Citations

Abstract Aims In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF. The effect of vericiguat in patients with HFrEF without recent worsening HF remains unknown. The VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial was designed to assess the efficacy and safety of vericiguat in patients with ejection fraction ≤40% without recent worsening HF on a background of current foundational HFrEF therapy. Methods The primary endpoint for VICTOR is time to first event for the composite of HHF or cardiovascular death. The trial will also assess the effect of vericiguat on time to cardiovascular death, time to HHF, total HHF, and all-cause death. As an event-driven trial, at least 1080 primary events are expected, but follow-up will continue until the targeted number of at least 590 cardiovascular deaths has been reached. Approximately 6000 participants will be randomized to vericiguat or placebo. Conclusion VICTOR is the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational guideline-directed medical therapy, in a compensated ambulatory HF population. VICTOR will add important information to the evidence of the effects of vericiguat across the spectrum of patients with HFrEF.

In the realm of innovative medical procedures, TEER (transcatheter edge-to-edge repair) has emerged as a promising field, showcasing significant growth and advancements. Mitral TEER has been performed for the last two decades; in contrast, tricuspid TEER is newer, with long-term outcomes pending. This article aims to provide a comprehensive review of the current literature, with a primary focus on outcomes and potential complications associated with both procedures. Both procedures carry a low risk of complications when done by experienced providers. A team approach involving specialists in cardiology, cardiothoracic surgery, cardiac imaging and heart failure ensures comprehensive care. A unified approach encompassing preprocedural workup, risk assessment, and standardised care throughout the procedure and recovery contributes to successful outcomes.

Background: Patients with persistent symptomatic iliopsoas tendonitis following total hip arthroplasty may benefit from iliopsoas fractional lengthening. We present an arthroscopic approach utilizing an air bursogram that provides safe and predictable access to the iliopsoas tendon for efficient tendon lengthening without violating the capsule or unintentional instrumentation of the nearby medial neurovascular bundle. Indications: Arthroscopic iliopsoas fractional lengthening is indicated for patients with clinical evidence of symptomatic iliopsoas tendonitis following total hip arthroplasty and have no radiographic evidence of frank acetabular malpositioning. A diagnosis of iliopsoas tendinitis amenable to surgical management can be established with substantial but nondurable relief following image-guided anesthetic injection to the iliopsoas bursa. Technique Description: Under fluoroscopic guidance, an air bursogram is employed in the anatomic plane of the iliopsoas tendon to accurately identify its course. This allows for hip portal placement with precise subsequent instrumentation. This technique is preferred in the setting of postarthroplasty anatomy because it avoids capsular violation and the challenge of working in an altered anatomic space with a nearby, medially based neurovascular bundle. Results: Arthroscopic and endoscopic approaches to iliopsoas release have been shown to provide excellent functional and patient-reported outcomes in >85% of patients, and several studies have shown that an arthroscopic approach not only provides a less invasive technique but also results in comparable or improved clinical outcomes with lower revision rates compared to open release or acetabular cup revision. Our technique for arthroscopic iliopsoas fractional lengthening using the air bursogram is both safe and reproducible and offers distinct advantages, including maintenance of an intact capsule, visual confirmation of the correct anatomic structure to be released, and percutaneous access with standard arthroscopic access cannulas without the need for hip distraction. Conclusions: Arthroscopic fractional iliopsoas lengthening is a minimally invasive and successful treatment option for patients with persistent groin pain after total hip arthroplasty, especially without substantial acetabular component malpositioning. This technique includes using an air bursogram to safely identify and navigate to the iliopsoas tendon without violating the hip capsule, thereby reducing the risk of inadvertent instrumentation of adjacent critical neurovascular structures. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Abstract Seizure localization is important for managing drug‐resistant focal epilepsy. Here, the capability of a novel deep learning‐based source imaging framework (DeepSIF) for imaging seizure activities from electroencephalogram (EEG) recordings in drug‐resistant focal epilepsy patients is investigated. The neural mass model of ictal oscillations is adopted to generate synthetic training data with spatio‐temporal‐spectra features similar to ictal dynamics. The trained DeepSIF model is rigorously validated using computer simulations and in a cohort of 33 drug‐resistant focal epilepsy patients with high‐density (76‐channel) EEG seizure recordings, by comparing DeepSIF estimates with surgical resection outcome and seizure onset zone (SOZ). These findings show that the trained DeepSIF model outperforms other methods in estimating the spatial and temporal information of origins of ictal activities. It achieves a high spatial specificity of 96% and a low spatial dispersion of 3.80 ± 5.74 mm when compared to the resection region. The source imaging results also demonstrate good coverage of SOZ, with an average distance of 10.89 ± 10.14 mm (from the SOZ to the reconstruction). These promising results suggest that DeepSIF has significant potential for advancing noninvasive imaging of the origins of ictal activities in patients with focal epilepsy, aiding management of intractable epilepsy.

With increased patient volumes and complexity, stroke occurrence in hospitalized patients has become relatively more common. The process of activating a code stroke in-hospital differs in many institutions. An emergency team-based response to inpatient acute code stroke is warranted, with many protocols modeled similarly to the cardiac arrest response. However, several studies have demonstrated delays in recognition and management of acute stroke in-hospital as compared to those arriving directly to the emergency department (ED). Furthermore, there are several shared challenges with code stroke resuscitation in the ED and the ward, which include the assembly of ad hoc teams and requirement of access to urgent imaging. Delays in activating in-hospital code stroke contributes to increased morbidity, mortality, prolonged hospitalization, and associated health care costs. In the following commentary, we discuss the current landscape of acute in-hospital code stroke protocols, review the differences in neurologic outcomes between inpatient vs ED/out-of-hospital code stroke patients, and propose future directions for in-hospital code stroke paradigms for improved patient outcomes and quality of care.

Abstract Background Glioblastoma is the most aggressive malignant brain tumor with poor survival due to its invasive nature driven by cell migration, with unclear linkage to transcriptomic information. The aim of this study was to develop a physics-based framework connecting to transcriptomics to predict patient-specific glioblastoma cell migration. Methods and Results We applied a physics-based motor-clutch model, a cell migration simulator (CMS), to parameterize the migration of glioblastoma cells and define physical biomarkers on a patient-by-patient basis. We reduced the 11-dimensional parameter space of the CMS into 3 principal physical parameters that govern cell migration: motor number—describing myosin II activity, clutch number—describing adhesion level, and F-actin polymerization rate. Experimentally, we found that glioblastoma patient-derived (xenograft) cell lines across mesenchymal (MES), proneural, and classical subtypes and 2 institutions (N = 13 patients) had optimal motility and traction force on stiffnesses around 9.3 kPa, with otherwise heterogeneous and uncorrelated motility, traction, and F-actin flow. By contrast, with the CMS parameterization, we found that glioblastoma cells consistently had balanced motor/clutch ratios to enable effective migration and that MES cells had higher actin polymerization rates resulting in higher motility. The CMS also predicted differential sensitivity to cytoskeletal drugs between patients. Finally, we identified 18 genes that correlated with the physical parameters, suggesting transcriptomic data alone could potentially predict the mechanics and speed of glioblastoma cell migration. Conclusions We describe a general physics-based framework for parameterizing individual glioblastoma patients and connecting to clinical transcriptomic data that can potentially be used to develop patient-specific anti-migratory therapeutic strategies.

Asthma is a heterogeneous chronic lung disease that affects nearly 340 million people globally. Airway hyperresponsiveness, remodeling (thickening and fibrosis), and mucus hypersecretion are some hallmarks of asthma. With several current treatments having serious side effects from long-term use and a proportion of patients with uncontrolled asthma, there is an urgent need for new therapies. With an increasing understanding of asthma pathophysiology, there is a recognized need to target therapies to specific cell types of the airway, which necessitates the identification of delivery systems that can overcome increased mucus and thickened airways. Nanoparticles (NPs) that are highly customizable (material, size, charge, and surface modification) are a potential solution for delivery systems of a wide variety of cargoes (nucleic acids, proteins, and/or small molecules), as well as sole therapeutics for asthma. However, there is a need to consider the safety of the NPs in terms of potential for inflammation, toxicity, nonspecific targets, and accumulation in organs. Ongoing clinical trials using NPs, some FDA-approved for therapeutics in other diseases, provide confidence regarding the potential safety and efficacy of NPs in asthma treatment. This review highlights the current state of the use of NPs in asthma, identifying opportunities for further improvements in NP design and utilization for targeting this chronic lung disease.