***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: Although we have reported the beneficial effect of continuous regional arterial infusion ( CRAI ) of protease inhibitor and antibiotic on acute necrotizing pancreatitis ( ANP ) , the optimal timing of the initiation of CRAI therapy has not been clarified . The present study was conducted to evaluate whether the difference of the timing of CRAI therapy may affect the clinical course and outcome in ANP . 73 patients with ANP were stratified into three groups according to the interval between the onset and initiation of CRAI therapy as follows : group I ( 32 patients in whom CRAI therapy was initiated within 48 h after the onset ) ; group II ( 22 patients in whom CRAI therapy was initiated between 48 and 72 h after the onset ) , and group III ( 19 patients in whom CRAI was initiated more than 72 h after the onset ) . The mortality rate was 3.2 % in group I , 9.1 % in group II , and 26.3 % in group III . The mortality rate was significantly low in group I compared with that in group III . The frequency of respiratory failure in group I was also significantly low compared with that in group III . CRP and APACHE II score were reduced rapidly in both groups I and II after the initiation of CRAI therapy . These results suggested that the optimal timing of CRAI therapy  in ANP should be considered to be within 72 h after the onset OBJECTIVE The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to improve the quality of r and omized controlled trial ( RCT ) reports . We assessed the quality of current Japanese RCT reports by conducting a cross-sectional study to examine the extent to which they adhere to the CONSORT statement . METHODS Reports of RCTs conducted in Japan that were published in medical journals between January and March 2004 were sample d from MEDLINE . The proportion of adherence to each item in the CONSORT checklist was evaluated for each report . Additionally , information on ethics reporting and funding sources was collected . RESULTS A total of 98 RCT reports from Japan were evaluated , and adherence to the CONSORT statement was found to be suboptimal . Only 6 of 29 items in the checklist were described in more than 80 % of reports . Adherence to key method ological items of the CONSORT statement was as follows : 23 % for sample size determination , 39 % for r and om sequence generation , 17 % for allocation concealment , 29 % for blinding , 53 % for numbers analyzed , and 6 % for inclusion of a flow diagram . Adherence to additional items was 82 % for ethics committee approval , 92 % for receiving informed consent , and 20 % for disclosing funding sources . CONCLUSION Our study on adherence of recent RCT reports from Japan to the CONSORT statement reveals that there is a significant need for improvement . Further investigation on the quality of RCT reports and ways to improve reporting quality is required In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Objectives To examine the reporting characteristics and method ological details of r and omised trials indexed in PubMed in 2000 and 2006 and assess whether the quality of reporting has improved after publication of the Consoli date d St and ards of Reporting Trials ( CONSORT ) Statement in 2001 . Design Comparison of two cross sectional investigations . Study sample All primary reports of r and omised trials indexed in PubMed in December 2000 ( n=519 ) and December 2006 ( n=616 ) , including parallel group , crossover , cluster , factorial , and split body study design s. Main outcome measures The proportion of general and method ological items reported , stratified by year and study design . Risk ratios with 95 % confidence intervals were calculated to represent changes in reporting between 2000 and 2006 . Results The majority of trials were two arm ( 379/519 ( 73 % ) in 2000 v 468/616 ( 76 % ) in 2006 ) parallel group studies ( 383/519 ( 74 % ) v 477/616 ( 78 % ) ) published in specialty journals ( 482/519 ( 93 % ) v 555/616 ( 90 % ) ) . In both 2000 and 2006 , a median of 80 participants were recruited per trial for parallel group trials . The proportion of articles that reported drug trials decreased between 2000 and 2006 ( from 393/519 ( 76 % ) to 356/616 ( 58 % ) ) , whereas the proportion of surgery trials increased ( 51/519 ( 10 % ) v 128/616 ( 21 % ) ) . There was an increase between 2000 and 2006 in the proportion of trial reports that included details of the primary outcome ( risk ratio ( RR ) 1.18 , 95 % CI 1.04 to 1.33 ) , sample size calculation ( RR 1.66 , 95 % CI 1.40 to 1.95 ) , and the methods of r and om sequence generation ( RR 1.62 , 95 % CI 1.32 to 1.97 ) and allocation concealment ( RR 1.40 , 95 % CI 1.11 to 1.76 ) . There was no difference in the proportion of trials that provided specific details on who was blinded ( RR 0.91 , 95 % CI 0.75 to 1.10 ) . Conclusions Reporting of several important aspects of trial methods improved between 2000 and 2006 ; however , the quality of reporting remains well below an acceptable level . Without complete and transparent reporting of how a trial was design ed and conducted , it is difficult for readers to assess its conduct and validity A controlled trial with synthetic protease inhibitor gabexelate mesilate ( FOY ) in the treatment of acute pancreatitis was conducted in a total of 42 patients . The age , sex , etiology of pancreatitis , initial serum amylase level , and amylase creatinine clearance ratio were comparable between  FOY-treated and control groups .  FOY did not alter the course of the disease , but there was a weak trend toward lower morbidity and mortality in the FOY-treated patients . These results may justify further , larger scale studies or evaluation of alternate dosage or route of administration In two prospect i ve studies the effect of proteinase inhibiting agents and glucagon in acute pancreatitis have been studied by a r and omised series . Moreover the effect of the basic therapy was examined in additional 103 patients .  Symptoms , clinical and laboratory chemical findings correspond to each other in all collectives . The results seem to be the best ones in those patients having been treated by basic therapy only Kallikrein is a protease involved in the inflammatory process causing acute pancreatitis . Attempts to prevent this process with antiprotease agents have been successful in experimental animal models but disappointing in humans . We studied 40 consecutive patients undergoing endoscopic papillosphincterotomy .  This procedure can induce a transient , moderate pancreatic inflammatory reaction , characterized by hyperamylasemia , which in 1 - 6 % of the patients may evolve to acute pancreatitis . To assess the capacity of C1 inhibitor , the main physiological inhibitor of kallikrein , to prevent such complications , we pretreated 20 patients with 3000 U of C1 inhibitor plasma concentrate i.v . ; 20 patients served as controls . Serum levels of amylase and functional C1 inhibitor were determined before the procedure and after 2 , 4 , 8 and 24 hours . Serum levels of amylase in the control group ( 146 + /- 21 IU ) and in the group treated with C1 inhibitor ( 158 + /- 25 IU ) were similar before treatment . Four and 8 hours after the end of the procedure , amylase levels were significantly lower ( p < 0.001 ) in the treated group ( 231 + /- 46 and 355 + /- 104 IU ) than in the control subjects ( 969 + /- 229 and 923 + /- 207 IU ) . After 24 hours both groups had normal amylase levels . In treated patients , functional levels of C1 inhibitor increased from 104 + /- 30 to 175 + /- 30 % and remained elevated throughout the observation period . These data indicate that C1 inhibitor plasma concentrate can prevent hyperamylasemia following pancreas injury , probably , by inhibiting the kallikrein-mediated inflammatory process . C1 inhibitor might benefit patients at high risk of pancreatitis who undergo endoscopic papillosphincterotomy BACKGROUND A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis . METHODS Two hundred twenty-three patients from 29 hospitals were entered in the r and omized , double-blind trial . Admission to the study was based on strict criteria excluding mild acute pancreatitis . The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days . All patients were followed up for 90 days after r and omization . The analysis was based on 14 complications , including death . RESULTS There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placebo and gabexate mesilate groups . CONCLUSIONS The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis BACKGROUND AND AIM Till now , no Italian studies providing information on acute pancreatitis have been published . The aim of this study was to evaluate the epidemiological and clinical characteristics of acute pancreatitis in Italy . MATERIAL S AND METHODS The study involved 37 Italian centres distributed homogeneously throughout the entire national territory and prospect ively collected epidemiological , anamnestic , laboratory , radiological , therapeutic ( pharmacological , endoscopic and surgical ) data , relevant to each individual case of acute pancreatitis consecutively observed during the period from September 1996 to June 2000 . RESULTS One thous and two hundred and six case report forms were collected , but 201 patients ( 16.6 % ) were subsequently eliminated from the final analysis . We therefore studied 1005 patients , 533 ( 53 % ) males and 472 ( 47 % ) females , mean age 59.6 + /- 20 years . On the basis of the Atlanta classification of acute pancreatitis , 753 patients of the 1005 cases analysed ( 75 % ) were mild and 252 patients ( 25 % ) severe . The aetiology was biliary in 60 % of the patients , related to alcohol abuse in 8.5 % , while in 21 % of the cases it could not be identified . Over 80 % of the patients ( 83 % ) were admitted to hospital within 24 h from the onset of clinical symptoms , while only 6 % were admitted after 48 h. In particular , 65 % of the patients were admitted to hospital within the first 12 h.  Antibiotics  were used in 85 % of the severe and 75 % of mild forms .  Endoscopic therapy  was carried out in 65 % of the severe cases , but only in 40 % it was carried out prior to 72 h. Eighty-five patients ( 8.5 % of the total , 34 % of the severe forms ) underwent surgical intervention : 20 % on the first day , 38.5 % within the fourth day , and the remaining ( 41.5 % of the cases ) later on for infected necrosis . The mean duration of hospitalisation for patients with mild pancreatitis was 13 + /- 8 days , while for the severe disease it was of 30 + /- 14 days . The overall mortality rate was 5 % , 17 % in severe and 1.5 % in mild pancreatitis . CONCLUSIONS Acute pancreatitis in Italy is more commonly a mild disease with a biliary aetiology . The treatment of the disease is not optimal and , on the basis of these data , needs to be st and ardised . Despite this , the overall mortality rate is low ( 5 % ) OBJECTIVE To evaluate the quality of reporting of  r and omized controlled trials in cardiothoracic surgery  , to identify factors associated with good reporting quality , and to assess the awareness of the Consoli date d St and ards for Reporting of Trials statement and ascertain the views of authors reporting r and omized controlled trials on 
    Output:
    
Conclusion The present meta- analysis re-confirmed that there is no solid evidence that supports the intravenous use of protease inhibitors to prevent death due to acute pancreatitis