Transcatheter valve repair of tricuspid regurgitation with the PASCAL system: TriCLASP study 30-day results.

BACKGROUND: Severe tricuspid regurgitation (TR) is independently associated with increased morbidity and mortality. Percutaneous transcatheter approaches may offer an alternative for patients not amenable to surgery. METHODS: TriCLASP is a prospective, single-arm, multicenter European post-market clinical follow-up study (NCT04614402) to evaluate the safety and performance of the PASCAL system (Edwards Lifesciences) in patients with severe or greater TR. At 30 days, a composite of major adverse events (MAEs) adjudicated by a clinical events committee, echocardiographic parameters adjudicated by core laboratory, and clinical, functional, and quality-of-life measures were evaluated. RESULTS: Mean age of the 74 enrolled patients was 80.3 years, with 58.1% female, 90.5% systemic hypertension, and 77.0% in New York Heart Association (NYHA) class III/IV. Mean Society for Thoracic Surgeons score (MV repair) was 9.0%. TR severity was significantly reduced at discharge (p < 0.001) and sustained at 30 days (p < 0.001), and 90.0% of patients achieved ≤moderate TR. The composite MAE rate at 30 days was 3.0%, including 4 events in 2 patients: cardiovascular mortality 1.5%, stroke 1.5%, renal complications requiring unplanned dialysis or renal replacement therapy 1.5%, and severe bleeding 1.5%. There were no nonelective tricuspid valve reinterventions, major access site and vascular complications, major cardiac structural complications, or device embolizations. NYHA class I/II was achieved in 55.8%, 6-minute walk distance improved by 38.2 m (p < 0.001), and Kansas City cardiomyopathy questionnaire scores improved by 13.4 points (p < 0.001). CONCLUSION: Experience with the PASCAL transcatheter valve repair system in a European post-market setting confirms favorable safety and effectiveness at 30 days. TR significantly reduced, and clinical, functional, and quality-of-life outcomes significantly improved. This study is ongoing. Clinical Trial Registration: The study is ongoing and registered on ClinicalTrials.gov as NCT04614402. The current analysis is an interim report.

Deterministic Shaping and Reshaping of Single-Photon Temporal Wave Functions.

Thorough control of the optical mode of a single photon is essential for quantum information applications. We present a comprehensive experimental and theoretical study of a light-matter interface based on cavity quantum electrodynamics. We identify key parameters like the phases of the involved light fields and demonstrate absolute, flexible, and accurate control of the time-dependent complex-valued wave function of a single photon over several orders of magnitude. This capability will be an important tool for the development of distributed quantum systems with multiple components that interact via photons.

[Cardioband®: Where do we stand, who are suitable patients?] / Cardioband®: Wo stehen wir, was sind geeignete Patienten?

Functional mitral regurgitation (FMR) is characterized by a dilatation of the mitral valve annulus resulting in an insufficient adaptation of the anterior and posterior mitral valve leaflets and/or severe tethering of the leaflets due to dilatation of the left ventricle. The Cardioband® system was introduced in 2015 and is a catheter-based direct mitral valve annuloplasty procedure for treatment of FMR. In the European CE approval study 60 patients with moderate or severe FMR were analyzed per protocol. There were no device or procedure-related deaths. The technical success rate of the procedure, defined as successful implantation and tightening was 97%. At 1 year, the overall survival and survival free of hospital readmission for heart failure were 87% and 66%, respectively. Currently, various interventional treatment procedures are available, such as the edge-to-edge technique as well as direct and indirect annuloplasty. In summary, patients with FMR as a result of a dilatation of the mitral valve annulus appear to be suitable for direct annuloplasty with the Cardioband® system.

GLIDE Score: Scoring System for Prediction of Procedural Success in Tricuspid Valve Transcatheter Edge-to-Edge Repair.

BACKGROUND: Tricuspid valve transcatheter edge-to-edge repair (T-TEER) is the most widely used transcatheter therapy to treat patients with tricuspid regurgitation (TR). OBJECTIVES: The aim of this study was to develop a simple anatomical score to predict procedural outcomes of T-TEER. METHODS: All patients (n = 168) who underwent T-TEER between January 2017 and November 2022 at 2 centers were included in the derivation cohort. Additionally, 126 patients from 2 separate institutions served as a validation cohort. T-TEER was performed using 2 commercially available technologies. Core laboratory assessment of procedural transesophageal echocardiograms was used to determine septolateral and anteroposterior coaptation gap, leaflet morphology, septal leaflet length and retraction, chordal structure density, tethering height, en face TR jet morphology and TR jet location, image quality, and the presence of intracardiac leads. A scoring system was derived using univariable and multivariable logistic regression. Endpoints assessed were immediate postprocedural TR reduction ≥2 grades and TR grade moderate or less. RESULTS: The median age was 82 years (Q1-Q3: 78-84 years); 48% of patients were women; and patients presented with severe (55%), massive (36%), and torrential (8%) TR. Five variables (septolateral coaptation gap, chordal structure density, en face TR jet morphology, TR jet location, and image quality) were identified as best predicting procedural outcome and were incorporated in the GLIDE (Gap, Location, Image quality, density, en-face TR morphology) score (range 0-5). TR reduction ≥2 grades and TR grade moderate or less were observed in >90% of patients with GLIDE scores of 0 and 1 and in only 5.6% and 16.7% of those with GLIDE scores ≥4. The GLIDE score was then externally validated in a separate cohort (area under the curve: 0.77; 95% CI: 0.69-0.86). TR reduction significantly correlated with functional improvement assessed by NYHA functional class and 6-minute walk distance at 3 months. CONCLUSIONS: The GLIDE score is a simple, 5-component score that is readily obtained during patient imaging and can predict successful T-TEER.

Hierarchical fractal Weyl laws for chaotic resonance states in open mixed systems.

In open chaotic systems the number of long-lived resonance states obeys a fractal Weyl law, which depends on the fractal dimension of the chaotic saddle. We study the generic case of a mixed phase space with regular and chaotic dynamics. We find a hierarchy of fractal Weyl laws, one for each region of the hierarchical decomposition of the chaotic phase-space component. This is based on our observation of hierarchical resonance states localizing on these regions. Numerically this is verified for the standard map and a hierarchical model system.

Effect of unconventional curing conditions and storage on pellets coated with Aquacoat ECD.

PURPOSE: Purpose of this study was to develop storage stable pellets coated with the aqueous ethylcellulose dispersion Aquacoat ECD. METHODS: The influence of accelerated curing/storage conditions on the release behavior of Aquacoat/HPMC-coated drug pellets were investigated as a function of various formulations (sealing, plasticizer content, and pore-former type/amount) and process parameters (process humidity, thermal curing, and organic processing). RESULTS: Conventionally cured Aquacoat/hydroxypropyl methylcellulose- coated pellets were storage stable at ambient conditions and 25 degrees C/60% relative humidity (RH) but showed a decreasing drug release at 40 degrees C/75% RH, which is a required test condition according to ICH guidelines. CONCLUSION: Only organic processing of dried Aquacoat or unconventionally harsh curing conditions (60 degrees C/75% RH or 80 degrees C) improved the storage stability of Aquacoat-coated pellets at accelerated conditions.

Stability of poly(D,L-lactide-co-glycolide) and leuprolide acetate in in-situ forming drug delivery systems.

In-situ forming drug delivery systems are prepared by dissolving a drug and a biodegradable polymer (poly(D,L-lactide-co-glycolide), PLGA) in a biocompatible organic solvent (In-situ implant, ISI) or further emulsified into an external phase (oil or aqueous solution), resulting in oil-in-oil or oil-in-water emulsions (In-situ forming microparticles, ISM). The chemical stability of PLGA and the drug is a major concern. In this study, the stability of PLGA and leuprolide acetate in the in-situ forming systems and lyophilized sponges was investigated. The degradation of PLGA increased with increasing storage temperature and water content in the biocompatible solvents. A faster degradation occurred in polar protic solvents (2-pyrrolidone, PEG 400, triethyl citrate) than in polar aprotic solvents (N-methyl-2-pyrrolidone, DMSO, triacetin, ethyl acetate). The presence of leuprolide acetate significantly accelerated PLGA degradation, especially in solution state. PLGA was stable in oily suspensions at 4 degrees C and degraded only slightly faster than solid powder at 25 degrees C. No interaction between the oils and the PLGA was observed as indicated by an unchanged T(g) of approx. 47 degrees C. PLGA underwent a slight degradation at 4 degrees C after 150 days in water and saturated sodium chloride solution. The degradation was slower in saturated sodium chloride solution than in water at 25 degrees C. Residual acetic acid in lyophilized sponges facilitated the PLGA degradation in contrast to dioxane. Leuprolide acetate did not affect the PLGA stability negatively. However, lidocaine significantly enhanced the polymer degradation in the sponges. Finally, leuprolide acetate was chemically stable in the sponges, the oils and the polymer solutions in suspension state, but unstable (aggregation) when dissolved in the polymer solutions and stored at 25 degrees C and 40 degrees C.

Kinetic evidence for a common binding site for substrates and inhibitors of the neuronal noradrenaline carrier.

The neuronal noradrenaline uptake mechanism (uptake1) has been further characterized. For a number of substrates of uptake1 the half-saturating concentration (Km) and the maximal initial transport rate (Vmax) were determined. Furthermore, the dissociation constants (KD) for binding of these substrates to the desipramine binding site of the neuronal noradrenaline carrier were measured. The uptake experiments were done on rat phaeochromocytoma cells (PC12 cells), the binding experiments on purified plasma membranes of PC12 cells. The substrates differed markedly in respect of Vmax, Km, and KD. Neither Km and Vmax nor KD and Vmax were found to be correlated. However, the discrepancy between Km and KD expressed as the ratio, Km/KD, was negatively correlated with Vmax (r = -0.9315, n = 7, p less than 0.01). For the interpretation of these results a model on the basis of the steady-state assumption has been proposed for uptake1. From the mathematics of that model the following conclusions can be drawn. (1) The half-saturating substrate concentration (Km) is not identical with the dissociation constant for the binding of a substrate to the substrate recognition site (KD). (2) The discrepancy between Km and KD is expected to be negatively correlated with the maximal initial transport rate of the substrate (Vmax). The experimental results are in good agreement with the proposed model for uptake1. Especially the negative correlation between Km/KD and Vmax supports the hypothesis that desipramine inhibits uptake1 via binding to the substrate recognition site of the neuronal noradrenaline carrier.

Cardiac troponin I plasma levels for diagnosis and quantitation of perioperative myocardial damage in patients undergoing coronary artery bypass surgery.

OBJECTIVE: The definition of a reliable and generally accepted diagnostic standard for perioperative myocardial damage is desirable. Cardiac troponin I (cTnI) is highly specific for myocardial tissue and can be measured rapidly. The aim of our study was to evaluate the diagnostic potential of cTnI for myocardial lesions in patients undergoing coronary artery bypass surgery (CABG). METHODS: A total of 119 patients with diffuse coronary artery disease were operated on using blood cardioplegia. Serial blood samples drawn before and after surgery were analyzed for the activity of creatine kinase MB isoenzyme (CKMB) and the concentrations of CKMB mass, cardiac troponins T and I. On the basis of the biochemical results (except cTnI) and the findings of electrocardiography/echocardiography, patients were classified and cTnI was studied for each group separately: group I, minor myocardial damage; group II, non-transmural infarction; group III, transmural infarction; and group IV, preoperative non-transmural infarction. RESULTS: In 87 patients of group I (73.1%) cTnI levels remained low; 19 patients (16.0%) were assigned to group II, 8 patients (6.7%) to group III, and 5 patients (4.2%) to group IV. For discrimination of patients without and with perioperative myocardial infarction (PMI) by one cTnI determination, the use of cutoff values of 6.5 ng/ml at 8 h, 9.8 ng/ml at 12 h, and 11.6 ng/ml at 24 h after aortic unclamping resulted in a diagnostic efficiency of 88, 94 and 98%). Especially, a cTnI value at 24 h had a sensitivity of 100% and a specificity of 97%. Cardiac troponin levels at 24 h were found to correlate closely with the well-recognized 2-48 h area-under-the-curve (P < 0.0001; R = 0.993), making serial determinations unnecessary. CONCLUSIONS: cTnI qualifies as a marker for diagnosis of PMI and quantitation of the amount of myocardial damage, because of the availability of a quick diagnostic test with high specificity, the high diagnostic efficiency, and especially the sufficient information gained by a single determination 24 h after aortic unclamping.

[Vascular architecture of the skin in the postmortem microangiogram]. / Gefässarchitektur der Haut im Mikroangiogramm post mortem.

To demonstrate the detailed vascular architecture of the skin, barium sulphate suspension was injected into the arteries of nine amputated lower limbs. Sections of skin from the foot were fixed in formalin and embedded in paraffin and then examined by high resolution radiography. Subsequently histological sections were prepared and correlated with the micro-angiographic appearances. This technique provided demonstration of the detailed vascular structure of the skin with very little super imposition. The capillary loops in the papillae, the sub-papillary plexus, the glandular components (with the capillaries surrounding the sweat glands), the fine arteries and smallest veins in the cutis could be demonstrated over a prolonged course. Microangiographic and histologic sections were carried out in parallel. These eliminated artifacts and clarified the micro-angiographic appearances. The value of microangiography for demonstrating the vascularity of the skin under normal, pathological and experimental conditions is the subject of further studies.

Bacillus sp. ATCC 27380: a spore with extreme resistance to dry heat.

An unusual mesophilic Bacillus sp. was isolated from heated soil, and a cleaned spore preparation showed extraordinary resistance to dry heat (D(125C) = 139 h) and relative sensitivity to moist heat (D(80C) = 61 min). Biochemical tests and morphology fit no described species.

Significance of postoperative stability for bony reparation of comminuted fractures. An experimental study.

The significance of postoperative mechanical stability to bone repair of comminuted fractures was investigated in an animal experimental study comparing four commonly employed operative methods of fracture stabilization: 1. Plate osteosynthesis combined with lag screw fixation; 2. Bridging plate osteosynthesis; 3. External fixation; 4. Static interlocking intramedullary nailing. As fracture model, a triple wedge osteotomy of the right sheep tibia was used. In regard to biomechanical strength, the method which gave best postoperative stability, plate osteosynthesis in combination with interfragmentary lag screws, did not result in the best bone repair. In this experimental setup, stabilization by bridging methods, inducing bone healing by secondary intention, gave better bone regeneration in the experimental fractures.

Oxidative metabolism of pulmonary phagocytes in acute pneumonia.

The oxidative response of activated phagocytes is a primary host defense mechanism in pneumonia, but is in addition capable of causing tissue damage. We evaluated amount and significance of the local oxidant production in immunocompetent and immunocompromised pneumonia patients; the relative contribution of neutrophils and alveolar macrophages to the total oxidant load was differentiated using chemiluminescence (CL) with different amplifiers. Luminol-enhanced CL correlated to neutrophil percentage and myeloperoxidase levels in the bronchoalveolar lavage and was markedly increased in both pneumonia groups. Lucigenin-enhanced CL was produced by both phagocyte types and not significantly increased. In both pneumonia groups elevated levels of serum proteins indicated severe alveolocapillary leakage. In conclusion the oxidative response in acute pneumonia was mainly due to neutrophil recruitment and activation; this defense mechanism was preserved even in severely immunocompromised patients.

[Pentoxifylline inhibits secretion of O2- and TNF-alpha by alveolar macrophages in patients with sarcoidosis]. / Pentoxifyllin hemmt die Sekretion von O2- und TNF-alpha durch Alveolarmakrophagen bei Patienten mit Sarkoidose.

Reactive oxygen species (ROS) and cytokines like tumor necrosis factor-alpha (TNF-alpha) play a crucial role as inflammatory mediators in pulmonary sarcoidosis. We examined the antiinflammatory effect of pentoxifylline (POF) on alveolar macrophages (AM) of patients with sarcoidosis in vitro. We could demonstrate that POF (above 4.10(-4) M) inhibited the secretion of superoxide anion and TNF-alpha by AM in a dose-dependent manner via a prostaglandin synthesis-dependent mechanism that was independent of the glucocorticoid receptor. POF is an interesting immunomodulating substance that should be further evaluated in clinical trials.

Acute hypoglycaemic coma--a rare, potentially lethal form of early onset Sheehan syndrome.

This case emphasizes the importance of intensive obstetric management that is required when confronted with prolonged postpartum haemorrhage. Anticipation of the possibility of acute hypoglycaemic coma as an initial manifestation of Sheehan syndrome and prompt recognition may prevent disastrous consequences, including maternal death.