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Anti-Inflammatory Properties of Plasma from Children with Short Bowel Syndrome.

ABSTRACT: Sepsis, resulting from a dysregulated host immune response to invading pathogens, is the leading cause of mortality in critically ill patients worldwide. Immunomodulatory treatment for sepsis is currently lacking. Children with short bowel syndrome (SBS) may present with less severe symptoms during gram-negative bacteremia. We, therefore, tested the hypothesis that plasma from children with SBS could confer protection against Escherichia coli sepsis. We showed that SBS plasma at 5% and 10% concentrations significantly (p < 0.05) inhibited the production of both TNF-α and IL-6 induced by either E. coli- or LPS-stimulated host cells when compared to plasma from healthy controls. Furthermore, mice treated intravenously with select plasma samples from SBS or healthy subjects had reduced proinflammatory cytokine levels in plasma and a significant survival advantage after E. coli infection. However, SBS plasma was not more protective than the plasma of healthy subjects, suggesting that children with SBS have other immunomodulatory mechanisms, in addition to neutralizing antibodies, to alleviate their symptoms during gram-negative sepsis.

SUBMITTER: Hajam IA

PROVIDER: S-EPMC8400962 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Anti-Inflammatory Properties of Plasma from Children with Short Bowel Syndrome.

Hajam Irshad Ahmed IA Ali Farhana F Young Jocelyn J Garcia Mary Abigail MA Cannavino Christopher C Ramchandar Nanda N Liu George Y GY

Pathogens (Basel, Switzerland) 20210813 8

Sepsis, resulting from a dysregulated host immune response to invading pathogens, is the leading cause of mortality in critically ill patients worldwide. Immunomodulatory treatment for sepsis is currently lacking. Children with short bowel syndrome (SBS) may present with less severe symptoms during gram-negative bacteremia. We, therefore, tested the hypothesis that plasma from children with SBS could confer protection against <i>Escherichia coli</i> sepsis. We showed that SBS plasma at 5% and 10 ...[more]

PMID: 34451485

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Project description:IntroductionParenteral nutrition (PN) dependence in short bowel syndrome (SBS) patients is linked to the functionality of the remnant small bowel (RSB). Patients may wean off PN following a period of intestinal adaptation that restores this functionality. Currently, plasma citrulline is the standard biomarker for monitoring intestinal functionality and adaptation. However, available studies reveal that the relationship the biomarker with the length and function of the RSB is arguable. Thus, having additional biomarkers would improve pointing out PN weaning.AimBy measuring concomitant changes in citrulline and the novel biomarker apolipoprotein AIV (Apo AIV), as well as taking into account the anatomy of the RSB, this exploratory study aims to a better understanding of the intestinal adaptation process and characterization of the SBS patients under PN.MethodsThirty four adult SBS patients were selected and assigned to adapted (aSBS) and non-adapted (nSBS) groups after reconstructive surgeries. Remaining jejunum and ileum lengths were recorded. The aSBS patients were either on an oral diet (ORAL group), those with intestinal insufficiency, or on oral and home parenteral nutrition (HPN group), those with chronic intestinal failure. Apo AIV and citrulline were analyzed in plasma samples after overnight fasting. An exploratory ROC analysis using citrulline as gold standard was performed.ResultsBiomarkers, Apo AIV and citrulline showed a significant correlation with RSBL in aSBS patients. In jejuno-ileocolic patients, only Apo AIV correlated with RSBL (rb = 0.54) and with ileum length (rb = 0.84). In patients without ileum neither biomarker showed any correlation with RSBL. ROC analysis indicated the Apo AIV cut-off value to be 4.6 mg /100 mL for differentiating between the aSBS HPN and ORAL groups.ConclusionsTherefore, in addition to citrulline, Apo AIV can be set as a biomarker to monitor intestinal adaptation in SBS patients. As short bowel anatomy is shown to influence citrulline and Apo AIV plasma values, both biomarkers complement each other furnishing a new insight to manage PN dependence.

Project description:ImportanceOptimal agents and duration of primary treatment for multisystem inflammatory syndrome in children (MIS-C) remain unclear.ObjectiveTo compare short-term patient outcomes based on initial treatment with corticosteroids, intravenous immunoglobulin (IVIG), or both.Design, setting, and participantsThis retrospective cohort study included patients in a tertiary-care pediatric hospital system who had MIS-C per the Centers for Disease Control and Prevention case definition during the period March 2020 to February 2021.ExposuresImmunomodulatory therapy within the first 24 hours (patients in the intensive care unit [ICU]) or 48 hours (non-ICU patients): corticosteroids alone, IVIG alone, and IVIG plus corticosteroids.Main outcomes and measuresPrimary outcome was failure of initial therapy, defined as therapy escalation due to fever or worsening or lack of improvement of laboratory, cardiac, or noncardiac clinical factors after 24 hours (ICU patients) or 48 hours (non-ICU patients) from time of therapy initiation, per clinician assessment. Secondary outcomes included presence of complications, cardiovascular outcomes, fever duration, length of hospital and ICU stays, corticosteroid use duration, and need for readmission.ResultsAmong 228 eligible patients, 215 patients were included in the univariate analysis; median age was 8 years, and 135 (62.8%) were boys. There were 69 patients in the corticosteroids group, 31 patients in the IVIG group, and 115 patients in the IVIG plus corticosteroids group. Patients in the corticosteroids group had milder disease at presentation. After propensity score weighting including 179 patients (68 in the corticosteroids group and 111 in the IVIG plus corticosteroids group), rates of initial treatment failure were similar between groups. Among patients whose initial treatment failed, treatment failure in the IVIG plus corticosteroids group was more likely to be based on laboratory parameters (odds ratio [OR], 1.96; 95% CI, 1.07-3.60) and less likely to be based on cardiovascular markers (OR, 0.39; 95% CI, 0.2-0.76), per clinician assessment. Patients in the IVIG plus corticosteroids group had a longer median inpatient stay (6 vs 5 days; P = .001) and longer median corticosteroid course duration (10 vs 5 days; P = .04) compared with the corticosteroids group. Forty-nine patients (71% of 69 in the corticosteroids group) recovered after receiving corticosteroid monotherapy for 10 days or less.Conclusions and relevanceCorticosteroid monotherapy is a reasonable management option for a subset of patients with MIS-C, particularly those with mild disease.

Project description:Short bowel syndrome (SBS) presents an increasing problem in pediatrics. SBS often results from surgical resection of necrotic bowel following necrotizing enterocolitis or treatment of anatomic gastrointestinal defects. SBS is associated with significant morbidity and mortality, and creates substantial burdens for patients, families, and the health system. Recent reports have demonstrated that the fecal microbiome of children with SBS is significantly different from healthy control and severe intestinal microbial imbalances is associated with poor growth. We hypothesized that children with SBS and adverse clinical features such as PN dependent, shorter bowel length and lack of ileocecal valve would demonstrate more gut dysbiosis compare with the SBS non-PN dependent. An improved understanding of SBS pathogenesis would enhance management and potentially suggest new interventions. We studied microbial communities of SBS and control non-SBS patients from the jejunum, obtained endoscopically or by ostomy aspiration, and stool. We enrolled SBS patients who did and did not require parenteral nutrition (PN), as a surrogate marker for the seriousness of their disease. We studied the microbiota using high-throughput DNA sequencing of 16S rRNA genes and statistical analyses. We found that microbial diversity was significantly greater in jejunal aspirate than in stool samples in SBS patients, unlike non-SBS patients; that SBS patients receiving enteral feeds had greater diversity, and that SBS patients on PN and enteral feeds had lower differences in diversity in jejunal vs. stool samples. We found a trend toward increased diversity in patients with an intact ileocecal valve, and found that certain taxa were more abundant in the certain sample types, and in SBS patients vs. non-SBS patients. SBS patients have lower microbial diversity, especially patients with more severe disease, patients requiring PN, and those lacking an ileocecal valve. SBS patients, particularly those with more complex characteristics, exhibit differences in their intestinal microbiota. Particular individual taxa were over- and under-represented in patients with more unfavorable disease. While diminished diversity and alterations in microbiota composition are likely consequences of SBS, future efforts aimed at increasing microbial diversity and interventions targeting specific microbiota characteristics might constitute a testable approach to ameliorate some clinical SBS clinical consequences.

Dataset Information

Anti-Inflammatory Properties of Plasma from Children with Short Bowel Syndrome.

Publications

Anti-Inflammatory Properties of Plasma from Children with Short Bowel Syndrome.

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