Randomized study of temporary diaphragm pacing for enhanced recovery after surgery in cardiac surgery patients at risk of prolonged mechanical ventilation.

Objective: Prolonged mechanical ventilation after cardiac surgery significantly increases morbidity and mortality. The aim of this study is to establish the role of diaphragmatic pacing to decrease mechanical ventilation burden in high-risk patients undergoing cardiac surgery.

Methods: This is a prospective, randomized trial of temporary diaphragmatic pacing electrode use in patients undergoing cardiac surgery (NCT04899856).

The prognostic utility of galectin-3 in patients undergoing cardiac surgery: a scoping review.

Objective: To review the utility of galectin-3 (Gal-3) as a biomarker for postoperative adverse outcomes in patients undergoing cardiac surgery.

Method: This review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic database search was conducted in October 2023.

Elevated myocardial extracellular volume fraction is associated with the development of conduction pathway defects following transcatheter aortic valve replacement.

Background: Transcatheter aortic valve replacement (TAVR) has become an established method of aortic stenosis treatment but suffers from the risk of heart block and pacemaker requirement. Risk stratification for patients who may develop heart block remains imperfect. Simultaneously, myocardial fibrosis as measured by cardiac magnetic resonance imaging (CMR) has been demonstrated as a prognostic indicator of ventricular recovery and mortality following TAVR.

Pericardial fluid troponin in cardiac surgery.

Background And Objective: Pericardial Fluid (PF) is a rich reservoir of biologically active factors. Due to its proximity to the heart, the biochemical structure of PF may reflect the pathological changes in the cardiac interstitial environment. This manuscript aimed to determine whether the PF level of cardiac troponins changes in patients undergoing cardiac surgery.

Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-β monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors.

Background: NIS793 is a human IgG2 monoclonal antibody that binds to transforming growth factor beta (TGF-β). This first-in-human study investigated NIS793 plus spartalizumab treatment in patients with advanced solid tumors.

Methods: Patients received NIS793 (0.

Temporal trends in mortality of aortic dissection and rupture in the UK, Japan, the USA and Canada.

Objective: Aortic dissection and aortic aneurysm rupture are aortic emergencies and their clinical outcomes have improved over the past two decades; however, whether this has translated into lower mortality across countries remains an open question. The purpose of this study was to compare mortality trends from aortic dissection and rupture between the UK, Japan, the USA and Canada.

Methods: We analysed the WHO mortality database to determine trends in mortality from aortic dissection and rupture in four countries from 2000 to 2019.

Transforming Growth Factor-β Blockade in Pancreatic Cancer Enhances Sensitivity to Combination Chemotherapy.

Background & Aims: Transforming growth factor-b (TGFb) plays pleiotropic roles in pancreatic cancer, including promoting metastasis, attenuating CD8 T-cell activation, and enhancing myofibroblast differentiation and deposition of extracellular matrix. However, single-agent TGFb inhibition has shown limited efficacy against pancreatic cancer in mice or humans.

Methods: We evaluated the TGFβ-blocking antibody NIS793 in combination with gemcitabine/nanoparticle (albumin-bound)-paclitaxel or FOLFIRINOX (folinic acid [FOL], 5-fluorouracil [F], irinotecan [IRI] and oxaliplatin [OX]) in orthotopic pancreatic cancer models.

Targeting the IL1β Pathway for Cancer Immunotherapy Remodels the Tumor Microenvironment and Enhances Antitumor Immune Responses.

High levels of IL1β can result in chronic inflammation, which in turn can promote tumor growth and metastasis. Inhibition of IL1β could therefore be a promising therapeutic option in the treatment of cancer. Here, the effects of IL1β blockade induced by the mAbs canakinumab and gevokizumab were evaluated alone or in combination with docetaxel, anti-programmed cell death protein 1 (anti-PD-1), anti-VEGFα, and anti-TGFβ treatment in syngeneic and humanized mouse models of cancers of different origin.

cIAP1/2 Antagonism Induces Antigen-Specific T Cell-Dependent Immunity.

Checkpoint blockade immunotherapy has failed in pancreatic cancer and other poorly responsive tumor types in part due to inadequate T cell priming. Naive T cells can receive costimulation not only via CD28 but also through TNF superfamily receptors that signal via NF-κB. Antagonists of the ubiquitin ligases cellular inhibitor of apoptosis protein (cIAP)1/2, also called second mitochondria-derived activator of caspases (SMAC) mimetics, induce degradation of cIAP1/2 proteins, allowing for the accumulation of NIK and constitutive, ligand-independent activation of alternate NF-κB signaling that mimics costimulation in T cells.

Water channel aquaporin 4 is required for T cell receptor mediated lymphocyte activation.

Aquaporins are a family of ubiquitously expressed transmembrane water channels implicated in a broad range of physiological functions. We have previously reported that aquaporin 4 (AQP4) is expressed on T cells and that treatment with a small molecule AQP4 inhibitor significantly delays T cell mediated heart allograft rejection. Using either genetic deletion or small molecule inhibitor, we show that AQP4 supports T cell receptor mediated activation of both mouse and human T cells.

Clinical impact of right ventricular pacing burden in patients with post-transcatheter aortic valve replacement permanent pacemaker implantation.

Aims: Patients who undergo permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR) have a worse outcome. The aim of this study was to identify risk factors of worse outcomes in patients with post-TAVR PPM implantation.

Methods And Results: This is a single-centre, retrospective study of consecutive patients who underwent post-TAVR PPM implantation from 11 March 2011 to 9 November 2019.

Cor-Knot Use in SAVR Facilitates Coplanar Angle Adjustment During TAVR.

The Cor-Knot surgical tying device (LSI Solutions) is an automated suture fastener with a titanium-crimpable sleeve that facilitates a fast and secure knot. The device is an alternative to hand tying, minimizing operation time, and its increasing use is anticipated for minimally invasive cardiac surgeries or in patients with small surgical anatomy. As its use expands, the likelihood of encountering this knotting device during structural interventions may increase.

Combination of the STING Agonist MIW815 (ADU-S100) and PD-1 Inhibitor Spartalizumab in Advanced/Metastatic Solid Tumors or Lymphomas: An Open-Label, Multicenter, Phase Ib Study.

Purpose: The stimulator of IFN genes (STING) is a transmembrane protein that plays a role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody against PD-1, in 106 patients with advanced solid tumors or lymphomas.

Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor.

Objectives: Sabatolimab is a humanized monoclonal antibody (hIgG4, S228P) directed against human T-cell immunoglobulin domain and mucin domain-3 (TIM-3). Herein, we describe the development and characterization of sabatolimab.

Methods: Sabatolimab was tested for binding to its target TIM-3 and blocking properties.

Preclinical Characterization and Phase I Study of an Anti-HER2-TLR7 Immune-Stimulator Antibody Conjugate in Patients with HER2+ Malignancies.

Immune-stimulator antibody conjugates (ISAC) combining tumor-targeting monoclonal antibodies with immunostimulatory agents allow targeted delivery of immune activators into tumors. NJH395 is a novel, first-in-class ISAC comprising a Toll-like receptor 7 (TLR7) agonist conjugated to an anti-HER2 antibody via a noncleavable linker payload. Preclinical characterization showed ISAC-mediated activation of myeloid cells in the presence of antigen-expressing cancer cells, with antigen targeting and TLR7 agonism contributing to antitumor activity.

Percutaneous mechanical thrombectomy and extracorporeal membranous oxygenation: A case series.

Background: Massive or high-risk pulmonary embolism (PE) is a potentially life-threatening diagnosis with significant morbidity and mortality if treatment is delayed. Extracorporeal membrane oxygenation (ECMO) and large bore thrombectomy (LBT) in isolation have been used to stabilize and treat patients with massive PE, however, literature describing the combination of both modalities is lacking. We present a case series involving 9 patients who underwent combined ECMO and LBT and their outcomes.

Pulmonary Artery Root Replacement for Leiomyosarcoma: A Viable Thoracic Oncovascular Operation.

Leiomyosarcoma of the pulmonary artery is a rare but potentially fatal disease. Due to its rarity, the treatment algorithm is not well-established. While there may be a role for both chemotherapy and radiotherapy, surgical management is the most definitive method.

Risk Stratification of New Persistent Left Bundle Branch Block After Transcatheter Aortic Valve Implantation.

Previous studies reported that new-onset persistent left bundle branch block (NOP-LBBB) was related to worse outcomes after transcatheter aortic valve implantation (TAVI). However, these results can be confounded by the presence of permanent pacemaker (PPM) implantation before and after TAVI. Long-term outcomes and the risk stratification of NOP-LBBB not having PPM implantation before and after TAVI have not been fully investigated.

Idiopathic posterior papillary muscle rupture; a case report.

Background: Papillary muscle rupture is a rare condition. Its clinical presentation, diagnosis and management can be very challenging for the clinician.

Case Presentation: A 73-year-old woman with hypertension presented with chest pain, ST-segment changes, and elevated serum troponin levels.