Early Mortality In Children Research Articles

Cardiovascular responses as predictors of mortality in children with acute brain injury.

Investigate the utility of cardiovascular responses such as heart rate (HR), blood pressure (BP), and heart rate variability (HRV) in the prognosis of children with acute acquired brain injury (ABI). Children under 18 years with severe acute acquired brain injury (ABI) who survived at least 12 h after PICU admission were included in a prospective observational cohort in a tertiary academic PICU. Physiological variables, neurological data, laboratory tests (chemistry and hematology), and medications were recorded within 12 h of admission. Linear and nonlinear HRV indices, CT scans, PICU scores, and survival rates were evaluated. Seventy-two children, median age 10.7 years (IQR 4.1-13.6), were eligible for the study; 28 (38.9%) were diagnosed with brain death (BD). Tachycardia, SBP and MBP < 5th percentile, and MBP and DBP> 99th percentile were significantly associated with mortality. Poincaré SD1/SD2 was significantly associated with mortality after adjusting for age, sex and ongoing medication. Tachycardia, systolic hypotension and median hypo and hypertension were associated to mortality in children with severe ABI. While further validation through larger, multicenter studies is necessary, the Poincaré SD1/SD2 ratio has shown promise as a prognostic tool for predicting mortality in children with severe ABI. This study explores cardiovascular changes, including heart rate and blood pressure, and linear/nonlinear HRV measures using ECG at 1000 Hz, and compare them with other prognostic factors like brain tomography and PICU scores. Tachycardia, hypo/hypertension in the early hours after admission are linked to early mortality in children with severe traumatic and non-traumatic brain injury. Linear/non-linear measures of HRV were also related to survival. Higher HRV values indicating better survival chances. We identified Poincaré SD1/SD2 ratio as a promising tool for predicting mortality in children with severe ABI.

Early mortality in children with cancer in Denmark and Sweden: The role of social background in a setting with universal healthcare.

Socioeconomic differences in overall survival from childhood cancer have been shown previously, but the underlying mechanisms remain unclear. We aimed to investigate if social inequalities were seen already for early mortality in settings with universal healthcare. From national registers, all children diagnosed with cancer at ages 0-19 years, during 1991-2014, in Sweden and Denmark, were identified, and information on parental social characteristics was collected. We estimated odds ratios (OR) and 95% confidence intervals (CI) of early mortality (death within 90 days after cancer diagnosis) by parental education, income, employment, cohabitation, and country of birth using logistic regression. For children with acute lymphoblastic leukaemia (ALL), clinical characteristics were obtained. Among 13,926 included children, 355 (2.5%) died within 90 days after diagnosis. Indications of higher early mortality were seen among the disadvantaged groups, with the most pronounced associations observed for maternal education (ORadj_Low_vs_High 1.65 [95% CI 1.22-2.23]) and income (ORadj_Q1(lowest)_vs_Q4(highest) 1.77 [1.25-2.49]). We found attenuated or null associations between social characteristics and later mortality (deaths occurring 1-5 years after cancer diagnosis). In children with ALL, the associations between social factors and early mortality remained unchanged when adjusting for potential mediation by clinical characteristics. In conclusion, this population-based cohort study indicated differences in early mortality after childhood cancer by social background, also in countries with universal healthcare. Social differences occurring this early in the disease course requires further investigation, also regarding the timing of diagnosis.

PB0263 ISTH DIC and SIC Score are Associated with Early Mortality in Children with Sepsis Induced Disseminated Intravascular Coagulation

PB0263 ISTH DIC and SIC Score are Associated with Early Mortality in Children with Sepsis Induced Disseminated Intravascular Coagulation

Tracheostomy experiences in chronic respiratory failure after congenital heart surgery

Introduction&#x0D; A small number of children with repaired congenital heart defects may require a tracheostomy for ongoing ventilatory support. Congenital airway anomalies, laryngomalacia, postoperative airway complications and genetic syndromes associated with airway and facial anomalies, such as DiGeorge Syndrome (22q11 deletion), can be counted among the reasons why patients are unable to be weaned from the ventilator. In this study, we aimed to define the outcomes of patients who required a tracheostomy due to chronic respiratory failure after congenital heart surgery, and the existing risk factors for in-hospital and post-discharge mortality.&#x0D; Materials and methods&#x0D; The files of 1382 patients who underwent surgery due to CHD in the Pediatric Cardiovascular Surgery Clinic in ……………., between February 2019 and February 2023, were retrospectively scanned. Patients’ age, gender, body weight, cardiac diagnosis, surgical intervention, length of stay in the intensive care unit, number of extubation attempts, total length of stay on the ventilator, need for ventilator at discharge, rates of weaning from tracheostomy and time of weaning from tracheostomy and mortality rates, were obtained from patient files and hospital database.&#x0D; Results&#x0D; Tracheostomy was performed in 15 of 1382 patients who underwent surgery during the four year study period. Mean (SD) duration of ventilation prior to tracheostomy was 35 days (IQR= 19 – 47). The median follow up time in patients was 224 days (IQR=116-538). Three patients were decannulated and six had died. Causes of death in six patients included sepsis (2), cardiac instability (1), neurological complications (2) and pulmonary haemorraghia (1). &#x0D; The median time to discharge after tracheostomy in patients was 51 days (IQR= 33.50 – 147). &#x0D; Eight patients (53.3%) were discharged on home ventilation. Causes of deaths were often multifactorial for children who died during their initial hospital stay. Mortality was seen in six patients, a rate of 40%. &#x0D; Conclusion&#x0D; The need for tracheostomy after cardiac surgery plays an important role in early and late mortality in children. Ventilator-dependent chronic respiratory failure is the most common cause of childhood tracheostomies. We believe that determining the optimal timing for tracheostomy in the pediatric population will be effective in reducing prolonged ventilation and tracheostomy-related morbidities.

Prognostic factors of early mortality in children and adolescents enrolled in oncology trials with a dose-finding part in the era of targeted and immune therapies: An Innovative Therapies for Children with Cancer (ITCC) study.

10020 Background: Phase I/II trials play a key role for children with relapsed/refractory tumors. Life expectancy beyond 8-12 weeks is a common eligibility criterion. However, there are no objective means to determine life expectancy for trial candidates. A better understanding of the risk factors associated with early mortality on trial could maximize the efficiency of such trials, whilst ensuring the ethical aspects of recruitment. Methods: Patients with relapsed/refractory solid tumors or lymphomas aged &lt; 18 years and participating in interventional clinical trials with a dose-finding part between 2000-2018 in 14 ITCC centers (across 5 European countries) were eligible. The mortality at 30 and 90 days (30-DM and 90-DM, respectively) from Cycle1-Day1 (C1D1) and its association with clinical, laboratory and efficacy data were assessed. Validated prognostic scores (RMH, MDACC) were correlated with early mortality rates. Results: Overall, 527 cases were included in the study; 19 subjects had participated in &gt; 1 trial, leaving a total of 507 subjects enrolled in their first phase I/II trial. Median age at C1D1 was 11.6 years (range, 0.5-17.9); male:female ratio 1.2:1; central nervous system (CNS) tumors (40%) Vs extra-CNS tumors (60%); 75% cases were treated in trials with at least one targeted therapy. The 30-DM (24/507) and 90-DM (116/507) were 4.7% (95%CI 3.1-7.0) and 23.0% (95%CI 19.3-26.8), respectively. At baseline the clinical variables which correlated with higher 90-DM in the univariate analysis were: performance status (Lansky or Karnofsky) ≤80%, no school/work attendance, requirement of opioids, ≥3 metastatic sites, Hb &lt; 100 g/dL and Total Bilirubin, LDH or AST above normal levels (up to the maximum permitted according to protocol eligibility criteria). Higher RMH and MDACC scores also correlated with higher 90-DM. Conclusions: To our knowledge this is the largest case series of children and adolescents participating in pediatric phase I/II trials to date, in which most of the patients were treated with targeted or immuno-oncology agents. The reported 30-DM and 90-DM will serve as a reference benchmark for future trials. Performance status ≤80%, no school/work attendance, requirement of opioids and ≥3 metastatic sites correlated with higher 90-DM. Adult prognostic scores (RMH, MDACC) showed good correlation with 90-DM in the pediatric population. Prognostic factors of early mortality should be given appropriate relevance at the time of study design, informing families and recruiting patients to these studies.

Relationship between Initial Lactate Level with Mortality in Children with Sepsis and Septic Shock: A Comparison with the PRISM-3 Score

Abstract Objective Sepsis and septic shock are leading causes of mortality and morbidity in intensive care units. Our study aimed to compare the pediatric risk of mortality (PRISM-3) score, which is used for predicting mortality risk among critically ill patients in pediatric intensive care units, with laboratory parameters, particularly lactate parameters. Methods This study included 38 patients aged 1 month to 18 years who were managed for sepsis and septic shock in a pediatric intensive care unit. Lactate, D-dimer, troponin T, and N-terminal prohormone of brain natriuretic peptide levels were measured at the 0th and 24th hours. The patients were divided into survivors and nonsurvivors and those with septic shock and those without. Results There were a total of 38 patients with a median age of 12 months, of whom 17 (44.7%) were males and 21 (55.3%) were females. Six (15.8%) patients died within 7 days after the diagnosis. Nonsurvivors had significantly higher median values of PRISM-3 (p = 0.002), C-reactive protein (p = 0.046), and partial arterial carbon dioxide pressure (p = 0.041). PRISM-3 showed a good discriminatory power (area under the curve [AUROC] = 0.878; p &lt; 0.0001) and baseline lactate level showed a moderate level of discriminatory power (AUROC = 0.734 p = 0.0254) for early mortality within 7 days. Conclusion PRISM-3 and baseline lactate predict early mortality in children with sepsis and septic shock. We suggest that adding lactate, which is not included in the PRISM-3 score, to the score may increase the score's predictive ability for mortality. We believe, however, that randomized, controlled, multicenter studies with larger sample sizes should be conducted to test this hypothesis.

Anticoagulation therapy and thromboembolic complications in pediatric patients undergoing the Fontan procedure

Objectives: We assessed the children with complex heart anomalies who undergone operative intervention of any form of Fontan intervention and analyzed them for thromboembolic complications after Fontan procedure performed at the Pediatric Clinic of Pristina.Background: Thromboembolic complications are a major cause of early and late mortality in children with single-ventricle congenital heart defects who have undergone a Fontan procedure.Thrombosis is an important and unpredictable complication, not only after Fontan operation but also associated with each stage of single-ventricle palliation. It is an important cause of morbidity, particularly when it leads to pulmonary embolism or stroke, and contributes to mortality.Methodology: The research was conducted at the Pediatric Clinic in the Cardiology and Intensive Care Service, during 2018-2021. The study includes patients who have undergone tertiary level intervention - one of the forms of the Fontan procedure, the research included 40 patients aged 0 -19 years. The children were divided into two groups: the group 29 patients using Aspirin therapy and the group of 11 patients without Aspirin therapy. In children after admission, laboratory tests were performed: hemogram, bleeding time, coagulation time, INR, PTT, and PT.Results: The mean age of children with antithrombotic therapy was 6.03 years (DS ± 5.84 years), those without therapy 3.27 years (DS ± 5.44 years). Aspirin as antithrombotic therapy was applied to 29 patients at a dose of 15 to 115 mg / 24 hours. In 6 patients the dose was less than 3-5 mg / kg body weight.Thepatients with congenital heart malformations after Fontan procedure receiving antithrombotic therapy are 1.4 times more likely to have reduced prothrombin time.Conclusions: Fontan procedure in children has been gratifying, with most survivors now leading lives of good quality into adulthood.

Upper Extremity Examination for Neuromuscular Diseases (U-EXTEND): Protocol for a Multimodal Feasibility Study.

Neuromuscular diseases, such as spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD), may result in the loss of motor movements, respiratory failure, and early mortality in young children and in adulthood. With novel treatments now available, new evaluation methods are needed to assess progress that is not currently captured in existing motor scale tests. With our feasibility study, our interdisciplinary team of investigators aims to develop a novel, multimodal paradigm of measuring motor function in children with neuromuscular diseases that will revolutionize the way that clinical trial end points are measured, thereby accelerating the pipeline of new treatments for childhood neuromuscular diseases. Through the Upper Extremity Examination for Neuromuscular Diseases (U-EXTEND) study, we hypothesize that the novel objective measures of upper extremity muscle structure and function proposed herein will be able to capture small changes and differences in function that cannot be measured with current clinical metrics. U-EXTEND introduces a novel paradigm in which concrete, quantitative measures are used to assess motor function in patients with SMA and DMD. Aim 1 will focus on the use of ultrasound techniques to study muscle size, quality, and function, specifically isolating the biceps and pronator muscles of the upper extremities for follow-ups over time. To achieve this, clinical investigators will extract a set of measurements related to muscle structure, quality, and function by using ultrasound imaging and handheld dynamometry. Aim 2 will focus on leveraging wearable wireless sensor technology to capture motion data as participants perform activities of daily living. Measurement data will be examined and compared to those from a healthy cohort, and a motor function score will be calculated. Data collection for both aims began in January 2021. As of July 2022, we have enrolled 44 participants (9 with SMA, 20 with DMD, and 15 healthy participants). We expect the initial results to be published in summer 2022. We hypothesize that by applying the described tools and techniques for measuring muscle structure and upper extremity function, we will have created a system for the precise quantification of changes in motor function among patients with neuromuscular diseases. Our study will allow us to track the minimal clinically important difference over time to assess progress in novel treatments. By comparing the muscle scores and functional scores over multiple visits, we will be able to detect small changes in both the ability of the participants to perform the functional tasks and their intrinsic muscle properties. DERR1-10.2196/40856.

Risk factors of early death in pediatric hemophagocytic lymphohistocytosis: Retrospective cohort study.

Hemophagocytic lymphocytosis (HLH) is a rare life-threatening hyperinflammatory syndrome in which early mortality remains high in patients with HLH. We retrospectively collected the medical records of all pediatric patients diagnosed with HLH at the West China Second Hospital of Sichuan University between January 2014 and December 2020. Collect demographic, laboratory, clinical, genetic profiles, treatment information and perform statistical analysis from records. Risk factors for death 30 days after admission were evaluated using a multivariable logistic regression model. A total of 110 pediatric HLH patients were enrolled. The median age of patients was 44 months (IQR 23-100.5) and 62 (56.4%) in males. The 30-day mortality rate for admission to this cohort was 34 (30.9%). Multivariate logistic regression analysis showed that heart failure (OR = 13.389, 95% CI, 1.671-107.256, p = 0.015) and hypoproteinemia (OR = 4.841, 95% CI, 1.282-18.288, p = 0.020) were associated with increased early mortality in children with HLH. These identified risk factors may help clinicians stratify patients with HLH and develop targeted treatment strategies. More research is needed to explore the best treatment strategies for patients with HLH to reduce early mortality in patients with HLH.

Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience.

Objective: Embryonal tumors with multilayered rosettes (ETMRs) are highly aggressive pediatric brain tumors with poor prognosis. No standard treatment strategy for them exists because of their rarity. This study aimed to share experiences on the clinical diagnosis and treatment of ETMRs at China Children’s Medical Center (CCMC). Methods: Patients who received a diagnosis of an ETMR between January 2017 and June 2020 were included. Clinical characteristics, such as age of onset, tumor size, stage, tumor site, treatment strategy, and clinical outcome, were retrospectively analyzed. Results: There were four boys and one girl within 4 years who received a diagnosis during this 4-year timeframe, and were thus included. The average age of morbidity was 29 months (range 16–66 months). The common clinical presentation was headaches and nausea caused by intracranial hypertension. All four patients were chromosome 19 microRNA cluster (C19MC) amplification positive. Two patients achieved complete remission, and one patient attained partial remission after multimodal treatment. Of the two deaths, one died from the rapid progression of the disease and another from tumor-related complications. Conclusion: ETMRs are extremely rare brain tumors with a high, early mortality in children. Surgery is the mainstream treatment for ETMRs. Some patients may also benefit from postoperative adjuvant chemotherapy and radiotherapy.

Central nervous system involvement and thrombocytopenia as predictors of mortality in children with hemophagocytic lymphohistiocytosis

IntroductionHemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition. This study aimed to evaluate treatment outcomes and identify prognostic-related factors in Thai children with HLH.Materials and methodsWe retrospectively reviewed the medical records of 76 pediatric patients with HLH who were treated at Ramathibodi Hospital between January 2004 and December 2019. Treatment outcomes were defined as early mortality (death within 30 days after diagnosis) and early treatment response (resolution of all clinical features and normalization of at least one HLH-related laboratory parameter within 4 weeks).ResultsThe overall mortality rate was 38% (29/76), with an early mortality rate of 45% (13/29). Malignancy-associated HLH had the highest mortality rate (88%), followed by primary HLH (56%). The predictors of early mortality were central nervous system (CNS) involvement [OR 13 (95%CI 2–83), p = 0.007] and platelet counts <44 × 106/mm3 [OR 8 (95%CI 1.3–49), p = 0.024]. The predictors of early treatment response were no CNS involvement [OR 6.6 (95%CI 1.5–28.8), p = 0.011], platelet counts more than 44 × 106/mm3 [OR 8 (95%CI 2.1–30.9), p = 0.003], and total bilirubin levels <1.8 mg/dL [OR 4 (95%CI 1.1–14.8), p = 0.036]. In the mixed-model analysis, platelet counts in non-survivors increased significantly less than those in survivors, with a mean difference in platelet changes between the two groups of 94.6 × 106/mm3 (p = 0.003).ConclusionThe independent predictors of early mortality in children with HLH were CNS involvement and low baseline platelet counts. A slow rate of platelet increases during the first week after diagnosis was also associated with mortality.

Association between early fluid overload and mortality in critically-ill mechanically ventilated children: a single-center retrospective cohort study

BackgroundPositive fluid overload (FO) may cause adverse effect. This study retrospectively analyzed the relationship between early FO and in-hospital mortality in children with mechanical ventilation (MV) in pediatric intensive care unit (PICU).MethodsThis study retrospectively enrolled 309 children (ages 28 days to 16 years) receiving invasive MV admitted to the PICU of Xinhua Hospital from March 2014 to March 2019. Children receiving MV for less than 48 h were excluded. The FO in the first 3 days of MV was considered to the early FO. Patients were divided into groups according to early FO and survival to evaluate the associations of early FO, percentage FO(%FO) > 10%, and %FO > 20% with in-hospital mortality.ResultsA total of 309 patients were included. The mean early FO was 8.83 ± 8.81%, and the mortality in hospital was 26.2% (81/309). There were no significant differences in mortality among different FO groups (P = 0.053) or in early FO between survivors and non-survivors (P = 0.992). Regression analysis demonstrated that use of more vasoactive drugs, the presence of multiple organ dysfunction syndrome, longer duration of MV, and a non-operative reason for PICU admission were related to increased mortality (P < 0.05). Although early FO and %FO > 10% were not associated with in-hospital mortality (β = 0.030, P = 0.090, 95% CI = 0.995–1.067; β = 0.479, P = 0.153, 95% CI = 0.837–3.117), %FO > 20% was positively correlated with mortality (β = 1.057, OR = 2.878, P = 0.029, 95% CI = 1.116–7.418).ConclusionsThe correlation between early FO and mortality was affected by interventions and the severity of the disease, but %FO > 20% was an independent risk factor for in-hospital mortality in critically ill MV-treated children.

Преждевременные роды – нерешенная проблема XXI века

The article discusses one of the most significant problems in the modern obstetric practice – preterm labor (PL). The upward trend in PL worldwide is related to an increase number of multiple pregnancies due to in vitro fertilization (IVF). PL is one of the main causes of early neonatal mortality and disability in children, also increases the survival rate of newborns with extremely low birth weight, and therefore it significantly changes the structure of surviving premature infants' morbidity. The greatest threat is represented by the «threshold» stages of the disease, with the development of which the process becomes almost irreversible and requires immediate treatment. To improve the perinatal outcomes of PL, the authors draw attention to two problems: first of them – to understand the mechanism of PL, the second one-to work out tactics that allow to carry out measures that can delay, prevent the distress syndrome, and improve fetal condition at any stage of the disease. Key words: preterm birth, in vitro fertilization, quality of life, retinopathy of prematurity.

Decreased Early Mortality in Young Adults with Acute Lymphoblastic Leukemia Treated at Specialized Cancer Centers in California

BackgroundA population-based study suggested that adolescent and young adults with acute lymphoblastic leukemia (ALL) have superior survival when treated at specialized cancer centers (SCC; versus community hospitals). However, the association of location of initial care with early mortality (death within 60 days) has not yet been evaluated in children and adolescents and young adults with ALL. Therefore, we examined the impact of location of initial care, sociodemographic factors and complications on early mortality in children (0-18 years) and adolescent and young adults (AYAs; 19-39 years) with ALL.MethodsUsing the California Cancer Registry linked to a hospitalization database in California, we identified children and AYAs with first primary diagnosis of ALL who received inpatient treatment within 60-days of diagnosis between 1991 and 2014. SCCs were defined as Children's Oncology Group or National Cancer Institute (NCI)-designated cancer centers for children and NCI-designated cancer center for AYAs. Children and AYAs were classified as receiving all or part/none of their care at a SCC within 60-days of diagnosis. Mulitple logistic regression was used to identify factors associated with receiving all initial care at a SCC and to build a propensity score separately for children and AYAs. Inverse probability-weighted, multivariable logistic regression models estimated the associations between location of care, sociodemographic characteristics, clinical factors and complications with early mortality. Results are presented as odds ratios (ORs) and 95% confidence intervals (CI).ResultsOf the 6,531 patients with ALL in our study, the overall early mortality rate for was 2.1% in children and 6.3% in AYAs. The majority of children received all of their care at an SCC (n=4752, 85.4%) compared to only 36.1% of AYAs (n=1779). Rates of early mortality varied significantly by location of care and age (children: all care at an SCC 1.9% vs part/none 3.2%, p=0.04; AYAs: all care at an SCC 3.9% vs part/none 7.7%, p=0.002). Among children, factors associated with receiving all care at a SCC were younger age, Hispanic race/ethnicity (vs non-Hispanic white), more recent diagnosis and having public/no insurance (vs private). Factors associated with receiving all care at a SCC among AYAs were younger age, non-Hispanic white race/ethnicity (vs Hispanic), public/no insurance, and living in a lower socioeconomic status (SES) neighborhood. In multivariable, inverse probability weighted models, receiving all care at a SCC (versus part/no care) was associated with significantly lower early mortality in AYAs (OR 0.44, CI 0.27-0.74), but not in children (OR 0.61, CI 0.34-1.08). Higher early mortality in children was associated with complications of bleeding (OR 5.73, CI 2.76-11.90), sepsis (OR 2.02, CI 1.01-4.04), renal (OR 4.1, CI 2.17-7.76) and respiratory failure (OR 5.48, CI 2.66-11.29). In AYAs, higher early mortality was associated with older age (>29), having a comorbidity (OR 1.83, CI 1.08-3.10) and complications of liver failure (OR 8.03, CI 2.41-26.76), renal failure (OR 2.45, CI 1.33-4.52) and respiratory failure (OR 11.89, CI 5.87-24.09). Early mortality was not associated with race/ethnicity, neighborhood SES or health insurance for either age group. Rates of complications were similar by location of care in children and AYAs except for thrombosis in children (all: 0.40% vs part/none: 1.00% p=0.03) and renal failure in AYAs (all: 14.3% vs part/none: 10.7% p=0.03).ConclusionsOur results suggest that treatment at a SCC is associated with a significantly lower early mortality for AYA patients after adjusting for sociodemographic and clinical factors. We observed a borderline difference in mortality by location of care in children, likely because, in contrast to AYAs, the vast majority of children are seen at SCCs. The reduction in mortality at SCCs may be due to access to clinical trials and other specialized services available at these types of institutions. DisclosuresWun:Janssen: Other: Study steering committee and research support (site PI); Pfizer: Other: Study steering committee and research support (site PI).

Natural history study of glycan accumulation in large animal models of GM2 gangliosidoses.

β-hexosaminidase is an enzyme responsible for the degradation of gangliosides, glycans, and other glycoconjugates containing β-linked hexosamines that enter the lysosome. GM2 gangliosidoses, such as Tay-Sachs and Sandhoff, are lysosomal storage disorders characterized by β-hexosaminidase deficiency and subsequent lysosomal accumulation of its substrate metabolites. These two diseases result in neurodegeneration and early mortality in children. A significant difference between these two disorders is the accumulation in Sandhoff disease of soluble oligosaccharide metabolites that derive from N- and O-linked glycans. In this paper we describe our results from a longitudinal biochemical study of a feline model of Sandhoff disease and an ovine model of Tay-Sachs disease to investigate the accumulation of GM2/GA2 gangliosides, a secondary biomarker for phospholipidosis, bis-(monoacylglycero)-phosphate, and soluble glycan metabolites in both tissue and fluid samples from both animal models. While both Sandhoff cats and Tay-Sachs sheep accumulated significant amounts of GM2 and GA2 gangliosides compared to age-matched unaffected controls, the Sandhoff cats having the more severe disease, accumulated larger amounts of gangliosides compared to Tay-Sachs sheep in their occipital lobes. For monitoring glycan metabolites, we developed a quantitative LC/MS assay for one of these free glycans in order to perform longitudinal analysis. The Sandhoff cats showed significant disease-related increases in this glycan in brain and in other matrices including urine which may provide a useful clinical tool for measuring disease severity and therapeutic efficacy. Finally, we observed age-dependent increasing accumulation for a number of analytes, especially in Sandhoff cats where glycosphingolipid, phospholipid, and glycan levels showed incremental increases at later time points without signs of peaking. This large animal natural history study for Sandhoff and Tay-Sachs is the first of its kind, providing insight into disease progression at the biochemical level. This report may help in the development and testing of new therapies to treat these disorders.

Early mortality in children with cancer in the National Institution of Pediatrics, Mexico.

e19004 Background: Children cancer represents the first cause of mortality by disease worldwide. Early mortality is defined as death within the first four weeks since the patient’s admission to the hospital, and it is an indicator to evaluate attention quality. It is considered that early mortality rate must be less than 5% in acute lymphoblastic leukemias, although it is not standardized in solid tumors. The aim of this study was to evaluate the early mortality rate in a third level pediatric center. Methods: We have conducted a retrospective analysis of oncology patient records dating from January 2012 to April 2017 diagnosed and treated in the National Institute of Pediatrics in Mexico. Patients who died in the first four weeks from diagnosis were included in our study. Clinical characteristics were analyzed with an univariate analyses using measures of central tendency for quantitative data and proportions for qualitative. We used SPSS-20 for all analyses. Results: A total of 1500 patients were diagnosed with neoplastic disease at the Institute within 2012 and 2017, 34 (2.26%) of them had an early death. Median age of diagnosis was 5 years. Central nervous system (CNS) tumors were the predominant group associated to early mortality (23.5%), followed by hepatocarcinoma, acute lymphoblastic leukemia (ALL), neuroblastoma, diffuse intrinsic pontine glioma (DIPG), and Wilms tumor (5.9% each). 70.6% had metastatic disease at diagnosis. Main cause of death was progression of disease (60%), followed by infectious complications (35%). Only one patient was treated by palliative care. Conclusions: In spite of children cancer care innovations, early death rates are still high, mainly because of delay in diagnosis at advanced stages of the disease. Another important factor in low-middle income countries is treatment abandonment, which is higher in patients who live in precarious conditions and live in isolated communities and must travel long distances to get medical attention. As healthcare professionals from a low-middle income country, we still have a lot to do to prevent our patients early mortality.

Nutritional status and personal hygiene practices of primary school children: A cross-sectional study from Meghalaya, India

Background:Poor nutritional status in primary school children can lead to several health problems such as easy susceptibility to common childhood diseases. Personal hygiene status is an important predictor of nutritional status and morbidity in children as water- and sanitation-related diseases are the leading causes of early morbidity and mortality in children. The present study was conducted to assess the nutritional status as well as personal hygiene practices of primary school going children.Method:The present study was a cross-sectional study conducted in selected urban and rural areas of Shillong in children 6–12 years of age. Two schools each from the rural and urban area were selected using simple random sampling. The total sample size calculated was 510. Height, weight, and BMI were taken for all the children following the standard procedures. WHO growth standards were used for grading of nutritional status. A questionnaire with scores was used for grading of personal hygiene status.Results:The overall prevalence of underweight in the children of 6–9 years was 74 (18.7%) and that of stunting was 68 (17.2%). The overall prevalence of thinness and stunting in children aged 10–12 was 38 (19.1%) and 46 (23.2%). The prevalence of nutritional deficiency syndromes was 192 (32.4%). Regarding the personal hygiene status, it was observed that 65 (11%) had very good personal hygiene, 292 (49.3%) were labeled as good, 200 (33.8%) were average, and 35 (5.9%) had poor personal hygiene.Conclusion:The primary school going children in Shillong had poor nutritional status but the majority of them had good personal hygiene practices. Mother's educational status played an important role in determining the nutritional and personal hygiene status of the children.

Early Mortality in Children and Adolescents with Acute Promyelocytic Leukemia: Experience of the Boldrini Children's Center.

Acute promyelocytic leukemia (APL) is currently considered a highly curable disease. However, an early death (ED) remains one of the main causes of APL treatment failure. In this retrospective study, we aimed to analyze the clinical characteristics of 91 children and adolescents with APL, who were consecutively registered at the (name of institution removed) Children's Center from January 1, 1998 to December 31, 2017. Data were assessed for age, sex, ethnicity, body mass index percentile, initial white blood cell count, peripheral blood blast count, and platelet count, hemoglobin value, partial thromboplastin time, prothrombin time, fibrinogen level, serum creatinine level, APL morphology subtype (classic vs. hypogranular variant M3v), and FLT3 gene mutations. ED occurred in 12 of 91 (13.1%) patients and was mainly related to cerebral thromboembolism. Overall 66% of deaths occurred in the second week after diagnosis. ED was associated with white blood cell ≥10×10 cells/L (odds ratio of 8.44; 95% confidence interval [CI]=1.48-48.26; P=0.0016), initial promyelocytes ≥20×10/L (odds ratio of 9.29; 95% CI=2.45-35.8; P=0.001), morphologic subtype M3v (odds ratio of 3.63; 95% CI=1.04-12.64; P=0.043), and creatinine serum levels >0.7 mg/dL (odds ratio of 6.78; 95% CI=1.83-25.13; P=0.004). In multivariate analyses, ED was associated with initial peripheral promyelocytes ≥20×10 blasts/L and creatinine serum levels >0.7 mg/dL. EDs were mainly caused by thrombohemorrhagic events and occurred within the second week after diagnosis. High peripheral promyelocytes and creatinine levels were predictors of ED in APL.

Elements Associated With Early Mortality in Children With B Cell Acute Lymphoblastic Leukemia in Chiapas, Mexico: A Case-control Study.

Childhood Lymphoblastic leukemia's (ALL) early mortality (EM) is an undesirable treatment outcome for a disease for which >90% long term success is achievable. In the Western world EM constitutes no >3%; yet, in Chiapas, Mexico, remains around 15%. With the objective of improving on EM, we determined associated elements in 28 ALL who died within 60 days of arriving at Hospital de Especialidades Pediátricas in Chiapas (HEP), by comparing them to those in 84 controls who lived beyond the first 90 days. χ, t test, and binary logistic regression (BLR) were used to determine significant individual and multiple variables associated to outcome. On arrival, fever, liver and spleen enlargement, active bleeding, lower albumin, less platelets, higher creatinine, and uric acid, more diploid and less hyperdiploid cases were associated with EM cases. Time to diagnosis, nutritional status, risk group and leukocyte count were not related. Antileukemic treatment approach was similar in both groups. The BLR model including fever, active bleeding, liver enlargement, <10,000 platelets/µL, and >2X upper normal lactic dehydrogenase, determined outcome in 66.7% EM and 90.2% controls. To improve on EM in ALL, patients with characteristics defined here ought to be treated differently at HEP.

Shock Index-A Useful Noninvasive Marker Associated With Age-Specific Early Mortality in Children With Severe Sepsis and Septic Shock: Age-Specific Shock Index Cut-Offs

Aim of the study was to analyze the association of shock index (SI) from 0 to 6 hours with early mortality in severe sepsis/septic shock and to explore its age-specific cut-off values. To investigate association of change in SI over first 6 hours with early mortality. A prospective cohort study of children (<14 years) admitted in emergency department, tertiary care hospital with severe sepsis or septic shock, divided into 3 groups: group 1: 1 month to <1 year; group 2: 1 to <6 years; group 3: 6 to 12 years. Shock index (SI = heart rate/systolic blood pressure) measured at admission (X0) and hourly till 6 hours (X1-6). Primary outcome was death within 48 hours of admission. Area under receiver operating characteristic curves were constructed for SI (0-6). Optimal cut-offs of SI 0 and SI 6, maximizing both sensitivity and specificity were determined and positive and negative predictive values (PPV, NPV) were calculated. From 2015 to 2016, 120 children were recruited. Septic shock was present at admission in 56.7% children. Early mortality was 50%. All hourly shock indices (SI 0-6) were higher among nonsurvivors in group 2 (P ≤ .03) and group 3 (P < .001). In group 1, SI after 2 hours was higher in nonsurvivors (P 2-6: ≤ .02). Area under receiver operating characteristic curves (95% CI) for SI at 0 hour was 0.72 (0.5-0.9), 0.66 (0.5-0.8), and 0.77 (0.6-0.9) and at 6 hours was 0.8 (0.6-1), 0.75 (0.6-0.9), and 0.8 (0.7-1) in 3 groups. The cut-off values of SI 0 (sensitivity; specificity; PPV; NPV) in 3 groups: 1.98 (77; 75; 67; 83), 1.50 (65; 65; 68; 63), and 1.25 (90; 67; 77; 83) and SI6: 1.66 (85; 80; 73; 89), 1.36 (73; 70; 73; 70), and 1.30 (74; 73; 78; 69). Improvement of SI over 6 hours was associated with better outcome. Children with higher SI at both time points had higher mortality than those with SI score below the cut-offs (P = .001). Age-specific SI cut-off values may identify children at high risk of early mortality in severe sepsis/septic shock and allow for better targeted management.