Sexually transmitted infection testing and diagnosis in adolescents and young adults with sickle cell disease.

BACKGROUND: Sexually transmitted infections (STIs) are common and disproportionately affect Black adolescents and young adults (AYAs). Less is known about STIs among Black AYAs with chronic conditions, such as sickle cell disease (AYAs-SCD). This study compared STI testing and diagnosis between AYAs-SCD and their peers, overall and among STI-related encounters. PROCEDURE: This retrospective, cross-sectional study used diagnosis and billing codes in the Pediatric Health Information System (PHIS) to identify inpatient and emergency department encounters from January 1, 2022 to May 31, 2023 among all AYAs 15-24 years and those with STI-related diagnoses (e.g., "cystitis"). STI testing and diagnosis rates were compared between AYAs-SCD, non-Black AYAs, and Black AYAs, controlling for age, sex, and encounter setting. RESULTS: We identified 3602 AYAs-SCD, 177,783 Black AYAs, and 534,495 non-Black AYAs. AYAs-SCD were less likely to be tested for STIs than non-Black AYAs (odds ratio [OR] = 0.26; adj. p < .001) and Black AYAs (OR = 0.53; adj. p < .001). When tested, AYAs-SCD were more likely to be diagnosed with an STI than non-Black AYAs (OR = 2.39; adj. p = .006) and as likely as Black AYAs (OR = 0.67; adj. p = .15). Among STI-related encounters, AYAs-SCD were less likely to be tested than non-Black AYAs (OR = 0.18; adj. p < .001) and Black AYAs (OR = 0.44; adj. p < .001). No significant differences in STI diagnoses were found in this subset between AYAs-SCD and non-Black AYAs (OR = 0.32; adj. p = .28) or Black AYAs (OR = 1.07; adj. p = .99). CONCLUSIONS: STI care gaps may disproportionately affect AYAs-SCD. STIs should be considered when evaluating symptomatic AYAs-SCD in acute settings. More research is needed to further contextualize STI care for AYAs-SCD.

Influenza vaccine uptake among youth with sickle cell disease who are seen in clinic before and after the COVID-19 pandemic.

Influenza vaccination is critical for children with sickle cell disease (SCD) due to risks of severe influenza infections. Despite declining influenza vaccination among children since the COVID-19 pandemic, less is known about influenza vaccine coverage among youth with SCD during this same period. We compared influenza vaccine uptake among youth with SCD seen by a SCD provider in clinic during the 2019-2020 and 2022-2023 influenza seasons and described infection characteristics. Overall, 85% (n = 220) of children received their influenza vaccine during 2019-2020 compared to 75% (n = 245) in 2022-2023 (p = 0.059). Participants seen during both seasons were more likely to shift from vaccinated in 2019-2020 to unvaccinated in 2022-2023 than vice versa (McNemar's OR = 3.0; p = 0.008). Among 66 documented infections, 25.8% resulted in hospitalization. We found high influenza vaccine uptake but those seen during both seasons were more likely to become unvaccinated. More research is needed to understand influenza vaccine decision-making in this population.

Characterizing age-related differences in Hodgkin lymphoma in children, adolescents and young adults.

Current studies describing younger children with Hodgkin lymphoma are limited by geographical region, small sample sizes and variable age groups. Although published data is lacking, there appears to be a trend toward a higher male to female ratio and a higher proportion of mixed cellularity subtype when compared to older cohorts. We performed a retrospective multicenter study utilizing the Pediatric Health Information System® database to evaluate patients aged 0-39 years with Hodgkin lymphoma. We identified 3,034 unique patients who met inclusion criteria. Younger age groups had a larger proportion of males, Hispanic/Latino ethnicity, and mixed cellularity subtype. Treatment-related complications, including mucositis, pain, bacterial infections, and thrombosis, were documented more frequently in older cohorts. We also found significant age-related differences in medical management. This study is the largest study evaluating age-related differences in patients with Hodgkin lymphomaand the first study to evaluate for differences in complicationsand supportive care management.

Comparison of Outcomes Between Surveillance Ultrasound and Completion Lymph Node Dissection in Children and Adolescents With Sentinel Lymph Node-Positive Cutaneous Melanoma.

OBJECTIVE: To determine the impact of nodal basin ultrasound (US) surveillance versus completion lymph node dissection (CLND) in children and adolescents with sentinel lymph node (SLN) positive melanoma. BACKGROUND: Treatment for children and adolescents with melanoma are extrapolated from adult trials. However, there is increasing evidence that important clinical and biological differences exist between pediatric and adult melanoma. METHODS: Patients ≤18 years diagnosed with cutaneous melanoma between 2010 and 2020 from 14 pediatric hospitals were included. Data extracted included demographics, histopathology, nodal basin strategies, surveillance intervals, and survival information. RESULTS: Of 252 patients, 90.1% (n=227) underwent SLN biopsy (SLNB), 50.9% (n=115) had at least 1 positive node. A total of 67 patients underwent CLND with 97.0% (n=65/67) performed after a positive SLNB. In contrast, 46 total patients underwent US observation of nodal basins with 78.3% (n=36/46) of these occurring after positive SLNB. Younger patients were more likely to undergo US surveillance (median age 8.5 y) than CLND (median age 11.3 y; P =0.0103). Overall, 8.9% (n=21/235) experienced disease recurrence: 6 primary, 6 nodal, and 9 distant. There was no difference in recurrence (11.1% vs 18.8%; P =0.28) or death from disease (2.2% vs 9.7%; P =0.36) for those who underwent US versus CLND, respectively. CONCLUSIONS: Children and adolescents with cutaneous melanoma frequently have nodal metastases identified by SLN. Recurrence was more common among patients with thicker primary lesions and positive SLN. No significant differences in oncologic outcomes were observed with US surveillance and CLND following the identification of a positive SLN.

Variability in Surveillance Strategies Following Resection of Sacrococcygeal Teratoma.

INTRODUCTION: Surveillance following sacrococcygeal teratoma (SCT) resection varies. The purpose of this study was to describe the clinical characteristics and outcomes of patients undergoing SCT resection and examine current institutional practices to detect recurrence. METHODS: A single-institution retrospective review of children who underwent resection of an SCT from January 1, 2010 to December 31, 2020 was performed. Data were summarized and surveillance strategies compared between histopathologic subtypes using nonparametric methods. RESULTS: Thirty six patients (75.0% female) underwent SCT removal at a median age of 8 d. Histopathology revealed 27 mature teratomas (75.0%), eight immature teratomas (22.2%), and one malignant germ cell tumor (2.8%). Median postoperative follow-up was 3.17 y (interquartile range [IQR]: 2.31-4.38 y). Patients had a median of 2.32 clinic visits per year (IQR: 2.00-2.70), alpha-fetoprotein levels were obtained at a median of 2.01 times per year (IQR: 0-1.66), and surveillance imaging was performed at a median of 2.31 times per year (IQR: 0-2.84). Patients with immature teratomas had alpha-fetoprotein laboratories obtained more frequently than patients with mature teratomas (3.10 times/year versus 0.93 times/year, P = 0.001). There was no significant difference in the number of imaging studies obtained between groups. Two patients (5.6%) developed recurrence, which were identified on magnetic resonance imaging at 191 and 104 d postresection, respectively. CONCLUSIONS: Postoperative surveillance practices varied widely. Recurrence was noted in a single malignant case in the first year following resection. Multi-institutional studies are needed to determine the optimal surveillance strategy to detect recurrence of SCT.

Increasing optimal coagulation factor dosing in the paediatric emergency department: Update to a quality improvement study.

INTRODUCTION: Prompt, appropriate coagulation factor replacement according to injury and bleeding severity in persons with haemophilia is required to prevent acute and long-term complications. AIMS: Increase proportion of persons with haemophilia A (HA) and B (HB) treated appropriately for an acute injury and bleeding episode at a tertiary children's emergency department (ED) from 65% to 85% and sustain for one year. Secondary aim: increase time interval between patient ED encounters with out-of-range factor dosing. METHODS: Utilizing quality improvement methodology and plan-do-study-analyze cycles, ED encounters for individuals with HA/HB receiving coagulation factor replacement for injuries were audited for in-range coagulation factor dosing. Goal factor dose defined as 50% correction for minor bleeds and 100% correction for major bleeds. Optimal dosing range defined as 90%-120% of the calculated goal dose to account for vial size variability. Interventions targeted communication via the EMR problem list and optimization of physician education. RESULTS: Our previous publication demonstrated 33.3% of ED encounters with out-of-range factor replacement. Following several interventions, the cumulative rate of encounters with out-of-range dosing decreased to 18%. Overall, there was an increase in the mean percent of encounters receiving optimal factor dosing for both HA/HB compared to baseline (82.2% vs. 71.1%), though this was not a statistically significant difference. CONCLUSION: Despite implementation of multiple interventions, out-of-range factor dosing continues to occur. Our team plans to reinstate simulation center education for ED staff and continue education efforts of pharmacists and hematology trainees with the goal of further reducing out-of-range dosing in our ED.

Comparison of thromboembolism outcomes in patients with sickle cell disease prescribed hormonal contraception.

Patients with sickle cell disease (SCD) are at a risk of thromboembolism (TE), and use of hormonal contraception can further increase that risk. This study aims to assess patterns of hormonal contraceptive use and compare risk of contraception-related TE between combined hormonal contraceptives (CHCs) and progestin-only contraceptives (POCs). Patients with SCD aged between 12 and 44 years with a new prescription of a hormonal contraceptive in the Centers for Medicare and Medicaid Services Medicaid Analytic eXtract database (2006-2018) were followed up to 1 year. We identified 7173 new users: 44.6% initiated CHC and 55.4% initiated POC. Combined oral contraceptive pills (OCPs; 36.5%) and progestin-only depot medroxyprogesterone acetate (33.9%) were the most frequently prescribed agents. A total of 1.8% of contraception users had a new diagnosis of TE within 1 year of the first identified contraception prescription. There were no significant differences in TE event rates between CHC and POC users (17.2 and 24.7 events per 1000 person-years, respectively). In patients prescribed OCP, there were no differences in TE event rates based on estrogen dose or progestin generation. Transdermal patch had a 2.4-fold increased risk of TE as compared with that of OCP. Although limited by the retrospective study design and use of administrative claims data, this study found no significant differences in TE rates between new users of CHC and POC in patients with SCD. Careful evaluation of underlying TE risk factors should be considered for each patient with SCD before initiation of hormonal contraception.

Pregnancy-related thromboembolism in women with sickle cell disease: An analysis of National Medicaid Data.

Pregnancy and sickle cell disease (SCD) both individually carry a risk of thromboembolism (TE). Pregnancy in people with SCD may further enhance the prothrombotic effect of the underlying disease. The objectives of this study were to determine the rate and risk factors for arterial and venous thrombosis in pregnant people with SCD. Administrative claims data from the United States Centers for Medicare and Medicaid Service Analytic eXtract from 2006 to 2018 were used. The study population included people with SCD from the start of their first identified pregnancy until 1 year postpartum and a control cohort of pregnant people without SCD of similar age and race. Outcomes of interest were identified with ICD-9 or 10 codes. Logistic regression analyses were used to analyze risk factors. We identified infant deliveries in 6388 unique people with SCD and 17 110 controls. A total of 720 venous thromboembolism (11.3%) and 335 arterial TE (5.2%) were observed in people with SCD compared to 202 (1.2%) and 95 (0.6%) in controls. People with SCD had an 8-11 times higher odds of TE compared to controls (p < .001). Within the SCD cohort, age, hemoglobin SS (HbSS) genotype, hypertension, and history of thrombosis were identified as independent risk factors for pregnancy-related TE. Pregnancy-specific factors (pre-eclampsia, eclampsia, multigestational pregnancy) were not associated with TE. In conclusion, the risk of pregnancy-related TE is considerably higher in people with SCD compared with controls without SCD. Hence, people with SCD, particularly those with multiple risk factors may be candidates for thromboprophylaxis during pregnancy and the postpartum period.

Peritoneal and Pleural Drains in Pediatric Hematopoietic Cell Transplant Recipients with Veno-Occlusive Disease are Safe and Do Not Adversely Impact Clinical Outcomes.

There is a lack of data on the safety and efficacy of peritoneal drain (PD) and chest tube (CT) in the management of effusions in stem cell transplant recipients with veno-occlusive disease (VOD). In this retrospective pediatric study, clinical outcomes and health resource utilization (HRU) were compared in 32 patients with VOD who had a PD (PD+) post-HCT versus 27 patients who did not (PD-). Nine patients also had a CT (7 PD+ and 2 PD-). PD + patients were more likely than PD-patients to have received myeloablative conditioning (100% vs. 85.2%; p = 0.04) and have severe or very severe VOD (100% vs. 56% p < 0.01). Mechanical obstruction (38%) and hypotension (38%) were common complications, and 13% developed peritonitis. While the frequencies of cardiac dysfunction and acute kidney injury were comparable between both groups, respiratory support and its median duration were higher in PD + patients. The hospital and intensive care unit length of stay, albumin use, and the duration of defibrotide and albumin therapy was significantly longer in PD + patients. At a median follow-up of 1.04 years (range:0.03-14.6), the 2-year overall survival was similar in both groups (53.8% vs. 51.5%; p = 0.73). Although PD use was similar between 1995 and 2007 vs. 2008-2021; (47% vs. 58%; p = 0.65), day+100 mortality was improved in recent years (53.3% vs. 17.8%; p = 0.01), coinciding with the use of defibrotide (0% vs. 84%; p < 0.01). PD in pediatric patients with VOD post-HCT, although associated with increased HRU, was safe when clinically indicated and did not adversely impact clinical outcomes.

Exploring the Role of Antithrombin in Nephrotic Syndrome-Associated Hypercoagulopathy: A Multi-Cohort Study and Meta-Analysis.

BACKGROUND: Nephrotic syndrome is associated with an acquired hypercoagulopathy that is thought to drive its predisposition for venous thromboembolism. Previous studies have suggested that urinary antithrombin (AT) loss leading to acquired AT deficiency is the primary mechanism underlying this hypercoagulopathy, but this hypothesis has not been directly tested. The objectives of this study were to test the influence of AT levels on hypercoagulopathy in nephrotic syndrome patient samples and perform meta-analyses to evaluate the likelihood of AT deficiency in patients with nephrotic syndrome. METHODS: Samples from three independent nephrotic syndrome cohorts were analyzed. AT antigen and activity assays were performed using ELISA and amidolytic assays, respectively. Plasma thrombin generation, albumin, and urine protein-to-creatinine ratios were determined using established methods. Meta-analyses were performed by combining these new data with previously published data. RESULTS: AT levels were not consistently related to either plasma albumin or proteinuria. AT was quantitatively related to hypercoagulopathy in adult nephrotic syndrome, whereas AT activity was inconsistently associated with hypercoagulopathy in childhood nephrotic syndrome. Notably, hypercoagulopathy did not differ between patients with normal AT levels and those with levels below the threshold used to define clinical AT deficiency (<70%). Moreover, ex vivo AT supplementation did not significantly alter hypercoagulopathy in AT-deficient plasma samples. The meta-analyses demonstrated that AT deficiency was not a uniform feature of nephrotic syndrome and was more common in children than adults. CONCLUSIONS: These data suggest that AT deficiency plays only a limited role in the mechanisms underlying the acquired hypercoagulopathy of nephrotic syndrome. Moreover, AT deficiency was not present in all patients with nephrotic syndrome and was more likely in children than adults despite the higher risk for venous thromboembolism in adults than children.

Assessing Bleeding Symptoms in Pediatric Patients With Generalized Joint Hypermobility.

OBJECTIVE: To assess bleeding symptoms in patients with generalized/benign joint hypermobility (GJH), compare bleeding scores to healthy historical pediatric controls, and determine whether a correlation exists between Beighton scores and bleeding scores. METHODS: Patients with GJH ages 6-21 years seen by the rheumatology department 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 the presence, severity, and frequency of bleeding symptoms. Scores of ≥3 have been associated with an underlying bleeding disorder in pediatric patients. RESULTS: Eighty-one patients agreed to participate. The median age was 13 years (interquartile range 10-16 years), and the 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 (P < 0.001). Although 75% of patients (95% confidence interval 64-84) had an abnormal bleeding score, only 12.3% were previously assessed by hematology for bleeding symptoms. Among patients with GJH, higher Beighton scores were not associated with higher bleeding scores (Spearman's correlation -0.08). CONCLUSION: In a cohort of pediatric patients with GJH, three-fourths of participants had abnormal bleeding scores, with the 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.

Sexual and Reproductive Health Outcomes in Females With Cloacal Malformations and Other Anorectal Malformations.

STUDY OBJECTIVE: 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. RESULTS: 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) (difference > 4.5). CONCLUSIONS: 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.

Accreditation Council for Graduate Medical Education Milestone Scores in Pediatrics: Pilot Study Exploring the Relationship Between Residency and Early Fellowship Scores.

BACKGROUND: 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. OBJECTIVE: To assess the relationship between final residency Milestones scores and first-year fellowship Milestones scores in the 11 common subcompetencies (CSCs) across pediatric subspecialties. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Intracardiac thrombi in pediatrics: anticoagulation approach and treatment outcomes.

Background: Intracardiac thrombi (ICT) are associated with significant morbidity and mortality. Anticoagulation is the first line of treatment and may be complemented by thrombectomy or thrombolysis. However, optimal anticoagulant duration remains ill-defined. High-risk features of ICT that may warrant long-term anticoagulation therapy have not been established. Objectives: To describe anticoagulation duration and patterns of ICT resolution. To identify potential risk factors for persistent ICT despite anticoagulation. Methods: A single-institution retrospective chart review identified patients diagnosed with ICT by echocardiogram between January 2014 and March 2022. Descriptive statistics and logistic regression were used. Results: Fifty-one patients with ICT were identified. Median age at diagnosis was 9.2 years (IQR, 0.4-15.2). The most common underlying diagnoses were congenital heart disease (41%), infection (25%), and malignancy (24%). The majority of ICT were in the right atrium (n = 30). The median longest ICT dimension was 1.5 cm (range, 0.4-4.0). The median duration of anticoagulation was 4.3 months (IQR, 2.2-9.1). Among 48 patients who received anticoagulation as first-line treatment, 32 had partial or complete response with 3 to 6 months of anticoagulation, while remaining 16 patients had no response to anticoagulation. Patients with a central venous line had a delayed resolution of ICT [hazards ratio = 0.45 (95% CI, 0.22-0.93)]. Conclusion: Our study demonstrates the wide variability in duration of anticoagulation for children with ICT. Majority of the individuals benefit from 3-to-6 month treatment; however, individuals with a central venous line may benefit from a longer course of anticoagulation. Further large-scale studies are recommended to validate our findings.

Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors.

Introduction: 177Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A. Methods: SST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by an experienced pathologist (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (<10%), 2 (10-50%), 3 (51-80%), or 4 (>80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (Range: 0-12). Results: A total of 120 tumor samples from 114 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean ± SD: 7.5 ± 3.6 [n=38]) and meningioma (5.7 ± 3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3 ± 0.6 [n=3]), ETMR (1.0 ± 0 [n=3]), ependymoma (grades I-III; 0.2 ± 0.7 [n=27]), and high-grade glioma (grades III-IV; 0.4 ± 0.7 [n=23]). Pineoblastoma (3.8 ± 1.5 [n=4]) and other embryonal tumors (2.0 ± 4.0 [n=7]) exhibited intermediate, variable expression. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.5 ± 3.1) than SHH (5.0 ± 3.3) molecular subgroups (p=0.033). In a subset of paired primary and recurrent specimens from four patients, SST2A IHC scores remained largely unchanged. Discussion: High membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors.

Intrauterine Device Outcomes in Young Women with Heavy Menstrual Bleeding: Comparing Patients with and without Inherited Bleeding Disorders.

STUDY OBJECTIVE: 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. CONCLUSIONS: 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.

Leveraging gene therapy to achieve long-term continuous or controllable expression of biotherapeutics.

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.

Multi-institutional analysis of central nervous system germ cell tumors in patients with Down syndrome.

PURPOSE: Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. METHODS: A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. RESULTS: Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9 years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n = 13; 31.7%), followed by posterior fossa (n = 7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. CONCLUSION: 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 to mitigate treatment-related complications and long-term neurocognitive sequelae.

Caregiver Perspectives on Patient Participation in Biological Pediatric Cancer Research.

Adolescent cancer patients and their caregivers have demonstrated willingness to participate in invasive biological sampling, either for their own potential benefit or for research purposes. However, many malignancies occur primarily in prepubescent patients and there are no similar studies in this population. Our study objective was to assess the willingness of caregivers to consent to research studies involving invasive biological sampling in children ≤ 13 years of age. Participants completed a survey assessing their willingness to allow various procedures both with and without clinical benefit to their children. Most respondents were willing to allow additional blood draws regardless of potential benefit to their children (95.6% were willing when there would be benefits and 95.6% were willing when there would not). Although the overall willingness was lower with other hypothetical procedures, the majority of respondents were still willing to allow additional biopsies for research purposes. Caregivers of young children with cancer will allow their children to undergo additional invasive procedures for research purposes. This willingness decreased with more invasive procedures without potential direct benefit, but interest remained in more than half of participants. Caregivers for young patients with cancer should be approached for participation in future biological/correlative studies.