The Role of Combined Inflammatory Biomarkers in the Diagnosis of High- and Low-Virulence FRI Among High-Risk Lower Extremity Fractures

Figures & data

Figure 1 Flow diagram of the study design.

Table 1 Demographics and Clinical Characteristics of FRI and Non-FRI Patients

Variable	Non-FRI Group (n=525)	FRI Group (n=51)	p-value^‡
Gender, male, n (%)	386 (73.5)	35 (68.6)	0.452
Age, yrs, mean ± SD	47.0±11.8	47.5±9.4	0.753
BMI, kg/m^2, mean ± SD	26.1±4.1	26.9±4.8	0.184
Tobacco use, n (%)	74 (14.1)	12 (23.5)	0.071
Comorbidities, n (%)
Hypertension	38 (7.2)	4 (7.8)	0.780
Diabetes mellitus	30 (5.7)	5 (9.8)	0.224
Coronary heart disease	17 (3.2)	2 (3.9)	0.681
Injury site, n (%)			0.217
Tibial plateau	336 (64.0)	37 (72.5)
Calcaneus	129 (24.6)	7 (13.7)
Pilon	60 (11.4)	7 (13.7)
Injury type, n (%)			0.249
High-energy	317 (60.4)	35 (68.6)
Low-energy	208 (39.6)	16 (31.4)
ISS, points, n (%)			0.632
0 pt	487 (92.8)	46 (90.2)
1 pt	36 (6.9)	5 (9.8)
4 pts or greater	2 (0.4)	0
Time to surgery, days, mean ± SD	5.8±2.0	5.9±1.3	0.797
ASA classification, n (%)			0.069
I	446 (85.0)	38 (74.5)
II or greater	79 (15.0)	13 (25.4)
Blood loss, mL, mean ± SD	201.4±114.5	197.5±102.5	0.803
Operative time, min, mean ± SD	116.1±64.1	125.5±45.4	0.335
Drainage use, n (%)	369 (70.3)	34 (66.7)	0.590

Note: ^‡Chi-squared analysis and Student’s t-test were performed to analyze categorical and continuous variables comparisons, retrospectively.

Abbreviations: SD, standard deviation; ISS, injury severity score; ASA, American society of Anesthesiologists.

Table 2 Distribution Tests Regarding Serological Levels of the Inflammatory Biomarkers

Inflammatory Biomarkers	Shapiro–Wilk W	P value^‡
CRP (mg/l)	0.89	<0.001*
ESR (mg/l)	0.98	0.021*
MLR	0.94	<0.001*
NLR	0.97	0.001*
PLR	0.97	0.001*

Note: ^‡Shapiro–Wilk normality test. *Denotes statistical significance with p<0.05.

Abbreviations: MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio.

Table 3 Comparison of Serum Inflammatory Biomarkers in the FRI/ Non-FRI

Variables	Non-FRI (n=252)	FRI (n=51)	p-value^‡
Median CRP, mg/l (IQR)	7.73 (4.92–11.35)	24.89 (18.39–28.54)	<0.001*
Median ESR, mg/l (IQR)	21.45 (16.43–26.84)	28.15 (23.01–35.33)	<0.001*
Median MLR (IQR)	0.2 (0.14–0.26)	0.33 (0.25–0.47)	<0.001*
Median NLR (IQR)	2.69 (1.81–3.55)	5.18 (4.65–6.06)	<0.001*
Median PLR (IQR)	149.43 (118.13–195.55)	185.28 (133.24–224.50)	0.067

Note: ^‡Mann-Whitney U-test. *Denotes statistical significance with p<0.05.

Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; IQR, interquartile range.

Table 4 Comparison of Serum Inflammatory Biomarkers in the High-/Low-virulence Groups

Variables	Low-Virulence (n=23)	High-Virulence (n=28)	p-value^‡
Median CRP, mg/l (IQR)	18.62 (14.82–24.99)	27.96 (22.95–29.93)	<0.001*
Median ESR, mg/l (IQR)	25.54 (23.5–29.2)	30.03 (23.0–35.75)	0.264
Median MLR (IQR)	0.32 (0.26–0.42)	0.33 (0.24–0.50)	0.454
Median NLR (IQR)	4.87 (4.27–5.50)	5.29 (4.76–6.37)	0.068*
Median PLR (IQR)	163.74 (135.86–202.6)	199.42 (116.15–247.50)	0.256

Note: ^‡Mann-Whitney U-test. *Denotes statistically marginal significance with p<0.1.

Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; IQR, interquartile range.

Figure 2 The violin plot shows the distribution of serum CRP and NLR levels in high-/low-virulence groups. The black line in the center indicates the median, the dashed lines above and below indicate the range of data, and the width of the violin indicates the density of data within that range.

Table 5 The Diagnostic Value of Serum Biomarkers

Valuable	CRP	NLR	CRP + NLR
Sensitivity	0.735	0.634	0.913
Specificity	0.824	0.8	0.75
PPV	0.893	0.929	0.75
NPV	0.609	0.348	0.913
LR+	8.333	13	3
LR-	0.643	1.875	0.095
Cut-off value*	18.77	4.39	0.377
AUC (95% CI)	0.826 (0.716–0.936)	0.650 (0.498–0.802)	0.873 (0.776–0.972)
Youden index	0.502	0.277	0.663

Note: *The optimal cut-off value was obtained by calculating the maximum Youden index (sensitivity + specificity – 1).

Abbreviations: CRP, C-reactive protein; NLR, neutrophil-to-lymphocyte ratio; PPV, positive predictive value; NPV, negative predictive value; LR, likelihood ratio; AUC, area under curve; CI, confidence interval.

Figure 3 ROC of the CRP, NLR and CRP+NLR for high- /low-virulence FRI diagnosis.