Early hemodynamics and clinical outcomes of isolated aortic valve replacement with stentless or transcatheter valve in intermediate-risk patients.

OBJECTIVE: Stentless aortic valves have been developed to overcome obstructive limitations associated with stented bioprostheses. The aim of the current multi-institutional study was to compare hemodynamics of transcatheter (TAVR) and the Freedom SOLO Stentless (FS) valve in an intermediate risk population undergoing surgical aortic valve replacement. METHODS: From 2010 to 2014, 420 consecutive patients underwent isolated surgical aortic valve replacement with FS and 375 patients underwent TAVR. Only patients with intermediate operative risk (Society of Thoracic Surgeons score 4-10) and small aortic annulus (≤23 mm) were included. After a propensity matched analysis 142 patients in each group were selected. Thirty-day postoperative clinical and echocardiographic parameters were evaluated. RESULTS: Mean prosthesis diameter was 22.2 ± 0.9 mm for FS and 22.4 ± 1.0 mm for TAVR. In-hospital mortality was 2.1% for FS and 6.3% for TAVR (P = .02). Postoperative FS peak gradients were 19.1 ± 9.6 mm Hg (mean 10.8 ± 5.9 mm Hg); TAVR peak gradients were 20.2 ± 9.5 mm Hg (mean 10.7 ± 6.9 mm Hg) P = .57 (P = .88). Postoperative effective orifice area was 1.93 ± 0.52 cm2 for FS and 1.83 ± 0.3 cm2 for TAVR (P = .65). There was no prostheses-patient mismatch in either group. Postoperative grade 2-3 paravalvular leak was present in 3.5% for TAVR and 0.7% for FS. Postoperative permanent pacemaker implant rate was 12% for TAVR and only 1 case (0.7%) in the FS group (P < .001). CONCLUSIONS: In patients with small aortic annulus and intermediate risk, both FS and TAVR demonstrated similar excellent hemodynamic performance. TAVR demonstrated greater mortality and rates of pacemaker insertion. Further studies are warranted to validate TAVR indications in this subset of patients.

Flex Robotic System in transoral robotic surgery: The first 40 patients.

BACKGROUND: The Flex Robotic System is a new robotic device specifically developed for transoral robotic surgery (TORS). METHODS: We performed a prospective clinical study, assessing the safety and efficacy of the Medrobotics Flex Robotic System. A total of 40 patients required a surgical procedure for benign lesions (n = 30) or T1 and T2 carcinomas (n = 10). Access and visualization of different anatomic subsites were individually graded by the surgeon. Setup times, access and visualization times, surgical results, as well as adverse events were documented intraoperatively. RESULTS: The lesions could be exposed and visualized properly in 38 patients (95%) who went on to have a surgical procedure performed with the Flex Robotic System, which were intraoperatively evaluated as successful. No serious adverse events occurred. CONCLUSION: Lesions in the oropharynx, hypopharynx, or supraglottic larynx could be successfully resected using the Flex Robotic System, thus making the system a safe and effective tool in transoral robotic surgery. © 2016 Wiley Periodicals, Inc. Head Neck 39: 471-475, 2017.

Pericardial Stentless Valve for Aortic Valve Replacement: Long-Term Results.

BACKGROUND: The Freedom Solo (FS) bovine pericardial valve (Sorin Group, Milan, Italy) is a stentless bioprosthesis that was introduced in 2004 and approved by the United States Food and Drug Administration in 2014. No long-term follow-up series are available to date. We report the multicenter experience of 4 European institutions that began implanting FS extensively from its introduction, providing the largest series with long-term follow-up. METHODS: From 2004 to 2009, 565 patients (242 women [42.8%]; mean age, 74.6 ± 8.3 years) underwent isolated (n = 350) or combined (n = 215) aortic valve replacement with the FS. Mean follow-up, including clinical and strict echocardiographic evaluation, was 6.9 ± 3.7 years (maximum, 11.8 years; cumulative 2,965 patient-years). Primary end point was freedom from structural valve deterioration (SVD), and secondary end points were freedom from reoperation and overall survival. RESULTS: Mean logistic European System for Cardiac Operative Risk Evaluation I was 10.3% ± 6.7%. Overall 30-day mortality was 3.7%, and no deaths were valve related. There was no severe prostheses-patient mismatch, and moderate prostheses-patient mismatch occurred only in 1 patient (0.17%). Twenty-eight patients (5.2%) underwent reoperation (20 surgical replacements, 8 transcatheter aortic valve-in-valve replacements) due to endocarditis in 9, blunt trauma in 1, and SVD in 18. SVD was reported in 5 other patients alive at time of censoring. Freedom from SVD and reoperation was 90.8% (95% confidence interval, 89.1% to 92.5%) and 87.3% (95% confidence interval, 85.6% to 89.0%), respectively, at 10 years of follow-up, and the overall actuarial survival was 56.4% (95% confidence interval, 53.3% to 59.5%). CONCLUSIONS: The FS valve provided excellent long-term durability and hemodynamic performance in this large, multicenter European experience. Moreover, the FS, given the low rate of SVD, along with a simple implantability, proved to be a reliable bioprosthesis in the aortic position as a valid alternative to stented bioprostheses.

Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins.

Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.

Synaptic membrane proteins form stable microdomains in early endosomes.

In the plasma membrane, membrane proteins are frequently organized in microdomains that are stabilized both by protein-protein and protein-lipid interactions, with the membrane lipid cholesterol being instrumental for microdomain stability. However, it is unclear whether such microdomains persist during endocytotic membrane trafficking. We used stimulated emission-depletion microscopy to investigate the domain structure of the endosomes. We developed a semiautomatic method for counting the individual domains, an approach that we have validated by immunoelectron microscopy. We found that in endosomes derived from neuroendocrine PC12 cells synaptophysin and several SNARE proteins are organized in microdomains. Cholesterol depletion by methyl-beta-cyclodextrin disintegrates most of the domains. Interestingly, no change in the frequency of microdomains was observed when endosomes were fused with protein-free liposomes of similar size (in what constitutes a novel approach in modifying acutely the lipid composition of organelles), regardless of whether the membrane lipid composition of the liposomes was similar or very different from that of the endosomes. Similarly, Rab depletion from the endosome membranes left the domain structure unaffected. Furthermore, labeled exogenous protein, introduced into endosomes by liposome fusion, equilibrated with the corresponding microdomains. We conclude that synaptic membrane proteins are organized in stable but dynamic clusters within endosomes, which are likely to persist during membrane recycling.

Upregulation of Id-1 via BMP-2 receptors induces reactive oxygen species in podocytes.

Bone morphogenetic proteins (BMPs) are secreted signaling molecules, which play a major role in kidney development and disease. Here, we show the existence of mRNA for BMP-2 and for the BMP receptors BMPR1A, BMPR1B, BMPRII, ACVR1A, ACVR2, and ACVR2B in differentiated mouse podocytes and the protein expression of BMPR1A in human glomerular podocytes. BMP-2 dose dependently increases the free cytosolic Ca(2+) concentration in podocytes proving the existence of a functional receptor in these cells. Recent data indicate that in a myoblastic cell line and in a breast cancer cell line, BMP-2 increases the expression of Id-1, a negative regulator of basic helix-loop-helix transcription factors, but the role of BMP-2 stimulated Id-1 expression in the kidney has not been further characterized. Here, we show that BMP-2 increases the expression of Id-1 in differentiated podocytes. To investigate a role of Id-1 for podocyte function, overexpression of Id-1 was induced in differentiated mouse podocytes. Id-1-overexpressing podocytes show an increased NADPH-dependent production of reactive oxygen species (ROS). This effect can be evoked by BMP-2 and can be antagonized by anti-Id-1 antisense oligonucleotides. The data indicate that BMP-2 may, via an increased expression of Id-1 and an increased generation of ROS, contribute to important cellular functions in podocytes. ROS supposedly play a major role in cell adhesion, cell injury, ion transport, fibrogenesis, angiogenesis and are involved in the pathogenesis of membranous nephropathy.

Structural domains required for channel function of the mouse transient receptor potential protein homologue TRP1beta.

Transient receptor potential proteins (TRP) are supposed to participate in the formation of store-operated Ca(2+) influx channels by co-assembly. However, little is known which domains facilitate the interaction of subunits. Contribution of the N-terminal coiled-coil domain and ankyrin-like repeats and the putative pore region of the mouse TRP1beta (mTRP1beta) variant to the formation of functional cation channels were analyzed following overexpression in HEK293 (human embryonic kidney) cells. MTRP1beta expressing cells exhibited enhanced Ca(2+) influx and enhanced whole-cell membrane currents compared to mTRP1beta deletion mutants. Using a yeast two-hybrid assay only the coiled-coil domain facilitated homodimerization of the N-terminus. These results suggest that the N-terminus of mTRP1beta is required for structural organization thus forming functional channels.