Association between age or duration of diagnosis in obstructive hypertrophic cardiomyopathy and response to mavacamten treatment: Exploratory analysis of the EXPLORER-HCM trial.

Background And Aims: In patients with symptomatic, obstructive hypertrophic cardiomyopathy (HCM), it is unclear if response to cardiac myosin inhibition varies with older age or a longer duration of diagnosis. This study evaluated the response of these subgroups to mavacamten therapy for all primary, secondary, and exploratory endpoints in the EXPLORER-HCM trial (ClinicalTrials.gov: NCT03470545).

Cost-effectiveness of comparative survey designs for helminth control programs: Post-hoc cost analysis and modelling of the Kenyan national school-based deworming program.

Background: Soil-transmitted helminths (STH) and schistosomiasis comprise the most wide-spread NTDs globally. Preventative chemotherapy is a cost-effective approach to controlling morbidity of both diseases, but relies on large scale surveys to determine and revise treatment frequency. Availability of detailed information on survey costs is limited despite recent methodological surveying innovations.

Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results from VALOR-HCM.

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128.

KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes.

Although significant progress has been achieved in elucidating the genetic architecture of systemic lupus erythematosus (SLE), identifying genes underlying the pathogenesis has been challenging. The NZM2410-derived lupus susceptibility Sle3 locus is associated with T cell hyperactivity and activated myeloid cells. However, candidate genes associated with these phenotypes have not been identified.

Intratumoral Injectable Redox-Responsive Immune Niche Improves the Abscopal Effect in Radiotherapy.

Radiotherapy (XRT) is often utilized to improve the immune checkpoint blockade response in cancer management. Such combination treatment can enhance the abscopal effect, facilitating a prolonged and durable systemic response. However, despite intense research efforts, only a minority of patients respond to this approach, and novel strategies to increase the abscopal effect are urgently needed.

Advanced Esophageal Endoscopy.

Recent advancements in endoscopy, including high-definition imaging, virtual chromoendoscopy, and optical magnification, have enhanced our ability to visualize and diagnose certain esophageal diseases. Innovative endoscopic tools and procedures have been developed to broaden the scope of therapeutic options for treating patients with various esophageal conditions. This comprehensive review aims to elucidate the esophageal anatomy and major disorders from an endoscopist's perspective and explore recent advances in endoscopic treatment.

Standard-of-Care Medication Withdrawal in Patients With Obstructive Hypertrophic Cardiomyopathy Receiving Aficamten in FOREST-HCM.

Background: Standard-of-care (SoC) medications for the treatment of obstructive hypertrophic cardiomyopathy (oHCM) are recommended as first-line therapy despite the lack of evidence from controlled clinical trials and well known off-target side effects.

Objectives: We describe the impact of SoC therapy downtitration and withdrawal in patients already receiving aficamten in FOREST-HCM (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in Hypertrophic Cardiomyopathy; NCT04848506).

Methods: Patients receiving SoC therapy (beta-blocker, nondihydropyridine calcium-channel blocker, and/or disopyramide) were eligible for protocol-guided SoC downtitration and withdrawal at the discretion of the investigator and after achieving a stable dose of aficamten for ≥4 weeks.

Optimized Fabrication of Dendritic Mesoporous Silica Nanoparticles as Efficient Delivery System for Cancer Immunotherapy.

In the past decade, cancer immunotherapy has revolutionized the field of oncology. Major immunotherapy approaches such as immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, cytokines, and immunomodulators have shown great promise in preclinical and clinical settings. Among them, immunomodulatory agents including cancer vaccines are particularly appealing; however, they face limitations, notably the absence of efficient and precise targeted delivery of immune-modulatory agents to specific immune cells and the potential for off-target toxicity.

The Kansas City Cardiomyopathy Questionnaire in Relation to New York Heart Association Class.

Background: In order to identify candidacy and treatment response for patients with obstructive hypertrophic cardiomyopathy (oHCM), clinicians need an accurate means of assessing symptoms, function, and quality of life. While the New York Heart Association (NYHA) Classification is most often used for this purpose, the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) is more accurate and sensitive to change, although less familiar to practicing clinicians. To support interpreting the KCCQ-23, we describe cross-sectional and longitudinal changes in KCCQ scores in the context of the NYHA.

A multifunctional targeted nano-delivery system with radiosensitization and immune activation in glioblastoma.

Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation.

Mavacamten-Associated Temporal Changes in Left Atrial Function in Obstructive HCM: Insights From the VALOR-HCM Trial.

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) trial showed that mavacamten reduced the eligibility for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients. Mavacamten also resulted in favorable cardiac remodeling, including improvement in biomarkers (eg, N-terminal pro-B-type natriuretic peptide and troponin T). However, the impact of mavacamten on left atrial (LA) function is unknown.

Collagen-targeted protein nanomicelles for the imaging of non-alcoholic steatohepatitis.

In vivo molecular imaging tools hold immense potential to drive transformative breakthroughs by enabling researchers to visualize cellular and molecular interactions in real-time and/or at high resolution. These advancements will facilitate a deeper understanding of fundamental biological processes and their dysregulation in disease states. Here, we develop and characterize a self-assembling protein nanomicelle called collagen type I binding - thermoresponsive assembled protein (Col1-TRAP) that binds tightly to type I collagen in vitro with nanomolar affinity.

Serial Changes in Ventricular Strain in Symptomatic Obstructive Hypertrophic Cardiomyopathy Treated With Mavacamten: Insights From the VALOR-HCM Trial.

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain.

Pathological Response and Outcomes in Patients With Metastatic Renal Cell Carcinoma (mRCC) Receiving Immunotherapy-Based Therapies and Undergoing Deferred Cytoreductive Nephrectomy (CN).

Unlabelled: In this study we evaluated outcomes of patients with metastatic renal cell carcinoma who received immunotherapy before surgery. We found that receiving immunotherapy combinations before surgery can offer patients benefits in reducing tumor size and improving disease control.

Background: Immunotherapy (IO) has improved outcomes for patients with metastatic renal cell carcinoma (mRCC).

Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy.

Background And Aims: Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten.

Methods: Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion.

North American Expert Consensus on the Post-procedural Care of Patients After Per-oral Endoscopic Myotomy Using a Delphi Process.

Background & Aims: There is significant variability in the immediate post-operative and long-term management of patients undergoing per-oral endoscopic myotomy (POEM), largely stemming from the lack of high-quality evidence. We aimed to establish a consensus on several important questions on the after care of post-POEM patients through a modified Delphi process.

Methods: A steering committee developed an initial questionnaire consisting of 5 domains (33 statements): post-POEM admission/discharge, indication for immediate post-POEM esophagram, peri-procedural medications and diet resumption, clinic follow-up recommendations, and post-POEM reflux surveillance and management.