Annette Geibel-Zehender’s research while affiliated with University of Freiburg and other places

Platelets can be found on the surface of inflamed and ruptured atherosclerotic plaques. Thus, targeting of activated platelets may allow for molecular imaging of vulnerable atherosclerotic lesions. We here investigated microbubbles (MB) functionalized with the selectin ligand sialyl Lewisa individually (MBsLea) or dually with sLea and an antibody targeting ligand-induced binding sites of the activated GPIIb/IIIa receptor (MBDual). Assessed by in vitro flow chamber, targeted MB exhibited increased adhesion to platelets as compared to MBControl. While MBsLea rolled slowly on the platelets’ surface, MBDual enhanced the percentage of firm adhesion. In vivo, MB were investigated by ultrasound in a model of ferric chloride induced non-occlusive carotid artery thrombosis. MBsLea and MBDual revealed a higher ultrasound mean acoustic intensity than MBControl (p < 0.05), however MBDual demonstrated no additional increase in mean signal intensity as compared to MBsLea. The degree of carotid artery stenosis on histology correlated well with the ultrasound acoustic intensity of targeted MB (p < 0.05). While dual targeting of MB using fast binding carbohydrate polymers and specific antibodies is a promising strategy to support adhesion to activated platelets under arterial shear stress, these advantages seem not readily translatable to in vivo models.

Restricted use of third-generation cephalosporins and fluoroquinolones has been linked to a reduced incidence of hospital-acquired infections with multidrug-resistant bacteria. We implemented an intensified antibiotic stewardship (ABS) programme in the medical service of a university hospital center aiming at a reduction by at least 30% in the use of these two drug classes. The ABS programme was focused on the 300-bed medical service. Prescription of third-generation cephalosporins was discouraged, whereas the use of penicillins was encouraged. Monthly drug use density was measured in WHO-ATC defined and locally recommended daily doses (DDD and RDD) per 100 patient days, to evaluate trends before (01/2008 to 10/2011) and after starting the intervention (1/2012 to 3/2013). The effect was analysed using interrupted time-series analysis with six non-intervention departments as controls. Following initiation of the ABS intervention, overall antibiotic use in the medical service declined (p < 0.001). There was a significant intervention-related decrease in the use of cephalosporins and fluoroquinolones (p < 0.001) outperforming the decreasing baseline trend. Trend changes observed in some of the control departments were smaller, and the difference between trend changes in the medical service and those in control departments were highly significant for overall use and cephalosporin use reductions (p < 0.001) as well as for the increasing use of penicillins (p < 0.001). Mean use density levels (in RDD per 100 patient days) dropped for cephalosporins from 16.3 to 10.3 (-37%) and for fluoroquinolones from 17.7 to 10.1 (-43%), respectively. During the same period, the use of penicillins increased (15.4 to 18.2; 18%). The changes in expenditures for antibiotics in the medical service compared to control services minus programme costs indicated initial net cost savings likely to be associated with the programme. An intensified ABS programme targeting cephalosporin und fluoroquinolone use in the setting of a large academic hospital is feasible and effective. The intervention may serve as a model for other services and hospitals with a similar structure and baseline situation.

To retrospectively investigate the potential cause of contained rupture of the aortic root in balloon-expandable transcatheter aortic valve implantation (TAVI) by means of pre- and postinterventional multislice computed tomography. Seventy-two patients (mean age 82±7 years, mean aortic valve area 0.69±0.19 cm(2)) underwent balloon-expandable TAVI using the EdwardsSAPIEN Transcatheter Heart Valve (23 mm, n=19; 26 mm, n=50; 29 mm, n=3). Aortic annulus dimensions were quantified by multislice computed tomography-based cross-sectional area assessment and average diameter calculation (CAAD) before and after TAVI. Post-TAVI multislice computed tomography data sets were available in 65 patients; contained aortic root rupture was diagnosed in 3 patients. Pre-TAVI CAAD was 23.1±1.8 mm; post-TAVI CAAD was 22.9±1.3 mm. Median relative change in CAAD pre- and post-TAVI was -0.5% (interquartile range, 3.6%). Relative increase of 5% to 10% was observed in 4 patients (1 with contained rupture), relative increase >10% in 2 patients, both with contained rupture. Mean relative oversizing, calculated as the relative difference in diameter between pre-TAVI CAAD and nominal diameter of the selected prosthesis, was 9.8%±7.8%. Relative oversizing was significantly higher in patients with contained rupture compared with patients without contained rupture (24.6%±5.4% versus 9.1%±6.6%; P<0.001). Relative oversizing ≥20% occurred in 6 patients (3 with contained rupture). Contained rupture of the aortic root in balloon-expandable TAVI is associated with severe prosthesis oversizing. Multislice computed tomography-based assessment of aortic annulus dimension in conjunction with adapted sizing guidelines may reduce the incidence of severe oversizing.

Cardiovascular diseases arise during 0,2% to 4% of all pregnancies in the industrialized world. In Germany, this type of complication, which is sometimes lethal, affects approximately 30 000 pregnant women per year. We performed a simple literature search in the NCBI databases for publications that appeared from 2008 to 2010 and that contained the search terms "pregnancy" and one of the following: "valvular disease," "endocarditis," "coronary heart disease," "cardiomyopathy," "hypertension," "anticoagulation." We also took consideration of the relevant international medical society guidelines and of the new database of the Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie in Berlin (Embryotox). There is a rising incidence, not only of hypertension during pregnancy, but also of valvular heart disease during pregnancy. Severe valvular stenosis, particularly mitral stenosis, raises the risk of pulmonary edema and should be treated before pregnancy, by valvuloplasty or surgically. Women with high-grade valvular insufficiency and restricted left-ventricular function are at risk of heart failure. For women with mechanical heart valves, the type of anticoagulation during pregnancy must be discussed on an individual basis. Coumarin derivatives are associated with an elevated risk of hemorrhage as well as coumarin embryopathy; recent studies have shown that the latter risk is low and dose-dependent. Spontaneous dissection of the coronary arteries is best treated by catheter intervention with the implantation of a bare metal stent. Women of child-bearing age who are at risk for, or already have, cardiovascular disease should receive early counseling and treatment, not just from their family physician, but from an interdisciplinary team composed of gynecologists, cardiologists, and, if necessary, cardiac surgeons.

ZUSAMMENFASSUNG Hintergrund: Kardiovaskuläre Erkrankungen treten bei 0,2 bis 4 Prozent der Schwangerschaften in den Industriena-tionen auf. In Deutschland sind etwa 30 000 Schwangere jährlich von diesen teilweise auch lebensbedrohlichen Komplikationen betroffen. Methoden: Einfache Literaturrecherche der Jahre 2008–2010 in den Datenbanken des NCBI mit den Suchbegriffen: "preg-nancy" AND "valvular disease", "endocarditis", "coronary heart disease", "cardiomyopathy", "hypertension" or "anti-coagulation". Zusätzlich Verwendung der Leitlinien der inter-nationalen Fachgesellschaften und der Datenbank "Embryo-tox". Ergebnisse: Neben den hypertensiven Schwangerschafts-erkrankungen nimmt der Anteil der Frauen mit Herzklap-penerkrankungen zu. Patientinnen mit schweren stenoti-schen Herzklappenerkrankungen, insbesondere der Mit-ralstenose, sind besonders bei der Entwicklung eines Lun-genödems gefährdet und sollten vor einer Schwanger-schaft katheterinterventionell oder operativ behandelt werden. Bei Patientinnen mit höhergradigen Klappeninsuf-fizienzen und eingeschränkter linksventrikulärer Funktion kann sich eine Herzinsuffizienz entwickeln. Die Antikoagu-lation bei mechanischem Herzklappenersatz muss indivi-duell besprochen werden. Cumarinderivate sind mit einem erhöhten Risiko für Blutungen und dem Risiko einer Cu-marin-Embryopathie verbunden, das aufgrund neuerer Studien als gering anzusehen ist und von der Dosis ab-hängt. Eine Spontandissektion der Koronararterien sollte bevorzugt katheterinterventionell mit Implantation eines unbeschichteten Stents behandelt werden.