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1.
Semin Perinatol ; 48(3): 151902, 2024 Apr.
Article En | MEDLINE | ID: mdl-38692996

The American Academy of Pediatrics (AAP) Standards for Levels of Neonatal Care, published in 2023, highlights key components of a Neonatal Patient Safety and Quality Improvement Program (NPSQIP). A comprehensive Neonatal Intensive Care Unit (NICU) quality and safety infrastructure (QSI) is based on four foundational domains: quality improvement, quality assurance, safety culture, and clinical guidelines. This paper serves as an operational guide for NICU clinical leaders and quality champions to navigate these domains and develop their local QSI to include the AAP NPSQIP standards.


Intensive Care Units, Neonatal , Patient Safety , Quality Improvement , Humans , Intensive Care Units, Neonatal/standards , Intensive Care Units, Neonatal/organization & administration , Patient Safety/standards , Infant, Newborn , Quality Assurance, Health Care , Practice Guidelines as Topic , United States , Organizational Culture , Safety Management/standards , Safety Management/organization & administration
2.
Am J Physiol Gastrointest Liver Physiol ; 325(5): G471-G491, 2023 11 01.
Article En | MEDLINE | ID: mdl-37697947

The liver plays a significant role in regulating a wide range of metabolic, homeostatic, and host-defense functions. However, the impact of liver injury on the host's ability to control bacteremia and morbidity in sepsis is not well understood. Leukocyte recruitment and activation lead to cytokine and chemokine release, which, in turn, trigger hepatocellular injury and elevate nucleotide levels in the extracellular milieu. P2Y2 purinergic receptors, G protein-coupled and activated by extracellular ATP/UTP, are expressed at the cell surface of hepatocytes and nonparenchymal cells. We sought to determine whether P2Y2 purinergic receptor function is necessary for the maladaptive host response to bacterial infection and endotoxin-mediated inflammatory liver injury and mortality in mice. We report that P2Y2 purinergic receptor knockout mice (P2Y2-/-) had attenuated inflammation and liver injury, with improved survival in response to LPS/galactosamine (LPS/GalN; inflammatory liver injury) and cecal ligation and puncture (CLP; polymicrobial sepsis). P2Y2-/- livers had attenuated c-Jun NH2-terminal kinase activation, matrix metallopeptidase-9 expression, and hepatocyte apoptosis in response to LPS/GalN and attenuated inducible nitric oxide synthase and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 protein expression in response to CLP. Implicating liver injury in the disruption of amino acid homeostasis, CLP led to lower serum arginine and higher bacterial load and morbidity in the WT mice, whereas serum arginine levels were comparable to sham-operated controls in P2Y2-/- mice, which had attenuated bacteremia and improved survival. Collectively, our studies highlight the pathophysiological relevance of P2Y2 purinergic receptor function in inflammatory liver injury and dysregulation of systemic amino acid homeostasis with implications for sepsis-associated immune dysfunction and morbidity in mice.NEW & NOTEWORTHY Our studies provide experimental evidence for P2Y2 purinergic receptor-mediated potentiation of inflammatory liver injury, morbidity, and mortality, in two well-established animal models of inflammatory liver injury. Our findings highlight the potential to target P2Y2 purinergic signaling to attenuate the induction of "cytokine storm" and prevent its deleterious consequences on liver function, systemic amino acid homeostasis, host response to bacterial infection, and sepsis-associated morbidity and mortality.


Bacteremia , Bacterial Infections , Sepsis , Mice , Animals , Lipopolysaccharides/pharmacology , Gene Deletion , Liver , Cytokines/genetics , Bacteremia/complications , Bacteremia/genetics , Nucleotides , Arginine , Receptors, Purinergic , Amino Acids , Mice, Inbred C57BL , Receptors, Purinergic P2Y2/genetics , Mice, Knockout
3.
J Pediatr ; 231: 215-222, 2021 04.
Article En | MEDLINE | ID: mdl-33359630

OBJECTIVE: To describe the clinical characteristics, outcomes, and adverse events of treatment for symptomatic infant catheter-related arterial thrombosis. STUDY DESIGN: Single-center retrospective medical record review of 99 infants (age <365 days) with catheter-related arterial thrombosis, either following indwelling arterial catheter placement or cardiac catheterization, who were treated with anticoagulation over an 8-year span at a pediatric tertiary care center. Outcomes measured include thrombosis progression, bleeding events, and thrombus resolution following the treatment period. RESULTS: Thromboses were secondary to indwelling arterial catheter placement in 51 (51.5%) and cardiac catheterization in 48 (48.5%). The median age at diagnosis of catheter-related arterial thrombosis was 52 days. All patients received therapeutic anticoagulation with either unfractionated heparin or low molecular weight heparin for a maximum of 28 days. Progression of catheter-related arterial thrombosis occurred in 8 (8.1%) patients. One (1%) major and 3 (3%) minor bleeding events occurred within the cohort. Complete thrombus resolution was observed in 60 (60.6%), partial resolution in 33 (33.3%), and no resolution in 6 (6.1%) following the treatment period. Factors associated with complete thrombus resolution included time from intervention to catheter-related arterial thrombosis diagnosis (median of 1 day vs 5 days in those who experienced thrombus resolution vs those who did not, P = .035), and iliac and/or femoral artery involvement (P = .015). CONCLUSIONS: Our treatment approach to infant catheter-related arterial thrombosis is safe and effective. Limitations of the study are its retrospective nature with a limited number of patients from a single institution. Additional prospective studies are needed to determine the optimal treatment approach to catheter-related arterial thrombosis in infants.


Anticoagulants/therapeutic use , Cardiac Catheterization/adverse effects , Catheters, Indwelling/adverse effects , Thrombosis/diagnosis , Thrombosis/drug therapy , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , Thrombosis/etiology , Treatment Outcome
4.
Neonatology ; 117(1): 127-130, 2020.
Article En | MEDLINE | ID: mdl-31751989

Maternal ingestion of naphthalene-containing mothballs is an uncommon cause of perinatal toxicity. Naphthalene toxicity is associated with methemoglobinemia, hypotension, hemolytic anemia, and hyperbilirubinemia, as well as other hepatic, renal, and respiratory complications. Naphthalene exposure is a common cause of toxicity in older children, but is rarely described in neonates. The neonatal cases described in the literature focus primarily on maternal inhalation as opposed to ingestion. We present a case of perinatal toxicity due to repeated maternal ingestion of naphthalene-containing mothballs during pregnancy. The patient presented with methemoglobinemia, hypotension, hemolytic anemia, and hyperbilirubinemia. Sepsis or pulmonary hypertension were the initial working diagnoses, as the mother did not provide the history of ingestion until after the patient's clinical status worsened. This case highlights the importance of obtaining a thorough maternal history and considering maternal ingestion when the etiology of symptoms is not clear.


Eating , Naphthalenes/toxicity , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/diagnosis , Adult , Anemia, Hemolytic/blood , Anemia, Hemolytic/chemically induced , Anemia, Hemolytic/diagnosis , Female , Humans , Hyperbilirubinemia/blood , Hyperbilirubinemia/chemically induced , Hyperbilirubinemia/diagnosis , Infant, Newborn , Naphthalenes/administration & dosage , Pregnancy , Prenatal Exposure Delayed Effects/blood
5.
Pediatr Dev Pathol ; 18(2): 155-8, 2015.
Article En | MEDLINE | ID: mdl-25535792

The usual route of acquisition for intrauterine herpes simplex virus (HSV) infection is transplacental. We evaluated a premature infant with in utero acquisition of HSV resulting from ascending infection. Histopathologic evidence of chronic chorioamnionitis and positive staining with immunohistochemistry for HSV in the placenta and umbilical cord established the diagnosis. The clinical presentation was also of interest in that the infant was initially healthy appearing.


Chorioamnionitis/virology , Herpes Simplex/transmission , Infant, Premature , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/virology , Simplexvirus/pathogenicity , Acyclovir/therapeutic use , Antigens, Viral/analysis , Antiviral Agents/therapeutic use , Biopsy , Chorioamnionitis/diagnosis , Chorioamnionitis/drug therapy , Female , Gestational Age , Herpes Simplex/diagnosis , Herpes Simplex/drug therapy , Herpes Simplex/virology , Humans , Immunohistochemistry , Infant, Newborn , Male , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Simplexvirus/immunology , Umbilical Cord/virology , Young Adult
6.
Expert Rev Anti Infect Ther ; 11(7): 695-707, 2013 Jul.
Article En | MEDLINE | ID: mdl-23879609

Neonatal sepsis and necrotizing enterocolitis (NEC) are associated with significant mortality and morbidity. Inflammation secondary to sepsis and NEC increases morbidity, especially those related to the lung, brain and eye. Therapeutic strategies that target inflammation and decrease the emergence of antibiotic resistance are urgently needed. Lactoferrin (Lf) is a multifunctional protein that modulates inflammation, cell growth and differentiation and has broad antimicrobial activity. Studies evaluating the efficacy and safety of Lf in the prevention of neonatal sepsis and NEC are currently in progress, and one completed study shows significant promise. In this article, the functions of this multifunctional molecule and current clinical evidence for its use in the newborn are reviewed. Lf prophylaxis and therapy may have a significant impact in improving clinical outcomes of vulnerable preterm neonates.


Anti-Infective Agents/therapeutic use , Enterocolitis, Necrotizing/drug therapy , Lactoferrin/therapeutic use , Sepsis/drug therapy , Animals , Anti-Infective Agents/adverse effects , Clinical Trials as Topic , Humans , Immunomodulation , Infant, Newborn , Lactoferrin/adverse effects , Mice , Treatment Outcome
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