Reducing pediatric ambulatory central line-associated bloodstream infections in patients at a single institution home health agency.

We conducted a quality improvement project from 2019 to 2021 at a single home health agency to reduce rates of central line-associated bloodstream infection in our ambulatory pediatric population. Annualized central line-associated bloodstream infection rates per 1,000 catheter line days decreased by 20 % during the study period, from a rate of 1.023 to 0.810. This decrease was sustained in the 10-month post-study period with a center line shift of 1.090 to 0.658.

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

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.

Normal mucus formation requires cAMP-dependent HCO3- secretion and Ca2+-mediated mucin exocytosis.

Evidence from the pathology in cystic fibrosis (CF) and recent results in vitro indicate that HCO3- is required for gel-forming mucins to form the mucus that protects epithelial surfaces. Mucus formation and release is a complex process that begins with an initial intracellular phase of synthesis, packaging and apical granule exocytosis that is followed by an extracellular phase of mucin swelling, transport and discharge into a lumen. Exactly where HCO3- becomes crucial in these processes is unknown, but we observed that in the presence of HCO3-, stimulating dissected segments of native mouse intestine with 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) induced goblet cell exocytosis followed by normal mucin discharge in wild-type (WT) intestines. CF intestines that inherently lack cystic fibrosis transmembrane conductance regulator (CFTR)-dependent HCO3- secretion also demonstrated apparently normal goblet cell exocytosis, but in contrast, this was not followed by similar mucin discharge. Moreover, we found that even in the presence of HCO3-, when WT intestines were stimulated only with a Ca2+-mediated agonist (carbachol), exocytosis was followed by poor discharge as with CF intestines. However, when the Ca2+-mediated agonist was combined with a cAMP-mediated agonist (isoproterenol (isoprenaline) or vasoactive intestinal peptide) in the presence of HCO3- both normal exocytosis and normal discharge was observed. These results indicate that normal mucus formation requires concurrent activation of a Ca2+-mediated exocytosis of mucin granules and an independent cAMP-mediated, CFTR-dependent, HCO3- secretion that appears to mainly enhance the extracellular phases of mucus excretion.

Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion.

The mechanisms underlying mucus-associated pathologies in cystic fibrosis (CF) remain obscure. However, recent studies indicate that CF transmembrane conductance regulator (CFTR) is required for bicarbonate (HCO3-) transport and that HCO3- is critical for normal mucus formation. We therefore investigated the role of HCO3- in mucus secretion using mouse small intestine segments ex vivo. Basal rates of mucus release in the presence or absence of HCO3- were similar. However, in the absence of HCO3-, mucus release stimulated by either PGE2 or 5-hydroxytryptamine (5-HT) was approximately half that stimulated by these molecules in the presence of HCO3-. Inhibition of HCO3- and fluid transport markedly reduced stimulated mucus release. However, neither absence of HCO3- nor inhibition of HCO3- transport affected fluid secretion rates, indicating that the effect of HCO3- removal on mucus release was not due to decreased fluid secretion. In a mouse model of CF (mice homozygous for the most common human CFTR mutation), intestinal mucus release was minimal when stimulated with either PGE2 or 5-HT in the presence or absence of HCO3-. These data suggest that normal mucus release requires concurrent HCO3- secretion and that the characteristically aggregated mucus observed in mucin-secreting organs in individuals with CF may be a consequence of defective HCO3- transport.