Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Predict Mortality in Patients with Diabetic Foot Ulcers Undergoing Amputations

Abstract

Purpose Elevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with poor outcomes in various diseases. The objectives of this study were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with diabetic foot ulcers (DFU) undergoing amputations. Patients and Methods A retrospective observational study was performed that included a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause death. According to the PLR and NLR cut-off values, patients were divided into two groups and Kaplan–Meier survival curves were constructed. Multivariable Cox regression was conducted to test the independent predictors of mortality in the study cohort. Results All-cause mortality was significantly higher in patients with a high PLR/NLR compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS) rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively ( p =0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were 85.2%, 58.6% and 23.9% ( p <0.001). According to the multivariate analysis, age (HR 1.074, 95% CI 1.045–1.104, p<0.001), Wagner classification (HR 2.274, 95% CI 1.351–3.828, p=0.002), PLR (HR 1.794, 95% CI 1.014–3.174, p=0.045), NLR (HR 2.029, 95% CI 1.177–3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001–1.004, p<0.001) and direct bilirubin (HR 1.154, 95% CI 1.081–1.232, p<0.001) were independent predictors of mortality following amputation. Conclusion Postoperative PLR and NLR values may be reliable predictive biomarkers of 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 practice.

Clinical, microbiological and inflammatory markers of severe diabetic foot infections

“…20 Another study reported that NLR and PLR were predictive factors of mortality following amputation. 19 However, mortality in that study was determined at 1, 3 and 5 years after amputation and whether NLR and PLR were determined at baseline or monitored during follow-up was not stated in the methods of the study. 19 This association should be clarified by further studies.…”

“…19 However, mortality in that study was determined at 1, 3 and 5 years after amputation and whether NLR and PLR were determined at baseline or monitored during follow-up was not stated in the methods of the study. 19 This association should be clarified by further studies. Neither PLR nor LMR were predictive factors for severe infections in either univariate or multivariate analysis in our experience.…”

Diabetic Wound-Healing Science

“…Studies have also shown that the severity of DFUs may be in part determined by the deficiency of the immune response in DFUs via deregulation of IL-6, macrophage migration inhibitory factor (MIF), and interferon-inducible protein (IP)-10 [ 118 ], and a compromised neutrophil response [ 119 , 120 , 121 ]. In recent years, it has been proposed that high platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte ratios (NLR) may be a biomarker for DFU severity [ 122 , 123 ], where high PLR levels reflect the increased platelet activity, inflammation, and the risk for thrombosis and atherogenesis [ 122 , 124 , 125 ], while high NLR levels lead to the upregulation of cytokines and of proteolytic enzymes that can cause tissue damage [ 122 , 123 ].…”

“…While a full evaluation of DFU biomarkers is outside the scope of this review, briefly, some recent reports of wound exudate biomarkers for DFU wound healing include epithelial neutrophil-activating protein (ENA)-78 [ 254 ], c-x-c motif chemokine ligand 6 (CXCL6) [ 255 ], and MMP-9 [ 256 ]. A number of serum biomarkers have been identified, including albumin [ 257 ], PLR and NLR [ 122 , 258 ], angiopoietin-like 2 (ANGPTL2) [ 259 ], lipoprotein-associated phospholipase A2 and interleukin-18 (IL-18) [ 260 ], pentraxin 3 [ 261 ], T-cell differentiation markers [ 262 ], stem/progenitor cells [ 263 ], as well as neutrophil extracellular traps (NETs)-specific markers [ 264 ]. Recent genomic analyses of DFU have utilized circRNAs [ 265 , 266 , 267 ], lncRNAs [ 268 ], miRNAs [ 99 , 100 , 269 ], genetic polymorphisms [ 270 , 271 , 272 ], cytokine arrays [ 273 ], and network maps [ 274 ] for the identification of other potential biomarkers for DFU diagnosis and prognosis.…”

Trends in the development of Medicine, Biology and Pharmacy

“…Increased NLR levels indicate endothelial damage and dysfunction as a result of increased neutrophil secretory activity, which can lead to an unfavorable prognosis in CVD [335]. According to the literature, in modern cardiology, studies have shown that NLR is an independent predictor of outcome in patients with stable coronary heart disease and a predictor of short -and long-term mortality in patients with acute coronary syndromes ((ST-segment elevation myocardial infarction) (STEMI)) and heart transplantation [333].…”