Death In Pediatric Patients Research Articles

Abstract LB254: PKA signaling: a friend or foe to pediatric medulloblastoma

Abstract Pediatric brain tumor is the leading cause of cancer-related deaths in pediatric patients ranging 0-19 years of age. Medulloblastoma is one of the most commonly occurring brain tumor in children. Sonic hedgehog (Shh) activated subgroup of medulloblastoma is considered to be highly aggressive and metastatic in nature. Recent studies and oncomine, a cancer microarray database has shown that GABAA receptor is down regulated in pediatric medulloblastoma. In this study, we have evaluated the anti-cancer effects of an anthelminthic drug ‘moxidectin' a GABAA receptor agonist. Treatment of medulloblastoma cells with moxidectin, resulted in reduced Protein kinase A (PKA) activity. Leading to the inhibition of Gli1, a major transcription factor of non-canonical Shh signaling. Moxidectin has inhibited the proliferation of Daoy, UW426, UW228, ONS76, and PFSK1 medulloblastoma cells and significantly induced apoptosis in a concentration and time dependent manner in all the cell lines. Western blotting and immunofluorescence microscopy demonstrated that moxidectin treatment significantly induced GABAA receptor expression and inhibited cAMP mediated PKA signaling. As a result, the non-canonical activation of Gli1 and its downstream effector molecules such as Pax-6, Oct-4, Sox-2 and Nanog were also inhibited by moxidectin treatment. Efficacy of moxidectin was also evaluated in subcutaneous and intracranial medulloblastoma tumor models. Our results demonstrated that daily oral administration of 2.5 mg/kg moxidectin suppressed the growth of medulloblastoma tumors by 55-70% in subcutaneous and intracranial models. Ex-vivo analysis of tumors by western blotting, IHC, TUNEL and H&E staining revealed that moxidectin suppressed medulloblastoma tumor progression by inhibiting PKA/Gli1 signaling axis indicating the significance of this pathway in medulloblastoma progression. To our knowledge, this study for the first time focuses on GABAA receptor agonist mediated PKA/Gli1 signaling inhibition. Most importantly, moxidectin is an FDA approved drug and is already in clinical use for the treatment of river blindness in humans with an established safety record, therefore any positive findings from our studies will prompt further clinical investigation into repositioning moxidectin for the treatment of MB patients. Citation Format: Itishree Kaushik, Sanjay Srivastava. PKA signaling: a friend or foe to pediatric medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB254.

Could the unfortunate outcome of pediatric acute myocarditis be predicted? Factors contributing to a poor outcome in myocarditis

ObjectiveMyocarditis has spontaneous resolution in 50% of patients. Our study aimed to define risk factors for developing dilated cardiomyopathy (DCM) and death in pediatric patients with acute myocarditis (AM). MethodsThe retrospective cohort study included all patients with treated AM. The Mother and Child Health Institute from January 2011 to March 2019. ResultsIn the study, 62 patients were included, 40 boys and 22 girls (11.15±5.86 years) with AM. Twelve out of sixty-two children had acute fulminant myocarditis. Four patients died in the acute phase of AM, and 11 developed DCM. Follow up was 27.14±36.52 months. Patients with poor outcome (DCM development) were under the age of seven (odds ratio [OR] 10.1; p=0.003), more likely to be girls (OR 4.6; p=0.03), and had fulminant myocarditis (OR 27.0; <0.001). An ejection fraction (EF) <55% and fractional shortening (FS) <30% increased risk of DCM 13- and 5-fold, respectively, but patients with EF between 40 and 55% remain at highest risk of developing DCM. There was a 12-fold increased risk for DCM in patients with left ventricular end-diastolic diameter Z score >2+. The receiver operator curve showed that the lactate dehydrogenase (LDH) cut-off value for developing DCM was 1780 mmol/l (sensitivity 80%, specificity 100%). ConclusionAcute fulminant myocarditis was an independent risk factor for DCM. Children with EF between 40 and 50% at admission were at highest risk of developing DCM. Lactate dehydrogenase value could be a significant prognostic value for the outcome of pediatric myocarditis.

Identification of neuroblastoma cell lines with uncommon TAZ+/mesenchymal stromal cell phenotype with strong suppressive activity on natural killer cells

BackgroundNeuroblastoma (NB) is the most common, extracranial childhood solid tumor arising from neural crest progenitor cells and is a primary cause of death in pediatric patients. In solid tumors, stromal...

Level of Comfort With Pediatric Trauma Transports: Survey of Prehospital Providers

Unintentional injury is the leading cause of death in pediatric patients. Despite a heavy burden of pediatric trauma, prehospital transport and triage of pediatric trauma patients are not standardized. Prehospital providers report anxiety and a lack of confidence in transport, triage, and care of pediatric trauma patients. Prehospital transport providers with 3 organizations across southeast Georgia and northeast Florida were contacted via email (n = 146) and asked to complete 2 Web-based surveys to evaluate their comfort level with performing tasks in the transport of pediatric and adult trauma patients. Bivariate statistics and qualitative thematic analyses were performed to assess comfort with pediatric trauma transports. Survey 1 (N = 35) showed that mean comfort levels of prehospital providers were significantly lower for pediatric patients than adult trauma patients in 7 out of 9 tasks queried, including airway management and interpreting children's physiology. The following themes emerged from survey 2 (N = 14) responses: additional clinical knowledge resources would be beneficial when caring for pediatric trauma patients, pediatric medication administration is a source of uncertainty, prehospital transport teams would benefit from additional pediatric trauma training, infrequent transport of pediatric trauma patients affects provider comfort level, and pediatric trauma generates higher levels of anxiety among providers. Prehospital transport of pediatric trauma patients is infrequent and a source of anxiety for prehospital providers. Rigs should be equipped with a reference tool addressing crucial tasks and deficiencies in training.

Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients

AbstractOutcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

Compassionate use of remdesivir in children with COVID-19.

Children represent a minority of total COVID-19 cases, but studies have reported severe disease and death in pediatric patients. Remdesivir (RDV) has recently demonstrated promising results in adults with COVID-19, but few data have been reported to date in children.A nationwide multicenter observational study was conducted on children with confirmed SARS-CoV-2 receiving compassionate treatment with RDV in Spain. Eight patients were included in the study, four infants and four older children [median age 5 years old; IQR 4 months–11.6 years old]. Half of them had complex underlying medical conditions, and the rest were mostly infants (3/4). Six out of eight children needed Pediatric Intensive Care Unit Admission. No RDV-related adverse outcomes were observed in our patients. Seven have reached successful clinical outcome, but one patient with serious clinical status died due to complications. However, she received RDV very late after the first COVID-19 symptom.Conclusions: In our cohort, most of the patients achieved successful clinical outcome, without observing adverse events. Clinical trials of RDV therapy for children with COVID-19 are urgently needed, to assess the safety, tolerability, efficacy, and pharmacokinetics of RDV in children, as this could be an effective treatment in severe cases.What is Known:• Remdesivir has not been approved to treat COVID-19 in children under 12 years old, although the drug is currently being prescribed in critically ill children.• Remdesivir has recently demonstrated promising results in adults with COVID-19, but few data have been reported to date in paediatric population.What is New:• We report a multicentre cohort of children with confirmed SARS-CoV-2 and severe COVID-19 disease receiving remdesivir during the first month of the pandemic in Spain.• No remdesivir-related adverse outcomes were observed in most of the cases. Seven patients reached successful clinical outcome, and one died due to complications (bacterial sepsis).Supplementary InformationThe online version contains supplementary material available at 10.1007/s00431-020-03876-1.

Outcomes of Adult and Pediatric Patients with Hematologic Malignancies and COVID-19: A Systematic Review and Meta-Analysis of 1847 Patients

Introduction: Clinical outcomes for patients with hematologic malignancy and COVID-19 have not been aggregated. We completed a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients.Methods: We searched Pubmed and EMBASE up to July 25, 2020, to identify reports of patients with hematologic malignancy and COVID-19 (including papers where the patients with hematologic malignancy were a subset of the total study population). The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included pooled estimates for the risk of ICU admission, mechanical ventilation, and non-invasive ventilation in hospitalized patients.Mortality data were stratified by age, treatment status, and malignancy subtype. For treatment status, “systemic anti-cancer therapy (SACT)” was defined as patients on any anti-cancer therapy. “Cytotoxic SACT” was defined as patients on cytotoxic therapy only. “Not on treatment” was defined as patients on observation or those who were at least 28 days beyond their last active treatment.Sensitivity analyses were conducted on the primary outcomes limiting to studies with low risk of bias, and to studies including both outpatients and hospitalized patients. Due to data limitations, only the primary outcome was assessed for pediatric studies. Pooled prevalence and risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model using MetaXL and Revman 5.4 software.Results: A total of 25 adult studies and 4 pediatric studies comprising 1847 patients from China, Europe, the United Kingdom, and North America were included (Figure 1 and Table 1). The majority of patients were hospitalized (83%). The overall risk of death amongst all patients was 36% (95% CI 31-41, N=1763), and amongst hospitalized patients was 40% (95% CI 36-45, 24 studies with 1295 patients) (Figure 2). Patients aged >60 years had a significantly higher risk of death than patients <60 years (46% vs. 26%, RR 1.56, 95%CI 1.15-2.13, N=597) (Figure 3). The pooled risk of death in pediatric patients was 4% (95% CI 1-9, N=102) (Figure 2).The risk of ICU admission among hospitalized adult patients was 23% (95% CI 17-29, N=1165); mechanical ventilation 16% (95% CI 12-21, N= 826); and non-invasive ventilation 16% (95% CI 9-26%, N=373).The estimated RR of death among patients on SACT compared to no treatment was 1.22 (95% CI 0.84-1.78; N=457, Figure 3a). The RR of death among patients on cytotoxic SACT versus no treatment was similar at 1.29 (95% CI 0.78-2.15; N=176, Figure 3b).All subgroups of hematologic malignancy had high risks of overall mortality: acquired bone marrow dysfunction syndromes 57% (95% CI 42-72, 11 studies, 42 patients); leukemias 44% (95% CI 31-58, 15 studies, 159 patients), plasma cell dyscrasias 38% (95% CI 29-47, 18 studies, 387 patients); lymphomas (including CLL) 32% (95% CI 26-38, 16 studies, 696 patients); lymphomas (excluding CLL) 32% (95% CI 18-48, 11 studies, 156 patients); CLL 31% (95% CI 24-39, 13 studies, 457 patients); myeloproliferative neoplasms 37% (95% CI 25-49, 9 studies, 62 patients).Sensitivity analysis including only studies with a low risk of bias showed a similar estimate for risk of death among all patients (37% (95% CI 31-42, 20 studies with 1412 patients)) compared to all studies. Sensitivity analysis including only studies reporting on a combination of outpatients and hospitalized patients also showed a similar estimate for risk of death among all patients (38% (95% CI 32-44), 11 studies with 1214 patients) compared to all studies.Conclusion: Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, appear to experience a high risk of dying (pooled risk estimate 36%). Older patients experience higher mortality, and pediatric patients appear to be relatively spared. Importantly, based on the observational data available to date, recent cancer treatment does not appear to significantly increase the risk of dying. These data highlight the need for robust strategies to prevent patients with hematologic malignancy from contracting COVID-19, and may help inform discussions about prevention strategies, treatment, and goals of care.DisclosuresCook:Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; IQVIA: Research Funding; Sanofi: Consultancy; Amgen: Consultancy; Roche: Consultancy; Karyopharm: Consultancy. Zwicker:Dova: Honoraria, Other: Advisory board; Portola: Honoraria, Other: Advisory board; Incyte: Research Funding; Quercegen: Research Funding; Parexel: Consultancy; Sanofi: Consultancy; CSL: Consultancy; Pfizer/BMS: Honoraria, Other: Advisory board. Scarfo:Gilead: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Wood:Pfizer: Research Funding; Best Doctors/Teladoc: Consultancy; Koneksa Health: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Elektra Labs: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ASH Research Collaborative: Honoraria; Genentech: Research Funding. Hicks:Gilead Sciences: Research Funding.

In-Hospital Management Might Reduce Induction Deaths in Pediatric Patients With Acute Lymphoblastic Leukemia: Results From a Japanese Cohort.

Induction deaths (ID) remain a critical issue in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL). The reported rate of ID in this population is 1% or higher. We speculate that this proportion might be lower in Japan because of mandatory hospitalization during induction therapy to manage complications. We retrospectively analyzed the incidence of ID among children with ALL enrolled in 4 Japanese study groups between 1994 and 2013. Among 5620 children, 41 (0.73%) cases of ID were noted. The median age was 6.5 years; 24 children were female, and 7 had T-cell ALL. Infection was the most common cause of ID (n=22), but the incidence (0.39%) was lower than that reported in western countries. Mortality within 48 hours from the onset of infection was low, comprising 25% of infection-related deaths. The incidence of infections caused by Bacillus species was low. Only 1 patient died because of Aspergillus infection. Fatal infections mostly occurred during the third week of induction therapy. Our findings suggest that close monitoring, stringent infection control, and immediate administration of appropriate antibiotics through hospitalization might be important strategies in reducing the rate of infection-related ID in pediatric patients with ALL.

Factors influencing in-hospital death for pediatric patients with isolated methylmalonic acidemia: a nationwide inpatient database analysis

BackgroundPatients with isolated methylmalonic acidemia (MMA) usually experience recurrent episodes of acute metabolic decompensation or metabolic stroke, require frequent hospitalization, and have a relatively high mortality rate. The aim of our study was to assess factors predicting the in-hospital death of pediatric patients with isolated MMA. We performed a retrospective study using data from the Hospital Quality Monitoring System, a national inpatient database in China collected from 2013 to 2017. All patients under 18 years old with a diagnosis of isolated MMA were included. Demographic, hospital-related, and clinical features were collected. Poisson regression was performed to identify potential influencing variables associated with in-hospital death.ResultsFrom 2013 to 2017, among 2317 admissions for pediatric patients diagnosed with isolated MMA, 1.77% had the outcome of death. In the univariate analysis, patients aged under 1 year had a higher risk of death than did those aged 1 year or older (odds ratio [OR] = 2.63, 95% confidence interval [CI]: 1.36–5.07). There was a higher risk of in-hospital death for patients admitted through emergency departments or via referrals than for those admitted through other routes (OR = 3.76, 95% CI: 1.84–7.67). Deaths were higher in hospitals with volumes of less than 50 patients with isolated MMA during the five study years (OR = 2.92, 95% CI: 1.46–5.83). Moreover, the risk of in-hospital death gradually decreased over time (OR = 0.72, 95% CI: 0.57–0.90). In the multivariate analysis, the abovementioned associations with the risk of in-hospital death remained statistically significant. However, no significant associations were observed between specific clinical signs and in-hospital death in either the univariate or the multivariate analysis.ConclusionsYounger age, admission to hospitals with low patient volumes, and admission through emergency departments or referrals are associated with higher risk of in-hospital death. The co-existence of specific clinical signs appears to have no effect on in-hospital death.

Safety and Activity of the Combination of Ceritinib and Dasatinib in Osteosarcoma.

Osteosarcoma (OS) is the second most common cause of cancer-related death in pediatric patients. The insulin-like growth factor (IGF) pathway plays a relevant role in the biology of OS but no IGF targeted therapies have been successful as monotherapy so far. Here, we tested the effect of three IGF specific inhibitors and tested ceritinib as an off-target inhibitor, alone or in combination with dasatinib, on the proliferation of seven primary OS cells. Picropodophyllin, particularly in combination with dasatinib and the combination ceritinib/dasatinib were effective in abrogating the proliferation. The ceritinib/dasatinib combination was applied to the primary cells of a 16-year-old girl with a long history of lung metastases, and was more effective than cabozantinib and olaparib. Therefore, the combination was used to treat the patient. The treatment was well tolerated, with toxicity limited to skin rush and diarrhea. A histopathological evaluation of the tumor after three months of therapy indicated regions of high necrosis and extensive infiltration of macrophages. The extension of the necrosis was proportional to the concentration of dasatinib and ceritinib in the area, as analysed by an ultra performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS). After the cessation of the therapy, radiological analysis indicated a massive growth of the patient’s liver metastases. In conclusion, these data indicate that the combination of ceritinib/dasatinib is safe and may be used to develop new therapy protocols.

Health professionals' experiences of grief associated with the death of pediatric patients: a systematic review.

The objective of this review was to synthesize the experiences of health professionals who have experienced grief as a result of a pediatric patient dying. There has been some research into health professionals' grief experiences associated with the death of pediatric patients, but there has not been a review that synthesizes the findings of these experiences. Other related reviews have focused on prenatal, perinatal or adult deaths or the coping strategies employed by health professionals. This review highlights the complexities of experiences faced by pediatric health professionals. Qualitative studies involving pediatric health professionals working in any healthcare setting who had experienced grief from the death of a patient were considered for inclusion. Studies were conducted in any country, at any time and published in English. The search was conducted in PubMed, CINAHL, Embase, PsycINFO, Scopus and ProQuest Dissertations and Theses. The search was completed in January 2019. The review followed principles of meta-aggregation in line with the JBI approach. Methodological quality assessment was based on representation of participants' voices and congruence between research methodology and both research question and analysis of data. Meta-aggregation led to three synthesized findings from 12 qualitative studies that met the inclusion and methodological quality criteria. Studies predominantly included nurses working in a hospital, with sample sizes ranging from six to 25 participants. The synthesized findings were physical, behavioral, psychological or spiritual symptoms; compounding grief; and alleviating grief. Physical, behavioral, psychological, or spiritual symptoms highlighted the various characteristics of grief experiences by health professionals. Compounding grief was the largest synthesized finding and incorporated the various factors that contributed to a poorer experience of grief. Alleviating grief showed the limited identified factors that improved the experience of grief. Methodological quality led to synthesized findings receiving a ConQual rating of low or moderate. The synthesized findings from this review highlight the varied reported experiences of grief in health professionals. The methodological quality and reporting of studies, however, led to decreased confidence in the synthesized findings and recommendations arising from this review. Healthcare professionals should be aware of the potential for experiencing grief when a patient dies and the compounding and alleviating factors associated with this. Further research could expand participant and language limitations, and improve methodological quality and reporting.

Outcomes After Prehospital Endotracheal Intubation in Suburban/Rural Pediatric Trauma

BackgroundTrauma is the leading cause of death in pediatric patients over 1 y of age. Controversy exists regarding prehospital airway management for these patients, with some studies suggesting that endotracheal intubation in the field or at a referring hospital is associated with increased mortality and complication rate. These studies were largely performed at urban centers, and it is unclear whether the results apply to suburban/rural networks with longer transport times and more stops at referring hospitals. The purpose of this study is to evaluate differential outcomes in pediatric trauma patients who underwent endotracheal intubation at the scene of injury, referring hospital, or pediatric trauma center in a predominantly rural/suburban setting. Materials and methodsA retrospective review was performed evaluating trauma patients age 18 y or younger at a single institution over 10 y (2004-2014). Patients were selected who underwent endotracheal intubation and were classified based on location of intubation (scene, referring hospital, or trauma center). Fischer's exact test and t-tests were performed for comparison. Univariate and multivariate regression analyses were performed. Results288 patients were identified. 155 (53.8%) were intubated at the scene of injury, 55 (19.1%) at a referring hospital, and 72 (25%) at the trauma center. Overall mortality was 21.9%, which was highest in the scene intubation group (29.7%) compared with the referring hospital (20%) and trauma center (5.6%) groups (P < 0.01). Patients intubated at the scene had higher Injury Severity Scores and lower Glasgow Coma Scale scores (P < 0.01). Duration of intubation was lowest in the trauma center group (P < 0.01). Complication rate was highest in the referring hospital group (P < 0.05). Multivariate analysis revealed that age, injury severity, and neurologic status were the key drivers of mortality rather than location of intubation. ConclusionsMortality and duration of intubation were lowest in trauma patients intubated at a pediatric trauma center. However, location of intubation was not a significant independent predictor of mortality or complications on multivariate analysis, suggesting that age, injury severity, and neurologic status are the main indicators of prognosis in severe pediatric trauma.

End-of-Life Care of Hospitalized Children with Advanced Heart Disease.

BackgroundDespite improvements in palliative care for critically ill children, the characteristics of end-of-life care for pediatric patients with advanced heart disease are not well-known. We investigated these characteristics among hospitalized children with advanced heart disease in a tertiary referral center in Korea.MethodsWe retrospectively reviewed the records of 136 patients with advanced heart disease who died in our pediatric department from January 2006 through December 2013.ResultsThe median age of patients at death was 10.0 months (range 1 day–28.3 years). The median duration of the final hospitalization was 16.5 days (range 1–690 days). Most patients (94.1%) died in the intensive care unit and had received mechanical ventilation (89.7%) and inotropic agents (91.2%) within 24 hours of death. The parents of 74 patients (54.4%) had an end-of-life care discussion with their physician, and the length of stay of these patients in the intensive care unit and in hospital was longer. Of the 90 patients who had been hospitalized for 7 days or more, the parents of 54 patients (60%) had a documented end-of-life care discussion. The time interval from the end-of-life care discussion to death was 3 days or less for 25 patients.ConclusionChildren dying of advanced heart disease receive intensive treatment at the end of life. Discussions regarding end-of-life issues are often postponed until immediately prior to death. A pediatric palliative care program must be implemented to improve the quality of death in pediatric patients with heart disease.

Pediatric Logistic Organ Dysfunction 2 Scoring System in Predicting the Prognosis of Death in Pediatric Patients with Clinical Sepsis

ABSTRACT&#x0D; Introduction. Sepsis is still one of the main causes of mortality and morbidity in children in industrialized and developing countries. Pediatric Logistic Organ Dysfunction 2 (PELOD 2) score aims to assess the degree of organ system disorder. In addition, PELOD score 2 also has a close relationship with death and can detect any organ dysfunction even in patients with low mortality. This study aims to determine the relationship between PELOD 2 score with the death of patients in pediatric surgical cases with clinical sepsis at Dr. Mohammad Hoesin Hospital (RSMH) Palembang.&#x0D; Methods. An observational analytic study with a cohort design was conducted at the Mohammad Hoesin Hospital in Palembang from August 2017 to December 2017. There were 30 samples of pediatric patients with clinical sepsis who met the inclusion criteria. Data frequency and distribution are explained in tabular form. The relationship between PELOD 2 score (Pediatric Logistic Organ Dysfunction 2) with death was analyzed by the Fisher Exact test. Survival rates are obtained by analyzing survival using Kaplan meier. Data analysis uses SPSS version 18.0.&#x0D; Results. In this study, the results showed that there were no differences in age, weight, height and sex between groups with mortality and life outcomes (p&gt; 0.05). With the Fisher Exact test, it was found that there was a significant relationship between PELOD 2 score and mortality in pediatric patients with clinical sepsis (RR = 13; RR&gt; 2; p = 0.000; p&gt; 0.05). Of 30 pediatric patients with clinical sepsis, there were 13 deaths (43.3%) of pediatric patients with clinical sepsis where 13 out of 15 people (86.7%) in the risk group and the comparison group did not get any deaths.&#x0D; Conclusions. It can be concluded that there is a significant relationship between PELOD 2 score (Pediatric Logistic Organ Dysfunction 2) with the death of patients in pediatric surgical cases with clinical sepsis at Dr. Mohammad Hoesin Hospital (RSMH) Palembang.

Blinatumomab in Pediatric Patients with Relapsed/Refractory B-Cell Precursor and Molecularly Resistant Acute Lymphoblastic Leukemia (R/R ALL): Updated Analysis of 110 Patients Treated in an Expanded Access Study (RIALTO)

Introduction: Although survival rates in children and adolescents with acute lymphoblastic leukemia (ALL) have improved significantly, relapsed or refractory (R/R) ALL remains a leading cause of cancer-related deaths in pediatric patients. Blinatumomab is a bispecific T-cell engager (BiTE®) immuno-oncology therapy that activates endogenous cytotoxic T cells to kill target B cells. We report the primary analysis results of RIALTO, an expanded access study, where pediatric patients with R/R ALL were treated with blinatumomab (NCT02187354). Methods: Enrolled in the study were children and adolescents &gt;28 days and &lt;18 years of age with R/R CD19+ ALL (defined as ≥2 relapses, relapse after allogeneic hematopoietic stem cell transplant [HSCT], or refractory to prior treatments) and ≥5% blasts or &lt;5% blasts but with minimal residual disease (MRD) level ≥10−3. Blinatumomab was given as continuous infusion in a 6-week cycle (4 weeks of treatment and 2 weeks of treatment-free interval) for up to 5 cycles. Patients with &lt;25% blasts were dosed at 15 µg/m2/day, whereas those with ≥25% blasts were dosed at 5 µg/m2/day (days 1-7 of cycle 1) followed by dose increase to 15 µg/m2/day. Any change in therapy (eg, HSCT) was off-protocol and per investigator preference. Primary endpoint was incidence of treatment-emergent (TE) and treatment-related (TR) adverse events (AEs). Secondary endpoints included incidence of morphological complete response (CR; &lt;5% blasts) and MRD response (&lt;10−4 blasts by PCR or flow cytometry) in the first 2 cycles, relapse-free survival (RFS), overall survival (OS), and HSCT rate after blinatumomab treatment. Data cutoff was September 27, 2018. Results: Of 110 patients enrolled (median age, 8.5 years [95% CI 0.4-17.0]), 60% were 7-17 years of age, 61% had &lt;50% blasts at baseline, and 11% had &lt;5% blasts (n=12; with MRD ≥10−3). Among 12 patients with &lt;5% blasts and MRD-positive disease at baseline, 0 had prior relapse after HSCT and 2 had chromosome translocation mutations. Prior treatments included HSCT (41%) and blinatumomab (5%); 56% of patients had ≥2 relapses and 40% relapsed after HSCT (Table 1). Of 98 patients with ≥5% blasts at baseline, 58 (59%) achieved CR (&lt;5% blasts), 0 achieved partial remission (PR; ≥5 to &lt;25% blasts), and 20 (20%) showed progressive disease (PD; ≥25% blasts) after the first 2 cycles. Of the 58 patients who reached CR, 39 (67%) achieved CR with full recovery of peripheral blood counts, 46 (47%) achieved an MRD response, and 36 (62%) proceeded to HSCT after achieving CR. The 2 patients with t(17;19) achieved CR with an MRD response. Of the 4 patients with germline trisomy 21 (Down syndrome), 3 achieved CR with an MRD response. Among the 12 patients with &lt;5% blasts but with MRD ≥10−3 at baseline, 11 (92%) achieved CR and MRD response and 1 (8%) had disease progression (Table 2). Overall, the response rates were higher among patients with lower tumor burden at baseline. Among 98 patients with ≥5% blasts at baseline, median OS was 13.1 months (95% CI, 9.8-21.3), with median follow-up time of 17.4 months. For patients reaching CR after the first 2 cycles, the median RFS was 8.5 months (95% CI, 3.4-NE), with a median follow-up time of 11.2 months; 38% of patients relapsed and 9% died. Of 110 patients treated with blinatumomab, 99% experienced TEAEs, with 65% being grade ≥3, including neurologic events (6%), cytokine release syndrome (CRS, 2%), cytopenias (38%), elevated liver enzymes (13%), infections (18%), and neutropenia (14%). TRAEs were reported in 74% of patients; 36% were grade ≥3 and 26% were deemed serious. Grade ≥3 TRAEs included neurologic events (5%), CRS (2%), cytopenias (9%), elevated liver enzyme (4%), infections (5%), and neutropenia (6%). Due to TRAEs, 22% of patients interrupted treatment and 5% discontinued treatment. The 9 fatal AEs, unrelated to blinatumomab, occurred due to relapse and progressive nature of the disease (Table 3). Conclusion: Overall, the safety profile of blinatumomab in this expanded access study in pediatric patients with R/R ALL was tolerable and consistent with that in other blinatumomab clinical trials. Patients, including those with persistent MRD and genetic disorders at baseline, achieved high rates of CR and MRD responses with low rates of relapse and disease progression. These findings support blinatumomab as a suitable treatment option for pediatric patients with R/R ALL. Disclosures Locatelli: BluebirdBio: Consultancy; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zugmaier:Amgen: Employment, Other: holds stock, Patents &amp; Royalties: &amp; other intellectual property. Bader:Amgen (Brasil), Novartis: Consultancy, Speakers Bureau; Medac: Patents &amp; Royalties, Research Funding; Riemser, Neovii: Research Funding; Celgene: Consultancy. Bourquin:Servier: Other: Travel support. Rossig:BMS, Pfizer, Roche: Other: speaker honoraria; Amgen, Celgene,EUSA Pharma, Genetech, Novartis, Roche: Other: advisory board.

Intermuscular S-ICD Implantation in Pediatric Patients

The use of conventional implantable cardioverter-defibrillators (ICDs) in children presents important technical challenges. We present the surgical technique necessary to adapt the subcutaneous ICD (S-ICD) implantation designed for adults, to children, including patients weighing less than 20 kg. The implant procedure implies a two-incision technique and interfascial serratus anterior-latissimus dorsi dissection to accommodate the device. S-ICD implantation was successfully performed in three patients of 19, 28, and 24 kg, respectively, two of them suffered cardiorespiratory arrest. Intermuscular thoracic implantation of S-ICD might represent an effective strategy for primary or secondary prevention of sudden cardiac death in pediatric patients.

Pediatric Exposures Reported to the Toxicology Investigators Consortium, 2010-2015.

Poisoning is the leading cause of injury death in pediatric patients. Hospital and provider readiness, including pharmacy stocking, depends on reliable surveillance data describing local patterns of age-specific clinically significant exposures and the therapeutic modalities employed in their treatment. We aimed to characterize trends in clinically significant toxic exposures and their management. We performed a retrospective review of patients 18 years or younger in the American College of Medical Toxicology's Toxicology Investigators Consortium (ToxIC) Registry, a self-reporting database completed by bedside consulting medical toxicologists. We reviewed cases from January 1, 2010, through December 31, 2015. In 2015, ToxIC included 101 health care facilities. Data collected included demographics, geographic region, encounter and exposure details, survival, and therapeutic modalities employed, including antidotes, antivenoms, gastric decontamination, enhanced elimination, hyperbaric oxygen therapy, and extracorporeal membrane oxygenation. From 2010 to 2015, 11,616 consults were recorded in ToxIC. Pediatric consultations increased from 934 (23.7%) in 2010 to 2425 (29.9%) in 2015 (P < 0.001). Exposures were most commonly reported in females (57.8%) and adolescents (59.4%). Intentional ingestions (55.5%) comprised the majority of cases. The most frequent agents of exposure were analgesics (21.0%). There were 38 deaths reported (0.9%). The antidote used most commonly was N-acetylcysteine (11.0%). Geographic variation was demonstrated in prevalence of envenomations and heavy metal exposures, their respective treatments, and overall use of decontamination. Toxicology consultations for pediatric exposures increased from 2010 to 2015. Understanding which pediatric exposures require toxicologist management, the therapies most frequently employed, and geographical patterns is paramount to facility-level planning, pharmacy stocking, and provider education.

Clinical Determination of Brain Death in Children Supported by Extracorporeal Membrane Oxygenation.

Children supported by extracorporeal membrane oxygenation (ECMO) are at risk of catastrophic neurologic injury and brain death. Timely determination of brain death is important for minimizing psychological distress for families, resource allocation, and organ donation. Reports of successful determination of brain death in pediatric patients supported by ECMO are limited. The determination of brain death by clinical criteria requires apnea testing, which has historically been viewed as challenging in patients supported by ECMO. We report eight pediatric patients who underwent a total of 14 brain death examinations, including apnea testing, while supported by veno-arterial ECMO (VA-ECMO), resulting in six cases of clinical determination of brain death. We performed a retrospective review of the medical records of pediatric patients who underwent brain death examination while supported by VA-ECMO between 2010 and 2018 at a single tertiary care children's hospital. Eight patients underwent brain death examination, including apnea testing, while supported by VA-ECMO. Six patients met criteria for brain death, while two had withdrawal of technical support after the first examination. During the majority of apnea tests (n=13/14), the ECMO circuit was modified to achieve hypercarbia while maintaining oxygenation and hemodynamic stability. The sweep flow was decreased prior to apnea testing in ten brain death examinations, carbon dioxide was added to the circuit during three examinations, and ECMO pump flows were increased in response to hypotension during two examinations. Clinical determination of brain death, including apnea testing, can be performed in pediatric patients supported by ECMO. The ECMO circuit can be effectively modified during apnea testing to achieve a timely rise in carbon dioxide while maintaining oxygenation and hemodynamic stability.

Modern aspects of the pathogenesis, diagnosis and therapy of hemostasis disorders in children with acute leukemias

Patients with oncohematological diseases, both children and adults, face high risks of thrombotic and hemorrhagic complications.About 40 % of pediatric patients with acute lymphoblastic leukemia develop bleedings, and the incidence of thrombosis in this disease ranges from 1 to 36 %. Most thromboses are associated with the use of central venous catheters and the use of L-asparaginase, which leads to a significant reduction in the synthesis of coagulation proteins.Massive hemorrhages account for two-thirds of all causes of early death in pediatric patients with acute myelogenous leukemia (AML). Absolute risks of death due to bleeding and leukostasis range from 1.8 % in the total population of children with AML to 14.3 % in a population with hyperleukocytosis more than 200 × 109 /l. The risk of thrombotic complications in children with AML varies between 3.4–11 %. In patients with AML, complex systemic coagulopathies may occur, such as disseminated intravascular coagulation (DIC), excessive fibrinolysis, or nonspecific proteolysis. This scale is not yet applicable due to the lack of research on its effectiveness in the pediatric population. The laboratory diagnostics of hemostasis is difficult due to the combined nature of thrombotic and hemorrhagic complications: bleeding, thrombosis and even DIC syndrome (combining both hyper- and hypocoagulation phases) can be expected in each specific patient with hemoblastosis. Because of the long-term nature of the treatment and the varying intensity of the various treatment units, the patient’s hemostasis during disease manifestation does not allow one to predict with any certainty the complications on induction or consolidation therapy. Involving all the components of the hemostasis system – vascular, platelet and plasma – into the pathological process makes prediction and diagnosis of thrombohemorrhagic complications impossible with the help of standard hemostatic tests and a general blood test, since these tests are designed to assess the concentrations of individual proteins and the functioning of individual components of the hemostatic system, and does not assess the balance between its procoagulant and anticoagulant components. Global hemostatic tests such as thromboelastography, thrombodynamics and thrombin generation test adequately reflect hypercoagulable conditions and can serve as a basis for the development of a new set of laboratory hemostasis tests.Conflict of interest. F.I. Ataullakhanov is co-founder of HemaCore LLC, which holds several patents and patent applications that are related to the diagnostic use of Thrombodynamics® (Ataullakhanov F.I., international patent applications: PCT/CH2007/000543 filing date 02.11.2007 and РСТ/RU2012/000570 filing date 16.07.2012). None of the other authors has any competing interests to declare.

Intraoperative sudden cardiac death in pediatric patients - Calamity yet to overcome?

Intraoperative sudden cardiac death in pediatric patients - Calamity yet to overcome?