Association of Pediatric Post-Cardiac Arrest Ventilation and Oxygenation with Survival Outcomes.

RATIONALE: Adult and pediatric studies provide conflicting data whether post-cardiac arrest hypoxemia, hyperoxemia, hypercapnia and/or hypocapnia are associated with worse outcomes. OBJECTIVES: Determine if post-arrest hypoxemia or post-arrest hyperoxemia are associated with lower rates of survival to hospital discharge compared to post-arrest normoxemia, and if post-arrest hypocapnia or hypercapnia are associated with lower rates of survival compared to post-arrest normocapnia. METHODS: Embedded prospective observational study during a multi-center interventional cardiopulmonary resuscitation trial from 2016-2021. Patients ≤18 years and ≥37 weeks corrected gestational age who received chest compressions for cardiac arrest in one of 18 ICUs were included. Exposures during the first 24 hours post-arrest were hypoxemia, hyperoxemia, or normoxemia defined as lowest PaO2 <60mmHg, highest PaO2 ≥200mmHg, or every PaO2 60-199mmHg, respectively, and hypocapnia, hypercapnia, or normocapnia defined as lowest PaCO2 <30mmHg, highest PaCO2 ≥50mmHg, or every PaCO2 30-49mmHg, respectively. Associations of oxygenation and carbon dioxide group with survival to hospital discharge were assessed using Poisson regression with robust error estimates. MEASUREMENTS AND MAIN RESULTS: The hypoxemia group was less likely to survive to hospital discharge compared with the normoxemia group (aRR 0.71, 0.58-0.87), whereas the hyperoxemia group survival did not differ from the normoxemia group (aRR 1.0, 0.87-1.15). The hypercapnia group was less likely to survive to hospital discharge compared with the normocapnia group (aRR 0.74, 0.64-0.84), whereas the hypocapnia group survival did not differ from the normocapnia group (aRR 0.91, 0.74-1.12). CONCLUSIONS: Post-arrest hypoxemia and hypercapnia were each associated with lower rates of survival to hospital discharge.

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.

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.

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.

Associations Between End-Tidal Carbon Dioxide During Pediatric Cardiopulmonary Resuscitation, Cardiopulmonary Resuscitation Quality, and Survival.

BACKGROUND: Supported by laboratory and clinical investigations of adult cardiopulmonary arrest, resuscitation guidelines recommend monitoring end-tidal carbon dioxide (ETCO2) as an indicator of cardiopulmonary resuscitation (CPR) quality, but they note that "specific values to guide therapy have not been established in children." METHODS: This prospective observational cohort study was a National Heart, Lung, and Blood Institute-funded ancillary study of children in the ICU-RESUS trial (Intensive Care Unit-Resuscitation Project; NCT02837497). Hospitalized children (≤18 years of age and ≥37 weeks postgestational age) who received chest compressions of any duration for cardiopulmonary arrest, had an endotracheal or tracheostomy tube at the start of CPR, and evaluable intra-arrest ETCO2 data were included. The primary exposure was event-level average ETCO2 during the first 10 minutes of CPR (dichotomized as ≥20 mm Hg versus <20 mm Hg on the basis of adult literature). The primary outcome was survival to hospital discharge. Secondary outcomes were sustained return of spontaneous circulation, survival to discharge with favorable neurological outcome, and new morbidity among survivors. Poisson regression measured associations between ETCO2 and outcomes as well as the association between ETCO2 and other CPR characteristics: (1) invasively measured systolic and diastolic blood pressures, and (2) CPR quality and chest compression mechanics metrics (ie, time to CPR start; chest compression rate, depth, and fraction; ventilation rate). RESULTS: Among 234 included patients, 133 (57%) had an event-level average ETCO2 ≥20 mm Hg. After controlling for a priori covariates, average ETCO2 ≥20 mm Hg was associated with a higher incidence of survival to hospital discharge (86/133 [65%] versus 48/101 [48%]; adjusted relative risk, 1.33 [95% CI, 1.04-1.69]; P=0.023) and return of spontaneous circulation (95/133 [71%] versus 59/101 [58%]; adjusted relative risk, 1.22 [95% CI, 1.00-1.49]; P=0.046) compared with lower values. ETCO2 ≥20 mm Hg was not associated with survival with favorable neurological outcome or new morbidity among survivors. Average 2 ≥20 mm Hg was associated with higher systolic and diastolic blood pressures during CPR, lower CPR ventilation rates, and briefer pre-CPR arrest durations compared with lower values. Chest compression rate, depth, and fraction did not differ between ETCO2 groups. CONCLUSIONS: In this multicenter study of children with in-hospital cardiopulmonary arrest, ETCO2 ≥20 mm Hg was associated with better outcomes and higher intra-arrest blood pressures, but not with chest compression quality metrics.

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.

Association of CPR simulation program characteristics with simulated and actual performance during paediatric in-hospital cardiac arrest.

AIM: To evaluate associations between characteristics of simulated point-of-care cardiopulmonary resuscitation (CPR) training with simulated and actual intensive care unit (ICU) CPR performance, and with outcomes of children after in-hospital cardiac arrest. METHODS: This is a pre-specified secondary analysis of the ICU-RESUScitation Project; a prospective, multicentre cluster randomized interventional trial conducted in 18 ICUs from October 2016-March 2021. Point-of-care bedside simulations with real-time feedback to allow multidisciplinary ICU staff to practice CPR on a portable manikin were performed and quality metrics (rate, depth, release velocity, chest compression fraction) were recorded. Actual CPR performance was recorded for children 37 weeks post-conceptual age to 18 years who received chest compressions of any duration, and included intra-arrest haemodynamics and CPR mechanics. Outcomes included survival to hospital discharge with favourable neurologic status. RESULTS: Overall, 18,912 point-of-care simulations were included. Simulation characteristics associated with both simulation and actual performance included site, participant discipline, and timing of simulation training. Simulation characteristics were not associated with survival with favourable neurologic outcome. However, participants in the top 3 sites for improvement in survival with favourable neurologic outcome were more likely to have participated in a simulation in the past month, on a weekday day, to be nurses, and to achieve targeted depth of compression and chest compression fraction goals during simulations than the bottom 3 sites. CONCLUSIONS: Point-of-care simulation characteristics were associated with both simulated and actual CPR performance. More recent simulation, increased nursing participation, and simulation training during daytime hours may improve CPR performance.

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.

Pediatric risk to orthotopic heart transplant (PRO) score: Insights from United Network for Organ Sharing (UNOS) waitlist mortality findings.

BACKGROUND: Pediatric heart transplant candidates on the waitlist have the highest mortality rate among all solid organ transplants. A risk score incorporating a candidate's individual risk factors may better predict mortality on the waitlist and optimize organ allocation to the sickest of those awaiting transplant. METHODS: Using the United Network for Organ Sharing (UNOS) database, we evaluated a total of 5542 patients aged 0-18 years old on the waitlist for a single, first time, heart transplant from January 2010 to June 2019. We performed a univariate analysis on two-thirds (N = 3705) of these patients to derive the factors most associated with waitlist mortality or delisting secondary to deterioration within 1 year. Those with a p <0.2 underwent a multivariate analysis and the resulting factors were used to build a prediction model using the Fine-Grey model analysis. This predictive scoring model was then validated on the remaining one-third of the patients (N = 1852). RESULTS: The Pediatric Risk to OHT (PRO) scoring model utilizes the following unique patient variables: blood type, diagnosis of congenital heart disease, weight, presence of ventilator support, presence of inotropic support, extracorporeal membrane oxygenation (ecmo) status, creatinine level, and region. A higher score indicates an increased risk of mortality. The PRO score had a predictive strength of 0.762 as measured by area under the ROC curve at 1 year. CONCLUSION: The PRO score is an improved predictive model with the potential to better assess mortality for patients awaiting heart transplant.

Genetic group and swim-up processing affect SYBR Green real-time PCR-based porcine semen sex ratio in Landrace and its crossbred boars.

Determination of factors affecting sex ratio is important while considering application of sex ratio enrichment approach. Present study aimed to design a SYBR Green qPCR-based method for measurement of primary sex ratio and to evaluate different factors (genetic group, sire, spermiogenic cycle and processing layer) affecting boar sperm sex ratio. The qPCR was based on relative copy number analysis of sex chromosome-specific single copy gene fragments with an autosomal gene as reference and was evaluated using DNA dilution series from pigs with numerically normal karyotype. The sex ratio was estimated from genomic DNA samples isolated from boar semen collected from different genetic groups at different time points and different processing layers. The X chromosome frequencies of semen samples revealed significant effect of genetic group. However, significant variation was observed neither within same genetic group nor between ejaculates of different spermatogenic cycles. Among the processing techniques studied, swim-up technique produced a significant X sperm enrichment in comparison to control whereas, Percoll density gradient failed to show any significant difference among layers. The lower layer in swim-up technique was found to contain higher proportion of X sperms. The designed qPCR is found to be an easy, less time-consuming method and does not require high end laboratory facilities or the specialized expertise. The lower layer of swim-up processing has a scope for X sperm enrichment in boar semen with proper validation.

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.

Calcium use during paediatric in-hospital cardiac arrest is associated with worse outcomes.

AIM: To evaluate associations between calcium administration and outcomes among children with in-hospital cardiac arrest and among specific subgroups in which calcium use is hypothesized to provide clinical benefit. METHODS: This is a secondary analysis of observational data collected prospectively as part of the ICU-RESUScitation project. Children 37 weeks post-conceptual age to 18 years who received chest compressions in one of 18 intensive care units from October 2016-March 2021 were eligible. Data included child and event characteristics, pre-arrest laboratory values, pre- and intra-arrest haemodynamics, and outcomes. Outcomes included sustained return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with favourable neurologic outcome. A propensity score weighted cohort was used to evaluate associations between calcium use and outcomes. Subgroups included neonates, and children with hyperkalaemia, sepsis, renal insufficiency, cardiac surgery with cardiopulmonary bypass, and calcium-avid cardiac diagnoses. RESULTS: Of 1,100 in-hospital cardiac arrests, median age was 0.63 years (IQR 0.19, 3.81); 450 (41%) received calcium. Among the weighted cohort, calcium use was not associated with sustained ROSC (aOR, 0.87; CI95 0.61-1.24; p = 0.445), but was associated with lower rates of both survival to hospital discharge (aOR, 0.68; CI95 0.52-0.89; p = 0.005) and survival with favourable neurologic outcome at hospital discharge (aOR, 0.75; CI95 0.57-0.98; p = 0.038). Among subgroups, calcium use was associated with lower rates of survival to hospital discharge in children with sepsis and renal insufficiency. CONCLUSIONS: Calcium use was common during paediatric in-hospital cardiac arrest and associated with worse outcomes at hospital discharge.

Nano-depletion of morbid spermatozoa up-regulate Ca2+ channel, depolarization of membrane potential and fertility in buffalo.

Despite recent advances in technique of spermatozoa cryopreservation, there are still ejaculates present that fail to meet strict quality standard; mainly due to detrimental effect of imbalance of free radicals. The omnipresence of dead/defective spermatozoa in ejaculates of eutherian species is a major source of excessive free radicals. Though sperm-selection techniques, as well as addition of antioxidants addressed the problem to a certain extent, the major source of free radicals in the semen remained, causing much damage. This study attempts to remove dead/damaged spermatozoa using negative fertility-marker. The effect is unraveled by Hypo-osmotic (HOS), and fluorescein-conjugated Pisum sativum agglutinin (FITC-PSA) assay, further confirmed by Ca2+-regulating mechanisms and depolarization of sperm membrane potential, reduction in concentration of free radicals and finally by in vitro fertility assay. The study involved functionalization of iron oxide nanoparticles (IONPs) with silane followed by bio-conjugation with anti-ubiquitin antibodies. The nano-purification of semen using anti-ubiquitin conjugated iron oxide nanoparticles (IONPs) (antibody concentrations 0.5, 1.0 and 2.0 µg/ml) was attempted. The efficiency of nano-purification was 18.1%-43.8% in the study. The results revealed greater (P ≤ 0.05) spermatozoa population with intact plasma membrane, acrosome integrity, high mitochondrial membrane potential and pattern-F (least intracellular Ca2+), evidence of low lipid peroxidation and higher total antioxidant capacity in nano-purified groups. More number of spermatozoa were bound to zona pellucida of matured oocytes from nano-depleted than non-depleted group. The findings demonstrate antibody concentration of 1.0 µg/ml bio-conjugated with IONPs as most efficient in enriching the ejaculate with functional spermatozoa with the highest percentage of zona binding.

An evidence of Humanin-like peptide and Humanin mediated cryosurvival of spermatozoa in buffalo bulls.

Buffalo spermatozoa are vulnerable to cryo-injuries due to inherent deficiency of endogenous antioxidants, high polyunsaturated fatty acids (PUFA) content in plasma membrane and low cholesterol/phospholipid (C/P) ratio. Humanin is a potent cytoprotective agent that protects the cells against oxidative stress and apoptosis. The present study was designed to establish the presence of Humanin in buffalo and effect of Humanin supplementation on freezability of buffalo spermatozoa. Indirect immunofluorescence test revealed presence of Humanin in ejaculated and epididymal spermatozoa, and, elongated spermatids and interstitial space in the testicular tissue section. Humanin levels in seminal plasma were significantly and positively correlated with sperm concentration and individual progressive motility (IPM) in good (n = 22; IPM >70%) and poor (n = 10; IPM <50%) quality ejaculates. For supplementation studies, a total of 24 ejaculates (IPM ≥70%) were collected and each ejaculate was then divided into four aliquots. First aliquot was diluted with egg yolk-tris-glycerol (EYTG) extender without Humanin and served as control group (Group I). Rest three aliquots were diluted with extender containing 2 (Group II), 5 (Group III) and 10 µM Humanin (Group IV), respectively. Semen was cryopreserved using standard protocol and evaluated at pre-freeze for lipid peroxidation (LPO) and post-thaw stages for spermatozoa kinematics, LPO, mitochondrial membrane potential (MMP), capacitation, apoptotic status and DNA integrity. The treatment group that showed best results (5 µM) was compared with control group for in vitro fertility assessment by homologous zona binding assay. The LPO levels were lower (p < 0.05) in 5 and 10 µM Humanin supplemented group. The MMP and DNA integrity were higher (p < 0.05) in 5 µM group than other groups. F-pattern was higher (p < 0.05) and B-pattern was lower (p < 0.05) in 5 and 10 µM Humanin supplemented groups. Lower apoptotic and higher viable spermatozoa (p < 0.05) were observed in 5 µM Humanin group. The mean number of spermatozoa bound to zona pellucida was higher (p < 0.05) in 5 µM Humanin treated group than the control group. The study established the presence of Humanin in buffalo spermatozoa and seminal plasma for very first time and concluded that Humanin supplementation at 5 µM concentration improves the freezability and in vitro fertility of buffalo spermatozoa.

A review on applications and toxicities of metallic nanoparticles in mammalian semen biology.

The advent of nanotechnology since the 1950s, when the well-known physicist Richard P. Feynman talked in his famous talk about "There's plenty of room at the bottom", has led to incredible contribution of nanotechnology in the fields of medical and veterinary therapeutics, diagnostics and other applications. Semen biology dealing with the study of spermatozoa and its related physiological and pathological aspects has not remained unscathed from the facets of nanotechnology. With each passing day investigators are revealing newer aspects of the nanoparticles, such as an antioxidants to relieve oxidative stress during semen cryopreservation, for the depletion of moribund spermatozoa from semen, gender selection of spermatozoa, bio-imaging of gametes, sperm mediated gene transfer, as well as for male fertility evaluation. As, the uses of various magnetic nanoparticles in the industry have gained acceleration, the evaluation of their effects, either beneficial or otherwise on the mammalian spermatozoa becomes obligatory. Many toxicological studies have also been conducted in respect to the harmful effects of different metallic nanoparticles related to their applicability, and industry borne adverse effects on the male germ cells in human beings and the animals. This review has been designed to focus on the beneficial as well as toxicological effects of various metallic nanoparticles on the mammalian spermatozoa and the future prospects related to their applicability in the semen biology.

Sodium Bicarbonate Use During Pediatric Cardiopulmonary Resuscitation: A Secondary Analysis of the ICU-RESUScitation Project Trial.

OBJECTIVES: To evaluate associations between sodium bicarbonate use and outcomes during pediatric in-hospital cardiac arrest (p-IHCA). DESIGN: Prespecified secondary analysis of a prospective, multicenter cluster randomized interventional trial. SETTING: Eighteen participating ICUs of the ICU-RESUScitation Project (NCT02837497). PATIENTS: Children less than or equal to 18 years old and greater than or equal to 37 weeks post conceptual age who received chest compressions of any duration from October 2016 to March 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Child and event characteristics, prearrest laboratory values (2-6 hr prior to p-IHCA), pre- and intraarrest hemodynamics, and outcomes were collected. In a propensity score weighted cohort, the relationships between sodium bicarbonate use and outcomes were assessed. The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Of 1,100 index cardiopulmonary resuscitation events, median age was 0.63 years (interquartile range, 0.19-3.81 yr); 528 (48.0%) received sodium bicarbonate; 773 (70.3%) achieved ROSC; 642 (58.4%) survived to hospital discharge; and 596 (54.2%) survived to hospital discharge with favorable neurologic outcome. Among the weighted cohort, sodium bicarbonate use was associated with lower survival to hospital discharge rate (adjusted odds ratio [aOR], 0.7; 95% CI, 0.54-0.92; p = 0.01) and lower survival to hospital discharge with favorable neurologic outcome rate (aOR, 0.69; 95% CI, 0.53-0.91; p = 0.007). Sodium bicarbonate use was not associated with ROSC (aOR, 0.91; 95% CI, 0.62-1.34; p = 0.621). CONCLUSIONS: In this propensity weighted multicenter cohort study of p-IHCA, sodium bicarbonate use was common and associated with lower rates of survival to hospital discharge.

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.

Supplementation of Mito TEMPO and acetovanillone in semen extender improves freezability of buffalo spermatozoa.

BACKGROUND: Oxidative stress is one of the leading factors responsible for poor post-thaw semen quality because of overproduction of reactive oxygen species (ROS) over neutralizing antioxidants present in semen. Mainly two ROS generation sites are present in spermatozoa, that is, mitochondria and plasma membrane. Therefore, the idea of targeting these specific sites for minimization of ROS production with the compounds having known mechanism of actions was built up as a core for this research. OBJECTIVE: Present study was done to investigate the effects of Mito TEMPO and acetovanillone individually and in combination on freezability of buffalo spermatozoa. MATERIALS AND METHODS: For the experiment, semen extender was supplemented with Mito TEMPO (50 µM), acetovanillone (50 µM), and a combination of Mito TEMPO + acetovanillone (50 µM+ 50 µM), designated as Group II, Group III, and Group IV, respectively. Control group without any supplementation was designated as Group I. A total of 24 ejaculates with individual progressive motility (IPM) of ≥70% were selected for the study. After final dilution, filling-sealing of straws, equilibration, and freezing were done as per the standard procedure. Semen samples were evaluated for IPM, plasma membrane integrity, lipid peroxidation, total antioxidant capacity (TAC), and cholesterol to phospholipids (C/P) ratio at both fresh and post-thaw stages. Evaluation of ROS, mitochondrial membrane potential (MMP), capacitation status (CTC assay), and in vitro fertility potential were conducted only on frozen-thawed samples. RESULTS: The addition of Mito TEMPO (50 µM) and acetovanillone (50 µM) individually and in combination significantly (p < 0.05) improved post-thaw semen quality in terms of IPM, plasma membrane integrity, TAC, cholesterol content, C/P ratio, MMP, Chlortetracycline (CTC)-Full (F) pattern, and zona binding ability of buffalo spermatozoa, while significantly (p < 0.05) reduced ROS production, lipid peroxidation, and capacitation like changes as compared to the control group. DISCUSSION: As Mito TEMPO acts as an SOD mimetic and also detoxifies ferrous iron at the mitochondria level, it aids in neutralization of excessive ROS production and minimizes oxidative stress-related damages that enhances the antioxidant potential of sperm mitochondria. Earlier studies also indicated improved post-thaw semen quality in 50 µM supplemented group. The improvement observed in acetovanillone (50 µM) group might be because of inhibition of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as this enzyme activation by various physical/chemical inducers during cryopreservation process leads to activation of CatSper channel resulting in calcium influx, premature capacitation, and acrosomal reaction like changes through activation of adenylate cyclase and cAMP/PKA-mediated tyrosine phosphorylation of sperm proteins. Acetovanillone also prevents NADPH oxidase-mediated inhibition of glutathione reductase activity, which has a vital role in protecting the structural and functional integrity of sperm plasma membrane. CONCLUSION: Results indicated beneficial effects of supplementation of Mito TEMPO and acetovanillone on sperm freezability and individual supplementation was as efficient as the combination group for sustaining post-thaw semen quality.

Pediatric interfacility transport effects on mortality and length of stay.

BACKGROUND: We aimed to evaluate the effects of interfacility pediatric critical care transport response time, physician presence during transport, and mode of transport on mortality and length of stay (LOS) among pediatric patients. We hypothesized that a shorter response time and helicopter transports, but not physician presence, are associated with lower mortality and a shorter LOS. METHODS: Retrospective, single-center, cohort study of 841 patients (< 19 years) transported to a quaternary pediatric intensive care unit and cardiovascular intensive care unit between 2014 and 2018 utilizing patient charts and transport records. Multivariate linear and logistic regression analyses adjusted for age, diagnosis, mode of transport, response time, stabilization time, return duration, mortality risk (pediatric index of mortality-2 and pediatric risk of mortality-3), and inotrope, vasopressor, or mechanical ventilation presence on admission. RESULTS: Four hundred and twenty-eight (50.9%) patients were transported by helicopter, and 413 (49.1%) were transported by ambulance. Physicians accompanied 239 (28.4%) transports. The median response time was 2.0 (interquartile range 1.4-2.9) hours. Although physician presence increased the median response time by 0.26 hours (P = 0.020), neither physician presence nor response time significantly affected mortality, ICU length of stay (ILOS) or hospital length of stay (HLOS). Helicopter transports were not significantly associated with mortality or ILOS, but were associated with a longer HLOS (3.24 days, 95% confidence interval 0.59-5.90) than ambulance transports (P = 0.017). CONCLUSIONS: These results suggest response time and physician presence do not significantly affect mortality or LOS. This may reflect the quality of pre-transport care and medical control communication. Helicopter transports were only associated with a longer HLOS. Our analysis provides a framework for examining transport workforce needs and associated costs.

Risk Factors Associated With Bleeding in Children With Cardiac Disease Receiving Extracorporeal Membrane Oxygenation: A Multi-Center Data Linkage Analysis.

Background: Bleeding is a common complication of extracorporeal membrane oxygenation (ECMO) for pediatric cardiac patients. We aimed to identify anticoagulation practices, cardiac diagnoses, and surgical variables associated with bleeding during pediatric cardiac ECMO by combining two established databases, the Collaborative Pediatric Critical Care Research Network (CPCCRN) Bleeding and Thrombosis in ECMO (BATE) and the Extracorporeal Life Support Organization (ELSO) Registry. Methods: All children (<19 years) with a primary cardiac diagnosis managed on ECMO included in BATE from six centers were analyzed. ELSO Registry criteria for bleeding events included pulmonary or intracranial bleeding, or red blood cell transfusion >80 ml/kg on any ECMO day. Bleeding odds were assessed on ECMO Day 1 and from ECMO Day 2 onwards with multivariable logistic regression. Results: There were 187 children with 114 (61%) bleeding events in the study cohort. Biventricular congenital heart disease (94/187, 50%) and cardiac medical diagnoses (75/187, 40%) were most common, and 48 (26%) patients were cannulated directly from cardiopulmonary bypass (CPB). Bleeding events were not associated with achieving pre-specified therapeutic ranges of activated clotting time (ACT) or platelet levels. In multivariable analysis, elevated INR and fibrinogen were associated with bleeding events (OR 1.1, CI 1.0-1.3, p = 0.02; OR 0.77, CI 0.6-0.9, p = 0.004). Bleeding events were also associated with clinical site (OR 4.8, CI 2.0-11.1, p < 0.001) and central cannulation (OR 1.75, CI 1.0-3.1, p = 0.05) but not with cardiac diagnosis, surgical complexity, or cannulation from CPB. Bleeding odds on ECMO day 1 were increased in patients with central cannulation (OR 2.82, 95% CI 1.15-7.08, p = 0.023) and those cannulated directly from CPB (OR 3.32, 95% CI 1.02-11.61, p = 0.047). Conclusions: Bleeding events in children with cardiac diagnoses supported on ECMO were associated with central cannulation strategy and coagulopathy, but were not modulated by achieving pre-specified therapeutic ranges of monitoring assays.