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To improve our understanding of reproductive health and sexual function in women with cloacal malformations and other anorectal malformations (ARMs) METHODS: An observational cross-sectional survey was administered to individuals assigned female at birth aged 12 to 55 with ARMs and cloacal malformations cared for at our institution. Data included age of thelarche/menarche and questions on body image, gynecologic anatomy, sexual function, and pregnancy.Twenty-one patients responded in the ARM group and 30 in the cloacal malformation group. There were no differences in median age of thelarche/menarche in patients with ARMs (11/12.5 years) compared with patients with cloacal malformation (11/12 years). Patients with ARMs were more likely to have native vaginal tissue than those with cloacal malformations (n = 18, 82% vs n = 12, 40%; P = .03). There were no differences between groups regarding concerns about dyspareunia and functionality of their vagina (P.05). Forty-two percent of patients with cloacal malformations and 30% of patients with ARMs reported having been sexually active. Two patients with cloacal malformations and 2 with ARMs reported having been pregnant. Patients with cloacal malformations reported a lower quality of life score (80.4) compared with those with ARMs (87.0) (difference4.5).Patients with a cloacal malformation were less likely to have native vaginal tissue and reported a lower quality of life than those with ARMs. Despite this, patients with a cloacal malformation had similar reproductive health and sexual function compared with patients with ARMs. Our results reinforce the need for comprehensive sexual and reproductive health care for all women with ARMs.

To assess initial evaluation patterns of patients presenting to the Emergency Department (ED) with abnormal uterine bleeding (AUB) including differences by race DESIGN: Retrospective multicenter cohort study from October 2015 through September 2020 SETTING: Forty-seven children's hospitals submitting data to the Pediatric Health Information System PARTICIPANTS: Female patients aged 8-21 with an ED encounter with AUB as the primary diagnosis code INTERVENTIONS AND MAIN OUTCOME MEASURES: Proportion of visits with at least 1 laboratory assessment for the evaluation of anemia, iron deficiency, and/or hemostatic disorders RESULTS: We identified 17,759 unique patients with AUB seen in the ED who met inclusion criteria. Median age was 16.3 years (IQR, 14.1-17.8 years). Most encounters (n = 11,576, 65.2%) included evaluation for anemia, but only 6.8% (n = 1,215) included assessment for iron deficiency and 26.2% (n = 4,654) for hemostatic disorders. Black patients accounted for 34.7% (n = 6,155) of AUB encounters yet constituted only 25% of all ED encounters (n = 198,192). Black patients with AUB were less likely to undergo bleeding disorder evaluation (OR = 0.76; 95% CI, 0.69-0.83) but more likely to receive evaluation for sexually transmitted infections (OR = 1.63; 95% CI, 1.48-1.80) compared with White patients, despite controlling for age and concomitant pain.In a national cohort of adolescents presenting to the ED with AUB, evaluations for anemia and hemostatic disorders were infrequently performed, and racial differences existed regarding initial assessment. Further studies are needed to understand the factors underlying racial differences in hematologic testing and the impact of this disparity on health outcomes for females with AUB.

Context Pediatric patients receiving chemotherapy experience unwanted therapy-induced side effects, commonly constipation and pain that diminish quality of life. To date, few studies have investigated the safety and feasibility of osteopathic manipulative treatment (OMT) in pediatric oncology. Objectives The primary objective of this study is to investigate the safety and feasibility of OMT in pediatric oncology outpatient clinics. Methods This is a single institutional pilot study evaluating children aged ≥2–21 years receiving chemotherapy for an oncological diagnosis at Nationwide Children’s Hospital (NCH). Permission was obtained from the NCH Institutional Review Board. Participants were enrolled for 8 weeks and received weekly OMT. OMT was deemed feasible by participating in six out of eight weekly treatments, and safety was assessed through adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE). During the clinic visit, patients answered validated surveys on constipation (Bristol Stool Scale) and pain (FACES Scale) pre/post-OMT. Feasibility was analyzed utilizing a one-sided exact binomial test while validated tools and adverse events were summarized descriptively. Results A total of 23 patients were enrolled, with 21 included in feasibility analyses. The majority of the patients were female (n=13, 61.9%), with a median age of 12 years at enrollment (range, 2.7–20.8 years). There were no serious adverse events attributed to OMT intervention, and among the patients assessed for feasibility, 100% of them participated in at least two-thirds of their weekly OMT treatments, meeting our defined feasibility criteria. The intervention lasted an average of 14.2 min (range, 7.2–19.2 min). There were no FACES or Bristol Stool Scale scores that correlated with worsening pain on constipation post-OMT intervention. Conclusions Pediatric oncology patients were feasibly and safely able to receive OMT during a regularly scheduled chemotherapy visit. The limitations include the small sample size. These findings support the need to further investigate the safety and feasibility, as well as efficacy, of OMT in the pediatric oncology clinical setting.

Sedation is often used to reduce pain and anxiety in pediatric patients with acute lymphoblastic leukemia (ALL) undergoing lumbar punctures (LPs). There is a potential for long-term effects on neurocognition with repeat sedative exposures in young children. The purpose of this study is to determine the practice habits regarding sedation for LPs in pediatric patients with ALL among multiple institutions.This is a retrospective study of 48 hospitals in the Pediatric Health Information Systems (PHIS) between October 2015 and December 2019. Children 1 to 18 years old with ALL who received intrathecal chemotherapy in an outpatient setting were included. We analyzed the prevalence of anesthesia usage and the types of anesthetics used.Of the 16,785 encounters with documented use of anesthetic medications, intravenous and inhaled anesthetics were used in 16,486 (98.2%) and local anesthetics alone in 299 (1.8%). The most commonly used medications used for sedation were propofol (n=13,279; 79.1%), midazolam (n=4228; 25.2%), inhaled fluranes (n=3169; 18.9%), and ketamine (n=2100; 12.5%).The majority of children's hospitals in the United States use intravenous and inhaled anesthetics for routine therapeutic LPs in pediatric patients with ALL. Propofol is one of the most common medications used for sedation.

There is paucity of data on COVID-19 vaccine hesitancy amongst parents of pediatric (age ≤ 17 years) hematopoietic cell transplant (HCT) recipients. We conducted a cross-sectional study to determined COVID-19 vaccine hesitancy, and COVID-19 impact on family and related distress in this population. A national group (n = 80) was recruited via social media (Facebook) from February−May 2021. With vaccine approval for ≥12 years in July 2021, a second group (n = 37) was recruited locally. Parents completed surveys including the Vaccine Hesitancy Questionnaire and COVID-19 Exposure and Family Impact Scale (CEFIS). Nonparametric statistics were used to analyze results and factors impacting Vaccine Hesitancy Scores (VHS). The majority of parents were non-Hispanic White (≥90%) and children ≥3 months post-HCT (85%). Mean CEFIS score (scale 0–60) was 41.11 (SD = 8.24), with higher scores indicating negative impact of the pandemic. Mean (± standard deviation) VHS was 2.87 (±0.79) on a scale of 1–4, with 1 indicating higher and 4 lower hesitancy. Concerns about vaccine related side effects, lower parental age, child age, household income, and education were associated with lower VHS. Receiving reliable information and recommendations by providers was associated with higher VHS. Improving vaccine acceptance in this population is critical in protecting pediatric HCT recipients.

To assess bleeding symptoms in patients with generalized joint hypermobility (GJH), compare bleeding scores to healthy historical pediatric controls, and determine if a correlation exists between Beighton scores and bleeding scores.Patients with GJH aged 6-21 years seen by rheumatology at Nationwide Children's Hospital in Columbus, Ohio were eligible. Participants/guardians completed the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool, a validated questionnaire defining presence, severity, and frequency of bleeding symptoms. Scores ≥ 3 have been associated with an underlying bleeding disorder in pediatric patients.Eighty-one patients agreed to participate. Median age was 13 years (IQR: 10-16 years) and mean Beighton score was 6.3 (range: 4-9). Commonly observed bleeding symptoms were oral bleeding (74%), easy bruising (59%), and bleeding with minor wounds (42%). Mean and median bleeding scores were 5.2 and 4, respectively, and were significantly higher than reported bleeding scores in pediatric controls, defined as those without bleeding symptoms or a previously diagnosed bleeding disorder (p0.001). Although 75% (95% CI: 64-84%) of patients had an abnormal bleeding score, only 12.3% were previously seen by hematology for bleeding symptoms. Among patients with GJH, higher Beighton scores were not associated with higher bleeding scores (Spearman's correlation -0.08).In a cohort of pediatric patients with GJH, three-quarters of participants had abnormal bleeding scores with mean bleeding score significantly elevated compared to healthy controls. We propose that screening for bleeding symptoms be integrated into routine care for GJH patients, with referral to hematology for patients with bleeding concerns. This article is protected by copyright. All rights reserved.

Introduction In the era of electronic medical records, pen-and-paper-based physician-administered bleeding assessment tools (BAT) remain under-utilized in the clinical setting, as they are noted to be time-consuming. Aim The current study reviews the use of an electronic self-administered bleeding assessment tool (eBAT) prospectively in a paediatric haematology clinic and in comparison with a physician administered BAT (pBAT). Materials and methods This was reviewed and approved in the current form because the aims statement includes the method regarding comparison of 2 groups. So no additional section required. Results A total of 94 BAT response pairs were available for analysis. The median time required for patients or parents to complete the eBAT was 8 min, with less than a third of the patients requiring over 10 min. The median bleeding scores noted in this study were 4 for both the BATs, with strong positive correlation between the eBAT and the physician administered bleeding questionnaire. The eBAT had a sensitivity of 93.8% (95% CI 82.8%-98.7%), a specificity of 34.8% (95% CI 21.4%-50.3%), a positive predictive value (PV) of 60.0% (95% CI 54.5%-65.2%) and a negative PV of 84.2% (95% CI 62.5%-94.5%) for identifying a bleeding disorder. Conclusions Findings indicate that eBAT is a valid and time-efficient screening tool for evaluating patients' bleeding symptoms, which can improve clinical applicability of BATs by reducing time for bleeding history review.

T cells redirected to cancer cells either via a chimeric antigen receptor (CAR-T) or a bispecific molecule have been breakthrough technologies; however, CAR-T cells require individualized manufacturing and bispecifics generally require continuous infusions. We created an off-the-shelf, single-dose solution for achieving prolonged systemic serum levels of protein immunotherapeutics via adeno-associated virus (AAV) gene transfer. We demonstrate proof of principle in a CD19 + lymphoma xenograft model using a single intravenous dose of AAV expressing a secreted version of blinatumomab, which could serve as a universal alternative for CD19 CAR-T cell therapy. In addition, we created an inducible version using an exon skipping strategy and achieved repeated, on-demand expression up to at least 36 weeks after AAV injection. Our system could be considered for short-term and/or repeated expression of other transgenes of interest for noncancer applications.

BACKGROUND Pleraxifor for peripheral blood stem cell (PBSC) mobilization in children with malignancies is often given following failure of standard mobilization (SM) rather than as a primary mobilizing agent. STUDY DESIGN AND METHODS In this retrospective multicenter study, we report the safety of plerixafor-based PBSC mobilization in children with malignancies and compare outcomes between patients who received plerixafor upfront with SM (Group A) with those who received plerixafor following failure of SM (Group B). In the latter pleraxifor was given either following a low peripheral blood (PB) CD34 (

Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-to-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru.Between 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997-2008 and 2009-2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, whereas prognostic factors were determined by univariate analysis (log-rank test).Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The 5-year OS was 62% (95% CI: 53%-74%), while EFS was 57% (95% CI: 48%-69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplastic; OS: HR = 3.4, p = .03), metastasis (OS: HR = 3.5, p = .01; EFS: HR = 4.3, p = .004), delay in radiation therapy of 31-60 days (compared to ≤30 days; EFS: HR = 2.1, p = .04), and treatment 2009-2013 cohort (OS: HR = 2.2, p = .02; EFS: HR = 2.0, p = .03).Outcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009-2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.

The Accreditation Council for Graduate Medical Education requires Milestone-based assessments of residents and fellows. In pediatrics, 11 subcompetencies are common to both residency and subspecialty fellowship training. It is unknown whether Milestone scores achieved during residency are related to Milestone scores achieved in early fellowship.To assess the relationship between final residency Milestones scores and first-year fellowship Milestones scores in the 11 common subcompetencies (CSCs) across pediatric subspecialties.This was a retrospective single-institution cohort study of pediatric fellows beginning fellowship training between July 2016 and July 2019. De-identified Milestone score sets for final residency scores (R), mid-year first-year fellowship scores (F1), and final first-year fellowship scores (F2) were collected. Spearman correlation and regression analyses were used to assess score relationships.Data for 85 of 98 eligible fellows were collected. Consistently, the F1 scores were lowest, and the R scores were highest. There was a weak positive correlation between the composite R scores and the composite F1 scores. There was a weak positive correlation between residency and fellowship scores for 6 CSCs and no significant correlation for the remaining 5.For the 11 pediatric CSCs, the final residency Milestone scores are consistently higher than and only weakly associated with early fellowship Milestone scores. There may be limitations to the use of residency scores for fellowship program directors in guiding individualized education for early fellows. This study provides groundwork for additional study of Milestone relationships and may help inform the next iteration of pediatric subspecialty Milestones.

To evaluate the use of intrauterine devices (IUDs) in two young women's hematology clinics and compare adverse events in adolescents with and without inherited bleeding disorders (BDs) DESIGN: Retrospective multicenter cohort study from February 2014 through February 2020 SETTING: Young women's hematology clinics at Nationwide Children's Hospital in Columbus, Ohio, and Children's Medical Center in Dallas, Texas PARTICIPANTS: Female patients evaluated for heavy menstrual bleeding (HMB) who underwent IUD placement INTERVENTIONS AND MAIN OUTCOME MEASURES: Rates of IUD expulsion, malposition, and ongoing HMB requiring additional medical treatment RESULTS: We identified 43 patients with BDs and 35 patients without BDs who underwent placement of an IUD for HMB. The mean age was 14.9 years (range 11.0-21.4 years) at the time of presentation and 15.8 years (range 11.0-21.4 years) at IUD placement. Those with BDs were younger at the time of IUD insertion. Most patients (90%) had previously failed other methods to control HMB. The annual rate of IUD adverse events was 0.25 per year of use, and all adverse events occurred in the first 20 months after placement. There were no significant differences in adverse IUD events in patients with and without BDs, although those without BDs requested IUD removal more frequently.In this cohort of adolescent females, the presence of a BD was not associated with a higher IUD expulsion rate. IUD placement should be considered a first-line option for adolescents with BDs who experience HMB.

Childhood acute lymphoblastic leukemia (ALL) fortunately has high survival rates, and understanding longer term implications of therapy is critical. In this study, we aimed to investigate kidney health outcomes by assessing the prevalence of renal dysfunction and hypertension (HTN) in children with ALL at 1-5 years after ALL diagnosis.This was a single-center, cross-sectional study of children with ALL who were 1-5 years post diagnosis. Glomerular filtration rate (GFR) measurements were calculated, and urine samples were collected to assess for protein/creatinine and albumin/creatinine. Blood pressure (BP) was determined by standard oscillometric technique, and children ≥6 years of age were eligible for ambulatory blood pressure monitoring (ABPM).Forty-five patients enrolled in the study, and 21 completed ABPMs. Fifteen patients (33%, 95% CI: 20%-49%) developed acute kidney injury (AKI) at least once. Thirteen (29%, 95% CI: 16%-44%) had hyperfiltration, and 11 (24%) had abnormal proteinuria and/or albuminuria. Prevalence of HTN based on clinic measurements was 42%. In the 21 ABPM patients, 14 had abnormal results (67%, 95% CI: 43%-85%), with the majority (11/21) demonstrating abnormal nocturnal dipping pattern.Among children with ALL, there is a high prevalence of past AKI. The presence of hyperfiltration, proteinuria, and/or albuminuria at 1-5 years after ALL diagnosis suggests real risk of developing chronic kidney disease (CKD) over time. There is a high prevalence of HTN on casual BP readings and even higher prevalence of abnormal ABPM in this group. The high prevalence of impaired nocturnal dipping by ABPM indicates an increased risk for future cardiovascular or cerebral ischemic events.

Malnutrition during cancer treatment increases treatment-related morbidity and mortality. Our study better characterizes variability in malnutrition identification and treatment by examining nutrition-related diagnoses and support for children with central nervous system (CNS) and non-CNS solid tumors during therapy. We examined diagnosis of malnutrition, use of tube feeding or parenteral nutrition (PN), and appetite stimulants.We retrospectively reviewed 0 to 21-year-old patients in the Pediatric Health Information System from 2015 to 2019. Patients were classified as having (1) billed malnutrition diagnosis, (2) malnutrition diagnosis or using PN and enteral nutrition ("functional malnutrition"), and (3) any previous criteria or prescribed appetite stimulants ("possible malnutrition"), as well as associated risk factors.Among 13,375 unique patients, CNS tumors were most common (24.4%). Overall, 26.5% of patients had malnutrition diagnoses, 45.4% met functional malnutrition criteria, and 56.0% had possible malnutrition. Patients with adrenal tumors had highest billed, functional, and possible malnutrition (36.6%, 64.1%, and 69.4%, respectively) followed by CNS tumors (29.1%, 52.4%, and 64.1%). Patients with adrenal tumors had highest rates of PN use (47.4%) and those with CNS tumors had the highest tube feeding use (26.8%). Hospital admissions with malnutrition had a longer hospital length of stay (LOS) (6 vs 3 days, P 0.0001), more emergency department admissions (24.4% vs 21.8%, P 0.0001), and more opioid use (58.6% vs 41.4%, P 0.0001).Variability in malnutrition diagnoses hinders clinical care and nutrition research in pediatric oncology. Improving disease-specific recognition and treatment of malnutrition can target nutrition support, ensure appropriate reimbursement, and potentially improve outcomes for children with solid tumors.

BACKGROUND: A standard-of-care has not been established for the management of patients with Down syndrome (DS) who develop primary central nervous system (CNS) germ cell tumors (GCTs) – the most common CNS neoplasm in DS – despite being more susceptible to treatment-related adverse events. METHODS: Data from large academic institutions were collected and a comprehensive review of the medical literature was conducted. RESULTS: Ten patients from six institutions (five USA, one Brazil) were reviewed. Additionally, thirty-one patients were identified in the literature from 1975-2021. Of the 41 total patients, mean age was ten years (range, birth to 35 years); males were predominant (61%). Basal ganglia were the most common tumor location (n=12; 29%), followed by posterior fossa (n=7; 17%). Sixteen patients had non-germinomatous germ cell tumors (NGGCTs) (39%), 14 had pure germinomas (34%), and eight had teratomas (20%); histology was unreported for two (5%). Nine patients (22%) experienced disease relapse, of which four died from tumor progression (one germinoma versus three teratoma). Fifteen patients (37%) experienced treatment-related complications - seven died (four germinoma versus three NGGCT). Of the germinoma patients, two died from chemotherapy-related sepsis, one from post-surgery cardiopulmonary failure, and one from Moyamoya following radiation-therapy (RT) only. Of the NGGCT patients, one died from chemotherapy-related sepsis, one from post-surgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival (OS) was 66% for all histological types - 62% germinoma, 79% for NGGCT, and 53% for teratoma. Three-year OS for patients who received RT or chemotherapy was 71% and 75% respectively. Twenty-seven patients remain alive at latest follow-up (mean follow-up from diagnosis: 46.8 months). CONCLUSIONS: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered for this patient population to mitigate treatment-related complications and long-term neurocognitive sequelae.

OBJECTIVES In 2009, a large multicenter study demonstrated that the rate of pediatric venous thromboembolism (VTE) across US children’s hospitals had significantly increased from 2001 to 2007. The objective of this study was to evaluate the rate of pediatric VTE from 2008 to 2019 using similar methodology. METHODS A retrospective cohort study using the Pediatric Health Information System (PHIS) database. Subjects from birth to RESULTS During the 12-year study period, there were 52 401 hospital admissions among 39 713 pediatric patients with a diagnosis of VTE. The VTE admission rate increased from 46 VTE cases per 10 000 admissions in 2008 to 106 VTE cases per 10 000 admissions in 2019, a 130% increase (P < .0001) in VTE events. The median age at admission was 6.1 years, and almost one-third (31.3%) of patients with VTE were in the adolescent age group (13–17 years). Most patients (78%) had an underlying chronic medical condition. CONCLUSIONS The rate of VTE in hospitalized pediatric patients continues to increase from a 70% increase reported from 2001 to 2007 to the 130% increase from 2008 to 2019. These findings support the need for more effective VTE prevention strategies. Clinical trials focused on risk stratification and VTE prevention are needed.

To define the incidence of acute kidney injury (AKI), chronic kidney disease (CKD), and hypertension (HTN) in pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) over a recent 9-year period.This study is a retrospective cohort study of all pediatric patients diagnosed with ALL at Nationwide Children's Hospital from January 1, 2008, to December 31, 2016. Patient demographic and clinical data including serum creatinine and blood pressure were collected at diagnosis up to 9 years post diagnosis.A total of 222 patients were identified for this study. The overall incidence of AKI in our cohort was high, with 101 subjects (45.5%, CI 38.8-52.3%) developing AKI at least once. CKD status could only be determined in 214 patients due to limited later GFR data. The incidence of CKD was low with only 5 of 214 patients developing CKD (2.3%, CI: 0.8-5.4%). The overall incidence of HTN at diagnosis was 45.6% (95% CI: 59.1-72%), and at 1 month post diagnosis was 65.8% (95% CI: 59.1-72.0%). Chronic HTN could only be determined in 216 patients due to limited blood pressure data. Chronic HTN was noted in 34.3% of patients (74/216, 95% CI: 28-41%).Among children with ALL, the incidence of AKI is relatively high at the time of diagnosis. However, development of CKD is relatively rare, suggesting good mid-term kidney prognosis. There is a high incidence of HTN at the time of diagnosis, 1 month post diagnosis, and chronic HTN that often goes untreated. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hematopoietic cell transplantation (HCT) is the sole curative option for congenital dyserythropoietic anemia (CDA), a rare type of hemolytic anemia characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. In this retrospective multicenter study, we report the outcomes of children with CDA who underwent HCT at participating Pediatric Transplantation and Cellular Therapy Consortium centers. Clinical information on HCT and associated outcomes was collected retrospectively using a common questionnaire. Data were analyzed using descriptive statistics and appropriate analysis. Eighteen patients with CDA who underwent allogeneic HCT between 2002 and 2020 were identified. The majority of patients (n = 13) had CDA type II, and the remainder had either CDA type I (n = 2) or CDA of unknown type (n = 3). Mutations were identified in 7 patients (39%), including SEC23B in 5, GATA1 in 1, and abnormality of chromosome 20 in 1. Thirteen patients had evidence of iron overload pre-HCT and received chelation therapy for a median duration of 10 months (range, 2 months to 17 years) pre-HCT. The median age at the time of HCT was 5.5 years (range, 0.7 to 26 years). Donors were HLA-matched (sibling, 4; unrelated, 10) and mismatched (haploidentical, 1; unrelated, 3). Graft sources were bone marrow in 15 patients, umbilical cord blood in 2 patients, or both in 1 patient. Conditioning included busulfan-based myeloablative (67%), fludarabine-based reduced-intensity (27%), or nonmyeloablative (6%) regimens. Five patients developed veno-occlusive disease, and 4 had viral reactivation. The cumulative incidence of acute graft-versus-host disease (GVHD) was 33%, and that of chronic GVHD was 22%. Four patients (22%) experienced graft failure; all engrafted following either a second HCT (n = 2) or third HCT (n = 2) but sustained considerable morbidities (3 GVHD, 1 death, 2 viral reactivation). With a median follow-up of 3.2 years (range, 0.6 to 14 years)), the 2-year overall survival, event-free survival (EFS), and GVHD-free EFS were 88% (95% confidence interval [CI], 73% to 100%), 65% (95% CI, 45% to 92%), and 60% (95% CI, 40% to 88%), respectively. Univariate analysis did not identify any patient- or transplantation-related variables impacting outcomes. Our study indicates that HCT can be curative for patients with CDA. Strategies such as aggressive chelation, use of preconditioning therapy, and early HCT in the presence of a suitable donor before comorbidities occur are needed to improve engraftment without increasing the risk for toxicity and mortality.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with Medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. METHODS: Between 1997-2013, data from 103 children older than three years with Medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997 – 2008 and 2009 – 2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, while prognostic factors were determined by univariate analysis (log-rank test). RESULTS: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The five-year OS was 62% (95% CI: 53 – 74%) while EFS was 57% (95% CI: 48 – 69%). The variables adversely affecting survival were anaplastic histology [compared to desmoplastic; OS: HR=3.4, p=0.03], metastasis [OS: HR=3.5, p=0.01; EFS: HR=4.3, p=0.004], delay in radiation therapy of 31-60 days [compared to ≤30 days; EFS: HR=2.1, p=0.04], and treatment 2009 – 2013 cohort[OS: HR=2.2, p=0.02; EFS: HR=2.0; p=0.03]. CONCLUSIONS: Outcomes for Medulloblastoma at INEN were low compared with HIC. Anaplastic sub-type, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009 - 2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.

Despite recommendations for vaccination after hematopoietic cell transplantation (HCT), immunization rates remain low leaving children at high risk for vaccine preventable infections (VPIs). However, the burden from VPIs in pediatric HCT recipients is not well known. We describe the prevalence, risk factors, and outcomes of VPI-associated hospitalizations at centers participating in the Pediatric Health Information System database. Children18 years who underwent allogeneic or autologous-HCT between 1/1/2010-31/12/2018, were identified and prevalence of overall VPI and of each infection were determined at five time-points within 5 years post-HCT. In total, 684 of 9591 pediatric HCT recipients had a VPI-associated hospitalization, most frequently in the first 6-12 months, for an overall prevalence of 7.1% (95% CI: 6.6-7.7%). Influenza, varicella, and invasive pneumococcal infections were the most frequent. Multivariable analyses identified younger age (OR = 0.96 [95% CI: 0.93-0.99]; p = 0.013), primary immune deficiency (PID) (OR = 1.78 [95% CI: 1.11-2.84]; p = 0.016), and GVHD (OR = 1.62 [95% CI: 1.05-2.48]; p = 0.028) as independent risk factors during the initial HCT-hospitalization. Children with VPI had longer duration of hospitalization (55[51] vs 36[24] days, p 0.001)

Mesenchymal stromal cells (MSCs) possess remarkable tumor tropism, making them ideal vehicles to deliver tumor-targeted therapeutic agents; however, their value in clinical medicine has yet to be realized. A barrier to clinical utilization is that only a small fraction of infused MSCs ultimately localize to the tumor. In an effort to overcome this obstacle, we sought to enhance MSC trafficking by focusing on the factors that govern MSC arrival within the tumor microenvironment. Our findings show that MSC chemoattraction is only present in select tumors, including osteosarcoma, and that the chemotactic potency among similar tumors varies substantially. Using an osteosarcoma xenograft model, we show that human MSCs traffic to the tumor within several hours of infusion. After arrival, MSCs are observed to localize in clusters near blood vessels and MSC-associated bioluminescence signal intensity is increased, suggesting that the seeded cells expand after engraftment. However, our studies reveal that a significant portion of MSCs are eliminated en route by splenic macrophage phagocytosis, effectively limiting the number of cells available for tumor engraftment. To increase MSC survival, we transiently depleted macrophages with liposomal clodronate, which resulted in increased tumor localization without substantial reduction in tumor-associated macrophages. Our data suggest that transient macrophage depletion will significantly increase the number of MSCs in the spleen and thus improve MSC localization within a tumor, theoretically increasing the effective dose of an anti-cancer agent. This strategy may subsequently improve the clinical efficacy of MSCs as vehicles for the tumor-directed delivery of therapeutic agents.

The sacral ratio has been used as a tool for evaluating sacral development in patients with anorectal malformations. Sacral ratios can be calculated by obtaining sacral radiographs in the anteroposterior (AP) and lateral planes.The objective of the study was to determine the correlation and agreement in sacral ratio calculations.In this single institution retrospective cohort study, we reviewed medical charts of all pediatric anorectal malformation patients treated between March 2014 and September 2018 who had both AP and lateral images of their sacrum. All sacral ratios were measured by three radiologists. Pearson's correlation coefficients and corresponding 95% confidence intervals (CIs) were used to assess the correlation between the AP and lateral radiographs. A weighted Kappa statistic was used to measure the agreement between how the AP and lateral sacral ratios categorized observations into risk groups.Our initial cohort consisted of 646 observations from patients with anorectal malformations who had radiographs obtained in both AP and lateral planes. We excluded all observations (n=76) where the radiographs were deemed to be inadequate or not appropriately centered to measure sacral ratio. For a given pair of measurements, the mean lateral sacral ratio was 0.07 units greater than the AP plane (95% CI 0.06-0.09, paired t-test P-value0.0001). AP and lateral images had a moderate positive correlation (Pearson's r=0.76, 95% CI 0.73-0.79, P0.0001) and moderate agreement in risk categorization (unweighted kappa = 0.60, P0.0001). AP and lateral readings conducted by all three radiologists had excellent inter-rater reliability with intraclass correlations for AP and lateral sacral ratios of 0.88 and 0.84, respectively.Even though the AP and lateral sacral ratios had moderate positive correlation, the mean sacral ratio determined by images in the lateral plane was 0.07 units greater than the AP plane. AP and lateral sacral ratios concluded different risk categories relatively often. Future studies are needed to determine whether AP or lateral sacral ratios correlate better with continence in patients with anorectal malformations.

BACKGROUND Needles are frequently required for routine medical procedures. Children with severe hemophilia require intensive intravenous (IV) therapy to treat and prevent life-threatening bleeding and undergo hundreds of IV procedures. Fear of needle-related procedures may lead to avoidance of future health care and poor clinical outcomes. Virtual reality (VR) is a promising distraction technique during procedures, but barriers to commercially available VR platforms for pediatric health care purposes have prevented widespread use. OBJECTIVE We hypothesized that we could create a VR platform that would be used for pediatric hemophilia care, allow clinician orchestration, and be safe and feasible to use for distraction during IV procedures performed as part of complex health care. METHODS We created a VR platform comprising wireless, adjustable, disposable headsets and a suite of remotely orchestrated VR games. The platform was customized for a pediatric hemophilia population that required hands-free navigation to allow access to a child’s hands or arms for procedures. A hemophilia nurse observing the procedure performed orchestration. The primary endpoint of the trial was safety. Preliminary feasibility and usability of the platform were assessed in a single-center, randomized clinical trial from June to December 2016. Participants were children with hemophilia aged 6-18 years. After obtaining informed consent, 25 patients were enrolled and randomized. Each subject, 1 caregiver, and 1 hemophilia nurse orchestrator assessed the degree of preprocedural nervousness or anxiety with an anchored, combined modified visual analog (VAS)/FACES scale. Each participant then underwent a timed IV procedure with either VR or standard of care (SOC) distraction. Each rater assessed the distraction methods using the VAS/FACES scale at the completion of the IV procedure, with questions targeting usability, engagement, impact on procedural anxiety, impact on procedural pain, and likability of the distraction technique. Participants, caregivers, and nurses also rated how much they would like to use VR for future procedures. To compare the length of procedure time between the groups, Mann-Whitney test was used. RESULTS Of the 25 enrolled children, 24 were included in the primary analysis. No safety concerns or VR sickness occurred. The median procedure time was 10 (range 1-31) minutes in the VR group and was comparable to 9 (range 3-20) minutes in the SOC group (P=.76). Patients in both the groups reported a positive influence of distraction on procedural anxiety and pain. Overall, in 80% (34/45) of the VR evaluations, children, caregivers, and nurses reported that they would like to use VR for future procedures. CONCLUSIONS We demonstrated that an orchestrated, VR environment could be developed and safely used during pediatric hemophilia care for distraction during IV interventions. This platform has the potential to improve patient experience during medical procedures. CLINICALTRIAL Clinical Trials.gov NCT03507582; https://clinicaltrials.gov/ct2/show/NCT03507582 (Archived by WebCite at http://www.webcitation.org/73G75upA3)

Background Allo-HCT recipients are at increased risk for vaccine-preventable infections. Early vaccination (EV) beginning at 3–6 months (mo) post-HCT has been shown to be safe, immunogenic, and is recommended. We assessed adherence and immunogenicity to EV in children post-allo-HCT. Methods Retrospective analysis of allo-HCT performed 1/1/10–6/30/18 at NCH. Children who died, relapsed, or received anti-CD20 biologics in the 6 mo preceding intended vaccination were excluded. Institutional guidelines recommend EV starting at 6 (+1) mo post-HCT with: 3 PCV13 + 1 PPSV23, IPV, HBV, DTaP and HIB. Vaccination rates were analyzed at 6(+1), 8(+1) and 10(+1) mo post-HCT and serologies were obtained pre- and ≥ 4 weeks post vaccination. Immunogenicity was defined as antibody (Ab) concentrations ≥ 1.3 µg/mL or a 4 fold rise ≥ 70% of 10 PCV13 serotypes, tetanus (T) and diphtheria (D) Ab ≥ 0.1 IU/mL, and HBs Ab ≥ 10 IU/mL. Non-parametric statistics were applied; correlations between T&B cell subsets and IgG pre-vaccination and specific Ab post-vaccination were performed. Results During the 8-year study period, 171 allo-HCT were performed: 131 children were eligible for EV (Table 1); however, EV occurred in only 49.6% (65/131) and was completed in 37.5% (45/120) of children at 10(+1) mo post-HCT. Vaccine immunogenicity of PCV13, HBV, T and D was achieved in 40/45, 34/36, 63/64, and 18/18 of evaluable children, respectively. Protective Ab response after EV for PCV13, HBV, T and D was found in 21/24 (87.5%), 14/16 (87.5%), 35/36 (97.2%), and 8/8 (100%) children, respectively. Specific IgG geometric mean concentration pre- and post-vaccination was similar in children whether they received early or delayed vaccination (median 9.8 mo post-HCT, IQR 8–14) (Figures 1 and 2). No correlations were found between absolute CD4, CD8, CD19 and IgG pre-vaccination and vaccines specific Abs post-vaccination (Figure 3). Conclusion Despite recommendations, adherence to EV was low among our cohort of allo-HCT recipients and identified opportunities for improvement. Overall, vaccines were immunogenic with no significant differences in Ab concentrations among patients receiving early vs. delayed vaccination. No robust correlations were found between number of T&B cells or total IgG and Ab titers. Disclosures All authors: No reported disclosures.

Menstruating women, with or without underlying bleeding disorders, are at increased risk for developing iron deficiency-related fatigue, even in the absence of anemia. Oral iron therapy has limitations which include poor absorption and non-adherence due to gastrointestinal side effects. We performed a prospective clinical trial of post-menarchal adolescent females with iron-deficiency with or without mild anemia and fatigue who received a standardized regimen of intravenous iron sucrose. The baseline mean (SD) hemoglobin was 11.96 g dl(-1) (1.05) in 20 girls (ages 14-21 years); with a range of 10.3-14.1 g dl(-1) . In this cohort, intravenous iron was well tolerated and patients demonstrated a sustained increase in ferritin levels with means (SD) of 13.4 ng ml(-1) (13.1) at baseline to 141.5 ng ml(-1) (104.5) at 6 weeks and 85.2 ng ml(-1) (128.4) at 6 months after the infusions. We used a standardized (Peds QL(TM) Multidimensional) fatigue scale to objectively measure fatigue and proxy scores by parents with mean screening scores (SD) of 35.2 (16.8) and 31.9 (19.6), respectively. We demonstrated a clinically significant improvement both in patient as well as parent fatigue scores (in 19 out of 20 subjects) at 6 weeks (Mean (SD) 58.3 (21.3) [P 0.0001] and 57 (24.4) [P 0.0001], respectively); as well as 3 and 6 months after the iron infusions. In nonanemic patients, iron administration did not significantly influence hemoglobin concentration. Therefore, the fatigue-reducing effects of iron therapy reflect the nonhematological functions of iron. Am. J. Hematol. 91:973-977, 2016. © 2016 Wiley Periodicals, Inc.