Updated consensus guidelines on the management of Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.

Association Between Continuous Kidney Replacement Therapy Clearance and Outcome in Pediatric Patients With Hyperammonemia Not Due to Inborn Error of Metabolism.

OBJECTIVES: To describe a single-center experience of pediatric patients with hyperammonemia not due to inborn errors of metabolism and determine the association between use of continuous kidney replacement therapy (CKRT) treatment and outcomes. DESIGN: Retrospective cohort study. SETTING: Tertiary-care children's hospital. PATIENTS: All children less than 21 years old admitted to the hospital with hyperammonemia defined as an elevated ammonia levels (>100 µmol/L) not due to inborn error of metabolism. INTERVENTIONS: None. MEASURES AND MAIN RESULTS: Of 135 children with hyperammonemia, the most common reason for admission was infection in 57 of 135 (42%), congenital heart disease in 20 of 135 (14%), and bone marrow transplantation in 10 of 135 (7%). The overall mortality was 61% (82 of 135), which increased with degree of hyperammonemia (17 of 23 [74%] in those with ammonia >250 µmol/L). After multivariable regression, hyperammonemia severity was not associated with mortality (aOR, 1.4; 95% CI, 0.92-2.1; p = 0.11). Of the 43 patients (32%) receiving CKRT, 21 were prescribed standard clearance and 22 high clearance. The most common indications for CKRT were fluid overload in 17 of 43 (42%) and acute kidney injury or uremia in 16 of 43 (37%). Mean CKRT duration was 13 days. There was no difference between standard and high clearance groups in risk of death (76% vs 86%; p = 0.39), cerebral edema on CT scan (19% vs 27%; p = 0.52), nor decrease in ammonia levels after 24 or 48 hours of CKRT ( p = 0.20, p = 0.94). Among those receiving CKRT, we failed to find an association between high clearance and decreased risk of death in multivariable analysis (aOR, 1.2; 95% CI, 0.64-2.3; p = 0.55). CONCLUSIONS: In our single-center retrospective study, we failed to find an association between clearance on CKRT and improved survival nor decreased cerebral edema on head imaging. In fact, we failed to find an association between ammonia level and mortality, after controlling for illness severity.

Mortality, Risk Factors and Disparities Associated with Esophageal Variceal Bleeding in Children's Hospitals in the US.

OBJECTIVES: To use a large administrative database to determine the mortality, risk factors, and comorbidities of esophageal variceal bleeding in children. STUDY DESIGN: Retrospective cohort study using Pediatric Health Information System data from 50 tertiary children's hospitals in the US. International Classification of Diseases (ICD) codes (FY 2020 ICD-10 update and revision 10 of ICD-9) from 2004 through 2019 identified children 18 years and younger with variceal bleeding and complications. Univariate analyses used the Student t -test for continuous variables (age) and the χ2 test for categorical variables (all others). A mixed-effects linear regression was performed for multiple variables. RESULTS: There were 1902 patients who had 3399 encounters for esophageal variceal bleeding. The mortality rate for variceal bleeding was 7.3%, increasing to 8.8% by 6 weeks; any mortality during the study was 20.1%. Transfusion was required in 54.7% of encounters, and 42.6% were admitted to the intensive care unit. Variceal bleeding encounters were complicated by peptic ulcer disease (6.9%), bacteremia (11.4%), acute renal failure (5.1%), mechanical ventilation (18%), ascites (21.3%), and peritonitis (3.3%). Multivariable mixed-effects logistic regression showed that Black race (OR, 2.59; P < .001) or Hispanic ethnicity (OR, 2.31; P = .001), but not sex, household income, or insurance type, were associated with increased mortality. Bacteremia, peritonitis, mechanical ventilation, acute renal failure, and transfusion were associated with higher mortality (ORs of 2.29, 2.18, 1.93, 6.33, and 1.81, respectively; P < .001, .005, .011, <.001, and .005, respectively). CONCLUSIONS: The 6-week mortality rate for variceal bleeding in children is 8.8%. Black or Hispanic children are at higher risk of dying. Serious morbidities associated with variceal hemorrhage impact mortality. These data can inform consideration of prophylactic or therapeutic interventions for children at risk.

Factors Affecting Higher Readmission Rates and Costs in Pediatric Patients With Hirschsprung Disease.

BACKGROUND: Hirschsprung disease is a relatively uncommon disorder of the developing gastrointestinal tract that requires surgical intervention to restore long-term function. While readmission for Hirschsprung-related complications is a known concern in these patients, we sought to identify patient-level factors associated with a prolonged hospital stay, increased costs at the time of a pull-through operation, as well as the risk for all-cause inpatient readmission after surgery. We hypothesized that higher level of care requirement during the operative stay, age at operation, and length of stay (LOS) would portend increased readmissions and disease-related complications such as Hirschsprung-associated enterocolitis. METHODS: Data was obtained from the Pediatric Health Information System database on all Hirschprung patients who underwent a pull-through operation between 2004 and 2019. Regression analyses were performed on this cohort of 3345 patients. Multivariable regression models were utilized to analyze the key outcome variables of postoperative LOS and adjusted charges. RESULTS: Post-operative LOS was significantly increased by the presence of a surgical complication, congenital/genetic defect, or neurologic/neuromuscular defect. Increased LOS was also seen in Black patients. The cost of pull-through operations was significantly higher in patients admitted to the NICU and ICU during index hospitalization, with a cost increase of approximately $75,000 and $57,000 respectively. Presence of a surgical complication, comorbid congenital/genetic defect, and need for mechanical ventilation were associated with higher odds of inpatient readmission. CONCLUSION: The management of patients with Hirschsprung disease is longitudinal and complex. Identification of key patient metrics can aid clinicians in developing targeted care and education strategies to minimize readmission and excessive hospital charges.

The Effects of Patient Demographics on Outpatient Endoscopy Utilization in Children With Eosinophilic Esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that requires esophagogastroduodenoscopy (EGD) for diagnosis and treatment monitoring. We aimed to identify the frequency of endoscopic monitoring in children with EoE and observe the effect of age, race, socioeconomic factors, and atopy on the rate of endoscopy. METHODS: We queried the Pediatric Health Information System over a 15-year period for ambulatory EGDs in children with EoE. Subjects with at least 1 year of data were included. Age, sex, ethnicity, race, insurance type, median household income, and atopy were collected for each subject. RESULTS: 16,517 subjects were included (mean age 8.5 years). 3211 (19%) of subjects had ≥1 EGD per subject year (EGD/SY). Subjects >13 years old were more likely to have ≥1 EGD/SY compared to children 6-12 years (odds ratio [OR] 2.29, P < 0.001, 95% confidence interval [CI] = 2.06-2.54). Males were more likely to have ≥1 EGD/SY compared to females (OR 1.19, P < 0.001, 95% CI = 1.08-1.31). African-American subjects were 16% less likely than Caucasian subjects to have ≥1 EGD/SY (OR 0.84, P = 0.05, 95% CI = 0.71-1.00). Subjects with allergic rhinitis or anaphylaxis, food allergy, and/or oral allergy syndrome were more likely to have ≥1 EGD/SY (OR 1.67, P < 0.001, 95% CI = 1.47-1.90 and OR 3.65, P < 0.001, 95% CI = 3.25-4.11, respectively). CONCLUSIONS: Nineteen percent of subjects had ≥1 EGD/SY. Older age, male sex, allergic rhinitis, and food allergies were associated with more frequent endoscopic monitoring in children with EoE. Caucasian subjects had more frequent endoscopy than African-American subjects. This study raises awareness about underrecognized variation in the care of children with EoE.

Inadequate Bowel Preparation in Pediatric Colonoscopy-Prospective Study of Potential Causes.

OBJECTIVES: Inadequate bowel preparation (IBP) for colonoscopy leads to missed diagnosis, longer anesthesia time, higher chance of complications and increased costs. Adult studies have demonstrated that patient characteristics such as male gender and obesity are associated with IBP. Little is known about factors affecting bowel preparation in children. Our aim was to determine factors associated with IBP in children. METHODS: We prospectively enrolled children undergoing outpatient colonoscopy. Quality of bowel preparation was assessed using Boston Bowel Preparation Scale (BBPS) score (range 0-9). Data collected included patient demographics, indication, and type of insurance. Patients were divided into two groups based on BBPS score-adequate (BBPS score > 5) and inadequate (BBPS score < 5) and groups were compared using Student t-test and chi-square test. Possible predictors were analyzed using multivariate logistic regression models. RESULTS: A total of 334 children were prospectively enrolled of whom 321 were studied further (age range 2-18 years; mean age 12.4 years; 60.4% female; 85.9% Caucasian). The mean BBPS score was 6.8 (standard deviation of ±2). IBP was reported in 12.8% (41/321). Multivariable logistic regression analysis did not show statistical differences between the groups in studied patient factors including age, gender, obesity, race, insurance type, and indication for colonoscopy. CONCLUSION: Contrary to several adult studies, the results of our prospective study did not show any relationship between examined patient factors and IBP in children. Interestingly, IBP was less prevalent in our pediatric study compared to published adult data (12.8% vs 20-40%).

Variation in hospital admission from the emergency department for children with cancer: A Pediatric Health Information System study.

BACKGROUND: Children with cancer experience a wide range of conditions that require urgent evaluation in the emergency department (ED), yet variation in admission rates is poorly documented. PROCEDURE: We performed a retrospective cohort study using the Pediatric Health Information System of ED encounters by children with cancer between July 2012 and June 2015. We compared demographics for admitted versus discharged using univariate statistics, and calculated admission rates by hospital, diagnosis, day of the week, and weekend versus weekday. We assessed the degree of interhospital admission rates using the index of dispersion (ID). RESULTS: Children with cancer had 60 054 ED encounters at 37 hospitals. Overall, 62.5% were admitted (range 43.2%-92.1%, ID 2.6) indicating overdispersed admission rates with high variability. Children with cancer that visited the ED for a primary diagnosis of fever experienced the largest amount of variability in admission with rates ranging from 10.4% to 74.1% (ID 8.1). Less variability existed among hospital admission rates for both neutropenia (range 60%-100%, ID 1.0) and febrile neutropenia (FN) (range 66.7%-100%, ID 0.83). Admission rates by day of the week did not demonstrate significant variability for any of the scenarios examined (overall P = 0.91). There were no differences by weekend versus weekday either (overall P = 0.52). CONCLUSION: The percentage of children with cancer admitted through the ED varies widely by institution and diagnosis. Standardization of best practices for children with cancer admitted through the ED should be an area of continued improvement.

Variation in hospital admission of sickle cell patients from the emergency department using the Pediatric Health Information System.

BACKGROUND: Universal newborn screening and improved treatment options have led to increased survival in sickle cell disease (SCD). However, patients with SCD still rely heavily on acute care services. OBJECTIVE: To determine the variation seen in hospitalizations for the top complaints for ED visits for children with SCD nationally. METHODS: We performed a retrospective review of the Pediatric Health Information Systems (PHIS) Database between October 2011 and September 2015. Emergency department (ED) encounters were selected by using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes for SCD with and without crisis, fever, and pain. Univariate analyses were performed, as well as index of dispersion (ID) to assess variation by day of the week and region. ANOVA and t-test were used to determine statistical significance. RESULTS: A total of 68 661 ED encounters at 36 hospitals met the criteria for inclusion. Of those encounters, 50.1% were admitted to the hospital. Pain and fever were the most common primary diagnoses among this population. Although variation in hospitalization was seen overall, as well as for a primary diagnosis of pain or fever, this variation was not explained by weekday/weekend designation. CONCLUSION: The results of our study confirm pain and fever as the most common primary diagnoses for children with SCD who seek acute care, as well as demonstrate that while significant variation in hospitalization exists, it is not associated with day of the week. Further studies to elucidate patient- and hospital-level factors that influence admission variation are necessary.

Cholangitis in Patients With Biliary Atresia Receiving Hepatoportoenterostomy: A National Database Study.

INTRODUCTION: Biliary atresia (BA) is a progressive form of liver disease in the neonatal period usually requiring hepatoportoenterostomy (HPE). Cholangitis is a common sequelae of HPE but data about which patients are at risk for this complication are limited. OBJECTIVE: The objective of the study was to determine risk factors associated with cholangitis in a large retrospective cohort after HPE. METHODS: The Pediatric Health Information System (PHIS) was queried for BA (ICD-9 975.61) and HPE (ICD-9-CM 51.37) admissions from 2004 to 2013. We performed univariate analysis and linear regression with dependent variables of ≥ 2 or ≥ 5 episodes of cholangitis, and independent variables of age at time of HPE, race, ethnicity, gender, insurance, ursodeoxycholic acid (UDCA) use, steroid use, presence of esophageal varices (EV), and portal hypertension (PH). RESULTS: We identified 1112 subjects with a median age at HPE of 63 days and median number of cholangitis episodes of 2 within 2 years. On multiple regression analysis, black race (odds ratio (OR) 1.51, P = 0.044) and presence of PH (OR 2.24, P < 0.001) were associated with increased risk of ≥ 2 episodes of cholangitis, whereas HPE at >90 days was associated with less risk (OR 0.46, P = 0.001). Among those with ≥5 episodes, Asian race (OR 2.66, P = 0.038), public insurance (OR 1.72, P = 0.043), EV (OR 1.81, P = 0.017), and PH (OR 2.88, P < 0.001) were associated with higher risk. CONCLUSIONS: Complications, such as cholangitis remain a common problem for patients, after HPE, with median of 2 episodes within 2 years. Higher rates of cholangitis are associated with portal hypertension whereas lower rate is associated with age at HPE of >90 days. Asians, patients with public insurance, and those with portal hypertension are more likely to have recurrent cholangitis.

A Retrospective Cohort Study of Growth in the First 2 Years of Life in Preterm Infants With Cystic Fibrosis.

BACKGROUND: Late preterm infants (born 34-36 weeks gestation) without cystic fibrosis (CF) are at risk for growth failure during the first 2 years of life. Infants with CF are at risk of being born premature, and thus at risk for growth failure. The aim for this study was to assess weight-for-length (WFL) at 2 years of age for late preterm infants compared with term infants with CF. METHODS: Data were collected from the US CF Foundation Patient Registry. We compared growth parameters between late preterm and term infants with CF born from 2010 to 2013. Our primary outcome was WFL <10 and <50 percentile at 2 years of age. A multivariate logistical regression analysis evaluated late preterm gestation and WFL<10 or <50 percentile. RESULTS: A total of 2955 infants were born from 2010 to 2013 with CF. Eight percentage late preterm. Forty-five percentage late preterm versus 43% term were below the 50th percentile for WFL at age 2 years (P = 0.75). Twelve percentage late preterm versus 6% term for WFL <10 percentile at age 2 years (P = 0.010). The multivariate regression model identified 2-fold increased odds of being <10th percentile for WFL at age 2 years (P = 0.025) for preterm over term. Late preterm infants used higher calorie dense feeds and more feeding tubes (P = 0.035 and P = 0.006). CONCLUSIONS: Late preterm infants with CF are at higher risk of being below the 10th percentile for WFL at 2 years of age compared with their term peers. This indicates a population that is at risk for growth failure.

Serologic, but Not Genetic, Markers Are Associated With Impaired Anthropometrics at Diagnosis of Pediatric Crohn's Disease.

OBJECTIVES: Children with Crohn's disease may present with malnutrition and linear growth impairment, which can be secondary to insufficient caloric intake, chronic inflammation, malabsorption, and suppression of growth-promoting hormones. We evaluated clinical, serologic, and genetic data to determine risk factors for impaired anthropometrics in Crohn's disease at diagnosis. METHODS: Our study evaluated 772 children newly diagnosed with Crohn's disease, inflammatory phenotype, enrolled in the RISK Stratification Project to determine the factors associated with anthropometric impairment. Data were collected on demographics, growth parameters, disease location, serologic and immunologic markers, and disease severity. We performed a genome-wide association study of genetic polymorphisms associated with inflammatory bowel disease. Regression analysis determined associations between anthropometrics and clinical, serologic, and genetic variables. RESULTS: There were 59 (7%) children with height z score <-2, 126 (14%) with a weight z score <-2, and 156 (17%) with a body mass index z score <-2. Linear growth impairment was associated with hypoalbuminemia (P = 0.0052), elevated granulocyte-macrophage colony stimulating factor autoantibodies (P = 0.0110), and elevated CBir antibodies against flagellin (P = 0.0117). Poor weight gain was associated with female sex (P = 0.0401), hypoalbuminemia (P = 0.0162), and thrombocytosis (P = 0.0081). Malnutrition was associated with hypoalbuminemia (P = 0.0061) and thrombocytosis (P = 0.0011). Children with moderate or severe disease had lower weight (P = 0.02 and P = 1.16×10, respectively) and body mass index z scores (P = 2.7 × 10 and P = 1.01 × 10, respectively) than children with quiescent and mild disease. There was no association between age of diagnosis, Tanner stage, or disease location and having impaired anthropometrics. There was no genome-wide association between the genetic polymorphisms and the serologic variables and anthropometric measurements. CONCLUSIONS: This is the largest study evaluating growth in treatment-naïve children with Crohn's disease, inflammatory phenotype. It is the first study to use genome-wide sequencing to assess for genetic determinants of growth impairment. Granulocyte-macrophage colony stimulating factor autoantibodies and CBir antibodies are more likely to be elevated in children with growth impairment. Future investigations should evaluate the relationship between genetic polymorphisms, pathologic immune responses, and the biological pathways regulating growth.

A survey of mobile technology usage and desires by caregivers of children with cancer.

BACKGROUND: The use of mobile health (mHealth) has grown exponentially, even by caregivers of vulnerable populations. The study objective was to understand mobile technology usage, barriers, and desires by caregivers of children with cancer. PROCEDURE: Paper surveys were mailed to caregivers of children diagnosed with cancer at Riley Hospital for Children between June 2015 and June 2017. The survey contained 13 questions, both fixed and open-ended, and was sent in both English and Spanish up to three times. RESULTS: Respondents (n = 121) were primarily parents (93.2%), median age was 40.7 years (range 23-63), and most were white, non-Hispanic (74.4%). The majority made under $100,000 annual household income (72.9%) and had an education of at least some college or greater (74.5%). Nearly all owned a smart phone (99.2%) and most (61.2%) owned a tablet. Among operating systems, the majority used iOS (62.8%), while 49.6% used Android. About a third (37.1%) reported no barriers to mobile technology use, but 22.4% experienced "data limitations." Overall, 86.2% wanted at least one medical management website/app: medical knowledge (61.2%), symptom tracking/management (49.1%), and medication reminders (44.8%). Further, 62.1% wanted access to child's medical record and 58.6% wanted communication with medical providers. Lower education was significantly associated with experiencing phone/plan barriers (P = 0.008). CONCLUSION: The majority of caregivers of children with cancer use mobile technology with minimal barriers; future research should focus on designing an mHealth tool to address the medical management needs by caregivers of children with cancer.

Incidence of Low Seroimmunity to Hepatitis B Virus in Children With Inflammatory Bowel Disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) often receive immunosuppressive therapy, which may make them vulnerable to infections such as hepatitis B. We hypothesized that hepatitis B virus titers are low in the vaccinated pediatric population with IBD. The aims of our study were to identify the incidence of lower titers of hepatitis B surface antibody (HBsAb) and determine which patient factors may be associated with lower HBsAb titers. METHODS: Patients with diagnosis of IBD, ages 5 to 18 years, were prospectively enrolled. Patients were confirmed to have had a full series of hepatitis B vaccination. Quantitative serum HBsAb titers were measured and logistic regression analysis with independent variables of age, sex, race, disease phenotype, surgery, medications and a dependent variable of adequate HBsAb titers (> 10 mIU/mL) was performed. RESULTS: Of the 116 patients enrolled, 57 were boys and 59 were girls. 75 patients had a diagnosis of Crohn disease; 32 had a diagnosis of ulcerative colitis; and 9 patients had been diagnosed as having indeterminate colitis. At the time of the study, 15 patients were taking corticosteroid, 66 on an immunomodulator, and 53 on a biologic. Sixty percent of patients in the 5- to 10-year age group had protective titers versus 22% to 27% in the older groups, P = 0.04. Only 28% of the 116 patients had HBsAb titers of >10m IU/mL. Twenty percent of the patients taking corticosteroids, 27% taking immunomodulators, and 24% taking biologics were found to be seroimmune. CONCLUSIONS: Nearly two-thirds of pediatric patients with IBD have low titers against hepatitis B virus. Titers were highest in the younger patients. No patient-specific variable, such as the use of immunosuppressants, appeared to influence these low titers.

Patterned progression of bacterial populations in the premature infant gut.

In the weeks after birth, the gut acquires a nascent microbiome, and starts its transition to bacterial population equilibrium. This early-in-life microbial population quite likely influences later-in-life host biology. However, we know little about the governance of community development: does the gut serve as a passive incubator where the first organisms randomly encountered gain entry and predominate, or is there an orderly progression of members joining the community of bacteria? We used fine interval enumeration of microbes in stools from multiple subjects to answer this question. We demonstrate via 16S rRNA gene pyrosequencing of 922 specimens from 58 subjects that the gut microbiota of premature infants residing in a tightly controlled microbial environment progresses through a choreographed succession of bacterial classes from Bacilli to Gammaproteobacteria to Clostridia, interrupted by abrupt population changes. As infants approach 33-36 wk postconceptional age (corresponding to the third to the twelfth weeks of life depending on gestational age at birth), the gut is well colonized by anaerobes. Antibiotics, vaginal vs. Caesarian birth, diet, and age of the infants when sampled influence the pace, but not the sequence, of progression. Our results suggest that in infants in a microbiologically constrained ecosphere of a neonatal intensive care unit, gut bacterial communities have an overall nonrandom assembly that is punctuated by microbial population abruptions. The possibility that the pace of this assembly depends more on host biology (chiefly gestational age at birth) than identifiable exogenous factors warrants further consideration.

Gallbladder Ejection Fraction Is Unrelated to Gallbladder Pathology in Children and Adolescents.

OBJECTIVES: Biliary dyskinesia is a common diagnosis that frequently results in cholecystectomy. In adults, most clinicians use a cut off value for the gallbladder ejection fraction (GBEF) of <35% to define the disease. This disorder is not well characterized in children. Our aim was to determine the relation between GBEF and gallbladder pathology using a large statewide medical record repository. METHODS: We obtained records from all patients of 21 years and younger who underwent hepatic iminodiacetic acid (HIDA) testing within the Indiana Network for Patient Care from 2004 to 2013. GBEF results were obtained from radiology reports using data mining techniques. Age, sex, race, and insurance status were obtained for each patient. Any gallbladder pathology obtained subsequent to an HIDA scan was also obtained and parsed for mention of cholecystitis, cholelithiasis, or cholesterolosis. We performed mixed effects logistic regression analysis to determine the influence of age, sex, race, insurance status, pathologist, and GBEF on the presence of these histologic findings. RESULTS: Two thousand eight hundred forty-one HIDA scans on 2558 patients were found. Of these, 310 patients had a full-text gallbladder pathology report paired with the HIDA scan. GBEF did not correlate with the presence of gallbladder pathology (cholecystitis, cholelithiasis, or cholesterolosis) when controlling for age, sex, race, insurance status, and pathologist using a mixed effects model. CONCLUSIONS: Hypokinetic gallbladders are no more likely to have gallbladder pathology than normal or hyperkinetic gallbladders in the setting of a patient with both a HIDA scan and a cholecystectomy. Care should be used when interpreting the results of HIDA scans in children and adolescents.

Early cow's milk introduction is associated with failed personal-social milestones after 1 year of age.

UNLABELLED: Both the American Academy of Pediatrics (AAP) and the Institute of Medicine (IOM) recommend delaying the introduction of cow's milk until after 1 year of age due to its low absorbable iron content. We used a novel computerized decision support system to gather data from multiple general pediatrics offices. We asked families whether their child received cow's milk before 1 year of age, had a low-iron diet, or used low-iron formula. Then, at subsequent visits, we performed a modified developmental assessment using the Denver II. We assessed the effect of early cow's milk or a low-iron diet on the later failure of achieving developmental milestones. We controlled for covariates using logistic regression. Early cow's milk introduction (odds ratio (OR) 1.30, p = 0.012), as well as a low-iron diet or low-iron formula (OR 1.42, p < 0.001), was associated with increased rates of milestone failure. Only personal-social milestones (OR 1.44, p = 0.002) showed a significantly higher rate of milestone failure. Both personal-social (OR 1.42, p < 0.001) and language (OR 1.22, p = 0.009) showed higher rates of failure in children with a low-iron diet. CONCLUSIONS: There is an association between the introduction of cow's milk before 1 year of age and the rate of delayed developmental milestones after 1 year of age. This adds strength to the recommendations from the AAP and IOM to delay cow's milk introduction until after 1 year of age.

Retrograde stent with external string for pediatric robotic pyeloplasty: does it reduce cost and complications?

Robotic-assisted pyeloplasty (RAP) is a mainstay in the treatment of ureteropelvic junction obstruction (UPJO) in children. At our institution, to limit planned operating rooms visits we have placed a ureteral stent with an external string (SWES) immediately prior to RAP. In this study, we sought to quantify the operative time, complications, and costs associated with this approach compared to the traditional approach, requiring subsequent stent removal in the operating room. We hypothesized the SWES cohort would have decreased cost, yet with similar operative time and complications. We retrospectively collected all RAPs performed at our institution using the SWES approach (Aug 2012-July 2017). We excluded those with a redo pyeloplasty, and/or a percutaneous nephrostomy tube for post-operative drainage. We collected 30-day costs linked to the patients' MRN using the Pediatric Health Information System (PHIS) database. We compared 30-day healthare costs for all patients following RAP. We compared our SWES group to a national cohort of all pediatric RAP during the same time period. Lastly, we sent an anonymous, electronic survey to urologists of all PHIS institutions to identify the predominant postoperative drainage, nationally. Within our institution, we reviewed all those treated with SWES (n = 85) (Table 1). The median 30-day cost was $10,548 among those with SWES (Table 2). This was significantly less than the overall, national cohort of all pediatric RAP during the same period ($14,119, p < 0.001). There was a 15.5 % rate of unplanned return to the hospital in the SWES group. Of those unplanned returns, 8.2 % (7/85) had unplanned return for a procedure (3 for unplanned stent removal, 2 for nephrostomy tube for persistent obstruction, 1 for omental hernia, and 1 for stent replacement). With a 42.5 % (37/87) response rate, our nationwide survey found 84.6 % primarily leave stents WITHOUT a string, 7.7 % left nephrostomy tubes, and 7.7 % stents with strings. During pediatric RAP, placement of a SWES takes little time, carries a risk of unplanned visit to the operating room, saves the patient a certain, second anesthetic for stent removal, and amounts to a cost savings of approximately 25 %.

Stratification of a Phelan-McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor.

Phelan-McDermid syndrome (PMS), caused by pathogenic variants in the SHANK3 gene or 22q13 deletions, is characterized by intellectual disability, autistic features, developmental delays, and neonatal hypotonia. Insulin-like growth factor 1 (IGF-1) and human growth hormone (hGH) have been shown to reverse neurobehavioral deficits in PMS. We assessed the metabolic profiling of 48 individuals with PMS and 50 controls and determined subpopulations by taking the top and bottom 25% of responders to hGH and IGF-1. A distinct metabolic profile for individuals with PMS showed a reduced ability to metabolize major energy sources and a higher metabolism of alternative energy sources. The analysis of the metabolic response to hGH or IGF-1 highlighted a major overlap between both high and low responders, validating the model and suggesting that the two growth factors share many target pathways. When we investigated the effect of hGH and IGF-1 on the metabolism of glucose, the correlation between the high-responder subgroups showed less similarity, whereas the low-responders were still relatively similar. Classification of individuals with PMS into subgroups based on responses to a compound can allow an investigation into pathogenic mechanisms, the identification of molecular biomarkers, an exploration of in vitro responses to candidate drugs, and eventually the selection of better candidates for clinical trials.

Identifying Patient-Centered Outcomes for Caregivers and Children With Musculoskeletal Infections.

Background: Musculoskeletal infections (MSKI), including osteomyelitis and septic arthritis, are among the most common invasive infections in children and have the potential to cause significant morbidity. Guidelines have been developed to optimize care based on clinician-developed endpoints. Patient-centered outcomes have not been defined for children with MSKI. This study identified outcomes most important to caregivers and patients with MSKI. Methods: This was a single-center prospective qualitative study of children 6 months to 18 years of age hospitalized with MSKI from November 2019 to September 2021. Using design-research methods, patients and caregivers participated in interviews and/or completed journals to describe their experiences during acute infection and recovery from MSKI. Results: A total of 51 patient/caregivers were approached to participate in the study, 35 of whom declined to participate, resulting in 8 interviews conducted and 14 journals collected from 16 patient/caregivers. From these, a journey map was created highlighting points of stress during the onset of symptoms, through hospitalization, and returning home with new challenges. In addition, patient-centered outcomes were identified. For caregivers, these included managing mental health, managing responsibilities, and receiving support. Both caregivers and patients shared the importance of understanding of treatment plans and responsibilities. For patients, improving mental and physical health was important. Conclusions: Management of children with MSKI is complex and requires a multidisciplinary team approach. Validation of the outcomes identified and development of a measurement tool are needed. Addressing the patient-centered outcomes we identified in this study can greatly improve the holistic care of children with MSKI.

Contemporary clinical characteristics, treatment, and outcomes of angiographically confirmed coronary stent thrombosis: results from a multicenter California registry.

OBJECTIVES: To describe the contemporary treatment and outcomes for patients with angiographically confirmed (definite) stent thrombosis (ST). BACKGROUND: Limited data are available on contemporary treatment patterns and outcomes of patients with ST in the United States. METHODS: In this multicenter California registry, consecutive cases of definite ST over 5 years were identified. Clinical characteristics, in-hospital outcomes, and long-term survival are reported. RESULTS: One hundred and sixty five consecutive episodes of ST were identified in 153 patients from January 2005 to February 2010. The distribution of acute (≤24 hr), subacute (24 hr to 30 days), late (30 days to 1 year), and very late (≥1 year) ST was 3.9%, 21.8%, 17.6%, and 50.3%, respectively. Only 41.2% of patients were on dual antiplatelet therapy at the time of presentation, while 22.4% of patients were on none. Of the 61.4% of patients treated with restenting, 71.1% of them received a drug-eluting stent. Procedural success was 88.1%, and in-hospital death, stroke, and CABG occurred in 5.5%, 0.6%, and 6.1% of subjects, respectively. All-cause mortality at 1 year was 14.3%. Although female gender, diabetes mellitus (DM), bifurcation disease, ejection fraction <40%, and cardiogenic shock at the time of presentation were associated with an increased risk of in-hospital mortality, only DM (P = 0.047) and bifurcation disease (P = 0.027) remained independent predictors of in-hospital death. CONCLUSION: In-hospital mortality from definite ST is lower than previously reported, but long-term mortality remains high. DM and bifurcation disease, but not type of percutaneous therapy, are independently associated with in-hospital mortality.