human
***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: OBJECTIVES To evaluate the efficacy of bovine lactoferrin ( BLF ) in preventing first episode of late-onset sepsis ( LOS ) in low birth weight ( LBW ) neonates . METHODS In this study conducted from May 2012 to July 2013 in the neonatal intensive care unit ( NICU ) of a tertiary care hospital , inborn asymptomatic neonates , < 2000 g , admitted to NICU in first 12 h of birth with no maternal risk factors for sepsis were r and omized to receive BLF or placebo from 1st to 28th day of life . The incidence of culture-proven sepsis and sepsis-attributable mortality after 72 h of life was recorded . Increasing doses of BLF were used with higher birth weights . RESULTS Incidence of first episode of culture-proven LOS was significantly lower in the BLF group vs. placebo [ 2/63 ( 3.2 % ) vs. 9/67(13.4 % ) ; risk ratio , 0.211 ; 95 % CI , 0.044 - 1.019 ; p = 0.036 ] . Statistically significant reduction in the sepsis-attributable mortality was also seen after use of prophylactic BLF [ 0/63 ( 0 % ) vs. 5/67 ( 7.5 % ) ; p = 0.027 ] . CONCLUSION BLF  supplementation in LBW neonates reduced the incidence of first episode of LOS Lactoferrin has broad-spectrum antimicrobial activity , and the authors hypothesized that recombinant human lactoferrin ( Talactoferrin alfa [ TLF ] ) would reduce mortality and morbidity in a coinfection model . The MIC50 ( minimum inhibitory concentration required to inhibit the growth of 50 % of organisms ) of TLF againstC and ida albicans and Staphylococcus epidermidis was determined . Neonatal Wistar rats were infected withCalbicans orS epidermidis or both , at doses of 2 × 108 colony-forming units ( CFUs ) given subcutaneously . Rat pups in each group were r and omly given TLF intraperitoneally at 40 mg/kg/dose or 300 mg/kg/dose , or saline in 0.2 mL , once a day for 4 d and were monitored for mortality , weight gain , and blood culture positivity . Trough serum levels of TLF were measured at 24 , 48 , 72 , 96 , and 144 h. MIC50 of TLF was 30 μg/mL and 500 μg/mL forC albicans and Sepidermidis , respectively . TLF prophylaxis significantly improved survival in the coinfection group at 40 mg/kg/dose ( by 16.1 % ; P=.019 ) and at 300 mg/kg/dose ( by 15.1 % ; P=.027 ) and in the Sepidermidis group at a dose of 40 mg/kg/dose ( by 1 8.6 % ; P=.04 ) . Weight gain was not affected by TLF prophylaxis . Serum trough levels of TLF were 1000-fold lower than in vitro MIC50 . The authors conclude that lactoferrin prophylaxis significantly enhanced survival in coinfection and in the subgroupof S epidermidis infection ( 40 mg/kg/dose ) through indirect mechanisms Summary Background : Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells . Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity . Studies in animal models have shown promising anti-cancer activity . The purpose of the present study was to evaluate the safety and tolerability of talactoferrin alfa ( talactoferrin ; TLF ) in humans , as well as pharmacokinetics and pharmacodynamics . Methods : Ten adult patients with progressive advanced solid tumors who had failed conventional chemotherapy  were administered oral TLF at doses from 1.5 to 9 g/day , using a 2 weeks on , 2 weeks off schedule . Patients were evaluated for drug toxicity , tumor growth rate , talactoferrin pharmacokinetics and cytokine markers . Results : Talactoferrin was very well tolerated . No hematological , hepatic , or renal toxicities were reported . A single patient had Grade 2 diarrhea , and there were no Grade 3 or 4 toxicities . Following oral administration , significant levels of talactoferrin  were undetectable in circulation , but a statistically significant increase in circulating IL-18 , a pharmacodynamic indicator of talactoferrin activity , was observed . Of the eight patients who were radiologically evaluable , five ( 63 % ) had stable disease by RECIST criteria two months after start of therapy , including one patient with a minor response . Seven patients ( 88 % ) had a decrease in their tumor growth rate . The three patients with non-small cell lung cancer ( NSCLC ) all survived for at least one year following the start of talactoferrin monotherapy . Conclusions : Talactoferrin is a promising , well-tolerated new agent that should be evaluated further in patients with refractory metastatic cancer CONTEXT Sepsis is a common and severe complication in premature neonates , particularly those with very low birth weight ( VLBW ) ( < 1500 g ) . Whether lactoferrin , a mammalian milk glycoprotein involved in innate immune host defenses , can reduce the incidence of sepsis is unknown . In animal models , the probiotic Lactobacillus rhamnosus GG ( LGG ) enhances the activity of lactoferrin but has not been studied in human infants . OBJECTIVE To establish whether bovine lactoferrin ( BLF ) , alone or in combination with LGG , reduces the incidence of late-onset sepsis in VLBW neonates . DESIGN , SETTING , AND PATIENTS Prospect i ve , multicenter , double-blind , placebo-controlled , r and omized trial conducted in 11 Italian tertiary neonatal intensive care units . Patients were 472 VLBW infants enrolled from October 1 , 2007 , through July 31 , 2008 , and assessed until discharge for development of sepsis . INTERVENTION Infants were r and omly assigned to receive orally administered BLF ( 100 mg/d ) alone ( n = 153 ) , BLF plus LGG ( 6 x 10(9 ) colony-forming units/d ) ( n = 151 ) , or placebo ( n = 168 ) from birth until day 30 of life ( day 45 for neonates < 1000 g at birth ) . MAIN OUTCOME MEASURE First episode of late-onset sepsis , ie , sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid . RESULTS Demographic , clinical , and management characteristics of the 3 groups were similar , including type of feeding and intake of maternal milk . Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups ( 9/153 [ 5.9 % ] and 7/151 [ 4.6 % ] , respectively ) than in the control group receiving placebo ( 29/168 [ 17.3 % ] ) ( risk ratio , 0.34 ; 95 % confidence interval , 0.17 - 0.70 ; P = .002 for BLF vs control and risk ratio , 0.27 ; 95 % confidence interval , 0.12 - 0.60 ; P < .001 for BLF plus LGG vs control ) . The decrease occurred for both bacterial and fungal sepsis . No adverse effects or intolerances to treatment occurred . CONCLUSION Compared with placebo , BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53107700 Background : Early onset neonatal sepsis ( EOS , occurring in the first 72 hours of life ) remains an important cause of illness and death among very low birth weight ( VLBW ) preterm infants . We previously reported a change in the distribution of pathogens associated with EOS from predominantly Gram-positive to primarily Gram-negative organisms . Objective : To compare rates of EOS and pathogens associated with infection among VLBW infants born at centers of the National Institute of Child Health and Human Development ( NICHD ) Neonatal Research Network during 3 time periods : 1991–1993 ; 1998–2000 ; and 2002–2003 . Study Design : Prospect ively collected data from the NICHD Neonatal Research Network VLBW registry were retrospectively review ed . Rates of blood culture confirmed EOS , selected maternal and infant variables and pathogens associated with infection were compared between 2002–2003 and 2 previously published cohorts . Results : During the past 13 years , overall rates of EOS have remained stable ( 15–19 per 1000 live births of infants 401–1500 g ) . More than one-half of early infections in the 2002–2003 cohort were caused by Gram-negative organisms ( 53 % ) , with Escherichia coli the most common organism ( 41 % ) . Rates of group B streptococcal infections remain low ( 1.8 per 1000 live births ) . Between 1991–1993 and 1998–2000 , there was a significant increase in rates of E. coli infections ; but in 2002–2003 , there was no significant change ( 7.0 per 1000 live births ) . Infants with EOS continue to be at significantly increased risk for death compared with uninfected infants . Conclusion : EOS remains an uncommon but important cause of morbidity and mortality among VLBW infants . Gram-negative organisms continue to be the predominant pathogens associated with EOS Hepatitis C virus ( HCV ) is associated with the development of cirrhosis and hepatocellular carcinoma . We recently found that bovine lactoferrin , a milk protein belonging to the iron transporter family , effectively prevented HCV infection in cultured human hepatocytes ( PH5CH8 ) . We tested the hypothesis that lactoferrin inhibits HCV viremia in patients with chronic hepatitis C. Eleven patients with chronic hepatitis C received an 8‐week course of bovine lactoferrin ( 1.8 or 3.6 g/day ) . At the end of lactoferrin treatment , a decrease in serum alanine transaminase and HCV RNA concentrations was apparent in 3 ( 75 % ) of 4 patients with low pretreatment serum concentrations of HCV RNA . However , 7 patients with high pretreatment concentrations showed no significant changes in these indices . This pilot study suggests that lactoferrin is one potential c and i date as an anti‐HCV reagent that may be effective for the treatment of patients with chronic hepatitis OBJECTIVE Late-onset sepsis ( occurring after 3 days of age ) is an important problem in very low birth weight ( VLBW ) infants . To determine the current incidence of late-onset sepsis , risk factors for disease , and the impact of late-onset sepsis on subsequent hospital course , we evaluated a cohort of 6956 VLBW ( 401 - 1500 g ) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period ( 1998 - 2000 ) . METHODS The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospect i ve registry of all VLBW neonates admitted to participating centers within 14 days of birth . Exp and ed infection surveillance was added in 1998 . RESULTS Of 6215 infants who survived beyond 3 days , 1313 ( 21 % ) had 1 or more episodes of blood culture-proven late-onset sepsis . The vast majority of infections ( 70 % ) were caused by Gram-positive organisms , with coagulase-negative staphylococci accounting for 48 % of infections . Rate of infection was inversely related to birth weight and gestational age . Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus , prolonged ventilation , prolonged intravascular access , bronchopulmonary dysplasia , and necrotizing enterocolitis . Infants who developed late-onset sepsis had a significantly prolonged hospital stay ( mean length of stay : 79 vs 60 days ) . They were significantly more likely to die than those who were uninfected ( 18 % vs 7 % ) , especially if they were infected with Gram-negative organisms ( 36 % ) or fungi ( 32 % ) . CONCLUSIONS Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors . Strategies to reduce late- 
    Output:
    
agent
Evidence of low quality suggests that lactoferrin supplementation to enteral feeds with or without probiotics decreases late-onset sepsis and NEC stage II or III in preterm infants without adverse effects .
***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: OBJECTIVES To evaluate the efficacy of bovine lactoferrin ( BLF ) in preventing first episode of late-onset sepsis ( LOS ) in low birth weight ( LBW ) neonates . METHODS In this study conducted from May 2012 to July 2013 in the neonatal intensive care unit ( NICU ) of a tertiary care hospital , inborn asymptomatic neonates , < 2000 g , admitted to NICU in first 12 h of birth with no maternal risk factors for sepsis were r and omized to receive BLF or placebo from 1st to 28th day of life . The incidence of culture-proven sepsis and sepsis-attributable mortality after 72 h of life was recorded . Increasing doses of BLF were used with higher birth weights . RESULTS Incidence of first episode of culture-proven LOS was significantly lower in the BLF group vs. placebo [ 2/63 ( 3.2 % ) vs. 9/67(13.4 % ) ; risk ratio , 0.211 ; 95 % CI , 0.044 - 1.019 ; p = 0.036 ] . Statistically significant reduction in the sepsis-attributable mortality was also seen after use of prophylactic BLF [ 0/63 ( 0 % ) vs. 5/67 ( 7.5 % ) ; p = 0.027 ] . CONCLUSION BLF  supplementation in LBW neonates reduced the incidence of first episode of LOS Lactoferrin has broad-spectrum antimicrobial activity , and the authors hypothesized that recombinant human lactoferrin ( Talactoferrin alfa [ TLF ] ) would reduce mortality and morbidity in a coinfection model . The MIC50 ( minimum inhibitory concentration required to inhibit the growth of 50 % of organisms ) of TLF againstC and ida albicans and Staphylococcus epidermidis was determined . Neonatal Wistar rats were infected withCalbicans orS epidermidis or both , at doses of 2 × 108 colony-forming units ( CFUs ) given subcutaneously . Rat pups in each group were r and omly given TLF intraperitoneally at 40 mg/kg/dose or 300 mg/kg/dose , or saline in 0.2 mL , once a day for 4 d and were monitored for mortality , weight gain , and blood culture positivity . Trough serum levels of TLF were measured at 24 , 48 , 72 , 96 , and 144 h. MIC50 of TLF was 30 μg/mL and 500 μg/mL forC albicans and Sepidermidis , respectively . TLF prophylaxis significantly improved survival in the coinfection group at 40 mg/kg/dose ( by 16.1 % ; P=.019 ) and at 300 mg/kg/dose ( by 15.1 % ; P=.027 ) and in the Sepidermidis group at a dose of 40 mg/kg/dose ( by 1 8.6 % ; P=.04 ) . Weight gain was not affected by TLF prophylaxis . Serum trough levels of TLF were 1000-fold lower than in vitro MIC50 . The authors conclude that lactoferrin prophylaxis significantly enhanced survival in coinfection and in the subgroupof S epidermidis infection ( 40 mg/kg/dose ) through indirect mechanisms Summary Background : Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells . Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity . Studies in animal models have shown promising anti-cancer activity . The purpose of the present study was to evaluate the safety and tolerability of talactoferrin alfa ( talactoferrin ; TLF ) in humans , as well as pharmacokinetics and pharmacodynamics . Methods : Ten adult patients with progressive advanced solid tumors who had failed conventional chemotherapy  were administered oral TLF at doses from 1.5 to 9 g/day , using a 2 weeks on , 2 weeks off schedule . Patients were evaluated for drug toxicity , tumor growth rate , talactoferrin pharmacokinetics and cytokine markers . Results : Talactoferrin was very well tolerated . No hematological , hepatic , or renal toxicities were reported . A single patient had Grade 2 diarrhea , and there were no Grade 3 or 4 toxicities . Following oral administration , significant levels of talactoferrin  were undetectable in circulation , but a statistically significant increase in circulating IL-18 , a pharmacodynamic indicator of talactoferrin activity , was observed . Of the eight patients who were radiologically evaluable , five ( 63 % ) had stable disease by RECIST criteria two months after start of therapy , including one patient with a minor response . Seven patients ( 88 % ) had a decrease in their tumor growth rate . The three patients with non-small cell lung cancer ( NSCLC ) all survived for at least one year following the start of talactoferrin monotherapy . Conclusions : Talactoferrin is a promising , well-tolerated new agent that should be evaluated further in patients with refractory metastatic cancer CONTEXT Sepsis is a common and severe complication in premature neonates , particularly those with very low birth weight ( VLBW ) ( < 1500 g ) . Whether lactoferrin , a mammalian milk glycoprotein involved in innate immune host defenses , can reduce the incidence of sepsis is unknown . In animal models , the probiotic Lactobacillus rhamnosus GG ( LGG ) enhances the activity of lactoferrin but has not been studied in human infants . OBJECTIVE To establish whether bovine lactoferrin ( BLF ) , alone or in combination with LGG , reduces the incidence of late-onset sepsis in VLBW neonates . DESIGN , SETTING , AND PATIENTS Prospect i ve , multicenter , double-blind , placebo-controlled , r and omized trial conducted in 11 Italian tertiary neonatal intensive care units . Patients were 472 VLBW infants enrolled from October 1 , 2007 , through July 31 , 2008 , and assessed until discharge for development of sepsis . INTERVENTION Infants were r and omly assigned to receive orally administered BLF ( 100 mg/d ) alone ( n = 153 ) , BLF plus LGG ( 6 x 10(9 ) colony-forming units/d ) ( n = 151 ) , or placebo ( n = 168 ) from birth until day 30 of life ( day 45 for neonates < 1000 g at birth ) . MAIN OUTCOME MEASURE First episode of late-onset sepsis , ie , sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid . RESULTS Demographic , clinical , and management characteristics of the 3 groups were similar , including type of feeding and intake of maternal milk . Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups ( 9/153 [ 5.9 % ] and 7/151 [ 4.6 % ] , respectively ) than in the control group receiving placebo ( 29/168 [ 17.3 % ] ) ( risk ratio , 0.34 ; 95 % confidence interval , 0.17 - 0.70 ; P = .002 for BLF vs control and risk ratio , 0.27 ; 95 % confidence interval , 0.12 - 0.60 ; P < .001 for BLF plus LGG vs control ) . The decrease occurred for both bacterial and fungal sepsis . No adverse effects or intolerances to treatment occurred . CONCLUSION Compared with placebo , BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53107700 Background : Early onset neonatal sepsis ( EOS , occurring in the first 72 hours of life ) remains an important cause of illness and death among very low birth weight ( VLBW ) preterm infants . We previously reported a change in the distribution of pathogens associated with EOS from predominantly Gram-positive to primarily Gram-negative organisms . Objective : To compare rates of EOS and pathogens associated with infection among VLBW infants born at centers of the National Institute of Child Health and Human Development ( NICHD ) Neonatal Research Network during 3 time periods : 1991–1993 ; 1998–2000 ; and 2002–2003 . Study Design : Prospect ively collected data from the NICHD Neonatal Research Network VLBW registry were retrospectively review ed . Rates of blood culture confirmed EOS , selected maternal and infant variables and pathogens associated with infection were compared between 2002–2003 and 2 previously published cohorts . Results : During the past 13 years , overall rates of EOS have remained stable ( 15–19 per 1000 live births of infants 401–1500 g ) . More than one-half of early infections in the 2002–2003 cohort were caused by Gram-negative organisms ( 53 % ) , with Escherichia coli the most common organism ( 41 % ) . Rates of group B streptococcal infections remain low ( 1.8 per 1000 live births ) . Between 1991–1993 and 1998–2000 , there was a significant increase in rates of E. coli infections ; but in 2002–2003 , there was no significant change ( 7.0 per 1000 live births ) . Infants with EOS continue to be at significantly increased risk for death compared with uninfected infants . Conclusion : EOS remains an uncommon but important cause of morbidity and mortality among VLBW infants . Gram-negative organisms continue to be the predominant pathogens associated with EOS Hepatitis C virus ( HCV ) is associated with the development of cirrhosis and hepatocellular carcinoma . We recently found that bovine lactoferrin , a milk protein belonging to the iron transporter family , effectively prevented HCV infection in cultured human hepatocytes ( PH5CH8 ) . We tested the hypothesis that lactoferrin inhibits HCV viremia in patients with chronic hepatitis C. Eleven patients with chronic hepatitis C received an 8‐week course of bovine lactoferrin ( 1.8 or 3.6 g/day ) . At the end of lactoferrin treatment , a decrease in serum alanine transaminase and HCV RNA concentrations was apparent in 3 ( 75 % ) of 4 patients with low pretreatment serum concentrations of HCV RNA . However , 7 patients with high pretreatment concentrations showed no significant changes in these indices . This pilot study suggests that lactoferrin is one potential c and i date as an anti‐HCV reagent that may be effective for the treatment of patients with chronic hepatitis OBJECTIVE Late-onset sepsis ( occurring after 3 days of age ) is an important problem in very low birth weight ( VLBW ) infants . To determine the current incidence of late-onset sepsis , risk factors for disease , and the impact of late-onset sepsis on subsequent hospital course , we evaluated a cohort of 6956 VLBW ( 401 - 1500 g ) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period ( 1998 - 2000 ) . METHODS The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospect i ve registry of all VLBW neonates admitted to participating centers within 14 days of birth . Exp and ed infection surveillance was added in 1998 . RESULTS Of 6215 infants who survived beyond 3 days , 1313 ( 21 % ) had 1 or more episodes of blood culture-proven late-onset sepsis . The vast majority of infections ( 70 % ) were caused by Gram-positive organisms , with coagulase-negative staphylococci accounting for 48 % of infections . Rate of infection was inversely related to birth weight and gestational age . Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus , prolonged ventilation , prolonged intravascular access , bronchopulmonary dysplasia , and necrotizing enterocolitis . Infants who developed late-onset sepsis had a significantly prolonged hospital stay ( mean length of stay : 79 vs 60 days ) . They were significantly more likely to die than those who were uninfected ( 18 % vs 7 % ) , especially if they were infected with Gram-negative organisms ( 36 % ) or fungi ( 32 % ) . CONCLUSIONS Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors . Strategies to reduce late- 
    Output:
    