Letters to the editorSomato-cognitive coordination therapy in a brain tumor survivor with attention-deficit/hyperactivity disorder symptoms and motor coordination impairmentsMasanobu Takeuchi, MD, PhD 1，Ayumi Kato, MD, PhD2，Masahiko Hara, MD, PhD 3Department of Pediatrics, Yokohama City University Hospital, Yokohama, JapanDepartment of Diagnostic Radiology, Yokohama City University Hospital, Yokohama, JapanDepartment of Neurology and Clinical Rehabilitation, mediVR Rehabilitation Center Tokyo, Tokyo, JapanCorrespondenceMasanobu Takeuchi3-9 Fukuura, Kanazawa, Yokohama, Kanagawa 236-0004, JapanPhone: (+81)-45-787-2800Fax: (+81)-45-787-2800mtake@yokohama-cu.ac.jpTotal Word counts: 831 wordsFigure: 1 FigureReference: 10 ReferencesKey words: Somato-cognitive coordination therapy, Attention-deficit/hyperactivity disorder, brain tumor survivor, cerebral blood flow

Background: The role of tumor genomics in influencing treatment outcomes remains a critical area of investigation in personalized medicine. This study is the first to evaluate the relationship between tumor mutational burden (TMB) and driver mutations (DM) in pediatric brain tumors, examining their association with treatment modalities and patient outcomes. Methods: We conducted a retrospective study of 160 pediatric patients (78 males, 82 females) with a median age of 9 years (range: 2 months to 26 years) who were diagnosed with primary CNS tumors across four academic institutions between 2008 and 2023. The analysis included TMB (high TMB ≥3 mutations/megabase, low TMB <3), DM, treatment modality, clinical outcomes, and matching status, defined as the alignment of tumor genomic markers with corresponding pharmacologic targets. Results: Low-grade glioma (42.5%) and high-grade glioma (22.5%) were the most common tumors, followed by medulloblastoma (10.6%), ependymoma (5%), ganglioglioma (4.4%), atypical teratoid rhabdoid tumor (2.5%), and other rare tumor types. Among patients receiving targeted or immunotherapy (N=30), most had matched therapy (N=19) and were found to have no significant survival advantage. High TMB tumors had better survival with standard therapy (p=0.026). Targeted and immunotherapy were used as second or later lines of treatment, with a non-significant trend suggesting better survival in recurrent or progressive disease. Conclusions: This study found no statistical significance linking matched therapy with molecular markers to improved overall survival. Most patients received targeted or immunotherapy as second-line or later treatment. High TMB tumors had better outcomes with standard therapy. The increased resistance and aggressiveness of recurrent tumors complicate the ability to evaluate targeted therapies as initial treatment options.

We report a case with multiple lineage switches, a rare event that mostly occurred in infants, in a ten-year-old girl with KMT2A-AFF1 positive ALL. Although she received standard chemotherapy, immunotherapy and hematopoietic stem cell transplantation (HSCT), the leukemic clone continuously switched on AML or ALL, maintaining immunoglobulin/T-cell receptor (IG/TR) rearrangements and showing a high grade of therapy-escaping. Since other genes are involved in this event, considering the selective pressure imposed by the applied treatment, it is mandatory to characterize the cell-of-origin that is capable to proliferate towards both lineages in the attempt to design a targeted therapy.

Since 2000, centers across Central America have shared treatment guidelines for Wilms tumor, using histology (anaplasia present or absent) and tumor stage to stratify patients into low, intermediate, and high-risk groups. Weekly virtual tumor board meetings involving local and international experts were held to ensure consistent treatment assignments. We analyzed data from 367 children with unilateral tumor treated per these guidelines. Five-year abandonment-sensitive event-free and overall survival estimates were: low-risk 82% ±3.8% and 86% ±3.6%, intermediate-risk 50% ±3.4% and 60% ±3.4%, and high-risk 36% ±7.6% and 45% ±7.9%. Survival outcomes were suboptimal, primarily due to advanced disease in fragile children at presentation and abandonment of treatment.

Thrombocytopenia is a common challenge in the neonatal intensive care unit, traditionally managed with platelet transfusions. However, transfusions are associated with significant risks, including increased mortality and neurodevelopmental impairment. This case series highlights the use of romiplostim, a thrombopoietin receptor agonist, in three neonates with thrombocytopenia. Each case demonstrated notable improvements in platelet counts without adverse events, reducing dependency on transfusions. These findings underscore romiplostim's potential as a safer alternative for managing neonatal thrombocytopenia. This report advocates for further research to explore romiplostim's efficacy and safety in this vulnerable population, emphasizing its promise in improving neonatal outcomes.

Background and Aims Nephron sparing surgery (NSS) is a standard technique for patients with bilateral Wilms tumor (WT) and unilateral WT with predisposing syndromes. The decision for intra-operative ureteral stent placement depends on the degree of disruption of the collecting system and must be balanced between the risk of post-operative urinary leak and the risk of stent-related urinary tract infection. The purpose of this study is to find predictors of urinary leak that may guide the decision for ureteral stenting. Methods Patients who underwent NSS for pre-operative diagnosis of renal masses at a single tertiary pediatric hospital between January 2010 and December 2023 were retrospectively reviewed. Exclusion criteria were post-operative diagnosis of non-neoplastic conditions and incomplete data. The following pre-operative variables were studied: laterality of the tumor, symptoms at diagnosis, timing of surgery, pre-operative chemotherapy toxicity grade 3 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE; version 5.0). Three intra-operative variables were studied: the need for intra-operative repair of distal calyces, total duration of surgery and duration of vascular clamping. Primary outcome was the occurrence of urinary leak. Secondary outcomes were post-operative renal dysfunction and post-operative length of hospitalization. Results Thirty-seven patients underwent NSS; seven of them were excluded for post-operative diagnosis of non-neoplastic disease or incomplete data. Twenty patients had unilateral disease and ten had bilateral disease or tumor on horseshoe kidney. Eight patients underwent upfront surgery and twenty-two received neoadjuvant chemotherapy. Ureteral stent was placed intra-operatively in three patients (10%). Urinary leakage was observed in four patients (13%) who did not undergo intraoperative stenting; all of them required delayed stent placement. Urinary leak was significantly associated with pre-operative chemotherapy toxicity (4/10 patients versus 0/20 patients, p = 0.0077). Post-operative renal dysfunction was significantly associated with pre-operative chemotherapy toxicity (8/10 patients vs 3/20 patients; p = 0.0010), bilateral disease (7/10 patients vs 4/20 patients; p = 0.0147) and surgery after neoadjuvant chemotherapy (11/22 patients vs 0/8 patients; p = 0.0140). Post-operative hospitalization was significantly longer in patients with pre-operative chemotherapy toxicity (median 10.5 days versus 7 days, p = 0.0255) and in patients who underwent surgery after neoadjuvant chemotherapy (median 9.5 days versus 6.5 days, p = 0.0053). Conclusions Patients with a history of severe pre-operative chemotherapy toxicity have a higher risk of post-operative urinary leak after NSS. In these patients planned intra-operative ureteral stenting should be considered.

Introduction: Children with sickle cell disease (SCD) remain at higher risk for invasive infection with Streptococcus pneumoniae compared to the general pediatric population. Penicillin prophylaxis, pneumococcal conjugate (PCV), and polysaccharide vaccines (PPSV) have reduced the incidence of pneumococcal disease. Methods: A single institution cohort of children with SCD aged <19 years was reviewed over the 14-year period after PCV13 licensure (January 2010 – December 2023) to identify and characterize the clinical features and outcomes of S. pneumoniae bacteremia, including serotypes and antibiotic susceptibility. Results: The cohort included 4,356 children with SCD (24,076 person-years). Thirty-eight pneumococcal bacteremia cases were identified (32 HbSS, 5 HbSC, 1 HbSβ +-thalassemia), 21 (55%) in children age ≥5 years. The median time to culture positivity was 10.6 hours (range 3.4–20.2) from collection. Meningitis occurred in 4 (11%) and acute chest syndrome in 13 (34%). Serotype information was available for 36 (95%) isolates, which included 16 (44%) PPSV23 serotypes and 1 (2.6%) PCV13 serotype (serotype 3). Penicillin nonsusceptibility occurred in 12/31 (39%) at meningitis and 1/31 (3%) at non-meningitis breakpoints. Three (8%) deaths occurred (serotypes 12F, 23B, and 15B), all in children age ≥5 years, who had discontinued prophylactic penicillin. Long-term sequelae occurred in 5 (14%) surviving children, including hearing loss, limb amputation, motor and neurocognitive defects. Conclusion: Pneumococcal bacteremia continues to occur in children with SCD, with a risk of rapid progression to severe disease. Pneumococcal prevention strategies and urgent empiric treatment for fever remain important for children and adolescents of all ages with SCD.

Background: Patients with vascular anomalies (VAs) experience poor communication and have unmet information needs. Online patient portals could mitigate communication barriers and support communication interventions. However, these portals are often underutilized. Procedure: We retrospectively queried audit-log data from the Electronic Health Record (EHR) of a single large academic healthcare center for all patients seen by clinicians from a multidisciplinary specialist clinic with a diagnosed VA from 1/2020 to 1/2024. We connected audit-log data with patient demographics to examine how patients used the portal, and whether use varied by patient characteristics. Results: We queried portal usage for 315 patients with vascular anomalies, of whom 43% were children, 19% were adolescents, and 38% were adults. Approximately half of patients’ portals were logged into during the study period (51%, n=162). Of users who ever logged into the portal, the median number of logins per year were 35 (interquartile range 15 to 95). Multiple regression results show that portal access was higher for patients who are White, reside in a metropolitan area, and have lower Area Deprivation Index. Of users who ever logged into the portal, 77% viewed clinician notes, 90% viewed test results, and 71% engaged in messaging with a clinician at least once. Conclusion: Half of patients and caregivers never use the portal, and patients from less urban areas with higher deprivation are even less likely to use the portal. As portals become more integrated into patient care, these inequities in portal access could lead to inequities in health outcomes.

Background: Autoimmune diseases might be linked to changes in gut microbiota. We studied microbiota pattern in newly diagnosed Idiopathic Thrombocytopenia (N-ITP) to report possible alteration of gut microbiota in N-ITP and impact on disease course. Methods: Fifty children with N-ITP aged 2-15 years and 30 control were assessed, for 7 specific microbiota genera in stool using real time PCR within the 1st week of presentation prior to therapy. Bleeding assessment tool and CBC were done initially, followed-up regularly for 3 months. Results: Most N-ITP cases had received steroids initially when indicated, early use of intravenous immunoglobulins (IVIG) in 10% and Eltrombopag was used in 20% of cases. Three quarters (n=38) of patients showed early remission. Three strains were only detected in ITP cases and absent in control group. Bifidobacterium spp. was significantly less in patient group, but in contrast was relatively higher in patients who progressed to persistent ITP (P-ITP). Lactobacillus and Phascolarctobacterium were significantly higher in patient group and the former was significantly highest in patients who showed early remission while Eubacterium was significantly higher in patients who continued as P-ITP than those who showed early remission. Lachnospiracceae was only detected in patients who showed early remission. Bacteroides was not detected neither in patients nor control. Conclusion: Gut microbiota was different in children with N-ITP, with significant difference between those with early remission and persistent ITP which might help to predict the disease course and might have an impact on ITP treatment in future.

Background: Spiritual care is recognized as an essential component of standard care for children with cancer and their families. Oncologists lack training in navigating spirituality discussions in primary cancer care. The current landscape of spiritual dialogue during clinical oncology encounters remains understudied. Procedures: This qualitative study aimed to describe the frequency, context, and content of religious and spiritual communication between pediatric neuro-oncologists, caregivers, and patients with brain tumors during disease reevaluation encounters. This study is part of the U-CHAT trial (NCT02846038), a prospective longitudinal investigation of realtime clinical communication across the trajectory of poor prognosis cancer. Patients with brain tumors and their caregivers were eligible if their primary oncologist estimated survival ≤ 50%. All disease reevaluation encounters for enrolled patients were audiorecorded and underwent rapid qualitative analysis to identify, summarize, and synthesize religious and spiritual communication. Results: Religious or spiritual references were identified in 23 (18%) of 129 total encounters. References usually comprised a single religious or spiritual term, with “prayer”-related language representing the majority of references. Caregivers introduced spirituality dialogue more often than oncologists (65% vs 35%). References were most often identified in the context of discussion about an uncertain or uncontrollable future. Conclusions: Results suggest oncologists rarely integrate spiritual care into disease reevaluation discussions. In light of recommendations from multiple consensus groups to integrate spiritual care into cancer care, future work should explore how generalist spiritual care training could better equip oncologists to attend to spiritual needs that arise along the cancer trajectory.

Health disparities in pediatric, adolescent, and young adult (AYA) oncology remain a significant challenge, with socioeconomic status, geographic location, race, and ethnicity contributing to unequal access to care and poorer outcomes. Emerging technologies, including artificial intelligence (AI) and immersive tools such as virtual and augmented reality (VR/AR), offer transformative solutions to address these inequities. AI has demonstrated potential in enhancing diagnostic accuracy, tailoring treatment plans, and providing personalized patient navigation to guide families through complex care pathways. Immersive technologies have shown promise in delivering equitable supportive care, including VR-based psychological support, pain management, physical rehabilitation, and patient education. This paper explores how integrating AI and immersive technology tools into cancer care can enhance quality of life, and bridge gaps in care delivery for pediatric and AYA patients. Additionally, the increasing availability of internet-enabled devices presents an unprecedented opportunity to overcome traditional barriers to care in underserved populations. The paper also addresses critical challenges, including the digital divide, ethical considerations, and cost barriers, while proposing strategies for equitable implementation. By leveraging these technologies, healthcare providers can create more inclusive and effective treatment environments, ensuring that the benefits of innovation reach all patients, regardless of background or circumstance.

Sickle cell acute pain crisis increase in frequency with age, and some patients develop chronic pain. Currently there are guidelines for management of acute pain crisis, but not for chronic pain. Chronic pain management defaults to long-term opioid therapy. Buprenorphine is a partial opioid agonist, a potent analgesic, with a respiratory ceiling effect. It may provide analgesic benefit and a ‘harms reduction approach’ in the management of chronic pain in pediatric patients with sickle cell disease. Buprenorphine is increasingly used in adult patients with sickle cell disease. We describe the inpatient micro-induction protocol we implemented in our pediatric center.

Chimeric antigen receptor (CAR) T-cells have shown remarkable promise in children, adolescents and young adults with B-cell malignancies. Such outcomes have shifted expectations for all phase I CAR T-cell trials to be equally successful. The juxtaposition of high expectations, uncertain outcomes, and potential for life-threatening toxicities raises unique ethical challenges. To aid patients and providers considering enrollment on early phase CAR T-cell trials, we discuss: (1) considerations for enrollment of pediatric patients, (2) understanding trial intent and expectations, (3) weighing risks and benefits, (4) considerations for informed consent discussions, (5) post CAR T-cell therapy expectations, and (6) barriers to access.

Background: Patients with sickle cell disease (SCD) experience painful vaso-occlusive episodes that increase with age; a subset develop chronic pain (CP). CP is usually managed with acute pain management guidelines despite evidence of ineffectiveness. Buprenorphine, a partial opioid agonist, a potent analgesic with less liking and has a respiratory ‘ceiling effect’. Buprenorphine therefore provides an alternative ‘harms reduction’ approach for CP management in pediatric SCD patients. Methods: This single urban center retrospective study assessed the feasibility of inpatient transition to buprenorphine-containing analgesics in adolescents with SCD and CP. Patients aged 12-20 years transitioned from FOA to buprenorphine between December 2020 and September 2022 were included. Acute care utilization, hospital length of stay, and FOA use in both inpatient and outpatient settings were compared pre- and post-buprenorphine induction for at least 6 months. Results: Fourteen adolescents with SCD underwent inpatient buprenorphine induction and maintenance therapy. Inpatient transition using a micro-induction approach was feasible and well tolerated in this population. There were low rates of adverse events such as opioid withdrawal signs. Maintenance on buprenorphine products was sustainable over the one-year post-induction period. Three patients (21.4%) discontinued buprenorphine during maintenance therapy. There was a significant reduction (p<0.05) in acute care utilization, length of stay, and FOA use (both inpatient and outpatient). Conclusion: Inpatient micro-induction to buprenorphine from FOA in adolescent SCD patients with CP is feasible with minimal signs of opioid withdrawals. This study suggests decreased acute care utilization with buprenorphine.

Purpose: This study aims to provide a comprehensive evaluation of the current state of pediatric radiation therapy (RT) in China, identifying key challenges in infrastructure, workforce, and access to advanced technologies while exploring opportunities for improving care delivery. Methods and Materials: A 29-item online questionnaire was distributed to radiation oncologists and clinical teams across China, with 123 responses from 103 hospitals. The survey explored six domains: hospital characteristics, radiotherapy equipment and techniques, pediatric oncology staffing, patient admission and treatment status, treatment and follow-up, and social work support and charitable partnerships. Results: Among the 103 hospitals, 66.0% provide pediatric RT, but only 7.4% have dedicated pediatric RT departments, and 57% lack pediatric radiation oncologist. Advanced techniques like Intensity Modulated Radiation Therapy (IMRT) and Volume Intensity Modulated Radiotherapy (VMAT) are widely used (95.1%), but only 11.7% of hospitals offer proton therapy, and just 8.7% have pediatric-specific radiotherapy machines. Anesthesia resources are inadequate, with only 27.2% of hospitals equipped for sedation. Furthermore, 78% of hospitals have not participated in clinical research, and only 33% adhere to standardized treatment protocols. Social work support and charitable partnerships are present in just 44% of facilities. Conclusions: Significant gaps in pediatric RT services, including shortages in workforce, advanced technologies, and holistic support systems, hinder equitable care. Addressing these deficiencies through workforce development, increased access to advanced RT modalities, and enhanced support systems is essential to improving outcomes for pediatric cancer patients in China.

Background And Aims: Invasive fungal infections (IFI) in children with newly diagnosed acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) are poorly characterized, especially in lower-middle income countries (LMICs). This study aims to identify the incidence, risk factors and outcomes of IFI in a pediatric cohort with ALL/LBL. Methods: We retrospectively analysed pediatric patients diagnosed with ALL/LBL between January and December 2023 at a tertiary cancer center in India. Patients were risk-stratified and treated per the modified ICiCLe protocol. IFIs were classified as proven, probable and possible according to the revised EORTC/MSG consensus definition. Results: Among 407 patients, 392 (96%) had ALL. The overall incidence of IFI was 24%, with probable/proven infections in 12%. Mold infections predominated (79 cases, 77%), followed by yeast infections (21 cases, 21%). In comparison to patients without IFIs, those with IFIs were more likely to have received dexamethasone (30% vs 20%; p=0.009) and anthracycline (28% vs 14%; p=0.001) during induction. Chemotherapy interruptions occurred in 56% of IFI cases, impacting treatment continuity. The 6-week mortality rate of patients with IFI was 15%, rising to 26% in probable/proven cases. Coexisting bacterial infection was associated with increased mortality (odds ratio: 19.2[95%CI: 3.5-105]; p=0.001). Conclusion: IFIs are common in newly diagnosed ALL/LBL patients in LMICs, particularly during early phases of therapy. These infections are associated with considerable mortality, often compounded by concomitant bacterial sepsis. Given these findings, consideration of antifungal prophylaxis is warranted to mitigate morbidity and mortality due to IFIs.

Background: Chronically transfused patients such as sickle cell disease (SCD) and beta thalassemia major (TM) develop iron overload. Objective: Determine the significance of pancreatic iron in SCD. Methods: Prospective study of 28 SCD and 40 TM patients who underwent research MRIs with liver and pancreas R2*. Patients with normal fasting glucose underwent oral glucose tolerance test. Results: Impaired fasting glucose (2 vs 9, p=0.27) and impaired glucose tolerance (1 vs 11, p=0.019) were less common in SCD compared with TM patients. No SCD patient had diabetes. Conclusion: 22% had significant pancreatic iron, with 1/3 of those having impaired fasting glucose.

Background: Hematopoietic Stem Cell Transplant (HSCT) is a curative procedure for many life-threatening hematological indications. Respiratory viral infections (RVI) cause substantial morbidity and mortality in pediatric transplant recipients, but the impact of mild/asymptomatic RVI is unclear. Some studies have identified certain viral infections as high-risk for post-transplant complications. To reduce transplant morbidity, a pre-transplant RVI screening program was started at Children’s National Hospital which included symptom screening and respiratory viral (RV) PCR testing for each HSCT patient within one week of and on the day of HSCT admission. The objective of this study was to evaluate the impact of RVI on HSCT outcomes. Methods: A retrospective review of pre-transplant RV PCR, symptom screening, and clinical outcomes was done for patients receiving allogeneic HSCT from 7/1/2016 to 3/31/2023. Exclusion criteria included missing pre-transplant RV PCR and SCID to prevent bias. Results: 161 patients were eligible to be included. Of the 161, 34 tested positive for RVs (26 low-risk, 8 high-risk). Outcomes were initially analyzed separately by low- and high-risk viruses. Within the first 100 days post-transplant, a positive pre-HSCT RVI was significantly associated with increased mortality (odds ratio (OR) = 5.57, p = 0.04 after adjusting for multiple testing) and requirement for ICU transfer (OR = 3.45, p = 0.006). Conclusions: Routine pre-transplant viral testing should be performed to increase the safety of HSCTs. Pre-transplant viral testing may allow providers to know when to monitor certain patients more closely post-transplant, and when to potentially delay elective transplant until the patient has cleared their virus.