Neuroblastoma in the Era of Precision Medicine: A Clinical Review.

The latest advances in treatment for patients with neuroblastoma are constantly being incorporated into clinical trials and clinical practice standards, resulting in incremental improvements in the survival of patients over time. Survivors of high-risk neuroblastoma (HRNBL), however, continue to develop treatment-related late effects. Additionally, for the majority of the nearly 50% of patients with HRNBL who experience relapse, no curative therapy currently exists. As technologies in diagnostic and molecular profiling techniques rapidly advance, so does the discovery of potential treatment targets. Here, we discuss the current clinical landscape of therapies for neuroblastoma in the era of precision medicine.

Pediatric Manubriosternal Dislocation: A Case Report and Review of Literature.

Pediatric sternal dislocation is an extremely rare event, with less than 15 cases reported in the literature. We report the case of a traumatic sternal segment dislocation in an 8-year-old male that was caused by an unsuccessful backflip resulting in a direct force to the chest. The diagnosis was made by chest computed tomography. Open reduction and internal fixation (ORIF) were performed with a good outcome noted at follow-up. In addition to a thorough description of this case, we have included an organized review of existing literature with an aim to establish trends in presentation, clinical course, and outcomes among sternal dislocation in the pediatric population.

Hemorrhagic Giant Cell Tumor of the Occipital Skull Base: A Case Report and Literature Review.

Giant cell tumor of bone is a benign but locally aggressive osteolytic neoplasm that represents 3% to 5% of all primary bone tumors, primarily found at the epiphyses of long bones. Less than 1% are of calvarial origin. Herein, we report a rare case of a nine-year-old girl with a hemorrhagic giant cell tumor of the left occipital skull base.

Vein of Galen Malformation Manifesting as High-Output Heart Failure.

The sudden onset of vomiting in a previously healthy term neonate has a broad differential requiring a thorough history and physical examination. When this does not reveal the underlying cause, a workup must be performed to rule out potentially devastating diagnoses that must be addressed in a timely fashion. In infants, this clinical presentation could be due to infections such as sepsis or meningitis, gastrointestinal causes such as anatomical abnormalities or ingestions, or cardiac causes such as congenital heart disease. Conversely, inborn errors of metabolism or neurologic issues such as vascular anomalies or a tumor with associated increased intracranial pressure could also be the culprit. In this report, we discuss the case of a previously healthy newborn with a rare cause of vomiting and feeding intolerance, which was ultimately discovered to be due to the vein of Galen malformation.

Bempegaldesleukin (BEMPEG; NKTR-214) efficacy as a single agent and in combination with checkpoint-inhibitor therapy in mouse models of osteosarcoma.

Survival of patients with relapsed/refractory osteosarcoma has not improved in the last 30 years. Several immunotherapeutic approaches have shown benefit in murine osteosarcoma models, including the anti-programmed death-1 (anti-PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) immune checkpoint inhibitors. Treatment with the T-cell growth factor interleukin-2 (IL-2) has shown some clinical benefit but has limitations due to poor tolerability. Therefore, we evaluated the efficacy of bempegaldesleukin (BEMPEG; NKTR-214), a first-in-class CD122-preferential IL-2 pathway agonist, alone and in combination with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors in metastatic and orthotopic murine models of osteosarcoma. Treatment with BEMPEG delayed tumor growth and increased overall survival of mice with K7M2-WT osteosarcoma pulmonary metastases. BEMPEG also inhibited primary tumor growth and metastatic relapse in lungs and bone in the K7M3 orthotopic osteosarcoma mouse model. In addition, it enhanced therapeutic activity of anti-CTLA-4 and anti-PD-1 checkpoint blockade in the DLM8 subcutaneous murine osteosarcoma model. Finally, BEMPEG strongly increased accumulation of intratumoral effector T cells and natural killer cells, but not T-regulatory cells, resulting in improved effector:inhibitory cell ratios. Collectively, these data in multiple murine models of osteosarcoma provide a path toward clinical evaluation of BEMPEG-based regimens in human osteosarcoma.

Severe Pancytopenia Induced by Valproic Acid.

Valproic acid is commonly used to treat pediatric epilepsy. This drug is usually well-tolerated; its side effects are typically mild, with hepatotoxicity being the most widely recognized one. Bone marrow suppression is a rarely seen complication in patients with valproic acid levels more than 125 mcg/mL. Reported cases indicate an increased incidence of hematologic toxicity; however, evidence for management is limited. We report a case of bone marrow suppression induced by a high dose of valproic acid in a 10-year-old male.

Group B Streptococcus Osteomyelitis in a Healthy Adolescent.

Group B Streptococcus (GBS), Streptococcus agalactiae, is a bacterium often screened for pregnant women and associated with neonatal infections. However, GBS disease is also rising among non-pregnant adults, especially among immunocompromised patients. The median age of non-pregnant adults with invasive GBS disease is 64 years. It can present as skin and soft tissue infection, osteomyelitis, pneumonia, urosepsis, and meningitis. There is very limited data on GBS disease occurring in the pediatric population past the infancy stage. In this report, we present a case of a 16-year-old male with GBS osteomyelitis.

Severe necrotizing pneumonia complicated by empyema in a neonate.

Necrotizing pneumonia is a severe complication of pneumonia, characterized by local destruction of lung tissue with development of multiple small cavities (abscesses) and may be associated with empyema. Empyema is an unusual complication in neonates with limited data reported. We present a healthy term neonate with late-onset sepsis caused by Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia due to severe necrotizing pneumonia associated with advanced stage empyema. To the best of our knowledge this is the youngest reported patient with multifocal lung abscesses associated with stage 2 empyema treated successfully without surgical intervention.

Spontaneous Tonsillar Hemorrhage due to Infectious Mononucleosis.

Spontaneous tonsillar hemorrhage is defined as continuous bleeding for more than one hour, or more than 250 mL of blood loss regardless of the duration of bleeding. It is associated with various pathologic conditions, including acute or chronic tonsillitis, peritonsillar or parapharyngeal abscess, infectious mononucleosis, carotid aneurysm or pseudoaneurysm, and tonsil cancer. It is a rare complication with very limited data reported in the literature. Reported cases indicate an increased incidence in young patients, associated with a higher mortality rate. We report a rare case of spontaneous tonsillar hemorrhage due to infectious mononucleosis in a previously healthy 16-year-old female.

Correction to: Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI.

There was a typo in author Andrew Wahba's name in the initial online publication. The original article has been corrected.

Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI.

PURPOSE: Medulloblastoma (MB) is the most common malignant brain tumor in children. Recent studies have shown the ability of natural killer (NK) cells to lyse MB cell lines in vitro, but in vivo successes remain elusive and the efficacy and fate of NK cells in vivo remain unknown. METHODS: To address these questions, we injected MB cells into the cerebellum of immunodeficient mice and examined tumor growth at various days after tumor establishment via bioluminescence imaging. NK cells were labeled with a fluorine-19 (19F) MRI probe and subsequently injected either intratumorally or contralaterally to the tumor in the cerebellum and effect on tumor growth was monitored. RESULTS: The 19F probe efficiently labeled the NK cells and exhibited little cytotoxicity. Fluorine-19 MRI confirmed the successful and accurate delivery of the labeled NK cells to the cerebellum of the mice. Administration of 19F-labeled NK cells suppressed MB growth, with the same efficacy as unlabeled cells. Immunohistochemistry confirmed the presence of NK cells within the tumor, which was associated with induction of apoptosis in tumor cells. NK cell migration to the tumor from a distal location as well as activation of apoptosis was also demonstrated by immunohstochemistry. CONCLUSIONS: Our results show that NK cells present a novel opportunity for new strategies in MB treatment. Further, 19F-labeled NK cells can suppress MB growth while enabling 19F MRI to provide imaging feedback that can facilitate study and optimization of therapeutic paradigms.