Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

The Prognostic Significance of the Preoperative Platelet-Lymphocyte Ratio in Japanese Patients with Localized Breast Cancer

Inflammation has been shown to be a factor in tumorigenesis. The circulating platelet to lymphocyte ratio (PLR) is a representative index of systemic inflammation. In this study, we analyzed the association between preoperative PLR levels and clinicopathological variables in two hundred sixty-four Japanese patients with localized breast carcinoma. We also evaluated the prognostic significance of preoperative PLR levels using the Cox proportional hazard model. Seventy-five patients (28.4%) had elevated PLR values, whereas 189 (71.6%) had depressed PLR values. The PLR correlated significantly with venous invasion (P < 0.05). Disease-free survival rates were significantly worse among patients with elevated PLR values than among those with lower PLR value (5-year survival, 81.6% vs. 90.7%, respectively;P < 0.05). In multivariate analysis, elevated PLR, nuclear grade, and lymph node involvement were significant prognostic factors for disease-free survival in patients with breast carcinoma (P < 0.05). Preoperative PLR levels may be an independent prognostic factor in patients with breast carcinoma.

Significances of Peripheral Inflammatory Cells and Neutrophil/Platelet-Lymphocyte Ratio in Breast Cancer after Resection

Introduction: Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) from our routine practice for the predictor of prognosis of breast cancer after resection. Patients and Methods: There were 574 breast cancer patients accepted surgical resection and registered in Cancer Registry Center of our hospital. Patient’s basic profiles, peripheral neutophil, lymphocyte and platelet count were measured for study. The scales of NLR and PLR were derived from the lower and higher normal range in cell count from neutrophil, lymphocyte and platelet respectively. Therefore, the scales for NLR and PLR were ≤1.62, 1.63 - 2.57, ≥2.58 and ≤224, 225 - 253, ≥254 respectively for analysis. Results: Poor 5-yr survival rate was found if higher cell counts of neutrophil and platelet (p ≤ 0.05). Three scales of NLR were ≤1.62, 1.63 - 2.57, ≥2.58, and their 5-year survival rates were 94%, 91% and 84% respectively (p = 0.019). In the subgroup of HER-2 (negative), and 3-Negative breast patients had a higher NLR of poor prognosis. But higher PLR was found less in 3-Negative and non in 3-Positive patients (p = 0.039). The PLR was ≤224, 225 - 253, ≥254 and their 5-year survival rates were 92%, 87%, and 64% respectively (p = 0.001);Multivariate Cox regression model for predictor of breast cancer patients who have 3.39 (PLR ≥ 254) and 2.45 (NLR ≥ 2.58 ) times risk (p = 0.02 and p = 0.002) of poor prognosis respectively. Conclusion: Peripheral inflammatory cell counts are easily to take in our clinical practice and have a potential role as predictors of prognosis. We have to pay attention to the trends of peripheral inflammatory cell count and their ratio in our clinical practice where possible.

Short-term impacts of air pollution on the platelet-lymphocyte ratio and neutrophil-lymphocyte ratio among urban adults in China

The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure.In this study,we included 3487 urban adults from the Wuhan-Zhuhai cohort.Individual inhalation exposure to air pollutants was estimated by combining participants’daily breath volume and ambient concentrations of six air pollutants (includingfine particulate matter (PM_(2.5)),inhalable particulate matter(PM_(10)),nitrogen dioxide (NO_(2)),sulfur dioxide (SO_(2)),carbon monoxide (CO) and ozone (O_(3))).The cumulative impacts were assessed by applying lag structures of up to 7 days before the survey date.Associations of air pollutants with PLR and NLR were assessed using a linear mixed model and Bayesian kernel machine regression (BKMR) model.We found that PLR was negatively related to PM_(2.5)(lag02-lag06),PM_(10)(lag02-lag07),NO_(2)(lag02-lag07),and SO_(2)(lag03-lag05) and NLR was negatively related to PM_(10)(lag05 and lag07).In the BKMR model,a negative joint association between the six-air-pollutant mixture and PLR and NLR was observed,whereas PM_(10)and NO_(2)appeared to be more important than the other pollutants in the mixture.The negative impact of air pollutants was stronger in males,participants with lower body mass index (<24 kg/m^(2)),those cooking meals at home,drinkers,and nonexercisers.In conclusion,short-term exposure to air pollutants is significantly related to PLR and NLR in peripheral blood.PLR and NLR may provide new insight into the molecular mechanism underlying the adverse health impact of air pollutants.

结合术前中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值构建喉恶性肿瘤进展风险的列线图模型

目的探究术前血小板与淋巴细胞比值(platelet-lymphocyte ratio,PLR)及中性粒细胞与淋巴细胞比值(neutrophil-lymphocyte ratio,NLR)在预测喉癌恶性肿瘤程度的价值并构建列线图模型进行验证。方法回顾性分析2016年1月~2022年6月在宁波市医疗中心李惠利医院接受喉部手术的339例患者临床、组织病理学和实验室资料,分为喉部良性病变组(n=113)、喉部癌前病变组(n=105)和喉恶性肿瘤(n=121)组,研究三组患者通过单因素分析和多因素Logistic回归分析研究喉部恶性病变的相关影响因素,采用R软件构建预测喉癌恶性肿瘤进展风险的列线图模型并进行内部验证。结果单因素分析显示年龄>60岁、吸烟、高PLR及高NLR与喉部病变程度有关(P<0.05)。多因素Logistic回归分析显示年龄>60岁、吸烟、高PLR及高NLR是喉部恶性病变的独立影响因素(P<0.05)。列线图模型C-index=0.809,95%CI=0.733、0.885,P<0.05,该列线图模型具有很强的预测能力。结论术前NLR、PLR、血小板分布宽度(PDW)是影响喉部恶性病变的因素,其中NLR高水平、PLR高水平在用于构建预测喉恶性肿瘤进展的列线图模型上准确性较强,有效的运用此模型可助于临床医师通过预测喉恶性肿瘤趋势为患者提供及时有效的用于早期筛查和疾病诊断的个性化方案。

Prognostic value of platelet-to-lymphocyte ratio in upper tract urothelial carcinoma patients treated with radical nephroureterectomy:A metaanalysis

Objective:To evaluate the prognostic value of platelet-to-lymphocyte ratio(PLR)in upper tract urothelial carcinoma(UTUC)patients treated with radical nephroureterectomy.Methods:This study was pre-registered in PROSPERO(No.CRD42020186645).Two reviewers independently performed a comprehensive literature search on PubMed,Web of Science,EMBASE,Cochrane Library databases,China Biology Medicine disc(CBM),Wanfang database,and China National Knowledge Infrastructure(CNKI)from inception to May 2021 for prospective or retrospective cohort studies evaluating the prognostic value of PLR.Literature was analyzed with inclusion and exclusion criteria.Data and other useful clinicopathological features were extracted and analyzed with fixed or random-effect models when applicable.Heterogeneity was assessed on the basis of Cochran’s Q test and I2 statistic.Publication bias was assessed with funnel plots and precisely assessed by Egger's tests.Results:A total of ten studies involving 3287 UTUC patients were included.Meta-analysis showed that elevated preoperative PLR was associated with worse overall survival(HR=1.51,95%CI 1.17-1.94,P=0.001),cancer specific survival(HR=1.52,95%CI 1.21-1.90,P<0.001),disease free survival(HR=1.32,95%CI 1.12-1.56,P=0.001),and progression free survival(HR=1.88,95%CI 1.41-2.52,P<0.001).Furthermore,the sensitivity analyses validated the stability and reliability of the results.Conclusion:The present meta-analysis demonstrates a significant association between elevated preoperative PLR and poor prognosis of UTUC patients treated with radical nephroureterectomy.Hence,PLR could be helpful as a potential prognostic biomarker to guide clinical decision-making and select individualized treatment strategies for UTUC patients.However,more prospective and large-scale trials are needed to provide more evidence.

Novel immunological and nutritional-based prognostic index for gastric cancer

AIM: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index(PNI), neutrophillymphocyte ratio(NLR), and platelet-lymphocyte ratio in gastric cancer.METHODS: We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate.Univariate and multivariate analyses were performed to identify risk factors for overall survival(OS). Propensity score analysis was performed to adjust variables to control for selection bias.RESULTS: Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring(hazard ratio, 1.668; 95% confidence interval:1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage Ⅱ-Ⅲ disease(P = 0.019, P < 0.001), T3-T4 tumors(P <0.001), or lymph node metastasis(P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS(P = 0.022, P = 0.030, P < 0.001, and P = 0.024,respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively.CONCLUSION: PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.

The relationship of blood cell-associated inflammatory indices and diabetic retinopathy: a Meta-analysis and systematic review

AIM: To explore the correlation between several blood cell-associated inflammatory indices including mean platelet volume(MPV), platelet distribution width(PDW), neutrophil to lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR), and the presence and severity of diabetic retinopathy(DR). METHODS: We searched for eligible studies from PubMed, EMBASE, Web of Science and CNKI up to December 13, 2017. Standardized mean difference(SMD) calculated with confidence interval(CI) of 95% was used to estimate the values of those indices. RESULTS: A total of 31 studies were included in the present Meta-analysis. As compared with type 2 diabetes mellitus(T2 DM) patients without DR, the values of MPV, PDW, NLR, and PLR were higher in patients with DR(SMD=0.67; 95%CI: 0.36 to 0.98; SMD=0.51; 95%CI: 0.27 to 0.75; SMD=0.77; 95%CI: 0.49 to 1.05 and SMD=1.18; 95%CI: 0.07 to 2.28). Additionally, it was also observed that MPV was closely correlated with the severity of DR. CONCLUSION: MPV, PDW, NLR, and PLR could be recommended as diagnostic biomarkers for DR, and MPV could be applied to assess the severity of DR.

Inflammation-related indicators to distinguish between gastric stromal tumors and leiomyomas:A retrospective study

BACKGROUND Gastric leiomyomas and gastric stromal tumors are the most common types of gastric tumors encountered.In recent years,the incidence of the two types of tumors has been increasing,but the differential diagnosis is still a challenge in clinical work.However,as there are many reports on stromal tumors and inflammation-related indicators are gradually being paid attention to as important factors in predicting tumor prognosis,the two main purposes of this study were to explore the inflammation-related differences between the two types of tumors and to develop a nomogram as a predictive model.AIM To explore the differences in platelet-lymphocyte ratio(PLR),neutrophillymphocyte ratio(NLR),lymphocyte mononuclear cell ratio(LMR),and SII between the two types of tumors,and simultaneously create the nomogram model.METHODS This study enrolled 88 patients in the gastric stromal tumor group and 56 patients in the gastric leiomyoma group,and the relevant data of the two groups were entered into the system for an integrated analysis.The primary objective of this study was to identify the differences in the inflammation index between the two types of tumors.RESULTS There were statistically significant differences between the two groups in sex,age,and tumor location.In comparison,gastric leiomyomas seem to be more common in women,young patients,and gastric cardia,which is in line with our previous research;the groups showed the following statistical differences:PLR(158.2%vs 134.3%,P=0.028),NLR(2.35 vs 1.68,P=0.000),LMR(5.75 vs 10.8,P=0.004),and SII(546.2 vs 384.3,P=0.003).The results of the multivariate logistic regression analysis showed that sex,age,tumor location,and LMR were independent risk factors for the identification of the two types of tumors.After considering the risk factors selected by the above analysis into the predictive model,a predictive model for distinguishing gastrointestinal stromal tumors from gastric leiomyomas was established as the nomogram.CONCLUSION Gastric leiomyomas and gastric stromal tumors are not only different in factors such as age of the patient,but also in inflammatory indicators such as LMR and PLR.We have established a predictive model related to the laboratory indicators and are looking forward to further research conducted in this clinical area.

Validation of novel Japanese indication criteria and biomarkers among living donor liver transplantation recipients with hepatocellular carcinoma - a single center retrospective study

Aim:To validate a novel Japanese indication criteria for liver transplantation(LT)for hepatocellular carcinoma(HCC),i.e.,the 5-5-500 criteria(nodule size≤5 cm in diameter,nodule number≤5,and alfa-fetoprotein(AFP)value≤500 ng/mL)and the Japanese double eligibility criteria(DEC)(patients meeting the Milan or the 5-5-500 criteria)in the University of Tokyo cohort.The usefulness of biomarkers in predicting the recurrence of HCC was also verified.Methods:The overall survival and recurrence rates of patients meeting the Milan,5-5-500,and the Japanese DEC were compared among 153 patients who underwent living donor LT(LDLT)between 1996 and 2019.A receiver-operating characteristics curve analysis was conducted to evaluate the usefulness of AFP,lens culinaris agglutinin-reactive fraction of AFP,des-gamma-carboxy prothrombin,neutrophil-lymphocyte ratio,and the platelet-lymphocyte ratio to detect recurrence.Results:The 5-year recurrence rate for all patients,those meeting the Japanese DEC,5-5-500 criteria,and the Milan criteria was 10.9%,9.2%,7.4%,and 7.6%,respectively.Compared with the conventional Milan criteria,the 5-5-500 criteria and the Japanese DEC could increase the number of eligible LDLT candidates by 6.1%and 11.4%.Among five biomarkers,the area under the curve value of AFP was the highest(0.852).Conclusion:The results suggest that the 5-5-500 criteria and the Japanese DEC are the appropriate selection criteria for patients with HCC in LDLT.Among five biomarkers investigated,AFP was most reliable to predict HCC recurrence,which justified the utilization of AFP in the 5-5-500 criteria and the Japanese DEC.

Hemogram Parameters in Fibromyalgia and Effects of Wet Cupping Therapy on Hemogram Parameters

Objective:Wet cupping therapy(WCT)is one of the complementary and traditional therapies that are still must be scientifically interpreted.This study aimed to assess hemogram parameters that are subclinical inflammatory markers in patients with fibromyalgia syndrome(FMS)and observe how they were affected with WCT.Methods:The present study consisted of two groups;patient group included participants who were diagnosed with FMS and who received WCT and control group included healthy participants who received WCT within the concept of preventive medicine.Results:Neutrophil-to-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)values were higher in the patient group(P=0.029and P=0.003,respectively).Considering that the participants had FMS,the optimal cutoff value for PLR was≥1.62,sensitivity was 70%,specificity was 56%,positive predictive value was 61.7%,and negative predictive value was 65.3%.Receiver operating characteristic(ROC)curve revealed a significant sensitivity and specificity(ROC area=0.664),(confidence interval[CI]:0.530–0.781)(P<0.023).The optimal cutoff value for PLR was≥146,sensitivity was 60%,specificity was 83%,positive predictive value was 78%,and negative predictive value was 67%.ROC curve revealed a statistically significant sensitivity and specificity(ROC area=0.726),(CI:0.59–0.83)(P<0.001).The optimal cutoff value for platelet was≥284,000,sensitivity was 83%,specificity was 40%,positive predictive value was 58%,and negative predictive value was 70%.ROC curve revealed a significant sensitivity and specificity(ROC area=0.65),(CI:0.51–0.76)(P=0.036).Conclusion:NLR,PLR,and thrombocyte count parameters can be useful in the process of diagnosing FMS.In addition,NLR,PLR,and MPV decreased in patients who received WCT.