Low Neutrophil-lymphocyte Ratio Research Articles

Association of neutrophil-lymphocyte ratio with all-cause and cardiovascular mortality in US adults with diabetes and prediabetes: a prospective cohort study

BackgroundThe neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status.MethodsData were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors.ResultsOver a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19–1.58) for all-cause mortality and 1.63 (95% CI, 1.29–2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03–1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08–2.04) remained statistically significant (both p-values for trend < 0.05) in prediabetes subjects. The 10-year cumulative survival probability was determined to be 70.34%, 84.65% for all-cause events, and 86.21%, 94.54% for cardiovascular events in top NLR tertile of diabetes and prediabetes individuals, respectively. Furthermore, each incremental unit in the absolute value of NLR was associated with a 16%, 12% increase in all-cause mortality and a 25%, 24% increase in cardiovascular mortality among diabetes and prediabetes individuals, respectively.ConclusionsThe findings of this prospective cohort study conducted in the US indicate a positive association of elevated NLR levels with heightened risks of overall and cardiovascular mortality among adults with diabetes and prediabetes. However, potential confounding factors for NLR and the challenge of monitoring NLR’s fluctuations over time should be further focused.

Red blood cell distribution width may predict the prognosis of vestibular neuritis

Objectives: The study aimed to determine whether red cell distribution width (RDW), as well as other inflammatory markers of complete blood count, have any predictive value for the etiology, diagnosis, and prognosis of vestibular neuritis (VN). Patients and Methods: Forty-two VN patients (28 females, 14 males; mean age: 46.7±11.0 years; range, 20 to 75 years) and 50 controls (32 females, 18 males; mean age: 44.4±6.0 years; range, 22 to 55 years) were included in the retrospective study between May 2016 and May 2018. Red cell distribution width and neutrophil, lymphocyte, platelet, and monocyte levels were documented from the hemogram records of all patients. Additionally, the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio were calculated. Results: In the VN group, NLR and PLR values were significantly high (p=0.001 and p&lt;0.001, respectively). Red cell distribution width, platelet, lymphocyte, and monocyte levels were significantly high and hemoglobin was significantly low in VN patients with long-lasting spontaneous nystagmus (p&lt;0.001, p=0.026, p=0.033, p=0.047, and p=0.006, respectively). Conclusion: High RDW and low hemoglobin levels may predict a poor prognosis in adult VN patients. Moreover, a low lymphocyte-monocyte ratio and high NLR and PLR values are supportive findings in the diagnosis of vestibular neuritis.

Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People's Hospital from May 2020 to August 2022 were selected. A total of 52 AAV patients were divided into active phase (>15 points) and remission phase (≤15 points) based on the Birmingham vasculitis activity score (BVAS). Serum IL-18 level was detected by enzyme-linked immunosorbent assay in three groups. Pearson product moment correlation analysis was performed to investigate the correlation between serum IL-18 levels and clinical laboratory indicators, and receiver operating characteristic (ROC) curve analysis was performed on serum IL-18, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and NLR in AAV patients. The levels of serum creatinine, parathyroid hormone, β2-microglobulin (β2-MG), ESR, CRP, and IL-18 in active stage of AAV were significantly higher than those in remission stage of AAV. Moreover, the serum IL-18 level of active AAV patients was significantly higher than that of disease control group (P < 0.05). The levels of eGFR, hemoglobin, and complement C3 were significantly lower than those during the remission (P < 0.05). Pearson product moment correlation analysis showed that serum IL-18 level in AAV patients was positively correlated with BVAS score and ESR level. The area under the curve of serum IL-18, NLR, CRP, ESR levels evaluated by ROC curve was 0.921, 0.899, 0.83, and 0.75, respectively. Kaplan-Meier survival curve showed that the cumulative survival rate of patients in low NLR group was significantly higher than that in high NLR group (68.36 vs 42.89%), with significant difference (Log-Rank = 6.745, P = 0.025 < 0.05). IL-18 may be adopted as one of the important biological markers to judge the disease of AAV, and the cumulative survival rate of patients with high NLR is low, which may be applied as an indicator to evaluate the poor prognosis of patients with AAV.

Development and Internal Validation of a Prediction Model for Nasopharyngeal Carcinoma: Using BMI and Inflammatory Response for Deciding Sequence of Chemotherapy.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-AC) and induction chemotherapy followed by concurrent chemoradiotherapy (IC-CRT) are among the best treatments in nasopharyngeal carcinoma (NPC). This study aimed to develop a model for deciding the sequence of chemotherapy in NPC. Data were separated into two cohorts. The CRT-AC cohort had 295 patients, while the IC-CRT cohort had 112. The predictors were standard factors with BMI and neutrophil-lymphocyte ratio (NLR) to predict overall survival (OS). A flexible parametric survival model was used. A total of 132 (44.7%) and 72 patients (64.3%) died in the CRT-AC and IC-CRT cohorts, respectively. The predictors in the final models were age, sex, T, N, NLR, and BMI. The models of OS for CRT-AC and IC-CRT had concordance indices of 0.689 and 0.712, respectively, with good calibration curves. When changing the burden of disease along with NLR and BMI, we found that CRT-AC was not significantly different OS from IC-CRT when low NLR (<3) and high burden of disease (T3N3). By contrast, CRT-AC was remarkably more effective when there were high levels of NLR (≥3) and BMI (≥25) with any burden of disease (anyT anyN). With additional BMI and NLR in model, it could be easier to decide between CRT-AC and IC-CRT in countries with limited health care resources.

The Neutrophil/Lymphocyte Ratio and Outcomes in Hospitalized Patients with Community-Acquired Pneumonia: A Retrospective Cohort Study.

We aimed to assess the prognostic role of the neutrophil/lymphocyte ratio (NLR) in community-acquired pneumonia (CAP) via a single-center retrospective cohort of hospitalized adult patients from 1/2009 to 12/2019. Patients were dichotomized into lower NLR (≤12) and higher NLR (>12). The primary outcome was mortality. ICU admission and hospital- and ICU-free days were secondary outcomes. The pneumonia severity index (PSI) and the NLR's ability to predict outcomes was also tested. An NLR ≤12 was observed in 2513 (62.2%) patients and >12 in 1526 (37.8%). After adjusting for PSI, the NLR was not associated with hospital mortality (odds ratio [OR] 1.115; 95% confidence interval [CI] 0.774, 1.606; p = 0.559), but it was associated with a higher risk of ICU admission (OR 1.405; 95% CI 1.216, 1.624; p < 0.001). The PSI demonstrated acceptable discrimination for mortality (area under the receiver operating characteristic curve [AUC] 0.78; 95% CI 0.75, 0.82) which was not improved by adding the NLR (AUC 0.78; 95% CI 0.75, 0.82, p = 0.4476). The PSI's performance in predicting ICU admission was also acceptable (AUC 0.75; 95% CI 0.74, 0.77) and improved by including the NLR (AUC 0.76, 95% CI 0.74, 0.77, p = 0.008), although with limited clinical significance. The NLR was not superior to the PSI for predicting mortality in hospitalized CAP patients.

Prognostic value of baseline neutrophil/lymphocyte ratio in HER2-positive metastatic breast cancer: exploratory analysis of data from the CLEOPATRA trial

PurposeThis study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab.Experimental designData from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed.ResultsThe baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07–1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12–1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20–1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model (P = 0.015 and 0.008, respectively).ConclusionsA low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.

Inflammatory parameters in NSCLC with driver mutation

Aim: The tumor microenvironment of NSCLC with driver mutations, such as EGFR, ALK and ROS, is less inflammatory. Materials &amp; methods: This retrospective study included 38 patients with NSCLC driver mutations. The relationship between clinical and inflammatory markers concerning progression-free survival and overall survival was analyzed based on Kaplan-Meier curves. Results: The mean age of the patients was 59.8 ± 11.9. Progression-free survival and overall survival were significantly longer in patients under 65 years of age and with low neutrophil–lymphocyte ratio, low systemic immune-inflammation index and high lymphocyte count (p &lt; 0.05). Conclusion: Unlike tumor biology, peripheral inflammatory parameters, such as neutrophil–lymphocyte ratio, systemic immune-inflammation index and lymphocyte count may be associated with survival in NSCLC patients with driver mutations.

Utilizing peripheral blood inflammatory biomarker (PBIB) to predict response to systemic therapy in patients with breast cancer.

Inflammation is a recognized factor in cancer progression and resistance to treatments. Several studies correlated inflammation-related peripheral blood inflammatory biomarkers (PBIB) to disease progression and poor survival in various cancer types and different populations. Nonetheless, inflammation is affected by the distinctive characteristics and environmental exposure of each population. There is no prior study addressing the association of pre-treatment inflammatory markers with outcomes in patients with breast cancer (BC) from Saudi Arabia. In this study, we evaluated the prognosis of locally advanced breast cancer (LABC) in relation to several PBIB. We retrospectively analyzed the data of female patients with LABC undergoing neoadjuvant chemotherapy (NACT). Demographics, body mass index (BMI), clinicopathologic characteristics and stage of the tumor, follow-up status, and response to treatment were collected. Outcomes were evaluated in relation to pre-treatment peripheral blood indices that were grouped based on the local laboratory cutoff values. Objective response rate (ORR) was predefined and assessed according to the post-NACT magnetic resonance imaging (MRI) breast and subcategorized into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). A total of 172 female patients with BC met the eligibility criteria from January 2014 to December 2019. The mean age at diagnosis was 53.4 ± 11, and BMI was 31.2 ± 6. Left BC accounted for 54.7%, and the majority was invasive ductal carcinoma (85.5%), moderately differentiated (51%), stage III (AJCC 8th edition) (73%), and estrogen receptor (ER)-positive tumor (79.1%). Human epidermal growth factor receptor 2 (HER2)-positive BC was reported in 32% and triple-negative breast cancer (TNBC) in 10%. Radiologic CR accounted for the majority of ORR (71.5%). Higher percentage of patients with normal red cell distribution width (RDW) of red blood cell (RBC) and low neutrophil-lymphocyte ratio (NLR) had CR with a significant P value of 0.003 and 0.014, respectively. Among several peripheral blood indices, RDW and NLR significantly influenced ORR. They can be explored further to potentially predict response after systemic therapy in patients with LABC. The great advantage of these biomarkers stems from their availability and affordability in routine clinical practice.

Neutrophil–lymphocyte ratio in patients with idiopathic pleuroparenchymal fibroelastosis

BackgroundIdiopathic pleuroparenchymal fibroelastosis (iPPFE), a progressive fibrotic disease, is characterised by upper lobe–dominant lung fibrosis involving the pleura and subpleural lung parenchyma. However, no prognostic markers have been established for...

OGC P02 Neutrophil/lymphocyte ratio and long-term survival after pancreatoduodenectomy for malignancy

Abstract Background Previous authors have highlighted that preoperative neutrophil/lymphocyte ratio (NLR) may be of prognostic importance in patients who undergo pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC), ampullary carcinoma (AA) or cholangiocarcinoma (CC) of the pancreatic head/periampullary region. Various cut-off thresholds have been suggested. This study aimed to compare the five-year survival rates of PD patients with high preoperative NLR to those with low preoperative NLR (using thresholds from recent studies). Methods Data was extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective cohort study of outcomes of PD performed for pancreatic head malignancy (29 centres in 8 countries, n=1484). Patients were grouped by their underlying cancer type and divided into “high NLR” (PDAC: ≥ 3.74, AA: ≥3.0, CC: ≥2.75) and “low NLR” (PDAC: &amp;lt;3.74, AA: &amp;lt;3.0, CC: &amp;lt;2.75) groups. Five-year survival rates were compared using Fisher’s exact test. Results Out of 1484 patients, 885 (59.6%) had PDAC, 394 (26.5%) had AA and 205 (13.8%) had CC, and NLR was available in 88.4%, 89.1% and 92.2% of cases, respectively. The median NLR was 2.7 (range: 0.1-34.0), 2.8 (range: 0.3-103.0) and 2.7 (range:0.1-83.3) for patients with PDAC, AA and CC, respectively. Low NLR did not correlate with improved five-year survival rates in any of the studied cancers (PDAC: 24.5% vs 23.8%, p=0.9, AA: 56.1% vs 51.2%, p=0.4, CC: 34.4% vs 25.8%, p=0.2). Conclusions In our multicentre study of PD outcomes, preoperative NLR was not useful for predicting five-year survival in patients with PDAC, AA or CC.

Prognostic nutritional index and neutrophil-lymphocyte ratio predict toxicities and prognosis in patients with cervical cancer treated with curative radiochemotherapy

BackgroundThis study aimed to investigate the influence of immunonutritional factors on treatment-related toxicities and survival outcomes in patients with cervical cancer undergoing definitive radiochemotherapy. MethodsPatients with cervical cancer who received curative radiochemotherapy between 2016 and 2021 were retrospectively investigated. Pretreatment prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were measured. Survival outcomes, acute and late toxicities were evaluated. ResultsAmong the 138 patients, those with larger tumor diameters had significantly lower pre-treatment PNI (p = 0.005). Pre-treatment immunonutritional factors were predictive of clinical survival, whereas post-treatment factors did not correlate with prognosis. Patients with low pre-treatment PNI (<49.5) or high NLR (>2.4) had shorter progression-free survival (PFS, HR: 1.86, p = 0.045 for PNI; HR: 3.15, p = 0.002 for NLR) and overall survival (OS, HR: 1.80, p = 0.048 for PNI; HR: 3.83, p = 0.015 for NLR). High pre-treatment NLR was associated with an increased risk of acute diarrhea (p = 0.049) and late severe toxicities (p = 0.046). Combined analysis revealed that pre-treatment good nutritional status and low systemic inflammation were linked to longer PFS (p = 0.007) and OS (p = 0.002), and poor nutritional status and substantial systemic inflammation were associated with higher rates of late severe toxicities (p = 0.036), with higher prognostic value in advanced stage patients. ConclusionPretreatment immunonutritional measures serve as quantitative biomarkers for predicting survivals and treatment toxicities in patients with cervical cancer treated with definitive radiochemotherapy.

Indications of Effective Hyperbaric Oxygen Therapy Combined With Steroid Therapy for Sudden Hearing Loss.

This study evaluated the therapeutic effect of hyperbaric oxygen therapy (HBOT) combined with steroid therapy to treat sudden hearing loss and examined the index associated with excellent therapeutic effect. We included 109 patients with sudden hearing loss. Patients were divided into the HBOT combination group (59 sides) treated with HBOT and steroid therapy and HBOT noncombination group (50 sides) involving steroid therapy only. The recovery rate of each group was compared according to the severity of hearing loss. Blood samples were evaluated and inflammatory markers, such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), were calculated and compared by severity. We evaluated the usefulness of inflammatory markers for predicting recovery rate, and calculated cutoff values were also evaluated. The HBOT combination group exhibited a higher overall recovery rate than the HBOT noncombination group, particularly in severe cases. However, there was no significant difference in the severity of hearing loss based on various inflammatory markers. NLR and PLR are useful for predicting the effect in patients treated with concomitant HBOT. By setting 2.43 and 146.67 as cutoff values for NLR and PLR, respectively, we observed that lower values resulted in better recovery rates. The use of HBOT is effective for severe cases and early blood flow disorders with low NLR and PLR and less inflammation. When determining treatment, not only should the severity of hearing loss be considered, but also the NLR and PLR should be evaluated and examined based on the cutoff values.

Evaluation of hematologic inflammatory markers in Graves’ disease

Introduction: The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) have been used as new inflammatory markers in certain autoimmune diseases to assess the severity of inflammation. The current study aimed to evaluate the changes in neutrophil and lymphocyte series in hyperthyroid patients and to investigate whether NLR, PLR, and SII may be markers of inflammation. Methods: This cross-sectional study was conducted with 207 Graves’ patients and 120 healthy controls between 2018-2022 years. Hematologic parameters, thyroid function tests, age and gender were recorded. The NLR, PLR and SII values of all subjects were calculated. Firstly, groups were composed as Graves' group and participants without thyroid disorder as control group. Secondly, Graves' patients composed as two groups before treatment and after antithyroid treatment. These groups were compared with each other in terms of descriptive data and hematological parameters. Results: The patient and control groups were similar in terms of gender (p=0.522) and age (p=0.051). Graves’ patients had a significantly lower NLR than the control group (p=0.004). There was no significant difference between the groups in terms of PLR (p=0.120) and SII (p=0.577). Patients’ baseline TSH-receptor antibodies (TRAb) levels had a significant positive correlation with fT3 (r:0.283, p&amp;lt;0.001), fT4 (r:0.252, p&amp;lt;0.001) and Thyroid stimulating immunoglobulin (TSI) (r:0.673, p&amp;lt;0.001). There was no significant correlation between TRAb and TSI levels, inflammatory markers, and hematological parameters. Conclusions: Graves’ patients had lower NLR compared to the control group. The patient and control groups did not have a significant difference with regard to PLR and SII. Thyroid autoantibody levels and inflammatory markers did not have a significant correlation. Keywords: Hyperthyroidism, inflammation, neutrophils, lymphocytes

Blood Immune Cells as Biomarkers in Long-Term Surviving Patients with Advanced Non-Small-Cell Lung Cancer Undergoing a Combined Immune/Chemotherapy.

An important challenge remains in identifying the baseline characteristics of cancer patients who will mostly benefit from immune checkpoint inhibitor (ICI) therapies. Furthermore, biomarkers could help in the choice of an optimal therapy duration after a primary therapy response. In this pilot study, the time courses of four different immune cell parameters were followed in 12 patients with advanced non-small-cell lung cancer (NSCLC) undergoing ICI therapy combined with chemotherapy and surviving at least 12 months. Blood was collected at the time point of the first and third antibody administration, as well as after 12 months of patients' survival. Using multi-color flow cytometry, two suppressive markers (neutrophil/lymphocyte ratio (NLR) and the frequency of circulating HLA-DRlow monocytes), as well as two markers of an ongoing immune response (6-Sulfo LacNAc (slan)+ non-classical monocytes and dendritic cell (DC) subtypes), were determined. In most of those who survived > 12 months, a low NLR and a low number of HLA-DRlow monocytes combined with clearly detectable numbers of slan+ non-classical monocytes and of DC subtypes were seen. Two of the patients had an increase in the suppressive markers paired with a decrease in slan+ non-classical monocytes and in DC subtypes, which, in at least one patient, was the correlate of an ongoing clinical progression. Our results implicate that the NLR, specific subtypes of monocytes, and the number of blood DCs might be useful predictive biomarkers for cancer patients during long-term treatment with ICI/chemotherapy.

Diagnostic and Prognostic Value of Neutrophil-Lymphocyte Ratio in Adrenocortical Carcinoma

BackgroundThe aim was to explore the value of neutrophil-lymphocyte ratio (NLR) as a biomarker for predicting the prognosis or diagnosis in adrenocortical carcinoma (ACC). MethodsWe identified 262 patients with adrenal gland disease who underwent operation at our institution between 2013 and 2018. According to postoperative pathology, patients were divided into 2 groups: ACC and non-ACC groups. The neutrophil and lymphocyte count of patients were recorded. Within the intergroup comparison, data obtained from ACC and non-ACC groups were evaluated using ANOVA test. The cut-off values of NLR for the prognosis in ACC were determined according to 3 methods. ResultsThe NLR values of ACC and non-ACC groups were 5.36 ± 5.30 and (1.73 ± 0.26) ∼ (2.56 ± 1.35), respectively (P < .001). NLR carry a differential property was evaluated with ROC curve to distinguish the above 2 groups. The cut-off value of NLR was estimated as 2.65 according to the Youden index. With this value, sensitivity was found as 67.5%, specificity was 83.8% and AUC was 0.749 (P < .001, confidence interval = 0.638-0.860). In ACC, the higher NLR group was not shown significantly poorer overall survival than the lower NLR group (NLR ≥2.65 vs. NLR < 2.65, NLR ≥5 vs. NLR <5, NLR ≥5.36 vs. NLR <5.36) (P > .05). ConclusionAccording to the data in this study, it can be said that adrenocortical tumors are likely to be malignant by 67.5% if the NLR value is greater than 2.65. When we use the NLR to predict the prognosis of ACC, there is not statistically significant.

The neutrophil–lymphocyte ratio as a risk factor for all-cause and cardiovascular mortality among individuals with diabetes: evidence from the NHANES 2003–2016

BackgroundEvidence regarding the neutrophil–lymphocyte ratio (NLR) and mortality risk in diabetes patients is scarce. This study investigated the relationship of the NLR with all-cause and cardiovascular mortality risk in diabetes patients.MethodsDiabetes patients (n = 3251) from seven National Health and Nutrition Examination Survey (NHANES) cycles (2003–2016) were included in this study. The cause of death and mortality status of the participants were obtained from National Death Index records. Restricted cubic spline (RCS) was used to visualize the association of the NLR with mortality risk. The maximally selected rank statistics method (MSRSM) was used to determine the optimal NLR cutoff value corresponding to the most significant association with survival outcomes. Weighted multivariable Cox regression models and subgroup analyses were adopted to assess the association of the NLR with all-cause and cardiovascular mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of the NLR in predicting survival outcomes.ResultsDuring a median follow-up of 91 months (interquartile range, 55–131 months), 896 (27.5%) of the 3251 diabetes patients died, including 261 (8.0%) with cardiovascular deaths and 635 (19.5%) with noncardiovascular deaths. The RCS regression analysis showed a positive linear association between the NLR and all-cause and cardiovascular mortality (both p > 0.05 for nonlinearity) in diabetes patients. Participants were divided into higher (> 3.48) and lower (≤ 3.48) NLR groups according to the MSRSM. In the multivariable-adjusted model, compared with participants with a lower NLR, those with a higher NLR had a significantly higher risk of both all-cause (HR 2.03, 95% confidence interval (CI) 1.64–2.51, p < 0.0001) and cardiovascular mortality (HR 2.76, 95% CI 1.84–4.14, p < 0.0001). The association was consistent in subgroup analyses based on age, sex, smoking status, drinking status, and hypertension, with no significant interaction between the aforementioned characteristics and the NLR (p interaction > 0.05). The time-dependent ROC curve showed that the areas under the curve of the 1-, 3-, 5-, and 10-year survival rates were 0.72, 0.66, 0.64, and 0.64 for all-cause mortality and 0.69, 0.71, 0.69 and 0.65, respectively, for cardiovascular mortality.ConclusionAn elevated NLR is independently associated with increased all-cause and cardiovascular mortality in diabetes patients.

Tertiary lymphoid structure and neutrophil-lymphocyte ratio coordinately predict outcome of pembrolizumab.

Emerging evidence suggests that the presence of tertiary lymphoid structures (TLS) and neutrophil-lymphocyte ratio (NLR) in peripheral blood is associated with the treatment response to checkpoint inhibitors (CPIs), whereas there is limited knowledge regarding whether these factors reciprocally impact the treatment outcomes of CPIs in metastatic urothelial carcinoma (mUC). Herein, we investigated treatment outcomes of platinum-refractory mUC patients (50 cases with whole-exome and transcriptome sequencing) treated with pembrolizumab. The pathological review identified 24% of cases of TLS in the specimens. There was no significant difference in the NLR between the TLS- and TLS+ groups (p = 0.153). In the lower NLR group, both overall survival and progression-free survival were significantly longer in patients with TLS than in those without TLS, whereas the favorable outcomes associated with TLS were not observed in patients in the higher NLR group. We explored transcriptomic differences in UC with TLS. The TLS was comparably observed between luminal (20%) and basal (25%) tumor subtypes (p = 0.736). Exploring putative immune-checkpoint genes revealed that ICOSLG (B7-H2) was significantly increased in tumors with lower NLR. KRT expression levels exhibited higher basal cell markers (KRT5 and KRT17) in the higher NLR group and lower differentiated cell markers (KRT8 and KRT18) in patients with TLS. In conclusion, the improved outcomes of pembrolizumab treatment in mUC are restricted to patients with lower NLR. Our findings begin to elucidate a distinct molecular pattern for the presence of TLS according to the NLR in peripheral blood.

Clinical relevance of neutrophil/lymphocyte ratio combined with APACHEII for prognosis of severe heatstroke

We evaluated clinical implication of neutrophil-lymphocyte ratio (NLR) for severe heatstroke and predictive value of combined acute physiology and chronic health evaluation (APACHEII) score for prognosis of severe heatstroke. Retrospectively, we studied 185 individuals that have been admitted at emergency department for severe heatstroke. On the basis of their prognosis, we sorted the patients into two categories, namely non-survival (n = 43) and survival groups (n = 142). The primary outcome was 30-day mortality. A considerably higher NLR was observed among the non-survivors compared to survivors (P < 0.05). After correction for confounders, statistical analysis using multi-variable Cox regression indicated NLR as an independent risk factor for patient death (HR = 1.167, 95%CI = 1.110–1.226, P < 0.001). Through receiver-operating characteristics (ROC) curve, we estimated area-under the curve (AUC) of NLR to be 0.7720 (95% CI [0.6953, 0.8488]). Also, transformation of NLR into a profile type analysis showed that the marker remained a risk factor for death, which showed trend variation (P for trend <0.001). Subgroup forest plot analysis showed robustness in the predictive ability of NLR after exclusion of confounders. Besides, we demonstrated through Kaplan-Meier (KM) survival analysis curve that high risk NLR mortality substantially exceeded low risk NLR. The combined prediction of NLR and APACHEII achieved higher efficacy than NLR and APACHEII alone (AUC = 0.880, 95% CI [0.8280, 0.9290]). Additionally, Delong test indicated that the combined prediction demonstrated a significantly greater ROC than NLR and APACHEII alone, while DCA showed a considerably higher clinical net benefit rate. Increased NLR is a high risk factor and has predictive value for death in individuals with severe heatstroke. Suggestively, combination of NLR and APACHEII have greater predictive value.

Association of Neutrophil-to-lymphocyte Ratio with Prognosis in Sepsis – An Observational Study from a Tertiary Care Center

Abstract Objectives: This study aims to determine the association of neutrophil-lymphocyte ratio (NLR) with sequential organ failure assessment (SOFA) score, ventilator use, duration of intensive care unit (ICU) stay, and mortality among patients with sepsis. Methods: This prospective observational study included 220 patients with sepsis admitted to the ICU. Details such as age, gender, comorbidities, complaints, SOFA score, diagnosis, and outcomes were collected. Routine investigations included complete blood count, C-reactive protein, and procalcitonin. NLR was derived using the Beckman Coulter DXH-800 Hematology Analyser. A cutoff of 9.11 was taken as high NLR. Patients were followed up till 28 days after treatment. The outcomes studied included 28-day mortality and ICU stay. Results: The mean SOFA score were 7.07 ± 2.56. Based on NLR cutoffs, 146 (66.36%) patients had high NLR while 74 (33.64%) cases had normal or low NLR. SOFA score showed no significant association with high NLR (P = 0.62). Ventilator was used in 118 (53.6%) cases with median of 3.5 days’ duration. The overall ICU stay was 5.6 ± 4.9 days. Mortality was seen in 46 (20.9%) cases. Compared to those with normal NLR, patients with high NLR had significantly more ventilator use (60.9% vs. 39.1%, P = 0.0027) and mortality (30.14% vs. 2.7%, P = 0.0004). The duration of ventilator use and ICU stay was statistically comparable. Conclusion: High NLR shows a significant association with adverse outcomes of sepsis patients in terms of ventilator use and mortality. Since it is cheap and easy to use, it can be applied in more basic settings while monitoring sepsis patients.

Predictive value of NLR and PLR for immune-related adverse events: a systematic review and meta-analysis.

Currently, there is a lack of affordable and accessible indicators that can accurately predict immune-related adverse events (irAEs) resulting from the use of immune checkpoint inhibitors (ICIs). In order to address this knowledge gap, our study explore the potential predictive value of two ratios, namely the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), for irAEs in cancer patients. A systematic search was performed inPubMed, Embase, and the Cochrane library.Studies involving NLR or PLR with irAEs were included.Quality and risk of bias of the selected studies were assessed. Forest plots were created based on Cox model analysis. Random effects meta-analyses were conducted to estimate odds ratio (OR) and its 95% confidence interval (CI). After screening 594 studies, a total of 7 eligible studies with 1068 cancer patients were included. Analysis based on Cox regression showed that low neutrophil-lymphocyte ratio (L-NLR) (OR = 3.02, 95% CI 1.51 to 6.05, P = 0.002) and low platelet-lymphocyte ratio (L-PLR) (OR = 1.83, 95% CI 1.21 to 2.76, P = 0.004) were associated with irAEs. In the subgroup analysis of cut-off value, when the NLR cut-off value was 3, irAEs was significantly correlated with NLR (OR = 2.63, 95% CI 1.63 to 4.26, P < 0.001). Both L-NLR and L-PLR have been found to be significantly associated with irAEs. Consequently, patients identified as being at a higher risk for irAEs should be subjected to more diligent monitoring and close observation.