***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: Purpose Ulinastatin , a serine protease inhibitor , inhibits several pro-inflammatory proteases and decreases inflammatory cytokine levels and mortality in experimental sepsis . We studied the effect of ulinastatin on 28-day all-cause mortality in a double-blind trial in patients with severe sepsis in seven Indian hospitals . Methods Patients with sepsis were r and omized within 48 h of onset of one or more organ failures to receive intravenous administration of ulinastatin ( 200,000 IU ) or placebo 12 hourly for 5 days . Results Of 122 r and omized subjects , 114 completed the study ( 55 receiving ulinastatin , 59 receiving placebo )  . At baseline , the  mean APACHE II score was 13.4 ( SD = 4.4 ) , 48 ( 42 % ) patients were receiving mechanical ventilation , 58 ( 51 % ) were on vasopressors , and 35 % had multiple organ failure . In the modified intention-to-treat analysis ( patients receiving six or more doses of study drugs ) , 28-day all-cause mortality was 7.3 % with ulinastatin ( 4 deaths ) versus 20.3 % ( 12 deaths ) with placebo ( p = 0.045 ) . On multivariate analysis too , treatment with ulinastatin ( odds ratio 0.26 , 95 % CI 0.07–0.95 ; p = 0.042 ) independently decreased 28-day all-cause mortality . However , the mortality difference did not reach statistical significance in the intention-to-treat analysis [ 10.2 % ( 6/59 deaths ) with ulinastatin versus 20.6 % ( 13/63 deaths ) in the placebo group ; p = 0.11 ] . The ulinastatin group had lower incidence of new-onset organ failure ( 10 vs. 26 patients , p = 0.003 ) , more ventilator-free days ( mean ± SD 19.4 ± 10.6 days vs. 10.2 ± 12.5 days , p = 0.019 ) , and shorter hospital stay ( 11.8 ± 7.1 days vs. 24.2 ± 7.2 days , p < 0.001 ) . Conclusions In this pilot study , intravenous administration of ulinastatin reduced mortality in patients with severe sepsis in the modified intention-to-treat analysis , but not in the intention-to-treat analysis Introduction Severe sepsis is associated with a high mortality rate despite implementation of guideline recommendations . Adjunctive treatment may be efficient and require further investigation . In light of the crucial role of immunologic derangement in severe sepsis , thymosin alpha 1 ( Tα1 ) is considered as a promising beneficial immunomodulatory drug . The trial is to evaluate whether Tα1 improves 28-day all-cause mortality rates and immunofunction in patients with severe sepsis . Methods We performed a multicenter r and omized controlled trial in six tertiary , teaching hospitals in China between May 12 , 2008 and Dec 22 , 2010 . Eligible patients admitted in ICU with severe sepsis were r and omly allocated by a central r and omization center to the control group or Tα1 group ( 1:1 ratio ) . The primary outcome was death from any cause and was assessed 28 days after enrollment . Secondary outcomes included dynamic changes of Sequential Organ Failure Assessment ( SOFA ) and monocyte human leukocyte antigen-DR ( mHLA-DR ) on day 0 , 3 , 7 in both groups . All analyses were done on an intention-to-treat basis . Results A total of 361 patients were allocated to either the control group ( n = 180 ) or Tα1 ( n = 181 ) group . The mortalities from any cause within 28 days in the Tα1 group and control group were 26.0 % and 35.0 % respectively with a marginal P value ( nonstratified analysis , P = 0.062 ; log rank , P = 0.049 ) ; the relative risk of death in the Tα1 group as compared to the control group was 0.74 ( 95 % CI 0.54 to 1.02 ) . Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 ( mean difference in mHLA-DR changes between the two groups was 3.9 % , 95 % CI 0.2 to 7.6 % , P = 0.037 ) and day 7 ( mean difference in mHLA-DR changes between the two groups was 5.8 % , 95 % CI 1.0 to 10.5 % , P = 0.017 ) than in the control group . No serious drug-related adverse event was recorded . Conclusions The use of Tα1 therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis . Trial registration Clinical Trials.gov NCT00711620 OBJECTIVE The aim of this study was to evaluate the potential efficacy of therapy with thymosin alpha(1 ) and ulinastatin for patients with sepsis due to carbapenem-resistant bacteria . DESIGN Prospect i ve , r and omized , parallel controlled clinical study . METHODS A total of 120 patients received a diagnosis of sepsis caused by infection with carbapenem-resistant bacteria and satisfied the study enrollment criteria . Sixty patients received carbapenems combined with thymosin alpha(1 ) and ulinastatin ( the CTU group ) , and the other 60 patients were treated with carbapenems and placebo ( the CP group ) . For both groups , flow cytometry was used to enumerate lymphocyte subsets , and ELISA was used to determine cytokine concentrations . RESULTS When the 2 groups were compared , the CTU group exhibited a better performance with respect to organ failure scores such as the Acute Physiology and Chronic Health Evaluation II score , the Multiple Organ Failure Score , and the Glasgow Coma Scale . The CTU group also showed significant improvements in CD4(+)CD8(+ ) count after initiation of treatment . In addition , compared with the CP group , in the CTU group the balance between proinflammatory mediators ( such as tumor necrosis factor-alpha , interleukin [IL]-1beta , IL-6 , and IL-8 ) and anti-inflammatory cytokines ( including IL-4 and IL-10 ) was better modulated , and the cumulative survival rate of the CTU group exceeded that of the CP group by 17.8 % at day 28 , 25.9 % at day 60 , and 27.4 % at day 90 . CONCLUSION Immunomodulatory therapy that combines thymosin alpha(1 ) and ulinastatin appears to improve the survival rate for patients infected with carbapenem-resistant bacteria . The number of patients in this study was relatively small , and although the same number of patients was initially enrolled in each study group , the groups were not the same size at the end of the study . Therefore , a larger clinical trial should be conducted to vali date this conclusion . TRIAL REGISTRATION The trial was registered with the Chinese State Food and Drug Administration ( Peking Science and Technology Development Plan , 2002[641 ] ) , ( registration number 2007Y0211 ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To investigate the immune and inflammation confusion state in severe sepsis and the effects of two way immunomodulation therapy with continuous blood purification ( CBP ) , thymosin alpha1 , and combined therapy of CBP and thymosin alpha(1 ) . METHODS 91 Patients with severe sepsis aged > 18 , with Marshall score>5 . were r and omly divided into 4 groups : CBP Group ( n = 22 ) undergoing continuous renal replacement therapy ( CRRT ) or molecular adsorbents recirculating system ( MARS ) therapy once a day for 3 days in addition to classical Surviving Sepsis Campaign ( SSC ) therapy , Thymosin alpha(1 ) Group ( n = 23 ) undergoing subcutaneous injection of thymosin alpha(1 ) 1.6 mg once a day for 7 days in addition to SSC therapy , Combined Therapy Group ( n = 22 ) undergoing CBP combined with thymosin alpha(1 ) treatment in addition to SSC therapy , and SSC Group ( treatment control group , n = 24 ) undergoing SSC therapy only . Peripheral blood sample s were collected before treatment , and 3 and 7 days after the beginning of treatment ( days 4 and 8) to detect the serum interleukin (IL)-6 , IL-10 , and tumor necrosis factor (TNF)-alpha . The levels of CD(14)(+ ) monocyte human leucocyte antigen (HLA)-DR and T lymphocytes were monitored . The mechanical ventilation time , ICU stay length , and mortality within 28 d and mortality within 90 d were observed . Ten healthy persons were used as healthy control group . RESULTS Thirty-four of the 91 patients  died within 28 d with a mortality of 77.4 % ( Death Group ) and other 57 patients were put in Survival Group . The levels of serum IL-6 , IL-10 , and TNFalpha , and IL-6/IL-10 at different time points of both Death and Survival Groups were all significantly higher , and the HLA-DR level , and CD(3)(+ ) , CD(4)(+ ) , and CD(8)(+ ) T lymphocyte numbers at different time points of both Death and Survival Groups were all significantly lower than those of the healthy controls ( P < 0.05 or < 0.01 ) . The levels of serum IL-6 , IL-6/IL-10 , TNFalpha , HLA-DR , and CD(3)(+ ) , CD(4)(+ ) , and CD(8)(+ ) T lymphocyte at different time points of Death Group were all significantly higher than those of Survival Group ( P < 0.05 or < 0.01 ) . The CD(3)(+ ) T lymphocyte number on day 8 of Thymosin Group was significantly higher than that of SSC Group ( all P < 0.05 ) . The serum IL-6 and TNFalpha and IL-6/IL-10 were decreased , and HLA-DR , and CD(3)(+ ) , CD(4)(+ ) , and CD(8)(+ ) were increased significantly on day 8 in CBP and Combined Therapy Groups . The level of TNFalpha decreased , and the numbers of CD(3)(+ ) and CD(4)(+ ) T lymphocytes increased significantly on day 4 in Combined Therapy Group ( P < 0.05 or P < 0.01 ) . Compared with Thymosin Group , almost all the indexes of CBP and Combined Therapy Groups were improved , only the CD(3)(+ ) T lymphocyte level on day 4 increased and the IL-6/IL-10 ratio on day 8 was decreased significantly in Combined Therapy Group ( both P < 0.05 ) . Compared with those of SSC Group , the mechanical ventilation time , length of ICU stay within 28 days , and 28 days mortality and 90 days mortality of the 3 treatment groups were all decreased , and there were statistical differences in the length of ICU stay of CBP Group and in the mechanical ventilation time and length of ICU stay within 28 days of Combined Therapy Group ( both P < 0.05 ) . CONCLUSION Systemic inflammatory response and immunodepression exist simultaneously in severe sepsis . Thymosin alpha(1 ) increases the cellular immunity , and CBP bi-modulates the immune turbulence , reduces the inflammatory mediators , and ameliorates the immune homeostasis . These 2 therapies also improve the clinical prognosis and the combination of both would be more effective Objectives : To study the effect of immunomodulatory therapy with ulinastatin plus thymosin α 1 on septic patients . Method : A total of 56 sepsis patients were r and omized into a treatment group , receiving immunomodulatory therapy , and a placebo group , a placebo .  Acute Physiology and Chronic Health Evaluation II scores , clinical data , lymphocyte subsets , immunological indexes , and coagulation parameters were determined before admission and on the 3rd , 8th , and 28th day after admission to the Intensive Care Unit . Results : The treatment group experienced a 78 % cumulative survival , the placebo group experienced a 60 % cumulative survival ; the survival difference was mirrored by Acute Physiology and Chronic Health Evaluation II scores and more quickly improved leukocyte counts , lymphocyte counts , coagulation parameters , and cytokine levels in the treatment . Conclusions : Combined immunomodulatory therapy with ulinastatin plus thymosin α1 appears to yield improved survival for patients with sepsis ; this finding should be verified in larger clinical trials OBJECTIVE To investigate the effect of ulinastatin ( UTI ) on the levels of immune regulatory cells , pro-inflammatory mediators , and the expression of human leukocyte antigen-DR ( HLA-DR ) in CD14⁺ monocytes . METHODS A total of sixty patients with severe sepsis who were admitted to intensive care unit 
    Output:
    
Treatment of severe sepsis with UCT reduced both the 28-day and the 90-day mortality , whereas treatment with TA reduced only the 28-day mortality .
The effects of UCT , UA , and TA on intensive care unit stay , mechanical ventilation , antibiotics and vasopressor use , and 28-day APACHE II scores of septic patients are still unclear .