Decision-making in valve reintervention: Redo-Transcatheter aortic valve replacement vs. explant surgery.

Objective: Data remain limited on factors influencing the selection of redo-transcatheter aortic valve replacement (TAVR) versus surgical explant in patients with failing transcatheter heart valves. This study aimed to identify clinical and procedural factors guiding treatment decisions.

Methods: This single-center, retrospective study included all patients who underwent aortic valve reintervention following prior TAVR at a U.

Inflammatory Memory of Stem Cells: Implications for Hematological Diseases.

Immunological memory in adaptive and innate immune cells is well-characterized, enabling enhanced responses upon secondary challenges. However, it has only been recently appreciated that the non-immune target cells of inflammation, particularly organ-specific stem cells, also exhibit memory of prior inflammatory exposures. Previous inflammation experience imprints on the stem cells and influences their regenerative potential and responses to subsequent inflammatory insults.

Impact of Calcified Raphe on TAVR in Bicuspid Patients: Predicting Redo-TAVR Feasibility and Virtual Planning Implications.

Background: Patients with bicuspid aortic stenosis who receive transcatheter aortic valve replacement (TAVR) may require subsequent valve interventions in their lifetime; however, the feasibility of redo-TAVR in this population is uncertain. We aimed to assess redo-TAVR feasibility in bicuspid patients and develop a predictive virtual valve planning algorithm.

Methods: We studied computed tomography scans of bicuspid patients who received a balloon-expandable transcatheter heart valve (THV) in the LRT trial (Low Risk TAVR).

PD-1 inhibition for relapse after allogeneic transplantation in acute myeloid leukemia and myelodysplastic syndrome.

Relapse of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains the primary source of mortality after allogeneic hematopoietic stem cell transplantation (HCT). Targeting programmed death-1 (PD-1) for reversing T-cell exhaustion and restoring the graft-versus-leukemia (GVL) effect may have logistical advantages over donor lymphocyte infusion. In a prospective phase 1B clinical trial, pembrolizumab was administered every 3 weeks to 16 patients with AML (n = 12) and MDS (n = 4) in relapse after HCT to assess graft-versus-host disease (GVHD), clinical response, and survival.

Correlates of Hemodynamic Instability During Non-Emergent Percutaneous Coronary Intervention: Refining High-Risk Criteria for Utilizing Mechanical Circulatory Support.

Background: Previous studies using high-risk criteria to select patients for mechanical circulatory support (MCS) during percutaneous coronary intervention (PCI) have not consistently shown a benefit in reducing adverse outcomes. Identifying correlates for intra-procedural hemodynamic instability (HI) may improve patient selection for MCS.

Methods: Consecutive, hemodynamically stable patients undergoing non-emergent PCI between 2018 and 2022 were reviewed.

Novel regulators of GVHD revealed through microbiome and metabolome patterns across distinct intestinal regions.

Microbial dysbiosis and metabolite changes in the gastrointestinal (GI) tract have been linked to pathogenesis and severity of many diseases, including graft-versus-host disease (GVHD), the major complication of allogeneic hematopoietic stem cell transplantation. However, published studies have only considered the microbiome and metabolome of excreted stool and do not provide insight into the variability of the microbial community and metabolite composition throughout the GI tract or the unique temporal dynamics associated with different gut locations. Because such geographical variations are known to influence disease processes, we used a multi-omics approach to characterize the microbiome and metabolite profiles of gut contents from different intestinal regions in well-characterized mouse models of GVHD.

Impella versus Non-Impella for Nonemergent High-Risk Percutaneous Coronary Intervention.

The benefit of mechanical circulatory support (MCS) with Impella (Abiomed, Inc, Danvers, MA) for patients undergoing nonemergent, high-risk percutaneous coronary intervention (HR-PCI) is unclear and currently the subject of a large randomized clinical trial (RCT), PROTECT IV. While contemporary registry data from PROTECT III demonstrated improvement of outcomes with Impella when compared with historical data (PROTECT II), there is lack of direct comparison to the HR-PCI cohort that did not receive Impella support. We retrospectively identified patients from our institution meeting PROTECT III inclusion criteria (left ventricular ejection fraction [LVEF] <35% with unprotected left main or last remaining vessel or LVEF <30% undergoing multivessel PCI), and compared this group (NonIMP) to the published outcomes data from the PROTECT III registry (IMP).

What Are the Implications of Choosing a TAVR-First Strategy in the Lifetime Management of Aortic Stenosis?: A Critical Review of TAVR-Explant- and Redo-TAVR.

Some patients with aortic stenosis may require multiple valve interventions in their lifetime, and choosing transcatheter aortic valve replacement (TAVR) as the initial intervention may be appealing to many. If their transcatheter heart valve degenerates later in life, most will hope to undergo redo-TAVR. However, if redo-TAVR is not feasible, some may have to undergo surgical explantation of their transcatheter heart valve (TAVR-explant).

Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease.

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs.

Antibiotic-associated neutropenia is marked by the depletion of intestinal and associated metabolites in pediatric patients.

Prolonged antibiotic exposure causes dangerous hematologic side effects, including neutropenia, in up to 34% of patients. Murine studies established a link between the intestinal microbiota and hematopoiesis. To identify factors that predispose to neutropenia in pediatric patients, we evaluated changes in microbiota-derived metabolites and intestinal microbiota composition after prolonged courses of antibiotics.

The impact of ventricular remodeling on quality-of-life outcomes after Transcatheter aortic valve replacement.

Background: Among patients with aortic stenosis, ventricular remodeling by hypertrophy can limit the augmentation of flow with exertion, even after valve intervention. However, the effect of hypertrophy on quality of life (QoL) improvement has not been studied. We aimed to determine the effect of ventricular hypertrophy on QoL outcomes after transcatheter aortic valve replacement (TAVR).

ISCCM Position Statement on the Management of Invasive Fungal Infections in the Intensive Care Unit.

Rationale: Invasive fungal infections (IFI) in the intensive care unit (ICU) are an emerging problem owing to the use of broad-spectrum antibiotics, immunosuppressive agents, and frequency of indwelling catheters. Timely diagnosis which is imperative to improve outcomes can be challenging. This position statement is aimed at understanding risk factors, providing a rational diagnostic approach, and guiding clinicians to optimize antifungal therapy.

Inflammation-induced epigenetic imprinting regulates intestinal stem cells.

It remains unknown whether and how intestinal stem cells (ISCs) adapt to inflammatory exposure and whether the adaptation leaves scars that will affect their subsequent regeneration. We investigated the consequences of inflammation on Lgr5 ISCs in well-defined clinically relevant models of acute gastrointestinal graft-versus-host disease (GI GVHD). Utilizing single-cell transcriptomics, as well as organoid, metabolic, epigenomic, and in vivo models, we found that Lgr5 ISCs undergo metabolic changes that lead to the accumulation of succinate, which reprograms their epigenome.

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus.

Two-year follow-up of transcatheter aortic valve replacement in low-risk patients with symptomatic severe bicuspid aortic valve stenosis.

Background: In 2019, the US Food and Drug Administration (FDA) approved transcatheter aortic valve replacement (TAVR) for low-risk patients with symptomatic severe tricuspid aortic stenosis. However, bicuspid aortic valve (BAV) patients were included only in single-arm registries of pivotal low-risk TAVR trials, resulting in limited data for this subgroup.

Methods: The LRT (Low Risk TAVR) trial was an investigator-initiated, prospective, multicenter study and the first FDA-approved investigational device exemption trial to evaluate the feasibility of TAVR with balloon-expandable or self-expanding valves in low-risk patients with symptomatic severe BAV stenosis.

High-risk percutaneous coronary intervention with or without mechanical circulatory support: Will Impella show superiority in the PROTECT IV randomized trial?

Background: PROTECT IV is a current enrolling randomized controlled trial evaluating high-risk percutaneous coronary intervention (HR-PCI) with prophylactic Impella versus no Impella to reduce the composite primary endpoint of all-cause death, stroke, myocardial infarction (MI), or cardiovascular hospitalization. In a PROTECT IV-like cohort of patients who underwent HR-PCI without Impella, we aimed to report the rate of major adverse events to determine whether the trial is adequately powered.

Methods And Results: A total of 700 patients meeting similar inclusion/exclusion criteria of PROTECT IV who underwent HR-PCI without Impella at a single tertiary center from 2008 to 2022 were included in the analysis.

Impella Versus Non-Impella for Nonemergent High-Risk Percutaneous Coronary Intervention.

The benefit of mechanical circulatory support with Impella (Abiomed, Inc., Danvers, Massachusetts) for high-risk percutaneous coronary intervention (HR-PCI) is uncertain. PROTECT III registry data showed improved outcomes with Impella compared with historical data (PROTECT II) but lack a direct comparison with the HR-PCI cohort without Impella support.

Bioprosthetic Aortic Valve Thrombosis: Definitions, Clinical Impact, and Management: A State-of-the-Art Review.

Bioprosthetic aortic valve thrombosis is frequently detected after transcatheter and surgical aortic valve replacement due to advances in cardiac computed tomography angiography technology and standardized surveillance protocols in low-surgical-risk transcatheter aortic valve replacement trials. However, evidence is limited concerning whether subclinical leaflet thrombosis leads to clinical adverse events or premature structural valve deterioration. Furthermore, there may be net harm in the form of bleeding from aggressive antithrombotic treatment in patients with subclinical leaflet thrombosis.

Impact of Significant Hemoglobin Drop Without Bleeding in Patients Undergoing Transcatheter Aortic Valve Replacement.

Background: Hemoglobin (Hgb) drop without bleeding is common among patients undergoing transcatheter aortic valve replacement; however, the clinical implications of significant Hgb drop have not been fully evaluated.

Methods And Results: Consecutive patients undergoing transcatheter aortic valve replacement at our institution from 2011 to 2021 were retrospectively reviewed. Three groups were assessed: no Hgb drop and no bleed (NoD-NoB [reference group]), Hgb drop with bleed, and Hgb drop and no bleed (D-NoB).