***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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    Input: BACKGROUND A substantial minority of neurologically normal children with sickle cell disease have lesions consistent with cerebral infa rct ion as seen on magnetic resonance imaging ( MRI ) . OBJECTIVES To determine if transfusion therapy affects the rate at which silent infa rcts develop and to evaluate the contribution of MRI of the brain to stroke prediction by transcranial Doppler ( TCD ) ultrasonography . STUDY DESIGN Children with elevated TCD ultrasonographic velocity were r and omized to receive long-term transfusion therapy or st and ard care .  Magnetic resonance imaging of the brain was obtained at r and omization , annually , and with clinical neurologic events . The risk for new silent lesions and /or stroke was compared for each treatment arm . RESULTS Among the 37 % of subjects with silent infa rcts , those receiving st and ard care were significantly more likely to develop new silent lesions or stroke than were those who received transfusion therapy . For subjects receiving st and ard care , those with lesions at baseline were significantly more likely to develop stroke or new silent lesions than those whose MRI studies showed no abnormality . CONCLUSIONS Transfusion therapy lowers the risk for new silent infa rct or stroke for children having both abnormal TCD ultrasonographic velocity and silent infa rct . However , those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infa rct or stroke than are those whose initial MRI showed no abnormality . The finding of a silent infa rct reinforces the need for TCD ultrasonographic screening and consideration of transfusion therapy if the abnormalities are seen . Similarly , elevated TCD ultrasonographic velocity warrants MRI of the brain because children with both abnormalities seem to be at increased risk for developing new silent infa rct or stroke Although long-term transfusion therapy is at least 90 % effective in preventing recurrent strokes after an initial cerebrovascular accident in patients with sickle cell disease , it is unknown how long transfusion therapy should be continued . To address this question , we prospect ively discontinued transfusions  in 10 patients with sickle cell disease whose median duration of transfusion therapy after an initial stroke was 9 1/2 years ( range 5 to 12 years ) . Before the transfusions were discontinued , patients were examined by  cerebral angiography , magnetic resonance imaging of the head , neuropsychologic testing , electroencephalography  , and a complete neurologic examination . Within 12 months after transfusion therapy was stopped , 5 of 10 patients had had an ischemic event . Three events caused relatively mild deficits in the same areas as those originally affected . Two were associated with massive intracranial hemorrhage , including one on the contralateral side of original involvement . An additional patient died suddenly of unknown causes . Of the four remaining patients , three declined to resume transfusion and are relatively well at greater than or equal to 18 months after therapy was stopped . The studies performed before transfusions were stopped were not predictive of recurrent stroke . The risk of recurrent cerebrovascular accident in this group was significantly greater than the estimated risk of 10 % in patients who are receiving long-term transfusion therapy  ( p = 0.002 ) . This adverse outcome suggests that patients with sickle cell disease who have had a stroke must receive long-term transfusion indefinitely or a suitable therapeutic alternative must be devised OBJECTIVE The Stroke Prevention Trial ( STOP ) demonstrated that chronic transfusion is highly effective in reducing the risk of stroke in children with sickle-cell disease and an abnormal transcranial Doppler ultrasonography examination result . Our objective was to determine whether chronic transfusion therapy reduces the incidence of pain and acute chest syndrome . METHODS During STOP , 130 children with sickle-cell anemia or sickle beta(0)-thalassemia and abnormal transcranial Doppler ultrasonography examination result were r and omly assigned to chronic transfusion  ( n = 63 ) or observation ( n = 67 ) . In addition to monitoring for stroke , nonneurologic sickle-cell complications were identified and recorded . RESULTS Mean age at STOP study entry was 8.3 + /- 3.3 years , and mean follow-up was 19.6 + /- 6.5 months . Hospitalization rates ( based on intent-to-treat analysis ) for acute chest syndrome were 4.8 and 15.3 per 100 patient-years ( P = .0027 ) and for pain were 16.2 and 27.6 per 100 patient-years ( P = .13 ) in the chronic transfusion and observed groups , respectively . If analyzed according to treatment actually received , the difference in pain rate becomes significant ( 9.7 vs 27.1 events per 100 patient-years , P = .014 ) , and transfusion remains protective from acute chest syndrome ( 2.2 vs 15.7 events per 100 patient-years , P = .0001 ) . CONCLUSIONS Compliance with aggressive chronic transfusion reduces the frequency of acute chest syndrome and pain episodes BACKGROUND Blood transfusions prevent recurrent stroke in children with sickle cell anemia , but the value of transfusions in preventing a first stroke is unknown . We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then r and omly assigned them to receive st and ard care or transfusions to prevent a first stroke . METHODS To enter the study , children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher . The patients were r and omly assigned to receive st and ard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration . The incidence of stroke ( cerebral infa rct ion or intracranial hemorrhage ) was compared between the two groups . RESULTS A total of 130 children ( mean [ + /-SD ] age , 8.3+/-3.3 years ) were enrolled ; 63 were r and omly assigned to receive transfusions and 67 to receive st and ard care . At base line , the transfusion group had a slightly lower mean hemoglobin concentration ( 7.2 vs. 7.6 g per deciliter , P=0.001 ) and hematocrit ( 20.4 vs. 21.7 percent , P=0.002 ) . Ten patients dropped out of the transfusion group , and two patients crossed over from the st and ard-care group to the transfusion group . There were 10 cerebral infa rct ions and 1 intracerebral hematoma in the st and ard-care group , as compared with 1 infa rct ion in the transfusion group -- a 92 percent difference in the risk of stroke ( P<0.001 ) . This result led to the early termination of the trial . CONCLUSIONS Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography OBJECTIVE To determine the effect of a transfusion program on risk of stroke recurrence in children with sickle cell disease . DESIGN The clinical course and experience with transfusion therapy at eight centers were review ed for subjects whose initial stroke occurred after January 1988 . RESULTS Sixty subjects were observed for 191.7 patient-years . Eight had a single recurrent stroke ( two intracranial hemorrhages and six infa rct ions ) for a prevalence of 13.3 % , or one recurrence for each 24 patient-years of observation . Thirteen subjects had 15 transient neurologic events ; two of these had subsequent strokes , but the overall risk was similar for those who did and those did not have transient events . Hemoglobin S levels were greater than the desired maximum of 30 % at the time of 7 of 16 transient events and five of six recurrent infa rct ions . The stroke recurrence rate was similar to those in previous reports of children receiving long-term transfusion therapy  but significantly less than that reported for children who did not receive transfusions ( p < 0.001 ) . CONCLUSIONS We conclude that maintenance of hemoglobin S at a level less than 30 % appears to be effective in reducing the rate of recurrent infa rct ion but does not prevent transient neurologic events . Transient neurologic events are common but do not appear to be related to recurrent stroke The stroke prevention study in sickle cell disease ( STOP ) demonstrated a 90 % reduction in stroke risk with transfusion  among patients with time-averaged mean cerebral blood velocity ( TAMV ) of 200 cm/s or more as measured by transcranial Doppler ( TCD ) . In STOP , 232 brain magnetic resonance angiograms ( MRAs ) were performed on 100 patients , 47 in the transfusion arm and 53 in the st and ard care arm . Baseline MRA findings were interpreted as normal in 75 patients and as indicating mild stenosis in 4 patients and severe stenosis in 21 patients . Among 35 patients who underwent magnetic resonance angiography within 30 days of r and om assignment , the TAMV was significantly higher in 7 patients with severe stenosis compared with 28 patients with normal MRA findings or mild stenosis ( 276.7 + /- 34 vs 215 + /- 15.6 cm/s ; P<.001 ) . In the st and ard care arm , 4 of 13 patients with abnormal MRA findings had strokes compared with 5 of 40 patients with normal MRA findings ( P=.03 ) . In this arm , TAMV became normal ( less than 170 cm/s ) or conditional ( 170 - 199 cm/s ) in 26 of 38 patients with normal or mildly abnormal baseline MRA but remained abnormal in 8 of 10 patients with severely abnormal baseline MRA . These results suggest that TCD often detects flow abnormalities indicative of stroke risk before MRA lesions become evident . Furthermore , patients with abnormal MRA findings and higher TCD velocities are at higher risk for stroke , and their cerebral TAMVs are unlikely to decrease without transfusion Stroke occurs in 7 - 8 % of children with Sickle Cell Disease ( Hb SS ) and is a major cause of morbidity . Rates of recurrence have been reduced from 46 - 90 % to less than 10 % through chronic blood transfusions . Prevention of first stroke , however , would be preferable because even one stroke can cause irreversible brain injury . Transcranial Doppler ( TCD ) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk . By combining TCD screening and a potentially effective treatment , first stroke may be prevented . The Stroke Prevention Trial in Sickle Cell Anemia ( STOP ) is the first stroke prevention trial in Hb SS and the first r and omized , controlled use of transfusion in Hb SS . This multi-center trial is design ed to test whether reducing sickle hemoglobin to 30 % or less with periodic blood transfusions will reduce first-time stroke by at least 70 % compared to st and ard care . Primary endpoints will be clinical ly evident symptoms of cerebral infa rct ion with consistent findings on Magnetic Resonance Imaging and Angiography ( MRI/MRA ) or symptomatic intracranial hemorrhage . Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints . The design calls for a 6-month start-up interval , 18 months of TCD screening and r and omization , and observation for stroke from entry through month 54 . Key features of the trial are st and ardized TCD and MRI/MRA protocol s interpreted blindly , and blinded adjudication of endpoints . The sample size ( 60 per treatment group ) is based on prospect i ve data relating TCD velocity to risk of stroke . A time-averaged mean velocity of > or = 200 cm/sec is associated with a 46 % risk of cerebral infa rct ion over 39 months . The sample size is sufficient to detect 70 % reduction in the primary endpoint at 90 % power . This trial will determine if  transfusion  is effective in the primary prevention of stroke . Secondary aims may further the underst and ing of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS Purpose Chronic red cell transfusion has been used for prevention of recurrent stroke in patients with sickle cell disease for three decades , and its effectiveness in primary prevention was recently shown . Iron overload , the inevitable result of chronic transfusion , is commonly monitored with serum ferritin concentration . Patients and Methods Sixty-one patients at high risk for stroke received chronic transfusion in a clinical trial of stroke prevention . A serum ferritin level of less than 500 ng/mL was required for study entry . Ferritin levels were obtained quarterly . Fifty patients who had four or more ferritin measurements were included in this analysis . Transfusions were administered as exchange or simple , with washed , reconstituted , or packed red blood cells , at the discretion of the site investigator . Results Serum ferritin levels increased linearly with cumulative transfusion volume during the first four ferritin measurements , but the rate of increase varied widely among patients . Rates of increase varied similarly among 23 patients who received exclusively simple transfusion with packed red cells  and in five patients who received exchange transfusions . Thirty-two patients received a total transfusion volume of more than 250 mL/kg . Ferritin continued to increase linearly after the first four measurements in 14 , but the remaining 1 
    Output:
    
REVIEW ER 'S CONCLUSIONS While the included study demonstrated a significantly reduced risk of stroke in patients receiving regular blood transfusions  , the degree of risk must be balanced against the burden of a chronic transfusion regime .