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Cell population data in identifying active tuberculosis and community-acquired pneumonia

  • Tingting Sun , Bin Wu , Zhonglan Luo , Jing Wang EMAIL logo , Shaoli Deng EMAIL logo and Qing Huang EMAIL logo
Published/Copyright: August 11, 2021

Abstract

Objective

Leukocyte morphological parameters known as CPD (cell population data) is detected by hematology analyzer UniCel DxH800 with VCS technology. This study aimed to investigate the diagnostic efficacy of morphological changes in CPD parameters in distinguishing active tuberculosis from community-acquired pneumonia.

Methods

From October 2018 to February 2019, 88 patients with active tuberculosis, 78 patients with community-acquired pneumonia, and 89 healthy controls were enrolled in this study. CPD was obtained using Unicel DxH800 analyzer for all whole blood samples, one-way ANOVA (non-parametric) and area analysis under ROC curve were performed.

Results

The neutrophil mean conductivity (NMC), monocyte mean volume (MMV), monocyte mean conductivity (MMC), lymphocyte percentage (LY%), and monocyte percentage (MO%) were significantly higher in the active tuberculosis group than in the community-acquired pneumonia group. The white blood cell (WBC) count and neutrophil percentage (NE%) were significantly lower in the active tuberculosis group than in the community-acquired pneumonia group. The analysis of the area under the ROC curve proved that WBC count, neutrophil percentage (NE%), lymphocyte percentage (LY%), and monocyte percentage (MO%) did not achieve a higher area under the curve (AUC: 0.63, 0.71, 0.62, and 0.7, respectively). However, the AUC of NMC, MMV, and MMC in the CPD parameters was 0.951, 0.877, 0.98, respectively, and the simultaneous measurement of the three parameters was 0.99. The sensitivity and specificity were 98.5% and 91.1%, respectively.

Conclusion

The combined diagnosis of NMC, MMV, and MMC could assist the clinical diagnosis of active tuberculosis and community-acquired pneumonia.

1 Introduction

Active tuberculosis (ATB) and community-acquired pneumonia (CAP) have similar symptoms, such as fever, cough, and expectoration; also, similarities are found in the imaging findings of pulmonary inflammation [1]. When the two diseases are combined, the patient’s condition will become more complicated, increasing the difficulty of identification and diagnosis. The two diseases often cover each other’s symptoms. The symptoms of the first disease are more obvious, which may cause missed diagnosis and misdiagnosis of another disease. There are many cases of tuberculosis as the first disease with secondary pneumonia, while the cases of pneumonia as the first, causing neglected treatment of tuberculosis reports are seldom. Currently, distinguishing the two diseases clinically is still difficult [2]. Therefore, a simple, fast, and accurate method is needed to distinguish ATB from CAP. The cell population data (CPD) can measure the inherent biological characteristics of more than 8,000 white blood cells simultaneously using the VCS technology of the blood analyzer UniCel DxH800. The VCS technology uses the direct current impedance to detect cell volume (V), the exact size of all cell types, and the conductivity of the internal structure of the cell (C) by radiofrequency opacity. Multiple angles light scatter (S) includes upper medium angle light scatter (UMALS), medium angle light scatter (MALS), lower medium angle light scatter (LMALS), and lower angle light scatter (LALS) to detect cell particle size and membrane morphology and axial light loss (AL2) so as to analyze cell transparency. Leukocytes are detected and analyzed by simultaneously obtaining three morphological parameters directly related to cell morphology. In three-dimensional space, a series of parameters can be obtained by comprehensively measuring the cell volume, size, and particle size, which can be accurately and quickly used to perform a microscopic evaluation of the WBC morphology [3,4,5]. In this study, the morphological changes in leukocyte CPD parameters were evaluated to investigate its diagnostic efficacy in distinguishing active tuberculosis from community-acquired pneumonia.

2 Material and methods

2.1 Case selection

This study included 88 patients with ATB from Chongqing Infectious Disease Medical Center from October 2018 to February 2019, 78 patients including CAP inpatients in the Department of Laboratory Medicine, Daping Hospital, Army Medical University, and 89 healthy controls who visited the physical examination center for health checkups.

The inclusion criteria for patients with ATB, in accordance with the “Public Health Organization Standards of the People’s Republic of China for the diagnosis of tuberculosis WS 288-2017,” were as follows: sputum culture, sputum antacid staining, at least one positive molecular diagnosis, and chest X-ray findings consistent with TB imaging lesions. Selected patients were all newly diagnosed patients with no history of anti-TB treatment.

The admission criteria for CAP and the diagnosis complied with the guidelines for the diagnosis and treatment of acquired pneumonia issued by the Respiratory Branch of the Chinese Medical Association in 2016 [6]. The criteria were as follows: (1) community incidence; (2) pneumonia-related clinical manifestations: (i) new symptoms of cough, sputum, or pre-existing respiratory disease worsened, with or without chest pain, and purulent sputum, (ii) signs of consolidation of the lungs and/or smell of wet rales, (iii) fever, (iv) the number of peripheral blood leukocytes >10 × 109/L or <4 × 109/L, with or without a nuclear shift to the left; and (3) chest imaging showing newly appearing patchy infiltrates, lobes, or segments with consolidated shadows, ground-glass opacity, or interstitial changes with or without pleural effusion. Patients with any of the aforementioned criteria who were diagnosed with bacterial pneumonia through bacterial staining and culture, excluding lung tumors, TB, noninfectious pulmonary interstitial disease, pulmonary embolism, pulmonary edema, atelectasis, pulmonary eosinophil infiltration, and pulmonary vasculitis.

The inclusion criteria for the healthy control group were as follows: individuals who went to the hospital for physical examination during the same period; no history of exposure to patients with TB; normal chest X-ray; negative results for interferon-gamma release assay T-SPOT; and no fever and cough. The liver function, kidney function, hepatitis B, and routine blood tests were normal.

The exclusion criteria were as follows: age <18 years; pregnant women; HIV infection; cancer; patients with severe abnormalities in liver and kidney function; patients with autoimmune diseases; patients who received immunosuppressants such as glucocorticoids; or patients who received anti-TB treatment.

  1. Ethical approval: The study protocol was approved by the hospital ethics committee.

2.2 Testing method

2.2.1 CPD parametric analysis

All samples were collected in EDTA-anticoagulated tubes by the experienced phlebotomists and analyzed within 4 h after specimen collection using UniCel DxH800 blood analyzer except coagulation and hemolysis. The following parameters were evaluated: WBC count, neutrophil percentage (NE%), lymphocyte percentage (LY%), monocyte percentage (MO%), and CPD parameters (V, V-SD, C, C-SD, UMALS, UMALS-SD, MALS, MALS-SD, LMALS, LMALS-SD, LALS, LALS-SD, AL2, and AL2-SD).

2.3 Statistical methods

The GraphPad Prism 8.0 statistical software (GraphPad Software, San Diego, CA, USA) was used for all data processing. After specimen testing, we obtained the data of all specimens and calculated the average value of testing results for all parameters in different groups. Data were exhibited by the mean ± standard deviation depending on the data characteristics, and the differences were evaluated using the independent sample t test in comparisons between two groups. Comparison among three means was performed using the one-way ANOVA (and nonparametric). The parameters with the statistical difference between the ATB and CAP were analyzed by the receiver operating characteristic (ROC) curve and appraised the diagnostic value. The cutoff value was defined based on the max You-den’s index. A p-value <0.05 was considered a statistically significant difference.

3 Results

3.1 Basic information of each parameter

This study retrospectively analyzed 88 patients with ATB (mean age 49.8 ± 14.5 years; male/female: 42/46 years), 78 patients with community-acquired pneumonia (age: 50.9 ± 19.1 years; male/female: 35/43 years), and 89 healthy controls (age: 51.9 ± 19.1 years; male/female: 41/48 years). The values of the following 27 indicators were significantly higher in the ATB group compared with the CAP group (LY%, MO%, NMV-SD, NMC, NMC-SD, N-MALS, N-MALS-SD, N-UMALS, N-LMALS-SD, N-LALS-SD, N-AL2, LMV-SD, LMC, LMC-SD, L-MALS,L-MALS-SD, L-UMALS, L-UMALS-SD, L-LMALS-SD, L-LALS-SD, L-AL2-SD, MMV, MMV-SD, MMC, MMC-SD, M-MALS, M-UMALS; P < 0.05). The values of 11 parameters (WBC, NE%, N-LALS, L-AL2, M-MALS-SD, M-UMALS-SD, M-LMALS-SD, M-LALS, M-LALS-SD, M-AL2, and M-AL2-SD; P < 0.05) was significantly lower in the ATB group than in the CAP group, while the values of NMV, N-UMALS-SD, N-LMALS, N-AL2-SD, LMV, L-LMALS, L-LALS, and M-LMALS were not statistically significantly different between active TB and community-acquired pneumonia groups (Table A1).

3.2 Sensitivity and specificity of CPD parameters to identify active TB and community-acquired pneumonia

The area under the ROC curve of CPD parameters had significant differences between ATB and CAP groups. WBC, NE%, LY%, and MO% did not show high sensitivity and specificity, and their area under the curve (AUC, 0.63, 0.71, 0.62, and 0.7) was less than 0.75 (Table 1). Conversely, in the analysis of CPD parameters, there are 13 parameters with AUC area above 0.8 (Table A2), of which three parameters (NMC, MMV, and MMC) achieved higher AUC compared with other parameters, which were 0.951, 0.877, and 0.98, respectively (Table 1). Combined measurement of NMC, MMV, and MMC could achieve an AUC as high as 0.99, and its sensitivity and specificity to distinguish ATB from CAP group were 98.5% and 91.1%, respectively (Table 1 and Figure 1).

Table 1

Sensitivity and specificity of cut-off values for each parameter in the analysis of active tuberculosis and community-acquired pneumonia groups

Parameters AUC Cut-off value Sensitivity (%) Specificity (%)
WBC 0.63 >8.450 38.46 85.57
NE% 0.71 >66.70 69.23 64.95
LY% 0.62 <13.08 39.74 85.57
MO% 0.70 <9.550 85.9 52.58
NMC 0.951 <149.5 83.33 93.81
MMV 0.877 <169.5 71.79 89.69
MMC 0.98 <129.5 92.31 89.69
NMC + MMV + MMC 0.99 98.5 91.1

WBC: white blood cells, NE%: neutrophil percentage, LY%: lymphocyte percentage, MO%: monocyte percentage, NMC: neutrophil mean conductivity, MMV: monocyte mean volume, MMC: monocyte mean conductivity.

Figure 1 
                  Analysis each parameter between ATB and CAP which under the ROC curve. Diagnostic value was appraised by the receiver operating characteristic (ROC) curve. Cutoff value was defined based on the max You-den’s index, which is the value when the difference between the sensitivity and 1-specificity of all points on the ROC curve is the largest. Compared with the WBC count and three of WBC conventional differential count, the CPD parameter achieved a higher AUC, and the maximum area under the AUC curve obtained by combining MNC, MMV, and MMC was 0.99. WBC, white blood cells; NE%, neutrophil percentage; LY%, lymphocyte percentage; MO%, monocyte percentage; NMC, neutrophil mean conductivity; MMV, monocyte mean volume; MMC, monocyte mean conductivity.
Figure 1

Analysis each parameter between ATB and CAP which under the ROC curve. Diagnostic value was appraised by the receiver operating characteristic (ROC) curve. Cutoff value was defined based on the max You-den’s index, which is the value when the difference between the sensitivity and 1-specificity of all points on the ROC curve is the largest. Compared with the WBC count and three of WBC conventional differential count, the CPD parameter achieved a higher AUC, and the maximum area under the AUC curve obtained by combining MNC, MMV, and MMC was 0.99. WBC, white blood cells; NE%, neutrophil percentage; LY%, lymphocyte percentage; MO%, monocyte percentage; NMC, neutrophil mean conductivity; MMV, monocyte mean volume; MMC, monocyte mean conductivity.

4 Discussion

Pneumonia is an infectious disease characterized by the inflammation of the terminal airways, alveoli, and interstitial lungs, affecting people worldwide, including developed and developing countries. In Asian countries, 1 million adults are affected by community-acquired pneumonia alone [7]. Pneumonia can be caused by pathogenic microorganisms, immune damage, physical and chemical factors, allergies, and drugs. The common pathogens of infectious pneumonia include bacteria, viruses, mycoplasma, fungi, rickettsia, chlamydia, and protozoa. Among these, bacterial pneumonia is the most common cause of pneumonia, accounting for 80% of all types of adult infectious pneumonia. Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity [8]. In recent years, with the aging of the population, the abuse of antibacterial drugs, the increase in immune damage, and the changes in the human living environment have led to great difficulty in the diagnosis and treatment of pneumonia [9,10,11,12]. Rapid and accurate diagnosis, timely treatment and management of the patients, and proper use of antibiotics need urgent attention.

TB has long been a global health problem. According to WHO global tuberculosis report in 2019 that there were 10 million new people suffer from TB, and the number of deaths caused by TB has been higher than that caused by HIV/AIDS in the last 5 years. China is 1 of the 22 countries with the largest TB epidemic burden in the world; the number of patients with TB is second to that of India [13]. However, if diagnosed and treated correctly, most patients with TB can be cured. The diagnosis of TB is mainly based on medical history, clinical manifestations, chest X-ray examination, and examination of sputum TB bacteria; however, the bacteriological examination is time consuming [14,15]. The clinical manifestations of TB, such as cough, fever, and the diversity of chest X-ray results, account for the lack of specificity. Hence, it is easily confused with community-acquired pneumonia, leading to the failure to diagnose and treat in time.

In this study, the VCS technology of the UniCel DxH800 blood analyzer was used to directly examine the peripheral blood of patients with active TB and community-acquired pneumonia. The results confirmed statistically significant differences in NMC, MMV, and MMC between the two groups (P < 0.0001; Table 1 and Figure 1). These three parameters were combined to obtain the area under the ROC curve of 0.99, the sensitivity and specificity were 98.5% and 91.1%, respectively. Compared with the WBC count and WBC differential percentage, the combination of NMC, MMV, and MMC had higher sensitivity and specificity with higher diagnostic efficacy for distinguishing ATB from CAP.

Studies have shown that phagocytes, such as monocytes, macrophages, and multinuclear neutrophils, are the first line of defense against the invasion of bacterial pathogens. During bacterial invasion, macrophages are identified by surface exposure, and vesicle or cytoplasmic pattern recognition receivers recognize bacteria and initiate phagocytic cells for phagocytosis. Neutrophils leave the circulation and migrate to inflammatory lesions to deal with the infection. Therefore, after the body is infected by bacteria, there are changes in the size of the white blood cell subpopulation, the number of particles, the nuclear-to-cytoplasmic ratio, and the cell membrane. These differences might vary in different diseases. The results of this study showed that among all CPD parameters, neutrophils, and monocytes, had statistically significant differences in the identification of active TB and community-acquired pneumonia. These changes indicated that the volume of activated cells and volume heterogeneity increase after infection. The nuclear/cytoplasmic ratio was high (the nucleus was more naïve). In the anti-TB immune response, various cytokines are secreted, the number of particles increases in the cytoplasm, and the membrane morphology changes, resulting in a significant change in the electrical conductivity of the cells.

In conclusion, leukocyte community parameters were easily obtained from blood CPD parameters, and the detection cost was low. These parameters could quickly, accurately, and objectively reflect the inherent biological characteristics of cells, thus having potential clinical application value in providing quick and easy reference indicators of ATB and CAP.


Tingting Sun and Bin Wu contributed equally to this study.


  1. Funding information: This study was supported by Chongqing Municipal Social People’s Livelihood Technology Innovation Project (CSTC2015SHMSZX120102) and 973 project sub-topics (K2015CB755401) and Major Project (2018XLC2027) of Army Medical University.

  2. Conflict of interest: The authors declare that there are no conflicts of interest in this work.

  3. Data availability statements: All data generated or analyzed during this study are included in this published article.

Appendix

Table A1

parameters in active tuberculosis and community-acquired pneumonia and healthy control (Mean ± SD)

Parameter 1 2 3 P
ATB (N = 88) CAP (N = 78) HC (N = 89) 1 vs 2 1 vs 3 2 vs 3
WBC 6.614 ± 2.224 8.175 ± 4.097 7.086 ± 2.746 0.0208 Ns Ns
NE% 64.18 ± 9.191 71.31 ± 13.1 68.74 ± 12.46 <0.0001 0.0075 Ns
LY% 20.7 ± 8.047 18.04 ± 13.6 21.23 ± 10.25 0.0302 Ns 0.0348
MO% 9.899 ± 3.522 7.945 ± 2.992 7.466 ± 2.579 <0.0001 <0.0001 Ns
neutrophil CPD parameter
NMV 144.2 ± 6.266 145.2 ± 7.995 145.7 ± 7.233 Ns Ns Ns
NMV-SD 20.32 ± 3.177 18.81 ± 2.633 17.85 ± 2.107 0.0059 <0.0001 Ns
NMC 153.4 ± 2.645 139.8 ± 7.314 151.5 ± 3.526 <0.0001 0.0003 <0.0001
NMC-SD 9.042 ± 3.948 5.863 ± 1.734 5.536 ± 1.051 <0.0001 <0.0001 Ns
N-MALS 134.3 ± 5.684 128.99.347 136.6 ± 4.945 0.0006` 0.0262 <0.0001
N-MALS-SD 14.95 ± 5.118 12.73 ± 2.612 11.05 ± 1.572 0.0305 <0.0001 <0.0001
N-UMALS 137.8 ± 4.474 124.2 ± 11.22 136.3 ± 5.342 <0.0001 Ns <0.0001
N-UMALS-SD 14.5 ± 4.385 16.82 ± 6.577 11.85 ± 1.68 Ns <0.0001 <0.0001
N-LMALS 126.8 ± 9.128 127.3 ± 11.23 133 ± 6.441 Ns <0.0001 0.0016
N-LMALS-SD 19.16 ± 6.887 16.26 ± 4.386 14.05 ± 2.624 0.0008 <0.0001 0.0004
N-LALS 155.2 ± 20.28 163.6 ± 18 170.9 ± 13.64 0.011 <0.0001 Ns
N-LALS-SD 41.1 ± 6.712 34.27 ± 7.237 33.03 ± 6.652 <0.0001 <0.0001 Ns
N-AL2 142.8 ± 3.893 140.7 ± 4.248 140.7 ± 5.399 0.0023 0.0048 Ns
N-AL2-SD 15.72 ± 4.343 15.73 ± 3.459 11.56 ± 1.843 Ns <0.0001 <0.0001
lymphocyte CPD parameter
LMV 89.19 ± 4.457 89.1 ± 4.323 87.49 ± 3.956 Ns 0.0409 Ns
LMV-SD 17.55 ± 3.883 15.38 ± 2.686 15.31 ± 2.534 0.0011 <0.0001 Ns
LMC 119.6 ± 3.204 111.7 ± 6.74 120.4 ± 3.021 <0.0001 Ns <0.0001
LMC-SD 13.09 ± 2.558 9.642 ± 3.156 9.136 ± 1.923 <0.0001 <0.0001 Ns
L-MALS 61.27 ± 6.314 51.29 ± 13.23 64.53 ± 7.477 <0.0001 0.0029 <0.0001
L-MALS-SD 19.65 ± 2.614 17.42 ± 1.702 17.59 ± 1.808 <0.0001 <0.0001 Ns
L-UMALS 64.13 ± 8.007 44.54 ± 20.61 66 ± 9.197 <0.0001 Ns <0.0001
L-UMALS-SD 21.91 ± 2.516 19.99 ± 2.875 19.41 ± 1.508 <0.0001 <0.0001 Ns
L-LMALS 54.03 ± 5.828 51.71 ± 7.47 58.43 ± 6.191 Ns <0.0001 <0.0001
L-LMALS-SD 21.67 ± 2.818 20.19 ± 1.55 20.36 ± 1.664 <0.0001 <0.0001 Ns
L-LALS 39.85 ± 4.814 38.87 ± 2.894 37.65 ± 2.692 Ns <0.0001 0.0207
L-LALS-SD 14.94 ± 4.987 12.38 ± 1.96 11.69 ± 1.637 <0.0001 <0.0001 Ns
L-AL2 75.76 ± 3.785 79.28 ± 3.407 75.23 ± 2.807 <0.0001 Ns <0.0001
L-AL2-SD 12.78 ± 3.313 11.91 ± 2.354 10.94 ± 1.366 0.0223 <0.0001 0.0195
monocyte CPD parameter
MMV 182.4 ± 11.35 166 ± 10.34 166.8 ± 7.935 <0.0001 <0.0001 Ns
MMV-SD 21.96 ± 2.533 20.51 ± 3.783 18.95 ± 3.034 0.0004 <0.0001 0.0108
MMC 132.5 ± 2.389 119.4 ± 6.561 128.9 ± 3.146 <0.0001 <0.0001 <0.0001
MMC-SD 7.266 ± 3.161 6.811 ± 2.953 6.087 ± 1.876 0.0216 <0.0001 Ns
M-MALS 84.27 ± 3.353 74.19 ± 12.72 86.59 ± 5.088 0.0002 0.0002 <0.0001
M-MALS-SD 10.91 ± 1.396 13.31 ± 2.944 11.74 ± 1.295 <0.0001 <0.0001 0.0012
M-UMALS 94.48 ± 5.368 76.29 ± 18.02 94.69 ± 6.135 <0.0001 Ns <0.0001
M-UMALS-SD 11.87 ± 1.99 16.48 ± 4.544 12.73 ± 1.858 <0.0001 0.0015 <0.0001
M-LMALS 71.01 ± 2.845 67.46 ± 9.699 75.58 ± 5.032 Ns <0.0001 <0.0001
M-LMALS-SD 14.07 ± 3.399 16.77 ± 3.094 14.73 ± 1.617 <0.0001 0.0001 <0.0001
M-LALS 81.4 ± 11.04 87.42 ± 14.32 90.58 ± 12.19 0.0001 <0.0001 Ns
M-LALS-SD 23.19 ± 4.195 25.94 ± 3.796 26.43 ± 3.898 <0.0001 <0.0001 Ns
M-AL2 131.6 ± 5.154 134.2 ± 4.587 131.3 ± 4.686 0.0003 Ns 0.0001
M-AL2-SD 12.45 ± 2.246 14.71 ± 3.824 12.64 ± 2.588 <0.0001 Ns <0.0001

ATB: Active Tuberculosis, CAP: Community-acquired pneumonia, HC: Health control, WBC: White blood count, NE%: neutrophil percentage, LY%: lymphocyte percentage, MO%: monocyte percentage, NMV: Neutrophil mean volume,NMV-SD: Neutrophil mean volume standard deviation, NMC: Neutrophil mean conductivity, NMC-SD: Neutrophil mean conductivity standard deviation, N-MALS: Neutrophil medium angle light scatter, N-MALS-SD: Neutrophil medium angle light scatter standard deviation: N-UMALS: Neutrophil upper medium angle light scatter, N-UMALS-SD: Neutrophil upper medium angle light scatter standard deviation, N-LMALS: Neutrophil lower medium angle light scatter, N-LMALS-SD: Neutrophil lower medium angle light scatter standard deviation, N-LALS: Neutrophil lower angle light scatter, N-LALS-SD: Neutrophil lower angle light scatter standard deviation, N-AL2: Neutrophil axial light loss measurement, N-AL2-SD: Neutrophil axial light loss measurement standard deviation, LMV: Lymphocyte mean volume, LMV-SD: Lymphocyte mean volume standard deviation, LMC: Lymphocyte mean conductivity,LMC-SD: Lymphocyte mean conductivity standard deviation, L-UMALS:Lymphocyte upper median angle light scatter, L-UMALS-SD: Lymphocyte upper median angle light scatter standard deviation, L-MALS: Lymphocyte medium angle light scatter, L-MALS-SD: Lymphocyte medium angle light scatter standard deviation, L-LMALS: Lymphocyte lower median angle light scatter, L-LMALS-SD: Lymphocyte lower median angle light scatter standard deviation, L-LALS: Lymphocyte lower angle light scatter, L-LALS-SD: Lymphocyte lower angle light scatter standard deviation, L-AL2: Lymphocyte axial light loss measurement, L-AL2-SD: Lymphocyte axial light loss measurement standard deviation, MMV: Monocyte mean volume, MMV-SD: Monocyte mean volume standard deviation, MMC: Monocyte mean conductivity, MMC-SD: Monocyte mean conductivity standard deviation, M-UMALS: Monocyte upper median angle light scatter, M-UMALS-SD: Monocyte upper median angle light scatter standard deviation, M-MALS: Monocyte medium angle light scatter, M-MALS-SD: Monocyte medium angle light scatter standard deviation, M-LMALS: Monocyte lower median angle light scatter, M-LMALS-SD: Monocyte lower median angle light scatter standard deviation, M-LALS: Monocyte lower angle light scatter, M-LALS-SD: Monocyte lower angle light scatter standard deviation, M-AL2: Monocyte axial light loss measurement, M-AL2-SD: Monocyte axial light loss measurement standard deviation.

Table A2

Sensitivity and specificity at the designated cut-off values of parameters for differentiating active tuberculosis from community-acquired pneumonia

Parameter AUC Cutoff value Sensitivity (%) Specificity (%)
NMC 0.951 <149.5 83.33 93.81
NMC-SD 0.807 <6.475 79.49 69.07
N-UMALS 0.874 <132.5 75.64 88.66
LMC 0.816 <114.4 64.1 96.91
LMC-SD 0.836 <10.88 82.05 81.44
L-MALS-SD 0.809 <18.04 76.92 79.38
L-AL2 0.803 >76.5 83.33 64.95
MMV 0.877 <169.5 71.79 89.69
MMC 0.98 <129.5 92.31 89.69
M-MALS-SD 0.806 >11.82 66.67 84.54
M-UMALS 0.803 <87.5 65.38 97.94
M-UMALS-SD 0.846 >12.29 80.77 74.23
M-LMALS-SD 0.829 >15.06 71.79 86.6

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Received: 2020-10-06
Revised: 2021-05-28
Accepted: 2021-07-01
Published Online: 2021-08-11

© 2021 Tingting Sun et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  12. LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
  13. Case Report
  14. Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
  15. Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
  16. Research Articles
  17. TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
  18. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
  19. LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
  20. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
  21. Rapid Communication
  22. COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
  23. Case Report
  24. Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
  25. An infertile female delivered a baby after removal of primary renal carcinoid tumor
  26. Research Articles
  27. Hypertension, BMI, and cardiovascular and cerebrovascular diseases
  28. Case Report
  29. Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
  30. Research Articles
  31. Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
  32. Review Articles
  33. Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
  34. Research Articles
  35. Thermography in the diagnosis of carpal tunnel syndrome
  36. Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
  37. Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
  38. The influence of smoking in minimally invasive spinal fusion surgery
  39. Impact of body mass index on left atrial dimension in HOCM patients
  40. Expression and clinical significance of CMTM1 in hepatocellular carcinoma
  41. miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
  42. Comparison of multiple flatfoot indicators in 5–8-year-old children
  43. Early MRI imaging and follow-up study in cerebral amyloid angiopathy
  44. Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
  45. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
  46. Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
  47. Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
  48. Review Articles
  49. The ambiguous role of mannose-binding lectin (MBL) in human immunity
  50. Case Report
  51. Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
  52. Fertility problems in males carrying an inversion of chromosome 10
  53. Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
  54. Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
  55. Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
  56. Skull hemophilia pseudotumor: A case report
  57. Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
  58. Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
  59. Clinicopathologic features of Good’s syndrome: Two cases and literature review
  60. Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
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