Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis

Хаертынов, Х. С.; Boichuk, Sergei; Khaiboullina, Svetlana F.; Анохин, В. А.; Андреева, А. А.; Lombardi, Vincent; Сатрутдинов, М. А.; Агафонова, Е.А.; Rizvanov, Albert A.

doi:10.1155/2017/8601063

Cited by 51 publications

(55 citation statements)

References 29 publications

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“…The unproven neonatal sepsis patients were excluded from this study to avoid incorporation bias. This bias would appear if the possible predictive factors became part of the diagnostic criteria [3,34].…”

Section: Discussionmentioning

confidence: 99%

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Predictive model for bacterial late-onset neonatal sepsis in a tertiary care hospital in Thailand

et al. 2020

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Background: Early diagnosis of neonatal sepsis is essential to prevent severe complications and avoid unnecessary use of antibiotics. The mortality of neonatal sepsis is over 18%in many countries. This study aimed to develop a predictive model for the diagnosis of bacterial late-onset neonatal sepsis. Methods: A case-control study was conducted at Queen Sirikit National Institute of Child Health, Bangkok, Thailand. Data were derived from the medical records of 52 sepsis cases and 156 non-sepsis controls. Only proven bacterial neonatal sepsis cases were included in the sepsis group. The non-sepsis group consisted of neonates without any infection. Potential predictors consisted of risk factors, clinical conditions, laboratory data, and treatment modalities. The model was developed based on multiple logistic regression analysis. Results: The incidence of late proven neonatal sepsis was 1.46%. The model had 6 significant variables: poor feeding, abnormal heart rate (outside the range 100-180 x/min), abnormal temperature (outside the range 36 o -37.9°C), abnormal oxygen saturation, abnormal leucocytes (according to Manroe's criteria by age), and abnormal pH (outside the range 7.27-7.45). The area below the Receiver Operating Characteristics (ROC) curve was 95.5%. The score had a sensitivity of 88.5% and specificity of 90.4%.Conclusion: A predictive model and a scoring system were developed for proven bacterial late-onset neonatal sepsis. This simpler tool is expected to somewhat replace microbiological culture, especially in resource-limited settings.

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Section: Discussionmentioning

confidence: 99%

“…Unfortunately, the sensitivity of this method is low. Thus, the diagnosis of sepsis cannot be excluded even when the results are negative [34,35]. When the cultures are negative, but the infant manifests signs consistent with an infection, it may be assumed that they have clinical sepsis [3].…”

Section: Introductionmentioning

confidence: 99%

Predictive model for bacterial late-onset neonatal sepsis in a tertiary care hospital in Thailand

et al. 2020

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“…Neonatal sepsis is associated with increased levels of inflammatory cytokines which plays a significant part in its pathogenesis and severity 41 . Narciclasine has shown to exhibit anti-inflammatory properties and suggested to be used in inflammation related disorders 20 .…”

Section: Discussionmentioning

confidence: 99%

Narciclasine improves outcome in sepsis among neonatal rats via inhibition of calprotectin and alleviating inflammatory responses

Kingsley

Bhat

Badhe

et al. 2020

Sci Rep

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Sepsis is associated with exacerbated inflammatory response which subsequently results in multiple organ dysfunction. Sepsis accounts for high mortality and morbidity among newborns worldwide. Narciclasine is a plant alkaloid which has shown to possess anti-inflammatory properties. In this study we investigated the effect and mechanism of action of narciclasine in neonatal sepsis rat models. The excessive release of S100A8/A9 or calprotectin in neonatal sepsis could be detrimental as it could exacerbate the inflammatory responses. We found that narciclasine significantly reduced the plasma levels of S100A8/A9 and also suppressed its expression in the liver and lung. The systemic and local bacterial load was also reduced in the narciclasine treated rats. The systemic and local production of pro-inflammatory cytokines in plasma and organs (liver and lungs) was significantly reduced in the narciclasine treated rats. The histopathological studies showed that narciclasine prevents the organ damage associated with sepsis and improved the survival of neonatal rats. Sepsis increased the phosphorylated NF-κβ p65 protein expression in the liver. Narciclasine suppressed the phosphorylation of nf-κβ p65 and the degradation of NF-κβ inhibitory protein alpha. It could also suppress the expression of adaptor proteins of the toll like receptor signaling pathway viz., myeloid differentiation factor 88 (MyD88), Interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor associated factor 6 (TRAF6). These results suggest that narciclasine protects against sepsis in neonatal rats through the inhibition of calprotectin, pro-inflammatory cytokines and suppression of NF-κβ signaling pathway.Infection is the most important cause of morbidity and mortality in intensive care units worldwide. As the immune response to infection during the neonatal period is mostly immature it is characterized by high rates of morbidity and mortality 1-3 . Most adults are usually able to restrict the bacterial infection whereas neonates are not able to restrict the bacterial infection and develop a severe systemic inflammatory response. Sepsis is a life threatening health condition which occurs due to the severe and systemic inflammatory response to infection. This syndrome starts with dysregulated inflammation, systemic inflammatory response syndrome (SIRS) progressing to severe sepsis and septic shock 4 . It is the most common cause of death in critically ill patients in non-coronary intensive care units 5 .Despite the advancement of medical care, sepsis is one of the leading causes of morbidity and mortality among babies in the neonatal intensive care units 6 . This is mainly due to the non-specific signs and symptoms of neonatal sepsis 2 . Antibiotics and supportive care are the mainstay of treatment at present. The nosocomial pathogens are increasingly becoming resistant to the antimicrobials currently being used. Thus alternative therapeutic options such as anti-inflammatory drugs could be beneficial as neonatal sepsis is characterized by elev...

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“…This "cytokine storm" can lead to organ dysfunction and death. [29,42,43] Furthermore, excessive in ammation in the neonatal period has been associated with neurodegenerative effects and cogitative de ciencies. [44,45] Excessive in ammation in the lungs predispose infants to an increased risk of bronchopulmonary dysplasia, while cardiac in ammation has been associated with the development of ventricular failure.…”

Section: Discussionmentioning

confidence: 99%

Targeting the eCIRP/TREM-1 Interaction with a Small Molecule Inhibitor Improves Cardiac Dysfunction in Neonatal Sepsis

Denning

Aziz

et al. 2020

Preprint

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Background: Neonatal sepsis and the associated myocardial dysfunction remain a leading cause of infant mortality. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a ligand of triggering receptor expressed on myeloid cells-1 (TREM-1). M3 is a small CIRP-derived peptide that inhibits the eCIRP/TREM-1 interaction. We hypothesize that the eCIRP/TREM-1 interaction in cardiomyocytes contributes to sepsis-induced cardiac dysfunction in neonatal sepsis, while M3 is cardioprotective. Methods: Serum was collected from neonates in the Neonatal Intensive Care Unit (NICU). 5-7-day old C57BL/6 mouse pups were used in this study. Primary murine neonatal cardiomyocytes were stimulated with recombinant murine (rm) CIRP with M3. TREM-1 mRNA and supernatant cytokine levels were assayed. Mitochondrial oxidative stress, ROS, and membrane potential were assayed. Neonatal mice were injected with rmCIRP and speckle-tracking echocardiography was conducted to measure cardiac strain. Sepsis was induced by i.p. cecal slurry. Mouse pups were treated with M3 or vehicle. After 16 h, echocardiography was performed followed by euthanasia for tissue analysis. A 7-day survival study was conducted. Results: Serum CIRP levels were elevated in septic human neonates. rmCIRP stimulation of cardiomyocytes increased TREM-1 gene expression. Stimulation of cardiomyocytes with rmCIRP upregulated TNF-α and IL-6 in the supernatants, while this upregulation was inhibited by M3. Stimulation of cardiomyocytes with rmCIRP resulted in a reduction in mitochondrial membrane potential (MMP) while M3 treatment returned MMP to near baseline. rmCIRP caused mitochondrial calcium overload; this was inhibited by M3. rmCIRP injection impaired longitudinal and radial cardiac strain. Sepsis resulted in cardiac dysfunction with a reduction in cardiac output and left ventricular end diastolic diameter. Both were improved by M3 treatment. Treatment with M3 attenuated serum, cardiac, and pulmonary levels of pro-inflammatory cytokines compared to vehicle-treated septic neonates. M3 dramatically increased sepsis survival. Conclusions: Inhibition of eCIRP/TREM-1 interaction with M3 is cardioprotective, decreases inflammation, and improves survival in neonatal sepsis. Trial registration: Retrospectively registered.

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Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis

Cited by 51 publications

References 29 publications

Predictive model for bacterial late-onset neonatal sepsis in a tertiary care hospital in Thailand

Predictive model for bacterial late-onset neonatal sepsis in a tertiary care hospital in Thailand

Narciclasine improves outcome in sepsis among neonatal rats via inhibition of calprotectin and alleviating inflammatory responses

Targeting the eCIRP/TREM-1 Interaction with a Small Molecule Inhibitor Improves Cardiac Dysfunction in Neonatal Sepsis

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