***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 
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    ***EXAMPLES*** 
    Input: Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury , but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth . This study reports a multicenter , r and omized , controlled , pilot trial of moderate systemic hypothermia ( 33 degrees C ) vs normothermia ( 37 degrees C ) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event . The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers , and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vinel and tests between normothermic and hypothermic groups . Thirty-two hypothermic and 33 normothermic neonates were enrolled . The entry criteria selected a severely affected group of neonates , with 77 % Sarnat stage III . Ten  hypothermia ( 10/32 , 31 % ) and 14 normothermia ( 14/33 , 42 % ) patients expired . Controlling for treatment group , outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers ( odds ratio 10.7 , 95 % confidence interval 1.3 - 90 ) . Severely abnormal motor scores ( Psychomotor Development Index < 70 ) were recorded in 64 % of normothermia patients and in 24 % of hypothermia patients . The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group ( 52 % ) than the normothermia group ( 84 % ) ( P = 0.019 ) . Although these results need to be vali date d in a large clinical trial , this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury OBJECTIVE To assess the safety of selective head cooling in birth-asphyxiated term newborn infants while maintaining the rectal temperature at 35.0 degrees C or 34.5 degrees C. METHODS Twenty-six term infants with Apgar < or=6 at 5 minutes or cord/first arterial pH < 7.1 , plus evidence of encephalopathy , were studied . After parental consent had been obtained , 13 infants received selective head cooling with the rectal temperature maintained at 35.0 degrees C in 6 infants and at 34.5 degrees C in 7 infants . The remaining 13 infants were normothermic . Cooling was achieved by circulating water at 10 degrees C through a cap placed around the head . Rectal , fontanelle , and nasopharyngeal temperatures were monitored . RESULTS One cooled infant died 2 days after rewarming , and 3 control infants died . Seizures occurred in 9 (69%)of 13 cooled infants and 5 ( 38 % ) of 13 control infants . Respiratory support within the first 72 hours of life was required in 10 of 13 infants in both the cooled and control groups . Three cooled infants and 1 control infant received nitric oxide for persistent pulmonary hypertension . During the same interval , 6 of the cooled infants and 4 of the control infants had episodes in which their blood pressure fell to < 40 mm Hg ; in 2 infants in each group , the lowest blood pressure was below 35 mm Hg . No requirement for volume expansion or increased inotropic support was seen in any infant during stepwise rewarming . All of the cooled infants demonstrated a fall in heart rate during cooling , but the rate was < 80/min in only 2 cases and no infant had a rate < 70/min . No infant demonstrated an abnormal rhythm or was clinical ly compromised by the change in heart rate . One infant cooled to a rectal temperature of 34.5 degrees C had a prolonged QT interval of 570 ms associated with a heart rate of 85/min on electrocardiogram aged 34 hours . This returned to normal after rewarming . Platelet counts below 150 x 10(9)/L , hypoglycemia below 2.6 mmol/L , and highest creatinine were not statistically different between cooled and control infants . Positive precooling blood cultures were found in 1 cooled and 1 control infant . The mean cap water input temperature used during cooling was 10 + /- 1 degrees C. During active cooling , the mean difference between rectal and nasopharyngeal temperature was 1.4 degrees C in the infants who were not receiving respiratory support , but this gradient could not be measured in those who were receiving respiratory support that involved delivery of warmed gases to the nasopharynx . CONCLUSIONS This study suggests that selective head cooling combined with mild systemic hypothermia of 34.4 degrees C or 35.0 degrees C is a stable , well-tolerated method of reducing cerebral temperature in term newborn infants after perinatal asphyxia In order to test the practicability and safety of whole-body cooling in term neonates with moderate-to-severe hypoxic-ischaemic encephalopathy ( HIE ) and to report outcomes , a prospect i ve pilot study was carried out in 25 term infants ( median postmenstrual age 38 weeks , range 36 to 41 weeks ; 20 males , five females ) .  Whole-body cooling , to a target core temperature of 33 to 34 degrees C , started within 6 hours of birth and was maintained for 72 hours . Of the 25 newborn infants ( 19 Sarnat II and six Sarnat III , 18 outborn ) , 18  survived  , including 13 ( 72 % ) with normal cerebral signal by MRI . Temperature instability occurred during cooling in 15 infants , but neither severe haemodynamic instability nor renal failure was seen . Thrombocytopenia developed in 12 infants , including seven with biological disseminated intravascular coagulation . One patient had hypoxaemia with right-to-left shunting through the ductus arteriosus , and seven had limited meningeal or subdural bleeding .  Whole-body cooling is feasible in term neonates , with no life-threatening adverse events . Improvements are needed to obtain stable hypothermia for 72 hours Hypoxic-ischemic encephalopathy ( HIE ) remains one of the most important neurologic complications in the newborn . Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage . Furthermore , recent data have suggested that platelet-activating factor ( PAF ) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury . The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia . In addition , we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid ( CSF ) after hypoxic-ischemic brain injury . The group of asphyxiated infants ( Group 1 ) consisted of 21 full-term ( gestational age > 37 weeks ) . These infants were r and omized and divided into either a st and ard therapy group ( Group 1a ; n=10 ) or cooling group ( Group 1b ; n=11 ) . Head cooling combined with minimal hypothermia ( rectal temperature 36.5 - 36 degrees C ) was started as soon as practicable after birth . The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h . The control group ( Group 2 ) consisted of seven full-term infants and none of these infants showed any sign of asphyxia . To measure PAF concentration in CSF , CSF with lumbar puncture was collected into tubes immediately before the cooling ( 1 - 3h after birth ) and again after 36h . We had no evidence of severe adverse events related to hypothermia . In Group 1a , two infants died after 72h of life ; however , all newborn infants in Group 1b survived . Convulsion required treatment in three infants of st and ard therapy group ( 1a ) ; none of the infants in Group 1b had clinical seizure activity . Abnormal EEG patterns were found in four infants of Group 1a ; no EEG abnormalities were noted in Group 1b ( P<0.05 ) . On admission ( before cooling ) , PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control ( P<0.001 ) . Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups ( Group 1a vs. 1b ) ( P>0.05 ) . Obtained PAF level in CSF after 36h , showed a profound decline in cooling group of infants compared to Group 1a infants ( P<0.01 ) . In conclusion , the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging . Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants Twenty-six infants with hypoxic-ischemic encephalopathy ( HIE ) were r and omized to normothermia or to systemic hypothermia . The hypothermia group had less cortical gray matter signal abnormality on magnetic resonance imaging ( MRI ) ( 1/12 vs 7/14 infants in the normothermic group ; P = .036 ) , which may indicate differing regional benefit from systemic hypothermia Background . There is extensive experimental evidence to support the investigation of treatment with mild hypothermia after birth asphyxia . However , clinical studies have been delayed by the difficulty in predicting long-term outcome very soon after birth and by concern about adverse effects of hypothermia . Objectives . The objectives of this study were to determine whether it is feasible to select infants with a bad neurological prognosis and to begin hypothermic therapy within 6 hours of birth , and to observe the effect of this therapy on relevant physiologic variables . Methods . Sixteen newborn infants with clinical features of birth asphyxia ( median cord blood pH : 6.74 ; range : 6.58–7.08 ) were assessed by amplitude integrated electroencephalography ( aEEG ) , and mild whole body hypothermia was instituted within 6 hours of birth in the 10 infants with an aEEG prognostic of a bad outcome .  Rectal temperature was maintained at 33.2 ± ( st and ard deviation ) .6 ° C for 48 hours . Rectal and tympanic membrane temperature , blood pressure , heart rate , blood gases , blood lactate , full blood count , blood electrolytes , high and low shear rate viscosity , and coagulation studies were monitored during and after cooling . A preliminary assessment of neurological outcome was made by repeated magnetic resonance imaging ( MRI ) and neurological examination . Results . All infants selected to receive hypothermia developed convulsions and a severe encephalopathy . During 48 hours of hypothermia infants had prolonged metabolic acidosis ( median pH : 7.30 ; base excess : −6.3 mmol · L− 1 , a high blood lactate ( median lactate : 5.3 mmol · L− 1 ) and low blood potassium levels ( median value : 3.9 mmol · L− 1 ) . Hypothermia was associated with lower heart rate and higher mean blood pressure . However , these changes did not seem to be clinical ly relevant and no significant complication of hypothermia was encountered . Blood viscosity and coagulation studies were similar during and after cooling . Unusual MRI findings were noted in 3 infants : transverse sinus thrombosis with subsequent small cerebellar infa rct ; probable thrombosis in the straight sinus ; and hemorrhagic cerebral infa rct ion . Six of the 10 cooled infants had minor abnormalities only or normal follow-up neurological examination ; 3 infants died and 1 had major abnormalities . None of the 6 infants with a normal aEEG developed severe neonatal encephalopathy or neurological sequel . Conclusions . After birth asphyxia infants can be objective ly selected by aEEG and hypothermia started within 6 hours of birth in infants at high risk of developing severe neonatal encephalopathy . Prolonged mild hypothermia to 33 ° C to 34 ° C is associated with minor physiologic abnormalities . Further studies of both the safety and efficacy of mild hypothermia , including further neuroimaging studies , are warranted Aims . To determine the practicality and safety of head cooling with mild or minimal systemic hypothermia in term neonates with moderate to severe hypoxic-ischemic encephalopathy . Methods . Study group infants ≥37 weeks ' gestation , who had an umbilical artery pH ≤7.09 or Apgars ≤6 at 5 minutes , plus evidence of encephalopathy . Infants with major congenital abnormalities were excluded . Trial Design . Infants were r and omized to either no cooling ( controls ; rectal temperature = 37.0 ± 0.2 ° C , n = 10 ) or sequentially , either minimal systemic cooling ( rectal temperature = 36.3 ± 0.2 ° C , n = 6 ) or mild systemic cooling ( rectal temperature =  
    Output:
    
Cardiac arrhythmias and thrombocytopenia were more common with hypothermia ; however , they were clinical ly benign .
In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy , hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention