Heparin-binding Protein Levels Research Articles

Diagnostic and prognostic value of heparin-binding protein in pediatric community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) and its associated complications pose a noteworthy public health apprehension in the pediatric population, leading to considerable morbidity and mortality. The objective of this study was to assess the diagnostic and prognostic value of heparin-binding protein (HBP) as a promising biomarker in children hospitalized with CAP.MethodsThis prospective, single-center study included 50 children admitted to the Pediatric Pulmonology Unit between April 2023 and January 2024 with a diagnosis of CAP, as well as age-matched 50 healthy children as a control group. Demographic, clinical, and laboratory data were recorded. The measurement of serum HBP was conducted upon admission utilizing the enzyme-linked immunosorbent assay technique.ResultsSerum HBP was elevated in the CAP group in comparison to the control group (p < 0.001). Out of 50 patients, 27 (54.0%) had non-complicated pneumonia, and 23 (46.0%) had complicated pneumonia. The levels of HBP were significantly elevated in patients compared to the healthy control group and even higher in patients with complicated CAP compared to those with non-complicated CAP (p < 0.001). Analysis of the ROC curve revealed that the HBP level of ≥ 34.97 ng/ml was linked to a significantly higher AUC of 0.837 (95% CI 0.722–0.951, P < 0.001).ConclusionThe level of HBP was observed to be notably elevated in patients as compared to the healthy control, thereby indicating its potential applicability in the early detection of CAP. Moreover, elevated HBP was an independent prognostic factor for complicated CAP in children.

Prediction of Clinical Severity of COVID-19 Using a Combination of Heparin-Binding Protein, Interleukin-6, and C-Reactive Protein: A Retrospective Study.

Systemic inflammation stands as a pivotal factor tightly interwoven with the progression of COVID-19. This study endeavors to elucidate the significance of three key inflammatory molecules, that is, heparin-binding protein (HBP), interleukin-6 (IL-6), and C-reactive protein (CRP), in assessing the severity and prognostic implications of COVID-19. The demographic, clinical, and laboratory data were retrospectively collected from a cohort of 214 adult patients diagnosed with COVID-19. Patients were divided into two groups: nonsevere (n = 93; 43.5%) and severe (n = 121; 56.5%). Additionally, based on their organ function, patients were categorized into nonorgan failure (n = 137) and organ failure (n = 77) groups. The levels of inflammation-related cytokines were then compared among these defined groups. The severe group was characterized by a higher proportion of males, older age, and longer hospital stays compared to nonsevere cases. Additionally, severe cases exhibited a higher prevalence of underlying diseases and organ failure. Statistical analysis revealed significantly elevated levels of HBP, IL-6, and CRP in the severe group. HBP, IL-6, and CRP were identified as independent risk factors for severe COVID-19. Furthermore, a combined assessment of these biomarkers demonstrated superior diagnostic sensitivity (85.10%) and specificity (95.70%) for predicting COVID-19 severity. A positive relationship between elevated HBP, IL-6, and CRP levels and impaired organ function was also observed. The predictive efficiency significantly increased (hazard ratio = 3.631, log-rank p = 0.003) when two or more of them were combinedly used. Notably, elevated levels of HBP, IL-6, and CRP were associated with an increased risk of mortality. In conclusion, the combined assessment of HBP, IL-6, and CRP offers enhanced accuracy and specificity in predicting the severity, organ failure, and mortality risk associated with COVID-19.

Diagnostic and prognostic value of heparin-binding protein in sepsis: A systematic review and meta-analysis.

Sepsis remains a leading cause of death worldwide. In this context, heparin-binding protein (HBP) has emerged as a possible biomarker, drawing significant attention for its diagnostic and prognostic usefulness in septic patients. Despite this advancement, the literature yields conflicting results. This study is intended to critically evaluate the diagnostic and prognostic value of HBP in critically ill septic patients. We searched multiple databases, including PubMed, SCOPUS, Web of Science, and EBSCO, to identify relevant studies on April 27, 2023. We included studies investigating sepsis or its severe outcomes that reported HBP levels and the required data to create 2 × 2 tables. We used R version 4.2.2 and R Studio to analyze the pooled diagnostic accuracy outcomes. The diagmeta package was utilized to calculate the optimum cutoff value. In our meta-analysis, we incorporated 28 studies including 5508 patients. The analysis revealed that HBP has a sensitivity of 0.71 (95% CI: 0.60; 0.79) and a specificity of 0.68 (95% CI: 0.51; 0.81) in diagnosing sepsis, respectively. HBP demonstrated moderate prognostic accuracy for mortality at a cutoff value of 161.415 ng/mL, with a sensitivity and specificity of 72%, and for severe sepsis outcomes at a cutoff value of 58.907 ng/mL, with a sensitivity and specificity of 71%. Our findings indicate a relatively moderate diagnostic and prognostic accuracy of HBP for sepsis. Future studies are required to verify the accuracy of HBP as a biomarker for sepsis.

Heparin-binding protein as a biomarker for the diagnosis of sepsis in the intensive care unit: a retrospective cross-sectional study in China

ObjectivesThis study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid,...

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.

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit : a propensity score matched study.

Patients with diabetes mellitus (DM) are vulnerable to community-acquired pneumonia (CAP), which have a high mortality rate. We aimed to investigate the value of heparin-binding protein (HBP) as a prognostic marker of mortality in patients with DM and CAP. This retrospective study included CAP patients who were tested for HBP at intensive care unit (ICU) admission from January 2019 to April 2020. Patients were allocated to the DM or non-DM group and paired with propensity score matching. Baseline characteristics and clinical outcomes up to 90 days were evaluated. The primary outcome was the 10-day mortality. Receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, and Cox regression were used for statistical analysis. Among 152 enrolled patients, 60 pairs were successfully matched. There was no significant difference in 10-day mortality, while more patients in the DM group died within 28 d (P=0.024) and 90 d (P=0.008). In the DM group, HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors (median 182.21 [IQR: 55.43-300] ng/ml vs. median 66.40 [IQR: 34.13-107.85] ng/mL, P=0.019), and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747. The cut-off value, sensitivity, and specificity were 160.6 ng/mL, 66.7%, and 90.2%, respectively. Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day (HR 7.196, 95%CI: 1.596-32.455, P=0.01), 28-day (HR 4.381, 95%CI: 1.449-13.245, P=0.009), and 90-day mortality (HR 4.581, 95%CI: 1.637-12.819, P=0.004) in patients with DM. Plasma HBP at ICU admission was associated with the 10-day, 28-day, and 90-day mortality, and might be a prognostic factor in patients with DM and CAP.

The potential role of heparin-binding protein in neonatal sepsis: research progress.

Neonatal sepsis is a major global health challenge, leading to significant morbidity and mortality in newborns. The search for precise biomarkers for its early prediction in clinical settings has been ongoing, with heparin-binding protein (HBP) emerging as a promising candidate. Originating from granules in neutrophils, HBP is released into the bloodstream in response to infection and plays a pivotal role in the body's inflammatory response. Its significance extends beyond its inflammatory origins; research indicates dynamic changes in HBP levels are strongly linked to reduce in-hospital mortality, offering a prognostic advantage over existing biomarkers. Furthermore, HBP has demonstrated considerable clinical utility in the early diagnosis and stratification of neonatal sepsis, suggesting its potential as a reliable blood marker for early prediction of the disease and its severity. Its application may extend to guiding the judicious use of antibiotics in treating newborns, addressing a critical aspect of neonatal care. Despite these encouraging results, the precise clinical utility of HBP for diagnosing and treating sepsis in neonates still demands further clarification through extensive research. This review delves into the current scientific understanding of HBP's contribution to diagnosing, prognosticating, and treating neonatal sepsis, while considering its future clinical applications.

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.

Determination of Serum Calprotectin, Heparin-Binding Protein, and Some Inflammatory Factors in Patients with COVID-19

Background: Among the serum biomarkers of infectious diseases, calprotectin and heparin-binding protein (HBP) seem to be of clinical and diagnostic value in patients with COVID-19. Objectives: This study aimed to investigate the serum levels of calprotectin, HBP, and some other inflammatory markers in COVID-19 patients. Methods: In this case-control study, serum samples of 35 outpatients with COVID-19 and 35 healthy individuals were collected, and the levels of calprotectin, HBP, C-reactive protein (CRP), ferritin (FERR), as well as platelet (PLT) and neutrophil (NEU) counts and LDH activity, were determined. Results: At first, SARS-CoV2 viral RNA was detected in the pharyngeal swab specimens of COVID-19 patients. Calprotectin, FERR, and CRP levels, LDH activity, and PLT and NEU counts were found to be significantly higher in COVID-19 patients compared with controls (P &lt; 0.05), whereas no statistically significant difference was observed in HBP level (P &gt; 0.05). Serum calprotectin showed a significant correlation with CRP and FERR levels, LDH activity, and NEU count (P &lt; 0.001). Conclusions: Our findings showed that an increment in serum calprotectin level, together with increased CRP levels, might be a promising indicator of SARS-CoV2 infection.

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.