A combined model of serum neutrophil extracellular traps, CD8+ T cells, and tumor proportion score provides better prediction of PD-1 inhibitor efficacy in patients with NSCLC.

Immune checkpoint inhibitors provide a definite survival benefit for patients with driver-negative advanced non-small cell lung cancer (NSCLC), but predictors of efficacy are still lacking. There may be a relationship between immune inflammatory state and tumor immune response. We explored the relationship of serum neutrophil extracellular traps (NETs) with infiltrating cells in the tumor tissues of patients with NSCLC as well as their relationship with the therapeutic efficacy of programmed cell death protein 1 (PD-1) inhibitors. Serum myeloperoxidase (MPO)-double-stranded DNA (dsDNA) was detected as a marker of NET serum concentration. T cells were detected by immunohistochemical staining, and neutrophils were counted by MPO immunofluorescence staining. Of the 31 patients with NSCLC, a longer progression-free survival after PD-1 inhibitor treatment was associated with higher levels of CD3+ T cells, a lower neutrophil : CD3+-T-cell ratio (NEU/CD3+) and lower neutrophil : CD8+-T-cell ratio (NEU/CD8+) in tumor tissues. Patients with higher serum NETs were more likely to develop progressive disease after treatment (P = 0.003) and to have immune-related adverse events (IrAEs) as well as higher NEU/CD3+ and NEU/CD8+. The combined model of serum NETs, CD8+ T cells, and tumor proportion score (TPS) significantly improved the prediction of PD-1 inhibitor efficacy [P = 0.033; area under the curve (AUC) = 0.881]. Our results indicate that serum NETs are effective predictors of PD-1 inhibitor response and reflect the tissue neutrophil-to-lymphocyte ratio and IrAE levels. The combined model of serum NETs, CD8+ T cells, and TPS is a powerful tool for predicting the efficacy of PD-1 inhibitor treatment in patients with NSCLC.

Prognostic value of neutrophil-to-lymphocyte ratio dynamics in patients with septic acute kidney injury: a cohort study.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined. METHODS: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses. RESULTS: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs. 46.6%, p < 0.001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality (p = 0.004), need for renal replacement therapy (p = 0.011), and developing stage-3 AKI (p = 0.040) according to the adjusted models. CONCLUSIONS: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.

Low Hemoglobin Level and Elevated Inflammatory Hematological Ratios Associated With Depression and Sleep Disturbance.

BACKGROUND: The relationship between blood cell profiles, including hemoglobin (Hb) levels and inflammatory hematological ratios, and mental health problems currently remains unclear. AIM: This study aimed to investigate the relationship between blood cell profiles and mental health issues, including depressive state and sleep disturbance, while adjusting for potential demographic confounders. METHODOLOGY: This retrospective, cross-sectional, observational study used a population-based medical database from the Tohoku Medical Megabank Project with more than 60,000 volunteers. Data on age, sex, daily tobacco use, body mass index, and self-reported scores on the Kessler Psychological Distress Scale (K6), Athens Insomnia Scale (AIS), and the Center for Epidemiologic Studies Depression Scale (CES-D) were collected. RESULTS: A total of 62,796 volunteers (23,663 males and 39,133 females), aged ≥20 years at the time of the blood test, agreed to participate in this study. Among the evaluated blood cell profiles, Hb, hematocrit, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were significantly correlated with the K6, AIS, and CES-D scores, with strong statistical significance (p<0.0001 for all) in bivariate correlation analyses. A significant adjusted odds ratio (aOR) of the Hb level for elevated CES-D scores (aOR=0.965 [95% CI: 0.949-0.981], p<0.0001) was confirmed after adjusting for demographic data and daily tobacco use using a logistic regression model. Sensitivity analyses revealed that these associations existed in both males and females but were more prominent in the former. In male participants, a low Hb level was significantly associated with an elevated AIS score. The evaluated inflammatory hematological ratios, including NLR, PLR, and monocyte-to-lymphocyte ratio (MLR), also showed significant aORs with the K6, AIS, and CES-D scores after adjusting for demographic background. CONCLUSION: Low Hb levels and elevated inflammatory hematological ratios (NLR, MLR, and PLR) were associated with depressive state and sleep disturbances in the general population.

Association of early seizures after ischemic stroke with diffusion-weighted imaging-alberta stroke program early CT score (DWI-ASPECTS) and neutrophil-to-lymphocyte ratio.

BACKGROUND: Post-stroke seizure (PSS) is a common considerable complication of acute ischemic stroke (AIS). Early risk assessment can clinical practitioners to plan effective prevention and management. We aimed to determine whether assessing Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score (DWI-ASPECTS), and neutrophil indices allows for identifying patients at risk of PSS. METHODS: This prospective study included AIS patients with cortical involvement admitted to a single academic center between January 2020 to October 2023. For all included subjects, DWI-Brain MRI, blood neutrophils, and platelet counts were obtained and the DWI-ASPECTS score was calculated. Then, the patients were followed up for 6 months in terms of PSS occurrence. Based on the occurrence of PSS, patients were divided into two groups of PSS and non-PSS. For analysis, imaging and laboratory data were compared between two groups. Logistic regression was applied to determine the relationship between DWI-ASPECTS and neutrophil indices, with early PSS. Finally, the sensitivity and specificity of these variables for PSS were estimated. RESULTS: A total of 309 were included in the final statistical analysis. DWI-ASPECT and neutrophil-to-lymphocyte ratio (NLR) were significantly associated with early PSS with OR of 0.74 and OR of 1.13, respectively (P < 0.05). Further analysis showed that, a combination of DWI-ASPECTS, NLR had an area under the curve (AUC) of 0.72 for predicting the occurrence of early PSS. CONCLUSION: DWI-ASPECTS and NLR are associated with the occurrence of early PSS after cortical ischemic stroke. A combination of these predictors had higher sensitivity and specificity for PSS rather than each factor alone. These findings may be helpful for determining the risk of PSS if validated in future studies.

Neutrophil-to-Lymphocyte Ratio as a Potential Biomarker to Managing Type 2 Diabetes Mellitus and Predicting Disease Progression.

Introduction Diabetes is a chronic disease that causes dysregulation of blood glucose. Type 2 diabetes mellitus (T2DM) could result in long-term inflammatory conditions that affect different organs of the body. Despite the availability of diagnostic markers like glycated hemoglobin (HbA1c) for T2DM, it is essential to find an appropriate marker that could predict long-term complications. This study evaluates the potential role of neutrophil-to-lymphocyte ratio (NLR) in predicting disease progression and treatment responses.  Methods This case-control study was carried out among 160 T2DM patients and 132 non-diabetic persons. Blood samples were collected from each participant and were processed for hemoglobin, HbA1c, iron, ferritin, and complete blood picture (NLR).  Results The study showed that there was a significant variation in the serum levels of ferritin (264.8±611.6 ng/ml versus 168.3±364.7 ng/ml, p=0.392), iron (4.095±8.851 mcg/dl versus 55.20±37.62 mcg/dl, p=0.0111), and HbA1c (8.169±1.635% versus 5.668±0.5260% p<0.0001) among T2DM patients compared to non-diabetic persons. The NLR values (4.189±4.154 versus 4.095±8.851, p=0.009) among patients with T2DM significantly varied with that of non-diabetic persons. A significant negative correlation was noticed between the serum levels of iron and NLR (r=-0.17, p=0.014) and a positive correlation was noticed between HbA1c and NLR (r=0.19, p=0.014). The serum levels of iron revealed a significant positive correlation with the serum levels of ferritin (r=0.24, p=0.002) and hemoglobin percentage (r=0.41, p=0.008). HbA1c revealed a significant positive correlation with NLR (r=0.19, p=0.014). Additionally, a significant negative correlation was observed between iron with NLR (r=-0.17, p=0.029) and hemoglobin percentage with NLR (r=-0.30, p=0.005). However, no such correlation was demonstrated among non-diabetic persons. With an accuracy of 89.85% and high sensitivity and specificity, NLR showed diagnostic accuracy like HbA1c.  Conclusions NLR demonstrated equivalent efficacy to HbA1c in predicting glycemic control. Since diabetes affects different organs of the body, evaluating NLR probably predicts inflammation. Therefore, NLR could be useful in the management of T2DM and in predicting long-term complications.

Prognostic value of systemic immune-inflammation index in the diagnosis of preeclampsia.

Background: Preeclampsia is a serious complication of pregnancy with negative consequences for the mother and fetus. It was aimed to investigate whether the systemic immune inflammation index is a parameter that will facilitate the diagnosis of preeclampsia. Methods: This retrospective and single-center study included patients diagnosed with preeclampsia after admission to the emergency department and those who met the inclusion criteria. Vital parameters, demographic data, medical history, white blood cell count, platelet count, neutrophil count, systemic immune-inflammation index values, biochemical parameters, and gestational weeks were analyzed in each patient. Results: A total of 40 patients with preeclampsia (preeclampsia group) and 40 normal pregnant women (control group) were included. Laboratory tests revealed that the mean WBC, neutrophil, and lymphocyte counts were significantly higher in the preeclampsia group than in the control group, whereas the preeclampsia group had a significantly lower mean platelet count than the control group (p < 0.001). The sensitivity and specificity for the cut-off value of 758.39 × 109/L systemic immune-inflammation index in pregnant patients with preeclampsia was 77.5% and 67.5%, respectively (AUC: 0.705; 95% CI: 0.587-0.823; p = 0.002). No significant difference was observed between the mean neutrophil-to-lymphocyte ratio in preeclampsia diagnosis. Conclusion: The systemic immune-inflammation index may be used as a marker to help in establishing the diagnosis of preeclampsia. We believe that this index is an important prognostic indicator because it concurrently evaluates neutrophil and lymphocyte values-which indicate the inflammation process-and platelet count, i.e., an indicator of coagulopathy.

Correlation of Hemoglobin Level With New Inflammatory Markers in the Emergency Department: A Retrospective Study Exploring Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte, and Mean Platelet Volume-to-Platelet Count Ratios.

Background Anemia of chronic disease is known to be associated with inflammation. However, the relationship between hemoglobin (Hb) levels and potential inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count ratio (MPV/PC) has not been extensively studied. The primary objective of this retrospective analytical study conducted at Al Zahraa Hospital University Medical Center (ZHUMC), Beirut, was to investigate the correlation between Hb levels and potential inflammatory markers (NLR, MLR, PLR, MPV/PC) in patients visiting the emergency department (ED), across different genders and age groups. The secondary objectives were to compare Hb levels and inflammatory markers values between the referred medical ward group (the hospitalized patients who were admitted to the medical ward), and the non-referred to medical ward group (the patients who were discharged home from the ED), and to evaluate the predictability of inflammatory markers and Hb levels for referral to the medical ward, including the determination of optimal cutoff values for hospital admission to the medical ward. Methods We analyzed the blood parameters of 379 adult patients who presented to the ED with various medical complaints between September 1, 2022, and November 30, 2022 (three months). These patients were included in the study after we checked their eligibility regarding the verification of all our inclusion and exclusion criteria. Results Our findings revealed a significant negative correlation between Hb levels and PLR (r = -0.24) in both genders and across different age groups. The group referred to the medical ward exhibited lower Hb levels and higher NLR, MLR, and PLR values (P < 0.001). NLR/Hb ratio emerged as a predictive factor for admission in genitourinary (R² = 0.158; OR = 5.62) and respiratory groups (R² = 0.206; OR = 5.89), with specific cutoff values of 0.533 (Sensitivity = 57.1% & Specificity = 84.2%) and 0.276 (Sensitivity = 85% & Specificity = 51.1%), respectively. Conclusions Our study demonstrates that hemoglobin level negatively correlates with PLR. NLR, MLR, and PLR stand as important inflammatory markers. Moreover, we present the first study in the literature to show that NLR/Hb ratio can serve as a predictor for referral to the medical ward, particularly in the genitourinary and respiratory patient groups, underscoring its value in risk assessment as a prognostic marker reflecting the need for admission when the case is more serious.

Meta-analysis of the Relationship Between Neutrophil to Lymphocyte Ratio and Nasal Polyps.

Our study aimed to enhance understanding of nasal polyp pathophysiology by reviewing the data for variations of NLR values between patients with nasal polyp and healthy controls. We searched Web of Science, PubMed, ProQuest, and Scopus up to 2 April 2023. The search strategy was not limited to any specific language. Twelve studies were included in our study. Of them, ten studies, involving 898 nasal polyp patients and 590 control patients, were included in the meta-analysis. The NLR levels in nasal polyp patients were statistically greater than in the control group (SMD = 0.56; 95%CI 0.04-1.08, P = 0.036). Subgroup analysis based on study design yielded that patients with nasal polyp exhibited significantly higher NLR levels than healthy controls in retrospective studies (SMD = 0.83; 95%CI 0.30-1.35, P = 0.002) but not in prospective studies (SMD = 0.10; 95%CI = -1.03 to 1.23, P = 0.85). Also, we found that the NLR levels in nasal polyp patients were significantly higher than healthy controls in high-quality studies (SMD = 1.00; 95%CI 0.38-1.62, P = 0.002) but not in low-quality studies (SMD = 0.11; 95%CI = -0.69 to 0.91, P = 0.79). A total of 312 patients with recurrence and 550 patients without recurrence were included in the study. The combined results revealed that NLR levels in nasal polyp recurrence patients were significantly higher than those of the nasal polyp without recurrence group (SMD = 0.06, 95% CI 0.39-0.81, P = 0.000). These results showed the relationship between the NLR in nasal polyps and can help medical doctors to predict the recurrence of the disease in such patients.

The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people.

Background: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-ß42 (Aß42), total tau (t-tau), and phosphorylated tau181 (p-tau), as well as the trajectories of these CSF measures obtained longitudinally. Results: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aß-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aß42 (ß=-12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (ß = 26.812, p = 0.019) and p-tau (ß = 3.441, p = 0.015), but not Aß42. In the NYU cohort alone, subjects classified as Aß+ (n = 38) displayed a stronger association between the NLR and t-tau (ß = 100.476, p = 0.037) compared to Aß- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. Conclusions: We report associations between the NLR and Aß42 in the older ADNI cohort, and between the NLR and t-tau and p-tau181 in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio: Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events.

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor (ICI) and the occurrence of immune-related adverse events (irAEs). The predictive potential of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in determining ICI effectiveness has been extensively investigated, while limited research has been conducted on predicting irAEs. Furthermore, the combined model incorporating NLR and PLR, either with each other or in conjunction with additional markers such as carcinoembryonic antigen, exhibits superior predictive capabilities compared to individual markers alone. NLR and PLR are promising markers for clinical applications. Forthcoming models ought to incorporate established efficacious models and newly identified ones, thereby constituting a multifactor composite model. Furthermore, efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease: A meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is commonly utilized as a prognostic indicator in end-stage liver disease (ESLD), encompassing conditions like liver failure and decompensated cirrhosis. Nevertheless, some studies have contested the prognostic value of NLR in ESLD. AIM: To investigate the ability of NLR to predict ESLD. METHODS: Databases, such as Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Weipu, and Wanfang, were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD. Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1. RESULTS: A total of thirty studies involving patients with end-stage liver disease (ESLD) were included in the evaluation. Among the pooled results of eight studies, it was observed that the Neutrophil-to-Lymphocyte Ratio (NLR) was significantly higher in non-survivors compared to survivors (random-effects model: standardized mean difference = 1.02, 95% confidence interval = 0.67-1.37). Additionally, twenty-seven studies examined the associations between NLR and mortality in ESLD patients, reporting either hazard ratios (HR) or odds ratios (OR). The combined findings indicated a link between NLR and ESLD mortality (random-effects model; univariate HR = 1.07, 95%CI = 1.05-1.09; multivariate HR = 1.07, 95%CI = 1.07-1.09; univariate OR = 1.29, 95%CI = 1.18-1.39; multivariate OR = 1.29, 95%CI = 1.09-1.49). Furthermore, subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality, with Asian studies demonstrating a more pronounced effect. CONCLUSION: Increased NLR in patients with ESLD is associated with a higher risk of mortality, particularly in Asian patients. NLR is a useful prognostic biomarker in patients with ESLD.

Association of pretreatment neutrophil-to-lymphocyte ratio with clinical outcomes in cancer immunotherapy: An evidence synthesis from 30 meta-analyses.

BACKGROUND: The Neutrophil-to-lymphocyte ratio (NLR) holds relevance in cancer immunotherapy outcomes, yet its validation remains limited. Thus, we conducted an umbrella review to comprehensively assess the association between pretreatment NLR and immunotherapy outcomes, along with evaluating their credibility and strength. METHODS: Electronic databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane, were systematically searched for eligible systematic reviews and meta-analyses. Quality assessment and evidence grading utilized AMSTAR, GRADE, and additional classification criteria, following PRISMA and PRIOR guidelines. RESULTS: Thirty unique meta-analyses were included, with 24 associations (80%) exhibiting statistical significance. Notably, associations between pretreatment NLR and the prognosis of renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer garnered highly suggestive or convincing evidence grading. CONCLUSIONS: Elevated pretreatment NLR correlates with poor outcomes in cancer immunotherapy, suggesting its potential as a biomarker for identifying appropriate treatment populations and predicting clinical outcomes. Nevertheless, further validation through prospective cohort studies is warranted.

Evaluation of the preoperative neutrophil-to-lymphocyte ratio as a predictor of the micropapillary component of stage IA lung adenocarcinoma.

OBJECTIVE: To assess the ability of markers of inflammation to identify the solid or micropapillary components of stage IA lung adenocarcinoma and their effects on prognosis. METHODS: We performed a retrospective study of clinicopathologic data from 654 patients with stage IA lung adenocarcinoma collected between 2013 and 2019. Logistic regression analysis was used to identify independent predictors of these components, and we also evaluated the relationship between markers of inflammation and recurrence. RESULTS: Micropapillary-positive participants had high preoperative neutrophil-to-lymphocyte ratios. There were no significant differences in the levels of markers of systemic inflammation between the participants with or without a solid component. Multivariate analysis showed that preoperative neutrophil-to-lymphocyte ratio (odds ratio [OR] = 2.094; 95% confidence interval [CI], 1.668-2.628), tumor size (OR = 1.386; 95% CI, 1.044-1.842), and carcinoembryonic antigen concentration (OR = 1.067; 95% CI, 1.017-1.119) were independent predictors of a micropapillary component. There were no significant correlations between markers of systemic inflammation and the recurrence of stage IA lung adenocarcinoma. CONCLUSIONS: Preoperative neutrophil-to-lymphocyte ratio independently predicts a micropapillary component of stage IA lung adenocarcinoma. Therefore, the potential use of preoperative neutrophil-to-lymphocyte ratio in the optimization of surgical strategies for the treatment of stage IA lung adenocarcinoma should be further studied.

Evaluation of systemic inflammatory indices in the diagnosis of early onset neonatal sepsis in very low birth weight infants.

BACKGROUND: Previously, not six systemic inflammatory indices were evaluated in the diagnosis of early onset sepsis (EOS) in very low birth weight (VLBW, <1500g) premature infants. OBJECTIVES: We evaluated the effectiveness of systemic inflammatory indices in the diagnosis of EOS in VLBW infants. METHODS: Premature infants with birth weight <1500 g were included in the study. Six systemic inflammatory indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were compared in patients with EOS (treatment group) and without EOS (control group). RESULTS: Of 917 infants enrolled, 204 infants were in the EOS group and 713 infants comprised the control group. NLR, MLR and SIRI values were significantly higher in the EOS group than in the control group (p < 0.001). The AUC value of SIRI for the predictivity of EOS was 0.803. CONCLUSIONS: The SIRI can be used together with other parameters as both an easily accessible and the reliable systemic inflammatory indices in the diagnosis of EOS in VLBW preterm infants.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions'; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils' functions and their potential influence on perioperative outcomes.

Effect of Intraoperative Opioid Dose on Perioperative Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio in Glioma.

Background: The neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) are inflammatory biomarkers. Until now, it is unknown the impact of opioid dosage on perioperative immunity in glioma patients. The aim of this study was to explore the effect of intraoperative opioid dosage on perioperative immune perturbations using NLR and LMR as inflammatory biomarkers and evaluate the correlation between inflammatory biomarkers and pathological grade of glioma. Methods: The study included 208 patients with primary glioma who underwent glioma resection from February 2012 to November 2019 at Harbin Medical University Cancer Hospital. Complete blood count (CBC) was collected at 3 time points: one week before surgery, and 24 hours and one week after surgery. Patients were divided into high-dose and low-dose groups, based on the median value of intraoperative opioid dose. The relationships between perioperative NLR, LMR and intraoperative opioid dosage were analyzed using repeated measurement analysis of variance (ANOVA). Correlations between preoperative various factors and pathological grade were analyzed by Spearman analysis. Receiver operating characteristic (ROC) curves were performed to assess the predictive performance of the NLR and LMR for pathological grade. Results: The NLR (P=0.020) and lower LMR (P=0.037) were statistically significant different between high-dose and low-dose groups one week after surgery. The area under the curve (AUC) of the NLR to identify poor diagnosis was 0.685, which was superior to the LMR (AUC: 0.607) and indicated a correlation between the NLR with pathological grade. The preoperative NLR (P=0.000), LMR (P=0.009), age (P=0.000) and tumor size (P=0.001) exhibited a significant correlation with the pathological grade of glioma. Conclusion: Intraoperative opioids in the high-dose group were associated with higher NLR and lower LMR in postoperative glioma patients. The preoperative NLR and LMR demonstrated predictive value for distinguishing between high-grade and low-grade gliomas.

A meta-analysis on first-trimester blood count parameters-is the neutrophil-to-lymphocyte ratio a potentially novel method for first-trimester preeclampsia screening?

Objective: Meta-analysis focusing on the role of first-trimester neutrophil-to-lymphocyte ratio (NLR) in the prediction of preeclampsia. Data sources: PubMed, Scopus, Web of Science, Cochrane Library, and Embase databases were queried from inception up to December 31, 2022. Study eligibility criteria: The study included all types of original research that was conducted in humans and values of NLR were measured during the first trimester, among patients who later developed preeclampsia, compared to the values of control groups. Study appraisal and synthesis methods: Two reviewers independently performed data abstraction and quality appraisal, and disagreements were resolved by consensus and, if necessary, by the opinion of a third reviewer. During the analysis, PRISMA and MOOSE guidelines were followed. All statistical analyses were made with R. Results: For the research on the predictive role of NLR values in the first trimester for preeclampsia, a total of 6 studies were selected for analysis, covering 2,469 patients. The meta-analysis revealed a 95% confidence interval (CI) for the effect size of 0.641 to 1.523, with a prediction interval of 0.027 to 2.137. Conclusion: Based on the analysis, NLR is a promising biochemical marker for future pieces of research that try to find new screening methods for first-trimester preeclampsia. We encourage other researchers to examine NLR's predictive value combined with other markers in preeclampsia screening, this way being able to find new and affordable protocols for first-trimester preeclampsia screening. Systematic review registration: identifier CRD42023392663.

Blood Whispers: Exploring Hematologic Indicators for Diagnosing and Predicting Severity of Vogt-Koyanagi-Harada Syndrome.

PURPOSE: To investigate the association of clinical findings and indocyanine green angiography (ICGA) score with inflammatory markers derived from complete blood count (CBC) parameters in patients with Vogt-Koyanagi-Harada (VKH) to determine the diagnostic and predictive role. METHODS: Demographic characteristics, presenting complaints, ocular findings, optical coherence tomography findings, ICGA scores and best corrected visual acuity were recorded in treatment-naive VKH patients at presentation. Patients were divided into two groups as acute stage and chronic recurrent stage. CBC parameters were noted in patients at presentation and healthy controls (HC, n = 25). Neutrophil-lymphocyte-platelet-monocyte counts, neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), monocyte/lymphocyte and systemic immune-inflammation index (SII) were recorded. The association between these markers and clinical severity were evaluated. RESULTS: Thirty-two patients with VKH (23 females/9 males) with a mean age of 34.1 ± 14.6 years were included in the study. There was an increase in neutrophil count, NLR and SII in patients with VKH compared to HC (p < 0.001). The cut-off values for these three parameters were 4.37, 2.24 and 562.35, respectively. Twenty-six patients presented in the acute stage and six patients presented in the chronic recurrent stage. Choroidal thickness, early stromal hyperfluorescence and total ICGA scores were higher in patients presenting in the acute stage (p < 0.001, 0.001 and 0.025, respectively). Patients with higher disease severity at presentation were treated earlier. Early stromal vessel hyperfluorescence and choroidal vasculitis scores were correlated with decreased lymphocyte count, increased NLR, PLR and SII (p < 0.05). CONCLUSION: CBC-derived inflammatory parameters indicate that VKH is a systemic inflammation. These parameters can be used in the diagnosis and determination of disease severity of VKH.

Association of Neutrophil-to-Lymphocyte Ratio With All-Cause Mortality in the Elderly Population in China: A Retrospective Cohort Study.

Neutrophil-to-lymphocyte ratio (NLR) is an emerging systemic inflammation marker associated with disease progression and mortality in patients. However, there is limited research on the predictive value of NLR in the general population. This study aimed to investigate the relationship between NLR and all-cause mortality in an elderly Chinese population. A retrospective cohort study was conducted based on health examination in a community in Shanghai, China, between 2015 and 2020. Among 6364 participants (aged ≥ 55 years), a total of 169 (2.66%) participants died during a median follow-up period of 5.37 years. The median NLR was 1.63 (interquartile range: 1.29, 2.11). Multivariate analysis revealed that the upper 2 quartiles of NLR were positively associated with all-cause mortality (Q3 vs Q1: hazard ratio [HR] = 1.82, 95% confidence interval [CI]: 1.07-3.09; Q4 vs Q1: HR = 2.22, 95% CI: 1.34-3.68, P for trend <.001). The stratified and interaction analyses showed that age, sex, body mass index (BMI), history of diabetes, or history of hypertension did not significantly modify the association between NLR and all-cause mortality. Elevated NLR was independently associated with an increased risk of all-cause mortality in the elderly Chinese population.

Apatinib beyond first progression is associated with prolonged overall survival in patients with advanced breast cancer: Results from an observational study.

In the present study, the efficacy and safety of a low dose of apatinib in the treatment of patients with advanced breast cancer (ABC) in a real-world setting were assessed, the impact of continuous anti-angiogenic therapy beyond progression was determined and the factors associated with efficacy were evaluated. A total of 63 patients with ABC who were treated with apatinib and for whom several lines of treatment had failed were retrospectively analyzed in Tangshan People's Hospital (Tangshan, China) between January 2016 and October 2022. Apatinib was administered orally combined with chemotherapy, endocrine therapy, targeted therapy or monotherapy at a dose of 250 mg per day. Apatinib administration was continued in certain patients beyond first progressive disease (PD), and these patients were defined as the continued anti-angiogenic treatment beyond first progression (CABF) group, while those who discontinued apatinib were defined as the non-CABF group. In the evaluation of the first efficacy, the objective response rate was 33.3%. A total of 26 patients continued to receive apatinib post-first PD and were allocated to the CABF group. The median overall survival (OS) time of the 63 patients was 16 months. Log-rank univariate analysis revealed that the OS time was significantly associated with molecular subtype (P=0.014), CABF (P=0.004), and the neutrophil-to-lymphocyte ratio (NLR) (P=0.011). Multivariate Cox regression analysis revealed that being in the non-CABF group and a high NLR were independent risk factors for lower OS time (P=0.017 and P=0.041, respectively). These results support the continued administration of low-dose apatinib beyond progression and the use of NLR as an easily accessible prognostic marker in patients with ABC treated with apatinib.