Open issues in transcatheter aortic valve implantation. Part 2: procedural issues and outcomes after transcatheter aortic valve implantation.

This article provides an overview on procedure-related issues and uncertainties in outcomes after transcatheter aortic valve implantation (TAVI). The different access sites and how to select them in an individual patient are discussed. Also, the occurrence and potential predictors of aortic regurgitation (AR) after TAVI are addressed. The different methods to quantify AR are reviewed, and it appears that accurate and reproducible quantification is suboptimal. Complications such as prosthesis-patient mismatch and conduction abnormalities (and need for permanent pacemaker) are discussed, as well as cerebrovascular events, which emphasize the development of optimal anti-coagulative strategies. Finally, recent registries have shown the adoption of TAVI in the real world, but longer follow-up studies are needed to evaluate the outcome (but also prosthesis durability). Additionally, future studies are briefly discussed, which will address the use of TAVI in pure AR and lower-risk patients.

Open issues in transcatheter aortic valve implantation. Part 1: patient selection and treatment strategy for transcatheter aortic valve implantation.

An exponential increase in the use of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis has been witnessed over the recent years. The current article reviews different areas of uncertainty related to patient selection. The use and limitations of risk scores are addressed, followed by an extensive discussion on the value of three-dimensional imaging for prosthesis sizing and the assessment of complex valve anatomy such as degenerated bicuspid valves. The uncertainty about valvular stenosis severity in patients with a mismatch between the transvalvular gradient and the aortic valve area, and how integrated use of echocardiography and computed tomographic imaging may help, is also addressed. Finally, patients referred for TAVI may have concomitant mitral regurgitation and/or coronary artery disease and the management of these patients is discussed.

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES Survival, stroke, and New York Heart Association functional class. RESULTS Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.

Higher order parametric excitation modes for spaceborne quadrupole mass spectrometers

This paper describes a technique to significantly improve upon the mass peak shape and mass resolution of spaceborne quadrupolemass spectrometers (QMSs) through higher order auxiliary excitation of the quadrupole field. Using a novel multiresonant tank circuit, additional frequency components can be used to drive modulating voltages on the quadrupole rods in a practical manner, suitable for both improved commercial applications and spaceflight instruments. Auxiliary excitation at frequencies near twice that of the fundamental quadrupole RF frequency provides the advantages of previously studied parametric excitation techniques, but with the added benefit of increased sensed excitation amplitude dynamic range and the ability to operate voltage scan lines through the center of upper stability islands. Using a field programmable gate array, the amplitudes and frequencies of all QMS signals are digitally generated and managed, providing a robust and stable voltage control system. These techniques are experimentally verified through an interface with a commercial Pfeiffer QMG422 quadrupole rod system. When operating through the center of a stability island formed from higher order auxiliary excitation, approximately 50% and 400% improvements in 1% mass resolution and peak stability were measured, respectively, when compared with traditional QMS operation. Although tested with a circular rod system, the presented techniques have the potential to improve the performance of both circular and hyperbolic rod geometry QMS sensors.

Enabling the Next Generation of Spaceborne Quadrupole Mass Spectrometers

The quadrupole mass spectrometer (QMS) has over 30 years of spaceflight heritage in making important neutral gas and low energy ion observations. Given their geometrical constraints, these instruments are currently operated at the extreme limit of their capabilities. However, a technique called higher order auxiliary excitation provides a set of novel, robust, electronics-based solutions for improving the performance of these sensors. By driving the quadrupole rods with an additional frequency nearly twice that of the normal RF operating frequency, substantially increased abundance sensitivity, maximum attainable mass resolution, and peak stability can be achieved through operation of voltage scan lines through the center of formed upper stability islands. Such improvements are modeled using numerical simulations of ion trajectories in a quadrupole field with and without applied higher order auxiliary excitation. When compared to a traditional QMS with a mass range up to 500Da, sensors can be designed with the same precision electronics to have expected mass ranges beyond 1500Da with a power increase of less than twice that of its heritage implementations.

Treatment of posttraumatic cubitus varus in children and adolescents. Supracondylar humeral osteotomy using radial external fixation

OBJECTIVE Precise adaptable fixation of a supracondylar humerus osteotomy with a radial/lateral external fixator to correct posttraumatic cubitus varus. INDICATIONS Acquired, posttraumatic cubitus varus as a result of a malhealed and unsatisfactorily treated supracondylar humerus fracture. Idiopathic, congenital cubitus varus (very seldom) if the child (independent of age and after complete healing) is cosmetically impaired; stability of the elbow is reduced due to malalignment (hyperextension); secondary problems and pain (e. g., irritation of the ulnar nerve) are expected or already exist; or there is an explicit wish of the child/parents (relative indication). CONTRAINDICATIONS In principle there are no contraindications provided that the indication criteria are filled. The common argument of age does not represent a contraindication in our opinion, since angular remodeling at the distal end of the humerus is practically nonexistent. SURGICAL TECHNIQUE Basically, the surgical technique of the radial external fixator is used as previously described for stabilization of complex supracondylar humeral fractures. With the patient in supine position, the arm is placed freely on an arm table. Using a 4-5 cm long skin incision along the radial, supracondylar, the extracapsular part of the distal humerus is prepared, whereby great caution regarding the radial nerve is advised. In contrast to the procedure used in radial external fixation for supracondylar humeral fracture treatment, two Schanz screws are always fixed in each fragment at a distance of 1.5-2 cm. The osteotomy must allow the fragment to freely move in all directions. The proximal and distal two Schanz screws are then connected with short 4 mm carbon or stainless steel rods. These two rods are connected with each other over another rod using the tub-to-tub technique. Now the preliminary correction according the clinical situation can be performed and the clamps are tightened. Anatomical axis and function are checked. If these are radiologically and clinically perfect, all clamps are definitively tightened; if the alignment or the function is not perfect, then further adjustments can be made. POSTOPERATIVE MANAGEMENT Due to the excellent stability, further immobilization not necessary. Immediate functional follow-up treatment performed according to pain. RESULTS Adequate healing is usually expected within 6 weeks. At this time the external fixator can be removed in the fracture clinic. Because the whole operation is performed in an extraarticular manner and the mobility of the elbow is not affected, deterioration of function has never been observed. Also regarding the cosmetic/anatomical situation, good results are expected because they were already achieved intraoperatively.

Metamorphosis of human lumbar vertebrae induced by VEPTR growth modulation and stress shielding

INTRODUCTION Distraction-based spinal growth modulation by growing rods or vertical expandable prosthetic titanium ribs (VEPTRs) is the mainstay of instrumented operative strategies to correct early onset spinal deformities. In order to objectify the benefits, it has become common sense to measure the gain in spine height by assessing T1-S1 distance on anteroposterior (AP) radiographs. However, by ignoring growth changes on vertebral levels and by limiting measurement to one plane, valuable data is missed regarding the three-dimensional (3D) effects of growth modulation. This information might be interesting when it comes to final fusion or, even more so, when the protective growing implants are removed and the spine re-exposed to physiologic forces at the end of growth. METHODS The goal of this retrospective radiographic study was to assess the growth modulating impact of year-long, distraction-based VEPTR treatment on the morphology of single vertebral bodies. We digitally measured lumbar vertebral body height (VBH) and upper endplate depth (VBD) at the time of the index procedure and at follow-up in nine patients with rib-to-ileum constructs (G1) spanning an anatomically normal lumbar spine. Nine patients with congenital thoracic scoliosis and VEPTR rib-to-rib constructs, but uninstrumented lumbar spines, served as controls (G2). All had undergone more than eight half-yearly VEPTR expansions. A Wilcoxon signed-rank test was used for statistical comparison of initial and follow-up VBH, VBD and height/depth (H/D) ratio (significance level 0.05). RESULTS The average age was 7.1 years (G1) and 5.2 year (G2, p > 0.05) at initial surgery; the average overall follow-up time was 5.5 years (p = 1). In both groups, VBH increased significantly without a significant intergroup difference. Group 1 did not show significant growth in depth, whereas VBD increased significantly in the control group. As a consequence, the H/D ratio increased significantly in group 1 whereas it remained unchanged in group 2. The growth rate for height in mm/year was 1.4 (group 1) and 1.1 (group 2, p = 0.45), and for depth, it was -0.3 and 1.1 (p < 0.05), respectively. CONCLUSIONS VEPTR growth modulating treatment alters the geometry of vertebral bodies by increasing the H/D ratio. We hypothesize that the implant-related deprivation from axial loads (stress-shielding) impairs anteroposterior growth. The biomechanical consequence of such slender vertebrae when exposed to unprotected loads in case of definitive VEPTR removal at the end of growth is uncertain.

Microbiota at teeth and implants in partially edentulous patients. A 10-year retrospective study.

OBJECTIVE To determine the microbiota at implants and adjacent teeth 10 years after placement of implants with a sandblasted and acid-etched surface. MATERIAL AND METHODS Plaque samples obtained from the deepest sites of 504 implants and of 493 adjacent teeth were analyzed for certain bacterial species associated with periodontitis, for staphylococci, for aerobic gram-negative rods, and for yeasts using nucleic acid-based methods. RESULTS Species known to be associated with periodontitis were detectable at 6.2-78.4% of the implants. Significantly higher counts at implants in comparison with teeth were assessed for Tannerella forsythia, Parvimonas micra, Fusobacterium nucleatum/necrophorum, and Campylobacter rectus. Higher counts of periodontopathogenic species were detectable at implants of current smokers than at those of non-smokers. In addition, those species were found in higher quantities at implants of subjects with periodontitis. The prevalence of Prevotella intermedia, Treponema denticola, C. rectus, and moreover of Staphylococcus warneri might be associated with peri-implant inflammation. Selected staphylococcal species (not Staphylococcus aureus), aerobic gram-negative rods, and yeasts were frequently detected, but with the exception of S. warneri, they did not show any association with periodontal or peri-implant diseases. CONCLUSIONS Smoking and periodontal disease are risk factors for colonization of periodontopathic bacteria at implants. Those bacterial species may play a potential role in peri-implant inflammation. The role of S. warneri needs further validation.

Confocal analysis of synaptic connectivity of the rod pathway in the rabbit retina

The retina is a specialized neuronal structure that transforms the optical image into electrical signals which are transmitted to the brain via the optic nerve. As part of the strategy to cover a stimulus range as broad as 10 log units, from dim starlight to bright sunlight, retinal circuits are broadly divided into rod and cone pathways, responsible for dark and light-adapted vision, respectively. ^ In this dissertation, confocal microscopy and immunocytochemical methods were combined to study the synaptic connectivity of the rod pathway from the level of individual synapses to whole populations of neurons. The study was focused on synaptic interactions at the rod bipolar terminal. The purpose is to understand the synaptic structure of the dyad synapse made by rod bipolar terminals, including the synaptic components and connections, and their physiological functions in the rod pathway. In addition, some additional components and connections of the rod pathway were also studied in these experiments. The major results can be summarized as following: At the dyad synapse of rod bipolar terminals, three postsynaptic components—processes of All amacrine cells and the varicosities of S1 or S2 amacrine cells express different glutamate receptor subunits, which may underlie the functional diversity of these postsynaptic neurons. A reciprocal feedback system is formed by rod bipolar terminals and S1/S2 amacrine cells. Analysis showed these two wide-field GABA amacrine cells have stereotyped synaptic connections with the appropriate morphology and distribution to perform specific functions. In addition, S1 and S2 cells have different coupling patterns and, in general, there is no coupling between the two types. Besides the classic rod pathway though rod bipolar cells and All amacrine cells, the finding of direct connections between certain types of OFF cone bipolar cells and rods indicates the presence of an alternative rod pathway in the rabbit retina. ^ In summary, this dissertation presents a detailed view of the connection and receptors at rod bipolar terminals. Based on the morphology, distribution and coupling, different functional roles were identified for S1 and S2 amacrine cells. Finally, an alternative to the classic rod pathway was found in the rabbit retina. ^

Diversity of neuronal connexins in the mammalian retina

Many neurons in the mammalian retina are electrically coupled by intercellular channels or gap junctions, which are assembled from a family of proteins called connexins. Numerous studies indicate that gap junctions differ in properties such as conductance and tracer permeability. For example, A-type horizontal cell gap junctions are permeable to Lucifer Yellow, but B-type horizontal cell gap junctions are not. This suggests the two cell types express different connexins. My hypothesis is that multiple neuronal connexins are expressed in the mammalian retina in a cell type specific manner. Immunohistochemical techniques and confocal microscopy were used to localize certain connexins within well-defined neuronal circuits. The results of this study can be summarized as follows: AII amacrine cells, which receive direct input from rod bipolar cells, are well-coupled to neighboring AIIs. In addition, AII amacrine cells also form gap junctions with ON cone bipolar cells. This is a complex heterocellular network. In both rabbit and primate retina, connexin36 occurs at dendritic crossings in the AII matrix as well as between AIIs and ON cone bipolar cells. Coupling in the AII network is thought to reduce noise in the rod pathway while AII/bipolar gap junctions are required for the transmission of rod signals to ON ganglion cells. In the outer plexiform layer, connexin36 forms gap junctions between cones and between rods and cones via cone telodendria. Cone to cone coupling is thought to reduce noise and is partly color selective. Rod to cone coupling forms an alternative rod pathway thought to operate at intermediate light intensity. A-type horizontal cells in the rabbit retina are strongly coupled via massive low resistance gap junctions composed from Cx50. Coupling dramatically extends the receptive field of horizontal cells and the modulation of coupling is thought to change the strength of the feedback signal from horizontal cells to cones. Finally, there are other coupled networks, such as B-type horizontal cells and S1/S2 amacrine cells, which do not use either connexin36 or Cx50. These results confirm the hypothesis that multiple neuronal connexins are expressed in the mammalian retina and these connexins are localized to particular retinal circuits. ^

Functional architecture of mammalian horizontal cells

In the rabbit retina, there are two kinds of horizontal cells (HCs). The A-type HC is a large axonless cell which contacts cones exclusively. The B-type HC is an axon bearing cell. While the somatic dendrites of B-type HCs also contact cones, the axon expands into an elaborately branched structure, the axon terminal (AT), which contacts a large number of rods. It is difficult to label the different HCs selectively by immunochemical methods. Therefore, we developed dye injection methods to label each type of HC. Then it was possible, (1) to describe the detailed structure of the AT (2) to identify the glutamate receptors mediating cone input to A and B-type HCs and rod input to ATs and (3) to test the hypothesis that the B-type HCs are coupled via Cx57 gap junctions. ^ To obtain well filled examples of single HCs, it was necessary to block gap junction coupling to stop the spread of Neurobiotin through the network. We used dye coupling in A-type HCs to screen a series of potential gap junction antagonists. One of these compounds, meclofenamic acid (MFA), was potent, water soluble and easily reversible. This compound may be a useful tool to manipulate gap junction coupling. ^ In the presence of MFA, Neurobiotin passed down the axon of B-type HCs to reveal the detailed structure of the AT. We observed that only one AT ending entered each rod spherule invagination. This observation was confirmed by calculation and two dye injections. ^ Glutamate is the neurotransmitter used by both rods and cones. AMPA receptors were colocalized with the dendrites of A and B-type HCs at each cone pedicle. In addition, AMPA receptors were located on the AT ending at each rod spherule. Thus rod and cone input to HCs is mediated by AMPA receptors. ^ A-type and B-type HCs may express different connexins because they have different dye-coupling properties. Recently, we found that connexin50 (Cx50) is expressed by A-type HCs. B-type HCs and B-type ATs are also independently coupled. Cx57 was expressed in the OPL and double label studies showed that Cx 57 was colocalized with the AT matrix but not with the somatic dendrites of B-type HCs. ^ In summary, we have identified a useful gap junction antagonist, MFA. There is one AT ending at each rod spherule, rods inputs to ATs is mediated by AMPA receptors and coupling in the AT matrix is mediated by Cx57. This confirms that HCs with different properties use distinct connexins. The properties of ATs described in this research are consistent. The connections and properties reported here suggest that ATs functions as rod HCs and provide a negative feedback signal to rods. ^

(Table 2) Mineralogy, stable isotopes, and mineral percentages of the carbonate fraction of samples from the South China Sea

Chemoherm carbonates, as well as numerous other types of methane seep carbonates, were discovered in 2004 along the passive margin of the northern South China Sea. Lithologically, the carbonates are micritic containing peloids, clasts and clam fragments. Some are highly brecciated with aragonite layers of varying thicknesses lining fractures and voids. Dissolution and replacement is common. Mineralogically, the carbonates are dominated by high magnesium calcites (HMC) and aragonite. Some HMCs with MgCO3 contents of between 30-38 mol%-extreme-HMC, occur in association with minor amounts of dolomite. All of the carbonates are strongly depleted in d13C, with a range from -35.7 to -57.5 per mil PDB and enriched in d18O (+ 4.0 to + 5.3 per mil PDB). Abundant microbial rods and filaments were recognized within the carbonate matrix as well as aragonite cements, likely fossils of chemosynthetic microbes involved in carbonate formation. The microbial structures are intimately associated with mineral grains. Some carbonate mineral grains resemble microbes. The isotope characteristics, the fabrics, the microbial structure, and the mineralogies are diagnostic of carbonates derived from anaerobic oxidation of methane mediated by microbes. From the succession of HMCs, extreme-HMC, and dolomite in layered tubular carbonates, combined with the presence of microbial structure and diagenetic fabric, we suggest that extreme-HMC may eventually transform into dolomites. Our results add to the worldwide record of seep carbonates and establish for the first time the exact locations and seafloor morphology where such carbonates formed in the South China Sea. Characteristics of the complex fabric demonstrate how seep carbonates may be used as archives recording multiple fluid regimes, dissolution, and early transformation events.

Compilation of scientific results of the OASIS project

Seamounts are of great interest to science, industry and conservation because of their potential role as 'stirring rods' of the oceans, their enhanced productivity, their high local biodiversity, and the growing exploitation of their natural resources. This is accompanied by rising concern about the threats to seamount ecosystems, e.g. through over-fishing and the impact of trawling. OASIS described the functioning characteristics of seamount ecosystems. OASIS' integrated hydrographic, biogeochemical and biological information. Based on two case studies. The scientific results, condensed in conceptual and mass balanced ecosystem models, were applied to outline a model management plan as well as site-specific management plans for the seamounts investigated. OASIS addressed five main objectives: Objective 1: To identify and describe the physical forcing mechanisms effecting seamount systems Objective 2: To assess the origin, quality and dynamics of particulate organic material within the water column and surface sediment at seamounts. Objective 3: To describe aspects of the biodiversity and the ecology of seamount biota, to assess their dynamics and the maintenance of their production. Objective 4: Modelling the trophic ecology of seamount ecosystems. Objective 5: Application of scientific knowledge to practical conservation.

Diversity and identification of heterotrophic bacteria from Antarctic Rocks of the McMurdo Dry Valleys (Ross Desert)

Diversity of endolithic Dry Valley rock microorganisms was studied by evaluating the presence of morphotypes in enrichments. Storage of rock samples for 16 h over dry ice affected the diversity of endolithic organisms, especially that of algae and fungi. Diversity in various samples depended on rock location and exposure, on the rock type, and to some extent on the pH of the pulverized rock samples. In most cases sandstone contained more morphotypes than dolerite or granite. Presence of many different phototrophs resulted in greater diversity of the heterotrophs in the enrichments. Samples from Linnaeus Terrace and Battleship Promontory had higher morphotype (MT) numbers than those from more exposed sites such as New Mountain, University Valley, Dais, or Mt. Fleming. Beacon sandstone (13 samples) from Linnaeus Terrace varied greatly with respect to MT numbers, although the pH values ranged only from 4.2-5.3. The highest MT number of 24 per sample was obtained from the upper surface of a flat boulder tilted to the North. Only two MT's were found in a hard sandstone sample from the wind-exposed and more shaded east side of the Terrace. 15 sandstone samples from Battleship Promontory contained more diverse populations: there occurred a total of 131 different MT's in these samples as compared to only 68 in Linnaeus Terrace samples. Cysts of colorless flagellates were found in some Battleship Promontory samples; rnost samples were populated with a wealth of different cyanobacteria. Studies on the distribution of actinomycete morphotypes in Linnaeus Terrace sandstone revealed great differences between individual boulders. Identification tests and lipid analyses made with representative strains of the isolated 1500 pure cultures led to genus names such as Caulobacter, Blastobacter, Hyphomicrobium, Micrococcus, Arthrobacter, Brevibacterium, Corynebacterium, Bifidobacterium, Mycobacterium, Nocardia (Amycolata), Micromonospora, Streptomyces, Blastococcus, and Deinococcus. Our data demonstrate the great diversity of Antarctic endolithic microbial populations.

(Table 1) Typical trace-fossil occurrences in DSDP Holes 56-436 and 56-435A

Trace fossils are in places abundant in cores from DSDP Leg 56 sites. They are particularly rich in the pelagic-clay sequence at Site 436. Some significant trace fossils, including Zoophycos, Teichichnus, Chondrites, rind and solid burrows, and pellet-armored rods, are described. The ichnofauna, except for pellet-armored rods in diatomaceous mudstone of the landward trench slope, is characterized by cosmopolitan bathyal to abyssal forms.