Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study.

OBJECTIVES: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes. DESIGN: This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing. SETTING: Eighteen PICUs and pediatric cardiac ICUs in the United States. PATIENTS: Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded. INTERVENTIONS: The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01). CONCLUSIONS: In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration.

Survival With Favorable Neurologic Outcome and Quality of Cardiopulmonary Resuscitation Following In-Hospital Cardiac Arrest in Children With Cardiac Disease Compared With Noncardiac Disease.

OBJECTIVES: To assess associations between outcome and cardiopulmonary resuscitation (CPR) quality for in-hospital cardiac arrest (IHCA) in children with medical cardiac, surgical cardiac, or noncardiac disease. DESIGN: Secondary analysis of a multicenter cluster randomized trial, the ICU-RESUScitation Project (NCT02837497, 2016-2021). SETTING: Eighteen PICUs. PATIENTS: Children less than or equal to 18 years old and greater than or equal to 37 weeks postconceptual age receiving chest compressions (CC) of any duration during the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,100 children with IHCA, there were 273 medical cardiac (25%), 383 surgical cardiac (35%), and 444 noncardiac (40%) cases. Favorable neurologic outcome was defined as no more than moderate disability or no worsening from baseline Pediatric Cerebral Performance Category at discharge. The medical cardiac group had lower odds of survival with favorable neurologic outcomes compared with the noncardiac group (48% vs 55%; adjusted odds ratio [aOR] [95% CI], aOR 0.59 [95% CI, 0.39-0.87], p = 0.008) and surgical cardiac group (48% vs 58%; aOR 0.64 [95% CI, 0.45-0.9], p = 0.01). We failed to identify a difference in favorable outcomes between surgical cardiac and noncardiac groups. We also failed to identify differences in CC rate, CC fraction, ventilation rate, intra-arrest average target diastolic or systolic blood pressure between medical cardiac versus noncardiac, and surgical cardiac versus noncardiac groups. The surgical cardiac group had lower odds of achieving target CC depth compared to the noncardiac group (OR 0.15 [95% CI, 0.02-0.52], p = 0.001). We failed to identify a difference in the percentage of patients achieving target CC depth when comparing medical cardiac versus noncardiac groups. CONCLUSIONS: In pediatric IHCA, medical cardiac patients had lower odds of survival with favorable neurologic outcomes compared with noncardiac and surgical cardiac patients. We failed to find differences in CPR quality between medical cardiac and noncardiac patients, but there were lower odds of achieving target CC depth in surgical cardiac compared to noncardiac patients.

Early Cardiac Arrest Hemodynamics, End-Tidal C o2 , and Outcome in Pediatric Extracorporeal Cardiopulmonary Resuscitation: Secondary Analysis of the ICU-RESUScitation Project Dataset (2016-2021).

OBJECTIVES: Cannulation for extracorporeal membrane oxygenation during active extracorporeal cardiopulmonary resuscitation (ECPR) is a method to rescue patients refractory to standard resuscitation. We hypothesized that early arrest hemodynamics and end-tidal C o2 (ET co2 ) are associated with survival to hospital discharge with favorable neurologic outcome in pediatric ECPR patients. DESIGN: Preplanned, secondary analysis of pediatric Utstein, hemodynamic, and ventilatory data in ECPR patients collected during the 2016-2021 Improving Outcomes from Pediatric Cardiac Arrest study; the ICU-RESUScitation Project (ICU-RESUS; NCT02837497). SETTING: Eighteen ICUs participated in ICU-RESUS. PATIENTS: There were 97 ECPR patients with hemodynamic waveforms during cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 71 of 97 patients (73%) were younger than 1 year old, 82 of 97 (85%) had congenital heart disease, and 62 of 97 (64%) were postoperative cardiac surgical patients. Forty of 97 patients (41%) survived with favorable neurologic outcome. We failed to find differences in diastolic or systolic blood pressure, proportion achieving age-based target diastolic or systolic blood pressure, or chest compression rate during the initial 10 minutes of CPR between patients who survived with favorable neurologic outcome and those who did not. Thirty-five patients had ET co2 data; of 17 survivors with favorable neurologic outcome, four of 17 (24%) had an average ET co2 less than 10 mm Hg and two (12%) had a maximum ET co2 less than 10 mm Hg during the initial 10 minutes of resuscitation. CONCLUSIONS: We did not identify an association between early hemodynamics achieved by high-quality CPR and survival to hospital discharge with favorable neurologic outcome after pediatric ECPR. Candidates for ECPR with ET co2 less than 10 mm Hg may survive with favorable neurologic outcome.

Diastolic Blood Pressure Threshold During Pediatric Cardiopulmonary Resuscitation and Survival Outcomes: A Multicenter Validation Study.

OBJECTIVES: Arterial diastolic blood pressure (DBP) greater than 25 mm Hg in infants and greater than 30 mm Hg in children greater than 1 year old during cardiopulmonary resuscitation (CPR) was associated with survival to hospital discharge in one prospective study. We sought to validate these potential hemodynamic targets in a larger multicenter cohort. DESIGN: Prospective observational study. SETTING: Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020. PATIENTS: Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive BP waveform data and Utstein-style CPR data were collected, including prearrest patient characteristics, intra-arrest interventions, and outcomes. Primary outcome was survival to hospital discharge, and secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Multivariable Poisson regression models with robust error estimates evaluated the association of DBP greater than 25 mm Hg in infants and greater than 30 mm Hg in older children with these outcomes. Among 1,129 children with inhospital cardiac arrests, 413 had evaluable DBP data. Overall, 85.5% of the patients attained thresholds of mean DBP greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in older children. Initial return of circulation occurred in 91.5% and 25% by placement on extracorporeal membrane oxygenator. Survival to hospital discharge occurred in 58.6%, and survival with favorable neurologic outcome in 55.4% (i.e. 94.6% of survivors had favorable neurologic outcomes). Mean DBP greater than 25 mm Hg for infants and greater than 30 mm Hg for older children was significantly associated with survival to discharge (adjusted relative risk [aRR], 1.32; 1.01-1.74; p = 0.03) and ROSC (aRR, 1.49; 1.12-1.97; p = 0.002) but did not reach significance for survival to hospital discharge with favorable neurologic outcome (aRR, 1.30; 0.98-1.72; p = 0.051). CONCLUSIONS: These validation data demonstrate that achieving mean DBP during CPR greater than 25 mm Hg for infants and greater than 30 mm Hg for older children is associated with higher rates of survival to hospital discharge, providing potential targets for DBP during CPR.

Identification of post-cardiac arrest blood pressure thresholds associated with outcomes in children: an ICU-Resuscitation study.

INTRODUCTION: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that post-arrest systolic and diastolic BP thresholds would be higher than the currently recommended post-cardiopulmonary resuscitation BP targets and would be associated with higher rates of survival to hospital discharge. METHODS: We performed a secondary analysis of prospectively collected BP data from the first 24 h following return of circulation from index IHCA events enrolled in the ICU-RESUScitation trial (NCT02837497). The lowest documented systolic BP (SBP) and diastolic BP (DBP) were percentile-adjusted for age, height and sex. Receiver operator characteristic curves and cubic spline analyses controlling for illness category and presence of pre-arrest hypotension were generated exploring the association of lowest post-arrest SBP and DBP with survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). Optimal cutoffs for post-arrest BP thresholds were based on analysis of receiver operator characteristic curves and spline curves. Logistic regression models accounting for illness category and pre-arrest hypotension examined the associations of these thresholds with outcomes. RESULTS: Among 693 index events with 0-6 h post-arrest BP data, identified thresholds were: SBP > 10th percentile and DBP > 50th percentile for age, sex and height. Fifty-one percent (n = 352) of subjects had lowest SBP above threshold and 50% (n = 346) had lowest DBP above threshold. SBP and DBP above thresholds were each associated with survival to hospital discharge (SBP: aRR 1.21 [95% CI 1.10, 1.33]; DBP: aRR 1.23 [1.12, 1.34]) and survival to hospital discharge with favorable neurologic outcome (SBP: aRR 1.22 [1.10, 1.35]; DBP: aRR 1.27 [1.15, 1.40]) (all p < 0.001). CONCLUSIONS: Following pediatric IHCA, subjects had higher rates of survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome when BP targets above a threshold of SBP > 10th percentile for age and DBP > 50th percentile for age during the first 6 h post-arrest.

The Temporal Association of the COVID-19 Pandemic and Pediatric Cardiopulmonary Resuscitation Quality and Outcomes.

OBJECTIVES: The COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes. DESIGN: Multicenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021). SETTING: Data source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial. PATIENTS: Children (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic ( p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0-3] vs 0 [0-2]; p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35-2.04] FSS points; p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03-3.46]; p = 0.04). CONCLUSIONS: Using the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors.

Management of Hypertrophic Cardiomyopathy in a Newborn with Dextro-Transposition of the Great Arteries.

Impaired maternal glucose metabolism during pregnancy can have significant effects on the cardiovascular system of the developing fetus. Early in pregnancy the teratogenic effects may lead to structural heart defects, while later in gestation a form of hypertrophic cardiomyopathy can develop due to overgrowth driven by fetal hyperinsulinism. We describe an infant with the uncommon combination of both dextro-transposition of the great arteries and hypertrophic cardiomyopathy. We emphasize the importance of a longitudinal multi-disciplinary approach, from fetal diagnosis to post-operative management, that allowed for an excellent outcome in this rare combination of severe cardiac malformations.

Effect of Physiologic Point-of-Care Cardiopulmonary Resuscitation Training on Survival With Favorable Neurologic Outcome in Cardiac Arrest in Pediatric ICUs: A Randomized Clinical Trial.

Importance: Approximately 40% of children who experience an in-hospital cardiac arrest survive to hospital discharge. Achieving threshold intra-arrest diastolic blood pressure (BP) targets during cardiopulmonary resuscitation (CPR) and systolic BP targets after the return of circulation may be associated with improved outcomes. Objective: To evaluate the effectiveness of a bundled intervention comprising physiologically focused CPR training at the point of care and structured clinical event debriefings. Design, Setting, and Participants: A parallel, hybrid stepped-wedge, cluster randomized trial (Improving Outcomes from Pediatric Cardiac Arrest-the ICU-Resuscitation Project [ICU-RESUS]) involving 18 pediatric intensive care units (ICUs) from 10 clinical sites in the US. In this hybrid trial, 2 clinical sites were randomized to remain in the intervention group and 2 in the control group for the duration of the study, and 6 were randomized to transition from the control condition to the intervention in a stepped-wedge fashion. The index (first) CPR events of 1129 pediatric ICU patients were included between October 1, 2016, and March 31, 2021, and were followed up to hospital discharge (final follow-up was April 30, 2021). Intervention: During the intervention period (n = 526 patients), a 2-part ICU resuscitation quality improvement bundle was implemented, consisting of CPR training at the point of care on a manikin (48 trainings/unit per month) and structured physiologically focused debriefings of cardiac arrest events (1 debriefing/unit per month). The control period (n = 548 patients) consisted of usual pediatric ICU management of cardiac arrest. Main Outcomes and Measures: The primary outcome was survival to hospital discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1 to 3 or no change from baseline (score range, 1 [normal] to 6 [brain death or death]). The secondary outcome was survival to hospital discharge. Results: Among 1389 cardiac arrests experienced by 1276 patients, 1129 index CPR events (median patient age, 0.6 [IQR, 0.2-3.8] years; 499 girls [44%]) were included and 1074 were analyzed in the primary analysis. There was no significant difference in the primary outcome of survival to hospital discharge with favorable neurologic outcomes in the intervention group (53.8%) vs control (52.4%); risk difference (RD), 3.2% (95% CI, -4.6% to 11.4%); adjusted OR, 1.08 (95% CI, 0.76 to 1.53). There was also no significant difference in survival to hospital discharge in the intervention group (58.0%) vs control group (56.8%); RD, 1.6% (95% CI, -6.2% to 9.7%); adjusted OR, 1.03 (95% CI, 0.73 to 1.47). Conclusions and Relevance: In this randomized clinical trial conducted in 18 pediatric intensive care units, a bundled intervention of cardiopulmonary resuscitation training at the point of care and physiologically focused structured debriefing, compared with usual care, did not significantly improve patient survival to hospital discharge with favorable neurologic outcome among pediatric patients who experienced cardiac arrest in the ICU. Trial Registration: ClinicalTrials.gov Identifier: NCT02837497.

Survival and Cardiopulmonary Resuscitation Hemodynamics Following Cardiac Arrest in Children With Surgical Compared to Medical Heart Disease.

OBJECTIVES: To assess the association of diastolic blood pressure cutoffs (≥ 25 mm Hg in infants and ≥ 30 mm Hg in children) during cardiopulmonary resuscitation with return of spontaneous circulation and survival in surgical cardiac versus medical cardiac patients. Secondarily, we assessed whether these diastolic blood pressure targets were feasible to achieve and associated with outcome in physiology unique to congenital heart disease (single ventricle infants, open chest), and influenced outcomes when extracorporeal cardiopulmonary resuscitation was deployed. DESIGN: Multicenter, prospective, observational cohort analysis. SETTING: Tertiary PICU and cardiac ICUs within the Collaborative Pediatric Critical Care Research Network. PATIENTS: Patients with invasive arterial catheters during cardiopulmonary resuscitation and surgical cardiac or medical cardiac illness category. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hemodynamic waveforms during cardiopulmonary resuscitation were analyzed on 113 patients, 88 surgical cardiac and 25 medical cardiac. A similar percent of surgical cardiac (51/88; 58%) and medical cardiac (17/25; 68%) patients reached the diastolic blood pressure targets (p = 0.488). Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients (p = 0.018), but not medical cardiac patients (p = 0.359). Fifty-three percent (16/30) of patients with single ventricles attained the target diastolic blood pressure. In patients with an open chest at the start of chest compressions, 11 of 20 (55%) attained the target diastolic blood pressure. In the 33 extracorporeal cardiopulmonary resuscitation patients, 16 patients (48%) met the diastolic blood pressure target with no difference between survivors and nonsurvivors (p = 0.296). CONCLUSIONS: During resuscitation in an ICU, with invasive monitoring in place, diastolic blood pressure targets of greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in children can be achieved in patients with both surgical and medical heart disease. Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients, but not medical cardiac patients. Diastolic blood pressure targets were feasible to achieve in 1) single ventricle patients, 2) open chest physiology, and 3) extracorporeal cardiopulmonary resuscitation patients.

Interstage Survival for Patients with Hypoplastic Left Heart Syndrome After ECMO.

There is a reported 5-20 % incidence of extracorporeal membrane oxygenation (ECMO) following stage I palliation for hypoplastic left heart syndrome (HLHS). This study compares the interstage mortality of HLHS patients supported with ECMO (HLHS-ECMO) to those who were not supported with ECMO (HLHS-nECMO) using the National Pediatric Cardiology Quality Improvement Initiative database. Patients with HLHS who survived to hospital discharge after stage I palliation were analyzed. HLHS-ECMO patients were compared to HLHS-non-ECMO patients with respect to demographics, surgical variables, and interstage survival. A total of 931 patients were identified in the database. Sixty-six (7.1 %) patients were supported with ECMO during their stage I palliation admission. There were no statistically significant differences between the groups with respect to demographics or anatomic subtype. HLHS-ECMO patients were more likely to have a preoperative risk factor identified (62 vs. 48 %, p = 0.03) or require ECMO prior to stage I palliation (3 vs. 0.5 %, p = 0.03). HLHS-ECMO patients had a significantly higher incidence of death or transplant versus the HLHS-nECMO group (18 vs. 9 %, p = 0.03). Despite survival to discharge, patients with HLHS requiring ECMO after their palliation continue to have an increased risk of death/cardiac transplant versus patients that do not require ECMO. ECMO use is likely a marker for a high-risk patient group. These patients may benefit from closer follow-up during the interstage period.

Antioxidant and neuroprotector effect of Lepidium meyenii (maca) methanol leaf extract against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells.

Reactive oxygen species (ROS) are normally produced during cell metabolism, there is strong evidence to suggest that ROS produced in excess impair the cell and may be etiologically related to various neurodegenerative diseases. This study was undertaken to examine the effects of Lepidium meyenii (MACA) methanol leaf extract on neurotoxicity in PC12 cell exposed to 6-hydroxydopamine (6-OHDA). Fresh samples of "maca" leaves were processed in order to obtain foliar extracts and to evaluate the neurobiological activity on PC12 cells, subjected to the cytotoxic effect of 6-OHDA through the determination of the capacity antioxidant, cell viability and cytotoxicity assays on PC12 cells. The results of the tests of antioxidant activity, showed maximum values of 2262.37 and 1305.36 expressed in Trolox equivalents (TEAC), for the methanolic and aqueous fractions respectively. Cell viability assays at a dose of 10 µg extract showed an increase of 31% and 60% at 6 and 12 h of pretreatment, respectively. Cytotoxicity assays at the same dose and exposure time showed a 31.4% and 47.8% reduction in lactate dehydrogenase (LDH) activity and an increase in superoxide dismutase (SOD) activity. The results allow us to affirm that the methanolic foliar extract of "maca" presents in vitro neurobiological activity of antioxidant protection, increase in cell viability and reduction of cytotoxicity against oxidative stress generated by 6-OHDA. In conclusion, the present study shows a protective role for Lepidium meyenii leaf extract on 6-OHDA-induced toxicity by an antioxidant effect.

Arrhythmias After Stage I Hybrid Palliation in Single-Ventricle Patients.

The hybrid procedure is an alternative palliative strategy for patients with single-ventricle physiology. No data exist documenting the incidence of arrhythmias after the hybrid procedure. Goal of this study was to determine the incidence and type of arrhythmias in patients undergoing the hybrid procedure. A retrospective chart review was performed including all patients undergoing the hybrid procedure between January of 2010 through December of 2013. Sixty-five patients underwent the hybrid procedure during this time period (43 HLHS, 22 other). Average gestational age at admission was 37.7 weeks. Average age at time of procedure was 7.6 days. Five patients had documented arrhythmias (7.7 %). Four were supraventricular tachycardias, and 1 was a sinus bradycardia. One patient with arrhythmia died during hospitalization, and another patient with arrhythmia died during the interstage period. Hybrid palliation for patients with single-ventricle physiology has a low incidence of arrhythmias. In this cohort of patients, arrhythmias did not contribute to mortality. There was a trend toward association between arrhythmias and longer total length of hospital stay.

Arrhythmias Following Comprehensive Stage II Surgical Palliation in Single Ventricle Patients.

Post-operative arrhythmias are common in pediatric patients following cardiac surgery. Following hybrid palliation in single ventricle patients, a comprehensive stage II palliation is performed. The incidence of arrhythmias in patients following comprehensive stage II palliation is unknown. The purpose of this study is to determine the incidence of arrhythmias following comprehensive stage II palliation. A single-center retrospective chart review was performed on all single ventricle patients undergoing a comprehensive stage II palliation from January 2010 to May 2014. Pre-operative, operative, and post-operative data were collected. A clinically significant arrhythmia was defined as an arrhythmia which led to cardiopulmonary resuscitation or required treatment with either pacing or antiarrhythmic medication. Statistical analysis was performed with Wilcoxon rank-sum test and Fisher's exact test with p < 0.05 significant. Forty-eight single ventricle patients were reviewed (32 hypoplastic left heart syndrome, 16 other single ventricle variants). Age at surgery was 185 ± 56 days. Cardiopulmonary bypass time was 259 ± 45 min. Average vasoactive-inotropic score was 5.97 ± 7.58. Six patients (12.5 %) had clinically significant arrhythmias: four sinus bradycardia, one 2:1 atrioventricular block, and one slow junctional rhythm. No tachyarrhythmias were documented for this patient population. Presence of arrhythmia was associated with elevated lactate (p = 0.04) and cardiac arrest (p = 0.002). Following comprehensive stage II palliation, single ventricle patients are at low risk for development of tachyarrhythmias. The most frequent arrhythmia seen in these patients was sinus bradycardia associated with respiratory compromise.

Ultrasound assessment of mesenteric blood flow in neonates with hypoplastic left heart before and after hybrid palliation.

BACKGROUND: Altered mesenteric perfusion may be a contributor to the development of necrotising enterocolitis in patients with hypoplastic left heart syndrome. The goal of this study was to document mesenteric flow patterns in patients with hypoplastic left heart syndrome pre- and post-hybrid procedure. METHODS: A prospective study on all patients with hypoplatic left heart syndrome undergoing the hybrid procedure was conducted. Doppler ultrasound analysis of the coeliac and superior mesenteric artery was performed. RESULTS: A total of 13 patients were evaluated. There was a significant difference in the coeliac artery effective velocity-time intergral pre- and post-hybrid procedure (8.69±3.84 versus 12.51±4.95 cm, respectively). There were significant differences in the superior mesenteric artery antegrade velocity-time integral pre- and post-hybrid procedure (6.86±2.45 versus 10.52±2.64 cm, respectively) and superior mesenteric artery effective velocity-time integral pre- and post-hybrid procedure (6.22±2.68 versus 9.73±2.73 cm, respectively). There were no significant differences between the coeliac and superior mesenteric artery Doppler indices in the pre-hybrid procedure; there were, however, significant differences in the post-hybrid procedure between coeliac and superior mesenteric artery antegrade velocity-time integral (13.8 2±5.60 versus 10.52±2.64 cm, respectively) and effective velocity-time integral (13.04±4.71 versus 9.73±2.73 cm, respectively). CONCLUSION: Doppler mesenteric indices of perfusion improve in patients with hypoplastic left heart syndrome after the hybrid procedure; however, there appears to be preferential flow to the coeliac artery versus the superior mesenteric artery in these patients post-procedure.

Chest compressions for pediatric organized rhythms: A hemodynamic and outcomes analysis.

AIM: Pediatric cardiopulmonary resuscitation (CPR) guidelines recommend starting CPR for heart rates (HRs) less than 60 beats per minute (bpm) with poor perfusion. Objectives were to (1) compare HRs and arterial blood pressures (BPs) prior to CPR among patients with clinician-reported bradycardia with poor perfusion ("BRADY") vs. pulseless electrical activity (PEA); and (2) determine if hemodynamics prior to CPR are associated with outcomes. METHODS AND RESULTS: Prospective observational cohort study performed as a secondary analysis of the ICU-RESUScitation trial (NCT028374497). Comparisons occurred (1) during the 15 seconds "immediately" prior to CPR and (2) over the two minutes prior to CPR, stratified by age (≤1 year, >1 year). Poisson regression models assessed associations between hemodynamics and outcomes. Primary outcome was return of spontaneous circulation (ROSC). Pre-CPR HRs were lower in BRADY vs. PEA (≤1 year: 63.8 [46.5, 87.0] min-1 vs. 120 [93.2, 150.0], p < 0.001; >1 year: 67.4 [54.5, 87.0] min-1 vs. 100 [66.7, 120], p < 0.014). Pre-CPR pulse pressure was higher among BRADY vs. PEA (≤1 year (12.9 [9.0, 28.5] mmHg vs. 10.4 [6.1, 13.4] mmHg, p > 0.001). Pre-CPR pulse pressure ≥ 20 mmHg was associated with higher rates of ROSC among PEA (aRR 1.58 [CI95 1.07, 2.35], p = 0.022) and survival to hospital discharge with favorable neurologic outcome in both groups (BRADY: aRR 1.28 [CI95 1.01, 1.62], p = 0.040; PEA: aRR 1.94 [CI95 1.19, 3.16], p = 0.008). Pre-CPR HR ≥ 60 bpm was not associated with outcomes. CONCLUSIONS: Pulse pressure and HR are used clinically to differentiate BRADY from PEA. A pre-CPR pulse pressure >20 mmHg was associated with improved patient outcomes.

Snf1-related kinase inhibits colon cancer cell proliferation through calcyclin-binding protein-dependent reduction of ß-catenin.

Sucrose nonfermenting 1 (Snf1)-related kinase (SNRK) is a serine/threonine kinase with sequence similarity to AMP-activated protein kinase (AMPK); however, its function is not well characterized. We conducted a gene array to determine which genes are regulated by SNRK. The array demonstrated that SNRK overexpression increased the levels of genes involved in cell proliferation, including calcyclin-binding protein (CacyBP), a member of the ubiquitin ligase complex that targets nonphosphorylated ß-catenin for degradation. We confirmed that SNRK increased CacyBP mRNA and protein, and decreased ß-catenin protein in HCT116 and RKO colon cancer cells. Furthermore, SNRK inhibited colon cancer cell proliferation, and CacyBP down-regulation reversed the SNRK-mediated decrease in proliferation and ß-catenin. SNRK overexpression also decreased ß-catenin nuclear localization and target gene transcription, and ß-catenin down-regulation reversed the effects of SNRK knockdown on proliferation. SNRK transcript levels were reduced in human colon tumors compared to normal tissue by 35.82%, and stable knockdown of SNRK increased colon cancer cell tumorigenicity. Our results demonstrate that SNRK is down-regulated in colon cancer and inhibits colon cancer cell proliferation through CacyBP up-regulation and ß-catenin degradation, resulting in reduced proliferation signaling. These findings reveal a novel function for SNRK in the regulation of colon cancer cell proliferation and ß-catenin signaling.

Outcomes and characteristics of cardiac arrest in children with pulmonary hypertension: A secondary analysis of the ICU-RESUS clinical trial.

BACKGROUND: Previous studies have identified pulmonary hypertension (PH) as a relatively common diagnosis in children with in-hospital cardiac arrest (IHCA), and preclinical laboratory studies have found poor outcomes and low systemic blood pressures during CPR for PH-associated cardiac arrest. The objective of this study was to determine the prevalence of PH among children with IHCA and the association between PH diagnosis and intra-arrest physiology and survival outcomes. METHODS: This was a prospectively designed secondary analysis of patients enrolled in the ICU-RESUS clinical trial (NCT02837497). The primary exposure was a pre-arrest diagnosis of PH. The primary survival outcome was survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline). The primary physiologic outcome was event-level average diastolic blood pressure (DBP) during CPR. RESULTS: Of 1276 patients with IHCAs during the study period, 1129 index IHCAs were enrolled; 184 (16.3%) had PH and 101/184 (54.9%) were receiving inhaled nitric oxide at the time of IHCA. Survival with favorable neurologic outcome was similar between patients with and without PH on univariate (48.9% vs. 54.4%; p = 0.17) and multivariate analyses (aOR 0.82 [95%CI: 0.56, 1.20]; p = 0.32). There were no significant differences in CPR event outcome or survival to hospital discharge. Average DBP, systolic BP, and end-tidal carbon dioxide during CPR were similar between groups. CONCLUSIONS: In this prospective study of pediatric IHCA, pre-existing PH was present in 16% of children. Pre-arrest PH diagnosis was not associated with statistically significant differences in survival outcomes or intra-arrest physiologic measures.

Ambient intelligence systems for personalized sport training.

Several research programs are tackling the use of Wireless Sensor Networks (WSN) at specific fields, such as e-Health, e-Inclusion or e-Sport. This is the case of the project "Ambient Intelligence Systems Support for Athletes with Specific Profiles", which intends to assist athletes in their training. In this paper, the main developments and outcomes from this project are described. The architecture of the system comprises a WSN deployed in the training area which provides communication with athletes' mobile equipments, performs location tasks, and harvests environmental data (wind speed, temperature, etc.). Athletes are equipped with a monitoring unit which obtains data from their training (pulse, speed, etc.). Besides, a decision engine combines these real-time data together with static information about the training field, and from the athlete, to direct athletes' training to fulfill some specific goal. A prototype is presented in this work for a cross country running scenario, where the objective is to maintain the heart rate (HR) of the runner in a target range. For each track, the environmental conditions (temperature of the next track), the current athlete condition (HR), and the intrinsic difficulty of the track (slopes) influence the performance of the athlete. The decision engine, implemented by means of (m, s)-splines interpolation, estimates the future HR and selects the best track in each fork of the circuit. This method achieves a success ratio in the order of 80%. Indeed, results demonstrate that if environmental information is not take into account to derive training orders, the success ratio is reduced notably.

A Call to Action to Address the Health Needs and Support Systems to Care for Central American Migrant Families.

The ongoing immigration crisis at the U.S. southern border represents a challenge to society and institutions. The socio-political discussion of immigration has reached and is likely to stay in the position of a top news category. It is hard to ignore the health care implications and negative health outcomes aff ecting Central American migrant families through their long journey to the U.S.-Mexico border. Additionally, radical changes in refugee/asylum policies are affecting how new migrants are being processed and connected to resources, which is affecting their care while detained. As individuals with familial ties to Central America, we share our knowledge of and perspective on contextual factors affecting migrant health. As health care professionals and scholars, we aim to trigger conversation and present a "call to action" to all stakeholders to address the health care needs of vulnerable Central American migrant families, who deserve high-quality and humanitarian care.

Innervation of supraclavicular adipose tissue: A human cadaveric study.

Functional brown adipose tissue (BAT) was identified in adult humans only in 2007 with the use of fluorodeoxyglucose positron emission tomography imaging. Previous studies have demonstrated a negative correlation between obesity and BAT presence in humans. It is proposed that BAT possesses the capacity to increase metabolism and aid weight loss. In rodents it is well established that BAT is stimulated by the sympathetic nervous system with the interscapular BAT being innervated via branches of intercostal nerves. Whilst there is evidence to suggest that BAT possesses beta-3 adrenoceptors, no studies have identified the specific nerve branch that carries sympathetic innervation to BAT in humans. The aim of this study was to identify and trace the peripheral nerve or nerves that innervate human BAT in the supraclavicular region. The posterior triangle region of the neck of cadaveric specimens were dissected in order to identify any peripheral nerve branches piercing and/or terminating in supraclavicular BAT. A previously undescribed branch of the cervical plexus terminating in a supraclavicular adipose depot was identified in all specimens. This was typically an independent branch of the plexus, from the third cervical spinal nerve, but in one specimen was a branch of the supraclavicular nerve. Histological analysis revealed the supraclavicular adipose depot contained tyrosine hydroxylase immunoreactive structures, which likely represent sympathetic axons. This is the first study that identifies a nerve branch to supraclavicular BAT-like tissue. This finding opens new avenues for the investigation of neural regulation of fat metabolism in humans.