CD64 Index Research Articles

Predictive nomogram of high-risk patients with active tuberculosis in latent tuberculosis infection.

The absence of predictive models for early latent tuberculosis infection (LTBI) progression persists. This study aimed to create a screening model to identify high-risk LTBI patients prome to active tuberculosis (ATB) reactivation. Patients with confirmed ATB were enrolled alongside LTBI individuals as a reference, with relevant clinical data gathered. LASSO regression cross-validation reduced data dimensionality. A nomogram was developed using multiple logistic regression, internally validated with Bootstrap resampling. Evaluation included C-index, receiver operating characteristic (ROC) curve, and calibration curves, with clinical utility assessed through decision curve analysis. The final nomogram incorporated serum albumin (OR = 1.337, p = 0.046), CD4+ (OR = 1.010, p = 0.004), and CD64 index (OR = 0.009, p = 0.020). The model achieved a C-index of 0.964, an area under the ROC curve of 0.962 (95% CI: 0.926-0.997), sensitivity of 0.971, and specificity of 0.910. Internal validation showed a mean absolute error of 0.013 and 86.4% identification accuracy. The decision curve indicated substantial net benefit at a risk threshold exceeding 10% (1: 9). This study established a biologically-rooted nomogram for high-risk LTBI patients prone to ATB reactivation, offering strong predictability, concordance, and clinical value. It serves as a personalized risk assessment tool, accurately identifying patients necessitating priority prophylactic treatment, complementing existing host risk factors effectively.

Neutrophil CD64 index as a potential blood biomarker for the diagnosis of neurosyphilis in secondary and tertiary syphilis: A retrospective study

ObjectiveTo examine the correlation of neutrophil CD64 (nCD64) index with neurosyphilis (NS) across different stages of syphilis. MethodsA total of 1243 syphilis patients at different stages (344 of primary, 385 of secondary, and 514 of tertiary) included in this study were divided into NS and non-NS (NNS). Correlations of nCD64 index with currently used syphilis biomarkers were explored using Spearman correlation test. Relationships between nCD64 index and NS at different stages were investigated by stratified analysis and restricted cubic spline model. The diagnostic performance of nCD64 index for NS was assessed by receiver operating characteristic (ROC) curve. ResultsSignificant statistical correlations of nCD64 index with cerebrospinal fluid (CSF) NS indicators were found in secondary and tertiary syphilis. Increased nCD64 index was associated with increased risk of NS in secondary and tertiary syphilis. ROC analysis values further confirmed the diagnostic potential of nCD64 index for NS. Marked decrease of nCD64 index was observed in NS patients after effective antisyphilitic treatments. ConclusionsThe nCD64 index may help to the diagnosis of NS in secondary and tertiary syphilis.

Neutrophil CD64 index as a new early predictive biomarker for infected pancreatic necrosis in acute pancreatitis

ObjectiveInfectious pancreatic necrosis (IPN) is a serious complication of acute pancreatitis, and early recognition and timely intervention are the keys to improving clinical outcomes. The purpose of this study was to investigate the predictive capacity of the neutrophil CD64 index (nCD64 index) on IPN in patients with acute pancreatitisMethodsThis study comprises two independent cohorts: the training cohort consisted of 202 patients from Hunan Provincial People's Hospital, and the validation cohort consisted of 100 patients from Changsha Central Hospital. Peripheral blood samples were collected on the day of admission and on the 3rd, 5th, 7th, and 10th days of hospitalization, and the nCD64 index was detected by flow cytometry. Additionally, relevant clinical characteristics and laboratory biomarkers were collected and analyzed.ResultsWe observed that nCD64 index on admission was significantly higher in the IPN group than Non-IPN group (p < 0.001). In the training cohort, a higher occurrence rate of IPN was observed in the high nCD64 index group compared to the moderate and low nCD64 index group (p < 0.001). Further analysis showed that nCD64 index was significant positive correlated with the incidence rate of IPN (p < 0.001, correlation coefficient = 0.972). Furthermore, logistic regression analysis showed that high expression of the nCD64 index on admission was a risk factor for the occurrence of IPN (OR = 2.971, p = 0.038). We further found that the nCD64 index of IPN patients was significantly higher than the Non-IPN patients on the days 1, 3, and 5 after admission, and the nCD64 index of IPN patients before and after the onset (p < 0.05). At the same time, this study revealed that the nCD64 index on admission showed good predictive efficacy for IPN (AUC = 0.859, sensitivity = 80.8%, specificity = 87.5%), which was comparable to APACHE II score. And this finding was further validated in an independent cohort of 100 participants (AUC = 0.919, Sensitivity = 100.0%, Specificity = 76.6%).ConclusionThis study demonstrated the clinical value of nCD64 index in patients with IPN patients for the first time through two independent cohort studies. The nCD64 index can be used as an early prediction and risk assessment tool for the occurrence of IPN, contributing to the improvement of patient outcomes and efficiency of medical resource allocation.

Diagnostic and Prognostic Value of Peripheral Neutrophil CD64 Index in Elderly Patients with Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in the elderly. The peripheral blood neutrophil CD64 (nCD64) index is increasingly recognized for its association with poor pneumonia prognosis. A comprehensive investigation involving 128 elderly patients diagnosed with CAP, including 96 with non-severe CAP and 32 with severe CAP, from January 2020 to January 2021 was performed. The nCD64 index, CD4+, CD8+, C-reactive protein (CRP), white blood cell (WBC) count, procalcitonin (PCT), neutrophil (NEUT), and B lymphocyte count were determined using flow cytometry. Our findings reveal that patients with severe CAP exhibited significantly higher levels of nCD64 index, NEUT, WBC, CRP, and PCT. Intriguingly, lower CRP, nCD64 index, CURB-65 score, and PCT were associated with a higher survival rate. Notably, the nCD64 index demonstrated remarkable predictive efficiency for 28-d survival in CAP patients [area under the curve (AUC) = 0.907], surpassing other markers and even showing enhanced predictive power when combined with the CURB-65 score (AUC = 0.905). Furthermore, a negative association was observed between the nCD64 index and both CD4+, CD4+/CD8+ ratios, and B lymphocytes, highlighting its potential role in immune dysregulation. These findings underscore the critical importance of the nCD64 index in the early diagnosis, risk stratification, and prognostic evaluation of infections and immune responses in elderly CAP patients.

Neutrophil CD64 index as a good biomarker for early diagnosis of bacterial infection in pregnant women during the flu season.

Pregnant women are at high risk of developing febrile illness during the flu season. Early identification of a viral or bacterial infection is crucial in the management of febrile pregnant patients. Neutrophil CD64 (nCD64) has been shown to have more important diagnostic value in sepsis than traditional inflammatory indicators. The pregnant women enrolled were divided into three groups according to disease: influenza A infection, bacterial infection and healthy controls. Peripheral blood CD64, leukocyte, C-reactive protein (CRP), procalcitonin (PCT) and human Th1/Th2-related cytokines levels were routinely measured. The correlation between and diagnostic value of the nCD64 index and other biomarkers were evaluated using Spearman's correlation test and receiver operating characteristic (ROC) curve analysis. Pregnant women with bacterial infection had significantly elevated levels of leukocytes (8.4 vs. 5.95, 109/L; P = 0.004), CRP (89.70 vs. 50.05 mg/mL; P = 0.031), PCT (0.13 vs. 0.04 ng/mL; P = 0.010) and TNF-α (0.46 vs. 0.38 pg/mL; P = 0.012) and an elevated nCD64 index (12.16 vs. 0.81; P < 0.001) compared with those with influenza A infection. The area under the receiver operating characteristic (AUROC) curve of the nCD64 index to discriminate bacterial infection among pregnant women (AUROC = 0.9183, P < 0.0001) was the largest. The sensitivity and specificity of the nCD64 index at an optimal cut-off value of 3.16 were 84% and 100%, respectively, with a negative predictive value (NPV) of 94%. Our study demonstrates the clinical value of the nCD64 index in distinguishing between bacterial infection and influenza A in pregnant women.

IMMUNOSUPPRESSION CORRELATES WITH THE DETERIORATION OF SEPSIS-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION.

Background: The dysregulated host responses play a crucial role in the pathophysiology process of sepsis-induced disseminated intravascular coagulation (DIC). The study aimed to characterize the dynamic alternation of immune-related biomarkers and their relationship with the progression of DIC during sepsis. Methods: A prospective, observational study was conducted in a tertiary care academic hospital. Six hundred forty patients with sepsis were classified into three groups according to the International Society on Thrombosis and Hemostasis (ISTH) score: 383 involved patients without DIC (ISTH = 0), 168 sepsis with nonovert DIC (ISTH = 1-4), and 89 sepsis with overt DIC (ISTH ≥5). Eighteen immune-related biomarkers and six routine coagulation variables were examined at D1, D3, and D7 upon enrollment. The association between the immune parameters and the DIC deterioration was assessed during sepsis. Results: The study showed a 40% coagulation disorder and a 14% incidence of overt DIC in patients with sepsis. The patients with overt DIC displayed pronounced immune disorders from D1 to D7 upon sepsis, which was characterized by the decreased percentage of monocyte HLA-DR (mHLA-DR), increased percentage of regulatory T cells, the levels of procalcitonin, neutrophil CD64 index, and systemic inflammatory cytokines relative to nonovert DIC or non-DIC patients. In multivariate analysis, the combination of anti-inflammatory cytokine IL-10 and mHLA-DR at D1 upon enrollment had a superior predictive value for predicting DIC deterioration in sepsis (area under the curve = 0.87, P < 0.0001). Conclusion: These data illustrate that immunosuppression can crosstalk with coagulation disorder during sepsis and present an additional evaluation tool to predict DIC deterioration.

Neutrophil CD64 index for diagnosis of infectious disease in the pediatric ICU: a single-center prospective study

BackgroundInfection is a major cause of death in children, and it is particularly important to identify biological indicators of early infection. Previous studies showed that the neutrophil CD64 (nCD64) index may be a useful biomarker for infection. The purpose of this study was to investigate use of the nCD64 index to identify infection in children from a pediatric ICU (PICU) in China.MethodsThis prospective observational study enrolled 201 children who were admitted to our PICU and were divided into an infection group and a non-infection group. In each patient, C-reactive protein (CRP), nCD64 index, procalcitonin (PCT), and white blood cell count were measured during the first 24 h after admission. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity, specificity, and diagnostic value of the nCD64 index for infection.ResultsAmong all 201 children, the infection group had greater levels of CRP, nCD64 index, and PCT (all p < 0.05). ROC analysis indicated the nCD64 index had a sensitivity of 68.8%, specificity of 90.7%, accuracy of 80.5%, and an optimal cut-off value of 0.14, which had better diagnostic value than CRP or PCT. For children with postoperative fever, the nCD64 index also distinguished systemic inflammatory response syndrome (SIRS) from infection with accuracy of 79%.ConclusionsThe nCD64 index is a useful biomarker for the diagnosis of early infection in children admitted to the PICU.

Neutrophil CD64 index as a superior indicator for diagnosing, monitoring bacterial infection, and evaluating antibiotic therapy: a case control study

BackgroundNeutrophil CD64 (nCD64) index has been widely studied as an indication of bacteria-infected diseases, but the exact usage of nCD64 index in monitoring infections remains debated. So this study aims to investigate the functionality of nCD64 index in tracking infections’ progression and evaluating antibiotic therapy.Methods160 participants (36 healthy controls, 34 culture-negative patients, 56 respiratory tract infected patients, and 34 bloodstream infected patients) were recruited and divided into groups. Data on nCD64 index, T lymphocyte subsets, and conventional indicators, including white blood cell count, neutrophil to lymphocyte ratio, procalcitonin, and C-reactive protein, were tested and compared.ResultsBacteria-infected patients had significantly higher nCD64 indexes (p < 0.05), especially patients with both bloodstream and respiratory tract infections. The nCD64 index could identify infected patients from culture-negative patients or controls, which conventional indicators cannot achieve. We followed up with 24 infected patients and found that their nCD64 indexes were promptly down-regulated after effective antibiotic therapy (3.16 ± 3.01 vs. 1.20 ± 1.47, p < 0.001).ConclusionThe nCD64 index is a sensitive indicator for clinical diagnosis of bacterial infection, especially in monitoring infection and evaluating antibiotics’ efficacy. Therefore, nCD64 has the potential to improve diagnostic accuracy and provide rapid feedback on monitoring disease progression in infected patients.

Standardization of neutrophil CD64 and monocyte HLA-DR measurement and its application in immune monitoring in kidney transplantation.

Infections cause high mortality in kidney transplant recipients (KTRs). The expressions of neutrophil CD64 (nCD64) and monocyte HLA-DR (mHLA-DR) provide direct evidence of immune status and can be used to evaluate the severity of infection. However, the intensities of nCD64 and mHLA-DR detected by flow cytometry (FCM) are commonly measured by mean fluorescence intensities (MFIs), which are relative values, thus limiting their application. We aimed to standardize nCD64 and mHLA-DR expression using molecules of equivalent soluble fluorochrome (MESF) and to explore their role in immune monitoring for KTRs with infection. The study included 50 KTRs diagnosed with infection, 65 immunologically stable KTRs and 26 healthy controls. The blood samples were collected and measured simultaneously by four FCM protocols at different flow cytometers. The MFIs of nCD64 and mHLA-DR were converted into MESF by Phycoerythrin (PE) Fluorescence Quantitation Kit. The intraclass correlation coefficients (ICCs) and the Bland-Altman plots were used to evaluate the reliability between the four FCM protocols. MESFs of nCD64 and mHLA-DR, nCD64 index and sepsis index (SI) with the TBNK panel were used to evaluate the immune status. Comparisons among multiple groups were performed with ANOVA one-way analysis. Receiver operating characteristics (ROC) curve analysis was performed to diagnose infection or sepsis. Univariate and multivariate logistic analysis examined associations of the immune status with infection. MESFs of nCD64 and mHLA-DR measured by four protocols had excellent reliability (ICCs 0.993 and 0.957, respectively). The nCD64, CD64 index and SI in infection group were significantly higher than those of stable KTRs group. Patients with sepsis had lower mHLA-DR but higher SI than non-sepsis patients. ROC analysis indicated that nCD64 had the highest area under the curve (AUC) for infection, and that mHLA-DR had the highest AUC for sepsis. Logistic analysis indicated that nCD64 > 3089 and B cells counts were independent risk factors for infection. The standardization of nCD64 and mHLA-DR made it available for widespread application. MESFs of nCD64 and mHLA-DR had good diagnostic performance on infection and sepsis, respectively, which could be promising indicators for immune status of KTRs and contributed to individualized treatment.

The use of neutrophil CD64 and monocyte HLA-DR sepsis index in the diagnosis of neonatal sepsis

BackgroundNeonatal septicemia remains one of the main causes of neonatal morbidity and mortality. However, there are challenges hindering the early diagnosis.ResultsnCD64 percent and MFI were not of statistical significance between the confirmed sepsis, clinical sepsis, and control groups (p = 0.453 and 0.149, respectively); meanwhile, the mHLA-DR percent and MFI were both of statistical significance (p = 0.001, 0.0001, respectively) with lower values in the proven sepsis group. Calculating the sepsis index, its value was 74.1% ± 45 SD in the control, 105.5% ± 73 SD probable sepsis group, and 180.6% ± 143 SD in the proven sepsis group; this was of a high statistical significance (p = 0.0001).ConclusionHLA-DR expression on monocytes and nCD64/mHLA-DR sepsis index are reliable indices for the early diagnosis of neonatal sepsis. The sepsis index could be feasibly analyzed by automated flow cytometry even in developing countries. In the future, these markers should be widely assessed as their results are rapid, reliable, and of low cost.

Monocyte HLADR and Immune Dysregulation Index as Biomarkers for COVID-19 Severity and Mortality.

Immune dysregulation in COVID-19 is the major causal factor associated with disease progression and mortality. Role of monocyte HLA-DR (mHLA-DR), neutrophil CD64 (nCD64) and Immune dysregulation index (IDI) were studied in COVID-19 patients for assessing severity and outcome. Results were compared with other laboratory parameters. Antibody bound per cell for mHLA-DR, nCD64 and IDI were measured in 100 COVID-19 patients by flow cytometry within 12 h of hospital admission. Thirty healthy controls (HC) were included. Clinical and laboratory parameters like C - reactive protein (CRP), Procalcitonin (PCT), Absolute Lymphocyte count (ALC), Absolute Neutrophil count (ANC) and Neutrophil to Lymphocyte ratio (NLR) were recorded. Patients were followed up until recovery with discharge or death. Parameters from 54 mild (MCOV-19), 46 severe (SCOV-19) and 30 HC were analysed. mHLA-DR revealed significant and graded down regulation in MCOV-19 and SCOV-19 as compared to HC whereas IDI was lowest in HC with increasing values in MCOV-19 and SCOV-19. For diagnostic discrimination of MCOV-19 and SCOV-19, IDI revealed highest AUC (0.99). All three immune parameters revealed significant difference between survivors (n = 78) and non-survivors (n = 22). mHLA-DR < 7010 and IDI > 12 had significant association with mortality. Four best performing parameters to identify patients with SCOV-19 at higher risk of mortality were IDI, NLR, ALC and PCT. mHLA-DR and IDI, in addition to NLR and ALC at admission and during hospital stay can be utilized for patient triaging, monitoring, early intervention, and mortality prediction. IDI reported for the first time in this study, appears most promising. Immune monitoring of ‘in hospital’ cases may provide optimized treatment options.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12291-022-01087-z.

Clinical Value of Neutrophil CD64 Index, PCT, and CRP in Acute Pancreatitis Complicated with Abdominal Infection.

Objective: To study the clinical diagnostic value of neutrophil CD64 index, PCT, and CRP in patients with acute pancreatitis with abdominal infection. Methods: A number of patients with acute pancreatitis (n = 234) participated in the study. According to the infection and health conditions, they were further divided into the non-infection group (n = 122), infection group (n = 78), and sepsis group (n = 34), and 40 healthy subjects were selected in the control group (n = 40). Expression levels of infection indexes, such as CD64 index, PCT, and CRP, were detected and compared. ROC curves were drawn to compare the efficacy of each index in the diagnosis of acute pancreatitis with abdominal infection and sepsis. The study was retrospectively registered under the China Clinical Trial Registry as a trial number ChiCTR2100054308. Results: All indexes were significantly higher in three clinical groups than the healthy control group (p < 0.05). The CD64 index, CD64 positive rate, and PCT in the infected group were significantly higher than those in the uninfected group (ALL p < 0.05). The PCT of patients infected with Gram-negative bacteria was significantly higher than that of Gram-positive bacteria-infected patients (p < 0.05). CD64 index had the best diagnostic efficiency for acute pancreatitis infection, with 82.14% sensitivity, 88.51% specificity, and 0.707 Youden indexes. The CD64 Youden index (0.780) for sepsis diagnosis was the highest, while the AUC of PCT was the highest (0.897). Conclusion: CD64 index combined with PCT has good sensitivity and specificity in diagnosing acute pancreatitis infection and sepsis.

The Clinical Value of Neutrophil CD64 Index in Hematological Malignancies with Pulmonary Infection

To investigate the clinical value of neutrophil CD64 index in hematological malignancies with pulmonary infection. The cohort study method was used to retrospectively analyze the clinical data of 125 patients with hematological malignancies and pulmonary infections who were treated in The Third Affiliated Hospital of Soochow University. All the patients were divided into four stages according to the diagnosis and treatment process: non-infected stage (T1), the symptoms of infection had appeared before using antibiotics (T2), one week after anti-infective treatment (T3), and after stopping antibiotics (T4). CD64 index, C-reactive protein (CRP), blood cell count, and immune cell level were compared before and after infection (T1 vs T2), the correlation between CD64 index and other indicators were explored, the change trends of the significantly different indicators in the course of the disease were observed, and the diagnostic efficacy of CD64 index and CRP were compared. The surviving patients were followed up for whether reinfection occurred within 30 days after discharge, and the re-examination results of indices before discharge (in stage of T4) between reinfected and non-reinfected patients were compared to find the risk factors of reinfection. Before and after infection, the CD64 index, CRP, CD14+HLA-DR+, CD4+, and lymphocyte counts were significantly different (all P<0.05). There was a negative correlation of CD64 index with CD14+HLA-DR+ (r=-0.395, P<0.001), a negative correlation with CD3+ (r=-0.1.87, P=0.047), and a negative correlation with lymphocyte count (r=-0.230, P=0.006), while a positive correlation with CRP(r=0.313, P<0.001). The area under the curve of CD64 index, CRP, and CD64 index combined with CRP was 0.790 (95%CI: 0.711-0.868), 0.754(95%CI: 0.667-0.841), and 0.835(95%CI: 0.762-0.907), respectively; the sensitivity was 59.6%, 72.7%, and 74.7%, the specificity was 89.2%, 73.0%, and 78.4%, and the cut-off value was 0.488, 0.457, and 0.531, respectively. There were only two re-examination indexes showed significantly different before discharge between reinfected patients and non-reinfected patients: CD14+HLA-DR+ (F=8.524, P=0.004) and CD64 index (F=9.993, P=0.002). The increase of CD64 index was an independent risk factor for reinfection within 30 days after discharge from the hospital (HR=1.790, 95%CI: 1.343-2.386, P<0.001). CD64 index has diagnostic value in patients with hematological malignancies and pulmonary infection, and its specificity is higher than that of CRP. The combination of the two indicators can improve the diagnostic sensitivity. CD64 index has a predictive value for reinfection within 30 days after infection treatment.

Multi-marker approach using C-reactive protein, procalcitonin, neutrophil CD64 index for the prognosis of sepsis in intensive care unit: a retrospective cohort study

BackgroundWe aimed to explore the prognostic utilities of C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD64 (nCD64) index, in combination or alone, in septic patients.MethodsWe retrospectively included 349 septic patients (based on Sepsis 3.0 definition). The primary outcome was 28-day all-cause mortality. Cox regression model, receiver-operating characteristic (ROC) curve, reclassification analysis, Kaplan–Meier survival curves were performed to evaluate the predictive efficacy of the above parameters.ResultsCRP, nCD64 index were independent predictors of 28-day mortality for sepsis in the Cox regression model [CRP, HR 1.004 (95% CI 1.002–1.006), P < 0.001; nCD64 index, HR 1.263 (95% CI 1.187–1.345, P < 0.001]. Area under the ROC curve (AUC) of CRP, PCT, nCD64 index, nCD64 index plus PCT, nCD64 index plus CRP, were 0.798 (95% CI 0.752–0.839), 0.833 (95% CI 0.790–0.871), 0.906 (95% CI 0.870–0.935), 0.910 (95% CI 0.875–0.938), 0.916 (95% CI 0.881–0.943), respectively. nCD64 plus CRP performed best in prediction, discrimination, and reclassification of the 28-day mortality risk in sepsis. The risk of 28-day mortality increased stepwise as the number of data exceeding optimal cut-off values increased.ConclusionsnCD64 index combined with CRP was superior to CRP, PCT, nCD64 index and nCD64 index plus PCT in predicting 28-day mortality in sepsis. Multi-marker approach could improve the predictive accuracy and be beneficial for septic patients.

NCD64 index as a novel inflammatory indicator for the early prediction of prognosis in infectious and non-infectious inflammatory diseases: An observational study of febrile patients

BackgroundGenerally, febrile patients admitted to the Department of Infectious Diseases, Fudan University Affiliated Huashan Hospital, China may eventually be diagnosed as infectious (ID) or non-infectious inflammatory diseases (NIID). Furthermore, mortality from sepsis remains incredibly high. Thus, early diagnosis and prognosis evaluation of sepsis is necessary. Here, we investigated neutrophil (n)CD64 index profile in a cohort of febrile patients and explored its diagnostic and prognostic value in ID and NIID.MethodsThis observational cohort study enrolled 348 febrile patients from the Emergency Department and Department of Infectious Diseases. nCD64 index were detected using flow cytometry, and dynamically measured at different timepoints during follow-up. Procalcitonin (PCT), C-reactive protein (CRP), and ferritin levels were measured routinely. Finally, the diagnostic and prognostic value of nCD64 index were evaluated by receiver operating characteristic (ROC) analysis and Kaplan-Meier curve analysis.ResultsOf included 348 febrile patients, 238, 81, and 29 were categorized into ID, NIID, and lymphoma groups, respectively. In ID patients, both SOFA score and infection site had impact on nCD64 index expression. In NIID patients, adult-onset Still’s disease patients had the highest nCD64 index value, however, nCD64 index couldn’t distinguish between ID and NIID. Regardless of the site of infection, nCD64 index was significantly higher in bacterial and viral infections than in fungal infections, but it could not discriminate between bacterial and viral infections. In bloodstream infections, gram-negative (G-) bacterial infections showed an obvious increase in nCD64 index compared to that of gram-positive (G+) bacterial infections. nCD64 index has the potential to be a biomarker for distinguishing between DNA and RNA virus infections. The routine measurement of nCD64 index can facilitate septic shock diagnosis and predict 28-day hospital mortality in patients with sepsis. Serial monitoring of nCD64 index in patients with sepsis is helpful for evaluating prognosis and treatment efficacy. Notably, nCD64 index is more sensitive to predict disease progression and monitor glucocorticoid treatment in patients with NIID.ConclusionsnCD64 index can be used to predict 28-day hospital mortality in patients with sepsis and to evaluate the prognosis. Serial determinations of nCD64 index can be used to predict and monitor disease progression in patients with NIID.

Analysis of bacterial spectrum, activin A, and CD64 in chronic obstructive pulmonary disease patients complicated with pulmonary infections.

BACKGROUNDPulmonary infections often lead to poor prognoses in patients with chronic obstructive pulmonary disease (COPD). Activin A and CD64 play crucial pathological roles in the development of COPD.AIMTo explore the bacterial spectrum via analysis of activing A levels, CD64 index, and related mechanisms in COPD patients complicated with pulmonary infection. METHODSBetween March 2015 and January 2018, a total of 85 patients with COPD, who also suffered from pulmonary infections, were enrolled in this study as the pulmonary infection group. In addition, a total of 96 COPD patients, without pulmonary infection, were selected as the control group. Sputum samples of patients in the pulmonary infection group were cultivated for bacterial identification prior to administration of antibiotics. The neutrophil CD64 index was measured using flow cytometry, serum activin A levels were detected via an enzyme-linked immunosorbent assay, and activin A, Smad3, TLR4, MyD88, and NFκB protein expression was analyzed by Western blotting.RESULTSGram-negative bacteria were identified in 57.65% of the sputum samples in the pulmonary infection group. The most prevalent Gram-negative species were Pseudomonas aeruginosa and Klebsiella pneumoniae. Conversely, Gram-positive bacteria were identified in 41.18% of the sputum samples in the pulmonary infection group. The most common Gram-positive species was Streptococcus pneumoniae. Fungi were identified in 1.17% of the sputum samples in the pulmonary infection group. The CD64 index was significantly higher in the pulmonary infection group (0.91 ± 0.38) than in the control group (0.23 ± 0.14, P < 0.001). The serum activin A levels were significantly higher in the pulmonary infection group (43.50 ± 5.22 ng/mL), compared to the control group (34.82 ± 4.16 ng/mL, P < 0.001). The relative expression levels of activin A, Smad3, TLR4, MyD88, and NFκB were all significantly higher in the pulmonary infection group, compared to the control group (all P < 0.001). CONCLUSIONPulmonary infections in COPD patients are mainly caused by Streptococcus pneumoniae, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Pulmonary infections can significantly increase neutrophil CD64 index and serum levels of activin A, thereby activating the activin A/Smad3 signaling pathway, which may positively regulate the TLR4/MyD88/NFκB signaling pathway.

Diagnostic Utility of CD64 and CD38 Biomarkers for the Differential Diagnosis of Infections.

Purpose: Identification of infection type in patients with fever is particularly important in the emergency departments (EDs) of hospitals. This study was designed to evaluate the performance of two biomarkers, the modified neutrophil CD64 (nCD64) index and CD38 presence on T cells, using flow cytometry. Methods: A total of 305 potentially infected patients with fever were admitted to the ED of Zhongda Hospital (Nanjing, China) between March 2021 and August 2021. This study included three groups of patients: bacterial (N = 180), viral (N = 30) , and uninfected (N = 65) based on their final diagnostic outcomes and clinical records. Results: The expression level of traditional/modified nCD64 was significantly increased in the bacterial infection group, especially in case of patients infected with Gram-negative bacteria. The most prevalent species were Staphylococcus spp. and Escherichia coli. In contrast, CD3+CD38+ cell percentages were elevated in patients with viral infections, which were mostly caused by Epstein-Barr virus and cytomegalovirus. CD38 expression is age dependent, and higher percentages of CD3+CD38+ cells were observed in children with viral infections. For the prediction of bacterial infections, the area under the curve (AUC) of modified nCD64 (AUC: 0.800) was significantly higher than that of C-reactive protein and heparin-binding protein but slightly lower than that of traditional nCD64 (AUC: 0.831). The AUC, specificity, and sensitivity values for the prediction of viral infections using CD3+CD38+ cells percentages in children were 0.899 (0.785-1.000), 96.2%, and 85.9%, respectively. Conclusion: nCD64 levels and CD3+CD38+ cell percentage are potential biomarkers that facilitate identification of patients with bacterial and viral infections.

Serum and Synovial Biomarkers for Distinguishing Between Chronic Periprosthetic Joint Infections and Rheumatoid Arthritis: A Prospective Cohort Study.

Inflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA. This prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society definition of PJI was utilized for the classification of cases as aseptic or infected. Serum d-dimer, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 (IL-6), as well as synovial IL-6, percentage of polymorphonuclear neutrophils, and CD64 index level were measured preoperatively. An increase in biomarker concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86% and a specificity of 93.33%. Current serum biomarkers (erythrocyte sedimentation rate, C-reactive protein, IL-6, and d-dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.

The value of neutrophil CD64 index in the diagnosis of patients with sepsis in intensive care unit

To investigate the diagnostic value of neutrophil CD64 index in sepsis patients in intensive care unit (ICU). A prospective case-control study was conducted, the patients admitted to ICU of Jiangbei People's Hospital Affiliated to Nantong University from December 2016 to June 2020 were enrolled. According to the criteria of Sepsis 3, 107 patients diagnosed with sepsis were classified as the sepsis group, 112 patients without infection were classified as control group. Peripheral venous blood samples were collected within 24 hours after ICU admission, neutrophil CD64 index, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC) were detected. Receiver operating characteristic curve (ROC curve) was used to evaluate the diagnostic value of neutrophil CD64 index, CRP, PCT and WBC for sepsis. The neutrophil CD64 index, CRP and PCT in sepsis group were significantly higher than those in control group [neutrophil CD64 index: 9.03±5.59 vs. 3.18±1.50, CRP (mg/L): 146.9±68.3 vs. 46.5±35.8, PCT (ng/L): 31.82±14.71 vs. 1.87±1.42, all P < 0.05]. ROC curve analysis showed that neutrophil CD64 index, CRP and PCT had certain diagnostic value for sepsis, the area under ROC curve (AUC) were 0.924, 0.915 and 0.879, respectively, the 95% confidence intervals (95%CI) were 0.871-0.978, 0.855-0.975, 0.807-0.951, respectively, P values were 0.016, 0.017 and 0.026, respectively. Among the three indicators, the diagnostic value of neutrophil CD64 index was much higher. When the optimal cut-off value was 4.32, the sensitivity and specificity were 83.6% and 88.7%, respectively, which were higher than the sensitivity (75.1%, 76.3%) and specificity (87.2%, 82.5%) of CRP and PCT. Neutrophil CD64 index is a valuable biomarker for the diagnosis of sepsis in ICU.

Assessment of continuous neutrophil CD64 index measurement for diagnosing sepsis and predicting outcome in a Chinese pediatric intensive care unit: a prospective study.

BackgroundThe high affinity immunoglobulin-Fc fragment receptor I CD64 on neutrophils is widely assumed to be a useful biomarker in the early identification of sepsis, and it improves outcomes. We aimed to determine its ability to diagnose sepsis and predict its prognosis with continuous measurements.MethodsA total of 335 patients admitted to a Chinese PICU were prospectively stratified into two groups according to the presence of sepsis (defined by clinical criteria for sepsis) between 2018 and 2019. Serum concentrations of the nCD64 index, C-reactive protein (CRP), and procalcitonin (PCT) were measured. Sensitivity, specificity and receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic value for sepsis. A multiple logistic regression model was used to estimate the prognostic value of continuous nCD64 index measurement for in-hospital death.ResultsThe baseline nCD64 index and levels of PCT and CRP were significantly higher in septic children than in nonseptic children (P<0.05). The nCD64 index presented a higher sensitivity (0.90), specificity (0.78) and area under the ROC curve [0.91 (0.90, 0.93)] than CRP and PCT in discriminating septic children with an optimal cutoff value of 5.78. The nCD64 index decreased with the progression of sepsis, and the baseline nCD64 index was strongly associated with in-hospital death (OR: 2.18, 95% CI: 1.02–4.74). Moreover, the more rapidly the nCD64 index declined, the lower the in-hospital death rate was (OR: 0.89, 95% CI: 0.63–1.35) after adjusting for the baseline nCD64 index and other confounders.ConclusionsThe nCD64 index was not only effective for the early diagnosis of childhood sepsis but also positively associated with the prognosis of sepsis. Moreover, the nCD64 decline was inversely associated with the in-hospital death rate.