Concurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription.

The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.

Interhospital Variability in 180-day Infections Following Cardiac Surgery.

Objective: This study sought to: (1) evaluate hospital-level variation in infections following cardiac surgery and (2) develop and evaluate a 180-day infection quality metric.

Methods: This study evaluated Medicare claims that were merged with institutional Society of Thoracic Surgeons Adult Cardiac Surgery Database files among patients undergoing cardiac surgery across 33 Michigan centers. The primary outcome was an infection within 180 days of surgery.

Aspirin and Hemocompatibility After LVAD Implantation in Patients With Atherosclerotic Vascular Disease: A Secondary Analysis From the ARIES-HM3 Randomized Clinical Trial.

Importance: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance.

Objective: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD.

Multicenter Analysis of the Relationship Between Operative Team Familiarity and Safety and Efficiency Outcomes in Cardiac Surgery.

Background: Safety in cardiac surgical procedures is predicated on effective team dynamics. This study associated operative team familiarity (ie, the extent of clinical collaboration among surgical team members) with procedural efficiency and Society of Thoracic Surgeons (STS) adjudicated patient outcomes.

Methods: Institutional STS adult cardiac surgery registry and electronic health record data from 2014 to 2021 were evaluated across 3 quaternary hospitals.

Pump exchange for major device related infection in patients receiving a durable left ventricular assist device.

Background: Device-related infection (DRI) remains a cause of morbidity and mortality following durable left ventricular assist device (dLVAD) implantation. We evaluated outcomes following pump exchange (PE) for DRI following dLVAD implantation.

Methods: Forty-nine patients underwent PE between 1/2007 and 12/2022 for major DRI.

A gift of life, not immortality: Evaluation of a strategy of heart transplant listing in the older patient with advanced heart failure.

Patients 65 years of age or older represent the fastest-growing demographic group added to the U.S. heart transplant (HT) list.

Disparities in Skilled Nursing Facility Use and Outcomes After Cardiac Surgery.

Introduction: Cardiac surgery remains highly morbid and requires significant postoperative care. The use of postacute care facilities, such as skilled nursing facilities (SNFs) has grown in popularity to reduce healthcare spendings. Currently, sex and race disparities associated with SNF use after cardiac surgery are poorly understood.

Advancing patient-centered metrics for heart transplantation: The role of days alive and outside the hospital.

Background: Heart transplantation (HT) survival and waitlist times are established outcome metrics. Patient-centered HT outcomes are insufficiently characterized. This study evaluates the role of days alive and outside the hospital (DAOH) as a candidate patient-centered HT performance measure.

The Society of Thoracic Surgeons Intermacs 2024 Annual Report: Focus on Outcomes in Younger Patients.

The 15th Annual Report from The Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support includes 29,634 continuous-flow left ventricular assist devices from the 10-year period between 2014 and 2024. The outcomes reported here demonstrate continued improved survival in the current era of fully magnetically levitated devices, with a significantly higher 1-year (85.7% vs 78.

A retrospective multicenter study of operating room extubation and extubation timing after cardiac surgery.

Background: In an effort to enhance recovery after cardiac surgery, intraoperative extubation has been targeted as possibly beneficial. This multicenter cohort study aimed to assess this by evaluating the outcomes of operating room (OR) extubation versus extubation within 6 hours of intensive care unit (ICU) arrival (early ICU extubation). Furthermore, we assessed time to ICU extubation and mortality and morbidity.

Complete retinal pigment epithelium and outer retinal atrophy: Is it really an end-stage atrophy?

Geographic atrophy (GA), a late manifestation of age-related macular degeneration (AMD), leads to irreversible vision loss. Early identification of precursor lesions, such as incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA), is crucial for predicting GA formation. The latter stage has been associated with irreversible and progressive changes, and the eventual development of a dense scotoma on the compromised area.

ACTION-ARC Pediatric and Adult Congenital Heart Disease Ventricular Assist Device Adverse Event Definitions-2023.

Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions.

Outcomes of nonemergency cardiac surgery after overnight operative workload: A statewide experience.

Objective: Cardiac surgeons experience unpredictable overnight operative responsibilities, with variable rest before same-day, first-start scheduled cases. This study evaluated the frequency and associated impact of a surgeon's overnight operative workload on the outcomes of their same-day, first-start operations.

Methods: A statewide cardiac surgery quality database was queried for adult cardiac surgical operations between July 1, 2011, and March 1, 2021.

Enhancing Qualitative and Quantitative Data Linkages in Complex Mixed Methods Designs: Illustrations from a Multi-Phase Healthcare Delivery Study.

While mixed methods research is increasingly used to examine determinants of unwarranted variability in healthcare delivery and outcomes, novel integrative approaches are required to meet the needs of mixed methods healthcare delivery research. This article describes novel refining strategies that enhance the linkage between qualitative and quantitative dimensions of a mixed methods healthcare delivery research study. Leveraging our study experiences, this paper demonstrates several refining strategies: (1) using mediated allocation concealment to facilitate qualitative sampling; (2) informing qualitative inquiry through quantitative analytics; and (3) training and immersing multidisciplinary researchers in qualitative data collection and analysis.

Defining optimal left ventricular assist device short-term outcomes may provide insight into programmatic quality assessment.

Background: Patients have substantial variability in perioperative outcomes after left ventricular assist device (LVAD) implant. A perioperative multidimensional tool integrating mortality, adverse events (AEs), and patient-reported outcomes to assist in quality improvement initiatives is needed.

Methods: Patients undergoing HeartMate 3 LVAD implant (January 1, 2017 to January 31, 2024) in the Society of Thoracic Surgeons' Intermacs registry were studied.

Aortic Annular Enlargement vs Isolated Aortic Valve Replacement in Patients With Matched Annulus.

Background: We aimed to determine the effect of aortic annular enlargement on the midterm outcomes of aortic valve replacement surgery by comparing patients with the same-sized (≤23 mm) native aortic annuli.

Methods: From January 2011 to June 2022, 1328 patients underwent isolated aortic valve replacement-1163 without aortic annular enlargement (AVR group) and 165 with aortic annular enlargement (AVR+AAE group). Propensity score matching identified 112 pairs, controlling for native aortic annulus diameter, age, sex, diabetes, chronic lung disease, dialysis, ejection fraction, prior cardiac surgery, indication, hypertension, dyslipidemia, valve type, prior stroke, prior myocardial infarction, and case status.

Extrinsic outflow graft obstruction of the HeartMate 3 LVAD: A state-of-the-art review.

While notable improvements in survival, the incidence of hemocompatibility-related adverse events, hospitalizations, and cost have been demonstrated with the only commercially available durable left ventricular assist device, a category of pump malfunctions characterized by outflow graft obstruction has been noted with broader use and clinical follow-up of recipients of this technology. Of particular concern is the accumulation of acellular biodebris between the outflow graft and bend relief covering the outflow graft at its origin with the pump (which we term extrinsic outflow graft obstruction at the bend relief). This process tends to be insidious, occurs late in the postoperative course, can be challenging to diagnose, and can result in significant morbidity and mortality.

Optimizing Triage of Ambulatory Patients With Advanced Heart Failure: 2-Year Outcomes From REVIVAL.

Background: Left ventricular assist device (LVAD) use remains uncommon in advanced heart failure (HF) patients not dependent on inotropes.

Objectives: Before considering a randomized trial comparing a strategy of earlier use of LVAD to continued medical therapy, a better understanding is needed of the clinical trajectory of ambulatory patients with advanced systolic HF on optimal guideline-directed medical therapy (GDMT).

Methods: REVIVAL enrolled 400 patients with advanced ambulatory systolic HF, ≥1 HF mortality risk marker (≥2 HF hospitalizations past year; or HF hospitalization and high natriuretic peptide; or no HF hospitalizations but low peak oxygen consumption, 6-minute walk, serum sodium, HF survival score or Seattle HF model predicted survival), and no LVAD contraindication at 21 LVAD centers from July 2015 to June 2016.

Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure.

Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing event. A slow RNAPII mutant and chromatin-modifying chemicals that reduce the rate of RNAPII elongation induce exon skipping whereas chemicals that create a more relaxed chromatin exon inclusion.

Increasing Adoption of Left Atrial Appendage Occlusion in Isolated Coronary Artery Bypass Grafting.

Background: Recent randomized trial data showed fewer strokes with left atrial appendage occlusion (LAAO) after cardiac surgery in patients with atrial fibrillation. This study developed a quality initiative to increase LAAO adoption.

Methods: Among 11,099 patients who underwent isolated coronary artery bypass grafting (CABG) between January 2019 and March 2021 at 33 hospitals in Michigan, those patients with atrial fibrillation who underwent first-time, on-pump CABG were eligible (n = 1241).