Combination of NCCN Risk Stratification System and Pre-Transplant Minimal Residual Disease Levels for the Prognosis of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Background Numerous studies have confirmed that National Comprehensive Cancer Network (NCCN) risk stratification or pre-transplant minimal residual disease (MRD) levels can predict the risk of recurrence and survival after transplantation. But it is unclear whether combining these two parameters can more accurately predict prognosis. Methods We retrospectively analyzed 85 patients with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and constructed a new risk stratification tool combining NCCN risk stratification and pre-MRD levels. All patients were grouped by NCCN risk stratification (favorable/intermediate prognosis and poor prognosis group), pre-MRD levels (MRD (-) group (<0.1%) and MRD (+) group (≥0.1%)) and a combination of the above (low, intermediate and high risk groups), and graft-versus-host disease (GVHD) and prognosis were compared between groups. Results Relative to the favorable/intermediate prognosis group, OS and RFS were poorer in the poor prognosis group (71% vs 82%, P= .156; 60% vs 74%, P= .101) and CIR (29% vs 20%, P= .229) and NRM (23% vs 14%, P= .200) were better. The incidence of aGVHD and cGVHD was slightly lower in the favorable/intermediate prognosis group than in the poor prognosis group (38% vs 46%, P= .415; 10% vs 11%, P=. 572). Relative to the MRD (+) group, the MRD (-) group had significantly better OS and RFS (89% vs 59%, P= .002; 79% vs 50%, P= .003), lower CIR and NRM (15.1% vs 37.5%, P= .011; 11.3% vs 28%, P= .040), and a lower incidence of cGVHD (6% vs 19%, P= .022). The new risk stratification tool stratified patients into low, intermediate and high risk groups. Patients in the high-risk group had the highest incidence of aGVHD and cGVHD (42% vs 35% vs 53%, P= .606; 6% vs 11% vs 20%, P= .157). The difference in cGVHD between the low- and high-risk groups was significant (P= .038). Three-year OS was 93.9%, 70% and 60% (P= .011) and RFS was 85%, 62% and 46.7% (P= .009) for low-, intermediate- and high-risk patients, respectively. The differences in OS and RFS between the low- and intermediate-risk groups were statistically significant (P= .010; P= .025), as were the differences in OS and RFS between the low- and high-risk groups (P= .001; P= .001). Patients in the high-risk group had the highest CIR and NRM relative to those in the low- and intermediate-risk groups (9% vs 32% vs 33.3%, P= .027; 6% vs 24.3% vs 26.7%; P= .059). The differences in CIR (P= .012) and NRM (P= .028) were statistically significant in both the low-risk and intermediate-risk groups, as well as in the low- and high-risk groups (CIR: P= .028; NRM: P= .021). Multivariate analysis indicated that time to ANC recovery, time from diagnosis to transplantation, and novel risk stratification were independent prognostic factors. Conclusions Both pre-MRD levels and NCCN risk stratification predict AML prognosis after allo-HSCT, and combining the two can more accurately predict post-transplant prognosis. Disclosures No relevant conflicts of interest to declare.

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Preclinical markers of carotid atherosclerosis and cardiovascular risk assessed by the ESH/ESC scale (2003, 2007, 2009)

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2011-4-14-20 ◽

2011 ◽

Vol 10 (4) ◽

pp. 14-20 ◽

Cited By ~ 1

Author(s):

S. Sh. Urazalina ◽

A. N. Rogoza ◽

T. V. Balakhonova ◽

R. P. Myasnikov ◽

T. E. Kolmakova ◽

...

Keyword(s):

High Risk ◽

Risk Stratification ◽

European Society ◽

Risk Group ◽

Intima Media Thickness ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

European Society Of Cardiology

Aim. To assess the degree of cardiovascular (CV) risk adjustment in patients with low and intermediate risk by the SCORE scale, who were further examined in accordance with the European Society of Hypertension/European Society of Cardiology Guidelines (2003, 2007, 2009), and also underwent carotid artery (CA) ultrasound, as an extension of the ambulatory examination protocol. Material and methods. The study included 600 individuals aged 30-65 years (445 women, 155 men), with low to intermediate SCORE-assessed risk, and without diagnosed atherosclerosis or diabetes mellitus. The algorithm of CV risk stratification included SCORE scale, the ESH/ESC Guidelines (2003, 2007, 2009) and duplex CA ultrasound, with intima-media thickness (IMT) and atherosclerotic plaque (AP) assessment. Results. At the first stage of CV risk classification, which included routine examinations only, 73,8 % of the patients remained in the “low-risk” group, 14,5 % remained in the “intermediate-risk” group, and 11,7 % were moved to the “high-risk” group. After taking into account the duplex CA ultrasound results, the “low-risk”, “intermediaterisk”, and “high-risk” groups included 35,7 %, 33,5 %, and 30,8 % of the patients, respectively. In the “low-risk” and “intermediate-risk” groups, most patients had normal blood pressure levels (72,8 % and 83,5 %, respectively), while most patients in the “high-risk” group had arterial hypertension (56,7 %). The reason for moving the patients to the “high-risk” group was visualization of AP in CA (100 %). The percentage of subjects with one AP in this group was 22,7 %. In total, AP were visualized in 358 out of 600 participants (59,6 %). Out of these 358 patients, 26 (7,2 %) had IMT value >0,9 mm. Out of 242 patients without AP in CA, 2 (0,8 %) had IMT value >0,9 mm. Conclusion. At both risk stratification stages, the most prevalent causes of moving the patients to the groups of higher CV risk were dyslipidemia (81,3 % and 92,5 %, respectively), smoking (26,7 % and 22,2 %), abdominal obesity (77,7 %), and metabolic syndrome (98,5 %). The level of CV risk was affected by AP presence to a substantially greater extent than by IMT.

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Risk Stratification for Diffuse Large B-Cell Lymphoma by Integrating Interim Evaluation and International Prognostic Index: A Multicenter Retrospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.754964 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xue Shi ◽

Xiaoqian Liu ◽

Xiaomei Li ◽

Yahan Li ◽

Dongyue Lu ◽

...

Keyword(s):

High Risk ◽

Risk Stratification ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Risk Groups ◽

High Risk Group ◽

Stratification System ◽

Risk Stratification System

The baseline International Prognostic Index (IPI) is not sufficient for the initial risk stratification of patients with diffuse large B-cell lymphoma (DLBCL) treated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The aims of this study were to evaluate the prognostic relevance of early risk stratification in DLBCL and develop a new stratification system that combines an interim evaluation and IPI. This multicenter retrospective study enrolled 314 newly diagnosed DLBCL patients with baseline and interim evaluations. All patients were treated with R-CHOP or R-CHOP-like regimens as the first-line therapy. Survival differences were evaluated for different risk stratification systems including the IPI, interim evaluation, and the combined system. When stratified by IPI, the high-intermediate and high-risk groups presented overlapping survival curves with no significant differences, and the high-risk group still had >50% of 3-year overall survival (OS). The interim evaluation can also stratify patients into three groups, as 3-year OS and progression-free survival (PFS) rates in patients with stable disease (SD) and progressive disease (PD) were not significantly different. The SD and PD patients had significantly lower 3-year OS and PFS rates than complete remission and partial response patients, but the percentage of these patients was only ~10%. The IPI and interim evaluation combined risk stratification system separated the patients into low-, intermediate-, high-, and very high-risk groups. The 3-year OS rates were 96.4%, 86.7%, 46.4%, and 40%, while the 3-year PFS rates were 87.1%, 71.5%, 42.5%, and 7.2%. The OS comparison between the high-risk group and very high-risk group was marginally significant, and OS and PFS comparisons between any other two groups were significantly different. This combined risk stratification system could be a useful tool for the prognostic prediction of DLBCL patients.

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Impact of allogeneic hematopoietic stem cell transplantation on pediatric acute myeloid leukemia of FAB subtypes M4 and M5

10.21203/rs.3.rs-30250/v1 ◽

2020 ◽

Author(s):

Yu-juan Xue ◽

Pan Suo ◽

Yi-fei Cheng ◽

Ai-dong Lu ◽

Yu Wang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

High Risk ◽

Myeloid Leukemia ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Hematopoietic Stem ◽

Pediatric Acute Myeloid Leukemia ◽

Acute Myeloid

Abstract Background: FAB-M4 and M5 are unique subgroups of pediatric acute myeloid leukemia. However, for these patients, few studies have demonstrated the clinical and biological characteristics and efficacy of hematopoietic stem cell transplantation (HSCT), and especially haplo-HSCT. Procedure: We retrospectively evaluated the outcomes of 70 children with FAB-M4/M5 enrolled in our center from January 2013 to December 2017. Results: Of the patients, 32, 23, and 15 were in low-risk, intermediate-risk, and high-risk groups, respectively. T(16;16), inv16/CBFB-MYH11 was the most frequent cytogenetic abnormality. Among detected genetic alterations, WT1 was mutated at the highest frequency, followed by FLT3-ITD, NPM1, and CEBPA. Thirty-three patients received HSCT (haplo-HSCT = 30), of which four, 18, and 11 were in low-risk, intermediate-risk, and high-risk groups, respectively. For all patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 85.3 ± 4.3%, 69.0 ± 5.7%, and 27.9 ± 5.2%, respectively. By multivariate analysis, low-risk stratification predicted superior OS, EFS, and PLT ≤ 50 × 109/L at diagnosis, with FLT3-ITD mutations predicting higher CIR and poorer EFS. In intermediate- and high-risk groups, HSCT was independently associated with higher EFS and lower CIR. With a median post-transplant observation time of 30.0 months, the 3-year OS, EFS, CIR, and non-relapse mortality in the haplo-HSCT group were 74.2 ± 8.6%, 68.3 ± 8.9, 24.6 ± 7.6%, and 6.6 ± 4.1%, respectively. Conclusions: Risk-oriented treatment is important for pediatric FAB-M4/M5. For intermediate- and high-risk groups, HSCT significantly improved survival and haplo-HSCT might be a viable alternative approach.

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Varying Importance of Prognostic Factors in Subgroups of Myelodysplastic Syndromes Defined by Blast Count, Cytogenetic Risk Group, or WHO Classification.

Blood ◽

10.1182/blood.v114.22.2776.2776 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2776-2776

Author(s):

Andrea Kuendgen ◽

Corinna Strupp ◽

Kathrin Nachtkamp ◽

Barbara Hildebrandt ◽

Rainer Haas ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

High Risk ◽

Research Funding ◽

Risk Group ◽

Univariate Analysis ◽

Risk Groups ◽

High Risk Group ◽

Intermediate Risk ◽

Blast Count

Abstract Abstract 2776 Poster Board II-752 Introduction: We wondered whether prognostic factors have similar relevance in different subpopulations of MDS patients. Methods: Our analysis was based on patients with primary, untreated MDS, including 181 RA, 169 RARS, 649 RCMD, 322 RSCMD, 79 5q-syndromes, 290 RAEB I, 324 RAEB II, 266 CMML I, 64 CMML II, and 209 RAEB-T. The impact of prognostic variables in univariate analysis was compared in subpopulations of patients defined by medullary blast count, namely <5%, ≥5% (table), ≥10%, and ≥20% (not shown), as well as 3 subpopulations defined by the cytogenetic risk groups according to IPSS (table). Multivariate analysis of prognostic factors was performed for cytogenetically defined subgroups and WHO-subtypes. Results: Strong prognostic factors in all blast-defined subgroups were hemoglobin, transfusion dependency, increased WBC, age, and LDH. However, all variables became less important in patients with ≥20% blasts (RAEB-T) and increased WBC was rare. Platelet count and cytogenetic risk groups were relevant in patients with <5%, ≥5%, and ≥10% marrow blasts, but not in RAEB-T. Marrow fibrosis was important in patients with <5% or ≥5% blasts, but not ≥10%. Gender and ANC <1000/μl were significant only in patients with a normal blast count. Furthermore, we looked for the effect of the karyotypes, relevant for IPSS scoring (-Y, del5q, del20q, others, del7q/-7, complex), and found a comparable influence on survival, irrespective whether patients had < or ≥5% marrow blasts. In subpopulations defined by cytogenetic risk groups, several prognostic factors were highly significant in univariate analysis, if patients had a good risk karyotype. These included hemoglobin, sex, age, LDH, increased WBC, transfusion need, and blast count (cut-offs 5%, 10%, and 20%). In the intermediate risk group only LDH, platelets, WBC, and blasts were significant prognostic factors, while in the high risk group only platelets and blast count remained significant. Multivariate analysis was performed for the cytogenetic risk groups and for subgroups defined by WHO subtypes. The analysis considered blast count (</≥5%), hemoglobin, platelets, ANC, cytogenetic risk group, transfusion need, sex, and age. In the subgroup including RA, RARS, and 5q-syndrome, LDH, transfusion, and age in descending order were independent prognostic parameters. In the RCMD+RSCMD group, karyotype, age, transfusion, and platelets were relevant factors. In the RAEB I+II subgroup, the order was hemoglobin, karyotype, age, and platelets, while in CMML I+II only hemoglobin had independent influence. In RAEB-T none of the factors examined was of independent significance. Looking at cytogenetic risk groups, in the favorable group, several variables independently influenced survival, namely transfusion, blasts, age, sex, and LDH (in this order). Interestingly, in the intermediate and high risk group, only blast count and platelets retained a significant impact. Conclusion: Univariate analysis showed prognostic factors (except ANC) included in IPSS and WPSS are relevant in most subgroups defined by marrow blast percentage. However, they all lose their impact if the blast count exceeds 20%. Regarding cytogenetic risk groups, several prognostic factors lose their influence already in the intermediate risk group. This underscores the prognostic importance of MDS cytogenetics. Multivariate analysis showed MDS subpopulations defined by WHO types also differ with regard to prognostic factors. In particular, CMML and RAEB-T stand out against the other MDS types. Disclosures: Kuendgen: Celgene: Honoraria. Hildebrandt:Celgene: Research Funding. Gattermann:Novartis: Honoraria, Participation in Advisory Boards on deferasirox clinical trials. Germing:Novartis, Celgene: Honoraria, Research Funding.

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High Prognostic Impact of Flowcytometric Minimal Residual Disease Detection In Acute Myeloid Leukemia: Prospective Data From the HOVON/SAKK 42a Study

Blood ◽

10.1182/blood.v116.21.760.760 ◽

2010 ◽

Vol 116 (21) ◽

pp. 760-760

Author(s):

Monique Terwijn ◽

Angèle Kelder ◽

Wim L.J. van Putten ◽

Alexander N. Snel ◽

Vincent H.J. van der elden ◽

...

Keyword(s):

Prognostic Factors ◽

Risk Stratification ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Residual Disease ◽

Risk Groups ◽

Prognostic Impact ◽

Induction Cycle ◽

Minimal Residual

Abstract Abstract 760 Currently, the most important prognostic factors for acute myeloid leukemia (AML) include molecular aberrancies and karyotype of the leukemic blasts. Although these factors have showed to be of utmost importance in upfront risk stratification in current treatment schedules, the treatment outcome of patients within as such defined risk groups is still quite heterogeneous. Therefore, there is an unmet need for therapy-dependent prognostic factors which can be implemented into risk-adapted treatment strategies. Minimal residual disease (MRD) frequency is such a parameter. MRD cells are considered responsible for the outgrowth of AML after treatment, leading to a relapse in 30–40% of the patients in complete remission (CR). In this study, we are the first to report prospective multicenter data on the prognostic impact of MRD frequency in adult AML. In our retrospective study (N.Feller et al. Leukemia 2004), we explored which cut-off points for percentage of MRD cells would define MRD positive (levels above cut-off, MRD+) patients with a relatively poor prognosis, from MRD negative (levels below cut-off, MRD-) patients who showed a longer overall and relapse-free survival (OS and RFS). In search for the most optimal cut-off level which can be used for clinical purpose in risk stratification-directed therapy, we used these cut-offs to evaluate the prognostic value in the current prospective setting. Diagnosis and follow-up samples were collected of 462 patients treated uniformly according to the HOVON/SAKK42a protocol (www.hovon.nl) and MRD frequency was assessed blindly without knowledge of clinical course. MRD detection was accomplished by immunophenotyping by flow cytometry (FCM) through aberrant expression of markers on AML blasts. Together with the expression of normal immature cell markers and/or myeloid lineage markers, this offers a leukemia associated phenotype (LAP). Each LAP was individually designed for each patient in diagnosis bone marrow (BM) or peripheral blood. Subsequently, BM samples obtained during follow-up were analysed for the presence of LAP-positive cells. MRD frequency was expressed as a percentage of leukocytes. The median MRD frequencies of patients in clinical CR after first induction cycle (n=164), second induction cycle (n=182) and consolidation (n=121) were 0.040%, 0.022% and 0.020%, respectively. The cut-off levels for MRD frequency as defined retrospectively were all significant in the identification of patients with adverse (MRD+) and favourable (MRD-) OS and RFS, respectively. After the first cycle, the most significant cut-off was 0.8%, leading to 17 MRD+ patients who showed a median RFS of only 8.6 months, while 147 MRD- patients had a median RFS of >47 months (p=0.003,A). The relative risk of relapse (RR) was 2.9 (95% c.i. 1.4–6.0, p=0.004). After the second induction cycle, a cut-off level of 0.06% was most significant. Above this cut-off, 49 patients showed a median RFS of 7 months, while 133 MRD- patients showed a RFS of more than 47 months (p<0.00001, fig B). The RR was 3.2 (95% c.i. 2.0–5.0, p<0.00001). After consolidation therapy, 11 MRD+ patients with extremely poor prognosis were identified (median RFS 7.3 months vs. >47 months for 110 MRD- patients, p<0.00001, fig C), with a RR of 10.6 (95% c.i. 4.9–22.8, p<0.00001). Multivariate analysis was performed with conventional prognostic factors for AML: cytogenetic risk groups and time to achieve CR. After every cycle of therapy, MRD frequency was an independent prognostic factor for RFS after all cycles (1st cycle: p=0.010, 2nd cycle and consolidation p<0.00001) and for OS after 1st (p=0.023) and 2nd induction cycle (p=0.010). In this prospective multicenter study, already after first induction cycle, MRD detection by FCM was an independent significant factor in the identification of poor prognostic patients. In future treatment studies, risk stratification, e.g. for allogeneic stem cell transplantation, should not only be based on risk estimation determined at diagnosis, but also on MRD frequency as a therapy-dependent prognostic factor. This work was supported by Netherlands Cancer Foundation KWF. Disclosures: No relevant conflicts of interest to declare.

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Prognostic Factors and a Nomogram Predicting Overall Survival and Cancer-Specific Survival for Patients with Collecting Duct Renal Cell Carcinoma

BioMed Research International ◽

10.1155/2021/6736008 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Ruotao Xiao ◽

Cheng Liu ◽

Wei He ◽

Lulin Ma

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

High Risk ◽

Poor Prognosis ◽

Collecting Duct ◽

Tumor Grade ◽

Risk Groups ◽

Intermediate Risk ◽

Cancer Specific Survival ◽

N Stage

Background. Collecting duct renal cell carcinoma (CDRCC) is a rare type of renal cancer characterized by a poor prognosis. The aim of this work was to develop a nomogram predicting the overall survival (OS) and cancer-specific survival (CSS) for patients with CDRCC. Methods. A total of 324 eligible patients diagnosed with CDRCC from 2004 to 2015 were identified using the data from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier curve was used to estimate the 1-, 3-, and 5-year OS and CSS of these patients. Univariate and multivariate Cox regression models were performed to identify the independent risk factors associated with OS and CSS. The nomogram was developed based on these factors and evaluated by the concordance index (C-index) and calibration curves using the bootstrap resample method. The predictive accuracy of the nomogram was also compared with the manual of the American Joint Committee on Cancer (AJCC). Results. The estimated 1-, -3, and 5-year OS and CSS rates in the analytic cohorts were 56.4% and 60%, 32.5% and 37.3%, and 28.7% and 33.6%, respectively. The multivariate model revealed that age, tumor size, tumor grade, N stage, M stage, surgical type, and chemotherapy were independent predicted factors for OS, while tumor size, tumor grade, N stage, M stage, surgical type, and chemotherapy were independently linked to CSS. A nomogram was developed using these factors with relatively good discrimination and calibration. The C-index for OS and CSS was 0.764 (95% CI: 0.735~0.793) and 0.783 (95% CI: 0.754~0.812), which was superior to the AJCC stage (C-index: 0.685 (95% CI: 0.654~0.716) and 0.703 (95% CI: 0.672~0.734)). Patients were divided into low-risk, intermediate-risk, and high-risk groups according to the total points calculated by the nomogram. Patients in the low-risk group (97 mo and not reached) experienced significantly long median OS and CSS compared to the intermediate-risk (17 mo and 18 mo) and high-risk groups (5 mo for both). The calibration curves showed a good agreement between the predicted and actual probability related to OS and CSS. Conclusion. CDRCC has an aggressively biologic behavior with relatively poor prognosis. A survival prediction nomogram making an individualized evaluation of OS and CSS in patients with CDRCC was presented, potentially helping urologists to make a better risk stratification.

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A novel hyperinflammation clinical risk tool, HI5-NEWS2, predicts mortality following early dexamethasone use in an observational cohort of hospitalised COVID-19 patients.

10.1101/2021.06.16.21259011 ◽

2021 ◽

Author(s):

Michael R Ardern-Jones ◽

Hang T.T. Phan ◽

Florina Borca ◽

Matthew Stammers ◽

James Batchelor ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Dexamethasone Treatment ◽

Dexamethasone Therapy ◽

Risk Patients ◽

Anti Inflammatory

Background The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. Methods Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. Findings Of 1265 patients, high risk of HI (high HI5-NEWS2) (n=367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n= 455, 36.0%). An intermediate risk group (n= 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p=0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p=0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p=0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p =0.31). Interpretation The HI5-NEWS2 measured at COVID-19 diagnosis, strongly predicts mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention. Funding No external funding.

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A Risk Signature Established From Three Coagulation-fibrinolysis Genes Predicts Prognosis in Digestive System Pancancer

10.21203/rs.3.rs-1157925/v1 ◽

2022 ◽

Author(s):

Xingyun Wang ◽

Jinli Ji ◽

Ying Jiang ◽

Yiyang Zhao ◽

Zheyao Song ◽

...

Keyword(s):

High Risk ◽

Poor Prognosis ◽

Digestive System ◽

Risk Group ◽

Epigenetic Modification ◽

Enrichment Analysis ◽

Risk Groups ◽

High Risk Group ◽

Gene Set Enrichment Analysis ◽

Cox Analysis

Abstract Venous thromboembolism (VTE) is one of the major complications of digestive system cancer, and coagulation-fibrinolysis genes play an important role in VTE. We used univariate Cox analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analysis to construct 3-PCFGs (prognostic coagulation-fibrinolysis genes) model based on six prognostic coagulation-fibrinolysis genes. Gene set enrichment analysis (GSEA) was used to analyze the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the high- and low-risk groups. In addition, we classified digestive system pancancer patients into three clusters A, B, and C based on 3-PCFGs by K means. High-risk group and cluster C were associated with poor prognosis in digestive system pancancer. The m6A-related genes ALKBH5, FTO, RBM15, YTHDC1, and YTHDC2 (P<0.001) were highly expressed in the high-risk group and cluster C. The risk score was positively correlated with cancer-associated fibroblasts and endothelial cells. Cluster C had the highest immune score and stromal score. The poor prognosis in the high-risk group and cluster C may be affected by m6A epigenetic modification and immune microenvironment components in the digestive system pancancer.

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IVIM Parameters on MRI Could Predict ISUP Risk Groups of Prostate Cancers on Radical Prostatectomy

Frontiers in Oncology ◽

10.3389/fonc.2021.659014 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chun-Bi Chang ◽

Yu-Chun Lin ◽

Yon-Cheong Wong ◽

Shin-Nan Lin ◽

Chien-Yuan Lin ◽

...

Keyword(s):

High Risk ◽

Radical Prostatectomy ◽

Risk Stratification ◽

Risk Group ◽

Area Under The Curve ◽

Region Of Interest ◽

Risk Groups ◽

High Risk Group ◽

Multivariable Logistic Regression Analysis ◽

Perfusion Fraction

PurposeTo elucidate the usefulness of intravoxel incoherent motion (IVIM)/apparent diffusion coefficient (ADC) parameters in preoperative risk stratification using International Society of Urological Pathology (ISUP) grades.Materials and MethodsForty-five prostate cancer (PCa) patients undergoing radical prostatectomy (RP) after prostate multiparametric magnetic resonance imaging (mpMRI) were included. The ISUP grades were categorized into low-risk (I-II) and high-risk (III-V) groups, and the concordance between the preoperative and postoperative grades was analyzed. The largest region of interest (ROI) of the dominant tumor on each IVIM/ADC image was delineated to obtain its histogram values (i.e., minimum, mean, and kurtosis) of diffusivity (D), pseudodiffusivity (D*), perfusion fraction (PF), and ADC. Multivariable logistic regression analysis of the IVIM/ADC parameters without and with preoperative ISUP grades were performed to identify predictors for the postoperative high-risk group.ResultsThirty-two (71.1%) of 45 patients had concordant preoperative and postoperative ISUP grades. Dmean, D*kurtosis, PFkurtosis, ADCmin, and ADCmean were significantly associated with the postoperative ISUP risk group (all p < 0.05). Dmean and D*kurtosis (model I, both p < 0.05) could predict the postoperative ISUP high-risk group with an area under the curve (AUC) of 0.842 and a 95% confidence interval (CI) of 0.726–0.958. The addition of D*kurtosis to the preoperative ISUP grade (model II) may enhance prediction performance, with an AUC of 0.907 (95% CI 0.822–0.992).ConclusionsThe postoperative ISUP risk group could be predicted by Dmean and D*kurtosis from mpMRI, especially D*kurtosis. Obtaining the biexponential IVIM parameters is important for better risk stratification for PCa.

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Assessing the Presence and Position of Carotid Plaque Improves Risk Stratification for Cardiovascular Disease Prediction Among Patients With Hypertension

10.21203/rs.3.rs-574219/v1 ◽

2021 ◽

Author(s):

Hui-Juan Zuo ◽

Xian-Tao Song ◽

Jin-Wen Wang ◽

Hong-Xia Yang ◽

Jie Lin

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

High Risk ◽

Risk Stratification ◽

Carotid Plaque ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Traditional Risk Factors

Abstract Background: Ischemic cardiovascular disease (ISCVD) is a massive public health problem. ISCVD risk prediction models based on traditional risk factors as predictors is limited. Carotid atherosclerosis plays a fundamental value in the occurrence of ISCVD. The aim of this study was to evaluate the value of risk stratification plus carotid plaque improving the prediction of ISCVD. Methods: Between June 2016 and June 2017, 3998 subjects with hypertension were prospectively recruited and completed traditional risk factors survey and carotid ultrasound measurements in Anzhen Hospital, Beijing, China. Results: A total of 2010 (50.3%) subjects were detected carotid plaque. Among patients free from ISCVD (n=3479), there were 884 patients (25.4%) at high risk for ISCVD, and 868 (25.0%), 1727 (49.6%) was classified as intermediate risk or low risk according to Chinese cardiovascular risk score chart. The detected rate of carotid plaque was 64.7%, 53.7%, and 38.5% among patients at high risk to low risk, respectively. Carotid plaques and risk stratification alone or in combination were significantly associated with ischemic stroke, and negatively correlated with coronary heart disease (all P>0.05). Adding carotid plaque to risk stratification, the ischemic stroke prevalence increased from 5.3% to 9.1% in the low-risk group (P=0.001), 5.4% to 12.3% in the intermediate-risk group (P<0.001) and 8.2% to 14.4% than in the high-risk group (P=0.004). Intermediate risk plus carotid plaque (443/3998) were reclassified to a new high-risk group, high risk only (749/3998) and low risk plus carotid plaque (353/3998) were reclassified to a new intermediate risk group; and intermediate risk only (553/3998) were reclassified to a new low risk group. According to the reclassification, there were 1635 subjects (40.9%) at high risk, and 1102 (27.6%), 1261 (31.5%) was classified as intermediate risk or low risk. Conclusions: Carotid plaque has an important position as it plus risk stratification may improve the risk assessment of ischemic stroke and have resulted in reclassification.

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