Resource utilization among children presenting with cannabis poisonings in the emergency department.

BACKGROUND: Exploratory pediatric cannabis poisonings are increasing. The aim of this study is to provide a national assessment of the frequency and trends of diagnostic testing and procedures in the evaluation of pediatric exploratory cannabis poisonings. METHODS: This is a retrospective cross-sectional study of the Pediatric Health Information Systems database involving all cases of cannabis poisoning for children age 0-10 years between 1/2016 and 12/2021. Cannabis poisoning trends were assessed using a negative binomial regression model. A new variable named "ancillary testing" was created to isolate testing that would not confirm the diagnosis of cannabis poisoning or be used to exclude co-ingestion of acetaminophen or aspirin. Ancillary testing was assessed with regression analyses, with ancillary testing as the outcomes and year as the predictor, to assess trends over time. RESULTS: A total of 2001 cannabis exposures among 1999 children were included. Cannabis exposures per 100,000 ED visits increased 68.7% (95% CI, 50.3, 89.3) annually. There was a median of 4 (IQR 2.0, 6.0) diagnostic tests performed per encounter. 64.5% of encounters received blood tests, 28.8% received a CT scan, and 2.4% received a lumbar puncture. Compared to White individuals, Black individuals were more likely to receive ancillary testing (OR 1.52 [95% CI, 1.23, 1.89]). Compared to those 2-6 years, those <2 years were more likely to receive ancillary testing (OR 1.55 [95% CI, 1.19, 2.02). We found no significant annual change in the odds of receiving ancillary testing (OR 1.04 [95% CI, 0.97, 1.12]). CONCLUSIONS: We found no change in the proportion of encounters associated with ancillary testing, despite increases in exploratory cannabis poisonings over the study period. Given the increasing rate of pediatric cannabis poisonings, emergency providers should consider this diagnosis early in the evaluation of a pediatric patient with acute change in mental status. While earlier use of urine drug screening may reduce ancillary testing and invasive procedures, even a positive urine drug screen does not rule out alternative pathologies and should not replace a thoughtful evaluation.

Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: a new role for lymphatic endothelial cells.

Until recently, the known roles of lymphatic endothelial cells (LECs) in immune modulation were limited to directing immune cell trafficking and passively transporting peripheral Ags to lymph nodes. Recent studies demonstrated that LECs can directly suppress dendritic cell maturation and present peripheral tissue and tumor Ags for autoreactive T cell deletion. We asked whether LECs play a constitutive role in T cell deletion under homeostatic conditions. In this study, we demonstrate that murine LECs under noninflamed conditions actively scavenge and cross-present foreign exogenous Ags to cognate CD8(+) T cells. This cross-presentation was sensitive to inhibitors of lysosomal acidification and endoplasmic reticulum-golgi transport and was TAP1 dependent. Furthermore, LECs upregulated MHC class I and the PD-1 ligand PD-L1, but not the costimulatory molecules CD40, CD80, or CD86, upon Ag-specific interactions with CD8(+) T cells. Finally, Ag-specific CD8(+) T cells that were activated by LECs underwent proliferation, with early-generation apoptosis and dysfunctionally activated phenotypes that could not be reversed by exogenous IL-2. These findings help to establish LECs as APCs that are capable of scavenging and cross-presenting exogenous Ags, in turn causing dysfunctional activation of CD8(+) T cells under homeostatic conditions. Thus, we suggest that steady-state lymphatic drainage may contribute to peripheral tolerance by delivering self-Ags to lymph node-resident leukocytes, as well as by providing constant exposure of draining peripheral Ags to LECs, which maintain tolerogenic cross-presentation of such Ags.

International Survey on the Use of Arginine Vasopressin in the Postoperative Management of Single Ventricle Patients.

Management of patients with single ventricle physiology after surgical palliation is challenging. Arginine vasopressin has gained popularity in recent years as a non-catecholamine vasoactive medication due to its unique properties. However, data regarding its use in the pediatric population is limited. Therefore, we designed a survey to explore whether and how clinicians use this medication in intensive care units for the postoperative management of single ventricle patients. This international survey aimed to assess usage, practices, and concepts related to arginine vasopressin in pediatric intensive care units worldwide. Directors of pediatric intensive care units who are members of the following international professional societies: European Society of Pediatric Neonatal Intensive Care, Association for European Pediatric and Congenital Cardiology, and Pediatric Cardiac Intensive Care Society were invited to participate in this survey. Of the 62 intensive care unit directors who responded, nearly half use arginine vasopressin in the postoperative management of neonatal single ventricle patients, and 90% also use the drug in subsequent surgical palliation. The primary indications are vasoplegia, hemodynamic instability, and refractory shock, although it is still considered a second-line medication. Conceptual benefits include improved hemodynamics and end-organ perfusion and decreased incidence of low cardiac output syndrome. Those practitioners who do not use arginine vasopressin cite lack of availability, fear of potential adverse effects, unclear indication for use, and lack of evidence suggesting improved outcomes. Both users and non-users described increased myocardial afterload and extreme vasoconstriction as potential disadvantages of the medication. Despite the lack of conclusive data demonstrating enhanced clinical outcomes, our study found arginine vasopressin is used widely in the care of infants and children with single ventricle physiology after the first stage and subsequent palliative surgeries. While many intensive care units use this medication, few had protocols, offering an area for further growth and development.

Trends in Management of Simple Febrile Seizures at US Children's Hospitals.

OBJECTIVE: We sought to measure trends in evaluation and management of children with simple febrile seizures (SFSs) before and after the American Academy of Pediatrics updated guidelines published in 2011. METHODS: In this retrospective, cross-sectional analysis, we used the Pediatric Health Information System database comprising 49 tertiary care pediatric hospitals in the United States from 2005 to 2019. We included children aged 6 to 60 months with an emergency department visit for first SFS identified using codes from the International Classification of Diseases, Ninth Revision, and International Classification of Diseases 10th Revision. RESULTS: We identified 142 121 children (median age 21 months, 42.4% female) with an emergency department visit for SFS. A total of 49 668 (35.0%) children presented before and 92 453 (65.1%) after the guideline. The rate of lumbar puncture for all ages declined from 11.6% (95% confidence interval [CI], 10.8% to 12.4%) in 2005 to 0.6% (95% CI, 0.5% to 0.8%) in 2019 (P < .001). Similar reductions were noted in rates of head computed tomography (10.6% to 1.6%; P < .001), complete blood cell count (38.8% to 10.9%; P < .001), hospital admission (19.2% to 5.2%; P < .001), and mean costs ($1523 to $601; P < .001). Reductions in all outcomes began before, and continued after, the publication of the American Academy of Pediatrics guideline. There was no significant change in delayed diagnosis of bacterial meningitis (preperiod 2 of 49 668 [0.0040%; 95% CI, 0.00049% to 0.015%], postperiod 3 of 92 453 [0.0032%; 95% CI, 0.00066% to 0.0094%]; P = .99). CONCLUSIONS: Diagnostic testing, hospital admission, and costs decreased over the study period, without a concomitant increase in delayed diagnosis of bacterial meningitis. These data suggest most children with SFSs can be safely managed without lumber puncture or other diagnostic testing.

A Randomized Double Blind Trial of Needle-free Injected Lidocaine Versus Topical Anesthesia for Infant Lumbar Puncture.

OBJECTIVES: Lumbar punctures (LPs) are commonly performed in febrile infants to evaluate for meningitis, and local anesthesia increases the likelihood of LP success. Traditional methods of local anesthesia require injection that may be painful or topical application that is not effective immediately. Recent advances in needle-free jet injection may offer a rapid alternative to these modalities. We compared a needle-free jet-injection system (J-Tip) with 1% buffered lidocaine to topical anesthetic (TA) cream for local anesthesia in infant LPs. METHODS: This was a single-center randomized double-blind trial of J-Tip versus TA for infant LPs in an urban tertiary care children's hospital emergency department. A computer randomization model was used to allocate patients to either intervention. Patients aged 0 to 4 months were randomized to J-Tip syringe containing 1% lidocaine and a placebo TA cream or J-Tip syringe containing saline and TA. The primary outcome was the difference between the Neonatal Faces Coding Scale (NFCS) before the procedure and during LP needle insertion. Secondary outcomes included changes in heart rate (HR) and NFCS throughout the procedure, difficulty with LP, number of LP attempts, provider impression of pain control, additional use of lidocaine, skin changes at LP site, and LP success. RESULTS: We enrolled 66 subjects; 32 were randomized to J-Tip with lidocaine and 34 to EMLA. Six participants were excluded from the final analysis due to age greater than 4 months, and the remaining 58 were analyzed in their respective groups (32 J-Tip, 34 TA). There was no difference detected in NFCS between the two treatment groups before the procedure and during needle insertion for the LP (p = 0.58, p = 0.37). Neither HR nor NCFS differed among the groups throughout the procedure. Median perception of pain control by the provider and the need for additional lidocaine were comparable across groups. LPs performed with a J-Tip were twice as likely to be successful compared to those performed using TA (relative risk = 2.0; 95% confidence interval = 1.01-3.93; p = 0.04) with no difference in level of training or number of prior LPs performed by providers. CONCLUSIONS: In a randomized controlled trial of two modalities for local anesthesia in infant LPs, J-Tip was not superior to TA cream as measured by pain control or physiologic changes. Infant LPs performed with J-Tip were twice as likely to be successful.

VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics.

Tumor expression of the lymphangiogenic factor VEGF-C is correlated with metastasis and poor prognosis, and although VEGF-C enhances transport to the draining lymph node (dLN) and antigen exposure to the adaptive immune system, its role in tumor immunity remains unexplored. Here, we demonstrate that VEGF-C promotes immune tolerance in murine melanoma. In B16 F10 melanomas expressing a foreign antigen (OVA), VEGF-C protected tumors against preexisting antitumor immunity and promoted local deletion of OVA-specific CD8(+) T cells. Naive OVA-specific CD8(+) T cells, transferred into tumor-bearing mice, were dysfunctionally activated and apoptotic. Lymphatic endothelial cells (LECs) in dLNs cross-presented OVA, and naive LECs scavenge and cross-present OVA in vitro. Cross-presenting LECs drove the proliferation and apoptosis of OVA-specific CD8(+) T cells ex vivo. Our findings introduce a tumor-promoting role for lymphatics in the tumor and dLN and suggest that lymphatic endothelium in the local microenvironment may be a target for immunomodulation.