Deep-learning-based personalized prediction of absolute neutrophil count recovery and comparison with clinicians for validation.

Neutropenia and its complications are major adverse effects of cytotoxic chemotherapy. The time to recovery from neutropenia varies from patient to patient, and cannot be easily predicted even by experts. Therefore, we trained a deep learning model using data from 525 pediatric patients with solid tumors to predict the day when patients recover from severe neutropenia after high-dose chemotherapy. We validated the model with data from 99 patients and compared its performance to those of clinicians. The accuracy of the model at predicting the recovery day, with a 1-day error, was 76%; its performance was better than those of the specialist group (58.59%) and the resident group (32.33%). In addition, 80% of clinicians changed their initial predictions at least once after the model's prediction was conveyed to them. In total, 86 prediction changes (90.53%) improved the recovery day estimate.

Incidence and Mortality Trends in Critically Ill Children: A Korean Population-Based Study.

BACKGROUND: Monitoring mortality trends can help design ways to improve survival, but observation of national mortality trends in critically ill children is lacking for the Korean population. METHODS: We analyzed the incidence and mortality trends of children younger than 18 years admitted to an intensive care unit (ICU) from 2012 to 2018 using the Korean National Health Insurance database. Neonates and neonatal ICU admissions were excluded. Multivariable logistic regression analyses were performed to estimate the odds ratio of in-hospital mortality according to admission year. Trends in incidence and in-hospital mortality of subgroups according to admission department, age, presence of intensivists, admissions to pediatric ICU, mechanical ventilation, and use of vasopressors were evaluated. RESULTS: The overall mortality of critically ill children was 4.4%. There was a significant decrease in mortality from 5.5% in 2012 to 4.1% in 2018 (P for trend < 0.001). The incidence of ICU admission in children remained around 8.5/10,000 population years (P for trend = 0.069). In-hospital mortality decreased by 9.2% yearly in adjusted analysis (P < 0.001). The presence of dedicated intensivists (P for trend < 0.001, mortality decrease from 5.7% to 4.0%) and admission to pediatric ICU (P for trend < 0.001, mortality decrease from 5.0% to 3.2%) were associated with significant decreasing trends in mortality. CONCLUSION: Mortality among critically ill children improved during the study period, and the improving trend was prominent in children with high treatment requirements. Varying mortality trends, according to ICU organizations, highlight that advances in medical knowledge should be supported structurally.

Influenza Vaccine Effectiveness in Children at the Emergency Department during the 2018-2019 Season: the First Season School-aged Children Were Included in the Korean Influenza National Immunization Program.

BACKGROUND: For the 2018-2019 season, the national influenza immunization program expanded to cover children aged from 6 months to 12 years in Korea. This study aimed to analyze vaccine effectiveness (VE) against influenza in children visiting the pediatric emergency room at a tertiary hospital during the 2018-2019 season. METHODS: Patients tested for influenza antigens from October 1st 2018 to May 31st 2019 at the pediatric emergency room of Samsung Medical Center were included. Patients' influenza antigen test results, influenza vaccination history, and underlying medical conditions were reviewed retrospectively. VE was estimated from the test-negative design study. RESULTS: Among the 2,901 visits with influenza test results 1,692 visits of 1,417 patients were included for analysis. Among these 1,417 patients, 285 (20.1%) were positive (influenza A, n = 211, 74.0%; influenza B, n = 74, 26.0%). The VE in all patients was 36.4% (95% confidence interval [CI], 13.9 to 53.1). The VE for influenza A was 37.6% (95% CI, 12.6 to 55.5) and VE for influenza B was 24.0% (?38.5 to 58.3). The VE in the age group 6 months to 12 years was significant with a value of 35.6% (95% CI, 10.5 to 53.7); it was not statistically significant in the age group 13 to 18 years. In a multivariate logistic regression model, patients who received an influenza vaccination were less likely to get influenza infection (OR, 0.6; 95% CI, 0.4 to 0.8; P = 0.001), with significant confounding factors such as age group 13 to 18 years (OR, 0.5; 95% CI, 0.3 to 0.8; P = 0.003) and underlying hematology-oncology disease (OR, 0.3; 95% CI, 0.1 to 0.6; P = 0.002). CONCLUSION: We report moderate effectiveness of influenza vaccination in previously healthy children aged from 6 months to 12 years in the 2018-2019 season.

Predictors of survival in patients with high-risk neuroblastoma who failed tandem high-dose chemotherapy and autologous stem cell transplantation.

OBJECTIVE: This study aims to explore prognostic factors for high-risk neuroblastoma patients with response failure to tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT). METHODS: Survival outcomes were compared according to characteristics at initial diagnosis, at relapse/progression, and after relapse/progression in patients who experienced relapse/progression after tandem HDCT/auto-SCT from 2006 to 2018. RESULTS: Forty-nine patients experienced relapse/progression after tandem HDCT/auto-SCT during the study period: 43 received salvage treatment and 30 underwent allogeneic SCT (allo-SCT) after reinduction treatment. Although all six patients who did not undergo salvage treatment died, 13 of the 43 patients who did remain alive. The 3-year probabilities of event-free survival (EFS) and overall survival (OS) from initial relapse/progression among the 49 patients were 14.4% ± 5.2% and 21.2% ± 6.4%, respectively. A higher neuron-specific enolase (NSE) level (>24 ng/mL) at relapse/progression was an independent prognostic factor for worse OS. Nine of 30 patients who underwent allo-SCT remain alive, and the 3-year probabilities of EFS and OS from allo-SCT were 16.5% ± 7.2% and 21.6% ± 8.3%, respectively. A higher NSE level and no incorporation of high-dose 131 I-metaiodobenzylguanidine (HD-MIBG) treatment into allo-SCT were independent prognostic factors for worse EFS and OS after allo-SCT. CONCLUSION: The results suggest that a higher serum NSE level at relapse/progression is a predictor of worse prognosis in patients with response failure to tandem HDCT/auto-SCT, and that incorporation of HD-MIBG treatment into allo-SCT may improve outcomes.

Clinical Significance of Segmental Chromosomal Aberrations in Patients with Neuroblastoma: First Report in Korean Population.

BACKGROUND: This study aimed to investigate the incidence and clinical significance of segmental chromosomal aberrations (SCAs) in Korean patients with neuroblastoma. METHODS: Patients diagnosed with neuroblastoma from 2012 to 2018 were included for retrospective review. Fluorescence in situ hybridization (FISH) was used to analyze four SCAs (MYCN amplification, 1p deletion, 11q deletion, and 17q gain). Clinical characteristics at diagnosis, early tumor response (reduction in primary tumor volume and neuron-specific enolase level after the first three cycles of chemotherapy), and survival rates were compared according to SCAs. RESULTS: Among 173 patients with FISH results, 92 (53.2%) had at least one of the four SCAs, while 25 (14.5%) had two co-aberrations, and eight (4.6%) had three co-aberrations. SCAs detected in our study were MYCN amplification (n = 17, 9.8%), 1p deletion (n = 26, 15.2%), 11q deletion (n = 44, 25.6%), and 17q gain (n = 46, 27.1%). Patients with MYCN amplification showed a better early response but a worse survival than those without (5-year overall survival: 46.2% ± 13.1% vs. 88.6% ± 3.4%). Furthermore, 1p deletion was associated with a better early response but a worse survival; however, it was not an independent factor for survival. We could not find any prognostic significance associated with 11q deletion or 17q gain. CONCLUSION: This is the first study investigating SCAs in Korean neuroblastoma patients. Prognostic significance of SCAs other than MYCN amplification was different from those reported in western countries. Further study with a larger cohort and longer follow-up is needed to confirm our findings.

Clinical significance of MYCN amplification in patients with high-risk neuroblastoma.

BACKGROUND: This study investigated the clinical significance of MYCN amplification within high-risk neuroblastoma (NB). METHODS: Medical records of 135 patients who were diagnosed with high-risk NB from 2004 to 2016 were reviewed. RESULTS: Fifty-one (38%) patients had MYCN amplified tumors, and the remaining 84 (62%) had nonamplified tumors. MYCN amplification was associated with abdominal primary site, less differentiated pathology, higher levels of lactate dehydrogenase and neuron-specific enolase (NSE), lower vanillylmandelic acid level, and larger primary tumor volume at diagnosis. MYCN amplification was associated with a better early response (faster reduction of primary tumor volume and NSE level). The proportion of patients in complete response or very good partial response after induction treatment was relatively higher in MYCN amplified tumors than in nonamplified tumors; however, all progressions during induction treatment occurred only in MYCN amplified tumors (P = 0.007). The time to progression was shorter (median 1.5 years vs. 1.9 years, P = 0.037) and survival after relapse/progression was worse in MYCN amplified tumors (3 year overall survival: 7.7 ± 7.4% vs. 20.5 ± 8.8%, P = 0.046). There was no difference in event-free survival and overall survival between MYCN amplified and nonamplified tumors. CONCLUSION: MYCN amplification was associated with more aggressive features at diagnosis and a better early response, but a higher progression rate during induction treatment and lower chance of survival after relapse/progression. There was no difference in survival rates according to MYCN amplification in patients with high-risk NB.

Toxicity of tandem high-dose chemotherapy and autologous stem cell transplantation using carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens for malignant brain tumors in children and young adults.

The number of studies examining the use of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) to treat high-risk or recurrent brain tumors is increasing. However, studies addressing the toxicity associated with tandem HDCT/auto-SCT, particularly during the second HDCT/auto-SCT, are very limited. For this reason, we retrospectively evaluated the toxicity of tandem HDCT/auto-SCT with carboplatin-thiotepa-etoposide (CTE) and cyclophosphamide-melphalan (CM) regimens when used to treat high-risk or recurrent brain tumors. A total of 109 patients who received a first HDCT/auto-SCT and 100 who proceeded to a second HDCT/auto-SCT between May 2005 and December 2013 were included. Hematologic recovery was rapid during both the first and second HDCT/auto-SCT. In the first HDCT/auto-SCT, mucositis-related gastrointestinal toxicity was frequent, and two (1.8 %) patients died from toxicity [one hepatic veno-occlusive disease (VOD) and one sepsis]. In the second HDCT/auto-SCT, mucositis-related toxicity was milder than in the first round. However, hepatic VOD frequency was high (20.0 %), and six (6.0 %) patients died from toxicity (four hepatic VODs, one asphyxia, and one sepsis). Multivariate analysis indicated that age younger than 8 years was the only significant predictor for hepatic VOD. All six patients who died from toxicity during the second HDCT/auto-SCT were younger than 9 years of age. This study demonstrates that tandem HDCT/auto-SCT using CTE/CM regimens was generally feasible. However, dose reduction during the second HDCT/auto-SCT in young children might be needed to decrease the death rate from toxicity.

Diffuse cerebral vasospasm with infarct after intrathecal cytarabine in childhood leukemia.

Although the varied neurotoxicity of intrathecal (IT) chemotherapy for treatment of childhood acute leukemia is well known, most are related to transient post-puncture headache, drug-induced arachnoiditis, or leukoencephalopathy after methotrexate or cytarabine. Cerebral vasospasm leading to acute infarct after IT chemotherapy is very uncommon in children. Reported herein is a rare case of diffuse cerebral vasospasm with subsequent cerebral infarct after IT cytarabine in a 7-year-old boy with acute lymphoblastic leukemia, who successfully recovered with supportive management, and a review of the literature.

Virtual, augmented, and mixed reality: potential clinical and training applications in pediatrics.

BACKGROUND: COVID-19 pandemic has significantly impacted the field of medical training, necessitating innovative approaches to education and practice. During this period, the use of novel technologies like virtual reality (VR), augmented reality (AR), and mixed reality (MR) has become increasingly vital. These technologies offer the advantage of transcending the limitations of time and space, thus enabling medical professionals to access various personalized programs for both education and service delivery. This shift is particularly relevant in the realm of pediatric medicine, where traditional training and clinical methods face unique challenges. PURPOSE: The primary aim of this study is to explore the application of VR, AR, and MR technologies in pediatric medical settings, with a focus on both clinical applications and the training of pediatric medical professionals. We aim to comprehensively search and review studies that have utilized these technologies in the treatment of pediatric patients and the education of healthcare providers in this field. METHODS: Peer-reviewed articles published in PubMed, the Cochrane Library, ScienceDirect, Google Scholar, and Scopus from January 1, 2018, to March 1, 2023, were comprehensively searched. The review was conducted according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) guidelines. Among the 89 studies, 63 investigated the clinical applications of VR (n=60) or AR (n=3) in pediatric patients, and 25 investigated the applications of VR (n=19), AR (n=5), or MR (n=1) for training medical professionals. RESULTS: A total of 36 randomized controlled trials (RCTs) for clinical application (n=31) and medical training (n=5) were retrieved. Among the RCTs, 21 reported significant improvements in clinical applications (n=17) and medical training (n=4). CONCLUSION: Despite a few limitations in conducting research on innovative technology, such research has rapidly expanded, indicating that an increasing number of researchers are involved in pediatric research using these technologies.

Adoption of Augmented Reality in Educational Programs for Nurses in Intensive Care Units of Tertiary Academic Hospitals: Mixed Methods Study.

BACKGROUND: In the wake of challenges brought by the COVID-19 pandemic to conventional medical education, the demand for innovative teaching methods has surged. Nurse training, with its focus on hands-on practice and self-directed learning, encountered significant hurdles with conventional approaches. Augmented reality (AR) offers a potential solution to addressing this issue. OBJECTIVE: The aim of this study was to develop, introduce, and evaluate an AR-based educational program designed for nurses, focusing on its potential to facilitate hands-on practice and self-directed learning. METHODS: An AR-based educational program for nursing was developed anchored by the Kern six-step framework. First, we identified challenges in conventional teaching methods through interviews and literature reviews. Interviews highlighted the need for hands-on practice and on-site self-directed learning with feedback from a remote site. The training goals of the platform were established by expert trainers and researchers, focusing on the utilization of a ventilator and extracorporeal membrane oxygenation system. Intensive care nurses were enrolled to evaluate AR education. We then assessed usability and acceptability of the AR training using the System Usability Scale and Technology Acceptance Model with intensive care nurses who agreed to test the new platform. Additionally, selected participants provided deeper insights through semistructured interviews. RESULTS: This study highlights feasibility and key considerations for implementing an AR-based educational program for intensive care unit nurses, focusing on training objectives of the platform. Implemented over 2 months using Microsoft Dynamics 365 Guides and HoloLens 2, 28 participants were trained. Feedback gathered through interviews with the trainers and trainees indicated a positive reception. In particular, the trainees mentioned finding AR particularly useful for hands-on learning, appreciating its realism and the ability for repetitive practice. However, some challenges such as difficulty in adapting to the new technology were expressed. Overall, AR exhibits potential as a supplementary tool in nurse education. CONCLUSIONS: To our knowledge, this is the first study to substitute conventional methods with AR in this specific area of critical care nursing. These results indicate the multiple principal factors to take into consideration when adopting AR education in hospitals. AR is effective in promoting self-directed learning and hands-on practice, with participants displaying active engagement and enhanced skill acquisition. TRIAL REGISTRATION: ClinicalTrials.gov NCT05629663; https://clinicaltrials.gov/study/NCT05629663.