Three-dimensional electroanatomic entrainment map in atypical atrial flutter late after heart transplantation

Atrial flutter in the donor part of orthotopic heart transplants has been reported and successfully treated by radiofrequency ablation of the cavotricuspid isthmus, but mapping and ablation of atypical flutter circuits may be challenging.(1) Entrainment mapping has been used in combination with activation mapping to define the mechanism of atypical atrial flutter. Here, we report a case where colour-coded three-dimensional (3D) entrainment mapping allowed us to accurately determine and visualize the 3D location of the reentrant circuit and to plan the ablation of a left atrial flutter without the need for activation mapping.

Relationship between the logistic EuroSCORE and the Society of Thoracic Surgeons Predicted Risk of Mortality score in patients implanted with the CoreValve ReValving system--a Bern-Rotterdam Study

Background Surgical risk scores, such as the logistic EuroSCORE (LES) and Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score, are commonly used to identify high-risk or “inoperable” patients for transcatheter aortic valve implantation (TAVI). In Europe, the LES plays an important role in selecting patients for implantation with the Medtronic CoreValve System. What is less clear, however, is the role of the STS score of these patients and the relationship between the LES and STS. Objective The purpose of this study is to examine the correlation between LES and STS scores and their performance characteristics in high-risk surgical patients implanted with the Medtronic CoreValve System. Methods All consecutive patients (n = 168) in whom a CoreValve bioprosthesis was implanted between November 2005 and June 2009 at 2 centers (Bern University Hospital, Bern, Switzerland, and Erasmus Medical Center, Rotterdam, The Netherlands) were included for analysis. Patient demographics were recorded in a prospective database. Logistic EuroSCORE and STS scores were calculated on a prospective and retrospective basis, respectively. Results Observed mortality was 11.1%. The mean LES was 3 times higher than the mean STS score (LES 20.2% ± 13.9% vs STS 6.7% ± 5.8%). Based on the various LES and STS cutoff values used in previous and ongoing TAVI trials, 53% of patients had an LES ≥15%, 16% had an STS ≥10%, and 40% had an LES ≥20% or STS ≥10%. Pearson correlation coefficient revealed a reasonable (moderate) linear relationship between the LES and STS scores, r = 0.58, P < .001. Although the STS score outperformed the LES, both models had suboptimal discriminatory power (c-statistic, 0.49 for LES and 0.69 for STS) and calibration. Conclusions Clinical judgment and the Heart Team concept should play a key role in selecting patients for TAVI, whereas currently available surgical risk score algorithms should be used to guide clinical decision making.

MAP kinase kinase 1 (MKK1) is essential for transmission of Trypanosoma brucei by Glossina morsitans

MAP kinase kinase 1 (MKK1) is encoded by a single copy gene in Trypanosoma brucei. It has been shown recently that MKK1 is not essential for bloodstream forms [14]. To investigate the requirement for MKK1 in other life-cycle stages we generated null mutants in procyclic forms of a fly-transmissible strain. These grew normally in culture and were able to establish midgut infections in tsetse at normal rates and intensities, but were incapable of colonising the salivary glands. Transformation of null mutants with an ectopic copy of MKK1 enabled parasites to complete the life cycle in tsetse and infect mice. This is the first example of a gene that is indispensable for transmission of T. brucei. It also raises the possibility that activating the MKK1 signalling cascade in vitro might trigger the differentiation and proliferation of life-cycle stages of T. brucei that are currently refractory to culture.

Combined anatomical and clinical factors for the long-term risk stratification of patients undergoing percutaneous coronary intervention: the Logistic Clinical SYNTAX score

The SYNTAX score (SXscore), an anatomical-based scoring tool reflecting the complexity of coronary anatomy, has established itself as an important long-term prognostic factor in patients undergoing percutaneous coronary intervention (PCI). The incorporation of clinical factors may further augment the utility of the SXscore to longer-term risk stratify the individual patient for clinical outcomes.

Metabolomics reveals the metabolic map of procainamide in humans and mice

Procainamide, a type I antiarrhythmic agent, is used to treat a variety of atrial and ventricular dysrhythmias. It was reported that long-term therapy with procainamide may cause lupus erythematosus in 25-30% of patients. Interestingly, procainamide does not induce lupus erythematosus in mouse models. To explore the differences in this side-effect of procainamide between humans and mouse models, metabolomic analysis using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) was conducted on urine samples from procainamide-treated humans, CYP2D6-humanized mice, and wild-type mice. Thirteen urinary procainamide metabolites, including nine novel metabolites, derived from P450-dependent, FMO-dependent oxidations and acylation reactions, were identified and structurally elucidated. In vivo metabolism of procainamide in CYP2D6-humanized mice as well as in vitro incubations with microsomes and recombinant P450s suggested that human CYP2D6 plays a major role in procainamide metabolism. Significant differences in N-acylation and N-oxidation of the drug between humans and mice largely account for the interspecies differences in procainamide metabolism. Significant levels of the novel N-oxide metabolites produced by FMO1 and FMO3 in humans might be associated with the development of procainamide-induced systemic lupus erythematosus. Observations based on this metabolomic study offer clues to understanding procainamide-induced lupus in humans and the effect of P450s and FMOs on procainamide N-oxidation.

Using Micro-Gravity Techniques to Map Alluvium Thickness and Pleistocene Location of the West Branch of the Susquehanna River Near Muncy, Pennsylvania

Laurentide glaciation during the early Pleistocene (~970 ka) dammed the southeast-flowing West Branch of the Susquehanna River (WBSR), scouring bedrock and creating 100-km-long glacial Lake Lesley near the Great Bend at Muncy, Pennsylvania (Ramage et al., 1998). Local drill logs and well data indicate that subsequent paleo-outwash floods and modern fluvial processes have deposited as much as 30 meters of alluvium in this area, but little is known about the valley fill architecture and the bedrock-alluvium interface. By gaining a greater understanding of the bedrock-alluvium interface the project will not only supplement existing depth to bedrock information, but also provide information pertinent to the evolution of the Muncy Valley landscape. This project determined if variations in the thickness of the valley fill were detectable using micro-gravity techniques to map the bedrock-alluvium interface. The gravity method was deemed appropriate due to scale of the study area (~30 km2), ease of operation by a single person, and the available geophysical equipment. A LaCoste and Romberg Gravitron unit was used to collect gravitational field readings at 49 locations over 5 transects across the Muncy Creek and Susquehanna River valleys (approximately 30 km2), with at least two gravity base stations per transect. Precise latitude, longitude and ground surface elevation at each location were measured using an OPUS corrected Trimble RTK-GPS unit. Base stations were chosen based on ease of access due to the necessity of repeat measurements. Gravity measurement locations were selected and marked to provide easy access and repeat measurements. The gravimeter was returned to a base station within every two hours and a looping procedure was used to determine drift and maximize confidence in the gravity measurements. A two-minute calibration reading at each station was used to minimize any tares in the data. The Gravitron digitally recorded finite impulse response filtered gravity measurements every 20 seconds at each station. A measurement period of 15 minutes was used for each base station occupation and a minimum of 5 minutes at all other locations. Longer or multiple measurements were utilized at some sites if drift or other externalities (i.e. train or truck traffic) were effecting readings. Average, median, standard deviation and 95% confidence interval were calculated for each station. Tidal, drift, latitude, free-air, Bouguer and terrain corrections were then applied. The results show that the gravitational field decreases as alluvium thickness increases across the axes of the Susquehanna River and Muncy Creek valleys. However, the location of the gravity low does not correspond with the present-day location of the West Branch of the Susquehanna River (WBSR), suggesting that the WBSR may have been constrained along Bald Eagle Mountain by a glacial lobe originating from the Muncy Creek Valley to the northeast. Using a 3-D inversion model, the topography of the bedrock-alluvium interface was determined over the extent of the study area using a density contrast of -0.8 g/cm3. Our results are consistent with the bedrock geometry of the area, and provide a low-cost, non-invasive and efficient method for exploring the subsurface and for supplementing existing well data.