Baseline Neutrophil-to-lymphocyte Ratio Research Articles

Peripheral Neutrophil to Lymphocyte Ratio (NLR), a cogent clinical adjunct for Ki-67 in breast cancer

BackgroundClinical utility of Ki-67 immunohistochemistry (IHC) in breast cancer (BC) is mainly limited to decide for the use of chemotherapy and estimate prognosis in patients with either Ki-67 index < 5% or > 30%; however, lacunae still exists pertaining to its analytical validity. Neutrophilia is common in cancer with accompanying lymphocytopenia. Neutrophil to lymphocyte ratio (NLR) captures the intricate balance between pro-tumor neutrophilia and anti-tumor lymphocyte immunity. This study aimed to correlate cellular proliferation in breast cancer with NLR.MethodsAn observational study was carried out including 73 cases of BC; pre-treatment NLR and Ki-67 grading were performed. NLR < 3 was considered low, while ≥ 3 was high. The Ki-67 expression was graded as low ≤ 5%, intermediate 6–29%, or high ≥ 30%. Various clinico-pathological variables were studied, and the association of categorical variables was analyzed using Pearson’s chi-square test, and a p-value of < 0.05 was taken as significant.ResultsKi-67 correlated significantly with modified Scarff-Bloom-Richardson (SBR) grade (p < 0.01), and tumor-node-metastasis (TNM) stage (p < 0.001). Correlation of NLR was not significant with SBR grade (p > 0.05) and molecular subtype (p > 0.05); however, NLR was found to be significantly correlated with TNM stage (p < 0.001) and Ki-67 (p < 0.001).ConclusionNLR is fast emerging as a personalized theranostic marker in breast cancer. Instead of determining a generalized cut-off value, individual baseline NLR and its dynamics with disease progression will help manage patients better, obviating some of the drawbacks associated with Ki-67.

Changes in serum DAMPs and cytokines/chemokines during near-infrared photoimmunotherapy for patients with head and neck cancer.

Near-infrared photoimmunotherapy (NIR-PIT) for head and neck cancer is a recently developed therapy. However, there is limited data on patients receiving NIR-PIT in real clinical settings. Seven NIR-PIT sessions were administered to five patients with head and neck squamous cell carcinoma (HNSCC). Serum damage-associated molecular patterns (DAMPs) (HMGB1 and Hsp70 levels), and cytokine and chemokine production, were compared before and after NIR-PIT. The serum concentration of HMGB1 increased after NIR-PIT (p = 0.031, Wilcoxon test) in all patients except one who did not achieve a clinical response. Chemokines MIP-1α (CCL3) and MIP-1β (CCL4) increased significantly 1-3 days after treatment (CCL3, p = 0.0036; CCL4, p = 0.0016, Wilcoxon test). A low pre-treatment neutrophil-to-lymphocyte ratio (NLR) was associated with a better response to therapy and survival. The release of DAMPs, and cytokine/chemokine production, were detected in the patients' peripheral blood. The baseline NLR may predict patient outcomes in response to NIR-PIT.

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.

Comparative analysis of neutrophil-to-lymphocyte ratio and remnant cholesterol in predicting cardiovascular events and mortality in general adult population

This study aimed to investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and Remnant Cholesterol (Remnant-C) in relation to cardiovascular events and all-cause mortality in the general population. A population-based study. We conducted a retrospective cohort study analyzing data from the National Health and Nutrition Examination Survey (NHANES) spanning the years of 2011–2018, with follow-up for mortality status until December 31, 2019. Kaplan‒Meier and Cox proportional hazards regression analyses were used to evaluate the associations between NLR, Remnant-C, and cardiovascular events as well as all-cause mortality. Overall, 9409 individuals with both complete blood count and blood lipids were included in the analysis. Baseline NLR and Remnant-C were calculated. During the follow-up (median, 59.3 months), 177 cardiovascular events and 561 all-cause mortality occurred. In fully adjusted model, people with NLR > 2.26 were significantly associated with higher risk of cardiovascular events (HR 2.14, 95% CI 1.30–3.52, P < 0.001) and all-cause mortality (HR 1.66, 95% CI 1.30–2.12, P < 0.001). NLR exhibited a positive correlation with Remnant-C (r = 0.04, P < 0.001). Elevated NLR levels shown stronger association with cardiovascular events (HR 1.21, 95% CI 1.14–2.28, P < 0.001) compared with Remnant-C (HR 1.02, 95% CI 1.00–1.04, P = 0.020). Our findings suggest that NLR and Remnant-C are potential predictive markers for cardiovascular events in the general population. We observed a correlation between NLR and Remnant-C, and high NLR levels demonstrate a stronger association with the prediction of cardiovascular events and all-cause mortality compared with Remnant-C.

Prognostic Factors of Platinum-Refractory Advanced Urothelial Carcinoma Treated with Pembrolizumab.

Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.

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.

Associations of circulating immunomarkers with the efficacy of immunotherapy for primary hepatic carcinoma.

Peripheral blood immunomarkers are associated with prognosis in patients with solid tumors receiving chemotherapy or immunotherapy. In this study, the associations of circulating neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR), as well as their dynamic changes were investigated in relation to the efficacy of immunotherapy in patients with primary liver cancer. Comparisons were made between NLR, MLR, and PLR among individuals exhibiting disease control (defined as the best response of partial response [PR] or stable disease [SD]) and those with progressive disease (PD). Additionally, disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) were compared between individuals with different NLR, MLR, and PLR levels before initiating palliative immunotherapy. Furthermore, comparisons were made between patients with different alterations in the ratios at the second cycle of immunotherapy compared to baseline. These analyses were performed using univariate and multivariate approaches. A total of 119 Chinese patients with liver cancer who underwent immunotherapy were included in this study, which focused on hepatocellular carcinoma (HCC). In cases with HCC (n = 104), the cutoffs of NLR, MLR, and PLR to differentiate treatment responders from nonresponders were 3.38, 0.28, and 227.18, respectively. Patients with the best response of PR or SD had significantly lower NLR and MLR. Patients with NLR <3.38 and those with MLR <0.28 significantly had longer OS and PFS than their counterparts, and those with PLR <227.18 had significantly longer PFS, both in overall patients and in various patient subgroups. Lower NLR, MLR, or PLR was associated with earlier BCLC stage, fewer metastatic sites, less frequent extrahepatic metastasis, or better performance status. For individuals who had an unfavorable baseline NLR ≥3.38, MLR ≥0.28, or a favorable baseline PLR <227.18 prior to first immunotherapy, a decrease in NLR, MLR, or PLR at Cycle 2 of immunotherapy was significantly associated with a higher DCR. Among patients with HCC who received immunotherapy, lower NLR, and MLR at baseline in overall patients were significantly associated with better disease control and more favorable survival outcomes (both OS and PFS), and lower PLR was significantly associated with longer PFS. The findings of this research may offer useful hints foranoptimized selection of patients with liver cancer who may benefit more from immunotherapy.

Subacute postoperative atrial fibrillation after heart surgery: Incidence and predictive factors in cardiac rehabilitation.

Postoperative atrial fibrillation (POAF) is the most common arrhythmia following cardiac surgery (CS). It may occur between the 1st and the 4th postoperative day as acute POAF or between the 5th and the 30th as subacute (sPOAF). sPOAF is associated with higher thromboembolic risk, which consistently increase patients' morbidity. Neutrophil-to-lymphocyte ratio (NLR) is a low-cost inflammatory index proposed as possible POAF predictor. Identification of patients' risk categories might lead to improved postoperative outcomes. The aim was to assess the incidence of sPOAF and to identify possible predictors in patients performing cardiovascular rehabilitation (CR) after CS. A single-center cohort study was performed on 737 post-surgical patients admitted to CR on sinus rhythm. Continuous monitoring with 12-lead ECG telemetry was performed. We evaluated the predictive role of anamnestic, clinical, and laboratory data, including baseline NLR. Subacute POAF was documented in 170 cases (23.1%). At the multivariate analysis, age (OR 1.03; p = .001), mitral valve surgery (OR 1.77; p = .012), acute POAF (OR 2.97; p < .001), and NLR at baseline (OR 1.13; p = .042) were found to be independent predictive factors of sPOAF following heart surgery. sPOAF is common after CS. Age, mitral valve procedures, acute POAF, and preoperative NLR were proved to increase sPOAF occurrence in CR. NLR is an affordable and reliable parameter which might be used to qualify the risk of arrhythmias at CR admission. Identification of new predictors of postoperative atrial fibrillation may allow to improve patients' prognosis.

Association of Neutrophil-to-Lymphocyte Ratio and Absolute Lymphocyte Count With Clinical Outcomes in Advanced Breast Cancer in the MONARCH 2 Trial.

Established prognostic factors for treatment response to cyclin-dependent kinases 4 and 6 inhibitors are currently lacking. We aimed to investigate the relationship of pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) to abemaciclib outcomes. This was a post hoc analysis of data from MONARCH 2, a phase III study of abemaciclib or placebo plus fulvestrant in hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer that progressed on endocrine therapy. Patients were divided into high and low categories based on baseline NLR (cutoff: 2.5) and ALC (cutoff: 1.5 × 109/L). The association of baseline NLR and ALC with progression-free survival (PFS) and overall survival (OS) was explored using Cox models and Kaplan-Meier estimates. Tumor response and safety were also examined. NLR and ALC data were available for 645 patients (abemaciclib: N = 426; placebo: N = 219). Low-baseline NLR or high-baseline ALC was consistently associated with positive PFS and OS trends; low-baseline NLR subgroups also showed trends for better response. The abemaciclib treatment effect against placebo was observed regardless of baseline NLR or ALC. Univariate analyses showed baseline NLR and ALC were prognostic of PFS and OS. Baseline NLR remained significant in the multivariate model (P < .0001). No unexpected differences in safety were observed by baseline NLR or ALC. Baseline NLR was independently prognostic of PFS and OS. Low-baseline NLR was associated with numerically better efficacy outcomes, but the benefit of adding abemaciclib to fulvestrant was similar irrespective of baseline NLR status.

Optimizing inhaled corticosteroid use in patients with chronic obstructive pulmonary disease: assessing blood eosinophils, neutrophil-to-lymphocyte ratio, and mortality outcomes in US adults.

Accurate biomarkers for evaluating mortality rates in patients with chronic obstructive pulmonary disease (COPD) remain scarce. This study aimed to explore the relationships between mortality rates in patients with COPD and blood eosinophil counts, neutrophil counts, and lymphocyte counts, along with the neutrophil-to-lymphocyte ratio (NLR). Additionally, we sought to identify the optimal response values for these biomarkers when utilizing inhaled corticosteroids (ICS). Utilizing a nationally representative, multistage cross-sectional design and mortality correlation study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 involving US adults aged 40 years or older with COPD. The primary endpoint was all-cause mortality, with Kaplan-Meier survival curves and restricted cubic splines applied to illustrate the relationship between leukocyte-based inflammatory markers and mortality. The analysis was conducted in 2023. Our analysis included 1,715 COPD participants, representing 6,976,232 non-institutionalized US residents [weighted mean age (SE), 62.09 (0.28) years; range, 40-85 years]. Among the participants, men constituted 50.8% of the population, and the weighted mean follow-up duration was 84.9 months. In the ICS use group, the weighted proportion of participants over 70 years old was significantly higher compared with the non-ICS use group (31.39% vs 25.52%, p < 0.0001). The adjusted hazard ratios for all-cause mortality related to neutrophil counts, lymphocyte counts, and NLR were 1.10 [95% confidence interval (CI), 1.04-1.16, p < 0.001], 0.83 (95% CI, 0.71-0.98; p = 0.03), and 1.10 (95% CI, 1.05-1.15; p < 0.0001), respectively. Optimal ICS response was linked with higher levels of eosinophil count (≥240 cells/μL), neutrophil count (≥3,800 cells/μL), NLR (≥4.79), and lower levels of lymphocyte count (<2,400 cells/μL). Adjusted baseline neutrophil, lymphocyte counts, and NLR serve as independent risk factors for all-cause mortality in patients with COPD. Further, ICS application appears to mitigate mortality risk, particularly when NLR levels reach 4.79 or higher, underlining the importance of ICS in COPD management.

The combination of baseline neutrophil to lymphocyte ratio and dynamic changes during treatment can better predict the survival of osteosarcoma patients.

Osteosarcoma is a primary malignant bone tumor with a high metastatic potential that accounts for a significant proportion of all bone tumors. The prognosis for patients with metastatic or recurrence disease remains poor. The neutrophil-to-lymphocyte ratio (NLR) has become a potential prognostic biomarker for cancer. Recent evidence suggests that the dynamic changes in neutrophil-to-lymphocyte ratio (NLR) during treatment may be more informative in predicting patient prognosis, but the value of dynamic NLR in osteosarcoma has not yet been determined. This retrospective study retrospectively analyzed the clinical information of 251 osteosarcoma patients diagnosed and treated in West China Hospital of Sichuan University, explored the impact of baseline NLR and changes in NLR during treatment on the prognosis of osteosarcoma patients, and further combined baseline NLR with Delta NLR to build an NLR staging system. The results showed that both baseline NLR and delta NLR had some predictive ability for the prognosis of osteosarcoma patients (P = 6.90e-4, P = 0.022). Patients with high baseline NLR were more likely to have a decrease in delta NLR (P = 1.24e-10). The NLR stage had a better predictive ability than baseline NLR and delta NLR, and was an independent prognostic factor for overall survival in osteosarcoma patients HR: 2.456 (1.625-3.710) (P = 1.97e-05). NLR has value in continuous monitoring, and continuous monitoring of NLR can better predict the survival of osteosarcoma patients compared to baseline NLR.

Radiotherapy-induced dynamic changes in the lymphocyte-to-monocyte ratio in patients with laryngeal cancer indicate poor prognosis.

We hypothesized that markers of inflammation correlate with response to radiotherapy in patients with non-metastatic laryngeal cancer (LC). Our aim was to assess peripheral and local markers of inflammation including lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), infiltrating CD8+ lymphocytes (TILsCD8), and programmed death 1 ligand (PD-L1) expression. We performed a retrospective single-center analysis of LC patients administered definitive (R-RT) or postoperative radiotherapy (PORT). The primary endpoint was overall survival (OS) in relation to peripheral and local inflammatory markers and their dynamic changes during RT. Study group included 215 patients (R-RT, n=116; PORT, n=99). The baseline (t0) NLR and LMR were significantly correlated with OS in the R-RT group. In patients with high and low NLR at t0, the five-year OS was 33% and 56% (p=0.010) and in high and low LMR at t0, the five-year OS was 56% and 27% (p=0.003), respectively. The LMR increase during R-RT predicted better prognosis: the five-year OS in high and low LMR was 57% and 31% at t2 (after 2 weeks of RT) (p=0.015), 49% and 26% at t4 (p< 0.001), and 50% and 25% at t6 (p=0.013), respectively. Multivariable analysis shows that the worse performance status (p=0.003), the presence of nodal metastases (p=0.0001), and low baseline LMR (p=0.049) in the R-RT group, and the presence of nodal metastases (p=0.035) and completion treatment on time (p=0.042) in PORT group were associated with poor prognosis. The PD-L1 expression had no significant prognostic value in any of the examined patients. The baseline LMR and its dynamic changes during R-RT and baseline NLR are independent prognostic factors in patients with nonmetastatic LC. PD-L1 expression and number of TILsCD8 have no prognostic value in R-RT and PORT group.

The Association Between Peripheral Blood Neutrophil-to-Lymphocyte Ratio and Cirrhosis Complications in Adults with Compensated Liver Cirrhosis in Ahvaz, Iran

Background: The neutrophil-to-lymphocyte ratio (NLR) is an inflammation biomarker in patients with liver cirrhosis. While increased NLR is linked to poor clinical outcomes and mortality in diseases like cancers, its association with cirrhosis complications has been sparsely examined. Objectives: This study aimed to evaluate the association between NLR and cirrhosis complications in patients with compensated liver cirrhosis. Methods: This retrospective cohort study was conducted on 256 patients with compensated liver cirrhosis visiting the Gastroenterology Clinic of Imam Khomeini Hospital, Ahvaz, Iran, in 2020. The peripheral blood lymphocyte and neutrophil counts were evaluated, and the NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Cirrhosis complications were assessed based on clinical and laboratory evaluation during 1 year of follow-up. Results: During the retrospective follow-up period, 59 patients (23.05%) experienced cirrhosis complications such as spontaneous bacterial peritonitis (n = 23), gastrointestinal bleeding (n = 22), and hepatic encephalopathy (n = 14). The baseline NLR, Model for End-Stage Liver Disease (MELD) score and Child-Pugh score were significantly higher in patients who later developed complications than in those who did not (P &lt; 0.0001). The NLR with an optimal cut-off of &gt; 1.95 had a sensitivity of 84.75% and specificity of 93.91% in predicting complications during the 1-year follow-up (AUC = 0.905, P &lt; 0.0001). Conclusions: Our results indicated that the NLR is a simple, non-invasive, and cost-effective marker for predicting short-term complications in patients with compensated liver cirrhosis.

Utility of baseline D-dimer and neutrophil-to-lymphocyte ratio (NLR) in predicting the severity among COVID-19 patients in an Indian cohort during the first wave of the pandemic

Introduction and Aim: COVID-19 outbreak was declared as pandemic by WHO Director-General on 11th March 2020 in his opening remarks at the media briefing. The global population infected by Corona virus appeared to be responding at different levels in the first wave which warranted WHO to categorise the disease as mild, moderate, and severe. Haematological, biochemical, and radiological parameters played a crucial role in critically triaging and following-up disease progression. Amongst various laboratory parameters, this work aimed to identify the most specific marker in predicting disease severity. Materials and Methods: Blood samples from study population of 510 laboratory confirmed COVID-19 cases admitted in our hospital were selected. The patients who were classified as having mild, moderate, and severe disease were analysed for biochemical and haematological inflammatory markers. Results were analysed by ANOVA and post-hoc tests. ROC curves were derived to determine the cut-off values between severe and non-severe groups. Correlation between D-dimer and NLR was done by Pearson’s correlation. Results: Patients with co-morbidities were likely to develop severe complications which could lead to poor outcome. From ROC curves, we determine that NLR, with highest area under curve, is the best marker of disease severity. A significant positive correlation was found between D-dimer and NLR (p=0.000) across groups. Baseline cut-off values for D-dimer and NLR based to differentiate between severe and non-severe cases were 0.5 and 4.875 respectively. Conclusion: We conclude that baseline NLR is a simple and most useful tool that would assist clinicians in designing treatment strategies for a COVID-19 infected patient.

The predictive role of hematologic markers in resectable NSCLC patients treated with neoadjuvant chemoimmunotherapy: a retrospective cohort study.

Neoadjuvant chemoimmunotherapy is an important therapeutic modality for resectable nonsmall cell lung cancer (NSCLC). The roles of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in predicting the efficacy and prognosis of patients with resectable NSCLC receiving neoadjuvant chemoimmunotherapy remain uncertain. This study aimed to explore the association of baseline and preoperative NLR, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio with the treatment response and survival of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy. Data of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy between May 2019 and July 2022 at our institute, were retrospectively analyzed. Peripheral blood cell counts were obtained at baseline and before surgery. Data that may affect treatment efficacy were also collected and analyzed, including age, sex, BMI, cumulative smoking exposure, pathological type, clinical stage, PD-L1 tumor proportion score, immune checkpoint inhibitors, dosage of neoadjuvant therapy, duration from final therapy to surgery, and baseline and preoperative oncological markers. The present work has been reported in compliance with REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria and guidelines (Supplemental Digital Content 1, http://links.lww.com/JS9/A860 ). A total of 116 patients were included in the study. Univariate logistic regression analysis showed that a higher baseline NLR ( P =0.001) and preoperative NLR ( P =0.001) were associated with a lower incidence of pathological complete response (pCR) following neoadjuvant therapy. Multivariate analysis indicated that a lower incidence of pCR was achieved in the high baseline NLR group ( P =0.014). Higher baseline NLR ( P =0.021), preoperative NLR ( P =0.004) and higher preoperative CEA levels ( P =0.059) were associated with shorter disease-free survival (DFS). Multivariate Cox proportional hazard regression analyses showed that shorter DFS was achieved in the high preoperative NLR group ( P =0.033). In patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy, a higher baseline NLR was associated with a lower incidence of pCR, and a higher preoperative NLR was associated with a shorter DFS. However, a future prospective study with a large sample size and long-term follow-up is needed to verify the predictive value of NLR in these patients.

Prognostic Significance of PD-L2 Expression in Association with Neutrophil-to-Lymphocyte Ratio in Urothelial Carcinoma of the Bladder.

The prognostic significance of tumoral programmed death-ligand 2 (PD-L2) expression in urothelial bladder cancer (UBCs) is under-investigated , although it can potentially to become a regulatory agent of cancer immunity. In the search for supporting biomarkers, the neutrophil-to-lymphocyte ratio (NLR) as a readily available surrogate marker of immune status has been associated with clinical outcomes and other prognostic factors in various types of cancer. Here we evaluate the prognostic ability of baseline NLR in addition to PD-L2 expression in bladder cancer. We used a retrospective cohort of UBCs patients from the authors' institutions. We classified patients according to their PD-L2 and NLR levels. We associated the prognostic outcome of each group with disease-free survival (DFS) and overall survival (OS). Thirty patients had a tumor with positive PD-L2 expression. We found no significant correlation between PD-L2 expression and NLR. PD-L2 status failed to provide a significant prognostic impact (disease-free survival [DFS] and overall survival [OS] rate at 5 years, 42.85% in PD-L2-high versus 65.75% in PD-L2-low patients; p = 0.057, 42.85% in PD-L2-high patients versus 62.5% in PD-L2-low patients; p = 0.112, respectively). NLR status also failed to exhibit a significant prognostic impact (DFS and OS rate at 5 years, 44.44% in PD-L2-high versus 66.66% in PD-L2-low patients; p = 0.232, 55.55% in PD-L2-high versus 71.43% in PD-L2-low patients; P = 0.894, respectively). When PD-L2 status and NLR status were combined, the NLR-low and PD-L2-low were significant factors to predict a favorable disease-free survival (hazard ratio, 4.525 [95% confidence interval, 1.020 to 20.080]; P = 0.047. However, the multivariate analysis failed to show it as an independent factor. These findings suggest that the prognostic impact of PD-L2 expression could be affected by the NLR status.

The Association Between Neutrophil-Lymphocyte Ratio and Variability with New-Onset Dementia: A Population-Based Cohort Study.

Previous studies identified that neutrophil-to-lymphocyte ratio (NLR) may be a predictor of dementia. However, the associations between NLR and dementia at the population level were less explored. This retrospective population-based cohort study was designed to identify the associations between NLR and dementia among patients visiting for family medicine consultation in Hong Kong. The patients were recruited from January 1, 2000, to December 31, 2003, and followed up until December 31, 2019. The demographics, prior comorbidities, medications, and laboratory results were collected. The primary outcomes were Alzheimer's disease and related dementia and non-Alzheimer's dementia. Cox regression and restricted cubic spline were applied to identify associations between NLR and dementia. A cohort of 9,760 patients (male: 41.08% ; baseline age median: 70.2; median follow-up duration: 4756.5 days) with complete NLR were included. Multivariable Cox regression identified that patients with NLR >5.44 had higher risks of developing Alzheimer's disease and related dementia (hazard ratio [HR]: 1.50, 95% Confidence interval [CI]: 1.17-1.93) but not non-Alzheimer's dementia (HR: 1.33; 95% CI: 0.60-2.95). The restricted cubic splines demonstrated that higher NLR was associated with Alzheimer's disease and related dementia. The relationship between the NLR variability and dementia was also explored; of all the NLR variability measures, only the coefficient of variation was predictive of non-Alzheimer's dementia (HR: 4.93; 95% CI: 1.03-23.61). In this population-based cohort, the baseline NLR predicts the risks of developing dementia. Utilizing the baseline NLR during family medicine consultation may help predict the risks of dementia.

Inflammation associated with lung function abnormalities in COVID-19 survivors

BackgroundActivation of inflammatory pathways promotes organ dysfunction in COVID-19. Currently, there are reports describing lung function abnormalities in COVID-19 survivors; however, the biological mechanisms remain unknown. The aim of this study was to analyze the association between serum biomarkers collected during and following hospitalization and pulmonary function in COVID-19 survivors.MethodsPatients recovering from severe COVID-19 were prospectively evaluated. Serum biomarkers were analyzed from admission to hospital, peak during hospitalization, and at the time of discharge. Pulmonary function was measured approximately 6 weeks after discharge.Results100 patients (63% male) were included (age 48 years, SD ± 14) with 85% having at least one comorbidity. Patients with a restrictive spirometry pattern (n = 46) had greater inflammatory biomarkers compared to those with normal spirometry (n = 54) including peak Neutrophil-to-Lymphocyte ratio (NLR) value [9.3 (10.1) vs. 6.5 (6.6), median (IQR), p = 0.027] and NLR at hospital discharge [4.6 (2.9) vs. 3.2 (2.9) p = 0.005] and baseline C-reactive protein value [164.0 (147.0) vs. 106.5 (139.0) mg/dL, p = 0.083). Patients with an abnormal diffusing capacity (n = 35) had increased peak NLR [8.9 (5.9) vs. 5.6 (5.7) mg/L, p = 0.029]; baseline NLR [10.0 (19.0) vs. 4.0 (3.0) pg/ml, p = 0.002] and peak Troponin-T [10.0 (20.0) vs. 5.0 (5.0) pg/ml, p = 0.011] compared to patients with normal diffusing capacity (n = 42). Multivariable linear regression analysis identified predictors of restrictive spirometry and low diffusing capacity, but only accounted for a low degree of variance in pulmonary function outcome.ConclusionOverexpression of inflammatory biomarkers is associated with subsequent lung function abnormalities in patients recovered from severe COVID-19.

Investigating the Prognostic Role of Peripheral Inflammatory Markers in Mild Cognitive Impairment

Growing evidence suggests that neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases. Peripheral markers of inflammation, including blood cell counts and their ratios, such as the neutrophil-to-lymphocyte ratio (NLR), have been reported as an easily accessible and reliable proxy of central nervous system inflammation. However, the role of peripheral inflammation in dementia and Mild Cognitive Impairment (MCI) still needs to be clarified. In the current study, we aimed to assess the prognostic role of the NLR and other peripheral markers of inflammation in a sample of 130 amnestic MCI, followed up for two to five years. The Mini-Mental state examination (MMSE) score at baseline and follow-up visits was used to assess global cognitive status at each visit and the degree of cognitive decline over time. Baseline peripheral markers of inflammation included blood cell counts and ratios, specifically the NLR, the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), and the systemic immune inflammation index (SII). After classifying subjects into CONVERTERS and non-CONVERTERS (respectively, patients converting to dementia and subjects showing stability at the last available follow-up), we compared peripheral markers of inflammation among groups ed correlated them with cognitive measures, testing the ability of significant factors to predict conversion to dementia. In our cohort, CONVERTERS showed lower baseline MMSE scores (p-value = 0.004) than non-CONVERTERS. In addition, CONVERTERS had statistically elevated NLR (p-value = 0.005), PLR (p-value = 0.002), and SII levels (p-value = 0.015), besides a lower number of lymphocytes (p-value = 0.004) compared with non-CONVERTERS. In a logistic regression analysis, baseline MMSE scores and NLR predicted conversion to dementia. Tertiles analysis showed that MCI with the highest NLR values had a higher conversion risk. Our study supports the hypothesis that a dysregulation of peripheral inflammation involving both lymphocytes and neutrophils may play a role in the pathogenesis of dementia, even at the early stages of neurodegeneration, as in the MCI condition.

Neutrophil-lymphocyte ratio and clinical outcomes in 19,697 patients with atrial fibrillation: Analyses from ENGAGE AF- TIMI 48 trial

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is the ratio between neutrophil and lymphocyte counts measured in peripheral blood. NLR is easily calculable based on a routine blood test available worldwide and may reflect systemic inflammation. However, the relationship between NLR and clinical outcomes in atrial fibrillation (AF) patients is not well-described. MethodsWe calculated NLR at baseline in ENGAGE AF-TIMI 48, a randomized trial comparing edoxaban versus warfarin in patients with AF followed for 2.8 years (median). The association of baseline NLR with major bleeding events, major adverse cardiac events (MACE), cardiovascular death, stroke/systemic embolism, and all-cause mortality were calculated. ResultsThe median baseline NLR in 19,697 patients was 2.53 (interquartile range 1.89–3.41). NLR was associated with major bleeding events (HR 1.60; 95% CI 1.41–1.80), stroke/systemic embolism (HR 1.25; 95% CI, 1.09–1.44), MI (HR 1.73; 95% CI 1.41–2.12), MACE (HR 1.70; 95% CI 1.56–1.84), CV (HR 1.93; 95% CI 1.74–2.13) and all-cause mortality (HR 2.00; 95% CI 1.83–2.18). The relationships between NLR and outcomes remained significant after adjustment for risk factors. Edoxaban consistently reduced major bleeding. MACE, and CV death across NLR groups vs. warfarin. ConclusionsNLR represents a widely available, simple, arithmetic calculation that could be immediately and automatically reported during a white blood cell differential measurement to identify patients with AF at increased risk of bleeding, CV events, and mortality.