Pediatric Sepsis Research: Where Are We and Where Are We Going?

Massaud-Ribeiro, Letícia; Silami, Pedro Henrique Nunes Costa; Lima‐Setta, Fernanda; Prata‐Barbosa, Arnaldo

doi:10.3389/fped.2022.829119

Cited by 11 publications

(15 citation statements)

References 41 publications

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“…The modulation of the gene expression profile during sepsis is largely described in adults. However, the young population had pathophysiological characteristics and is particularly vulnerable to septic shock [ 45 , 46 ]. Thus, evaluating the transcriptomic response in the young is an important issue to (i) improve knowledge about pathophysiological mechanisms and (ii) adapt therapeutic care.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

Dupas

Persello

Blangy-Letheule

et al. 2022

IJMS

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The young population, which is particularly at risk of sepsis, is, paradoxically, rarely studied. Acute stimulation of O-GlcNAcylation, a post-translational modification involved in metabolic regulation, cell survival and stress response, is beneficial in young rats with sepsis. Considering that sepsis impacts the gene expression profile and that O-GlcNAcylation is a regulator of transcription, the aims of this study are to (i) unveil beneficial mechanisms of O-GlcNAcylation and (ii) decipher the relationship between O-GlcNAcylation and transcription during sepsis. Endotoxemic challenge was induced in 28-day-old male rats using a lipopolysaccharide injection (E. coli O111:B4, 20 mg·kg−1) and compared to control rats (NaCl 0.9%). One hour after, rats were assigned to no therapy or fluidotherapy (NaCl 0.9%, 10 mL.kg−1) ± NButGT (10 mg·kg−1) to stimulate O-GlcNAc levels. Cardiac O-GlcNAcylation levels were evaluated via Western blot and gene transcription using 3′ SRP analysis. Lipopolysaccharide injection favorizes inflammatory state with the overexpression of genes involved in the NF-κB, JAK/STAT and MAPK pathways. NButGT treatment increased cardiac O-GlcNAcylation levels (p < 0.05). Yet, the mRNA expression was not impacted two hours after fluidotherapy or NButGT treatment. In conclusion, O-GlcNAc stimulation-induced beneficial effects are not dependent on the gene expression profile at the early phase of sepsis.

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Section: Discussionmentioning

confidence: 99%

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

Dupas

Persello

Blangy-Letheule

et al. 2022

IJMS

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“…Hence, this paper seeks to expand our knowledge of the application of the transcript to the study of sepsis. Specifically, this scoping review aims to examine peer review literature identifying the utilization of transcriptomic information applied to clinical sepsis (2012-2021), including the exploration for enhanced sepsis biomarking using the transcript (26). The aim was to identify and assimilate the application of gene-expression data, thus highlighting existing gaps in knowledge.…”

Section: An Inflammatory Cascade Termed Systemic Inflammatory Responsementioning

confidence: 99%

“…Thereby, this paper seeks to expand our knowledge of the application of the transcript to the study of sepsis. Specifically, this scoping review aims to examine peer review literature identifying the utilization of transcriptomic information applied to clinical sepsis over the past decade (2012-2021), including the potential for enhanced sepsis biomarking (26).…”

Section: Introduction Current Challenges In Sepsis Definition and The...mentioning

confidence: 99%

Applying Transcriptomics for an Enhanced Clinical Research Framework, Implications for an Improved Research Strategy based on an Omics Approach: A Scoping Review

Rashid

Wiredu

Hanisch

et al. 2022

Preprint

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Background Sepsis is a syndromic response to infection that carries a significant global health burden, with 11 million deaths reported globally in 2017. Many biomarkers have been developed over the years for early identification and prognosis in patients with sepsis. However, they lack the sensitivity and specificity for routine use in clinical practice. A significant challenge in developing a sepsis biomarker has been the lack of a robust pathobiological framework: a factor with a weak immunological basis to assess therapeutic efficacy. The transcript can aid in extrapolating immunological changes to the clinical arena. Given that transcriptomic processing forms a part of a systems biology analysis, we undertook to address the question: What is known about the relationship of the transcript to clinical sepsis? Objective Consequently, this review article envisages a systems-based approach to better understand sepsis using mRNA gene expression information. This was achieved through an examination of peer-reviewed literature identifying the relationship of the transcript to clinical sepsis. Methods Information sources included peer-reviewed PubMed-indexed journals using the PubMed database. Articles specific to sepsis were selected, being published between the years 2012 to 2022 inclusive. A content analysis of findings was conducted. Results The search strategy elicited 14,048 studies. Keywords and or mesh terms were applied as single terms or Boolean string search combinations, generating 36 studies. Literature was analyzed concerning the specific use of the transcript and its application to sepsis. Five main descriptive Sepsis categories were identified: (1) Definition; (2) Classification; (3) Severity, (4) Molecular Biomarkers, and (5) Benchmarking. Conclusions Evidence of the connection of the transcript to clinical sepsis was identified. This provided a systems perspective, interfacing transcriptomic data to parameters important in the clinical arena. The use of transcriptomic data in advancing patient sepsis care, thereby aiming to improve precision, requires further investigation.

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“…The neonate’s innate immune system is underdeveloped, which increases the risk of sepsis development. In particular, the innate immune response to infection begins with neutrophils, but infants have physiological neutropenia, and neutrophils have inhibited migratory and phagocytic abilities [ 5 ]. Monocytes, which produce antimicrobial components such as CRP, have diminished antigen-presenting abilities in newborns [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, its role in neonatal sepsis has not yet been determined. One of the key models in the development of sepsis-mediated immunosuppression is programmed death receptor (PD) PD-1/PDL-1, but its role in newborns is still poorly described [ 5 , 7 ]. PD-1 plays an important role in the immune response by down-regulating T cell activity during immune responses to prevent autoimmune tissue damage.…”

Section: Introductionmentioning

confidence: 99%

The Presence of PDL-1 on CD8+ Lymphocytes Is Linked to Survival in Neonatal Sepsis

et al. 2022

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Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Neonatal sepsis is the main cause of death in newborns, especially preterm infants. The pathogenesis of sepsis is based on a hyper-inflammatory syndrome combined with an immunosuppressive mechanism in sepsis. This study aimed to find critical parameters that are associated with the outcome of newborns with suspected sepsis. Understanding the association might have clinical relevance for immuno-monitoring, outcome prediction, and targeted therapy. Methods: A total of 210 newborn infants no older than 4 days with suspected sepsis at admission in Karaganda (Kazakhstan) were prospectively enrolled. Blood cultures were incubated, and pathogens in positive cultures were determined by MALDI-TOF. An immunological assay for blood cell components was conducted by flow cytometry with antibody cocktails. The diagnostic criteria for neonatal sepsis were identified by qualified neonatologists and included both clinical sepsis and/or positive blood culture. The analyzed infants were grouped into non-septic infants, surviving septic infants, and deceased septic infants. The results showed that deceased septic newborns had a lower level of CD8+ lymphocytes and higher PDL-1 expression in comparison with surviving septic newborns. PDL-1 expression on CD8+ T cells might play an immunosuppressive role during neonatal sepsis and might be used as a laboratory biomarker in the future.

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Pediatric Sepsis Research: Where Are We and Where Are We Going?

Cited by 11 publications

References 41 publications

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

Applying Transcriptomics for an Enhanced Clinical Research Framework, Implications for an Improved Research Strategy based on an Omics Approach: A Scoping Review

The Presence of PDL-1 on CD8+ Lymphocytes Is Linked to Survival in Neonatal Sepsis

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