Neutrophil-to-lymphocyte Ratio In Blood Research Articles

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study

BackgroundPeriprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA).MethodsWe performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated.ResultsCompared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688–0.823), 0.758 (95% CI: 0.687–0.821), 0.714 (95% CI: 0.639–0.781), 0.709 (95% CI: 0.634–0.777), 0.723 (95% CI: 0.649–0.789), and 0.728 (95% CI: 0.654–0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499–0.653) and 0.694 (95% CI: 0.619–0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790–0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015).ConclusionOur study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

The value of combined detection D-dimer and NLR in judging the severity and short-term prognosis of acute cardiogenic cerebral embolism in elderly patients

ObjectiveTo assess the utility of combined neutrophil-to-lymphocyte ratio (NLR) and D-dimer detection in determining the severity and short-term prognosis of acute cardiogenic cerebral embolism (ACCE) in older adults. MethodsWe selected 202 elderly non-valvular atrial fibrillation patients hospitalized at the Third Affiliated Hospital of Anhui Medical University from April 1, 2020, to April 1, 2023. They were divided into an observation group (69 cases combined with ACCE) and a control group (133 cases with non-valvular atrial fibrillation alone) based on whether acute cardioembolic cerebral embolism occurred. According to the National Institutes of Health Stroke Scale (NIHSS), the observation group was divided into a mild cerebral infarction group (MICI group), a moderate cerebral infarction group (MOCI group), and a severe cerebral infarction group (SCI group), with 26 cases, 29 cases, and 14 cases, respectively. According to the modified Rankin scale (mRS), after 3 months, 30 cases were divided into the good prognosis group and 39 cases were divided into the poor prognosis group. We detected and compared the differences in D-dimer and NLR levels among different groups of patients, as well as differences in some important laboratory indicators. Logistic regression analysis was used to identify factors influencing the short-term prognosis of patients with acute cardioembolic cerebral infarction, and ROC curves were plotted to evaluate the value of D-dimer and NLR in predicting the short-term prognosis of patients with acute cardioembolic cerebral infarction. ResultsThe levels of D-dimer and NLR in peripheral blood in SCI group [1.82 (0.58–6.71) mg/l, 4.55 (3.14,7.21)] were higher than those in MOCI group [1.16 (0.65–1.90) mg/l, 3.84 (2.31,6.68)] and MICI group [0.53 (0.32–0.90) mg/l, 2.46 (2.09–3.79)]. The difference between groups was statistically significant (P < 0.05). Logistic regression analysis showed that D-dimer and NLR were independent risk factors for poor prognosis in patients with acute cardiogenic cerebral embolism (OR values were 1.772 and 1.603, and 95 %CI were 1.060–2.963 and 1.100–2.338, respectively, both P < 0.05). The AUC for the prediction of poor prognosis in acute cardioembolic stroke by combining D-dimer and NLR was 0.812 [95 % CI: 0.710–0.914], higher than the individual detections of D-dimer at 0.756 [95% CI: 0.642–0.869] and NLR at 0.733 [95 % CI: 0.613–0.854]. ConclusionPeripheral blood D-dimer combined with NLR detection is helpful for the risk stratification and short-term prognosis assessment of patients with acute cardiogenic cerebral embolism. Clinical detection is of great significance for the prevention and monitoring of disease development.

Utility of neutrophil-to-lymphocyte ratio as an indicator of tumor immune status in non-small cell lung cancer.

Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic biomarker in non-small cell lung cancer (NSCLC); however, the underlying biological rationale remains unclear. The present study aimed to explore the potential utility of NLR as a surrogate biomarker for immune response to cancer and to elucidate the underlying mechanism. This retrospective study included the medical records of 120 patients with NSCLC who underwent surgery at the study institution in 2012. NLR in peripheral blood was determined from blood test within 30days before surgery. Tumor immune status was evaluated using immunohistochemical staining to identify CD3+, CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs), and the relationship of NLR, with clinicopathologic characteristics including 5-year overall survival (OS), and the tumor immune status was investigated. The median values of NLR and TIL count were used as cutoff points. The 5-year OS was significantly better in patients with low NLR (<2.2) than in those with high NLR (≥2.2) (70.1% vs. 56.8%, P=0.042) and in patients with high CD3+ TIL count (≥242) than in those with low CD3+ TIL count (<242) (70% vs. 56.8%, P=0.019). Additionally, the CD3+ TIL count was negatively correlated with preoperative NLR (P=0.005). NLR might potentially reflect the immune status of tumor microenvironment, explaining its impact on prognosis of patients with NSCLC.

Neutrophil-to-lymphocyte ratio associates with nutritional parameters, intratumoral immune profiles, and clinical outcomes of pembrolizumab in head and neck squamous cell carcinoma.

The relationship between the tumor-immune microenvironment and systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), is unclear. We examined the characteristics of systemic inflammatory markers and tumor immune microenvironments in relation to treatment outcomes in 29 consecutive patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) who received pembrolizumab, using 14-marker multiplex immunohistochemistry and image cytometry. NLR ≥4.5 (high NLR) at pretreatment status significantly correlated with short overall survival (OS) and progression-free survival-2 (PFS2) and malnutrition status. High NLR in peripheral blood was significantly correlated with low lymphoid cell and high tumor-associated macrophage counts in tissues, especially myeloid-to-lymphoid cell ratios, suggesting an association between circulating and intratumoral immune complexity profiles. This study suggests a link between NLR in circulating blood, systemic nutritional status, and immune composition within the tumor.

Correlations of baseline neutrophil-lymphocyte ratio with prognosis of patients with lupus nephritis: A single-center experience.

We aimed to evaluate the correlations among the neutrophil-to-lymphocyte ratio (NLR), lupus nephritis (LN) clinical characteristics, and renal prognosis of patients with LN. We enrolled 122 patients who were diagnosed with LN at the Rheumatology Department of the People's Hospital, Xinjiang Uygur Autonomous Region from January 2013 to April 2022. We determined the occurrence of renal adverse events in patients with LN by reviewing medical records and follow-up data. Correlations were analyzed using the Spearman test, and the quartile method was applied to classify all of the 122 patients who had completed follow-up into low, medium, and high NLR groups. The Kaplan-Meier survival curve was used to conduct survival analysis, and Cox regression analyses were used to explore possible potential risk factors. The baseline NLR of patients with LN was positively correlated with C-reactive protein (CRP), serum creatinine, blood urea nitrogen, and systemic lupus erythematosus disease activity index scores (P < 0.05) and negatively correlated with estimated glomerular filtration rate (eGFR) and serum albumin (P < 0.05). Patients who completed follow-up were divided into three NLR groups based on their NLR values: 30 in the low (NLR ≤ 2.21), 62 in the medium (NLR > 2.21 and NLR ≤ 6.17), and 30 in the high NLR group (NLR > 6.17). The patient survival time before developing poor renal prognosis was significantly different among the three groups (P < 0.05). High NLR (hazard ratio [HR] = 3.453, 95% confidence interval [CI]: 1.260-9.464), CRP (HR = 1.009, 95% CI: 1.002-1.017), eGFR (HR = 0.979, 95% CI: 0.963-0.995), and 24-h proteinuria values (HR = 1.237, 95% CI: 1.025-1.491) as well as anti-double stranded DNA antibody positivity (HR = 3.056, 95% CI:1.069-8.736) were independent risk factors associated with a poor renal prognosis for patients with LN. The baseline NLR in peripheral blood can be used as a reference index for evaluating renal function and disease activity in patients with LN, and a high NLR has predictive value for the prognosis of patients with LN.

Clinical markers predict the efficacy of several immune checkpoint inhibitors in patients with non-small cell lung cancer in China.

Immune checkpoint inhibitors (ICIs) are one of the most significant oncological treatment modalities as a result of the rapid advancement of immunotherapy. Programmed Cell Death-Ligand 1 (PD-L1) and tumor mutational burden (TMB) have emerged as key markers for predicting the efficacy and prognosis of ICIs in non-small cell lung cancer (NSCLC), and the predictive role of tumor-infiltrating lymphocytes (TILs) has also received significant attention. However, the prognosis of some individuals cannot be determined by these indicators; for instance, some patients with low PD-L1 expression also benefit from longer survival. Therefore, the purpose of this research was to investigate the connection between new haematological and pathological markers and clinical outcomes in NSCLC patients receiving ICIs. Seventy-six patients with stage III-IV NSCLC treated with ICIs were included in this study. We used the Mann-Whitney test, COX regression and Kaplan-Meier analysis to retrospectively analyze peripheral blood indicators and survival prognostic data of 76 patients in order to investigate the relationship between baseline neutrophil-to-lymphocyte ratio (NLR) and the efficacy of ICIs. To investigate the correlation between CXCL13, CXCR5, CD8 and the efficacy of ICIs, we assessed the expression levels of aforementioned indicators in biopsied tissues of 10 non-small cell lung tumors by immunohistochemistry (IHC) and immunofluorescence (IF) and performed statistical analysis. Disease control rate (DCR) was higher in patients with baseline NLR <3.4 (p=0.016) and neutrophil percentage <71% (P=0.015). Baseline NLR (HR=2.364, P=0.003) and neutrophil percentage (HR=2.824, P=0.013) had the greatest influence on patients' survival prognosis, with baseline NLR exhibiting a stronger predictive value (AUC=0.717), according to univariate and multifactorial COX regression analyses of progression-free survival (PFS) and overall survival (OS). In NSCLC tissues, higher expression of CXCL13 was associated with better clinical outcomes (P=0.032) and higher expression of CD8 was associated with prolonged survival (P=0.022). Low baseline NLR in peripheral blood and high expression of CD8 in tissues are associated with longer PFS and may have a potential predictive value for patients with stage III-IV NSCLC using ICIs.

Correlation of neutrophil-to-lymphocyte ratio and stromal tumor infiltrating lymphocytes across early breast cancer subtypes.

e12558 Background: The tumor microenvironment plays a key role in the treatment response and prognosis of breast cancer (BC) patients, but the integrity of the peripheral immune system is also relevant. Understanding the biological correlation of immune-related prognostic factors, such as neutrophil-to-lymphocyte ratio (NLR) and stromal tumor infiltrating lymphocytes (sTIL), is necessary to improve its clinical applicability and the possible generation of more complex biomarkers that can direct treatment. Methods: Observational and single-center cohort of 1006 early BC patients (2009-2020). Pre-treatment NLR in peripheral blood and sTIL at diagnostic biopsy were determined. The correlation between NLR and sTIL (Spearman's Rho) overall and by subtypes, as well as its prognostic value for overall (OS) or disease-free survival (DFS) by Cox regression were evaluated. Results: NLR could be determined in 965 (96%) patients; in536 (53%) patients both NLR and sTIL were available. No statistical differences in baseline characteristics between both cohorts were found. Median age: 50 (range: 24-89); 93% infiltrating ductal carcinoma; 39.4% grade 3; 42.2% stage III; subtypes: hormone receptor (HR)+/HER2- (78.2%), HER2+/HR(+/-)(9.9%), triple negative breast cancer (TNBC) (11.9%); 70.5% treated with neoadjuvant chemotherapy. Median sTIL was 5% (SD: 16.2) with higher values in grade 3 (p &lt; 0.001), HR- (p &lt; 0.001) and HER2+ (p = 0.001). The median NLR was 1.95 (SD: 1.20), with no differences by subtype. There was no overall relationship between NLR and sTIL (ρ:0.32, p = 0.456). Correlation was also ruled out for each molecular subtype: HR+/HER2- (ρ:0.05, p = 0.301), HER2+/HR(+/-) (ρ:0.16, p = 0.251) and TNBC (ρ:0.21, p = 0.104). In a univariate predictive model for survival (N = 965), NLR showed prognostic value for DFS (HR 0.96, 95%CI: 0.80-1.17, p = 0.711) or OS (HR 1.02, 95%CI: 0.85-1.23, p = 0.798), neither in the whole group nor in the analysis by immunochemical subtypes. Conclusions: No correlation was observed between two of the most relevant biomarkers of immune activation in the tumor (sTIL) and peripheral (NLR) compartment in a series of early BC patients. NLR was not predictor of survival in our cohort. The absence of relationship between sTIL and NLR could suggest differences in the immune response in both compartments or else the need to find more accurate peripheral immune activation markers.

The inflammatory cytokine profiles and ocular biometric characteristics of primary angle-closure glaucoma.

To investigate the pathogenesis of primary angle-closure disease (PACG) by measuring the anatomical structures of the anterior and posterior segments of the eye and inflammatory markers in the peripheral blood. This case-control study enrolled patients diagnosed with acute PACG (APACG) and chronic PACG (CPACG). It also enrolled control subjects without PACG. The anterior and posterior anatomical features were measured in all study participants. The levels of interleukin (IL)-6, tumour necrosis factor-α and the neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood were measured. This study analysed a total of 99 eyes: 34 eyes from 34 patients with APACG, 28 eyes from 28 patients with CPACG and 37 eyes from 37 control patients with senile cataract. The axis length, corneal diameter, anterior chamber depth and anterior chamber volume were significantly smaller in the APACG and CPACG groups compared with the controls. The level of IL-6 in the peripheral blood of patients with PACG was significantly lower than that of the controls. The NLR in the peripheral blood of patients with PACG was significantly greater than that of the controls. Changes in the ocular anatomy and some inflammatory markers might be involved in the pathogenesis of PACG.

Correlation between neutrophil to lymphocyte and platelet to lymphocyte ratios and renal involvement in systemic lupus erythematosus in Central Vietnam

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations and relapsing - remitting disease course. Nephritis is a major cause of morbidity and mortality in patients with lupus. Many clinical parameters and laboratory markers can be used to evaluate disease activity and nephritis. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are positively associated with inflammatory disorders. Objectives: To evaluate the correlation between NLR and PLR in peripheral blood and renal involvement in systemic lupus erythematosus. Methods: 63 patients were diagnosed with SLE according to the criteria of the Systemic Lupus International Collaborating Clinics 2012 (SLICC 2012) and were treated at the Internal Medicine Department of Hue University of Medicine and Pharmacy Hospital, Thua Thien Hue province, in central Vietnam, from February 2020 to July 2021. This study included 41 SLE patients with lupus nephritis (LN) and 22 SLE patients without renal involvement. Results: The mean age of the study group was 31.67 ± 12.10. The most common age group was 21-50 years old, accounting for 69.8%. Females accounted for 90.5% and the female-to-male ratio stood at 9.5:1. Clinical and laboratory characteristics: acute cutaneous lupus 50.8%, subacute cutaneous lupus 11.1%, oral ulcers 27%, non - scarring alopecia 47.6%, arthritis 61.9%, pleural or pericardial effusion 30.2%, renal involvement 65.1%, neuropsychiatric damage 4.8%, anemia 81.0%, leukopenia 22.2%, neutropenia 11.1%, lymphopenia 41.3%, thrombocytopenia 15.9%, hemolytic anemia 15.9%, positive ANA antibody 61.9%, positive anti-ds DNA antibody 52.4%. Acute cutaneous lupus and arthritis in SLE patients without the nephritis group were higher than in the LN group (p &lt; 0.05). Anemia, lymphopenia, thrombocytopenia, positive ANA, anti-ds DNA in the LN group were higher than SLE patients without nephritis (p &lt; 0.05). SLE patients with LN had higher levels of NLR than those without nephritis. While PLR had no remarkable difference between these two groups. NLR was positively correlated with CRP, serum creatinine, and 24-hour urinary protein. PLR was positively correlated with the SLEDAI score. The best NLR to predict LN was 4.97 with a sensitivity of 51.2% and a specificity of 95.5% (AUC = 0.742, 95% CI, 0.617 - 0.866, p = 0.002). Conclusion: Most of the clinical manifestations in SLE patients according to SLICC 2012 criteria were lupus nephritis, arthritis, and acute cutaneous lupus. PLR was positively correlated with the SLEDAI score. NLR could predict renal involvement in SLE patients. Keywords: Lupus nephritis, ANA, anti-ds DNA, NLR, PLR.

Application of the neutrophil to lymphocyte ratio in the diagnosis and activity determination of ulcerative colitis: A meta-analysis and systematic review.

Background:The neutrophil to lymphocyte ratio (NLR) may be a potential biomarker to evaluate the condition of ulcerative colitis (UC), but whether it can determine the activity of UC is still controversial. So we conducted this meta-analysis to study the relationship between them.Methods:We searched the databases of Pubmed, Embase, Cochrane, Wanfang, and CNKI to collect qualified articles. Random effect or fixed effect model is used to calculate the standard mean difference (SMD) with 95% confidence interval (CI).Results:A total of 11 articles (including 1741 participants) were included in this meta-analysis. The results showed that the level of NLR in peripheral blood of patients with UC was significantly higher than that of control group (SMD = 1.04, 95% CI = 0.71-1.36). The NLR value of active patients was significantly higher than that of inactive patients (SMD = 1.35, 95% CI = 0.87-1.83).Conclusion:NLR may be a useful index to determine the severity and activity of UC, and it is expected to be widely used in clinical practice in the future.

The Ratio of Preoperative Serum Biomarkers Predicts Prognosis in Patients With Oral Squamous Cell Carcinoma

BackgroundDynamic changes in circulating immune-inflammatory cells have been regarded as simple and convenient prognostic biomarkers in various cancers. However, studies on the prognostic values of their ratios in oral squamous cell carcinoma (OSCC) remain limited.Materials and MethodsA total of 493 OSCC patients were included in the present study. Here, we investigated the prognostic values of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-white blood cell ratio (NWR), and lymphocyte-to-white blood cell ratio (LWR) in OSCC. The correlations of the NLR, LMR, NWR, and LWR with clinicopathological characteristics were statistically analyzed using the Chi-square test, Kaplan-Meier curves, and univariate and multivariate Cox regression models.ResultKaplan-Meier analyses revealed that OSCC patients with a high LMR and low NWR had prolonged overall survival (OS, P<0.001) and disease-free survival (DFS, P<0.001 and P=0.003, respectively), but there were no significant differences in metastasis-free survival (MFS, P=0.053 and P=0.052, respectively). In contrary, a high NLR and low LWR were associated with poor OS (P<0.001 and P=0.0016, respectively), DFS (P=0.0014 and 0.0012, respectively) and MFS (P=0.021 and 0.008, respectively). Additionally, Cox multivariate analyses showed that the LMR was an independent prognostic factor for both OS (P=0.007) and DFS (P=0.017), while the LWR was an independent prognostic factor for MFS (P=0.009).ConclusionPreoperative NLR, LMR, NWR, and LWR in the peripheral blood are significant prognostic factors for OSCC and might be helpful in predicting OSCC progression.

Predictive Value of Pretreatment Peripheral Neutrophil-to-Lymphocyte Ratio for Response to Neoadjuvant Chemotherapy and Breast Cancer Prognosis.

BackgroundNeutrophil-to-lymphocyte ratio (NLR) is connected with the response to neoadjuvant chemotherapy (NAC) and prognosis. In addition, residual lymph node burden after NAC is likely important for prognosis. However, most studies have focused on the predictive value of NLR for NAC pathological complete response (pCR) rate. The relationship between NLR and post-operative residual lymph node ratio (LNR), and their prognostic values remain to be determined.MethodsWe retrospectively studied 282 patients with breast cancer who underwent curative surgery after NAC from 2008 to 2018. We collected pretreatment NLR in peripheral blood, the response to NAC, and the amount of axillary lymph nodes (positive and total) from patients who received axillary lymph node dissection (ALND). We followed up all patients from 2 to 116 months, with an average of 63 months. We analyzed the predictive value of pretherapeutic NLR in peripheral blood on the response of NAC, including pCR rate and postoperative LNR. The prognostic value of NLR and LNR was also analyzed.ResultsA pCR was achieved in 20 (27.0%) of 74 patients with low NLR, and 34 (16.3%) of 208 with high NLR (P = 0.045). In luminal A and luminal B tumors, patients with high NLR tended to have elevated LNR (LNR>0.5; P=0.041). In Kaplan–Meier analysis, overall survival of patients with low NLR (NLR < 1.8; P = 0.033) was longer than that of patients with high NLR (NLR ≥ 1.8). Moreover, by multivariable analysis, LNR was negatively correlated with overall survival (P < 0.05) and disease-free survival (DFS) (P < 0.05).ConclusionpCR rate, post-operative remaining lymph node involvement and overall survival in all patients who received NAC may be predicted by NLR. Low NLR and LNR may suggest favorable outcomes.

Abstract 1767: Peripheral blood neutrophil-to-lymphocyte ratio (NLR), a predictor of poor survival in cancer patients, was positively associated with the percentage of circulating low-density neutrophil fraction

Abstract Low density (LDNs) and high density (HDNs) are two neutrophil subsets that can be separated through gradient centrifugation. LDNs was shown to be a tumor-promoting phenotype and high percentage of circulating LDNs was associated with poor cancer prognosis. In the last decade, it has also been suggested that neutrophil-to-lymphocyte ratio (NLR) is a marker of cancer-associated inflammation and high peripheral blood NLR was associated with poor cancer patient survival. Our study therefore aimed to i) establish the correlation between the percentage of circulating LDN fraction and blood NLR in cancer patients; ii) determine the differences between LDN and HDN protein expression; iii) compare the protein expression of neutrophils between cancer patients and healthy volunteers. Materials &amp; methods: Peripheral blood of esophageal/gastric cancer patients with clinical stage of II-III were collected. Circulating LDNs and HDNs were isolated using differential density centrifugation, and protein expression determined by immunophenotyping of cells using 12 different markers. Immunophenotyping of neutrophils from healthy volunteers was compared with that of cancer patients using the same panel of markers. Results: The percentage of circulating LDN fraction varied between 0.2% to 40% in cancer patients with an average higher than that in healthy volunteers. LDN fraction was significantly elevated in patients with high peripheral blood NLR (NLR above 4). We observed a positive Pearson's correlation between NLR and LDN fraction in blood of cancer patients. Compared to HDNs, pro-tumor LDNs was bigger in size and exhibited a higher expression of Arginase 1 (Arg1), CD66b (CEACA-8), and CXCR2. Peripheral blood neutrophils (PBNs) in cancer patients, containing both HDN and LDN fractions, showed a lower expression of Arg1 and neutrophil elastase (NE). Conclusion: Higher percentage of circulating LDNs in patients with elevated blood NLR may explain the correlation between high NLR and poor survival in cancer patients. High Arg1 expression of LDNs compared to HDNs can contribute to LDNs pro-tumor activity. Decreased expression of Arg1 and NE in PBNs of cancer patients compared to healthy subjects could be due to the degranulation of PBNs in cancer patients. Citation Format: Ramin Rohanizadeh, Olivia Koufos, Xin Su, Ariane Brassard, Betty Giannias, France Bourdeau, Roni Rayes, Jonathan Spicer, Veena Sangwan, Swneke Bailey, Lorenzo Ferri, Jonathan Cools-Lartigue. Peripheral blood neutrophil-to-lymphocyte ratio (NLR), a predictor of poor survival in cancer patients, was positively associated with the percentage of circulating low-density neutrophil fraction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1767.

Neutrophil-to-Lymphocyte Ratio in Asthmatic Patients and Healthy People: A Meta-analysis

Objectives: The purpose of this study was to investigate the differences in neutrophil-to-lymphocyte ratio (NLR) between asthmatic patients and healthy individuals. Methods: PubMed, EMBASE, and Cochrane Library databases were searched for studies on NLR among asthmatic patients and healthy people. Review Manager (RevMan) software was used for statistical analysis. Results: Six studies, including 1584 patients, were analyzed in this study. NLR was significantly different between asthmatic patients and healthy people. Conclusions: NLR in the peripheral blood of asthmatic patients was higher than that of healthy people. This result has certain clinical value in distinguishing asthma patients from healthy people.

Neutrophil-to-lymphocyte ratio in malignant pleural fluid: Prognostic significance.

Predicting survival of patients with malignant pleural effusions (MPEs) is notoriously difficult. A robust prognostic marker can guide clinical decision making. The neutrophil-to-lymphocyte ratio (NLR) in blood has been shown to predict survival in many cancers. Pleural fluid bathes the malignant pleural tissues, thus the NLR of the pleural fluid may reflect more closely the local tumour environment. The objective of this study was to explore the prognostic significance of pleural effusion NLR for MPE. We analysed matched effusion and blood from 117 patients with malignant and 24 with benign pleural effusions. Those who had received recent chemotherapy or had a pleurodesis were excluded. Neutrophil and lymphocyte counts in effusions were performed by manual review of cytospin cell preparations by trained observers. Clinical data were extracted from a state-wide hospital database. We found significantly fewer neutrophils (expressed as percentage of total leukocyte count) in pleural fluid than in corresponding blood (9% vs 73%; p<0.001). The NLR was an order of magnitude lower in pleural fluid than in corresponding blood: median [IQR] = 0.20 [0.04–1.18] vs 4.9 [3.0–8.3], p<0.001. Correlation between blood and pleural fluid NLR in MPE patients was moderate (rs = 0.321, p<0.001). In univariate analysis, NLR (>0.745)) in malignant pleural fluid was predictive of poorer survival (HR = 1.698 [1.0054–2.736]; p = 0.030), and remained significant after adjustment for age, sex, presence of a chest drain, cancer type, concurrent infection and subsequent treatment with chemotherapy (HR = 1.786 [1.089–2.928]; p = 0.022). Patients with pleural fluid NLR > 0.745 had a significantly shorter median survival of 130 (95% CI 0–282) days compared to 312 (95% CI 195–428) days for pleural NLR < 0.745, p = 0.026. The NLR in blood was also predictive of poorer survival in MPE patients (HR = 1.959 [1.019–3.096]; p<0.001). The proportion of neutrophils in pleural fluid was predictive of prognosis more strongly than lymphocytes. This study provides evidence that NLR in malignant effusions can predict survival, and therefore may provide prognostic information for this cohort. This prognostic association in the fluid is driven by the presence of neutrophils.

The Role of Inflammation in Contributing to Vascular Risk in Subclinical Hyperthyroidism: Randomized Controlled Trial

Background: Subclinical hyperthyroidism (SH, defined by low or undetectable serum thyroid stimulating hormone and normal thyroid hormones) is associated with increased cardiovascular risk (CVR) such as atrial fibrillation. Few studies also showed an increased risk of vascular disease and mortality in SH. Inflammation has been shown to play a significant role in the pathogenesis of cardiovascular disease. Increased levels of C-reactive protein (CRP), lipoprotein associated phospholipase A2 (Lp-PLA2, an inflammatory marker which plays a critical role in atherosclerosis), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) have been reported in conditions with increased cardiovascular risk. We aimed to ascertain whether abnormal CRP, Lp-PLA2, NLR and MLR contribute to an increased CVR in SH. Methods: CRP, Lp-PLA2, NLR and MLR in peripheral blood were measured in 30 SH subjects at baseline and after 6 months of treatment with either carbimazole or placebo in a randomized placebo-controlled design. Results: There was no significant difference in CRP, Lp-PLA2, NLR and MLR between carbimazole and placebo treated groups at 6 months. There was also no statistical difference in the above parameters if we compared the change or difference between two visits (visit 2 and visit 0 levels) in both groups. Conclusion: There is no evidence of chronic inflammation in our small cohort of SH subjects. Our finding needs to be confirmed in future studies with larger number of SH subjects. J Endocrinol Metab. 2021;11(1):28-32 doi: https://doi.org/10.14740/jem723

The Role of Inflammation in Contributing to Vascular Risk in Subclinical Hyperthyroidism: Randomized Controlled Trial

Background: Subclinical hyperthyroidism (SH, defined by low or undetectable serum thyroid stimulating hormone and normal thyroid hormones) is associated with increased cardiovascular risk (CVR) such as atrial fibrillation. Few studies also showed an increased risk of vascular disease and mortality in SH. Inflammation has been shown to play a significant role in the pathogenesis of cardiovascular disease. Increased levels of C-reactive protein (CRP), lipoprotein associated phospholipase A2 (Lp-PLA2, an inflammatory marker which plays a critical role in atherosclerosis), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) have been reported in conditions with increased cardiovascular risk. We aimed to ascertain whether abnormal CRP, Lp-PLA2, NLR and MLR contribute to an increased CVR in SH. Methods: CRP, Lp-PLA2, NLR and MLR in peripheral blood were measured in 30 SH subjects at baseline and after 6 months of treatment with either carbimazole or placebo in a randomized placebo-controlled design. Results: There was no significant difference in CRP, Lp-PLA2, NLR and MLR between carbimazole and placebo treated groups at 6 months. There was also no statistical difference in the above parameters if we compared the change or difference between two visits (visit 2 and visit 0 levels) in both groups. Conclusion: There is no evidence of chronic inflammation in our small cohort of SH subjects. Our finding needs to be confirmed in future studies with larger number of SH subjects. J Endocrinol Metab. 2021;11(1):28-32 doi: https://doi.org/10.14740/jem723

Analysis of Prostate-Specific Antigen-Related Indexes, Neutrophil-to-Lymphocyte Ratio in Patients with Concurrent Benign Prostatic Hyperplasia and Histologic Prostatitis.

This study was performed to explore the total prostate-specific antigen (tPSA) concentration, free PSA (fPSA) concentration, free-to-total PSA ratio (% fPSA), tPSA density (tPSAD), and neutrophil-to-lymphocyte ratio (NLR) in blood in patients with concurrent benign prostatic hyperplasia (BPH) and histologic prostatitis, and to provide new ideas for the diagnosis of prostatitis. Patients who underwent transurethral bipolar plasmakinetic prostatectomy from June 2017 to June 2018 were retrospectively divided into two groups according to the degree of pathological inflammation of the resected prostate tissue: group A (BPH with histologic acute and chronic inflammation), group B (BPH with histologic chronic inflammation). The preoperative PSA-related indexes and NLR in blood were respectively compared between two groups. Groups A and B comprised 59 and 41 cases, respectively. The values of tPSA, tPSAD, and NLR were all significantly higher in group A than B, and the value of % fPSA was significantly lower in group A than B (p < 0.05). There was no significant difference for the value of fPSA between the two groups (p > 0.05). Histologic acute prostatitis can cause changes of PSA-related indexes and NLR in blood, which has important clinical significance in diagnosis of prostatitis.

Utilization of combined PD-L1 expression and neutrophil-to-lymphocyte ratio prior to surgery as a prognostic factor in non-small cell lung cancer with brain metastasis.

BackgroundThis study was undertaken to investigate the expression of programmed death-ligand 1 (PD-L1) in the pulmonary primary tumor and brain metastases (BM) tumor as well as neutrophil-to-lymphocyte ratio (NLR) in preoperative peripheral blood samples in advanced non-small cell lung cancer. The potential association between both PD-L1 expression and NLR value and therapeutic sensitivity along with prognosis was explored.MethodsEleven patients pathologically confirmed as non-small cell lung cancer (NSCLC) with BM were enrolled. The expression of PD-L1 in pulmonary primary tumor and BM tumor was evaluated with immunohistochemistry. NLR value was calculated from blood cell count. DFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to assess differences between groups.ResultsHigh expression of PD-L1 was observed in 4 pulmonary primary tumors and 3 BM tumors respectively. The NLR in peripheral blood before brain surgery was shown to be efficient to discriminate patients whose brain metastatic lesion reached disease control from others (AUC: 0.917 95% CI: 0.731–1.000, P=0.041). Five patients had an NLR value higher than the cutoff value of 3.0553. Eight patients with low expression of PD-L1 in BM lesions had 27 months of median OS, which was signifcantly longer than patients with high expression of PD-L1 with 10 months of median OS (Log-Rank, P=0.012). Five patients with both low expression of PD-L1 in BM lesions and low NLR value (≤3.0553) reached 36 months mOS significantly longer than others with only 10 months of mOS (Log-Rank, P=0.034, HR =0.133, 95% CI: 0.861–65.819, P=0.068).ConclusionsHigh expression of PD-L1 along with high NLR value is associated with less sensitivity of response to treatment and poor prognosis.

Abstract P3-10-19: Significance of baseline neutrophil-to-lymphocyte ratio for progression-free survival of patients with HER2-positive locally advanced and metastatic breast cancer treated with trastuzumab emtansine

Abstract Purpose The prognosis of human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancers (MBCs) has dramatically improved due to the introduction of trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1). The efficacy of T-DM1 is prolonged for some patients; however, the predictive factors remain unknown. There is a report that T-DM1 induced antitumor immunity in patients treated with neoadjuvant therapy, with tumor infiltrating lymphocytes (TILs) increasing after the administration of T-DM1. Based on these observations, the benefits of T-DM1 for prognosis may be mediated by an immune reaction against breast cancers, at least in part. As an indicator of cancer immunity, in addition to TILs, the neutrophil-to-lymphocyte ratio (NLR) has been established in early breast cancers. In the present study, we investigated the usefulness of the NLR for treatment efficacy of T-DM1 in HER2-positive MBCs. Methods Fifty-three advanced or metastatic breast cancers treated with T-DM1 were retrospectively recruited from three institutes. The NLR in the peripheral blood was measured at baseline (just before the start of T-DM1) and after one cycle (just before the start of cycle 2). The cutoff value of the NLR was set at 2.56 (median value) and progression-free survival (PFS) and overall survival (OS) according to NLR levels were evaluated. Results The PFS of patients with NLR-low at baseline (NLR&amp;lt;2.56; n=26; median, not reached) was significantly better than that of patients with NLR-high (NLR≥2.56; n=27; median, 4.13 months; hazard ratio [HR], 0.226; 95% confidence interval [CI], 0.112-0.493; p=0.0001). There was a significant association between improved OS and a low NLR (HR, 0.384; 95% CI, 0.170-0.910; p=0.0296). In the subgroup analysis, patients with NLR-low consistently had improved PFS compared to those with NLR-high irrespective of the number of prior chemotherapy regimens, prior trastuzumab use, visceral metastasis, estrogen receptor status, and HER2 immunohistochemical staining score. According to univariable analysis of each clinical and biological factor for PFS, the NLR-low group was solely and significantly associated with favorable PFS compared with the NLR-high group (HR, 0.226; 95% CI, 0.112-0.493; p=0.0001). The NLR at baseline was significantly decreased (p=0.0010) and lymphocyte count was significantly increased after one cycle treatment (p=0.0005). Interestingly, the PFS of patients whose NLR was high at baseline but changed to low after one cycle (n=12; median PFS, 6.47 months) was better than that of patients with a consistently high NLR (n=14; median PFS, 3.27 months). Conclusion and Discussion A low baseline NLR was found to be significantly associated with improved PFS for patients treated with T-DM1. Interestingly, lymphocyte count was significantly increased in patients in the NLR-low group but not in the NLR-high group after one cycle treatment. Although detailed mechanisms remain unknown, the treatment efficacy of T-DM1 may be partly mediated by immunoreaction on the basis of present data. A low baseline NLR appears to be beneficial for treatment with T-DM1 in HER2-positive breast cancers. Citation Format: Imamura M, Morimoto T, Egawa C, Miyagawa Y, Miyoshi Y. Significance of baseline neutrophil-to-lymphocyte ratio for progression-free survival of patients with HER2-positive locally advanced and metastatic breast cancer treated with trastuzumab emtansine [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-19.