***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 / AIMS The effect of vitamin E administration on clinical and laboratory parameters of liver function and on markers of fibrogenesis was assessed in patients with mild to moderate alcoholic hepatitis in a double blind placebo controlled r and omized trial . METHODS Twenty-five patients received 1000  I.U.  of vitamin E per day , while 26 patients received placebo for 3 months . The patients were followed for 1 year after entry into the trial . RESULTS Vitamin E did not result in significant greater decreases in serum aminotransferases and serum bilirubin or in greater increases in serum albumin as compared with placebo .  Prothrombin time did not change , while serum creatinine remained in the normal range . Monocyte nuclear nuclear factor-kappa B binding activity decreased in patients who remained abstinent , regardless of whether they received vitamin E. As regards markers of hepatic fibrogenesis , vitamin E treatment decreased serum hyaluronic acid ( P<0.05 ) while serum aminoterminal peptide of type III procollagen did not change in either group . Four patients in the treatment group and five in the placebo group died during the 1-year study . CONCLUSIONS Vitamin E treatment improves serum hyaluronic acid but has no beneficial effects on tests of liver function in patients with mild to moderate alcoholic hepatitis BACKGROUND & AIMS Severe alcoholic hepatitis ( AH ) is a life-threatening disease for which adequate oral nutritional support is recommended . We performed a r and omized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH . METHODS We enrolled 136 heavy consumers of alcohol ( age , 18 - 75 y ) with recent onset of jaundice and biopsy-proven severe AH in our study , performed at 18 hospitals in Belgium and 2 in France , from February 2010 through February 2013 . Subjects were assigned r and omly ( 1:1 ) to groups that received either intensive enteral nutrition plus methylprednisolone or conventional nutrition plus methylprednisolone ( controls ) . In the intensive enteral nutrition group , enteral nutrition was given via feeding tube for 14 days . The primary end point was patient survival for 6 months . RESULTS In an intention-to-treat analysis , we found no significant difference between groups in 6-month cumulative mortality : 44.4 % of patients died in the intensive enteral nutrition group ( 95 % confidence interval [ CI ] , 32.2%-55.9 % ) and 52.1 % of controls died ( 95 % CI , 39.4%-63.4 % ) ( P = .406 ) . The enteral feeding tube was withdrawn prematurely from 48.5 % of patients , and serious adverse events considered to be related to enteral nutrition occurred in 5 patients . Regardless of group , a greater proportion of patients with a daily calorie intake less than 21.5 kcal/kg/day died ( 65.8 % ; 95 % CI , 48.8 - 78.4 ) than patients with a higher intake of calories ( 33.1 % ; 95 % CI , 23.1%-43.4 % ) ( P < .001 ) . CONCLUSIONS In a r and omized trial of patients with severe AH treated with corticosteroids , we found that intensive enteral nutrition was difficult to implement and did not increase survival . However , low daily energy intake was associated with greater mortality , so adequate nutritional intake should be a main goal for treatment . Clinical Trials.gov number : NCT01801332 BACKGROUND & AIMS An earlier pilot study from our liver unit suggested benefit from treatment with pentoxifylline ( PTX ) , an inhibitor of tumor necrosis factor ( TNF ) , in severe acute alcoholic hepatitis . The aim of the present study was to evaluate this treatment in a larger cohort of patients . METHODS One hundred one patients with severe alcoholic hepatitis ( Maddrey discriminant factor > or = 32 ) entered a 4-week double-blind r and omized trial of PTX ( 400 mg orally 3 times daily ) vs. placebo . Primary endpoints of the study were the effect of PTX on ( 1 ) short-term survival and ( 2 ) progression to hepatorenal syndrome . On r and omization , there were no differences in demographic and clinical characteristics or laboratory values ( including TNF ) between the 2 groups . RESULTS Twelve ( 24.5 % ) of the 49 patients who received PTX and 24 ( 46.1 % ) of the 52 patients who received placebo  died during the index hospitalization ( P = 0.037 ; relative risk , 0.59 ; 95 % confidence interval , 0.35 - 0.97 ) . Hepatorenal syndrome was the cause of death in 6 ( 50 % ) and 22 ( 91.7 % ) patients ( P = 0.009 ; relative risk , 0.29 ; 95 % confidence interval , 0.13 - 0.65 ) . Three variables ( age , creatinine level on r and omization , and treatment with PTX ) were independently associated with survival . TNF values on r and omization were not predictive of survival ; however , during the study period they increased markedly in nonsurvivors compared with survivors in both groups . CONCLUSIONS Treatment with PTX improves short-term survival in patients with severe alcoholic hepatitis . The benefit appears to be related to a significant decrease in the risk of developing hepatorenal syndrome . Increasing TNF levels during the hospital course are associated with an increase in mortality rate UNLABELLED Steroids improve the outcome in alcoholic hepatitis ( AH ) , but up to 40 % of patients fail to respond adequately . Interleukin-2 ( IL-2 ) exacerbates steroid resistance in vitro . We performed a prospect i ve study to determine if intrinsic steroid sensitivity correlates with response to steroids in individuals with severe AH and if IL-2 receptor blockade can reverse this . Peripheral blood mononuclear cells ( P BMC s ) were isolated from 20 patients with AH and a Maddrey 's score > 32 . Patients were treated with oral prednisolone plus full supportive measures . Clinical resistance to oral steroid treatment was defined as a drop in serum bilirubin of < 25 % within 7 days or death within 6 months . In vitro steroid resistance was measured in P BMC using the dexamethasone suppression of lymphocyte proliferation assay and repeated after the addition of the anti-IL-2 receptor ( anti-CD25 ) monoclonal antibody , basiliximab . Suppression of lymphocyte proliferation < 60 % was considered to indicate steroid resistance . In all , 82 % ( 9/11 ) of in vitro steroid-resistant patients were dead at 6 months as compared to 21 % ( 2/9 ) of steroid-sensitive patients ( P = 0.03 ) . Similarly , 91 % ( 10/11 ) of in vitro steroid-resistant patients failed to show a significant fall in bilirubin at day 7 as compared to 44 % ( 4/9 ) of steroid-sensitive patients ( P < 0.05 ) . Basiliximab improved the maximal proliferation count in 91 % ( 10/11 ) of in vitro steroid-resistant patients ( P = 0.003 ) . CONCLUSION Clinical outcome of steroid therapy in this patient cohort correlated with in vitro steroid resistance . IL-2 blockade improved in vitro steroid sensitivity . This suggests that intrinsic lack of steroid sensitivity may contribute to poor clinical response to steroids in severe AH . IL-2 receptor blockade represents a possible mechanism to overcome this Chronic obstructive pulmonary disease ( COPD ) is a common , progressive respiratory disease that causes great morbidity and mortality despite treatment . Tumor necrosis factor alpha ( TNF-alpha ) plays a central role as a pro-inflammatory cytokine in COPD . TNF-alpha release is markedly inhibited by phosphodiesterase type 4 ( PDE4 ) inhibitors that have proven efficacious in COPD clinical trials . The aim of this study was to compare the in vitro activities of the novel selective PDE4 inhibitors CI-1044 compared to well-known PDE4 inhibitors , rolipram and cilomilast , and to the glucocorticoid dexamethasone at reducing lipopolysaccharide (LPS)-induced TNF-alpha release in whole blood from COPD patients and healthy subjects . In the whole blood from COPD patients pre-incubation with PDE4 inhibitors or dexamethasone result ed in a dose-dependent inhibition of LPS-induced TNF-alpha release with IC(50 ) values of 1.3+/-0.7 , 2.8+/-0.9 microM , higher to 10 microM and lesser than 0.03 microM for CI-1044 , rolipram , cilomilast and dexamethasone , respectively . We observed a similar inhibition in the whole blood from healthy volunteers with , however , higher IC(50 ) values . These results indicate that CI-1044 inhibits in vitro LPS-induced TNF-alpha release in whole blood from COPD patients better than rolipram and cilomilast and suggested that it could be a useful anti-inflammatory therapy in COPD Two hundred eighty-one alcoholic patients were prospect ively evaluated by clinical , biochemical , and histologic parameters during a 4-yr period to assess their prognosis . They were stratified into four categories of injury : 1 ) fatty liver ( 26 patients ) , 2 ) acute alcoholic hepatitis ( 106 ) , 3 ) cirrhosis ( 39 ) , and 4 ) cirrhosis with superimposed alcoholic hepatitis ( 111 ) . The rate of survival and variables correlating with survival varied according to the group . At 48 months , 70 % of the patients with fatty liver were alive , 58 % in the alcoholic hepatitis group , 49 % in cirrhosis , and 35 % in alcoholic hepatitis superimposed upon cirrhosis . Within group one , deaths were due to causes unrelated to liver disease . In the alcoholic hepatitis group , factors significantly correlating with survival were ascites , alanine amino-transferase levels , grams of alcohol consumed , continuation of alcohol intake , and clinical severity of disease . Survival in patients of group three correlated significantly with prothrombin time and histologic severity score .  Patients with combined cirrhosis and alcoholic hepatitis exhibited the worst prognosis , with the most significant predictors of survival being age , grams of alcohol consumed , the ratio of serum aminotransferases ( AST : ALT ) and the histologic and clinical severity of the disease . Although a different pattern of correlates was observed for each pathologic level of injury , knowledge of the various correlates aids in prognostic assessment IMPORTANCE Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis , a life-threatening disease . The benefit of their combination is unknown . OBJECTIVE To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone . DESIGN , SETTING , AND PARTICIPANTS Multicenter , r and omized , double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis , as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32 . Duration of follow-up was 6 months . The last included patient completed the study in October 2010 . None of the patients were lost to follow-up for the main outcome . INTERVENTION Patients were r and omly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day ( n=133 ) for 28 days , or 40 mg of prednisolone and matching placebo ( n=137 ) for 28 days . MAIN OUTCOMES AND MEASURES Six-month survival , with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model , which defines treatment nonresponders after 7 days of initiation of treatment . RESULTS In intention-to-treat analysis , 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups ( 69.9 % [ 95 % CI , 62.1%-77.7 % ] vs 69.2 % [ 95 % CI ; 61.4%-76.9 % ] , P = .91 ) , corresponding to 40 vs 42 deaths , respectively . In multivariable analysis , only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival . At 7 days , response to therapy assessed by the Lille model was not significantly different between the 2 groups ( Lille model score , 0.41 [ 95 % CI , 0.36 - 0.46 ] vs 0.40 [ 95 % CI , 0 
    Output:
    
Best Practice Advice 7 : Presence of systemic inflammatory response syndrome ( SIRS ) on admission is associated with an increased risk of multi‐organ failure ( MOF ) syndrome .
Methylprednisolone does not improve survival beyond 28 days , and the benefits for < 28 days are modest .