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Continuous monitoring of neutrophils to lymphocytes ratio for estimating the onset, severity, and subsequent prognosis of immune related adverse events.

ABSTRACT: Immune checkpoint inhibitors (ICIs) play a central role in various cancers. ICIs can cause immune-related adverse events (irAEs). As severe irAEs can be life-threatening, biomarkers for estimating irAE onset are crucial. The neutrophils-to-lymphocytes ratio (NLR) reflects the systemic immune condition and known as a prognostic marker in ICI treatment. Our study evaluated if the NLR corresponded with irAEs, and its feasibility as a biomarker for irAE onset. We retrospectively analyzed 275 cancer patients treated with anti-PD-1 monotherapy. We observed 166 irAEs in 121 patients. The NLR was significantly elevated during irAEs. Patients experiencing interstitial pneumonitis showed NLR elevation 4 weeks before initial symptoms and diagnosis. Analyzing receiver operating characteristics curves revealed that elevated NLR distinguished subsequent pneumonitis severity with high accuracy (AUC 0.93, sensitivity 88.9%, specificity 88.2%, cut-off 2.37, p?=?0.0004). After a severe irAE occurred, two NLR trends were observed. Patients who showed a prompt reduction in elevated NLRs had favorable progression-free survival (hazard ratio 0.32, 95% CI 0.10-1.01, p?=?0.0140) and overall survival (hazard ratio 0.23, 95% CI 0.06-0.86, p?=?0.0057) compared to the patients who maintained elevated NLRs. These findings suggest that continuous monitoring of NLR trends may predict irAE onset and severity and subsequent prognosis.

SUBMITTER: Matsukane R

PROVIDER: S-EPMC7809015 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Continuous monitoring of neutrophils to lymphocytes ratio for estimating the onset, severity, and subsequent prognosis of immune related adverse events.

Matsukane Ryosuke R Watanabe Hiroyuki H Minami Haruna H Hata Kojiro K Suetsugu Kimitaka K Tsuji Toshikazu T Masuda Satohiro S Okamoto Isamu I Nakagawa Takashi T Ito Takamichi T Eto Masatoshi M Mori Masaki M Nakanishi Yoichi Y Egashira Nobuaki N

Scientific reports 20210114 1

Immune checkpoint inhibitors (ICIs) play a central role in various cancers. ICIs can cause immune-related adverse events (irAEs). As severe irAEs can be life-threatening, biomarkers for estimating irAE onset are crucial. The neutrophils-to-lymphocytes ratio (NLR) reflects the systemic immune condition and known as a prognostic marker in ICI treatment. Our study evaluated if the NLR corresponded with irAEs, and its feasibility as a biomarker for irAE onset. We retrospectively analyzed 275 cancer ...[more]

PMID: 33446685

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Project description:BackgroundNeutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are both inflammatory ratios that can be easily calculated from a simple blood count. They are frequently reported and tested as prognostic factors in several medical disciplines. Pregnancy involves special reference values for laboratory assays.ObjectiveThe aim of this study was to define pregnancy-related reference values for NLR and PLR according to trimester, background morbidity and according to the patient's age.Study designA retrospective analysis of a large cohort undergoing community-based pregnancy surveillance between the years 2011-2016. Data were analyzed according to high-risk patient versus normal-risk patient.ResultsA total of 11,415 patients were included. Mean PLR and NLR values were 136.3±44.3, 2.6±1, respectively during the first trimester, 144.6±47.1, 4.0±1.4 respectively during the second trimester and 118.1±42.0, 3.5±1.2 respectively during the third trimester. No difference was detected between the high-risk and the normal population (P-values 0.3, 0.5 and 0.4 for PLR in each trimester respectively and 0.3, 0.4, 0.6 for NLR in each trimester, respectively). No differences were detected among parity categories. The correlation between patient's age and either PLR and NLR was a weak positive correlation (though statistically significant). Both PLR and NLR reached a maximum value during the second trimester. The differences between mean NLR and PLR between trimesters were significant (P <0.01 for all differences tested). PLR rises in the presence of anemia, reaching statistical significance (P-value for PLR in each trimester was <0.01). NLR showed an opposite trend (P-values for NLR were 0.4, 0.005 and 0.06 in each trimester, respectively).ConclusionsIn our cohort, there were generally no differences between the high-risk and the normal population, excluding patients with a fibroid uterus or inflammatory bowel disease who presented a significantly elevated PLR through all trimesters. Both PLR and NLR reached a maximum value during the second trimester and were positively correlated with age. We anticipate that the population-based data will assist in providing accurate reference values for future research testing NLR and PLR measures during pregnancy.

Project description:BackgroundLipid and inflammatory molecules play a key role in the development of inflammation. Neutrophil counts are used as markers of inflammation duration, and HDL-C is used as an anti-atherosclerosis component. However, few studies have been found to integrate these two indicators to explore coronary stenosis. We suggested that neutrophil count as a marker of inflammation persistence and HDL-C as an anti-atherosclerotic component should be integrated into a single biomarker NHR to explore its correlation with CAD degree and predict the severity of coronary stenosis among CAD patients.MethodsWe examined 404 eligible patients who underwent coronary angiography. Based on the results of coronary angiography, patients in CAD+ group (n = 155) were defined as those having angiographic coronary stenosis of at least 50% lumen reduction in at least one major coronary artery (including left anterior descending artery, left circumflex artery, left main coronary artery, right coronary artery). Patients with luminal stenosis but no more than 50% were defined as CAD- group (n = 49), and patients without luminal stenosis (n = 200) were regarded as control group. The relationship between various serum markers and the severity of coronary stenosis was examined by Spearman correlation analysis. Logistic regression analysis was performed to identify the influencing factors of the severity of coronary artery disease.ResultsThe modified Gensini score was positively correlated with neutrophil HDL-C ratio and negatively correlated with albumin and HDL-C. Multiple regression analysis showed that neutrophil HDL-C ratio were significantly associated with CAD. Neutrophil HDL-C ratio is an independent predictor of CAD. The ROC analysis provided a cut-off value of 1.51 for neutrophil HDL-C ratio to predict CAD with 94.8% sensitivity and 0.024 Yoden index, and area under the ROC curve of 0.617 (95% CI 0.560-0.675, P < 0.001).ConclusionNeutrophil HDL-C ratio is not only closely related to coronary artery stenosis, but also an independent predictor of severe coronary stenosis.

Project description:BackgroundAcute kidney injury (AKI) is a frequent consequence of sepsis and has been linked to poor prognosis. In critically ill patients, the ratio of neutrophils to lymphocytes and platelets (N/LP) has been confirmed as an inflammation-related marker connected with the development of renal dysfunction. However, the effect of the N/LP ratio on the initiation and development of AKI in patients with sepsis remained unclear. The purpose of this study was to determine if the N/LP ratio on intensive care unit (ICU) admission was associated with the occurrence of sepsis-associated AKI (S-AKI) and severe AKI.MethodsAdult septic patients from the Medical Information Mart for Intensive Care-IV database were screened and classified into three categories (low, middle, or high) based on their N/LP ratio quartiles. The Cox proportional hazard and competing risk models were used to determine the risk of S-AKI in various N/LP groups, whilst the logistic regression model and restricted cubic splines (RCS) analysis were employed to investigate the link between N/LP ratios and the occurrence of severe AKI. Finally, we did a doubly robust estimation, a subgroup analysis, and a sensitivity analysis to determine the findings' robustness.ResultsWe categorized 485, 968, and 485 septic patients into three groups based on their N/LP ratios: low, intermediate, and high. According the Cox proportional hazard model, the hazard rate (95% CI) for those in the middle and high N/LP groups on the incidence of S-AKI were 1.30(1.07, 1.58) and 1.27(1.02, 1.59), respectively, as compared to those in the low N/LP group. And the Fine-Gray proportional subdistribution hazards model indicated that mortality was not a substantial competing risk for S-AKI. Additionally, multivariate logistic regression revealed that the risk of severe AKI increased 1.83 fold in the high group compared to the low group. The RCS result also suggested that the probability of severe AKI rose significantly when N/LP > 9.5. The consistency of these findings was confirmed using doubly robust estimation. However, subgroup and sensitivity analyses revealed that the association between N/LP and the incidence of S-AKI, severe AKI varied considerably between different populations and diagnostic criteria.ConclusionA raised initial N/LP level may induce the development of S-AKI and severe AKI within 7 days after ICU admission in septic patients. These influences were enhanced in elder, male, septic shock, and those with poor health condition. Furthermore, high NLP was more strongly connected to the risk of S-AKI and severe AKI in sepsis patients on the urine output-based AKI criteria than on the serum creatinine-based criteria.

Project description:BackgroundCurrent adverse event reporting practices do not document longitudinal characteristics of adverse effects, and alternative methods are not easily interpretable and have not been employed by clinical trials. Introducing time parameters in the evaluation of safety that are comprehensive yet easily interpretable could allow for a better understanding of treatment quality. In this study, we developed and applied a novel adverse event reporting method based on longitudinal adverse event changes to aid describing, summarizing, and presenting adverse event profile. We termed it the "Adverse Event Load, Onset, and Maximum Grade" method.MethodsWe developed two adverse event summary metrics to complement the traditional maximum grade report. Onset time indicates the time period in which the maximum grade for a specific adverse event occurred and was defined as "early" (i.e. maximum grade happened for the first time before 6 weeks) or "late" (i.e. after the 6th week). Adverse event load indicates the overall severity of a specific adverse event over the entire treatment. Higher adverse event load indicates a worse overall experience. These metrics can be calculated for adverse events with different maximum grades, in treatments with planned changes (e.g. dosage changes), using data sets with different number of adverse event data points between treatments (e.g. treatments with longer cycle lengths may have less adverse event data points) and on data sets with different adverse event data availability (e.g. cycle basis and patient-outcome reports). We tested the utility of this method using individual patient data from two major backbone therapies ("Irinotecan" and "Oxaliplatin") from the N9741 trial available in the Fondation ARCAD database (fondationarcad.org). We investigated profiles of diarrhea, neutropenia/leukopenia, and nausea/vomiting.ResultsOur method provided additional information compared to traditional adverse event reports. For example, for nausea/vomiting, while patients in Irinotecan had a higher risk of experiencing maximum grade 3-4 (15.6% vs 7.6%, respectively; p < 0.001), patients in both groups experienced similar severity over time (adverse effect load = 0.102 and 0.096, respectively; p = 0.26), suggesting that patients in Oxaliplatin experienced a lower-grade but more persistent nausea/vomiting. For neutropenia/leukopenia, more patients in Irinotecan experienced their maximum grade for the first time early in the treatment compared to patients in Oxaliplatin (67.9% vs 41.7%; p < 0.001), regardless of maximum grade. Longitudinal information can help compare treatments or guide clinicians on choosing appropriate interventions for low-grade but persistent adverse event or early adverse event onset.ConclusionWe developed an adverse event reporting method that provides clinically relevant information about treatment toxicity by incorporating two longitudinal adverse event metrics to the traditional maximum grade approach. Future research should establish clinical benchmarks for metrics included in this adverse event reporting method.

Dataset Information

Continuous monitoring of neutrophils to lymphocytes ratio for estimating the onset, severity, and subsequent prognosis of immune related adverse events.

Publications

Continuous monitoring of neutrophils to lymphocytes ratio for estimating the onset, severity, and subsequent prognosis of immune related adverse events.

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