***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 
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    Input: The mechanisms of correcting immune disorders in patients with pancreatic cancer requiring major surgery procedures by introducing perioperative immune-enhancing diet ( immunonutrition ) are still unclear . The purpose of our study was to investigate the effect of pancreatic cancer , extensive surgery and immunonutrition versus enteral st and ard nutrition on the apoptotic signaling pathways . The r and omized studies were performed in 72 patients before and after pancreatic cancer resection with preoperative st and ard ( Group I ) or enteral immunonutrition ( Group II ) . The expressions of Bcl-2 , Bax , caspases-3 , -9 , NF-κB , PARP-1/89 kDa , TNFR1/CD120a and Fas/CD95 in peripheral blood lymphocytes were assessed by western blot analysis and flow cytometry before and on day 1 , 3 and 7 after surgery . In malnourished patients before and after surgery , the expression of Bcl-2 , Bax , NF-κB , PARP-1 was significantly lower , whereas the expression of caspases , as well as the percentage of cells with death receptors were significantly higher when compared with the control group . There was no difference in Bcl-2 , Bax and PARP-1 expression between the control group and the patients with normal nutritional status ( Group III ) before surgery . In comparison to the st and ard nutrition , the preoperative immunonutrition increased the Bcl-2 and Bax expression inconsiderably but significantly increased the percentage of CD95- and CD120a-positive lymphocytes after surgery . In malnourished patients with pancreatic cancer , the overwhelming expression of caspases and the decrease expression of anti-apoptotic proteins may lead to inappropriate lymphocyte apoptosis and higher cell depletion . The preoperative enteral immunonutrition prevents the postoperative decrease in lymphocyte subsets , but a higher level of lymphocyte susceptibility to undergo accelerated apoptosis can also be considered Introduction Septic shock remains a major health care problem worldwide . Sepsis-induced immune alterations are thought to play a major role in patients ' mortality and susceptibility to nosocomial infections . Programmed death-1 ( PD-1 ) receptor system constitutes a newly described immunoregulatory pathway that negatively controls immune responses . It has recently been shown that PD-1 knock-out mice exhibited a lower mortality in response to experimental sepsis . The objective of the present study was to investigate PD-1-related molecule expressions in septic shock patients . Methods This prospect i ve and observational study included 64 septic shock patients , 13 trauma patients and 49 healthy individuals .  PD-1-related-molecule  expressions were measured by flow cytometry on circulating leukocytes . Plasmatic interleukin (IL)-10 concentration as well as ex vivo mitogen-induced lymphocyte proliferation were assessed . Results We observed that septic shock patients displayed increased PD-1 , PD-Lig and 1 ( PD-L1 ) and PD-L2 monocyte expressions and enhanced PD-1 and PD-L1 CD4 + T lymphocyte expressions at day 1 - 2 and 3 - 5 after the onset of shock in comparison with patients with trauma and healthy volunteers . Importantly , increased expressions were associated with increased occurrence of secondary nosocomial infections and mortality after septic shock as well as with decreased mitogen-induced lymphocyte proliferation and increased circulating IL-10 concentration . Conclusions These findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations . Results should be confirmed in a larger cohort of patients . This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease The objective of this study was to refine the APACHE ( Acute Physiology , Age , Chronic Health Evaluation ) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults . We prospect ively collected data on 17,440 unselected adult medical/surgical intensive care unit ( ICU ) admissions at 40 US hospitals ( 14 volunteer tertiary-care institutions and 26 hospitals r and omly chosen to represent intensive care services nationwide ) . We analyzed the relationship between the patient 's likelihood of surviving to hospital discharge and the following predictive variables : major medical and surgical disease categories , acute physiologic abnormalities , age , preexisting functional limitations , major comorbidities , and treatment location immediately prior to ICU admission . The APACHE III prognostic system consists of two options : ( 1 ) an APACHE III score , which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups ; and ( 2 ) an APACHE III predictive equation , which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients . A five-point increase in APACHE III score ( range , 0 to 299 ) is independently associated with a statistically significant increase in the relative risk of hospital death ( odds ratio , 1.10 to 1.78 ) within each of 78 major medical and surgical disease categories . The overall predictive accuracy of the first-day APACHE III equation was such that , within 24 h of ICU admission , 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed ( r2 = 0.41 ; receiver operating characteristic = 0.90 ) . Recording changes in the  APACHE III score on each subsequent day of ICU therapy provided daily up date s in these risk estimates . When applied across the individual ICUs , the first-day APACHE III equation accounted for the majority of variation in observed death rates ( r2 = 0.90 , p less than 0.0001 ) Introduction Studies on the role of programmed death-1(PD-1 ) and its main lig and ( PD-L1 ) during experimental models of sepsis have shown that the PD-1/PD-L1 pathway plays a pathologic role in altering microbial clearance , the innate inflammatory response and accelerated apoptosis in sepsis . However , the expression of PD-1 and PD-L1 and their role during the development of immune suppression in septic patients have not been eluci date d. The present study was design ed to determine whether the expression of PD-1 and PD-L1 is upregulated in septic shock patients and to explore the role of this pathway in sepsis-induced immunosuppression . Methods Nineteen septic shock patients and 22 sex-matched and age-matched healthy controls were prospect ively enrolled .  Apoptosis in lymphocyte sub population s and PD-1/PD-L1 expression on peripheral T cells , B cells and monocytes were measured using flow cytometry . Apoptosis of T cells induced by TNFα or T-cell receptor ligation in vitro and effects of anti-PD-L1 antibody administration were measured by flow cytometry . CD14 + monocytes of septic shock patients were purified and incubated with either lipopolysaccharide , anti-PD-L1 antibody , isotype antibody , or a combination of lipopolysaccharide and anti-PD-L1 antibody or isotype antibody . Supernatants were harvested to examine production of cytokines by ELISA . Results Compared with healthy controls , septic shock induced a marked increase in apoptosis as detected by the annexin-V binding and active caspase-3 on CD4 + T cells , CD8 + T cells and CD19 + B cells . Expression of PD-1 on T cells and of PD-L1 on monocytes was dramatically upregulated in septic shock patients . PD-1/PD-L1 pathway blockade in vitro with anti-PD-L1 antibody  decreased apoptosis of T cells induced by TNFα or T-cell receptor ligation . Meanwhile , this blockade potentiated the lipopolysaccharide-induced TNFα and IL-6 production and decreased IL-10 production by monocytes in vitro . Conclusions The expression of PD-1 on T cells and PD-L1 on monocytes was upregulated in septic shock patients . The PD-1/PD-L1 pathway might play an essential role in sepsis-induced immunosuppression Patients with sepsis have impaired host defenses that contribute to the lethality of the disorder . Recent work implicates lymphocyte apoptosis as a potential factor in the immunosuppression of sepsis . If lymphocyte apoptosis is an important mechanism , specific subsets of lymphocytes may be more vulnerable . A prospect i ve study of lymphocyte cell typing and apoptosis was conducted in spleens from 27 patients with sepsis and 25 patients with trauma . Spleens from 16 critically ill nonseptic ( 3 prospect i ve and 13 retrospective ) patients were also evaluated . Immunohistochemical staining showed a caspase-9-mediated profound progressive loss of B and CD4 T helper cells in sepsis . Interestingly , sepsis did not decrease CD8 T or NK cells . Although there was no overall effect on lymphocytes from critically ill nonseptic patients ( considered as a group ) , certain individual patients did exhibit significant loss of B and CD4 T cells . The loss of B and CD4 T cells in sepsis is especially significant because it occurs during life-threatening infection , a state in which massive lymphocyte clonal expansion should exist . Mitochondria-dependent lymphocyte apoptosis may contribute to the immunosuppression in sepsis by decreasing the number of immune effector cells . Similar loss of lymphocytes may be occurring in critically ill patients with other disorders Introduction Although major changes of the immune system have been described in sepsis , it has never been studied whether these may differ in relation to the type of underlying infection or not . This was studied for the first time . Methods The statuses of the innate and adaptive immune systems were prospect ively compared in 505 patients .  Whole blood was sample d within less than 24 hours of advent of sepsis ; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer . Results Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis . The rate of apoptosis of natural killer ( NK ) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia ( VAP ) and hospital-acquired pneumonia ( HAP ) compared with sepsis . The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis , primary bacteremia and VAP/HAP compared with sepsis . Regarding adaptive immunity , absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia ( CAP ) and intraabdominal infections compared with sepsis . Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis . Conclusions Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection . These results may have a major impact on therapeutics Introduction The impact of gender on outcome in critically ill patients is unclear . Weinvestigated the influence of gender on the epidemiology of severe sepsis and associated morbidity and mortality in a large cohort of ICU patients in the regionof Piedmont in Italy . Methods This was a post-hoc analysis of data from a prospect i ve , multicenter , observational study in which all patients admitted to one of 24 participatingmedical and /or surgical ICUs between 3 April 2006 and 29 September 2006 wereincluded . Results Of the 3,902 patients included in the study , 63.5 % were male . Female patients weresignificantly older than male patients ( 66 ± 16 years vs. 63 ± 16 years , P < 0.001 ) . Female patients were less likely to have severe sepsis and septic shock on admission to the ICU and to develop these syndromes during theICU stay . ICU mortality was similar in men and women in the whole cohort ( 20.1%vs . 19.8 % , P = 0.834 ) , but in patients with severe sepsis wassignificantly greater in women than in men ( 63.5 % vs. 46.4 % , P = 0.007).In multivariate logistic regression analysis with ICU outcome as the dependentvariable , female gender was independently associated with a higher risk of ICUdeath in patients with severe sepsis ( odds ratio = 2.33 , 95 % confidence interval = 1.23 to 4.39 , P = 0.009 ) but not in the whole cohort ( odds ratio = 1.07,95 % confidence interval = 0.87 to 1.34 ) . Conclusion In this large regional Italian cohort of ICU patients , there were more male thanfemale admissions . The prevalence of severe sepsis was lower in women than in men , but female gender was independently associated with a higher risk of death in theICU for patients with severe sepsis Although salutary effects of female sex steroids have been demonstrated not only in proestrus females but also in male animals treated with estradiol in different models of trauma , it remains unknown whether sex hormones influence post-traumatic immune response in humans . We therefore investigated the effect of sex and age on organ dysfunction and clinical course in patients with multiple injuries . Polytraumatized patients ( 
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Major elective surgery overcame many of these method ological limitations .