Early Prediction of Sepsis Incidence in Critically Ill Patients Using Specific Genetic Polymorphisms

David, Vlad Laurentiu; Ercisli, Muhammed Furkan; Rogobete, Alexandru Florin; Boia, Eugen Sorin; Horhat, Razvan Mihai; Niţu, Răzvan; Diaconu, Mircea; Pirtea, Laurențiu; Ciucă, Ioana; Horhat, Delia Ioana; Horhat, Florin George; Licker, Monica; Popovici, Sonia Elena; Tănăsescu, Sonia; Tătaru, Călin Petru

doi:10.1007/s10528-016-9785-2

Cited by 28 publications

(33 citation statements)

References 57 publications

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“…Various studies have attempted to evaluate the possibility that genetic variability of cytokines might lead to differences in immune responses with impact on sepsis susceptibility and severity and some of them indicated a role for TNF-α in generating and promoting the inflammatory response in systemic infection [42,55]. Polymorphisms in the promoter region seem to have an increased association with the development of sepsis and septic shock in some population groups, due to differentiated gene transcription [56]. Still, published results fail to reach consensus.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

et al. 2020

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Background: The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. Methods: We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A,-238G/A,-376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. Results: TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. Conclusions: TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

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Section: Discussionmentioning

confidence: 99%

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

et al. 2020

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“…Diverse approaches were used to identify more precise, practical, quicker, safer and cheaper chemicals or physical changes that may indicate the urgent need and adequacy of antimicrobial therapy or its redundancy to reduce adverse events, microbial resistance and financial costs. Current research is more focused on molecular (PCR, MALDI-TOF) and/or system-based (genomics, transcriptomics, proteonomics, metabolomics) methods for sepsis diagnosis [26–29], but these techniques are not fully developed, practical or widely available.…”

Section: Discussionmentioning

confidence: 99%

Procalcitonin kinetics after burn injury and burn surgery in septic and non-septic patients – a retrospective observational study

et al. 2018

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BackgroundEarly sepsis diagnosis is crucial for the correct management of burn patients, and it clearly influences outcomes. The systemic inflammatory response triggered by burns mimics sepsis presentation and complicates early sepsis diagnosis. Biomarkers were advocated to aid the diagnosis of early sepsis. Serum procalcitonin (PCT) exhibits fair accuracy and good correlation with sepsis severity, being used in diverse clinical settings. However, few studies have evaluated perioperative changes in PCT levels in burn patients. The present study evaluated PCT kinetics during the first days after burn injury and subsequent surgical interventions to assess PCT utility in distinguishing septic from non-septic inflammatory responses.MethodsThis study was a retrospective observational study of all burn patients admitted to the Coimbra Burns Unit (Portugal) between January 2011 and December 2014 who presented with a total burn surface area ≥ 15% and who underwent subsequent surgery. PCT kinetics were investigated a) during the first five days after burn injury and b) preoperatively during the five days after surgery in three subsets of patients, including those with no preoperative and no postoperative sepsis (NN), no preoperative but postoperative sepsis (NS), and preoperative and postoperative sepsis (SS). A total of 145 patients met the selection criteria and were included in the analysis.ResultsPCT levels in the first five days after burn injury were significantly higher in patients who developed at least one sepsis episode (n = 85) compared with patients who did not develop sepsis (n = 60). PCT values > 1.00 ng/mL were clearly associated with sepsis. Study participants (n = 145) underwent a total of 283 surgical interventions. Their distribution by preoperative/postoperative sepsis status was 142 (50.2%) in NN; 62 (21.9%) in NS; and 79 (27.9%) in SS. PCT values exhibited a parallel course in the three groups that peaked on the second postoperative day and returned to preoperative levels on the third day or later. The lowest PCT values were found in NN, and the highest values were observed in SS; the NS values were intermediate.ConclusionsPCT kinetics coupled with a clinical examination may be helpful for sepsis diagnosis during the first days after burn injury and burn surgery.Electronic supplementary materialThe online version of this article (10.1186/s12871-018-0585-6) contains supplementary material, which is available to authorized users.

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“…Shimada's study [34] indicated the combined panel of TNFA − 308G/A and IL1B -31C/T plus APACHE II score might enable more accurate prediction of outcome in septic patients. Laurentiu et al [8] summarized a few genetic variants observed in sepsis and suggested speci c genetic polymorphisms could be applied for early prediction of sepsis incidence in the future. In our previous study [35], we also indicated eight functional polymorphisms (IL1B -1470, IL1B -511, IL1B -31, IL4 -589, IL6 -572, IL8 -251, IL10 -819, and TNFA − 308) could be combined together to predict the risk of sepsis and organ dysfunction after trauma.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, whether genetic heterogeneity might have signi cant impact on sepsis development is an important question. Evidences from animal experiments and human genetic association studies demonstrated that genetic heterogeneity contributed to a signi cant portion of susceptibility to sepsis [7,8]. In recent years, increasing numbers of sepsis predisposing variants have been identi ed by candidate gene and genomewide association studies (GWAS) [9,10].…”

Section: Introductionmentioning

confidence: 99%

Polygenic risk score for early prediction of sepsis risk in the polytrauma screening cohort

Wen

Sun

et al. 2020

Preprint

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Background: Increasing genetic variants associated with sepsis have been identified by candidate-gene and genome-wide association studies, but single variant conferred minimal alterations in risk prediction. Our aimed to evaluate whether a weighted genetic risk score (wGRS) that aggregate information from multiple variants could improve risk discrimination of traumatic sepsis.Methods: 64 genetic variants potential relating to sepsis were genotyped in Chinese trauma cohort. Genetic variants with mean decrease accuracy (MDA) > 1.0 by random forest algorithms were selected to construct the multilocus wGRS. Area under curve (AUC) and Net reclassification improvement (NRI) were adopted to evaluate the discriminatory and reclassification ability of wGRS.Results: Seventeen variants were extracted to construct the wGRS in 883 trauma patients. The wGRS was significantly associated with sepsis after trauma (OR = 2.19, 95%CI = 1.53–3.15, P = 2.01 × 10− 5) after adjusted by age, sex, and ISS. Patients with higher wGRS have an increasing incidence of traumatic sepsis (Ptrend=6.81 × 10− 8), higher SOFA (Ptrend=5.00 × 10− 3) and APACHE II score (Ptrend=1.00 × 10− 3). The AUC of risk prediction model incorporating wGRS into the clinical variables was 0.768 (95%CI = 0.739–0.796), with an increase of 3.40% (P = 8.00 × 10− 4) versus clinical factors-only model. Furthermore, the NRI increased 25.18% (95%CI = 17.84–32.51%) (P = 6.00 × 10− 5).Conclusions: Our finding indicated that genetic variants could enhance the predictive power of risk model for sepsis and highlighted the application among trauma patients, suggesting that the sepsis risk assessment model will be a promising screening and prediction tool for high risk population.

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Early Prediction of Sepsis Incidence in Critically Ill Patients Using Specific Genetic Polymorphisms

Cited by 28 publications

References 57 publications

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

Procalcitonin kinetics after burn injury and burn surgery in septic and non-septic patients – a retrospective observational study

Polygenic risk score for early prediction of sepsis risk in the polytrauma screening cohort

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