***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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    ***EXAMPLES*** 
    Input: BACKGROUND AND PURPOSE Leukocytes have been implicated in the development of ischemic atherosclerotic vascular diseases . In a prospect i ve study we investigated whether the plasma concentrations of inflammatory mediators , ie , proteases and cytokines , as markers for systemic leukocyte activation , are increased in patients with acute ischemic cerebrovascular diseases . METHODS Using enzyme-linked immunosorbent assays , we measured the plasma levels of neutrophil gelatinase-associated lipocalin ( NGAL ) , neutrophil proteinase 4 ( NP4 ) , tumor necrosis factor-alpha ( TNF ) , and soluble TNF receptor protein-1 p55 ( sTNFR-1 )  in 120 patients with acute ischemic cerebrovascular insult ( 72 with stroke and 48 with transient ischemic attack [ TIA ] ) and in 35 age- and sex-matched healthy subjects . RESULTS Compared with the control group , plasma NGAL levels were higher in the stroke group ( P < .0001 ) and the TIA group ( P < .01 ) ; plasma NP4 levels were higher in the stroke group ( P < .0001 ) and the TIA group ( P < .01 ) ; and plasma sTNFR-1 levels were higher in the stroke group ( P < .04 ) . There was significant correlation between the plasma levels of fibrinogen and those of both sTNFR-1 ( r = .32 ; P = .005 ) and NGAL ( r = .40 ; P = .0001 ) and between the erythrocyte sedimentation rate and the plasma levels of both sTNFR-1 ( r = .35 ; P = .001 ) and NGAL ( r = .34 ; P = .002 ) . CONCLUSIONS Our study demonstrated that markers for systemic leukocyte activation , ie , plasma levels of cytokines and proteases , were higher in patients with acute ischemic cerebrovascular disease than in healthy control subjects . Activated leukocytes and leukocytic mediators may have an important role in acute cerebrovascular ischemia and its consequences Neutrophil gelatinase‐associated lipocalin ( NGAL ) is a measure of acute kidney injury . Renal dysfunction portends significant risk after discharge from acute heart failure ( AHF ) . Thus , a sensitive marker of renal injury might also help to risk stratify HF patients OBJECTIVES The aim of this study was to test the hypothesis that , without diagnostic changes in serum creatinine , increased neutrophil gelatinase-associated lipocalin ( NGAL ) levels identify patients with sub clinical acute kidney injury ( AKI ) and therefore worse prognosis . BACKGROUND Neutrophil gelatinase-associated lipocalin detects sub clinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function . METHODS We analyzed pooled data from 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospect i ve observational studies of NGAL .  We used the terms NGAL(- ) or NGAL(+ ) according to study -specific NGAL cutoff for optimal AKI prediction and the terms sCREA(- ) or sCREA(+ ) according to consensus diagnostic increases in serum creatinine defining AKI . A priori-defined outcomes included need for renal replacement therapy ( primary endpoint ) , hospital mortality , their combination , and duration of stay in intensive care and in-hospital . RESULTS Of study patients , 1,296 ( 55.8 % ) were NGAL(-)/sCREA(- ) , 445 ( 19.2 % ) were NGAL(+)/sCREA(- ) , 107 ( 4.6 % ) were NGAL(-)/sCREA(+ ) , and 474 ( 20.4 % ) were NGAL(+)/sCREA(+ ) . According to the 4 study groups , there was a stepwise increase in subsequent renal replacement therapy initiation-NGAL(-)/sCREA(- ) : 0.0015 % versus NGAL(+)/sCREA(- ) : 2.5 % ( odds ratio : 16.4 , 95 % confidence interval : 3.6 to 76.9 , p < 0.001 ) , NGAL(-)/sCREA(+ ) : 7.5 % , and NGAL(+)/sCREA(+ ) : 8.0 % , respectively , hospital mortality ( 4.8 % , 12.4 % , 8.4 % , 14.7 % , respectively ) and their combination ( 4-group comparisons : all p < 0.001 ) . There was a similar and consistent progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity : NGAL(-)/sCREA(- ) : 4.2 and 8.8 days ; NGAL(+)/sCREA(- ) : 7.1 and 17.0 days ; NGAL(-)/sCREA(+ ) : 6.5 and 17.8 days ; NGAL(+)/sCREA(+ ) : 9.0 and 21.9 days ; 4-group comparisons : p = 0.003 and p = 0.040 , respectively . Urine and plasma NGAL indicated a similar outcome pattern . CONCLUSIONS In the absence of diagnostic increases in serum creatinine , NGAL detects patients with likely sub clinical AKI who have an increased risk of adverse outcomes . The concept and definition of AKI might need re- assessment BACKGROUND Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque , leading to intracoronary thrombosis and clinical sequelae . The proximate cause of plaque rupture is unknown . Accordingly , we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family in acute coronary ischemia . METHODS AND RESULTS Coronary atherectomy specimens  from patients with atherosclerosis and an acute ischemic syndrome consistent with recent plaque rupture ( unstable angina ) ( n = 12 ) were immunostained for the presence of 92-kD gelatinase ; the results were compared with those obtained by identical study of atherectomy specimens from patients with atherosclerosis and angina but without acute ischemia ( stable angina ) ( n = 12 ) .  Positive immunostaining for 92-kD gelatinase  was present in 83 % of specimens from both unstable and stable angina patients . However , intracellular localization of enzyme ( indicating active synthesis ) was documented in 10 of 10 positively stained specimens from patients with unstable angina compared with 3 of 10 positively stained specimens from patients with stable angina . Macrophages and smooth muscle cells were the major sources of 92-kD gelatinase in all specimens examined by immunostaining of adjacent sections . CONCLUSIONS 92-kD gelatinase is commonly expressed in coronary arterial atherosclerotic lesions . Active synthesis of 92-kD gelatinase by macrophages and smooth muscle cells in atherosclerotic lesions may play a pathogenic role in the development of acute coronary ischemia Acute kidney injury ( AKI ) is a frequent complication of cardiac surgery and increases morbidity and mortality . The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions . Here , we conducted a prospect i ve , multicenter cohort study involving 1219 adults undergoing cardiac surgery  to evaluate whether early postoperative measures of urine IL-18 , urine neutrophil gelatinase-associated lipocalin ( NGAL ) , or plasma NGAL  could identify which patients would develop AKI and other adverse patient outcomes . Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery . After multivariable adjustment , the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI , respectively , compared with the lowest quintiles . Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay , longer intensive care unit stay , and higher risk for dialysis or death . The clinical prediction model for AKI had an area under the receiver-operating characteristic curve ( AUC ) of 0.69 . Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75 , respectively . Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement ( NRI ) and integrated discrimination improvement ( IDI ) . In conclusion , urine IL-18 , urine NGAL , and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery BACKGROUND The identification of patients at risk for worse outcome is still a challenge . We hypothesized that cystatin C , a marker of renal function , and neutrophil gelatinase-associated lipocalin ( NGAL ) , a marker of acute renal injury , would have a role in the prognostic stratification of these patients . METHODS We prospect ively evaluated 121 patients admitted for acute HF .  Serum NGAL and cystatin C levels  were measured on the first morning after admission . The outcome measures used were the occurrence of death from all causes , and the combined endpoint defined as the first occurrence of either death or hospital admission . Patients were followed for up to 3 months . RESULTS The variables associated with a higher occurrence of death in a univariate approach were older age and higher levels of BNP , cystatin C and NGAL , and those associated with the occurrence of the combined endpoint were older age , Diabetes mellitus , lower GFR , type 1 cardio-renal syndrome , BNP , cystatin C and NGAL . BNP and NGAL remained independent predictors of the occurrence of both all-cause death and the combined endpoint . NGAL levels in the 75th percentile ( > 167.5 ng/mL ) were associated with a 2.7-fold increase in the risk of death and a 2.9-fold increase in the risk of the first occurrence of either death or hospitalization . CONCLUSIONS Serum NGAL , a marker of acute renal injury , is an independent predictor of worse short term prognosis in patients with acute HF . This suggests a role of renal damage , apart from renal function , in the prognosis of these patients 
    Output:
    
NGAL is highly expressed in the heart , both in failing myocardium and myocarditis , and is also expressed in atherosclerotic plaques .
Areas of co-localization of NGAL and matrix metalloproteinase (MMP)-9 exhibited increased MMP-9 proteolytic activity .