***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: Background — Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome ( no , or nondisabling , symptoms ) . Any improvement in functional outcome distribution has value , and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay , age , and stroke severity . Methods — Prespecified pooled analysis of 6756 patients from 9 r and omized trials comparing alteplase versus placebo/open control . Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay , age , stroke severity , and relevant interaction term(s ) . Results — Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset , with a greater benefit with earlier treatment . Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation . For the observed case mix of patients treated within 4.5 hours of stroke onset ( mean 3 hours and 20 minutes ) , the net absolute benefit from alteplase ( ie , the difference between those who would do better if given alteplase and those who would do worse ) was 55 patients per 1000 treated ( 95 % confidence interval , 13–91 ; P=0.004 ) . Conclusions — Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum , including the over 80s and across all severities of stroke studied ( top versus bottom fifth means : 22 versus 4 ) ; the earlier that treatment is initiated , the greater the benefit Background and Purpose — Remote ischemic preconditioning is a phenomenon by which a short period of sublethal ischemia to an organ protects against subsequent ischemia in another organ . We have recently demonstrated that remote ischemic conditioning by transient hind limb ischemia delivered during ischemia and before reperfusion can provide potent cardioprotection , a phenomenon we termed per-conditioning . This study evaluated whether remote ischemic per-conditioning may provide neuroprotection in a clinical ly relevant rat model of acute ischemic stroke . Methods — Remote ischemic conditioning by transient limb ischemia was used in a rat transient middle cerebral artery occlusion model of acute stroke . A total of 39 P60 rats were r and omly allocated to receive preconditioning , per-conditioning , or sham conditioning . Cerebral ischemia was maintained for 120 minutes followed by reperfusion . The result ing infa rct size at 24 hours was quantified using computerized image analysis of 2–3 - 5-triphenyl tetrazolium chloride-stained brain sections . Results — Compared with control , both pre- and per-conditioning significantly reduced brain infa rct size with the more clinical ly relevant per-conditioning stimulus being superior to preconditioning . Conclusions — Remote per-conditioning by transient limb ischemia is a facile , clinical ly relevant stimulus that provides potent neuroprotection in a model of regional brain ischemia – reperfusion injury . Further studies are required to better underst and the mechanisms and biology of this response before translation to r and omized controlled trials of remote per-conditioning for acute ischemic stroke Background and Purpose — Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia . We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke . Methods — Open-label blinded outcome proof-of-concept study of prehospital , paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke . After neurological examination and MRI , patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months . The primary end point was penumbral salvage , defined as the volume of the perfusion – diffusion mismatch not progressing to infa rct ion after 1 month . Results — Four hundred forty-three patients were r and omized after provisional consent , 247 received rPerC and 196 received st and ard treatment . Patients with a nonstroke diagnosis ( n=105 ) were excluded from further examinations . The remaining patients had transient ischemic attack ( n=58 ) , acute ischemic stroke ( n=240 ) , or hemorrhagic stroke ( n=37 ) . Transient ischemic attack was more frequent ( P=0.006 ) , and National Institutes of Health Stroke Scale score on admission was lower ( P=0.016 ) in the intervention group compared with controls . Penumbral salvage , final infa rct size at 1 month , infa rct growth between baseline and 1 month , and clinical outcome after 3 months did not differ among groups . After adjustment for baseline perfusion and diffusion lesion severity , voxelwise analysis showed that rPerC  reduced tissue risk of infa rct ion ( P=0.0003 ) . Conclusions — Although the overall results were neutral , a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects . Future clinical trials should take such immediate effects , and their duration , into account . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00975962 Background One or more brief episodes of coronary artery occlusion protect or “ precondition ” the myocardium perfused by that artery from a subsequent episode of sustained ischemia . We sought to determine whether ischemic preconditioning protects only those myocytes subjected to brief coronary occlusion or whether brief occlusions in one vascular bed also limit infa rct size and for attenuate contractile dysfunction in remote virgin myocardium subjected to subsequent sustained coronary occlusion . Methods and Results In the preliminary limb of the study , six anesthetized dogs underwent four episodes of 5-minute circumflex branch occlusion plus 5-minute reperfusion , followed by 1 hour of sustained left anterior descending coronary artery occlusion and 4.5 hours of reflow . Subendocardial blood flow during left anterior descending coronary artery occlusion ( measured by injection of radiolabeled microspheres ) was 0.07±0.03 mL. min-1 . g tissue-1 , similar to the value of 0.07±0.02 mL. min-1 . g-1 observed in a group of eight concurrent control dogs . However , infa rct size ( assessed by triphenyltetrazolium staining ) in the circumflex preconditioned group averaged 4±1 % of the myocardium at risk , significantly less ( p<0.05 ) than the value of 13 + 4 % observed in the concurrent controls . An additional 18 dogs were then r and omized to undergo either four episodes of circumflex branch occlusion ( n=8 ) or no intervention ( n=10 ) before 1 hour of left anterior descending coronary artery occlusion and 4.5 hours of reflow . Subendocardial blood flow averaged 0.08±0.02 versus 0.08±0.03 mL. min-1 . g-1 in the control versus circumflex preconditioned groups , yet infa rct size was significantly smaller in circumflex preconditioned dogs than in the controls ( 6±2 % versus 16±5 % of the risk region ; p<0.05 ) . At 4.5 hours following reperfusion , segment shortening in the left anterior descending coronary artery bed ( assessed by sonomicrometry ) averaged -21 + 19%o of baseline in control animals versus 13±12 % of baseline in the preconditioned group ( p = NS ) . Circumflex preconditioning did not , however , have an independent beneficial effect on contractile function : Regression analysis revealed that the trend toward improved function in circumflex preconditioned dogs reflected the smaller infa rct sizes in this group . Conclusions Brief episodes of ischemia in one vascular bed protect remote , virgin myocardium from subsequent sustained coronary artery occlusion in this canine model . These data imply that preconditioning may be mediated by factor(s ) activated , produced , or transported throughout the heart during brief ischemia/reperfusion Background — Myocyte necrosis as a result of elective percutaneous coronary intervention ( PCI ) occurs in approximately one third of cases and is associated with subsequent cardiovascular events . This study assessed the ability of remote ischemic preconditioning ( IPC ) to attenuate cardiac troponin I ( cTnI ) release after elective PCI . Methods and Results — Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited . Subjects were r and omized to receive remote IPC ( induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm , followed by 5-minute intervals of reperfusion ) or control ( an uninflated cuff around the arm ) before arrival in the catheter laboratory . The primary outcome was cTnI at 24 hours after PCI . Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months . The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group ( 0.06 versus 0.16 ng/mL ; P=0.040 ) . After remote IPC  , cTnI was < 0.04 ng/mL in 44 patients ( 42 % ) compared with 24 in the control group ( 24 % ; P=0.01 ) . Subjects who received remote IPC experienced less chest discomfort ( P=0.0006 ) and ECG ST-segment deviation ( P=0.005 ) than control subjects . At 6 months , the major adverse cardiac and cerebral event rate was lower in the remote IPC group ( 4 versus 13 events ; P=0.018 ) . Conclusion — Remote IPC reduces ischemic chest discomfort during PCI , attenuates procedure-related cTnI release , and appears to reduce subsequent cardiovascular events A pilot r and omized controlled trial that evaluated the effect of remote ischemic preconditioning ( RIPC ) on clinical outcomes following major vascular surgery was performed . Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair , endovascular aortic aneurysm repair , carotid endarterectomy , and lower limb revascularization procedures . Patients were r and omized to RIPC or to control groups .  The primary outcome was a composite clinical end point comprising any of cardiovascular death , myocardial infa rct ion , new-onset arrhythmia , cardiac arrest , congestive cardiac failure , cerebrovascular accident , renal failure requiring renal replacement therapy , mesenteric ischemia , and urgent cardiac revascularization . Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values . The primary outcome occurred in 19 ( 19.2 % ) of 99 controls and 14 ( 14.1 % ) of 99 RIPC group patients ( P = .446 ) . There were no significant differences in secondary outcomes . Our trial generated data that will guide future trials . Further trials are urgently needed BACKGROUND Management of traumatic brain injury ( TBI ) is focused on preventing secondary brain injury . Remote ischemic conditioning ( RIC ) is an established treatment modality that has been shown to improve patient outcomes secondary to inflammatory insults . The aim of our study was to assess whether RIC in trauma patients with severe TBI could reduce secondary brain injury . METHODS This prospect i ve consented interventional trial included all TBI patients admitted to our Level 1 trauma center with an intracranial hemorrhage and a Glasgow Coma Scale ( GCS ) score of 8 or lower on admission . In each patient , four cycles of RIC were performed within 1 hour of admission . Each cycle consisted of 5 minutes of controlled upper limb ( arm ) ischemia followed by 5 minutes of reperfusion using a blood pressure cuff .  Serum biomarkers of acute brain injury , S-100B , and neuron-specific enolase ( NSE ) were measured at 0 , 6 , and 24 hours . Outcome measure was reduction in the level of serum biomarkers after RIC . RESULTS A total of 40 patients ( RIC , 20 ; control , 20 ) were enrolled . The mean ( SD ) age was 46.15 ( 18.64 ) years , the median GCS score was 8 ( interquartile range , 3–8 ) , and the median head Abbreviated Injury Scale ( AIS ) score was 3 ( interquartile range , 3–5 ) , and there was no difference between the RIC and control groups in any of the baseline demographics or injury characteristics including the type and size of intracranial bleed or skull fracture patterns . There was no difference in the 0-hour S-100B ( p = 0.9 ) and NSE ( p = 0.72 ) level between the RIC and the control group . There was a significant reduction in the mean levels of S-100B ( p = 0.01 ) and NSE ( p = 0.04 ) at 6 hours and 24 hours in comparison with the 0-hour level in the RIC group . CONCLUSION This study showed that RIC significantly decreased the st and ard biomarkers of acute brain injury in patients with severe TBI . Our study highlights the novel therapeutic role of RIC for preventing secondary brain insults in TBI patients . LEVEL OF EVIDENCE Therapeutic study , level III Purpose — The aim of this guideline is to provide a focused up date of the current 
    Output:
    
AUTHORS ' CONCLUSIONS We found low- quality evidence that RIC may reduce the risk of recurrent stroke in participants with intracerebral artery stenosis and reduce stroke severity in participants undergoing carotid stenting , but it may increase death or dependence in participants with acute ischaemic stroke who are undergoing intravenous thrombolysis .