scholarly journals A 3-LncRNA Risk Scoring System for Prognosis of Adult Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5253-5253
Author(s):  
Yuandong Feng ◽  
Yachun Jia ◽  
Ying Shen ◽  
Hongli Chen ◽  
Yue Peng ◽  
...  
Keyword(s):  
Risk Score ◽  
Scoring System ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Status ◽  
Threshold Score ◽  
Risk Scoring ◽  
De Novo Aml ◽  
Risk Scoring System ◽  
Risk Categories

Abstract Background: Acute myeloid leukemia (AML) is the most common form of hematological malignant tumors that threatens human health. In the last decades, the rapid evolution in cytogenetics and molecular abnormalities made a breakthrough in the diagnosis and prognosis prediction of AML. However, there still has high heterogeneity among AML patients. Recently, researchers focused on long non-coding RNAs (lncRNAs), which once were addressed as products of "junk DNA", may play a key role in the initiation and progression of AML. Furthermore, a study from Ohio State's Comprehensive Cancer Center built a useful prognostic lncRNA score system for elder patients (>60 years) with cytogenetically normal AML by 48 lncRNAs [Garzon et al. PNAS 2014; 111:18679-84]. It can be expected that lncRNAs will promote the diagnosis and risk categories of AML in the near future. In this study, a risk scoring system was constructed upon 3 lncRNAs in de novo AML patients. We also sought to explore the functionality of these lncRNAs. Methods: By using Arraystar Human LncRNA Array V4.0, we obtained deregulated transcripts in AML, including 3,499 lncRNAs and 3,105 mRNAs (GSE103828). Expression patterns of all deregulated transcripts were extracted from 151 AML patients of The Cancer Genome Atlas (TCGA) RNA sequencing data. Through mathematical modeling, we identified 3 lncRNAs whose expression levels were independently associated with overall survival (OS). We then constructed a risk scoring system based on the 3 lncRNAs, age and 2008 WHO risk categories. Then the Receiver Operating Characteristic (ROC) was used to identify its test power and the best threshold score for 3-year survival status. Bone marrow samples from patients with AML and iron deficiency anemia (IDA) were collected. qRT-PCR was performed to verify the expression of lncRNAs in AML patients and IDA controls. Results: In the TCGA dataset, the area under ROC curve was 0.765, which indicated the risk scoring system has a good efficiency to predict 3-year survival status for AML patients, and the threshold score 1.639 was recommended to distinguish the high and low risk score groups (Figure A). Patients with higher risk score had a shorter OS (median 440.31 days vs. 886.16 days, p<0.001, Figure B) than those with lower risk score. To promote the practicality of the risk scoring system, we constructed Nomogram predictive modeling. The patient with 1.639 risk score was shown in the Nomogram (Figure C). We then performed qRT-PCR to verify the expression of lncRNAs and the availability of the risk scoring system. All of the 3 lncRNAs, RP11-222K16.2, LINC00899 and RP11-305O6.3, showed significantly lower expression in AML (n=46) compared to IDA controls (n=17, P<0.05), and the risk scoring system performed remarkable predicting effectiveness among AML patients (Figure D). Conclusion: We identified 3 deregulated lncRNAs in AML and constructed a risk scoring system based on the it, which provided distinct insights into the clinical and biological implications of lncRNAs expression in de novo AML patients. It may improve the risk stratification of newly-diagnosed AML patients. Further studies on the mechanisms of the lncRNAs are in process. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Efficacy of Risk Score System Establishment and Methylprednisolone Stratification Treatment for Pre-Engraftment Syndrome after Unrelated Cord Blood Transplantation: A Retrospective (development) and a Prospective (validation) Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4501-4501
Author(s):  
Xiaoyu Zhu ◽  
Jiang Zhu ◽  
Baolin Tang ◽  
Kaidi Song ◽  
Linlin Jin ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Score ◽  
Cumulative Incidence ◽  
Scoring System ◽  
Cord Blood Transplantation ◽  
High Risk Factors ◽  
Risk Scoring ◽  
Risk Scoring System ◽  
Different Doses

Introduction Pre-engraftment syndrome (PES) is a common immune reaction prior to neutrophil engraftment after unrelated cord blood transplantation (UCBT), with a unique clinical manifestation of non-infectious fever and skin rash. The reported incidence of PES ranges from 20% to 78%. Although many researchers believe that PES is associated with a high incidence of acute graft-versus-host disease (GVHD) but not with transplant-related mortality (TRM) , relapse, or overall survival (OS), they did not stratify the risk factors of PES, and how to carry out different doses of methylprednisolone (MP) stratified intervention therapy still remains unknown. Method s First, 136 hematological malignancy patients treated with UCBT from April 2000 to February 2012 in our transplantation center were retrospectively analysis. Among them, 92 patients occurred PES. High-risk factors for 180-day TRM in PES patients were established by univariate and multivariate analysis. Then, from January 2013 to August 2016, 221 PES patients were scored according to the risk scoring system and stratified treated with different doses of MP. Finally, in order to validate the efficacy of MP stratification treatment, we conducted a prospective, open label and non-randomized clinical trial including 240 PES patients who underwent UCBT from September 2016 to December 2018. This trial is registered at www.chictr.org.cn as ChiCTR-ONC-16009013. Results The cumulative incidence of neutrophil and platelet engraftment was significantly higher in PES group than non-PES group (97.8% vs 70.5%, P<0.001; 75.0% vs 54.5%, P=0.05). In 92 PES patients, multivariate analysis showed that failed MP treatment, multiple clinical symptoms and early onset of PES were independent high risk factors affecting180-day TRM. One high risk factor was scored as 1. The 92 PES patients were divided into PES-0, PES-1,PES-2 and PES-3, and the higher the score, the higher the TRM (17.7% vs 21.9% vs 62.5% vs 100%,respectively; P<0.001), and the lower the OS (68.3% vs 56.2% vs 25.0% vs 0%, respectively; P<0.001). Then, from January 2013 to August 2016, 221 PES patients were scored as PES-0, PES-1 and PES-2 according to the following two high risk factors (multiple clinical symptoms and early onset of PES) and stratified treated with different doses of MP (0.5mg/kg/d for PES-0, 1mg/kg/d for PES-1 and 2mg/kg/d for PES-2). Compared to the previous PES patients with the same risk score, the 180-day TRM of PES-1 and PES-2 patients was significantly reduced and the OS, disease free survival (DFS), and GVHD-free and Relapse-free survival (GRFS) were significantly increased after stratified treatment. The results in the prospective trial were similar to the retrospective study. In addition, although stratified therapy could significantly improve the prognosis of PES-2 patients cohort, the cumulative incidence of acute GVHD and GRFS are still the worst compared with other risk score patients. Therefore, how to improve the outcomes of PES-2 patients remains to be further studied. Conclusion s PES after UCBT is benefit for engraftment, but should be graded according the risk scoring system. Different doses of MP stratified intervention therapy can significantly improve the prognosis of severe PES patients. The risk scoring system of PES after UCBT and MP stratification treatment are worthy of clinical application. But the cumulative incidence of acute GVHD and GRFS in severe PES patients still need to be ameliorated in the further study. Disclosures No relevant conflicts of interest to declare.

A risk scoring system for African-American (AA) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line abiraterone (ABA) or enzalutamide (ENZ).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 51-51
Author(s):  
Jacqueline T Brown ◽  
Yuan Liu ◽  
Jennifer Ann LaFollette ◽  
Omer Kucuk ◽  
Melvin R. Moore ◽  
...  
Keyword(s):  
Risk Score ◽  
Scoring System ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Grade Group ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Response ◽  
Risk Scoring ◽  
Risk Scoring System

51 Background: AA pts represented < 3% of the COU-AA-302 and PREVAIL trial cohorts that led to the approval of ABA and ENZ in the 1st line treatment of mCRPC. We characterized the clinical outcomes (CO) and developed a risk score for AA pts with mCRPC on these agents. Methods: We retrospectively reviewed 77 AA pts with mCRPC treated with 1st line ABA or ENZ at Grady Memorial Hospital from 2015-2018. The CO included median overall survival (mOS), progression-free survival (mPFS) and PSA response (PSAr) as defined by a ≥ 50% drop in PSA over the 1st 12 weeks of treatment. Cox proportional hazard model and Kaplan-Meier method were used for association with OS and PFS and logistic regression model for PSAr. The risk score was built by regression coefficient-based scoring system using OS as the 1° outcome. Covariates included grade group (GG), baseline (bl) PSA, albumin, and BMI, ECOG status, and age. Results: Median age was 60 years with median follow-up of 11.5 months (mos). 50 pts received ABA; 27 received ENZ. The overall mOS was 45.7 mos, mPFS was 12.9 mos, and PSAr was 84.4%. CO did not differ significantly for ABA vs. ENZ with a 24-month OS of 66.6% vs. 57.7% and PFS of 34.3% vs. 45%. 1 point was assigned for each of the following: GG > 3, bl PSA ≥ 108, or bl albumin ≤ 4.2. The total was classified into low (0-1), intermediate (2), and high (3) risk and associated with CO via univariate (UVA) and multivariate (MVA) analyses (Table). Conclusions: We present the efficacy of ABA and ENZ in a cohort of AA pts with mCRPC. Risk grouping using bl PSA, bl albumin and GG may predict CO in this population. These results should be validated in a larger, prospective study.[Table: see text]

A Simple, Powerful, and Widely Applicable Micro-RNA Scoring System in Prognostication of De Novo Myeloid Leukemia Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 71-71
Author(s):  
Ming-Kai Chuang ◽  
Yu-Chiao Chiu ◽  
Wen-Chien Chou ◽  
Hsin-An Hou ◽  
Eric Y. Chuang ◽  
...  
Keyword(s):  
Scoring System ◽  
De Novo ◽  
Cox Model ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Microrna Expression ◽  
Expression Levels ◽  
Risk Scoring ◽  
Cox Analysis ◽  
Risk Scoring System

Abstract Introduction Acute myeloid leukemia (AML) is a highly heterogeneous disease with various cytogenetic and molecular abnormalities, some of which bear prognostic significance. Expression levels of some single microRNAs are influential for prognosis, but a system integrating several together and considering the weight of each should be more powerful. We sought to define a simple microRNA signature to predict prognosis in the patients. Method A cohort of 195 de novo AML patients who had cryopreserved marrow cells for study were subjected to global microRNA analysis. Analysis for overall survival (OS) was based on the 138 patients who received standard intensive chemotherapy (NTUH cohort). The AML cohort from the Cancer Genome Atlas (TCGA), which contains publically available data of microRNA and clinical information, serves as a validation cohort. To build a risk scoring system based on the global microRNA expression, we first analyzed the association between OS and the expression levels of individual microRNAs using univariate Cox proportional hazards regression model. MicroRNAs whose expression levels harbored top significance on OS (univariate Cox P < 0.005) were then analyzed with the multivariate Cox model. These microRNAs with independent survival significance (multivariate Cox P < 0.1) were selected to generate a risk scoring system, in which the expression of component microRNAs went through another round of multivariate Cox regression test to get beta values as weights for each microRNA. We also analyzed the global mRNA expression profiles from ours and TCGA cohort to sort out the physiologic pathways associated with high/low scores. Results Eleven microRNAs were significantly associated with OS by univariate Cox analysis (P < 0.005). After introducing the expression of these microRNAs into a multivariate Cox model, we identified high expression of hsa-miR-9-5p and hsa-miR-155-5p were independently associated with poor OS, while that of hsa-miR-203 had a trend of association with favorable OS. We constructed a risk scoring system: Risk = 0.4908 [Zhsa-miR-9-5p] + 0.2243 [Zhsa-miR-155-5p] - 0.7187 [Zhsa-miR-203], where the weights of microRNAs are beta values from multivariate Cox analysis and ZmicroRNA means the levels of specific microRNA expression after z-transformation. AML patients with higher scores had significantly shorter OS compared with those with lower scores in ours (median 13.5 months vs. not reached, P < 0.0001, Figure 1) as well as in the validation TCGA AML cohort (median 12.2 vs 26.4 months, P = 0.008, Figure 2). When restricting the analysis in our patients with a normal karyotype, the OS of patients with higher scores still fared worse (median 17.0 months vs. not reached, P = 0.006). Moreover, high score appeared to be an unfavorable prognostic factor independent of age, white cell count, cytogenetics, and gene mutation in both ours (HR=2.079, 95% CI 1.407-3.073, p<0.001) and TCGA cohort (HR=1.544, 95% CI 1.229-1.940, p<0.001). We also noted that the 3-microRNA signature outperformed all the single microRNA expression in prognostic significance. By analyzing the mRNA expression profiles, we sorted out several cancer-related pathways highly correlated with the microRNA prognostic signature. Since the scoring system was designed by z-transformed microRNA expression levels as inputs, cohort mean and cohort standard deviation of each of the three microRNAs are required for that formula. We provide the calculating formula we used in the NTUH dataset: Risk = 0.4908 (-Delta Cthsa-miR-9-5p+15.71)/3.60 + 0.2243 (-Delta Cthsa-miR-155-5p+6.94)/1.45 - 0.7187 (-Delta Cthsa-miR-203+17.16)/2.66. Here the Delta Ct values are Ct of the microRNA subtract Ct of the endogenous control MAMMU6; 15.71 and 3.60 are the mean and standard deviation of Delta Ct hsa-miR-9-5p. The same annotation applies to hsa-miR-155-5p and hsa-miR-203. For each newly diagnosed patient, the expression levels of hsa-miR-9-5p, hsa-miR-155-5p, hsa-miR-203, and MAMMU6 as determined by real-time PCR is sufficient to get a prognostic score, which will then be compared with our cohort median score 0.0031 to stratify the risk group. Conclusion We present a simple and user-friendly 3-microRNA signature as a powerful prognostic factor for AML through multiple rounds of statistical analyses on our cohort and further validation by another independent patient group. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Characterization of a 4 lncRNAs-based prognostic risk scoring system in adults with acute myeloid leukemia

2020 ◽  
Vol 88 ◽  
pp. 106261 ◽  
Author(s):  
Hui Zeng ◽  
Haibing Wu ◽  
Minchao Yan ◽  
Lun Tang ◽  
Xiaojun Guo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Scoring System ◽  
Myeloid Leukemia ◽  
Risk Scoring ◽  
Risk Scoring System ◽  
Acute Myeloid

scholarly journals Benefit of Risk Score-Guided Prophylaxis in Pregnant Women at Risk of Thrombotic Events: A Controlled Before-and-After Implementation Study

2018 ◽  
Vol 118 (09) ◽  
pp. 1564-1571 ◽  
Author(s):  
Céline Chauleur ◽  
Jean-Christophe Gris ◽  
Silvy Laporte ◽  
Céline Chapelle ◽  
Laurent Bertoletti ◽  
...  
Keyword(s):  
At Risk ◽  
Pregnant Women ◽  
Risk Score ◽  
Scoring System ◽  
Vascular Complications ◽  
Vascular Events ◽  
Before And After ◽  
Risk Scoring ◽  
The Impact ◽  
Risk Scoring System

Background Management of pregnant women at risk of venous thromboembolism (VTE) and placental vascular complications (PVCs) remains complex. Guidelines do not definitively specify optimal strategies. Objective Our objective was to evaluate the impact of employing risk score-driven prophylaxis strategies on VTE and PVC rates in at-risk pregnant women. Materials and Methods This study, conducted in 21 French maternity units, compared VTE and PVC rates before and after implementation of a risk scoring system to determine prophylactic strategies. Results A total of 2,085 pregnant women at risk of VTE or PVC were enrolled. Vascular events occurred in 190 (19.2%) patients before and 140 (13.0%) after implementation of risk score-driven prophylaxis (relative risk [RR] = 0.68 [0.55; 0.83]). The incidence of deep vein thrombosis during pregnancy was reduced (RR = 0.30 [0.14; 0.67]). PVC comprised mainly pre-eclampsia, occurring in 79 patients before and 42 patients after risk score implementation (RR = 0.52 [0.36; 0.75]). Post-partum haemorrhage occurred in 32 patients (3.2%) before and 48 patients (4.5%) after risk score implementation (RR = 1.38 [0.89; 2.13], p = 0.15). Conclusion Use of a simple risk scoring system, developed by experts in VTE and PVC research to guide prophylaxis, reduced the risk of thrombotic events during pregnancy without any significant increase in bleeding risk.

A 6-Lncrna Scoring System for Prognostication of Adult Myelodysplastic Syndromes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4344-4344
Author(s):  
Chi-Yuan Yao ◽  
Ching-Hsuan Chen ◽  
Whai-Shuan Huang ◽  
Hsin-An Hou ◽  
Chien-Chin Lin ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Expression Profiling ◽  
Scoring System ◽  
Cross Validation ◽  
De Novo ◽  
Leukemic Transformation ◽  
Risk Scoring ◽  
Risk Scoring System ◽  
Fold Cross Validation ◽  
Very High

Abstract Background: Myelodysplastic syndromes (MDS) are highly heterogeneous regarding pathogenesis and clinical outcome. Traditionally, the revised international prognostic scoring system (IPSS-R)incorporating clinical features and cytogenetic abnormalities has been the standard for prognostication, while in recent years, recurrent somatic mutations are becoming increasingly important for this purpose. Additionally, gene expression profiling of coding genes and microRNAs has also emerged as a powerful tool to separate patients into distinct prognostic categories. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides without protein-coding capacity. lncRNAs not only participate in normal hematopoiesis, but perturbation of their expressions may contribute to development of acute leukemia. However, the impact of lncRNA expression profiling on the prognosis of MDS patients has not yet been explored to date. Aims: This study was aimed to evaluate lncRNAs expression profiling in MDS and to find out lncRNAs whose expression levels were associated with clinical outcomes. A scoring system was constructed to better risk-stratify MDS patients. We also tried to seek clues to the functionality of these lncRNAs. Materials & Methods: By using the Affymetrix Human Transcriptome Array 2.0 platform, we obtained the global expression profiles of 24120 lncRNAs in 176 adult patients with de novo MDS diagnosed according to the 2008 WHO classification. Through mathematical modeling, we identified six lncRNAs whose expression levels were significantly associated with overall survival (OS). We then constructed a risk scoring system with the weighted sum of each of these six lncRNAs, and evaluated the correlation of the scores with clinical features,cytogenetic abnormalities, gene mutations, andtreatment outcomesof the MDS patients.The reliability of our lncRNA scoring system was assured based on the coefficient of variance obtained from a permutation test, and further validated by using a five-fold cross-validation, in which 80% of the patients were used as the training samples to develop the scoring model, whose prediction performances were evaluated by using the rest of the 20% of the patients. Analysis of mutations in 21 genes was performed by conventional Sanger sequencing technique. Results: Higher lncRNA scores were positively associated with refractory anemia with excess of blasts (RAEB)-1 or RAEB-2 subtypes, complex cytogenetic changes, and IPSS-R high and very high risks, but inversely associated with RCUD, RARS, RCMD subtypes, a normal karyotype, and IPSS-R low risk. Patients with higher lncRNA scores had more frequent RUNX1, ASXL1, TP53, EZH2, SRSF2 and ZRSR2 mutations, shorter OS (median 14.0 months vs. 77.3 months, P<0.001, Figure 1), and higher five-year leukemic transformation rate (72.0% vs. 17.9%, P<0.001), compared with those with lower lncRNA scores. The predictive power of this 6-lncRNA model was validated by a five-fold cross validation procedure. In multivariable analyses, a higher lncRNA score remained an independent unfavorable risk factor for OS (RR 2.428, 95% CI 1.751-3.367, P<0.001) after adjusting for other clinical and molecular variables. Moreover, the survival difference between higher-score and lower-score patients remained statistically significant in both IPSS-R higher-risk (high and very high risks) and lower-risk (very low, low and intermediate risks) subgroups (Figure 2). We also correlated our lncRNA score with mRNA expression profiling, and identified that higher lncRNA scores were associated with pathways related to acute myeloid leukemia and hematopoiesis. Conclusion: Our integrated 6-lncRNA risk scoring system provides distinct insights into the clinical and biological implications of lncRNAs expression in de novo MDS patients. The scoring system represents an independent prognostic factor for survival and leukemic transformation. It may assist improving risk stratification of newly-diagnosed MDS patients. Further prospective trials are necessary to confirm the findings of our study. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Development and Validation of a Risk Score for Predicting 1-Year Mortality Risk of STEMI Based on a Nationwide Cohort in China

2021 ◽  
Author(s):  
Si Chen ◽  
Qianzi Che ◽  
Yan Zhang ◽  
Jia Jia ◽  
Yiqun Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Risk Score ◽  
Mortality Risk ◽  
Scoring System ◽  
Validation Cohort ◽  
Predictive Score ◽  
Inferior Wall ◽  
Risk Scoring ◽  
Risk Scoring System

Abstract BackgroundA risk assessment for identifying long-term risk of post-discharge mortality in Chinese STEMI patients remains a concern. The aim of this study is to establish a bedside available risk scoring system for predicting 1-year mortality risk among Chinese STEMI patients. Methods STEMI patients(n=12611) were enrolled from the China STEMI Care Project Phase 2(CSCAP-2) collected between 2015 and 2016. Confounding bias was controlled using propensity score matching. Epidemiological, clinical, laboratory, and imaging variables, treatment strategy and medicine records were screened using extreme gradient boosting and nomogram according to the hazard ratio of Cox regression analysis to construct a predictive score. A validation cohort included 7342 patients collected in 2017 from CSCAP-2 was analyzed using receiver ROC and expectation (E)/observation (O) ratio to validate the risk scoring system. Results From 39 potential predictors, 8 variables were independent predictive factor and were included in the risk score: Killip class, early reperfusion strategy, Non-PCI intraoperative anticoagulants, heart rate, gender, age, anterior-wall myocardial infarction (AWMI) and inferior-wall myocardial infarction (IWMI). The new model demonstrated an excellent discrimination and calibration. The c-statistic and E/O ratio were 0.87(95%CI, 0.80-0.93) and 1.14(95%CI, 0.93-1.39) in the train set, 0.88 (95%CI, 0.78-0.96) and 1.15(95%CI, 0.85-1.56) in the test set, meanwhile, 0.89(95%CI, 0.82-0.95) and 1.00(95%CI, 0.81-1.23) in the validation cohort. The score has better sensitivity than the GRACE score and can recognize risk stratification among STEMI patients (P<0.001).Conclusions We developed a risk scoring system for predicting 1-year mortality risk of STEMI in a large Chinese population. The new score is easy-to-use and demonstrating a good discriminatory accuracy in predicting both short-term and long-term mortality risk in Chinese patients with STEMI.

scholarly journals A Risk Scoring System for Prognosis of Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4748-4748
Author(s):  
Yachun Jia ◽  
Guangyao Kong ◽  
Aili He
Keyword(s):  
Multiple Myeloma ◽  
Risk Score ◽  
Scoring System ◽  
Clinical Characteristics ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
The Cancer Genome Atlas ◽  
Newly Diagnosed ◽  
Risk Scoring ◽  
Risk Scoring System

Abstract A Risk Scoring System for Prognosis of Multiple Myeloma Background: Multiple myeloma (MM) is the second most frequently-occurring hematologic malignancy characterized by anemia, renal damage, osteolytic lesions and hypercalcemia (Kumar, et al. 2017), without specific prognostic indicators. Protein arginine methyltransferases 3 (PRMT3) is an enzyme which participates in the progression of some malignant diseases (Xiao, et al. 2017). However, the prognostic value of PRMT3 in MM remains unclear. In this study, we developed a risk scoring system based on the expression of PRMT3 to distinguish MM cohorts with different clinical characteristics. Methods: we integrated 4 datasets from The Cancer Genome Atlas (TCGA) or gene expression omnibus (GEO) and analyzed the correlation between PRMT3 expression and R-ISS stage, diseases progression, clinical characteristics or prognosis. Furthermore, we collected a cohort of newly diagnosed MM and healthy donor samples and then performed qRT-PCR to verify the expression of PRMT3. A risk scoring system was established to point out the prognostic indicator for clinical outcome of MM. The predictive power was evaluated by using Receiver Operating Characteristic (ROC) and Kaplan-Meier survival curve. Results: By extensive data analysis, we found the expression of PRMT3 was upregulated during the progression of myeloma (Figure 1 A p=0.573, 0.028, 0.02, respectively). The expression level of PRMT3 in relapsed MM patients was higher than that in newly diagnosed MM patients (Figure 1 B p=0.02, 0.016, 0.002, respectively). Meanwhile, the expression of PRMT3 was also increased in MM patients with advanced R-ISS stage (Figure 1 C p=0.001, 0.042, respectively). Moreover, the validation in a new cohort of MM samples showed the expression of PRMT3 was higher in MM patients compared to normal controls (Figure 1 D p=0.012). MM patients with high expression of PRMT3 showed prolonged Event Free Survival (EFS) and Overall Survival (OS) (Figure 2 A&B EFS: p=0.008, OS: p=0.001). Furthermore, we found the expression of PRMT3 had a positive correlation with B2M(p=0.018), HGB (p=0.001), aspirate plasma cells (p=0.002) and bone marrow biopsy plasma cells (p=0.001 Table not shown). Meanwhile, univariate and multivariate analysis showed that B2M, LDH, ALB, MRI and PRMT3 were independent adverse prognostic factors for OS in MM patients (p&lt;0.001, p&lt;0.001, p=0.0044, 0.0403, 0.0312, Table not shown). Finally, we established a risk scoring system which performed remarkable predicting effectiveness among MM patients. The ROC curve showed that the risk model performed well in 3-year OS (Figure 2 C AUC=0.749). A threshold score 1.26897 was recommended to distinguish the high and low risk score groups. Patients with higher risk score had a shorter OS than those with lower risk score (median 27.45 months vs. 50.13 months, p&lt;0.001 Figure 2 D). Conclusion: Our study identified that PRMT3 was upregulated in MM patients and that increased PRMT3 was an independent adverse prognostic factor for OS in MM. The risk scoring system based on the expression of PRMT3 provided distinct insights into the prognosis of MM patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Novel Clinical Risk Scoring Model for Predicting Amputation in Patients With Necrotizing Fasciitis: The ANF Risk Scoring System

2021 ◽  
Vol 8 ◽  
Author(s):  
Natthaya Chaomuang ◽  
Patcharin Khamnuan ◽  
Nipaporn Chuayunan ◽  
Acharaporn Duangjai ◽  
Surasak Saokaew ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Necrotizing Fasciitis ◽  
Risk Score ◽  
Scoring System ◽  
Characteristic Curve ◽  
Positive Likelihood Ratio ◽  
Clinical Predictors ◽  
Clinical Risk ◽  
Risk Scoring ◽  
Risk Scoring System

Background: Necrotizing fasciitis (NF) is a life-threatening infection of the skin and soft tissue that spreads quickly and requires immediate surgery and medical treatment. Amputation or radical debridement of necrotic tissue is generally always required. The risks and benefits of both the surgical options are weighed before deciding whether to amputate or debride. This study set forth to create an easy-to-use risk scoring system for predicting the risk scoring system for amputation in patients with NF (ANF).Methods: This retrospective study included 1,506 patients diagnosed with surgically confirmed NF at three general hospitals in Thailand from January 2009 to December 2012. All diagnoses were made by surgeons who strictly observed the guidelines for skin and soft tissue infections produced by the Infectious Diseases Society of America. Patients were randomly allocated to either the derivation (n = 1,193) or validation (n = 313) cohort. Clinical risk factors assessed at the time of recruitment were used to create the risk score, which was then developed using logistic regression. The regression coefficients were converted into item scores, and the total score was calculated.Results: The following four clinical predictors were used to create the model: female gender, diabetes mellitus, wound appearance stage 3 (skin necrosis and gangrene), and creatinine ≥1.6 mg/dL. Using the area under the receiver operating characteristic curve (AuROC), the ANF system showed moderate power (78.68%) to predict amputation in patients with NF with excellent calibration (Hosmer-Lemeshow χ2 = 2.59; p = 0.8586). The positive likelihood ratio of amputation in low-risk (score ≤ 4) and high-risk (score ≥ 7) patients was 2.17 (95%CI: 1.66–2.82) and 6.18 (95%CI: 4.08–9.36), respectively. The ANF system showed good performance (AuROC 76.82%) when applied in the validation cohort.Conclusion: The developed ANF risk scoring system, which includes four easy to obtain predictors, provides physicians with prediction indices for amputation in patients with NF. This model will assist clinicians with surgical decision-making in this time-sensitive clinical setting.

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