Change In Neutrophil-lymphocyte Ratio Research Articles

Comparison of Changes in the Neutrophil-lymphocyte Ratio (NLR) and Post-surgery Outcomes in Child Patients with COVID-19 and Non-COVID-19

Background Pediatric patients with COVID-19 who undergo surgery have two actual problems, both the presence of a viral inflammatory response and an inflammatory response to surgery, which can affect the outcome of surgery and therapy. NLR is considered a fairly accurate predictor of surgery and COVID-19 infection. Objective This study aims to investigate the effect of changes in neutrophil-lymphocyte (NLR) on post-surgery outcomes in pediatric patients with COVID-19 infection. Methods It is a retrospective cohort study with an observational analysis. This research is a multi-center study on COVID-19 patients using a data bank of pediatric patients with COVID-19 and control patients non COVID-19 children undergoing surgery in three hospitals. Data recorded were age, gender, nutritional status, anesthetic status before surgery, length of stay, repeat surgery, sepsis, septic shock, and mortality. Statistical analysis was performed by the U-mann Whitney test. Results The study sample consisted of 87 total samples consisting of 2 groups, namely the group of pediatric patients with 29 samples with COVID-19 and 58 non-COVID-19 samples. Gender, nutritional status, length of stay, the incidence of reoperation, sepsis, septic shock, and mortality were not significantly different between the two groups with a p<0.05. Risk analysis by looking at the incidence of sepsis and septic shock obtained an intersection point of 2.175 and 2.225, respectively. Analysis of changes in the NLR (delta-NLR) in the mortality events of the COVID-19 group and non-COVID-19 found that the NLR of the COVID-19 group was two times greater than the cut-off NLR of 2,175. Conclusion There is no difference in the outcome of surgery for children with COVID-19 and non-COVID-19 based on the NLR change analysis.

The predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure

Objective: To determine the predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure. Methods: Patients with acute-on-chronic hepatitis B liver failure who were hospitalized in the Department of Hepatology of Qilu Hospital of Shandong University from January 2010 to July 2023 were retrospectively enrolled. According to the clinical outcomes of patients within 30 days of admission, they were divided into the survival group and the death group. The dynamic changes in NLR and initial values on day 3, 5, 8, and 12 in two groups were analyzed for the diagnostic value of 30-day prognosis in patients with acute-on-chronic hepatitis B liver failure. Logistic regression analysis and machine learning XGBoost algorithm were used to evaluate the risk factors influencing the prognosis of patients at 30 days. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of NLR and initial value change combined with MELD score on day 12 of admission in patients with chronic acute hepatitis B liver failure. Results: A total of 243 patients were enrolled in the study, including 145 patients in the survival group [115 males, 30 females, aged 25-74 (47±11)] and 98 patients in the death group [80 males, 18 females, aged 22-80 (49±13) ]. The median initial NLR of survival group and death group were 3.5 (2.1, 5.3) and 4.9 (2.9, 8.3), respectively, and the difference was statistically significant (P=0.003). The variation of NLR from the initial value on day 3, 5, 8, and 12 in the survival group [1.6 (0, 4.3), 1.9 (-0.2, 4.1), 2.0 (-0.1, 4.3) and 2.9 (0.3, 7.0), respectively] were lower than that in the death group [3.2 (0.9, 7.5), 5.1 (1.8, 7.6), 5.8 (2.0, 10.6) and 9.6 (3.5, 16.4), respectively] (all P<0.001). Logistic regression multivariate analysis showed that the changes in NLR on the 12th day and initial value (OR=1.07,95%CI:1.01-1.14, P=0.014), the changes in NLR on the 3rd day and initial value (OR=2.71, 95%CI: 1.32-5.55, P=0.007), the initial value of NLR (OR=1.18,95%CI:1.01-1.37,P=0.035) and fibrinogen (OR=0.21,95%CI:0.05-0.96,P=0.044) were related factors for death within 30 days. Machine learning XGBoost algorithm showed that the weight of the change between the NLR on the 12th day and the initial value was the highest. The area under the ROC curve of the combined MELD score was 0.812 (95%CI: 0.728-0.895), the specificity was 67.78%, and the sensitivity was 82.35%. Conclusion: Dynamic change of NLR combined with MELD score has high predictive value for the short-term prognosis of patients with acute-on-chronic hepatitis B liver failure.

Progressive Changes of Colitis Into Colorectal Cancer Associated With Changes in Neutrophil Lymphocyte Ratio, Serum, Micrornas and Infiltrate Neutrophils

Introduction: Understand the progression of colorectal cancer from the beginning until the advance stages is difficult and challenging. However, this could be overcome with a good animal model. Methods: In this study, a modified approach had been used to develop colorectal cancer model. The model was developed and monitored from colitis formation until the late stage of colorectal cancer. The changes of neutrophil lymphocyte ratio (NLR), serum microRNAs and infiltrate neutrophil in different stages of colorectal cancer were assessed in this study. Results: Results showed that the progression of the disease is correlated with NLR as early as the formation of colitis (r=0.121, p&lt;0.026). Meanwhile, the size of the tumor at each stage is also associated with the NLR value (r=0.185, p&lt;0.0012). In the serum microRNAs study, it was found microRNAs expression in blood serum change in different stages of colorectal cancer. In the early stage of colitis formation, miR223 (&gt; 3 fold expression, p &lt; 0.0025) were abundantly found in the blood serum. Meanwhile in others stage mild (miRNA345 &gt; 2.5 fold, p&lt;0.0011), moderate (miRNA347 &amp; miR512 &gt; 3 fold, p&lt;0.002) and severe (miR31 &amp; miR145 &gt; 2 fold, p&lt;0.0001) microRNAs were also found expressed differently. The quantities of infiltrate neutrophil were varied in different stages of the disease. Conclusion: This study provides an insight into the immunity and molecular level of colorectal cancer and it allows a progressive monitoring on the changes in the molecular, cellular and histological level.

Neutrophil-Lymphocyte Ratio in Patients With Acute Schizophrenia.

Introduction Schizophrenia symptom severity is linked to neuroinflammation. Certain blood cell indexes such as neutrophil-lymphocyte ratio (NLR) and neutrophil-albumin ratio (NAR) have been used as biomarkers in various diseases, including schizophrenia. In acute clinical practice, it is challenging to decide whether to provide intravenous antipsychotic treatment in some cases due to the lack of objective biomarkers of psychiatric symptoms. The NLR of individuals with schizophrenia is thought to be associated with disease severity, and changes in NLR may reflect a patient's response to antipsychotic treatment. We investigated the application of NLR as a biomarker for identifying acute severity and determining acute treatment response in patients withschizophrenia. Methods We retrospectively examined 251 inpatients diagnosed with schizophrenia and classified them according to treatment (intravenous haloperidol vs. oral antipsychotic medication during the acute phase) and investigated their NLR and NAR while receiving inpatient care. Results A total of 48 inpatients were given intravenous haloperidol to manage their acute symptoms; 208 were given oral antipsychotics. The intravenous haloperidol group experienced more severe symptoms, such as agitation and disorganized thinking, during the acute phase. Further, those who received intravenous haloperidol had significantly higher Clinical Global Impression-Severity (CGI-S) scores than the oral antipsychotic group. NLR and NAR were also significantly higher in the haloperidol intravenous group. Conclusion Elevated NLR and NAR could be easily measured in patients with psychomotor agitation who should be treated at any facility. Further, they are useful biomarkers for determining disease severity and the effects of treatment on psychomotor excitement in patients who require intravenous haloperidol.

Prognostic Significance of Neutrophil-Lymphocyte Ratio in Patients of High-Grade Glioma Undergoing Adjuvant Chemoradiation: A Prospective Study.

High-grade gliomas are highly fatal disease with poor prognosis despite multimodality management. Inflammatory biomarkers are widely used for prognostication in various solid malignancies to stratify high risk patients. The current research was conducted to investigate whether any change in neutrophil-lymphocyte ratio (NLR) during adjuvant chemoradiotherapy has any prognostic significance in high-grade glioma patients. Seventy-three biopsy proven high-grade glioma patients treated with adjuvant chemoradiotherapy were enrolled in this study. Haematological parameters were collected before treatment, weekly during treatment, and at 4th week after chemoradiotherapy along with baseline characteristics. Overall survival (OS) was determined using Kaplan-Meier curve. Variables found statistically significant in univariate analysis by Cox regression model were subjected to final multivariable analysis. The median follow-up was around 17 months with a median OS of 17.2 months (95%CI 14.7-23). The best prognosis was seen in patients who had a baseline NLR< 3.5 with decline in NLR during treatment achieving a 1-year survival of 100% and median overall survival of 36.5 months. Patients who had baseline NLR ≥3.5 without a decline in NLR had worst prognosis with a 1-year survival of 25% (95%CI 9.4%-66.6%) and median OS of 7.1 months. On multivariate analysis, age [HR 1.025, p=0.040)], ECOG performance status≤1 [HR 0.089, p<0.001], extent of surgery [HR 0.305, p=0.001] and decline in NLR during treatment [HR 0.452, p=0.026] were found to be significant predictors of OS. This study demonstrated that NLR is a cost-effective biomarker that has prognostic significance in predicting overall survival for high-grade glioma patients.

Baseline and early changes in the neutrophil–lymphocyte ratio (NLR) predict survival outcomes in advanced colorectal cancer patients treated with immunotherapy

BackgroundSystemic inflammation plays a role in carcinogenesis and is related to overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). The neutrophil–lymphocyte ratio (NLR) is calculated by circulating neutrophil to lymphocyte counts, which represents an indicator of the balance between the deleterious roles of neutrophilia and the beneficial roles of lymphocyte-mediated immunity. We hypothesized that the NLR may predict outcomes in metastatic colorectal cancer (mCRC) patients treated with immunotherapy. Materials and MethodsThis retrospective study included 110 mCRC patients who were treated with immunotherapy at Sun Yat-sen University Cancer Center. Several inflammatory biomarkers were measured at baseline and after two cycles of treatment. The X-tile program was used to obtain the cutoff values. We examined the impact of both baseline and posttreatment inflammatory index levels on overall survival (OS). ResultsIn univariate analysis, both a low baseline NLR (P = 0.014) and a decreased NLR after 2 cycles of immunotherapy (P < 0.001) were considerably correlated with better OS. In multivariate analysis, age, liver metastasis, baseline lymphocyte-monocyte ratio (LMR), baseline NLR and early changes in NLR independently predicted OS. Patients with both a low baseline NLR and an early NLR reduction had the longest OS (median, 29.63 months). The best outcomes were remarkably observed in patients who had both an early NLR reduction and a high tumor mutational burden (TMB) (≥10 mut/Mb) (P < 0.0001). ConclusionsBoth a low baseline NLR and an early NLR reduction are significantly associated with a better prognosis in mCRC patients treated with immunotherapy. Further analysis indicated that the combination of NLR and TMB could obtain additional predictive power.

Association of malignant ascites with systemic inflammation and muscle loss after treatment in advanced-stage ovarian cancer.

Malignant ascites is prevalent in advanced-stage ovarian cancer and may facilitate identification of the drivers of muscle loss. This study aimed to evaluate the association of ascites with changes in systemic inflammation and muscle after treatment of advanced-stage ovarian cancer. We evaluated 307 patients with advanced-stage (III/IVA) ovarian cancer who underwent primary debulking surgery and adjuvant platinum-based chemotherapy between 2010 and 2019. The changes in skeletal muscle index (SMI) and radiodensity (SMD) were measured using pre-surgery and post-chemotherapy portal-venous phase contrast-enhanced computed tomography scans at L3. Systemic inflammation was measured using albumin levels, prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR). Primary endpoint was the changes in SMI and SMD after treatment. Linear regression analysis was used to test associations between muscle change and other covariates. Mediation analysis was used to determine the mediator. The median (range) age was 53 (23-83) years. The median duration (range) of follow-up was 5.2 (1.1-11.3) years. Overall, 187 (60.9%) patients had ascites. The changes in muscle and systemic inflammatory markers after treatment were significantly different between patients with and without ascites (SMI: -3.9% vs. 2.2%, P<0.001; SMD: -4.0% vs. -0.4%, P<0.001; albumin: -4.4% vs. 2.1%, P<0.001; PNI: -8.4% vs. -0.1%, P<0.001; NLR: 20.6% vs. -29.4%, P<0.001; and PLR: 1.7% vs. -19.4%, P<0.001). The changes in SMI and SMD were correlated with the changes in albumin, PNI, NLR, and PLR (all P<0.001). In multiple linear regression, ascites and NLR changes were negatively while albumin change was positively correlated with SMI change (ascites: β=-3.19, P<0.001; NLR change: β=-0.02, P=0.003; albumin change: β=0.37, P<0.001). Ascites and NLR changes were negatively while PNI change was positively correlated with SMD change (ascites: β=-1.28, P=0.02; NLR change: β=-0.02, P<0.001; PNI change: β=0.11, P=0.04). In mediation analysis, ascites had a direct effect on SMI change (P<0.001) and an indirect effect mediated by NLR change (indirect effects=-1.61, 95% confidence interval [CI]: -2.22 to -1.08) and albumin change (indirect effects=-2.92, 95% CI: -4.01 to -1.94). Ascites had a direct effect on SMD change (P<0.001) and an indirect effect mediated by NLR change (indirect effects=-1.76, 95% CI: -2.34 to -1.22) and PNI change (indirect effects=-2.00, 95% CI: -2.79 to -1.36). Malignant ascites was associated with enhanced systemic inflammation and muscle loss after primary debulking surgery and adjuvant chemotherapy in advanced-stage ovarian cancer. The association between ascites and muscle loss may be mediated by systemic inflammation.

Changes and Rate of Change in Neutrophil-Lymphocyte Ratio (∆NLR) as an Early Prognostic Marker for the Severity of Outcomes in Patients With COVID-19 and Its Applicability in Other Viral and Bacterial Diseases.

COVID-19 is a global pandemic that has spread rapidly and resulted in numerous deaths worldwide. Many inflammatory markers such as neutrophil-lymphocyte ratio (NLR), D-dimer, serum ferritin, C-reactive protein (CRP), and interleukin-6 (IL-6) were used for the diagnosis and prognosis of COVID-19. We have proposed using Delta NLR (0-48 hours) (∆NLR) as an early diagnostic marker for COVID-19 and other inflammatory disorders. We have created a prediction model based on six variables: overall severity, death, shifting to the ICU, length of stay, oxygen requirement, and ventilator support. Prediction models help us prepare for future pandemics through early diagnosis and management. A total of 1,865 patient records were retrieved from the database. The final sample available for analysis was 461. Change in NLR or ∆NLR was significant for all the models (except for length of stay) created by logistic regression. An independent predictor of the poor prognosis of COVID-19 is the severity of the disease in the initial one or two days. ∆NLR is a unique marker, and its scope of use in other disorders' prognoses must be further researched. The prediction models also help us in decision-making strategies and also prepare us for future pandemics.

Predictive Value of the Changes in Neutrophil-Lymphocyte Ratio for Outcomes After Off-Pump Coronary Surgery.

The neutrophil-to-lymphocyte ratio (NLR) is an extensively analyzed prognostic inflammatory index in cardiac patients. The degree of change in NLR values before and after surgery (delta-NLR) can represent the inflammatory response induced by surgery and serve as a meaningful prognostic biomarker in surgical patients; however, this has not been well investigated. We aimed to investigate the predictive value of the perioperative NLR and delta-NLR for outcomes of off-pump coronary artery bypass (OPCAB) surgery by evaluating "days alive and out of hospital (DAOH)", a novel patient-centered outcome. In this single-center retrospective study, perioperative data, including NLR data, from 1322 patients were analyzed. The primary endpoint was DOAH at 90 days postoperatively (DAOH 90), and the secondary endpoint was long-term mortality. Linear regression analysis and Cox regression analysis were performed to identify independent risk factors for the endpoints. In addition, Kaplan-Meier survival curves were plotted to assess long-term mortality. The median NLR values significantly increased from 2.2 (1.6-3.1) at baseline to 7.4 (5.4-10.3) postoperatively, with median delta-NLR values of 5.0 (3.2-7.6). Preoperative NLR and delta-NLR were independent risk factors for short DAOH 90 in the linear regression analysis. In Cox regression analysis, delta-NLR, but not preoperative NLR, was an independent risk factor for long-term mortality. When patients were divided into two groups according to delta-NLR, the high delta-NLR group had a shorter DAOH 90 than the low delta-NLR group. Kaplan-Meier curves showed higher long-term mortality in the high delta-NLR group than in the low delta-NLR group. In OPCAB patients, preoperative NLR and delta-NLR were significantly associated with DAOH 90, and delta-NLR was an independent risk factor for long-term mortality, indicating their role in risk assessment, which is essential for perioperative management.

Association of peripheral blood neutrophil-lymphocyte ratio (NLR) and red cell distribution width (RDW) with immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (mUC).

540 Background: Determining a benefit from ICIs radiographically may take months and may be confounded by pseudoprogression. The NLR &amp; RDW are readily accessible inflammatory markers from routine peripheral blood analysis and have been associated with outcomes in malignancies. We evaluated the association of early changes in NLR and RDW within 4 weeks after initiating ICI with any regression of tumor (ART) and overall survival (OS) in mUC. Methods: This study included de-identified data from Dana-Farber Cancer Institute in pts with mUC who were treated with ICIs from 2015 to 2020. Age, gender, setting (untreated vs. post-platinum), sites of metastasis (mets), performance status (PS), platelet count, RDW, and NLR at baseline and 3-4 weeks after initiating the ICI were collected. The primary objective was to assess the association of early increase in NLR by ≥1.0 from baseline or RDW at 3-4 weeks (as a continuous variable) post-ICI therapy with ART and OS. ART was assessed via subsequent imaging at any time point while on ICI. A multivariable logistic regression model and Cox proportional-hazards model were employed to identify the association of NLR changes with ART and OS, respectively, using backward selection. Results: A total of 330 pts were evaluable. The median age was 70 years, 72.1% (n = 298) were male and 69.4% (n= 227) received post-platinum ICI (remaining were platinum naïve). 46.5% (n = 146) experienced ART and the median OS was 13 months (11.14-16.14). An increase in NLR ≥ 1 in 3-4 weeks was associated with a lower rate of ART (OR: 0.41, 95% CI 0.24-0.70; p: 0.001) and worse OS (hazard ratio [HR]: 1.84, 95% CI 1.37-2.46; p &lt; 0.0001) on multivariable analysis (Table). Higher RDW values at 3-4 weeks were associated with worse OS (HR: 1.08, 95% CI 1.03-1.14; p: 0.0004) but were not associated with ART. Conclusions: In pts with mUC initiating ICI, an early increase in NLR ≥ 1 and higher RDW in 3-4 weeks were associated with poor outcomes. Early changes in these readily available variables may enable early modification or intensification of therapy to improve outcomes. External validation of these findings is warranted. [Table: see text]

Varikoseli olan hastalarda nötrofil/lenfosit oranı (NLR), platelet/ lenfosit oranı (PLR), monosit/eozinofil oranı (MER) gibi enflamatuvar belirteçlerin varikoselektomi sonrası spermiogram parametrelerinin değişimine etkisini öngörme

OBJECTIVE: In this study, we aimed to predict the changes in postoperative spermiogram parameters in patients who underwent varicocelectomy by using pre- and post-operative hemogram parameters and inflammatory blood markers. MATRERIAL and METHODS: 25 patients who underwent microscopic varicocelectomy in our clinic and met the study criteria were included in the study. Hemogram parameters were measured just before and twenty (20) days after the surgery, and spermiogram parameters were measured 6 months after the surgery. The patients seperated into two groups. Patients with &gt;50% improvement in postoperative Total Motile Sperm Count (TMS) were included in the recovered patients group, and patients with less than 50% improvement were included in the non-recovered patients group. Neutrophil / lymphocyte ratio (NLR), platelet / lymphocyte ratio (PLR), monocyte / eosinophil ratio (MER), and blood counts such as neutrophil, lymphocyte, platelet, monocyte, eosinophil were compared in groups, also were compared before and after surgery, separate RESULTS: Improvement in TMS was observed in patients with a statistically significant decrease in postoperative NLR (p = 0.009; p &lt;0.01). As a result of the calculations, cut-off point for the NLR change was accepted as 1.06% and above. PLR and MER parameters were not statistically significant in predicting the improvement of TMS. Among the neutrophil, lymphocyte, platelet, monocyte, eosinophil counts, preoperative neutrophil and preoperative monocyte counts were found to be higher in patients with postoperative TMS improvement. Cut-off points for these preoperative neutrophil and monocyte counts were calculated as 3.77 and 0.47, respectively. In our study, we could not reach any statistically significant result for lymphocyte, eosinophil and platelet counts. CONCLUSION: Preoperative and postoperative results of NLR, neutrophil or monocyte counts can be used as a marker to predict improvement in TMS. Keywords: varicocele, NLR, PLR, MER, inflammation

421P The association between early changes in neutrophil-lymphocyte ratio and survival in patients treated with immunotherapy

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data is limited. We evaluated the association between neutrophil-lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. Additionally, we created an NLR-based compound prognostic score.

The effect of ziltivekimab on the neutrophil-lymphocyte ratio: analysis from RESCUE

Abstract Background The neutrophil-lymphocyte ratio (NLR), derived from the complete blood count, independently predicts atherosclerotic events and is a potential biomarker for residual inflammatory risk. A previous study showed that interleukin (IL)-1β inhibition reduces the NLR, but whether inhibition with IL-6, a cytokine downstream of IL-1, also lowers the NLR is unknown. Purpose To evaluate whether ziltivekimab, a monoclonal antibody targeting the IL-6 ligand, dose-dependently lowers the NLR compared to placebo. Methods The phase II RESCUE trial randomized 264 patients with moderate to severe chronic kidney disease (CKD) and high-sensitivity CRP (hsCRP) &amp;gt;2mg/L in a 1:1:1:1 ratio to placebo or ziltivekimab 7.5 mg, 15 mg, and 30 mg subcutaneously once every four weeks. As previously reported, the trial met its primary endpoint as demonstrated by hsCRP reductions of 4% in the placebo group as compared to 77%, 88%, and 92% at 12 weeks in the ziltivekimab 7.5, 15, and 30 mg groups, respectively. Using RESCUE trial data, we further evaluated the percent change from baseline in the NLR at 12 weeks and sought evidence of correlation between any observed changes in the NLR with changes in other measured biomarkers. Results Ziltivekimab dose-dependently reduced the NLR starting at week one and sustained through week 12 (Table). The median change in the NLR at 12 weeks, the primary pre-specified endpoint, was −13.5% in the 7.5 mg group, −14.3% in the 15 mg group, and −22.4% in the 30 mg group compared to 1.56% in the placebo group. The estimated treatment difference was −14.6% (p=0.004), −15.3% (p=0.004), and −23.6% (p&amp;lt;0.0001) in the ziltivekimab 7.5, 15, and 30 mg groups respectively. These changes were driven largely by reductions in the absolute neutrophil count with minimal change in lymphocyte count. The change in NLR with ziltivekimab correlated modestly with the changes in hsCRP (R=0.26, p=0.0006), fibrinogen (R=0.18, p=0.02), and haptoglobin (R=0.17, p=0.03), but not serum amyloid A, ApoA1, ApoB, ApoB/ApoA ratio, or traditional risk markers. Conclusions IL-6 inhibition with ziltivekimab lowers the NLR. The ongoing ZEUS cardiovascular (CV) outcomes trial will assess whether ziltivekimab can reduce CV event rates among individuals with stage 3 to 4 CKD, known atherosclerotic disease, and elevated hsCRP. If ziltivekimab reduces CV risk, it would provide further evidence for critical inter-relationships between bone marrow function and atherothrombosis. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novo Nordisk

Non-invasive early prediction of immune checkpoint inhibitor efficacy in non-small-cell lung cancer patients using on-treatment serum CRP and NLR.

We determined the clinical relevance of early C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) change in blood as surrogate markers of pro-tumor inflammation (PTI) for predicting clinical outcome of programmed cell death (PD)-1/programmed cell death ligand (PD-L) 1 inhibitor treatment in non-small-cell lung carcinoma (NSCLC). We retrospectively reviewed NSCLC patients treated with anti-PD-1 or PD-L1 inhibitors. Early CRP change was defined as the ratio of 6weeks CRP to baseline CRP, and early NLR change was defined as that of the 6weeks NLR to baseline NLR. PTI index was determined by combinatorial evaluation of early CRP change and early NLR change, PTI index low: both of these were low, intermediate: either of these was low, high; both of these were high. The study included 217 patients. Early CRP change and early NLR change were both associated with PFS and OS. The combinatorial evaluation using these two markers enabled the clear stratification of PFS and OS. The median PFS in patient with PTI index low was 13.9months, while the median PFS in those with PTI index high was 2.5months (p < 0.01, log-rank test). The median OS in patients with PTI index low was not reached; the median OS in those with PTI index high was only 15.4months (p < 0.01, log-rank test). The combinatorial early CRP change and early NLR change as PTI biomarkers have clinical potential in identifying NSCLC patients who can achieve a durable response and long-term survival using PD-1/PD-L1 inhibitors.

The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy.

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil–lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531–17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626–0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.

Systematic Review of Existing Stroke Guidelines: Case for a Change.

Methods We systematically searched for guideline recommendation on the day-to-day use of peripheral inflammatory markers such as NLR published in the English language between January 1, 2005, and October 2020. Any other evidence of system biology-based approach or recommendation was explored within the selected guidelines for this scoping review. Only the latest guideline per writing group was selected. Each guideline was analyzed independently by 2 to 4 authors to determine clinical scenarios explained/given, scientific evidence used, and recommendations presented in the context of system biology. Results The scoping review found 2,911 titles at the beginning of the search. Final review included with 15 guidelines. Stroke-related organizations wrote sixty-five percent of the guidelines while national ministries wrote a fewer number of guidelines. We were primarily interested in recommendations for acute management in AIS published in the English language. Fifteen eligible guidelines were identified from 15 different countries/regions. None of the guidelines recommended the routine use of peripheral markers of inflammation, such as NLR, among their acute assessment and management recommendations. None of the existing guidelines explored the system biology approach to one of the most complex diseases affecting the human brain, stroke. Conclusions This systematic review has identified a significant evidence-practice gap in all existing national stroke guidelines published in English medium as of October 2020. These guidelines included the only current “living stroke guidelines,” stroke guidelines from Australia with a real opportunity to modernize the living stroke guidelines with systems biology approach, and provide 2020 vision towards better stroke care globally. Investigation of complex disease such as stroke is best served through a systems biology approach. One of the easiest places to start is simple blood tests such as total white cell count and NLR. Systems biology approach point us towards simple tools such immune-inflammatory index (SII) and serial systemic immune inflammatory indices (SSIIi) which should pave the way for the stroke physician community address the challenges in systems biology approach in stroke care. These challenges include translating bench research to the bedside, managing big data (continuous pulse, blood pressure, sleep, oxygen saturation, progressive changes in NLR, SII, SSIIi, etc.). Working with an interdisciplinary team also provides a distinct advantage. Recent adoption of historic WHO-IGAP calls for immediate action. The 2022 World Brain Day campaign on Brain Health for All is the perfect opportunity to raise awareness and start the process.

Peripheral blood immune cell dynamics reflect antitumor immune responses and predict clinical response to immunotherapy

BackgroundDespite treatment advancements with immunotherapy, our understanding of response relies on tissue-based, static tumor features such as tumor mutation burden (TMB) and programmed death-ligand 1 (PD-L1) expression. These approaches are...

Sarcopenia and the rate of change of the neutrophil/lymphocyte ratio as predictors of pembrolizumab efficacy in advanced urothelial carcinoma.

The objective was to evaluate the usefulness of sarcopenia and the neutrophil/lymphocyte ratio (NLR) as therapeutic efficacy predictors in patients who received pembrolizumab after platinum-based chemotherapy for advanced urothelial carcinoma (aUC). Forty-four patients with aUC were enrolled. Patients' background characteristics and clinical factors, the skeletal muscle index, and the psoas muscle index were evaluated. The NLR before and during treatment was calculated, and the rate of change of NLR was calculated. The median age was 70 years; the follow-up period was 13.2 months. The response rate was 54%. The nonresponding group had significantly more sarcopenia cases (P = 0.007) and a high rate of change of NLR (P = 0.0076). Progression-free survival (PFS) was significantly shorter in the group with sarcopenia (P = 0.002). Both PFS and overall survival were significantly shorter with an NLR rate of change greater than or equal to 1 (P = 0.001 and P = 0.002). On multivariate analysis, the presence of immune-related adverse events [hazard ratio (HR), 0.3723; 95% confidence interval (CI), 0.14-0.97; P = 0.04] and the NLR rate of change (HR, 3.986; 95% CI, 1.01-15.70; P = 0.048) were independent predictors of PFS. Sarcopenia and the rate of change of NLR appear to be useful as predictors of pembrolizumab efficacy in aUC.

Early changes in peripheral blood neutrophil-lymphocyte ratio (NLR) to predict outcomes with immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (mUC).

449 Background: ICIs have provided advances in the therapy of mUC. However, the objective determination of benefit from ICIs determined by radiographic imaging may take months and may be confounded by pseudoprogression. Peripheral blood cells appear to reflect tumor microenvironment immune infiltrating cells. Given the known prognostic impact of baseline peripheral blood NLR, we aimed to investigate dynamic early changes in NLR as a biomarker of benefit in patients (pts) with mUC. Methods: Deidentified data from mUC pts who were treated with ICIs at Dana Farber Cancer Institute from 2015 to 2020 were reviewed retrospectively. Demographic data (age, gender), setting (untreated vs. post-platinum), sites of metastasis, performance status (PS), platelet count, and NLR at baseline and 3-4 weeks after initiating the ICI were collected. We assessed the association of NLR at baseline and 3-4 weeks after starting the ICI with any regression of tumor (ART) and overall survival (OS). A multivariable logistic regression model and Cox proportional-hazards model was employed to identify the association of NLR changes with ART and OS, respectively, using backward selection. Results: A total of 144 pts were included. The median age was 76 years and 100 (69.3%) were male. Overall, 54.8% (n=79) had ART and the median OS was 15.2 (12.2-23.5) months. 37.5% (n=54) were platinum naive and the remaining received post-platinum ICI therapy. In the multivariable models (Table), an increase in NLR, defined as an increase in NLR by ≥1.0 from baseline at 3-4 weeks was significantly associated with lower odds of ART (Odds Ratio (OR)= 0.80; 95% CI = 0.70-0.90; p = 0.0004) and worse OS (HR = 1.08; 95% CI = 1.05-1.11; p &lt; 0.0001). The presence of liver metastasis was associated with lower odds of ART (OR = 0.30; 95% CI = 0.13-0.70; p = 0.006) and OS (HR 2.73; 95% CI 1.71 - 4.36; p&lt;0.0001). Conclusions: Change in NLR in the first 4 weeks after initiating ICI for mUC was associated with tumor regression and survival in pts with mUC. Change in NLR may assist in early identification of benefit as well as identification of pts who may have progression of disease. Further validation is warranted to facilitate the early discrimination of benefit from ICIs in pts with mUC.[Table: see text]

Neutrophil–lymphocyte ratio and monocyte–lymphocyte ratio as predictors of cardiovascular risk and mortality in end-stage renal disease

Background The neutrophil–lymphocyte ratio (NLR) and monocyte–lymphocyte ratio (MLR) in the peripheral blood are used as indicators of systemic inflammation and predictors of cardiovascular (CV) diseases. Aims To study the relation between both NLR and MLR and the prediction of cardiovascular events (CVE) in end-stage renal disease (ESRD) patients on regular hemodialysis. Patients and methods In all, 70 ESRD patients on regular hemodialysis were followed up for 12 months. NLR, MLR, and their individual components were determined at baseline and in the follow-up months. The changes in NLR and MLR after 12 months were compared. High-sensitivity C-reactive protein and echocardiography studies were done at baseline and after 12 months. Major CVE were recorded. Results Total leukocyte, absolute neutrophil, and monocyte counts were significantly increased over time. The presence of valvular calcification was associated with an increase in both NLR and MLR (P=0.004 and 0.001, respectively) after 12 months. The mean monocyte counts were significantly higher in patients with CV complications. The baseline monocyte count was the best to predict CV complications with a cutoff point more than 0.54 × 103/µl (sensitivity 100%, specificity 73.85%) in the receiver-operating characteristic curve. Conclusion In ESRD patients, leukocyte counts are in a dynamic change. There was no significant change in NLR or MLR over time and their changes could not predict the occurrence of CVE. The monocyte count is an excellent predictor of CV diseases. The presence of valvular calcification is associated with increases in both NLR and MLR over time.