How GDPR Enhances Transparency and Fosters Pseudonymisation in Academic Medical Research.

The European General Data Protection Regulation (GDPR) has dotted the i's and crossed the t's in the context of academic medical research. One year into GDPR, it is clear that a change of mind and the uptake of new procedures is required. Research organisations have been looking at the possibility to establish a code-of-conduct, good practices and/or guidelines for researchers that translate GDPR's abstract principles to concrete measures suitable for implementation. We introduce a proposal for the implementation of GDPR in the context of academic research which involves the processing of health related data, as developed by a multidisciplinary team at the University Hospitals Leuven. The proposal is based on three elements, three stages and six specific safeguards. Transparency and pseudonymisation are considered key to find a balance between the need for researchers to collect and analyse personal data and the increasing wish of data subjects for informational control.

Variation of the clavicle's muscle insertion footprints - a cadaveric study.

The muscle footprint anatomy of the clavicle is described in various anatomical textbooks but research on the footprint variation is rare. Our goal was to assess the variation and to create a probabilistic atlas of the muscle footprint anatomy. 14 right and left clavicles of anatomical specimens were dissected until only muscle fibers remained. 3D models with muscle footprints were made through CT scanning, laser scanning and photogrammetry. Then, for each side, the mean clavicle was calculated and non-rigidly registered to all other cadaveric bones. Muscle footprints were indicated on the mean left and right clavicle through the 1-to-1 mesh correspondence which is achieved by non-rigid registration. Lastly, 2 probabilistic atlases from the clavicle muscle footprints were generated. There was no statistical significant difference between the surface area (absolute and relative), of the originally dissected muscle footprints, of male and female, and left and right anatomical specimens. Visualization of all muscle footprints on the mean clavicle resulted in 72% (right) and 82% (left) coverage of the surface. The Muscle Insertion Footprint of each specimen covered on average 36.9% of the average right and 37.0% of the average left clavicle. The difference between surface coverage by all MIF and the mean surface coverage, shows that the MIF location varies strongly. From the probabilistic atlas we can conclude that no universal clavicle exists. Therefore, patient-specific clavicle fracture fixation plates should be considered to minimally interfere with the MIF. Therefore, patient-specific clavicle fracture fixation plates which minimally interfere with the footprints should be considered.

Added diagnostic value and impact on antimicrobial therapy of 16S rRNA PCR and amplicon sequencing on resected heart valves in infective endocarditis: a prospective cohort study.

OBJECTIVES: For adequate management and therapy of infective endocarditis (IE), identification of the causative pathogen is crucial but molecular testing results are not currently included in diagnostic criteria. The added diagnostic value and impact on antimicrobial therapy of 16S rRNA PCR and amplicon sequencing (16S rRNA PCR) performed on excised heart valves from patients with IE was evaluated alongside the effect of pre-operative antibiotics on the performance of blood culture (BC), valve culture (VC) and 16S rRNA PCR. METHODS: All patients undergoing valve surgery for definite or possible IE, according to modified Duke Criteria, were prospectively included from July 2013 up to and including June 2016. RESULTS: In all, 127 patients were included. Sensitivity for detecting the causative micro-organism in 120 post-operative definite IE patients was 26% for VC and 87% for BC and 16S rRNA PCR. 16S rRNA PCR, VC and BC were equally sensitive for different valve types and causative pathogens. In 27 (21%) definite IE patients, 16S rRNA PCR clarified discrepant culture results or was the only method identifying the causative pathogen. In 12 (10%) post-operative definite IE cases, molecular testing results influenced antimicrobial therapy. CONCLUSIONS: The very good performance characteristics, added diagnostic value and impact on antimicrobial therapy of molecular testing of heart valves should support the incorporation of molecular testing in diagnostic criteria and guidelines for IE.

Automated Delineation of Vessel Wall and Thrombus Boundaries of Abdominal Aortic Aneurysms Using Multispectral MR Images.

A correct patient-specific identification of the abdominal aortic aneurysm is useful for both diagnosis and treatment stages, as it locates the disease and represents its geometry. The actual thickness and shape of the arterial wall and the intraluminal thrombus are of great importance when predicting the rupture of the abdominal aortic aneurysms. The authors describe a novel method for delineating both the internal and external contours of the aortic wall, which allows distinguishing between vessel wall and intraluminal thrombus. The method is based on active shape model and texture statistical information. The method was validated with eight MR patient studies. There was high correspondence between automatic and manual measurements for the vessel wall area. Resulting segmented images presented a mean Dice coefficient with respect to manual segmentations of 0.88 and a mean modified Hausdorff distance of 1.14 mm for the internal face and 0.86 and 1.33 mm for the external face of the arterial wall. Preliminary results of the segmentation show high correspondence between automatic and manual measurements for the vessel wall and thrombus areas. However, since the dataset is small the conclusions cannot be generalized.

Post-operative echocardiographic evaluation of bioprosthetic mitral valve implantation in sheep.

The ovine model is generally considered to be the best for testing bioprosthetic heart valve durability. Although echocardiography is the method of choice for the interim evaluation of the valve, literature on sheep echocardiography is scarce. Within the context of a study on treatment of pericardial heart valve prostheses, 19 adolescent sheep underwent transthoracic echocardiography six days after mitral implantation of bioprosthetic valves. Echocardiographic examination was performed under mild anesthesia and animals were put in a right lateral decubitus position. Four images were obtained: right parasternal long axis four and five chamber views, right parasternal long axis view with left ventricular outflow, and right parasternal short axis view through the mitral valve. We measured aortic annulus and velocity time integral over the aortic valve to determine stroke volume, cardiac output and cardiac index. The mitral valve was evaluated through color Doppler imaging for valvular and paravalvular leakages. Pulsed wave spectral Doppler was used for the measurement of velocities, pressures and velocity time integrals. For the evaluation of valve stenosis deceleration time and pressure half-time were determined. Effective orifice area of the mitral valve was derived. And, although not measured, other structures could clearly be visualized: right and left ventricle and atrium, wall thicknesses, tricuspid valve. This study shows that echocardiography in sheep is feasible, and that right parasternal images, obtained in animals in a right lateral decubitus position, are well qualified for the interim evaluation of bioprosthetic valves implanted in the mitral position. Besides the implanted valve, other cardiac structures like atria and ventricles can be visualized and evaluated.

High-quality conforming hexahedral meshes of patient-specific abdominal aortic aneurysms including their intraluminal thrombi.

In order to perform finite element (FE) analyses of patient-specific abdominal aortic aneurysms, geometries derived from medical images must be meshed with suitable elements. We propose a semi-automatic method for generating conforming hexahedral meshes directly from contours segmented from medical images. Magnetic resonance images are generated using a protocol developed to give the abdominal aorta high contrast against the surrounding soft tissue. These data allow us to distinguish between the different structures of interest. We build novel quadrilateral meshes for each surface of the sectioned geometry and generate conforming hexahedral meshes by combining the quadrilateral meshes. The three-layered morphology of both the arterial wall and thrombus is incorporated using parameters determined from experiments. We demonstrate the quality of our patient-specific meshes using the element Scaled Jacobian. The method efficiently generates high-quality elements suitable for FE analysis, even in the bifurcation region of the aorta into the iliac arteries. For example, hexahedral meshes of up to 125,000 elements are generated in less than 130 s, with 94.8 % of elements well suited for FE analysis. We provide novel input for simulations by independently meshing both the arterial wall and intraluminal thrombus of the aneurysm, and their respective layered morphologies.

Steam ablation versus radiofrequency and laser ablation: an in vivo histological comparative trial.

OBJECTIVE: There is an increasing use of minimal invasive techniques to treat saphenous vein reflux. Among these radiofrequency ablation (RFA), endovenous laser ablation (EVLA), and foam sclerotherapy are frequently used. A new method of thermal ablation is the steam vein sclerosing (SVS) system. This study evaluates the histological changes after ablation of the saphenous veins in goats with RFA, EVLA, and SVS. METHODS: Twelve saphenous veins in six goats were treated with one of the three treatment modalities: four veins with RFA, four with EVLA, four with SVS. Seven days after treatment occlusion and diameter changes were evaluated by ultrasound imaging and histological changes were examined microscopically. RESULTS: Vein length, mean diameter, and the amount of tumescence was comparable between the three groups. Histological examination showed extensive vein wall destruction, the least in the outer layer of the vein wall. The total vein wall damage was 9.2/15 (SD 3.5) for EVLA, 13.3/15 (SD 3.3) for RFA, and 11.2/15 (SD 2.8) for SVS group. There was no significant difference among the three groups. Perivenous tissue damage was low. No extrafascial damage was seen. CONCLUSION: Histological findings after steam ablation are similar to the RFA and EVLA with a low perivenous tissue destruction score and a high vein wall destruction score.

Assessment of strain and strain rate by two-dimensional speckle tracking in mice: comparison with tissue Doppler echocardiography and conductance catheter measurements.

AIMS: This study was designed in order to compare the strain and strain rate deformation parameters assessed by speckle tracking imaging (STI) with those of tissue Doppler imaging (TDI) and conductance catheter measurements in chronic murine models of left ventricular (LV) dysfunction. METHODS AND RESULTS: Twenty-four male C57BL/6J mice were assigned to wild-type (n = 8), myocardial infarction (n = 8) and transaortic constriction (n = 8) groups. Echocardiographic and conductance measurements were simultaneously performed at rest and during dobutamine infusion (5 µg/kg/min) in all animals 10 weeks post-surgery. The LV circumferential strain (Scirc) and the strain rate (SRcirc) were derived from grey scale and tissue Doppler data at frame rates of 224 and 375 Hz, respectively. Scirc and SRcirc by TDI/STI correlated well with the preload recruitable stroke work (PRSW) (r = -0.64 and -0.71 for TDI; r = -0.46 and -0.50 for STI, P < 0.05). Both modalities showed a good agreement with respect to Scirc and SRcirc (r = 0.60 and r = 0.63, P < 0.05). During stress, however, TDI-estimated Scirc and SRcirc values were predominantly higher than those measured by STI (P < 0.05). The similarity of Scirc and SRcirc measurements with respect to the STI/TDI data was examined by the Bland-Altman analysis. CONCLUSION: In mice, the STI- and TDI-derived strain and strain rate deformation parameters relate closely to intrinsic myocardial function. At low heart rate-to-frame rate ratios (HR/FR), both STI and TDI are equally acceptable for assessing the LV function non-invasively in these animals. At HR/FR (e.g. dobutamine challenge), however, these methods cannot be used interchangeably as STI underestimates S and SR at high values.

The relative value of strain and strain rate for defining intrinsic myocardial function.

It is well accepted that strain and strain rate deformation parameters are not only a measure of intrinsic myocardial contractility but are also influenced by changes in cardiac load and structure. To date, no information is available on the relative importance of these confounders. This study was designed to investigate how strain and strain rate, measured by Doppler echocardiography, relate to the individual factors that determine cardiac performance. Echocardiographic and conductance measurements were simultaneously performed in mice in which individual determinants of cardiac performance were mechanically and/or pharmacologically modulated. A multivariable analysis was performed with radial and circumferential strains and peak systolic radial and circumferential strain rates as dependent parameters and preload recruitable stroke work (PRSW), arterial elastance (E(a)), end-diastolic pressure, and left ventricular myocardial volume (LVMV) as independent factors representing myocardial contractility, afterload, preload, and myocardial volume, respectively. Radial strain was most influenced by E(a) (ß = -0.58, R(2) = 0.34), whereas circumferential strain was strongly associated with E(a) and moderately with LVMV (ß = 0.79 and -0.52, respectively, R(2) = 0.54). Radial strain rate was related to both PRSW and LVMV (ß = 0.79 and -0.62, respectively, R(2) = 0.50), whereas circumferential strain rate showed a prominent correlation only with PRSW (ß = -0.61, R(2) = 0.51). In conclusion, strain (both radial and circumferential) is not a good surrogate measure of intrinsic myocardial contractility unless the strong confounding influence of afterload is considered. Strain rate is a more robust measure of contractility that is less influenced by changes in cardiac load and structure. Thus, peak systolic strain rate is the more relevant parameter to assess myocardial contractile function noninvasively.

Response of mouse brain perfusion to hypo- and hyperventilation measured by arterial spin labeling.

We aimed to setup a noninvasive and well-controlled methodology for evaluation of the cerebrovascular response in mice (C57BL/6J; 12 weeks). Therefore we applied a normo-, hypo-, and hyperventilation paradigm combined with arterial spin labeling and monitoring of the expired CO(2) (expCO(2)) (n=7) or arterial pCO(2) (apCO(2)) (n=12). Reducing the tidal volume by 25% and the respiratory rate by 20% resulted in hypercapnia (apCO(2) from 33 ± 6 mmHg to 64 ± 16 mmHg). Increasing the respiratory rate by 25% and the tidal volume by 20% decreased apCO(2) to 22 ± 5 mmHg. Cerebral blood flow (CBF) was 82 ± 21, 163 ± 41 and 64 ± 18 mL/100 g/min during normo, hypo-, and hyperventilation, respectively (midbrain). The correlation of apCO(2) and CBF levels resulted in a cerebrovascular response of 2.7 ± 0.3, 2.1 ± 0.3, 2.1 ± 0.3, and 3.7 ± 0.5 mL/100 g/min/mmHg for midbrain, cortex, hippocampus and thalamus, respectively. As expCO(2) levels were correlated with apCO(2) (r(2)=0.86; n=4) and CBF (r(2)=0.67) a cerebrovascular response based on simultaneously recorded CBF and expCO(2) levels could be derived (3.3 ± 0.5, 2.5 ± 0.4, 3.0 ± 0.4, and 4.5 ± 0.6 mL/100 g/min/mmHg; order as above). A cross-over experiment resulted in similar responses. In conclusion, this protocol allows evaluating basal CBF and cerebrovascular response in mice under well-controlled conditions by simply changing ventilator settings and correlating CBF with apCO(2) and/or simultaneously obtained expCO(2).

Influence of heart rate reduction on Doppler myocardial imaging parameters in a small animal model.

In small animals studies, sick animals often have a significant reduction in heart rate while under anesthesia. The influence of heart rate reduction on Doppler myocardial imaging (DMI) parameters is not known. The aim of the present study was to assess the effect of heart rate reduction on DMI parameters in a small animal model. Twenty-four rats underwent transthoracic echocardiography at baseline and during the administration of ivabradine IV. In all rats, left ventricular (LV) systolic velocity, strain and strain rate were measured in the anteroseptal and inferolateral wall segments from short axis views. In 12 rats (group A), M-mode analysis was also performed for assessment of global LV function. In the other 12 rats (groups B), contractility was quantified invasively using the end-systolic pressure-volume relation (ESPVR) and the preload recruitable stroke work (PRSW). During ivabradine, administration heart rate decreased by 18% in group A (p < 0.001) and 36% in group B (p < 0.001). There was a slight increase in LVEDD and LVESD, with no change in cardiac output or LV ejection fraction. During ivabradine administration, DMI parameters did not change significantly in any group. No significant correlation between DMI parameters and heart rate (r(2) = 0.05) or ejection time (r(2) = 0.14) could be found. The absence of changes in contractility was confirmed by the absence of change in PRSW and end-systolic elastance (Ees). In conclusion, moderate heart rate reduction did not influence DMI measurements in this specific rat model. Therefore, in the interpretation of DMI data when performing small animal studies, moderate heart rate reduction does not need to be taken into account.

Nosocomial infective endocarditis: should the definition be extended to 6 months after discharge.

Because the microbiology and patient population of infective endocarditis (IE) have evolved, the traditional definition of nosocomial IE may require revision. The question of whether this definition should be extended to 6 months after discharge was explored, and a high rate of episodes with nosocomial pathogens (coagulase-negative staphylococci) and a low rate of episodes with community pathogens (streptococci) in the extended nosocomial group were found. Therefore, modification of the traditional definition is proposed, distinguishing between early (as traditionally described) and late nosocomial IE (IE in association with a significant invasive procedure performed during a hospitalization between 8 weeks and 6 months before the onset of symptoms).

Lack of the effect of superoxide dismutase and catalase on Na+,K+-ATPase activity in stunned rabbit hearts.

Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (+/-LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not prevented by antioxidant enzymes. These results suggest that administration of SOD and catalase in perfusate do not protect significantly against cardiac dysfunction in stunned rabbit myocardium.

Methicillin-resistant versus methicillin-sensitive Staphylococcus aureus infective endocarditis.

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is increasing. This study compared clinical characteristics and mortality in patients with methicillin-sensitive S. aureus (MSSA) IE versus MRSA IE, based on a prospectively collected series of 72 consecutive patients with definite S. aureus IE according to the modified Duke criteria between June 2000 and December 2006. Sixteen of 72 IE patients (22%) were caused by MRSA. Nosocomial origin, surgical site infection, surgery in the previous 6 months, the presence of a catheter and persistent bacteremia were significantly associated with MRSA. MSSA patients had significantly more unknown origin of bacteremia and experienced a significantly higher rate of major embolism than MRSA patients. MSSA patients underwent more frequently combined surgical and antimicrobial therapy, and MRSA patients were treated more frequently with antimicrobial therapy due to a contraindication to surgery. The 6-month mortality was higher in patients with MRSA than MSSA. In the MSSA group treated with antimicrobial therapy without an indication to surgery, all patients survived, and in the combined surgical and antimicrobial group 29% died. The mortality in MRSA patients was lowest if combined surgical and antimicrobial therapy was performed. Both in MSSA and MRSA patients with antimicrobial therapy due to a contraindication to surgery, the mortality was extremely high. These data suggest that in S. aureus IE patients with a nosocomial origin, the presence of a catheter or recent surgery, initial therapy should include antimicrobial agents active against MRSA. Antimicrobial therapy alone with close monitoring of the therapeutic effect and signs of complicated course is an acceptable approach in selected patients with MSSA IE. Denial of surgery because of local or general factors in patients that meet criteria for surgical intervention in acute IE is prognostically ominous.

[The effect of type II diabetes and the metabolic syndrome on cardiac second window preconditioning]. / Het effect van type ii diabetes en het metabool syndroom op cardiale tweede venster preconditionering.

Preconditioning is the most powerful endogenous mechanism, to protect the heart against ischemic damage. Conflicting data are published whether preconditioning can be induced in case of diabetes and the metabolic syndrome, which are clinically very relevant conditions. If preconditioning could be induced consistently and chronically in this population, an important reduction of surgical morbidity and mortality could be reached. In this project we induced hypoxic preconditioning in mice and used cardiac pressure-conductance catheterisation and infarct size as outcome parameters. In the first part, we found that hypoxic preconditioning was capable to reduce infarct size with 40% and preserve the load-independent parameters with 33% after coronary occlusion. A DKO (double knock-out: ob/ob; LDLR-/-) model for the metabolic syndrome developed a larger infarct size and had a reduced contractility. No preconditioning could be induced in this model. To detect the determing factor of the resistance to preconditioning, we used single knock-out models. A comparable preconditioning effect of wild type mice could be induced in the lipoprotein receptor deficient (LDLR-/-) model for dyslipidemia. The leptin deficient (ob/ob) model, characterized by insulin resistance and abdominal obesity had, identically to the DKO model, a larger infarct size. A second window of preconditioning could be induced, although it was less pronounced than the wild type and LDLR-/- model. Insulin resistance and abdominal obesity could be identified as the major factor in the resistance to preconditioning.

Infective endocarditis.

The diagnosis of infective endocarditis remains difficult. The complication rate is very high. Serious complications may occur and the overall mortality is still 20-25%. The sooner the treatment is started, the better the final result. Antibiotic therapy is essential but cardiac surgery is frequently necessary. Early surgery improves outcome. A multidisciplinary approach by internal medicine, cardiology and cardiac surgery facilitates the efficiency of diagnosis and treatment.

Evolving trends in infective endocarditis.

Infective endocarditis is a microbial infection of the endocardial surface and, despite improvements in diagnostic accuracy, medical therapy and surgical techniques, mortality remains high. This review focuses on changes in epidemiology, microbiology and diagnosis, as well as changes in medical and surgical management of infective endocarditis affecting native and prosthetic valves in adults, that have evolved during the past two decades. Significant changes have included an increasing involvement of prosthetic valves and nosocomially-acquired disease, an increased involvement of staphylococci as the causative agents, and a recognition that elderly individuals with degenerative valvular disease are the most vulnerable population. Topics still requiring study include whether and when valve replacement should be performed, and how to predict perivalvular complications or embolisation based on echocardiography findings. Optimisation of antimicrobial treatment schemes (choice of the antibiotic, dose and duration) also requires further investigation.