Predictive Role of Biomarkers in COVID-19 Mortality.

Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in high mortality among patients in critical intensive care units. Hence, identifying mortality markers in the follow-up and treatment of these patients is essential. This study aimed to evaluate the relationships between mortality rates in patients with COVID-19 and the neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic inflammation response index (SII), and systemic inflammatory response index (SIRI). Methodology In this study, we assessed 466 critically ill patients diagnosed with COVID-19 in the adult intensive care unit of Kastamonu Training and Research Hospital. Age, gender, and comorbidities were recorded at the time of admission along with NLR, dNLR, MLR, PLR, SII, and SIRI values from hemogram data. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and mortality rates over 28 days were recorded. Patients were divided into survival (n = 128) and non-survival (n = 338) groups according to 28-day mortality. Results A statistically significant difference was found between leukocyte, neutrophil, dNLR, APACHE II, and SIRI parameters between the surviving and non-surviving groups. A logistic regression analysis of independent variables of 28-day mortality identified significant associations between dNLR (p = 0.002) and APACHE II score (p < 0.001) and 28-day mortality. Conclusions Inflammatory biomarkers and APACHE II score appear to be good predictive values for mortality in COVID-19 infection. The dNLR value was more effective than other biomarkers in estimating mortality due to COVID-19. In our study, the cut-off value for dNLR was 3.64.

Derived Neutrophil-Lymphocyte Ratio and C-Reactive Protein as Prognostic Factors for Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.

Objectives: To explore the relationship between peripheral blood inflammation parameters and overall survival (OS) and progression-free survival (PFS) of early-stage non-small cell lung cancer patients who underwent stereotactic body radiotherapy (SBRT). Patients and methods: In this study, eligible patients treated with SBRT from 2013 to 2018, and both serum complete blood count and blood biochemical results were available prior to (within 60 days) radiotherapy were included. Results: A review of hospital registries identified 148 patients, and the 5-year OS and PFS of the entire cohort were 69.8% and 65.6%, respectively, with the median follow-up time was 52.8 months. Multivariable analysis showed that derived neutrophil-lymphocyte ratio (dNLR) ≥1.4 and C-reactive protein (CRP) ≥2.9 were statistically and independently associated with worse OS (HR = 4.62, 95% CI 1.89-11.27, p = 0.001; HR = 2.92, 95% CI 1.49-5.70, p = 0.002, respectively). The 5-year OS for patients with dNLR below and equal to or above the 1.4 were 85.3% and 62.9% (p = 0.002), respectively, and 76.7% for the low CRP group versus 58.5% for the high CRP group (p = 0.030). Higher serum level of post-treatment CRP also independent parameters for inferior PFS (HR = 4.83, 95% CI 1.28-18.25, p = 0.020). Conclusions: Our results demonstrate that dNLR and CRP are associated with the outcomes of early-stage NSCLC patients treated with SBRT, which may assist in selecting optimal nursing care and therapeutic scheme for every individual.

Prognostic value of a novel dNLR-PNI score in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

There is currently limited information on the prognostic value of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte ratio [dNLR] and prognostic nutritional index [PNI]) score for patients with acute coronary syndrome (ACS). We aimed to explore the predictive value of a dNLR-PNI score on the long-term prognosis of patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 1773 patients with ACS who underwent PCI were consecutively enrolled from January 2016 to December 2018. The cutoff values of dNLR and PNI to predict major adverse cardiovascular events (MACE) were calculated using receiver operating characteristic curves. The patients were divided into three groups based on the dNLR-PNI score, and Kaplan-Meier curves and Cox regression models were used for survival analysis. The endpoints were MACE, including all-cause mortality and rehospitalisation for severe heart failure during follow-up. A total of 1542 patients with ACS who underwent PCI were included. Kaplan-Meier curves showed that a higher level of dNLR, PNI, or dNLR-PNI score was associated with a higher risk of MACE (all p < .001). In multivariate Cox regression models, the dNLR-PNI two score (hazard ratio 3.049, 95% confidence interval 1.503-6.184, p = .002) was found to be an independent predictor of all-cause mortality and rehospitalization for severe heart failure. A high dNLR-PNI score was independently associated with a higher risk of developing MACE in patients with ACS undergoing PCI. The dNLR-PNI score may be a useful prognostic parameter for identifying high-risk ACS patients after PCI.

A composite indicator of derived neutrophil-lymphocyte ratio and lactate dehydrogenase correlates with outcomes in pancreatic carcinoma patients treated with PD-1 inhibitors.

Background: There are currently no established biomarkers that can predict whether advanced pancreatic carcinoma (PC) patients would benefit from immune checkpoint inhibitors (ICIs). Our study investigated whether the pretreatment composite biomarker of derived neutrophil-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) can be used as a reliable prognostic factor for the survival of PC patients receiving PD-1 inhibitor therapy. Methods: Patients with advanced PC treated with PD-1 inhibitors at a single center from September 2015 to September 2020 were included. The high levels of dNLR (≥3) and LDH (≥250 U/L) were considered to be risk factors. Based on these two risk factors, patients in this study were categorized into two risk groups: the good dNLR-LDH group, without risk factors, and the intermediate/poor dNLR-LDH group, with one to two risk factors. Overall survival (OS) and progression-free survival (PFS) served as this study's primary and secondary endpoints. Cox regression models were used to identify independent prognostic factors for survival benefit. Results: There were 98 patients in our study. The good group included 61 (62.2%) patients and the intermediate/poor group included 37 (37.8%). The overall patients with PC who received immunotherapy had a median OS of 12.1 months, and the good dNLR-LDH group had a significantly longer OS compared with the intermediate/poor dNLR-LDH group (44.2 vs. 6.4 months; p < 0.010); median PFS was 3.7 and 2.5 months (p = 0.010). The number of metastatic sites >2 and immunotherapy as third-line or later was associated with worse PFS, and the line of immunotherapy and the dNLR-LDH indicator were independent prognostic factors for OS, according to multivariate analysis. Conclusion: The pretreatment composite biomarker of dNLR and LDH can be used as a prognostic biomarker in patients with advanced PC treated with PD-1 inhibitors.

Prognostic value of preoperative inflammatory markers among different molecular subtypes of lower-grade glioma.

BACKGROUND: The inflammatory response is closely related to cancer progression and prognosis. The aim of this study was to determine the prognostic value of preoperative inflammatory markers among different molecular subtypes of lower-grade glioma (LGG). METHODS: We performed a retrospective analysis of 214 patients with LGG from 2001 to 2013, evaluating the effect of the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR) and derived NLR (dNLR) on prognosis among different molecular subtypes. Isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promotor mutations were detected by gene sequencing, and Chromosome arms 1p and 19q (1p/19q) codeletion was estimated via fluorescence in situ hybridization. RESULTS: Survival analysis showed that a high NLR, low LMR, and high dNLR were associated with poor prognosis, while the PLR had no prognostic significance. The subsequent molecular subtype analysis indicated that a high NLR and dNLR predicted worse survival in the IDH mutation only group, a high NLR and PLR predicted worse survival in the IDH and TERT promoter mutation group, and a high PLR was associated with shorter survival in the triple-positive group. Furthermore, univariate and multivariate Cox regression analysis suggested that the dNLR was an independent prognostic factor for LGG. Finally, the prognostic nomogram was developed by integrating the inflammatory marker dNLR and independent clinical risk factors. CONCLUSION: The results of this study indicated that a high dNLR was an independent risk factor for overall survival rates in patients with LGG, which may increase prognostic accuracy and improve patient outcomes.

The Prognostic Value of a Derived Neutrophil-Lymphocyte Ratio in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

The systemic immune-inflammatory index (SII) and derived neutrophil-lymphocyte ratio (dNLR) are novel indexes that simultaneously reflect the host inflammatory and immune status and have prognostic value in some cancers. SII was associated with major cardiovascular events in coronary artery disease patients who received percutaneous coronary intervention (PCI). However, dNLR correlations with clinical outcomes in acute coronary syndrome (ACS) patients undergoing PCI remain unclear. This study aimed to elucidate the predictive values of SII and dNLR on the long-term prognosis of patients with ACS undergoing PCI. In total, 1,553 ACS patients undergoing PCI were consecutively enrolled from January 2016 to December 2018. The subjects were divided into high and low SII and dNLR groups for comparison (high vs. low). The SII and dNLR cutoff values for predicting major adverse cardiovascular events (MACE) were calculated using receiver operating characteristic curves, and Kaplan-Meier curves and Cox regression models were used for survival analyses. The endpoint was a MACE, which included all-cause mortality and rehospitalization for severe heart failure during follow-up. The Kaplan-Meier curves showed that a higher SII or dNLR value was associated with a higher risk of MACE (all P < 0.001). Multivariate Cox regression models showed that SII (hazard ratio [HR]: 2.545; 95% confidence interval [CI]: 1.416-4.574; P = 0.002) and dNLR (HR: 2.610, 95% CI: 1.454-4.685, P = 0.001) were independent predictors for MACE. dNLR may be a suitable laboratory marker to identify high-risk ACS patients after PCI.

Novel hematological biomarkers predict survival in renal cell carcinoma patients treated with nephrectomy.

INTRODUCTION: The association between novel blood-based inflammatory indices and patient survival has been reported with reference to various cancers. The aim of this study was to investigate the prognostic value of preoperative platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR) and lymphocyte-monocyte ratio (LMR) in patients with renal cell carcinoma (RCC) treated with nephrectomy. MATERIAL AND METHODS: From 2003 to 2012, 455 patients who underwent partial or radical nephrectomy for RCC were enrolled in the study. The study endpoints were overall survival (OS) and cancer-specific survival (CSS). RESULTS: The median follow-up was 70 months. Groups of patients with high levels of PLR, NLR and dNLR and a low level of LMR more often underwent radical nephrectomy, had a higher cancer stage in the TNM classification, and were more frequently diagnosed with tumor necrosis in histopathological examination. Both cancer-specific mortality and overall mortality were significantly higher in patients with high PLR, NLR and dNLR and low LMR. Multivariate analysis of CSS, adjusted for standard clinicopathological factors, identified only dNLR (p = 0.006) as an independent prognostic factor. PLR (p = 0.0002), dNLR (p = 0.0003) and NLR (p = 0.002), but not LMR (p = 0.1), achieved prognostic significance in multivariable analysis regarding OS. CONCLUSIONS: Only dNLR was an independent prognostic factor for CSS and OS. Nevertheless, our study indicates that all examined complete blood count-based biomarkers may be useful tools in managing RCC patients treated with a surgical approach.

Prognostic role of pretreatment derived neutrophil to lymphocyte ratio in urological cancers: A systematic review and meta-analysis.

BACKGROUND: To investigate the possible prognostic role of pretreatment derived neutrophil-lymphocyte ratio (dNLR) in urological cancers, including renal cell carcinoma (RCC), prostate cancer (PCa), and urothelial cancer (UCa). MATERIALS AND METHODS: Eligible studies were comprehensively searched from PubMed, Embase, Cochrane Library and Web of Science, up to April 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the relationships. RESULTS: A total of 12 studies embracing 6585 patients were included in the meta-analysis. Our results indicated that a higher pretreatment dNLR was associated with a decreased cancer-specific survival (CSS, HR 2.67, 95% CI 1.06-6.71, P = 0.037) and disease-free survival (DFS, HR 2.02, 95% CI 1.03-3.94, P = 0.040) in RCC, but not for overall survival (OS, HR 1.05, 95% CI 0.71-1.53, P = 0.818). A higher dNLR was associated with an inferior biochemical recurrence-free survival (BRFS, HR 1.70, 95% CI 1.00-2.87, P = 0.049) and OS (HR 1.35, 95% CI 1.20-1.51, P < 0.001) in PCa. A higher dNLR was associated with a worse OS (HR 1.29, 95% CI 1.03-1.61, P = 0.029) and CSS (HR 1.51, 95% CI 1.06-2.15, P = 0.024) in UCa, but not for DFS (HR 1.44, 95% CI 0.89-2.34, P = 0.139). CONCLUSION: A higher dNLR level was negatively associated with OS, CSS, DFS and BRFS, forecasting that it could be an independent prognosis predictor in urological cancers.

Prognostic significance of peripheral blood-derived neutrophil/lymphocyte ratio in patients with digestive cancer.

Accumulating studies reported the clinical value of derived neutrophil/lymphocyte ratio (dNLR) regarding the prediction of survival outcomes in digestive cancers, however, the prognostic significances of dNLR in these cancers were inconsistent. This study was carried out to clarify the relationship between circulating dNLR and prognosis in gastrointestinal (GI) cancers. Eligible publications were collected and extracted by searching Pubmed, Embase, Web of Science, and Google Scholar up to November 21, 2018. The prognostic impact of dNLR in subjects with GI cancers was assessed with the overall hazard ratios (HRs). A total of 26 studies with up to 13,945 participants were recruited. Our findings showed that peripheral blood dNLR before treatment could be a useful prognostic predictor in digestive cancers, an elevated dNLR indicated a shorter overall survival (OS) in GI tumors (HR, 1.44; 95% confidence interval [CI], 1.36-1.51). Furthermore, its significant prognostic value for OS was also confirmed in subgroup analyses stratified by disease type, publication year, type of research, detection method, geographic location, cut-off value, treatment, analysis type, follow-up time and disease stage. In addition, high dNLR was significantly associated with worse cancer-specific survival (HR, 1.25; 95% CI, 1.04-1.47) and inferior event-free survival (HR, 1.22; 95% CI, 1.11-1.33) in patients with digestive cancers. Our study showed elevated peripheral blood dNLR may indicate unfavorable outcomes in digestive cancer.

Clinical impacts of inflammatory markers and clinical factors in patients with relapsed or refractory diffuse large B-cell lymphoma.

BACKGROUND: Systemic inflammatory response can be associated with the prognosis of diffuse large B cell lymphoma (DLBCL). We investigated the systemic factors significantly related to clinical outcome in relapsed/refractory DLBCL. METHODS: In 242 patients with DLBCL, several factors, including inflammatory markers were analyzed. We assessed for the correlation between the survivals [progression-free survival (PFS) and overall survival (OS)] and prognostic factors. RESULTS: In these patients, a high derived neutrophil/lymphocyte ratio (dNLR) (PFS, HR=2.452, P=0.002; OS, HR=2.542, P=0.005), high Glasgow Prognostic Score (GPS) (PFS, HR=2.435, P=0.002; OS, HR=2.621, P=0.002), and high NCCN-IPI (PFS, HR=2.836, P=0.003; OS, HR=2.928, P=0.003) were significantly associated with survival in multivariate analysis. Moreover, we proposed a risk stratification model based on dNLR, GPS, and NCCN-IPI, thereby distributing patients into 4 risk groups. There were significant differences in survival among the 4 risk groups (PFS, P<0.001; OS, P<0.001). CONCLUSION: In conclusion, dNLR, GPS, and NCCN-IPI appear to be excellent prognostic parameters for survival in relapsed/refractory DLBCL.

Clinical impacts of inflammatory markers and clinical factors in patients with relapsed or refractory diffuse large B-cell lymphoma

BACKGROUND: Systemic inflammatory response can be associated with the prognosis of diffuse large B cell lymphoma (DLBCL). We investigated the systemic factors significantly related to clinical outcome in relapsed/refractory DLBCL.METHODS: In 242 patients with DLBCL, several factors, including inflammatory markers were analyzed. We assessed for the correlation between the survivals [progression-free survival (PFS) and overall survival (OS)] and prognostic factors.RESULTS: In these patients, a high derived neutrophil/lymphocyte ratio (dNLR) (PFS, HR=2.452, P=0.002; OS, HR=2.542, P=0.005), high Glasgow Prognostic Score (GPS) (PFS, HR=2.435, P=0.002; OS, HR=2.621, P=0.002), and high NCCN-IPI (PFS, HR=2.836, P=0.003; OS, HR=2.928, P=0.003) were significantly associated with survival in multivariate analysis. Moreover, we proposed a risk stratification model based on dNLR, GPS, and NCCN-IPI, thereby distributing patients into 4 risk groups. There were significant differences in survival among the 4 risk groups (PFS, P<0.001; OS, P<0.001).CONCLUSION: In conclusion, dNLR, GPS, and NCCN-IPI appear to be excellent prognostic parameters for survival in relapsed/refractory DLBCL.

The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy.

BACKGROUND AND PURPOSE: The derived neutrophil-lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. MATERIALS AND METHODS: 258 patients were randomised to receive dCRT±cetuximab. Kaplan-Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). RESULTS: An elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29-2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17-2.29], p=0.004). Median OS was 36months (95% CI 27.8-42.4) if dNLR<2 and 18.4months (95% CI 14.1-24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. CONCLUSIONS: An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479].

Association of the Derived Neutrophil-Lymphocyte Ratio With Critical Limb Ischemia.

Neutrophil and leukocyte counts are laboratory parameters that reflect the systemic inflammatory response in patients with atherosclerotic diseases. Based on the means of these parameters, the derived neutrophil-lymphocyte ratio (dNLR) can be calculated. We investigated a possible association of critical limb ischemia (CLI) and the dNLR in patients with peripheral arterial disease (PAD). We performed a retrospective data analysis including 1995 patients with PAD treated at our department in the years 2005 to 2010. The cohort was divided into tertiles according to dNLR. Higher dNLR values were associated with an increased CLI rate. In the tertile with lowest dNLR, the CLI rate was 20.4%, in the second tertile the CLI rate was 26.1%, and in the third tertile the CLI rate was 36.1%. Statistical significance was shown using a Jonckheere-Terpstra test (P < .001). A high dNLR is associated with an increased rate of CLI in patients with PAD. This might be a useful parameter to highlight patients at increased risk of CLI.

The derived neutrophil/lymphocyte ratio predicts poor clinical outcome in soft tissue sarcoma patients.

BACKGROUND: Inflammation plays an important role in tumor proliferation and survival in cancer patients. The aim of this study was to investigate the prognostic impact of the pre-operative-derived neutrophil/lymphocyte ratio (dNLR) in a large cohort of soft tissue sarcoma (STS) patients after curative surgical resection. METHODS: The impact of preoperative dNLR on disease-free survival (DFS) and overall survival (OS) in retrospectively evaluated 340 STS patients was assessed using Kaplan-Meier curves and Cox proportional models. RESULTS: Applying receiver operating curve analysis, we determined a cut-off value of 2.39 for the dNLR to be optimal for discrimination of patients' survival in the whole cohort. Kaplan-Meier curves revealed a dNLR greater than or equal to 2.39 as a marker for decreased DFS (P = .031) and OS (P = .007, log-rank test) in STS patients. In multivariate analysis, increased dNLR was significantly associated with poor OS (hazard ratio 1.60, 95% confidence interval 1.07 to 2.40, P = .022). CONCLUSIONS: This study demonstrates that preoperative dNLR might represent a well-correlated surrogate marker for the widely validated NLR. The dNLR is easily obtainable and can provide important information for individual risk assessment in clinical trials.