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

OBJECTIVE: Infectious 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 pancreatitis METHODS: This 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. RESULTS: We 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%). CONCLUSION: This 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.

Serial Trend of Neutrophil CD64, C-reactive Protein, and Procalcitonin as a Prognostic Marker in Critically Ill Patients with Sepsis/Septic Shock: A Prospective Observational Study from a Tertiary Care ICU.

Aim and background: Neutrophil CD64 (nCD64) is evolving as a prognostic biomarker in sepsis. The primary objective of this study was to evaluate whether serial trend of nCD64, procalcitonin (PCT), and C-reactive protein (CRP) predict 28-day mortality in patients with sepsis/septic shock, as per Sepsis-3 criteria. Materials and methods: This prospective, observational single-center cohort study included 60 adult patients (age ≥18 years) with sepsis. Serial biomarker levels with SOFA score were measured at admission (day 0), on day 4, and on day 8. Results: Of the 60 patients, 42 (70%) had septic shock. Biomarker levels at admission did not differ between patients with sepsis and septic shock. Thirty-seven patients survived and 23 were non-survivors by day 28. There was a significant fall in serial trend of all three biomarkers from admission till day 8 (Friedman p < 0.001) in survivors compared to a non-significant change in non-survivors. On multivariate analysis, SOFA score at admission (OR 1.731), more days with vasopressor support (OR 1.077), rise in CD64 from day 0 to day 8 (OR 1.074), and rise in CRP from day 0 to 8 (OR 1.245) were the significant predictors of 28-day mortality (p < 0.05). The highest area under the ROC curve was obtained for more days of vasopressor therapy (0.857), followed by a rise in CD64 from day 0 to day 8 (0.798). Conclusion: Serial trend of biomarkers has prognostic utility. The rise in CD64 from day 0 to day 8 was a good predictor of mortality compared to the trend of other biomarkers. How to cite this article: Patnaik R, Azim A, Singh K, Agarwal V, Mishra P, Poddar B, et al. Serial Trend of Neutrophil CD64, C-reactive Protein, and Procalcitonin as a Prognostic Marker in Critically Ill Patients with Sepsis/Septic Shock: A Prospective Observational Study from a Tertiary Care ICU. Indian J Crit Care Med 2024;28(8):777-784.

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 Information: The online version contains supplementary material available at 10.1007/s12291-022-01087-z.

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

BACKGROUND: Neutrophil 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. METHODS: 160 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. RESULTS: Bacteria-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). CONCLUSION: The 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.

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

BACKGROUND: We aimed to explore the prognostic utilities of C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD64 (nCD64) index, in combination or alone, in septic patients. METHODS: We 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. RESULTS: CRP, 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. CONCLUSIONS: nCD64 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.

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

BACKGROUND: Infection 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. METHODS: This 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. RESULTS: Among 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%. CONCLUSIONS: The nCD64 index is a useful biomarker for the diagnosis of early infection in children admitted to the PICU.

Diagnostic value of neutrophil CD64, procalcitonin, and interleukin-6 in sepsis: a meta-analysis.

BACKGROUND: The aim of the study was to conduct a meta-analysis to evaluate the accuracy of neutrophil CD64, procalcitonin (PCT), and interleukin-6 (IL-6) as markers for the diagnosis of sepsis in adult patients. METHODS: Various databases were searched to collect published studies on the diagnosis of sepsis in adult patients using neutrophil CD64, PCT, and IL-6 levels. Utilizing the Stata SE 15.0 software, forest plots and the area under the summary receiver operating characteristic curves were drawn. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) were calculated. RESULTS: Fifty-four articles were included in the study. The pooled sensitivity, specificity, and AUC of neutrophil CD64 for the diagnosis of sepsis were 0.88 (95% confidence interval [CI], 0.81-0.92), 0.88 (95% CI, 0.83-0.91), and 0.94 (95% CI, 0.91-0.96), respectively. The pooled sensitivity, specificity, and AUC of PCT for the diagnosis of sepsis were 0.82 (95% CI, 0.78-0.85), 0.78 (95% CI, 0.74-0.82), and 0.87 (95% CI, 0.83-0.89), respectively. Subgroup analysis showed that the AUC for PCT diagnosis of intensive care unit (ICU) sepsis was 0.86 (95% CI, 0.83-0.89) and the AUC for PCT diagnosis of non-ICU sepsis was 0.82 (95% CI, 0.78-0.85). The pooled sensitivity, specificity, and AUC of IL-6 for the diagnosis of sepsis were 0.72 (95% CI, 0.65-0.78), 0.70 (95% CI, 0.62-0.76), and 0.77 (95% CI, 0.73-0.80), respectively. CONCLUSIONS: Of the three biomarkers studied, neutrophil CD64 showed the highest diagnostic value for sepsis, followed by PCT, and IL-6. On the other hand, PCT showed a better diagnostic potential for the diagnosis of sepsis in patients with severe conditions compared with that in patients with non-severe conditions.

Neutrophil CD64 a Diagnostic and Prognostic Marker of Sepsis in Adult Critically Ill Patients: A Brief Review.

INTRODUCTION: Sepsis is a life-threatening organ dysfunction with increased incidence of morbidity and mortality. Early diagnosis and prompt therapeutic intervention is the cornerstone of sepsis care. Biomarkers play an important role in sepsis having both diagnostic and prognostic implications. Neutrophil CD64 (nCD64) is a useful candidate biomarker for sepsis. Neutrophil CD64 also known as Fc receptor 1 (FcR1), is a high-affinity receptor present on neutrophils for Fc part of immunoglobulin-G (IgG) heavy chain. Its expression gets strongly upregulated in response to proinflammatory cytokines of infection within 4-6 hours. Neutrophil CD64 integrates function involving both innate and adaptive immune responses. The aim of this review is to present literature about nCD64 as a diagnostic and prognostic marker in patients with sepsis/septic shock. BACKGROUND: The authors searched articles over 13 years, i.e., from 2006 to 2019. They included articles written in English only and further reviewed the reference list of selected articles to obtain potentially relevant articles. Reviews, letters, commentaries, correspondences, case reports, conference abstracts, expert opinions, editorials, and animal experiments were excluded. Articles involving pediatric patients (≤18 years) were also excluded. REVIEW RESULTS: Several studies have indicated that nCD64 is a highly sensitive and specific marker for the diagnosis of sepsis. Various combinations of biomarkers have been used with nCD64 for a better diagnostic value. Neutrophil CD64 as a prognostic marker in critically ill patients needs to be explored more. Most of the existing literatures have highlighted its prognostic utility based on single value at enrolment. There are limited literatures on prognostic implications of serial trend and kinetics of nCD64. CONCLUSION: Neutrophil CD64 is a useful diagnostic and prognostic marker of sepsis in critically ill patients. Additional studies are needed on nCD64 in sepsis based on sepsis-3 criteria. Further trials with large sample size are needed to establish prognostic implications of serial nCD64 trend. HOW TO CITE THIS ARTICLE: Patnaik R, Azim A, Agarwal V. Neutrophil CD64 a Diagnostic and Prognostic Marker of Sepsis in Adult Critically Ill Patients: A Brief Review. Indian J Crit Care Med 2020;24(12):1242-1250.

[The role of neutrophil CD64 index in the diagnosis of infectious complications after colorectal resection]. / Rol' indeksa CD64-neitrofilov v diagnostike infektsionnykh oslozhnenii posle rezektsii tolstoi kishki.

OBJECTIVE: To determine diagnostic value of neutrophil CD64 index (iCD64n) in the diagnosis of postoperative infectious complications after colorectal resections. MATERIAL AND METHODS: Seventy-three patients underwent colorectal surgery for the period from January to December 2018. These patients were included into a single-center study. Peripheral blood samples were taken on 3 and 6 postoperative days (POD) to check iCD64n level. We analyzed incidence of postoperative infectious complications, sensitivity (Se) and specificity (Sp) of postoperative iCD64n level on the 3rd and 6th POD. RESULTS: Postoperative infectious complications developed in 10 (13.7%) patients. Median iCD64n was significantly higher (p=0.0017 for POD 3; p=0.018 for POD 6) in patients with infectious complications (1.6 on POD 3; 1.3 on POD 6) compared to those without complications (1.1 on POD 3; 0.9 on POD 6). Area under curve (AUC) on the 3rd POD was 0.8 with the cut-off value of 1.4, Se - 70%, Sp - 93.7% (p=0.002). On the 6th POD, AUC was 0.91 with cut-off value of 1.23, Se - 80%, Sp - 93.7% (p<0.001). CONCLUSION: Neutrophil CD64 index is a valuable predictor for the diagnosis of postoperative infectious complications after colorectal resections. It is a useful tool to ensure a safe early discharge.The study is registered on the website «clinictrials.gov¼ (registration number NCT03559335).

Diagnostic value of neutrophil CD64 combined with CRP for neonatal sepsis: A meta-analysis.

BACKGROUND: Sepsis is the leading cause of morbidity and mortality in newborns. CD64 combined with c-reactive protein (CRP) could improve the sensitivity and specificity of neonatal sepsis diagnosis, but the results were still controversial. Therefore, this meta-analysis was conducted to clarify the importance of CD64 combined with CRP in the diagnosis of neonatal sepsis. METHODS: The researches published as of December 24, 2018 were comprehensively searched in PubMed, Embase (included Embase and Medline), the Cochrane Library and Web of Science. Totally, 8 articles were included, involving 1114 objects. Statistical calculations were performed using Stata14.0 and Review Manager 5.3. RESULTS: The diagnostic accuracy of all included studies was pooled as follows: sensitivity, 0.95 (95% CI: 0.86-0.98); specificity, 0.86 (95% CI: 0.74-0.93); positive likelihood ratio (PLR), 6.8 (95% CI: 3.50-13.20); negative likelihood ratio (NLR), 0.06 (95% CI: 0.02-0.18); diagnostic odds ratio (DOR), 118.0 (95% CI: 25.00-549.00), and the area under the curve (AUC) was 0.96 (95% CI: 0.94-0.97). It was found that heterogeneity was not caused by threshold effect (P = 0.16), but the results of sensitivity (I2 = 87.57%) and specificity (I2 = 89.07%) analyses indicated significant heterogeneity between studies. CONCLUSIONS: The combined application of CD64 and CRP improved the accuracy of neonatal sepsis diagnosis.

Neutrophil CD64 index in cerebrospinal fluid as a marker of bacterial ventriculitis in children with external ventricular drainage.

BACKGROUND: Bacterial ventriculitis is a common complication in children with temporary external ventricular drains (EVD) and the diagnosis is challenging. The present study compared the diagnostic accuracy of novel cerebrospinal fluid (CSF) marker - CD64 expression on neutrophils measured as neutrophil CD64 index (CD64in) to routine laboratory CSF and blood markers for bacterial ventriculitis in children with EVD. METHODS: We conducted a prospective, observational study, enrolling children with EVD. CD64in in CSF together with CSF markers (leukocyte count, percentage of neutrophils, glucose, and proteins) and blood markers (leukocyte and differential count, C-reactive protein (CRP), and procalcitonin (PCT)) were studied at the time of suspected bacterial ventriculitis. CD64in was measured by flow cytometry. Diagnostic accuracy determined by the area under the receiver-operating characteristic (ROC) curves (AUC) was defined for each marker. RESULTS: Thirty-three episodes of clinically suspected ventriculitis in twenty-one children were observed during a 26-month period. Episodes were classified into those with microbiologically proven ventriculitis (13 episodes) and into those with microbiologically negative CSF (20 episodes). CD64in and leukocyte count were the only CSF markers that could differentiate between groups with diagnostic accuracy of 0.875 and 0.694, respectively. Among blood markers only CRP and band neutrophils differentiated between groups with diagnostic accuracy of 0.792 and 0.721, respectively. CONCLUSIONS: CD64in in CSF is a promising diagnostic marker of bacterial ventriculitis in children with EVD as it has higher diagnostic accuracy than routine blood and CSF markers for diagnosing bacterial ventriculitis at the time of clinical suspicion.

Correlation of Neutrophil CD64 with Clinical Profile and Outcome of Sepsis Patients during Intensive Care Unit Stay.

INTRODUCTION: Neutrophil CD64 (nCD64) has been found to identify sepsis from nonseptic patients. It is also reported to be a predictor of survival and severity of sepsis. The goal of this study was to correlate serial nCD64 with Intensive Care Unit (ICU) outcome and severity of sepsis. MATERIALS AND METHODS: A prospective observational study was conducted in 12-bedded critical care unit of a tertiary care center. Adult patients with sepsis were included in this study. Demographics, illness severity scores, clinical parameters, laboratory data, and 28-day outcome were recorded. Serial nCD64 analysis was done (on days 0, 4, and 8) in consecutive patients. RESULTS: Fifty-one consecutive patients were included in the study. Median Acute Physiology and Chronic Health Evaluation II was 16 (12-20) and mean Sequential Organ Failure Assessment was 9 (8-10). Compared to survivors, nonsurvivors had higher nCD64 on day 8 (P = 0.001). nCD64 was higher in the septic shock group compared to sepsis group on days 0 and 8 (P < 0.05). Survivors showed improving trend of nCD64 over time while nonsurvivors did not. This trend was similar in the presence or absence of septic shock. nCD64 count was a good predictor of the septic shock on day 0 (area under the curve [AUC] = 0.747, P = 0.010) and moderate predictor at day 8 (AUC = 0.679, P = 0.028). CONCLUSION: Monitoring serial nCD64 during ICU stay may be helpful in determining the clinical course of septic patients.

Clinical application of neutrophil CD64 quantification for differential diagnosis of acute scrotum.

The management of acute scrotum can be challenging, especially in infants or patients with a neurological or neurodevelopmental disorder in whom presentation, diagnosis and definitive management tends to be delayed. This leads to poor outcomes, such as loss of the affected testis. Here we present two cases of testicular torsion in patients with neurodevelopmental disorders, and a further two cases of epidydimo-orchitis in whom measurement of CD64 expression on neutrophils was helpful for differential diagnosis. These data suggest that the levels of expression of CD64 by neutrophils, known as a marker of infection, could also be useful for differentiating between testicular torsion and infection in acute scrotum.

Neutrophil CD64 Expression as a Diagnostic Marker in Patients Hospitalized with Exacerbations of COPD: A Prospective Observational Study.

PURPOSE: The expression of the neutrophil high-affinity Fc-gamma receptor (CD64) can be used as a diagnostic marker for bacterial infection and sepsis. The aims of this study were to determine the diagnostic accuracy of CD64 compared to C-reactive protein (CRP) and white blood cell count (WBC) in patients hospitalized with acute exacerbations of COPD (AECOPD) and to investigate the kinetics of CD64 expression. METHODS: The present study is a prospective, single-centre observation study. Blood samples were collected from patients hospitalized with AECOPD at admission and after 6, 24 and 48 h. Retrospective reviews on the patients' medical records were performed blinded to the CD64 results. The CD64 was measured using the Leuko64 kit from Trillium Diagnostics, LLC (Maine, USA) with the CELL-DYN Sapphire Haematology System (Abbott Laboratories, Illinois, USA). Diagnostic accuracy of the CD64, CRP and WBC was compared using a receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 113 patients were included. Thirty-six patients (32 %) had pulmonary infiltrate on chest X-ray at admission (PI). The CD64 was higher in samples from patients with AECOPD and PI than those without PI at admission (median 1.25 vs. 0.60, p = 0.002) and during 48 h of follow-up. The area under the ROC curve of CD64, CRP and WBC was 0.69, 0.73 and 0.64, respectively, (p = 0.42 for the test of difference). CONCLUSION: Neutrophil CD64 expression has about the same diagnostic accuracy as CRP in diagnosing pneumonia in patients hospitalized with AECOPD, but does not add to the diagnostic accuracy of CRP and WBC count.

Neutrophil CD64 expression: a reliable diagnostic marker of infection in advanced cancer patients?

Infection and sepsis are major health problems in cancer patients. There is a need for the identification and validation of biomarkers to improve their early diagnosis and treatment. Emerging evidence showed that neutrophil CD64 is a highly sensitive and specific marker for systemic infection and sepsis in critically ill patients with various diseases but data on patients bearing solid tumors are still lacking. Using a dedicated flow cytometric assay we evaluated neutrophil CD64 expression in patients with advanced cancer without active infections to verify if it could be utilized as a reliable biomarker of early infections also in oncologic patients.

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

INTRODUCTION: 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. METHODOLOGY: 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. RESULTS: 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). CONCLUSIONS: 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.

Kinetics of CD169, HLA-DR, and CD64 expression as predictive biomarkers of SARS-CoV2 outcome.

INTRODUCTION: Discriminating between virus-induced fever from superimposed bacterial infections is a common challenge in intensive care units. Superimposed bacterial infections can be detected in severe SARS-CoV2-infected patients, suggesting the important role of the bacteria in COVID-19 evolution. However, indicators of patients' immune status may be of help in the management of critically ill subjects. Monocyte CD169 is a type I interferon-inducible receptor that is up-regulated during viral infections, including COVID-19. Monocyte HLA-DR expression is an immunologic status marker, that decreases during immune exhaustion. This condition is an unfavorable prognostic biomarker in septic patients. Neutrophil CD64 upregulation is an established indicator of sepsis. METHODS: In this study, we evaluated by flow cytometry the expression of cellular markers monocyte CD169, neutrophil CD64, and monocyte HLA-DR in 36 hospitalized patients with severe COVID-19, as possible indicators of ongoing progression of disease and of patients' immune status. Blood testings started at ICU admission and were carried on throughout the ICU stay and extended in case of transfer to other units, when applicable. The marker expression in mean fluorescence intensity (MFI) and their kinetics with time were correlated to the clinical outcome. RESULTS: Patients with short hospital stay (≤15 days) and good outcome showed higher values of monocyte HLA-DR (median 17,478 MFI) than long hospital stay patients (>15 days, median 9590 MFI, p= 0.04) and than patients who died (median 5437 MFI, p= 0.05). In most cases, the recovery of the SARS-CoV2 infection-related signs was associated with the downregulation of monocyte CD169 within 17 days from disease onset. However in three surviving long hospital stay patients, a persistent upregulation of monocyte CD169 was observed. An increased neutrophil CD64 expression was found in two cases with a superimposed bacterial sepsis. CONCLUSION: Monocyte CD169, neutrophil CD64, and monocyte HLA-DR expression can be used as predictive biomarkers of SARS-CoV2 outcome in acutely infected patients. The combined analysis of these indicators can offer a real-time evaluation of patients' immune status and of viral disease progression versus superimposed bacterial infections. This approach allows to better define the patients' clinical status and outcome and may be useful to guide clinicians' decisions. Our study focused on the discrimination between the activity of viral and bacterial infections and on the detection of the development of anergic states that may correlate with an unfavorable prognosis.

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

OBJECTIVE: To investigate the clinical value of neutrophil CD64 index in hematological malignancies with pulmonary infection. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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

BACKGROUND: The 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: The 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.

Comparison of neutrophil CD64 and monocytic HLA-DR with existing biomarkers for the diagnosis and prognosis of sepsis.

INTRODUCTION: We measured the expression of serum procalcitonin (PCT), quantitative C-reactive protein (QCRP), neutrophil CD64 (nCD64) and monocytic HLA-DR (mHLA-DR) sequentially in patients admitted to the intensive care unit (ICU) and correlated the expression of these biomarkers to predict development of sepsis and its outcome. MATERIAL AND METHODS: Consenting adult patients of more than 18 years of age, who developed sepsis during an observation period of 20 days with a sequential organ failure assessment score (SOFA) score ≥ 2 or those who already had sepsis at admission to the ICU were included. SOFA score, serum PCT, QCRP, nCD64 and mHLA-DR assays were recorded on the first and third day of admission to the ICU. A total of 27 sepsis cases and 24 controls (all admitted to the ICU) were included in the study. RESULTS: SOFA score, serum PCT, QCRP, nCD64 were significantly higher and mHLA-DR was significantly lower in cases compared to controls, both on day 1 and day 3. There was no significant difference in any of the parameters between day 1 and day 3. PCT and nCD64, both with sensitivity of 77.8% and specificity of 70.8% (95% CI, 0.73-0.95), had the best predictive value for diagnosing sepsis. Lower mHLA-DR (< 5000/cell) was associated with higher mortality among cases. CONCLUSIONS: Serum PCT and nCD64 are the best biomarkers with similar sensitivity and specificity in detecting sepsis. mHLA-DR could have a role in prognosis as lower levels were associated with higher mortality.