***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: Since initial reports of its association with ischemic stroke appeared in 1988 , there has been continued controversy regarding the existence and strength of the association between patent foramen ovale ( PFO ) and ischemic stroke . Many case-control studies have reported an association between incident cryptogenic ischemic stroke and PFO , yet population -based studies have failed to confirm this association . Studies of the risk of recurrent stroke in patients with cryptogenic stroke with or without PFO have not shown an increased risk of recurrent stroke in patients with PFO . Meanwhile , use of devices to close PFOs and atrial septal defects percutaneously has increased dramatically since their introduction . Completion of the r and omized clinical trials of PFO closure currently in progress is vital to determine if the benefits of PFO closure in cryptogenic stroke outweigh its risks BACKGROUND Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown . We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age . METHODS In this prospect i ve , multicenter , r and omized , event-driven trial , we r and omly assigned patients , in a 1:1 ratio , to medical therapy alone or closure of the patent foramen ovale . The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated . RESULTS We enrolled 980 patients ( mean age , 45.9 years ) at 69 sites . The medical-therapy group received one or more antiplatelet medications ( 74.8 % ) or warfarin ( 25.2 % ) . Treatment exposure between the two groups was unequal ( 1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group , P=0.009 ) owing to a higher dropout rate in the medical-therapy group . In the intention-to-treat cohort , 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke ( hazard ratio with closure , 0.49 ; 95 % confidence interval [ CI ] , 0.22 to 1.11 ; P=0.08 ) . The between-group difference in the rate of recurrent stroke was significant in the prespecified per- protocol cohort ( 6 events in the closure group vs. 14 events in the medical-therapy group ; hazard ratio , 0.37 ; 95 % CI , 0.14 to 0.96 ; P=0.03 ) and in the as-treated cohort ( 5 events vs. 16 events ; hazard ratio , 0.27 ; 95 % CI , 0.10 to 0.75 ; P=0.007 ) . Serious adverse events occurred in 23.0 % of the patients in the closure group and in 21.6 % in the medical-therapy group ( P=0.65 ) . Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group ( 4.2 % ) , but the rate of atrial fibrillation or device thrombus was not increased . CONCLUSIONS In the primary intention-to-treat analysis , there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic  ischemic stroke . However , closure was superior to medical therapy alone in the prespecified per- protocol and as-treated analyses , with a low rate of associated risks . ( Funded by St. Jude Medical ; RESPECT Clinical Trials.gov number , NCT00465270 . ) Background and Purpose The etiology of ischemic stroke affects prognosis , outcome , and management . Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke . A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) . Methods A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies . “ Possible ” and “ probable ” diagnoses can be made based on the physician 's certainty of diagnosis . The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria . The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients , first based only on clinical features and then after review ing the results of diagnostic tests . Results The TOAST classification denotes five subtypes of ischemic stroke : 1 ) large-artery atherosclerosis , 2 ) cardioembolism , 3 ) small-vessel occlusion , 4 ) stroke of other determined etiology , and 5 ) stroke of undetermined etiology . Using this rating system , interphysician agreement was very high . The two physicians disagreed in only one patient . They were both able to reach a specific etiologic diagnosis in 11 patients , whereas the cause of stroke was not determined in nine . Conclusions The TOAST stroke subtype classification system is easy to use and has good interobserver agreement . This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke . Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke In a prospect i ve study of 1,805 hospitalized patients in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke , the 1,273 with infa rct ion were classified into diagnostic subtypes . Diagnosis was based on the clinical history , examination , and laboratory tests including computed tomography , noninvasive vascular imaging , and where safe and relevant , angiography .  Five hundred and eight cases ( fully 40 % ) were labeled as infa rcts of undetermined cause ( IUC ) , of which 138 ( 27 % ) were evaluated with both computed tomography and angiography . The clinical syndrome and computed tomographic and angiographic findings in 91 ( 65.9 % ) of these 138 IUC cases were clearly not attributable to large‐artery thrombosis and could permit reclassification of the infa rct as due to some form of embolism . Failure to define a source of embolus kept them in the category of IUC . Thirty‐one cases ( 22.5 % ) could be reclassified as due to stenosis or thrombosis of a large artery , and 16 ( 11.6 % ) as lacunar infa rct ion . To determine if those selected for angiography among the IUC patients differed from those with other final diagnoses , a stepwise multiple logistic model was used . The most important characteristics were young age , presence of a superficial infa rct , prior transient ischemic attack , low weakness score , and presentation with a nonlacunar syndrome . The results of the model suggest that angiography use was determined by clinical characteristics uniformly across centers and not by final diagnosis . Continued use of the category IUC may help clarify risk factors and stroke subtypes , allow new mechanisms of ischemic stroke to be uncovered , and prevent classification categories of stroke used in clinical trials from becoming too broad Patients with patent foramen ovale ( PFO ) and paradoxical embolism are at increased risk for recurrent events . Percutaneous PFO closure is a new treatment modality aim ed at secondary prevention . We report the multicenter experience of interventional closure of PFO using two different devices in 272 patients . The mean age was 51 ± 14.2 years and 52.9 % were males . The implantation procedure result ed in an initial complete shunt closure rate of 74.3 % with a periprocedural complication rate of 6.6 % . There were no deaths or pericardial tamponade . The mean procedure time was less than 44 min under either conscious sedation , local or general anesthesia . This is the largest report to date demonstrating the procedural safety , reliability , and feasibility of the transcatheter PFO closure technique with the STARFlex and CardioSEAL septal implants . R and omized clinical trials are currently in progress to identify patients most likely to benefit from this intervention . Catheter Cardiovasc Interv 2004;62:512–516 . © 2004 Wiley‐Liss , OBJECTIVES We sought to assess the risk of ischemic stroke from a patent foramen ovale ( PFO ) in the multiethnic prospect i ve cohort of northern Manhattan . BACKGROUND Patent foramen ovale has been associated with increased risk of ischemic stroke , mainly in case-control studies . The actual PFO-related stroke risk in the general population is unclear . METHODS The presence of PFO was assessed at baseline by using transthoracic 2-dimensional echocardiography with contrast injection in 1,100 stroke-free subjects older than 39 years of age ( mean age 68.7 + /- 10.0 years ) from the Northern Manhattan Study ( NOMAS ) . The presence of atrial septal aneurysm ( ASA ) also was recorded . Subjects were followed annually for outcomes . We assessed PFO/ASA-related stroke risk after adjusting for established stroke risk factors . RESULTS We detected PFO in 164 subjects ( 14.9 % ) ; ASA was present in 27 subjects ( 2.5 % ) and associated with PFO in 19 subjects . During a mean follow-up of 79.7 + /- 28.0 months , an ischemic stroke occurred in 68 subjects ( 6.2 % ) . After adjustment for demographics and risk factors , PFO was not found to be significantly associated with stroke ( hazard ratio 1.64 , 95 % confidence interval [ CI ] 0.87 to 3.09 ) . The same trend was observed in all age , gender , and race-ethnic subgroups . The coexistence of PFO and ASA did not increase the stroke risk ( adjusted hazard ratio 1.25 , 95 % CI 0.17 to 9.24 ) . Isolated ASA was associated with elevated stroke incidence ( 2 of 8 , or 25 % ; adjusted hazard ratio 3.66 , 95 % CI 0.88 to 15.30 ) . CONCLUSIONS Patent foramen ovale , alone or together with ASA , was not associated with an increased stroke risk in this multiethnic cohort . The independent role of ASA needs further assessment in appositely design ed and powered studies BACKGROUND The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale . We investigated whether closure is superior to medical therapy . METHODS We performed a multicenter , superiority trial in 29 centers in Europe , Canada , Brazil , and Australia in which the assessors of end points were unaware of the study -group assignments . Patients with a patent foramen ovale and ischemic stroke , transient ischemic attack ( TIA ) , or a peripheral thromboembolic event were r and omly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy . The primary end point was a composite of death , nonfatal stroke , TIA , or peripheral embolism . Analysis was performed on data for the intention-to-treat population . RESULTS The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group . The primary end point occurred in 7 of the 204 patients ( 3.4 % ) in the closure group and in 11 of the 210 patients ( 5.2 % ) in the medical-therapy group ( hazard ratio for closure vs. medical therapy , 0.63 ; 95 % confidence interval [ CI ] , 0.24 to 1.62 ; P=0.34 ) . Nonfatal stroke occurred in 1 patient ( 0.5 % ) in the closure group and 5 patients ( 2.4 % ) in the medical-therapy group ( hazard ratio , 0.20 ; 95 % CI , 0.02 to 1.72 ; P=0.14 ) , and TIA occurred in 5 patients ( 2.5 % ) and 7 patients ( 3.3 % ) , respectively ( hazard ratio , 0.71 ; 95 % CI , 0.23 to 2.24 ; P=0.56 ) . CONCLUSIONS Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy . ( Funded by St. Jude Medical ; Clinical Trials.gov number , NCT00166257 . ) Background : The optimal management of patients with cryptogenic ischemic stroke found to have a patent foramen ovale ( PFO ) at diagnostic workup remains unclear . The aims of this observational multicenter study were to evaluate : ( 1 ) the risk of recurrent cerebrovascular events in patients with cryptogenic minor ischemic stroke or transient ischemic attack ( TIA ) and PFO who either underwent percutaneous PFO closure or received only medical treatment  , and ( 2 ) the risk factors associated with recurrent events . Methods : Consecutive patients ( aged 55 years or less ) with first-ever cryptogenic minor ischemic stroke or TIA and PFO were recruited in 13 Italian hospitals between January 2006 and September 2007 and followed up for 2 years . Results : 238 patients were included in the study ( mean age 42.2 ± 10.0 years ; 118 males ) ; 117 patients ( 49.2 % ) received only antithrombotic therapy while 121 patients underwent percut 
    Output:
    
Safety analysis found that the overall risks for all-cause mortality and adverse events were similar in both the TDC and medical therapy groups .
The combined data from recent RCTs have shown no statistically significant differences between TDC and medical therapy in the prevention of recurrent ischemic stroke .
TDC closure was associated with an increased risk of atrial fibrillation but not with serious adverse events