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: Abstract Objective . The prevalence of anemia in inflammatory bowel disease ( IBD ) has been broadly described . The recurrence , type and burden of anemia remain unenlightened . The primary objective was to describe this . The secondary objective was to evaluate the implementation of European guidelines . Material s and methods . This longitudinal follow-up study included 300 IBD out patients from six centers in Sc and inavia . Patients were enrolled in a research cohort , in which each center included 5 % of their IBD cohort . The study was prospect ively planned , while data were retrospectively collected . The burden of anemia was calculated as number of months with anemia . A Markov model was used to calculate the probabilities of transitioning between stages . The European guidelines were used as the st and ard for anemia management . Results . Anemia affected > 50 % of IBD out patients during the 2-year observation period . Totally , 20 % of the total observation time was spent in anemia . Over the 7200 months of observation , anemia was found in 1410 months . The most frequent type was combined anemia ( 63 % ) . Combined anemia covers both anemia of chronic disease ( ACD ) and iron-deficiency anemia ( IDA ) . Pure ACD was present in 21 % of burden time , while pure IDA was present in 16 % of burden time . The European guidelines have mainly been implemented . Conclusion . Anemia affected a majority of the IBD out patients . One in five months , the patients were anemic . Anemia related to inflammation dominated the different types of anemia . Pure IDA was found in for 16 % . These findings , despite a fair implementation of guidelines BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) OBJECTIVES : Anemia is a frequent complication in patients with inflammatory bowel disease ( IBD ) . The optimal route for iron supplementation to replenish iron stores has not been determined so far . We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia ( IDA ) in patients with IBD . METHODS : A r and omized , prospect i ve , open-label , multicenter study was performed in 46 patients with anemia and transferrin saturation ≤20 % and /or serum ferritin concentrations ≤20 μg/L. The intravenous group received a single dose of iron sucrose of 7 mg iron/kg body weight , followed by five 200 mg infusions for the following 5 wks . The oral group received iron sulfate 100–200 mg per day for 6 wks . RESULTS : While a comparable increase in hemoglobin was observed for both administration routes ( median increase 0.25 g/L in the intravenous group vs 0.21 g/L in the oral group ) , only iron sucrose led to a rise in serum ferritin concentrations . Intractable gastrointestinal adverse events caused permanent study drug discontinuation in five patients ( 20.8 % ) receiving iron sulfate , whereas only one patient ( 4.5 % ) had to be withdrawn because of side effects due to iron sucrose . CONCLUSIONS : Although being equal in short-term efficacy and overall tolerability our results suggest a better gastrointestinal tolerability for iron sucrose . Larger trials are m and atory to prove a possible advantage of iron sucrose in short- and long-term efficacy as well as in tolerability over iron sulfate in the management of IDA in IBD BACKGROUND AND AIMS Infliximab ( IFX ) and iron sucrose ( FeS ) are of high value in inflammatory bowel disease ( IBD ) . We aim ed to assess the relative role of both therapies in IBD related anaemia and their safety when used in combination . METHODS IBD patients with anaemia receiving a first series of FeS infusions in addition to IFX were prospect ively followed . We investigated serum kinetics of erythropoietin ( EPO ) , soluble transferrin receptors ( sTFRs ) and vascular endothelial growth factor ( VEGF ) . RESULTS Data analysis included 87 patients of whom 49.4 % achieved the target Hb level of 12.0 g/dL.  IFX result ed in a significant increase of EPO and sTFR compared to baseline pre-IFX levels ( p=0.029 and p=0.005 respectively ) and after a 12-week combined FeS and IFX treatment , EPO and sTFR levels dropped significantly compared to pre-FeS levels ( p<0.001 for both ) . Infusion related adverse events were recorded in 2 IFX treated patients ( 2.3 % , 0.7 % of the infusions ) and were mild . Disease activity and quality of life were not affected . CONCLUSIONS In anaemic IBD patients treated with IFX  , combined administration of FeS is safe . Infliximab significantly increases serum EPO and sTFR levels result ing in an increased functional iron deficiency , which is restored after combined treatment with I.V. iron sucrose OBJECTIVES : In the largest head-to-head comparison between an oral and an intravenous ( IV ) iron compound in patients with inflammatory bowel disease ( IBD ) so far , we strived to determine whether IV iron isomaltoside 1,000 is non-inferior to oral iron sulfate in the treatment of iron deficiency anemia ( IDA ) . METHODS : This prospect i ve , r and omized , comparative , open-label , non-inferiority study was conducted at 36 sites in Europe and India . Patients with known intolerance to oral iron were excluded . A total of 338 IBD patients in clinical remission or with mild disease , a hemoglobin ( Hb ) < 12 g/dl , and a transferrin saturation ( TSAT ) < 20 % were r and omized 2:1 to receive either IV iron isomaltoside 1,000 according to the Ganzoni formula ( 225 patients ) or oral iron sulfate 200 mg daily ( equivalent to 200 mg elemental iron ; 113 patients ) . An interactive web response system method was used to r and omize the eligible patient to the treatment groups . The primary end point was change in Hb from baseline to week 8 . Iron isomaltoside 1,000 and iron sulfate was compared by a non-inferiority assessment with a margin of −0.5 g/dl . The secondary end points , which tested for superiority , included change in Hb from baseline to weeks 2 and 4 , change in s-ferritin , and TSAT to week 8 , number of patients who discontinued study because of lack of response or intolerance of investigational drugs , change in total quality of life ( QoL ) score to weeks 4 and 8 , and safety . Exploratory analyses included a responder analysis ( proportion of patients with an increase in Hb ≥2 g/dl after 8 weeks ) , the effect of regional differences and total iron dose level , and other potential predictors of the treatment response . RESULTS : Non-inferiority in change of Hb to week 8 could not be demonstrated . There was a trend for oral iron sulfate being more effective in increasing Hb  than iron isomaltoside 1,000 . The estimated treatment effect was −0.37 ( 95 % confidence interval ( CI ) : −0.80 , 0.06 ) with P=0.09 in the full analysis set ( N=327 ) and −0.45 ( 95 % CI : −0.88 , −0.03 ) with P=0.04 in the per protocol analysis set ( N=299 ) . In patients treated with IV iron isomaltoside 1,000 , the mean change in s-ferritin concentration was higher with an estimated treatment effect of 48.7 ( 95 % CI : 18.6 , 78.8 ) with P=0.002 , whereas the mean change in TSAT was lower with an estimated treatment effect of −4.4 ( 95 % CI : −7.4 , −1.4 ) with P=0.005 , compared with patients treated with oral iron . No differences in changes of QoL were observed . The safety profile was similar between the groups . The proportion of responders with Hb ≥2 g/dl ( IV group : 67 % ; oral group : 61 % ) were comparable between the groups ( P=0.32 ) . Iron isomaltoside 1,000 was more efficacious with higher cumulative doses of > 1,000 mg IV . Significant predictors of Hb response to IV iron treatment were baseline Hb and C-reactive protein ( CRP ) . CONCLUSIONS : We could not demonstrate non-inferiority of IV iron isomaltoside 1,000 compared with oral iron in this study . Based on the dose – response relationship observed with the IV iron compound , we suggest that the true iron dem and of IV iron was underestimated by the Ganzoni formula in our study . Alternative calculations including Hb and CRP should be explored to gauge iron stores in patients with IBD Background Studies on the association between iron supplementation and mortality in dialysis patients are rare and conflicting . Methods In our observational single-center cohort study ( INVOR study ) we prospect ively studied 235 incident dialysis patients . Time-dependent Cox proportional hazards models using all measured laboratory values for up to 7.6 years were applied to study the association between iron supplementation and all-cause mortality , cardiovascular and sepsis-related mortality . Furthermore , the time-dependent association of ferritin levels with mortality in patients with normal C-reactive protein ( CRP ) levels ( < 0.5 mg/dL ) and elevated CRP levels ( ≧0.5 mg/dL ) was evaluated by using non-linear P-splines to allow flexible modeling of the association . Results One hundred and ninety-one ( 81.3 % ) patients received intravenous iron , 13 ( 5.5 % ) patients oral iron , whereas 31 ( 13.2 % ) patients were never supplemented with iron throughout the observation period . Eighty-two ( 35 % ) patients died during a median follow-up of 34 months , 38 patients due to cardiovascular events and 21 patients from sepsis . Baseline CRP levels were not different between patients with and without iron supplementation . However , baseline serum ferritin levels were lower in patients receiving iron during follow up ( median 93 vs 251 ng/mL , p<0.001 ) . Iron supplementation was associated with a significantly reduced all-cause mortality [ HR ( 95%CI ) : 0.22 ( 0.08–0.58 ) ; p = 0.002 ] and a reduced cardiovascular and sepsis-related mortality [ HR ( 95%CI ) : 0.31 ( 0.09–1.04 ) ; p = 0.06 ] . Increasing ferritin concentrations in patients with normal CRP were associated with a decreasing mortality , whereas in patients with elevated CRP values ferritin levels>800 ng/mL were linked with increased mortality . Conclusions Iron supplementation is associated with reduced all-cause mortality in incident dialysis patients . While serum ferritin levels up to 800 ng/mL appear to be safe , higher ferritin levels are associated with increased mortality in the setting of con 
    Output:
    
agent
However , in patients with IBD flares and inadequate responses to or side effects with oral preparations , intravenous iron supplementation is the therapy of choice .
Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD , and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics .
Based on the data presented , oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency  anemia unless such patients are intolerant or have an inadequate response , whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron
***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: Abstract Objective . The prevalence of anemia in inflammatory bowel disease ( IBD ) has been broadly described . The recurrence , type and burden of anemia remain unenlightened . The primary objective was to describe this . The secondary objective was to evaluate the implementation of European guidelines . Material s and methods . This longitudinal follow-up study included 300 IBD out patients from six centers in Sc and inavia . Patients were enrolled in a research cohort , in which each center included 5 % of their IBD cohort . The study was prospect ively planned , while data were retrospectively collected . The burden of anemia was calculated as number of months with anemia . A Markov model was used to calculate the probabilities of transitioning between stages . The European guidelines were used as the st and ard for anemia management . Results . Anemia affected > 50 % of IBD out patients during the 2-year observation period . Totally , 20 % of the total observation time was spent in anemia . Over the 7200 months of observation , anemia was found in 1410 months . The most frequent type was combined anemia ( 63 % ) . Combined anemia covers both anemia of chronic disease ( ACD ) and iron-deficiency anemia ( IDA ) . Pure ACD was present in 21 % of burden time , while pure IDA was present in 16 % of burden time . The European guidelines have mainly been implemented . Conclusion . Anemia affected a majority of the IBD out patients . One in five months , the patients were anemic . Anemia related to inflammation dominated the different types of anemia . Pure IDA was found in for 16 % . These findings , despite a fair implementation of guidelines BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) OBJECTIVES : Anemia is a frequent complication in patients with inflammatory bowel disease ( IBD ) . The optimal route for iron supplementation to replenish iron stores has not been determined so far . We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia ( IDA ) in patients with IBD . METHODS : A r and omized , prospect i ve , open-label , multicenter study was performed in 46 patients with anemia and transferrin saturation ≤20 % and /or serum ferritin concentrations ≤20 μg/L. The intravenous group received a single dose of iron sucrose of 7 mg iron/kg body weight , followed by five 200 mg infusions for the following 5 wks . The oral group received iron sulfate 100–200 mg per day for 6 wks . RESULTS : While a comparable increase in hemoglobin was observed for both administration routes ( median increase 0.25 g/L in the intravenous group vs 0.21 g/L in the oral group ) , only iron sucrose led to a rise in serum ferritin concentrations . Intractable gastrointestinal adverse events caused permanent study drug discontinuation in five patients ( 20.8 % ) receiving iron sulfate , whereas only one patient ( 4.5 % ) had to be withdrawn because of side effects due to iron sucrose . CONCLUSIONS : Although being equal in short-term efficacy and overall tolerability our results suggest a better gastrointestinal tolerability for iron sucrose . Larger trials are m and atory to prove a possible advantage of iron sucrose in short- and long-term efficacy as well as in tolerability over iron sulfate in the management of IDA in IBD BACKGROUND AND AIMS Infliximab ( IFX ) and iron sucrose ( FeS ) are of high value in inflammatory bowel disease ( IBD ) . We aim ed to assess the relative role of both therapies in IBD related anaemia and their safety when used in combination . METHODS IBD patients with anaemia receiving a first series of FeS infusions in addition to IFX were prospect ively followed . We investigated serum kinetics of erythropoietin ( EPO ) , soluble transferrin receptors ( sTFRs ) and vascular endothelial growth factor ( VEGF ) . RESULTS Data analysis included 87 patients of whom 49.4 % achieved the target Hb level of 12.0 g/dL.  IFX result ed in a significant increase of EPO and sTFR compared to baseline pre-IFX levels ( p=0.029 and p=0.005 respectively ) and after a 12-week combined FeS and IFX treatment , EPO and sTFR levels dropped significantly compared to pre-FeS levels ( p<0.001 for both ) . Infusion related adverse events were recorded in 2 IFX treated patients ( 2.3 % , 0.7 % of the infusions ) and were mild . Disease activity and quality of life were not affected . CONCLUSIONS In anaemic IBD patients treated with IFX  , combined administration of FeS is safe . Infliximab significantly increases serum EPO and sTFR levels result ing in an increased functional iron deficiency , which is restored after combined treatment with I.V. iron sucrose OBJECTIVES : In the largest head-to-head comparison between an oral and an intravenous ( IV ) iron compound in patients with inflammatory bowel disease ( IBD ) so far , we strived to determine whether IV iron isomaltoside 1,000 is non-inferior to oral iron sulfate in the treatment of iron deficiency anemia ( IDA ) . METHODS : This prospect i ve , r and omized , comparative , open-label , non-inferiority study was conducted at 36 sites in Europe and India . Patients with known intolerance to oral iron were excluded . A total of 338 IBD patients in clinical remission or with mild disease , a hemoglobin ( Hb ) < 12 g/dl , and a transferrin saturation ( TSAT ) < 20 % were r and omized 2:1 to receive either IV iron isomaltoside 1,000 according to the Ganzoni formula ( 225 patients ) or oral iron sulfate 200 mg daily ( equivalent to 200 mg elemental iron ; 113 patients ) . An interactive web response system method was used to r and omize the eligible patient to the treatment groups . The primary end point was change in Hb from baseline to week 8 . Iron isomaltoside 1,000 and iron sulfate was compared by a non-inferiority assessment with a margin of −0.5 g/dl . The secondary end points , which tested for superiority , included change in Hb from baseline to weeks 2 and 4 , change in s-ferritin , and TSAT to week 8 , number of patients who discontinued study because of lack of response or intolerance of investigational drugs , change in total quality of life ( QoL ) score to weeks 4 and 8 , and safety . Exploratory analyses included a responder analysis ( proportion of patients with an increase in Hb ≥2 g/dl after 8 weeks ) , the effect of regional differences and total iron dose level , and other potential predictors of the treatment response . RESULTS : Non-inferiority in change of Hb to week 8 could not be demonstrated . There was a trend for oral iron sulfate being more effective in increasing Hb  than iron isomaltoside 1,000 . The estimated treatment effect was −0.37 ( 95 % confidence interval ( CI ) : −0.80 , 0.06 ) with P=0.09 in the full analysis set ( N=327 ) and −0.45 ( 95 % CI : −0.88 , −0.03 ) with P=0.04 in the per protocol analysis set ( N=299 ) . In patients treated with IV iron isomaltoside 1,000 , the mean change in s-ferritin concentration was higher with an estimated treatment effect of 48.7 ( 95 % CI : 18.6 , 78.8 ) with P=0.002 , whereas the mean change in TSAT was lower with an estimated treatment effect of −4.4 ( 95 % CI : −7.4 , −1.4 ) with P=0.005 , compared with patients treated with oral iron . No differences in changes of QoL were observed . The safety profile was similar between the groups . The proportion of responders with Hb ≥2 g/dl ( IV group : 67 % ; oral group : 61 % ) were comparable between the groups ( P=0.32 ) . Iron isomaltoside 1,000 was more efficacious with higher cumulative doses of > 1,000 mg IV . Significant predictors of Hb response to IV iron treatment were baseline Hb and C-reactive protein ( CRP ) . CONCLUSIONS : We could not demonstrate non-inferiority of IV iron isomaltoside 1,000 compared with oral iron in this study . Based on the dose – response relationship observed with the IV iron compound , we suggest that the true iron dem and of IV iron was underestimated by the Ganzoni formula in our study . Alternative calculations including Hb and CRP should be explored to gauge iron stores in patients with IBD Background Studies on the association between iron supplementation and mortality in dialysis patients are rare and conflicting . Methods In our observational single-center cohort study ( INVOR study ) we prospect ively studied 235 incident dialysis patients . Time-dependent Cox proportional hazards models using all measured laboratory values for up to 7.6 years were applied to study the association between iron supplementation and all-cause mortality , cardiovascular and sepsis-related mortality . Furthermore , the time-dependent association of ferritin levels with mortality in patients with normal C-reactive protein ( CRP ) levels ( < 0.5 mg/dL ) and elevated CRP levels ( ≧0.5 mg/dL ) was evaluated by using non-linear P-splines to allow flexible modeling of the association . Results One hundred and ninety-one ( 81.3 % ) patients received intravenous iron , 13 ( 5.5 % ) patients oral iron , whereas 31 ( 13.2 % ) patients were never supplemented with iron throughout the observation period . Eighty-two ( 35 % ) patients died during a median follow-up of 34 months , 38 patients due to cardiovascular events and 21 patients from sepsis . Baseline CRP levels were not different between patients with and without iron supplementation . However , baseline serum ferritin levels were lower in patients receiving iron during follow up ( median 93 vs 251 ng/mL , p<0.001 ) . Iron supplementation was associated with a significantly reduced all-cause mortality [ HR ( 95%CI ) : 0.22 ( 0.08–0.58 ) ; p = 0.002 ] and a reduced cardiovascular and sepsis-related mortality [ HR ( 95%CI ) : 0.31 ( 0.09–1.04 ) ; p = 0.06 ] . Increasing ferritin concentrations in patients with normal CRP were associated with a decreasing mortality , whereas in patients with elevated CRP values ferritin levels>800 ng/mL were linked with increased mortality . Conclusions Iron supplementation is associated with reduced all-cause mortality in incident dialysis patients . While serum ferritin levels up to 800 ng/mL appear to be safe , higher ferritin levels are associated with increased mortality in the setting of con 
    Output:
    