Systemic immune-inflammation index,neutrophilto-lymphocyte ratio,and platelet-to-lymphocyte ratio in patients with type 2 diabetes at different stages of diabetic retinopathy

AIM:To investigate systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),and plateletto-lymphocyte ratio(PLR)levels in patients with type 2 diabetes at different stages of diabetic retinopathy(DR).METHODS:This retrospective study included 141 patients with type 2 diabetes mellitus(DM):45 without diabetic retinopathy(NDR),47 with non-proliferative diabetic retinopathy(NPDR),and 49 with proliferative diabetic retinopathy(PDR).Complete blood counts were obtained,and NLR,PLR,and SII were calculated.The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic(ROC)curves.The relationships between DR stages and SII,PLR,and NLP were assessed using multivariate logistic regression.RESULTS:The average NLR,PLR,and SII were higher in the PDR group than in the NPDR group(P=0.011,0.043,0.009,respectively);higher in the NPDR group than in the NDR group(P<0.001 for all);and higher in the PDR group than in the NDR group(P<0.001 for all).In the ROC curve analysis,the NLR,PLR,and SII were significant predictors of DR(P<0.001 for all).The highest area under the curve(AUC)was for the PLR(0.929 for PLR,0.925 for SII,and 0.821 for NLR).Multivariate regression analysis indicated that NLR,PLR,and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM[odds ratio(OR)=1.122,95%confidence interval(CI):0.200–2.043,P<0.05;OR=0.038,95%CI:0.018–0.058,P<0.05;OR=0.007,95%CI:0.001–0.01,P<0.05,respectively).CONCLUSION:The NLR,PLR,and SII may be used as predictors of DR.

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 incor-porating 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.

Platelet-to-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer: A systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on platelet-to-lymphocyte ratio(PLR) as a risk factor for post-transplant hepatocellular cancer(HCC) recurrence. METHODS A systematic literature search was performed using PubM ed. Participants of any age and sex, who underwent liver transplantation for HCC were considered following these criteria:(1) studies comparing pre-transplant low vs high PLR values;(2) studies reporting post-transplant recurrence rates; and(3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measure was set for HCC recurrence after transplantation. RESULTS A total of 5 articles, published between 2014 and 2017, fulfilled the selection criteria. As for the quality of the reported studies, all the investigated articles presented an overall high quality. A total of 899 cases were investigated: 718 cases(80.0%) were males. Three studies coming from European countries and one from Japan presented HCV as the main cause of cirrhosis. On the opposite, one Chinese study presented a greater incidence of HBV-related cirrhotic cases. In all the studies apart one, the PLR cut-off value of 150 was reported. At meta-analysis, high PLR value was associated with a significant increase in recurrence after transplantation(OR = 3.33; 95%CI: 1.78-6.25; P < 0.001). A moderate heterogeneity was observed among the identified studies according to the Higgins I^2 statistic value.CONCLUSION Pre-transplant high PLR values are connected with an increased risk of post-operative recurrence of hepatocellular cancer. More studies are needed for better clarify the biological mechanisms of this results.

Combined preoperative platelet-to-lymphocyte ratio and serum carbohydrate antigen 19–9 level as a prognostic factor in patients with resected pancreatic cancer

Background: Carbohydrate antigen 19–9(CA19-9) is the most frequently used tumor marker and serves as a prognostic indicator in patients with pancreatic cancer(PC). The platelet-to-lymphocyte ratio(PLR) is thought to be an inflammation-related serum marker. An elevated PLR represents increased inflammatory status and is associated with poor prognosis in patients with various cancers including PC. Methods: This study involved 103 patients with a histopathological diagnosis of pancreatic ductal adenocarcinoma who underwent pancreatectomy. The patients were assessed to determine the prognostic significance of the combination of the PLR and CA19-9 level. Results: Based on the receiver operating characteristic analysis results, the patients were divided into PLR H igh(PLR ≥ 129.1) andPLRLow(PLR < 129.1) groups and into CA19-9High(CA19-9 ≥ 74.0 U/mL) and CA19-9Low(CA19-9 < 74.0 U/mL) groups. The cumulative 5-year overall survival(OS) and disease-specific survival(DSS) rates significantly differed by both the PLR(PLR H igh group: 19.5% and 22.9%;PLRLow group: 39.1% and 45.9%) and CA19-9(CA19-9 H igh group: 19.1% and 25.6%;CA19-9Low group: 41.0% and 41.0%). We then divided the patients into Groups A(PLR L ow/CA19-9Low), B(PLR Low/CA19-9High or PLRHigh/CA19-9Low), and C(PLR H igh/CA19-9High). The cumulative 5-year OS rates in Groups A, B, and C were 44.0%, 31.9%, and 11.9%, respectively( P = 0.002). The cumulative 5-year DSS rates in Groups A, B, and C were 47.7%, 36.4%, and 16.8%, respectively( P = 0.002). Multivariate analysis revealed that the combination of the PLR and CA19-9 was an independent prognostic factor in patients with resected PC. Conclusions: The combination of the PLR and CA19-9 is useful for predicting the prognosis of patients with resected PC.

The combined prognostic value of pretreatment neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in stage IE/IIE extranodal natural killer/T-cell lymphoma

Objective This study aimed to explore the combined prognostic value of pretreatment neutrophil-tolymphocyte ratio(NLR), lymphocyte-to-monocyte ratio(LMR), and platelet-to-lymphocyte ratio(PLR) in newly diagnosed IE/IIE extranodal natural killer/T-cell lymphoma(ENKTL) treated with a P-Gemox regimen combined with radiotherapy or radiotherapy alone.Methods A total of 132 patients from 2009 to 2017 at the Sichuan Cancer Hospital were enrolled in the study. The cutoff values of NLR, LMR, and PLR using overall survival(OS) rate as an endpoint were obtained by the receiver operating curve. Results The cutoff value of NLR was 3.5. Patients with high NLR had significantly shorter progressionfree survival(PFS)(P < 0.001) and OS(P < 0.001) than those with low NLR. Similarly, the cutoff value of LMR was 3.0. The high LMR group had significantly longer PFS(P=0.001) and OS(P < 0.001) than the low LMR group. Similarly, the cutoff value of PLR was 191.7. The high PLR group was significantly associated with poor PFS(P < 0.001) and OS(P < 0.001) than the low PLR group. Furthermore, combining NLR, LMR, and PLR to build a new model to stratify patients into low-, intermediate-, intermediate-high-, and high-risk groups, there were also significant differences in PFS(P < 0.001) and OS(P < 0.001). The univariate analysis showed that presenting B symptoms, stage IIE, local tumor invasion, Eastern Cooperative Oncology Group score ≥ 2, elevated lactate dehydrogenase level, elevated NLR, decreased LMR, and elevated PLR were significantly associated with poor survival. The multivariate analysis demonstrated that PLR was an independent prognostic factor for both PFS(hazard ratio [HR]= 2.073, 95% confidence interval [CI]= 1.080–3.981, P = 0.028) and OS(HR = 2.127, 95% CI = 1.102–4.107, P = 0.025).Conclusion Elevated pretreatment PLR was a novel simple predictor of poor survival in patients with stage IE/IIE ENKTL. Combining NLR, LMR, and PLR could provide additional stratification.

An elevated platelet-to-lymphocyte ratio is associated with a higher risk of intracranial atherosclerotic stenosis

Background:Previous studies have shown that inflammation plays an important role in intracranial atherosclerotic stenosis(ICAS).The platelet-to-lymphocyte ratio(PLR)has recently emerged as a potential inflammatory biomarker.This study aimed to explore the association of the PLR with ICAS in a Chinese Han population.Methods:A total of 2134 participants(518 with ICAS,1616 without ICAS)were enrolled in this study.ICAS was defined as atherosclerotic stenosis>50%or the occlusion of several main intracranial arteries.Multivariable logistic regression analyses were used to assess the association of the PLR with ICAS.Additional subgroup analyses were performed according to age(<60 vs.≥60 years)and acute ischemic stroke.Results:Multivariate regression analysis showed that a high PLR was associated with a higher risk of ICAS in all participants(P<0.001).Compared with the lowest quartile,the fourth PLR quartile was significantly associated with ICAS(OR 1.705,95%confidence interval 1.278–2.275,P<0.001).In the subgroups stratified by age,an association between the PLR and ICAS was found in the late-life group(P<0.001),but not in the mid-life group(P=0.650).In the subgroups stratified by acute ischemic stroke,the relationship between an elevated PLR and a higher risk of ICAS remained unchanged(stroke group,P<0.001;non-stroke group,P=0.027).Conclusions:An elevated PLR was associated with a higher risk of ICAS in a Chinese Han population.The PLR might serve as a potential biomarker for ICAS in the elderly population.

Stratified Platelet-to-lymphocyte Ratio:A Novel Target for Prognostic Prediction of Hepatocellular Carcinoma after Curative Liver Resection

Background and Aims:Platelet-to-lymphocyte ratio(PLR)has been shown to predict prognosis of cancers.We aimed to evaluate the prognostic value of stratification of PLR in patients after curative liver resection(CLR)for hepatocellular carcinoma(HCC).Methods:A total of 1804 patients who underwent CLR for suspected HCC between January 2007 and January 2014 were screened for the study.All of the patients were categorized into equal tertiles according to the number of patients and the distribution of PLR.Prognostic significance was determined for overall survival(OS)and was assessed using Kaplan-Meier analysis.Univariate and multi-variate Cox proportional hazard regression analyses were evaluated for association of all independent parameters with disease prognosis.Results:The optimal cut-off points of preoperative PLR were:(T1)11.98-75.00,(T2)75.00-113.33 and(T3)113.33-567.50.There were obvious differences in each PLR tertile with mortality within 36 months of CLR(Plog-rank<0.001).Multivariable analysis suggested that the level of PLR(HR=1.004,95%CI:1.001-1.008,P=0.006),portal vein thrombosis(HR=3.406,95%CI:1.185-9.794,P=0.023),number of nodules(HR=1.810,95%CI:1.345-2.437,P<0.001),Child-Turcotte-Pugh score(HR=1.741,95%CI:1.129-2.684,P=0.012)and microvascular invasion(HR=2.730,95%CI:1.777-4.196,P<0.001)were significant predictors of mortality.Kaplan-Meier analysis of overall survival(OS)demonstrated that each PLR tertile showed a progressively worse OS and apparent separation(Plog-rank=0.016).The highest 5-year OS rate following CLR(58%)was revealed in tertile 1.In contrast,the lowest 5-year OS rate(30%)was revealed in tertile 3.Conclusion:Stratified preoperative PLR could strengthen the predictive power for OS in HCC patients with CLR.

Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers

BACKGROUND Portal vein thrombosis(PVT),a complication of liver cirrhosis,is a major public health concern.PVT prediction is the most effective method for PVT diagnosis and treatment.AIM To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis.METHODS Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved.Following a 1:1 propensity score matching 572 patients with cirrhosis were screened,and relevant clinical data were collected.PVT risk factors were identified using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression analysis.Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables.A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT,and its predictive performance was verified using a receiver operating characteristic curve(ROC),calibration curves,and decision curve analysis(DCA).Finally,a network calculator was constructed based on the nomograms.RESULTS This study enrolled 286 cirrhosis patients with PVT and 286 without PVT.LASSO analysis revealed 13 variables as strongly associated with PVT occurrence.Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors,including etiology,ascites,gastroesophageal varices,platelet count,D-dimer,portal vein diameter,portal vein velocity,aspartate transaminase to neutrophil ratio index,and platelet-to-lymphocyte ratio.LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables.A nomogram was constructed based on the screened independent risk factors.The nomogram had excellent predictive performance,with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups,respectively.Calibration curves and DCA revealed its good clinical performance.Finally,the optimal cutoff value for the total nomogram score was 0.513.The sensitivity and specificity of the optimal cutoff values were 0.822 and 0.706,respectively.CONCLUSION A nomogram for predicting PVT occurrence was successfully developed and validated,and a network calculator was constructed.This can enable clinicians to rapidly and easily identify high PVT risk groups.

Clinical study of neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases.We categorize acute pancreatitis by etiology into acute biliary pancreatitis(ABP)and hypertriglyceridemia-induced acute pancreatitis(HTGP).AIM To investigate the clinical significance of NLR and PLR in assessing persistent organ failure(POF)in HTGP and ABP.METHODS A total of 1450 patients diagnosed with acute pancreatitis(AP)for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled.The patients were categorized into two groups according to the etiology of AP:ABP in 530 patients and HTGP in 241 patients.We collected and compared the clinical data of the patients,including NLR,PLR,and AP prognostic scoring systems,within 48 h of hospital admission.RESULTS The NLR(9.1 vs 6.9,P<0.001)and PLR(203.1 vs 160.5,P<0.001)were significantly higher in the ABP group than in the HTGP group.In the HTGP group,both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score≥3.Likewise,in the ABP group,NLR and PLR were significantly elevated in patients with severe AP,modified computed tomography severity index score≥4,Japanese Severity Score≥3,and modified Marshall score≥2.Moreover,NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups.CONCLUSION NLR and PLR vary between ABP and HTGP,are strongly associated with AP prognostic scoring systems,and have predictive potential for the occurrence of POF in both ABP and HTGP.

Development and validation of a novel nomogram for predicting overall survival in gastric cancer based on inflammatory markers

BACKGROUND Nearly 66%of occurrences of gastric cancer(GC),which has the second-highest death rate of all cancers,arise in developing countries.In several cancers,the predictive significance of inflammatory markers has been established.AIM To identify clinical characteristics and develop a specific nomogram to determine overall survival for GC patients.METHODS Nine hundred and four GC patients treated at the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2013 were recruited.Prognostic risk variables were screened for Cox analysis.The C index,receiver operator characteristic(ROC)curve,and decision curve analysis were used to evaluate the nomogram.RESULTS Tumor node metastasis stage,carcinoembryonic antigen,systemic immuneinflammation index,and age were identified as independent predictive variables by multivariate analysis.Systemic immune-inflammation index value was superior to that of other inflammatory indicators.The ROC indicated the nomogram had a higher area under the curve than other factors,and its C-index for assessing the validation and training groups of GC patients was extremely reliable.CONCLUSIONWe created a novel nomogram to forecast the prognosis of GC patients following curativegastrectomy based on blood markers and other characteristics. Both surgeons and patients canbenefit significantly from this new scoring system.

Does the preoperative platelet-tolymphocyte ratio and neutrophil-tolymphocyte ratio predict morbidity after gastrectomy for gastric cancer?

Background:Gastric cancer is the 2 nd most common cause of cancer-related deaths,and the morbidity rate after surgery is reported to be as high as 46%.The estimation of possible complications,morbidity,and mortality and the ability to specify patients at high risk have become substantial for an intimate follow-up and for proper management in the intensive care unit.This study aimed to determine the prognostic value of the preoperative platelet-tolymphocyte ratio(PLR)and neutrophil-to-lymphocyte ratio(NLR)and their relations with clinical outcomes and complications after gastrectomy for gastric cancer.Methods:This single-center,retrospective cohort study evaluated the data of 292 patients who underwent gastrectomy with curative intent between January 2015 and June 2018 in a tertiary state hospital in Ankara,Turkey.A receiver operating characteristic curve was generated to evaluate the ability of laboratory values to predict clinically relevant postoperative complications.The area under the curve was computed to compare the predictive power of the NLR and PLR.Then,the cutoff points were selected as the stratifying values for the PLR and NLR.Results:The area under the curve values of the PLR(0.60,95%CI 0.542–0.657)and NLR(0.556,95%CI 0.497–0.614)were larger than those of the other preoperative laboratory values.For the PLR,the diagnostic sensitivity and specificity were 50.00%and 72.22%,respectively,whereas for the NLR,the diagnostic sensitivity and specificity were 37.50%and 80.16%,respectively.The PLR was related to morbidity,whereas the relation of the NLR with mortality was more prominent.This study demonstrated that the PLR and NLR may predict mortality and morbidity via the ClavienDindo classification in gastric cancer patients.The variable was grade≥3 in the Clavien-Dindo classification,including complications requiring surgical or endoscopic interventions,life-threatening complications,and death.Both the PLR and NLR differed significantly according to Clavien-Dindo grade≥3.In this analysis,the PLR was related to morbidity,while the NLR relation with mortality was more intense.Conclusion:Based on the results of the study,the PLR and NLR could be used as independent predictive factors for mortality and morbidity in patients with gastric cancer.

Effective immune-inflammation index for ulcerative colitis and activity assessments

BACKGROUND The inverse association between systemic immune-inammation index(SII)and overall survival in tumors has been studied.AIM To evaluate the hematological indexes for assessing the activity of ulcerative colitis(UC).METHODS In this case-control study,172 UC patients and healthy participants were included.Comparisons were made among groups of white blood cells,hemoglobin,platelets,neutrophils,lymphocytes,monocytes,SII,neutrophil-tolymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).The relationship with hematological inflammation was verified by Spearman correlation analyses.The efficiency of SII,NLR,and PLR for distinguishing between UC and severe disease status was assessed by the receiver operator curve and logistic regression analyses.RESULTS The values of SII,NLR,and PLR were higher in UC patients than in controls(P<0.001)and were positively correlated with the Mayo endoscopic score,extent,Degree of Ulcerative Colitis Burden of Luminal Inflammation(DUBLIN)score,and Ulcerative Colitis Endoscopic Index of Severity(UCEIS).The cut-off NLR value of 562.22 predicted UC with a sensitivity of 79.65%and a specificity of 76.16%.Logistic regression analysis revealed that patients with SII and NLR levels above the median had a significantly higher risk of UC(P<0.05).Risk factors independently associated with DUBLIN≥3 included SII≥1776.80[odds ratio(OR)=11.53,P=0.027]and NLR value of 2.67-4.23(OR=2.96,P=0.047)on multivariate analysis.Compared with the first quartile,SII≥1776.80 was an independent predictor of UCEIS≥5(OR=18.46,P=0.012).CONCLUSION SII has a certain value in confirming UC and identifying its activity.

Towards an evaluation of alcoholic liver cirrhosis and nonalcoholic fatty liver disease patients with hematological scales

BACKGROUND Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance.Despite a growing number of studies in this field of hepatology,a certain role of hematological indices in the course of liver disorders has not been fully elucidated,yet.AIM To evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR)and mean platelet volume-to-platelet-ratio(MPR)in the course of alcoholic liver cirrhosis(ALC)and nonalcoholic fatty liver disease(NAFLD).METHODS One hundred forty-two patients with ALC,92 with NAFLD and 68 persons in control group were enrolled in the study.Hematological indices(NLR,PLR and MPR),indirect and direct markers of liver fibrosis(aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index,fibrosis-4,gamma-glutamyl transpeptidase to platelet ratio,procollagen Ⅰ carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,platelet-derived growth factor AB,laminin)were measured in each person.Model for end-stage liver disease(MELD)score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients.Receiver operating characteristic(ROC)curves and area under the curve(AUC)values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD.RESULTS MPR and NLR values in ALC patients were significantly higher in comparison to control group;PLR level was significantly lower.MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis.MPR,NLR and PLR correlated with MELD score.NLR level in NAFLD patients was significantly higher in comparison to controls.MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score.AUC values and proposed cut-offs for NLR,PLR and MPR in ALC patients were:0.821(>2.227),0.675(<70.445)and 0.929(>0.048),respectively.AUC values and proposed cut-offs for NLR,PLR and MPR in NAFLD group were:0.725(>2.034),0.528(>97.101)and 0.547(>0.038),respectively.CONCLUSION Hematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients.MPR and NLR turned out to be the most powerful parameters in ALC patients.

Correlation of neutrophil/lymphocyte and platelet/lymphocyte ratio with visual acuity and macular thickness in age-related macular degeneration

AIM：To investigate the place of neutrophil-to-lymphocyte ratio（NLR） and platelet-to-lymphocyte ratio（PLR） in the diagnosis of and prognosis for neovascular age-related macular degeneration（AMD）. METHODS：One hundred AMD patients and 100 healthy controls were included in the study. Blood samples were obtained from the venous blood, which is used for routine analysis, and these samples were subjected to complete blood count. NLR was defined as the neutrophil count divided by the number of lymphocytes, and PLR was defined as the platelet count divided by the number of lymphocytes. RESULTS：No statistically significant difference was observed between the two groups under consideration in terms of demographic features（P〉0.05）. The average NLR in the patient group was found to be significantly higher than that in the healthy control group（P〈0.05）. The average PLR was significantly higher in the patient group as compared to the control group（P〈0.05）. As best corrected visual acuity（BCVA） increased, both NLR and PLR decreased（significant negative correlations at 49.8% and 63.0%, respectively）, whereas as central macular thickness（CMT） increased, both NLR and PLR increased（significant positive correlations at 59.3% and 70.0%, respectively）.CONCLUSION：NLR and PLR levels are higher among neovascular AMD patients as compared to healthy control group. NLR and PLR levels were found to be inversely proportional to BCVA and directly proportional to CMT.

New indicators in evaluation of hemolysis,elevated liver enzymes,and low platelet syndrome:A case-control study

BACKGROUND Indices such as the neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),mean platelet volume(MPV),platelet distribution width(PDW),and red cell distribution width(RDW)are considered new markers of the systemic inflammatory response(SIR),and have been widely implemented for the diagnosis of patients with inflammatory diseases.These new indicators have also been widely investigated in preeclampsia(PE)but less analyzed in hemolysis,elevated liver enzymes,and low platelet(HELLP)syndrome.AIM To compare SIR markers among HELLP patients,PE only patients,and healthy gravidae.METHODS This retrospective case-control study enrolled 630 cases,including 210 patients with HELLP syndrome(HELLP group),210 patients with only PE(PE group)and 210 healthy gravidae(control group).The three groups were matched by age,parity,status of assisted reproduction,and multiple pregnancies.Birthweight,gestational age at complete blood count collection,gestational age at delivery,mode of delivery,etc.were recorded.The main indices as NLR,PLR,MPV,PDW,and RDW among the groups were compared,as well as some secondary outcomes including neutrophil,platelets,and hemoglobin.RESULTS The NLR(6.4 vs 4.3 vs 3.5),MPV(11.9 vs 11.2 vs 10.7),PDW(16.4 vs 13.3 vs 14.2),leukocyte(12.4×10^(9)/L vs 9.7×10^(9)/L vs 8.7×10^(9)/L)and neutrophil count(9.9×10^(9)/L vs 7.3×10^(9)/L vs 6.1×10^(9)/L)were highest in the HELLP group,lower in the PE group,and lowest in the control group.Both the overall comparisons between the three groups(all bP<0.01)and pairwise comparisons between every two groups elicited statistically significant differences(all dP<0.01,except control vs PE:cP<0.05 in PDW).The average lymphocyte counts were 1.4(1.1,2.0)×10^(9)/L in the HELLP group,1.6(1.3,2.0)×10^(9)/L in the PE group and 1.7(1.4,2.0)×10^(9)/L in the control group.The overall comparison of lymphocyte count within the three groups had statistically significant differences(P=0.000).The pairwise comparisons between every two groups demonstrated that the HELLP group had a lower lymphocyte count than both the PE(P=0.019)and control groups(P=0.000),but the difference between the PE and control groups was not statistically significant(P=0.432).The overall comparisons on platelet counts and the PLR among these three groups also showed statistically significant differences(both P=0.000),from low to high being those in the HELLP group(43.4×10^(9)/L,64.0),control group(180.5×10^(9)/L,103.6)and PE group(181.5×10^(9)/L,112.8).Pairwise comparisons of neither index displayed statistically significant differences between the PE and control groups(both P>0.05),while the differences in the two indices between the HELLP group and the two other groups were still statistically significant(all P=0.000).RDW values were highest in the HELLP group(14.5%[13.6,15.3]),lower in the control group(14.1%[13.5,14.8])and lowest in the PE group(13.9%[13.4,14.9]).The difference between the PE and control group did not show statistical significance(P=1.000),while RDW values in the HELLP group were higher than those in the other two groups(cP<0.05 vs control,dP<0.01 vs PE).CONCLUSION SIR markers such as NLR,RDW,MPV,and PDW were increased and PLR was decreased in HELLP.These SIR markers may become new indicators in the evaluation of HELLP syndrome.

Neutrophile-to-lymphocyte,lymphocyte-to-monocyte,and platelet-tolymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer

BACKGROUND Perioperative fluorouracil plus leucovorin,oxaliplatin,and docetaxel(FLOT)improves prognosis in locally advanced gastric cancer(LAGC).Neutrophil-to-lymphocyte(NLR),lymphocyte-tomonocyte(LMR),and platelet-to-lymphocyte(PLR)ratios are prognostic biomarkers but not predictive factors.AIM To assess blood ratios’(NLR,LMR and PLR)potential predictive response to FLOT and survival outcomes in resectable LAGC patients.METHODS This was a multicentric retrospective study investigating the clinical potential of NLR,LMR,and PLR in resectable LAGC patients,treated with at least one preoperative FLOT cycle,from 12 Portuguese hospitals.Means were compared through non-parametric Mann-Whitney tests.Receiver operating characteristic curve analysis defined the cut-off values as:High PLR>141 for progression and>144 for mortality;high LMR>3.56 for T stage regression(TSR).Poisson and Cox regression models the calculated relative risks/hazard ratios,using NLR,pathologic complete response,TSR,and tumor regression grade(TRG)as independent variables,and overall survival(OS)as the dependent variable.RESULTS This study included 295 patients(mean age,63.7 years;59.7% males).NLR was correlated with survival time(r=0.143,P=0.014).PLR was associated with systemic progression during FLOT(P=0.022)and mortality(P=0.013),with high PLR patients having a 2.2-times higher risk of progression[95% confidence interval(CI):0.89-5.26]and 1.5-times higher risk of mortality(95%CI:0.92-2.55).LMR was associated with TSR,and high LMR patients had a 1.4-times higher risk of achieving TSR(95%CI:1.01-1.99).OS benefit was found with TSR(P=0.015)and partial/complete TRG(P<0.001).Patients without TSR and with no evidence of pathological response had 2.1-times(95%CI:1.14-3.96)and 2.8-times(95%CI:1.6-5)higher risk of death.CONCLUSION Higher NLR is correlated with longer survival time.High LMR patients have a higher risk of decreasing T stage,whereas high PLR patients have higher odds of progressing under FLOT and dying.Patients with TSR and a pathological response have better OS and lower risk of dying.

Predictive significance of cancer related-inflammatory markers in locally advanced rectal cancer

BACKGROUND Locally advanced rectal cancer is treated using neoadjuvant chemoradiation(nCRT),followed by total mesorectal excision(TME).Tumor regression and pathological post-treatment stage are prognostic for oncological outcomes.There is a significant correlation between markers representing cancer-related inflammation,including high neutrophil-to-lymphocyte ratio(NLR),monocyteto-lymphocyte ratio(MLR),and platelet-to-lymphocyte(MLR)and unfavorable oncological outcomes.However,the predictive role of these markers on the effect of chemoradiation is unknown.AIM To evaluate the predictive roles of NLR,MLR,and PLR in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiation.METHODS Patients(n=111)with locally advanced rectal cancer who underwent nCRT followed by TME at the Minimally Invasive Surgery Unit,Siriraj Hospital between 2012 and 2018 were retrospectively analyzed.The associations between post-treatment pathological stages,neoadjuvant rectal(NAR)score and the pretreatment ratios of markers of inflammation(NLR,MLR,and PLR)were analyzed.RESULTS Clinical stages determined using computed tomography,magnetic resonance imaging,or both were T4(n=16),T3(n=94),and T2(n=1).The NAR scores were categorized as high(score>16)in 23.4%,intermediate(score 8-16)in 41.4%,and low(score<8)in 35.2%.The mean values of the NLR,PLR,and MLR correlated with pathological tumor staging(ypT)and the NAR score.The values of NLR,PLR and MLR were higher in patients with advanced pathological stage and high NAR scores,but not statistically significant.CONCLUSION In patients with locally advanced rectal cancer,pretreatment NLR,MLR and PLR are higher in those with advanced pathological stage but the differences are not significantly different.

Postoperative Elevations of Neutrophil-to-lymphocyte and Platelet-to- lymphocyte Ratios Predict Postoperative Pulmonary Complications in Non-small Cell Lung Cancer Patients: A Retrospective Cohort Study

The neutrophil-to-lymphocyte ratio(NLR)and the platelet-to-lymphocyte ratio(PLR)are found to increase in patients who develop postoperative complications(PCs).The aim of the present study was to explore the association of the perioperative changes of NLR(ANLR)and PLR(OPLR)with PCs in non-small cell lung cancer(NSCLC).Clinical data of 509 patients,who were diagnosed with NSCLC and underwent thoracoscopic radical resection between January 1,2014 and July 31,2016 at the Department of Thoracic Surgery,West China Hospital,were reviewed.Patients were divided into PC and non-PC groups,and clinical characteristics including ANLR and APLR were compared between them.The optimal cut-off values of ONLR and APLR were determined by receiver operating characteristics(ROC)curves and patients were assigned to high ANLR/APLR and low ONLR/OPLR groups in terms of the cut-off values.Clinicopathologic characteristics and the incidence of different PCs were compared between the dichotomized groups.Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for PCs.The results showed that the ANLR and APLR in the PC group were significantly higher than those in the non-PC group(P<0.001 for both).The optimal cutoff values of ANLR and APLR were 6.6 and 49,respectively.Patients with ANLR>6.6 or 0PLR>49 were more likely to experience postoperative pulmonary complications(PPCs)(P<0.001 for both).Multivariate logistic regression analysis demonstrated that smoking[odds ratio(OR):2.450,95%confidence interval(95%CI):1.084--5.535,P=0.031)],tumor size(OR:1.225,95%CI:1.047-1.433,P=0.011),ANLR>6.6(OR:2.453,95%CI:1.2244.914,P-0.011)and APLR>49(OR:2.231,95%CI:1.182-4.212,P-0.013)were predictive of PPCs.In conclusion,the ONLR and APLR may act as novel predictors for PPCs in NSCLC patients undergoing thoracoscopic radical lung resection,and patients with ONLR>6.6 or APLR>49 should be treated more actively to prevent or reduce PPCs.

Nomogram based on inflammation-related markers for predicting survival of patients undergoing hepatectomy for hepatocellular carcinoma

BACKGROUND Previous nomograms for hepatocellular carcinoma(HCC)did not include the neutrophil-to-lymphocyte ratio(NLR)or platelet-to-lymphocyte ratio(PLR).This study aimed to establish an effective nomogram capable of estimating the association between preoperative inflammatory factors and overall survival(OS)of HCC patients after hepatectomy.AIM To analyse the factors affecting the prognosis of HCC and establish a nomogram.METHODS A total of 626 HCC patients(410 training set patients from the First Affiliated Hospital of Anhui Medical University and 216 validation set patients from the First Affiliated Hospital of University of Science and Technology of China)underwent hepatectomy from January 2014 to December 2017 and were followed up every 3–6 mo.The nomogram was based on OS-related independent risk factors identified by Cox regression analysis.The C-index,calibration curve,and area under the curve(AUC)were used to evaluate the nomogram’s accuracy.RESULTS The 1-,2-and 3-year OS rates were 79.0%,68.0%and 45.4%in the training cohort(median OS=34 mo)and 92.1%,73.9%and 51.2%in the validation cohort(median OS=38 mo).Higherα-fetoprotein[hazard ratio(HR)=1.812,95%confidence interval(CI):1.343–2.444],NLR(HR=2.480,95%CI:1.856–3.312)and PLR(HR=1.974,95%CI:1.490–2.616),tumour size≥5 cm(HR=1.323,95%CI:1.002–1.747),and poor differentiation(HR=3.207,95%CI:1.944–5.290)were significantly associated with shortened OS.The developed nomogram integrating these variables showed good reliability in both the training(C-index=0.71)and validation cohorts(C-index=0.75).For predicting 1-,2-and 3-year OS,the nomogram had AUCs of 0.781,0.743 and 0.706 in the training cohort and 0.789,0.815 and 0.813 in the validation cohort.The nomogram was more accurate in predicting prognosis than the AJCC TNM staging system.CONCLUSION The prognostic nomogram combining pathological characteristics and inflammation indicators could provide a more accurate individualized risk estimate for the OS of HCC patients with hepatectomy.

Tumor-infiltrating platelets predict postoperative recurrence and survival in resectable pancreatic neuroendocrine tumor

BACKGROUND Platelets have been reported to participate in tumor cell growth,extravasation,epithelial–mesenchymal transition,metastasis,and drug resistance.However,the importance of platelets in pancreatic neuroendocrine tumor(pNET)lacks adequate literature support.The predictive value of tumor-infiltrating platelets(TIPs)in pNET remains unclear.AIM To investigate the relationship between TIPs and the prognosis of patients with pNET following radical resection.METHODS In total,113 patients who had undergone radical surgical resection with a pathologic diagnosis of pNET were enrolled in this study.Immunohistochemical analysis of cluster of differentiation 42b(CD42b)expression in the tumor specimens was performed to determine the presence of TIPs.Univariate and multivariate analyses were used to analyze the prognostic value of TIPs.RESULTS TIPs were observed in intratumoral areas in 54 patients.Neither basic characteristics nor preoperative platelet-associated indicators showed a significant relationship with the presence of TIPs(all P>0.05).Patients with positive intratumoral CD42b expression had worse overall survival(P=0.005)and recurrence-free survival(P<0.001)than those with negative intratumoral CD42b expression.Multivariate analysis demonstrated that TIPs were independent prognostic factors for overall survival(P=0.049)and recurrencefree survival(P=0.003).Nevertheless,platelet count,mean platelet volume,and platelet-to-lymphocyte ratio were not associated with postoperative survival or recurrence in pNET patients(all P>0.05).CONCLUSION TIPs are a useful prognostic biomarker for patients with resectable pNET,and their detection represents a promising tool for pNET treatment strategy decisions.