Hematoma evacuation modifies the relationship between early changes in neutrophil-to-lymphocyte ratio and mortality after intracerebral hemorrhage.

Neutrophil-to-Lymphocyte Ratio and 30-Day Mortality in Patients with Acute Intracerebral Hemorrhage

Predictive Accuracy of Neutrophil-to-Lymphocyte Ratio on Long-Term Outcome in Patients with Spontaneous Intracerebral Hemorrhage

ObjectiveInflammation participates in the pathology and progression of secondary brain injury after intracerebral hemorrhage (ICH). This meta-analysis intended to explore the prognostic role of inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell (WBC), and C-reactive protein (CRP) in ICH patients.MethodsEmbase, PubMed, Web of Science, and Cochrane Library were searched until June 2023. Two outcomes, including poor outcome and mortality were extracted and measured. Odds ratio (OR) and 95% confidence interval (CI) were presented for outcome assessment.ResultsForty-six studies with 25,928 patients were included in this meta-analysis. The high level of NLR [OR (95% CI): 1.20 (1.13–1.27), p < 0.001], WBC [OR (95% CI): 1.11 (1.02–1.21), p = 0.013], and CRP [OR (95% CI): 1.29 (1.08–1.54), p = 0.005] were related to poor outcome in ICH patients. Additionally, the high level of NLR [OR (95% CI): 1.06 (1.02–1.10), p = 0.001], WBC [OR (95% CI): 1.39 (1.16–1.66), p < 0.001], and CRP [OR (95% CI): 1.02 (1.01–1.04), p = 0.009] were correlated with increased mortality in ICH patients. Nevertheless, PLR was not associated with poor outcome [OR (95% CI): 1.00 (0.99–1.01), p = 0.749] or mortality [OR (95% CI): 1.00 (0.99–1.01), p = 0.750] in ICH patients. The total score of risk of bias assessed by Newcastle-Ottawa Scale criteria ranged from 7–9, which indicated the low risk of bias in the included studies. Publication bias was low, and stability assessed by sensitivity analysis was good.ConclusionThis meta-analysis summarizes that the high level of NLR, WBC, and CRP estimates poor outcome and higher mortality in ICH patients.

A growing body of evidence supports that inflammatory mechanisms are involved in secondary brain injury after intracerebral hemorrhage (ICH) which has implications on the morbidity and mortality of stroke patients. Neutrophil-to-lymphocyte ratio (NLR) is a comprehensive index marker of inflammation and immune status of a patient. The prognostic value of NLR in predicting in-hospital mortality and functional outcome of patients with spontaneous intracerebral hemorrhage will be assessed in this study. We retrospectively selected 151 hemorrhagic stroke patients, and demographic and clinical characteristics were collected and computed for NLR. Receiver operating characteristic analysis using Youden's index was utilized to determine the NLR cut-off value with the best sensitivity and specificity. The association of NLR with the in-hospital mortality and functional outcome was assessed using Logistic regression analysis. Pearson Product Model Correlation was employed to evaluate the correlation of NLR with ICH volume. Admission NLR >7 showed a significant association (p=<0.001 OR 7.99) with in-hospital mortality with a sensitivity of 70.83% and specificity of 72.82%. Furthermore, computed NLR of more than 6.4 showed significant association (p=0.040 OR 2.92) with poor functional outcome. However, our study revealed that admission NLR showed a low level of correlation (r=0.2968, p=0.002) with the volume of ICH. This study demonstrated that ICH patients with an elevated NLR is associated with increased in-hospital mortality and poor functional outcome and that NLR can be used to predict clinical outcome among patients with spontaneous ICH.

Intracranial pressure variability predicts short-term outcome after intracerebral hemorrhage: A retrospective study

BackgroundThe neutrophil to lymphocyte ratio (NLR) is known to be prognostic for patients with advanced cancers treated with immune checkpoint inhibitors (ICI), but has generally been evaluated as a single threshold value at baseline. We evaluated NLR at baseline and within first month during treatment in patients who received ICI for advanced cancer to evaluate the prognostic value of baseline and of changes from baseline to on-treatment NLR.MethodsA retrospective review of patients with advanced cancer treated with ICI from 2011 to 2017 at the Ohio State University was performed. NLR was calculated at the initiation of ICI and repeated at median of 21 days. Overall survival (OS) was calculated from the initiation of ICI to date of death or censored at last follow-up. Significance of Cox proportional hazards models were evaluated by log-rank test. Calculations were performed using the survival and survminer packages in R, and SPSS.Results509 patients were identified and included in the analysis. Patients with baseline and on-treatment NLR < 5 had significantly longer OS (P < 0.001). The change in NLR overtime was a predictor of OS and was observed to be non-linear in nature. This property remained statistically significant with P < 0.05 after adjusting for age, body mass index, sex, cancer type, performance status, and days to repeat NLR measurement. Patients with a moderate decrease in NLR from baseline had the longest OS of 27.8 months (95% CI 21.8–33.8). Patients with significant NLR decrease had OS of 11.4 months (95% CI 6.1–16.7). Patients with a significant increase in NLR had the shortest OS of 5.0 months (95% CI 0.9–9.1).ConclusionsWe confirmed the prognostic value of NLR in patients with advanced cancer treated with ICIs. We found that change in NLR over time is a non-linear predictor of patient outcomes. Patients who had moderate decrease in NLR during treatment with ICI were found to have the longest survival, whereas a significant decrease or increase in NLR was associated with shorter survival. To our knowledge, this is the first study to demonstrate a non-linear change in NLR over time that correlates with survival.

Background and Objectives: Neutrophil-to-lymphocyte ratio (NLR), a very low cost, widely available marker of systemic inflammation, has been proposed as a potential predictor of short-term outcome in patients with intracerebral hemorrhage (ICH). Methods: Patients with ICH admitted to the Neurology Department during a two-year period were screened for inclusion. Based on eligibility criteria, 201 patients were included in the present analysis. Clinical, imaging, and laboratory characteristics were collected in a prespecified manner. Logistic regression models and receiver operating characteristics (ROC) curves were used to assess the performance of NLR assessed at admission (admission NLR) and 72 h later (three-day NLR) in predicting in-hospital death. Results: The median age of the study population was 70 years (IQR: 61–79), median admission NIHSS was 16 (IQR: 6–24), and median hematoma volume was 13.7 mL (IQR: 4.6–35.2 mL). Ninety patients (44.8%) died during hospitalization, and for 35 patients (17.4%) death occurred during the first three days. Several common predictors were significantly associated with in-hospital mortality in univariate analysis, including NLR assessed at admission (OR: 1.11; 95% CI: 1.04–1.18; p = 0.002). However, in multivariate analysis admission, NLR was not an independent predictor of in-hospital mortality (OR: 1.04; 95% CI: 0.9–1.1; p = 0.3). The subgroup analysis of 112 patients who survived the first 72 h of hospitalization showed that three-day NLR (OR: 1.2; 95% CI: 1.09–1.4; p < 0.001) and age (OR: 1.05; 95% CI: 1.02–1.08; p = 0.02) were the only independent predictors of in-hospital mortality. ROC curve analysis yielded an optimal cut-off value of three-day NLR for the prediction of in-hospital mortality of ≥6.3 (AUC = 0.819; 95% CI: 0.735–0.885; p < 0.0001) and Kaplan–Meier analysis proved that ICH patients with three-day NLR ≥6.3 had significantly higher odds of in-hospital death (HR: 7.37; 95% CI: 3.62–15; log-rank test; p < 0.0001). Conclusion: NLR assessed 72 h after admission is an independent predictor of in-hospital mortality in ICH patients and could be widely used in clinical practice to identify the patients at high risk of in-hospital death. Further studies to confirm this finding are needed.

BACKGROUND: Immune-enhancing nutrition (IMN) strengthens the systematic inflammatory response and the immune system. Neutrophil to lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) are affected during cancer therapies.OBJECTIVE: We carried out an analysis of the dynamic changes in NLR and ALC over time in cancer patients with or without IMN supplementation.METHODS: 88 cancer patients receiving concurrent chemoradiotherapy (CCRT) were randomized into regular diet group, and regular diet and IMN group.Generalized estimation equation models were used to assess associations between patient’s characteristics, IMN, and dynamic changes in NLR and ALC over time.RESULTS: NLR and ALC at pre-CCRT were significantly associated with dynamic changes in NLR (adjusted 1.08, 95% confidence interval [CI]: 0.64–1.52) and ALC (adjusted 0.41, 95% CI: 0.36–0.46). The magnitudes of the NLR and ALC changes through CCRT were lower in patients receiving IMN, although the differences were not statistically significant except ALC at the end of CCRT in head and neck cancer patients ( 0.023).CONCLUSION: Dynamic negative changes in both markers were demonstrated throughout CCRT. There were non-significant trend in promising changes in both NLR and ALC values in the whole group in IMN supplementation.

PurposeTo examine the effect of dynamic changes in neutrophil-to-lymphocyte ratio (NLR) on tumor response and overall survival (OS) in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE).Patients and MethodsData from 181 patients with HCC were retrospectively collected. White blood cell, neutrophil and lymphocyte counts, and the NLR were obtained 1–3 days before as well as 3–6 weeks and 3 months after TACE. Patients were divided into two groups at each time point according to the mean value of NLR, and also divided into continuous decrease, fluctuating increase-decrease (I-D), fluctuating decrease-increase (D-I), and continuous increase groups according to the dynamic changes in the NLR. The dynamic changes in blood counts and NLR were analyzed using repeated-measures ANOVA. The odds ratios (ORs) for tumor response in different NLR groups were examined using a multivariate logistic regression model. Finally, the prognostic value of the dynamic changes in the NLR was examined using Cox regression models.ResultsContinuous decline of white blood cell counts, neutrophil counts and lymphocyte counts were observed at 3–6 weeks and 3 months after TACE treatment. The NLR increased slightly and then decreased substantially in responders, while it increased slightly and then significantly in non-responders, with a significant interaction effect of Time × Tumor response (P = 0.005). NLR grouping before TACE, 3–6 weeks and 3 months after TACE was not associated with tumor response, and only 3 months after TACE did, it shows a significant difference in univariate survival analyses (NLR > 2.5 vs NLR ≤ 2.5, hazard ratio [HR] = 2.442, 95% confidence interval (CI): 1.545, 3.860). The changes in the NLR were significantly correlated with tumor response and OS. Non-responders for TACE were more common in the continuous NLR increase group (OR = 6.230, 95% CI: 1.848–21.001) and in the fluctuating D-I group (OR = 5.702, 95% CI: 1.480–21.957). Multivariate analyses revealed that these two patient groups also showed poorer OS (HR = 2.351, 95% CI: 1.120–4.605 and HR = 2.320, 95% CI: 1.187–4.533, respectively).ConclusionDynamic changes in the NLR may be better predictors of tumor response and OS than static NLR values, but more data are needed.

9573 Background: Cancer related inflammatory processes have been shown to have an important role in tumourigenesis, disease progression, and patient prognosis. An elevated neutrophil to lymphocyte ratio (NLR) is associated with a worse outcome in several malignancies. The relationship between NLR and immune checkpoint blockade is poorly understood. We sought to investigate the role of NLR in patients receiving immune checkpoint inhibitors for metastatic melanoma (MM). We aimed to do this by comparing outcomes of patients with MM with high ( &gt; 3) and low ( &lt; 3) NLRs receiving immunotherapy, and investigating whether NLR acts as a prognostic biomarker. Methods: We performed a retrospective review of electronic medical records and collected data on 40 patients with MM treated with immunotherapy from 2013 to 2018 in MMUH, Dublin. NLR was defined as absolute neutrophil count divided by absolute lymphocyte count. Continuous variables were expressed as a median. We examined NLR at baseline and at 6 weeks (+-2 weeks). We also examined percentage change in NLR. These parameters were tested for association with PFS and OS using the log rank test. Results: 40 patients received immune checkpoint inhibitors in the form of ipilimumab, nivolumab, and pembrolizumab. The median age was 61.2 ( 29.7 to 77.1). The median baseline NLR was 3.39 ( 1.05 to 26.03). The median NLR at 6 weeks (+-2 weeks) was 2.86 ( 0.83 to 19.9). The median change in NLR was -8.02% (- 80.99% to 409.38%). Median time to progression was 4.7 months (0.4 to 51.4 months). Overall survival was 12.9 months (0.4 to 67.7 months). When baseline NLR &lt; 3 patients had a significantly longer PFS: 11.7 vs 2.8 months (p = 0.02). When NLR at approximately 6 weeks was &lt; 3, patients also had significantly longer PFS: 10.8 vs 2.9 months (p = 0.04). When NLR decreased by &gt; 20% from baseline, there was no significant difference in PFS (p = 0.82). When NLR &lt; 3, patients had significantly longer OS: 18 months vs 8.2 months (p = 0.02). When NLR at approximately 6 weeks was &lt; 3, patients had significantly longer OS: 20.3 months vs 7.4 months (p = 0.003). Conclusions: Baseline NLR &lt; 3 and NLR &lt; 3 approximately 6 weeks after initiation of treatment is associated with improved PFS and OS. Change in NLR after initiation of treatment is not significantly associated with improved outcomes, however our sample size was small. NLR may be used as a readily available and cheap prognostic marker in MM patients receiving immunotherapy.

e18201 Background: Neutrophil to Lymphocyte Ratio (NLR) is prognostic for cancer patients treated with immune checkpoint inhibitors (ICI). We showed the change in NLR early during treatment to be a stronger, curvilinear predictor, i.e. patients with an intermediate change in NLR performed better than those with large decreases or increases. This led us to re-examine whether NLR is an optimal predictor of overall survival (OS). Methods: A retrospective review of 467 patients with advanced cancer who received ICIs from 2011 to 2017 at the Ohio State University was performed with IRB approval. NLR was collected at the initiation of ICI and on-treatment (median 21, IQR 8 days) and calculated as ratio of absolute neutrophil to lymphocyte counts. Variable selection machine-learning algorithms included fast and frugal decision trees and random forest, performed in R. Results: The machine-learning algorithm fast and frugal decision trees identified the ratio of NLR on treatment to baseline NLR, the NLR on treatment, the change in NLR and the cubic change in NLR to be the most informative predictors of survival at 12 months. A random forest algorithm identified the same four variables as the most important for prediction accuracy. Age, sex and cancer type were the least informative predictors in the model, suggesting the on-treatment NLR variables are of value across wide range of demographics. Conclusions: NLR measured during treatment, and its derivative values of the ratio to baseline, change from baseline, and the cubic change from baseline, hold more predictive value than NLR measured at baseline. Common control variables such as age, and sex showed little effect on the model, suggesting on-treatment NLR is useful across wide demographic space. [Table: see text]

The complement cascade is activated and contributes to the brain injury after intracerebral hemorrhage (ICH). Complement component 4 (C4), an important component of complement cascade, has been associated with severity of neurological impairment that occurs during ICH. However, the correlation of plasma complement C4 levels with hemorrhagic severity and clinical outcome in ICH patients has not been reported. This study is a monocentric, real-world, cohort study. In this study, we measured the plasma complement C4 levels of 83 ICH patients and 78 healthy controls. The hematoma volume, the National Institutes of Health Stroke Scale (NIHSS) score, the Glasgow Coma Scale (GCS) score, and the permeability surface (PS) were used to assess and quantify neurological deficit following ICH. Logistic regression analysis was configured to determine the independent relation of plasma complement C4 levels to hemorrhagic severity and clinical outcomes. The contribution of complement C4 to secondary brain injury (SBI) was assessed by changes in plasma C4 levels between admission and at day 7 after ICH. There was a significant elevation of plasma complement C4 levels in ICH patients than in healthy controls (40.48 ± 1.07 vs. 35.25 ± 0.60, p < 0.0001), and the plasma complement C4 levels were closely related to the hemorrhagic severity. Moreover, plasma complement C4 levels of patients were positively correlated with the hematoma volume (r = 0.501, p < 0.001), NIHSS score (r = 0.362, p < 0.001), the GCS score (r = -0.490, p < 0.001), and PS (r = 0.683, p = 0.045) following ICH. Logistic regression analysis also confirmed that patients with high plasma complement C4 levels show a poor clinical outcome after ICH (p < 0.001). Meanwhile, the elevated plasma levels at day 7 after ICH indicated the correlation of complement C4 with SBI (p < 0.01). Plasma complement C4 levels are significantly elevated in ICH patients and positively correlated with the illness severity. Thus, these findings highlight the importance of complement C4 in brain injury after ICH and provide a novel predictor of clinical outcome for this disease.

539 Background: Previous studies have shown that the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are potential prognostic markers in many different cancers. However, the relationship between the changes of these ratios after concurrent chemoradiotherapy (CRT) and clinical outcome in rectal cancer patients was not reported yet. Accordingly, the aim of this study was to evaluate the prognostic relevance of the changes in NLR and PLR in patients with rectal cancer who treated with CRT followed by surgery. Methods: We enrolled 296 patients with histologically confirmed rectal adenocarcinoma who have received preoperative CRT at Kyungpook National University Medical Center (Daegu, Korea) between January 2006 and December 2015. We analyzed full hematological data both pre CRT (initial visit) and post CRT (before surgery) and oncologic outcomes including pathologic complete response (pCR), relapse-free survival (RFS), and overall survival (OS). An NLR≥5 and PLR ≥235 were considered to cut-off values according to previous studies. The ratio of change in NLR and PLR were calculated by following formula: ratio of change in NLR = (post NLR-pre NLR)/ pre NLR *100, ratio of change in PLR = (post PLR-pre PLR)/pre PLR *100. Significant cut-off value for ratio of change in NLR and PLR were calculated by simulation analysis (SAS Institute Japan, Tokyo, Japan). Results: Of the 296 patients, the majority were male (69.6%), with a median age of 59.1 years (range 25~88). Of these patients, 41 (13.9%) obtained pCR after CRT. Sixty-one patients (20.6%) had high PLR before CRT, which significantly correlated with pCR (p = 0.014) and RFS (p = 0.026), while high NLR was associated with pCR (p = 0.012) only. The optimal cut-off value for the ratio of change in PLR was 200 for RFS. The patients who had relatively higher ratio of change in PLR (ratio of change in PLR ≥ 200) showed better RFS compared to lower ratio of change (ratio of change in PLR &lt; 200) (3-year RFS 90.9% vs. 69.7%, p = 0.05). Changes in NLR did not correlate with oncologic outcomes. Conclusions: Changes in platelet/lymphocyte ratio could also be a potential clinical biomarker in predicting oncologic outcome in rectal cancer patients treated with preoperative CRT.

e20710 Background: Currently, prognostic markers associated with immunotherapy treatment outcomes in patients with metastatic NSCLC include PDL-1 expression, tumor mutational burden (TBM), and neutrophil to lymphocyte ratio (NLR). In this study we examine the influence of pretreatment changes in weight, BMI, and NLR in 237 patients treated with anti-PD-1/PDL-1 therapy (ICI) at our institution. Methods: This was a retrospective analysis of previously-treated stage IV NSCLC patients who received ICI. Pretreatment (≥ 6 weeks before starting therapy) values of weight, BMI, and NLR were compared to baseline values and NLR was analyzed as continuum and according to standard cutoffs of 3.5 and 5. The same variables were correlated with progression-free survival (PFS) and overall survival (OS) using the Log-Rank test. Results: 237 patients were analyzed: 45% were male, 73% were Caucasian, 72% were former smokers, and 25% were age ≥ 75 years. 148 patients had pretreatment NLR values. Of these, 32% had a ratio &lt; 3.5 and 54% had ratio &lt; 5. 34% had increased NLR at baseline, the majority of which (48/77) had a &gt; 5% increase. 187 patients had pretreatment weight and BMI. Of these, 14% had a pretreatment BMI &lt; 20. 71% had a negative change in BMI and 29% had a &gt; 5% decrease in BMI. 65% had a negative change in weight and 26% had a &gt; 5% decrease in weight. BMI decrease greater than 5% (p = 0.0039), negative weight change (p = 0.0371), and pretreatment NLR &gt; 5 (p = 0.0136) were associated with shorter PFS. Change in NLR trended towards decreased PFS but was not statistically significant (p = 0.07) though only 77 of 237 patients had both values available. There was no statistical PFS difference between patients less than or ≥ 75 years old. Conclusions: The results suggest that decrease in pretreatment BMI and weight along with high baseline NLR are associated with significantly shorter PFS in NSCLC treated with anti-PD-1/PDL-1 therapy. If confirmed, these observations raise the possibility that specific treatment which reverses cancer associated weight loss might enhance effectiveness of immunotherapy.

The Predictive Role of Postoperative Neutrophil to Lymphocyte Ratio for 30-Day Mortality After Intracerebral Hematoma Evacuation