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Monocyte Function and Clinical Outcomes in Febrile and Afebrile Patients With Severe Sepsis.

ABSTRACT: INTRODUCTION:Absence of fever is associated with higher mortality in septic patients, but the reason for this is unknown. Immune dysfunction may be a potential link between failure to mount a fever and poor outcomes. The purpose of this study was to evaluate monocyte function and clinical surrogates of immunity (i.e., mortality and acquisition of secondary infections) in febrile and afebrile septic patients. METHODS:Single-center, prospective cohort study of 92 critically ill septic patients. Patients were categorized into febrile (?38.0°C) and afebrile (<38.0°C) groups based on temperature measurements within 24?hours of sepsis diagnosis. HLA-DR expression and LPS-induced TNF-? production were quantified on days 1-2, days 3-4, and days 6-8 after sepsis diagnosis. A repeated measures mixed models analysis was used to compare these markers between the two groups. RESULTS:Forty-four patients (47.8%) developed a fever within 24?h of sepsis diagnosis. There were no significant differences in HLA-DR expression or LPS-induced TNF-? production between febrile and afebrile patients at any individual time point. However, HLA-DR expression significantly increased between days 1-2 and days 6-8 (median difference 8118 [IQR 1,662, 9,878] antibodies/cell, P?=?0.002) in febrile patients, but not in afebrile patients (median difference 403 [-3,382, 3,507] antibodies/cell, P?=?0.25). Afebrile patients demonstrated higher 28-day mortality (37.5% vs 18.2%) and increased acquisition of secondary infections (35.4% vs. 15.9%). CONCLUSIONS:Absence of fever is associated with suppressed HLA-DR expression over time, a finding suggestive of monocyte dysfunction in sepsis, as well as worse clinical outcomes.

SUBMITTER: Drewry AM

PROVIDER: S-EPMC5999533 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Monocyte Function and Clinical Outcomes in Febrile and Afebrile Patients With Severe Sepsis.

Drewry Anne M AM Ablordeppey Enyo A EA Murray Ellen T ET Dalton Catherine M CM Fuller Brian M BM Kollef Marin H MH Hotchkiss Richard S RS

Shock (Augusta, Ga.) 20181001 4

<h4>Introduction</h4>Absence of fever is associated with higher mortality in septic patients, but the reason for this is unknown. Immune dysfunction may be a potential link between failure to mount a fever and poor outcomes. The purpose of this study was to evaluate monocyte function and clinical surrogates of immunity (i.e., mortality and acquisition of secondary infections) in febrile and afebrile septic patients.<h4>Methods</h4>Single-center, prospective cohort study of 92 critically ill sept ...[more]

PMID: 29240644

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Project description:Genetic variants and dysfunctional monocyte had been reported to be associated with infection susceptibility in advanced cirrhotic patients. This study aims to explore genetic predictive markers and relevant immune dysfunction that contributed to severe sepsis in febrile acute de-compensated cirrhotic patents. Polymorphism analysis of candidate genes was undergone in 108 febrile acute de-compensated cirrhotic patients and 121 healthy volunteers. Various plasma inflammatory/regulatory cytokines, proportion of classical (CD 16-, phagocytic) and non-classical (CD16+, inflammatory) monocytes, lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) and intracellular/extracellular cytokines on cultured non-classical monocytes, mCD14/HLA-DR expression and phagocytosis of classical monocytes were measured. For TLR4+896A/G variant allele carriers with severe sepsis, high plasma endotoxin/IL-10 inhibits HLA-DR expression and impaired phagocytosis were noted in their classical monocyte. In the same group, increased non-classical monocyte subset, enhanced LPS-stimulated TLR4 expression and TNF?/nitrite production, and systemic inflammation [high plasma soluble CD14 (sCD14) and total nitric oxide (NOx) levels] were noted. For CD14-159C/T variant allele carriers with severe sepsis, persist endotoxemia inhibited mCD14/HLA-DR expression and impaired phagocytosis of their classical monocyte. In the same group, increased non-classical monocyte subset up-regulated TLR4-NF?B-iNOS and p38MAPK pathway, stimulated TNF?/nitrite production and elicited systemic inflammation. In febrile acute de-compensated cirrhotic patients, TLR4+896A/G and CD14-159C/T polymorphisms-related non-classical and classical monocytes dysfunction resulted in increased severe sepsis risk. Malnutrition, high plasma endotoxin and sCD14 levels, single TLR4+896A/G or CD14-159C/T variant allele carriers and double variant allele carriers are significant predictive factors for the development of severe sepsis among them.

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Project description:ObjectivesCase volume-outcome associations bolster arguments to regionalize severe sepsis care, an approach that may necessitate interhospital patient transfers. Although transferred patients may most closely reflect care processes involved with regionalization, associations between sepsis case volume and outcomes among transferred patients are unclear. We investigated case volume-outcome associations among patients with severe sepsis transferred from another hospital.DesignSerial cross-sectional study using the Nationwide Inpatient Sample.SettingUnited States nonfederal hospitals, years 2003-2011.PatientsOne hundred forty-one thousand seven hundred seven patients (weighted national estimate of 717,732) with severe sepsis transferred from another acute care hospital.InterventionsNone.Measurements and main resultsWe examined associations between quintiles of annual hospital severe sepsis case volume for the receiving hospital and in-hospital mortality among transferred patients with severe sepsis. Secondary outcomes included hospital length of stay and total charges. Transferred patients accounted for 13.2% of hospitalized severe sepsis cases. In-hospital mortality was 33.2%, with median length of stay 11 days (interquartile range, 5-22), and median total charge $70,722 (interquartile range, $30,591-$159,013). Patients transferred to highest volume hospitals had higher predicted mortality risk, greater number of acutely dysfunctional organs, and lower adjusted in-hospital mortality when compared with the lowest-volume hospitals (odds ratio, 0.80; 95% CI, 0.67-0.90). In stratified analysis (p < 0.001 for interaction of case volume by organ failure), mortality benefit associated with case volume was limited to patients with single organ dysfunction (n = 48,607, 34.3% of transfers) (odds ratio, 0.66; 95% CI, 0.55-0.80). Treatment at highest volume hospitals was significantly associated with shorter adjusted length of stay (incidence rate ratio, 0.86; 95% CI, 0.75-0.98) but not costs (% charge difference, 95% CI: [-]18.8, [-]37.9 to [+]0.3).ConclusionsHospital mortality was lowest among patients with severe sepsis who were transferred to high-volume hospitals; however, case volume benefits for transferred patients may be limited to patients with lower illness severity.

Dataset Information

Monocyte Function and Clinical Outcomes in Febrile and Afebrile Patients With Severe Sepsis.

Publications

Monocyte Function and Clinical Outcomes in Febrile and Afebrile Patients With Severe Sepsis.

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