Dataset Information

Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

ABSTRACT: Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT: 0.80 [0.73-0.88], <0.001; PCT/HLA-DRA: 0.85 [0.78-0.91], <0.001. In the multivariate analysis, the ratio showed a superior ability to predict sepsis compared to that of PCT (OR [CI 95%], p): PCT/HLA-DRA: 7.66 [1.82-32.29], 0.006; PCT: 4.21 [1.15-15.43] 0.030. Multivariate analysis was confirmed using a new surgical cohort with 74 sepsis patients and 21 controls: PCT/HLA-DRA: 34.86 [1.22-995.08], 0.038; PCT: 5.52 [0.40-75.78], 0.201. In conclusion, the combination of PCT with HLA-DRA is a promising strategy for improving sepsis detection in surgical patients.

SUBMITTER: Almansa R

PROVIDER: S-EPMC6086887 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

Almansa Raquel R Martín Silvia S Martin-Fernandez Marta M Heredia-Rodríguez María M Gómez-Sánchez Esther E Aragón Marta M Andrés Cristina C Calvo Dolores D Rico-Feijoo Jesus J Esteban-Velasco Maria Carmen MC Vaquero-Roncero Luis Mario LM Ortega Alicia A Gómez-Pesquera Estefania E Lorenzo-López Mario M de Cenarruzabeitia Iñigo López IL Benavides Diana D López-Sanchez Jaime J Doncel Cristina C González-Sanchez Carmen C Zarca Esther E Ríos-Llorente Alberto A Diaz Agustín A Sanchez-Barrado Elisa E de Heredia Juan Beltran JB Calvo-Vecino Jose Maria JM Muñoz-Bellvís Luis L Gomez-Herreras Jose Ignacio JI Aldecoa César C Tamayo Eduardo E Bermejo-Martin Jesus F JF

Scientific reports 20180810 1

Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quan ...[more]

PMID: 30097607

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Project description:A dysregulated immune response leading to sepsis is the most frequent cause of late posttraumatic deaths. We have found a novel anti-inflammatory pathway that is initiated by the acute phase protein, C-reactive protein (CRP), interacting with Fc? receptor (Fc?R) on monocytes. This pathway is protective in animal models of endotoxin shock. We hypothesized that genetic polymorphisms in the Fc?R might contribute to monocyte responses and susceptibility to infectious complications after severe trauma.We conducted an observational study on a prospectively identified cohort of adult patients with convenience enrollment admitted after severe trauma. We enrolled 66 patients and collected blood samples at enrollment and again at 48 hours and 72 hours. Patients were followed through their hospital stay, and any septic events before 14 days were recorded. Cytokine and CRP levels were determined in the plasma from all three blood draws. In addition, DNA was extracted from blood and analyzed for the 131 H/R Fc?RIIa polymorphism that strongly affects the binding of IgG and CRP to this receptor.Elevated levels of interleukin 8 (IL-8), IL-6, IL-10, monocyte chemotactic protein 1, and CRP were associated with reduced time to posttraumatic sepsis in Cox regression analysis. Expression of monocyte human leukocyte antigen DR less than 45% on patient monocytes was also associated with sepsis (hazard ratio, 3.15; 95% confidence interval, 1.45-6.93). Genetic analysis found that individuals with the polymorphism of the Fc?RIIa receptor that binds CRP poorly were also more likely to have decreased monocyte human leukocyte antigen DR and posttraumatic sepsis. In vitro studies showed that CRP could attenuate monocyte deactivation in volunteers with the polymorphism of the Fc?RIIa receptor that binds CRP.Our findings suggest that a common genetic variation in the Fc?RIIa receptor may contribute to infectious susceptibility in trauma patients. In vitro experiments suggest that this association is related to the inability of CRP to bind to this Fc?RIIa receptor variant.Prognostic study, level III.

Project description:BackgroundProcalcitonin (PCT) has been widely investigated as an infection biomarker. The study aimed to prove that serum PCT, combining with other relevant variables, has an even better sepsis-detecting ability in critically ill patients.MethodsWe conducted a retrospective cohort study in a regional teaching hospital enrolling eligible patients admitted to intensive care units (ICU) between July 1, 2016, and December 31, 2016, and followed them until March 31, 2017. The primary outcome measurement was the occurrence of sepsis. We used multivariate logistic regression analysis to determine the independent factors for sepsis and constructed a novel PCT-based score containing these factors. The area under the receiver operating characteristics curve (AUROC) was applied to evaluate sepsis-detecting abilities. Finally, we validated the score using a validation cohort.ResultsA total of 258 critically ill patients (70.9±16.3 years; 55.4% man) were enrolled in the derivation cohort and further subgrouped into the sepsis group (n = 115) and the non-sepsis group (n = 143). By using the multivariate logistic regression analysis, we disclosed five independent factors for detecting sepsis, namely, "serum PCT level," "albumin level" and "neutrophil-lymphocyte ratio" at ICU admission, along with "diabetes mellitus," and "with vasopressor." We subsequently constructed a PCT-based score containing the five weighted factors. The PCT-based score performed well in detecting sepsis with the cut-points of 8 points (AUROC 0.80; 95% confidence interval (CI) 0.74-0.85; sensitivity 0.70; specificity 0.76), which was better than PCT alone, C-reactive protein and infection probability score. The findings were confirmed using an independent validation cohort (n = 72, 69.2±16.7 years, 62.5% men) (cut-point: 8 points; AUROC, 0.79; 95% CI 0.69-0.90; sensitivity 0.64; specificity 0.87).ConclusionsWe proposed a novel PCT-based score that performs better in detecting sepsis than serum PCT levels alone, C-reactive protein, and infection probability score.

Dataset Information

Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

Publications

Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

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