scholarly journals Identification of a Minimal 3-Transcript Signature to Differentiate Viral from Bacterial Infection from Best Genome-Wide Host RNA Biomarkers: A Multi-Cohort Analysis

2021 ◽  
Vol 22 (6) ◽  
pp. 3148
Author(s):  
Alberto Gómez-Carballa ◽  
Ruth Barral-Arca ◽  
Miriam Cebey-López ◽  
Xabier Bello ◽  
Jacobo Pardo-Seco ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Bacterial Infections ◽  
High Performance ◽  
Meta Analysis ◽  
Cohort Analysis ◽  
Area Under The Curve ◽  
Gene Signature ◽  
Diagnostic Methods ◽  
Specific Response ◽  
Transcript Signature

The fight against the spread of antibiotic resistance is one of the most important challenges facing health systems worldwide. Given the limitations of current diagnostic methods, the development of fast and accurate tests for the diagnosis of viral and bacterial infections would improve patient management and treatment, as well as contribute to reducing antibiotic misuse in clinical settings. In this scenario, analysis of host transcriptomics constitutes a promising target to develop new diagnostic tests based on the host-specific response to infections. We carried out a multi-cohort meta-analysis of blood transcriptomic data available in public databases, including 11 different studies and 1209 samples from virus- (n = 695) and bacteria- (n = 514) infected patients. We applied a Parallel Regularized Regression Model Search (PReMS) on a set of previously reported genes that distinguished viral from bacterial infection to find a minimum gene expression bio-signature. This strategy allowed us to detect three genes, namely BAFT, ISG15 and DNMT1, that clearly differentiate groups of infection with high accuracy (training set: area under the curve (AUC) 0.86 (sensitivity: 0.81; specificity: 0.87); testing set: AUC 0.87 (sensitivity: 0.82; specificity: 0.86)). BAFT and ISG15 are involved in processes related to immune response, while DNMT1 is related to the preservation of methylation patterns, and its expression is modulated by pathogen infections. We successfully tested this three-transcript signature in the 11 independent studies, demonstrating its high performance under different scenarios. The main advantage of this three-gene signature is the low number of genes needed to differentiate both groups of patient categories.

scholarly journals Accuracy of proton magnetic resonance for diagnosing non-alcoholic steatohepatitis: a meta-analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tae-Hoon Kim ◽  
Chang-Won Jeong ◽  
Hong Young Jun ◽  
ChungSub Lee ◽  
SiHyeong Noh ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Imaging Modality ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Diagnostic Odds Ratio ◽  
Diagnostic Methods ◽  
Likelihood Ratios ◽  
Alcoholic Fatty Liver ◽  
Noninvasive Diagnostics ◽  
Alcoholic Steatohepatitis

Abstract Liver biopsy is the reference standard test to differentiate between non-alcoholic steatohepatitis (NASH) and simple steatosis (SS) in non-alcoholic fatty liver disease (NAFLD), but noninvasive diagnostics are warranted. The diagnostic accuracy in NASH using MR imaging modality have not yet been clearly identified. This study was assessed the accuracy of magnetic resonance imaging (MRI) method for diagnosing NASH. Data were extracted from research articles obtained after a literature search from multiple electronic databases. Random-effects meta-analyses were performed to obtain overall effect size of the area under the receiver operating characteristic(ROC) curve, sensitivity, specificity, likelihood ratios(LR), diagnostic odds ratio(DOR) of MRI method in detecting histopathologically-proven SS(or non-NASH) and NASH. Seven studies were analyzed 485 patients, which included 207 SS and 278 NASH. The pooled sensitivity was 87.4% (95% CI, 76.4–95.3) and specificity was 74.3% (95% CI, 62.4–84.6). Pooled positive LR was 2.59 (95% CI, 1.96–3.42) and negative LR was 0.17 (95% CI, 0.07–0.38). DOR was 21.57 (95% CI, 7.27–63.99). The area under the curve of summary ROC was 0.89. Our meta-analysis shows that the MRI-based diagnostic methods are valuable additions in detecting NASH.

scholarly journals Type I Interferon in Children with Viral or Bacterial Infections

2020 ◽  
Vol 66 (6) ◽  
pp. 802-808 ◽  
Author(s):  
Sophie Trouillet-Assant ◽  
Sébastien Viel ◽  
Antoine Ouziel ◽  
Lucille Boisselier ◽  
Philippe Rebaud ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Type I Interferon ◽  
Area Under The Curve ◽  
Pediatric Emergency ◽  
Type I ◽  
Discriminative Performance ◽  
Antibiotic Overuse ◽  
Reactive Protein

Abstract Background Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians’ decisions and limit antibiotic overuse. Methods Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Results Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). Conclusions IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. Clinical Trials Registration clinicaltrials.gov (NCT03163628).

scholarly journals Delta-Like Canonical Notch Ligand 1 in Patients Following Liver Transplantation—A Secondary Analysis of a Prospective Cohort Study

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 894
Author(s):  
Sebastian O. Decker ◽  
Dagmar Hildebrand ◽  
Thomas Bruckner ◽  
Christoph Lichtenstern ◽  
Klaus Heeg ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Bacterial Infection ◽  
Bacterial Infections ◽  
Plasma Concentrations ◽  
Secondary Analysis ◽  
Composite Endpoint ◽  
Observation Time ◽  
Diagnostic Methods ◽  
Notch Ligand ◽  
Patients At Risk

Opportunistic bacterial infections are dreaded risks in patients following liver transplantation (LTX), even though patients receive an antibiotic prophylaxis. The timely recognition of such an infection may be delayed, as culture-based diagnostic methods are linked with a relevant gap in performance. We measured plasma concentrations of Delta-like canonical Notch ligand 1 (DLL1) in 93 adult patients at seven consecutive time points after liver transplantation and correlated the results to the occurrence of culture-proven bacterial infection or a complicated clinical course (composite endpoint of two or more complications: graft rejection or failure, acute kidney failure, acute lung injury, or 90-day mortality). Patients exhibited elevated plasma concentrations after liver transplantation over the whole 28 d observation time. Patients with bacterial infection showed increased DLL1 levels compared to patients without infection. Persistent elevated levels of DLL1 on day 7 and afterward following LTX were able to indicate patients at risk for a complicated course. Plasma levels of DLL1 following LTX may be useful to support an earlier detection of bacterial infections in combination with C-reactive protein (CRP) and procalcitonin (PCT), or they may lead to risk stratification of patients as a single marker for post-operative complications. (Clinical Trial Notation. German Clinical Trials Register: DRKS00005480).

scholarly journals Association of vancomycin trough concentration on the treatment outcome of patients with bacteremia caused by Enterococcus species

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yujin Sohn ◽  
John Hoon Rim ◽  
Yunsuk Cho ◽  
Jonghoon Hyun ◽  
Yaejee Baek ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Trough Concentration ◽  
Bacterial Infections ◽  
Trough Level ◽  
Cohort Analysis ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
All Cause Mortality ◽  
Vancomycin Trough ◽  
Enterococcal Bacteremia

Abstract Background Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia. Methods A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality. Results A total of 37 patients were enrolled—26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia. Conclusions In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

scholarly journals Sputum colour as a marker for bacteria in acute exacerbations of COPD: protocol for a systematic review and meta-analysis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Ruan Spies ◽  
Matthew Potter ◽  
Ruan Hollamby ◽  
Stefan van der Walt ◽  
Ameer Hohlfeld ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bacterial Infection ◽  
Regression Model ◽  
Bacterial Infections ◽  
Meta Analysis ◽  
Grey Literature ◽  
Chronic Obstructive ◽  
Years Of Life Lost ◽  
Eligibility Criteria ◽  
Acute Exacerbations

Abstract Background Chronic obstructive pulmonary disease (COPD) is a major cause of years of life lost globally. Acute exacerbations of COPD (AECOPD) drive disease progression, reduce quality of life and are a source of mortality in COPD. Approximately 50% of AECOPD are due to bacterial infections. Diagnosing bacterial infection as the aetiology of AECOPD however remains challenging as investigations are limited by practicality, accuracy and expense. Clinicians have traditionally used sputum colour as a marker of bacterial infection in AECOPD, despite the lack of high-quality evidence for this practice. The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy of sputum colour in the diagnosis of bacterial causes of AECOPD. Methods Articles will be searched for in electronic databases (MEDLINE, Google Scholar Scopus, Web of Science, Africa-Wide, CINAHL and Health Source Nursing Academy) and we will conduct a review of citation indexes and the grey literature. Two reviewers will independently conduct study selection, against pre-defined eligibility criteria, data extraction and quality assessment of included articles using the QUADAS-2 tool. We will perform a meta‐analysis using a bivariate logistic regression model with random effects. We will explore heterogeneity through the visual examination of the forest plots of sensitivities and specificities and through the inclusion of possible sources of heterogeneity as covariates in a meta-regression model if sufficient studies are included in the analysis. We also perform a sensitivity analysis to explore the effect of study quality on our findings. The results of this review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement and will be submitted for peer-review and publication. Discussion The findings of this review will assist clinicians in diagnosing the aetiology of AECOPD and may have important implications for decision making in resource-limited settings, as well as for antimicrobial stewardship. Systematic review registration PROSPERO CRD42019141498

scholarly journals Meta-analysis of sonicate fluid in blood culture bottles for diagnosing periprosthetic joint infection

2018 ◽  
Vol 3 (5) ◽  
pp. 273-279 ◽  
Author(s):  
Cheng Li ◽  
Nora Renz ◽  
Cristina Ojeda Thies ◽  
Andrej Trampuz
Keyword(s):  
Blood Culture ◽  
Likelihood Ratio ◽  
Periprosthetic Joint Infection ◽  
Meta Analysis ◽  
Joint Infection ◽  
Area Under The Curve ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Methods ◽  
Summary Receiver Operating Characteristic

Abstract. Introduction: Periprosthetic joint infection (PJI) is the most serious complication after arthroplasty, and the diagnosis of PJI is still challenging with modern medical technology. To improve the diagnostic rate, combined diagnostic methods are gradually beginning to be used to diagnose PJI. Sonication is one accurate way to diagnose PJI, but there is minimal research regarding the diagnostic value of sonicate fluid (SF) in blood culture bottles (BCB). Therefore, we evaluated this combined diagnostic method by meta-analysis.Methods: We searched English publications in electronic databases regarding the use of sonicate fluid in blood culture bottles (SF-BCB) for diagnosing PJI, screened the literature according to inclusion criteria, assessed the quality of the selected literature, and collected information regarding SF-BCB.Results: This meta-analysis includes 4 studies that evaluated SF-BCB for the diagnosis of PJI. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) are 0.85 (95% Confidence interval [CI], 0.77 to 0.91), 0.86 (CI, 0.81 to 0.91), 5.34 (CI, 3.13 to 9.11), 0.16 (CI, 0.06 to 0.48) and 39.01 (CI, 9.04 to 168.35), respectively. The area under the curve (AUC) of the summary receiver operating characteristic (SROC) is 0.9186 (standard error, 0.0205).Conclusion: SF-BCB has great value for the microbiological diagnosis of PJ, especially for patients with prior antibiotic treatment.

scholarly journals Sputum Colour as a Marker for Bacteria in Acute Exacerbations of COPD: Protocol for a Systematic Review and Meta-Analysis.

2021 ◽  
Author(s):  
Ruan Spies ◽  
Matthew Wade Potter ◽  
Ruan Hollamby ◽  
Stefan van der Walt ◽  
Ameer Hohlfeld ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bacterial Infection ◽  
Regression Model ◽  
Bacterial Infections ◽  
Data Extraction ◽  
Meta Analysis ◽  
Grey Literature ◽  
Years Of Life Lost ◽  
Eligibility Criteria ◽  
Acute Exacerbations

Abstract BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of years of life lost globally. Acute exacerbations of COPD (AECOPD) drive disease progression, reduce quality of life and are a source of mortality in COPD. Approximately 50% of AECOPD are due to bacterial infections. Diagnosing bacterial infection as the aetiology of AECOPD however remains challenging as investigations are limited by practicality, accuracy and expense. Clinicians have traditionally used sputum colour as a marker of bacterial infection in AECOPD, despite the lack of high-quality evidence for this practice. The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy of sputum colour in the diagnosis of bacterial causes of AECOPD. MethodsArticles will be searched for in electronic databases (PubMed, Scopus, Web of Science, Africa-Wide, CINAHL and Health Source Nursing Academy) and we will conduct a review of citation indexes and the grey literature. Two reviewers will independently conduct study selection, against pre-defined eligibility criteria, data extraction and quality assessment of included articles using the QUADAS-2 tool. We will perform a meta‐analysis using a bivariate logistic regression model with random effects. We will explore heterogeneity through the visual examination of the forest plots of sensitivities and specificities and through the inclusion of possible sources of heterogeneity as covariates in a meta-regression model if sufficient studies are included in the analysis. We also perform a sensitivity analysis to explore the effect of study quality on our findings. The results of this review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement and will be submitted for peer-review and publication.DiscussionThe findings of this review will assist clinicians in diagnosing the aetiology of AECOPD and may have important implications for decision making in resource-limited settings, as well as for antimicrobial stewardship.Systematic review registration: PROSPERO CRD42019141498

scholarly journals Efficacy and Safety of Sitafloxacin in the Treatment of Acute Bacterial Infection: A Meta-analysis of Randomized Controlled Trials

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 106
Author(s):  
Chao-Kun Chen ◽  
I-Ling Cheng ◽  
Yu-Hung Chen ◽  
Chih-Cheng Lai
Keyword(s):  
Bacterial Infection ◽  
Clinical Response ◽  
Bacterial Infections ◽  
Response Rate ◽  
Meta Analysis ◽  
Clinical Response Rate ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Acute Bacterial Infections

This meta-analysis aimed to assess the efficacy and safety of sitafloxacin in treating acute bacterial infection. PubMed, Embase, and Cochrane databases were searched up to August 13, 2019. Only randomized controlled trials (RCTs) evaluating sitafloxacin and comparators in the treatment of acute bacterial infections were included. The outcomes were clinical and microbiological responses and the risk of adverse event (AE). Five RCTs were enrolled, including 375 and 381 patients who received sitafloxacin and the comparator, respectively. Overall, the clinical response rate of sitafloxacin in the treatment of acute bacterial infections was 94.6%, which was noninferior to that of the comparator (92.5%) (odds ratio (OR), 1.01; 95% CI, 0.24–4.32; I2 = 66%). For patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (APN), the clinical response rate of sitafloxacin and the comparator was 96.9% and 91.3%, respectively (OR, 2.08; 95% CI, 0.35–12.44; I2 = 54%). For patients with pneumonia, the clinical response rate of sitafloxacin was 88.6%, which was comparable to that of the comparator (OR, 0.36; 95% CI, 0.11–1.21; I2 = 0%). The microbiological response of sitafloxacin was 82.0%, which was noninferior to that of the comparator (77.8%) (OR, 1.59; 95% CI, 0.77–3.28; I2 = 47%). The risk of treatment-emergent adverse event (TEAE), drug-related TEAE, and all-cause mortality were similar between sitafloxacin and the comparators (TEAE, OR, 1.14; 95% CI, 0.64–2.01, drug-related TEAE, OR, 1.14; 95% CI, 0.48–2.69, mortality, OR, 0.93; 95% CI, 0.09–9.44). In conclusion, sitafloxacin is noninferior to other commonly used antibiotics with respect to both clinical and microbiological response rates in patients with an acute bacterial infection, including cUTI/APN and pneumonia. In addition, sitafloxacin is also as safe as the comparators.

scholarly journals Efficacy of Integrating a Novel 16-Gene Biomarker Panel and Intelligence Classifiers for Differential Diagnosis of Rheumatoid Arthritis and Osteoarthritis

2019 ◽  
Vol 8 (1) ◽  
pp. 50 ◽  
Author(s):  
Nguyen Phuoc Long ◽  
Seongoh Park ◽  
Nguyen Hoang Anh ◽  
Jung Eun Min ◽  
Sang Jun Yoon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Naive Bayes ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Gene Signature ◽  
Naïve Bayes ◽  
Clinical Samples ◽  
Support Vector ◽  
K Nearest Neighbors ◽  
Synovial Tissues

Introducing novel biomarkers for accurately detecting and differentiating rheumatoid arthritis (RA) and osteoarthritis (OA) using clinical samples is essential. In the current study, we searched for a novel data-driven gene signature of synovial tissues to differentiate RA from OA patients. Fifty-three RA, 41 OA, and 25 normal microarray-based transcriptome samples were utilized. The area under the curve random forests (RF) variable importance measurement was applied to seek the most influential differential genes between RA and OA. Five algorithms including RF, k-nearest neighbors (kNN), support vector machines (SVM), naïve-Bayes, and a tree-based method were employed for the classification. We found a 16-gene signature that could effectively differentiate RA from OA, including TMOD1, POP7, SGCA, KLRD1, ALOX5, RAB22A, ANK3, PTPN3, GZMK, CLU, GZMB, FBXL7, TNFRSF4, IL32, MXRA7, and CD8A. The externally validated accuracy of the RF model was 0.96 (sensitivity = 1.00, specificity = 0.90). Likewise, the accuracy of kNN, SVM, naïve-Bayes, and decision tree was 0.96, 0.96, 0.96, and 0.91, respectively. Functional meta-analysis exhibited the differential pathological processes of RA and OA; suggested promising targets for further mechanistic and therapeutic studies. In conclusion, the proposed genetic signature combined with sophisticated classification methods may improve the diagnosis and management of RA patients.

scholarly journals Inflammatory Cytokine and Chemokine Patterns in Paediatric Patients with Suspected Serious Bacterial Infection

Medicina ◽  
2019 ◽  
Vol 55 (1) ◽  
pp. 4 ◽  
Author(s):  
Linda Rautiainen ◽  
Jana Pavare ◽  
Ilze Grope ◽  
Peteris Tretjakovs ◽  
Dace Gardovska
Keyword(s):  
Emergency Department ◽  
Bacterial Infection ◽  
Bacterial Infections ◽  
Inflammatory Cytokine ◽  
Acute Infection ◽  
Area Under The Curve ◽  
Developed Countries ◽  
Characteristic Analysis ◽  
Additional Information ◽  
Cytokines And Chemokines

Background and objectives: In children, acute infection is the most common cause of visits to the emergency department. Although most of them are self-limiting, mortality due to severe bacterial infections (SBI) in developed countries is still high. When the risk of serious bacterial infection is too high to ignore, yet too low to justify admission and hospital observation, clinicians try to improve diagnostic accuracy by performing various laboratory tests. The aim of the study was to investigate whether an early inflammatory cytokine and chemokine panel can add information in diagnostics of SBI and assessment of efficacy of early therapies in hospitalized children with fever. Methods: This study included 51 children with febrile infections that were admitted to the emergency department (ED). Clinical examination and microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (1) patients with SBI (n = 21); (2) patients without SBI (n = 30). Inflammatory cytokine and chemokine panels were analyzed from the first routine blood samples at hospital admission and after 24 h. Results: Out of 12 cytokines and chemokines, only Eotaxin and granulocyte colony-stimulating factor (G-CSF) had statistically significant differences between groups at the time of inclusion. Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.679 for G-CSF. Conclusions: Analysis of inflammatory cytokine profiles may provide additional information in early diagnostics of SBI.

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