scholarly journals Preoperative Troponin Levels and Outcomes of Coronary Surgery Following Myocardial Infarction

2021 ◽  
Author(s):  
Nicholas Hess ◽  
Ibrahim Sultan ◽  
Yisi Wang ◽  
Floyd Thoma ◽  
Arman Kilic
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Artery Bypass ◽  
Multivariable Analysis ◽  
Risk Groups ◽  
Continuous Variable ◽  
High Risk Group ◽  
Lengths Of Stay ◽  
Risk Patients ◽  
The Impact

Background: This study evaluates the impact of peak preoperative troponin level on outcomes of coronary artery bypass grafting (CABG) for non-ST-elevation myocardial infarction (NSTEMI). Methods: This was a retrospective review of patients undergoing isolated CABG from 2011-2018 with presentation of NSTEMI. Patients were stratified into low- and high-risk groups based on median preoperative peak troponin (1.95ng/dL). Major cardiac and cerebrovascular events (MACCE) and mortality were compared. Multivariable analysis was performed to model risk factors for MACCE and mortality. Results: This study included 1,211 patients, 607 low- (≤1.95ng/dL) and 604 high-risk (>1.95ng/dL). Patients were well-matched with respect to age and comorbidity. High-risk patients had lower median preoperative ejection fraction (46.5% [IQR 35.0%-55.0%] vs 53.0% [IQR 40.0%-58.0%]) and higher incidence of preoperative intra-aortic balloon pump (15.9% vs 8.73%). Intensive care unit (47 hours [IQR 26-82] vs 43 hours [IQR 25-69]) and hospital lengths of stay (10 days [IQR 8-13] vs 9 days [IQR 8-12]) were longer in the high-risk group (each P<0.05). Postoperative complications and thirty-day, one- and five-year rates of both MACCE and survival were similar between groups. Peak troponin >1.95ng/dL was not associated with increased hazards for MACCE, mortality, or readmission in multivariable modeling. In sub-analyses, neither increasing troponin as a continuous variable nor peak troponin >10.00ng/mL were associated with increased hazards for these outcomes. Conclusions: Higher preoperative troponin levels are associated with longer lengths of stay but not MACCE or mortality following CABG. Dictating timing of CABG for NSTEMI based on peak troponin does not appear to be warranted.

Outcome of carotid endarterectomy under local anaesthesia with respect to the patients’ risk profile

VASA ◽  
2009 ◽  
Vol 38 (3) ◽  
pp. 225-233 ◽  
Author(s):  
Aleksic ◽  
Luebke ◽  
Brunkwall
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Carotid Endarterectomy ◽  
Complication Rate ◽  
Local Anaesthesia ◽  
High Risk Group ◽  
High Risk Patients ◽  
Hostile Neck ◽  
Risk Patients ◽  
Angioplasty And Stenting

Background: In the present study the perioperative complication rate is compared between high- and low-risk patients when carotid endarterectomy (CEA) is routinely performed under local anaesthesia (LA). Patients and methods: From January 2000 through June 2008 1220 consecutive patients underwent CEA under LA. High-risk patients fulfilled at least one of the following characteristics: ASA 4 classification, “hostile neck”, recurrent ICA stenosis, contralateral ICA occlusion, age ≥ 80 years. The combined complication rate comprised any new neurological deficit (TIA or stroke), myocardial infarction or death within 30 days after CEA, which was compared between patient groups. Results: Overall 309 patients (25%) were attributed to the high-risk group, which differed significantly regarding sex distribution (more males: 70% vs. 63%, p = 0,011), neurological presentation (more asymptomatic: 72% vs. 62%, p = 0,001) and shunt necessity (33% vs. 14%, p < 0,001). In 32 patients 17 TIAs and 15 strokes were observed. In 3 patients a myocardial infarction occurred. Death occurred in one patient following a stroke and in another patient following myocardial infarction, leading to a combined complication rate of 2,9% (35/1220). In the multivariate analysis only previous neurological symptomatology (OR 2,85, 95% CI 1,38-5,91) and intraoperative shunting (OR 5,57, 95% CI 2,69-11,55) were identified as independent risk factors for an increased combined complication rate. Conclusions: With the routine use of LA, CEA was not associated with worse outcome in high-risk patients. Considering the data reported in the literature, it does not appear justified to refer high-risk patients principally to carotid angioplasty and stenting (CAS) when LA can be chosen to perform CEA.

scholarly journals Pre-hospital risk assessment in suspected non-ST-elevation acute coronary syndrome: A prospective observational study

2018 ◽  
Vol 9 (1_suppl) ◽  
pp. 5-12 ◽  
Author(s):  
Dominique N van Dongen ◽  
Rudolf T Tolsma ◽  
Marion J Fokkert ◽  
Erik A Badings ◽  
Aize van der Sluis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Heart Score ◽  
Coronary Syndrome ◽  
Risk Patients ◽  
St Elevation

Background: Pre-hospital risk stratification of non-ST-elevation acute coronary syndrome (NSTE-ACS) by the complete HEART score has not yet been assessed. We investigated whether pre-hospital risk stratification of patients with suspected NSTE-ACS using the HEART score is accurate in predicting major adverse cardiac events (MACE). Methods: This is a prospective observational study, including 700 patients with suspected NSTE-ACS. Risk stratification was performed by ambulance paramedics, using the HEART score; low risk was defined as HEART score ⩽ 3. Primary endpoint was occurrence of MACE within 45 days after inclusion. Secondary endpoint was myocardial infarction or death. Results: A total of 172 patients (24.6%) were stratified as low risk and 528 patients (75.4%) as intermediate to high risk. Mean age was 53.9 years in the low risk group and 66.7 years in the intermediate to high risk group ( p<0.001), 50% were male in the low risk group versus 60% in the intermediate to high risk group ( p=0.026). MACE occurred in five patients in the low risk group (2.9%) and in 111 (21.0%) patients at intermediate or high risk ( p<0.001). There were no deaths in the low risk group and the occurrence of acute myocardial infarction in this group was 1.2%. In the high risk group six patients died (1.1%) and 76 patients had myocardial infarction (14.4%). Conclusions: In suspected NSTE-ACS, pre-hospital risk stratification by ambulance paramedics, including troponin measurement, is accurate in differentiating between low and intermediate to high risk. Future studies should investigate whether transportation of low risk patients to a hospital can be avoided, and whether high risk patients benefit from immediate transfer to a hospital with early coronary angiography possibilities.

P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Cardiovascular Events ◽  
Risk Group ◽  
Temporal Trends ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Plasma Cell ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

scholarly journals 291 Ticagrelor monotherapy after percutaneous coronary intervention in high-risk patients with prior myocardial infarction: a prespecified twilight substudy

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Mauro Chiarito ◽  
Davide Cao ◽  
Usman Baber ◽  
Carlo Pivato ◽  
Carlo Briguori ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Percutaneous Coronary Intervention ◽  
High Risk ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
High Risk Patients ◽  
Percutaneous Coronary ◽  
Risk Patients ◽  
History Of ◽  
The Impact

Abstract Aims Patients with history of myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) remain at risk of recurrent ischaemic events. The optimal antithrombotic strategy for this cohort remains debated. Methods and results In this prespecified analysis of the TWILIGHT trial, we evaluated the impact of prior MI on treatment effect of ticagrelor monotherapy vs. ticagrelor plus aspirin in patients undergoing PCI with at least one clinical and one angiographic high-risk feature and free from adverse events at 3 months after the index PCI. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5, the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization. 1937 (29.7%) patients with and 4595 (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. Patients with prior MI had increased rates of death, MI or stroke (5.7 vs. 3.2%, P &lt; 0.001) but similar BARC 2–5 bleeding (5.0 vs. 5.5%, P = 0.677). Ticagrelor monotherapy reduced the risk of BARC 2–5 bleeding in patients with [3.4% vs. 6.7%; hazard ratio (HR): 0.50; 95% confidence interval (CI): 0.33–0.76] and without prior MI [4.2% vs. 7.0%; HR: 0.58; 95% CI: 0.45–0.76; pinteraction = 0.54). Rates of the key secondary ischaemic outcome were similar between treatment groups irrespective of history of MI (prior MI: 6.0% vs. 5.5%; HR: 1.09; 95% CI: 0.75–1.58; no prior MI: 3.1% vs. 3.3%; HR: 0.92; 95% CI: 0.67–1.28; pinteraction = 0.52). Conclusions Ticagrelor monotherapy is associated with significantly lower risk of bleeding events as compared to ticagrelor plus aspirin without any compromise in ischaemic prevention among high-risk patients with history of MI undergoing PCI.

scholarly journals A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Junyu Huo ◽  
Jinzhen Cai ◽  
Ge Guan ◽  
Huan Liu ◽  
Liqun Wu
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Molecular Subtype ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Type I ◽  
Immune Microenvironment ◽  
Risk Patients

Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis.Methods: The training set (n = 609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) based on the prognosis-related genes associated with ferroptosis and pyroptosis. The intersecting differentially expressed genes (DEGs) among C1, C2, and C3 were used in univariate Cox and LASSO penalized Cox regression analysis for the construction of the risk score. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups.Results: Internal (TCGA, n = 370; GSE14520, n = 239) and external validation (ICGC, n = 231) suggested that the 12-gene risk score had high accuracy in predicting the OS, DSS, DFS, PFS, and RFS of HCC. As an independent prognostic indicator, the risk score could be applicable for patients with different clinical features tested by subgroup (n = 26) survival analysis. In the high-risk patients with a lower infiltration abundance of activated B cells, activated CD8 T cells, eosinophils, and type I T helper cells and a higher infiltration abundance of immature dendritic cells, the cytolytic activity, HLA, inflammation promotion, and type I IFN response in the high-risk group were weaker. The TP53 mutation rate, TMB, and CSC characteristics in the high-risk group were significantly higher than those in the low-risk group. Low-risk patients have active metabolic activity and a more robust immune response. The high- and low-risk groups differed significantly in histology grade, vascular tumor cell type, AFP, new tumor event after initial treatment, main tumor size, cirrhosis, TNM stage, BCLC stage, and CLIP score.Conclusion: The ferroptosis and pyroptosis molecular subtype-related signature identified and validated in this work is applicable for prognosis prediction, immune microenvironment estimation, stem cell characteristics, and clinical feature assessment in HCC.

scholarly journals Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Eunjin Lee ◽  
Ji Won Lee ◽  
Boram Lee ◽  
Kyunghee Park ◽  
Joonho Shim ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Genomic Feature ◽  
High Risk Patients ◽  
Dna Mismatch ◽  
Molecular Stratification ◽  
Recurrent Mutations ◽  
Risk Patients

Abstract Background MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification. Methods Fifty-eight whole exome sequencing (WES) and forty-eight whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. Results In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients. Conclusions This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.

Utilization patterns and clinical outcomes of rasburicase administration according to tumor risk stratification

2019 ◽  
Vol 26 (3) ◽  
pp. 529-535 ◽  
Author(s):  
Parisa R Khalighi ◽  
Kylee L Martens ◽  
Andrew A White ◽  
Shan Li ◽  
Emily Silgard ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Tumor Lysis Syndrome ◽  
Kidney Injury ◽  
Risk Groups ◽  
High Risk Group ◽  
Adherence To Guidelines ◽  
Tumor Lysis ◽  
Risk Patients ◽  
Utilization Patterns

Purpose Current guidelines for tumor lysis syndrome management recommend rasburicase for high-risk patients. Adherence to guidelines has not been well studied, and the correlation between uric acid reduction and clinically relevant outcomes, such as acute kidney injury, remains unclear. Our study aims to describe rasburicase utilization patterns and outcomes in cancer patients with varying risks for tumor lysis syndrome. Methods In this retrospective cohort study, we included cancer inpatients who received rasburicase for tumor lysis syndrome management at two affiliated academic hospitals from 2009 to 2015. Patients were classified by tumor lysis syndrome risk categories prior to drug administration. Primary outcomes included acute kidney injury incidence and renal recovery. Secondary outcomes included uric acid nadir, mortality, and hospital length-of-stay. Results Among 164 patients, 42 (26%) had high-, 63 (38%) had intermediate-, and 59 (36%) had low-risk for tumor lysis syndrome. A total of 94 patients (57%) had existing renal dysfunction prior to rasburicase use. This occurred more frequently in low- (68%) compared to intermediate- (57%) and high- (43%) risk patients ( p = 0.044). A greater proportion of patients in the high-risk group (78%) had renal recovery when compared to the intermediate- (61%) or low- (45%) risk groups ( p = 0.056). Despite a similar length of stay, the high-risk group had a significantly lower 30-day mortality (10%) when compared to intermediate- (25%) or low- (32%) risk groups ( p = 0.029). Conclusions Our results suggest that rasburicase may be frequently prescribed to treat hyperuricemia unrelated to tumor lysis syndrome in cancer patients. Improved education and adherence to guidelines may improve clinical and economic outcomes associated with rasburicase administration.

Impact of Stratification of Comorbidities on Nutrition Indices and Survival in Patients on Continuous Ambulatory Peritoneal Dialysis

2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 153-157 ◽  
Author(s):  
Narayan Prasad ◽  
Amit Gupta ◽  
Archana Sinha ◽  
Anurag Singh ◽  
Raj Kumar Sharma ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
High Risk ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Comorbid Illness ◽  
Medium Risk ◽  
Risk Patients

Background Case-mix comorbidities and malnutrition influence outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. In the present study, we analyzed the influence of stratified comorbidities on nutrition indices and survival in CAPD patients. Patients and Methods We categorized 373 CAPD patients (197 with and 176 without diabetes) into three risk groups: low—age under 70 years and no comorbid illness; medium—age 70 – 80 years, or any age with 1 comorbid illness, or age under 70 years with diabetes; high—age over 80 years, or any age with 2 comorbid illnesses. We then compared nutrition indices and malnutrition by subjective global assessment (SGA) between the three groups. Survival was compared using Kaplan–Meier survival analysis. Results Mean daily calorie and protein intakes in the low-risk group (21 ± 6.7 Kcal/kg, 0.85 ± 0.28 g/kg) were significantly higher than in the medium- (17.6 ± 5.2 Kcal/kg, 0.79 ± 0.25 g/kg) and high-risk (17.5 ± 6.1 Kcal/kg, 0.78 ± 0.26 g/kg) groups ( p = 0.001 and p = 0.04 respectively). Relative risk (RR) of malnutrition was less in the low-risk group (103/147, 70.06%) than in the medium-risk group [135/162, 83.3%; RR: 2.0; 95% confidence interval (CI): 2.1 to 3.4; p = 0.01] or the high-risk group (54/64, 84.4%; RR: 2.3; 95% CI: 2.1 to 4.9; p = 0.03). Mean survivals of patients in the low-, medium-, and high-risk groups were 51 patient–months (95% CI: 45.6 to 56.4 patient–months), 43.3 patient–months (95% CI: 37.8 to 48.7 patient–months), and 29.7 patient–months (95% CI: 23 to 36.4 patient–months) respectively (log-rank: 35.9 patient–months; p = 0.001). The 1-, 2-, 3-, 4-, and 5-year patient survivals in the low-, medium-, and high-risk groups were 96%, 87%, 79%, 65%, and 56%; 89%, 67%, 54%, 43%, and 34%; and 76%, 48%, 31%, 30%, and 30% respectively. Conclusions Intake of calories and protein was significantly lower in the medium-risk and high-risk groups than in the low-risk group. Survival was significantly better in low-risk patients than in medium- and high-risk patients.

scholarly journals Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma

2020 ◽  
Author(s):  
Eunjin Lee ◽  
Ji Won Lee ◽  
Boram Lee ◽  
Kyunghee Park ◽  
Joonho Shim ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Genomic Feature ◽  
High Risk Patients ◽  
Dna Mismatch ◽  
Recurrent Mutations ◽  
Whole Transcriptome Sequencing ◽  
Risk Patients

Abstract Background MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification.Results Fifty-eight whole exome sequencing (WES) and 48 whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair (MMR) associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients.Conclusions This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.

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