UNASSIGNED: Sepsis-associated acute kidney injury (S-AKI) is associated with increased morbidity and mortality. We aimed to develop a nomogram for predicting the risk of S-AKI patients.
UNASSIGNED: We collected data from septic patients admitted to the Provincial Hospital Affiliated with Shandong First Medical University from January 2019 to September 2022. Septic patients were divided into two groups based on the occurrence of AKI. A nomogram was developed by multiple logistic regression analyses. The performance of the nomogram was evaluated using C-statistics, calibration curves, and decision curve analysis (DCA). The validation cohort contained 70 patients between December 2022, and March 2023 in the same hospital.
UNASSIGNED: 198 septic patients were enrolled in the training cohort. Multivariate logistic regression analysis showed that neutrophil gelatinase-associated lipocalin (NGAL), platelet-to-lymphocyte ratio (PLR), and vasopressor use were independent risk factors for S-AKI. A nomogram was developed based on these factors. C-statistics for the training and validation cohorts were respectively 0.873 (95% CI 0.825-0.921) and 0.826 (95% CI 0.727-0.924), indicating high prediction accuracy. The calibration curves showed good concordance. DCA revealed that the nomogram was of great clinical value.
UNASSIGNED: The nomogram presents early and effective prediction for the S-AKI patients, and provides optimal intervention to improve patient outcomes.

OBJECTIVE: The objective was to evaluate the serum levels of neutrophil gelatinase-associated lipocalin (NGAL), hypoxia-induced factor-1 alpha (HIF-1α), and apelin 13 in patients with acute pulmonary thromboembolism (PE) and to investigate their diagnostic and prognostic role in PE patients with different mortality risk groups.
METHODS: This study was conducted in a tertiary referral center and included 124 subjects with 94 cases of PE and 30 cases of healthy control group. All subjects were 18 years of age or older. The diagnosis of PE was done with computed tomography angiography of the thorax. After the diagnosis of acute PE, the serum levels of neutrophil gelatinase-associated lipocalin (NGAL), hypoxia-induced factor-1 alpha (HIF-1α), and apelin 13 levels were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit.
RESULTS: The median and IQR (interquartile range) age of patients and control groups were 68 (56-76) and 61.5 (56-67) years, respectively. The majority of patients with PE had risk factors (97.88 %), and only two (2.12 %) had no known risk factors. HIF-1 alpha level was found to be higher in the patient group than in the control group (p = 0.03). At the same time, the HIF-1 alpha level was found to be higher in the high mortality risk group than in the control group, low mortality risk group and intermediate-low mortality risk group (p = 0.000, 0.011, 0.002, respectively). While there was no significant difference in NGAL level between the patient group and the control group, a significant difference was observed between the mortality groups. NGAL level was found to be higher in the high mortality risk group than the control group, low mortality risk group, and medium-low mortality risk group (p = 0.001, 0.000, 0.010, respectively). Apelin 13 levels did not differ significantly in all groups.
CONCLUSIONS: HIF-1 alpha is a promising biomarker in distinguishing between patients and control groups and in identifying those with high mortality risk in the patient group. At the same time, NGAL can be used as a successful biomarker in determining the group with high mortality risk in cases of PE.

UNASSIGNED: Acute kidney injury (AKI) defined by changes in serum creatinine (SCr), or oliguria is associated with increased morbidity and mortality in children who are critically ill. We derived and validated a clinical cutoff value for urine neutrophil gelatinase-associated lipocalin (NGAL), in a prospective multicenter study of children who were critically ill. We report the clinical performance of urine NGAL (uNGAL) to aid in pediatric AKI risk assessment.
UNASSIGNED: Eligible subjects were aged ≥ 90 days to < 22 years, admitted to an intensive care unit (ICU), and had 1 or more of the following: mechanical ventilation, vasoactive medication administration, solid organ or bone marrow transplantation, or hypotension within 24-hours of admission. uNGAL was assessed within 24-hours of admission. The primary outcome was SCr-based stage 2/3 AKI presence at 48- to 72-hours.
UNASSIGNED: Twenty-five (12.3%) derivation study patients had stage 2/3 AKI at 48- to 72-hours. uNGAL concentration of 125 ng/ml was the optimal cutoff. Forty-seven (9.1%) validation study patients had stage 2/3 AKI at 48- to 72-hours. The area under the curve of a receiver operator characteristics curve (AUC-ROC) for uNGAL performance was 0.83 (95% confidence interval [CI]: 0.77-0.90). Performance characteristics were sensitivity 72.3% (95% CI: 57.4%-84.4%), specificity 86.3% (95% CI: 82.8%-89.3%), positive predictive value 34.7% (95% CI: 28.5%-41.5%), and negative predictive value 96.9% (95% CI: 95.1%-98.0%).
UNASSIGNED: These prospective, pediatric, multicenter studies demonstrate that uNGAL in the first 24-hours performs very well to predict Kidney Disease Improving Global Outcomes (KDIGO) stage 2/3 AKI at 48- to 72-hours into an ICU course. We suggest that a uNGAL cut point of 125 ng/ml can aid in the risk assessment for stage 2/3 AKI persistence or development.

Chronic kidney disease (CKD) is one of the most important causes of chronic pediatric morbidity and mortality and places an important burden on the medical system. Current diagnosis and progression monitoring techniques have numerous sensitivity and specificity limitations. New biomarkers for monitoring CKD progression have been assessed. Neutrophil gelatinase-associated lipocalin (NGAL) has had some promising results in adults, but in pediatric patients, due to the small number of patients included in the studies, cutoff values are not agreed upon. The small sample size also makes the statistical approach limited. The aim of our study was to develop a fuzzy logic approach to assess the probability of pediatric CKD progression using both NGAL (urinary and plasmatic) and routine blood test parameters (creatinine and erythrocyte sedimentation rate) as input data. In our study, we describe in detail how to configure a fuzzy model that can simulate the correlations between the input variables ESR, NGAL-P, NGAL-U, creatinine, and the output variable Prob regarding the prognosis of the patient\'s evolution. The results of the simulations on the model, i.e., the correlations between the input and output variables (3D graphic presentations) are explained in detail. We propose this model as a tool for physicians which will allow them to improve diagnosis, follow-up, and interventional decisions relative to the CKD stage. We believe this innovative approach can be a great tool for the clinician and validates the feasibility of using a fuzzy logic approach in interpreting NGAL biomarker results for CKD progression.

Objectives: To investigate the association between the blood concentration of lipocalin-2 (LCN2) in local multiethnic residents and the increased risk for the development of metabolic syndrome (MS) in the Yanbian Korean Autonomous Prefecture population. Methods: A total of 2078 subjects with (study group) or without (control group) MS (1217 Korean-Chinese and 861 Han-Chinese subjects) were included in this study. MS subjects were divided into five groups according to ethnicity and MS components. They were assessed for smoking history, drinking history, past medical history, general demographic characteristics, and LCN2 concentrations. Results: LCN2 concentrations were higher in all ethnic MS groups than in the control group, and the highest concentrations were detected in Han-Chinese subjects with dyslipidemia. Moreover, LCN2 concentrations were significantly higher in Korean-Chinese individuals with all MS components than in the control group. Logistic regression analyses were conducted. In the unadjusted models, Korean-Chinese and Han-Chinese individuals with high LCN2 concentrations both faced a risk of MS with odds ratios (ORs) of 2.339 (95% confidence interval [CI]: 1.632-3.352) and 1.523 (95% CI: 1.101-2. 108), respectively. After the adjustment, the risk only remained in Korean-Chinese individuals, with an OR of 1.818 (95% CI: 1.031-3.207). Conclusion: Elevated circulating LCN2 was associated with the increased incidence of MS, and the effect in Korean-Chinese individuals was stronger than that in Han-Chinese individuals.

Cardiorenal syndrome (CRS) is defined as a broad spectrum of conditions encompassing both the heart and kidneys in which acute or chronic heart disorder may induce acute or chronic tubular injury in the kidneys and vice versa. Early diagnosis allows timely intervention and attenuates disease progression. Two well-established biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and brain (B-type) natriuretic peptide (BNP), are reflective of impaired cardiac and kidney function associated with poor prognosis in various cardiac disorders, including heart failure and coronary artery disease. Given the ongoing contribution of CRS to the high morbidity and mortality post-MI, early risk stratification and preventive measures are highly significant. In this review, we examine Surface Plasmon Resonance (SPR) optical biosensors for detection of these biomarkers and discuss potential implications of this highly sensitive and specific technology in CRS detection, treatment and outcomes.

UNASSIGNED: The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients.
UNASSIGNED: To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters.
UNASSIGNED: This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls.
UNASSIGNED: Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 μg/ml, 0.439 μg/ml, and 0.382 μg/ml) than the control group (0.243 μg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 μg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08).
UNASSIGNED: The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.

Parkinson\'s disease (PD) ranks as the second most prevalent neurodegenerative disorder globally, marked by a complex pathogenesis. Lipocalin-2 (LCN2) emerges as a crucial factor during the progression of PD. Belonging to the lipocalin family, LCN2 is integral to several biological functions, including glial cell activation, iron homeostasis regulation, immune response, inflammatory reactions, and oxidative stress mitigation. Substantial research has highlighted marked increases in LCN2 expression within the substantia nigra (SN), cerebrospinal fluid (CSF), and blood of individuals with PD. This review focuses on the pathological roles of LCN2 in neuroinflammation, aging, neuronal damage, and iron dysregulation in PD. It aims to explore the underlying mechanisms of LCN2 in the disease and potential therapeutic targets that could inform future treatment strategies.

BACKGROUND: lipocalin 2 (LCN2) is a secreted glycoprotein that plays key roles in tumorigenesis and progression. Interestingly, LCN2 appears to have a contradictory function in developing lung adenocarcinoma (LUAD). Thus, we intend to explore the role of LCN2 in LUAD through bioinformatics and experimental validation.
METHODS: LCN2 expression of LUAD was investigated in the TCGA, TIMER and HPA databases. The relationship between LCN2 and prognosis was investigated by KM plotter, TCGA and GEO databases. GO, KEGG and protein-protein interactions network analysis were conducted to investigate the potential mechanism of LCN2. The relevance of LCN2 to cancer-immune infiltrates was investigated in the TCGA and TIMER databases. Quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay were performed to identify the expression level of LCN2 in cells and serum samples. The CCK-8, wound healing and transwell assay were used to confirm the effect of LCN2 on cell proliferation, migration and invasion in LUAD. The receiver operating characteristic curve was utilized to assess the diagnostic efficiency of LCN2 further.
RESULTS: LCN2 expression was significantly upregulated in LUAD (P < 0.05), and was correlated with the clinical stage, tumor size, lymph node metastasis and distant metastasis (P < 0.05). There was a high correlation between high LCN2 and worse prognosis in LUAD. Functional network analysis suggested that LCN2 was associated with multiple signal pathways in cancers, such as JAK-STAT, TNF, NF-κB, HIF-1 and PI3K-Akt signal pathways. In addition, the knockdown of LCN2 significantly inhibited the ability of cell proliferation, migration and invasion. Immune infiltration analysis indicated that LCN2 is associated with multiple immune cell infiltration. Notably, LCN2 demonstrated high diagnostic efficiency for LUAD (AUC = 0.818, P < 0.05), especially for stage III-IV patients could reach 0.895.
CONCLUSIONS: LCN2 as an oncogenic glycoprotein promotes the cancer progression related to immune infiltrates, which might be a potential diagnostic and prognostic marker in LUAD.

BACKGROUND: The clinical value of the trajectory of temporal changes in acute kidney injury (AKI) biomarkers has not been well established among intensive care unit (ICU) patients.
METHODS: This is a single-center, prospective observational study, performed at a mixed ICU in a teaching medical institute in Tokyo, Japan. Adult ICU patients with an arterial line and urethral catheter were enrolled from September 2014 to March 2015. Patients who stayed in the ICU for less than 48 h and patients with known end-stage renal disease were excluded from the study. Blood and urine samples were collected for measurement of AKI biomarkers at 0, 12, 24, and 48 h after ICU admission. The primary outcome was major adverse kidney events (MAKE) at discharge, defined as a composite of death, dialysis dependency, and persistent loss of kidney function (≥ 25% decline in eGFR).
RESULTS: The study included 156 patients. Serum creatinine-based estimated glomerular filtration rate (eGFR), plasma neutrophil gelatinase-associated lipocalin (NGAL), and urinary liver-type fatty acid-binding protein (uL-FABP) were serially measured and each variable was classified into three groups based on group-based trajectory modeling analysis. While the trajectory curves moved parallel to each other (i.e., \"low,\" \"middle,\" and \"high\") for eGFR and plasma NGAL, the uL-FABP curves showed distinct trajectory patterns and moved in different directions (\"low and constant,\" \"high and exponential decrease,\" and \"high and exponential increase\"). These trajectory patterns were significantly associated with MAKE. MAKE occurred in 16 (18%), 16 (40%), and 9 (100%) patients in the \"low and constant,\" \"high and exponential decrease,\" and \"high and exponential increase\" groups, respectively, based on uL-FABP levels (p-value < 0.001). The initial value and the 12-h change in uL-FABP were both significantly associated with MAKE, even after adjusting for eGFR [Odds ratio (95% confidence interval): 1.45 (1.17-1.83) and 1.43 (1.12-1.88) for increase of initial value and 12-h change of log-transformed uL-FABP by 1 point, respectively].
CONCLUSIONS: Trajectory pattern of serially measured urinary L-FABP was significantly associated with MAKE in ICU patients.