Atypical hemolytic uremic syndrome during induction chemotherapy in neuroblastoma, a rare phenomenon or common congenital predisposition?

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy sometimes associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury arise due to aberrant complement protein activation in the circulation. A 13-month-old boy with metastatic neuroblastoma (NB) developed aHUS during his first cycle of induction chemotherapy with germline testing revealing a complement factor H (CFH) gene mutation, currently classified as a variant of uncertain significance (VUS). Now he is in disease remission after successful complement blockade therapy, thus highlighting a unique presentation of aHUS in a patient with newly diagnosed NB.

Sclerosing Epithelioid Fibrosarcoma Harboring the EWSR1 - CREB3L1 Gene Fusion: The Importance of Molecular Classification in Pediatric Sarcomas.

BACKGROUND: Sclerosing epithelioid fibrosarcoma (SEF) is a very rare soft tissue sarcoma that most commonly presents in middle-aged and elderly adults but has been rarely seen in children. SEF is a very aggressive tumor with over 50% of patients experiencing local recurrence and 40% to 80% of patients experiencing distant metastatic spread. This disease has been shown to be resistant to chemotherapy and is classically treated with surgical excision. CASE: We describe the case of a 10-year-old girl with Graves' disease who presented with protruding eyes (to a greater extent on the left side) and was found to have a large mass in her left inferior rectus muscle that was diagnosed as SEF. After treatment with incomplete resection, due to the benign-appearing nature of the tumor on imaging, and proton radiation therapy, she remains disease-free at 18 months post-therapy. DISCUSSION: SEF is typically identified via genetic testing and recognition of the EWSR1 - CREB3L1 gene fusion as well as MUC4 expression via immunohistochemistry. DNA methylation profiling, which has traditionally been used in brain tumors, can also efficiently identify this tumor, and we recommend expanding the use of this technology for difficult to classify pediatric sarcomas.

Retention of discharge instructions using an interdisciplinary model for at-risk children with cancer: A quality improvement initiative.

PURPOSE: We sought to improve caregiver retention of critical initial hospital discharge instructions using a multidisciplinary, team-based intervention for newly diagnosed pediatric cancer patients at high risk for unfavorable outcomes. MATERIALS AND METHODS: A multidisciplinary team of pediatric residents, nurses, social workers, pharmacists and hematology/oncology faculty implemented practices to optimize teaching of key discharge material as part of four Plan-Do-Study-Act intervention cycles. An 11-question survey distributed at the first post-discharge clinic visit assessed the efficacy of the intervention, as defined by caregiver retention of critical home instructions. RESULTS: Thirty-nine caregivers of pediatric cancer patients in an urban academic tertiary-care children's hospital took part in this project. Overall retention of key discharge information was greater in the post-intervention cohort compared to the baseline cohort (median total scores: 89 and 63, respectively; p = .001). Improvements in the proportions of correct responses post-intervention were also observed across all subject matters: from 0.57 to 0.88 for fever guidelines (p = .059), from 0.71 to 0.78 for signs of sepsis (p = .65), from 0.57 to 1.00 for accurate choice of on-call number (p = .004), and from 0.71 to 0.94 for antiemetic management (p = .14). CONCLUSION: Initiation of our comprehensive cancer-specific program to improve caregiver retention of discharge instructions at the first post-hospitalization clinic visit has been successful and sustainable. This project demonstrated that a multi-disciplinary collaborative team effort increases caregiver retention of critical health information, and this has potential to lead to improved outcomes for patients.

A nine-month-old boy with regression of milestones and severe constipation: an unusual case of a large spinal NTRK1 fusion pilocytic astrocytoma.

INTRODUCTION: Pilocytic astrocytoma, a World Health Organization grade 1 tumor, is the most common brain tumor in children between 5 and 14 years of age and the second most common in children younger than 5 and older than 14. Although classical to the cerebellum and hypothalamic regions, it can also arise in the spinal cord. Larotrectinib, a selective inhibitor of tropomyosin receptor kinase, has been effective in pediatric tumors with NTRK fusion mutations in children as young as 1-month-old. CASE: We share the case of a 9-month-old boy who presented with a 4-month history of regression of his milestones and severe constipation who was found to have a large spinal pilocytic astrocytoma with multiple intracranial periventricular lesions.

Respiratory Failure in a Child With Pulmonary Metastatic Osteosarcoma and COVID-19.

The novel coronavirus, SARS-CoV-2, causes much more severe disease in adults than in children. Although it is anticipated that immune compromised children and children with cancer may be at higher risk of developing severe or fatal COVID-19, there are no currently published reports of fatal disease in a child with cancer. Because of the discrepancy in disease severity between adult and pediatric patients, we report the case of an adolescent with pulmonary metastatic osteosarcoma who died of COVID-19 early in the course of the pandemic in New York City in the hope that heightening awareness that pulmonary metastatic disease may predispose to a more severe outcome will increase surveillance in this vulnerable population.

Systemic manifestations of extraskeletal myxoid chondrosarcoma associated with a novel t(2;22)(q34;q12) EWS translocation in a child and a review of the literature.

Extraskeletal myxoid chondrosarcoma (EMC), a soft-tissue sarcoma with unique clinicopathologic features and characteristic chromosomal translocations, is extremely rare in the pediatric population. We, herein, present the case of a 7-year-old boy with profound microcytic hypochromic anemia, poor weight gain and a mid-thoracic paraspinal mass that was identified as EMC. Systemic manifestations of localized, nonmetastatic EMC have never been described in the pediatric population, yet our patient's anemia and poor weight gain resolved after successful surgical resection of the tumor, suggesting that localized EMC can present with systemic manifestations. The tumor also contained a novel t(2;22)(q34;q12) translocation involving the EWSR1 gene, which is consistent with additional reports suggesting that a growing list of translocations can drive formation of, and potential new management strategies for, EMC.

Delayed Solid Tumor Presentations in Adolescent and Young Adults Patients in the Bronx.

Adolescent and young adults (AYAs) require support from their parents and caregivers. While there are formal programs available for patients with complex medical problems, <20% of pediatric practices are performing transition readiness processes in patients aged 12-17 years to effective transition. Although cancer is the most common cause of disease-related death in AYAs in high-income countries, AYA oncology patients have not attained the same clinical improvements as pediatric patients, and their outcomes remain poorer. While there are published data on an expected degree of lag time for patients presenting with solid tumors, due to the underlying biology and slow growth of the cancer, we have recently witnessed extreme delays in the presentation to medical care. In this article, we share the cases of two young adults.

Preventing Infection in Pediatric Patients Receiving Chemotherapy: A Survey of Provider Recommendations.

PURPOSE: Sepsis is the leading cause of mortality in patients with childhood cancer receiving cytotoxic chemotherapy. Pediatric hematology/oncology and transplant (PHOT) providers must counsel their patients on the safety of public activities and weigh the risk of infection exposure with the social and developmental benefits of in-person school and social outings. We hypothesize that there is significant variability in recommendations given by PHOT providers. METHODS: An electronic anonymous survey was developed and piloted by a group of PHOT providers to assess current methods for educating patients and families on limiting infectious exposures. Five clinical vignettes were created by the study team to explore how providers balance the competing priorities of safety and health-related quality of life (HRQoL). The electronic survey was institutional review board-approved and disseminated via email to all PHOT providers affiliated with the Children's Oncology Group across the United States. RESULTS: In total, 545 clinicians completed the survey. Most respondents were attending physicians (393, 72%), followed by fellows (61, 11%), advanced practice providers (APPs; 38, 7%), and nurses (37, 7%). On average, nurses and fellows made more conservative recommendations for avoiding infectious exposures compared with the recommendations from attending physicians and APPs (P < .0001). On average, providers with more years of clinical experience expressed less cautious recommendations, whereas those with less years of experience provided more cautious recommendations for avoiding infectious exposures (P = .0072). CONCLUSION: This survey demonstrates the importance of collaboration between all members of the care team in defining priorities for balancing safety risk and HRQoL to provide consistent messaging to patients. The variations in survey responses highlight the need for universal guidelines to standardize physician recommendations for limiting infectious exposures in pediatric patients on chemotherapy.

Polyamine Depletion by D, L-alpha-difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis.

Polyamine metabolism and signaling play important roles in multiple cancers but have not previously been studied in Ewing sarcoma. Here, we show that blocking polyamine synthesis with D, L-alpha-difluoromethylornithine (DFMO) causes a G1 cell cycle arrest, dose-dependent decreases in sarcosphere formation from Ewing sarcoma cell lines growing in non-adherent conditions and a decrease in clonogenic growth in soft agar. Further, we utilized our orthotopic implantation/amputation model of Ewing sarcoma metastasis to demonstrate that DFMO slowed primary tumor growth in addition to limiting metastasis. RNA sequencing demonstrated gene expression patterns consistent with induction of ferroptosis caused by polyamine depletion. Induction of ferroptosis was validated in vitro by demonstrating that ferrostatin-1, an inhibitor of ferroptosis, allows sphere formation even in the presence of DFMO. Collectively, these results reveal a novel mechanism by which DFMO prevents metastasis - induction of ferroptosis due to polyamine depletion. Our results provide preclinical justification to test the ability of DFMO to prevent metastatic recurrence in Ewing sarcoma patients at high risk for relapse.

Omicron variant of SARS-CoV-2, an epidemiologic assessment of pediatric oncology patients in the Bronx.

BACKGROUND: Children receiving cytotoxic therapy for cancer have increased risk of infection due to drug-induced neutropenia and are therefore treated empirically for bacteremia when febrile or ill-appearing. However, viral infections, which are not frequently life-threatening, are the most common etiology of febrile episodes and there has been increased effort to differentiate patients who may have a higher risk for adverse outcomes. CASE: We performed a retrospective chart review of pediatric oncology patients diagnosed with COVID-19 between December 20, 2021 and February 22, 2022 during the Omicron (B.1.1.529) surge at The Children's Hospital at Montefiore, a tertiary care center in the Bronx. CONCLUSION: We found that no patients in our cohort developed respiratory distress, bacteremia, or serious illness after COVID-19 infection during the Omicron surge. Future studies will aid in understanding the relationship between community-acquired infections and bacteremia, and this knowledge can then be applied to develop optimal infection prevention clinical care guidelines.

SAFER Care: Improving Caregiver Comprehension of Discharge Instructions.

BACKGROUND: One in five pediatric patients suffers from adverse events related to hospital discharge. Current literature lacks evidence on effective interventions to improve caregiver comprehension (CC) of discharge instructions. We examined if a standardized framework for written and verbal discharge counseling was associated with increased CC of key discharge instructions after discharge from a general pediatric inpatient unit. METHODS: An interprofessional team created the SAFER Care framework to encourage standard, comprehensive discharge counseling. Plan-do-study-act cycles included electronic health record smartphrases, educational initiatives, data feedback, visual aids, and family outreach. Caregivers were surveyed by phone within 4 days of discharge. Our primary outcome was the proportion of caregivers correctly responding to all questions related to discharge care, comparing pre- and postintervention periods. Data were plotted on a statistical process control chart to assess the effectiveness of interventions. RESULTS: A total of 171 surveys were analyzed in the preintervention period, and 262 surveys were analyzed in the postintervention period. A total of 37% of caregivers correctly responded to all questions in the preintervention period, compared with 62% of caregivers in the postintervention period, meeting rules for special cause variation. CONCLUSIONS: Development of the SAFER Care framework and its use in written and verbal discharge counseling was associated with significantly improved CC of discharge instructions in a general pediatric inpatient unit. Further studies should be focused on expanding this to other populations, particularly limited-English-proficiency families.

An 8-Year-Old Boy With Fever, Splenomegaly, and Pancytopenia.

An 8-year-old boy with no significant past medical history presented to his pediatrician with 5 days of fever, diffuse abdominal pain, and pallor. The pediatrician referred the patient to the emergency department (ED), out of concern for possible malignancy. Initial vital signs indicated fever, tachypnea, and tachycardia. Physical examination was significant for marked abdominal distension, hepatosplenomegaly, and abdominal tenderness in the right upper and lower quadrants. Initial laboratory studies were notable for pancytopenia as well as an elevated erythrocyte sedimentation rate and C-reactive protein. Computed tomography (CT) of the abdomen and pelvis showed massive splenomegaly. The only significant history of travel was immigration from Albania 10 months before admission. The patient was admitted to a tertiary care children's hospital and was evaluated by hematology-oncology, infectious disease, genetics, and rheumatology subspecialty teams. Our multidisciplinary panel of experts will discuss the evaluation of pancytopenia with apparent multiorgan involvement and the diagnosis and appropriate management of a rare disease.