Diagnosis of septic shock by serum measurement of human neutrophil lipocalin by a rapid homogeneous assay.

BACKGROUND: Human neutrophil lipocalin (HNL) is a marker of neutrophil activation and has a high efficacy in diagnosing bacterial infections. In this study, we applied the AlphaLISA technique to measure the serum level of HNL, evaluate HNL's efficacy in diagnosing septic shock, and identify any association between HNL level and septic patients' prognosis. METHODS: We collected 146 serum samples from the Fifth Medical Center of Chinese PLA General Hospital. HNL was measured by AlphaLISA and results were compared with commercial ELISA kits. We studied 78 patients admitted to the ICU with sepsis and data on their clinical and physiological characteristics were recorded. Blood levels of HNL, procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and lactate were measured. A receiver operating characteristic (ROC) curve was used to evaluate the performance of each marker. RESULTS: The AlphaLISA assay for serum HNL had a detection range from 1.5 ng/mL to 1000 ng/mL, with a detection limit of 1 ng/mL and a detection time of approximately 25 min. The AlphaLISA assay's results were in high agreement with ELISA results (R2 = 0.9413). HNL levels were analyzed in sepsis patients, and HNL was significantly higher in sepsis patients with shock compared to sepsis patients without shock (median 356.47 ng/mL vs 158.93 ng/mL, P < 0.0001) and in the 28-day non-survivor group compared to the 28-day survivor group (median 331.83 ng/mL vs 175.17 ng/mL, P < 0.0001). ROC curve analysis was performed for the biomarkers. In differentiating the diagnosis of septic shock from sepsis patients, HNL was the most effective marker (AUC = 0.857), followed by PCT (AUC = 0.754) and hs-CRP (AUC = 0.627). In predicting the prognosis of septic patients, lactate had the best effect (AUC = 0.805), followed by HNL (AUC = 0.784), PCT (AUC = 0.721), and hs-CRP (AUC = 0.583). CONCLUSIONS: As an assessment tool, we found that our AlphaLISA had good consistency with an ELISA and had several other advantages, including requiring a shorter processing time and detecting a wider range of serum HNL concentrations. Monitoring serum HNL levels of patients admitted to the ICU might be useful in distinguishing sepsis patients who have septic shock from other sepsis patients, indicating its value in the prediction of sepsis patient prognosis.

Diagnostic value of ROC curve evaluation of serum markers in acute cholecystitis with bacterial infection.

OBJECTIVE: To explore correlation of serum markers human neutrophil lipocalin and C-reactive protein with acute cholecystitis associated with bacterial infection, and to evaluate the diagnostic value of the markers. METHODS: The cross-sectional study was conducted from January 2018 to April 2020 at the Beijing Luhe Hospital, Capital Medical University, Beijing, China, and comprised acute cholecystitis patients who were divided into bacterial infection group A and non-bacterial infection group B. Serum human neutrophil lipocalin and C-reactive protein were measured for both the groups. Receiver operating characteristic curve was used to evaluate the diagnostic value of the two markers in acute cholecystitis associated with bacterial infection. Data was analysed using SPSS 25. RESULTS: Of the 145 patients, 65(45%) were in group A; 36(55.38%) males and 29(44.62%) females with a mean age of 45.79±2.50 years. In group B there were 80(55%) subjects; 45(56.25%) males and 35(43.75%) females with a mean age of 46.16±2.52 years (p>0.05). In group A, there were 60(92.31%) cases of acute calculous cholecystitis, and 5(7.69%) had acute acalculous cholecystitis compared to 73(91.25%) and 7(8.75%), respectively, in group B (p>0.05). Serum human neutrophil lipocalin and C-reactive protein levels in group A were higher than group B (p<0.001). Serum human neutrophil lipocalin showed a high positive correlation with C-reactive protein in group A (r=0.800, p<0.001), and a moderate positive correlation in group B (r=0.683, p<0.001). Area under the curve of serum human neutrophil lipocalin associated with C-reactive protein was 0.901 (95% confidence interval: 0.850-0.953), which was higher than that of serum human neutrophil lipocalin and C-reactive protein alone, with sensitivity 95.40% and specificity 80%. CONCLUSIONS: The combined use of serum human neutrophil lipocalin and C-reactive protein may be used as an effective indicator for early diagnosis, identification and monitoring of acute cholecystitis with bacterial infection.

Utility of Human Neutrophil Lipocalin as a Diagnosing Biomarker of Prosthetic Joint Infection: A Clinical Pilot Study.

Purpose: The discrimination of prosthetic joint infection (PJI) from aseptic failure is regarded as a major clinical challenge. The key function of human neutrophil lipocalin (HNL) in regulating bacterial infection rationalizes its potential as a biomarker to diagnose PJI. This work evaluated the accuracy of serum human neutrophil lipocalin as a biomarker to diagnose PJI. Methods: This prospective cohort study enrolled altogether 58 patients suffering from miserable knee or hip arthroplasty and receiving revision surgery from 2018 to 2020. Related laboratory and clinical information of these patients were retrieved. Following the Musculoskeletal Infection Society (MSIS) criteria, the diagnosis of PJI was conducted. Collecting preoperative blood samples, we measured HNL by the standard assay. Thereafter, plotting the receiver-operating characteristic curve (ROC), the area under the curve (AUC) values were calculated to analyze the diagnosis accuracy. Results: According to the MSIS criteria, 38 cases (65.5%) were classified into the PJI group, while 20 (34.5%) into the aseptic loosening group, with age ranging from 38 to 87 (median, 66.9) years. The median serum HNL level of the PJI patients was 199.01 (range, 85.34-357.79) ng/mL, significantly higher as compared with that of 64.81 (range, 20.73-157.89) ng/mL of the aseptic loosening group. Using the Youden index, the optimal threshold value was 105.1ng/mL, while the specificity, sensitivity, and AUC were 85.0%, 81.6%, and 0.919, respectively. Conclusion: Serum HNL is the creditable test that can be employed as the laboratory biomarker to screen PJI. The threshold HNL level is 105.1 ng/mL, which may distinguish PJI from aseptic failure.

Serum human neutrophil lipocalin: An effective biomarker for diagnosing bacterial infections.

BACKGROUND: Human neutrophil lipocalin (HNL) is used as a novel biomarker for infections. However, only a few studies have focused on the usefulness of HNL. The purpose of this study was to evaluate the diagnostic efficiency of HNL for identifying bacterial infections and to compare HNL with procalcitonin (PCT) and C-reactive protein (CRP). METHODS: Hospital patients with acute infections of bacterial origin (n = 439), viral origin (n = 71), and healthy volunteers (n = 67) were included in the study. The infection status of each patient was verified using microbiological, serological, and PCR testing. Additionally, CRP, HNL, and PCT levels were measured by established methods. RESULTS: In distinguishing bacterial and viral infections, area under the curve (AUC) analysis showed that, with a value of 0.81 (95% CI, 0.76-0.86), HNL was superior to CRP at 0.73 (0.68-0.79) and PCT at 0.64 (0.58-0.70). Interestingly, the combination of HNL, PCT, and CRP improved the diagnostic potential significantly with an AUC of 0.86 (0.82-0.90, P < 0.05). Furthermore, when comparing different infection site subgroups with healthy patients, HNL levels were higher in all bacterial groups, albeit to widely varying degrees (P < 0.0001), and HNL reached a higher level in bloodstream and abdominal infections. CRP levels showed the same trend as HNL levels. PCT levels were significantly increased in bloodstream infections, abdominal infections, and in bacterial pneumonia (P < 0.0001), while no significant differences were found in soft tissue (P = 0.4378) or urinary tract infections (P = 0.423). There was no difference in HNL and CRP levels between patients with Gram-negative bacterial (GNB) or Gram-positive bacterial infections. However, compared with controls, PCT was only increased in GNB-infected patients. CONCLUSION: HNL detection can help diagnose patients with infectious diseases, and the diagnostic efficacy of HNL is not affected by the infected site or by pathogenic bacterial species. The combination of HNL, PCT, and CRP has a superior performance at identifying bacterial infections compared with traditional biomarkers.

Utility of procalcitonin, human neutrophil lipocalin and neutrophil CD64 in early diagnosis of bacterial infection / 中国感染与化疗杂志

Objective To examine the expression levels of procalcitonin (PCT),neutrophils apolipoprotein (human neutrophil lipocalin,HNL) and neutrophil CD64 (CD64) in the blood of patients with bacterial infection and investigate their utility in early diagnosis and treatment of bacterial infection.Methods A total of 210 patients with confirmed infection who were treated in hospital from February 2013 to May 2017 were enrolled.The patients were classified into bacterial infection group (105 cases) and viral infection group (105 cases).Additionally,a cohort of 80 healthy subjects were randomly selected from health checkup during the same period as the control group.PCT and HNL were determined on the UPT up-converting phosphor microbial immunity analyzer provided by Beijing Hotgen Biotech Company.BD FACS calibur flow cytometer was used to measure and calculate CD64 percentage.Results The levels of PCT,HNL,CD64 and WBC were compared between bacterial infection group,viral infection group and control group.The between-group difference was statistically significant (P＜0.05).The CD64 and WBC levels were significantly different between viral infection group and control group (P＜0.05),but the PCT and HNL levels were not different significantly between viral infection group and control group (P＞0.05).The area under the ROC curve of PCT,namely AUC PCT,was 0.855,and AUC (HNL) was 0.930,AUC (CD64) 0.928,and AUC (WBC) 0.729.The cutoff value of PCT,HNL and CD64 for diagnosis of bacterial infections was ＞0.79 ng/mL,＞87.43 ng/mL,and ＞9.01％,respectively.Conclusions Bacterial infection is associated with elevated levels of PCT,HNL and CD64,which can be used in early diagnosis of bacterial infections.HNL may provide the highest diagnostic value.

Human neutrophil lipocalin in fMLP-activated whole blood as a diagnostic means to distinguish between acute bacterial and viral infections.

UNLABELLED: The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) in serum distinguishes acute infections with high accuracy, but in the emergency setting the assay time should be <15-20min, which excludes the use of serum samples. The aim was therefore to develop a novel rapid assay principle and test its clinical performance. METHODS: Serum and neutrophils obtained from 84 infected and 20 healthy subjects were used in the experimental study. 725 subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the clinical study. HNL was measured in EDTA-plasma by ELISA or in heparinized whole blood after fMLP activation by a prototype point-of-care assay. RESULTS: Increased release of HNL from neutrophils after activation with fMLP was seen already after 5 min incubation. The release of HNL from purified neutrophils after 15 min incubation with fMLP was significantly correlated to the HNL concentrations in serum obtained from the same patient (r = 0.74, p < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the ROC-curves were 0.95 (95% CI 0.91-0.97) and 0.88 (95% CI 0.84-0.91) for HNL in fMLP-activated whole blood and EDTA-plasma, respectively, (p < 0.001) and in the distinction between bacterial and viral infections 0.91 (95% CI 0.86-0.95) and 0.76 (95% CI 0.70-0.81), respectively (p < 0.001). CONCLUSION: The clinical performance of HNL in fMLP-activated whole blood was superior to HNL in EDTA-plasma and similar to HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

Clinical value of NHL detection in the differential diagnosis of bacterial and viral infections of elderly patients with acute respiratory infection / 国际检验医学杂志

Objective Toinvestigatetheclinicalvalueofhumanneutrophillipocalin(HNL)detectioninthedifferentialdiagnosis of bacterial and viral infections of elderly patients with acute respiratory infection .Methods 142 elderly patients with respiratory infection were divided the bacteria group (96 cases) and the virus group (46 cases) according to their infections ,42 healthy people in the corresponding period were enrolled as the control group .Enzyme-linked immunosorbent assay and highly sensitive dry chemi-cal particles enhanced immune turbidity assay were employed to detect their blood HNL and C-reactive protein(CRP) ,respectively , and virus-specific antibodies detection were performed simultaneously .Results Compared the blood HNL ,CRP levels and their positive rates of patients in bacteria group with those in the virus group ,control group ,respectively ,differences showed statistically significant(P0 .05) .Antibiotic treatment before and 24 ,48 and 72 hours after ,the concentrations of HNL were (216 .8 ± 64 .1) , (192 .0 ± 41 .2) ,(158 .0 ± 54 .5) and (87 .0 ± 12 .4)μg/L ,respectively ,while those of CRP were (50 .9 ± 40 .9) ,(46 .2 ± 18 .3) , (39 .6 ± 9 .6) and (12 .6 ± 9 .8) mg/L ,respectively .Sensitivity ,specificity ,positive predictive value and negative predictive value of HNL detection were 90 .6% ,90 .9% ,91 .5% and 89 .9% ,respectively ,which were higher than those of CRP (88 .5% ,85 .2% , 86 .7% and 87 .2% ,respectively) ,with statistically significant difference(P<0 .05) .Conclusion NHL detection possesses impor-tant significance in differential diagnosis between bacterial and viral infections of elderly patients with acute respiratory infection .