BACKGROUND:Early documentation of energy goals has been associated with better nutrition outcomes. We performed a successful project improving the rate of early documentation of energy goals from 30% to 97%. We then conducted a retrospective study of children admitted to the pediatric intensive care unit (PICU) the year before and after intervention to determine whether we improved initiation and delivery of nutrition. MATERIALS AND METHODS:We identified patients with PICU length of stay (LOS) of at least 48 h from Virtual Pediatrics Systems, LLC (VPS) from May 2020 to April 2022. We obtained clinical, demographic, and nutrition data for the first 96 h of admission from the electronic medical record and VPS. We defined early enteral nutrition (EEN) as delivery of 25% of goal calories within 48 h of admission. We analyzed data using Mann-Whitney test for continuous variables and chi-square test for categorical variables and multivariable regression analyses. RESULTS:A total of 1510 patients were included (702 preintervention, 808 postintervention). Median ICU LOS (4.05 vs 3.64 days; P = 0.030) and hospital LOS (8.25 vs 6.99 days; P = 0.009) were significantly reduced. EEN was significantly more likely to be initiated in the postintervention group than in the preintervention group (P < 0.0001), adjusted for age, sex, race, ethnicity, Pediatric Index of Mortality 3 (PIM3) score, and documentation of energy goal. CONCLUSION:Energy goal documentation improved EEN initiation and demonstrated shorter LOS in multivariable analysis. Findings highlight need for standardized documentation, greater dietitian involvement, and further study of how nutrition planning affects outcomes in critically ill children.
BACKGROUND:Expected ranges for several inflammatory markers in children were poorly defined during the COVID-19 pandemic, making it difficult to distinguish common infections from multisystem inflammatory syndrome in children (MIS-C). We evaluated less commonly obtained inflammatory markers in children with common bacterial infections. METHODS:We completed a retrospective cohort study at a tertiary children's hospital from March 2018 through April 2023 of hospitalized patients >60 days to 21 years with cellulitis, community-acquired pneumonia, or urinary tract infection. RESULTS:A total of 973 patients were included (median age, 5.6 years; interquartile range, 1.9-12.2; 61% female). Most inflammatory markers were elevated across infections, whereas troponin levels remained within the reference range for all diagnoses. DISCUSSION:We report values for less commonly obtained inflammatory markers in children hospitalized with common bacterial infections. Normal troponin levels may help distinguish these infections from MIS-C, which more commonly involves cardiac inflammation. Further research is needed to define clinically useful cutoff values for inflammatory markers to aid decision-making in the setting of emerging disease processes.
Background/Objectives: Increasing popularity, convenience, and access to processed foods are shifting the composition of dietary intake from whole to ultra-processed foods (UPF). This study aimed to assess the association between periconceptional UPF consumption and the incidence of adverse pregnancy outcomes (APOs). Methods: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). Patients were excluded if they were missing periconceptional diet data or if their pregnancy ended before 20 weeks. Food Frequency Questionnaire items were categorized using the NOVA Scale to calculate the proportion of total energy intake comprised of UPF (% kcal/day). Bivariate and multivariate analyses examined the relationships between UPF intake and preterm birth, hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), small-for-gestational-age (SGA) infants, large-for-gestational-age (LGA) infants, and fetal or neonatal demise. Results: A total of 6693 participants were included in the analysis. The sample was predominantly White (78%) and not Hispanic (84%), and a majority of participants had commercial insurance (76%). UPF accounted for an average of 51.3 ± 12.7% of participants' daily total energy intake. Mean UPF intake was higher among patients who identified as Black or non-Hispanic, patients with public insurance, less than a high school education, a household income below the federal poverty level (all p-values < 0.001), patients with chronic hypertension (p = 0.02), and patients who delivered vaginally (p = 0.002). Patients with preterm birth, HDP, SGA infants, and fetal or neonatal demise all had significantly higher proportions of daily UPF intake compared to patients without these adverse outcomes. After adjusting for potential confounders, higher UPF intake remained significantly associated with preterm birth (AOR 1.11, 95% CI 1.02-1.21) and HDP (AOR 1.05, 95% CI 1.001-1.11). Conclusions: On average, more than half of participants' daily energy intake was from UPF, and higher UPF intake correlated with several adverse pregnancy outcomes. Future efforts should focus on improving nutritional literacy regarding UPF consumption in pregnancy.
[This corrects the article DOI: 10.3389/fgwh.2026.1849806.].
BACKGROUND:Children with CHD are at increased risk for feeding difficulties, yet the prevalence and predictors of paediatric feeding disorder in this population remain underexplored. OBJECTIVE:To evaluate the prevalence of paediatric feeding disorder and identify consistent predictors of feeding difficulties in children with CHD 18-<25 months of age. METHODS:A retrospective review was conducted on 159 children diagnosed with CHD. Paediatric feeding disorder was defined using consensus criteria encompassing nutritional status and feeding skill domains. Feeding outcomes were assessed at 18-<25 months, regardless of the method of feeding (oral or tube-fed). Medical history, growth, and neurodevelopmental status were analysed to identify predictors of paediatric feeding disorder. RESULTS:At 18-<25 months, 58% of children met criteria for paediatric feeding disorder. Among exclusively orally fed children, 41% still qualified, indicating persistent dysfunction beyond tube dependence. Significant challenges were observed in nutrition and feeding skill domains. One-third relied on formula and overnight feeds, reflecting high energy needs and possibly inefficiencies. While 74% had transitioned to cup drinking, 21% struggled, particularly those born preterm or with neurodevelopmental delays. Texture progression was delayed: 29% had no table foods, and among those who did, 67% had chewing difficulties. Predictors of paediatric feeding disorder included medical/genetic comorbidities, low weight, prolonged hospitalisation, low maternal education, and delays in cognitive, language, and motor development. CONCLUSIONS:Paediatric feeding disorder is highly prevalent in children with CHD, including those feeding orally. Early risk factors are associated with domain-specific feeding challenges, emphasising the need for individualised, developmentally informed feeding and nutrition care plans in this high-risk population.
Background: Many barriers exist in disseminating the results of successful penicillin allergy delabels and preventing relabels. Methods: This study used electronic faxing to directly communicate the completion of successful direct oral challenges in children hospitalized or in the emergency department to outpatient pharmacies and out-of-network primary care providers. Results: This communication led to a decreased rate of the penicillin allergy label presence in pharmacy records, from 32% (36/112) to 12% (16/136) (p < 0.001). In conjunction with more conventional discharge communication mechanisms, allergy removal rates improved, from 61% (19/31) to 90% (18/20) (p = 0.029) for out-of-network primary care providers. Conclusion: This study demonstrated that the reliable, simple, and time-efficient direct communication between independent health-care systems and pharmacies can be successful when implemented in a streamlined bundled approach.
Endothelial cells (ECs) in the brain communicate with mural cells to facilitate vascular stability. Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) signaling mechanism at EC-mural cell interface helps stabilize the vasculature. How this paracrine signaling is mediated is not known. Our laboratory studies endothelial cilia, a microtubule-based organelle, and its role in promoting vascular stability. We discovered that brain endothelial cilia are located primarily on the basolateral side, and PDGF-BB is expressed in EC cilium. Thus, we hypothesized that endothelium cilium in conjunction with PDGF-BB on the basolateral side is responsible for mural cell recruitment. In this study, using a combination of zebrafish, mice, and human brain model systems, we have established a signaling paradigm wherein p21-activated kinase (PAK2) and ADP-ribosylation factor-13b (ARL13b) in ECs induce secretion of PDGF-BB. PDGF-BB associates with heparan sulfate proteoglycans (HSPGs) to form a gradient around ECs. Disrupting PAK2 affects ciliogenesis, HSPGs, and PDGF-BB gradient. We unravel a new mechanism involving endothelial cilia/PAK2-mediated PDGF-BB secretion, and retention by periendothelial HSPGs to promote vascular stability via recruiting mural cells.
BACKGROUND:Chimeric antigen receptor (CAR) T-cell therapy has expanded rapidly as an investigational treatment for advanced cancers. Studies in acute lymphoblastic leukemia (ALL) suggest health-related quality of life (HRQOL) may improve by 1-month post-infusion. However, patient-reported outcomes remain insufficiently characterized, particularly across the broader pediatric CAR T-cell population. PROCEDURE:English- or Spanish-speaking patients (ages 8-25 years) receiving CAR T-cell therapy for any malignancy were recruited from three US pediatric cancer centers. Patient-reported HRQOL (PedsQL) and symptom burden (Memorial Symptom Assessment Scale [MSAS]) were assessed serially through 12 months post-infusion, emphasizing the first month. Linear mixed models characterized score trajectories and examined associations between symptom burden and HRQOL. RESULTS:Fifty-nine patients completed baseline HRQOL assessments; 41% were treated for ALL. Median age was 17 years and 46% identified as female. Participants completed a median of six assessments, with nearly 75% obtained within the first month. Scores were worst at baseline (mean [SD]: PedsQL Generic: 64.9 [18.4], PedsQL Cancer: 70.0 [16.2], MSAS: 24.4 [19.4]) and improved post-infusion. The greatest gains from baseline to 4 weeks were seen in physical functioning (mean + 8) and worry (mean + 20). Across all timepoints, the most burdensome symptoms were fatigue, worry, pain, nervousness, and anorexia. Symptom burden demonstrated a strong negative correlation with HRQOL (r = - 0.81, p < 0.0001). CONCLUSIONS:Pediatric patients undergoing CAR T-cell therapy experience generally favorable HRQOL trajectories and modest, time-limited symptom burden. Serial patient-reported outcome collection is feasible in this population and provides actionable insight to guide supportive care delivery.
Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality, highlighting the need for effective methods to detect early identification and intervention. Previous data demonstrates that endothelial cilia, a microtubule-based organelle is responsible for vascular stability. Thus, we rationalized that proteins inside endothelial cilia may be candidates for conditions affected by dysregulated flow and barrier formation. Protein expression of four ciliary-associated candidates, including Platelet-Derived Growth Factor-BB (PDGF-BB), were quantified using Western blot and enzyme-linked immunosorbent assay (ELISA). Baseline characteristics were compared across groups, and logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate the association between PDGF-BB levels and PPH risk. Baseline characteristics were comparable across groups, except for maternal race and pre-pregnancy body mass index. Among the proteins evaluated, PDGF-BB demonstrated consistent differential expression across both analytical platforms. Higher PDGF-BB levels were independently associated with a lower risk of PPH in both unadjusted and adjusted models (adjusted OR 0.62, 95% CI 0.44-0.88; p = 0.0068). ROC analysis identified a PDGF-BB threshold of 11.5 pg/mL, yielding high discriminatory performance for PPH. These findings may suggest that low levels of PDGF-BB may be associated with risk of PPH, providing a potential early biomarker for this condition to inform management. Further prospective studies are needed to confirm the temporal relationship, causal pathway, and diagnostic utility of PDGF-BB for risk of PPH.
Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by sickle-shaped red blood cells (RBCs). Primary cilia are mechanosensory organelles and are projected in the lumen of blood vessels to detect blood flow. We previously reported that interaction between microvasculature endothelial cells and sickled RBCs resulted in altered blood flow that can elevate reactive oxygen species, leading to increased deciliation in SCD patients. However, the impact of deciliation mediated by sickled RBCs in the context of the ciliary protein profiles remains unclear. Here, we investigated cell-cilia stability under different physiological shear-stress magnitudes and examined cilia protein profiles in SCD, utilizing mouse models and human participants. Our results demonstrate that subjecting endothelial cilia to sickled RBCs at 5.0 dyn/cm2 led to significant deciliation events. The proteomic and bioinformatic analyses showed different ciliary protein profiles, distinct signaling pathways, and unique post-translational modification processes in the SCD mouse model. Consistent with the SCD mouse model results, our translational studies validated the enrichment of specific proteins, including Transferrin Receptor-1 (TfR1), Glyceraldehyde-3-Phosphate-Dehydrogenase (GAPDH), and ADP Ribosylation Factor Like GTPase-13B (ARL13B) in SCD patients. These findings underscore the clinical relevance of cilia in SCD and suggest that ciliary proteins are potential biomarkers for assessing vascular damage.
OBJECTIVE: To assess the association between mode of delivery and 2-year motor function in children with prenatal diagnosis of myelomeningocele. METHODS: A multisite retrospective cohort study of children with myelomeningocele across 14 NAFTNet (North American Fetal Therapy Network) centers born between 2007 and 2020 who had a physical examination available at 2 years of life. Exclusion criteria were in utero myelomeningocele repair, postnatal myelomeningocele diagnosis, missing data on fetal presentation at delivery, and contraindications to labor. The primary outcome was the difference between the anatomic level of the spinal lesion and functional motor level at age 2 years. A general linear model was used to determine the effect of mode of delivery on the primary outcome, and multivariable analysis was performed to control for presence of labor, gestational age at delivery, defect size and origin level, and presence of ventriculomegaly. RESULTS: Of 566 children with myelomeningocele, 305 met inclusion criteria, with 216 (70.8%) having been delivered by cesarean and 89 (29.2%) having been delivered vaginally. Children delivered by cesarean had a mean±SE level of motor function of 0.07±0.21 segments below the anatomic level at age 2 years compared with 0.57±0.32 for children delivered vaginally (P=.19). After controlling for potential confounders, both groups improved in motor function by age 2 years compared with anatomic level. However, there was no difference in motor improvement between groups by mode of delivery (0.07 cesarean vs 0.57 vaginal delivery, adjusted difference 0.37 segments, P=.63). CONCLUSION: In this multisite NAFTNet cohort, mode of delivery was not associated with lower-extremity motor function at age 2 years.
Dupilumab is an IL-4Rα and IL-13 inhibitor FDA-approved for the treatment of atopic dermatitis (AD) in patients 6 months and older. Guidelines recommend against live-attenuated vaccines due to limited safety data. We conducted a retrospective chart review of 233 patients aged 6 months to 10 years receiving dupilumab for AD at Children's Wisconsin, which showed that 19 received live vaccines during the study period. Four patients reported adverse events, including one requiring hospitalization. This study aims to evaluate the effects of live vaccines in children on dupilumab therapy and to assess associated adverse events, including in patients receiving their primary series of vaccines, a setting not previously described.
Clostridioides difficile is an obligate anaerobe and is primarily transmitted via the fecal–oral route. Data characterizing the microbiome changes accompanying transitions from non-colonized to C. difficile colonized subjects are currently lacking. In this retrospective cohort study, we examined 16S rRNA gene sequencing data in a total of 481 fecal samples belonging to 107 patients. Based on C. difficile status over time, patients were categorized as Negative-to-Positive, Negative Control, and Positive Control. A linear mixed effects model was fitted to investigate the changes in the Shannon α-diversity index over time. Zero-inflated negative binomial/Poisson mixed effects models or generalized linear mixed models with negative binomial/Poisson distribution were used to investigate the changes in taxon counts over time among different groups. A total of 107 patients were eligible for the study. The median number of stool samples per patient was 3 (IQR 2–4). A total of 42 patients transitioned from C. difficile negative to positive (Negative-to-Positive), 47 patients remained negative throughout their tests (Negative Control) and 18 were always C. difficile positive (Positive Control). A significant difference in microbiome composition between the last negative samples and the first positive samples were shown in Negative-to-Positive patients, ANOSIM p = 0.022. In Negative-to-Positive patients, the phylum Pseudomonadota and family Enterobacteriaceae increased significantly in the first positive samples compared to the last negative samples, p = 0.0075 and p = 0.0094, respectively. Within the first 21 days, Actinomycetota decreased significantly over time in the Positive Control group compared to the other two groups (p < 0.001) while Bacillota decreased in both the Negative-to-Positive group and Positive Control. These results demonstrate that the transition from C. difficile negative to C. difficile positive is associated with alterations in gut microbial communities and their compositional patterns over time. Moreover, these changes play an important role in both the emergence and intensification of the gut microbiome dysbiosis in patients who transitioned from C. difficile negative to positive and those who always tested positive.
BACKGROUND:Spontaneous hemoptysis is a well-recognized risk of palliated single ventricle circulation, yet published literature is limited to case reports and small case series. In this study, we sought to determine the long-term prevalence of spontaneous hemoptysis among patients with palliated single ventricle circulation at a single institution. Secondarily, we sought to characterize the clinical outcomes after spontaneous hemoptysis. METHODS:We conducted a retrospective study of patients with a history of Glenn or Fontan palliation seen from January 1, 1990 to January 21, 2023. Episodes of spontaneous hemoptysis were identified through 2 independent database screens that queried International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes and electronic medical records for "pulmonary hemorrhage" and "hemoptysis." Positive screens were subsequently confirmed or reclassified by manual chart review. RESULTS:Of 799 patients with palliated single ventricle circulation, 10.9% (87/799) screened positive for hemoptysis. Following verification with manual chart review, 3.4% (27/799) of patients with palliated single ventricle circulation had spontaneous hemoptysis. A total of 61 episodes of spontaneous hemoptysis occurred in 27 patients. Of all hemoptysis episodes, 83.6% (51/61) occurred after Fontan palliation. Of patients with hemoptysis, 51.9% (14/27) had multiple episodes of hemoptysis with recurrence at a median of 0.6 years (range 1 day-8.5 years) after the first episode. CONCLUSIONS:To our knowledge, this is the first study that quantifies prevalence of hemoptysis in a large cohort of patients with palliated single ventricle circulation. Overall, prevalence of spontaneous hemoptysis was low (3.4%) among patients with palliated single ventricle circulation and there was a moderate rate of recurrence (51.9%).
Objective: To comparematernal and neonatal outcomes in patients diagnosed with gestational hypertension or preeclampsia without severe features by outpatient versus inpatient management. Materials and methods: This was a single center, retrospective, cohort study of patients with hypertensive disorder of pregnancy (HDP) before 37 weeks' gestation from January 2014 to March 2022. Patients were triaged to inpatient or outpatient management at the discretion of their obstetrician. Patients with an initial presentation of severe features were excluded. Bivariate and multivariate analyses were used to compare the primary outcome, severe maternal morbidity (SMM) as defined by one or more of the 21 CDC maternal morbidity identifiers, and the secondary outcomes of maternal ICU admission, development of severe features, placental abruption, time from diagnosis to giving birth, preterm birth < 37 weeks, low birthweight (<2500 g), 5-minute Apgar score < 7, and stillbirth. Results: A total of 272 patients met the inclusion criteria with 229 (84.2 %) being managed outpatient and 43 (15.8 %) managed inpatient. In univariate analysis, outpatient management was associated with lower incidence of SMM, an increased interval from diagnosis of HDP to giving birth, an increased interval to onset of severe features, and a lower incidence of maternal ICU admission. In multivariate analysis, outpatient management remained associated with lower odds of SMM, (aOR 0.18, 95 % CI 0.05-0.59) and improved neonatal outcomes with lower incidence of 5-minute APGAR score less than 7 (aOR 0.32, 95 % CI 0.13-0.82), low birth weight (aOR 0.37 95 % CI 0.17-0.79), and preterm birth (aOR 0.31, 95 % CI 0.15-0.67). Conclusion: Outpatient management of HDP was associated with lower rates of SMM and adverse maternal and neonatal outcomes. While not all confounding factors were measured, the clinical decision regarding HDP management settings was associated with good diagnostic capability.
We compared the quantity of labs ordered in selected hospitalized children throughout the COVID-19 pandemic. Utilization of X-ray, magnetic resonance imaging (MRI), echocardiograms, and electrocardiograms (ECG), length of stay (LOS) and timing of antibiotics were secondary outcomes. Retrospective cohort study of patients >60 days to <22 years with cellulitis, pneumonia, and urinary tract infections discharged from hospital medicine March 2018 to February 2020 (pre-) March 2020 to February 2022 (peak) and March 2022 to April 2023 (post peak). Fisher-Freeman-Halton exact test was performed for categorical variables. Kruskal-Wallis test compared continuous variables. Patients admitted peak pandemic incurred more labs and ECGs and fewer MRIs and X-rays. There were no differences in echocardiograms, LOS, or timing of antibiotics. While lab utilization returned to pre-pandemic levels, increased ECG use continued. Increased lab and ECG utilization was observed in patients with certain bacterial infections during the peak of the pandemic, likely reflective of diagnostic uncertainty.
Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in the MCA compared to wildtype mice (AA) (0.67 ± 0.18 vs. 0.95 ± 0.15; p < 0.05). Comparison of the Lindegaard ratio between normoxia and hypoxia in SS mice suggested that the MCA underwent vasodilation (0.67 ± 0.18 vs. 0.95 ± 0.15; p < 0.05). Bilirubin, a potential biomarker for cerebral vasculopathies in SCD, was higher in SS than AA mice (0.56 ± 0.28 vs. 0.05 ± 0.07 mg/dL; p < 0.05). Correlation analyses revealed a significant association between bilirubin levels and blood velocities of MCA (r = −0.9377, p = 0.0002) and ICA (r = 0.8203, p = 0.0068), especially in hypoxic conditions of SS mice. We propose that the reactivity of cerebral vessels in SS mice is correlated with the elevated plasma bilirubin level.
Infants born to mothers with obesity have increased risk for later development of metabolic dysfunction-associated steatotic liver disease (MASLD); however early hepatic changes that occur in these infants remain unclear. We integrated metabolomic analysis of umbilical cord plasma and transcriptomic analysis of cord plasma-exposed hepatocytes to examine differences in the intrauterine environment of pregnancies with and without maternal obesity. We identified significantly higher abundance of fatty acids, bioactive lipids, and upregulation of glutathione metabolism in cord plasma from pregnancies with obesity compared to normal weight pregnancies. Hepatocytes exposed to cord plasma from pregnancies with obesity exhibited distinct transcriptional changes that favored cellular injury and inflammation, and impaired hepatocyte development compared to hepatocytes exposed to cord plasma of normal weight pregnancies. In integrated analysis, metabolite-gene relationships were distinct between pregnancies with and without obesity, and the abundance of lipids were positively correlated with the expression of KDM4D, DTX3, and NOTCH4 and negatively correlated with the expression of MT_TS1. Our findings provide novel insights into transcriptional changes induced in hepatocytes by circulating factors in the intrauterine environment of pregnancies with obesity. Excess intrauterine lipids may contribute to hepatic injury, inflammation, impaired mitochondrial function, and impaired hepatocyte development in infants of pregnancies with obesity.
BACKGROUND:Pediatric patients who are unable to void after orthopedic surgery can develop post-operative urinary retention (POUR). The aims of this study were to identify variables that contributed to POUR by comparing characteristics of children who did and did not require urinary intervention and to identify which variables predict patients who are at risk for POUR. METHODS:This retrospective chart review evaluated 73 pediatric patients who developed POUR after an orthopedic procedure and matched their characteristics to 73 pediatric patients who did not develop POUR. Multiple levels of analysis were performed to compare variables between groups. RESULTS:Groups were similar regarding patient characteristics of pre-op mobility, the presence of a neurological disorder, and the placement of an indwelling catheter (IUC) during surgery. The POUR group was had greater immobility after surgery (p < .001); received significantly more opioid (p < .001) for a longer period of time (p < .001). Conditional logistic regression identified post-operative immobility, opioid consumption, duration of opioid exposure, and the presence of patient-controlled analgesia (PCA) as predictors of POUR development. DISCUSSION:Nurses caring for pediatric patients following orthopedic surgery can assess for predictive factors and can plan for proactive bladder scanning to aid in early detection of POUR. This study adds to the literature by identifying comonalities in pediatric patients developing POUR after orthopedic surgery. PRACTICE IMPLICATIONS:Consideration should be given to assessing bladder fullness, establishing mobility, and reducing opioid need before removing the IUC or delaying the removal of the IUC for a short time.