SYSTEMIC INFLAMMATORY INDICES IN PATIENTS WITH MALIGNANT GLIOMAS AND EFFECTS OF PLATELET SECRETOME IN VITRO.

BACKGROUND: To date, no significant clinical progress has been achieved in the treatment of brain malignant gliomas (MG), and the active search for non-invasive circulating biomarkers continues. The prognostic significance of the ratio of the main peripheral blood cell populations of patients with MG is evaluated. Considerable attention is paid to the secretome of platelets (Pt) of peripheral blood. AIM: To evaluate the indicators of the peripheral blood cell population ratios in patients with brain MG and to study the influence of the secretome of Pt (SPt) of the peripheral blood of patients with brain MG in cell cultures in vitro. MATERIALS AND METHODS: We studied samples of peripheral blood from patients with glioma CNS WHO grade G2 (n = 5), G3 (n = 12), and G4 (n = 20). The peripheral blood cell counts were analyzed in the preoperative period on an automatic hematology analyzer. The in vitro study of SPt was performed on the U251 human glioblastoma cell line cultured with SPt from MG patients or SPt pre-incubated with anti-TGF-ß1 antibody. Cell cultures were observed for 72 h, and mitotic index (MI) was calculated. RESULTS: In MG patients, the count of peripheral blood leukocytes and neutrophils increased (p < 0.05). The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) increased by 2-3 times compared to control. Nevertheless, correlation analysis did not reveal significant relationships between quantitative indicators of peripheral blood cells and the tumor malignancy degree in MG patients. The MI in U251 cells increased under the influence of SPt from patients with MG (p < 0.021), correlated with the tumor degree of malignancy (r = 0.246, p = 0.014). Pre-incubation of SPt with anti-TGF-ß1 antibody tends to neutralize this promitotic effect. CONCLUSION: In MG patients, the integral indicators of NLR and SII increased but no significant relationship with the degree of tumor malignancy was found. In U251 cells, promitotic effects of SPt of MG patients partially decreased by anti-TGF-ß1 antibody.

Relationship between Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and Thrombosis in Patients with Portal Vein Thrombosis (PVT) without Acquired Risk Factor for Thrombosis.

BACKGROUND: Inflammation occurring after vascular endothelial damage plays a role in thrombus formation. Changes in various blood parameters that develop after the inflammatory condition can be used as a marker to predict thrombus. AIM: This study aimed to investigate the relationship between the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and portal vein thrombosis (PVT). MATERIALS AND METHODS: After applying the exclusion and inclusion criteria to the patients diagnosed with PVT and followed up in our center between January 2006 and May 2018, a total of 38 patients without acquired risk factors for the development of PVT and 52 healthy controls were included in the study. Clinical features and NLR and PLR at diagnosis were evaluated. RESULTS: NLR and PLR values were detected to be significantly higher in patients diagnosed with PVT compared to the control group (P < 0.001 for NLR, P < 0.001 for PLR). Findings were as follows: In acute PVT patients for NLR = 3.645 (area under the receiver operating characteristic (AUROC) 0.886, sensitivity 69.2%, specificity 96.2%, P < 0.001), for PLR = 196.24 (AUROC 0.754, sensitivity 53.2%, specificity 96.2%, P = 0.005), while in chronic PVT patients, for NLR = 3.645 (AUROC 0.744, sensitivity 40%, specificity 96.2%, P = 0.001), and for PLR = 195.93 (AUROC 0.715, sensitivity 44%, specificity 96.2%, P = 0.002). CONCLUSION: NLR and PLR were associated with the diagnosis of PVT. In PVT patients, NLR and PLR values were observed to be significantly higher than the control group. In our study, the relationship between NLR and PLR in patients with noncirrhotic, nonmalignant PVT without acquired risk factors for thrombosis was shown for the first time.

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).

Germline, mono-allelic mutations in RUNX1 cause familial platelet disorder (RUNX1-FPD) that evolves into myeloid malignancy (FPD-MM): MDS or AML. FPD-MM commonly harbors co-mutations in the second RUNX1 allele and/or other epigenetic regulators. Here we utilized patient-derived (PD) FPD-MM cells and established the first FPD-MM AML cell line (GMR-AML1). GMR-AML1 cells exhibited active super-enhancers of MYB, MYC, BCL2 and CDK6, augmented expressions of c-Myc, c-Myb, EVI1 and PLK1 and surface markers of AML stem cells. In longitudinally studied bone marrow cells from a patient at FPD-MM vs RUNX1-FPD state, we confirmed increased chromatin accessibility and mRNA expressions of MYB, MECOM and BCL2 in FPD-MM cells. GMR-AML1 and PD FPD-MM cells were sensitive to homoharringtonine (HHT or omacetaxine) or mebendazole-induced lethality, associated with repression of c-Myc, EVI1, PLK1, CDK6 and MCL1. Co-treatment with MB and the PLK1 inhibitor volasertib exerted synergistic in vitro lethality in GMR-AML1 cells. In luciferase-expressing GMR-AML1 xenograft model, MB, omacetaxine or volasertib monotherapy, or co-treatment with MB and volasertib, significantly reduced AML burden and improved survival in the immune-depleted mice. These findings highlight the molecular features of FPD-MM progression and demonstrate HHT, MB and/or volasertib as effective agents against cellular models of FPD-MM.

Platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio in glaucoma: a meta-analysis.

Aim: To explore the association between two systemic inflammation markers, platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), and glaucoma. Materials & methods: The authors searched PubMed, Embase and the Cochrane Library for eligible studies comparing PLR and LMR levels in glaucoma patients and healthy controls. Results: Analysis revealed that glaucoma patients exhibited significantly elevated PLR levels and reduced LMR compared with nonglaucoma controls. These findings were consistent across various glaucoma types, with the exception of secondary glaucoma, where the association with PLR was less significant. Conclusion: The authors found PLR and LMR to be potential valuable biomarkers for glaucoma identification and progression monitoring. These findings highlight the role of systemic inflammation in glaucoma pathogenesis.

Recent advances in microfluidic technology of arterial thrombosis investigations.

Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.

What is the context? To study the mechanism of arterial thrombosis, including the platelet adhesion and aggregation behavior and the coagulation process.Microfluidic technology is commonly used to study thrombosis. Microfluidic technology can simulate the real physiological environment on the microscopic scale in vitro, with high throughput, low cost, and fast speed.As an innovative experimental platform, microfluidic technology has made remarkable progress and has found applications in the fields of biology and medicine.What is new? This review summarizes the different fabrication methods of microfluidics and compares the advantages and disadvantages of these methods. Recent developments in microfluidic integrated systems and modular microfluidic systems have led to more diversified and automated microfluidic chips in the future.The different types and functions of microfluidic models are summarized. Platelet adhesion aggregation and coagulation processes, as well as arterial thrombus-related shear force changes and mechanical behaviors, were investigated by constructing artificial blood vessels and reproducing hemodynamics.Microfluidics can provide a basis for the development of personalized thrombosis treatment strategies. By analyzing the mechanism of action of existing drugs, using microfluidic technology for high-throughput screening of drugs and evaluating drug efficacy, more drug therapy possibilities can be developed.What is the impact?This review utilizes microfluidics to further advance the study of arterial thrombosis, and microfluidics is also expected to play a greater role in the biomedical field in the future.

microRNAs and thrombo-inflammation: relationship in sight.

PURPOSE OF REVIEW: Thrombo-inflammation is a multifaceted pathologic process involving various cells such as platelets, neutrophils, and monocytes. In recent years, microRNAs have been consistently implicated as regulators of these cells. RECENT FINDINGS: MicroRNAs play a regulatory role in several platelet receptors that have recently been identified as contributing to thrombo-inflammation and neutrophil extracellular trap (NET) formation. In addition, a growing body of evidence has shown that several intracellular and extracellular microRNAs directly promote NET formation. SUMMARY: Targeting microRNAs is a promising therapeutic approach to control thrombosis in patients with both infectious and noninfectious inflammatory diseases. Future research efforts should focus on elucidating the specific roles of microRNAs in thrombo-inflammation and translating these findings into tangible benefits for patients.

Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Distinguishing Lung Cancer in People with HIV.

Objective: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) demonstrate good diagnostic accuracy in distinguishing lung cancer patients from healthy individuals, primarily in HIV-negative populations. We determined the sensitivity (Se), specificity (Sp), and area under the curve (AUC) of the NLR and PLR in discriminating between people living with HIV (PLWH) with and without lung cancer. Methods: This is a comparative analysis of secondary data. Cases were PLWH with lung cancer from a retrospective cohort treated at the Uganda Cancer Institute. Controls were unmatched PLWH without lung cancer who were randomly selected from three HIV clinics in Uganda. Se, Sp, and AUC analysis and determination of optimal cutoffs were performed using receiver operating characteristic (ROC) curves. Results: Of 115 PLWH (18 cases and 97 controls), 83 (72.2%) were female, 110 (95.7) were on ART, and the median (IQR) age was 46 (38-51) years. The median (IQR) NLR was higher among cases than controls (3.53 (3.14-7.71) vs. 0.92 (0.67-1.09), p < 0.001). Similarly, the PLR was higher among cases than controls (237.5 (177.8-361.6) vs. 123.6 (100.6-155.4), p=0.001). At a cutoff of 2.44, the respective Se, Sp, and AUC of the NLR were 87.5% (95% CI: 61.7%-98.4%), 100% (95% CI: 96.2%-100%), and 0.94 (95% CI: 0.85-1.00, p < 0.001). Similarly, the respective Se, Sp, and AUC for the PLR were 75% (95% CI: 47.6%-92.7%), 87.2% (95% CI: 78.8%-93.2%), and 0.81 (95% CI: 0.70-0.93, p < 0.001) at a cutoff of 196.3. Conclusion: The NLR and PLR discriminated PLWH with and without lung cancer and could be useful in PLWH with respiratory symptoms in whom lung cancer can easily be misdiagnosed as other lung pathology.

Immune dysregulation is associated with symptom dimensions and cognitive deficits in schizophrenia: accessible evidence from complete blood count.

BACKGROUND: Schizophrenia (SCZ) is a psychotic disorder with an unknown pathogenesis accompanied by varying degrees of cognitive deficits. Recent studies have shown that immune dysregulation plays an important role in developing symptoms and cognitive deficits in SCZ. This study aimed to determine the complete blood count (CBC), including white blood cells, neutrophils, monocytes, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), in patients with SCZ and explore their correlations with SCZ symptom dimensions and cognitive function. METHODS: Seventy-four patients with SCZ and 57 age- and sex-matched healthy controls with available demographic and clinical information were recruited for this study. Blood samples were collected, and symptom dimensions and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) separately. RESULTS: Our results demonstrate that SCZ patients showed higher monocyte counts, PLR, MLR, and worse performance in the total MCCB than healthy controls. Neutrophil and lymphocyte counts and NLR were positively related to symptom severity and negatively related to depressive symptoms. White blood cell (WBC) count, monocyte count, and MLR were positively correlated with cognitive performance in patients with SCZ. CONCLUSION: In summary, this study suggests that cognitive deficits and symptom severity in patients were associated with dysregulation of immunity. Moreover, we found that WBC could be used as a marker for symptom severity and cognitive deficits in SCZ and that neutrophils are more closely related to the former and monocytes to the latter. We hope that clinicians will pay more attention to dysregulated immunity in patients with SCZ in the future.

The dynamic role of platelets in cancer progression and their therapeutic implications.

Systemic antiplatelet treatment represents a promising option to improve the therapeutic outcomes and therapeutic efficacy of chemotherapy and immunotherapy due to the critical contribution of platelets to tumour progression. However, until recently, targeting platelets as a cancer therapeutic has been hampered by the elevated risk of haemorrhagic and thrombocytopenic (low platelet count) complications owing to the lack of specificity for tumour-associated platelets. Recent work has advanced our understanding of the molecular mechanisms responsible for the contribution of platelets to tumour progression and metastasis. This has led to the identification of the biological changes in platelets in the presence of tumours, the complex interactions between platelets and tumour cells during tumour progression, and the effects of platelets on antitumour therapeutic response. In this Review, we present a detailed picture of the dynamic roles of platelets in tumour development and progression as well as their use in diagnosis, prognosis and monitoring response to therapy. We also provide our view on how to overcome challenges faced by the development of precise antiplatelet strategies for safe and efficient clinical cancer therapy.

Tumor-educated platelets.

Beyond traditional roles in homeostasis and coagulation, growing evidence suggests that platelets also reflect malignant transformation in cancer. Platelets are present in the tumor microenvironment where they interact with cancer cells. This interaction results in direct and indirect "education" as evident by platelet alterations in adhesion molecules, glycoproteins, nucleic acids, proteins and various receptors. Subsequently, these tumor-educated platelets (TEPs) circulate throughout the body and play pivotal roles in promotion of tumor growth and dissemination. Accordingly, platelet status can be considered a unique blood-based biomarker that can potentially predict prognosis and therapeutic success. Recently, liquid biopsies including TEPs have received much attention as safe, minimally invasive and sensitive alternatives for patient management. Herein, we provide an overview of TEPs and explore their benefits and limitations in cancer.

Improving the chances of response to splenectomy in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by isolated thrombocytopenia. Its pathogenesis is complex relying in large part on destruction of platelets recognized by autoantibodies within the spleen. However, other mechanisms, such as platelet desialylation, may play a role in platelet reduction by accelerating their clearance in the liver. In their study, Mendoza and colleagues reported on platelet scintigraphy performed in 51 ITP patients, showing a response in 87.5% when the sequestration occurred in the spleen versus 45% in case of non-splenic destruction. Platelet desialylation was also measured after splenectomy and found to be higher in non-responder patients. These latter results, while requiring confirmation prior to splenectomy, support platelet desialylation may also be a potential biomarker of non-response to splenectomy. Commentary on: Mendoza et al. Study of platelet kinetics in immune thrombocytopenia to predict splenectomy response. Br J Haematol 2024;204:315-323.

Phosphoinositides take a central stage in regulating blood platelet production and function.

Blood platelets are produced by megakaryocytes through a complex program of differentiation and play a critical role in hemostasis and thrombosis. These anucleate cells are the target of antithrombotic drugs that prevent them from clumping in cardiovascular disease conditions. Platelets also significantly contribute to various aspects of physiopathology, including interorgan communications, healing, inflammation, and thromboinflammation. Their production and activation are strictly regulated by highly elaborated mechanisms. Among them, those involving inositol lipids have drawn the attention of researchers. Phosphoinositides represent the seven combinatorially phosphorylated forms of the inositol head group of inositol lipids. They play a crucial role in regulating intracellular mechanisms, such as signal transduction, actin cytoskeleton rearrangements, and membrane trafficking, either by generating second messengers or by directly binding to specific domains of effector proteins. In this review, we will explore how phosphoinositides are implicated in controlling platelet production by megakaryocytes and in platelet activation processes. We will also discuss the diversity of phosphoinositides in platelets, their role in granule biogenesis and maintenance, as well as in integrin signaling. Finally, we will address the discovery of a novel pool of phosphatidylinositol 3-monophosphate in the outerleaflet of the plasma membrane of human and mouse platelets.

Evaluation of a diagnostic platelet aggregation test strategy for platelet rich plasma samples with low platelet counts.

INTRODUCTION: Light transmission aggregometry (LTA) is important for diagnosing platelet function disorders (PFD) and von Willebrand disease (VWD) affecting ristocetin-induced platelet aggregation (RIPA). Nonetheless, data is lacking on the utility of LTA for investigating thrombocytopenic patients and platelet rich plasma samples with low platelet counts (L-PRP). Previously, we developed a strategy for diagnostic LTA assessment of L-PRP that included: (1) acceptance of referrals/samples, regardless of thrombocytopenia severity, (2) tailored agonist selection, based on which are informative for L-PRP with mildly or severely low platelet counts, and (3) interpretation of maximal aggregation (MA) using regression-derived 95% confidence intervals, determined for diluted control L-PRP (C-L-PRP). METHODS: To further evaluate the L-PRP LTA strategy, we evaluated findings for a subsequent patient cohort. RESULTS: Between 2008 and 2021, the L-PRP strategy was applied to 211 samples (11.7% of all LTA samples) from 192 unique patients, whose platelet counts (median [range] × 109 /L) for blood and L-PRP were: 105 [13-282; 89% with thrombocytopenia] and 164 [17-249], respectively. Patient-L-PRP had more abnormal MA findings than simultaneously tested C-L-PRP (p-values <0.001). Among patients with accessible electronic medical records (n = 181), L-PRP LTA uncovered significant aggregation abnormalities in 45 (24.9%), including 18/30 (60%) with <80 × 109 platelets/L L-PRP, and ruled out PFD, and VWD affecting RIPA, in others. The L-PRP LTA strategy helped diagnose VWD affecting RIPA, Bernard Soulier syndrome, familial platelet disorder with myeloid malignancy, suspected ITGA2B/ITGB3-related thrombocytopenia, and acquired PFD. CONCLUSION: Diagnostic LTA with L-PRP, using a strategy that considers thrombocytopenia severity, is feasible and informative.

Role of platelet count in a murine stasis model of deep vein thrombosis.

Platelets are core components of thrombi but their effect on thrombus burden during deep vein thrombosis (DVT) has not been fully characterized. We examined the role of thrombopoietin-altered platelet count on thrombus burden in a murine stasis model of DVT. To modulate platelet count compared to baseline, CD1 mice were pretreated with thrombopoietin antisense oligonucleotide (THPO-ASO, 56% decrease), thrombopoietin mimetic (TPO-mimetic, 36% increase), or saline (within 1%). Thrombi and vein walls were examined on postoperative days (POD) 3 and 7. Thrombus weights on POD 3 were not different between treatment groups (p = .84). The mean thrombus weights on POD 7 were significantly increased in the TPO-mimetic cohort compared to the THPO-ASO (p = .005) and the saline (p = .012) cohorts. Histological grading at POD 3 revealed a significantly increased smooth muscle cell presence in the thrombi and CD31 positive channeling in the vein wall of the TPO-mimetic cohort compared to the saline and THPO-ASO cohorts (p < .05). No differences were observed in histology on POD 7. Thrombopoietin-induced increased platelet count increased thrombus weight on POD 7 indicating platelet count may regulate thrombus burden during early resolution of venous thrombi in this murine stasis model of DVT.

Deep vein thrombosis (DVT) is a pathology in which blood clots form in the deep veins of our body. Usually occurring in the legs, these clots can be dangerous if they dislodge and travel to the heart and are pumped into the lungs. Often these clots do not travel and heal where they formed. However, as the body heals the clot it may also cause damage to the vein wall and predispose the patient to future clots, i.e., the biggest risk factor for a second clot is the first clot. DVT can also cause symptoms of pain, swelling, and redness in the long-term, leading to post-thrombotic syndrome where the initial symptoms of the clot persist for a long time. All blood clots have common components of red blood cells, white blood cells, platelets, and fibrin in varying concentrations. Humans maintain a platelet count between 150 and 400 thousand platelets per microliter of our blood. However, diseases like cancer or medications like chemotherapy can cause a change in our body's platelet count. The effect of a changing platelet count on the size (clot burden) of DVT clot and how platelet count could affect DVT as the clot heals is not fully understood. Studying this might help us develop better targets and treat patients with a wide range of platelet counts who experience DVT. In this study, we intentionally decreased, left unchanged, and increased platelet counts in mice and then created a DVT to study what the effect of low, normal, and high platelet counts, respectively, would be on the clot burden. We observed that mice with higher platelet counts had a higher clot burden during the early part of the healing process of the clot. Within this study, we can conclude that higher platelet counts may lead to higher clot burden in DVT which furthers our understanding of how platelet count affects clot burden during DVT.

Peripheral blood inflammatory indexes in breast cancer: A review.

Immune and inflammatory responses play an important role in tumorigenesis and metastasis. Inflammation is an important component of the tumor microenvironment, and the changes in inflammatory cells may affect the occurrence and development of tumors. Complete blood count at the time of diagnosis and treatment can reflect the inflammatory status within the tumor. Studies have shown that the number of certain inflammatory cells in peripheral blood and their ratios are important prognostic factors for many malignancies, including neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index and pan-immune-inflammation-value. The value of peripheral blood inflammation indexes in predicting the efficacy and prognosis of breast cancer neoadjuvant therapy is worth recognizing. This review details the application of peripheral blood inflammation indexes in the evaluation of efficacy and prediction of prognosis in neoadjuvant therapy for breast cancer, aiming to provide a more comprehensive reference for the comprehensive diagnosis and treatment of breast cancer.

Effect of dynamic platelet-to-lymphocyte ratio on the prognosis of patients with esophageal squamous cell carcinoma receiving chemoradiotherapy.

Systemic inflammatory load affects the long-term developmental outcomes in patients with malignancy. The purpose of this study was to investigate the effect of the dynamic levels of platelet-to-lymphocyte ratio (PLR) at different treatment stages on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy. This study included 168 patients who received chemoradiotherapy between 2012 and 2018. PLR levels at different treatment stages were calculated based on blood test results. The association between PLR and overall survival (OS) was determined using the Kaplan-Meier method and Cox proportional regression models. The cutoff values of PLR before and after treatment of 168 patients with ESCC were 195.7 and 403.6, respectively. The 5-year OS rates of patients in the low and high pre-PLR groups were 42.1% and 21.7%, respectively. The overall 5-year OS rate of all patients was 27.1%. Multivariate analysis results showed that patient age (hazard ratio [HR] = 1.736; 95% confidence interval (CI) = 1.129-2.669; P = .012), alcohol consumption (HR = 1.622; 95%CI = 1.050-2.508; P = .029), T stage (HR = 12.483; 95%CI = 3.719-41.896; P < .001), pre-PLR (HR = 1.716; 95%CI = 1.069-2.756; P = .025), post-PLR (HR = 1.664; 95%CI = 1.106-2.503; P = .015) were independent factors of the prognosis of patients with ESCC. PLR at different treatment stages can be used to effectively evaluate the prognosis of patients with ESCC undergoing chemoradiotherapy.

The ratio of lymphocyte/red blood cells and platelets/lymphocytes are predictive biomarkers for lymph node metastasis in patients with breast cancer.

BACKGROUND: Axillary lymph node metastasis (LNM) affects the progression of breast cancer. However, it is difficult to preoperatively diagnose axillary lymph node status with high sensitivity. Therefore, we hypothesized that platelets/lymphocytes ratio (PLR) and lymphocytes/ red blood cells ratio (LRR) might help in the prognosis of lymph node metastasis in T1-T2 breast cancer. METHODS: 166 patients (Chang Ning Maternity & Infant Health Institute) were included in our study, and the associations of PLR and LPR with lymph node metastasis were investigated. Peripheral blood was collected one week before the surgery, and the patients were divided into different categories based on their PLR and LRR. RESULTS: The incidence of LNM was significantly increased in the high PLR group (p= 0.002) compared with the low PLR group; LNM was also significantly increased in the low LRR group (p= 0.036) compared with the high LPR group. Further, our study revealed that high PLR (p< 0.001, OR = 4.397, 95% CI = 2.005-9.645), low LRR (p= 0.017, OR = 0.336, 95%CI = 0.136-0.825) and high clinical T stage (p< 0.001, OR = 3.929, 95%CI = 1.913-8.071) are independent predictors of LNM. CONCLUSIONS: PLR and LRR could be identified as predictors of LNM in patients with T1/T2 breast cancer.

THE PROGNOSTIC ROLE OF PRE-TREATMENT PLATELET-TO-LYMPHOCYTE RATIO IN HEAD AND NECK SQUAMOUS CELL CARCINOMA: META-ANALYSIS AND TRIAL SEQUENTIAL ANALYSIS.

BACKGROUND: Evidence suggests that inflammation contributes to tumor development, from onset to progression and metastasis. Platelet-to-lymphocyte ratio (PLR) is a composite parameter that provides information from two distinct cellular elements, platelets, and lymphocytes. The purpose of this systematic review and meta-analysis is to evaluate the prognostic role of the PLR, in terms of overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS) and progression-free survival (PFS), in patients with primary head and neck squamous cell carcinoma treated with surgery followed or not by adjuvant therapies. MATERIALS AND METHODS: This systematic review was performed according to the guidelines reported in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Meta-analysis of OS and DFS was performed using the inverse of variance test. Random-effect models were used on the basis of high heterogeneity. Risk of bias assessment, quality of evidence within studies (GRADE) and trial sequential analysis (TSA) were also performed. RESULTS: The analysis revealed that a higher value of pretreatment PLR correlates with a statistically significant decrease of OS (HR, 1.85; 95% CI: [1.23, 2.80]; P < .00001), confirmed by TSA. The meta-analysis reports an association between high PLR and DFS (HR,1.46; 95% CI: [1.03, 2.06]; P = .003); but TSA suggests that it his should be considered as a false positive. Further studies are needed to validate the efficacy of PLR in predicting CSS and PFS outcomes. CONCLUSION: Pretreatment PLR is an independent prognostic factor for OS in HNSCC.

Prognostic value of neutrophil to lymphocyte ratio and platelet counts during chemotherapy in patients with advanced gastric cancer.

OBJECTIVES: To investigate the predictive significance of dynamic changes in the neutrophil to lymphocyte ratio (NLR) and platelet counts (PLTs) in patients with advanced gastric cancer (GC) during chemotherapy. METHODS: A total of 259 advanced GC patients receiving chemotherapy were enrolled and grouped by high or low NLR with a cut value of 2.5 and PLT with cut value of 300×109/L. The Kaplan-Meier survival model and the Log-rank test were carried out to determine the comparison on the overall survival differences. Cox regression analysis was employed to carry out both univariate and multivariate regression studies, aiming to explore potential prognostic factors acting independently. RESULTS: Higher pre-chemotherapy NLR exhibited an association with metastasis and advanced grade of Borrmann type, and higher NLR of pre- or post-chemotherapy GC patients was related with Borrmann type grade. Moreover, higher PLT counts are associated with advanced grades of Borrmann type. Interestingly, patients with lower post-chemotherapy NLR or decreasing NLR hold better overall response rate and disease control rate than those with higher NLR or increasing NLR. Furthermore, patients with high post-chemotherapy NLR alone or higher post-chemotherapy NLR plus higher post-chemotherapy PLT. CONCLUSION: Our study suggested that high post-chemotherapy NLR and post-chemotherapy PLT might be adverse prognostic markers in advanced GC patients undergoing chemotherapy.

Predictive value of platelet-to-lymphocyte ratio combined with CA199 levels in postoperative survival of patients with gastric cancer: A retrospective study.

OBJECTIVE: To develop a new scoring system based on platelet-to-lymphocyte ratio (PLR) and CA199 to predict the prognosis of gastric cancer. METHODS: PLR-CA199 was identified in a retrospective study that was conducted in a training cohort of 990 gastric cancer patients who underwent curable resection from 2012 to 2014 and validated in a validation cohort of 625 patients between 2015 and 2016. RESULTS: In the training cohort, PLR-CA199 was related to gender (P = 0.041), age (P = 0.014), tumor location (P = 0.015), tumor size (P < 0.001), Bormann type (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and TNM staging (P < 0.001). In the validation cohort, PLR-CA199 was related to tumor size (P < 0.001), Bormann type (P = 0.007), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and TNM staging (P < 0.001). Survival analysis showed that in the training cohort the mean disease-free survival (DFS) was 70.699 months for patients PLR-CA199 = 0, 51.223 months for patients PLR-CA199 = 1, and 32.152 months for patients PLR-CA199 = 2 (P < 0.001). The correlation between PLR-CA199 and DFS was further confirmed in the validation cohort (50.640 vs. 41.842 vs. 22.382, P < 0.001). Survival analysis showed that the mean disease special survival (DSS) was 76.668 months for patients PLR-CA199 = 0, 61.218 months for patients PLR-CA199 = 1, and 44.665 months for patients PLR-CA199 = 2 in the training cohort (P < 0.001). The correlation between PLR-CA199 and DSS was further confirmed in the validation cohort (53.858 vs. 46.385 vs. 44.665, P < 0.001). Furthermore, univariate and multivariate analyses showed that PLR-CA199 was an independent prognostic factor for DFS and DSS. CONCLUSIONS: Preoperative PLR-CA199 may be a useful prognostic indicator, and is a promising tool for predicting the prognosis for gastric cancer.