Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis-Study of Treatment's Echocardiographic Mechanisms (CLOVERS-STEM).

Importance: Receipt of fluid and vasopressors, common treatments in septic shock, may affect cardiac function.

Objectives: We sought to determine whether a liberal or restrictive fluid resuscitation strategy was associated with changes in cardiac function.

Design: We prospectively studied a subset of patients enrolled in the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial, performing echocardiography at baseline and at 24 hours after randomization.

Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness.

Rationale: Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood.

Objectives: To determine the temporal nature of the Hyperinflammatory and Hypoinflammatory phenotypes and assess the impact of transition between the phenotypes on mortality.

Methods: We used data from one prospective observational cohort (MARS) and two randomized controlled trials in ARDS (ALVEOLI) and sepsis (CLOVERS).

Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial.

Importance: Fostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19.

Objective: To evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia.

Design, Setting, And Participants: This multicenter, phase 3, placebo-controlled, double-blinded randomized clinical trial was conducted at 41 US sites and 21 international sites between November 17, 2021, and September 27, 2023; the last follow-up visit was December 31, 2023.

Benefit of early oseltamivir therapy for adults hospitalized with influenza A: an observational study.

Background: clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza.

Methods: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022-July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status.

Incorporating Aeroallergen Exposure Metrics into Clinical Asthma Care: A Pilot Study Using A Mixed-Methods Survey to Assess Aeroallergen Knowledge, Perceived Asthma Control, and Mitigation Strategies in Households of Children with Asthma.

Mitigation of household allergens is associated with the reduction of asthma exacerbations in those with allergic asthma and is recommended in recent asthma guidelines. However, we need to better understand patient knowledge of aeroallergens in their homes prior to integrating direct allergen measurement methods into standard asthma care. We conducted a mixed-methods sequential pilot study consisting of a survey and virtual interview with caregivers of children aged 3 to 15 with asthma diagnosis (any severity) about asthma control, household environment, mitigation knowledge and strategies, and knowledge of allergens and asthma.

Assessment and mitigation of bias in influenza and COVID-19 vaccine effectiveness analyses - IVY Network, September 1, 2022-March 30, 2023.

Background: In test-negative studies of vaccine effectiveness (VE), including patients with co-circulating, vaccine-preventable, respiratory pathogens in the control group for the pathogen of interest can introduce a downward bias on VE estimates.

Methods: A multicenter sentinel surveillance network in the US prospectively enrolled adults hospitalized with acute respiratory illness from September 1, 2022-March 31, 2023. We evaluated bias in estimates of VE against influenza-associated and COVID-19-associated hospitalization based on: inclusion vs exclusion of patients with a co-circulating virus among VE controls; observance of VE against the co-circulating virus (rather than the virus of interest), unadjusted and adjusted for vaccination against the virus of interest; and observance of influenza or COVID-19 against a sham outcome of respiratory syncytial virus (RSV).

Effectiveness of Original Monovalent and Bivalent COVID-19 Vaccines Against COVID-19-Associated Hospitalization and Severe In-Hospital Outcomes Among Adults in the United States, September 2022-August 2023.

Background: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

SEPSIGN: early identification of sepsis signs in emergency department.

Because 20-30% of patients with sepsis deteriorate to critical illness, biomarkers that provide accurate early prognosis may identify which patients need more intensive treatment versus safe early discharge. The objective was to test the performance of sVEGFR2, suPAR and PCT, alone or combined with clinical signs and symptoms, for the prediction of clinical deterioration. This prospective observational study enrolled patients with suspected infection who met SIRS criteria without organ dysfunction (delta SOFA <2 from baseline) from 16 emergency departments.

Peripheral innate immunophenotype in neurodegenerative disease: blood-based profiles and links to survival.

The innate immune system plays an integral role in the progression of many neurodegenerative diseases. In addition to central innate immune cells (e.g.

Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis.

Medical progress is reflected in the advance from broad clinical syndromes to mechanistically coherent diagnoses. By this metric, research in sepsis is far behind other areas of medicine-the word itself conflates multiple different disease mechanisms, whilst excluding noninfectious syndromes (e.g.

Association Between Neuromuscular Blocking Agents and Outcomes of Emergency Tracheal Intubation: A Secondary Analysis of Randomized Trials.

Study Objective: To examine the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt and severe complications during tracheal intubation of critically ill adults in an emergency department (ED) or ICU.

Methods: We performed a secondary analysis of data from 2 multicenter randomized trials in critically ill adults undergoing tracheal intubation in an ED or ICU. Using a generalized linear mixed-effects model with prespecified baseline covariates, we examined the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt (primary outcome) and severe complications during tracheal intubation (secondary outcome).

Cardiac arrest and microcirculatory dysfunction: a narrative review.

Purpose Of Review: This review provides an overview of the role of microcirculation in cardiac arrest and postcardiac arrest syndrome through handheld intravital microscopy and biomarkers. It highlights the importance of microcirculatory dysfunction in postcardiac arrest outcomes and explores potential therapeutic targets.

Recent Findings: Sublingual microcirculation is impaired in the early stage of postarrest and is potentially associated with increased mortality.

Cryo-PRO facilitates whole blood cryopreservation for single-cell RNA sequencing of immune cells from clinical samples.

Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) has enhanced our understanding of host immune mechanisms in small cohorts, particularly in diseases with complex and heterogeneous immune responses such as sepsis. However, PBMC isolation from blood requires technical expertise, training, and approximately two hours of onsite processing using Ficoll density gradient separation ('Ficoll') for scRNA-seq compatibility, precluding large-scale sample collection at most clinical sites. To minimize onsite processing, we developed Cryo-PRO (Cryopreservation with PBMC Recovery Offsite), a method of PBMC isolation from cryopreserved whole blood that allows immediate onsite sample cryopreservation and subsequent PBMC isolation in a central laboratory prior to sequencing.

Plasma for prevention and treatment of glycocalyx degradation in trauma and sepsis.

The endothelial glycocalyx, a gel-like layer that lines the luminal surface of blood vessels, is composed of proteoglycans, glycoproteins, and glycosaminoglycans. The endothelial glycocalyx plays an essential role in vascular homeostasis, and its degradation in trauma and sepsis can lead to microvascular dysfunction and organ injury. While there are no proven therapies for preventing or treating endothelial glycocalyx degradation, some initial literature suggests that plasma may have a therapeutic role in trauma and sepsis patients.

Molecular Phenotyping of Patients with Sepsis and Kidney Injury and Differential Response to Fluid Resuscitation.

Purpose: Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial.

Methods: We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]).

Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial.

Background: Early fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD.

Methods: This post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.

A standardized protocol using clinical adjudication to define true infection status in patients presenting to the emergency department with suspected infections and/or sepsis.

In absence of a "gold standard", a standardized clinical adjudication process was developed for a registrational trial of a transcriptomic host response (HR) test. Two physicians independently reviewed clinical data to adjudicate presence and source of bacterial and viral infections in emergency department patients. Discordant cases were resolved by a third physician.

Geriatric End-of-Life Screening Tool Prediction of 6-Month Mortality in Older Patients.

Importance: Emergency department (ED) visits by older adults with life-limiting illnesses are a critical opportunity to establish patient care end-of-life preferences, but little is known about the optimal screening criteria for resource-constrained EDs.

Objectives: To externally validate the Geriatric End-of-Life Screening Tool (GEST) in an independent population and compare it with commonly used serious illness diagnostic criteria.

Design, Setting, And Participants: This prognostic study assessed a cohort of patients aged 65 years and older who were treated in a tertiary care ED in Boston, Massachusetts, from 2017 to 2021.