In situ introducer sheath dilatation for complex aortic access.

Aortic access problems due to diseased or small peripheral vessels are a major issue in endovascular aneurysm repair (EVAR). In the emergency setting, like aortic rupture after blunt trauma, or in patients with a hostile abdomen, a more proximal access to the aorta is not a pleasant perspective. We developed in situ introducer sheath dilatation as a bail-out technique for patients with difficult aortic access under various circumstances including EVAR, intra-aortic balloon pump insertion and cannulation for perfusion. The method described allows to increase the access vessel diameter by 50% (from 6 to 9 mm) or the luminal circumference from 18 to 27 F. We have used this technique in five patients without complication, very much in contrast to the traditionally practiced 'forced device insertion'.

How to Preserve Renal Function in Transcatheter Aortic Valve Therapies

Background: Transcatheter aortic valve implantations (TAVI) are indicated in high risk patients requiring aortic valve replacement (AVR). However, CT-scans, coronary angiograms and intraoperative aortographies can induce contrast-related nephro-toxicity with a concrete risk of acute postoperative renal failure, especially in severely diseased patients. To prevent this complication, we routinely perform transapical (TA) TAVI guided by transesophageal echocardiogram and fluoroscopy without angiography. Material and Methods: From November 2008 to December 2009, 31 high-risk patients suffering from severe symptomatic aortic stenosis underwent TA-TAVI in our institution. The preoperative imaging assessment (cardiac CT-scan and coronary angiogram) was performed no less than 10 days before the TA-TAVI in all patients (to recover the renal function) with a low-dose protocol for injected contrast medium (equivalent to the patient's weight for the CT-scan). During the TA-TAVI, the stent-valve positioning was performed without any contrast injection. Results: 32 consecutive stent-valve were successfully positioned in 31 patients (mean age 80.76 8 8.3 years; mean EuroSCORE: 32.2 8 12.9%) through a transapical access (1 patient required 2 valves for valve embolisation). The mean preoperative creatinine and urea blood levels were 102.6 8 67.7 _ g/dl (range 53-339 _ g/dl) and 8.45 8 4.9 mmol/l, respectively. A chronic renal insufficiency affected 12 patients (38.7%) with 1 patient in pre-dialysis. Postoperatively, no patient developed acute myocardial infarction, atrio-ventricular block or acute renal insufficiency (mean creatinine level: 89.7 8 64.55 _ g/dl; urea level: 7.11 8 3.47 mmol/l) and the 30-days mortality was 9.67% (3 patients). Conclusion: Specific preoperative and intraoperative protocols that require lowdoses or absence of contrast medium are useful to preserve the renal function in high risk patients operated for TAVI.

Rapid prototyping of compliant human aortic roots for assessment of valved stents.

Adequate in-vitro training in valved stents deployment as well as testing of the latter devices requires compliant real-size models of the human aortic root. The casting methods utilized up to now are multi-step, time consuming and complicated. We pursued a goal of building a flexible 3D model in a single-step procedure. We created a precise 3D CAD model of a human aortic root using previously published anatomical and geometrical data and printed it using a novel rapid prototyping system developed by the Fab@Home project. As a material for 3D fabrication we used common house-hold silicone and afterwards dip-coated several models with dispersion silicone one or two times. To assess the production precision we compared the size of the final product with the CAD model. Compliance of the models was measured and compared with native porcine aortic root. Total fabrication time was 3 h and 20 min. Dip-coating one or two times with dispersion silicone if applied took one or two extra days, respectively. The error in dimensions of non-coated aortic root model compared to the CAD design was <3.0% along X, Y-axes and 4.1% along Z-axis. Compliance of a non-coated model as judged by the changes of radius values in the radial direction by 16.39% is significantly different (P<0.001) from native aortic tissue--23.54% at the pressure of 80-100 mmHg. Rapid prototyping of compliant, life-size anatomical models with the Fab@Home 3D printer is feasible--it is very quick compared to previous casting methods.

Meropenem prevents levofloxacin-induced resistance in penicillin-resistant pneumococci and acts synergistically with levofloxacin in experimental meningitis.

The aim of the present study was to investigate the potential synergy between meropenem and levofloxacin in vitro and in experimental meningitis and to determine the effect of meropenem on levofloxacin-induced resistance in vitro. Meropenem increased the efficacy of levofloxacin against the penicillin-resistant pneumococcal strain KR4 in time-killing assays in vitro and acted synergistically against a second penicillin-resistant strain WB4. In the checkerboard, only an additive effect (FIC indices: 1.0) was observed for both strains. In cycling experiments in vitro, levofloxacin alone led to a 64-fold increase in the MIC for both strains after 12 cycles. Addition of meropenem in sub-MIC concentrations (0.25 x MIC) completely inhibited the selection of levofloxacin-resistant mutants in WB4 after 12 cycles. In KR4, the addition of meropenem led to just a twofold increase in the MIC for levofloxacin after 12 cycles. Mutations detected in the genes encoding for topoisomerase IV (parC) and gyrase (gyrA) confirmed the levofloxacin-induced resistance in both strains. Addition of meropenem was able to completely suppress levofloxacin-induced mutations in WB4 and led to only one mutation in parE in KR4. In experimental meningitis, meropenem, given in two doses (2 x 125 mg/kg), produced a good bactericidal activity (-0.45 Deltalog10 cfu/ml.h) comparable to one dose (1 x 10 mg/kg) of levofloxacin (-0.44 Deltalog10 cfu/ml.h) against the penicillin-resistant strain WB4. Meropenem combined with levofloxacin acted synergistically (-0.93 Deltalog10 cfu/ml.h), sterilizing the CSF of all rabbits.

Setting in motion the immune mechanisms underlying genetically determined resistance and susceptibility to infection with Leishmania major.

The murine model of infection with Leishmania major has allowed the demonstration of a causal relationship between, on the one hand, genetically determined resistance to infection and the development of a Th1 CD4+ cell response, and on the other hand, genetically determined susceptibility and Th2 cell maturation. Using this murine model of infection, the role of cytokines in directing the functional differentiation pathway of CD4+ T cell precursors, has been demonstrated in vivo. Thus, IL-12 and IFN-gamma have been shown to favour Th1 cell development and IL-4 is crucial for the differentiation of Th2 responses. Maturation of a Th2 response in susceptible BALB/c mice following infection with L. major is triggered by the IL-4 produced during the first two days after parasite inoculation. This IL-4 rapidly renders parasite specific CD4+ T cells precursors unresponsive to IL-12. A restricted population of CD4+ T cells expressing the V beta 4V alpha 8 TCR heterodimer and recognizing a single epitope on the LACK (Leishmania Activated C-Kinase) antigen of L. major is responsible for this rapid production of IL-4, instructing subsequent differentiation towards the Th2 phenotype of CD4+ T cells specific for several parasite antigens.

Plant defense against herbivory: progress in identifying synergism, redundancy, and antagonism between resistance traits.

Plants respond to herbivore attack through a complex and variable system of defense, involving different physical barriers, toxic chemicals, and recruitment of natural enemies. To fully understand the relative role of each type of defense, their synergisms, redundancies, or antagonisms between traits, a variety of methods of enquiry, commonly used in plant physiology and ecology, have been employed. By overexpressing or silencing genes of interest, it is possible to understand the specific role of a particular defensive molecule or mode of action. We argue, however, that these types of experiments alone are not enough to holistically understand the physiological as well as ecological role of plant defenses. We thus advocate for the use of a combination of methods, including genetic modification, quantitative genetics, and phylogenetically controlled comparative studies.

Urgent reoperative transapical valve-in-valve shortly after a transapical aortic valve implantation.

Urgent reoperative transapical aortic valve-in-valve has never been proposed as a treatment option in case of a failed transcatheter aortic valve implantation (TAVI) or in case of worsening of an existing paravalvular leak, if this complication occurs right after, or a few days after, the primary transapical aortic valve implantation. Experienced surgeons should argue that after a transapical TAVI, the apex is damaged and fragile, with a high risk of irreparable ventricular tears and life-threatening bleeding if a second transapical procedure is scheduled during the acute phase. Nevertheless, if the patient is inoperable and the vascular status, including the ascending aorta, limits alternative accesses, the urgent reoperative transapical valve-in-valve becomes an alternative. We illustrate, for the first time ever, our experience with an 81-year old female patient who underwent a transapical (TA) TAVI with a Sapien? XT 23 mm. The day after the procedure, the patient haemodynamically worsened in combination with a worsening of a known (grade 1-2) paravalvular leak. Thus, on postoperative day two, an urgent transapical valve-in-valve was performed, and a second Sapien? XT 23 mm was placed, with an excellent haemodynamic result and absence of leak. The redo apical access did not appear very complicated and the postoperative recovery was uneventful.

Treatment of experimental endocarditis due to erythromycin-susceptible or -resistant methicillin-resistant Staphylococcus aureus with RP 59500.

RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against erythromycin-susceptible and -resistant gram-positive pathogens. The present experiments compared the therapeutic efficacy of RP 59500 with that of vancomycin against experimental endocarditis due to either of two erythromycin-susceptible or two constitutively erythromycin-resistant isolates of methicillin-resistant Staphylococcus aureus. RP 59500 had low MICs for the four test organisms as well as for 24 additional isolates (the MIC at which 90% of the isolates were inhibited was &lt; 1 mg/liter) which were mostly inducibly (47%) or constitutively (39%) erythromycin resistant. Aortic endocarditis in rats was produced with catheter-induced vegetations. Three-day therapy was initiated 12 h after infection, and the drugs were delivered via a computerized pump, which permitted the mimicking of the drug kinetics produced in human serum by twice-daily intravenous injections of 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Both antibiotics reduced vegetation bacterial titers to below detection levels in ca. 70% of animals infected with the erythromycin-susceptible isolates (P &lt; 0.05 compared with titers in controls). Vancomycin was also effective against the constitutively resistant strains, but RP 59500 failed against these isolates. Further experiments proved that RP 59500 failures were related to the very short life span of dalfopristin in serum (&lt; or = 2 h, compared with &gt; or = 6 h for quinupristin), since successful treatment was restored by artificially prolonging the dalfopristin levels for 6 h. Thus, RP 59500 is a promising alternative to vancomycin against methicillin-resistant S. aureus infections, provided that pharmacokinetic parameters are adjusted to afford prolonged levels of both of its constituents in serum. This observation is also relevant to humans, in whom the life span of dalfopristin in serum is also shorter than that of quinupristin.

Right-sided vegetation unmasks aortic endocarditis

Echocardiography is a key tool in the diagnosis of infective endocarditis. Although transthoracic echocardiography is the first step in the work-up, transoesophageal echocardiography is mandatory for the evaluation of the exact extent of the infectious process. Indeed, perivalvular abscess can fistulate towards different heart chambers, leading sometimes to critical clinical situations.

Transcatheter aortic valve implantation in a lung transplant recipient.

Transcatheter aortic valve implantation is a feasible therapeutic option for selected patients with severe aortic stenosis and high or prohibitive risk for standard surgery. Lung transplant recipients are often considered high-risk patients for heart surgery because of their specific transplant-associated characteristics and comorbidities. We report a case of successful transfemoral transcatheter aortic valve replacement in a lung transplant recipient with a symptomatic severe aortic stenosis, severe left ventricular dysfunction, and end-stage renal failure 9 years after bilateral lung transplantation.