ABSTRACT
INTRODUCTION: Despite the advancement in diagnostic modalities of sepsis, it is still a leading cause of morbidity and mortality. Differentiation between sepsis and non-infectious disease states remains a diagnostic challenge. Procalcitonin (PCT) is useful for the diagnosis of sepsis but it varies in cut-off ranges at different clinical settings. The aim of this study was to correlate serum PCT levels with cultures and to evaluate the best cut-off values with high sensitivity and specificity for PCT. METHODOLOGY: This prospective study included 305 patients from different medical wards; the patients were classified into group I: controls (n=46), group II: culture-negative sepsis (n=76) and group III: culture-positive sepsis (n=196). Mean p value <0.05 was considered significant. RESULTS: PCT levels were significantly higher in group II and group III as compared with group I. In group II, the best cut-off point for PCT was 1.3ng/ml with 87.30% sensitivity and 78.26% specificity (area under curve 0.86). In group III, the best cut-off value of 2.20ng/ml with 98.47% sensitivity and 89.13% specificity was found (AUC 0.96). CONCLUSION: Procalcitonin can accurately differentiate culture-negative and culture-positive sepsis from non-infectious diseases, thus making it a promising biomarker in diagnosis of bacterial sepsis.
Subject(s)
Bacteremia/diagnosis , Biomarkers/blood , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Procalcitonin/blood , Adult , Bacteremia/blood , Bacteremia/microbiology , Female , Gram-Negative Bacterial Infections/blood , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/blood , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/microbiology , Hospital Units , Humans , India , Male , Prospective Studies , Sensitivity and Specificity , Tertiary Care CentersABSTRACT
BACKGROUND: Translational research on miRNAs develops reliable biomarkers for diagnosis and prognosis of renal diseases. Bioinformatic analyses and systems biology could drive the research for knowing new informative miRNA targets. OBJECTIVES: This study proposes an approach to identify miRNA specific significant target genes, and single nucleotide polymorphisms (SNPs) associated with renal pathophysiology. METHODS: miRNAs were selected after removing duplicity, on the basis of techniques used, and disease spectrum width score. Target genes were predicted from different databases like miRWalk, miRTarBase, and DIANA-TarBase. SNPs were prioritized on the basis of target score and conserved energy score available in MirSNP database. miRNAs were characterized as "specific", "strong", "likely", "unlikely", and "irrelevant" biomarkers. PCR-SSP based genotyping was carried out to access the molecular profiling of hsa-miR-192 and TGF-ß1 followed by quantitative real time PCR to analyze expression level of TGF-ß1. The relative expression levels of mRNAs were analyzed by 2-ΔΔCt method. RESULTS: 170 renal associated miRNAs were found to be up-regulated, down-regulated or differentially expressed. Noticeably hsa-miR-192-3p expression was reported in nine diseases. 117 genes were associated with basic kidney diseases and end stage renal disease (ESRD). Threshold > 80% for 93 target genes was observed from mirSVR. Mutant genotypes for hsa-miR-192 (OR=4.64, p-value ≤ 0.0001) and its corresponding target gene TGF-ß1 (OR = 0.70, p-value = 0.0351) showed susceptible association with ESRD. More so, patients possessing mutant allele of TGF-ß1 showed elevated mRNA expression (Fold change = 9.83). CONCLUSION: Study proposed a new approach to identify specific miRNA biomarkers for particular diseases with corresponding target genes and SNPs and also highlighted the importance of hsa-miR-192 in renal diseases.
