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ORIGINAL RESEARCH

Neutrophil-to-Lymphocyte Ratio and

Platelet-to-Lymphocyte Ratio Predict Mortality in
Patients with Diabetic Foot Ulcers Undergoing
Amputations
This article was published in the following Dove Press journal:
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy

Wenwen Chen 1, * Purpose: Elevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio
Kun Chen 2, * (NLR) are associated with poor outcomes in various diseases. The objectives of this study
Zhixiao Xu 3 were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with
Yepeng Hu 1 diabetic foot ulcers (DFU) undergoing amputations.
Patients and Methods: A retrospective observational study was performed that included
Yiying Liu 1
a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause
Wenyue Liu 1
death. According to the PLR and NLR cut-off values, patients were divided into two groups
Xiang Hu 1
and Kaplan–Meier survival curves were constructed. Multivariable Cox regression was
Tingting Ye 1 conducted to test the independent predictors of mortality in the study cohort.
Jing Hong 1 Results: All-cause mortality was significantly higher in patients with a high PLR/NLR
Hong Zhu 1 compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS)
Feixia Shen 1 rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively
1
Department of Endocrinology and (p=0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were
Metabolism, The First Affiliated Hospital 85.2%, 58.6% and 23.9% (p<0.001). According to the multivariate analysis, age (HR 1.074,
of Wenzhou Medical University,
95% CI 1.045–1.104, p<0.001), Wagner classification (HR 2.274, 95% CI 1.351–3.828,
Wenzhou, People’s Republic of China;
2
Department of Thoracic Surgery, The p=0.002), PLR (HR 1.794, 95% CI 1.014–3.174, p=0.045), NLR (HR 2.029, 95% CI
First Affiliated Hospital of Wenzhou 1.177–3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001–1.004, p<0.001) and direct
Medical University, Wenzhou, People’s
Republic of China; 3Department of bilirubin (HR 1.154, 95% CI 1.081–1.232, p<0.001) were independent predictors of mortal­
Pulmonary and Critical Care Medicine, ity following amputation.
The First Affiliated Hospital of Wenzhou Conclusion: Postoperative PLR and NLR values may be reliable predictive biomarkers of
Medical University, Wenzhou, People’s
Republic of China mortality in patients following amputation for DFU. Considering the high mortality in those
patients, the patients with elevated PLR/NLR should be given more intensive in clinical
*These authors contributed equally to
practice.
this work
Keywords: amputation, platelet-to-lymphocyte ratio, PLR, neutrophil-to-lymphocyte ratio,
NLR, diabetic foot ulcer, mortality

Introduction
The prevalence of diabetes has been rising rapidly throughout the world. In 2019, the
Correspondence: Feixia Shen International Diabetes Federation (IDF) estimated that the prevalence of diabetes in
Department of Endocrinology and
Metabolism, The First Affiliated Hospital adults aged 18–99 years was approximately 9.3% and further predicted this to rise to
of Wenzhou Medical University, 10.9% by 2045.1 Foot ulcer is a major complication of diabetes and the risk of developing
Wenzhou, People’s Republic of China
Email [email protected] a diabetic foot ulcer (DFU) is around 25% during the lifetime of a diabetic patient.2

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Moreover, DFUs are associated with higher rates of lower cause death and these data were obtained from medical
extremity amputation (LEA) with the rate being 15-to 40- records or by telephone interviews. Patient data includ­
fold higher than in patients with DFUs compared to the gen­ ing demographic variables (age and sex), anthropometric
eral population.3 The mortality rate of patients following parameters (height and weight), type of diabetes, disease
amputation is also very high and at 5 years can reach 80% duration, history of previous amputations, history of
which is worse than that observed in several types of smoking, and alcohol abuse were collected from indivi­
cancers.4,5 Improving the management of patients with dual medical records upon admission according to spe­
DFUs remains critical towards reducing the mortality rate of cified definitions. All patients were examined to grade
patients and improved biomarkers to predict mortality rates the severity of infection according to the Infectious
following amputation due to DFUs are urgently required. Diseases Society of America and the International
Neutrophil–lymphocyte ratio (NLR) and platelet-to- Working Group on the Diabetic Foot (IDSA-IWGDF)
lymphocyte ratio (PLR) are novel biomarkers of systemic criteria. Foot ulcers were graded according to the
inflammation that can be obtained from routine blood exam­ Wagner’s classification12 which was used according to
inations and can be easily implemented into clinical practice. the ulcer depth and the presence of osteomyelitis or
It has been demonstrated that PLR and NLR are significant gangrene. Amputations below the ankle were classified
inflammatory markers that can predict mortality in popula­ as minor amputations whilst higher amputations were
tions suffering from cardiovascular diseases and cancers.6–9 defined as major amputations. PLR was calculated as
The exact mechanism through which high PLR/NLR results the ratio of platelets to lymphocytes and NLR calculated
in enhanced mortality remains unclear yet it is most likely as the ratio of the neutrophil to lymphocytes. BMI was
that inflammation plays an important role. Recently, PLR and calculated as body weight divided by the square of the
NLR have also been reported to have predictive power in height.
diabetic complications.10,11 To our best of knowledge, the
association between PLR/NLR and all-cause mortality after
amputation in DFU patients has not yet been reported. This Statistical Analysis
study aimed to determine the potential role of PLR and NLR Continuous variables are presented as the mean ± SD
as predictors of mortality in DFU patients following LEA. and were compared using a Student’s t-test. The cate­
gorical variables are presented as frequencies and per­
centages and were analyzed using the Pearson’s χ2-test.
Patients and Methods The predictive values of PLR and NLR for the primary
Study Population endpoint were also evaluated by calculating the area
This retrospective cohort study included 348 adult patients under the curve (AUC) from the receiver operating
to explore the predictive value of NLR and PLR on all- characteristic (ROC) curves. Patients were divided into
cause mortality in DFU patients following LEA. For our two groups based on the cut-off values of the PLR and
analysis, the following inclusion criteria were used: (1) NLR. Survival analysis was estimated using the Kaplan–
patients diagnosed with type 2 diabetes mellitus and dia­ Meier survival curves and differences between the sur­
betic foot ulcers, and (2) patients who had consented to vival curves assessed using a Log rank test. Univariate
receive amputation at The First Affiliated Hospital of and multivariate survival analyses were conducted using
Wenzhou Medical University between 2015 and 2019. the Cox proportional hazards model. In the multivariate
Patients were excluded according to the following criteria: Cox model, the predictor was included based on the
(1) patients who lacked laboratory or follow-up data, (2) score and the best selection criteria. The independent
patients with severe systemic infections or blood diseases association between PLR/NLR and mortality were iden­
that affect neutrophils and lymphocytes, and (3) patients tified by multivariate Cox regression analysis and the
with complications including serious dysfunctions of the variables which showed significant associations with
heart, lung, kidney, brain and other organs. survival in univariate Cox analysis were included. All
statistical analyses were performed using the IBM SPSS
Methods and Calculations 25.0 software for Windows. Statistical tests and 95%
Three hundred and forty-eight patients were eligible for confidence intervals (CIs) were 2-sided, with
inclusion in the study. The primary end-point was all- a significance level of 0.05.

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Results mean ages of 65.37±9.61 years and 68.23±9.51 years,

Baseline Demographic and Clinical respectively. Amongst all patients, 314 (90.23%) had per­
Characteristics ipheral arterial disease, 269 (77.29%) patients had hyper­
Three hundred and forty-eight patients were recruited to tension, 25 (7.2%) patients had coronary heart disease, 34
the study that included 228 males and 120 females, with (9.7%) patients had cerebral vascular disease, 119 (34%)

Table 1 Summary of Baseline Patient Characteristics

High PLR N=200 Low PLR N=148 High NLR N=155 Low NLR N=193

Clinical Parameters N (N% or SD) N (N% or SD) p-value N (N% or SD) N (N% or SD) p-value

Age 67.31±9.49 65.07±9.77 0.033 68.11±9.74 64.95±0.68 0.002

Sex 0.813 0.216

Male 130(65%) 98(66.21%) 107(69.03%) 121(62.69%)
Female 70(35%) 50(33.78%) 48(30.97%) 72(37.3%)

BMI, kg/m2 22.65±6.25 23.64±4.02 0.101 23.04±5.24 23.04±5.51 0.852

SBP (mmHg) 145.31±22.86 142.46±24.40 0.269 143.87±24.03 144.28±23.18 0.873

DBP (mmHg) 74.98±12.91 76.18±12.55 0.383 74.84±13.66 76.01±13.66 0.398

Duration of diabetes (years) 12.46±8.22 12.16±7.2 0.417 13.18±8.286 11.65±7.296 0.007

Coronary heart disease 16(8%) 9(6.08%) 0.493 12(7.74%) 13(6.73%) 0.436

Cerebral vascular disease 20(10%) 14(9.45%) 0.867 19(12.25%) 15(7.77%) 0.158

Lower extremity arterial diseases 180(90%) 130 (90.5%) 0.867 138(89.03%) 176(91.19%) 0.500

Wagner classification 0.01 0.110

2 and 3 79(39.5%) 79(53.37%) 63(40.65%) 95(49.22%)
4 and 5 121(60.5%) 69(46.63%) 92(59.35%) 98(50.78%)

Smoking history (current or ever) 67(33.5%) 52(35.1%) 0.751 54(34.83%) 65(33.68%) 0.821

Prior history of amputation 23(14.7%) 10(8.3%) 0.168 16(10.32%) 22(11.39%) 0.749

Laboratory data
HbA1c% 9.49±2.29 9.63±2.39 0.598 9.42±2.38 9.62±2.25 0.472

FBG 8.99±3.11 8.57±3.15 0.265 9.30±3.26 8.56±3.10 0.033

White blood cell 7.06±2.66 6.57±1.98 0.055 8.22±2.60 5.826±1.60 0.004

Mean platelet volume 9.83±1.02 10.53±1.09 <0.001 9.94±1.15 10.29±1.06 <0.001

Fibrinogen 7.16±1.82 6.09±1.90 <0.001 6.95±1.84 6.51±1.97 0.037

Total bilirubin 7.48±3.15 8.39±5.21 0.062 7.46±3.6 8.19±4.57 0.103

Direct bilirubin 3.45±1.94 3.81±3.28 0.195 3.55±2.79 3.64±2.43 0.738

Indirect bilirubin 4.03±1.74 4.57±2.79 0.38 3.91±1.60 4.54±2.65 0.006

Albumin 30.7±5.39 32.24±4.71 0.006 30.3±4.97 32.19±5.17 0.001

Creatinine 136.51±163.12 108.01±141.7 0.083 158.65±189.36 96.87±113.33 <0.001

Uric acid 295.03±118.54 294.11±99.2 0.939 314.65±124.56 278.50±95.23 0.003

Blood urea nitrogen 7.73±7.94 6.674±3.71 0.024 8.41±5.25 6.37±3.51 <0.001

Note: Data are presented as the means ± standard deviation (SD), the median (interquartile range) for continuous variables or the number (%) for categorical variables.
Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose.

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patients were smokers, 102 (29.1%) patients were drinkers fibrinogen, albumin, creatinine, blood urea nitrogen
and 38 (10.9%) patients had prior histories of amputation. (BUN), and uric acid (UA). In the high NLR group, age,
The mean values of PLR and NLR were 189.96±87.10, FBG, and WBC were significantly higher and the duration
and 3.21±2.59, respectively. According to the cut-off value of diabetes was longer compared to the low NLR group.
of the PLR, 148 (42.53%) subjects were included in the low Also, WBC, fibrinogen, creatinine, and uric acid were
PLR group (PLR<160.05), whereas the remaining 200 significantly higher in the high PLR group. Albumin,
(57.47%) subjects were included the high PLR group indirect bilirubin and MPV were significantly higher in
(PLR≥160.05). From the cut-off value of the NLR, two the low NLR group. All other parameters were not statis­
groups were defined as the high (NLR≥2.76) and low tically different across the patient groups.
(NLR<2.76) NLR groups that contained 155 and 193 ROC curve analysis suggested that the optimum PLR
patients, respectively. The demographic characteristics and (AUC = 0.598, 95% CI 0.530–0.667) cut-off point for
laboratory findings of patients are summarized in Table 1. predicting mortality was 160.05, with a sensitivity of
73.1% and specificity of 47%. Similar analysis showed
The results indicated that when the patients were sepa­
the optimum NLR (AUC = 0.679, 95% CI 0.612–0.746)
rated into two groups according to the PLR cut-off value,
cut-off point for predicting mortality was 2.76, with
significant differences were observed in the Wagner classifi­
a sensitivity of 69.2% and specificity of 62.6% (Figure 1).
cation (p=0.01), mean platelet volume (MPV) (p<0.001),
fibrinogen (p<0.001), albumin (p=0.006). Fibrinogen and
Predictors of Mortality After Amputation
the grade of Wagner classification were significantly higher
A Log rank test of the Kaplan–Meier curves indicated that
in the high PLR group, whilst albumin and MPV were sig­
patients in the high PLR and NLR groups had a lower OS
nificantly higher in the low PLR group. All other parameters
rate compared to patients in the low PLR and NLR groups
were not statistically different across the patient groups.
(Figure 2). In the low NLR group, OS rates at 1, 3, and 5
When the patients were separated into two groups
years after amputation were 96.8%, 84%, 80.1%, respec­
according to the NLR cut-off value, significant differences
tively. In the high NLR group, the corresponding OS rates
were observed in the following variables: age, duration of
at 1, 3, and 5 years after amputation were 85.2%,58.6% and
diabetes mellitus, fasting blood glucose (FBG), white 23.9% (p<0.001). The median survival time in the high
blood cell (WBC), mean platelet volume (MPV), NLR group was 50±3.68 months (95% CI 42.78–53.22) .
The OS rates at 1, 3, and 5 years after amputation in low
PLR group were 95.7%, 83.9% and 74.8%, respectively. In
the high PLR group, the corresponding OS rates at 1, 3, and
5 years after amputation were 88.6%, 64.5% and 47.6%
(p=0.001). Patients were also divided into two groups based
on the cut-off values of the neutrophil, the reciprocal of the
lymphocyte and platelet counts, respectively. Patients in the
high neutrophil groups had a lower OS rate compared to
patients in the low neutrophil groups. In the low reciprocal
of the lymphocyte group, OS is higher, while the result of
platelet was not significant (Supplementary Figure 1).
As shown in Table 2, univariate Cox regression analy­
sis suggested that OS was associated with the following
variables: age, Wagner classification, creatinine, systolic
blood pressure (SBP), PLR, NLR, direct bilirubin, UA,
blood urea nitrogen (BUN). After adjusting other co-
Figure 1 ROC curves for predicting the primary endpoint (all-cause mortality) for
variates, the HR of UA, BUN and SBP became non-
baseline NLR and PLR. The optimum cut-off values were NLR ≥ 2.76 (sensibility significant, whereas the direct bilirubin became significant.
69.2%, specificity 62.6%) and PLR ≥ 160.05 (sensibility 73.1%, specificity 47%).
Abbreviations: ROC, receiver operating characteristic; NLR, neutrophil-to- The age, Wagner classification, PLR, NLR, creatinine
lymphocyte ratio; PLR, platelet-to-lymphocyte ratio. remained significant predictors in the multivariate models.

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Dovepress Chen et al

Figure 2 Kaplan–Meier analysis showing cumulative mortality according to the optimal cut off value. (A) Platelet-to-lymphocyte ratio (160.05). (B) Neutrophil-to-
lymphocyte ratio (2.76).
Abbreviation: OS, overall survival.

Discussion Many studies have focused on total bilirubin function and

This retrospective study investigated the values of postopera­ have not differentiated direct and indirect bilirubin from total
tive PLR and NLR in predicting all-cause death following bilirubin. Chen et al demonstrated that indirect but not direct
amputation in DFU. As expected, the patients undergoing bilirubin were independent risk factors for the severity of
LEA in our study had high mortality (mean survival 48.946 diabetic foot20 whilst Wang et al found that direct bilirubin
±1.369 months), which is consistent with previously but not indirect bilirubin levels were associated with
reported13–15. Thus, the independent prognostic factors that increased risk of type 2 DM.21 Accordingly, further studies
used for predicting mortality in DFU patients undergoing are required to accurately determine the differential effects of
LEA are vital. Considering the association of postoperative different types of bilirubin.
PLR and NLR are increasingly recognized as systemic
NLR and PLR with higher mortality, we purpose using post­
markers of overall inflammation.22 Inflammation, procoagu­
operative PLR and NLR as independent prognostic markers
lant imbalance and endothelial dysfunction play important
to predict mortality in DFU patients LEA.
roles in the development of diabetes and diabetic complica­
In agreement with previous studies, we demonstrated that tions. Inflammatory disorders often cause tissue damage,
increased age, higher Wagner grade and renal disease are microangiopathy and macrovascular complications in diabetic
associated with mortality in diabetic patients after LEA.16–18 patients,10,23,24 often leading to end-organ damage that is asso­
In the multivariate Cox regression analysis, we have adjusted ciated with mortality. Also, cardiovascular events are
the age, Wagner classification, creatinine, PLR and NLR. a frequent cause for mortality in patients with DM.25 DFU is
Although patients in the higher NLR/PLR group were older a complex generalized disease that is the main reason for LEA
with a higher burden of comorbidities, this association in diabetic patients and patients requiring LEA often suffer
remained significant in multivariate analysis. We also found from more severe cardiovascular diseases.26 There is also
that direct bilirubin was independently associated with mor­ a close connection between mortality and infectious complica­
tality (HR 1.154, 95% CI 1.081–1.232, p=0.006). tions such as, sepsis, pneumonia. DFU patients with LEA,
As a potent endogenous antioxidant, bilirubin inhibits always come with tissue necrosis, systemic infection, and
lipid peroxidation and is associated with diabetes and many inflammation, which can increase mortality. Based on these
diabetic complications in several cross-sectional studies.19,20 observations, the adoption of PLR and NLR should be con­
However, the potential protective effect of bilirubin in dia­ sidered as important predictive tools of mortality in these
betes and diabetic complications remains controversial. patients.

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Table 2 Univariate and Multivariate Analyses of the Overall Survival of Patients with Diabetic Foot Ulcers Undergoing Amputations
Covariate Univariate Multivariate

HR (95% CI) p-value HR (95% CI) p-value

Age 1.072(1.045–1.099) <0.001 1.074(1.045–1.104) <0.001

Sex
Male 1 - -
Female 0.960(0.597–1.545) 0.868 - -

Coronary heart disease 1.360(0.653–2.830) 0.411 -

Cerebral vascular disease 0.862(0.375–1.985) 0.728 - -

Wagner classification
2 and 3 1 - -
4 and 5 2.366(1.443–3.878) <0.001 2.274(1.351–3.828) 0.002

Smoking history (current or ever) 0.700(0.427–1.147) 0.157 - -

Prior history of amputation 1.002(0.515–1.948) 0.996 - -

Systolic blood pressure (mmHg) 1.017(1.005–1.028) 0.005 1.007(0.997–1.018) 0.149

Diastolic blood pressure (mmHg) 1.003(0.984–1.022) 0.775 - -

PLR≥ 155.41 3.335(2.059–5.402) <0.001 1.794(1.014–3.174) 0.045

NLR≥ 3.06 2.224(1.347–3.670) 0.002 2.029(1.177–3.499) 0.011

FBG 0.962(0.888–1.043) 0.347 - -

Platelet 1.000(0.998–1.002) 0.840 - -

Mean platelet volume 0.952(0.780–1.162) 0.627 - -

Fibrinogen 1.052(0.934–1.185) 0.399 - -

Total bilirubin 1.007(0.953–1.064) 0.797 - -

Direct bilirubin 1.069(0.998–1.144) 0.055 1.154 (1.081–1.232) <0.001

Indirect bilirubin 0.909(0.796–1.038) 0.159 - -

Albumin 0.984(0.943–1.028) 0.474 - -

Creatinine 1.002(1.002–1.003) <0.001 1.003(1.001–1.004) <0.001

Uric acid 1.003(1.002–1.005) <0.001 1.001(0.999–1.003) 0.277

BUN 1.086(1.052–1.122) <0.001 0.998(0.931–1.071) 0.964

Note: In the multivariate model, the following variables were added as independent variables: age, Wagner classification, PLR, NLR, creatinine, direct bilirubin, uric acid and
blood urea nitrogen.
Abbreviations: HR, hazard ratio; CI, confidence interval; SBP, systolic blood pressure; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; BUN, blood
urea nitrogen; FBG, fasting blood glucose.

Growing evidence has shown that PLR and NLR are for mortality have demonstrated the predictive value of
associated with an increase in all-cause mortality risk in these markers. Zeng et al demonstrated that elevated PLR
the general population and patients with cardiovascular was independently associated with an increased 5-year all-
disease and cancers.8,9,27,28 In the present study, it was cause mortality risk in patients with chronic kidney disease
shown that patients with elevated postoperative PLR or (CKD).29 Hudzik et al reported that the PLR is an inde­
NLR were independently associated with increased risk of pendent risk factor for early and late mortality in patients
mortality. Most studies that have evaluated NLR and PLR with DM.30 The results of the current study are consistent

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Dovepress Chen et al

with other reports demonstrating that higher NLR and PLR In the present study, we also performed a comparison
values are associated with increased mortality rates. of the NLR and PLR biomarkers of inflammation.
A high PLR occurs when the platelet counts become Although both markers have shown predictive value in all-
high or when lymphocyte count becomes low. In gen­ cause mortality, few studies have directly compared their
eral, high platelet counts are associated with increased predictive power. We have found that although PLR was
platelet activity.31 Studies have shown that increased shown to be an independent risk factor for high mortality
platelet activity may reflect the aggravated release of risk, NLR was more sensitive and was a more useful
inflammatory mediators and to promote the destructive marker in the ROC curve. As shown in Figure 1, the
inflammatory process.32 High platelet counts represent discriminatory performance for predicting the primary
increased thrombosis and the release of mediators which endpoint was better for NLR (AUC = 0.679, 95% CI
enhance atherosclerosis and inflammation. It may indi­ 0.612–0.746) than for PLR (AUC=0.598, 95% CI 0.530–­
cate ongoing inflammatory conditions and prothrombotic 0.667). Considering the association between PLR/NLR
activities. Research findings suggest that platelet hyper­ and worse outcomes in DFU patients undergoing LEA,
activity in parallel with thrombosis has a principal role PLR and NLR can be used as prognostic biomarkers,
in the pathophysiology of atherogenesis33 and the sig­ allowing physicians to generate a risk estimate of survival
after LEA.
nificant action in creating illness and death from athero­
We acknowledge our study had several limitations.
sclerosis is due to platelet adhesion and aggregation at
Firstly, the present trial was performed as a retrospective,
the site of endothelial damage or the site of rupture of
single-center study design with a relatively small sample
atherogenic plaque. The second constituent of PLR is
size. The results may therefore not accurately represent the
the lymphocyte-count which highly influences inflamma­
general population of patients with diabetes-related ampu­
tory states. During systemic inflammation, lymphocytes
tations. Second, we did not compare PLR and NLR with
exert a modulatory effect on the inflammatory response
other inflammatory markers (such as C-reactive protein or
and lymphocytopenia occurs as a result of accelerated
myeloperoxidase) because they were not routinely
apoptosis in lymphocytes. Lymphocytes could also
obtained in our study. Lastly, patient information was
induce the expression of interleukin-10 and promote
obtained from medical records or by telephone interviews
tissue repairment.34 These results emphasize the value
and in most cases, the cause of death could not be verified.
of PLR in predicting outcomes in LEA patients.
A larger and prospective study is required to highlight the
NLR is a biomarker that can be used to evaluate the
clinical importance and to further validate PLR and NLR
inhibitory and excitatory activities of the immune system.
as predictive biomarkers in DFU patients.
Neutrophils could infiltrate vascular wall and secretion of
superoxide radicals, cytokines, and a variety of proteoly­ Conclusions
tic enzymes which can cause endothelial damage, whilst In our study, we found that an increased PLR and NLR
lymphocytes can modulate the effect of neutrophils and levels were reliable predictive biomarkers of mortality in
also have an anti-atherosclerotic role. A high NLR repre­ DFU patients following LEA. Both of them can be easily
sents endothelial damage and dysfunction as a result of obtained from simple complete blood count parameters in
higher neutrophilic activity that can lead to worse out­ clinical practice. Considering the high mortality in DFU
comes. In the study from Dinc et al, it was shown that patients undergoing LEA, we purpose using postoperative
higher NLR was related to increased mortality in patients PLR and NLR to predict mortality and the patients with
who underwent LEA.35 Spark et al also reported that elevated PLR/NLR should be given more intensive and
elevated NLR is associated with higher mortality in longer duration therapy aiming to more aggressively con­
patients with chronic critical limb ischemia (CLI).36 In trol other risk factors.
our study, after adjusting for several risk factors includ­
ing age, Cr, Wagner classification, BUN, and UA, NLR Ethic Statement
could predict mortality rates in DFU patients. These This study has been reviewed by the ethics committee in
results emphasize the value of NLR in assessing the clinical research of the First Affiliated Hospital of
inflammatory mechanisms in response to infection in Wenzhou Medical University. Due to the retrospective
predicting outcomes in LEA patients. nature of the study, the informed consent was exempted.

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In conducting this clinical study, we compliance with the 11. Turkmen K, Erdur FM, Ozcicek F, et al. Platelet-to-lymphocyte ratio
better predicts inflammation than neutrophil-to-lymphocyte ratio in
ethical principles of the relevant laws, regulations and end-stage renal disease patients. Hemodial Int. 2013;17(3):391–396.
rules of China, WMA Helsinki Declaration and the ethical doi:10.1111/hdi.12040
review measures for biomedical research involving 12. Wagner FW. The dysvascular foot: a system for diagnosis and
treatment. Foot Ankle. 1981;2(2):64–122. doi:10.1177/
humans (2016) of the Ministry of Health. The study fol­ 107110078100200202
lowed a clinical protocol approved by local ethics com­ 13. López-Valverde ME, Aragón-Sánchez J, López-de-Andrés A, et al.
Perioperative and long-term all-cause mortality in patients with dia­
mittee. This study also protected the health and rights of
betes who underwent a lower extremity amputation. Diabetes Res
patients and the patient data were confidentiality. Clin Pract. 2018;141:175–180. doi:10.1016/j.diabres.2018.05.004
14. Wrobel JS, Herman WH, Munson M, et al. Foot complications and
mortality. J Am Podiatr Med Assoc. 2016;106(1):7–14. doi:10.7547/
Acknowledgment 14-115
The authors thank the staff at the Department of 15. Lopez-de-Andres A, Jimenez-Garcia R, Esteban-Vasallo MD, et al.
Time trends in the incidence of long-term mortality in T2DM patients
Endocrinology and Metabolism, the First Affiliated who have undergone a lower extremity amputation. Results of
Hospital of Wenzhou Medical University, and all the a descriptive and retrospective cohort study. J Clin Med. 2019;8
(10):1597. doi:10.3390/jcm8101597
patients who participated in the study.
16. Jupiter DC, Thorud JC, Buckley CJ, et al. The impact of foot ulcera­
tion and amputation on mortality in diabetic patients. I: from ulcera­
tion to death, a systematic review. Int Wound J. 2016;13(5):892–903.
Disclosure doi:10.1111/iwj.12404
The authors report no conflicts of interest in this work. 17. Icks A, Scheer M, Morbach S, et al. Time-dependent impact of
diabetes on mortality in patients after major lower extremity amputa­
tion: survival in a population-based 5-year cohort in Germany.
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