Gene Expression Profiling in Pediatric Appendicitis DOI
Bhavjinder K. Dhillon, Simone Kortbeek, Arjun Baghela

et al.

JAMA Pediatrics, Journal Year: 2024, Volume and Issue: 178(4), P. 391 - 391

Published: Feb. 19, 2024

Importance Appendicitis is the most common indication for urgent surgery in pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) perforated (PA) on presentation may help direct further diagnostic workup appropriate therapy selection, including antibiotic choice timing surgery. Objective To provide mechanistic understanding differences disease objective developing improved diagnostics treatments, specifically population. Design, Setting, Participants The Gene Expression Profiling Pediatric (GEPPA) study was single-center prospective exploratory transcriptomic profiling peripheral blood collected from cohort children aged 5 to 17 years abdominal pain suspected between November 2016 April 2017 at Alberta Children’s Hospital Calgary, Alberta, Canada, data analysis reported August 2023. There no patient follow-up this study. Exposure SA, PA, or nonappendicitis pain. Main Outcomes Measures Blood transcriptomics used develop hypothesis underlying SA PA build hypotheses blood-based diagnostics. Results Seventy-one (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) emergency department were investigated using whole-blood transcriptomics. A central role immune system pathways revealed dampening major innate interferon responses. expression changes patients consistent downregulation response inflammation shared similarities gene signatures derived sepsis, severe sepsis endotypes. Despite challenges identifying early biomarkers appendicitis, 4-gene signature that predictive compared an accuracy 85.7% (95% CI, 72.8-94.1) identified. Conclusions This found complicated by dysregulated response. finding should inform severity, management strategies, prevention postsurgical

Language: Английский

Carvacrol protects mice against LPS-induced sepsis and attenuates inflammatory response in macrophages by modulating the ERK1/2 pathway DOI Creative Commons

Chenghua Yan,

Wendong Kuang,

LJ Jin

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Aug. 7, 2023

Abstract Macrophages play an important role in the development of life-threatening sepsis, which is characterized by multiorgan dysfunction, through their ability to produce inflammatory cytokines. Carvacrol a phenolic compound that has been confirmed possess strong anti‑inflammatory activity. In this study, we mainly investigated effect carvacrol on lipopolysaccharide (LPS)-induced macrophage proinflammatory responses and endotoxic shock. The results showed significantly reduced mouse body weight loss ameliorated pathological damage liver, lung, heart under LPS-induced sepsis. attenuated inhibiting production cytokine interleukin-6 (IL-6) vivo vitro. Mechanistically, inhibited IL-6 ERK1/2 signalling pathway macrophages. Furthermore, improved survival septic mice. This study sheds light pathogenesis thus, its potential treating sepsis patients may be considered.

Language: Английский

Citations

16
The Role of Transcriptomics in Redefining Critical Illness DOI Creative Commons

Tiana Maria Pelaia,

Maryam Shojaei, Anthony S. McLean

et al.

Critical Care, Journal Year: 2023, Volume and Issue: 27(1)

Published: March 21, 2023

Abstract This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023 . Further information about available https://link.springer.com/bookseries/8901

Language: Английский

Citations

14
Extending the ‘host response’ paradigm from sepsis to cardiogenic shock: evidence, limitations and opportunities DOI Creative Commons

Marie Buckel,

Patrick Maclean,

Julian C. Knight

et al.

Critical Care, Journal Year: 2023, Volume and Issue: 27(1)

Published: Nov. 27, 2023

Language: Английский

Citations

14
The ‘analysis of gene expression and biomarkers for point-of-care decision support in Sepsis‘ study; temporal clinical parameter analysis and validation of early diagnostic biomarker signatures for severe inflammation andsepsis-SIRS discrimination DOI Creative Commons
Tamás Szakmány,

Eleanor Fitzgerald,

Harriet Garlant

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 25, 2024

Introduction Early diagnosis of sepsis and discrimination from SIRS is crucial for clinicians to provide appropriate care, management treatment critically ill patients. We describe identification mRNA biomarkers peripheral blood leukocytes, able identify severe, systemic inflammation (irrespective origin) differentiate Sepsis SIRS, in adult patients within a multi-center clinical study. Methods Participants were recruited Intensive Care Units (ICUs) multiple UK hospitals, including fifty-nine with abdominal sepsis, eighty-four pulmonary forty-two Out-of-Hospital Cardiac Arrest (OOHCA), sampled at four time points, addition thirty healthy control donors. Multiple parameters measured, SOFA score, many differences observed between groups. Differential gene expression analyses performed using microarray hybridization data analyzed combination parametric non-parametric statistical tools. Results Nineteen high-performance, differentially expressed identified combined SIRS/Sepsis groups (FC>20.0, p<0.05), termed ‘indicators inflammation’ (I°I), CD177, FAM20A OLAH. Best-performing minimal signatures e.g. FAM20A/OLAH showed good accuracy determination (AUC>0.99). Twenty entities, ‘SIRS or Sepsis’ (S°S) biomarkers, (FC>2·0, p-value<0.05). Discussion The best performing signature discriminating was CMTM5/CETP/PLA2G7/MIA/MPP3 (AUC=0.9758). I°I S°S variably other independent datasets, this may be due technical variation the study/assay platform.

Language: Английский

Citations

5
Gene Expression Profiling in Pediatric Appendicitis DOI
Bhavjinder K. Dhillon, Simone Kortbeek, Arjun Baghela

et al.

JAMA Pediatrics, Journal Year: 2024, Volume and Issue: 178(4), P. 391 - 391

Published: Feb. 19, 2024

Importance Appendicitis is the most common indication for urgent surgery in pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) perforated (PA) on presentation may help direct further diagnostic workup appropriate therapy selection, including antibiotic choice timing surgery. Objective To provide mechanistic understanding differences disease objective developing improved diagnostics treatments, specifically population. Design, Setting, Participants The Gene Expression Profiling Pediatric (GEPPA) study was single-center prospective exploratory transcriptomic profiling peripheral blood collected from cohort children aged 5 to 17 years abdominal pain suspected between November 2016 April 2017 at Alberta Children’s Hospital Calgary, Alberta, Canada, data analysis reported August 2023. There no patient follow-up this study. Exposure SA, PA, or nonappendicitis pain. Main Outcomes Measures Blood transcriptomics used develop hypothesis underlying SA PA build hypotheses blood-based diagnostics. Results Seventy-one (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) emergency department were investigated using whole-blood transcriptomics. A central role immune system pathways revealed dampening major innate interferon responses. expression changes patients consistent downregulation response inflammation shared similarities gene signatures derived sepsis, severe sepsis endotypes. Despite challenges identifying early biomarkers appendicitis, 4-gene signature that predictive compared an accuracy 85.7% (95% CI, 72.8-94.1) identified. Conclusions This found complicated by dysregulated response. finding should inform severity, management strategies, prevention postsurgical

Language: Английский

Citations

5