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.

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.

Neuroblastoma: an ongoing cold front for cancer immunotherapy.

Neuroblastoma is the most frequent extracranial childhood tumour but effective treatment with current immunotherapies is challenging due to its immunosuppressive microenvironment. Efforts to date have focused on using immunotherapy to increase tumour immunogenicity and enhance anticancer immune responses, including anti-GD2 antibodies; immune checkpoint inhibitors; drugs which enhance macrophage and natural killer T (NKT) cell function; modulation of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway; and engineering neuroblastoma-targeting chimeric-antigen receptor-T cells. Some of these strategies have strong preclinical foundation and are being tested clinically, although none have demonstrated notable success in treating paediatric neuroblastoma to date. Recently, approaches to overcome heterogeneity of neuroblastoma tumours and treatment resistance are being explored. These include rational combination strategies with the aim of achieving synergy, such as dual targeting of GD2 and tumour-associated macrophages or natural killer cells; GD2 and the B7-H3 immune checkpoint; GD2 and enhancer of zeste-2 methyltransferase inhibitors. Such combination strategies provide opportunities to overcome primary resistance to and maximize the benefits of immunotherapy in neuroblastoma.

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.

Using Real-Time Interaction Analysis to Explore Human-Robot Interaction.

Despite the increasing presence of social robots (SRs) in Human-Robot Interaction, there are few studies that quantify these interactions and explore children's attitudes by analyzing real-time data as they communicate with SRs. Therefore, we attempted to explore the interaction between pediatric patients and SRs by analyzing the interaction log collected from real-time. This study is a retrospective analysis of data collected in a prospective study conducted on 10 pediatric cancer patients at tertiary hospitals in Korea. Using the Wizard of Oz method, we collected the interaction log during the interaction between pediatric cancer patients and the robot. Out of the collected data, 955 sentences from the robot and 332 sentences from the children were available for analysis, except for the logs that were missing due to environmental errors. we analyzed the delay time from saving the interaction log and the sentence similarity of the interaction log. The interaction log delay time between robot and child was 5.01 seconds. And the child's delay time averaged 7.2 seconds, which was longer than the robot's delay time of 4.29 seconds. Additionally, as a result of analyzing the sentence similarity of the interaction log, the robot (97.2%) was higher than the children (46.2%). The results of the sentiment analysis of the patient's attitude toward the robot were 73% neutral, 13.59% positive, and 12.42% negative. The observational evaluations of pediatric psychological experts identified curiosity (n=7, 70.0%), activity (n=5, 50.0%), passivity (n=5, 50.0%), sympathy (n=7, 70.0%), concentration (n=6, 60.0%), high interest (n=5, 50.0%), positive attitude (n=9, 90.0%), and low interaction initiative (n=6, 60.0%). This study made it possible to explore the feasibility of interaction with SRs and to confirm differences in attitudes toward robots according to child characteristics. To increase the feasibility of human-robot interaction, measures such as improving the completeness of log records by enhancing the network environment are required.

Trends in Incidences and Survival Rates in Pediatric In-Hospital Cardiopulmonary Resuscitation: A Korean Population-Based Study.

Background Although the outcome of cardiopulmonary resuscitation (CPR) is still unsatisfactory, there are few studies about temporal trends of in-hospital CPR incidence and mortality. We aimed to evaluate nationwide trends of in-hospital CPR incidence and its associated risk factors and mortality in pediatric patients using a database of the Korean National Health Insurance between 2012 and 2018. Methods and Results We excluded neonates and neonatal intensive care unit admissions. Incidence of in-hospital pediatric CPR was 0.58 per 1000 admissions (3165 CPR/5 429 471 admissions), and the associated mortality was 50.4%. Change in CPR incidence according to year was not significant in an adjusted analysis (P=0.234). However, CPR mortality increased significantly by 6.6% every year in an adjusted analysis (P<0.001). Hospitals supporting pediatric critical care showed 37.7% lower odds of CPR incidence (P<0.001) and 27.5% lower odds of mortality compared with other hospitals in the adjusted analysis (P<0.001), and they did not show an increase in mortality (P for trend=0.882). Conclusions Temporal trends of in-hospital CPR mortality worsened in Korea, and the trends differed according to subgroups. Study results highlight the need for ongoing evaluation of CPR trends and for further CPR outcome improvement among hospitalized children.

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.

Effect of life-sustaining treatment decision law on pediatric in-hospital cardiopulmonary resuscitation rate: A Korean population-based study.

AIM: The 2018 life-sustaining treatment (LST) decision law is expected to improve end-of-life quality in Korea. This study evaluated the national effect of the LST decision law on the cardiopulmonary resuscitation (CPR) rate among pediatric patients who died during hospital admission. METHODS: This retrospective cohort study was based on the Korean National Health Insurance database. Pediatric admissions within 12 months before or after implementation of the LST decision law were compared, allowing a 1-month transition period (February 2018). The changes in mortality, CPR, and documentation of LST decision were evaluated. RESULTS: The CPR rate of patients who died in hospital decreased after establishment of the LST decision law (49.6 vs 43.4 %, P = 0.04), without change of in-hospital mortality between pre/post-LST decision law activation (0.83 vs 0.81 per 1000 admissions, P = 0.67). In addition, in-hospital CPR (0.73 vs 0.67 per 1000 admissions, P = 0.15) and survival to discharge after in-hospital CPR (43.6 vs 47.2 %, P = 0.27) were slightly improved, although there was no statistical significance. Patients with LST decision documentation were less frequently mechanically ventilated (69.8 % vs 80.4 %, P < 0.01) and used fewer inotropes (76.5 % vs 90.1 %, P < 0.01) and more frequent opioids (67.1 % vs 57.4 %, P = 0.04). CONCLUSIONS: The legally guided process of LST decision can decrease the CPR rate of children who die in hospitals. This result highlights the possibility of improving end-of-life quality by reducing non-beneficial in-hospital CPR.

Factors Associated with the Underuse of Sedatives and Neuromuscular Blocking Agents for Pediatric Emergency Endotracheal Intubation in Korea.

PURPOSE: Rapid sequence intubation (RSI) using sedatives and neuromuscular blocking agents (NMBAs) is recommended for pediatric emergency endotracheal intubation (ETI), but is not frequently performed in Korea. This study aimed to verify factors associated with the underuse of RSI medications. MATERIALS AND METHODS: This multicenter retrospective study reviewed patients aged under 18 years who underwent an ETI within 24 hours of arrival at the emergency department between 2016 and 2019. Any cases of ETI during cardiopulmonary resuscitation were excluded. We investigated the characteristics of the patients, intubators, RSI medications, and outcomes. The study cases were classified into no-medication, sedative-only, and sedative-with-NMBA groups. Multivariable logistic regression analysis of RSI medication use was conducted. RESULTS: A total of 334 cases with a median age of 3.4 years were included in this study. Sedatives and NMBAs were used in 63.8% and 32.9%, respectively. In comparing the no-medication (n=121), sedative-only (n=103), and sedative-with-NMBA (n=110) groups, patient age (median; 1.0 year vs. 2.8 years vs. 11.3 years; p<0.001), underlying medical conditions (77.7% vs. 56.3% vs. 36.4%; p<0.001), and pediatricians as intubators (76.9% vs. 54.4% vs. 17.3%; p<0.001) were different. The factors that influenced sedatives with NMBA use were patient age [for a year increment; adjusted odds ratio (aOR), 1.182; 95% confidence interval (CI), 1.120-1.249], no underlying medical conditions (aOR, 2.109; 95% CI, 1.093-4.070), and intubators other than pediatricians (aOR, 5.123; 95% CI, 2.257-11.626). CONCLUSION: RSI accounted for 32.9% of pediatric emergency ETI in Korea. The underuse of RSI medications is associated with younger patient age, underlying medical conditions, and pediatricians as intubators.

Impact of Intubator's Training Level on First-Pass Success of Endotracheal Intubation in Acute Care Settings: A Four-Center Retrospective Study.

(1) Background: First-pass success (FPS) of endotracheal intubation is more challenging in children than in adults. We aimed to identify factors associated with FPS of intubation in acute care settings. (2) Methods: We analyzed data of children aged <10 years who underwent intubation within ≤24 h of arrival at four Korean emergency departments (2016−2019). Variables were compared according to FPS. A logistic regression was performed to quantify the association of factors with FPS. An experienced intubator was defined as a senior resident or a specialist. (3) Results: Of 280 children, 169 (60.4%) had FPS. The children with FPS were older (median age, 23.0 vs. 11.0 months; p = 0.018), were less frequently in their infancy (36.1% vs. 50.5%; p = 0.017), and were less likely to have respiratory compromise (41.4% vs. 55.0%; p = 0.030). The children with FPS tended to be more often intubated by experienced intubators than those without FPS (87.0% vs. 78.4%; p = 0.057). Desaturation was rarer in those with FPS. Factors associated with FPS were experienced intubators (aOR, 1.93; 95% CI, 1.01−3.67) and children's age ≥12 months (1.84; 1.13−3.02). (4) Conclusion: FPS of intubation can be facilitated by deploying or developing clinically competent intubators, particularly for infants, in acute care settings.

An Augmented Reality-Based Guide for Mechanical Ventilator Setup: Prospective Randomized Pilot Trial.

BACKGROUND: Recently, the demand for mechanical ventilation (MV) has increased with the COVID-19 pandemic; however, the conventional approaches to MV training are resource intensive and require on-site training. Consequently, the need for independent learning platforms with remote assistance in institutions without resources has surged. OBJECTIVE: This study aimed to determine the feasibility and effectiveness of an augmented reality (AR)-based self-learning platform for novices to set up a ventilator without on-site assistance. METHODS: This prospective randomized controlled pilot study was conducted at Samsung Medical Center, Korea, from January to February 2022. Nurses with no prior experience of MV or AR were enrolled. We randomized the participants into 2 groups: manual and AR groups. Participants in the manual group used a printed manual and made a phone call for assistance, whereas participants in the AR group were guided by AR-based instructions and requested assistance with the head-mounted display. We compared the overall score of the procedure, required level of assistance, and user experience between the groups. RESULTS: In total, 30 participants completed the entire procedure with or without remote assistance. Fewer participants requested assistance in the AR group compared to the manual group (7/15, 47.7% vs 14/15, 93.3%; P=.02). The number of steps that required assistance was also lower in the AR group compared to the manual group (n=13 vs n=33; P=.004). The AR group had a higher rating in predeveloped questions for confidence (median 3, IQR 2.50-4.00 vs median 2, IQR 2.00-3.00; P=.01), suitability of method (median 4, IQR 4.00-5.00 vs median 3, IQR 3.00-3.50; P=.01), and whether they intended to recommend AR systems to others (median 4, IQR 3.00-5.00 vs median 3, IQR 2.00-3.00; P=.002). CONCLUSIONS: AR-based instructions to set up a mechanical ventilator were feasible for novices who had no prior experience with MV or AR. Additionally, participants in the AR group required less assistance compared with those in the manual group, resulting in higher confidence after training. TRIAL REGISTRATION: ClinicalTrials.gov NCT05446896; https://beta.clinicaltrials.gov/study/NCT05446896.

Genetic changes during leukemic transformation to secondary acute myeloid leukemia from myeloproliferative neoplasms.

Leukemic transformation (LT) is the main cause of death for patients with myeloproliferative neoplasms (MPNs). To study genetic changes associated with the LT, we performed targeted sequencing in 26 MPN patients including 21 with paired samples. We observed that, besides three driver genes, IDH2 (19%) and ASXL1 (14%) were also frequently mutated at MPN diagnosis. Although variant allele frequencies (VAFs) of mutations in DNA methylation and spliceosome did not expand during LT, they were enriched in patients with LT (the LT group). At follow-up, we also observed acquisition of mutations, mostly in the LT group. When considering dynamics of VAF from diagnosis to follow-up, VAFs in the LT group expanded (median VAF, 36.7-43.7%, p = 0.045). In contrast, mutations in patients with no clinical progression was stable (median VAF, 36.3-35.7%, p = 0.739). Overall, the present study demonstrates genetic changes during LT and provides the potential for prognostic application.

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.

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.

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.

Safety and immune cell kinetics after donor natural killer cell infusion following haploidentical stem cell transplantation in children with recurrent neuroblastoma.

INTRODUCTION: Under the hypothesis that early natural killer cell infusion (NKI) following haploidentical stem cell transplantation (haplo-SCT) will reduce relapse in the early post-transplant period, we conducted a pilot study to evaluate the safety and feasibility of NKI following haplo-SCT in children with recurrent neuroblastoma who failed previous tandem high-dose chemotherapy and autologous SCT. METHODS: We used the high-dose 131I-metaiodobenzylguanidine and cyclophosphamide/fludarabine/anti-thymocyte globulin regimen for conditioning and infused 3 × 107/kg of ex-vivo expanded NK cells derived from a haploidentical parent donor on days 2, 9, and 16 post-transplant. Interleukin-2 was administered (1 × 106 IU/m2/day) subcutaneously to activate infused donor NK cells on days 2, 4, 6, 9, 11, 13, 16, 18, and 20 post-transplant. RESULTS: Seven children received a total of 19 NKIs, and NKI-related acute toxicities were fever (n = 4) followed by chills (n = 3) and hypertension (n = 3); all toxicities were tolerable. Grade ≥II acute GVHD and chronic GVHD developed in two and five patients, respectively. Higher amount of NK cell population was detected in peripheral blood until 60 days post-transplant than that in the reference cohort. Cytomegalovirus and BK virus reactivation occurred in all patients and Epstein-Barr virus in six patients. Six patients died of relapse/progression (n = 5) or treatment-related mortality (n = 1), and one patient remained alive. CONCLUSION: NKI following haplo-SCT was relatively safe and feasible in patients with recurrent neuroblastoma. Further studies to enhance the graft-versus-tumor effect without increasing GVHD are needed.

Outcomes of mechanical ventilation according to WIND classification in pediatric patients.

BACKGROUND: The outcomes of weaning processes are not well known in pediatric patients, and the International Conference Classification on weaning from mechanical ventilation showed limited application. We evaluate the relationship between the new Weaning according to a New Definition (WIND) classification and outcome in pediatric patients. METHODS: We conducted a retrospective cohort study in a tertiary pediatric intensive care unit (ICU). We included patients under 18 years of age who received invasive mechanical ventilation for more than 24 h and excluded cases with other than the first ICU admissions, tracheostomy with home ventilation before admission, intubation or weaning processes conducted in other ICU, and weaning with extracorporeal membrane oxygenation. Weaning processes were classified into four groups according to weaning duration after the first separation attempt (SA): no-SA, short weaning (< 24 h), difficult weaning (24 h-7 days), and prolonged weaning (> 7 days). Mortality rates were compared across groups using the Kruskal-Wallis test, and risk factors for the no-SA group were analyzed by multivariate logistic regression tests with age, sex, severity score at admission, admission type, and underlying disease as variables. RESULTS: Among 313 patients, 224 were enrolled and had a median age of 2.1 (interquartile range 0.5-6.6) years. Spontaneous breathing tests were done in 70.1% of enrolled patients. The median duration of intubation to the first SA was 4 (range 0-36) days, and 92.8% patients underwent the first SA within 14 days. The mortality rate was 0% in the short (0/99) and difficult (0/53) weaning groups and 17.9% (5/28) in the prolonged weaning group (p < 0.001). The mortality rate of the no-SA group was 93.2% (41/44). Admission severity (hazard ratio 1.036, confidence interval 1.022-1.050) and underlying oncologic disease (hazard ratio 7.341, confidence interval 3.008-17.916) were independent risk factors for lack of SA. CONCLUSIONS: In conclusion, WIND classification is associated with ICU mortality in pediatric patients. Further studies of this association are required to improve protocols associated with the weaning process and clinical outcomes. Trial registration Retrospectively registered.

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.

Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma.

PURPOSE: The purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma. MATERIALS AND METHODS: TH mRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance of TH expression in PB at diagnosis was evaluated. RESULTS: TH expression was positive in 60 patients (28.6%). Fifty of 60 TH-positive patients had metastatic tumors and the remaining 10 had localized tumors. TH expression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, and MYCN amplification) at diagnosis. Among TH-positive patients, higher TH expression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower in TH-positive patients than in TH-negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower in TH-positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). Among TH-positive patients, a higher expression level of TH was associated with a worse outcome. In multivariate analyses, positive TH expression in PB at diagnosis was an independent poor prognostic factor for PFS. CONCLUSION: The treatment intensity should be tailored according to TH expression in PB at diagnosis.