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Effectively neutralizing inflammatory cytokines is crucial for managing a variety of inflammatory disorders. Current techniques that target only a subset of cytokines often fall short due to the intricate nature of redundant and compensatory cytokine networks. A promising solution to this challenge is using cell membrane-coated nanoparticles (CNPs). These nanoparticles replicate the complex interactions between cells and cytokines observed in disease pathology, providing a potential avenue for multiplex cytokine scavenging. While the development of CNPs using experimental animal models has shown great promise, their effectiveness in scavenging multiple cytokines in human diseases has yet to be demonstrated. To bridge this gap, this study selected macrophage membrane-coated CNPs (MФ-CNPs) and assessed their ability to scavenge inflammatory cytokines in serum samples from patients with COVID-19, sepsis, acute pancreatitis, or type-1 diabetes, along with synovial fluid samples from patients with rheumatoid arthritis. The results show that MФ-CNPs effectively scavenge critical inflammatory cytokines, including interleukin (IL)-6, IL-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, in a dose-dependent manner. Overall, this study demonstrates MФ-CNPs as a multiplex cytokine scavenging formulation with promising applications in clinical settings to treat a range of inflammatory disorders.

OBJECTIVE: There is widespread overuse of antibiotics in neonatal intensive care units (NICUs). The objective of this study was to safely reduce antibiotic use in participating NICUs by targeting early-onset sepsis (EOS) management. STUDY DESIGN: Twenty-eight NICUs participated in this statewide multicenter antibiotic stewardship quality improvement collaborative. The primary aim was to reduce the total monthly mean antibiotic utilization rate (AUR) by 25% in participant NICUs. RESULT: Aggregate AUR was reduced by 15.3% (p

Introduction: Determining which patients who meet systemic inflammatory response syndrome (SIRS) criteria have bacterial sepsis is a difficult challenge for emergency physicians. We sought to determine whether the neutrophil-to-lymphocyte ratio (NLR) could be used to exclude bacterial sepsis in adult patients who meet ≥2 SIRS criteria and are being evaluated for sepsis.Methods: Consenting adult patients meeting ≥2 SIRS criteria and undergoing evaluation for sepsis were enrolled. We recorded patient age, gender, vital signs, and laboratory results. We then later reviewed health records for culture results, end organ dysfunction, survival to discharge, and final diagnoses.Patients were classified as having sepsis if they met ≥2 SIRS criteria and were ultimately diagnosed with a bacterial source. We analyzed data using descriptive statistics and sensitivity and specificity analyses. A receiver operating characteristic curve (ROC) was created to determine test characteristics.Results: A total of 231 patients had complete datasets. Patients’ median age was 69 (interquartile range [IQR] 54–81), and 49.6% were male. There were 154 patients (66.7%) ultimately diagnosed with sepsis with an identified bacterial source, while 77 patients with ≥2 SIRS criteria had non-infectious reasons for their presentations (33.3%). Septic patients had a median NLR 12.36 (IQR [interquartile range] 7.29–21.69), compared to those without sepsis (median NLR 5.62, IQR 3.89–9.11, P < 0.001). The NLR value of 3 applied as a cutoff for sepsis had a sensitivity of 96.8 (95% confidence interval [CI] 92.2–98.8), and a specificity of 18.2 (95% CI 10.6–29.0). The ROC for NLR had an area under the curve of 0.74.Conclusion: The neutrophil-to-lymphocyte ratio is a sensitive tool to help determine which patients with abnormal SIRS screens have bacterial sepsis.

OBJECTIVES: To determine the predictive value of social determinants of health (SDoH) variables on 30-day readmission following a sepsis hospitalization as compared with traditional clinical variables. DESIGN: Multicenter retrospective cohort study using patient-level data, including demographic, clinical, and survey data. SETTINGS: Thirty-five hospitals across the United States from 2017 to 2021. PATIENTS: Two hundred seventy-one thousand four hundred twenty-eight individuals in the AllofUs initiative, of which 8909 had an index sepsis hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Unplanned 30-day readmission to the hospital. Multinomial logistic regression models were constructed to account for survival in determination of variables associate with 30-day readmission and are presented as adjusted odds rations (aORs). Of the 8909 sepsis patients in our cohort, 21% had an unplanned hospital readmission within 30 days. Median age (interquartile range) was 54 years (41-65 yr), 4762 (53.4%) were female, and there were self-reported 1612 (18.09%) Black, 2271 (25.49%) Hispanic, and 4642 (52.1%) White individuals. In multinomial logistic regression models accounting for survival, we identified that change to nonphysician provider type due to economic reasons (aOR, 2.55 [2.35-2.74]), delay of receiving medical care due to lack of transportation (aOR, 1.68 [1.62-1.74]), and inability to afford flow-up care (aOR, 1.59 [1.52-1.66]) were strongly and independently associated with a 30-day readmission when adjusting for survival. Patients who lived in a ZIP code with a high percentage of patients in poverty and without health insurance were also more likely to be readmitted within 30 days (aOR, 1.26 [1.22-1.29] and aOR, 1.28 [1.26-1.29], respectively). Finally, we found that having a primary care provider and health insurance were associated with low odds of an unplanned 30-day readmission. CONCLUSIONS: In this multicenter retrospective cohort, several SDoH variables were strongly associated with unplanned 30-day readmission. Models predicting readmission following sepsis hospitalization may benefit from the addition of SDoH factors to traditional clinical variables.

BACKGROUND: Hypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype. METHODS: We studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. RESULTS: The PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a common and life-threatening infection that imposes up to 30% mortality even when appropriate therapy is used. Despite in vitro efficacy determined by minimum inhibitory concentration (MIC) breakpoints, antibiotics often fail to resolve these infections in vivo, resulting in persistent MRSA bacteremia. Recently, several genetic, epigenetic, and proteomic correlates of persistent outcomes have been identified. However, the extent to which single variables or their composite patterns operate as independent predictors of outcome or reflect shared underlying mechanisms of persistence is unknown. To explore this question, we employed a tensor-based integration of host transcriptional and cytokine datasets across a well-characterized cohort of patients with persistent or resolving MRSA bacteremia outcomes. This method yielded high correlative accuracy with outcomes and immunologic signatures united by transcriptomic and cytokine datasets. Results reveal that patients with persistent MRSA bacteremia exhibit signals of granulocyte dysfunction, suppressed antigen presentation, and deviated lymphocyte polarization. In contrast, patients with resolving bacteremia heterogeneously exhibit correlates of robust antigen-presenting cell trafficking and enhanced neutrophil maturation corresponding to appropriate T lymphocyte polarization and B lymphocyte response. These results suggest that transcriptional and cytokine correlates of persistent versus resolving bacteremia outcomes are complex and may not be disclosed by conventional modeling. In this respect, a tensor-based integration approach may help to reveal consensus molecular and cellular mechanisms and their biological interpretation.

OBJECTIVE:  Severe maternal morbidity (SMM) is increasing and characterized by substantial racial and ethnic disparities. Analyzing trends and disparities across time by etiologic or organ system groups instead of an aggregated index may inform specific, actionable pathways to equitable care. We explored trends and racial and ethnic disparities in seven SMM categories at childbirth hospitalization. STUDY DESIGN:  We analyzed California birth cohort data on all live and stillbirths ≥ 20 weeks gestation from 1997 to 2017 (n = 10,580,096) using the Centers for Disease Control and Preventions SMM index. Cases were categorized into seven nonmutually exclusive indicator categories (cardiac, renal, respiratory, hemorrhage, sepsis, other obstetric, and other medical SMM). We compared prevalence and trends in SMM indicator categories overall and by racial and ethnic group using logistic and linear regression. RESULTS:  SMM occurred in 1.16% of births and nontransfusion SMM in 0.54%. Hemorrhage SMM occurred most frequently (27 per 10,000 births), followed by other obstetric (11), respiratory (7), and sepsis, cardiac, and renal SMM (5). Hemorrhage, renal, respiratory, and sepsis SMM increased over time for all racial and ethnic groups. The largest disparities were for Black individuals, including over 3-fold increased odds of other medical SMM. Renal and sepsis morbidity had the largest relative increases over time (717 and 544%). Sepsis and hemorrhage SMM had the largest absolute changes over time (17 per 10,000 increase). Disparities increased over time for respiratory SMM among Black, U.S.-born Hispanic, and non-U.S.-born Hispanic individuals and for sepsis SMM among Asian or Pacific Islander individuals. Disparities decreased over time for sepsis SMM among Black individuals yet remained substantial. CONCLUSION:  Our research further supports the critical need to address SMM and disparities as a significant public health priority in the United States and suggests that examining SMM subgroups may reveal helpful nuance for understanding trends, disparities, and potential needs for intervention. KEY POINTS: · By SMM subgroup, trends and racial and ethnic disparities varied yet Black individuals consistently had highest rates.. · Hemorrhage, renal, respiratory, and sepsis SMM significantly increased over time.. · Disparities increased for respiratory SMM among Black, U.S.-born Hispanic and non-U.S.-born Hispanic individuals and for sepsis SMM among Asian or Pacific Islander individuals..

OBJECTIVE: Recent clinical guidelines for sepsis management emphasize immediate antibiotic initiation for suspected septic shock. Though hypotension is a high-risk marker of sepsis severity, prior studies have not considered the precise timing of hypotension in relation to antibiotic initiation and how clinical characteristics and outcomes may differ. Our objective was to evaluate antibiotic initiation in relation to hypotension to characterize differences in sepsis presentation and outcomes in patients with suspected septic shock. METHODS: Adults presenting to the emergency department (ED) June 2012-December 2018 diagnosed with sepsis (Sepsis-III electronic health record [EHR] criteria) and hypotension (non-resolving for ≥30 min, systolic blood pressure 60 min after (late) treatment. RESULTS: Among 2219 patients, 55% received early treatment, 13% immediate, and 32% late. The late subgroup often presented to the ED with hypotension (median 0 min) but received antibiotics a median of 191 min post-ED presentation. Clinical characteristics notable for this subgroup included higher prevalence of heart failure and liver disease (p