13 research outputs found
T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation
No full textCritical role for the chemokine receptor CXCR6 in NK cell–mediated antigen-specific memory of haptens and viruses
No full textGeneration of gut-homing IgA-secreting B cells by intestinal dendritic cells
No full textNormal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators
Towards an Understanding of Best Practice - The Good, The Bad and the Future of Cardiogenic Shock Teams.
No full textCardiogenic shock (CS) remains a high-mortality condition that demands rapid diagnosis, coordinated multidisciplinary management, and timely initiation of mechanical circulatory support. As more institutions implement dedicated CS teams, substantial heterogeneity has emerged in how these teams are structured, activated, and sustained. To better characterize this variability and begin defining the components of an optimal CS team, the Society of Critical Care Cardiology (SoCCC), in partnership with the Society for Cardiovascular Angiography and Interventions (SCAI), convened the Inaugural Cardiogenic Shock Teams Think Tank. Held on October 17, 2024, as a pre-conference program to SCAI SHOCK 2024 in Washington, DC, the meeting brought together national leaders in CS care, mechanical circulatory support, and resuscitation to identify shared challenges and propose practical solutions. This manuscript summarizes key insights from this inaugural Think Tank, which represents the first in an ongoing series of collaborative efforts aimed at informing the standardization and optimization of CS teams nationwide. Specifically, we review the ideal composition and core competencies of a CS team; the rationale and emerging evidence supporting dedicated team-based CS care; activation algorithms and operational workflows; and common barriers to establishing and sustaining such teams. We also outline future directions and opportunities to strengthen collaborative infrastructure, refine clinical pathways, and enhance the reliability, responsiveness, and effectiveness of cardiogenic shock teams across diverse healthcare settings
Antigen Availability Determines CD8+ T Cell-Dendritic Cell Interaction Kinetics and Memory Fate Decisions
No full textSummaryT cells are activated by antigen (Ag)-bearing dendritic cells (DCs) in lymph nodes in three phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8+ T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, whereas higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation but yielded different transcriptome signatures at 12 hr and 24 hr. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure, resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics
Acute Decompensated Valvular Disease in the Intensive Care Unit
No full textAcute decompensated valvular disease encompasses a group of complex and challenging conditions, which are often the primary reason for admission to the cardiac intensive care unit and can also complicate the management of other primary cardiac disorders. Critically ill patients with valvular disease also present unique diagnostic and management challenges. Historically, medical and percutaneous interventional therapies have been limited and surgery was the only definitive treatment; however, surgical risk can at times be prohibitive. High-quality evidence to direct management of acute valvular disorders in this population is lacking and societal guidelines largely do not address treatment options for critically ill patients with decompensated valvular disease. In this review, we discuss the clinical presentation and epidemiology of commonly encountered valvular diseases in the modern cardiac intensive care unit, highlight key pathophysiology, detail gaps in evidence, describe the pivotal role of multidisciplinary Heart Teams, and provide guidance for management
Need for a Cardiogenic Shock Team Collaborative—Promoting a Team‐Based Model of Care to Improve Outcomes and Identify Best Practices
No full textCardiogenic shock continues to carry a high mortality rate despite contemporary care, with no breakthrough therapies shown to improve survival over the past few decades. It is a time‐sensitive condition that commonly results in cardiovascular complications and multisystem organ failure, necessitating multidisciplinary expertise. Managing patients with cardiogenic shock remains challenging even in well‐resourced settings, and an important subgroup of patients may require cardiac replacement therapy. As a result, the idea of leveraging the collective cognitive and procedural proficiencies of multiple providers in a collaborative, team‐based approach to care (the “shock team”) has been advocated by professional societies and implemented at select high‐volume clinical centers. A slowly maturing evidence base has suggested that cardiogenic shock teams may improve patient outcomes. Although several registries exist that are beginning to inform care, particularly around therapeutic strategies of pharmacologic and mechanical circulatory support, none of these are currently focused on the shock team approach, multispecialty partnership, education, or process improvement. We propose the creation of a Cardiogenic Shock Team Collaborative—akin to the successful Pulmonary Embolism Response Team Consortium—with a goal to promote sharing of care protocols, education of stakeholders, and discovery of how process and performance may influence patient outcomes, quality, resource consumption, and costs of care
