human
***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 : The Mayo score and a noninvasive 9‐point partial Mayo score are used as outcome measures for clinical trials assessing therapy for ulcerative colitis ( UC ) . There are limited data assessing what defines a clinical ly relevant change in these indices . We sought to assess what constitutes a clinical ly meaningful change in these indices using data from a recently completed placebo‐controlled clinical trial . Methods : In all , 105 patients were enrolled in a 12‐week r and omized , placebo‐controlled trial assessing rosiglitazone for treatment of mild to moderate UC . We compared the change in  the Mayo score , the partial Mayo score , and a 6‐point score composed just of the stool frequency and bleeding components of the Mayo score to the patient 's perception of disease activity at week 0 and week 12 . Optimal cutpoints were calculated as the maximal product of sensitivity and specificity . Results : Each index was strongly correlated with the patient 's rating of disease activity at week 12 ( Spearman correlations 0.61–0.71 , P < 0.0001 for all correlations ) . The maximal product of sensitivity and specificity to identify patient reported improvement of disease activity was achieved using cutpoints for change of 2.5 for the Mayo score ( sensitivity 88 % , specificity 80 % ) , 2.5 for the partial Mayo score ( sensitivity 88 % , specificity 87 % ) , and 1.5 for the 6‐point score ( sensitivity 88 % , specificity 80 % ) . Conclusions : The partial Mayo score and the 6‐point score composed solely of the stool frequency and bleeding components performed as well as the full Mayo score to identify patient perceived clinical response OBJECTIVE --To assess the safety and efficacy of a preparation of mesalazine ( 5-aminosalicylic acid ) coated with a pH dependent resin ( Eudragit L ) as compared with sulphasalazine in patients with active mild to moderate ulcerative colitis . DESIGN --Eight week r and omised double blind parallel group study . SETTING --Forty six gastroenterology outpatient clinics in seven countries . PATIENTS --Two hundred and twenty patients aged 18 - 70 who met the following criteria : clinical activity index greater than or equal to 6 and endoscopic index greater than or equal to 4 ; no concomitant treatment for ulcerative colitis ; no hypersensitivity to salicylates or sulphonamides . Of the 164 patients eligible for efficacy analysis , 87 received the coated preparation of mesalazine and 77 sulphasalazine . Most of the remaining patients ( 28 in each group ) were ineligible for the efficacy analysis because of treatment with steroid enemas . All pretrial characteristics were comparable in the two treatment groups . INTERVENTIONS --Coated mesalazine ( Mesasal ) 1.5 g daily or sulphasalazine 3.0 g daily for eight weeks . Compliance monitored by pill counts . END POINT-- Clinical and endoscopic remission . MEASUREMENTS AND MAIN RESULTS -- Clinical activity measured by daily diary cards , assessment by investigators , and laboratory findings . Endoscopic evaluation at week 8 . After four weeks 50 of 70 patients ( 71 % ) taking coated mesalazine and 38 of 58 ( 66 % ) taking sulphasalazine had achieved remission of their disease by eight weeks remission rates were 74 % ( 37/50 patients ) and 81 % ( 35/43 ) in the two treatment groups respectively . Endoscopic remission at eight weeks was recorded in 20 of 41 patients ( 49 % ) taking coated mesalazine and 18 of 38 ( 47 % ) taking sulphasalazine . There was a higher incidence of adverse events among patients taking sulphasalazine ( 25/105 ; 24 % ) than among those taking coated mesalazine ( 16/115 ; 14 % ) . CONCLUSION --Mesalazine coated with Eudragit L is a safe , logical alternative to sulphasalazine The efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon . Seventy-six patients received active medication and 77 received a placebo .  There were 20 dropouts ( 6 in the active group and 14 in the placebo group ) during the study because of insufficient efficacy . After 6 wk of therapy , 48 of the 76 patients ( 63 % ) receiving 5-aminosalicylic acid were considered to be " much improved " by the study physician compared to 22 of the 77 patients ( 29 % ) on placebo ( p = 0.001 ) . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mean disease activity index declined 55 % for patients on 5-aminosalicylic acid and 24 % for patients on placebo ( p = 0.0001 ) . Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20 - 40 cm from the anus . Response was not affected by concurrent sulfasalazine , but patients requiring concurrent oral steroids had a diminished response . Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation . 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon Background Persistent active endoscopic and histological inflammation is associated with poorer outcomes in ulcerative colitis ( UC ) . Fecal calprotectin is a surrogate marker of endoscopic and histological remission . Aims To confirm the correlation between fecal calprotectin and endoscopic or histological disease activity and to define the optimal cutoff value to detect endoscopic and histological remission . Methods From a prospect ively maintained data base , we analyzed 61 UC patients who had fecal calprotectin measurement and endoscopy performed within 1 month .  Endoscopic activity was grade d using the Mayo endoscopic subscore ( MES ) . Histological remission was defined as normal histology or quiescent histological activity . Results Eighteen patients ( 29.5 % ) and five patients ( 8.1 % ) had endoscopic remission defined as MES ≤ 1 or MES = 0 , respectively . We observed a significantly lower median level of fecal calprotectin in patients with endoscopic remission than those with endoscopic activity for both definition of endoscopic remission , i.e. , MES ≤ 1 ( 158 vs 490 µg/g , p = 0.0005 ) or MES = 0 ( 94 vs 414 µg/g , p = 0.013 ) . Seven patients ( 11.5 % ) were in histological remission . They had a lower median level of fecal calprotectin than those with active histological inflammation ( 107 vs 416 µg/g , p = 0.016 ) . Using a ROC curve , fecal calprotectin < 250 µg/g predicted endoscopic remission ( MES ≤ 1 ) with a sensitivity of 67 % and specificity of 77 % , while fecal calprotectin < 200 µg/g predicted histological remission with a sensitivity of 71 % and specificity of 76 % . Conclusion Fecal calprotectin level correlated with both endoscopic activity and histological activity and is a reliable biomarker in assessing mucosal healing in UC BACKGROUND There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago . In an uncontrolled study , 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy . METHODS We conducted a r and omized , double-blind , controlled trial in which cyclosporine ( 4 mg per kilogram of body weight per day ) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy .  A response to therapy was defined as an improvement in a numerical symptom score ( 0 indicated no symptoms , and 21 severe symptoms ) leading to discharge from the hospital and treatment with oral medications . Failure to respond to therapy result ed in colectomy , but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine . RESULTS Nine of 11 patients ( 82 percent ) treated with cyclosporine had a response within a mean of seven days , as compared with 0 of 9 patients who received placebo ( P < 0.001 ) . The mean clinical -activity score fell from 13 to 6 in the cyclosporine group , as compared with a decrease from 14 to 13 in the placebo group . All five patients in the placebo group who later received cyclosporine therapy had a response . CONCLUSIONS Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis Objective Faecal calprotectin ( FC ) is the most relevant noninvasive biomarker for monitoring inflammatory status , response to treatment and for predicting clinical relapse in ulcerative colitis ( UC ) . The aim of this study was to evaluate the role of FC in predicting both clinical /endoscopic activity and clinical relapse in a large UC patient cohort . Patients and methods A two-phase prospect i ve study was carried out . In the first phase , the relationship between FC and clinical /endoscopic activity was evaluated . In the second phase , a cohort of asymptomatic patients with endoscopic mucosal healing was followed up using clinical and FC level determinations . Results One hundred and twenty-one UC patients were enrolled . The  FC concentrations were directly correlated with both clinical and endoscopic activity ( r=0.76 and 0.87 , respectively , P<0.05 ) and were capable of differentiating between different degrees of endoscopic severity ( P<0.01 ) . An FC cut-off value of 110 & mgr;g/g was highly predictive ( 95 % ) of endoscopic activity . Seventy-four patients in clinical remission with mucosal healing were followed up for a year or until relapse and 27 % developed a clinical relapse . The  FC concentration of nonrelapsed patients ( 48 & mgr;g/g ) versus relapsed patients ( 218 & mgr;g/g ) was significantly different ( P<0.01 ) . An FC cut-off value of 193 & mgr;g/g had an accuracy of 89 % in predicting clinical relapse . High FC levels were associated with clinical relapse using survival analysis and multivariate analysis . Conclusion Our data strongly support the use of FC for staging the activity of disease , predicting relapse and leading decision-making in a UC setting Background  Clinical activity and quality of life ( QOL ) indices assess disease activity in Crohn ’s disease ( CD ) and ulcerative colitis ( UC ) . However , a paucity of data exists on the validity of these indices according to disease characteristics . Aims To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics . Methods We used a prospect i ve registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Question naire scores ( SIBDQ ) , Harvey – Bradshaw Index ( HBI ) and simple endoscopic scores for CD ( SES-CD ) , and Simple Clinical Colitis Activity Index ( SCCAI ) and Mayo endoscopic score for UC . We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics . Results Among 282 CD patients , we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics . Conversely , among 226 UC patients  , clinical activity and QOL had good correlation to Mayo endoscopic score ( r = 0.55 and −0.56 , respectively ) with better correlations observed with left-sided versus extensive colitis ( r = 0.73 vs. 0.45 , p = 0.005 ) and shorter duration of disease ( r = 0.61 vs. 0.37 , p = 0.04 ) . Conclusions Our data suggest good correlation between SCCAI and endoscopic disease activity in UC , particularly in left-sided disease . Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes BACKGROUND & AIMS Ulcerative colitis ( UC ) is a chronic relapsing inflammatory bowel disease . We aim ed to assess whether clinical , biological , and histologic parameters in quiescent UC predict time to clinical relapse . METHODS Seventy-four patients with clinical ly and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse .  Serum erythrocyte sedimentation rate ; C-reactive protein , interleukin (IL)-1beta , IL-6 , and IL-15 values ; anti-neutrophil cytoplasmic antibody titers ; and rectal biopsy specimens  were obtained at baseline , at 6 and 12 months , and /or at relapse . Multivariate survival analysis was performed to determine independent predictors of clinical relapse . RESULTS Twenty-seven patients relapsed  ( 19/42 women ; 8/32 men ) . Multivariate Cox regression analysis retained younger age ( P = 0.0 
    Output:
    
agent
***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 : The Mayo score and a noninvasive 9‐point partial Mayo score are used as outcome measures for clinical trials assessing therapy for ulcerative colitis ( UC ) . There are limited data assessing what defines a clinical ly relevant change in these indices . We sought to assess what constitutes a clinical ly meaningful change in these indices using data from a recently completed placebo‐controlled clinical trial . Methods : In all , 105 patients were enrolled in a 12‐week r and omized , placebo‐controlled trial assessing rosiglitazone for treatment of mild to moderate UC . We compared the change in  the Mayo score , the partial Mayo score , and a 6‐point score composed just of the stool frequency and bleeding components of the Mayo score to the patient 's perception of disease activity at week 0 and week 12 . Optimal cutpoints were calculated as the maximal product of sensitivity and specificity . Results : Each index was strongly correlated with the patient 's rating of disease activity at week 12 ( Spearman correlations 0.61–0.71 , P < 0.0001 for all correlations ) . The maximal product of sensitivity and specificity to identify patient reported improvement of disease activity was achieved using cutpoints for change of 2.5 for the Mayo score ( sensitivity 88 % , specificity 80 % ) , 2.5 for the partial Mayo score ( sensitivity 88 % , specificity 87 % ) , and 1.5 for the 6‐point score ( sensitivity 88 % , specificity 80 % ) . Conclusions : The partial Mayo score and the 6‐point score composed solely of the stool frequency and bleeding components performed as well as the full Mayo score to identify patient perceived clinical response OBJECTIVE --To assess the safety and efficacy of a preparation of mesalazine ( 5-aminosalicylic acid ) coated with a pH dependent resin ( Eudragit L ) as compared with sulphasalazine in patients with active mild to moderate ulcerative colitis . DESIGN --Eight week r and omised double blind parallel group study . SETTING --Forty six gastroenterology outpatient clinics in seven countries . PATIENTS --Two hundred and twenty patients aged 18 - 70 who met the following criteria : clinical activity index greater than or equal to 6 and endoscopic index greater than or equal to 4 ; no concomitant treatment for ulcerative colitis ; no hypersensitivity to salicylates or sulphonamides . Of the 164 patients eligible for efficacy analysis , 87 received the coated preparation of mesalazine and 77 sulphasalazine . Most of the remaining patients ( 28 in each group ) were ineligible for the efficacy analysis because of treatment with steroid enemas . All pretrial characteristics were comparable in the two treatment groups . INTERVENTIONS --Coated mesalazine ( Mesasal ) 1.5 g daily or sulphasalazine 3.0 g daily for eight weeks . Compliance monitored by pill counts . END POINT-- Clinical and endoscopic remission . MEASUREMENTS AND MAIN RESULTS -- Clinical activity measured by daily diary cards , assessment by investigators , and laboratory findings . Endoscopic evaluation at week 8 . After four weeks 50 of 70 patients ( 71 % ) taking coated mesalazine and 38 of 58 ( 66 % ) taking sulphasalazine had achieved remission of their disease by eight weeks remission rates were 74 % ( 37/50 patients ) and 81 % ( 35/43 ) in the two treatment groups respectively . Endoscopic remission at eight weeks was recorded in 20 of 41 patients ( 49 % ) taking coated mesalazine and 18 of 38 ( 47 % ) taking sulphasalazine . There was a higher incidence of adverse events among patients taking sulphasalazine ( 25/105 ; 24 % ) than among those taking coated mesalazine ( 16/115 ; 14 % ) . CONCLUSION --Mesalazine coated with Eudragit L is a safe , logical alternative to sulphasalazine The efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon . Seventy-six patients received active medication and 77 received a placebo .  There were 20 dropouts ( 6 in the active group and 14 in the placebo group ) during the study because of insufficient efficacy . After 6 wk of therapy , 48 of the 76 patients ( 63 % ) receiving 5-aminosalicylic acid were considered to be " much improved " by the study physician compared to 22 of the 77 patients ( 29 % ) on placebo ( p = 0.001 ) . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mean disease activity index declined 55 % for patients on 5-aminosalicylic acid and 24 % for patients on placebo ( p = 0.0001 ) . Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20 - 40 cm from the anus . Response was not affected by concurrent sulfasalazine , but patients requiring concurrent oral steroids had a diminished response . Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation . 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon Background Persistent active endoscopic and histological inflammation is associated with poorer outcomes in ulcerative colitis ( UC ) . Fecal calprotectin is a surrogate marker of endoscopic and histological remission . Aims To confirm the correlation between fecal calprotectin and endoscopic or histological disease activity and to define the optimal cutoff value to detect endoscopic and histological remission . Methods From a prospect ively maintained data base , we analyzed 61 UC patients who had fecal calprotectin measurement and endoscopy performed within 1 month .  Endoscopic activity was grade d using the Mayo endoscopic subscore ( MES ) . Histological remission was defined as normal histology or quiescent histological activity . Results Eighteen patients ( 29.5 % ) and five patients ( 8.1 % ) had endoscopic remission defined as MES ≤ 1 or MES = 0 , respectively . We observed a significantly lower median level of fecal calprotectin in patients with endoscopic remission than those with endoscopic activity for both definition of endoscopic remission , i.e. , MES ≤ 1 ( 158 vs 490 µg/g , p = 0.0005 ) or MES = 0 ( 94 vs 414 µg/g , p = 0.013 ) . Seven patients ( 11.5 % ) were in histological remission . They had a lower median level of fecal calprotectin than those with active histological inflammation ( 107 vs 416 µg/g , p = 0.016 ) . Using a ROC curve , fecal calprotectin < 250 µg/g predicted endoscopic remission ( MES ≤ 1 ) with a sensitivity of 67 % and specificity of 77 % , while fecal calprotectin < 200 µg/g predicted histological remission with a sensitivity of 71 % and specificity of 76 % . Conclusion Fecal calprotectin level correlated with both endoscopic activity and histological activity and is a reliable biomarker in assessing mucosal healing in UC BACKGROUND There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago . In an uncontrolled study , 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy . METHODS We conducted a r and omized , double-blind , controlled trial in which cyclosporine ( 4 mg per kilogram of body weight per day ) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy .  A response to therapy was defined as an improvement in a numerical symptom score ( 0 indicated no symptoms , and 21 severe symptoms ) leading to discharge from the hospital and treatment with oral medications . Failure to respond to therapy result ed in colectomy , but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine . RESULTS Nine of 11 patients ( 82 percent ) treated with cyclosporine had a response within a mean of seven days , as compared with 0 of 9 patients who received placebo ( P < 0.001 ) . The mean clinical -activity score fell from 13 to 6 in the cyclosporine group , as compared with a decrease from 14 to 13 in the placebo group . All five patients in the placebo group who later received cyclosporine therapy had a response . CONCLUSIONS Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis Objective Faecal calprotectin ( FC ) is the most relevant noninvasive biomarker for monitoring inflammatory status , response to treatment and for predicting clinical relapse in ulcerative colitis ( UC ) . The aim of this study was to evaluate the role of FC in predicting both clinical /endoscopic activity and clinical relapse in a large UC patient cohort . Patients and methods A two-phase prospect i ve study was carried out . In the first phase , the relationship between FC and clinical /endoscopic activity was evaluated . In the second phase , a cohort of asymptomatic patients with endoscopic mucosal healing was followed up using clinical and FC level determinations . Results One hundred and twenty-one UC patients were enrolled . The  FC concentrations were directly correlated with both clinical and endoscopic activity ( r=0.76 and 0.87 , respectively , P<0.05 ) and were capable of differentiating between different degrees of endoscopic severity ( P<0.01 ) . An FC cut-off value of 110 & mgr;g/g was highly predictive ( 95 % ) of endoscopic activity . Seventy-four patients in clinical remission with mucosal healing were followed up for a year or until relapse and 27 % developed a clinical relapse . The  FC concentration of nonrelapsed patients ( 48 & mgr;g/g ) versus relapsed patients ( 218 & mgr;g/g ) was significantly different ( P<0.01 ) . An FC cut-off value of 193 & mgr;g/g had an accuracy of 89 % in predicting clinical relapse . High FC levels were associated with clinical relapse using survival analysis and multivariate analysis . Conclusion Our data strongly support the use of FC for staging the activity of disease , predicting relapse and leading decision-making in a UC setting Background  Clinical activity and quality of life ( QOL ) indices assess disease activity in Crohn ’s disease ( CD ) and ulcerative colitis ( UC ) . However , a paucity of data exists on the validity of these indices according to disease characteristics . Aims To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics . Methods We used a prospect i ve registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Question naire scores ( SIBDQ ) , Harvey – Bradshaw Index ( HBI ) and simple endoscopic scores for CD ( SES-CD ) , and Simple Clinical Colitis Activity Index ( SCCAI ) and Mayo endoscopic score for UC . We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics . Results Among 282 CD patients , we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics . Conversely , among 226 UC patients  , clinical activity and QOL had good correlation to Mayo endoscopic score ( r = 0.55 and −0.56 , respectively ) with better correlations observed with left-sided versus extensive colitis ( r = 0.73 vs. 0.45 , p = 0.005 ) and shorter duration of disease ( r = 0.61 vs. 0.37 , p = 0.04 ) . Conclusions Our data suggest good correlation between SCCAI and endoscopic disease activity in UC , particularly in left-sided disease . Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes BACKGROUND & AIMS Ulcerative colitis ( UC ) is a chronic relapsing inflammatory bowel disease . We aim ed to assess whether clinical , biological , and histologic parameters in quiescent UC predict time to clinical relapse . METHODS Seventy-four patients with clinical ly and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse .  Serum erythrocyte sedimentation rate ; C-reactive protein , interleukin (IL)-1beta , IL-6 , and IL-15 values ; anti-neutrophil cytoplasmic antibody titers ; and rectal biopsy specimens  were obtained at baseline , at 6 and 12 months , and /or at relapse . Multivariate survival analysis was performed to determine independent predictors of clinical relapse . RESULTS Twenty-seven patients relapsed  ( 19/42 women ; 8/32 men ) . Multivariate Cox regression analysis retained younger age ( P = 0.0 
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