***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: PURPOSE : The feasibility and safety of stem cell-based therapy with exp and ed adipose-derived stem cells ( ASCs ) has been investigated in a phase I clinical trial . The present study was design ed as a phase II multicenter , r and omized controlled trial to further investigate the effectiveness and safety of ASCs in the treatment of complex perianal fistulas . METHODS : Patients with complex perianal fistulas ( cryptogl and ular origin , n = 35 ; associated with Crohn 's disease , n = 14 ) were r and omly assigned to intralesional treatment with fibrin glue or fibrin glue plus 20 million ASCs .  Fistula healing and quality of life ( SF-12 question naire ) were evaluated at eight weeks and one year . If healing was not seen at eight weeks , a second dose of fibrin glue or fibrin glue plus 40 million ASCs was administered . RESULTS : Fistula healing was observed in 17 ( 71 percent ) of 24 patients who received ASCs in addition to fibrin glue compared with 4 ( 16 percent ) of 25 patients who received fibrin glue alone ( relative risk for healing , 4.43 ; confidence interval , 1.74 - 11.27 ) ; P < 0.001 ) . The proportion of patients with healing was similar in Crohn 's and non-Crohn 's subgroups . ASCs were also more effective than fibrin glue alone in patients with a suprasphincteric fistulous tract ( P = 0.001 ) . Quality of life scores were higher in patients who received ASCs than in those who received fibrin glue alone . At one year follow-up , the recurrence rate in patients treated with ASCs was 17.6 percent . Both treatments were well tolerated . CONCLUSION : Administration of exp and ed ASCs ( 20 to 60 million cells ) in combination with fibrin glue is an effective and safe treatment for complex perianal fistula and appears to achieve higher rates of healing than fibrin glue alone BACKGROUND & AIMS Therapies for perianal fistulas in patients with Crohn 's disease are often ineffective in producing long-term healing . We performed a r and omized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic exp and ed adipose-derived stem cells ( Cx601 ) in patients with Crohn 's disease and perianal fistulas . METHODS We performed a double-blind study at 49 hospitals in Europe and Israel , comprising 212 patients with Crohn 's disease and treatment-refractory , draining , complex perianal fistulas . Patients were r and omly assigned ( 1:1 ) to groups given a single local injection of 120 million Cx601 cells or placebo ( control ) , in addition to the st and ard of care . Efficacy endpoints evaluated in the modified intention-to-treat population ( r and omly assigned , treated , and with 1 or more post-baseline efficacy assessment ) at week 52 included combined remission ( closure of all treated external openings draining at baseline with absence of collection s > 2 cm , confirmed by magnetic resonance imaging ) and clinical remission ( absence of draining fistulas ) . RESULTS The study 's primary endpoint , at week 24 , was previously reported ( combined remission in 51.5 % of patients given Cx601 vs 35.6 % of controls , for a difference of 15.8 percentage points ; 97.5 % confidence interval [ CI ] 0.5 - 31.2 ; P = .021 ) . At week 52 , a significantly greater proportion of patients given Cx601 achieved combined remission ( 56.3 % ) vs controls ( 38.6 % ) ( a difference of 17.7 percentage points ; 95 % CI 4.2 - 31.2 ; P = .010 ) , and clinical remission ( 59.2 % vs 41.6 % of controls , for a difference of 17.6 percentage points ; 95 % CI 4.1 - 31.1 ; P = .013 ) . Safety was maintained throughout week 52 ; adverse events occurred in 76.7 % of patients in the Cx601 group and 72.5 % of patients in the control group . CONCLUSION In a phase 3 trial of patients with Crohn 's disease and treatment-refractory complex perianal fistulas , we found Cx601 to be safe and effective in closing external openings , compared with placebo , after 1 year . Clinical Trials.gov no : NCT01541579 In patients with Crohn 's disease , perianal fistulas recur frequently , causing substantial morbidity . We performed a 12-patient , 6-month , phase 1 trial to determine whether autologous mesenchymal stem cells , applied in a bioabsorbable matrix , can heal the fistula . Fistula repair was not associated with any serious adverse events related to mesenchymal stem cells or plug placement . At 6 months , 10 of 12 patients ( 83 % ) had complete clinical healing and radiographic markers of response . We found placement of mesenchymal stem cell-coated matrix fistula plugs in 12 patients with chronic perianal fistulas to be safe and lead to clinical healing and radiographic response in 10 patients . Clinical Trials.gov Identifier : NCT01915927 Background : Few data are available regarding the evolution of Crohn 's disease  after discontinuing a successful course of infliximab BACKGROUND & AIMS Early intensive therapy in Crohn 's disease should be considered only in patients with disabling disease . The aim of our study was to identify at diagnosis factors predictive of a subsequent 5-year disabling course . METHODS Among the 1526 patients seen at our unit with Crohn 's disease diagnosed between 1985 and 1998 , we excluded patients operated on within the first month of the disease , patients with inadequate data , and patients with severe chronic nondigestive disease . In the 1188 remaining patients , Crohn 's disease course within the first 5 years of the disease was categorized as disabling when at least 1 of the criteria of clinical severity , conventionally predefined , was present . RESULTS Among the 1123 patients with follow-up data allowing full 5-year course classification , the rate of disabling disease was 85.2 % . Independent factors present at diagnosis and significantly associated with subsequent 5-year disabling were the initial requirement for steroid use ( OR 3.1 [ 95 % CI : 2.2 - 4.4 ] ) , an age below 40 years ( OR 2.1 [ 95 % CI : 1.3 - 3.6 ] ) , and the presence of perianal disease ( OR 1.8 [ 95 % CI : 1.2 - 2.8 ] ) . The positive predictive value of disabling disease in patients with 2 and 3 predictive factors of disabling disease was 0.91 and 0.93 , respectively . These values were 0.84 and 0.91 , respectively , when tested prospect ively in an independent group of 302 consecutive patients seen at our institution from 1998 . CONCLUSIONS At diagnosis of Crohn 's disease in a referral center , factors predictive of subsequent 5-year disabling course are an age below 40 years , the presence of perianal disease , and the initial requirement for steroids Many perianal fistulae in Crohn 's disease do not respond to conventional surgical and medical management and recurrence rates are high . The study evaluated the safety and feasibility of allogeneic adipose‐derived stem cells for the treatment of perianal fistula in Crohn 's disease Purpose The management of perianal fistula in patients with Crohn ’s disease is an extremely challenging medical problem as many fistulas do not respond to available treatments . The objectives were to assess the safety and efficacy of a suspension of exp and ed adipose-derived allogeneic mesenchymal stem cells ( eASCs ) for the treatment of complex perianal fistula in Crohn ’s disease Methods An open-label , single-arm clinical trial was conducted at six Spanish hospitals . Twenty-four patients were administered  intralesionally  with 20 million eASCs in one draining fistula tract . A subsequent administration of 40 million eASCs was performed if fistula closure was incomplete at week 12 . Subjects were followed until week 24 after the initial administration . Results Treatment-related adverse events did not indicate any clinical safety concerns after 6 months follow-up . The full analysis of efficacy data at week 24 showed 69.2 % of the patients with a reduction in the number of draining fistulas , 56.3 % of the patients achieved complete closure of the treated fistula achieved , and 30 % of the cases presenting complete closure of all existing fistula tracts . Of note , closure was strictly defined as : absence of suppuration through the external orifice and complete re-epithelization , plus absence of collection s measured by magnetic resonance image scan ( MRI ) . Furthermore , MRI Score of Severity showed statistically significant differences at week 12 with a marked reduction at week 24 . Conclusions Locally injected eASCs appear to be a simple , safe , and beneficial therapy for perianal fistula in Crohn ’s disease patients . Additional studies are needed to further confirm the efficacy of the eASCs BACKGROUND & AIMS Patients with perianal fistulizing Crohn 's disease have a poor prognosis because these lesions do not heal well . We evaluated the effects of local administration of bone marrow-derived mesenchymal stromal cells ( MSCs ) to these patients from healthy donors in a double-blind , placebo-controlled study . METHODS Twenty-one patients with refractory perianal fistulizing Crohn 's disease were r and omly assigned to groups given injections of 1 × 10(7 ) ( n = 5 , group 1 ) , 3 × 10(7 ) ( n = 5 , group 2 ) , or 9 × 10(7 ) ( n = 5 , group 3 ) MSCs , or placebo ( solution with no cells , n = 6 ) , into the wall of curettaged fistula , around the trimmed and closed internal opening . The primary outcome , fistula healing , was determined by physical examination 6 , 12 , and 24 weeks later ; healing was defined as absence of discharge and < 2 cm of fluid collection -the latter determined by magnetic resonance imaging at week 12 . All procedures were performed at Leiden University Medical Center , The Netherl and s , from June 2012 through July 2014 . RESULTS No adverse events were associated with local injection of any dose of MSCs .  Healing at week 6 was observed in 3 patients in group 1 ( 60.0 % ) , 4 patients in group 2 ( 80.0 % ) , and 1 patient in group 3 ( 20.0 % ) , vs 1 patient in the placebo group ( 16.7 % ) ( P = .08 for group 2 vs placebo ) . At week 12 , healing was observed in 2 patients in group 1 ( 40.0 % ) , 4 patients in group 2 ( 80.0 % ) , and 1 patient in group 3 ( 20.0 % ) , vs 2 patients in the placebo group ( 33.3 % ) ; these effects were maintained until week 24 and even increased to 4 ( 80.0 % ) in group 1 . At week six , 4 of 9 individual fistulas had healed in group 1 ( 44.4 % ) , 6 of 7 had healed in group 2 ( 85.7 % ) , and 2 of 7 had healed in group 3 ( 28.6 % ) vs 2 of 9 ( 22.2 % ) in the placebo group ( P = .04 for group 2 vs placebo ) . At week twelve , 3 of 9 individual fistulas had healed in group 1 ( 33.3 % ) , 6 of 7 had healed in group 2 ( 85.7 % ) , 2 of 7 had healed in group 3 ( 28.6 % ) , and 3 of 9 had healed in the placebo group ( 33.3 % ) . These effects were stable through week 24 and even increased to 6 of 9 ( 66.7 % ) in group 1 ( P = .06 group 2 vs placebo , weeks 12 and 24 ) . CONCLUSIONS Local administration of allogeneic MSCs was not associated with severe adverse events in patients with perianal fistulizing Crohn 's disease . Injection of 3 × 10(7 ) MSCs appeared to promote healing of perianal fistulas . Clinical Trials.gov ID NCT01144962 The present study was design ed to evaluate the safety and potential of adipose tissue-derived stem cells ( ASCs ) for the treatment of Crohn 's fistula . In this dose escalation study , patients were sequentially enrolled into three dosing groups with at least three patients per group . The first three patients ( group 1 ) were given 1 × 107 cells/ml . After 4 weeks , this dose was deemed safe , and so an additional four patients ( group 2 ) were given 2 × 107 cells/ml . Four weeks later , after which this second dose was deemed safe , a third and final group of three patients were given 4 × 107 cells/ml . Each patient was followed for a minimum of 8 weeks . Patients who showed complete healing at week 8 were followed up for an additional 6 months . Efficacy endpoint was complete healing at week 8 after injection , defined as complete closure of the fistula track and internal and external openings without drainage or signs of inflammation . There were no grade 3 or 4 severity ad 
    Output:
    
There was no significant increase in adverse events ( OR = 1.14 ; P = 0.54 ; 95 % CI 0.75 , 1.74 ) in patients treated with MSCs  and no major MSC-related adverse event has been reported so far .
Local administration of MSCs is an effective and safe method for pCD .
It also represents hope for effective treatment of refractory pCD