Calprotectin and Neutrophil Gelatinase-Associated Lipocalin As Biomarkers of Acute Kidney Injury in Acute Coronary Syndrome

BackgroundAcute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACS) and it is associated with higher short-term and long-term morbidity and mortality. Therefore, it is of paramount importance to identify those ACS patients at risk for the development of AKI. The objective of this study was to evaluate two different plasma biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) in early detecting the development of AKI in ACS patients.Methods172 ACS patients admitted to the Coronary Care Unit in Yantai Yuhuangding Hospital were prospectively enrolled. Their blood samples were obtained on admission and subjected to enzyme-linked immunosorbent assay to determine the levels of novel biomarkers. The clinical data and biomarkers were recorded and analyzed.ResultsIn this study, 23 (13.4%) patients had a diagnosis of AKI. Statistical analysis demonstrated that in ACS patients with AKI, the following two biomarkers were significantly higher than these without AKI: plasma calprotectin (5942.26 ± 1955.88 ng/mL vs. 3210.29 ± 1833.60 ng/mL, p < 0.001) and plasma NGAL (164.91 ± 43.63 ng/mL vs. 122.48 ± 27.33 ng/mL, p < 0.001). Plasma calprotectin and NGAL could discriminate the development of AKI respectively with an area under the ROC curve (AUC) of 0.864 and 0.850. A combination of the two plasma biomarkers calprotectin and NGAL could early discriminate AKI in ACS patients with an AUC of 0.898.ConclusionsThis study demonstrated a promising panel of plasma calprotectin and NGAL as early diagnostic biomarkers for AKI in ACS patients.     

B-type natriuretic peptide in the early diagnosis and risk stratification of acute chest pain

Background

Myocardial ischemia is a strong trigger of B-type natriuretic peptide (BNP) release. As ischemia precedes necrosis in acute myocardial infarction, we hypothesized that BNP might be useful in the early diagnosis and risk stratification of patients with acute chest pain.

Methods

In a prospective, international multicenter study, BNP was measured in 1075 unselected patients with acute chest pain. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed long term regarding mortality.

Results

Acute myocardial infarction was the adjudicated final diagnosis in 168 patients (16%). BNP levels at presentation were significantly higher in acute myocardial infarction as compared with patients with other diagnoses (median 224 pg/mL vs. 56 pg/mL, P <.001). The diagnostic accuracy of BNP for the diagnosis of acute myocardial infarction as quantified by the area under the receiver operating characteristic curve (AUC) (0.74; 95% confidence interval [CI], 0.70-0.78) was lower compared with cardiac troponin T at presentation (AUC 0.88; 95% CI, 0.84-0.92; P <.001). Cumulative 24-month mortality rates were 0.5% in the first, 2.1% in the second, 7.0% in the third, and 22.9% in the fourth quartile of BNP (P <.001). BNP predicted all-cause mortality independently of and more accurately than cardiac troponin T: AUC 0.81 (95% CI, 0.76-0.86) versus AUC 0.70 (95% CI, 0.62-0.77; P <.001). Net reclassification improvement for BNP was 0.10 (P = .04), and integrated discrimination improvement 0.068 (P = .01).

Conclusions

BNP accurately predicts mortality in unselected patients with acute chest pain independently of and more accurately than cardiac troponin T, but does not seem to help in the early diagnosis of acute myocardial infarction.     

B-Type Natriuretic Peptide Predicts Benefit From a Home-Based Nurse Care in Chronic Heart Failure

BackgroundHome-based nurse care (HBNC) can reduce adverse events in patients with chronic heart failure. However, which patients really benefit from such an intervention remains unclear. We investigated if B-type natriuretic peptide (BNP), a strong prognostic marker in chronic heart failure, can predict benefit from HBNC.Methods and ResultsAfter discharge from heart failure hospitalization, 96 patients were randomized to either HBNC for 12 months or usual care. The combined endpoint of death or heart failure hospitalization was evaluated after 12 and 24 months. The median value of BNP (267 pg/mL) was used as a cutoff value to predict benefit from the HBNC. HBNC reduced the endpoint after 12 (P = .013) and 24 months (P = .033, relative risk [RR] (95% confidence intervals): 0.42 [0.20-0.78] and 0.55 [0.31-0.98], respectively). This benefit from HBNC was dependent on BNP. In patients with supramedian BNP, the endpoint was significantly reduced after 12 (P = .002) and 24 months (P = .003, RR: 0.39 [0.20-0.76] and 0.50 [0.30-0.83], respectively), whereas in patients with inframedian BNP no significant changes occurred.ConclusionsA high BNP can predict benefit from HBNC in patients with chronic heart failure and may assist in selecting patients for such an intervention.     

Myocardial Apelin Production is Reduced in Humans With Left Ventricular Systolic Dysfunction

BackgroundApelin is a novel endogenous peptide with inotropic and vasodilatory properties that is the ligand for the APJ receptor. Apelin and APJ are widely distributed in the vasculature of a number of organs and peripheral venous apelin is reduced in heart failure (HF). The location of apelin production in humans with and without HF was investigated.Methods and ResultsPlasma apelin and brain natriuretic peptide (BNP) concentrations in coronary sinus (CS), aorta (Ao), and renal vein (RV) of individuals with HF (n = 9) were compared to subjects with normal structural hearts (n = 8). In HF the concentration of CS apelin was reduced compared with controls (310 pg/mL [interquartile range 290-390] vs. 470 pg/mL [340-570], P < .035) but Ao apelin (330 pg/mL [275-375] vs. 340 pg/mL [230-455], P = .76) and RV apelin (290 pg/mL [280-360] vs. 370 pg/mL [273-410], P = .56) were unchanged. Plasma BNP was increased at all sampling sites in patients with HF as compared with controls. A step down from CS to Ao to RV in all subjects was observed. The step down in apelin from CS to Ao (470 pg/mL [310-595] vs. 320 pg/mL [225-482], P < .04) in control subjects was not apparent in patients with HF.ConclusionsThese novel data show that apelin is produced in the human heart and that production is reduced in individuals with HF. In contrast to BNP, apelin production is not exclusive to the heart.     

Use of B-type natriuretic peptide in the risk stratification of acute exacerbations of COPD

BACKGROUND: In patients with COPD, prognosis might be determined at least in part by the extent of cardiac stress induced by hypoxia and pulmonary arterial hypertension. METHODS: B-type natriuretic peptide (BNP), a quantitative marker of cardiac stress, was determined in 208 consecutive patients presenting to the emergency department with an acute exacerbation of COPD (AECOPD). The accuracy of BNP to predict death at a 2-year follow-up was evaluated as the primary end point. The need for intensive care and in-hospital mortality were determined as secondary end points. RESULTS: BNP levels were significantly elevated during the acute exacerbation compared to recovery (65 pg/mL; interquartile range [IQR], 34 to 189 pg/mL; vs 45 pg/mL; IQR, 25 to 85 pg/mL; p < 0.001), particularly in those patients requiring ICU treatment (105 pg/mL; IQR, 66 to 553 pg/mL; vs 60 pg/mL; IQR, 31 to 169 pg/mL; p = 0.007). In multivariate Cox regression analysis, BNP accurately predicted the need for ICU care (hazard ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.24 for an increase in BNP of 100 pg/mL; p = 0.008). In a receiver operating characteristic analysis to evaluate the potential of BNP levels to predict short-term and long-term mortality rates, areas under the curve were 0.55 (SD, 0.71; 95% CI, 0.41 to 0.68) and 0.56 (SD, 0.53; 95% CI, 0.45 to 0.66, respectively). CONCLUSIONS: In patients with AECOPD, BNP levels independently predict the need for intensive care. However, BNP levels failed to adequately predict short-term and long-term mortality rates in AECOPD patients.     

Acute kidney injury after allogeneic hematopoietic stem cell transplantation – Predictors and survival impact: A single center retrospective study

Introduction and objectivesAcute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting.Patients and methodsWe performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019.ResultsAKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p = 0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p = 0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p < 0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p = 0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p = 0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p = 0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p = 0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p = 0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p = 0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival.ConclusionPatients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit.     

Prognosis of Stage A or B Heart Failure Patients With Elevated B-type Natriuretic Peptide Levels

BackgroundHeart failure (HF) patients have a poor prognosis, yet outcomes might be improved by early identification of risk. We investigated the prognostic value of B-type natriuretic peptide (BNP) in patients at risk for HF (American College of Cardiology [ACC]/American Heart Association [AHA] HF Stages A and B), and compared prognosis with Stage C/D patients.Methods and ResultsOutpatients referred for echocardiogram (n = 829) were stratified by ACC/AHA HF stage and BNP levels (cutpoint of 100 pg/mL). Primary outcome was death or cardiac hospitalization at 1 year. BNP levels increased with increasing numbers of cardiovascular risk factors and with HF stage. Stage A/B patients with high BNP had a similar or worse prognosis than Stage C/D patients with low BNP. In fact, the prognosis of Stage C/D patients with low BNP did not significantly differ from the prognosis of Stage A/B patients with low BNP (adjusted HR 1.21, 95% CI 0.62–2.37), whereas Stage A/B patients with high BNP did have a significantly worse prognosis (adjusted HR 1.91, 95% CI 1.11–3.28).ConclusionsIndividuals without any history of HF but with BNP ≥100 pg/mL are at equal or higher risk than those with a HF history whose BNP is <100 pg/mL. BNP may be useful to identify asymptomatic individuals at high risk for future cardiovascular events.     

Acute Kidney Injury Following Aortic Valve Replacement in Patients Without Chronic Kidney Disease

BackgroundThe data on acute kidney injury (AKI) in patients without chronic kidney disease (CKD) after transcatheter aortic valve replacement (TAVR) are limited. The study sought to compare the incidence of AKI and its impact on 5-year mortality after TAVR and surgical aortic valve replacement (SAVR) in patients without CKD.MethodsThis registry included data from 6463 consecutive patients who underwent TAVR or SAVR. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. For sensitivity analysis, propensity-score matching between TAVR and SAVR was performed.ResultsThe study included 4555 consecutive patients (TAVR, n = 1215 and SAVR, n = 3340) without CKD. Propensity-score matching identified 542 pairs. Patients who underwent TAVR had a significantly lower incidence of AKI in comparison to those who underwent SAVR (unmatched 4.7% vs 16.4%, P < 0.001, multivariable analysis: odds ratio, 0.29, 95% confidence interval [CI], 0.20-0.41; matched 5.9% vs 19.0%, P < 0.001). Patients with AKI had significantly increased 5-year mortality compared with those without AKI (unmatched 36.0% vs 19.1%, log-rank P < 0.001; matched 36.3% vs 24.0%, log-rank P < 0.001). The adjusted hazard ratios for 5-year mortality were 1.58 (95% CI, 1.20-2.08) for AKI grade 1, 3.27 (95% CI, 2.09-5.06) for grade 2, and 4.82 (95% CI, 2.93-8.04) for grade 3.ConclusionsTAVR in patients without CKD was associated with a significantly less frequent incidence of AKI compared with SAVR. AKI significantly increased the risk of 5-year mortality after either TAVR or SAVR, and increasing severity of AKI was incrementally associated with 5-year mortality.     

Serum B-type natriuretic peptide levels on admission predict not only short-term death but also angiographic success of procedure in patients with acute ST-elevation myocardial infarction treated with primary angioplasty

Background

B-type natriuretic peptide (BNP) levels are predictive of short-term death in patients with acute coronary syndromes. Few data are available for BNP levels obtained on admission in patients with acute ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).

Methods

Blood samples for BNP estimation, obtained on admission in 126 consecutive patients (mean age, 58.8 ± 10.7 years) with STEMI, were measured at the bedside by using a simple point-of-care test in a 15-minute period before PCI. Follow-up up to 42 days was performed.

Results

A baseline BNP value of 331 pg/mL had a sensitivity of 87.9% and a specificity of 90% for predicting death in a follow-up study. There was no difference in subgroups by median BNP (100 pg/mL) in Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 before PCI, although higher BNP levels were observed among patients with TIMI <3 after PCI than among those with TIMI 3 (356.7 ± 350.8 vs 144.9 ± 191.2 pg/mL; P < .0001). In multivariate logistic regression analysis, admission BNP was the independent predictor for the following: death (odds ratio [OR], 16.3; 95% confidence interval [CI], 1.4 to 186.7; P = .03), TIMI grade <3 after PCI (OR, 3.4; 95% CI, 1.2 to 9.6; P = .02), and the no-reflow phenomenon (OR, 6.2; 95% CI, 1.7 to 23; P = .007) after adjusting for other variables.

Conclusions

BNP levels obtained on admission are a powerful, independent predictor of short-term death and angiographic success after PCI in patients with STEMI. The no-reflow phenomenon may be predicted in STEMI on the basis of high serum BNP values on admission.     

Meta-analysis of procalcitonin as a predictor for acute kidney injury

Background:Procalcitonin (PCT) was used for predicting the development of acute kidney injury (AKI) in several studies recently. We aimed to investigate the accuracy of PCT for predicting AKI in this study.Methods:Studies that assessed the predictive performance of PCT for the development of AKI in adult patients were searched from Medline, Embase, and the Cochrane Library from inception to June 2020. We calculated the pooled sensitivities and specificities and the area under the summary receiver-operating characteristic (SROC) curves. I² was used to test the heterogeneity and the potential heterogeneity was investigated by meta-regression.Results:In total, 9 of 119 studies with 4852 patients were included, 1272 were diagnosed with AKI. In the overall analysis, the area under the SROC curve was 0.82 (95% CI, 0.79–0.85) and the pooled sensitivity and specificity were 0.76 (95% confidence interval [CI], 0.64–0.85) and 0.75 (95% CI, 0.61–0.86), respectively. In the subgroup analysis among septic patients, the pooled sensitivity and specificity were 0.59 (95% CI, 0.29–0.84) and 0.53 (95% CI, 0.31–0.74), and the area under the SROC was 0.57 (95% CI, 0.53–0.62).Conclusion:PCT may be a potential predictor for the development of AKI.     

Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Predicting Worsening Renal Function in Acute Decompensated Heart Failure

BackgroundThe development of worsening renal function (WRF, defined as creatinine rise ≥0.3 mg/dL) occurs frequently in the setting of acute decompensated heart failure (ADHF) and strongly predicts adverse clinical outcomes. Neutrophil gelatinase–associated lipocalin (NGAL) is produced by the nephron in response to tubular epithelial damage and serves as an early marker for acute renal tubular injury. We sought to determine the relationship between admission serum NGAL levels and WRF in the setting of ADHF.Methods and ResultsWe measured serum NGAL levels in 91 patients admitted to the hospital with ADHF. Patients were adjudicated by independent physician into those that did or did not develop WRF over the ensuing 5 days of in-hospital treatment. In our study cohort (68% male, mean age 61 ± 15 years, mean left ventricular ejection fraction 31 ± 14%), median admission serum NGAL level was 165 ng/mL (interquartile range [IQR] 108–235 ng/mL). Thirty-five patients (38%) developed WRF within the 5-day follow-up. Patients who developed WRF versus those without WRF had significantly higher median admission serum NGAL levels (194 [IQR 150–292] ng/mL vs. 128 [IQR 97–214] ng/mL, P = .001). High serum NGAL levels at admission were associated with greater likelihood of developing WRF (odds ratio: 1.92, 95% confidence interval 1.23–3.12, P = .004). In particular, admission NGAL ≥140 ng/mL had a 7.4-fold increase in risk of developing WRF, with a sensitivity and specificity of 86% and 54%, respectively.ConclusionsThe presence of elevated admission serum NGAL levels is associated with heightened risk of subsequent development of WRF in patients admitted with ADHF.     

Effects of dairy products consumption on inflammatory biomarkers among adults: A systematic review and meta-analysis of randomized controlled trials

AimsThis study aimed to summarize earlier studies on the effects of dairy consumption on inflammatory biomarkers in adults and to quantify these effects through meta-analysis.Data synthesisA comprehensive search of all relevant articles, published up to December 2019 indexed in PubMed, ISI (Institute for Scientific Information), EmBase, Scopus, and Google Scholar was done using relevant keywords. Randomized controlled trials (RCTs) that examined the effect of dairy products consumption, compared with low or no dairy intake, on inflammatory biomarkers in adults were included. Overall, 11 RCTs with 663 participants were included in this meta-analysis. We found that high consumption of dairy products, compared with low or no dairy intake, might significantly reduce CRP [weighed mean difference (WMD): −0.24 mg/L; 95% CI, −0.35, −0.14], TNF-α (WMD:- 0.66 pg/mL; 95% CI, −1.23, −0.09), IL-6 (WMD: −0.74 pg/mL; 95% CI, −1.36, −0.12), and MCP concentrations (WMD: −25.58 pg/mL; 95% CI, −50.31, −0.86). However, when the analyses were confined to cross-over trials, no such beneficial effects of dairy intake on inflammation were observed. In addition, high dairy intake might result in increased adiponectin levels (WMD: 2.42 μg/mL; 95% CI, 0.17, 4.66). No significant effect of dairy consumption on serum leptin (WMD: −0.32 ng/mL; 95% CI, −3.30, 2.65), ICAM-1 (WMD: −3.38 ng/ml; 95% CI, −15.57, 8.96) and VCAM-1 (WMD: 3.1 ng/mL; 95% CI, −21.38, 27.58) levels was observed.ConclusionsIn summary, the current meta-analysis indicated that dairy intake might improve several inflammatory biomarkers in adults. In most subgroups without heterogeneity, effects tended to be null. Study design and participants’ age were the main sources of heterogeneity. More research, with a particular focus on fat content of dairy foods, is recommended.     

N-terminal pro B-type natriuretic peptide in the early evaluation of suspected acute myocardial infarction

Background

Myocardial ischemia is a strong trigger of N-terminal pro-B-type natriuretic peptide (NT-proBNP) release. As ischemia precedes necrosis in acute myocardial infarction, we hypothesized that NT-proBNP might be useful in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction.

Methods

In a prospective multicenter study, NT-proBNP was measured at presentation in 658 consecutive patients with acute chest pain. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed long term regarding mortality.

Results

Acute myocardial infarction was the adjudicated final diagnosis in 117 patients (18%). NT-proBNP levels at presentation were significantly higher in acute myocardial infarction as compared with patients with other final diagnoses (median 886 pg/mL vs 135 pg/mL, P <.001). The diagnostic accuracy of NT-proBNP for acute myocardial infarction as quantified by the area under the receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval [CI], 0.75-0.83). When added to cardiac troponin T, NT-proBNP significantly increased the AUC from 0.89 (95% CI, 0.84-0.93) to 0.91 (95% CI, 0.88-0.94; P = .033). Cumulative 24-month mortality rates were 0% in the first, 1.3% in the second, 8.3% in the third, and 23.3% in the fourth quartile of NT-proBNP (P <.001). NT-proBNP (AUC 0.85, 95% CI, 0.81-0.89) predicted all-cause mortality independently of and more accurately than both cardiac troponin T (AUC 0.66, 95% CI, 0.58-0.74; P <.001) and the Thrombolysis in Myocardial Infarction risk score (AUC 0.79, 95% CI, 0.74-0.84; P <.001). Net reclassification improvement (Thrombolysis in Myocardial Infarction vs additionally NT-proBNP) was 0.188 (P <.009), and integrated discrimination improvement was 0.100 (P <.001).

Conclusions

Use of NT-proBNP improves the early diagnosis and risk stratification of patients with suspected acute myocardial infarction.     

Prevalence,risk factors,and short-term outcomes of postparacentesis acute kidney injury using revised criteria of the international club of ascites

Acute kidney injury (AKI) can become complicated after paracentesis due to extrarenal fluid loss and inadequate blood flow to the kidneys. The objective of this study was to explore the incidence and clinical implications of postparacentesis AKI.A retrospective cohort of 137 liver cirrhosis patients (mean age: 61.3 ± 11.8 years, male: 100 [73.0%], viral hepatitis: 93 [67.9%]) who underwent paracentesis was analyzed. The incidence of AKI as defined by the international club of ascites (ICA) criteria, the risk factors, and its impact on early mortality were all assessed.Thirty two patients (23.4%) developed AKI after paracentesis. In multivariate analysis, the Model for end-stage liver disease (MELD)-Na score was an independent factor associated with AKI development (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.07–1.23) after paracentesis. The incidence of early mortality was significantly higher for those with AKI than without AKI (71.9% [23/32 patients] vs 11.4% [12/105 patients], P < .001). AKI (hazard ratio [HR], 7.56; 95% CI, 3.40–16.8) and MELD-Na score (HR, 1.08; 95% CI, 1.02–1.14) were independent factors associated with early mortality. In subgroup analysis, AKI after paracentesis was associated with significantly higher early mortality in both MELD-Na groups, that is, patients with a MELD-Na score >26 (87.5% vs 22.2%, P < .001) and those with a MELD-Na score ≤26 (56.3% vs 9.2%, P < .001).Postparacentesis AKI occurred frequently in cirrhotic patients. Furthermore, it was associated with early mortality. Baseline MELD-Na score was associated with AKI, indicating that careful attention is required for those with a higher MELD-Na score who are being considered for therapeutic paracentesis.     

A Combined-Biomarker Approach to Clinical Phenotyping Renal Dysfunction in Heart Failure

BackgroundDifferentiating heart failure (HF) induced renal dysfunction (RD) from intrinsic kidney disease is challenging. It has been demonstrated that biomarkers such as B-type natriuretic peptide (BNP) or the blood urea nitrogen to creatinine ratio (BUN/creat) can identify high- vs low-risk RD. Our objective was to determine if combining these biomarkers could further improve risk stratification and clinical phenotyping of patients with RD and HF.Methods and ResultsA total of 908 patients with a discharge diagnosis of HF were included. Median values were used to define elevated BNP (>1296 pg/mL) and BUN/creat (>17). In the group without RD, survival was similar regardless of BNP and BUN/creat (n = 430, adjusted P = .52). Similarly, in patients with both a low BNP and BUN/creat, RD was not associated with mortality (n = 250, adjusted hazard ratio [HR] = 1.0, 95% confidence interval [CI] 0.6–1.6, P = .99). However, in patients with both an elevated BNP and BUN/creat those with RD had a cardiorenal profile characterized by venous congestion, diuretic resistance, hypotension, hyponatremia, longer length of stay, greater inotrope use, and substantially worse survival compared with patients without RD (n = 249, adjusted HR = 1.8, 95% CI 1.2–2.7, P = .008, P interaction = .005).ConclusionsIn the setting of decompensated HF, the combined use of BNP and BUN/creat stratifies patients with RD into groups with significantly different clinical phenotypes and prognosis.     

Serum neutrophil gelatinase-associated lipocalin concentration reflects severity of coronary artery disease in patients without heart failure and chronic kidney disease

Serum neutrophil gelatinase-associated lipocalin (NGAL) is recognized as a useful biomarker for acute kidney injury. Recently, elevated NGAL levels were reported in patients with heart failure and cardiac events, but the association between serum NGAL and severity of coronary artery disease (CAD) has not been investigated adequately. This study aimed to evaluate the association between serum NGAL concentration and CAD severity in patients without heart failure and chronic kidney disease. Two-hundred thirteen patients [mean age: 66.2 ± 9.2 (SD)] without heart failure and chronic kidney disease (estimated glomerular filtration rate >60 mL/min/1.73 m²) who underwent coronary angiography were retrospectively analyzed using the SYNTAX score. The mean concentration of serum NGAL was 134.3 ± 111.3 ng/mL. A statistically significant correlation was observed between serum NGAL levels and the SYNTAX score (R = 0.18, P = 0.0091). Multivariable analysis also showed elevated serum NGAL as an independent risk factor for a high SYNTAX score (P < 0.01). Moreover, we evaluated the association of serum NGAL and brain natriuretic peptide (BNP) with the SYNTAX score. Patients with high levels of serum NGAL (>100 ng/mL) and high levels of BNP (>25 pg/mL) had a higher SYNTAX score (low–low vs. high–high: 13.8 ± 13.4 vs. 20.8 ± 18.9, P < 0.05). Serum NGAL levels were positively and significantly associated with CAD severity, and the evaluation of both serum NGAL and BNP was useful for predicting CAD in patients without renal dysfunction and heart failure. Serum NGAL might be a biomarker for CAD severity.     

The Additive Prognostic Value of Serial Plasma Interleukin-6 Levels over Changes in Brain Natriuretic Peptide in Patients with Acute Heart Failure

BackgroundElevated plasma interleukin-6 (IL-6) concentrations are frequently observed in patients with acute heart failure (AHF). However, the predictive value of serial IL-6 measurements beyond brain natriuretic peptide (BNP) remains poorly characterized.Methods and ResultsThis was a retrospective analysis of the PROTECT cohort (2033 patients with AHF). Plasma IL-6 and BNP levels were determined on days 1, 2, 7 and 14 after admission for AHF in 1591 (78.3%), 1462 (71.9%), 1445 (71.1%) and 1451 (71.4%) patients, respectively. The primary endpoint was 180-day all-cause mortality. The median day-1 IL-6 concentration was 11.1 pg/mL (IQR: 6.6, 20.9) and decreased to 10.1 pg/mL (IQR: 5.6-18.5) at day-7. Higher cross-sectional IL-6 concentrations at all time-points predicted the primary endpoint, independent of a risk model for this cohort and changes in BNP. Each doubling of IL-6 between day-1 and day-7 predicted the primary endpoint independent of baseline IL-6 concentrations, the risk model, baseline BNP and changes in BNP [HR (95% CI): 1.18 (1.07-1.30), p=0.0013]. Collectively, 214 (17%) patients experienced at least a doubling of their IL-6 concentrations between day-1 and day-7.ConclusionsWe demonstrate that the temporal evolution patterns of IL-6 in patients with AHF have additive prognostic value independent of changes in BNP.     

Valuable clinical indicators for identifying infantile-onset inflammatory bowel disease patients with monogenic diseases

BACKGROUNDInfantile-onset inflammatory bowel disease (IO-IBD) occurs in very young children and causes severe clinical manifestations, which has poor responses to traditional inflammatory bowel disease (IBD) treatments. At present, there are no simple and reliable laboratory indicators for early screening IO-IBD patients, especially those in whom the disease is caused by monogenic diseases.AIMTo search for valuable indicators for early identifying IO-IBD patients, especially those in whom the disease is caused by monogenic diseases.METHODSA retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years. Based on the next-generation sequencing results, they were divided into a monogenic IBD group (M-IBD) and a non-monogenic IBD group (NM-IBD). Forty age-matched patients with allergic proctocolitis (AP) were included in a control group. The clinical manifestations and the inflammatory factors in peripheral blood were evaluated. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD, respectively.RESULTSAmong the 44 M-IBD patients, 35 carried IL-10RA mutations, and the most common mutations were c.301C>T (p.R101W, 30/70) and the c.537G>A (p.T179T, 17/70). Patients with higher serum tumor necrosis factor (TNF)-α value were more likely to have IBD [odds ratio (OR) = 1.25, 95% confidence interval (CI): 1.05-1.50, P = 0.013], while higher serum albumin level was associated with lower risk of IBD (OR = 0.86, 95%CI: 0.74-1.00, P = 0.048). The cut-off values of TNF-α and albumin were 17.40 pg/mL (sensitivity: 0.78; specificity: 0.88) and 36.50 g/L (sensitivity: 0.80; specificity: 0.90), respectively. The increased ferritin level was indicative of a genetic mutation in IO-IBD patients. Its cut-off value was 28.20 ng/mL (sensitivity: 0.93; specificity: 0.92). When interleukin (IL)-10 level was higher than 33.05 pg/mL (sensitivity: 1.00; specificity: 0.84), or the onset age was earlier than 0.21 mo (sensitivity: 0.82; specificity: 0.94), the presence of disease-causing mutations in IL-10RA in IO-IBD patients was strongly suggested. CONCLUSIONSerum TNF-α and albumin level could differentiate IO-IBD patients from allergic proctocolitis patients, and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.     

Serum NGAL Is Superior to Cystatin C in Predicting the Prognosis of Acute-on-Chronic Liver Failure

Introduction and aim. Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality, and predicting the prognosis is challenging. This study aimed to compare the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) in predicting the 90-day mortality in patients with hepatitis B virus (HBV)-associated ACLF (HBV-ACLF). Materials and methods. This prospective, observational study enrolled 54 patients with HBV-ACLF. The serum NGAL and CysC levels were determined. A multivariate logistic regression analysis was used to analyze the independent risk factors of mortality. Results. Serum NGAL, but not CysC, was found to significantly correlate with the total bilirubin, international normalized ratio, and model for end-stage liver disease (MELD). Serum NGAL [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.004-1.012; P < 0.01], but not CysC, was an independent risk factor for developing hepatorenal syndrome. Moreover, NGAL (OR, 1.005; 95% CI, 1.001-1.010; P < 0.01) along with the MELD score was independently associated with the overall survival in patients with HBV-ACLF. Patients with HBV-ACLF were stratified into two groups according to the serum NGAL level at baseline (low risk: <217.11 ng/mL and high risk: ≥ 217.11 ng/mL). The 90-day mortality rate was 22.73% (5/22) in the low-risk group and 71.88% (23/32) in the high-risk group. Moreover, NGAL, but not CysC, significantly improved the MELD score in predicting the prognosis of HBV-ACLF. Conclusion. The serum NGAL might be superior to CysC in predicting the prognosis of HBV-ACLF with the normal creatinine level.     

Diagnostic value of B-Type natriuretic peptide and chest radiographic findings in patients with acute dyspnea

PURPOSE: To compare chest radiographic findings and circulating B-type natriuretic peptide (BNP) levels as an adjunct to clinical findings in the diagnosis of heart failure in patients presenting with acute dyspnea. METHODS: The diagnostic performance of radiographic evidence of cardiomegaly/redistribution and BNP levels > or =100 pg/mL as indicators of heart failure were assessed in 880 patients presenting with acute dyspnea to the emergency departments of five U.S. and two European teaching hospitals. BNP levels were determined by a rapid, point-of-care device. Two blinded cardiologists reviewed all clinical data and categorized patients as to whether they had acute heart failure (n = 447) or not (n = 433). RESULTS: Three-factor analyses showed that BNP levels > or =100 pg/mL contributed significantly to the prediction of heart failure over each of the radiographic indicators. In a multivariate logistic regression analysis, both BNP levels > or =100 pg/mL (odds ratio [OR] = 12.3; 95% confidence interval [CI]: 7.4 to 20.4) and radiographic findings of cardiomegaly (OR = 2.3; 95% CI: 1.4 to 3.7), cephalization (OR = 6.4; 95% CI: 3.3 to 12.5), and interstitial edema (OR = 7.0; 95% CI: 2.9 to 17.0) added significant, predictive information above historical and clinical predictors of heart failure. CONCLUSION: In patients presenting to the emergency department with acute dyspnea, BNP levels and chest radiographs provide complementary diagnostic information that may be useful in the early evaluation of heart failure.