 months after stroke with the Barthel Index, Rivermead Motor Assessment of Gross Function, Rivermead Motor Assessment of Leg/Trunk, Rivermead Motor Assessment of Arm, and Nottingham Extended Activities of Daily Living (except on admission). Data were analyzed using random effects ordinal logistic models adjusting for case-mix and multiple testing. Results— Patients in the UK center were more likely to stay in lower Rivermead Motor Assessment of Gross Function classes compared with patients in the German center (&Dgr;OR, 2.4; 95% CI, 1.3 to 4.3). In the Swiss center, patients were less likely to stay in lower Nottingham Extended Activities of Daily Living classes compared with patients in the UK center (&Dgr;OR, 0.7; 95% CI, 0.5 to 0.9). The latter were less likely to stay in lower Barthel Index classes compared with the patients in the German center (&Dgr;OR, 0.6; 95%CI, 0.4 to 0.8). Recovery patterns of Rivermead Motor Assessment of Leg/Trunk and Rivermead Motor Assessment of Arm were not significantly different between centers. Conclusions— Gross motor and functional recovery were better in the German and Swiss centers compared with the UK center, respectively. Personal self-care recovery was better in the UK compared with the German center. Previous studies in the same centers indicated that German and Swiss patients received more therapy per day. This was not the result of more staff but of a more efficient use of human resources. This study indicates potential for improving rehabilitation outcomes in the UK and Belgian centers.