Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent.

Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%, p < 0.01) and within the first 90 days of treatment (25.7% vs. 37.7%, p = 0.01). This negative association was confirmed by multivariable analysis. Higher mean steroid doses were observed among non-responders, and cumulative doses were inversely correlated with the disease control rate (DCR) around ICI initiation. Remarkably, poorer outcomes were observed even in patients belonging to the lowest dose quartile compared to the steroid-naïve population. The exposure to steroids after 6 months of ICI was not associated with worse survival outcomes. Our results suggest that the potential impact of steroids on ICI efficacy may be time-dependent, prevailing around ICI initiation, and dose-dependent, with modulation of neutrophil-to-lymphocyte ratio as a possible underlying mechanism.

Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes.

PURPOSE: The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). METHODS: We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. RESULTS: NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). CONCLUSION: These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.

Long-term analysis of hematological parameters as predictors of recurrence patterns and treatment outcomes in cervical cancer patients undergoing definitive chemoradiotherapy.

PURPOSE: This study sought to determine the predictive and prognostic value of clinicopathological parameters and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin (Hgb) level in predicting recurrence patterns and locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) in cervical cancer patients receiving definitive chemoradiotherapy (ChRT). METHODS: This study included 261 cervical cancer patients treated with ChRT. The primary endpoints were the predictors of local recurrence (LR) and distant metastasis (DM), whereas the secondary endpoints were LRFS and DMFS. The association of survival with potential prognostic factors was analyzed using Cox regression analysis, and the predictors of LR and DM were identified using logistic regression analysis. RESULTS: The median follow-up time was 10.9 years. Recurrences occurred in 132 patients (50.6%) within a median of 11.2 months after definitive ChRT. NLR and PLR values were significantly higher in patients with LR and DM than in those without, with no significant differences in Hgb levels in patients with or without LR and DM. In the multivariable logistic regression analysis, lymph node metastasis, elevated NLR, and low Hgb level were significantly correlated with LR and DM. In the multivariable analysis, large tumor size, presence of lymph node metastasis, and elevated NLR were the independent predictors for poor LRFS and DMFS, and Hgb level was an additional prognostic factor for DMFS. CONCLUSION: Hematological markers, particularly NLR and Hgb, may serve as cost-effective and readily accessible indicators for predicting recurrence and survival in cervical cancer patients, contributing to their practical use in routine assessments.

Tumor mutational burden adjusted by neutrophil-to-lymphocyte ratio serves as a potential biomarker for atezolizumab-treated patients with extensive stage small cell lung cancer.

BACKGROUND: There is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC. METHODS: The data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC. RESULTS: We have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB < 10 mut/Mb adjusted by NLR ≥ median was an independent factor of OS for atezolizumab-treated SCLC patients (hazard ratio [HR], 2.82; 95% confidence interval; 1.52-5.24; P = 0.001). Both univariate and multivariate cox regression analysis showed that for patients with SCLC harboring low NLR and high TMB, survival is significantly longer in those treated with atezolizumab than those treated with placebo. Survival benefit is significantly higher in atezolizumab-treated patients with SCLC than those treated with placebo (P = 0.018 for TMB cutoff = 10 mut/Mb, P = 0.034 for TMB cutoff = 16 mut/Mb). CONCLUSION: Our findings provide a promising insight into the utility of NLR-adjusted TMB in the prognosis and immune responses in patients with SCLC.

Prognostic value of sarcopenia and inflammatory indices synergy in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy.

BACKGROUND AND PURPOSE: Sarcopenia has been demonstrated to be adversely correlated with the prognosis of various cancers. Our study aimed to estimate the prognostic value of sarcopenia in conjunction with inflammatory indices [neutrophil-to-lymphocyte ratio (NLR)] for evaluating the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy. MATERIALS AND METHODS: This study retrospectively analyzed 255 patients with ESCC who received chemoradiotherapy from January 2012 to December 2018. Multivariate Cox regression analysis was employed to identify prognostic values of assessed factors following a novel prognostic scoring system (SMI-NLR), covering sarcopenia and NLR during different treatment courses. RESULTS: Kaplan-Meier analysis revealed significantly greater overall survival (OS) rates in the nonsarcopenia group than in the sarcopenia group (P = 0.011). The low NLR group (< 4.84) demonstrated significantly higher OS rates than the high NLR group (≥ 4.84) (P < 0.001). The SMI-NLR prognostic model was established through multivariate analysis, revealing that Karnofsky performance status [hazard ratio (HR) = 0.285; 95% confidence interval (CI) = 0.117-0.699; P = 0.006], clinical staging (HR = 5.223; 95% CI = 1.879-14.514; P = 0.002), and preSMI-NLR (HR = 0.544; 95% CI = 0.330-0.898; P = 0.017) were independent factors affecting the prognosis of patients with ESCC. Nomograms were constructed based on these data providing more accurate 1-, 3-, and 5-year survival rates for patients with ESCC. CONCLUSION: Our study indicates the effectiveness of the combined sarcopenia and NLR prognostic model for the prognostic evaluation of patients with ESCC having undergone chemoradiotherapy.

Preoperative peripheral inflammatory markers are predictors of postoperative central diabetes insipidus in craniopharyngioma patients: a retrospective study.

BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.

Diagnostic performances of methylated septin9 gene, CEA, CA19-9 and platelet-to-lymphocyte ratio in colorectal cancer.

BACKGROUND: This study was designed to compare the diagnostic efficacy of mSEPT9 to four blood markers (CEA, CA19-9, platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR)). In addition, we aimed to determine the combined diagnostic efficacy of mSEPT9, CEA, CA19-9, PLR and NLR in colorectal cancer. METHODS: A total of 567 participants were enrolled in the study, including 308 CRC patients, 61 colorectal polyp patients and 198 healthy subjects confirmed by colonoscopy and/or tissue biopsy. Plasma samples were collected for tests. RESULTS: The positive rate of mSEPT9 in CRC (71.8%) was markedly higher than that in either the colorectal polyps group (27.9%) or the healthy controls (6.1%) (P < 0.001). The levels of CEA, CA19-9, NLR and PLR in the CRC group were significantly higher than those in the non-CRC groups (P < 0.05). ROC curves comparison analyses showed that the diagnostic efficacy of mSEPT9 alone in CRC was significantly higher than CEA, CA19-9, NLR and PLR alone. The combination of mSEPT9 with CEA, CA19-9 and PLR showed superior diagnostic value. In addition, binary logistic regression was also used to build a better model for clinical diagnosis of CRC. On univariable analyses, age, mSEPT9, CEA, CA 19-9, PLR and NLR were independent predictors of CRC. When these covariates were fitted in multivariable models, the ones with positive detection of mSEPT9, CEA, CA 19-9 and PLR were more likely to have CRC. CONCLUSIONS: This research revealed a significant association between mSEPT9 status and the clinicopathological characteristics of CRC patients, and the combination of mSEPT9, CEA, CA19-9 and PLR could significantly improve diagnostic efficacy in CRC.

Neutrophil to lymphocyte ratio as an assessment tool to differentiate between uterine sarcoma and myoma: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to determine the potential value of neutrophil to lymphocyte ratio (NLR) as an assessment tool in the clinical distinction between uterine sarcoma and uterine leiomyoma. METHODS: We comprehensively searched Web of Science, Scopus, and PubMed for relevant papers published before March 19, 2023. The standardized mean difference (SMD) was provided, along with a 95% confidence interval (CI). The random-effects model was employed to derive pooled effects due to the high levels of heterogeneity. The Newcastle-Ottawa scale was used for the quality assessment. Our study was registered in PROSPERO (CRD42023478331). RESULTS: Overall, seven articles were included in the analysis. A random-effect model revealed that patients with uterine sarcoma had higher NLR levels compared to those with uterine myoma (SMD = 0.60, 95% CI = 0.22-0.98; p = 0.002). In the subgroup analysis according to sample size, we found that patients with uterine sarcoma had elevated levels of NLR compared to those with uterine myoma in either large studies (SMD = 0.58, 95% CI = 0.04-1.13; P < 0.001) or small studies (SMD = 0.64, 95% CI = 0.33-0.96; P = 0.32). In the sensitivity analysis, we found that the final result was not significantly changed when single studies were removed, suggesting that the finding of this meta-analysis was stable. The pooled sensitivity of NLR was 0.68 (95% CI = 0.61-0.73), and the pooled specificity was 0.64 (95% CI = 0.59-0.69). CONCLUSION: NLR might be utilized as an assessment tool in clinics to help clinicians differentiate between patients with uterine sarcoma and those with myoma.

Combined score based on plasma fibrinogen and platelet-lymphocyte ratio as a prognostic biomarker in esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has showed that inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and fibrinogen can be used as predictors in the prognosis of esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore prognostic value of these biomarkers and evaluate the clinicopathological and prognostic significance of combined score based on plasma fibrinogen and platelet-lymphocyte ratio (F-PLR score). METHODS: A total of 506 patients with ESCC were enrolled in this study. Harrell's concordance index (c-index) was used to determine the optimal cut-off values of these markers and evaluate their prognostic significance. The relationship between factors with survival rates (including overall survival [OS] and disease-free survival [DFS]) was explored by Kaplan-Meier curve, univariate analysis and multivariate cox hazard analysis. RESULTS: Our result indicated that high F-PLR score was significantly associated with longer tumor length and deeper depth of tumor invasion (p < 0.01). The result of Cox multivariable analysis showed that F-PLR score was an independent prognostic factor for OS (p = 0.002) and DFS (p = 0.003). In addition, F-PLR score presented the greater c-index values for OS and DFS compared with NLR, PLR and fibrinogen level. Our result also showed that the c-index values for OS and DFS were both greater in TNM + F-PLR than those in TNM stage alone. CONCLUSIONS: In conclusion, F-PLR score is a predictive biomarker for prognosis in patients with ESCC.

Pretreatment systemic inflammatory markers predict survival in endometrial cancer: A Japanese Gynecologic Oncology Group 2043 exploratory data analysis.

OBJECTIVE: We investigated whether pretreatment systemic inflammatory markers are associated with survival outcomes in patients with endometrial cancer (EC). METHODS: Data from the Japanese Gynecologic Oncology Group 2043 were analyzed. Patients who did not receive chemotherapy or were lost to follow-up were excluded. Associations of pretreatment systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, with progression-free survival (PFS) and overall survival (OS) were analyzed. The optimal NLR, PLR, and HALP score cutoff values for PFS and OS were determined. Survival estimates were calculated and compared using the Kaplan-Meier method and log-rank test. RESULTS: We included 712 patients (median age: 55 [range, 28-74] years; body mass index [BMI]: 21.1 [15.2-38.6] kg/m2). For PFS, optimal NLR, PLR, and HALP score cutoff values were 1.48, 0.017, and 35.52, respectively, and for OS, the values were 1.88, 0.026, and 19.87, respectively. At optimal PFS-related cutoff values, NLR was associated with BMI; PLR with age, BMI, and clinical stage; and HALP score with BMI, clinical stage, and lymph node metastasis. At optimal OS-related cutoff values, NLR was associated with BMI, PLR, and BMI; the HALP score was associated with age and BMI. The HALP score was a prognostic factor for PFS (p = 0.025), while PLR and HALP scores were prognostic factors for OS (both p = 0.028). CONCLUSIONS: Pretreatment systemic inflammatory markers are associated with survival outcomes in patients with EC, with the HALP score being a prognostic factor for PFS and OS.

Neutrophil to lymphocyte ratio in myelofibrosis patients treated with ruxolitinib may predict prognosis and rate of discontinuation.

BACKGROUND: Myelofibrosis (MF) is a clonal Philadelphia chromosome negative myeloproliferative neoplasm (Ph-MPN). MF is featured by an inflammatory condition that can also drive the progression of disease. Ruxolitinib (ruxo) is the-first-in-class Jak1/2 inhibitor approved for treatment of MF, proved to reduce spleen volume and decrease symptom burden. In various malignancies neutrophil-to-lymphocyte ratio (NLR) has been indicated as predictor of progression free survival (PFS) and overall survival (OS). NLR might reflect the balance between systemic inflammation and immunity and is emerging as a prognostic biomarker in several neoplasms, including the hematological ones. METHODS: We analyzed a cohort of 140 MF patients treated with ruxo to validate baseline NLR (as a continuous variable and as a cut-off 2) as predictor of OS and of ruxo treatment discontinuation. RESULTS: We found that both baseline NLR as a continuous variable [HR 0.8 (95% CI: 0.7-0.9) (p = .006)] and NLR (<2 vs. ≥2) [HR 3.4 (95% CI: 1.6-7.0) (p = .001)] were significantly associated with OS. Censoring for patients undergone allotransplant, baseline NLR <2 was predictive of an earlier ruxo any-other-cause discontinuation [HR 3.7 (95%CI 1.7-8.3) (p < .001)]. CONCLUSIONS: NLR before starting ruxo treatment may be used as a simple and early predictor of OS and earlier ruxo discontinuation in clinical practice.

Peripheral immune profile and neutrophil-to-lymphocyte ratio in progressive supranuclear palsy: Case-control study and meta-analysis.

BACKGROUND AND PURPOSE: Peripheral inflammation is probably involved in the pathogenesis of progressive supranuclear palsy (PSP) and it may be a common feature with Parkinson's disease (PD). The peripheral immune profile in PSP remains unclear, as well as whether the inflammatory pathways differ from those in PD. The neutrophil-to-lymphocyte ratio (NLR) has been proven to be a well-established biomarker of systemic inflammation. This study aimed to evaluate the peripheral immune profile in PSP compared with PD. METHODS: A cross-sectional study was conducted including patients with PSP and PD and healthy controls (HCs). Leukocyte subpopulations and the NLR were measured in peripheral blood. Multivariate linear regression and post hoc tests were applied. Electronic databases were searched in November 2023 to perform meta-analyses to clarify the peripheral immune profile in PSP. RESULTS: Our cohort included 121 patients with PSP, 127 patients with PD and 266 HCs. The NLR was higher in PSP and PD compared with HCs. PSP had a higher neutrophil count compared with HCs. Whilst a lower lymphocyte count was found in PD compared with HCs, the lymphocyte count did not differ between PSP and HCs. The meta-analyses supported this immune profile. CONCLUSIONS: PSP and PD show an increased peripheral inflammation and a higher NLR compared with HCs. Different pathogenic inflammatory mechanisms are probably involved in PSP and PD, since in PSP this altered peripheral immune profile is mainly driven by neutrophils. Understanding the neutrophils' role in PSP may allow for the development of targeted therapies.

Peripheral immunity changes are associated with neurodegeneration and worse clinical outcome in idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) pathogenesis is multifactorial. Systemic inflammation might have a role in gathering clinical-pathological trajectories. We aimed to shape the peripheral immune profile of iNPH and establish correlations with cerebrospinal fluid (CSF) markers, ventricular enlargement, and clinical outcomes. METHODS: We conducted a single-center retrospective-longitudinal study, including 38 iNPH patients and 38 controls. Baseline iNPH Grading Scale and modified Rankin Scale (mRS) scores were collected with peripheral blood cell count, CSF amyloid-ß42 (Aß42), total tau (t-tau), phosphorylated-181-tau, and Evans index. Depending on 5-year outcome, iNPH patients were grouped into "poor outcome" (PO; mRS ≥ 5) and "favorable outcome" (FO; mRS < 5). Biomarkers were compared and correlated with each other. Receiver operating characteristic analysis was performed. RESULTS: iNPH patients compared to controls had higher neutrophil-to-lymphocyte ratio (NLR; 2.43 ± 1.04 vs. 1.61 ± 0.47, p < 0.001), higher neutrophils (4.22 ± 0.86 1000/mL vs. 3.48 ± 1.34, p = 0.033), and lower lymphocytes (1.45 ± 0.55 1000/mL vs. 2.07 ± 0.86, p = 0.038), with the expected CSF biomarkers signature. In the patients' cohort, NLR was associated directly with t-tau and inversely with Aß42. NLR directly correlated with Evans index. PO patients compared to those with FO had higher NLR (3.25 ± 1.40 vs. 2.01 ± 0.77, p = 0.035) and higher t-tau (274.76 ± 114.39 pg/mL vs. 150.28 ± 72.62, p = 0.017), with an area under the curve of 0.786 and 0.793, respectively. CONCLUSIONS: iNPH patients present a proinflammatory state associated with neurodegeneration and predicting poor clinical outcome. Systemic inflammation represents a factor in the clinical-pathological progression of iNPH, and the NLR emerges as a potential prognostic index.

Preoperative Neutrophil-to-Lymphocyte Ratio in Postmenopausal Breast Cancer Patients.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR) has been recognized as a marker of systemic inflammation with a prognostic impact in patients with various cancers, including breast cancer. The aim of this study was to investigate the relationships between the preoperative NLR and breast cancer prognosis in the patients before and after menopausal age, and its relationship with other prognostic factors. METHODS: A total of 1868 patients with clinical Stage I-III primary breast cancer were enrolled. The associations between clinicopathological factors and the preoperative NLR were analyzed, and relapse-free survival (RFS) and overall survival (OS) were estimated. RESULTS: Statistical analyses stratified by the menopausal status revealed that a high NLR was significantly associated with worse RFS (P < 0.001) and OS (P = 0.001) in postmenopausal patients, but not in premenopausal patients. Although the postmenopausal patients with relapsed cancer tended to have higher NLR levels than those without relapse (P = 0.079), NLR levels of premenopausal patients with relapsed cancer were significantly lower than that of relapse-free patients (P = 0.024). In postmenopausal patients, a high NLR was only associated with worse RFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (P < 0.001), in those managed without adjuvant chemotherapy (P = 0.003); this association was not observed in patients who received adjuvant chemotherapy. CONCLUSIONS: The preoperative NLR can be a useful prognostic marker, especially in postmenopausal breast cancer patients. The relationships between the NLR and breast cancer prognosis may be more evident when patients are assessed according to their menopausal status.

Prognostic value of hemogram parameters in osteosarcoma: The French OS2006 experience.

BACKGROUND: Previous studies have shown that neutrophil-to-lymphocyte (NLR) ratio at diagnosis and early lymphocytes recovery on doxorubicin-based chemotherapy, may impact the outcome in patients with osteosarcoma (OST). This study aimed to evaluate the prognostic value of hemogram parameters in patients with OST treated with high-dose methotrexate and etoposide/ifosfamide (M-EI) chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed the prognostic value of various hemogram parameters at diagnosis and during therapy in a large consecutive cohort of patients with OST included in the French OS2006 trial and treated with M-EI chemotherapy. RESULTS: A total of 164 patients were analyzed. The median age was 14.7 years (interquartile range [IQR]: 11.7-17). Median follow-up was 5.6 years (IQR: 3.3-7.7 years). Three-year event-free survival (EFS) and overall survival (OS) were 71.5% (95% confidence interval [CI]: 64%-78%) and 86.4% (95% CI: 80%-91%), respectively. In univariate analysis, blood count parameters at diagnosis and early lymphocyte recovery at Day 14 were not found prognostic of survival outcomes. By contrast, an increase of NLR ratio at Day 1 of the first EI chemotherapy (NLR-W4) was associated with reduced OS in univariate (p = .0044) and multivariate analysis (hazards ratio [HR] = 1.3, 95% CI: 1.1-1.5; p = .002), although not with EFS. After adjustment on histological response and metastatic status, an increase of the ratio NLR-W4 of 1 was associated with an increased risk of death of 30%. CONCLUSIONS: We identified NLR-W4 as a potential early biomarker for survival in patients with OST treated with M-EI chemotherapy. Further studies are required to confirm the prognostic value of NLR and better identify immune mechanisms involved in disease surveillance.

Predictors of futile recanalization after endovascular treatment of acute ischemic stroke.

OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.

Clinical diagnostic value of methylated SEPT9 combined with NLR, PLR and LMR in colorectal cancer.

PURPOSE: This study aimed to investigate clinical diagnostic values of mSEPT9 combined with NLR, PLR and LMR in CRC. METHODS: 329 subjects composed of 120 CRC patients, 105 polyps patients and 104 healthy participants were prospectively recruited. Clinicopathologic features were collected and analyzed. Plasma samples were collected for mSEPT9, NLR, PLR and LMR test. The sensitivity, specificity and AUC of each biomarker separately or in combination were estimated by the ROC curve. RESULTS: The levels of NLR, PLR and the PDR of mSEPT9 in CRC patients were significantly higher than those in non-CRC subjects, while LMR was the opposite. The PDR of mSEPT9 in CRC patients was significantly correlated with age, tumor size, tumor stage and M stage. ROC curve analysis demonstrated moderate diagnostic values of mSEPT9, NLR, PLR and LMR in CRC patients with AUC of 0.78 (Se = 0.68, and Sp = 0.89), 0.78 (Se = 0.68, and Sp = 0.83), 0.80 (Se = 0.68, and Sp = 0.81), and 0.77 (Se = 0.72, and Sp = 0.73), respectively. Moreover, combination of these four biomarkers dramatically enhanced the diagnostic accuracy of CRC (AUC = 0.92, Se = 0.90, and Sp = 0.87), especially for CRC patients with large tumors (AUC = 0.95) or distal metastasis (AUC = 0.95). CONCLUSION: mSEPT9, NLR, PLR and LMR showed the potential to be reliable biomarkers for the diagnosis of CRC. And the combined application of these biomarkers further improved the diagnostic accuracy of CRC significantly.

Factors associated with the efficacy of first-line nivolumab plus chemotherapy in advanced gastric cancer patients with deficient mismatch repair.

BACKGROUND: We aimed to investigate clinicopathologic factors leading to different clinical outcomes in patients with deficient mismatch repair protein (d-MMR) gastric cancer (GC) treated with nivolumab plus chemotherapy (nivolumab chemotherapy). METHODS: This retrospective study included 28 patients with d-MMR advanced GC treated with first-line nivolumab chemotherapy. As a control group, 68 treated with first-line chemotherapy alone were included. Clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and PD-L1 combined positive score (CPS), were analyzed with regards to the efficacy outcomes. RESULTS: Progression-free survival (PFS) was longer (median PFS; not reached [NR] vs. 5.2 months, hazard ratio [HR] 0.28, P < 0.001), and overall survival (OS) tended to be longer (median OS; NR vs. 17.9 months, HR 0.43, P = 0.057) in patients treated with nivolumab chemotherapy than those treated with chemotherapy. The PFS benefit of nivolumab chemotherapy over chemotherapy was pronounced in the subgroup with a lower NLR (< 3.80 [median NLR]) (HR 0.10), whereas it was less prominent in patients with a high NLR (≥ 3.80) (HR 0.58). Among patients treated with nivolumab chemotherapy, PFS was worse in patients with a higher NLR (≥ 3.80) than in those with a lower NLR (< 3.80), and survival outcomes were similar between those with PD-L1 CPS ≥ 5 and < 5. CONCLUSION: Nivolumab chemotherapy was associated with better efficacy outcomes than chemotherapy alone among patients with d-MMR GC, but survival outcomes were poor even with nivolumab chemotherapy for those with a high NLR. Survival outcomes were not different according to PD-L1 CPS among d-MMR patients treated with nivolumab chemotherapy.

Platelet distribution width as an useful indicator of influenza severity in children.

PURPOSE: The present study aims to investigate the potential of platelet distribution width as an useful parameter to assess the severity of influenza in children. METHODS: Baseline characteristics and laboratory results were collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to joint detection of inflammatory markers for influenza positive children, and the scatter-dot plots were used to compare the differences between severe and non-severe group. RESULTS: Influenza B positive children had more bronchitis and pneumonia (P < 0.05), influenza A infected children had more other serious symptoms (P = 0.007). Neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), and platelet parameters performed differently among < 4 years and ≥ 4 years children with influenza. Combined detection of platelet parameters and other indicators could better separate healthy children from influenza infected children than single indicator detection. The levels of platelet distribution width of children with severe influenza (A and B) infection was significantly dropped, compared with non-severe group (P < 0.05). CONCLUSIONS: Platelet distribution width could be a very useful and economic indicator in distinction and severity assessment for children with influenza.

Baseline Serum neutrophil-to-lymphocyte ratio in acral melanoma compared with nonacral melanoma and its prognostic significance.

BACKGROUND: Acral lentiginous melanoma (ALM), a cutaneous melanoma subtype, exhibits a poorer prognosis than nonacral cutaneous melanoma (NACM). The neutrophil-to-lymphocyte ratio (NLR) is emerging as a prognostic indicator across diverse cancers. OBJECTIVE: We explored the baseline NLR disparities between ALM and NACM, and the NLR's prognostic significance in patients with ALM. METHODS: We reviewed records of patients with ALM and NACM diagnosed between 1997 and 2022, analyzing medical data. RESULTS: Among 327 and 159 patients with ALM and NACM, respectively, baseline NLR varied based on distinct clinicopathologic factors between ALM and NACM. In stage 3 to 4 melanomas, the median NLR for ALM (2.18; IQR, 1.70-3.08) significantly surpassed NACM (1.74; IQR, 1.33-2.53) (P = .029). In patients with ALM, high NLR (hazard ratio, 1.64; 95% CI, 1.02-2.66; P = .043) was independently correlated with poor progression-free survival when adjusting for ulceration, Breslow thickness of ≥2 mm, and nodal invasion. LIMITATIONS: Single-center, retrospective design. CONCLUSION: Advanced-stage ALM exhibited a significantly higher baseline NLR compared with that of NACM. Evaluating baseline NLR could provide valuable prognostic insights for patients with ALM.