Effect of N-acetyl cysteine in children with metabolic dysfunction-associated steatotic liver disease-A pilot study.

BACKGROUND: Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction-associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N-acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and (LS) in children with obesity and biopsy-confirmed MASLD. METHODS: Thirteen children (n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double-blind, placebo-controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high-sensitivity c-reactive protein (hs-CRP), and interleukin-6 (IL-6) were also measured. HOMA-IR was calculated. RESULTS: Sixteen-week NAC treatment improved (baseline adjusted between-group p < .05 for all) markers of inflammation (IL-6 and hs-CRP), oxidative stress (GSH), and insulin resistance (HOMA-IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes. CONCLUSIONS: Sixteen-week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD.

Impact of intravenous fluid administration on cardiac output and oxygenation during cardiopulmonary resuscitation.

BACKGROUND: The effect of intravenous fluid (IVF) administration during cardiopulmonary resuscitation (CPR) is an unexplored factor that may improve cardiac output (CO) during CPR. The aim of this study was to determine the effect of IVF administration on CO and oxygenation during CPR. METHODS: This experimental animal study was performed in a critical care animal laboratory. Twenty-two Landrace-Yorkshire female piglets weighing 27-37 kg were anesthetized, intubated, and placed on positive pressure ventilation. Irreversible cardiac arrest was induced with bupivacaine. CPR was performed with a LUCAS 3 mechanical compression device. Pigs were randomized into IVF or no-IVF groups. Pigs in the IVF group were given 20 mL/kg of Plasma-Lyte (Baxter International, Deerfield, IL USA), infused from 15 to 35 min of CPR. CPR was maintained for 50 min with serial measurements of CO obtained using ultrasound dilution technology and partial pressure of oxygen (PaO2). RESULTS: A mixed-effects repeated measures analysis of variance was used to compare within-group, and between-group mean changes in CO and PaO2 over time. CO and PaO2 for the piglets were measured at 10-min intervals during the 50 min of CPR. CO was greater in the IVF compared with the control group at all time points during and after the infusion of the IVF. Mean PaO2 decreased with time; however, at no time was there a significant difference in PaO2 between the IVF and control groups. CONCLUSIONS: Administration of IVF during CPR resulted in a significant increase in CO during CPR both during and after the IVF infusion. There was no statistically significant decrease in PaO2 between the IVF and control groups.

Branched-chain Amino Acids and Relationship With Inflammation in Youth With Obesity: A Randomized Controlled Intervention Study.

CONTEXT: Elevated concentrations of branched-chain amino acids (BCAA) are strong predictors of type 2 diabetes mellitus (T2DM). Their association with cardiovascular disease (CVD) remains uncertain, particularly in youth. OBJECTIVE: We investigated the role of BCAA and aromatic amino acids (AAA) in obesity, their relationships with novel biomarkers of CVD, and response to a physical activity-based lifestyle intervention (PAL-I) in a randomized controlled study in youth with normal weight (NW) and obesity (OB). METHODS: Age (14-18 years) and Tanner stage (≥IV) matched youth (OB, n = 15 and NW, n = 6) were studied; the 15 participants with OB underwent a 3-month randomized controlled PAL-I. Circulating amino acid profile, glucose, insulin, lipids, adiponectin, retinol binding protein-4, fibrinogen, high-sensitivity C-reactive protein, interleukin-6, and 25-hydroxy vitamin-D, along with body composition, were measured at baseline and after PAL-I. Independent t tests, analysis of covariance, and mixed-effect models were used for analysis of the data. RESULTS: Compared with NW, the concentration of various amino acids, including BCAA and AAA, were altered in OB (P < 0.05). BCAA and AAA showed baseline correlations with body composition and novel biomarkers of CVD, particularly inflammatory factors (all P < 0.05). The PAL-I produced only negligible effects (P > 0.05) on BCAA and AAA. Glutamine, glycine, and aspartic acid decreased with PAL-I (all P < 0.05). CONCLUSION: The novel finding of the BCAA-inflammation relationship, along with strong correlations with nontraditional biomarkers of CVD, may raise the prospect of BCAA as a biomarker of CVD and evoke a potential link between obesity, T2DM, and CVD.

Effect of positive end-expiratory pressure on additional passive ventilation generated by CPR compressions in a porcine model.

BACKGROUND: Compressions given during cardiopulmonary resuscitation generate small, ineffective passive ventilations through oscillating waves. Positive end-expiratory pressure increases the volume of these passive ventilations; however, its effect on passive ventilation is unknown. Our objective was to determine if increasing positive end-expiratory pressure during cardiopulmonary resuscitation increases passive ventilation generated by compressions to a clinically significant point. This study was conducted on 13 Landrace-Yorkshire pigs. After inducing cardiac arrest with bupivacaine, cardiopulmonary resuscitation was performed with a LUCAS 3.1. During cardiopulmonary resuscitation, pigs were ventilated at a positive end-expiratory pressure of 0, 5, 10, 15, 20 cmH2O (randomly determined) for 9 min. Using the NM3 respiratory monitoring device, expired minute ventilation and volumetric capnography were measured. Arterial blood gas was obtained for each positive end-expiratory pressure level to compare the effects of positive end-expiratory pressure on carbon dioxide. RESULTS: Increasing positive end-expiratory pressure from 0 to 20 cmH2O increased the mean (SEM) expired minute ventilation from 6.33 (0.04) to 7.33 (0.04) mL/min. With the 5-cmH2O incremental increases in positive end-expiratory pressure from 0 to 20 cmH2O, volumetric capnography increased from a mean (SEM) of 94.19 (0.78) to 115.18 (0.8) mL/min, except for 15 cmH2O, which showed greater carbon dioxide exhalation with volumetric capnography compared with 20 cmH2O. PCO2 declined significantly as positive end-expiratory pressure was increased from 0 to 20 cmH2O. CONCLUSIONS: When increasing positive end-expiratory pressure from 0 to 20, the contribution to overall ventilation from gas oscillations generated by the compressions became more significant, and may even lead to hypocapnia, especially when using positive end-expiratory pressures between 15 and 20.

Epidemiology and prognostic factors of pediatric brain tumor survival in the US: Evidence from four decades of population data.

Brain tumors, a group of heterogeneous diseases, are the second most common cancer and the leading cause of cancer-related deaths in children. Insight into the prognosis of pediatric brain tumor survival has led to improved outcomes and could be further advanced through precision in prognosis. We analyzed the United States SEER population-based dataset of 15,723 pediatric brain tumor patients diagnosed and followed between 1975 and 2016 using a stratified Cox proportional hazards model. Mortality risk declined with increased age at diagnosis, the adjusted hazard ratio (aHR) (95 % confidence interval) was 0.60 (0.55, 0.67) and 0.47 (0.42, 0.52) for ages at diagnosis 1-10 years and 10-19 years, respectively, when compared with infants. Non-Hispanic Caucasian patients showed a lower risk of mortality than non-Hispanic African Americans (1.21 (1.11, 1.32)) and Hispanics (1.21 (1.11, 1.32)). Primary tumor sites, grades, and histology showed substantial heterogeneity in mortality risk. Brainstem (2.62 (2.41, 2.85)) and Cerebrum (1.63 (1.46, 1.81)) had an elevated risk of mortality than lobes. Similarly, Grade II (1.32 (1.07, 1.62)), Grade III (3.39 (2.74, 4.19)), and Grade IV (2.18 (1.80, 2.64)) showed an inflated risk of mortality than Grade I. Compared to low-grade glioma, high-grade glioma (7.92 (7.09, 8.85)), Primitive neuroectodermal tumors (4.72 (4.15, 5.37)), Medulloblastoma (3.11 (2.79, 3.47)), and Ependymal-tumors (2.20 (1.95, 2.48)) had increased risk of mortality. County-level poverty and geographic region showed substantial variation in survival. This large population-based comprehensive study confirmed identified prognostic factors of pediatric brain tumor survival and provided estimates as epidemiologic evidence with greater generalization.

Durability of Changes in Biomarkers of Cardiometabolic Disease: 1-Year Family-Based Intervention in Children with Obesity.

Background: The sustainability of health benefits in response to lifestyle-based interventions remains unclear in children with overweight and obesity, and cardiometabolic disease (CMD). We determined the changes in novel biomarkers of CMD in a 1-year family-based intervention (FBI) program, during 6-month active monitoring phase and at 12-month follow-up. Methods: Children with an age-adjusted body mass index (BMI) percentile ≥85 (N = 130; age 8-11 years) were recruited for a 1-year (6-month monitored and 6-month unmonitored) randomized controlled FBI program. Anthropometry and selected biomarkers of CMD were measured in 87 participants, randomly allocated to intervention (INT) and education-only (EDU) groups, at baseline, immediately after a 6-month active intervention or control period, and at 12-month unmonitored follow-up. Results: Samples from 87 participants (age 10.00 ± 0.11 years and Tanner stage ≤3) with obesity (BMI%ile = 97.45 ± 0.15) were available. Overall intervention effect (between groups), was observed for total (T) and high molecular weight (HMW) adiponectin, ratio of total to HMW adiponectin, fibrinogen, and interleukin (IL)-6 (P < 0.05 for all). However, between-group beneficial changes after adjusting for baseline levels were limited to BMI percentile, T and HMW adiponectin and their ratio, IL-6, and fibrinogen (P < 0.05 for all) mainly during the 6-month period of monitored intervention. Changes in traditional risk factors such as lipids and triglycerides were inconsistent. During the 6-month follow-up period, the changes in biomarkers leveled-off, except for T and HMW adiponectin, IL-6, and fibrinogen that continued to show benefits (P < 0.05) from the 6- to 12-month follow-up. Conclusions: The FBI program beneficially altered novel biomarkers of CMD during the monitored intervention phase in school-age children with obesity, but they mostly moved back toward baseline during the unmonitored follow-up phase. The changes in novel biomarkers of CMD appear to be more sensitive compared to the traditional risk factors. The study implies the need for refinements in lifestyle-based approaches in the preservation of cardiovascular health and calls for robust biomarkers to monitor the changes. The study was registered at ClinicalTrials.gov (NCT01146314).

The effect of positive end-expiratory pressure on cardiac output and oxygen delivery during cardiopulmonary resuscitation.

BACKGROUND: Positive end-expiratory pressure (PEEP) is used to optimize oxygenation by preventing alveolar collapse. However, PEEP can potentially decrease cardiac output through cardiopulmonary interactions. The effect of PEEP on cardiac output during cardiopulmonary resuscitation (CPR) is not known. METHODS: This was a preclinical randomized, controlled, animal study conducted in an animal research facility on 25 Landrace-Yorkshire pigs. After inducing cardiac arrest, CPR was performed with LUCAS 3. During CPR, pigs were ventilated at a PEEP of 0, 5, 10, 15, 20 cmH2O (randomly determined via lottery) for 9 min. Cardiac output, obtained via ultrasound dilution, and PaO2 were measured, and oxygen delivery calculated for each PEEP. RESULTS: A mixed-effects repeated-measures analysis of variance was used to compare the baseline value adjusted mean cardiac output, PaO2, and oxygen delivery between PEEP groups. Least significant difference test was used to conduct pairwise comparisons between PEEP groups. To determine optimum PEEP, Gaussian mixture model was applied to the adjusted means of cardiac output and oxygen delivery. Increasing PEEP to 10 and higher resulted in significant declines in cardiac output. A PEEP of 15 and higher resulted in significant declines in oxygen delivery. As PEEP was increased from 0 to 20, PaO2 increased significantly. Gaussian mixture model identified the 0-5 PEEP group as providing optimal cardiac output and oxygen delivery, with PEEP of 5 providing the highest oxygen delivery. CONCLUSIONS: A PEEP of 0-5 resulted in the optimal oxygen delivery and cardiac output during CPR, with PEEP of 5 resulting in higher oxygen delivery, and a slightly lower, statistically insignificant cardiac output than PEEP of 0.

Use of pulse contour technology for continuous blood pressure monitoring in pediatric patients.

OBJECTIVES: This study evaluates the accuracy of continuous blood pressure monitoring using pulse contour technology with the ClearSight monitoring device, a noninvasive alternative to placing an invasive arterial line, in pediatric patients. METHODS: Children younger than 18 years admitted to a pediatric ICU, who required an arterial line, and fit into the ClearSight finger cuff were included. Blood pressure measurement for systolic, diastolic, and mean arterial pressures (MAP) obtained by the ClearSight device were compared with those obtained with the intra-arterial catheter as well as automated cuff measurements using the mixed-effects model. Analysis was conducted for entire cohort, and measurements obtained with and without vasopressor use. RESULTS: There were 213 measurements from 10 patients. There was a statistically significant difference in systolic blood pressure when comparing arterial line and ClearSight systolic and diastolic measurements between the two methods (P < 0.001). There was no statistical difference between arterial MAP and ClearSight MAP (P = 0.957). Results were similar when ClearSight measurements were compared with automated cuff measurements. Both the vasopressor use and nonvasopressor use groups showed a statistically significant difference between arterial and ClearSight measurements for systolic and diastolic pressures, but not for the MAP. CONCLUSIONS: Measurements of MAP obtained by the ClearSight device were almost identical to those obtained by the intra-arterial catheter. Although there was a difference in systolic blood pressures between the two methods, in those patients receiving inotropic support, the difference was within the range of what is considered acceptable in validating blood pressure devices.

Effects of age, sex, race/ethnicity, and allergy status in obesity-related pediatric asthma.

RATIONALE: Obesity in children increases the risk for new asthma. How age, sex, race/ethnicity, and allergy status affect the relationship between obesity and asthma is unclear. This study describes the relationship between high body mass index (BMI) and incident asthma. METHODS: We conducted a retrospective cohort study to compare asthma incidence among normal weight, overweight, and obese 2 to 6, 7 to 11, and 12 to 17 year olds to define the effects of sex, race/ethnicity, and allergy status. Weight status was determined at baseline and asthma incidence was defined as ≥2 asthma encounters and ≥1 asthma prescriptions. We used multivariable Poisson regression to estimate adjusted incident asthma rates and risk ratios. RESULTS: Data from 192 843 2 to 6 year olds, 157 284 7 to 11 year olds, and 157 369 12 to 17 year olds were included. The relative risks (95% confidence interval [CI]) of new asthma among obese children in 2 to 6 year olds, 7 to 11 year olds, and 12 to 17 year olds were 1.25 (1.15, 1.37), 1.49 (1.32, 1.69) and 1.40 (1.21, 1.63), respectively. Among children with underlying allergic rhinitis, obesity did not increase the risk of new asthma. In children without allergic rhinitis, the risk for obesity-related asthma was highest in 7 to 11 year olds (risk ratio = 1.50 95% CI, 1.33, 1.60). Before age 12, females had a higher risk for obesity-related asthma; but after age 12, obese males had a higher asthma risk (interaction P-value < .05). CONCLUSION: Obesity is a major preventable risk factor for pediatric asthma that appears to vary along the pediatric age continuum and depends on sex, race/ethnicity and atopy status.

Promoting Adherence to Influenza Vaccination Recommendations in Pediatric Practice.

OBJECTIVES: In the United States, nonadherence to seasonal influenza vaccination guidelines for children and adolescents is common and results in unnecessary morbidity and mortality. We conducted a quality improvement project to improve vaccination rates and test effects of 2 interventions on vaccination guidelines adherence. METHODS: We conducted a cluster randomized control trial with 11 primary care practices (PRACTICE) that provided care for 11 293 individual children and adolescents in a children's health care system from September 2015 through April 2016. Practice sites (with their clinicians) were randomly assigned to 4 arms (no intervention [Control], computerized clinical decision support system [CCDSS], web-based training [WBT], or CCDSS and WBT [BOTH]). RESULTS: During the study, 55.8% of children and adolescents received influenza vaccination, which improved modestly during the study period compared with the prior influenza season ( P = .009). Actual adherence to recommendations, including dosing, timeliness, and avoidance of missed opportunities, was 46.4% of patients cared for by the PRACTICE. The WBT was most effective in promoting adherence with vaccination recommendations with an estimated average odds ratio = 1.26, P < .05, to compare between preintervention and intervention periods. Over the influenza season, there was a significantly increasing trend in odds ratio in the WBT arm ( P < .05). Encouraging process improvements and providing longitudinal feedback on monthly rate of vaccination sparked some practice changes but limited impact on outcomes. CONCLUSIONS: Web-based training at the start of influenza season with monthly reports of adherence can improve correct dose and timing of influenza vaccination with modest impact on overall vaccination rate.

Factors Associated With Pickup of Pediatric Discharge Prescriptions.

BACKGROUND AND OBJECTIVES: Lack of medication pickup is associated with worse clinical outcomes for select patients. Identification of risk factors for not picking up discharge medications or approaches to this problem have received little study. We sought to identify factors associated with medication pickup rates after hospitalization at a tertiary care children's hospital. METHODS: We conducted a retrospective cohort study of 178 discharges from a children's hospital. We contacted pharmacies that received electronic prescriptions to ascertain whether patients and families picked up medications. The principal outcome was pickup of all medications within 48 hours of discharge. Covariates included demographic data, insurance type, discharge diagnosis, home zip code median income, medication number and/or class, and pharmacy type (on-site versus off-site). We performed a multivariable logistic regression analysis. RESULTS: Overall, 142 of 178 (80%) discharges involved medication pickup. Patient age and sex, diagnosis, discharge day, primary language, and hospitalization length had no statistically significant association with medication pickup. On the multivariable analysis, a higher home zip code median income (P = .045; highest versus lowest groups) had a statistically significant association with increased medication pickup. Private insurance had a statistically significant association with higher pickup rate on the univariable analysis (P = .01) but not on the multivariable analysis, which included zip code income (P = .072). On-site pharmacy use (P = .048) and prescription of an anti-infective (P = .003) had statistically significant associations with higher medication pickup rates. CONCLUSIONS: Certain factors are associated with rates of medication pickup after discharge. Use of an on-site hospital pharmacy may represent a strategy to improve medication pickup rates in children who are hospitalized.

Fish Oil Supplementation in Overweight/Obese Patients with Uncontrolled Asthma. A Randomized Trial.

Rationale: Omega-3 fatty acid (n3PUFA) supplementation has been proposed as a promising antiasthma strategy. The rs59439148 ALOX5 polymorphism affects leukotriene production and possibly inflammatory responses to n3PUFA. Objectives: Assess the effects of n3PUFA supplementation and ALOX5 genotype on asthma control in patients with obesity and uncontrolled asthma. Methods: This multicenter trial among 12- to 25-year-olds with overweight/obesity and uncontrolled asthma randomized subjects in a 3:1 allotment to n3PUFA (4 g/d) or soy oil control for 24 weeks. Asthma Control Questionnaire was the primary outcome; secondary outcomes included blood leukocyte n3PUFA levels, urinary leukotriene-E4, spirometry, and asthma-related events. The number of SP1 tandem repeats in rs59439148 determined ALOX5 genotype status. Simple and multivariable generalized linear models assessed effects on outcomes. Results: Ninety-eight participants were randomized (77 to PUFA, 21 to control), and more than 86% completed all visits. Asthma and demographic characteristics were similar among treatment groups. n3PUFA treatment increased the n3-to-n6 PUFA ratio in circulating granulocytes (P = 0.029) and monocytes (P = 0.004) but did not affect mean Asthma Control Questionnaire change at 6 months (n3PUFA: mean, -0.09; 95% confidence interval [CI], 0.09 to 0.10; vs. control: mean, -0.18; 95% CI, -0.42 to 0.06; P = 0.58). Changes in urinary leukotriene-E4 (P = 0.24), forced expiratory volume in 1 second % predicted (P = 0.88), and exacerbations (relative risk [RR], 0.92; 95% CI, 0.30-2.89) at 6 months were similar in both groups. n3PUFA treatment was associated with reduced asthma-related phone contacts (RR, 0.34; 95% CI, 0.13-0.86; P = 0.02). ALOX5 genotype did not affect n3PUFA treatment responses. Conclusions: We did not find evidence that n3PUFA use improves most asthma-related outcomes and cannot recommend it as a prevention strategy for overweight/obese patients with asthma. Clinical trial registered with www.clinicaltrials.gov (NCT01027143).

Genotype tailored treatment of mild symptomatic acid reflux in children with uncontrolled asthma (GenARA): Rationale and methods.

Asthma causes enormous suffering and cost for children in the US and around the world [1-3]. Co-morbid gastroesophageal reflux disease (GERD) makes asthma management more difficult due to increased symptoms. Proton pump inhibitor (PPI) drugs are effective at improving to GERD symptoms, however they have demonstrated only modest and variable effects on asthma control in the setting of co-morbid GERD. Importantly, PPI metabolism and efficacy depend on CYP2C19 genotype. The Genotype Tailored Treatment of Symptomatic Acid Reflux in Children with Uncontrolled Asthma (GenARA) study is a randomized, double-blind, placebo-controlled trial to determine if genotype-tailored PPI dosing improves asthma symptoms among children with inadequately controlled asthma and GERD symptoms. This study has an innovative design to both assess the efficacy of genotype-tailored PPI dosing and perform pharmacokinetic modeling of the oral PPI Lansoprazole. Children ages 6-17 years old with clinician-diagnosed asthma and mild GERD symptoms will submit a saliva sample for CYP2C19 genotyping. Participants will undergo a two-step randomization to: (1) genotype-tailored versus conventional dosing of open-label oral lansoprazole for pharmacokinetic modeling, and (2) genotype-tailored lansoprazole daily versus placebo for 24 weeks to determine the effect of genotype-tailored PPI dosing on asthma control. Measures of asthma control, spirometry, and nasal washes during acute illnesses will be collected at 8-week intervals throughout the study. GenARA will better define the effects of CYP2C19 genotype on the dose response of lansoprazole in children and adolescents and assess if a novel dosing regimen improves GERD and asthma control.

Being Overweight or Obese and the Development of Asthma.

OBJECTIVES: Adult obesity is linked to asthma cases and is estimated to lead to 250 000 new cases yearly. Similar incidence and attributable risk (AR) estimates have not been developed for children. We sought to describe the relationship between overweight and obesity and incident asthma in childhood and quantify AR statistics in the United States for overweight and obesity on pediatric asthma. METHODS: The PEDSnet clinical data research network was used to conduct a retrospective cohort study (January 2009-December 2015) to compare asthma incidence among overweight and/or obese versus healthy weight 2- to 17-year-old children. Asthma incidence was defined as ≥2 encounters with a diagnosis of asthma and ≥1 asthma controller prescription. Stricter diagnostic criteria involved confirmation by spirometry. We used multivariable Poisson regression analyses to estimate incident asthma rates and risk ratios and accepted formulas for ARs. RESULTS: Data from 507 496 children and 19 581 972 encounters were included. The mean participant observation period was 4 years. The adjusted risk for incident asthma was increased among children who were overweight (relative risk [RR]: 1.17; 95% confidence interval [CI]: 1.10-1.25) and obese (RR: 1.26; 95% CI: 1.18-1.34). The adjusted risk for spirometry-confirmed asthma was increased among children with obesity (RR: 1.29; 95% CI: 1.16-1.42). An estimated 23% to 27% of new asthma cases in children with obesity is directly attributable to obesity. In the absence of overweight and obesity, 10% of all cases of asthma would be avoided. CONCLUSIONS: Obesity is a major preventable risk factor for pediatric asthma.

Roux-en-Y gastric bypass surgery in youth with severe obesity: 1-year longitudinal changes in spexin.

BACKGROUND: Spexin is a novel peptide predominantly produced in human white adipose tissue and has recently been implicated as a potential signal in the regulation of body weight, energy homeostasis, and satiety. The effect of bariatric surgery on spexin is unknown. OBJECTIVES: To study the effect of Roux-en-Y gastric bypass (RYGB) surgery on endogenous spexin concentration and various risk factors of type 2 diabetes and cardiovascular disease in youth with severe obesity. SETTING: University hospital, United States METHODS: Spexin, body mass index (BMI), insulin, glucose, total and high molecular weight adiponectin, leptin, and high sensitivity C- reactive protein were measured longitudinally (baseline, 6 mo, and 12 mo) after RYGB surgery in girls with severe obesity (n = 12; age = 16.7 ± 1.5 years; BMI = 51.6 ± 2.9 kg/m2). RESULTS: Serum spexin concentration increased (P = .01) at 6 months after surgery and stabilized afterward. Spexin level correlated negatively with homeostatic model assessment insulin resistance, HOMA-IR (Spearman correlation r = -.796, P < .001) and positively with high molecular weight adiponectin (Spearman correlation r = .691, P = .011). The change in spexin concentration, from baseline to 6 months after surgery, was inversely correlated with the corresponding change in BMI (Spearman correlation r = -.573, P = .051). Furthermore, the 6-month changes in spexin and HOMA-IR were inversely correlated (slope [standard error, SE] = -.0084 (.0019), P = .001)], even after adjusting for the change in BMI. CONCLUSIONS: The enhancement of circulating spexin concentration in response to RYGB and correlations with beneficial postoperative changes in various adipokines in youth are novel findings that require further validation.

Cryptorchidism in Boys With Cerebral Palsy Is Associated With the Severity of Disease and With Co-Occurrence of Other Congenital Anomalies.

BACKGROUND: Cryptorchidism is reported in 40-50% of small case series of cerebral palsy (CP) and attributed to hypothalamic-pituitary-gonadal axis abnormalities, intellectual disability (ID), or cremaster spasticity. We collected demographic and clinical data to define the frequency of cryptorchidism and clinical comorbidities in a large CP population. METHODS: Electronic health record data were collected for all male patients ≥7 years of age seen in a large, multidisciplinary CP clinic between 2000 and 2016. Variables including age, testicular position, surgical findings, CP severity, birth history, and comorbidities were tested for association using univariable and stepwise backward logistic regression analyses. RESULTS: Of 839 established patients, testis position was scrotal in 553, undescended in 185 (24%), retractile in 38 (5%), and undocumented in 63 cases. Cryptorchidism were diagnosed at a mean age of 5.8 years, with 20% documented as acquired, and testes were most commonly in the superficial inguinal pouch (41%) and associated with an inguinal hernia (56%). Severity was bilateral in 114/166 (69%) undescended and 24/36 (66%) retractile cases, respectively. Mean birth weight and the frequency of prematurity (55, 58, and 54%) and multiple birth (14, 13, and 9%) were not significantly different among the three groups. We observed a strong ordinal trend in the frequency of comorbidities, including quadriplegia, syndromic features/known genetic disease, intrauterine growth restriction (IUGR), death, brain malformations, seizures, gastrostomy, absent continence, ID and hearing, speech or visual impairment, with the retractile group holding the intermediate position for the majority. The stepwise multivariable analysis showed independent positive associations of cryptorchidism with quadriplegia, syndromic features/known genetic disease, hearing loss, and absent continence, and inverse associations with gestational age and multiple birth. CONCLUSION: These data suggest that cryptorchidism is less common than previously reported in CP cases, but most strongly associated with quadriplegia. Delayed diagnosis may be related to an acquired condition or to the multiple additional functional deficits that occur in this population. Our data suggest that UDT and CP may both be components of malformation syndromes occurring in singleton births whose clinical features are more likely to include earlier delivery, IUGR, hearing loss, and/or global spasticity.

Vitamin D Status and Cardiovascular Risk in Obesity: Effect of Physical Activity in Nonvitamin D Supplemented Adolescents.

BACKGROUND: The relationship among inadequate vitamin D status, obesity, and cardiometabolic risk and the potential impact of physical activity-based interventions on vitamin D status are poorly characterized in children. This study aimed to address these issues. METHODS: We studied a total of 21 adolescents (15 obese and 6 normal weight; age: 14-18 years; Tanner stage>IV). Adolescents with obesity (n = 15) underwent a randomized controlled (8 in the intervention group and 7 in the control group) 3-month physical activity-based lifestyle intervention. 25-Hydroxy vitamin D [25(OH)D] by mass spectrometry, adiponectin, leptin, high-sensitivity C-reactive protein (CRP), insulin, and glucose were measured and body composition was assessed by dual-energy x-ray absorptiometry (DXA). Analysis of covariance and mixed-effects model were used to compare mean change in 25(OH)D between intervention and nonintervention groups. Bootstrap method was used to validate the estimates and principle component analysis reduced the variables in the data for adjustment. RESULTS: 25(OH)D was lower (P < 0.001) in the obese versus lean adolescents. Homeostasis model assessment-insulin resistance, CRP, fat mass (FM), and body mass index z-score were negatively correlated with baseline 25(OH)D, while adiponectin showed a positive correlation. After adjustment for baseline biomarkers of cardiometabolic risk, the concentration of 25(OH)D increased in the obese intervention group (P = 0.06), but not in the nonintervention group. Fat-free mass increased and FM decreased (P < 0.05 for both) in the intervention group. The magnitudes of increase in 25(OH)D and decrease in FM directly correlated (P < 0.05). CONCLUSIONS: The increase in circulating 25(OH)D concentration by physical activity-based lifestyle-only intervention in adolescents with obesity, who did not receive vitamin D supplementation, suggests a putative independent role of physical activity-based interventions in the regulation of vitamin D status and potentially in the mitigation of risk factors of cardiovascular disease.

Survival differences in childhood and young adult acute myeloid leukemia: A cross-national study using US and England data.

BACKGROUND: Acute myeloid leukemia (AML) is a serious disease with complex etiology and marked variation in survival. Known prognostic factors include AML subtypes, age at diagnosis and sex. However, survival outcomes may vary across healthcare systems. In this study, we evaluated the survival patterns in individuals diagnosed with AML at ages 0-24 years in the US and England between prognostic features and across countries. METHODS: We obtained data on 4387 and 2194 subjects from the US Surveillance Epidemiology and End Result registries and UK National Cancer Data Repository. Subjects were diagnosed and followed in 1995-2014. Kaplan-Meier curve and stratified Cox proportional hazards regression were used in the analysis. RESULTS: Overall risk of mortality was 23% lower in English patients compared to that in the US patients (adjusted hazard ratio (aHR), 95% confidence Interval (CI): 0.77, 0.71-0.84). Survival difference of similar extent was observed in subgroups of sex and age at diagnosis. However, mortality risks between two countries varied substantially across AML subtypes, especially in AML inv(16) (1.81, 0.61-5.34), AML with minimal differentiation (0.54, 0.25-1.17), AML without maturation (0.38, 0.20-0.74) and AML with maturation (0.52, 0.31-0.86). CONCLUSIONS: Similar to the population trend, mortality risk across sex, age at diagnosis, and most AML subtypes was lower in England. Survival outcome for AML with and without maturation in England was better than the population trend, while that for AML inv(16) was worse. Our findings suggest that future etiologic and policy research may uncover the underlying mechanisms and contribute to closing these morality gaps.

Lung Rest During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure-Practice Variations and Outcomes.

OBJECTIVE: Describe practice variations in ventilator strategies used for lung rest during extracorporeal membrane oxygenation for respiratory failure in neonates, and assess the potential impact of various lung rest strategies on the duration of extracorporeal membrane oxygenation and the duration of mechanical ventilation after decannulation. DATA SOURCES: Retrospective cohort analysis from the Extracorporeal Life Support Organization registry database during the years 2008-2013. STUDY SELECTION: All extracorporeal membrane oxygenation runs for infants less than or equal to 30 days of life for pulmonary reasons were included. DATA EXTRACTION: Ventilator type and ventilator settings used for lung rest at 24 hours after extracorporeal membrane oxygenation initiation were obtained. DATA SYNTHESIS: A total of 3,040 cases met inclusion criteria. Conventional mechanical ventilation was used for lung rest in 88% of cases and high frequency ventilation was used in 12%. In the conventional mechanical ventilation group, 32% used positive end-expiratory pressure strategy of 4-6 cm H2O (low), 22% used 7-9 cm H2O (mid), and 43% used 10-12 cm H2O (high). High frequency ventilation was associated with an increased mean (SEM) hours of extracorporeal membrane oxygenation (150.2 [0.05] vs 125 [0.02]; p < 0.001) and an increased mean (SEM) hours of mechanical ventilation after decannulation (135 [0.09] vs 100.2 [0.03]; p = 0.002), compared with conventional mechanical ventilation among survivors. Within the conventional mechanical ventilation group, use of higher positive end-expiratory pressure was associated with a decreased mean (SEM) hours of extracorporeal membrane oxygenation (high vs low: 136 [1.06] vs 156 [1.06], p = 0.001; mid vs low: 141 [1.06] vs 156 [1.06]; p = 0.04) but increased duration of mechanical ventilation after decannulation in the high positive end-expiratory pressure group compared with low positive end-expiratory pressure (p = 0.04) among survivors. CONCLUSIONS: Wide practice variation exists with regard to ventilator settings used for lung rest during neonatal respiratory extracorporeal membrane oxygenation. Use of high frequency ventilation when compared with conventional mechanical ventilation and use of low positive end-expiratory pressure strategy when compared with mid positive end-expiratory pressure and high positive end-expiratory pressure strategy is associated with longer duration of extracorporeal membrane oxygenation. Further research to provide evidence to drive optimization of pulmonary management during neonatal respiratory extracorporeal membrane oxygenation is warranted.

Socioeconomic status (SES) and childhood acute myeloid leukemia (AML) mortality risk: Analysis of SEER data.

Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3651 pediatric AML patients, aged 0-19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility; F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02-1.12) and 1.05(1.00-1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1 (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3 (high economic/educational disadvantage, high-mobility) and Cluster 6 (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI)=1.19(1.0-1.4) and 1.23 (1.1-1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features.