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Background: The neutrophil-lymphocyte ratio (NLR) is an easily accessible and inexpensive biomarker that has been shown to predict morbidity and mortality in congenital cardiac surgery. However, its regulatory mechanism remains unclear. This study aims to compare and correlate the tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10 messenger RNAs (mRNAs) with the NLR in patients with tetralogy of Fallot (ToF) and ventricular septal defect (VSD). Methods: A prospective translational study was conducted on 10 children with ToF and 10 with VSD, aged between 1 and 24 months. The NLR was calculated from the blood count taken 24 hours before surgery. The expression of these mRNAs was analyzed in the myocardial tissue of the right atrium prior to cardiopulmonary bypass. Results: Patients with ToF exhibited a higher NLR [ToF 0.46 (interquartile range; IQR) 0.90; VSD 0.28 (IQR 0.17); P=0.02], longer mechanical ventilation time [ToF 24 h (IQR 93); VSD 5.5 h (IQR 8); P<0.001], increased use of vasoactive drugs [ToF 2 days (IQR 1.75); VSD 0 (IQR 1); P=0.01], and longer ICU [ToF 5.5 (IQR 1); VSD 2 (IQR 0.75); P=0.02] and hospital length of stays [ToF 18 days (IQR 17.5); VSD 8.5 days (IQR 2.5); P<0.001]. A negative correlation was found between NLR and oxygen saturation (SaO2) (r=-0.44; P=0.002). In terms of mRNA expression, the ToF group showed a lower expression of IL-10 mRNA (P=0.03). A positive correlation was observed between IL-10-mRNA and SaO2 (r=0.40; P=0.07), and a negative correlation with NLR (r=-0.27; P=0.14). Conclusions: Patients with ToF demonstrated a higher preoperative NLR and lower IL-10 mRNA expression by what appears to be a pro-inflammatory phenotype of cyanotic patients.
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Annexin A1 (AnxA1) is highly secreted by neutrophils and binds to formyl peptide receptors (FPRs) to trigger anti-inflammatory effects and efferocytosis. AnxA1 is also expressed in the tumor microenvironment, being mainly attributed to cancer cells. As recruited neutrophils are player cells at the tumor sites, the role of neutrophil-derived AnxA1 in lung melanoma metastasis was investigated here. Melanoma cells and neutrophils expressing AnxA1 were detected in biopsies from primary melanoma patients, which also presented higher levels of serum AnxA1 and augmented neutrophil-lymphocyte ratio (NLR) in the blood. Lung melanoma metastatic mice (C57BL/6; i.v. injected B16F10 cells) showed neutrophilia, elevated AnxA1 serum levels, and higher labeling for AnxA1 in neutrophils than in tumor cells at the lungs with metastasis. Peritoneal neutrophils collected from naïve mice were co-cultured with B16F10 cells or employed to obtain neutrophil-conditioned medium (NCM; 18 h incubation). B16F10 cells co-cultured with neutrophils or with NCM presented higher invasion, which was abolished if B16F10 cells were previously incubated with FPR antagonists or co-cultured with AnxA1 knockout (AnxA1-/-) neutrophils. The depletion of peripheral neutrophils during lung melanoma metastasis development (anti-Gr1; i.p. every 48 h for 21 days) reduced the number of metastases and AnxA1 serum levels in mice. Our findings show that AnxA1 secreted by neutrophils favors melanoma metastasis evolution via FPR pathways, addressing AnxA1 as a potential biomarker for the detection or progression of melanoma.
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Anexina A1 , Melanoma , Animales , Ratones , Anexina A1/metabolismo , Melanoma/metabolismo , Ratones Endogámicos C57BL , Neutrófilos/metabolismo , Fagocitosis , Microambiente TumoralRESUMEN
Purpose: To assess the relationship and prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with poor final best-corrected visual acuity (BCVA) after surgical repair of open globe injuries (OGI) in adults. Design: Retrospective analysis of data from an ongoing prospective cohort of consecutive patients. Methods: In a tertiary university hospital, 197 eyes of 197 patients were included between 2013 and 2017. NLR and PLR were obtained from pre-operative blood tests to analyze its relationship with poor final BCVA. Results: Severe visual impairment (SVI) was defined as ≤20/200, and was observed in 96 (48.7%) patients after surgical repair of OGI. SVI patients had higher NLR (7.4 ± 6.6 vs. 4.0 ± 3.2, p < 0.001), and PLR (167 ± 92 vs. 139 ± 64; p = 0.021) than non-SVI. NLR ≥ 3.47 and PLR ≥ 112.2 were the best cut-off values for SVI, were univariate risk factors for SVI, and had sensitivity: 69.0, 71.4, and specificity: 63.6, 44.8, respectively. In multivariate analysis, only OTS, athalamia, and hyphema remained as risk factors. NLR had significant correlation with ocular trauma score (OTS) (r = -0.389, p < 0.001) and final BCVA (r = 0.345, p < 0.001). Limitations: Simultaneous trauma in other parts of the body that could influence the laboratory findings. Conclusion: Patients with SVI after a repaired OGI had increased pre-operative NLR and PLR levels. High NLR and PLR are risk factors for SVI in univariate analysis. It is confirmed that low OTS is a risk factor for SVI. High NLR and PLR could be used as a prognostic tool to identify patients at higher risk for SVI after repair of OGI.
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Abstract Background: The neutrophil/ lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have the potential to be inflammatory markers that reflect the activity of many inflammatory diseases. The aim of this study was to evaluate the NLR and PLR as potential markers of disease activity in patients with ankylosing spondylitis. Methods: The study involved 132 patients with ankylosing spondylitis and 81 healthy controls matched in terms of age and gender. Their sociodemographic data, disease activity scores using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and white blood cell, neutrophil, lymphocyte and platelet counts were recorded. The patients with ankylosing spondylitis were further divided according to their BASDAI scores into patients with inactive disease (BASDAI < 4) and patients with active disease (BASDAI ≥4). The correlations between the NLR, PLR and disease activity were analysed. Results: There was a statistically significant difference in the NLR and PLR between the active and inactive ankylosing spondylitis patients (2.31 ± 1.23 vs. 1.77 ± 0.73, p = 0.002), (142.04 ± 70.98 vs. 119.24 ± 32.49, p < 0.001, respectively). However, there was no significant difference in both the NLR and PLR between the healthy control group and ankylosing spondylitis patients (p > 0.05). In addition, the PLR was significantly higher in both the active and inactive groups compared to those in the healthy control group (142.04 ± 70.98 vs. 99.32 ± 33.97, p = 0.014), (119.24 ± 32.49 vs. 99.32 ± 33.97, p = 0.019). The BASDAI scores were positively correlated with the PLR (r = 0.219, p = 0.012) and the NLR, but they were not statistically significant with the later (r = 0.170, p = 0.051). Based on the ROC curve, the best NLR cut-off value for predicting severe disease activity in ankylosing spondylitis patients was 1.66, with a sensitivity of 61.8% and a specificity of 50.6%, whereas the best PLR cut-off value was 95.9, with a sensitivity of 70.9% and a specificity of 55.5%. Conclusion: The PLR may be used as a useful marker in the assessment and monitoring of disease activity in AS together with acute phase reactants such as the ESR.
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Adulto , Femenino , Humanos , Masculino , Espondilitis Anquilosante/sangre , Recuento de Plaquetas , Biomarcadores/sangre , Estudios de Casos y Controles , Curva ROC , Sensibilidad y Especificidad , Recuento de Linfocitos , Área Bajo la Curva , Recuento de Leucocitos , NeutrófilosRESUMEN
BACKGROUND: Inflammatory biomarkers have recently attracted attention as valuable prognosticators and predictors of survival outcomes in many cancers. We describe a new pre-treatment biomarker, expressed as the eosinophil-lymphocytes ratio (ELR) and validate other biomarkers such as the level of circulating eosinophils, neutrophil-lymphocytes ratio (NLR), platelet-lymphocytes ratio (PLR) and systemic immune-inflammatory index (SII) as prognostic factors in cervical cancer (CC) patients. METHODS: A retrospective cohort of 151 consecutive patients diagnosed with CC and treated according to the European guidelines with radiotherapy and/or chemotherapy and/or surgery in our institution from 2009 to 2016 were evaluated. Patients were categorized into two different groups based on the optimal cut-off for each biomarker, according to the receiver operating characteristic (ROC) curves. Impact of blood biomarkers on overall survival (OS), cancer-specific survival (CCS) and progression-free survival (PFS) were examined. RESULTS: Higher values of ELR, eosinophils and age ≥ 50 years were associated with better OS in univariate Cox analysis, while high NLR, PLR, SII, neutrophils ≥ 7.0, Bulky tumor and FIGO stage III-IV at diagnosis were prognosticators of worse survival outcomes. In multivariate analysis, the only factors independently impacting OS were ELR ≥ 0.07 (HR = 0.49, p = 0.048) and FIGO stage III-IV (HR = 2.5, p = 0.018). High PLR and SII were associated with shorter PFR. CONCLUSIONS: Increased values of ELR and eosinophils portend better OS in CC. To our best knowledge, this is the first report describing eosinophils-related biomarker as an independent prognostic factor in CC.
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Biomarcadores de Tumor/análisis , Plaquetas/patología , Eosinófilos/patología , Inflamación/mortalidad , Linfocitos/patología , Neutrófilos/patología , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inflamación/etiología , Inflamación/patología , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: Circulating tumor cell (CTC) count and the host inflammatory response are two independent predictors for patients with various malignant disease. Several inflammation-based indicators have been demonstrated to have prognostic value in many malignant solid tumors, including systemic immune-inflammation index (SII), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutrition index (PNI). The aim of this study was to evaluate the predictive value of the inflammation-based indexes including SII, NLR PLR, and PNI for CTC detection of gastric cancer patients before surgery. METHODS: CTCs were measured using the isolation method by size of epithelial tumor cells and Wright staining for 60 patients with gastric cancer who underwent surgery. The indicators of SII, NLR, PLR, and PNI were calculated based on clinical laboratory testing. RESULTS: The detected CTC number was correlated with extension of tumor invasion (p = 0.037), lymph node metastasis (p < 0.001), and TNM stage (p < 0.001). The CTC detection ratio was significantly correlated with T stage (p = 0.041), lymph node metastasis (p = 0.001), nerve fiber invasion of tumor outside the lymph nodes (p = 0.017), and TNM stage (p < 0.001). Statistical analysis showed that SII (p < 0.001), NLR (p < 0.001), PLR (p < 0.001), and PNI (p < 0.001) were significantly associated with positive CTC count and CTC detection rate. CONCLUSIONS: This study provides evidence that preoperative indicators consisting of SII, NLR, PLR, and PNI are robust predictors for CTC detection in gastric cancer patients undergoing tumor resection.