***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background —Extracorporeal circulation induces a systemic inflammatory response , which may adversely affect organ function . One manifestation of this response is increased fibrinolysis . Antifibrinolytic drugs such as aprotinin and & egr;-aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation ; however , the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known . This study examined the effects of aprotinin and & egr;-aminocaproic acid on plasma levels of proinflammatory [ interleukin-6 ( IL-6 ) ] and anti-inflammatory [ interleukin-10 ( IL-10 ) ] cytokines during and after extracorporeal circulation . Methods and Results —Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were r and omly assigned in a double-blind study to receive high-dose aprotinin , & egr;-aminocaproic acid , or saline placebo .  Plasma levels of IL-6 and IL-10 were measured at 5 time points before , during , and after extracorporeal circulation . In all 3 groups , both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day . Compared with saline , aprotinin significantly reduced IL-10 ( P = 0.02 ) and peak IL-6 ( P = 0.02 ) after extracorporeal circulation . In contrast , none of the reductions in IL-6 and IL-10 by & egr;-aminocaproic acid achieved statistical significance . Both aprotinin and & egr;-aminocaproic acid decreased blood loss compared with saline , but there was no significant difference in the number of patients receiving blood products among the treatment groups . Conclusions —These data suggest that aprotinin and & egr;-aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation . Aprotinin but not & egr;-aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10 . Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes OBJECTIVES To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization . DESIGN A prospect i ve r and omized study . SETTING A university hospital . PARTICIPANTS Forty-three patients were r and omly assigned to either group A , 21 patients treated with 2 x 10(6 ) kallikrein inhibitor units ( KIU ) of aprotinin in the cardiopulmonary bypass ( CPB ) prime , or group B , 22 patients , untreated . INTERVENTIONS Patients , scheduled for elective coronary surgery , were treated with 2 x 10(6 ) KIU of aprotinin in the CPB prime .  Markers of coagulation and fibrinolysis were evaluated . MEASUREMENTS AND MAIN RESULTS Surgical times , number of reopenings , and allogeneic blood requirements were collected for each patient . Blood sample s were obtained before and after surgery for assessing coagulation ( prothrombin time [ PT ] , activated partial thromboplastin time [ aPTT ] , ethanol test , factor VII , antithrombin III [ AT III ] , thrombin-antithrombin III complex [ TAT ] , fragment 1.2 of prothrombin [ F1.2 ] ) and fibrinolysis ( fibrin degradation products [ FOP ] , plasmin-antiplasmin complexes [ PAP ] , D-dimers ) markers variations . In group A surgical times were faster , there were fewer reopenings ( 0 v 3 ) , and fewer blood transfusions ( 1 patient v 4 patients ) . The two groups did not differ for PT , aPTT , and fibrinogen measurements . Postoperative FDP ( measurable in more patients of group B at the end of the operation ) , PAP , and D-dimers postoperatory levels ( less increased in aprotinin group ) show the antifibrinolytic properties of the drug . Regarding the coagulation markers , factor VII decreased , whereas TAT and F1.2 increased , all to a lesser extent in the aprotinin group compared with the untreated patients , at the end of operation . CONCLUSION Pump-prime aprotinin minimized , even if not completely inhibited , the activation of coagulation and fibrinolysis during CPB , possibly ensuring a less complicated and safer postoperative recovery . It seemed to allow the maintenance of a correct balance of hemostatic systems , avoiding the risk of thrombotic phenomena The serine proteinase inhibitor aprotinin significantly reduces postoperative blood loss in patients requiring cardiac surgery using cardiopulmonary bypass . This study compared two low‐dose regimens with administration of high‐dose aprotinin and a control protocol to determine whether the dose of aprotinin could be greatly decreased but still maintain efficacy after primary cardiac surgery . Some 100 patients were r and omly assigned to one of four groups : control group ( 0·9 per cent saline placebo , n = 25 ) ; high‐dose group ( aprotinin 2 × 106 kallikrein inactivator ( KI ) units intravenous patient bolus and 0·5 × 106 KI units h−1 plus 2 × 106 KI units into pump prime , n = 25 ) ; prime group ( aprotinin 2 × 106 KI units added to the pump prime , n = 24 ) ; and patient group ( aprotinin 106 KI units intravenous patient bolus plus 106 KI units added to the pump prime , n = 26 ) . Only patients from the high‐dose and patient groups had reduced intraoperative blood loss , but patients from all three aprotinin‐treated groups demonstrated a significant decrease in median postoperative blood loss compared with the control group ( high‐dose 350 ml , prime 420 ml , patient 340 ml versus control 780 ml ; P < 0·001 ) . There was an even greater reduction in measured median postoperative haemoglobin loss within the chest drains in the treated compared with the control patients ( high‐dose 15 g , prime 24 g , patient 14 g versus control 47 g ; P < 0·001 ) . These decreases were statistically the same for all the treated groups ; it is possible to lower the dose of aprotinin to approximately one‐third of the currently recommended dosage and still obtain significantly reduced postoperative blood loss in primary cardiac surgery To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Background Patients on cardiopulmonary bypass ( CPB ) have an increased susceptibility to postoperative bleeding . Previous reports using desmopressin acetate ( DDAVP ) for the prevention of postoperative bleeding have given contradictory results , whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery . This r and omized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB . Methods and Results One hundred nine of 122 eligible patients were r and omized to four different groups : Group A ( n=28 ) received aprotinin starting with a bolus of 2 × 106 KIU followed by a continuous infusion of 0.5 × 106 KIU/h until the end of surgery ; group B ( n=25 ) received of DDAVP 0.3 μ/kg IV on completion of CPB ; group C ( n=28 ) received two doses of DDAVP , the first as in group B and an additional dose 6 hours after surgery ; group D ( n=28 ) received no treatment . There was a marked reduction of postoperative blood loss either at 12 hours ( P<.01 ) or 72 hours ( P<.02 ) in the aprotinin group compared with all other groups , whereas no significant effect was observed in either of the two DDAVP regimens . A significant reduction in the amount of blood used was observed only in the aprotinin group ( P<.01 ) . Of the plasma fibrinolytic components assayed , there was a significant reduction of the fibrin degradation product generation in the aprotinin group ( P<.001 ) , whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group . No side effects related to the study drugs were observed in any patient . Conclusions Aprotinin inhibited fibrinolysis ; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB . Neither one nor two doses of DDAVP had a beneficial effect . Aprotinin offers better alternative than DDAVP in the prevention of bleeding after CPB BACKGROUND Aprotinin therapy is now widely used during cardiac surgery . This study examined the clinical and economic effectiveness of high-dose or low-dose aprotinin in comparison to placebo . METHODS In a double blind , r and omized study , three groups of 50 patients received  high-dose aprotinin costing AUS$614 per patient ( AUS$ = Australian dollars ) , low-dose aprotinin costing AUS$220 per patient or placebo .  Re source use influenced by aprotinin therapy was measured . RESULTS Both doses were effective in reducing chest drainage and postoperative transfusion requirements , high-dose being more effective than low-dose . Both doses reduced the rate of reoperations for hemostasis . A base case of statistically significant differences associated with the high-dose and low-dose aprotinin showed cost savings of AUS$77 and AUS$348 per patient , respectively . If the demonstrated less significant reductions in operating room and ward stay are included , these savings become AUS$463 and AUS$715 , respectively . Alternately , if cross-matches are replaced by group- and -hold and cell savers are not used , the savings per patient would be AUS$196 and AUS$467 , respectively . CONCLUSIONS While high-dose aprotinin is clinical ly more effective than low-dose aprotinin , low-dose therapy demonstrates greater cost savings The effectiveness and mechanism of aprotinin reduced bleeding after cardiopulmonary bypass surgery was studied in a double blind r and omised study of 106 patients undergoing valve replacement surgery .  Aprotinin therapy was associated with significant reduction in perioperative bleeding and postoperative blood transfusion requirements . Although initially tissue plasminogen activator ( t-PA ) activity was lower in the aprotinin than placebo group , as surgery proceeded this difference was reversed due to less plasminogen activator inhibitor-1 release in the aprotinin group . This indicates that aprotinin-mediated suppression of fibrinolysis as demonstrated by reduced D-dimer concentration was not related to t-PA . Furthermore , similar perioperative reduction of plasminogen levels in aprotinin and placebo groups indicated a similar degree of conversion of plasminogen to plasmin . However , less plasmin bound with alpha 2-antiplasmin in the plasma in the aprotinin group as it was already complexed with aprotinin where it remained protected from the natural inhibitor on the intact fibrin surface . The reduced fibrinolytic activity of the aprotinin group was thus brought about by the complexing of aprotinin with the plasmin which was bound to the fibrin surface Sixty consecutive patients undergoing elective open-heart surgery were prospect ively enrolled in a study to compare the efficacy of 3 different antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous blood requirements in combination with blood-saving techniques and restrictive indications for blood transfusion . The patients were r and omized to 1 of 4 intraoperative treatment regimens : 1 ) control ( no antifibrinolytic therapy ) ; 2 ) epsilon-aminocaproic acid  ( 10 g IV at induction of anesthesia , followed by infusion of 2 g/h for 5 hours ) ; 3 ) tranexamic acid ( 10 mg/kg IV within 30 minutes after induction of anesthesia , followed by infusion of 1 mg/kg per hour for 10 hours ) ; or 4 ) high-dose aprotinin ( 2 million KIU IV at induction 
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Conclusions This study demonstrates that investigators evaluating aprotinin were not adequately citing previous research , result ing in a large number of RCTs being conducted to address efficacy questions that prior trials had already definitively answered .