***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE This pharmacologic protection trial was conducted to test the hypothesis that allopurinol , a scavenger and inhibitor of oxygen free radical production , could reduce death , seizures , coma , and cardiac events in infants who underwent heart surgery using deep hypothermic circulatory arrest ( DHCA ) .  DESIGN This was a single center , r and omized , placebo-controlled , blinded trial of allopurinol in infant heart surgery using DHCA .  Enrolled infants were stratified as having hypoplastic left heart syndrome ( HLHS ) and all other forms of congenital heart disease ( non-HLHS ) . Drug was administered before , during , and after surgery . Adverse events and the clinical efficacy endpoints death , seizures , coma , and cardiac events were monitored until infants were discharged from the intensive care unit or 6 weeks , whichever came first . RESULTS Between July 1992 and September 1997 , 350 infants were enrolled and 348 subsequently r and omized . A total of 318 infants ( 131 HLHS and 187 non-HLHS ) underwent heart surgery using DHCA . There was a nonsignificant treatment effect for the primary efficacy endpoint analysis ( death , seizures , and coma ) , which was consistent over the 2 strata . The addition of cardiac events to the primary endpoint result ed in a lack of consistency of treatment effect over strata , with the allopurinol treatment group experiencing fewer events ( 38 % vs 60 % ) in the entire HLHS stratum , compared with the non-HLHS stratum ( 30 % vs 27 % ) . In HLHS surgical survivors , 40 of 47 ( 85 % ) allopurinol-treated infants did not experience any endpoint event , compared with 27 of 49 ( 55 % ) controls . There were fewer seizures-only and cardiac-only events in the allopurinol versus placebo groups . Allopurinol did not reduce efficacy endpoint events in non-HLHS infants . Treated and control infants did not differ in adverse events . CONCLUSIONS Allopurinol provided significant neurocardiac protection in higher-risk HLHS infants who underwent cardiac surgery using DHCA . No benefits were demonstrated in lower risk , non-HLHS infants , and no significant adverse events were associated with allopurinol treatment.congenital heart defects , hypoplastic left heart syndrome , induced hypothermia , ischemia-reperfusion injury , neuroprotective agents , allopurinol , xanthine oxidase , free radicals , seizures , coma Background : It is unknown whether intraoperative hyperglycemia in infants is associated with worse neurodevelopmental outcomes after  low-flow cardiopulmonary bypass ( LF ) , deep hypothermic circulatory arrest ( CA ) , or both . Methods : In a data base review of a prospect i ve trial of 171 infants undergoing arterial switch for D-transposition of the great arteries who were r and omly assigned to predominately LF or CA , glucose was measured after induction ( T1 ) , 5 min after cardiopulmonary bypass onset ( T2 ) , at the onset of CA or LF ( T3 ) , 5 min after CPB resumption ( T4 ) , at rewarming to 32 ° C ( T5 ) , 10 min after cardiopulmonary bypass weaning ( T6 ) , and 90 min after CA or LF ( T7 ) . Outcomes included seizures , electroencephalographic findings , and neurodevelopmental evaluation at 1 , 4 , and 8 yr . Results : Glucose concentrations were affected by support strategy and age at surgery . Lower glucose in the entire group at T6–T7 tended to predict electroencephalographic seizures ( P = 0.06 and P = 0.007 ) but was not related to clinical seizures . Within the predominantly CA group , higher glucose did not correlate with worse outcomes . Rather , it was associated with more rapid electroencephalographic normalization of “ close burst ” and “ relative continuous ” activity at all times except T2 ( P ≤ 0.03 ) , a finding more pronounced in infants aged 7 days old or younger . Intraoperative serum glucose concentrations were unrelated to neurodevelopmental outcomes at ages 1 , 4 , and 8 yr . Conclusions : Low glucose after cardiopulmonary bypass tended to relate to electroencephalographic seizures and slower electroencephalogram recovery , independent of CA duration . High glucose concentrations were not associated with worse neurodevelopmental outcomes . Avoiding hypoglycemia may be preferable to restricting glucose in infants undergoing heart surgery OBJECTIVE : The goal was to examine biochemical , neurophysiologic , anatomic , and clinical changes associated with erythropoietin administration to neonates with hypoxic-ischemic encephalopathy ( HIE ) . METHODS : We conducted a prospect i ve case-control study with 45 neonates in 3 groups , a normal healthy group ( N = 15 ) , a HIE-erythropoietin group ( N = 15 ; infants with mild/moderate HIE who received human recombinant erythropoietin , 2500 IU/kg , subcutaneously , daily for 5 days ) , and a HIE-control group ( N = 15 ; did not receive erythropoietin ) .  Serum concentrations of nitric oxide ( NO ) were measured at enrollment for the normal healthy neonates and at enrollment and after 2 weeks for the 2 HIE groups . The 2 HIE groups underwent electroencephalography at enrollment and at 2 to 3 weeks .  Brain MRI  was performed at 3 weeks . Neurologic evaluations and Denver Developmental Screening Test II assessment s were performed at 6 months . RESULTS : Compared with normal healthy neonates , the 2 HIE groups had greater blood NO concentrations ( P < .001 ) . At enrollment , the 2 HIE groups did not differ in clinical severity , seizure incidence , NO concentrations , or electroencephalographic findings . At 2 weeks of age , electroencephalographic background s improved significantly ( P = .01 ) and NO concentrations decreased ( P < .001 ) in the HIE-erythropoietin group , compared with the HIE-control group ; MRI findings did not differ between groups . At 6 months of age , infants in the HIE-erythropoietin group had fewer neurologic ( P = .03 ) and developmental ( P = .03 ) abnormalities . CONCLUSION : This study demonstrates the feasibility of early administration of human recombinant erythropoietin to term neonates with HIE , to protect against encephalopathy Objectives To evaluate plasma brain specific proteins and cytokines as biomarkers of brain injury in newborns with hypoxic‐ischemic encephalopathy ( HIE ) and , secondarily , to assess the effect of erythropoietin ( Epo ) treatment on the relationship between biomarkers and outcomes . Study design A study of c and i date brain injury biomarkers was conducted in the context of a phase II multicenter r and omized trial evaluating Epo for neuroprotection in HIE . Plasma was collected at baseline ( < 24 hours ) and on day 5 . Brain injury was assessed by magnetic resonance imaging ( MRI ) and neurodevelopmental assessment s at 1 year . The relationships between Epo , brain‐specific proteins ( S100B , ubiquitin carboxy‐terminal hydrolase‐L1 [ UCH‐L1 ] , total Tau , neuron specific enolase ) , cytokines ( interleukin [IL]‐1&bgr ; , IL‐6 , IL‐8 , IL‐10 , IL‐12P70 , IL‐13 , interferon‐gamma [ IFN‐&ggr ; ] , tumor necrosis factor alpha [ TNF‐&agr ; ] , brain‐derived neurotrophic factor [ BDNF ] , monocyte chemoattractant protein‐1 ) , and brain injury were assessed . Results In 50 newborns with encephalopathy , elevated baseline S100B , Tau , UCH‐L1 , IL‐1&bgr ; , IL‐6 , IL‐8 , IL‐10 , IL‐13 , TNF‐&agr ; , and IFN‐&ggr ; levels were associated with increasing brain injury severity by MRI . Higher baseline Tau and lower day 5 BDNF were associated with worse 1 year outcomes . No statistically significant evidence of Epo treatment modification on biomarkers was detected in this small cohort . Conclusions Elevated plasma brain‐specific proteins and cytokine levels in the first 24 hours of life are associated with worse brain injury by MRI in newborns with HIE . Only Tau and BDNF levels were found to be related to neurodevelopmental outcomes . The effect of Epo treatment on the relationships between biomarkers and brain injury in HIE requires further study . Trial registration Clinical Trials.gov : 01913340 Objective : Infants are potentially more susceptible to cell death mediated via glutamate excitotoxicity attributed to cardiopulmonary bypass . We hypothesized that ketamine , via N-methyl D-aspartate receptor blockade and anti-inflammatory effects , would reduce central nervous system injury during cardiopulmonary bypass . Methods : We r and omized 24 infants , without chromosomal abnormalities , to receive ketamine ( 2 mg/kg , n = 13 ) or placebo ( saline , n = 11 ) before cardiopulmonary bypass for repair of ventricular septal defects . Plasma markers of inflammation and central nervous system injury were compared at the end of surgery , and 6 , 24 , and 48 hrs after surgery . Magnetic resonance imaging and spectroscopy before cardiopulmonary bypass and at the time of hospital discharge were performed in a subset of cases and controls ( n = 5 in each group ) . Cerebral hemodynamics were monitored postoperatively using near-infrared spectroscopy , and neurodevelopmental outcomes were assessed using Bayley Scales of Infant Development-II before and 2–3 wks after surgery . Results : Statistically significant differences were noted in preoperative inspired oxygen levels , intraoperative cooling and postoperative temperature , respiratory rate , platelet count , and bicarbonate levels . The peak concentration of C-reactive protein was lower in cases compared to controls at 24 hrs ( p = .048 ) and 48 hrs ( p = .001 ) . No significant differences were noted in the expression of various cytokines , chemokines , S100 , and neuron-specific enolase between the cases and controls . Magnetic resonance imaging with spectroscopy studies showed that ketamine administration led to a significant decrease in choline and glutamate plus glutamine/creatine in frontal white matter . No statistically significant differences occurred between pre- and postoperative Bayley Scales of Infant Development-II scores . Conclusions : We did not find any evidence for neuroprotection or neurotoxicity in our pilot study . A large , adequately powered r and omized control trial is needed to discern the central nervous system effect of ketamine on the developing brain . brain . Trial Registration : The trial is registered at www . Clinical Trials.gov , NCT00556361 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE : The purpose of this study was to evaluate the efficacy and safety of erythropoietin in neonatal hypoxic-ischemic encephalopathy ( HIE ) , by using a r and omized , prospect i ve study design . METHODS : A total of 167 term infants with moderate/severe HIE were assigned r and omly to receive either erythropoietin ( N = 83 ) or conventional treatment ( N = 84 ) . Recombinant human erythropoietin , at either 300 U/kg ( N = 52 ) or 500 U/kg ( N = 31 ) , was administered every other day for 2 weeks , starting < 48 hours after birth . The primary outcome was death or disability . Neurodevelopmental outcomes were assessed at 18 months of age . RESULTS : Complete outcome data were available for 153 infants . Nine patients dropped out during treatment , and 5 patients were lost to follow-up monitoring . Death or moderate/severe disability occurred for 35 ( 43.8 % ) of 80 infants in the control group and 18 ( 24.6 % ) of 73 infants in the erythropoietin group ( P = .017 ) at 18 months . The primary outcomes were not different between the 2 erythropoietin doses . Subgroup analyses indicated that erythropoietin improved long-term outcomes only for infants with moderate HIE ( P = .001 ) and not those with severe HIE ( P = .227 ) . No negative hematopoietic side effects were observed . CONCLUSION : Repeated , low-dose , recombinant human erythropoietin treatment reduced the risk of disability for infants with moderate HIE , without apparent side effects Background — Complex neonatal cardiac surgery is associated with cerebral injury . In particular , aortic arch repair , requiring either deep hypothermic circulatory arrest ( DHCA ) or ante grade cerebral perfusion ( ACP ) , entails a high risk of perioperative injury . It is unknown whether ACP results in less cerebral injury than D 
    Output:
    
Erytropoietin , ketamine and dextromethorphan  showed no neuroprotective effects .
Conclusions : Allopurinol seems promising for future trials in congenital heart disease infants to reduce brain injury given the early neuroprotective effects in hypoplastic left heart syndrome infants .