Availability of Circulating microRNAs As a Biomarker for the Early Diagnosis of Diffuse Large B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2988-2988 ◽  
Author(s):  
Katsushige Inada ◽  
Yasushi Okoshi ◽  
Yukiko Cho ◽  
Hitoaki Saito ◽  
Tatsuo Iijima ◽  
...  

Abstract Introduction: MicroRNA (miRNA) is a class of non-coding small RNA (~22 nucleotides), which regulates post-transcriptional gene expression through binding to complementary sites of target messenger RNA. Recent studies have revealed that miRNA plays important roles in oncogenesis mainly by regulating oncogenes or tumor suppressor genes. As miRNA exists not only within cells but also in peripheral blood, circulating miRNA can be an easily obtainable cancer biomarker. Furthermore, circulating miRNA, which exists within exosomes or as a complex with particular proteins such as argonaute2, is a suitable and convenient sample for handling because of its stability. Based on these findings, this study planned to pursue the possibility that circulating miRNA could be used for the early diagnosis of diffuse large B-cell lymphoma (DLBCL). Materials and Methods: This study was performed with the permission of our IRB. Expression levels of mature miRNA (both the 5p and 3p strands) were evaluated using different types of materials, namely serum, exosome-enriched serum, and formalin-fixed paraffin-embedded (FFPE) tissue. Serum samples were obtained from patients with newly diagnosed DLBCL (n=33) or healthy volunteers (n=22) at our institution between 2012 and 2014. The exosome-enriched samples were obtained from serum using a total exosome isolation reagent (Invitrogen, CA). The FFPE biopsy samples were obtained from DLBCL lesions, mainly from lymph nodes (n=22), or from reactive hyperplastic lymph nodes (n=6). Based on the results of previous reports, ten miRNAs (the 5p and 3p strands of miR-15a, miR-21, miR-155, miR-181a, and miR-210) were selected as candidate biomarkers. Expression levels of miRNA were analyzed by the quantitative Real-Time PCR method, and were normalized to hsa-miR-24-3p. Diagnostic accuracy was evaluated using receiver operating characteristics (ROC) curve analysis. Results and Discussion: In serum samples, the expression levels of hsa-miR-15a-3p, hsa-miR-21-5p, hsa-miR-181a-5p, and hsa-miR-210-5p were significantly different between DLBCL patients and healthy volunteers (p<0.05). ROC curve analysis revealed that hsa-miR-15a-3p and hsa-miR-21-5p were valuable biomarkers for differentiating patients with DLBCL from healthy volunteers with an area under the ROC curve (AUC) of 0.676 (p=0.029) and 0.711 (p=0.009), respectively. However, substantial percentages of false-positive and false-negative samples were also observed. To improve diagnostic accuracy, we next analyzed the expression levels of miRNAs in exosome-enriched serum samples. Among the candidate miRNAs, expression levels of hsa-miR-15a-3p, hsa-miR-21-5p, and hsa-miR-181a-5p were significantly different between DLBCL and healthy volunteer in exosome-enriched serum samples (p<0.05). ROC curve analysis revealed that hsa-miR-15a-3p, hsa-miR-21-5p, and hsa-miR-181a-5p were valuable biomarkers with AUCs of 0.714 (p=0.033), 0.779 (p=0.001), and 0.672 (p=0.047), respectively. Contrary to these results, expression levels of these miRNAs in FFPE were not significantly different between DLBCL and reactive lymph nodes. We thus consider that some miRNAs in serum or exosome-enriched serum might be useful in the differential diagnosis of DLBCL. These miRNAs seem to be produced outside of the lymphoma tissue. To use miRNAs as an accurate and sensitive diagnostic biomarker, it is necessary to first identify lymphoma cell-derived miRNA in blood. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 209-209
Author(s):  
Izumi Ohno ◽  
Shuichi Mitsunaga ◽  
Motoyasu Kan ◽  
Masafumi Ikeda ◽  
Hironobu Tsubouchi ◽  
...  

209 Background: There is a clear need to identify a non-invasive biomarker for early diagnosis of PaCa, in order to improve the overall survival of PaCa patients. Secretion of large amounts of proteases is a hallmark of PaCa, which results in an abundance of protease-induced cleavage products being excreted in the urine. This has led to speculation that measurement of PaCa-specific fragments in the urine might be useful as a tool for discrimination between PaCa patients and healthy controls. Herein, we introduce urinary KNG fragments as a promising biomarker for early diagnosis of PaCa. Methods: Urine samples were collected from PaCa patients and healthy volunteers, with the written informed consent, from January 2014 to July 2016. Urinary protein tryptic fragments derived from protein C-termini were measured using isobaric tags (iTRAQ) for their relative quantitation, and the diagnostic ability of the urinary levels of these fragments was evaluated by receiver operating characteristic (ROC) curve analysis. The fragments which showed an area-under-the-curve (AUC) of over 0.8 were selected as candidate fragments for further validation by the multiple-reaction-monitoring technique (MRM) combined with high-speed liquid chromatography. The urinary level of each candidate fragment was quantified by MRM, and the diagnostic capability of each for discriminating PaCa patients from healthy controls was evaluated by ROC curve analysis. Results: Urine samples of 39 PaCa patients (7 resectable, 32 unresectable) and 42 healthy controls were examined by iTRAQ to find 12,783 fragments. ROC curve analysis was carried out to select two candidate fragments (fragments A, B), both of which turned out to be KNG cleavage products. The urinary levels of the two fragments were measured in 23 resectable PaCa, 118 unresectable PaCa patients, and 42 healthy volunteers using high-speed-LC-/MRM. The AUCs of serum CA19-9 and urinary levels of fragments A and B for discriminating patients of PaCa from healthy controls were 0.89, 0.81 and 0.70, respectively. Conclusions: Urinary KNG fragments showed favorable diagnostic capability and were considered as promising, noninvasively measurable biomarkers of PaCa.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5104-5104
Author(s):  
Chikako Ohwada ◽  
Takeharu Kawaguchi ◽  
Naomi Shimizu ◽  
Masahiro Takeuchi ◽  
Emiko Sakaida ◽  
...  

Abstract Abstract 5104 Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of malignant lymphoma, characterized by the selective growth of lymphoma cells within the lumina of vessels in various organs. Although recent reports showed that prompt and accurate diagnosis lead to better outcomes, absence of typical clinical manifestations and its aggressive behavior frequently makes it difficult. LR11 (also called SorLA or SORL1) is a type I membrane protein, from which a soluble form (sLR11) is released by proteolytic shedding. sLR11 is originally known to be a biomarker of carotid intima-media thickness. We have recently found that LR11 is expressed on human leukemia cell lines, and sLR11 is released in its culture medium. Serum sLR11 levels are significantly elevated in patient serum samples with acute leukemia and B cell lymphomas, and are associated with tumor burden and bone marrow invasion. Based on these findings, we hypothesized that LR11 may be also expressed and released from IVLBCL cells; therefore we evaluated its clinical importance in IVLBCL. Materials and methods: Serum samples and paraffin embedded tumor specimens were obtained from 6 patients who were histologically diagnosed as IVLBCL from 2009 to 2012. Specimens were subjected to immunostaining using anti-LR11 antibody, and serum sLR11 levels were measured by ELISA method. Patient laboratory and clinical data were collected retrospectively. Also, serum samples from 75 healthy volunteers, and 10 patients with collagen diseases presenting similar clinical manifestations as IVLBCL were analyzed. Results: Tissue samples of IVLBCL were obtained by bone marrow biopsy (N=2), transbronchial lung biopsy (N=2), and random skin biopsy (N=2). Biopsy specimens showed that cytoplasm of IVLBCL cells were specifically immunoreacted against the anti-LR11 antibody (Figure 1). Median serum sLR11 level of IVLBCL patients was 86. 0 ng/ml (mean ± SD: 201. 8 ± 260. 0 ng/ml), which was significantly elevated than those of healthy volunteers (median: 8. 4 ng/ml, mean±SD: 8. 8 ± 1. 8 ng/ml, p<0. 0001) and patients with collagen diseases (median: 14. 4 ng/ml, mean ± SD: 15. 9 ± 5. 9 ng/ml, p<0. 0001). Paired sample analysis showed that elevated sLR11 levels at disease diagnosis were decreased to normal range when disease remission was achieved (median: 13. 3 ng/ml, mean ± SD: 11. 0 ± 3. 3 ng/ml). Conclusions: We have identified LR11 as a novel molecule which was proven to be expressed in IVLBCL cells and circulated in patients' serum. LR11 immunostaining clearly highlights the tumor cells and sLR11 enables to distinguish IVLBCL from other differential diagnosis by serum evaluation. These findings suggest that LR11 is a useful diagnostic tool for IVLBCL, and serum sLR11 is a sensitive biomarker for diagnosis and disease monitoring of this challenging disease. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 11 ◽  
Author(s):  
Kaiyu Sun ◽  
Hui Wang ◽  
Xianqun Xu ◽  
Xiuqi Wei ◽  
Jingyu Su ◽  
...  

AimsTo evaluate the value of tumor-educated platelet (TEP) miR-18a-3p in the early diagnosis and chemotherapy efficacy monitoring of nasopharyngeal carcinoma (NPC).MethodsExpression levels of miR-18a-3p in platelets and plasma were detected by relative quantitative real-time PCR in NPC patients (n=54) and normal subjects (n=36). Diagnostic values of TEP miR-18a-3p for NPC was assessed by receiver operating characteristic (ROC) curve analysis. Follow up study was carried out to observe the dynamic changes of TEP miR-18a-3p with chemotherapy on 3 NPC patients.ResultsThe expression levels of TEP miR-18a-3p in NPC patients were significantly higher than that in healthy controls (p &lt; 0.0001). ROC curve analysis showed that the area under the curve (AUC) value was 0.841, the sensitivity and specificity for the diagnosis of NPC were 87% and 72.7%. No correlation was found between expression levels of TEP miR-18a-3p and patients’ clinical parameters and their NPC tumor-node-metastasis (TNM) stage. The positive rate of TEP miR-18a-3p and EBV DNA for NPC diagnosis were 85.4% and 66.7%. TEP miR-18a-3p expression were down-regulated after 77.8% (7 of 9) of chemotherapy, and in 66.7% (2 of 3) patients, TEP miR-18a-3p levels decreased after 3 cycles of chemotherapy.ConclusionThe expression levels of TEP miR-18a-3p are upregulated in NPC and have a high probability to downregulated after chemotherapy, indicating a significant clinical value. TEP miR-18a-3p might serve as a novel type of liquid-biopsy biomarker for early diagnosis and chemotherapy efficacy monitoring in NPC.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Siyu Wu ◽  
Wanchan Peng ◽  
Yunli Zhang ◽  
Jingjing Guo ◽  
Jinfang Fu ◽  
...  

Abstract Background Polymorphonuclear (PMN) elastase plays an important role in a variety of inflammatory disorders. Our aim was to analyse PMN elastase in idiopathic inflammatory myopathies (IIMs) and its association with disease activity. Methods PMN elastase levels were measured using enzyme-linked immunosorbent assay in serum samples obtained from 74 patients with myositis (58 with dermatomyositis [DM] and 16 with polymyositis [PM]) and 22 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminant capacity of PMN elastase level and PMN elastase-to-neutrophil ratio (ENR) in patients with active and remission myositis. The association of serum PMN elastase level and ENR with disease variables was evaluated in patients with IIMs. The disease specificity of PMN elastase level and ENR was further examined in 60 patients with other systemic autoimmune diseases. Results PMN elastase level and ENR were significantly higher in patients with active IIMs, DM, and PM than in patients with remission. ROC curve analysis revealed that PMN elastase level and ENR both outperformed creatine kinase (CK), the currently used laboratory marker, and strongly discriminated patients with active disease and those with remission of IIMs, DM, and PM (area under the ROC curve [AUC] 0.9, 0.9, and 0.88 for PMN elastase; AUC 0.96, 0.96, and 1.0 for ENR; AUC 0.72, 0.70, and 0.80 for CK, respectively). PMN elastase level and ENR were positively correlated with myositis disease activity assessment, CK, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and erythrocyte sedimentation rate. PMN elastase level and ENR were higher in the anti-PM-Scl positive myositis group than those in the anti-PM-Scl negative myositis group. Nevertheless, PMN elastase was not a specific disease marker for IIMs when compared with other autoimmune diseases. Conclusions PMN elastase, particularly ENR, were significantly correlated with disease activity and could serve as useful biochemical markers for evaluating the disease activity of patients with IIMs. Thus, they are potentially helpful in monitoring disease progression and guiding treatment.


2021 ◽  
Author(s):  
Marjan Ostovarpour ◽  
Mohammad Khalaj-Kondori ◽  
Tayyebeh Ghasemi

Abstract Colorectal cancer is one of the most common cancers in the world. Studies demonstrated that lncRNA FER1L4 was downregulated in different cancers and its expression was positively correlated with RB1 in a competing endogenous RNAs network. We investigated expression levels of FER1L4 lncRNA and RB1 in patients with colorectal cancer. 50 paired colorectal tumor and non-tumor marginal tissues, as well as 30 paired adenomatous colorectal polyps and matched adjacent normal tissues were obtained from the patients. Total RNA was extracted from the samples and cDNAs were synthesized. Their expression were quantified by qRT-PCR. Correlation between FER1L4 and RB1 expression levels was analyzed by Pearson correlation test. Finally, ROC curve analysis was used to evaluate their biomarker potency. We observed significant downregulation of FER1L4, but upregulation of RB1 in the colorectal tumors compared with non-tumor as well as with the adenomatous colorectal polyp tissues. However, RB1 expression was positively correlated with the FER1L4 expression both in the tumor and polyp samples. ROC curve analysis showed that both FER1L4 and RB1 expression levels could discriminate tumor from non-tumor and tumor from polyp samples. None of clinicopathological characteristics of patients were associated with FER1L4 or RB1 expression levels. Despite downregulation of FER1L4 and upregulation of RB1 in tumors compared with non-tumor tissues, the expression of RB1 was positively correlated with the expression of FER1L4 in the colorectal tumor as well as in the adenomatous colorectal polyp tissues. FER1L4 expression level might be considered as a potential biomarker for colorectal cancer development.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1553-1553
Author(s):  
Alessandro Rambaldi ◽  
Cristina Boschini ◽  
Federica Delaini ◽  
Elena Oldani ◽  
Andrea Rossi ◽  
...  

Abstract Abstract 1553 Background and Aim The number and type of lymphocytes and monocytes/macrophages detectable in the peripheral blood and the lymph nodes of patients with Hodgkin and non-Hodgkin lymphomas has been recently extensively investigated and interesting results indicate they may possibly affect the pathogenesis and prognosis of these diseases. Recent results indicate that the lymphocyte/monocyte ratio (LMR), when assessed at diagnosis by a simple automatic blood count, may predict the clinical outcome of diffuse large B cell lymphoma patients (DLBCL) treated with the R-CHOP chemotherapy program (Li Z-M et al.: PLoS ONE 7(7):2012). The main objective of our study was to evaluate whether: a) the prognostic value of LMR could be confirmed either in patients treated with CHOP and Rituximab (R-CHOP) as well as in those treated with CHOP alone and b) the LMR could improve the prognostic profile as defined by the International Prognostic Index (IPI). Patients and Methods We retrospectively reviewed the clinical outcome of 973 DLBCL patients treated (549 with R-CHOP) and regularly followed at our institutions from 1984 to 2012. The median age of this patients cohort was 61 years (range, 18–86), the Male/Female ratio 55% and the median follow up 44 months (range, 2 – 330). According to the IPI score, 61% of patients were in the low (0–2) risk group, while 39% were in the intermediate or high-risk groups (3–5). A receiver operating characteristic (ROC) curve analysis was used to illustrate in our data set the best cut off values of peripheral blood lymphocyte absolute count (ALC), monocyte absolute count (AMC) or LMR. The relationship between IPI and the LMR was analyzed by the Fisher exact test. Univariate analysis to evaluate differences between variables was performed by the log rank. A multivariate analysis was performed by Cox proportional-hazards models. Results A preliminary ROC curve analysis performed on all patients (treated with or without rituximab) failed to identify any meaningful relationship between Overall Survival (OS) and the ALC, the AMC or the LMR. However, when the same analysis was restricted to patients treated with R-CHOP, we could confirm not only the positive correlation between ALC and AMC and OS, but most importantly that a LMR value >2.6 is the most sensitive (70%) and specific (53%) cut off to predict the OS. Within the R-CHOP treated cohort (N=549), we further investigated the relationships between LMR and the most relevant clinical features measured at diagnosis. Patients with a LMR ≤ 2.6 (52%) had a worst ECOG PS (p= 0.000), a higher LDH level (P= 0.000), a higher IPI (p= 0.000) and more frequently they were male (p= 0.02) and had an advanced Ann Arbor disease stage (p= 0.002). On the contrary, no statistical correlation was observed with age and the presence of extranodal sites. The proportion of patients achieving a complete response or a very good partial response was 95% in patients with a LMR >2.6 and 87% for those with a LMR ≤ 2.6 (p=0.018). More interestingly, among patients failing to achieve CR the proportion of those with a LMR ≤ 2.6 was 79% as compared to 21% among those with a LMR >2.6. The Event Free Survival of patients with a LMR >2.6 was significantly better when compared to those with a LMR ≤ 2.6 (71% vs. 59% at 5 years, p= 0.01) while no difference was observed for the Disease Free Survival. By univariate and multivariate analysis we could show that, similarly to a high IPI, a LMR ≤ 2.6 strongly predict a poor OS (p= 0.0000) (Figure 1). In addition, we could demonstrate a strong interaction between IPI and LMR since patients with a high IPI and LMR ≤ 2.6 are characterized by a very poor prognosis when compared to all the others (p= 0.000). Conclusions Our results confirm that a LMR ≤ 2.6 when assessed at diagnosis by a simple automatic blood count is not only a strong predictor of poor survival but it may help to better define a very poor prognostic subgroup in R-CHOP treated DLBCL. This novel prognostic marker is irrelevant when applied to patients receiving chemotherapy alone, giving further support to the notion that lymphocytes and/or monocytes play a crucial role on the therapeutic activity of Rituximab. Disclosures: Rambaldi: Hoffman-La Roche: Consultancy, Honoraria. Ladetto:Hoffman-La Roche: Consultancy, Honoraria. Gianni:Hoffman-La Roche: Consultancy, Honoraria. Tarella:Hoffman-La Roche: Consultancy, Honoraria.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5555-5555
Author(s):  
David G. Grenache ◽  
Zivjena Vucetic

5555 Background: Distinguishing between benign and malignant disease in women with a pelvic mass is difficult. OVA1 and ROMA are two multi-marker serum tests that are FDA-cleared to assess risk of malignancy in individuals with a pelvic mass. This study compared the accuracy of these tests for the prediction of ovarian cancer (OCa) in women with a pelvic mass. Methods: OVA1 and ROMA risk scores were determined in a subset of 146 serum samples obtained prospectively from pelvic mass patients. Patients were categorized by an initial cancer risk assessment (ICRA) performed by a physician and true cancer status determined surgically. 31 patients with malignancy (6 with a benign ICRA) and 115 patients with benign disease (25 with a malignant ICRA) were evaluated. Quest Diagnostics performed the OVA1 tests (CA-125, prealbumin, apolipoprotein A-1, β2-microglobulin, transferrin) and calculated and interpreted the risk score. ROMA tests (CA-125 and HE-4) were determined by automated immunoassay using an Abbott Architect analyzer. ROMA risk scores were calculated using published formulas and interpreted against cutpoints previously established for automated CA-125 and HE-4 performed by manual ELISA. Results: There were 70 pre- and 76 post-menopausal subjects. Of the 31 with malignancy, 26 had OCa (54% >stage II), 5 with an ICRA of benign. ROC curve analysis of the entire cohort produced an AUC of 0.88 (95% CI 0.80-0.95) and 0.93 (95% CI 0.87-0.99) for OVA1 and ROMA, respectively. OVA1 had a sensitivity of 0.97 and a specificity of 0.55. ROMA had a sensitivity of 0.84 and a specificity of 0.83. The sensitivity of OVA1 for OCa in the ICRA benign cohort (N = 5) was 0.80 and for ROMA was 0.40. The respective specificity for benign disease in this cohort (N=90) was 0.64 and 0.90. The sensitivity of ROMA for OCa increased to 0.60 with a slight decrease in specificity (0.87) when a cutpoint determined by ROC curve analysis was used. Conclusions: Overall, OVA1 and ROMA have similar performance characteristics. In women with an ICRA of benign, OVA1 was more sensitive among those who had OCa but ROMA was more specific among those who did not. The use of a ROMA cutpoint specific for the combination of automated CA-125 and HE-4 tests improved sensitivity.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Santos ◽  
S Paula ◽  
I Almeida ◽  
H Santos ◽  
H Miranda ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients (P) with acute heart failure (AHF) are a heterogeneous population. Risk stratification at admission may help predict in-hospital complications and needs. The Get With The Guidelines Heart Failure score (GWTG-HF) predicts in-hospital mortality (M) of P admitted with AHF. ACTION ICU score is validated to estimate the risk of complications requiring ICU care in non-ST elevation acute coronary syndromes. Objective To validate ACTION-ICU score in AHF and to compare ACTION-ICU to GWTG-HF as predictors of in-hospital M (IHM), early M [1-month mortality (1mM)] and 1-month readmission (1mRA), using real-life data. Methods Based on a single-center retrospective study, data collected from P admitted in the Cardiology department with AHF between 2010 and 2017. P without data on previous cardiovascular history or uncompleted clinical data were excluded. Statistical analysis used chi-square, non-parametric tests, logistic regression analysis and ROC curve analysis. Results Among the 300 P admitted with AHF included, mean age was 67.4 ± 12.6 years old and 72.7% were male. Systolic blood pressure (SBP) was 131.2 ± 37.0mmHg, glomerular filtration rate (GFR) was 57.1 ± 23.5ml/min. 35.3% were admitted in Killip-Kimball class (KKC) 4. ACTION-ICU score was 10.4 ± 2.3 and GWTG-HF was 41.7 ± 9.6. Inotropes’ usage was necessary in 32.7% of the P, 11.3% of the P needed non-invasive ventilation (NIV), 8% needed invasive ventilation (IV). IHM rate was 5% and 1mM was 8%. 6.3% of the P were readmitted 1 month after discharge. Older age (p &lt; 0.001), lower SBP (p = 0,035) and need of inotropes (p &lt; 0.001) were predictors of IHM in our population. As expected, patients presenting in KKC 4 had higher IHM (OR 8.13, p &lt; 0.001). Older age (OR 1.06, p = 0.002, CI 1.02-1.10), lower SBP (OR 1.01, p = 0.05, CI 1.00-1.02) and lower left ventricle ejection fraction (LVEF) (OR 1.06, p &lt; 0.001, CI 1.03-1.09) were predictors of need of NIV. None of the variables were predictive of IV. LVEF (OR 0.924, p &lt; 0.001, CI 0.899-0.949), lower SBP (OR 0.80, p &lt; 0.001, CI 0.971-0.988), higher urea (OR 1.01, p &lt; 0.001, CI 1.005-1.018) and lower sodium (OR 0.92, p = 0.002, CI 0.873-0.971) were predictors of inotropes’ usage. Logistic regression showed that GWTG-HF predicted IHM (OR 1.12, p &lt; 0.001, CI 1.05-1.19), 1mM (OR 1.10, p = 1.10, CI 1.04-1.16) and inotropes’s usage (OR 1.06, p &lt; 0.001, CI 1.03-1.10), however it was not predictive of 1mRA, need of IV or NIV. Similarly, ACTION-ICU predicted IHM (OR 1.51, p = 0.02, CI 1.158-1.977), 1mM (OR 1.45, p = 0.002, CI 1.15-1.81) and inotropes’ usage (OR 1.22, p = 0.002, CI 1.08-1.39), but not 1mRA, the need of IV or NIV. ROC curve analysis revealed that GWTG-HF score performed better than ACTION-ICU regarding IHM (AUC 0.774, CI 0.46-0-90 vs AUC 0.731, CI 0.59-0.88) and 1mM (AUC 0.727, CI 0.60-0.85 vs AUC 0.707, CI 0.58-0.84). Conclusion In our population, both scores were able to predict IHM, 1mM and inotropes’s usage.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuichiro Shimoyama ◽  
Osamu Umegaki ◽  
Noriko Kadono ◽  
Toshiaki Minami

Abstract Objective Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. Results Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320).


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiajia Liu ◽  
Xiaoyi Tian ◽  
Yan Wang ◽  
Xixiong Kang ◽  
Wenqi Song

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.


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