Real-world assessment of multipolar and point-by-point mapping for premature ventricular contraction ablation.

AIMS: We aimed to assess the acute and midterm efficacy of premature ventricular contraction (PVC) ablation guided by multielectrode and point-by-point (PbP) mapping. METHODS AND RESULTS: This is a retrospective, international multicentre study of consecutive patients referred for PVC ablation in 10 hospital centres from January 2017 to December 2021. Based on the mapping approach, two cohorts were identified: the 'Multipolar group', where a dedicated high-density mapping catheter was employed, and the 'PbP group', where mapping was performed with the ablation catheter. Procedural endpoints, safety, and acute (procedural) and midterm efficacies were assessed. Of the 698 patients included in this study, 592 received activation mapping [46% males, median age of 55 (41-65) years]-248 patients in the Multipolar group and 344 patients in the PbP group. A higher number of activation points [432 (217-843) vs. 95 (42-185), P < 0.001], reduced mapping time (40 ± 38 vs. 61 ± 50 min, P < 0.001), and shorter procedure time (124 ± 60 vs. 143 ± 63 min, P < 0.001) were reported in the Multipolar group. Both groups had high acute success rates (84.7% with Multipolar mapping vs. 81.3% with PbP mapping, P = 0.63), as well as midterm efficacy (83.4% vs. 77.4%, P = 0.08), with no significant differences in the risk of adverse events (6.0% vs. 3.5%, P = 0.24). However, for left-sided PVC ablation specifically, there was a higher midterm efficacy in the Multipolar group (80.7% vs. 69.5%, P = 0.04), with multipolar mapping being an independent predictor of success [adjusted OR = 2.231 (95% CI, 1.476-5.108), P = 0.02]. CONCLUSION: The acute and midterm efficacies of PVC ablation are high with both multipolar and PbP mapping, although the former allows for quicker procedures and may potentially improve the outcomes of left-sided PVC ablation.

Exploring Molecular Heteroencoders with Latent Space Arithmetic: Atomic Descriptors and Molecular Operators.

A variational heteroencoder based on recurrent neural networks, trained with SMILES linear notations of molecular structures, was used to derive the following atomic descriptors: delta latent space vectors (DLSVs) obtained from the original SMILES of the whole molecule and the SMILES of the same molecule with the target atom replaced. Different replacements were explored, namely, changing the atomic element, replacement with a character of the model vocabulary not used in the training set, or the removal of the target atom from the SMILES. Unsupervised mapping of the DLSV descriptors with t-distributed stochastic neighbor embedding (t-SNE) revealed a remarkable clustering according to the atomic element, hybridization, atomic type, and aromaticity. Atomic DLSV descriptors were used to train machine learning (ML) models to predict 19F NMR chemical shifts. An R2 of up to 0.89 and mean absolute errors of up to 5.5 ppm were obtained for an independent test set of 1046 molecules with random forests or a gradient-boosting regressor. Intermediate representations from a Transformer model yielded comparable results. Furthermore, DLSVs were applied as molecular operators in the latent space: the DLSV of a halogenation (H→F substitution) was summed to the LSVs of 4135 new molecules with no fluorine atom and decoded into SMILES, yielding 99% of valid SMILES, with 75% of the SMILES incorporating fluorine and 56% of the structures incorporating fluorine with no other structural change.

Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial.

BACKGROUND: Optimal timing for catheter ablation of ventricular tachycardia is an important unresolved issue. There are no randomized trials evaluating the benefit of ablation after the first implantable cardioverter defibrillator (ICD) shock. METHODS: We conducted a 2-phase, prospective, multicenter, randomized clinical trial. Patients with ischemic or nonischemic dilated cardiomyopathy and primary or secondary prevention indication for ICD were enrolled in an initial observational phase until first appropriate shock (phase A). After reconsenting, patients were randomly assigned 1:1 in phase B to immediate ablation (within 2 months from shock delivery) or continuation of standard therapy. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. Amiodarone intake was not allowed except for documented atrial tachyarrhythmias. On July 23, 2021, phase B of the trial was interrupted as a result of the first interim analysis on the basis of the Bayesian adaptive design. RESULTS: Of the 517 patients enrolled in phase A, 154 (30%) had ventricular tachycardia, 56 (11%) received an appropriate shock over a median follow-up of 2.4 years (interquartile range, 1.4-4.4), and 47 of 56 (84%) agreed to participate in phase B. After 24.2 (8.5-24.4) months, the primary end point occurred in 1 of 23 (4%) patients in the ablation group and 10 of 24 (42%) patients in the control group (hazard ratio, 0.11 [95% CI, 0.01-0.85]; P=0.034). The results met the prespecified termination criterion of >99% Bayesian posterior probability of superiority of treatment over standard therapy. No deaths were observed in the ablation group versus 8 deaths (33%) in the control group (P=0.004); there was 1 worsening heart failure hospitalization in the ablation group (4%) versus 4 in the control group (17%; P=0.159). ICD shocks were less frequent in the ablation group (9%) than in the control group (42%; P=0.039). CONCLUSIONS: Ventricular tachycardia ablation after first appropriate shock was associated with a reduced risk of the combined death or worsening heart failure hospitalization end point, lower mortality, and fewer ICD shocks. These findings provide support for considering ventricular tachycardia ablation after the first ICD shock. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01547208.

Impact of different activation wavefronts on ischemic myocardial scar electrophysiological properties during high-density ventricular tachycardia mapping and ablation.

INTRODUCTION: Scar-related ventricular tachycardia (VT) usually results from an underlying reentrant circuit facilitated by anatomical and functional barriers. The later are sensitive to the direction of ventricular activation wavefronts. We aim to evaluate the impact of different ventricular activation wavefronts on the functional electrophysiological properties of myocardial tissue. METHODS: Patients with ischemic heart disease referred for VT ablation underwent high-density mapping using Carto®3 (Biosense Webster). Maps were generated during sinus rhythm, right and left ventricular pacing, and analyzed using a new late potential map software, which allows to assess local conduction velocities and facilitates the delineation of intra-scar conduction corridors (ISCC); and for all stable VTs. RESULTS: In 16 patients, 31 high-resolution substrate maps from different ventricular activation wavefronts and 7 VT activation maps were obtained. Local abnormal ventricular activities (LAVAs) were found in VT isthmus, but also in noncritical areas. The VT isthmus was localized in areas of LAVAs overlapping surface between the different activation wavefronts. The deceleration zone location differed depending on activation wavefronts. Sixty-six percent of ISCCs were similarly identified in all activating wavefronts, but the one acting as VT isthmus was simultaneously identified in all activation wavefronts in all cases. CONCLUSION: Functional based substrate mapping may improve the specificity to localize the most arrhythmogenic regions within the scar, making the use of different activation wavefronts unnecessary in most cases.

Vitreous humor proteome: unraveling the molecular mechanisms underlying proliferative and neovascular vitreoretinal diseases.

Proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and neovascular age-related macular degeneration (nAMD) are among the leading causes of blindness. Due to the multifactorial nature of these vitreoretinal diseases, omics approaches are essential for a deeper understanding of the pathophysiologic processes underlying the evolution to a proliferative or neovascular etiology, in which patients suffer from an abrupt loss of vision. For many years, it was thought that the function of the vitreous was merely structural, supporting and protecting the surrounding ocular tissues. Proteomics studies proved that vitreous is more complex and biologically active than initially thought, and its changes reflect the physiological and pathological state of the eye. The vitreous is the scenario of a complex interplay between inflammation, fibrosis, oxidative stress, neurodegeneration, and extracellular matrix remodeling. Vitreous proteome not only reflects the pathological events that occur in the retina, but the changes in the vitreous itself play a central role in the onset and progression of vitreoretinal diseases. Therefore, this review offers an overview of the studies on the vitreous proteome that could help to elucidate some of the pathological mechanisms underlying proliferative and/or neovascular vitreoretinal diseases and to find new potential pharmaceutical targets.

Rational Engineering of (S)-Norcoclaurine Synthase for Efficient Benzylisoquinoline Alkaloids Biosynthesis.

(S)-Norcoclaurine is synthesized in vivo through a metabolic pathway that ends with (S)-norcoclaurine synthase (NCS). The former constitutes the scaffold for the biosynthesis of all benzylisoquinoline alkaloids (BIAs), including many drugs such as the opiates morphine and codeine and the semi-synthetic opioids oxycodone, hydrocodone, and hydromorphone. Unfortunately, the only source of complex BIAs is the opium poppy, leaving the drug supply dependent on poppy crops. Therefore, the bioproduction of (S)-norcoclaurine in heterologous hosts, such as bacteria or yeast, is an intense area of research nowadays. The efficiency of (S)-norcoclaurine biosynthesis is strongly dependent on the catalytic efficiency of NCS. Therefore, we identified vital NCS rate-enhancing mutations through the rational transition-state macrodipole stabilization method at the Quantum Mechanics/Molecular Mechanics (QM/MM) level. The results are a step forward for obtaining NCS variants able to biosynthesize (S)-norcoclaurine on a large scale.

Nursing Interventions for Patients With Neurogenic Bowel Dysfunction Arising From Complete Spinal Cord Injury: A Scoping Review.

PURPOSE: We mapped key concepts and identified 4 fundamental nursing interventions for patients with neurogenic bowel dysfunction due to complete spinal cord injury (SCI). METHODS: A scoping review was conducted according to the recommendations of the Joanna Briggs Institute. SEARCH STRATEGY: Searches were performed in PubMed, LILACS, CINAHL, COCHRANE, and SCOPUS electronic databases. We use searched the gray literature using the Google Scholar search engine. We formulated a question to guide the search, based on the participants, concept, and context format: "What are the key manual nursing interventions performed in patients with neurogenic bowel dysfunction resulting from complete spinal cord injury?" We included nursing intervention strategies that may be performed by health professionals, patients, or caregivers. Two reviewers independently participated in the selection; disagreements were resolved by a third reviewer and 5 experts. FINDINGS: Thirteen studies conducted between 1998 and 2019 were selected; 5 were randomized clinical trials. Four main interventions were identified for conservative management of neurogenic bowel dysfunction in patients with complete SCI. They were digital-anal stimulation, manual extraction of feces, abdominal massage, and strategies used to stimulate the gastrocolic reflex. CONCLUSIONS: Research suggests that each of these interventions, administered alone or in combination, supports bowel evacuation in patients with a complete SCI. Each of these interventions may be performed by a nurse, and taught to the patient and/or lay caregiver. IMPLICATIONS FOR PRACTICE: An individualized bowel management program for patients with neurogenic bowel dysfunction due to SCI is necessary to ensure regular bowel evacuation, preserve fecal continence, and support dignity and health-related quality of life. The conservative interventions identified in this scoping review should be incorporated in protocols or guidelines for management of neurogenic bowel dysfunction in this vulnerable population.

An Overview of Robotic Colorectal Surgery Adoption and Training in Brazil.

Background and Objectives: Robotic surgical systems have rapidly become integrated into colorectal surgery practice in recent years, particularly for rectal resections, where the advantages of robotic platforms over conventional laparoscopy are more pronounced. However, as with any technological advancement, the initial high costs can be a limiting factor, leading to unequal health service access, especially in middle- and lower-income countries. Materials and Method: A narrative review was conducted with the objective of providing an overview of the escalating adoption, current training programmes, and certification process of robotic colorectal surgery in Brazil. Results: Brazil has witnessed a rapid increase in robotic platforms in recent years. Currently, there are 106 robotic systems installed nationwide. However, approximately 60% of the medical facilities which adopted robotic platforms are in the Southeast region, which is both the most populous and economically prosperous in the country. The Brazilian Society of Coloproctology recently established clear rules for the training programme and certification of colorectal surgeons in robotic surgery. The key components of the training encompass theoretical content, virtual robotic simulation, observation, assistance, and supervised procedures in colorectal surgery. Although the training parameters are well established, no colorectal surgery residency programme in Brazil has yet integrated the teaching and training of robotic surgery into its curriculum. Thus far, the training process has been led by private institutions and the industry. Conclusion: Despite the fast spread of robotic platforms across Brazil, several challenges still need to be addressed to democratise training and promote the widespread use of these platforms. It is crucial to tackle these obstacles to achieve greater integration of robotic technology in colorectal surgery throughout the country.

Novel "late potential map" algorithm: Abnormal potentials and scar channels detection for ventricular tachycardia ablation.

BACKGROUND: Automated systems for substrate mapping in the context of ventricular tachycardia (VT) ablation may annotate far-field rather than near-field signals, rendering the resulting maps hard to interpret. Additionally, quantitative assessment of local conduction velocity (LCV) remains an unmet need in clinical practice. We evaluate whether a new late potential map (LPM) algorithm can provide an automatic and reliable annotation and localized bipolar voltage measurement of ventricular electrograms (EGMs) and if LCV analysis allows recognizing intrascar conduction corridors acting as VT isthmuses. METHODS: In 16 patients referred for scar-related VT ablation, 8 VT activation maps and 29 high-resolution substrate maps from different activation wavefronts were obtained. In offline analysis, the LPM algorithm was compared to manually annotated substrate maps. Locations of the VT isthmuses were compared with the corresponding substrate maps in regard to LCV. RESULTS: The LPM algorithm had an overall/local abnormal ventricular activity (LAVA) annotation accuracy of 94.5%/81.1%, which compares to 83.7%/23.9% for the previous wavefront algorithm. The resultant maps presented a spatial concordance of 88.1% in delineating regions displaying LAVA. LAVA median localized bipolar voltage was 0.22 mV, but voltage amplitude assessment had modest accuracy in distinguishing LAVA from other abnormal EGMs (area under the curve: 0.676; p < .001). LCV analysis in high-density substrate maps identified a median of two intrascar conduction corridors per patient (interquartile range: 2-3), including the one acting as VT isthmus in all cases. CONCLUSION: The new LPM algorithm and LCV analysis may enhance substrate characterization in scar-related VT.

Prediction of the Phase Composition Profile of Three-Compound Mixtures in Liquid-Liquid Equilibrium: A Chemoinformatics Approach.

Machine-learning models were developed to predict the composition profile of a three-compound mixture in liquid-liquid equilibrium (LLE), given the global composition at certain temperature and pressure. A chemoinformatics approach was explored, based on the MOLMAP technology to encode molecules and mixtures. The chemical systems involved an ionic liquid (IL) and two organic molecules. Two complementary models have been optimized for the IL-rich and IL-poor phases. The two global optimized models are highly accurate, and were validated with independent test sets, where combinations of molecule1+molecule2+IL are different from those in the training set. These results highlight the MOLMAP encoding scheme, based on atomic properties to train models that learn relationships between features of complex multi-component chemical systems and their profile of phase compositions.