Heparin-binding Protein Levels Research Articles

Hepcidin, in contrast to heparin binding protein, does not portend acute kidney injury in patients with community acquired septic shock.

Acute kidney injury (AKI) is a common and severe complication in patients treated at an Intensive Care Unit (ICU). The pathogenesis of AKI has been reported to involve hypoperfusion, diminished oxygenation, systemic inflammation, and damage by increased intracellular iron concentration. Hepcidin, a regulator of iron metabolism, has been shown to be associated with sepsis and septic shock, conditions that can result in AKI. Heparin binding protein (HBP) has been reported to be associated with sepsis and AKI. The aim of the present study was to compare serum hepcidin and heparin binding protein (HBP) levels in relation to AKI in patients admitted to the ICU. One hundred and forty patients with community acquired illness admitted to the ICU within 24 hours after first arrival to the hospital were included in the study. Eighty five of these patients were diagnosed with sepsis and 55 with other severe non-septic conditions. Logistic and linear regression models were created to evaluate possible correlations between circulating hepcidin and heparin-binding protein (HBP), stage 2-3 AKI, peak serum creatinine levels, and the need for renal replacement therapy (RRT). During the 7-day study period, 52% of the 85 sepsis and 33% of the 55 non-sepsis patients had been diagnosed with AKI stage 2-3 already at inclusion. The need for RRT was 20% and 15%, respectively, in the groups. Hepcidin levels at admission were significantly higher in the sepsis group compared to the non-sepsis group but these levels did not significantly correlate to the development of stage 2-3 AKI in the sepsis group (p = 0.189) nor in the non-sepsis group (p = 0.910). No significant correlation between hepcidin and peak creatinine levels, nor with the need for RRT was observed. Stage 2-3 AKI correlated, as expected, significantly with HBP levels at admission in both groups (Odds Ratio 1.008 (CI 1.003-1.014, p = 0.005), the need for RRT, as well as with peak creatinine in septic patients. Initial serum hepcidin, and HBP levels in patients admitted to the ICU are biomarkers for septic shock but in contrast to HBP, hepcidin does not portend progression of disease into AKI or a later need for RRT. Since hepcidin is a key regulator of iron metabolism our present data do not support a decisive role of initial iron levels in the progression of septic shock into AKI.

Heparin-Binding Protein Promotes Acute Lung Injury in Sepsis Mice by Blocking the Aryl Hydrocarbon Receptor Signaling Pathway.

This study aimed to explore the therapeutic effect and potential mechanism of heparin-binding protein (HBP) reduction on sepsis-related acute lung injury. We utilized a murine model of sepsis-induced by intraperitoneal injection of lipopolysaccharides (LPS) in C57BL/6J mice divided into four groups: Control, LPS, Anti-HBP, and ceftriaxone (CEF). Following sepsis induction, Anti-HBP or CEF treatments were administered, and survival rates were monitored for 48 h. We then used reverse-transcription quantitative PCR to analyze the expression levels of HBP in lung tissues, immunohistochemistry for protein localization, and Western blotting for protein quantification. Pulmonary inflammation was assessed using enzyme-linked immunosorbent assays of proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and interferon-γ). The activation state of the aryl hydrocarbon receptor (AhR) signaling pathway was determined via Western blotting, evaluating both cytoplasmic and nuclear localization of AhR and the expression of cytochrome P450 1A1 protein by its target gene. Anti-HBP specifically reduced HBP levels. The survival rate of mice in the Anti-HBP and CEF groups was much higher than that in the LPS group. The severity of lung injury and pulmonary inflammatory response in the Anti-HBP and CEF groups was significantly lower than that in the LPS group. AhR signaling pathway activation was observed in the Anti-HBP and CEF groups. Additionally, there was no significant difference in the above indices between the Anti-HBP and CEF groups. HBP downregulation in lung tissues significantly improved LPS-induced lung injury and the pulmonary inflammatory response, thereby prolonging the survival of sepsis mice, suggesting activation of the AhR signaling pathway. Moreover, the effect of lowering the HBP level was equivalent to that of the classical antibiotic CEF. Not applicable.

Diagnostic, monitoring, and prognostic value of combined detection of cerebrospinal fluid heparin-binding protein, interleukin-6, interleukin-10, and procalcitonin for post-neurosurgical intracranial infection

ObjectiveIntracranial infection is a common complication after neurosurgery and can increase the length of hospital stay, affect patient prognosis, and increase mortality. We aimed to investigate the value of the combined detection of cerebrospinal fluid (CSF) heparin-binding protein (HBP), interleukin-6 (IL-6), interleukin-10 (IL-10), and procalcitonin (PCT) for post-neurosurgical intracranial infection. MethodsThis study assessed the diagnostic values of CSF HBP, IL-6, IL-10, PCT levels, and combined assays for post-neurosurgical intracranial infection with the area under the receiver operating characteristic (ROC) curve by retrospectively analysing biomarkers of post-neurosurgical patients. ResultsThe CSF HBP, IL-6, IL-10, and PCT levels were significantly higher in the infected group than the uninfected group and the control group (P < 0.001). The indicators in the groups with severe intracranial infections were significantly higher than those in the groups with mild intracranial infections (P < 0.001), and the groups with poor prognoses had significantly higher indexes than the groups with good prognoses. According to the ROC curve display, the AUC values of CSF HBP, IL-6, IL-10, and PCT were 0.977 (95 % CI 0.952–1.000), 0.973 (95 % CI 0.949–0.998), 0.884 (95 % CI 0.823–0.946), and 0.819 (95 % CI 0.733–0.904), respectively. The AUC of the combined test was 0.996 (95 % CI 0.989–1.000), which was higher than those of the four indicators alone. ConclusionThe combined detection can be an important indicator for the diagnosis and disease monitoring of post-neurosurgical intracranial infection.

Utility of heparin-binding protein following cardiothoracic surgery using cardiopulmonary bypass

Cardiothoracic surgery using cardiopulmonary bypass (CPB) triggers an inflammatory state that may be difficult to differentiate from infection. Heparin-binding protein (HBP) is a candidate biomarker for sepsis. As data indicates that HBP normalizes rapidly after cardiothoracic surgery, it may be a suitable early marker of postoperative infection. We therefore aimed to investigate which variables influence postoperative HBP levels and whether elevated HBP concentration is associated with poor surgical outcome. This exploratory, prospective, observational study enrolled 1475 patients undergoing cardiothoracic surgery using CPB, where HBP was measured at ICU arrival. Patients with HBP in the highest tercile were compared to remaining patients. Multivariable logistic regressions were performed to identify factors predictive of elevated HBP and 30-day mortality. Overall median HBP was 30.0 ng/mL. Patients undergoing isolated CABG or surgery with CPB-duration ≤ 60 min had a median HBP of 24.9 ng/mL and 23.2 ng/mL, respectively. Independent predictors of elevated postoperative HBP included increased EuroSCORE, prolonged CPB-duration and high intraoperative temperature. Increased HBP was an independent predictor of 30-day mortality. This study confirms the promising characteristics of HBP as a biomarker for identification of postoperative sepsis, especially after routine procedures. Further studies are required to investigate whether HBP may detect postoperative infections.

Systemic Inflammatory Status of Patients with Obstructive Sleep Apnea Syndrome and the Predictive Value of Heparin-Binding Protein.

Objective: To investigate the alteration of the systemic inflammatory status of patients with obstructive sleep apnea syndrome (OSAS) and the predictive value of heparin-binding protein (HBP) for OSAS. Methods: Patients with OSAS who were hospitalized in our hospital from 2020 January to 2022 December and diagnosed by polysomnography (PSG) (OSAS group, n = 79) were retrospectively studied and their relevant examination findings and demographic characteristics were recorded. Sex- and age-matched non-OSAS patients hospitalized at the same time were selected as the control group (control group, n = 28). Differences in peripheral blood neutrophil counts, lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), and HBP were compared between the 2 groups. The predictive value of these markers for OSAS was analyzed using the receiver operating characteristic curve, and independent risk factors for OSAS were determined using logistic regression analysis. Peripheral blood was drawn from all patients in the fasting state of the morning. Results: The number of peripheral blood neutrophils, lymphocytes, and HBP was higher in the OSAS group than in the control group, and the differences were statistically significant (P all <.05), while the differences in NLR and PCT between the 2 groups were not statistically significant (P all >.05). Plasma HBP level had an area under the curve (AUC) of 0.79 (P < .0001) in determining OSAS, with a sensitivity of 80.49% and a specificity of 70.83% and the best cutoff value was >10.73 ng/ml. Combining body mass index (BMI), neutrophil, lymphocyte, and HBP improved the predictive value of OSAS with an AUC of 0.89 (P < .0001), a sensitivity of 80.49%, and a specificity of 87.50%. Logistic regression analysis showed that both BMI and HBP were independent risk factors for OSAS (PBMI < .001, PHBP < .01), while neutrophils and lymphocytes were not (P all >.05). Conclusions: This is the first study to objectively examine HBP in OSAS patients, and HBP is an independent risk factor that may serve as a diagnostic biomarker in OSAS. Patients with OSAS have an altered systemic inflammatory state and may be more prone to severe bacterial infections.

Tamibarotene targets heparin-binding protein for attenuating lung injury in sepsis.

Excessively active pulmonary inflammation is a hallmark of sepsis-induced lung damage. A synthetic retinoid drug called tamibarotene reduces inflammation in a variety of conditions, including acute promyelocytic leukemia (APL), renal fibrosis, and neuroinflammation. Its effect on sepsis-related lung injury, however, has not been explained. The purpose of the study was to investigate how tamibarotene affected lung damage induced by cecal ligation and puncture (CLP) procedure. A CLP sepsis mouse model was developed, and tamibarotene was pretreated to determine whether it improved lung injury and survival. The degree of lung injury was evaluated using the Hematoxylin and eosin staining and lung injury score. In order to determine pulmonary vascular permeability, measurements were taken for total protein and cell content of bronchoalveolar lavage fluid (BALF), wet/dry ratio of the lung, and Evans blue stain. The BALF inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-17A were discovered by enzyme-linked immunosorbent serologic assay (ELISA). Then, the levels of heparin-binding protein (HBP), and phospho-nuclear factor kappa-B (p-NF-κB) P65, and NF-κB P65 were determined using ELISA and Western blot analysis, respectively. Tamibarotene considerably increases survival and lessens lung damage stimulated by sepsis. Specifically, tamibarotene significantly relieves pulmonary vascular permeability and inhibits inflammation response in sepsis. Moreover, we further confirmed that these ameliorating effects of tamibarotene on sepsis may be exerted by targeting HBP and regulating the activation of NF-κB signaling pathway. These findings demonstrated that tamibarotene lessens sepsis-induced lung injury, and the effect could be exerted by targeting HBP and thereby deregulating the NF-κB signaling pathway.

A novel HCP (heparin-binding protein-C reactive protein-procalcitonin) inflammatory composite model can predict severe acute pancreatitis

Severe acute pancreatitis (SAP) presents with an aggressive clinical presentation and high lethality rate. Early prediction of the severity of acute pancreatitis will help physicians to further precise treatment and improve intervention. This study aims to construct a composite model that can predict SAP using inflammatory markers. 212 patients with acute pancreatitis enrolled from January 2018 to June 2020 were included in this study, basic parameters at admission and 24 h after hospitalization, and laboratory results such as inflammatory markers were collected. Pearson's test was used to analyze the correlation between heparin-binding protein (HBP), procalcitonin (PCT), and C-reactive protein (CRP). Risk factors affecting SAP were analyzed using multivariate logistic regression, inflammatory marker models were constructed, and subject operating curves were used to verify the discrimination of individual as well as inflammatory marker models and to find the optimal cut-off value based on the maximum Youden index. In the SAP group, the plasma levels of HBP, CRP, and PCT were 139.1 ± 74.8 ng/mL, 190.7 ± 106.3 mg/L and 46.3 ± 22.3 ng/mL, and 25.3 ± 16.0 ng/mL, 145.4 ± 67.9 mg/L and 27.9 ± 22.4 ng/mL in non-SAP patients, with a statistically significant difference between the two groups (P < 0.001), The Pearson correlation analysis showed a positive correlation between the three values of HBP, CRP, and PCT. The results of the multivariate logistic regression analysis showed that HBP (OR = 1.070 [1.044–1.098], P < 0.001), CRP (OR = 1.010 [1.004–1.016], P = 0.001), and PCT (OR = 1.030[1.007–1.053], P < 0.001) were risk factors for SAP, and the area under the curve of the HBP-CRP-PCT model was 0.963 (0.936–0.990). The HCP model, consisting of HBP, CRP, and PCT; is well differentiated and easy to use and can predict the risk of SAP in advance.

Heparin-binding protein as a marker of ventriculostomy related infection and central nervous system inflammation in neuro-intensive care

ObjectiveDiagnosis of ventriculostomy related infections (VRI) in the neuro-intensive care unit remains challenging and current biomarkers lack adequate precision. The aim of this study was to explore the potential of Heparin-binding protein (HBP) in cerebrospinal fluid (CSF) as a diagnostic biomarker of VRI. MethodsAll patients treated with an external ventricular drain (EVD) between January 2009 and March 2010 at Skåne university hospital in Lund, Sweden, were consecutively included. CSF samples obtained during routine care were analyzed for HBP. VRI was defined as a positive bacterial microbiology test result on a CSF sample with an erythrocyte-corrected leukocyte count of > 50 × 106/l. HBP levels at VRI diagnosis was compared to peak HBP levels in non-VRI controls. ResultsIn total, 394 CSF samples from 103 patients were analyzed for HBP. Seven patients (6.8%) fulfilled VRI criteria. Levels of HBP were significantly higher in VRI subjects (31.7 ng/mL [IQR 26.9–40.7 ng/mL]) compared to non-VRI controls (7.7 ng/mL [IQR 4.1–24.5 ng/mL]) (p = 0.024). The AUC of the receiver operating characteristic (ROC) curve was 0.76 (95% confidence interval [CI], 0.62–0.90). Among non-VRI patients, HBP was highest in patients with acute bacterial meningitis. Patients with subarachnoid hemorrhage displayed higher HBP levels than those with traumatic brain injury or shunt dysfunction. ConclusionsHBP levels were higher in VRI subjects and varied between patients and different diagnoses. To validate the clinical usefulness and added value of HBP as a biomarker for VRI, the results need to be confirmed in larger studies with head-to-head comparisons to current biomarkers.

Heparin-Binding Protein: A Prognostic Biomarker Associated with Severe or Complicated Community-Acquired Pneumonia in Children.

Heparin-binding protein (HBP) is a novel biomarker for inflammatory diseases. This study aimed to investigate the role of serum HBP in community-acquired pneumonia (CAP) in children and the association of HBP with the severity and prognosis. A total of 125 children with CAP admitted to the hospital were enrolled in this retrospective study. We analyzed the differences in clinical characteristics and examination findings between patients with different levels of HBP. The severe or complicated CAP was defined as having severe radiographic findings and/or systemic manifestations. Receiver operator characteristic (ROC) curves detected the performance of biomarkers in identifying patients with severe or complicated pneumonia. The multivariate logistic regression models assessed the association between HBP levels and the severity and prognosis. Finally, we constructed a predictive model based on HBP. The rate of severe or complicated CAP for patients with upper-quartile HBP concentration (≥60 ng/mL) was 54.8%, significantly higher than that of patients with lower HBP concentration (26.6%). The level of HBP is substantially correlated with neutrophil counts, C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A protein (r = 0.31, 0.26, 0.36, and 0.26, respectively). HBP achieved the highest level of discrimination for severe or complicated CAP among the biomarkers. Higher HBP concentration (≥60 ng/mL) was associated with a three-fold higher risk of severe or complicated CAP (adjusted odds ratio = 3.11, p < 0.05). A predictive model including four characteristics (HBP, lactate dehydrogenase, age and non-viral infection) for predicting severe or complicated CAP (with area under the ROC curve = 0.75) was built to create a nomogram. Substantially elevated serum HBP is significantly associated with severe or complicated CAP and poor prognosis in children. This finding warrants further investigation of the function of HBP in the pathogenesis of CAP.

Changes in Heparin-Binding Protein, Procalcitonin, and C-Reactive Protein Within the First 72 Hours Predict 28-Day Mortality in Patients Admitted to the Intensive Care Unit with Septic Shock.

BACKGROUND This study aimed to evaluate the possible associations of heparin-binding protein (HBP), procalcitonin (PCT), and C-reactive protein (CRP) levels with 28-day mortality in septic shock patients admitted to Intensive Care Units (ICUs). MATERIAL AND METHODS Blood samples were taken at ICU admission and measured again 72 h later to calculate changes in HBP (ΔHBP), changes in PCT (ΔPCT), changes in CRP (ΔCRP), and changes in Sequential Organ Failure Assessment (DSOFA) relative to baseline. RESULTS Variables included in the univariable logistic regression model for survival were age, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, decreasing ΔSOFA, decreasing DHBP, decreasing ΔPCT, and decreasing ΔCRP. Survival was directly related to decreasing ΔHBP with odds ratio (OR)=9.95 (95% confidence interval [CI] 4.63 to 21.35; P<0.001), decreasing ΔPCT with OR=7.85 (3.74 to 16.49; P<0.001), decreasing ΔCRP with OR=5.83 (2.84 to 11.97; P<0.001), decreasing ΔSOFA with OR=1.93 (1.00 to 3.75; P=0.051) and APACHE II score with OR=1.93 (1.14 to 1.68; P=0.001). In a multivariable logistic regression model for survival, only decreasing DHBP with OR=7.18 (2.91 to 17.69; P<0.001), decreasing ΔPCT with OR=5.17 (2.12 to 12.56; P<0.001), and decreasing ΔCRP with OR=4.33 (1.77 to 10.61; P=0.001) remained significant. CONCLUSIONS Measuring changes in HBP, PCT, and CRP within 72 h of admission may aid in predicting 28-day mortality for patients with septic shock in ICUs.

Heparin-binding protein as a biomarker of severe sepsis in the pediatric intensive care unit: A multicenter, prospective study

ObjectivesThe aim of this study is to assess Heparin-binding protein (HBP) as a diagnostic and prognostic biomarker of severe sepsis in the pediatric intensive care unit (PICU). MethodsA multicenter, prospective study was conducted among children with sepsis in nine PICUs in China from October 2019 to June 2021. Plasma levels of HBP, procalcitonin (PCT), C-reactive protein (CRP), lactate, and white blood cell (WBC) count were determined at enrollment and 72 h after enrollment. ResultsOf 355 included patients, 132 patients were diagnosed with non-severe sepsis (referred to as sepsis), 223 patients had severe sepsis. Patients with severe sepsis had significantly elevated levels of HBP compared with sepsis (median 170.5 vs. 74.1 ng/mL, P < 0.001). Adding HBP to a diagnostic model with PCT and lactate could significantly improve the diagnostic capability for severe sepsis. The plasma levels of HBP correlated positively with the number of dysfunctional organs. After adjusting for confounding factors, the declined levels of HBP at 72 h had a significant association with decreased in-hospital mortality (adjusted odds ratio (aOR) 0.242, P < 0.001). The levels of HBP showed weak positive correlations with PCT, CRP, WBC, and no correlation to lactate. ConclusionsHBP at enrollment can be an independent indicator for severe sepsis and the dynamic changes at 72 h can be a predictor for in-hospital mortality in PICU.

HIGH HEPARANASE LEVEL IN SURVIVORS OF COVID-19 - INDICATOR OF VASCULAR AND PULMONARY RECOVERY?

Background: Severe progression of coronavirus disease 2019 (COVID-19) causes respiratory failure and critical illness. Recently, COVID-19 has been associated with heparanase (HPSE)-induced endothelial barrier dysfunction and inflammation, so called endothelitis, and therapeutic treatment with heparin or low-molecular-weight heparin (LMWH) targeting HPSE has been postulated. Because, up to this date, clinicians are unable to measure the severity of endothelitis, which can lead to multiorgan failure and concomitant death, we investigated plasma levels of HPSE and heparin-binding protein (HBP) in COVID-19 intensive care patients to render a possible link between endothelitis and these plasma parameters. Therefore, a prospective prolonged cohort study was conducted, including 47 COVID-19 patients from the intensive care unit. Plasma levels of HPSE, and HBP were measured daily by enzyme-linked immunosorbent assay in survivors (n = 35) and nonsurvivors (n = 12) of COVID-19 from admission until discharge or death. All patients were either treated with heparin or LMWH, aiming for an activated partial thromboplastin time of ≥60 seconds or an anti-Xa level of >0.8 IU/mL using enoxaparin, depending on the clinical status of the patient (patients with extracorporeal membrane oxygenation or >0.1 μg/kg/min noradrenaline received heparin, all others enoxaparin). Results: We found significantly higher plasma levels of HPSE and HBP in survivors and nonsurvivors of COVID-19, compared with healthy controls. Still, interestingly, plasma HPSE levels were significantly higher ( P < 0.001) in survivors compared with nonsurvivors of COVID-19. In contrast, plasma HBP levels were significantly reduced ( P < 0.001) in survivors compared with nonsurvivors of COVID-19. Furthermore, when patients received heparin, they had significantly lower HPSE ( P = 2.22 e - 16) and significantly higher HBP ( P = 0.00013) plasma levels as when they received LMWH. Conclusion: Our results demonstrated that patients, who recover from COVID-19-induced vascular and pulmonary damage and were discharged from the intensive care unit, have significantly higher plasma HPSE level than patients who succumb to COVID-19. Therefore, HPSE is not suitable as marker for disease severity in COVID-19 but maybe as marker for patient's recovery. In addition, patients receiving therapeutic heparin treatment displayed significantly lower heparanse plasma level than upon therapeutic treatment with LMWH.

Clinical value of serum sTREM-1 and HBP levels in combination with traditional inflammatory markers in diagnosing hospital-acquired pneumonia in elderly

BackgroundThe clinical presentation of hospital-acquired pneumonia (HAP) in older patients is often complex and non-specific, posing a diagnostic challenge. This study evaluates the value of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and heparin-binding protein (HBP) in combination with traditional inflammatory markers procalcitonin (PCT) and C-reactive protein (CRP) in diagnosing HAP in older patients.MethodsThirty-eight elderly male patients with HAP (≥ 80 years old) and 46 age-matched controls, who were hospitalized for other reasons than HAP, were enrolled. The serum sTREM-1, HBP, PCT and CRP levels were measured by ELISA on the first day after enrollment. In addition, routine blood test, blood gas, sputum analysis, clinical pulmonary infection score (CPIS) assessment, and chest X-ray were performed, and the correlations with HAP were analyzed.ResultsThe serum sTREM-1 (n = 38, 170.75 ± 158.33 pg/ml), HBP (2.08 ± 0.50), PCT (9.44 ± 17.73) and CRP (79.63 ± 71.37) were all significantly higher in the HAP group, when compared to the control group (P < 0.05). Furthermore, the values were positively correlated with the CPIS. The ROC curve analysis revealed that the AUC for sTREM-1 (0.667) and HBP (0.711) were lower, when compared to that for PCT (AUC = 0.839) and CRP (AUC = 0.840). The combination of PCT and CRP with sTREM-1 (AUC = 0.927) or HBP (AUC = 0.930) had the highest AUC values.ConclusionSerum sTREM-1, HBP, PCT and CRP can all be used as diagnostic markers for HAP in the elderly. The combination of traditional inflammatory markers PCT and CRP with novel inflammatory marker sTREM-1 or HBP further improves the diagnostic performance.

Heparin-Binding Protein Aggravates Acute Lung Injury in Septic Rats by Promoting Macrophage M1 Polarization and NF-κB Signaling Pathway Activation.

Objective Heparin-binding protein (HBP) plays an important role in sepsis and is a prognostic biomarker in patients with sepsis, but the role of HBP in the pathogenesis of sepsis-associated acute lung injury (ALI) remains unclear. This study aimed to investigate the role of HBP in sepsis-induced ALI and its underlying molecular mechanisms. Methods The cecal ligation and puncture (CLP) model was used to induce ALI in mice and randomly divided into 4 groups: control group, CLP (rats treated with cecal ligation and puncture), HBP (rats treated with CLP and HBP injection), and HBP + UFH (rats treated with CLP and injection of HBP and unfractionated heparin). Subsequently, HBP expression in rat serum and lung tissues was detected by qRT-PCR, edema and pathological changes in lung tissue by lung wet-to-dry weight ratio (W/D) and HE staining, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities in lung tissues by detection kits. Additionally, ELISA and western blot were applied for the determination of IL-6, TNF-α, and IL-1β expression in rat bronchoalveolar lavage fluid, and iNOS, Arg-1, Mrc1, NF-κBp65, IKKα, IκBα, and p-IκBα expression in lung tissues. Results The expression levels of HBP in serum and lung tissues of rats in the HBP group were significantly increased, the lung tissues were severely injured, accompanied by a significant increase in MPO activity but a significant decrease in SOD activity, and the levels of IL-6, TNF-α, and IL-1β in bronchoalveolar lavage fluid were significantly increased. In addition, the expression levels of iNOS, NF-κB p65, IKKα, and p-IκBα in the lung tissues of rats in the HBP group were significantly increased, while the addition of unfractionated heparin reversed the above results. Conclusion HBP aggravates ALI in septic rats, and its mechanism may be related to the promotion of macrophage M1 polarization and activation of the NF-κB signaling pathway.

Development and application of amplified luminescent proximity homogeneous assay for quantitation of heparin-binding protein

A fast and highly sensitive amplified luminescent proximity homogeneous assay (AlphaLISA) method was developed for quantitation of plasma heparin-binding protein levels. In this study, a method directly coupling donor and acceptor beads modified with aldehyde groups to anti-HBP antibodies was proposed, which can effectively simplify the steps and shorten the reaction time to achieve faster detection. Therefore, the developed method required only 15 min of reaction time to generate results. Compared with the approved commercial kit, the developed method had a wider linear range (2.78–500 ng/mL). The excellent linear range means that the method can better exploit the value of HBP in clinical applications. Meanwhile, results of amplified luminescent proximity homogeneous assay and fluorescence dry quantitative immunoassay had good correlation and consistency (ρ = 0.9181). Moreover, the plasma HBP concentrations of patients with bacterial infection were significantly higher than those of healthy individuals (P < 0.0001), indicating the potential applicability of the proposed method for predicting the incidence of bacterial infections. Importantly, the newly developed method is expected to serve as an alternative to the traditional assay method and provides a completely new platform for other biomarkers that require rapid detection.

Analysis of Cerebrospinal Fluid Routine Biochemical Level, Pathogenic Bacteria Distribution, and Risk Factors in Patients with Secondary Intracranial Infection after Brain Tumor Surgery

Purpose Analysis of routine biochemical levels of cerebrospinal fluid (CSF), distribution of pathogenic bacteria, and risk factors in patients with intracranial infections secondary to brain tumour surgery. Methods A total of 208 patients admitted to our hospital for brain tumour surgery from January 2020 to May 2022 were selected. Fully automated biochemical analyzer was employed for CSF routine and for measuring biochemical parameters such as white blood cell (WBC), micrototal protein (M-TP), glucose (GLU), and chlorine (CI). Double antibody sandwich assay for CSF procalcitonin (PCT), heparin-binding protein (HBP), and matrix metalloproteinase-9 (MMP-9) was performed. Fully automated microbiological analyzer for pathogen identification was utilized. Based on the above results, we determined whether the patients had secondary intracranial infections after surgery and analyzed the risk factors for secondary intracranial infections after brain tumour surgery by univariate and multifactorial logistic regression. Results Among 208 patients with brain tumour surgery, 65 cases (31.25%) had secondary intracranial infection and 143 cases (68.75%) had no secondary intracranial infection. The levels of WBC, M-TP, CI, PCT, HBP, and MMP-9 in the CSF of intracranially infected patients were significantly higher than those of uninfected patients (P < 0.05), and GLU was significantly lower than that of uninfected patients (P < 0.05), and the levels of PCT, HBP, and MMP-9 in infected patients were significantly lower than those before treatment after 3, 7, and 10 d and tended to decrease over time (P < 0.05). A total of 62 pathogenic strains were isolated from 65 intracranial infections, of which 41 (66.13%) were Gram-negative bacteria, mainly resistant to amikacin and ciprofloxacin and sensitive to meropenem and imipenem; 19 (30.65%) were Gram-positive bacteria, mainly highly resistant to penicillin and erythromycin and sensitive to vancomycin. Univariate analysis showed that age, gender, tumour type, history of glucocorticoid application, and prophylactic application of antibiotics were not associated with secondary intracranial infection after brain tumour surgery (P > 0.05); tumour site, operation time, postoperative indwelling drainage time, postoperative cerebrospinal fluid leakage, and history of diabetics were all associated with secondary intracranial infection after brain tumour surgery (P < 0.05). Multivariate logistic regression analysis showed that infratentorial tumour, operation time ≥4 h, postoperative indwelling drainage time ≥24 h, and postoperative cerebrospinal fluid leakage were independent risk factors for secondary intracranial infection after brain tumour surgery (P < 0.05). Conclusion Patients with intracranial infections secondary to brain tumour surgery have abnormal levels of CSF routine and biochemical parameters, and the detection rate of Gram-negative bacteria is higher than that of Gram-positive bacteria in patients. Treatment should be based on the characteristics of pathogenic bacteria and risk factors with targeted interventions to reduce intracranial infections.

Prognostic value of heparin-binding protein for mortality in severe COVID-19 pneumonia.

Aim: The study investigated heparin-binding protein (HBP) levels in patients with severe COVID-19 pneumonia and their relation to prognosis. Methods: A total of 134 patients with serious COVID-19 pneumonia were prospectively analyzed. HBP levels were statistically compared between both the patient and healthy control groups and within the patient group itself. Results: HBP was defined to be significantly higher in the patient group compared with the control group. There was a statistically significant distinction between the patients who survived and those who died with regard to HBP levels. When the cutoff value of HBP was >13.47, sensitivity (89.8%), specificity (74.1%) had area under the curve values of 0.806 (p < 0.001). Conclusion: HBP level may be used for prognosis prediction of patients with COVID-19.

Hepcidin discriminates sepsis from other critical illness at admission to intensive care

Initial differential diagnosis and prognosis for patients admitted to intensive care with suspected sepsis remain arduous. Hepcidin has emerged as a potential biomarker for sepsis. Here we report data on the relevance of levels of hepcidin versus other biomarkers as a diagnostic and prognostic tool for sepsis. 164 adult patients admitted to the intensive care unit (ICU) within 24 h upon arrival to the hospital were included. Blood samples collected daily for seven consecutive days and hepcidin levels, heparin binding protein (HBP) levels and standard biomarkers were determined. Blood cultures were initiated at inclusion. Clinical scores were evaluated daily and mortality after 28- and 180-days was recorded. One hundred of the patients were found to fulfil the criteria for sepsis whereas 64 did not. Hepcidin levels at admission were significantly higher in the septic than in the non-septic patients. In septic patients hepcidin levels declined significantly already at 24 h followed by a steady decline. A significant negative correlation was observed between hepcidin levels and SAPS 3 in patients with sepsis. Hepcidin levels at inclusion were significantly higher among septic patients that survived 180-days and predicted mortality. Our data show that hepcidin levels are indicative of sepsis in patients admitted to the ICU and has a prognostic value for mortality.

Heparin-binding protein-enhanced quick SOFA score improves mortality prediction in sepsis patients.

PurposeThe Quick Sequential Organ Failure Assessment (qSOFA) score proposed by Sepsis-3 as a sepsis screening tool has shown suboptimal accuracy. Heparin-binding protein (HBP) has been shown to identify early sepsis with high accuracy. Herein, we aim to investigate whether or not HBP improves the model performance of qSOFA.MethodsWe conducted a multicenter prospective observational study of 794 adult patients who presented to the emergency department (ED) with presumed sepsis between 2018 and 2019. For each participant, serum HBP levels were measured and the hospital course was followed. The qSOFA score was used as the comparator. The data was split into a training dataset (n = 556) and a validation dataset (n = 238). The primary endpoint was 30-day all-cause mortality.ResultsCompared with survivors, non-survivors had significantly higher serum HBP levels (median: 71.5 ng/mL vs 209.5 ng/mL, p < 0.001). Serum level of HBP weakly correlated with qSOFA class (r2 = 0.240, p < 0.001). Compared with the qSOFA model alone, the addition of admission HBP level to the qSOFA model significantly improved 30-day mortality discrimination (AUC, 0.70 vs. 0.80; P < 0.001), net reclassification improvement [26% (CI, 17–35%); P < 0.001], and integrated discrimination improvement [12% (CI, 9–14%); P < 0.001]. Addition of C-reactive protein (CRP) level or neutrophil-to-lymphocyte ratio (NLR) to qSOFA did not improve its performance. A web-based mortality risk prediction calculator was created to facilitate clinical implementation.ConclusionThis study confirms the value of combining qSOFA and HBP in predicting sepsis mortality. The web calculator provides a user-friendly tool for clinical implementation. Further validation in different patient populations is needed before widespread application of this prediction model.

Heparin Binding Protein in Early Differential Diagnosis of Bacterial Meningitis.

Heparin-binding protein is a serine protease that is mobilized rapidly from emigrating polymorphonuclear leukocytes that acts as a chemoattractant activator of monocyte and macrophages. We investigated the potential role and efficacy of serum and cerebrospinal fluid heparin binding protein in differentiating bacterial meningitis from tuberculosis and viral meningitis. A case diagnosed with acute bacterial meningitis (n:37), viral meningitis (n:30) and tuberculous meningitis (n:30) was included in this study. The diagnosis was based on history, clinical criteria, cerebrospinal fluid examination, latex agglutination and culture, and response to therapy. Heparin-binding protein was measured using enzyme-linked immunosorbent technique in both cerebrospinal fluid and serum. Cerebrospinal fluid heparin-binding protein levels were 7.81 ± 0.23ng/mL in bacterial meningitis, 6.11 ± 0.3ng/mL in tuberculosis meningitis and 5.75 ± 0.1ng/mL in viral meningitis. The mean serum level was 14.98 ± 1.1ng/mL in bacterial meningitis, 6.89 ± 0.4ng/mL in tuberculosis meningitis, and 6.02 ± 0.4ng/mL in viral meningitis. Both heparin-binding protein levels were significantly higher in patients with bacterial meningitis. We found that serum and cerebrospinal fluid heparin binding protein is a useful marker for differentiating bacterial meningitis from non-bacterial meningitis.