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Background: This study provides a comprehensive analysis of Acinetobacter baumannii in aquatic environments and fish microbiota by integrating culture-dependent methods, 16S metagenomics, and antibiotic resistance profiling., Methods: A total of 83 A. baumannii isolates were recovered using culture-dependent methods from intra-hospital infections (IHI) and wastewater (WW) and surface water (SW) samples from two southern Romanian cities in August 2022. The antibiotic susceptibility was screened using disc diffusion, microdilution, PCR, and Whole Genome Sequencing assays., Results: The highest microbial load in the analyzed samples was found in Glina, Bucharest, for both WW and SW samples across all investigated phenotypes. For Bucharest isolates, the resistance levels corresponded to fluoroquinolones > aminoglycosides > β-lactam antibiotics. In contrast, A. baumannii from upstream SW samples in Târgoviște showed the highest resistance to aminoglycosides. The bla OXA-23 gene was frequently detected in IHI, WW, and SW isolates in Bucharest, but was absent in Târgoviște. Molecular phylogeny revealed the presence of ST10 in Târgoviște isolates and ST2 in Bucharest isolates, while other minor STs were not specifically correlated with a sampling point. Using 16S rRNA sequencing, significant differences in microbial populations between the two locations was identified. The low abundance of Alphaproteobacteria and Actinobacteria in both locations suggests environmental pressures or contamination events., Conclusions: These findings indicate significant fecal contamination and potential public health risks, emphasizing the need for improved water quality monitoring and management.

The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS- b -PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.

Objectives: In infants with single-ventricle congenital heart disease, prematurity and low weight at the time of the Norwood operation are risk factors for mortality. Reports assessing outcomes (including neurodevelopment) post Norwood palliation in infants ≤2.5 kg are limited., Methods: All infants who underwent a Norwood-Sano procedure between 2004 and 2019 were identified. Infants ≤2.5 kg at the time of the operation (cases) were matched 3:1 with infants >3.0 kg (comparisons) for year of surgery and cardiac diagnosis. Demographic and perioperative characteristics, survival, and functional and neurodevelopmental outcomes were compared., Results: Twenty-seven cases (mean ± standard deviation: weight 2.2 ± 0.3 kg and age 15.6 ± 14.1 days at surgery) and 81 comparisons (3.5 ± 0.4 kg and age 10.9 ± 7.9 days at surgery) were identified. Post-Norwood, cases had a longer time to lactate ≤2 mmol/L (33.1 ± 27.5 vs 17.9 ± 12.2 hours, P  < .001), longer duration of ventilation (30.5 ± 24.5 vs 18.6 ± 17.5 days, P  = .005), greater need for dialysis (48.1% vs 19.8%, P  = .007), and greater need for extracorporeal membrane oxygenation support (29.6% vs 12.3%, P  = .004). Cases had significantly greater postoperative (in-hospital) (25.9% vs 1.2%, P  < .001) and 2-year (59.2% vs 11.1%, P  < .001) mortality. Neurodevelopmental assessment showed the following for cases versus comparisons, respectively: cognitive delay (18.2% vs 7.9%, P  = .272), language delay (18.2% vs 11.1%, P  = .505), and motor delay (27.3% vs 14.3%, P  = .013)., Conclusions: Infants ≤2.5 kg at Norwood-Sano palliation have significantly increased postoperative morbidity and mortality up to 2-year follow-up. Neurodevelopmental motor outcomes were worse in these infants. Additional studies are warranted to assess the outcome of alternative medical and interventional treatment plans in this patient population., (© 2023 The Author(s).)

The pesticide pollution of surface water and wastewater has been recognized as a major worldwide concern due to their persistence in the aquatic environment and the potential adverse effects on human, flora, and fauna health. Apart from pesticides, bio-contamination with various bacterial populations leads to waterborne diseases. Hence, it becomes vital to remove the above-mentioned pollutants from water using a suitable process. Consequently, our study emphasized the potential benefits of a highly porous, chemically cross-linked 3D chitosan (CSGA) cryogel in the removal of pesticides and bacteria. The CSGA sponges were prepared using a facile and cost-effective approach that consisted of a three-step cryogenic process: (i) freezing at -18 °C, (ii) storage in a frozen state for a certain period, and (iii) thawing at room temperature. Batch adsorption experiments were performed under different environments, where the effects of several parameters, such as pH, contact time, and initial pollutant concentration were evaluated to identify the appropriate adsorption conditions for maximum pesticide removal. The CSGA-based cryogel sponges exhibited a theoretical maximum adsorption capacity of 160.82 mg g -1 for the Fastac 10EC pesticide and very good recyclability at room temperature. In addition, the antibacterial activities of these sponges were also investigated against various bacterial pathogens. The rates of killing Escherichia coli , Listeria monocytogenes , and Staphylococcus aureus were close to 82%, 100%, and 99%, respectively. These results demonstrated that CSGA cryogels could be efficiently used in water remediation and find applications in the removal of pesticides and disinfection.

Background: Compared with those born at term gestation, infants with complex congenital heart defects (CCHD) who were delivered before 37 weeks gestational age and received neonatal open-heart surgery (OHS) have poorer neurodevelopmental outcomes in early childhood. We aimed to describe the growth, disability, functional, and neurodevelopmental outcomes in early childhood of preterm infants with CCHD after neonatal OHS. Prediction models were evaluated at various timepoints during hospitalization which could be useful in the management of these infants. Study Design: We studied all preterm infants with CCHD who received OHS within 6 weeks of corrected age between 1996 and 2016. The Western Canadian Complex Pediatric Therapies Follow-up Program completed multidisciplinary comprehensive neurodevelopmental assessments at 2-year corrected age at the referral-site follow-up clinics. We collected demographic and acute-care clinical data, standardized age-appropriate outcome measures including physical growth with calculated z- scores; disabilities including cerebral palsy, visual impairment, permanent hearing loss; adaptive function (Adaptive Behavior Assessment System-II); and cognitive, language, and motor skills (Bayley Scales of Infant and Toddler Development-III). Multiple variable logistic or linear regressions determined predictors displayed as Odds Ratio (OR) or Effect Size (ES) with 95% confidence intervals. Results: Of 115 preterm infants (34 ± 2 weeks gestation, 2,339 ± 637 g, 64% males) with CCHD and OHS, there were 11(10%) deaths before first discharge and 21(18%) deaths by 2-years. Seven (6%) neonates had cerebral injuries, 7 had necrotizing enterocolitis; none had retinopathy of prematurity. Among 94 survivors, 9% had cerebral palsy and 6% had permanent hearing loss, with worse outcomes in those with syndromic diagnoses. Significant predictors of mortality included birth weight z- score [OR 0.28(0.11,0.72), P = 0.008], single-ventricle anatomy [OR 5.92(1.31,26.80), P = 0.021], post-operative ventilation days [OR 1.06(1.02,1.09), P = 0.007], and cardiopulmonary resuscitation [OR 11.58 (1.97,68.24), P = 0.007]; for adverse functional outcome in those without syndromic diagnoses, birth weight 2,000-2,499 g [ES -11.60(-18.67, -4.53), P = 0.002], post-conceptual age [ES -0.11(-0.22,0.00), P = 0.044], post-operative lowest pH [ES 6.75(1.25,12.25), P = 0.017], and sepsis [ES -9.70(-17.74, -1.66), P = 0.050]. Conclusions: Our findings suggest preterm neonates with CCHD and early OHS had significant mortality and morbidity at 2-years and were at risk for cerebral palsy and adverse neurodevelopment. This information may be important for management, parental counseling and the decision-making process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cheung, Hajihosseini, Dinu, Switzer, Joffe, Bond and Robertson.)

Objective: To demonstrate feasibility of a music medicine intervention trial in pediatric intensive care and to obtain information on sedation and analgesia dose variation to plan a larger trial., Material and Methods: Pilot randomized controlled trial (RCT) was conducted at the Stollery Children's Hospital general and cardiac intensive care units (PICU/PCICU). The study included children 1 month to 16 years of age on mechanical ventilation and receiving sedation drugs. Patients were randomized in a 1:1:1 ratio to music, noise cancellation or control. The music group received classical music for 30 min three times/day using headphones. The noise cancellation group received the same intervention but with no music. The control group received usual care., Results: A total of 60 patients were included. Average enrollment rate was 4.8 patients/month, with a consent rate of 69%. Protocol adherence was achieved with patients receiving > 80% of the interventions. Overall mean (SD) daily Sedation Intensity Score was 52.4 (30.3) with a mean (SD) sedation frequency of 9.75 (7.21) PRN doses per day. There was a small but statistically significant decrease in heart rate at the beginning of the music intervention. There were no study related adverse events. Eighty-eight percent of the parents thought the headphones were comfortable; 73% described their child more settled during the intervention., Conclusions: This pilot RCT has demonstrated the feasibility of a music medicine intervention in critically ill children. The study has also provided the necessary information to plan a larger trial.

Bio-conjugated hydrogels merge the functionality of a synthetic network with the activity of a biomolecule, becoming thus an interesting class of materials for a variety of biomedical applications. This combination allows the fine tuning of their functionality and activity, whilst retaining biocompatibility, responsivity and displaying tunable chemical and mechanical properties. A complex scenario of molecular factors and conditions have to be taken into account to ensure the correct functionality of the bio-hydrogel as a scaffold or a delivery system, including the polymer backbone and biomolecule choice, polymerization conditions, architecture and biocompatibility. In this review, we present these key factors and conditions that have to match together to ensure the correct functionality of the bio-conjugated hydrogel. We then present recent examples of bio-conjugated hydrogel systems paving the way for regenerative medicine applications.

Background: Stress induced by pain and anxiety is common in pediatric intensive care unit (PICU) patients. Sedation/analgesia in PICU is usually achieved through various analgesics and sedatives. Excessive use of these drugs can put patients at risk for hemodynamic/respiratory instability, prolonged ventilation, withdrawal, delirium, and critical illness polyneuromyopathy.The use of non-pharmacologic interventions has been recommended by sedation guidelines. However, non-pharmacological measures in PICU, including music and noise reduction, have been inadequately studied., Methods: The Music Use for Sedation in Critically ill Children (MUSiCC trial) pilot study is an investigator-initiated, three-arm, randomized controlled trial (RCT) on the use of music for sedation in PICU. The main goal of the study is to demonstrate feasibility of a music trial in PICU and to obtain the necessary information to plan a larger trial. The study compares music versus noise cancelation versus control in sedated and mechanically ventilated children admitted to PICU. In the music group, children receive the music (modified classical music) three times a day for 30 min at a time. Music is delivered with noise cancelation headphones. The noise cancelation group receives the same intervention but with a no music (sham playlist). The control group receives usual care with no specific intervention. Children remain in the study until extubation or a maximum of 7 days. The primary outcomes of the study are feasibility and sedation/analgesia requirements. Secondary outcomes include change in vital signs before and during the intervention, ICU delirium, and adverse effects related to the intervention. The estimated sample size is 20 subjects per group for a total of 60 children., Discussion: Despite being recommended by current guidelines, evidence to support the use of music in PICU is lacking. Music has the potential to reduce sedation requirements and their negative side effects. This pilot RCT will demonstrate feasibility and provide the necessary information to plan a larger trial focusing on the effectiveness of the intervention., Trial Registration: The study was registered at ClinicalTrials.gov (NCT03497559) on April 13, 2018., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Background: Urea cycle disorders (UCD) and organic acid disorders classically present in the neonatal period. In those who survive, developmental delay is common with continued risk of regression. Liver transplantation improves the biochemical abnormality and patient survival is good. We report the neurocognitive and functional outcomes post-transplant for nine UCD, three maple syrup urine disease, and one propionic acidemia patient., Methods: Thirteen inborn errors of metabolism (IEM) patients were individually one-to-two matched to 26 non-IEM patients. All patients received liver transplant. Wilcoxon rank sum test was used to compare full-scale intelligence-quotient (FSIQ) and Adaptive Behavior Assessment System-II General Adaptive Composite (GAC) at age 4.5 years. Dichotomous outcomes were reported as percentages., Results: FSIQ and GAC median [IQR] was 75 [54, 82.5] and 62.0 [47.5, 83] in IEM compared with 94.5 [79.8, 103.5] and 88.0 [74.3, 97.5] in matched patients ( P -value <.001), respectively. Of IEM patients, 6 (46%) had intellectual disability (FSIQ and GAC <70), 5 (39%) had autism spectrum disorder, and 1/13 (8%) had cerebral palsy, compared to 1/26 (4%), 0, 0, and 0% of matched patients, respectively. In the subgroup of nine with UCDs, FSIQ (64[54, 79]), and GAC (56[45, 75]) were lower than matched patients (100.5 [98.5, 101] and 95 [86.5, 99.5]), P = .005 and .003, respectively., Conclusion: This study evaluated FSIQ and GAC at age 4.5 years through a case-comparison between IEM and matched non-IEM patients post-liver transplantation. The neurocognitive and functional outcomes remained poor in IEM patients, particularly in UCD. This information should be included when counselling parents regarding post-transplant outcome., Competing Interests: Shailly Jain‐Ghai has participated in advisory boards and received honoraria and travel grants from Sanofi‐Genzyme, Horizon Pharmaceutical, Amicus, BioMarin and Shire. Ari R Joffe, Gwen Y Bond, Komudi Siriwardena, Alicia Chan, Jason Y K Yap, Morteza Hajihosseini, Irina A Dinu, Bryan V Acton and Charlene MT Robertson have no conflicts of interest to declare., (© 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: We aimed to determine predictors of, and outcomes after, veno-arterial extracorporeal membrane oxygenation instituted within 48 h after cardiac surgery (early ECMO) in young infants., Methods: Patients ≤ 6 weeks old having cardiac surgery from 2003 to 2012 were enrolled prospectively. Patients cannulated pre-operatively, intra-operatively, or ≥ 48 h post-operatively were excluded. Variables at p  ≤ 0.1 on univariate regression were entered into multiple logistic regression to predict early ECMO. Early-ECMO cases were matched 1:2 for six demographic variables, and death by age 2 years old (determined using conditional logistic regression; presented as odds ratio (OR), 95% confidence interval (CI)) and General Adaptive Composite scores at age 2 years (determined using Wilcoxon rank sum) were compared; p  ≤ 0.05 was considered statistically significant., Results: Of 565 eligible patients over the 10-year period, 20 had early ECMO instituted at a mean (standard deviation) of 12.4 (11.4) h post-operatively, 10 of whom had extracorporeal cardiopulmonary resuscitation. Of early-ECMO patients, 8 (40%) were found to have residual anatomic defects requiring intervention with catheterization ( n  = 1) and/or surgery ( n  = 7). On multiple regression, the post-operative day 1 highest vasoactive-inotrope score (OR 1.02; 95%CI 1.06,1.08; p  < 0.001), highest lactate (OR 1.2; 95%CI 1.06,1.35; p  = 0.003), and lowest base deficit (OR 0.82; 95%CI 0.71,0.94; p  = 0.004), CPB time (OR 1.01; 95%CI 1.00,1.02; p  = 0.002), and single-ventricle anatomy (OR 5.35; 95%CI 1.66,17.31; p  = 0.005) were associated with early ECMO. Outcomes at 2 years old compared between early-ECMO and matched patients were mortality 11/20 (55%) vs 11/40 (28%) (OR 3.22, 95%CI 0.98,10.63; p  = 0.054) and General Adaptive Composite median 65 [interquartile range (IQR) 58, 81.5] in 9 survivors vs 93 [IQR 86.5, 102.5] in 29 survivors ( p  = 0.02)., Conclusions: The identified risk factors for, and outcomes after, having early ECMO may aid decision making in the acute period and confirm that neurodevelopmental follow-up for these children is necessary. The hypothesis that earlier institution of ECMO may improve long-term outcomes requires further study., Competing Interests: The Health Research Ethics Board of the University of Alberta approved this study [Pro00001030]. All parents/guardians signed an informed consent form.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The purpose of this study was to determine whether a clinical outcome score derived from early postoperative events is associated with Bayley-III scores at 18 to 24 months among infants undergoing cardiopulmonary bypass surgery., Methods: Included were infants aged 6 weeks or less who underwent surgery between 2005 and 2009, all of whom were referred for neurodevelopmental evaluation at 18 to 24 months. We excluded children with chromosomal abnormalities. The prespecified clinical outcome score had a range of 0 to 7. Lower scores indicated a more rapid postoperative recovery. Patients requiring extracorporeal life support were assigned a score of 7., Results: One hundred and ninety-nine subjects were included. Surgical procedures were arterial switch (72), Norwood (60), repair of total anomalous pulmonary venous connection (29), and other (38). Nine subjects had postoperative extracorporeal life support. Mean clinical outcome score in the Norwood group was 4.0 ± 1.4 versus the arterial switch group (2.6 ± 1.5, p < 0.001), total anomalous pulmonary venous connection group (2.8 ± 1.8, p < 0.01), and other group (4.0 ± 1.8, p = not significant). Among children who had a clinical outcome score of 4 or greater, there was a decrease in Bayley-III cognitive score of 5.7 (95% confidence interval: 1.5 to 9.9, p = 0.009), a decrease in language score of 10.0 (95% confidence interval: 4.9 to 15.1, p < 0.001), and a decrease in motor score of 9.7 (95% confidence interval: 4.8 to 14.5, p < 0.001). Time until lactate of 2.0 mmol/L or less and highest 24-hour inotrope score increased with increasing clinical outcome score (p < 0.0001)., Conclusions: Clinical outcome scores of 4 or greater were associated with significantly lower Bayley-III scores at 18 to 24 months. This score may be valuable as an endpoint when evaluating novel potential therapies for this high-risk population., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Survival after pediatric cardiac extracorporeal life support (ECLS) is guarded, and neurological morbidity varies widely. Our objective is to report our 10-year experience with cardiac ECLS, including survival and kindergarten entry neurocognitive outcomes; to identify predictors of mortality or adverse neurocognitive outcomes; and to compare 2 eras, before and after 2005., Methods and Results: From 2000 to 2009, 98 children had venoarterial cardiac ECLS. Sixty-four patients (65%) survived to hospital discharge, and 50 (51%) survived ≤5 years of age. Neurocognitive follow-up of survivors was completed at mean (SD) age of 52.9 (8) months using Wechsler Preschool and Primary Scale of Intelligence. Logistic regression analysis found the longer time (hours) for lactate to fall below 2 mmol/L on ECLS (hazard ratio, 1.39; 95% confidence interval, 1.05, 1.84; P=0.022), and the amount of platelets (mL/kg) given in the first 48 hours (hazard ratio, 1.18; 95% confidence interval, 1.06, 1.32; P=0.002) was independently associated with higher in-hospital mortality. Receiving ECLS after the year 2005 was independently associated with lower risk of in-hospital mortality (hazard ratio, 0.36; 95% confidence interval, 0.13, 0.99; P=0.048). Extracorporeal cardiopulmonary resuscitation was not independently associated with mortality or neurocognitive outcomes. Era was not independently associated with neurocognitive outcomes. The full-scale intelligence quotient of survivors without chromosomal abnormalities was 79.7 (16.6) with 25% below 2 SD of the population mean., Conclusions: Mortality has improved over time; time for lactate to fall on ECLS and volume of platelets transfused are independent predictors of mortality. Extracorporeal cardiopulmonary resuscitation and era were not independently associated with neurocognitive outcomes., (© 2015 American Heart Association, Inc.)

Stimulus-sensitive systems at the nanoscale represent ideal candidates for improving therapeutic and diagnostic approaches by producing rapid responses to the presence of specific molecules or conditions either by changing properties or by acting "on demand". Here we introduce an optimized light-sensitive nanoreactor based on encapsulation of a photosensitizer inside polymer vesicles to serve as an efficient source of reactive oxygen species (ROS) "on demand". Two types of amphiphilic block copolymers, poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyloxazoline), PMOXA-PDMS-PMOXA, and poly(N-vinylpyrrolidone)-block-poly(dimethylsiloxane)-block-poly(N-vinylpyrrolidone), PNVP-PDMS-PNVP, were used to encapsulate Rose Bengal-bovine serum albumin (RB-BSA) inside the cavity of vesicles. The difference of copolymers molecular properties (hydrophobic to hydrophilic ratio, different chemical nature of the hydrophilic block) influenced the encapsulation ability, and uptake by cells, allowing therefore a selection of the most efficient polymer system. Nanoreactors were optimized in terms of (i) size, (ii) stability, and (iii) encapsulation efficiency based on a combination of light scattering, TEM, and UV-vis spectroscopy. By illumination, encapsulated RB-BSA conjugates generated in situ ROS, which diffused through the polymer membrane to the environment of the vesicles, as proved by electron spin resonance spectroscopy (ESR). Optimum illumination conditions were obtained based on the effect of the illumination time on the amount of ROS produced in situ by the encapsulated RB-BSA conjugates. ROS diffusion monitored by ESR was dependent on the molecular weight of copolymer that influences the thickness of the polymer membrane. Upon uptake into HeLa cells our nontoxic nanoreactors acted as a Trojan horse: they produced illumination-controlled ROS in sufficient amounts to induce cell death under photodynamic therapy (PDT) conditions. Straightforward production, stability, and Trojan horse activity inside cells support our light-sensitive nanoreactors for medical applications which require ROS to be generated with precise time and space control.

Objectives: This study investigated the relationship between early postoperative serum C-reactive protein (CRP) levels, a marker of systemic inflammatory response, and 2-year neurodevelopment-associated outcomes among survivors after undergoing the Norwood procedure., Methods: Among 53 neonates with hypoplastic left heart syndrome undergoing the Norwood procedure during 2003-2009, CRP was measured in 43 patients twice weekly within postoperative day 20. Two-year cognition, language, and motor scores were assessed with Bayley Scales of Infant and Toddler Development III in 26 patients (9 deaths, 2 lost, and 6 assessed with Bayley Scales of Infant Development II). Peak CRP levels of the 26 patients were recorded, with peak total and differential white blood cell counts (lowest lymphocytes) and glucose. Demographic data included age at surgery, socioeconomic status of the families, durations of cardiopulmonary bypass and aortic crossclamp, deep hypothermic circulatory arrest, and intensive care unit stay., Results: The cognitive score was 91 ± 13, language score was 86 ± 13, and motor score was 85 ± 17. The peak CRP level was 79 ± 37 mg/L. Univariate regression showed that the cognitive score significantly and negatively correlated with peak CRP level (P = .004), and trended to a negative correlation with age at surgery (P = .097). The language score significantly and negatively correlated with peak CRP level (P < .0001) and age (P = .005). The motor score trended to a negative correlation with age (P = .08). Multivariate regression showed that both cognitive and language scores significantly and negatively correlated only with peak CRP level (P < .01 for both)., Conclusions: The magnitude of systemic inflammatory response, among the perioperative factors examined, may be an important determinant for adverse 2-year cognition and language outcomes after the Norwood procedure. Confirmatory studies in larger populations, including those undergoing other types of cardiac surgeries, are warranted., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Our goal was to determine if a clinical outcome score derived from early postoperative events is associated with 18- to 24-month Psychomotor Developmental Index (PDI) score among infants undergoing cardiopulmonary bypass surgery., Methods: We included infants aged ≤6 weeks who underwent surgery during 2002-2006, all of whom were referred for neurodevelopmental evaluation at age 18 to 24 months. We excluded children with chromosomal abnormalities, hearing loss, cerebral palsy, or a Bayley III assessment. The prespecified clinical outcome score had a range of 0 to 7. Lower scores indicated a more rapid postoperative recovery. Patients requiring extracorporeal membrane oxygenation were assigned a score of 7., Results: Ninety-nine subjects were included. Surgical procedures were arterial switch (n = 36), Norwood (n = 26), repair of total anomalous pulmonary venous connection (n = 16), and other (n = 21). Four subjects had postoperative extracorporeal membrane oxygenation. Clinical outcome scores were highest in the Norwood group (mean 4.1 ± 1.4) compared with the arterial switch group (1.9 ± 1.6) (P < .001), total anomalous pulmonary venous connection group (1.6 ± 2.0) (P < .001), and other group (3.3 ± 1.6, P = not significant). A mean decrease in PDI of 10.9 points (95% confidence interval, 4.9-16.9; P = .0005) was observed among children who had a clinical outcome score ≥3, compared with those with a clinical outcome score <3. Time until lactate ≤2.0 mmol/L increased with increasing clinical outcome score (P = .0003), as did highest 24-hour inotrope score (P < .0001)., Conclusions: Clinical outcome scores of ≥3 were associated with a significantly lower PDI at age 18 to 24 months. This score may be valuable as an end point when evaluating novel potential therapies for this high-risk population., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: To determine the health-related quality of life at 4 years of age in children who had undergone cardiac surgery for congenital heart disease in early infancy., Methods: A prospective cohort study of infants undergoing cardiac surgery at 6 weeks of age or younger from July 2000 to June 2005 at the Stollery Children's Hospital. The quality of life was assessed using the Pediatric Quality of Life Inventory, version 4.0, generic core scales, and compared with normative values for the same age. The association between the perioperative variables and health-related quality of life was explored., Results: A total of 242 infants underwent complex heart surgery during the study period. Of the 166 eligible survivors, 130 were included. No significant differences were present between the children with single ventricle versus biventricular repairs, except for lower physical health summary scores in the single ventricle patients (P = .007). Compared with the normative data, the children with biventricular repair had lower total Pediatric Quality of Life Inventory, version 4.0, scores (P = .001) and psychosocial health summary scores (P < .001). The children with single ventricle repair also had lower physical health summary scores (P = .003). Older age at surgery and markers of postoperative low cardiac output syndrome were associated with worse health-related quality of life, and greater socioeconomic status was associated with better quality of life., Conclusions: At 4 years of age, health-related quality of life was significantly lower in children who had undergone surgery for congenital heart disease in early infancy. An association was found between age at surgery and postoperative low cardiac output and socioeconomic status and quality of life., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Survival after heart transplant has improved and more attention is focused on developmental outcomes. We aimed to determine the survival, morbidity, and developmental outcomes of young children after heart transplant., Methods: All children under 6 years of age having a heart transplant in Edmonton between 1999 and 2006 were included in this inception cohort study. Demographics, pretransplant, transplant, and posttransplant variables were collected. The association of potentially predictive variables with neurodevelopmental outcomes at least 12 months posttransplant were determined by univariate and multiple regression analyses., Results: Thirty-three children had a heart transplant; 18 with congenital heart disease (CHD) and 15 with cardiomyopathy-myocarditis (non-CHD). Mortality during 19 (8) months of follow-up was 12% (95% confidence interval [CI] 3% to 28%). Survivors had frequent low weight (28%) and height (31%), and delay in language (41%), motor (52%), mental (34%), and general adaptive composite (48%) scores. Only CHD was associated with death-disability-mental delay on multiple regression (odds ratio 7.94; 95% CI 1.6 to 39.4, p=0.011). The CHD was also associated with mental and language delay on multiple regressions. Mental delay occurred in 8 (53%) with CHD and 2 (14%) with non-CHD (p=0.05). Mental score of 85 or greater was found in 13.4% of patients with CHD compared with 50% with non-CHD (p=0.05)., Conclusions: In this single-center inception cohort study, adverse neurodevelopmental outcomes in survivors of heart transplant before the age 6 years were common, particularly in those with CHD. Careful pretransplant and posttransplant counseling are needed, and close follow-up with early intervention for these high-risk children is imperative., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Newly emerging health technologies are being developed to care for children with complex cardiac defects. Neurodevelopmental and childhood school-related outcomes are of great interest to parents of children receiving this care, care providers, and healthcare administrators. Since the 1970s, neonatal follow-up clinics have provided service, audit, and research for preterm infants as care for these at-risk children evolved. We have chosen to present for this issue the mechanism for longitudinal follow-up of survivors that we have developed for western Canada patterned after neonatal follow-up. Our program provides registration for young children receiving complex cardiac surgery, heart transplantation, ventricular assist device support, and extracorporeal life support among others. The program includes multidisciplinary assessments with appropriate neurodevelopmental intervention, active quality improvement evaluations, and outcomes research. Through this mechanism, consistently high (96%) follow-up over two years is maintained.

Background: Red blood cell transfusions may or may not improve oxygen delivery to the tissues. Some studies suggest transfusion might contribute to adverse outcomes. This study investigated the association between hemoglobin concentration and transfusion with outcome in cyanotic neonates undergoing Norwood operations., Methods: Infants 6 weeks old or younger with hypoplastic left heart syndrome undergoing staged Norwood operations between September 1996 and July 2005 were included. Demographics and preoperative, operative, and postoperative variables were collected prospectively. Hemoglobin concentration, transfusion, fluid balance, and chest tube losses were collected retrospectively. The association of variables with outcomes, including early and 2-year mortality, mental and psychomotor developmental indices at 18 to 24 months of age, and ventilator days were determined by univariate and multiple regression analyses., Results: Ninety-four patients had Norwood operations. Excluded were 10 requiring postoperative extracorporeal life support and 2 with chromosomal abnormalities. By multiple regression analysis, only a higher nadir hemoglobin on days 2 to 5 postoperatively was associated with higher early mortality (odds ratio, 2.09; 95% confidence interval [CI], 1.14 to 3.87; p = 0.018), and the highest preoperative dopamine dose and highest epinephrine dose on day 2 to 5 postoperatively were associated with 2-year mortality; however, neither hemoglobin concentration nor number of transfusions were associated with mental or psychomotor developmental indices. The number of transfusions on day 2 to 5 postoperatively was associated with ventilator days in multiple variable analysis (effect size, 1.85; 95% CI, 0.33 to 3.36; p = 0.018)., Conclusions: This single-center cohort study found transfusion was not associated with improved outcomes in neonates undergoing Norwood operations., (Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to assess the 5-year neurocognition and health of an interprovincial inception cohort undergoing the arterial switch operation for transposition of the great arteries., Methods: Sixty-nine consecutive neonates had operations from 1996-2003 with full-flow cardiopulmonary bypass and selective deep hypothermic circulatory arrest. Outcomes were recorded at 58 +/- 9 months of age. Univariate and multivariate analyses were used to identify outcome predictors, including surgical subtype and preoperative, operative, and postoperative variables., Results: There was 1 (1.5%) operative death. Two children were lost to follow-up, and 1 was excluded because of postdischarge meningitis. Outcomes are reported for 65 survivors. Two (3%) children have cerebral palsy, and 7 (11%) have language disorders, 4 of whom also meet the criteria for autism spectrum disorder. Two of the 4 children with autism have an affected older sibling. Of the 61 children without autism, scores approach those of peers, with a full-scale intelligence quotient of 97 +/- 16, a verbal intelligence quotient of 97 +/- 18, a performance intelligence quotient of 96 +/- 15, and a visual-motor integration score of 95 +/- 16. Mother's education, birth gestation or weight, and postoperative plasma lactate values account for 21% to 32% of the variance of these scores. Septostomy adds 7% to the variance of visual-motor integration scores., Conclusions: Most preschool children do well after surgical correction for transposition of the great arteries, including complex forms. Potentially modifiable variables include high preoperative plasma lactate levels and septostomy. A minority of children were given diagnoses of language disorders, including autism, in which familial factors likely contribute to outcome.

Objective: Comprehensive outcome assessment of children receiving cardiac extracorporeal life support., Methods: From 2000 to 2004, 39 consecutive children (aged 1 day to 4.4 years) had cardiac extracorporeal life support. Neurodevelopmental follow-up of all survivors was performed more than 6 months after life support (aged 53 +/- 12 months). Developmental delay was defined as a score of less than 70 on the Bayley Scales of Infant Development II or Wechsler Preschool and Primary Scale of Intelligence. Predictor variables for mortality (at 2 years' follow-up) and delay were examined by univariate and multivariate analyses., Results: Indications for extracorporeal life support were progressive low cardiac output in 14 (36%), failed weaning from cardiopulmonary bypass in 13 (33%), cardiac arrest in 9 (23%), and hypoxia in 3 (8%). Cardiac anatomy was single ventricle in 16 (41%), biventricular in 21 (54%), and myocarditis in 2 (5%). Survival was 18 (46%) at hospital discharge and 16 (41%) at 2 years. In survivors, mental score was 73 +/- 16 (normal 100 +/- 15), and 8 (50%) had mental delay. Initiating extracorporeal life support during cardiopulmonary resuscitation and duration of this resuscitation were not associated with death or mental delay. On multivariable Cox regression, lactate on admission to the pediatric intensive care unit (hazard rate 1.13; 95% confidence intervals 1.08-1.27) and single ventricle anatomy (hazard rate 3.93; 95% confidence intervals 1.62-9.49) were associated with death at 2 years. Stepwise multiple regression found time for lactate to normalize on extracorporeal life support, highest inotrope score during 120 hours of life support, and chromosomal abnormality explained 76.7% of the variance in mental score., Conclusion: Cardiac extracorporeal life support had a 41% 2-year survival. Potentially modifiable variables (time for lactate to normalize and highest inotrope score early during extracorporeal life support) explained 69% of mental score variance.