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Our study aims to report the prevalence of potentially actionable oncogenic variants in a sample of pediatric tumors from a single institution using a reference laboratory for tumor profiling. We investigated genomic alterations and immunotherapy biomarkers such a tumor mutation burden, microsatellite instability, and programmed death-ligand 1. Patients treated in the Cook Children's Health Care System who had tumor profiling performed by Foundation Medicine between January 1, 2013, and May 1, 2019, were included. Demographic variables, results of tumor profiling, and subsequent use of targeted therapies were captured. Eighty-one patients were in our final data set; patients had diagnoses of central nervous system tumors (n=5), leukemia and lymphoma (n=4), neuroblastoma (n=32), and other solid tumors (n=40). One or more genomic alterations were identified in 68 (84%) of patients, 34 of which had potential targeted therapies available. In all, 44/51 patients tested for tumor mutation burden had low tumor burden, and the rest had intermediate burden. All 41 patients tested for microsatellite instability status were microsatellite stable. Six of 34 patients tested for programmed death-ligand 1 status were positive. Twelve patients received targeted therapy. This study highlights a subset of pediatric tumors harboring targetable genetic alterations and describes the use of a reference laboratory for tumor profiling.

Dystrophinopathies result from mutations to the DMD gene. We report 5 boys in 3 families with heterogenous phenotypes due to a point mutation in the DMD gene: a hemizygous tyrosine-to-cysteine change in exon 15 (c.1724TC) resulting in an amino acid substitution of leucine to proline at codon 575. This mutation has been reported before, with at least 3 prior patients presenting with similar clinical findings of myalgia, myoglobinuria, and occasional muscle cramping. The mutation on DMD c.1724TC (p.Leu575Pro) is listed in the Clinvar database as a variant of unknown significance. Our report provides contributing evidence that this alteration should be classified as pathogenic.

Background: Ureteral reimplantation remains the primary surgical method used for patients with vesicoureteral reflux (VUR). Cystoscopy is commonly performed first to visualize anatomy and rule out possible abnormalities. Urine cultures may also be obtained. The objective of this study is to evaluate the prudency of preoperative urine cultures and cystoscopies in pediatric patients undergoing ureteral reimplantation. Methods: Pediatric urologists were surveyed regarding collecting urine cultures in asymptomatic patients and cystoscopies before reimplantation. A retrospective review was also conducted of patients who underwent ureteral reimplantation for VUR between March 2018 and April 2021 at Cook Children’s Medical Center. Results: When physicians were asked the frequency they obtain urine cultures before reimplantation on asymptomatic patients, 36% said “never” and 38% said “always.” Regarding cystoscopy, 53% said “never” and 32% said “always.” Inclusion criteria were met by 101 patients. Cystoscopies were performed in 46 patients and never altered the reimplantation. There were 20 preoperative, 90 intraoperative, and 61 postoperative urine cultures. Complications were associated with positive cultures of urine collected intraoperatively and postoperatively only. Conclusion: Cystoscopies and asymptomatic urine cultures obtained before ureteral reimplantation provide no additional benefit while increasing cost for patients’ families. Further research is needed to thoroughly identify the prudency of such practices in ureteral reimplantation for VUR.

Children with certain brain tumors often present with malnutrition and experience a decline in nutritional status throughout treatment. This can negatively affect outcomes. Studies have demonstrated that proactive enteral feeding can be beneficial to childhood cancer patients in helping to maintain or improve their nutritional status. To date, no classification parameters exist for pediatric brain tumor diagnoses and their corresponding nutritional risk. Our neuro-oncology team set out to develop a nutrition risk classification for pediatric brain tumors with a corresponding decision aid for nutrition intervention. We report the use of this decision aid in 15 pediatric brain tumor patients at high risk for nutritional deficits. Despite being high risk, weight loss did not exceed 5% in 93% (14/15) and 87% (13/15) of our patients from diagnosis to start of cycle 2 of chemotherapy and from diagnosis to end of therapy, respectively. Patients underweight at diagnosis (5/15) experienced improvements in nutritional status, and only 1 patient had a negative change in body mass index z-score ≥1 SD from diagnosis to end of therapy. This strategy was well-accepted by parents who reported satisfaction with the approach, their child's nutritional status throughout treatment, and the psychosocial aspects of feeding.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a congenital small vessel disease of the brain due to NOTCH3 gene mutations. Although adult-onset CADASIL is well documented, more cases are being described within the pediatric population. We describe three siblings with NOTCH3 mutations with various symptomatic presentations of early-onset CADASIL and one sibling with concurrent moyamoya syndrome.Review of electronic medical records of identified patients.A 19-year-old male who has experienced behavioral dysregulation, hallucinations, and memory loss along with a hyperintense signal abnormality in his temporal lobe; his 15-year-old sister who has the mildest presentation in terms of normal imaging results but experiences severe headaches, anxiety, and depression; and the youngest sibling, a 13-year-old with first reported case of a NOTCH3 mutation associated with moyamoya syndrome and a TREX1 gene mutation of uncertain clinical significance. She had multiple strokes before age five years.Our set of siblings share many similarities with other reported pediatric cases of CADASIL, all with NOTCH3 gene mutations and with early-onset symptoms that range from abnormalities in the cognitive/behavioral/psychiatric field to neurological deficits, migraines, and strokes. Gene testing and imaging studies in symptomatic children with a family history suggestive of CADASIL might aid in early diagnosis, even though there is no effective therapy. We believe that the correlation of clinical presentations and gene mutations together with increased research into the molecular mechanisms underlying CADASIL (and related arteriopathies such as moyamoya syndrome) are critical to the eventual development of targeted therapies.

Context It is important for colleges of osteopathic medicine (COMs) to provide opportunities for osteopathic medical students (OMSs) to conduct research under the guidance of professional researchers. However, COMs historically lag behind allopathic medical schools in research offerings for medical students. The literature would benefit from a synopsis of research opportunities for OMSs at COMs. Objectives This study aims to assess the availability of research opportunities currently offered to OMSs and to identify structured research programs (SRPs) to provide data that may help COMs expand such opportunities. Methods Two online surveys were developed. The General Survey asked about general research opportunities, research requirements, and SRPs, which we define as optional, intramural, and mentored research programs. The follow-up SRP Survey sought to understand the history, funding, and organizational structure of SRPs. Between February and June 2021, the General and SRP Surveys were sent to all COMs in the United States. Response data were analyzed descriptively. Results Responses were received from 32 (84.2%) of 38 COMs. Nearly all COMs offered research symposia, offered third- or fourth-year research elective rotations, and provided some form of funding for OMSs to participate in research. Fourteen (43.8%) COMs had mandatory research requirements. Twenty COMs (62.5%) offered 31 SRPs, and surveys were completed for 25 (80.6%) SRPs. SRPs were founded a median (range) of 7 (1–43) years prior and accommodated 20 (4–50) OMSs annually. Among the responding SRPs, 12.0% had external funding, 96.0% required applications, 50.0% interviewed applicants prior to acceptance into the program, 72.0% required OMSs to identify their own mentors, 68.0% offered stipends to OMSs, 28.0% offered course credits, 96.0% had clinical research opportunities, and 68.0% offered research-oriented didactics. In 84.0% of SRPs, OMSs worked predominantly in the summer after OMS-I; for these SRPs, students had 4–10 weeks of dedicated time for participation in research. Conclusions Findings from our surveys provide a synopsis of the research opportunities currently provided by COMs in the United States. Our data demonstrated wide variability of research opportunities among COMs.

Introduction: Recognition of tethered cord syndrome (TCS) in children is important because as the child grows, the spinal cord is stretched, leading to ischemia and subsequent neurological deficits, including bowel or bladder dysfunction, back and leg pain, or lower extremity weakness. Imaging findings raising concerns for tethering include presence of a fatty and/or thickened filum or a conus medullaris located caudal to L2. Objectives: The objective of this study was to describe the symptomatic presentation of TCS in our institution, detect demographic and diagnostic predictors of signs and symptoms, assess changes in symptoms over time, and examine whether demographic and diagnostic variables affect changes in symptoms over time. Methods: Using a retrospective chart review from patients who underwent detethering at our institution between April 1, 2015 and March 31, 2019, we report on the signs and symptoms of patients undergoing detethering surgery at presentation and examine possible demographic and diagnostic predictors of those symptoms and changes in symptoms over time. Logistic regression analyses were used to determine whether symptoms at presentation were related to demographic and diagnostic predictors and to assess a change in symptoms over time. Results: A total of 273 patients underwent detethering and were analyzed. Of these, 144 (53%) were Conclusion: In the population studied, several presenting symptoms, particularly constipation, were commonly reported. Children

Hemophagocytic lymphohistiocytosis (HLH) is a rare yet potentially fatal systemic disease arising from uncontrolled activation of the immune system. According to the Histiocyte Society’s 2004 guidelines, patients must meet five of eight criteria to be diagnosed with HLH [1]. HLH may be classified into primary and secondary. Primary, or familial, HLH is attributed to underlying defects in genes that control natural killer (NK) and cytotoxic T-lymphocyte (CTL) cell degranulation. Secondary HLH, in contrast, may occur in the context of triggers, such as malignancy, rheumatologic disease, or infection. Systemic-onset juvenile idiopathic arthritis (SoJIA) is a well-recognized trigger of HLH and both share overlapping features (e.g. fever and elevated ferritin). Management of SoJIA includes the immunomodulator Anakinra, an interleukin 1 (IL-1) receptor antagonist hypothesized to dampen an overactive immune system. Three patients treated for HLH with concomitant SoJIA diagnosis at Cook Children’s Medical Center between 2014 and 2019 are described below in order to examine the role of immunomodulators in their clinical course and outcome.Three Hispanic patients (aged 8-15) presented with a constellation of systemic symptoms, including fever, generalized rash, fatigue, and weight loss. Upon fulfilment of necessary criteria and subsequent diagnosis of HLH, they were treated accordingly with HLH-2004 protocol. Case 3, whose HLH was suspected to be secondary to Epstein-Barr Virus (EBV) infection, rapidly responded to treatment and, therefore, briefly discontinued Etoposide; however, she tolerated this poorly and resumed treatment after a six-week hiatus with the addition of weekly Rituximab to mitigate rising EBV titers. All patients achieved remission.Past medical history for case 3 included autoimmune disorders such as celiac disease, type 1 diabetes and suspected idiopathic juvenile arthritis for which she did not require ongoing care prior to presenting with features of secondary HLH. Cases 1 and 2 were diagnosed with SoJIA following their HLH diagnosis. Cases 1 and 3 relapsed with HLH within months of their initial encounter. Due to their concurrent diagnosis of SoJIA, both received daily Anakinra. Case 3 experienced rapid resolution of symptoms. In contrast, Case 1 had unsatisfactory response of musculoskeletal manifestations prompting switch from Anakinra to weekly Tocilizumab—another biologic that antagonizes IL-6 receptor—with favorable response. Case 2 was started on daily Anakinra immediately following his diagnosis of SoJIA and has yet to relapse. In summary, all cases have yet to experience an additional relapse following introduction of Anakinra or Tocilizumab. Figure 1 provides the treatment timelines for Cases 1-3 who had 5.37, 2.87, and 4.62 years of follow up, respectively.The diagnosis of HLH remains elusive and is often accompanied with multiple systemic manifestations that overlap with other disorders. Though traditional therapy for HLH includes intensive courses of etoposide and corticosteroids, biologics represent a newer class of medications highly effective in treating diseases with inflammatory or immune-mediated components [2]. This case series reinforces that immunomodulators, such as Anakinra, are promising treatment options in pediatric patients with HLH secondary to SoJIA.

Context Medical students, especially at osteopathic medical schools, have limited research exposure. Systematic instruction in research, supervised by qualified mentors, could motivate osteopathic medical students to pursue research in their careers, thereby increasing the number of future clinician-scientists. Recruiting and retaining suitable research mentors are crucial to sustaining such programs, but this task is also particularly challenging for osteopathic medical schools. Objectives To assess mentors' experiences in a voluntary student-mentor medical research program. Methods An online survey was sent to 76 university- or hospital-based participants who previously mentored 219 medical students between 2014 and 2019. The questionnaire consisted of 13 items with responses in checklist, five-point Likert scale, and categorical multiple-choice formats, assessing motivation for participation, satisfaction with the program, and interest in future participation. Data were analyzed descriptively, and responses from mentors at the university and hospital were compared using univariate logistic and ordinal regression analyses. Results Among 70 (92.1%) mentors who responded to the survey, 61 (87.1%) reported being motivated by a desire to help medical students learn research. Forty-nine (70.0%) mentors indicated that furthering their own research productivity was a motivation, and hospital-based mentors were statistically significantly more likely to endorse this source of motivation (OR=2.02; 95% CI=1.18–3.45; p=0.01). Most respondents were satisfied with the quality of the students' work (59 [84.3%]) and with the program (59 [85.5%]). However, 46 (65.7%) suggested the program could be enhanced by requiring medical students to be physically present in the clinic or laboratory for a minimum amount of time. Importantly, most (58 [84.1%]) mentors reported that they would be interested in participating in future mentored research programs. Conclusions Mentors were motivated to participate in the voluntary research program for both altruistic and professional reasons. Since most mentors reported being satisfied with the program, it is likely they would participate in future mentored research programs. Our results suggest that mentors viewed this voluntary research program as mutually beneficial.

Objectives Given their established role in hepatic function and insulin resistance for adults, early screening of type 2 diabetes mellitus (T2DM) in the pediatric population may potentially be improved by the assessment of elevated liver enzymes. Methods Our study enrolled 151 nondiabetic children aged 10–14 years. Patients were assessed for demographics and five risk factors for T2DM. The levels of γ-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels were determined in serum samples. The effects of demographics and risk factors on abnormal liver enzyme levels were assessed with univariate chi-square analyses and also with multivariate logistic regression analyses, which were controlled for gender. Results Frequencies for abnormal liver enzyme values were as follows: 13 (9%) for GGT, 5 (3%) for ALT, and 20 (13%) for ALP. Across analyses, two results were consistently statistically significant. Females were more likely to have abnormal ALP levels, and patients with BMI percentile ≥95% and with acanthosis nigricans were more likely to have abnormal GGT levels. Conclusions Our study suggests GGT as potential marker for T2DM discovery in children. Subsequent long-term longitudinal studies would help to more clearly delineate GGT’s association with T2DM. Additionally, future studies that elucidate the molecular contribution of GGT elevation to T2DM pathogenesis are needed.

This study aimed to evaluate the impact of a Pediatric Acute Pain Guideline on postsurgical pain scores, opioid exposure, and discharge opioid prescribing habits in postappendectomy patients.This was a retrospective single-center quality improvement project, including patients admitted for an appendectomy at a pediatric medical center between April 1 and December 31, 2018. Patients 0-17 years of age, who underwent a laparoscopic appendectomy without complications, were inpatient for at least 1 calendar day, and designated as presurgical American Society of Anesthesiologists (ASA) category 1 or 2 were included.Two hundred fifty-eight patients met inclusion criteria (n = 92 pre-, n = 166 post-guideline implementation). There was a decrease in the number of as needed opioid doses used (p = 0.014) and length of hospitalization (p = 0.003) post-guideline implementation compared to pre-guideline implementation. A decrease in the number of as needed doses of opioids used (p 0.001) and in opioid exposure (p = 0.038) during hospitalization was also seen when the nonopioid pain agent was scheduled.The implementation of the Pediatric Acute Pain Guideline was associated with a decrease in the number of as needed opioid doses used during hospitalization, which may have contributed to a decreased length of hospitalization. Scheduling nonopioid pain medications decreased opioid exposure.Treatment study level III.

Introduction: Diazoxide is the first line and only Federal Drug Agency approved pharmacological agent for the treatment of hyperinsulinism. Its use has increased over the years to include patients with various genetic forms of hyperinsulinism, perinatal stress hyperinsulinism and infants of diabetic mothers with more babies than ever being exposed to this therapy. Methods: We performed a retrospective analysis of 194 patients with hyperinsulinism in our clinic and looked for those who had experienced serious adverse events (SAE) including pulmonary hypertension and neutropenia. We compared the rates of SAE in the different types of hyperinsulinism. Results: Out of 194 patients with hyperinsulinism, 165 (85.1%) were treated with diazoxide. There were 17 SAEs in 16 patients including 8 cases of pulmonary hypertension and 8 of neutropenia. These data show that overall the frequency of SAE associated with diazoxide use is 9.7%, but that those with perinatal stress hyperinsulinism have a much higher rate than those with genetic forms of hyperinsulinism (16.7 vs. 3.6%; p = 0.01). We also found diazoxide is associated with pulmonary hypertension (4.8% of patients treated). Although more patients with perinatal stress hyperinsulinism (7.6%) were affected than genetic hyperinsulinism (1.2%), the difference was not significant (p = 0.088). Conclusion: The rate of SAEs associated with (not necessarily caused by) diazoxide has been demonstrated. The rate of SAE in newborns with perinatal stress hyperinsulinism is significantly higher than that of otherwise healthy babies with genetic forms of hyperinsulinism, suggesting that caution should be used when prescribing diazoxide to this population. This information should help balance the risk benefit of treatment and provide guidance on screening for these complications in the population of treated patients.

Objective Children with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma often experience significant weight gain during induction therapy. However, a subgroup of patients may experience weight loss, which can impact outcomes; thus, identifying and understanding this underrecognized concern is important. Our aim was to identify the prevalence and predictors for weight loss during ALL induction therapy. Methods This was a single-institution retrospective study of 187 patients, ages 2 to 20 y, diagnosed with ALL or lymphoblastic lymphoma. We analyzed weight trends during induction therapy and predictors of weight loss. Results Significant weight loss (≥5%) occurred in 17% of patients. Having high-risk disease, trisomy 21, overweight/obese status at the time of diagnosis, and/or hyperglycemia were positively associated with weight loss and negatively associated with weight gain during induction therapy. Conclusion Future studies should aim to better understand the etiology and importance of weight loss during induction therapy.

Introduction: Cardiac disease is one of the leading causes of stroke in children. In an effort to separate pulmonary and systemic circulations, patients with single ventricle physiology undergo the Fontan surgery. Watershed strokes have been reported as a complication of Fontan surgery but literature on its prevalence and associated risk factors is lacking. Methods: Retrospective review of records of patients who underwent Fontan operation at our center from 2007 to 2018. Demographic, clinical, imaging, and outcome data were documented for all patients. Key risk factors evaluated:cardiac diagnosis, presence of significant AV-valve regurgitation, poor ventricular function, cardio-pulmonary bypass (CPB) time, Hematocrits, mean arterial pressure (Map) and significance of post-operative resuscitation measured by cardiac index and vasoactive infusion score. Univariate logistic regression was used for analyses, and a p-value of Results: We identified 149 patients;14 (10%) had clinical evidence and radiographic confirmation of a watershed stroke. There were no arterial ischemic strokes.From all the variables analyzed (Table 1), patients with significant A-V valve regurgitation pre- and post-operatively, depressed single ventricular function, and underlying diagnosis of hypoplastic left heart syndrome (HLHS) were at a higher risk for watershed strokes. No other risk factors were identified. (Table 1). All had no significant motor deficits at discharge. Conclusion: At our center, watershed infarcts occurred in 10% of patients undergoing Fontan surgery. Cardiac disease diagnosis and factors associated to cardiac function were significant risk factors for watershed stroke rather than surgical related variables.

Asparaginase-induced acute pancreatitis (AAP) is a concerning adverse effect in the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Typically, treatment of AAP follows a nil per os (NPO) approach with or without parenteral nutrition (PN). However, with accounts of increased risk of adverse events like bacterial translocation and multiorgan failure when PN is used in lieu of enteral nutrition (EN), recent literature has advocated for a change in practice to the early use of EN for children and adults with acute pancreatitis. Despite these recommendations, there remains a gap in the literature regarding whether or not early enteral feedings are currently being used in pediatric oncology patients with acute pancreatitis. In our case series, we account the successful use of EN to manage AAP in three pediatric ALL/LL patients. Additionally, we describe the development of an early enteral feeding protocol for pediatric oncology patients with pancreatitis. To the best of our knowledge, this is the first case series chronicling the nutritional management of AAP using EN in the pediatric oncology population. The successful use of EN we have seen in our patients supports the shift in treatment practice to the use of EN in lieu of PN for this population.

Literature in adult palliative care (PC) boasts fewer invasive procedures, shorter lengths of stay, and decreased cost of care. Benefits of pediatric PC are under-researched and are important to identify to optimize care.Our aim was to estimate the influence and utilization of PC on pediatric patient care.We evaluated the electronic medical record of 43 patients at Cook Children's Medical Center (CCMC) with complex chronic conditions, who died between January 1, 2013, and December 31, 2014, comparing the length and frequency of hospitalizations, number of medications administered and procedures performed, and established limits of resuscitation between patients who received PC and those who did not.Data analyses were performed using SAS Enterprise (version 6.1; SAS Institute, Inc., Cary, NC). Continuous variables were described as medians and ranges and analyzed with Wilcoxon rank-sum test for ordinal data. Categorical variables were described as percentages and analyzed with chi-square test of independence. Repeated-measures analyses were performed utilizing multilevel linear modeling, which examined the data at the level of the 236 visits rather than the 43 patients.Twelve (28%) eligible patients were seen by PC. PC patients had more hospitalizations, longer lengths of stay, and fewer medications and procedures than those patients without PC services. PC patients were also more likely to have a medical orders for scope of treatment in place.These data demonstrate that PC services at CCMC are underutilized and support the need for PC services by decreased medications and procedures and identified family wishes for medical treatment.

Background Excessive iodine exposure is an often overlooked cause of neonatal hypothyroidism. Case presentation We present an infant with iodine-induced hypothyroidism, which was detected at age 15 days by newborn screening. The infant’s iodine excess resulted from maternal intake of seaweed soup both during and after pregnancy. Treatment included discontinuation of seaweed soup, temporary interruption of breastfeeding and short-term levothyroxine therapy. By age 4 months, the infant’s hypothyroidism had resolved, and her growth and development were normal. Conclusions This case illustrates the importance of considering excess dietary iodine as a possible cause of hypothyroidism in infants.

Background Measures of atherogenic cholesterol, with and without concomitant use of lipid-lowering medications (LLMs), are reported with up to 52 weeks of sebelipase alfa treatment in children and adults with lysosomal acid lipase deficiency (LAL-D) participating in the phase 3 Acid Lipase Replacement Investigating Safety and Efficacy study (NCT01757184). Objective To examine the effects of sebelipase alfa on levels of atherogenic biomarkers in the Acid Lipase Replacement Investigating Safety and Efficacy study. Methods Data were prospectively collected for LDL particle (LDL-P) number, LDL-C, HDL-C, apolipoprotein B (apoB), apolipoprotein A1 (apoA1), and LDL-P size. Differences at week 20 between the sebelipase alfa and placebo groups were assessed for the overall LAL-D cohort and for patients receiving and not receiving LLMs. Changes from baseline after up to 52 weeks of treatment were also calculated for the overall cohort and separately for patients receiving and not receiving LLMs. Results Baseline values for LDL-C, LDL-P number, and apoB were elevated while HDL-C and apoA1 were low. Treatment with sebelipase alfa for 20 weeks significantly improved atherogenic measures compared with placebo irrespective of LLM usage. The reduction in LDL-C with sebelipase alfa was associated with a reduction in the LDL-P number. Treatment for up to 52 weeks was associated with sustained improvements of LDL-P, LDL-C, HDL-C, apoB, and apoA1, regardless of LLM use. Conclusion Patients with LAL-D have high atherogenic risk. It is essential to address the underlying LAL deficiency to restore cholesterol homeostasis in LAL-D patients, as treatment with sebelipase alfa improves atherogenic measures regardless of LLM use and for a sustained period. Sebelipase alfa appears to reduce LDL-C by decreasing the LDL-P number, suggesting improvement in cardiovascular disease risk in LAL-D patients.

Obesity following treatment of pediatric acute lymphoblastic leukemia (ALL) has become a significant long-term concern. Excessive weight gain often occurs during treatment, particularly during induction and the first 6 months of maintenance therapy, and it may be potentially modifiable. This retrospective study aimed to evaluate the impact of an early, 3-visit nutrition intervention on weight gain during maintenance therapy in ALL patients. Medical records of the intervention group were compared with historical controls who were treated on the same ALL treatment protocols during an earlier time period. Anthropometrics were collected throughout intensive therapy and at every monthly visit during the first 12 months of maintenance therapy. In total, 67 patients were evaluated (33 in the intervention group and 34 in the control group). After controlling for significant predictors of body mass index (BMI) z-scores in maintenance therapy-including higher BMI at diagnosis and weight gain throughout intensive therapy-the intervention group demonstrated more controlled weight gain during maintenance therapy (P

Drug toxicities during treatment of acute lymphoblastic leukemia play a pivotal role in influencing the outcome as certain toxicities may impair treatment compliance. Polymorphisms in CEP72 have been linked to increased incidence of vincristine-induced toxicities, namely peripheral neuropathy. We hypothesize that polymorphisms in the same gene may increase a patient's risk of developing hepatotoxicity when receiving potentially hepatotoxic agents during chemotherapy. This report describes hepatotoxicity that first developed during consolidation in a patient homozygous for the CEP72 risk alleles. Bilirubin levels normalized following dose reduction of 6-mercaptopurine. The patient continues to tolerate maintenance therapy at a reduced dose of 6-mercaptopurine.

Objective Statistical methods can be utilized to optimize the order for reflex diagnostic testing to attenuate patient and hospital costs without affecting quality of care. Our objective is to demonstrate the method of developing an order for testing and to apply this method to an illustrative example. Methods An algorithm was developed for minimizing costs for any given number of diagnostic tests, and it was retrospectively applied to a sample. Results The actual scenario of using both tests on all patients was compared to 2 other hypothetical reflex testing approaches: all patients are given 1 test, and those patients who tested negative were then given the second test. The 2 scenarios would have saved 37.1% and 17.4% in testing costs, respectively. Conclusion These calculations could be applied to numerous situations to reduce costs for patients and hospitals. We propose that this methodology would be best used in conjunction with any existing quality improvement initiatives.

In this study, the author examined potential mediators of the negative relationship between the absolute difference in items’ lengths and their inter-item correlation size. Fifty-two randomly ordered items from five personality scales were administered to 622 university students, and 46 respondents from a survey website rated the items’ readability, clarity, and generality. Based on prior research, the author hypothesized that the difference in mean ratings of item pairs’ generality, but not readability or clarity, would mediate the negative relationship between the difference in the item pairs’ lengths and their inter-item correlation size. In pairs of items, difference in item length was negatively correlated with inter-item correlation size. However, only difference in ratings of generality, not readability or clarity, was associated with correlation size, and as predicted, it mediated the relationship between item length and correlation size. Theoretical and practical implications are discussed.

Rates of pediatric hypertension have increased, but adherence to the current diagnostic criteria for hypertension (HTN) in pediatrics is not well known. We investigated the timeline and predictors of time to referral for those referred to nephrology for elevated blood pressure (EBP). A retrospective study was conducted on patients, aged 3–18 years, referred to a nephrology clinic for EBP over a 3-year period. Patients were excluded if they were referred previously, were referred for other conditions, or did not have ≥ 1 prior visit with EBP. Analyses were performed to determine whether sex, age, ethnicity, socioeconomic status, and obesity predicted number of prior visits with EBP and time to referral. There were 120 patients (64% male; 53% obese) included and 82 (68%) had ≥ 3 prior visits with EBP ≥ 95%. Medians were as follows: 15.08 years of age at referral; 5 visits with EBP and 3.45 years from first EBP ≥ 90%; 4 visits with EBP and 1.42 years from third EBP ≥ 95%. No variables significantly predicted number of prior visits with EBP or time to referral from the first EBP. Starting with the third EBP ≥ 95%, only obesity significantly predicted number of prior visits and time to referral: Obese patients had more visits (p = 0.01), and took longer to be referred (p = 0.03) than healthy patients. Patients with EBP were generally not referred to nephrology promptly, which was especially true for obese patients. Further research is needed to identify interventions to improve time to referral for EBP.

This study examined the predictors and psychometric outcomes of survey satisficing, wherein respondents provide quick, “good enough” answers (satisficing) rather than carefully considered answers (optimizing). We administered surveys to university students and respondents—half of whom held college degrees—from a for-pay survey website, and we used an experimental method to randomly assign the participants to survey formats, which presumably differed in task difficulty. Based on satisficing theory, we predicted that ability, motivation, and task difficulty would predict satisficing behavior and that satisficing would artificially inflate internal consistency reliability and both convergent and discriminant validity correlations. Indeed, results indicated effects for task difficulty and motivation in predicting survey satisficing, and satisficing in the first part of the study was associated with improved internal consistency reliability and convergent validity but also worse discriminant validity in the second part of the study. Implications for research designs and improvements are discussed.

Abstract. Using two meta-analytic datasets, we investigated the effect that two scale-item characteristics – number of item response categories and item response-category label format – have on the reliability of multi-item rating scales. The first dataset contained 289 reliability coefficients harvested from 100 samples that measured Big Five traits. The second dataset contained 2,524 reliability coefficients harvested from 381 samples that measured a wide variety of constructs in psychology, marketing, management, and education. We performed moderator analyses on the two datasets with the two item characteristics and their interaction. As expected, as the number of item response categories increased, so did reliability, but more importantly, there was a significant interaction between the number of item response categories and item response-category label format. Increasing the number of response categories increased reliabilities for scale-items with all response categories labeled more so than for other item response-category label formats. We explain that the interaction may be due to both statistical and psychological factors. The present results help to explain why findings on the relationships between the two scale-item characteristics and reliability have been mixed.

This investigation examined the effects of 3 item characteristics-the average number of words per item, within-scale variability in item length, and item "direction"-on internal consistency reliability and interitem correlation. In Study 1, we examined the effects of these variables on overall scale-level reliability using 444 subscales from 9 personality scales. In Study 2, we examined interitem correlation at the paired-item level using 477 nonredundant item pairs from 14 personality scales. Lower scale reliability was associated with more average words per item, greater within-scale variability in item length, and a greater percentage of reverse-keyed items. Similarly, smaller interitem correlations were associated with a greater degree of mismatch in item length between the paired items and with a mismatch (vs. match) in the items' respective "directions." The pattern of results across both studies supports our notion that lower internal consistency results from increased context switching; that is, from the confusion that occurs when respondents must switch back and forth between the interpretive frames pertaining to short versus long items, or between items pertaining to one pole of a personality dimension and its "opposite" pole. Suggestions for maximizing the internal consistency of personality scales are proposed.

OBJECTIVE Various options exist for right ventricular outflow tract (RVOT) reconstruction in congenital heart disease. The Freestyle porcine aortic root may be used but its longevity is not well defined. DESIGN We performed a retrospective review of all non-Ross RVOT reconstructions using the Freestyle root in our institution. Survival and reintervention, either by surgery, transcatheter valve implantation, balloon valvuloplasty, or bare metal stent placement, were recorded. Factors associated with reintervention were assessed using Cox regression. RESULTS Between January 2002 and December 2015, there were 182 patients identified. Sixteen patients were lost to follow-up and 3 patients died, unrelated to cardiac surgery. Of the remaining 163 patients, the median age was 12.2 years (interquartile range 6.4-16.4), median weight was 39.0 kg (interquartile range 19.9-59.3), and the median body surface area was 1.23 m2 (interquartile range 0.79-1.64). Ninety-three (57%) patients had tetralogy of Fallot. The median follow-up was 5.4 years (interquartile range 2.9-8 years). There were no operative or cardiac-related deaths. Thirty-eight patients (23%) required reintervention. The rate of freedom from reintervention was 93.2% (95% CI 86.7%-96.6%) at 5 years and 48.4% (95% CI 34.9%-60.6%) at 10 years. Age < 10 years, weight < 39 kg, and body surface area

Routine and selective cholesterol screening of children is an effective tool to help identify those with familial hypercholesterolemia. In children found to have elevated levels of cholesterol, secondary causes should be excluded, including hypothyroidism. Thyroid hormone has multiple effects on the regulation of lipid synthesis, absorption, and metabolism. In this case report, we described a 2-year-old with a history of congenital hypothyroidism who was found to have severe hypercholesterolemia. A detailed medical history and appropriate screening tests are important in determining the underlying cause of elevated low-density lipoprotein cholesterol to help inform clinical decision-making.

This study tested implications of the context switching perspective proposed by Hamby, Ickes, and Babcock ( 2016 ). Using trained raters to assess the amount of reframing required to interpret the meaning of the subsequent (second) item within all adjacent item pairs, we first established that this process variable could be measured reliably. Then, in the data for 18 personality measures drawn from 3 individual-difference domains, we found that the amount of reframing (i.e., context switching) needed to interpret successive items predicted both lower interitem correlations and a greater percentage of misresponders. Similarly, item pairs that were mismatched in "directional" wording also predicted both lower interitem correlations and more misresponders. Finally, item pairs representing different factors predicted lower interitem correlations. Although the effects of direction switching and factor switching were partially mediated by the amount of reframing required, they remained significant even when the mediating effect of reframing was statistically controlled. These results indicate that interpreting the meaning of test items is a task for which the level of difficulty can vary with each successive item, as a function of how the current item compares to the previous item in aspects such as its context generality or specificity, directional wording, and content domain.

The present study meta-analytically compared coefficient alpha reliabilities reported for free and for-pay Big Five scales. We collected 288 studies from five previous meta-analyses of Big Five traits and harvested 1,317 alphas from these studies. We found that free and for-pay scales measuring Big Five traits possessed comparable reliabilities. However, after we controlled for the numbers of items in the scales with the Spearman-Brown formula, we found that free scales possessed significantly higher alpha coefficients than for-pay scales for each of the Big Five traits. Thus, the study offers initial evidence that Big Five scales that are free more efficiently measure these traits for research purposes than do for-pay scales.

Using meta-analytic data, we investigated three attributes of personality scales – their readability, the average number of words per item, and whether adjectives or statements were used – to determine the effects that these qualities have on scale reliability (Cronbach’s α). From a large pool of studies examined in three prior meta-analyses, we extracted the relevant data for seven personality traits measured in 167 independent samples (N = 55,593), and obtained measures of the traits’ readability, the average number of words per item, and whether adjectives or statements were used as the item format. We found strong and consistent evidence that using fewer words per item produced higher scale reliabilities, and there was also evidence in favor of using adjectives, as opposed to statements, as the item format when measuring broad traits. In contrast, the results for readability were inconsistent and mostly nonsignificant. These results have practical implications for scale developers as well as researchers, and they raise the possibility that shorter and more “de-contextualized” items do a better job of assessing personality traits.

Background The Practice Management Committee (PMC) of the Pediatric Endocrine Society (PES) conducted a survey of its membership in February/March, 2016 to assess the current state of pediatric diabetes care delivery across multiple practice types in the United States. Methods The PES distributed an anonymous electronic survey (Survey Monkey) via email to its membership and requested that only one survey be completed for each practice. Results Ninety-three unique entries from the US were entered into analysis. Care is predominantly delivered by multidisciplinary teams, based at academic institutions (65.6%), with >85% of the provider types being physicians. Each 1.0 full time equivalent certified diabetes educators serves on average 367 diabetic youth. Fee-for-service remains the standard method of reimbursement with 57% of practices reporting financial loss. Survey respondents identified under-reimbursement as a major barrier to improving patient outcomes and lack of behavioral health (BH) providers as a key gap in services provided. Conclusions Our survey reveals wide variation in all aspects of pediatric diabetes care delivery in the United States. Pediatric Endocrinologists responding to the survey identified a lack of resources and the current fee for service payment model as a major impediment to practice and the lack of integrated BH staff as a key gap in service. The respondents strongly support its organizations' involvement in the dissemination of standards for care delivery and advocacy for a national payment model aligned with chronic diabetes care in the context of our emerging value-based healthcare system.

Background: Cerebral sinus vein thrombosis (CSVT) involves the thrombosis of the dural sinus and/or cerebral veins and it is considered a form of stroke. The estimated incidence of CSVT in children is 0.6 per 100,000 children per year. Poor outcomes, including death, happen in 9 to 29% of patients affected by CSVT. In addition, neurologic deficits, affecting primarily cognition and behavior, are seen in 50% of affected children. No randomized clinical trials have been conducted on pediatric CSVT so current guidelines for treatment have been extrapolated primarily from adult studies. Published guidelines by the American College of Chest Physicians, American Heart Association and American Society of Hematology, support the use of anticoagulation with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). These same guidelines also suggest that catheter directed thrombolysis (CDT) with tissue plasminogen activator (tPA) and mechanical thrombectomy (MT) could be used when there has been clinical deterioration or no improvement (clot progression) despite anticoagulation. In all cases, these are based on uncontrolled case series and expert opinion. There is very little data on the safety and efficacy of CDT and/or MT for pediatric CSVT. Method: Pediatric patients with CSVT seen at Cook Children's Medical Center from January 1, 2008 to December 31, 2018 were identified by searching EMR using ICD-9 and ICD-10 codes. From this group, patients treated with MT and CDT in addition to anticoagulation were selected and reviewed. Results: Five children (4 to 14 y/o) were treated with MT and CDT after failing anticoagulation with UFH or LMWH. Diagnosis was made by MRI/MRV and all had CSVT of multiple sinuses. Four patients had more than one underlying disorders/factors that increased their risk for thrombosis including: Ulcerative Colitis in 2, severe anemia in 2, Systemic Lupus Erythematosus (SLE) in 1, use of oral contraceptives together with obesity and bacterial sepsis in 1. Two patients did have a thrombophilia: Protein S deficiency in 1 and Protein S and C deficiency in another. One patient with SLE had a positive hexagonal phase neutralization test but rest of evaluation was negative. Three patients had systemic bleeding prior initiation of UFH and MT/CDT. All children were treated with UFH, and due to clinical neurologic deterioration and/or worsening of imaging findings (4 comatose and 1 with persistent increased ICP), all underwent thromboaspiration and catheter directed infusion of tPA for 17 to 48 hours at a dose of 1 to 2 mg/hr. All patients continued anticoagulation with UFH during catheter directed tPA infusion and after the catheter was removed. All cases had partial resolution of the sinus vein thrombosis, although 1 had quick reocclusion. Post procedure bleeding happened in 1 patient who had also had an external ventricular drainage placed and developed parenchymal and intraventricular hemorrhage that led to discontinuation of tPA infusion, and 2 patients developed petechial brain hemorrhages. Four patients had great neurologic recovery and minimal deficits, but 1 had significant neurologic deficits. One patient died from lupus complications. (Table) Conclusion: Endovascular therapy including MT and CDT with tPA in conjunction with systemic UFH, may have a role in pediatric patients with CSVT who have deterioration despite initial anticoagulation. In our series, after procedures, all patients had partial resolution of their CSVT (but 1 had quick reocclusion) and 4 out of 5 patients had good neurologic outcomes despite bad predictor signs (coma, extensive CSVT). Further studies are needed to identify which patients would benefit from early endovascular treatment. Table Disclosures No relevant conflicts of interest to declare.

10063 Background: Diagnosis and treatment of childhood cancer place survivors at risk for lower educational attainment, the increased burden of chronic conditions on attainment has not been examined. Methods: Participants included 16724 survivors (48% female; mean diagnosis age 9.1 years, current age 36.2 years, time since diagnosis 26.6 years) and 4098 siblings (mean current age 39.3 years) Educational attainment was categorized as college graduation (yes/no) among survivors ≥ age 25 years. Chronic conditions occurring before age 25 years of age were graded using Common Terminology for Adverse Events 4.3. Modified Poisson regression models estimated relative risks (RR) and 95% confidence intervals (CI) of treatment exposures and chronic conditions on education attainment, adjusting for age at diagnosis and sex. Results: College graduation was reported by 8391 (51%) survivors and 2410 (59%) siblings. Survivors of all diagnoses were more likely to not graduate compared to siblings (all p’s < 0.05), with survivors of CNS tumor (RR1.36, CI 1.25-1.49), leukemia (RR 1.17, CI 1.07-1.28), and Hodgkin lymphoma (RR 1.17, CI 1.07-1.29) being at higher risk than survivors of neuroblastoma. Compared to survivors with no history of cranial radiation therapy (CRT), higher risk of not graduating college was seen in those who received 20-30Gy (RR 1.16, CI 1.09-1.25), 30-50Gy (RR 1.37, CI 1.26-1.49) and ≥50Gy (RR 1.35, CI 1.28-1.42). Among survivors not exposed to CRT, dexamethasone had a protective effect on college education (RR 0.88, CI 0.80-0.97) compared to no corticosteroid exposure. Male sex and older age (≥ 5 years) at diagnosis were associated with being more likely to not graduate college. survivors reporting any serious/life threatening chronic condition prior to age 25 years (grades 3-4) were more likely to not graduate college (RR 1.14, 95% CI 1.10-1.18) compared to no or mild/moderate conditions (grades < 3). Conclusions: Survivors reporting chronic conditions are less likely to complete a college education by age 25 years and may need additional early educational or vocational resources.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon yet potentially devastating systemic disease, arising from uncontrolled activation of the immune system. While the primary form of this disease can be caused by genetic mutation(s), the secondary form may be triggered by infection and hematologic, malignant, and metabolic conditions. The diagnosis of HLH remains a clinical challenge due to nonspecific symptoms. Proper diagnosis is significantly more difficult among patients with acute leukemia who have received chemotherapy. The objective of this study is to describe three unique cases of secondary HLH, describe the specific treatment, and improve the awareness of this condition. Two patients with acute myeloid leukemia (AML) and one with acute lymphoblastic leukemia were diagnosed with HLH, having fulfilled the criteria as outlined in the HLH-2004 protocol. They then received HLH-specific treatment. Two patients passed – one from refractory HLH and one from primary disease (i.e., AML) – and one patient remains alive 22 months after her allogeneic bone marrow transplant. The diagnosis of HLH requires the presence of any five of the eight criteria. Due to its heterogeneous presentation, it remains imperative that treating clinicians remain cognizant about HLH so that prompt diagnosis may allow appropriate treatment.

Summary Introduction Testicular torsion (TT), a common surgical emergency worldwide, is typically treated with orchiectomy or orchiopexy. It is widely accepted that the chance of salvaging the testicle declines with time and degree of torsion. The impact of ethnicity on outcome is less well understood, and the association between weather and onset of TT remains a controversy. Objectives It is important to know the signs of TT so that appropriate treatment can be given quickly. The purpose of this study was to provide a detailed analysis of registered cases of TT in adolescent patients diagnosed at a single institution to better understand the association between clinical indicators and surgical outcomes and to examine some remaining controversies in the literature on TT. Study design A retrospective chart review was conducted, using medical records from the present institution. Data were collected for 165 patients who met the following inclusion criteria: 1) adolescent males between 10 and 18 years of age at the time of diagnosis, and 2) TT between January 2001 and June 2013. Results Of the 165 patients, 38% had orchiectomies. Patients with orchiectomies had longer wait times for surgery ( p p = 0.02). Assuming that patients without reference to presence of bell clapper deformity in their medical notes did not have the deformity, those with orchiectomies were less likely to have bell clapper deformity than were those with orchiopexies ( p p = 0.02). Discussion and conclusion Wait time to surgery positively correlates with orchiectomy. Early identification and intervention is vital to testicular salvage. As the degree of torsion increases, the blood supply to the affected testis decreases and the time required to inflict testicular vascular damage decreases. Our results showed the presence of the bell clapper deformity moderated the relationship between temperature and TT: Those without the deformity had torsions on colder days than did those with the deformity. A comprehensive multi-centered study could help draw further conclusions regarding temperature correlation and the bell clapper deformity. Table . Differences in clinical characteristics by surgical outcome. Variable Orchiopexy Orchiectomy p Triage to provider, minutes 27.55 ± 30.47 31.12 ± 28.27 0.47 Triage to surgery, minutes 216.63 ± 110.23 334.29 ± 250.51 Driving distance, miles 26.37 ± 43.56 39.83 ± 169.37 0.54 Driving time, minutes 31.42 ± 38.93 41.78 ± 141.75 0.57 Degree of torsion, degrees 458.29 ± 179.51 505.10 ± 173.13 0.15 Bell clapper Yes 34 (33%) 9 (14%) No 68 (67%) 54 (86%) Temperature, Fahrenheit 64.05 ± 15.62 61.54 ± 18.73 0.36

Background:Early diagnosis and expeditious treatment of newborns with congenital hypothyroidism (CH) is necessary to avoid mental retardation.Methods:A survey of 44 practitioners in the southern US was conducted to better understand common practices regarding neonatal CH and the findings were compared with current guidelines in the US and Europe.Results:Responses indicated some consensus that 10–15 μg of thyroid hormone/kg/day was the appropriate dosage. However, despite guidelines advocating their use, practitioners reported that they did not commonly use imaging or laboratory tests, though experienced providers apparently used them more often.Conclusions:Together, these results show moderate adherence to published guidelines for treating and diagnosing CH. Further research is needed to determine why providers deviate from these guidelines and to generalize these results to other populations.