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AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

Abstract Polycomb group proteins, as part of the Polycomb repressive complexes, are essential in gene repression through chromatin compaction by canonical PRC1, mono-ubiquitylation of histone H2A by non-canonical PRC1 and tri-methylation of histone H3K27 by PRC2. Despite prevalent models emphasizing tight functional coupling between PRC1 and PRC2, it remains unclear whether this paradigm indeed reflects the evolution and functioning of these complexes. Here, we conduct a comprehensive analysis of the presence or absence of cPRC1, nPRC1 and PRC2 across the entire eukaryotic tree of life, and find that both complexes were present in the Last Eukaryotic Common Ancestor (LECA). Strikingly, ~42% of organisms contain only PRC1 or PRC2, showing that their evolution since LECA is largely uncoupled. The identification of ncPRC1-defining subunits in unicellular relatives of animals and fungi suggests ncPRC1 originated before cPRC1, and we propose a scenario for the evolution of cPRC1 from ncPRC1. Together, our results suggest that crosstalk between these complexes is a secondary development in evolution.

We report a case of a clinically asymptomatic patient with extreme P-wave separation on the electrocardiogram mimicking atrial tachycardia with atrioventricular block. The accurate examination of the patient, analysis of the electrocardiogram, and echocardiographic findings led to proper diagnosis, management, and treatment. (Level of Difficulty: Intermediate.)

This paper presents an overview of the history, conceptualization, and development of the Database of Byzantine Book Epigrams, an ongoing research project hosted at Ghent University. It also offers a glimpse into current and future research threads carried out within the project, with an eye on long-term sustainability. The first part of the paper pinpoints the position of DBBE within the broad field of Digital Humanities and addresses the question of how and why Byzantine metrical paratexts have been collected in an open-access online database. In the second part of the article, we describe the main features of the relational database currently available, both from the perspective of its users and from a technical point of view. The third section of the paper includes the description of four subprojects connected to DBBE, which at present involve the development of a graph database complementary to the relational one, the implementation of natural language pre-processing applied to the DBBE corpus, the linguistic analysis of formulaicity in book epigrams, and the exploration of the broad implications of the study of book epigrams for a better understanding of Byzantine book culture.

For critically ill patients, hemodynamic fluctuations can be life-threatening; this is particularly true for patients experiencing cardiac comorbidities. Patients may suffer from problems with heart contractility and rate, vascular tone, and intravascular volume, resulting in hemodynamic instability. Unsurprisingly, hemodynamic support provides a crucial and specific benefit during percutaneous ablation of ventricular tachycardia (VT). Mapping, understanding, and treating the arrhythmia during sustained VT without hemodynamic support is often infeasible due to patient hemodynamic collapse. Substrate mapping in sinus rhythm can be successful for VT ablation, but there are limitations to this approach. Patients with nonischemic cardiomyopathy may present for ablation without exhibiting useful endocardial and/or epicardial substrate-based ablation targets, either due to diffuse extent or a lack of identifiable substrate. This leaves activation mapping during ongoing VT as the only viable diagnostic strategy. By enhancing cardiac output, percutaneous left ventricular assist devices (pLVAD) may facilitate conditions for mapping that would otherwise be incompatible with survival. However, the optimal mean arterial pressure to maintain end-organ perfusion in presence of nonpulsatile flow remains unknown. Near infrared oxygenation monitoring during pLVAD support provides assessment of critical end-organ perfusion during VT, enabling successful mapping and ablation with the continual assurance of adequate brain oxygenation. This focused review provides practical use case scenarios for such an approach, which aims to allow mapping and ablation of ongoing VT while drastically reducing the risk of ischemic brain injury.

New Cinema History broadened film studies by emphasising the complexity of cinema as a multifaceted phenomenon that includes the socio-economic context in which films were made, circulated, shown and received. As part of the digital turn, the discipline adopted computational methods and created quantitative research data to research this socio-economic context at scale. However, not all datasets created in this context adhere to FAIR principles, decreasing their reusability. By reconciling 14 cinema-related datasets, Cinema Belgica facilitates research into the history of Belgian cinema. This research paper documents and critically reflects on the choices made when selecting, modelling and reconciling information for the Cinema Belgica database.

TIC-Collaborative was a collaborative digital humanities project that focused on transnational intellectual cooperation (TIC) in the long nineteenth century, in particular on transnational connections in the field of social reform. The dataset contains information on over 1650 international congresses and 450 organizations and conference series related to the social question. The project focussed on the Low Countries and a selection of reform areas.

Background. Atrial fibrillation (AF) is considered the most common human arrhythmia. In nonvalvular AF, around 99% of thrombi are formed in the left atrial appendage (LAA). Nevertheless, there is not a consensus in the community about the relevant factors to stratify the AF population according to thrombogenic risk. Objective. To demonstrate the need for combining left atrial morphological and haemodynamics indices to improve the thrombogenic risk assessment in nonvalvular AF patients. Methods. A cohort of 71 nonvalvular AF patients was analysed. Statistical analysis, regression models, and random forests were used to analyse the differences between morphological and haemodynamics parameters, extracted from computational simulations built on 3D rotational angiography images, between patients with and without transient ischemic attack (TIA) or cerebrovascular accident (CVA). Results. The analysis showed that models composed of both morphological and haemodynamic factors were better predictors of TIA/CVA compared with models based on either morphological or haemodynamic factors separately. Maximum ostium diameter, length of the centreline, blood flow velocity within the LAA, oscillatory shear index, and time average wall shear stress parameters were found to be key risk factors for TIA/CVA prediction. In addition, TIA/CVA patients presented more flow stagnation within the LAA. Conclusion. Thrombus formation in the LAA is the result of multiple factors. Analyses based only on morphological or haemodynamic parameters are not precise enough to predict such a phenomenon, as demonstrated in our results; a better patient stratification can be obtained by jointly analysing morphological and haemodynamic features.

Background: The association of known cardiovascular risk factors with poor prognosis of coronavirus disease 2019 (COVID-19) has been recently emphasized. Coronary artery calcium (CAC) score is considered a risk modifier in the primary prevention of cardiovascular disease. We hypothesized that the absence of CAC might have an additional predictive value for an improved cardiovascular outcome of hospitalized COVID-19 patients.Materials and methods: We prospectively included 310 consecutive hospitalized patients with COVID-19. Thirty patients with history of coronary artery disease were excluded. Chest computed tomography (CT) was performed in all patients. Demographics, medical history, clinical characteristics, laboratory findings, imaging data, in-hospital treatment, and outcomes were retrospectively analyzed. A composite endpoint of major adverse cardiovascular events (MACE) was defined.Results: Two hundred eighty patients (63.2 ± 16.7 years old, 57.5% male) were included in the analysis. 46.7% patients had a CAC score of 0. MACE rate was 21.8% (61 patients). The absence of CAC was inversely associated with MACE (OR 0.209, 95% CI 0.052–0.833, p = 0.027), with a negative predictive value of 84.5%.Conclusion: The absence of CAC had a high negative predictive value for MACE in patients hospitalized with COVID-19, even in the presence of cardiac risk factors. A semi-qualitative assessment of CAC is a simple, reproducible, and non-invasive measure that may be useful to identify COVID-19 patients at a low risk for developing cardiovascular complications.

Abstract Background In uveal melanomas, immune infiltration is a marker of poor prognosis. This work intended to decipher the biological characteristics of intra‐tumor immune population, compare it to other established biomarkers and to patients' outcome. Methods Primary, untreated, and mainly large uveal melanomas with retinal detachment were analyzed using: transcriptomic profiling (n = 15), RT‐qPCR (n = 36), immunohistochemistry (n = 89), Multiplex Ligation‐dependent Probe Amplification (MLPA) for copy number alterations (CNA) analysis (n = 89), array‐CGH (n = 17), and survival statistics (n = 86). Results Gene expression analysis divided uveal melanomas into two groups, according to the IFNγ/STAT1‐IRF1 pathway activation. Tumors with IFNγ‐signature had poorer prognosis and showed increased infiltration of CD8+ T lymphocytes and macrophages. Cox multivariate analyses of immune cell infiltration with MLPA data delineated better prognostic value for three prognostic groups (three‐tier stratification) than two (two‐tier stratification). CNA‐based model comprising monosomy 3, 8q amplification, and LZTS1and NBL1 deletions emerged as the best predictor for disease‐free survival. It outperformed immune cell infiltration in receiver operating characteristic curves. The model that combined CNA and immune infiltration defined risk‐groups according to the number of DNA alterations. Immune cell infiltration was increased in the high‐risk group (73.7%), where it did not correlate with patient survival, while it was associated with poorer outcome in the intermediate risk‐group. Conclusions High degree of immune cell infiltration occurs in a subset of uveal melanomas, is interferon‐gamma‐related, and associated with poor survival. It allows for two‐tier stratification, which is prognostically less efficient than a three‐tier one. The best prognostic stratification is by CNA model with three risk‐groups where immune cell infiltration impacts only some subgroups.

We have read with interest the comment by Vankrunkelsven P. [...]

A global, comprehensive and open access listing of approved anticancer drugs does not currently exist. Partial information is available from multiple sources, including regulatory authorities, national formularies and scientific agencies. Many such data sources include drugs used in oncology for supportive care, diagnostic or other non-antineoplastic uses. We describe a methodology to combine and cleanse relevant data from multiple sources to produce an open access database of drugs licensed specifically for therapeutic antineoplastic purposes. The resulting list is provided as an open access database, (http://www.redo-project.org/cancer-drugs-db/), so that it may be used by researchers as input for further research projects, for example literature-based text mining for drug repurposing.

Introduction: Data regarding the efficacy of catheter ablation in patients with atrial fibrillation (AF) and patients’ previous history of pulmonary lobectomy/pneumonectomy are scanty. We sought to evaluate the efficacy and long-term follow-up of catheter ablation in this highly selected group of patients. Material and Methods: Twenty consecutive patients (8 females, 40%; median age 65.2 years old) with a history of pneumonectomy/lobectomy and paroxysmal or persistent AF, treated by means of pulmonary vein isolation (PVI) at ten participating centers were included. Procedural success, intra-procedural complications, and AF recurrences were considered. Results: Fifteen patients had a previous lobectomy and five patients had a complete pneumonectomy. A large proportion (65%) of PV stumps were electrically active and represented a source of firing in 20% of cases. PVI was performed by radiofrequency ablation in 13 patients (65%) and by cryoablation in the remaining 7 cases. Over a median follow up of 29.7 months, a total of 7 (33%) AF recurrences were recorded with neither a difference between patients treated with cryoablation or radiofrequency ablation or between the two genders. Conclusions: Catheter ablation by radiofrequency ablation or cryoablation in patients with pulmonary stumps is feasible and safe. Long-term outcomes are favorable, and a similar efficacy of catheter ablation has been noticed in both males and females.

This multicenter European survey systematically evaluated the impact of using contact force-sensing catheters (CFSCs) on fluoroscopy and procedure time in interventional electrophysiology. Data from 25 participating centers were collected and analyzed, also considering important confounders. With the use of CFSCs, fluoroscopy time was reduced for right- and left-sided atrial ablations (median −6.4 to −9.6 min, p < 0.001 for both groups), whereas no such effect could be found for ventricular ablations. Moreover, the use of CFSCs was associated with an increase in procedure time for right-sided atrial and ventricular ablations (median +26.0 and +44.0 min, respectively, p < 0.001 for both groups), but not for left-sided atrial ablations. These findings were confirmed independent of career level and operator volume, except for very highly experienced electrophysiologists, in whom the effect was blunted. In the subset of pulmonary vein isolations (PVIs), CFSCs were shown to reduce both fluoroscopy and procedure time. In conclusion, the use of CFSCs was associated with a reduced fluoroscopy time for atrial ablations and an increased procedure time for right atrial and ventricular ablations. These effects were virtually independent of the operator experience and caseload. When considering only PVIs as an important subset, CFSCs were shown to reduce both fluoroscopy and procedure time.

Abstract Lung cancer patients often experience potentially life-threatening medical urgencies and emergencies, which may be a direct or indirect result of the underlying malignancy. This pictorial review addresses the most common thoracic, neurological and musculoskeletal medical emergencies in lung cancer patients, including superior vena cava syndrome, pulmonary embolism, spontaneous pneumothorax, cardiac tamponade, massive haemoptysis, central airway obstruction, oesophagorespiratory fistula, malignant spinal cord compression, carcinomatous meningitis, cerebral herniation and pathological fracture. Emphasis is placed on imaging findings, the role of different imaging techniques and a brief discussion of epidemiology, pathophysiology and therapeutic options. Since early diagnosis is important for adequate patient management and prognosis, radiologists have a crucial role in recognising and communicating these urgencies and emergencies. Teaching points • Multiplanar multidetector computed tomography is the imaging examination of choice for thoracic urgencies and emergencies. • Magnetic resonance imaging is the imaging modality of choice for investigating central nervous system emergencies. • Urgencies and emergencies can be the initial manifestation of lung cancer. • Radiologists have a crucial role in recognising and in communicating these urgencies/emergencies.

Long coronavirus disease 2019 (COVID-19) was described in patients recovering from COVID-19, with dyspnea being a frequent symptom. Data regarding the potential mechanisms of long COVID remain scarce. We investigated the presence of subclinical cardiac dysfunction, assessed by transthoracic echocardiography (TTE), in recovered COVID-19 patients with or without dyspnea, after exclusion of previous cardiopulmonary diseases. A total of 310 consecutive COVID-19 patients were prospectively included. Of those, 66 patients (mean age 51.3 ± 11.1 years, almost 60% males) without known cardiopulmonary diseases underwent one-year follow-up consisting of clinical evaluation, spirometry, chest computed tomography, and TTE. From there, 23 (34.8%) patients reported dyspnea. Left ventricle (LV) ejection fraction was not significantly different between patients with or without dyspnea (55.7 ± 4.6 versus (vs.) 57.6 ± 4.5, p = 0.131). Patients with dyspnea presented lower LV global longitudinal strain, global constructive work (GCW), and global work index (GWI) compared to asymptomatic patients (−19.9 ± 2.1 vs. −21.3 ± 2.3 p = 0.039; 2183.7 ± 487.9 vs. 2483.1 ± 422.4, p = 0.024; 1960.0 ± 396.2 vs. 2221.1 ± 407.9, p = 0.030). GCW and GWI were inversely and independently associated with dyspnea (p = 0.035, OR 0.998, 95% CI 0.997–1.000; p = 0.040, OR 0.998, 95% CI 0.997–1.000). Persistent dyspnea one-year after COVID-19 was present in more than a third of the recovered patients. GCW and GWI were the only echocardiographic parameters independently associated with symptoms, suggesting a decrease in myocardial performance and subclinical cardiac dysfunction.

BACKGROUND: In patients with persistent atrial fibrillation (PersAF), catheter ablation aiming for pulmonary vein isolation (PVI) is associated with moderate clinical effectiveness. We investigated the benefit of continuing previously ineffective class 1C or 3 antiarrhythmic drug therapy (ADT) in the setting of a standardized PVI-only ablation strategy. METHODS: In this multicenter, randomized controlled study, patients with PersAF (≥7 days and <12 months) despite ADT were prospectively randomized 1:1 to PVI with ADT continued versus discontinued beyond the blanking period (ADT ON versus ADT OFF). Standardized catheter ablation was performed aiming for durable isolation with stable, contiguous, and optimized radio frequency applications encircling the pulmonary veins (CLOSE protocol). Clinical visits and 1-to-7-day Holter were performed at 3, 6, and 12 months. The primary end point was any documented atrial tachyarrhythmia lasting >30 seconds beyond 3 months. Prospectively defined secondary end points included repeat ablations, unscheduled arrhythmia-related visits, and quality of life among groups. RESULTS: Of 200 PersAF patients, 98 were assigned to ADT OFF and 102 to ADT ON. The longest atrial fibrillation episode qualifying for PersAF was 28 (10-90) versus 30 (11-90) days. Clinical characteristics and procedural characteristics were similar. Recurrence of atrial tachyarrhythmia was comparable in both groups (20% OFF versus 21.2% ON). No differences were observed in repeat ablations and unscheduled arrhythmia-related visits. Marked improvement in quality of life was observed in both groups. CONCLUSIONS: In patients with PersAF, there is no benefit in continuing previously ineffective ADT beyond the blanking period after catheter ablation. The high success rate of PVI-only might be explained by the high rate of durable isolation after optimized PVI and the early stage of PersAF (POWDER-AF2). [ABSTRACT FROM AUTHOR]

According to clinical studies, around one third of patients with atrial fibrillation (AF) will suffer a stroke during their lifetime. Between 70 and 90% of these strokes are caused by thrombus formed in the left atrial appendage. In patients with contraindications to oral anticoagulants, a left atrial appendage occluder (LAAO) is often implanted to prevent blood flow entering in the LAA. A limited range of LAAO devices is available, with different designs and sizes. Together with the heterogeneity of LAA morphology, these factors make LAAO success dependent on clinician's experience. A sub-optimal LAAO implantation can generate thrombi outside the device, eventually leading to stroke if not treated. The aim of this study was to develop clinician-friendly tools based on biophysical models to optimize LAAO device therapies. A web-based 3D interactive virtual implantation platform, so-called VIDAA, was created to select the most appropriate LAAO configurations (type of device, size, landing zone) for a given patient-specific LAA morphology. An initial LAAO configuration is proposed in VIDAA, automatically computed from LAA shape features (centreline, diameters). The most promising LAAO settings and LAA geometries were exported from VIDAA to build volumetric meshes and run Computational Fluid Dynamics (CFD) simulations to assess blood flow patterns after implantation. Risk of thrombus formation was estimated from the simulated hemodynamics with an index combining information from blood flow velocity and complexity. The combination of the VIDAA platform with in silico indices allowed to identify the LAAO configurations associated to a lower risk of thrombus formation; device positioning was key to the creation of regions with turbulent flows after implantation. Our results demonstrate the potential for optimizing LAAO therapy settings during pre-implant planning based on modeling tools and contribute to reduce the risk of thrombus formation after treatment.

Three-dimensional echocardiography (3DE) is advised for right ventricular (RV) assessment. Data regarding the optimal acquisition settings and optimization are still scarce. We aimed to evaluate the feasibility, reproducibility and validation of 3DE for RV volume and function assessment, using cardiac magnetic resonance (CMR) as gold standard. Thirty healthy volunteers and 36 consecutive patients were prospectively included. CMR was performed in the latter. Standard apical four-chamber view (A4CV), focused A4CV and modified A4CV were used for 3DE RV acquisition. Feasibility (and the effect of changes in settings) was evaluated. Intra and interobserver analyses were performed by three observers (expert vs. novice). RV parameters by echocardiography were compared to CMR. Feasibility of acquisition was 16.7% for A4CV, 80.0% for focused A4CV and 16.7% for modified A4CV. Changes in settings had no significant influence on feasibility and further analysis. Intraobserver variability was good in both expert and novice, interobserver variability was good between experienced observers. Compared to CMR, 3DE volumes were significantly lower with fair to moderate correlation (EDV: 91.1 ± 24.4 mL vs. 144.3 ± 43.0 mL (p < 0.001), r = 0.653 and ESV: 48.1 ± 16.4 mL vs. 60.4 ± 21.2 mL (p < 0.001), r = 0.530, by multi-beat 3DE and CMR respectively). These findings suggest that standardization is needed in order to implement this technique in clinical practice, thus further studies are required.

Aim: To determine the prevalence of asymptomatic carriers of Staphylococcus aureus resistant to methicillin (MRSA) in the nasal mucosa of health professionals. Method: Cross-sectional study with 29 health professionals from a teaching hospital, from March to April 2012, through the collection swab of the the nasal mucosa. Microbiological tests were performed at the University of Santa Cruz do Sul. The data were analyzed descriptively and it was given an α risk

In the wake of rapid advancement in cardiovascular procedural technologies, physician-led preprocedural planning utilizing multi-modality imaging training is increasingly recognized as invaluable for procedural accuracy. Left atrial appendage occlusion (LAAO) is one such procedure in which complications such as device leak, cardiac injury, and device embolization can be decreased substantially with incorporation of physician driven imaging and digital tools. We discuss the benefits of cardiac CT and 3D printing in preprocedural planning for the Heart Team, as well as novel applications by physicians of intraprocedural 3D angiography and dynamic fusion imaging. Furthermore, incorporation of computational modeling and artificial intelligence (AI) may yield promise. For optimal patient-centric procedural success, we advocate for standardized preprocedural imaging planning by physicians within the Heart Team as an essential part of LAAO. [ABSTRACT FROM AUTHOR]

Klippel-Trénaunay syndrome is a rare disorder characterized by a triad of port-wine stains, varicose veins, and bony and soft tissue hypertrophy usually involving an extremity. Visceral involvement in Klippel-Trénaunay syndrome is rare, but has been described in the colon, small bowel, bladder, kidney, spleen, liver, mediastinum and brain. In this paper we present the case of a 45-year-old woman with Klippel-Trénaunay syndrome in whom routine physical examination unexpectedly revealed the presence of a left upper quadrant mass. Abdominal US, contrast enhanced CT and whole-body PET-CT demonstrated multiple large cystic lesions within a massively enlarged spleen. Based on the clinical history and imaging findings diffuse hemangiomatosis of the spleen was suspected. This diagnosis was confirmed by pathologic examination after splenectomy.

The CT-imaging findings of primary renal PNET/Ewing’s sarcoma in two patients were retrospectively assessed. A large renal mass with heterogenous contrast enhancement and necrotic and hemorrhagic areas were the predominant characteristics. In adolescents or young adults presenting with a large renal mass, PNET/Ewing’s sarcoma may be included in the differential diagnosis.