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Introduction: Dexmedetomidine (DEX) use in children receiving noninvasive ventilation such as BiPAP and CPAP has been reported to be effective for achieving patient tolerance of the interface. DEX use in HFNC has not been described though it is anecdotally used with the thought that it helps alleviate anxiety and agitation impeding effective respiratory effort. Our primary aim was to describe the use of DEX in children with bronchiolitis requiring HFNC. Our secondary objective was to compare characteristics and outcomes between patients who received DEX to those that did not. Methods: We performed a single center, retrospective cohort study using the Virtual Pediatric Systems (VPS) database from 2018-2024. All patients admitted to our pediatric intensive care unit with a diagnosis of bronchiolitis and requiring the use of HFNC were included. Univariate analyses were performed to compare characteristics and outcomes between patients who received DEX and those that did not. Significant factors identified in the univariate analyses were used in multivariate analyses to confirm the independent associations with the use of DEX. Results: Among 1,756 children admitted to the PICU with bronchiolitis, 699 (39.8%) received DEX. The DEX group had a higher proportion of male patients (63.3% vs. 55.5%, p=0.002) and more frequent diagnoses of bronchiolitis due to RSV (70.3% vs. 44.8%, p< 0.001). PRISM III risk of mortality was slightly higher in the DEX group (median 0.56 vs. 0.51, p< 0.001). Use of DEX was associated with increased rate of escalation from HFNC to NIPPV (6.3% vs. 3.5%, p=0.01) and from HFNC to IMV (7.4% vs. 4.3%, p=0.02). PICU length of stay was slightly longer in the DEX group (median 2.51 vs. 2.13 days, p< 0.001), though hospital LOS was not significantly different. Logistic regression adjusting for age, sex, and PRISM III risk of mortality showed that DEX use was associated with increased odds of escalation from HFNC to NIPPV (adjusted OR 1.77, 95% CI 1.10–2.85), and from HFNC to IMV (adjusted OR 1.77, 95% CI 1.15–2.74). Conclusions: Our findings show that DEX use was associated with increased escalation of respiratory support. Future work, including multicenter analyses, is necessary to further characterize the role of DEX in escalation of respiratory support in children with bronchiolitis.

Background: Dysregulated inflammation and oxidative stress are strongly implicated in the pathogenesis of inflammatory bowel disease. We have developed a novel therapeutic that targets inflammation and oxidative stress. It is comprised of microRNA-146a (miR146a)-loaded cerium oxide nanoparticles (CNPs) (CNP-miR146a). We hypothesized that oral delivery of CNP-miR146a would reduce colonic inflammation in a mouse model of established, chronic, T cell-mediated colitis. Methods: The stability of CNP-miR146a and mucosal delivery was assessed in vitro with simulated gastrointestinal fluid and in vivo after oral gavage by quantitative real-time RT-PCR. The efficacy of orally administered CNP-miR146a was tested in mice with established colitis using the model of adoptive naïve T-cell transfer in recombinant activating gene 2 knockout (Rag2-/-) mice. Measured outcomes included histopathology; CD45+ immune cell infiltration; oxidative DNA damage (tissue 8-hydroxy-2'-deoxyguanosine; 8-OHdG); expression of IL-6 and TNF mRNA and protein, and flow cytometry analysis of lamina propria Th1 and Th17 cell populations. Results: miR146a expression remained stable in simulated gastric and intestinal conditions. miR146a expression increased in the intestines of mice six hours following oral gavage of CNP-miR146a. Oral delivery of CNP-miR146a in mice with colitis was associated with reduced inflammation and oxidative stress in the proximal and distal colons as evidenced by histopathology scoring, reduced immune cell infiltration, reduced IL-6 and TNF expression, and decreased populations of CD4+Tbet+IFNg+ Th1, CD4+RorgT+IL17+ Th17, as well as pathogenic double positive IFNg+IL17+ T cells. Conclusions: CNP-miR146a represents a novel orally available therapeutic with high potential to advance into clinical trials.

Twenty-one pediatric and young adult patients (1.1–24.7 years) with hematologic malignancies underwent myeloablative T-cell replete haploidentical bone marrow transplant (haplo-BMT) between October 2015 to December 2019. Fifty-seven percent of the patients were ethnic or racial minorities. Thirteen patients had B-cell precursor acute lymphoblastic leukemia (B-ALL) with 10 receiving 1,200 cGy fractionated total body irradiation with fludarabine while the remaining 11 patients had targeted dose-busulfan, fludarabine, melphalan conditioning. Graft-vs.-host disease (GvHD) prophylaxis consisted of post-transplant cyclophosphamide (15 patients) or cyclophosphamide and bendamustine (six patients), with all patients receiving tacrolimus and mycophenolate mofetil. Twelve patients were in first or second remission at time of transplant with five in >2nd remission and four with measurable disease. Three patients had failed prior transplants and three CAR-T cell therapies. Only one patient developed primary graft failure but engrafted promptly after a second conditioned T-replete peripheral blood stem cell transplant from the same donor. An absolute neutrophil count of 0.5 × 109/L was achieved at a median time of 16 days post-BMT while platelet engraftment occurred at a median of 30 days. The cumulative incidence of grades III to IV acute GvHD and chronic GvHD was 15.2 and 18.1%, respectively. With a median follow-up of 25.1 months the relapse rate is 17.6% with an overall survival of 84.0% and a progression-free survival of 74.3%. The chronic graft-vs.-host-free relapse-free survival (CRFS) is 58.5% while acute and chronic graft-vs.-host-free relapse-free survival (GRFS) is 50.1%. Myeloablative conditioned T-replete haploidentical BMT is a viable alternative to matched unrelated transplantation for children and young adults with high-risk hematologic malignancies.

PurposeThere is a lack of scholarly reports on pediatric emergency department (PED) exposure to hyperbilirubinemia. We aimed to describe the epidemiology of hyperbilirubinemia in patients presenting to a PED over a three-year period.MethodsThis was a retrospective cohort study, completed at an urban quaternary academic PED. Patients were included if they presented to the PED from 2010 to 2012, were 0 to 18 years in age, and had an elevated serum bilirubin for age. A chart review was completed to determine the incidence of hyperbilirubinemia, etiology, diagnostic work up and prognosis. The data set was stratified into four age ranges.ResultsWe identified 1,534 visits where a patient was found to have hyperbilirubinemia (0.8% of all visits). In 47.7% of patients hyperbilirubinemia was determined to have arisen from an identifiable pathologic etiology (0.38% of all visits). First-time diagnosis of pathologic hyperbilirubinemia occurred in 14% of hyperbilirubinemia visits (0.11% of all visits). There were varying etiologies of hyperbilirubinemia across age groups but a male predominance in all (55.0%). 15 patients went on to have a liver transplant and 20 patients died. First-time pathologic hyperbilirubinemia patients had a mortality rate of 0.95% for their initial hospitalization.ConclusionHyperbilirubinemia was not a common presentation to the PED and a minority of cases were pathologic in etiology. The etiologies of hyperbilirubinemia varied across each of our study age groups. A new discovery of pathologic hyperbilirubinemia and progression to liver transplant or death during the initial presentation was extremely rare.

Hypokalemia in children following cardiac surgery occurs frequently, placing them at risk of life-threatening arrhythmias. However, renal insufficiency after cardiopulmonary bypass warrants careful administration of potassium (K+). Two different nurse-driven protocols (high dose and tiered dosing) were implemented to identify an optimal K+ replacement regimen, compared to an historical low-dose protocol. Our objective was to evaluate the safety, efficacy, and timeliness of these protocols. A retrospective cohort review of pediatric patients placed on intravenous K+ replacement protocols over 1 year was used to determine efficacy and safety of the protocols. A prospective single-blinded review of K+ repletion was used to determine timeliness. Pediatric patients with congenital or acquired cardiac disease. Twenty-four-bed cardiothoracic intensive care unit in a tertiary children's hospital. Efficacy was defined as fewer supplemental potassium chloride (KCl) doses, as well as a higher protocol to total doses ratio per patient. Safety was defined as a lower percentage of serum K+ levels ≥4.8 mEq/L after a dose of KCl. Between-group differences were assessed by nonparametric univariate analysis. There were 138 patients with a median age of 3.0 (interquartile range: 0.23-10.0) months. The incidence of K+ levels ≥4.8 mEq/L after a protocol dose was higher in the high-dose protocol versus the tiered-dosing protocol but not different between the low-dose and tiered-dosing protocols (high dose = 2.2% vs tiered dosing = 0.5%, P = .05). The ratio of protocol doses to total doses per patient was lower in the low-dose protocol compared to the tiered-dosing protocol (P < .05). Protocol doses were administered 45 minutes faster (P < .001). The tiered-dosed, nurse-driven K+ replacement protocol was associated with decreased supplemental K+ doses without increased risk of hyperkalemia, administering doses faster than individually ordered doses; the protocol was effective, safe, and timely in the treatment of hypokalemia in pediatric patients after cardiac surgery.

The current gold standard for pediatric complete and partial nephrectomy is the open surgical approach. Despite its short surgical times and excellent long-term outcomes, the open surgical approach has historically been associated with increased hospital stays and morbidity. The open approach often requires the patients to be on high doses of narcotics for postoperative pain management. This, in turn, has led to increased postoperative complications of refractory pain and constipation, which could potentially lead to readmission for their treatment. Laparoscopy provides an alternative approach in performing complete and partial nephrectomy. This approach is associated with less pain, shorter hospitalization, and more rapid recovery time compared to its open counterpart. However, laparoscopy is technically more demanding, leading to potentially higher rates of intraoperative complications, surgical time, and costs.

To determine whether utilization of a hospital-based clinical practice guideline for the care of pediatric iatrogenic opioid dependence (IOD) would promote a decrease in opioid exposure and improve management of opioid abstinence syndrome (AS). This study is a retrospective chart review of critically ill patients from a tertiary care children's hospital. Inclusion criteria included mechanically ventilated patients up to 18 years of age who received continuous opioid infusions for at least 7 days and any length of methadone administration. Data on IOD patients from January 2005 to June 2010 was divided into 3 periods: baseline, phase 1, and phase 2. Primary outcome was decrease in opioid exposure, measured by methadone duration of use and any additional opioid bolus doses used in AS management. Documentation of additional opioid bolus doses was regarded as a surrogate measure of AS. Secondary outcomes included total cumulative fentanyl dose, continuous fentanyl infusion duration of use, and hospital and pediatric intensive care unit length of stay. There was a significant decrease in methadone duration of use in IOD patients from 15.3 ± 8.7 days at baseline to 9.5 ± 3.7 days during phase 1 (p = 0.002), to 8.1 ± 3.7 days on phase 2 (reduction not significant, p = 0.106) of this evaluation. Additional opioid bolus doses were significantly lower from baseline to phase 1 (5.5 ± 5.1 vs. 1.8 ± 2.3, p = 0.001) and from phase 1 to phase 2 (1.8 ± 2.3 vs. 0.2 ± 1.5, p = 0.003). For the remaining outcomes, differences were not observed among the evaluation periods, except for the total cumulative fentanyl dose, which was reduced from 2.8 ± 3.7 mg/kg at baseline to 1 ± 1 mg/kg only during phase 1 (p = 0.017). Introduction of a standardized, hospital-based clinical practice guideline for children with IOD reduced the length of exposure to opioids and improved opioid AS management.