Emergency Department Sepsis Triage Scoring Tool Elements Associated With Hypotension Within 24 Hours in Children With Fever and Tachycardia.

OBJECTIVE: Pediatric sepsis screening is becoming the standard of care for children presenting to the emergency department (ED) and has been shown to improve recognition of severe sepsis, but it is unknown if these screening tools can predict progression of disease. The objective of this study was to determine if any elements of a sepsis triage trigger tool were predictive of progression to hypotensive shock in children presenting to the ED with fever and tachycardia. METHODS: This study is a retrospective case-control study of children ≤18 years presenting to an ED with fever and tachycardia, comparing those who went on to develop hypotensive shock in the subsequent 24 hours (case) to those who did not (control). Primary outcome was the proportion of encounters where the patient had specific abnormal vital signs or clinical signs as components of the sepsis triage score. The secondary outcomes were the proportion of encounters where the patient had a sepsis risk factor. RESULTS: During the study period, there were 94 patients who met case criteria and 186 controls selected. In the adjusted multivariable model, the 2 components of the sepsis triage score that were more common in case patients were the presence of severe cerebral palsy (adjusted odds ratio, 9.4 [3.7, 23.9]) and abnormal capillary refill at triage (adjusted odds ratio, 3.1 [1.4, 6.9]). CONCLUSIONS: Among children who present to a pediatric ED with fever and tachycardia, those with prolonged capillary refill at triage or severe cerebral palsy were more likely to progress to decompensated septic shock, despite routine ED care.

The 4 S's of Disaster Management Framework: A Case Study of the 2022 Pediatric Tripledemic Response in a Community Hospital.

Most children in the United States present to community hospitals for emergency department (ED) care. Those who are acutely ill and require critical care are stabilized and transferred to a tertiary pediatric hospital with intensive care capabilities. During the fall of 2022 "tripledemic," with a marked increase in viral burden, there was a nationwide surge in pediatric ED patient volume. This caused ED crowding and decreased availability of pediatric hospital intensive care beds across the United States. As a result, there was an inability to transfer patients who were critically ill out, and the need for prolonged management increased at the community hospital level. We describe the experience of a Massachusetts community ED during this surge, including the large influx in pediatric patients, the increase in those requiring critical care, and the total number of critical care hours as compared with the same time period (September to December) in 2021. To combat these challenges, the pediatric ED leadership applied a disaster management framework based on the 4 S's of space, staff, stuff, and structure. We worked collaboratively with general emergency medicine leadership, nursing, respiratory therapy, pharmacy, local clinicians, our regional health care coalition, and emergency medical services (EMS) to create and implement the pediatric surge strategy. Here, we present the disaster framework strategy, the interventions employed, and the barriers and facilitators for implementation in our community hospital setting, which could be applied to other community hospital facing similar challenges.

Characteristics and Outcomes of Culture-Positive and Culture-Negative Pediatric Sepsis.

OBJECTIVES: To compare the outcomes of pediatric severe sepsis and septic shock among patients with culture-positive and culture-negative sepsis and to determine if there are differentiating markers of disease severity between these 2 populations during their initial presentation and emergency department (ED) stay. STUDY DESIGN: Retrospective cohort study of patients ≤21 years of age who presented to the ED of a single children's hospital with severe sepsis or septic shock from June 1, 2017 to June 5, 2019. RESULTS: There were 235 patients who met criteria for severe sepsis or septic shock. Of these, 139 (59.1%) had culture-negative sepsis and 96 (40.9%) had culture-positive sepsis. In the adjusted multivariable model, children with culture-negative sepsis had more intensive care unit (ICU)-free days than those with culture-positive sepsis (27.3 vs 24.1; adjusted median differences [aMD] -2.6 [-4.4, -0.8]). There were no differences in mortality or hospital-free days. On initial presentation, there were no differences in fever, hypothermia, tachycardia, tachypnea, or hypotension between the 2 groups. There were no differences in proportion of patients receiving the following interventions: intravenous (IV) antibiotics, IV fluids, vasoactive medications, CPR, intubation, or time from arrival to provision of these interventions. CONCLUSIONS: Culture-negative sepsis constitutes a substantial proportion of pediatric severe sepsis and septic shock. In this study, patients with culture-negative and culture-positive sepsis presented similarly on arrival to the ED and received similar treatments while there. Patients with culture-negative sepsis had more ICU-free days than those with culture-positive sepsis, although differences in hospital length of stay (LOS) and mortality were not observed.

Resolution of Fever in the Pediatric Emergency Department and Bacteremia.

To determine whether a lack of response to antipyretics was associated with bacteremia, we performed a cross-sectional study involving children with an initial temperature ≥38°C presenting to a pediatric emergency department (ED) from 2012 to 2020 who received an antipyretic and had a blood culture obtained. We assessed the association of resolution of fever at specific time points after antipyretic administration with bacteremia adjusting for age, complex chronic condition, blood culture source, type of antipyretic, and height of temperature. Among 6319 febrile children, 242 (3.8%) had bacteremia. The adjusted odds ratio of bacteremia was 1.6 (95% confidence interval: 1.2-2.2) among children who remained febrile at 180 minutes and 1.7 (1.2-2.4) among children who remained febrile at 240 minutes. Among febrile children presenting to a tertiary care ED for whom a blood culture was obtained, the response to an antipyretic varies based on the presence or absence of bacteremia.

Radiculoneuritis due to Lyme disease in a North American child.

Lyme disease is the most frequently reported vector-borne illness in the United States. It is caused by infection with Borrelia burgdorferi via the bite of an infected blacklegged tick (Ixodes spp.) Lyme disease has three stages: early localized, early disseminated, and late. Early disseminated Lyme disease may include neurologic manifestations such as cranial nerve palsy, meningitis, and radicular pain (also called radiculoneuritis). Isolated radiculoneuritis is a rare presentation of early disseminated Lyme disease and is likely underrecognized. We report a case of isolated Lyme radiculoneuritis in a child in Massachusetts characterized by fever and allodynia of the upper back that was treated in the emergency department. Laboratory investigation demonstrated elevated inflammatory markers and positive Lyme testing. Magnetic resonance imaging with gadolinium contrast revealed nerve root enhancement in C5-C6 and C6-C7. The symptoms resolved with oral doxycycline. Neuropathic pain should raise suspicion for neurologic manifestations of Lyme disease in North America even in the absence of meningitis and cranial nerve palsy. We report how timely recognition of this rare syndrome in North America is important and may prevent progression to late disease.

Case of an Infant with Intermittent Eye Swelling.

CASE PRESENTATION: An eight-week-old infant presented to the emergency department with two weeks of fluctuating swelling and erythema of her right upper eyelid. On examination, she had swelling of the right upper eyelid with ptosis and proptosis as well as a nevus simplex on the upper eyelid. Orbital magnetic resonance imaging demonstrated a proliferating orbital hemangioma. DISCUSSION: Periorbital erythema and swelling are often infectious or allergic, but in infants with a fluctuating course, underlying vascular malformation must be considered. Without early provider recognition, periocular hemangiomas have the potential to cause vision-related complications.

Pediatric sepsis survival in pediatric and general emergency departments.

OBJECTIVE: Understanding differences in mortality rate secondary to sepsis between pediatric and general emergency departments (EDs) would help identify strategies to improve pediatric sepsis care. We aimed to determine if pediatric sepsis mortality differs between pediatric and general EDs. METHODS: We performed a nationally representative, retrospective cohort study using the 2008-2017 Nationwide Emergency Department Sample (NEDS) to examine visits by patients less than 19 years old with a diagnostic code of severe sepsis or septic shock. We generated national estimates of study outcomes using NEDS survey weights. We compared pediatric to general EDs on the outcomes of ED mortality and hospital mortality. We determined adjusted mortality risk using logistic regression, controlling for age, gender, complex care code, and geographic region. RESULTS: There were 54,129 weighted pediatric ED visits during the study period with a diagnosis code of severe sepsis or septic shock. Of these visits, 285 died in the ED (0.58%) and 5065 died during their hospital stay (9.8%). Mortality risk prior to ED disposition in pediatric and general EDs was 0.31% and 0.72%, respectively (adjusted odds ratio (aOR), 95% confidence interval (CI): 0.36 (0.14-0.93)). Mortality risk prior to hospital discharge in pediatric and general EDs was 7.5% and 10.9%, respectively (aOR, 95% CI: 0.55 (0.41-0.72)). CONCLUSIONS: In a nationally representative sample, pediatric mortality from severe sepsis or septic shock was lower in pediatric EDs than in general EDs. Identifying features of pediatric ED care associated with improved sepsis mortality could translate into improved survival for children wherever they present with sepsis.

Effect of a Sepsis Screening Algorithm on Care of Children with False-Positive Sepsis Alerts.

OBJECTIVES: To determine if implementation of an automated sepsis screening algorithm with low positive predictive value led to inappropriate resource utilization in emergency department (ED) patients as evidenced by an increased proportion of children with false-positive sepsis screens receiving intravenous (IV) antibiotics. STUDY DESIGN: Retrospective cohort study comparing children <18 years of age presenting to an ED who triggered a false-positive sepsis alert during 2 different 5-month time periods: a silent alert period when alerts were generated but not visible to clinicians and an active alert period when alerts were visible. Primary outcome was the proportion of patients who received IV antibiotics. Secondary outcomes included proportion receiving IV fluid boluses, proportion admitted to the hospital, and ED length of stay (LOS). RESULTS: Of 1457 patients, 1277 triggered a false-positive sepsis alert in the silent and active alert periods, respectively. In multivariable models, there were no changes in the proportion administered IV antibiotics (27.0% vs 27.6%, aOR 1.1 [0.9,1.3]) or IV fluid boluses (29.7% vs 29.1%, aOR 1.0 [0.8,1.2]). Differences in ED LOS and proportion admitted to the hospital were not significant when controlling for similar changes seen across all ED encounters. CONCLUSIONS: An automated sepsis screening algorithm did not lead to changes in the proportion receiving IV antibiotics or IV fluid boluses, department LOS, or the proportion admitted to the hospital for patients with false-positive sepsis alerts.

MAPK-activated protein kinase 2 contributes to Clostridium difficile-associated inflammation.

Clostridium difficile infection (CDI) results in toxin-induced epithelial injury and marked intestinal inflammation. Fecal markers of intestinal inflammation correlate with CDI disease severity, but regulation of the inflammatory response is poorly understood. Previous studies demonstrated that C. difficile toxin TcdA activates p38 kinase in tissue culture cells and mouse ilium, resulting in interleukin-8 (IL-8) release. Here, we investigated the role of phosphorylated mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2 kinase, pMK2), a key mediator of p38-dependent inflammation, in CDI. Exposure of cultured intestinal epithelial cells to the C. difficile toxins TcdA and TcdB resulted in p38-dependent MK2 activation. Toxin-induced IL-8 and GROα release required MK2 activity. We found that p38 and MK2 are activated in response to other actin-disrupting agents, suggesting that toxin-induced cytoskeleton disruption is the trigger for kinase-dependent cytokine response. Phosphorylated MK2 was detected in the intestines of C. difficile-infected hamsters and mice, demonstrating for the first time that the pathway is activated in infected animals. Furthermore, we found that elevated pMK2 correlated with the presence of toxigenic C. difficile among 100 patient stool samples submitted for C. difficile testing. In conclusion, we find that MK2 kinase is activated by TcdA and TcdB and regulates the expression of proinflammatory cytokines. Activation of p38-MK2 in infected animals and humans suggests that this pathway is a key driver of intestinal inflammation in patients with CDI.

A soluble form of the high affinity IgE receptor, Fc-epsilon-RI, circulates in human serum.

Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum.

Relationships between levels of serum IgE, cell-bound IgE, and IgE-receptors on peripheral blood cells in a pediatric population.

BACKGROUND: Elevated serum immunoglobulin (Ig) E is a diagnostic marker of immediate-type allergic reactions. We hypothesize that serum IgE does not necessarily reflect total body IgE because in vivo IgE can be bound to cell surface receptors such as FcepsilonRI and FcepsilonRII (CD23). The aim of this study was to analyze the relationships between levels of serum IgE, cell-bound IgE, and IgE-receptors on peripheral blood cells in a pediatric population. METHODOLOGY: Whole blood samples from 48 children (26 boys, 22 girls, mean age 10,3+/-5,4 years) were analyzed by flow cytometry for FcepsilonRI, CD23, and cell-bound IgE on dendritic cells (CD11c+MHC class II+), monocytes (CD14+), basophils (CD123+MHC class II-) and neutrophils (myeloperoxidase+). Total serum IgE was measured by ELISA and converted into z-units to account for age-dependent normal ranges. Correlations were calculated using Spearman rank correlation test. PRINCIPAL FINDINGS: Dendritic cells, monocytes, basophils, and neutrophils expressed the high affinity IgE-receptor FcepsilonRI. Dendritic cells and monocytes also expressed the low affinity receptor CD23. The majority of IgE-receptor positive cells carried IgE on their surface. Expression of both IgE receptors was tightly correlated with cell-bound IgE. In general, cell-bound IgE on FcepsilonRI+ cells correlated well with serum IgE. However, some patients carried high amounts of cell-bound IgE despite low total serum IgE levels. CONCLUSION/SIGNIFICANCE: In pediatric patients, levels of age-adjusted serum IgE, cell-bound IgE, and FcepsilonRI correlate. Even in the absence of elevated levels of serum IgE, cell-bound IgE can be detected on peripheral blood cells in a subgroup of patients.

Characterization of Fusarium oxysporum f. sp. loti Forma Specialis nov., a Monophyletic Pathogen Causing Vascular Wilt of Birdsfoot Trefoil.

Fusarium wilt, a vascular wilt caused by Fusarium oxysporum, has been a serious problem for birdsfoot trefoil (Lotus corniculatus) production in parts of New York and Vermont since the 1970s, causing wilt, severe root necrosis, and rapid plant death. Analysis of F. oxysporum isolates causing this disease indicated that the pathogen has a unique host range relative to previously designated F. oxysporum formae speciales and is monophyletic. Pathogenic isolates from New York and Vermont caused severe vascular wilt of trefoil and moderate vascular wilt of pea but no disease on alfalfa, red clover, soybean, or dry bean. The host range of trefoil isolates was distinct from F. oxysporum isolates pathogenic to other legumes. F. oxysporum isolates pathogenic to trefoil belonged to a single vegetative compatibility group separate from nonpathogenic isolates and shared identical mitochondrial small subunit rDNA, translation elongation factor 1-alpha, and nuclear rDNA intergenic spacer haplotypes. Phylogenetic analysis of the concatenated sequence data assigned isolates pathogenic to trefoil to a single, well-supported clade distinct from other pathogenic F. oxysporum. We propose designating the fungus Fusarium oxysporum Schlechtendahl emend. Snyder & Hansen f. sp. loti forma specialis nova.