Tuft cells mediate commensal remodeling of the small intestinal antimicrobial landscape.

Succinate produced by the commensal protist Tritrichomonas musculis (T. mu) stimulates chemosensory tuft cells, resulting in intestinal type 2 immunity. Tuft cells express the succinate receptor SUCNR1, yet this receptor does not mediate antihelminth immunity nor alter protist colonization. Here, we report that microbial-derived succinate increases Paneth cell numbers and profoundly alters the antimicrobial peptide (AMP) landscape in the small intestine. Succinate was sufficient to drive this epithelial remodeling, but not in mice lacking tuft cell chemosensory components required to detect this metabolite. Tuft cells respond to succinate by stimulating type 2 immunity, leading to interleukin-13-mediated epithelial and AMP expression changes. Moreover, type 2 immunity decreases the total number of mucosa-associated bacteria and alters the small intestinal microbiota composition. Finally, tuft cells can detect short-term bacterial dysbiosis that leads to a spike in luminal succinate levels and modulate AMP production in response. These findings demonstrate that a single metabolite produced by commensals can markedly shift the intestinal AMP profile and suggest that tuft cells utilize SUCNR1 and succinate sensing to modulate bacterial homeostasis.

Direct thrombin inhibitors fail to reverse the negative effects of heparin on lung growth and function after murine left pneumonectomy.

Neonates with congenital diaphragmatic hernia (CDH) frequently require cardiopulmonary bypass and systemic anticoagulation. We previously demonstrated that even subtherapeutic heparin impairs lung growth and function in a murine model of compensatory lung growth (CLG). The direct thrombin inhibitors (DTIs) bivalirudin and argatroban preserved growth in this model. Although DTIs are increasingly used for systemic anticoagulation clinically, patients with CDH may still receive heparin. In this experiment, lung endothelial cell proliferation was assessed following treatment with heparin-alone or mixed with increasing concentrations of bivalirudin or argatroban. The effects of subtherapeutic heparin with or without DTIs in the CLG model were also investigated. C57BL/6J mice underwent left pneumonectomy and subcutaneous implantation of osmotic pumps. Pumps were preloaded with normal saline, bivalirudin, or argatroban; treated animals received daily intraperitoneal low-dose heparin. In vitro, heparin-alone decreased endothelial cell proliferation and increased apoptosis. The effect of heparin on proliferation, but not apoptosis, was reversed by the addition of bivalirudin and argatroban. In vivo, low-dose heparin decreased lung volume compared with saline-treated controls. All three groups that received heparin demonstrated decreased lung function on pulmonary function testing and impaired exercise performance on treadmill tolerance testing. These findings correlated with decreases in alveolarization, vascularization, angiogenic signaling, and gene expression in the heparin-exposed groups. Together, these data suggest that bivalirudin and argatroban fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of low-dose heparin with DTIs on CDH outcomes are warranted.NEW & NOTEWORTHY Infants with pulmonary hypoplasia frequently require cardiopulmonary bypass and systemic anticoagulation. We investigate the effects of simultaneous exposure to heparin and direct thrombin inhibitors (DTIs) on lung growth and pulmonary function in a murine model of compensatory lung growth (CGL). Our data suggest that DTIs fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of heparin with DTIs on clinical outcomes are thus warranted.

A Medium-Chain Fatty Acid Analogue Prevents Intestinal Failure-Associated Liver Disease in Preterm Yorkshire Piglets.

BACKGROUND & AIMS: At least 20%-30% of patients with intestinal failure receiving long-term parenteral nutrition will develop intestinal failure-associated liver disease (IFALD), for which there are few therapeutic options. SEFA-6179 is a first-in-class structurally engineered medium-chain fatty acid analogue that acts through GPR84, PPARα, and PPARγ agonism. We hypothesized that SEFA-6179 would prevent biochemical and histologic liver injury in a preterm piglet model of IFALD. METHODS: Preterm Yorkshire piglets were delivered by cesarean section, and parenteral nutrition was provided for 14 days via implanted central venous catheters. Animals were treated with either medium-chain triglyceride vehicle control or SEFA-6179. RESULTS: Compared to medium-chain triglyceride vehicle at day of life 15, SEFA-6179 prevented biochemical cholestasis (direct bilirubin: 1.9 vs <0.2 mg/dL, P = .01; total bilirubin: 2.7 vs 0.4 mg/dL, P = .02; gamma glutamyl transferase: 172 vs 30 U/L, P = .01). SEFA-6179 also prevented steatosis (45.6 vs 13.9 mg triglycerides/g liver tissue, P = .009), reduced bile duct proliferation (1.6% vs 0.5% area cytokeratin 7 positive, P = .009), and reduced fibrosis assessed by a masked pathologist (median Ishak score: 3 vs 1, P = 0.007). RNA sequencing of liver tissue demonstrated that SEFA-6179 broadly impacted inflammatory, metabolic, and fibrotic pathways, consistent with its in vitro receptor activity (GPR84/PPARα/PPARγ agonist). CONCLUSIONS: In a preterm piglet model of IFALD, SEFA-6179 treatment prevented biochemical cholestasis and steatosis and reduced bile duct proliferation and fibrosis. SEFA-6179 is a promising first-in-class therapy for the prevention and treatment of IFALD that will be investigated in an upcoming phase II clinical trial.

Assessment of rare bleeding disorders in adolescents with heavy menstrual bleeding.

INTRODUCTION: There are a significant number of patients with mucocutaneous bleeding, specifically heavy menstrual bleeding (HMB), who do not have a diagnosed bleeding disorder. These patients receive nontargeted interventions and may have suboptimal treatments. Functional assays, particularly for fibrinolytic and rare platelet function defects, are not robust and not readily available. AIM: We aimed to prospectively evaluate the prevalence of genetic defects associated with rare bleeding disorders and describe alterations of coagulation and fibrinolysis in a cohort of adolescents with HMB. METHODS: We performed a prospective observational cohort study of patients with HMB and unexplained bleeding. The study utilized a next generation sequencing panel and investigational global assays of coagulation and fibrinolysis. Additionally, specific functional assays were performed to help characterize novel variants that were identified. RESULTS: In 10 of the 17 patients (∼59%), genetic variants were identified on molecular testing. Thrombin generation by calibrated thromboelastography was not significantly altered in this patient population. The clot formation and lysis assay showed a trend towards increased fibrinolysis with rapid phase of decline in 23% of the patients. Further corresponding functional assays and study population are described. CONCLUSION: Our study describes a unique correlative model in a homogenous cohort of patients with HMB and unexplained bleeding which may inform future diagnostic algorithms, genotype-phenotype correlations as well as aid in specific targeted treatment approaches. Larger future studies may inform risk stratification of patients and improve health related outcomes in patients with HMB.

Use of central venous access devices outside of the pediatric intensive care units.

BACKGROUND: Central venous access devices (CVAD) are associated with central line associated bloodstream infection (CLABSI) and venous thromboembolism (VTE). We identified trends in non-intensive care unit (ICU) CVAD utilization, described complication rates, and compared resources between low and high CVAD sites. METHODS: We combined data from the Pediatric Health Information System (PHIS) database and surveys from included hospitals. We analyzed 10-year trends in CVAD encounters for non-ICU children between 01/2012-12/2021 and described variation and complication rates between 01/2017-12/2021. Using Fisher's exact test, we compared resources between low and high CVAD users. RESULTS: CVAD use decreased from 6.3% to 3.8% of hospitalizations over 10 years. From 2017-2021, 67,830 encounters with CVAD were identified. Median age was 7 (IQR 2-13) years; 46% were female. Significant variation in CVAD utilization exists (range 1.4-16.9%). Rates of CLABSI and VTE were 4.0% and 3.4%, respectively. Survey responses from 33/41 (80%) hospitals showed 91% had vascular access teams, 30% used vascular access selection guides, and 70% used midline/long peripheral catheters. Low CVAD users were more likely to have a team guiding device selection (100% vs 43%, p = 0.026). CONCLUSIONS: CVAD utilization decreased over time. Significant variation in CVAD use remains and may be associated with hospital resources. IMPACT: Central venous access device (CVAD) use outside of the ICU is trending down; however, significant variation exists between institutions. Children with CVADs hospitalized on the acute care units had a CLABSI rate of 4% and VTE rate of 3.4%. 91% of surveyed institutions have a vascular access team; however, the services provided vary between institutions. Even though 70% of the surveyed institutions have the ability to place midline/long peripheral catheters, the majority use these catheters less than a few times per month. Institutions with low CVAD use are more likely to have a vascular access team that guides device selection.

A serum-induced gene signature in hepatocytes is associated with pediatric nonalcoholic fatty liver disease.

OBJECTIVE: Pediatric nonalcoholic fatty liver disease (NAFLD) is a growing problem, but its underlying mechanisms are poorly understood. We used transcriptomic reporter cell assays to investigate differences in transcriptional signatures induced in hepatocyte reporter cells by the sera of children with and without NAFLD. METHODS: We studied serum samples from 45 children with NAFLD and 28 children without NAFLD. The sera were used to induce gene expression in cultured HepaRG cells and RNA-sequencing was used to determine gene expression. Computational techniques were used to compare gene expression patterns. RESULTS: Sera from children with NAFLD induced the expression of 195 genes that were significantly differentially expressed in hepatocytes compared to controls with obesity. NAFLD was associated with increased expression of genes promoting inflammation, collagen synthesis, and extracellular matrix remodeling. Additionally, there was lower expression of genes involved in endobiotic and xenobiotic metabolism, and downregulation of peroxisome function, oxidative phosphorylation, and xenobiotic, bile acid, and fatty acid metabolism. A 13-gene signature, including upregulation of TREM1 and MMP1 and downregulation of CYP2C9, was consistently associated with all diagnostic categories of pediatric NAFLD. CONCLUSION: The extracellular milieu of sera from children with NAFLD induced specific gene profiles distinguishable by a hepatocyte reporter system. Circulating factors may contribute to inflammation and extracellular matrix remodeling and impair xenobiotic and endobiotic metabolism in pediatric NAFLD.

Operative Complications, Vaginal Bleeding, and Practice Considerations for Patients on Testosterone Undergoing Gender-Affirming Hysterectomy.

STUDY OBJECTIVE: To evaluate operative complications and healthcare utilization in transgender patients on testosterone undergoing minimally invasive gender-affirming hysterectomy compared to control patients. DESIGN: We performed a retrospective cohort study. Operative reports were used to gather information on intraoperative complications. We collected information on postoperative complications, electronic medical record (EMR) messages, phone calls, emergency department utilization, and clinic visits through a 90-day postoperative period. Healthcare utilization reasons were categorized as vaginal bleeding, pain, vaginal discharge, dysuria, urinary retention, bowel concern, incision concern, or other. SETTING: Tertiary care academic medical center. PATIENTS: Patients aged 18 to 55 who underwent a benign minimally invasive hysterectomy with or without oophorectomy performed between January 2014 and December 2022. The testosterone-using cohort consisted of patients who had a gender identity of male, transgender male, genderqueer, or nonbinary with documented testosterone use prior to surgery (n = 88). The control cohort consisted of patients who identified as female, genderqueer, or nonbinary with no documented testosterone use (n = 242). INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Patients using testosterone were younger, had a lower body mass index, lower American Society of Anesthesiologists class, and were more likely to be nulliparous. The median time patients used testosterone was 2.5 years (1.5-5.0). Patients on testosterone are at increased risk of intraoperative perineal lacerations requiring repair (RR 3.3, CI 95% [1.03-10.5]). A higher number of patients on testosterone reported vaginal bleeding via EMR message or phone call (RR 1.74 CI 95% [1.1-2.7]) compared to controls. No difference in reasons for emergency department visits was noted. The use of postoperative vaginal estrogen started at the postoperative visit was more frequent in the testosterone-using patients (7 [8.0%] vs 4 [1.7%], p = .01). CONCLUSION: This study demonstrates that testosterone use preoperatively may increase risk of intraoperative vaginal laceration requiring repair. Testosterone use also correlates with increased reports of vaginal bleeding through EMR message, phone call, and clinic visit. These results contribute new evidence to include in preoperative counseling and support existing evidence surrounding the safety of gender-affirming hysterectomy.

Pediatric dermatofibromas: Truncal predominance in younger children.

Pediatric dermatofibromas are considered rare in young children and have not been well characterized, often misdiagnosed clinically. We performed a retrospective case series of children younger than 18 years with histopathologically diagnosed dermatofibromas at our institutions and evaluated age at onset and diagnosis, sex, lesion location, and size, associated symptoms, change over time, and pre-biopsy diagnosis. Overall, dermatofibromas were most common on the back and chest (20/53; 38%), followed by the legs (15/53; 28%) and arms (12/53; 23%) with the most common pre-biopsy diagnosis of "cyst" (23/53; 43%), followed by dermatofibroma (16/53; 30%), and pilomatricoma (12/53; 23%). Our study reinforces previous findings of truncal predominance of pediatric dermatofibromas, different from adults.

Multimodal Assessment and Intramodal Comparison of Imaging Techniques for Pediatric Pulmonary Vein Stenosis with Pulmonary Hypertension.

Pulmonary vein stenosis (PVS) is a rare, serious, and progressive disease in the pediatric population. Evaluation is complex and involves multimodality imaging. Diagnosis is important as early treatment to prevent progressive pulmonary hypertension and right ventricular dysfunction is essential. Adult studies have shown good correlation between various imaging modalities; however, there are limited data in children. This is a single-center retrospective pilot study to determine the reliability of measurement of pulmonary vein stenosis and pulmonary hypertension across different imaging modalities-computed tomography angiography (CTA), echocardiography (echo), lung perfusion scan (LPS), and cardiac catheterization (cath). PVS was defined as > 2 mmHg by echo and cath and/or 50% reduction in diameter by CTA. Patients had to have an echo, CTA and cath performed within a 1-month timeframe of one another to be included in the study, with LPS data included if testing was completed at initial evaluation. Fifteen total patients were enrolled; 87% were categorized as primary PVS; a condition not directly related to direct injury or prior surgical intervention. Twenty-seven total stenotic pulmonary veins were identified (mean 1.8, range 1-4). CTA had a slightly better agreement with cath than echo in identifying PVS in different vein locations except in the LLPV. Additionally, echo and CTA had excellent sensitivity (91%) and specificity (100%) compared to cath for diagnosis of PH. We conclude that non-invasive imaging of echo and CTA has an acceptable correlation to cardiac catheterization for screening and initial evaluation of PVS and PH, as directly related to PVS, in pediatrics.

Profibrotic COVID-19 subphenotype exhibits enhanced localized ER-dependent HSP47+ expression in cardiac myofibroblasts in situ.

We recently described a subgroup of autopsied COVID-19 subjects (∼40%), termed 'profibrotic phenotype,' who exhibited clusters of myofibroblasts (Mfbs), which were positive for the collagen-specific chaperone heat shock protein 47 (HSP47+) in situ. This report identifies increased, localized (hot spot restricted) expression of αSMA, COLα1, POSTN and FAP supporting the identity of HSP47+ cells as myofibroblasts and characterizing a profibrotic extracellular matrix (ECM) phenotype. Coupled with increased GRP78 in COVID-19 subjects, these data could reflect induction of the unfolded protein response for mitigation of proteostasis (i.e., protein homeostasis) dysfunction in discrete clusters of cells. ECM shifts in selected COVID-19 subjects occur without significant increases in either global trichrome positive staining or myocardial injury based quantitively on standard H&E scoring. Our findings also suggest distinct mechanism(s) for ECM remodeling in the setting of SARS-CoV-2 infection. The ratio of CD163+/CD68+ cells is increased in hot spots of profibrotic hearts compared with either controls or outside of hot spots in COVID-19 subjects. In sum, matrix remodeling of human COVID-19 hearts in situ is characterized by site-restricted profibrotic mediated (e.g., HSP47+ Mfbs, CD163+ Mφs) modifications in ECM (i.e., COLα1, POSTN, FAP), with a strong correlation between COLα1 and HSP47+cells within hot spots. Given the established associations of viral infection (e.g., human immunodeficiency virus; HIV), myocardial fibrosis and sudden cardiac death, early screening tools (e.g., plasma biomarkers, noninvasive cardiac magnetic resonance imaging) for diagnosis, monitoring and treatment of fibrotic ECM remodeling are warranted for COVID-19 high-risk populations.

A Digestive Cartridge Reduces Parenteral Nutrition Dependence and Increases Bowel Growth in a Piglet Short Bowel Model.

OBJECTIVE: To determine whether the use of an immobilized lipase cartridge (ILC) to hydrolyze fats in enteral nutrition (EN) reduces parenteral nutrition (PN) dependence in a porcine model of short bowel syndrome with intestinal failure (SBS-IF). BACKGROUND: SBS-IF occurs after intestinal loss resulting in malabsorption and PN dependence. Limited therapeutic options are available for achieving enteral autonomy. METHODS: Eleven Yorkshire piglets underwent 75% jejunoileal resection and were randomized into control (n=6) and treatment (n = 5) groups. PN was initiated postoperatively and reduced as EN advanced if predefined clinical criteria were fulfilled. Animals were studied for 14 days and changes in PN/EN calories were assessed. Intestinal adaptation, absorption, and nutrition were evaluated at the end of the study (day 15). Comparisons between groups were performed using analysis of covariance adjusted for baseline. RESULTS: ILC animals demonstrated a 19% greater reduction in PN calories ( P < 0.0001) and higher mean EN advancement (66% vs 47% of total calories, P < 0.0001) during the 14-day experiment. Treatment animals had increased intestinal length (19.5 vs 0.7%, P =0.03) and 1.9-fold higher crypt cell proliferation ( P =0.02) compared with controls. By day 15, ILC treatment resulted in higher plasma concentrations of glucagon-like peptide-2 ( P = 0.02), eicosapentaenoic acid ( P < 0.0001), docosahexaenoic acid ( P = 0.004), vitamin A ( P = 0.02), low-density lipoprotein ( P = 0.02), and high-density lipoprotein ( P = 0.04). There were no differences in liver enzymes or total bilirubin between the two groups. CONCLUSIONS: ILC use in conjunction with enteral feeding reduced PN dependence, improved nutrient absorption, and increased bowel growth in a porcine SBS-IF model. These results support a potential role for the ILC in clinical SBS-IF.

Effects of systemic anticoagulation in a murine model of compensatory lung growth.

BACKGROUND: Neonates with congenital diaphragmatic hernia (CDH) suffer from pulmonary hypoplasia (PH) and may require extracorporeal membrane oxygenation (ECMO) and anticoagulation, often with unfractionated heparin (UFH). UFH interacts with vascular endothelial growth factor (VEGF), a factor important in lung development. We investigated the effects of UFH, low molecular weight heparin (LMWH), and bivalirudin (BV) on a murine model of compensatory lung growth (CLG). METHODS: Proliferation and apoptosis were assessed in microvascular lung endothelial cells (HMVEC-L) treated with anticoagulants. Eight-week-old C57Bl/6J mice underwent left pneumonectomy and anticoagulation with low- or high-dose UFH, LMWH, BV, or saline control. Lung volume, pulmonary function tests, morphometrics, treadmill exercise tolerance, and pulmonary protein expression were examined. RESULTS: UFH and LMWH inhibited HMVEC-L proliferation. BV promoted proliferation and decreased apoptosis. UFH and LMWH-treated mice had reduced lung volume, total lung capacity, alveolar volume, and septal surface area compared to controls, while BV did not affect these measures. UFH and LMWH-treated mice had lower exercise tolerance compared to controls. CONCLUSIONS: UFH and LMWH impair pulmonary growth, alveolarization, and exercise tolerance, while BV does not. Alternative anticoagulants to heparin may be considered to improve functional outcomes for neonates with CDH and pulmonary hypoplasia. IMPACT: Unfractionated heparin and low molecular weight heparin may modify compensatory lung growth by reducing microvascular lung endothelial cell proliferation and affecting pulmonary angiogenic signaling. Functional effects of unfractionated heparin and low molecular weight heparin on murine compensatory lung growth include reduction in exercise tolerance. Bivalirudin, a direct thrombin inhibitor, may increase microvascular lung endothelial cell proliferation and preserves lung volume, alveolarization, and exercise tolerance in a murine compensatory lung growth model. Anticoagulants alternative to heparin should be further investigated for use in neonates with pulmonary hypoplastic diseases to optimize lung growth and development and improve outcomes.

Pharmacogenetic profiling via genome sequencing in children with medical complexity.

BACKGROUND: Children with medical complexity (CMC) are a priority pediatric population, with high resource use and associated costs. Genome-wide sequencing is increasingly organized for CMC early in life as a diagnostic test. Polypharmacy becomes common as CMC age. Clinically relevant pharmacogenetic (PGx) information can be extracted from existing genome sequencing (GS) data via GS-PGx profiling. The role of GS-PGx profiling in the CMC population is unclear. METHODS: Prescribed medications were extracted from care plans of 802 eligible CMC enrolled in a structured Complex Care Program over a 10-year period. Drug-gene associations were annotated using curated Clinical Pharmacogenetics Implementation Consortium data. GS-PGx profiling was then performed for a subset of 50 CMC. RESULTS: Overall, 546 CMC (68%) were prescribed at least one medication with an established PGx association. In the GS-PGx subgroup, 24 (48%) carried variants in pharmacogenes with drug-gene guidelines for one or more of their current medications. All had findings of potential relevance to some medications, including 32 (64%) with variants in CYP2C19 that could affect their metabolism of proton-pump inhibitors. CONCLUSION: GS-PGx profiling at the time of diagnostics-focused genetic testing could be an efficient way to incorporate precision prescribing practices into the lifelong care of CMC. IMPACT: Polypharmacy and genetic test utilization are both common in children with medical complexity. The role of repurposing genome sequencing data for pharmacogenetic profiling in children with medical complexity was previously unclear. We identified a high rate of medication use with clinically relevant drug-gene associations in this priority pediatric population and demonstrated that relevant pharmacogenetic information can be extracted from their existing genome sequencing data. Pharmacogenetic profiling at the time of diagnostics-focused genetic testing could be an efficient way to incorporate precision prescribing practices into the lifelong care of children with medical complexity.

Implementation of a Bleeding Risk Screening Tool and Hematology Referral Process Prior to Pediatric Endoscopy.

OBJECTIVES: Gastrointestinal (GI) endoscopic procedures are considered low risk with an overall bleeding risk for upper and lower endoscopies of 0.11%. However, a certain population of patients may have a higher risk for bleeding, and there is not a standardized process for screening patients to determine who these patients are. METHODS: At Children's Wisconsin, our gastroenterology and hematology divisions adapted an abbreviated version of a validated, history-based bleeding risk screening tool and implemented a hematology referral process to identify those at risk for bleeding prior to their first endoscopy. Provider compliance with the bleeding screen, referral to hematology, time to be seen in hematology clinic, new diagnoses of bleeding disorders, and bleeding complications were assessed from 2019 to 2021 across 3 phases. RESULTS: Provider compliance with the bleeding screen improved throughout our study from 48% (120/251) to 75% (189/253). For those who screened positive, compliance with referral to hematology ranged from 38% to 74% across our phases. The overall time to be seen by hematology decreased from 30 days to 7.5 days. Eighteen patients ultimately screened positive and were seen in hematology clinic, of whom 22% (4/18) were diagnosed with a new bleeding disorder. No bleeding complications were seen in our study population. CONCLUSIONS: Our quality improvement project provided a standardized screening tool to assess preoperative bleeding risk and reinforced the value of a history-based screening tool. This modified screening tool identified those with an undiagnosed bleeding disorder and preventative measures were undertaken to prevent procedural bleeding complications.

A Cross-Sectional Study of Pediatric Feeding Disorder in Children with Cystic Fibrosis.

BACKGROUND: The exact prevalence of feeding problems in children with cystic fibrosis (CF) is unknown. Pediatric feeding disorder (PFD) encompasses poor oral intake with associated medical, nutrition, psychosocial, or feeding skill dysfunction. We hypothesized that PFD is common in CF and aimed to categorize feeding dysfunction across various domains in children with CF. METHODS: An observational cross-sectional study was conducted in children with CF. Data collected included anthropometrics, nutrition data (including need for tube feeding/enteral nutrition [EN] or high-energy beverages, dietary diversity), feeding skills (Pediatric version of the Eating Assessment tool [pEAT]), and psychosocial function (About Your Child's Eating questionnaire [AYCE] in children 2-17 years of age/Behavioral Pediatric Feeding Assessment Scale [BPFAS] in children 12-23 months of age). PFD was defined as poor oral intake with: (a) pEAT score > 5; and/or (b) AYCE or BPFAS score > 2 standard deviation of normative controls; and/or (c) nutrition dysfunction (body mass index/weight-for-length z score < -1 and/or preference of oral high energy beverages or dependence on EN and/or decreased dietary diversity). RESULTS: Of 103 children in the study, 62 (60.1%) had PFD, 7 children (6.8%) were malnourished, 10 needed EN (9.7%), and 30 (29.1%) needed oral high-energy beverages. Dietary diversity was decreased in 42 children (41.5%), 1 child had feeding skill dysfunction, and 11 (10.8%) met criteria for psychosocial dysfunction. CONCLUSION: Almost 2/3rd of children with CF have PFD and many have poor dietary diversity. A significant percentage of children rely on EN and oral supplements, but psychosocial dysfunction is less prevalent.

Adolescent Drug Ingestions Requiring ICU Stay: Single-Center Retrospective Cohort Study.

OBJECTIVES: Ingestions are a prevalent form of self-harm in teenagers and are unfortunately an increasingly common reason for admission to both acute care and critical care services. The goal of this study was to identify characteristics associated with requiring PICU stay among adolescents hospitalized for ingestions. DESIGN: Retrospective cohort study comparing patients admitted to hospital medicine service and critical care service from January 2019 to December 2019. SETTING: Freestanding children's hospital in the midwestern United States. PATIENTS: Adolescents 12-18 years old hospitalized for ingestion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 209 patients included in the study cohort, 95 required PICU admission. High-risk behaviors (having had sex or usage of alcohol, drugs, tobacco, or vaping) were endorsed by 190 of 209 patients (91%). We compared patient characteristics, ingestion history, workup, and pharmacological and PICU-specific interventions between patients hospitalized on the hospital medicine service and the PICU. We failed to identify an association between reason for ingestion, substance ingested, and previously identified suicide risk factors including previous suicide attempt, previous self-harm, and psychiatric comorbidity and admission to PICU, as opposed to non-PICU admission. PICU stay was associated with longer peak corrected QT interval value, receiving a pharmacological intervention, and longer duration of hospital stay. Fifteen of 95 patients (16% [95% CI, 9-25%]) in the PICU received a PICU-specific intervention. CONCLUSIONS: We failed to identify specific patient demographics or mental behavioral health characteristics associated with PICU stay after ingestion. Therefore, we believe that all adolescents hospitalized due to ingestion-irrespective of disposition-should receive standardized high-risk behavior screening due to the pervasive nature of these behaviors among this patient population. PICU-specific care, beyond observation, could be needed in as high as one-in-four PICU admissions. Further research is needed to inform optimal disposition and resource allocation for this patient population.

Intralesional measles, mumps, and rubella vaccine after failure of intralesional Candida antigen for the treatment of recalcitrant pediatric warts.

Numerous studies have investigated the efficacy of intralesional immunotherapy for warts, but there are a lack of studies investigating the efficacy of alternative intralesional immunotherapies following failure of initial intralesional immunotherapy. In this retrospective study, we aimed to investigate the efficacy of intralesional measles, mumps, and rubella vaccine for the treatment of pediatric warts following failure of intralesional therapy with Candida antigen. Following intralesional measles, mumps, and rubella vaccine administration, 8/51 (15.5%) patients had complete resolution of their warts, 6/51 (12%) had near complete resolution, 19/51 (37%) had partial improvement, 12/51 (23.5%) had no change, and 6/51 (12%) had worsening. Although limited by retrospective nature and low sample size, our results demonstrate that intralesional immunotherapy with measles, mumps, and rubella vaccine provides an alternative therapeutic option for the treatment of recalcitrant pediatric warts in patients who fail to respond to intralesional Candida antigen.

Vaccines and use of immunosuppressive and immunomodulatory therapy in a pediatric dermatology clinic-A single institution experience.

Vaccine type and timing are critical issues to prevent unintended infections in those on immunosuppressive therapies. We retrospectively chart reviewed patients at Children's Wisconsin Pediatric Dermatology Clinic on immunosuppressives and immunomodulators between 11/1/2012 and 6/1/2020 and found that approximately 76% of patient encounters do not have documented vaccine counseling in the medical chart before initiation of immunosuppressives and immunomodulators. As age increased, vaccine counseling was less likely to be documented (odds ratio: 0.89; 95% confidence interval: 0.84-0.95, p = .001). In addition, 13 patient encounters (4%) were not up to date with live vaccines before immunosuppressive or immunomodulating therapy. There is an opportunity to improve clinical processes to ensure documentation of vaccination status and vaccine counseling before starting immunosuppressive and immunomodulator medications in a pediatric dermatology clinic.

Clinical Variables Associated with Pre-Fontan Aortopulmonary Collateral Burden.

Aortopulmonary collaterals (APCs) develop universally, but to varying degrees, in patients with single ventricle congenital heart disease (CHD). Despite their ubiquitous presence, APCs remain poorly understood. We sought to evaluate the association between APC burden and common non-invasive clinical variables. We conducted a single center, retrospective study of patients with single ventricle CHD and previous Glenn palliation who underwent pre-Fontan cardiac magnetic resonance (CMR) imaging from 3/2018 to 3/2021. CMR was used to quantify APC flow, which was normalized to aortic (APC/QAo) and pulmonary vein (APC/QPV) blood flow. Univariate, multivariable, and classification and regression tree (CART) analyses were done to investigate the potential relationship between CMR-quantified APC burden and clinical variables. A total of 29 patients were included, all of whom had increased APC flow (APC/QAo: 26.9, [22.0, 39.1]%; APC/QPV: 39.4 [33.3, 46.9]%), but to varying degrees (APC/QAo: range 11.9-44.4%; APC/QPV: range 17.7-60.0%). Pulmonary artery size (Nakata index, at pre-Fontan CMR) was the only variable associated with APC flow on multivariable analysis (APC/QAo: p = 0.020, R2 = 0.19; APC/QPV: p = 0.0006, R2 = 0.36) and was the most important variable associated with APC burden identified by CART analysis (size inversely related to APC flow). APC flow is universally increased but highly variable in patients with single ventricle CHD and Glenn circulation. Small branch pulmonary artery size is a key factor associated with increased APC burden; however, the pathogenesis of APCs is likely multifactorial. Further research is needed to better understand APC pathogenesis, including predisposing and mitigating factors.

Respiratory viral infections are prevalent but uncomplicated in single ventricle CHD.

BACKGROUND: Patients with single ventricle CHD have significant morbidity and healthcare utilisation throughout their lifetime, including non-cardiac hospital admissions. Respiratory viral infections are the main cause of hospitalisation in children, but few data exist for single ventricle patients. We sought to identify how respiratory viral infections impact patients with single ventricle CHD and potential differences between Glenn and Fontan circulation. METHODS: We conducted a retrospective study of patients seen from 01/01/2011-12/31/2020. We identified patients with a history of single ventricle CHD and Glenn palliation, and a normoxic control group with isolated atrial septal defect requiring surgical closure. We compared viral-related clinical presentations, admissions, and admission characteristics. RESULTS: A total of 312 patients were included (182 single ventricle, 130 atrial septal defect). Single ventricle patients were more likely than children with isolated atrial septal defect to be admitted with a respiratory virus (odds ratio 4.15 [2.30-7.46]), but there was no difference in mechanical ventilation or hospital length of stay (p = 0.4709). Single ventricle patients with Glenn circulation were more likely than those with Fontan circulation to present and be admitted (odds ratio 3.25 [1.62-6.52]), but there was no difference in ICU admission, mechanical ventilation, or hospital length of stay (p = 0.1516). CONCLUSIONS: Respiratory viral infections are prevalent but uncomplicated in patients with single ventricle CHD. Viral-related presentations and admissions are more prevalent during the period of Glenn circulation compared to Fontan circulation; however, rate of mechanical ventilation and hospital length of stay are similar.