Adverse Long-Term Outcomes and an Immune Suppressed Endotype in Sepsis Patients with Reduced Interferon-γ ELISpot: A Multicenter, Prospective Observational Study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 13, 2023

Sepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting and immunological endotyping septic has generally relied on using blood protein or mRNA biomarkers, static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.

Language: Английский

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Pathways to Reduce Late Mortality of Hemorrhagic Shock

IntechOpen eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: April 22, 2024

Patients with progressing hemorrhagic shock (HS) die rapidly of cardiac arrest by insufficient venous return or within days second-hit multiple organ dysfunction/failure (MOD/MOF). Once earliest source control has been effectuated and macro-hemodynamics is normalized, only three variables affect mortality, namely microcirculation, temperature, oxygen. Late, non-immediate, mortality usually preceded a period cryptic shock, essentially disease microcirculation in the midst seemingly functional macrocirculation. The persistence effects ischemia-reperfusion toxemia (IRT) underlying subclinical fundamental pathogenetic factors for clinical observed second hit deterioration. Rewarming hypothermic patient administration supplementary high dosages oxygen are standard practices management acute phase. A complete shift paradigm prospects an answer to above tactics’ limitations, drawbacks, contra-indications. Mild-to-moderate hypothermia, titrated oxygen, timely-given vasodilators should instead be given during damage surgery (DCS) advanced aim reducing ischemia repercussion injury (IRI) e dysfunction. new strategy suggested: preoperative hypothermia before hemorrhage control, intra-operative vasodilation anti-inflammatory tactics after control.

Language: Английский

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Damage control surgery in a patient with cardiac arrest from necrotizing soft tissue infection

Trauma Surgery & Acute Care Open, Journal Year: 2024, Volume and Issue: 9(1), P. e001428 - e001428

Published: Oct. 1, 2024

Language: Английский

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Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Abstract The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident cell‐mediated neuroinflammation peripheral cell (eg, T cell) infiltration into have been shown to significantly contribute Alzheimer's disease (AD) pathology, nature extent responses context AD related dementias (ADRD) remain unclear. Furthermore, roles driving ADRD pathology incompletely elucidated. In March 2023, Association convened International Conference (AAIC), Advancements: Immunity, discuss ADRD. A wide range topics were discussed, such as animal models that replicate human immune‐related biomarkers clinical trials, lessons from other fields describing neurodegeneration. This manuscript presents highlights conference outlines avenues for future research on immunity Highlights plays central role pathogenesis disease. exerts numerous effects throughout amyloid‐beta, tau, pathways. 2023 AAIC, encouraged discussions collaborations understanding system.

Language: Английский

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Immune‐mediated inflammatory diseases as long‐term sepsis complications: Long‐term persistence of host dysregulation?

Journal of Internal Medicine, Journal Year: 2023, Volume and Issue: 295(2), P. 123 - 125

Published: Dec. 13, 2023

Sepsis results from the dysregulated host response to bacterial, viral, or fungal infections. Recent data suggest that 28-day outcome of sepsis patients depends on features immune reaction host. Four 10% with septic shock present an entirely pro-inflammatory course a high risk for early death and mimicking macrophage activation syndrome (MALS)—that is, liver dysfunction, disseminated intravascular coagulation, increases blood ferritin triglycerides. Almost 30% immunoparalysis, failure circulating mononuclear cells production cytokines upon ex vivo stimulation defective antigen presentation, often leading T cell exhaustion. However, function majority lies at intermediate state between MALS immunoparalysis [1]. It may well be case this classification guides long-term outcomes sepsis—a condition called chronic critical illness (CCI) persistent inflammation, immunosuppression, catabolism (PICS). There are several factors impact progression into CCI PICS. The most important age, presence cachexia, site infection primary episode. These have profound disabilities associated lymphopenia increased expression PD-1, expansion myeloid-derived stem regulatory dysfunctional erythropoiesis [2]. is suggested 1-year mortality survivors approaches 40%, persisting dysregulations. article by Mageau et al. in issue Journal Internal Medicine breaks boundaries goes beyond traditional approach survivors. Taking consideration complex dysregulation sepsis, authors ask themselves whether original phenomena lead predisposition immune-mediated inflammatory diseases (IMIDs) among For their analysis, they used French PMSI database, collecting information January November 2020 460,708 index cases sepsis. They study as comparators 62,258 acute myocardial infarction (AMI). To avoid confounding bias, 62,257 were selected match AMI using matching criteria sex, active cancer, malignant hematologic condition, HIV infection, history organ transplantation. Survivors followed up 9 months, all new diagnoses IMIDs recorded. Results striking, incidence was 2.80 times higher than time started increase after 16 days hazard ratio greater thrombocytopenia, Sjögren's syndrome, autoimmune hemolytic anemia, systemic lupus erythematosus, ANCA-associated vasculitis. In series sensitivity analyses, proved remained irrespective etiology bacterial viral patient's comorbidities [3]. recent publications sequelae focus cardiovascular events—mainly composite AMI, stroke, death—and report 5-year follow-up period case. these publications, preexisting (CVDs) excluded analysis. One analysis Ontario April 2007 2017 followed-up 254,251 hospitalized matched them similar number other reasons. hospitalization 1.30 CVDs. Interestingly, 1.66 aged 40 years less [4]. This confirms one meta-analysis 27 studies published 2005 2017, which 7 population-based rest based patients. retrospective almost 2.25 million adult hospital OptumLabs Data Warehouse, coronary heart disease, failure, arrhythmia 1.26, 1.51, 1.35, 1.45, respectively [5]. At first glance, it somehow difficult find association observed CVDs As noted above, recently described immunotypes MALS. triggered excess interleukin (IL)-1β tissue macrophages Priming IL-1β makes prone supported CANTOS trial LoDoCo2 investigators. trial, episode high-sensitivity C-reactive protein above 2 mg/L randomized treatment placebo canakimumab once every 3 months. Canakinumab monoclonal antibody targets IL-1β. showed 15% decrease relative major CVD events, including [6]. investigator consortium 5478 evidence disease 500 mg colchicine daily. endpoint event defined death, ischemic ischemia-driven revascularization. significantly decreased 31% [7]. Both prove importance drive complications because canakinumab directly blocks activity inhibits formation NLRP3 inflammasome, splits proactive intracellular pro-IL-1β prospective our group, we monitored over-time high-mobility group 1 (HMGB1) We split those peak HMGB1—notably before days—and late HMGB1. HMGB1 danger-associated molecular pattern: released dying cells, stimulates binding Toll-like receptor (TLR)-4. Indeed, had levels interferon-gamma, indirect signature TLR-4 activation. HMGB1, only if medical such type diabetes mellitus, congestive renal [8]. synergy primed unfavorable outcome. also explain why incident events arrive year when organism likely persists. Rehospitalization infections another sequel An 159,864 Germany revealed 45.0% rehospitalized whereas 56.6% received antibiotics outpatients. post-sepsis 9.6% compared pre-sepsis [9]. explained immunotype episode, persists during significance future comes SAVE-MORE controlled trial. Patients severe COVID-19 respiratory due IL-1 cascade indicated biomarker suPAR (soluble urokinase plasminogen activator receptor) standard-of-care anakinra. Anakinra recombinant antagonist both IL-1α. Early anakinra prevented post-acute COVID [10]. [3] sheds light aspect consequences, namely, IMIDs. backgrounds greatly influenced With point view, precision immunotherapy becomes necessity influence not but consequences. elaborate necessity, congratulated ground-breaking contribution. Evangelos J. Giamarellos-Bourboulis has honoraria Abbott Products Operations AG, bioMérieux, Brahms, GSK, InflaRx, Swedish Orphan BioVitrum AB; independent educational grants Johnson & Johnson, MSD, UCB, Biovitrum funding Horizon European Grants ImmunoSep RISCinCOVID Health grant EPIC-CROWN-2 (granted Hellenic Institute Study Sepsis).

Language: Английский

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Temporal Changes in Innate and Adaptive Immunity During Sepsis as Determined by ELISpot

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 14, 2023

ABSTRACT Background The inability to evaluate host immunity in a rapid quantitative manner patients with sepsis has severely hampered development of novel immune therapies. ELISpot assay is functional bioassay that measures the number cytokine-secreting cells and relative amount cytokine produced at single-cell level. A key advantage its excellent dynamic range enabling more precise quantifiable assessment immunity. Herein, we tested hypothesis on whether can detect changes both innate adaptive as they often occur during sepsis. We also could effect drug therapies modulate Methods Mice were made septic using sublethal cecal ligation puncture (CLP). Blood spleens harvested serially ex vivo IFN-γ TNF-α production compared by ELISA. capability due therapy dexamethasone, IL-7, arginine was evaluated. Results confirmed decreased responsiveness progression. More importantly, able response immune-modulatory reagents, for example arginine, IL-7 readily manner, predicted reagents known mechanisms action. ELISA results tended parallel one another although some differences noted. Conclusion offers unique assess status over time. presented herein demonstrate be used follow effects drugs ameliorate sepsis-induced dysfunction. This would major advance guiding new

Language: Английский

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Transcriptomic Differences in Peripheral Monocyte Populations in Septic Patients Based on Outcome

Shock, Journal Year: 2024, Volume and Issue: 62(2), P. 208 - 216

Published: May 2, 2024

Postsepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness with suboptimal outcomes. The underlying immunological response that determines these clinical trajectories remains poorly defined at transcriptomic level. As classical nonclassical monocytes are key leukocytes in both innate adaptive immune systems, we sought to delineate cell types. Using single-cell RNA sequencing pathway analyses, identified gene expression patterns between two groups consistent differences TNF-α production based on outcome. This may provide therapeutic targets for those risk order improve their phenotype/endotype, morbidity, long-term mortality.

Language: Английский

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Response to: Comment on: Nutritional support for the trauma and emergency general surgery patient: What you need to know

Journal of Trauma and Acute Care Surgery, Journal Year: 2024, Volume and Issue: 98(1), P. e4 - e5

Published: Nov. 26, 2024

Hartwell, Jennifer L. MD, FACS; Evans, David Martin, Matthew J. FACS Author Information

Language: Английский

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Unique lymphocyte transcriptomic profiles in septic patients with chronic critical illness

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 3, 2024

Despite continued improvement in post-sepsis survival, long term morbidity and mortality remain high. Chronic critical illness (CCI), defined as persistent inflammation organ injury requiring prolonged intensive care, is a harbinger of poor long-term outcomes sepsis survivors. Current dogma states that survivors are immunosuppressed, particularly CCI. Investigation this immune suppression heterogeneous populations across distinct clinical trajectories outcomes, along with limited sampling access, accessible via single-cell RNA sequencing (scRNA-seq).

Language: Английский

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Surgical Decision-Making in Postinjury Multiple Organ Failure

Published: Jan. 1, 2024

Language: Английский

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