scholarly journals Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis

TH Open ◽  
2020 ◽  
Vol 04 (01) ◽  
pp. e59-e65 ◽  
Author(s):  
Alex C. Spyropoulos ◽  
Concetta Lipardi ◽  
Jianfeng Xu ◽  
Colleen Peluso ◽  
Theodore E. Spiro ◽  
...  

AbstractAn individualized approach to identify acutely ill medical patients at increased risk of venous thromboembolism (VTE) and a low risk of bleeding to optimize the benefit and risk of extended thromboprophylaxis (ET) is needed. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk score has undergone extensive external validation in medically ill patients for in-hospital use and a modified model was used in the MARINER trial of ET also incorporating an elevated D-dimer. The MAGELLAN study demonstrated efficacy with rivaroxaban but had excess bleeding. This retrospective analysis investigated whether the modified IMPROVE VTE model with an elevated D-dimer could identify a high VTE risk subgroup of patients for ET from a subpopulation of the MAGELLAN study, which was previously identified as having a lower risk of bleeding. We incorporated the modified IMPROVE VTE score using a cutoff score of 4 or more or 2 and 3 with an elevated D-dimer (>2 times the upper limit of normal) to the MAGELLAN subpopulation. In total, 56% of the patients met the high-risk criteria. In the placebo group, the total VTE event rate at Day 35 was 7.94% in the high-risk group and 2.83% for patients in the lower-risk group. A reduction in VTE was observed with rivaroxaban in the high-risk group (relative risk [RR]: 0.68, 95% confidence interval [CI]: 0.51–0.91, p = 0.008) and in the lower-risk group (RR: 0.69, 95% CI: 0.40 -1.20, p = 0.187). The modified IMPROVE VTE score with an elevated D-dimer identified a nearly threefold higher VTE risk subpopulation of patients where a significant benefit exists for ET using rivaroxaban.

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1631
Author(s):  
Anna Astarita ◽  
Giulia Mingrone ◽  
Lorenzo Airale ◽  
Fabrizio Vallelonga ◽  
Michele Covella ◽  
...  

Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting ‘CVAEs risk score’ distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.


2021 ◽  
Author(s):  
Yanjia Hu ◽  
Jing Zhang ◽  
Jing Chen

Abstract Background Hypoxia-related long non-coding RNAs (lncRNAs) have been proven to play a role in multiple cancers and can serve as prognostic markers. Lower-grade gliomas (LGGs) are characterized by large heterogeneity. Methods This study aimed to construct a hypoxia-related lncRNA signature for predicting the prognosis of LGG patients. Transcriptome and clinical data of LGG patients were obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). LGG cohort in TCGA was chosen as training set and LGG cohorts in CGGA served as validation sets. A prognostic signature consisting of fourteen hypoxia-related lncRNAs was constructed using univariate and LASSO Cox regression. A risk score formula involving the fourteen lncRNAs was developed to calculate the risk score and patients were classified into high- and low-risk groups based on cutoff. Kaplan-Meier survival analysis was used to compare the survival between two groups. Cox regression analysis was used to determine whether risk score was an independent prognostic factor. A nomogram was then constructed based on independent prognostic factors and assessed by C-index and calibration plot. Gene set enrichment analysis and immune cell infiltration analysis were performed to uncover further mechanisms of this lncRNA signature. Results LGG patients with high risk had poorer prognosis than those with low risk in both training and validation sets. Recipient operating characteristic curves showed good performance of the prognostic signature. Univariate and multivariate Cox regression confirmed that the established lncRNA signature was an independent prognostic factor. C-index and calibration plots showed good predictive performance of nomogram. Gene set enrichment analysis showed that genes in the high-risk group were enriched in apoptosis, cell adhesion, pathways in cancer, hypoxia etc. Immune cells were higher in high-risk group. Conclusion The present study showed the value of the 14-lncRNA signature in predicting survival of LGGs and these 14 lncRNAs could be further investigated to reveal more mechanisms involved in gliomas.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Congyu Shi ◽  
Shan Liu ◽  
Xudong Tian ◽  
Xiaoyi Wang ◽  
Pan Gao

Abstract Background Tumor protein p53 (TP53) is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSC), and TP53 mutations are associated with inhibited immune signatures and poor prognosis. We established a TP53 mutation associated risk score model to evaluate the prognosis and therapeutic responses of patients with HNSC. Methods Differentially expressed genes between patients with and without TP53 mutations were determined by using data from the HNSC cohort in The Cancer Genome Atlas database. Patients with HNSC were divided into high- and low-risk groups based on a prognostic risk score that was generated from ten TP53 mutation associated genes via the multivariate Cox regression model. Results TP53 was the most common mutant gene in HNSC, and TP53 mutations were associated with immunogenic signatures, including the infiltration of immune cells and expression of immune-associated genes. Patients in the high-risk group had significantly poorer overall survival than those in the low-risk group. The high-risk group showed less response to anti-programmed cell death protein 1 (PD-1) therapy but high sensitivity to some chemotherapies. Conclusion The risk score based on our TP53 mutation model was associated with poorer survival and could act as a specific predictor for assessing prognosis and therapeutic response in patients with HNSC.


2021 ◽  
Author(s):  
Shaopei Ye ◽  
Wenbin Tang ◽  
Ke Huang

Abstract Background: Autophagy is a biological process to eliminate dysfunctional organelles, aggregates or even long-lived proteins. . Nevertheless, the potential function and prognostic values of autophagy in Wilms Tumor (WT) are complex and remain to be clarifed. Therefore, we proposed to systematically examine the roles of autophagy-associated genes (ARGs) in WT.Methods: Here, we obtained differentially expressed autophagy-related genes (ARGs) between healthy and Wilms tumor from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology. Then univariate COX regression analysis and multivariate COX regression analysis were performed to acquire nine autophagy genes related to WT patients’ survival. According to the risk score, the patients were divided into high-risk and low-risk groups. The Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis.Results: Eighteen DEARGs were identifed, and nine ARGs were fnally utilized to establish the FAGs based signature in the TCGA cohort. we found that patients in the high-risk group were associated with mutations in TP53. We further conducted CIBERSORT analysis, and found that the infiltration of Macrophage M1 was increased in the high-risk group. Finally, the expression levels of crucial ARGs were verifed by the experiment, which were consistent with our bioinformatics analysis.Conclusions: we emphasized the clinical significance of autophagy in WT, established a prediction system based on autophagy, and identified a promising therapeutic target of autophagy for WT.


2021 ◽  
Vol 105 (1-3) ◽  
pp. 559-563
Author(s):  
Seungmin Lee ◽  
Kwang Yeol Paik

Background The aim of this study is to examine whether pancreaticogastrostomy (PG) or pancreaticojejunostomy (PJ) is the better reconstructive method to reduce postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) according to the fistula risk. Methods An institutional database was reviewed for patients undergoing PD between January 2008 and August 2019. A total of 159 patients were stratified into 4 groups according to the Clinical Risk Score-Pancreatic Fistula. POPF according to 4 risk groups was compared between PJ and PG. Results Of the 159 patients, 82 underwent PG (51.6%) and 77 underwent PJ (48.4%) reconstruction. POPF rate was 17.1% (n = 14) in the PG group and 12.9% (n = 10) in the PJ group (P = 0.51). POPF rates were not different in intermediate, low, and negligible risks between 2 reconstructive methods. In the high-risk group (n = 47), there were 4 POPFs (22.2%) in PJ group and 9 (31.0%) in the PG group, respectively (P = 0.74). Conclusion In PD, there was no superior method of reconstruction with regard to POPF, even in high-risk glands.


2007 ◽  
Vol 38 (8) ◽  
pp. 1203-1210 ◽  
Author(s):  
J. Suvisaari ◽  
L. Häkkinen ◽  
J. Haukka ◽  
J. Lönnqvist

BackgroundPrevious studies suggest that offspring of mothers with psychotic disorders have an almost two-fold higher mortality risk from birth until early adulthood. We investigated predictors of mortality from late adolescence until middle age in offspring of mothers with psychotic disorders.MethodThe Helsinki High-Risk Study follows up offspring (n=337) of women treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975. Factors related to mortality up to 2005 among offspring of these mothers was investigated with a survival model. Hazard rate ratios (HRR) were calculated using sex, diagnosis of psychotic disorder, childhood socio-economic status, maternal diagnosis, and maternal suicide attempts and aggressive symptoms as explanatory variables. The effect of family was investigated by including a frailty term in the model. We also compared mortality between the high-risk group and the Finnish general population.ResultsWithin the high-risk group, females had lower all-cause mortality (HRR 0.43, p=0.05) and mortality from unnatural causes (HRR 0.24, p=0.03) than males. Having themselves been diagnosed with a psychotic disorder was associated with higher mortality from unnatural causes (HRR 4.76, p=0.01), while maternal suicide attempts were associated with higher suicide mortality (HRR 8.64, p=0.03). Mortality in the high-risk group was over two-fold higher (HRR 2.44, p<0.0001) than in the general population, and remained significantly higher when high-risk offspring who later developed psychotic disorders were excluded from the study sample (HRR 2.30, p<0.0001).ConclusionsOffspring of mothers with psychotic disorder are at increased risk of several adverse outcomes, including premature death.


2020 ◽  
Author(s):  
Lumeng Luo ◽  
Minghe Lv ◽  
Xuan Li ◽  
Tiankui Qiao ◽  
Kuaile Zhao ◽  
...  

Abstract Background: Recent advances in immune checkpoint inhibitors (ICIs) have dramatically changed the therapeutic strategy against lung squamous cell carcinoma (LUSC). In the era of immunotherapy, effective biomarkers to better predict outcomes and inform treatment decisions for patients diagnosed with LUSC are urgently needed. We hypothesized that immune contexture of LUSC is potentially dictated by tumor intrinsic events, such as autophagy. Thus, we attempted to construct an autophagy-related risk signature and examine its prediction value for immune phenotype in LUSC.Method: The expression profile of LUSC was obtained from the cancer genome atlas (TCGA) database and the profile of autophagy-related genes (ARGs) was extracted. The survival‑related ARGs (sARGs) was screened out through survival analyses. Random forest was performed to select the sARGs and construct a prognostic risk signature based on these sARGs. The signature was further validated by receiver operating characteristic (ROC) analysis and Cox regression. GEO dataset was used as an independent testing dataset. Patients were divided into high-risk and low-risk group based on the risk score. Then, gene set enrichment analysis (GSEA) was conducted between the two groups. The Single-Sample GSEA (ssGSEA) was introduced to quantify the relative infiltration of immune cells. The correlations between risk score and several main immune checkpoints were examined. And the ESTIMATE algorithm was used to calculate the estimate/immune/stromal scores of the LUSC. Results: Four ARGs (CFLAR, RGS19, PINK1 and CTSD) with the most significant prognostic values were enrolled to construct the risk signature. Patients in high-risk group had better prognosis than the low-risk group (P < 0.0001 in TCGA; P < 0.01 in GEO) and considered as an independent prognosis factor. We also found that high-risk group indicated an immune-suppression status and had higher levels of infiltrating regulatory T cells and macrophages, which are correlated with worse outcome. Besides, risk score showed a significantly positive correlation with the expression of PD-1 and CTLA4, as well as estimate score and immune score.Conclusion: This study established a novel autophagy-related four-gene prognostic risk signature, and the autophagy-related scores are associated with immune landscape of LUSC, with higher score indicating a stronger immune-suppression status.


2020 ◽  
Author(s):  
FengLing Shao ◽  
Zhenni Wang ◽  
Shan Wang

Abstract BackgroundDue to the extremely high mortality rate of children with high-risk Neuroblastoma (NB), there is an urgent need for new indicators to further classify children in the high-risk group for more precise treatment. The purpose of our research is to explore the immune-related genes in NB in the high-risk group, and to further identify and develop a prognostic nomogram based on immune IRG signatures. MethodsThrough bioinformatics analysis to explore the abnormal expression of immune-related genes in the high-risk group. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify the immune and overall survival (OS) related mRNA. The accuracy of the risk score is evaluated by Kaplan-Meier method and receiver operating characteristics (ROC) analysis, which is used to build a nomogram in combination with other clinical characteristics.. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the accuracy of our results. ResultsA total of 127 common differentially expressed immune genes were found between the high-risk group and the non-high-risk group of the two data sets. Four immune-related genes (IRG) related to prognosis were identified and a risk score was established. Kaplan–Meier survival analysis and time-dependent ROC analysis showed that the 4-IRG risk score has satisfactory predictive potential and achieved consistency in the verification of external data sets. Subsequently, the risk score combined with clinical characteristics draws a nomogram. The reliability of the results was verified on 29 cases of NB tissues by qRT-PCR. ConclusionsOverall, we have developed a powerful multi-gene classifier that can effectively classify NB patients into low- and high-risk groups with poor prognosis, and draw a nomogram for children in the high-risk group. This feature can help select high-risk patients who need more aggressive adjuvant target therapy or immunotherapy.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 715-715
Author(s):  
Rupert M. Bauersachs ◽  
Joachim Dudenhausen ◽  
Andree Faridi ◽  
Thorsten Fischer ◽  
Samson Fung ◽  
...  

Abstract Women with a history of VTE, thrombophilia or both are at increased risk for VTE during pregnancy, but the optimal management strategy, and the need for thromboprophylaxis is not well defined in clinical guidelines because of limited trial data. The EThIG (Efficacy of Thromboprophylaxis as an Intervention during Gravidity) is a multicenter trial that prospectively enrolled 810 pregnant women at risk of VTE. Women were assigned to one of 3 management strategies: Low risk group I (including women with prior secondary VTE, or asymptomatic thrombophilia) with “watchful waiting” management, and dalteparin prophylaxis postpartum (50–100 IU/kg), or earlier if additional risk factors occurred; high risk group II (e.g. idiopathic VTE or symptomatic thrombophilia) receiving 50–100 IU/kg dalteparin; and very high-risk group III (e.g. acute VTE, prior long-term OAC, symptomatic AT-deficiency or antiphospholipid syndrome), receiving 100–200 IU/kg dalteparin. Primary efficacy outcome measure was symptomatic VTE, main safety outcome measures were haemorrhages, osteoporosis, thromboctopenia and pregnancy outcome. Results (mean ± SD / 95% CI): 810 women (age 30.8±5.4 years, weight 73.6±16.1kg) were enrolled, 28 % in group I, 58 % in II and 14% in III, including 66 women with acute VTE. 60.1% had prior VTE, 75.4% had thrombophilia (42.1 % FV-Leiden, 2.1 % homozygous, 9.5 % FII G20210A, 4.1% PC-, 1 % AT-deficiency; 17.4 % APS). 35.8 % had previous miscarriage, still birth or physical malformation. Comorbid conditions included lupus erythematosus, liver transplantation, ventricular septum defect, paraplegia, hepatitis C, nephrotic syndrome, asthma, chronic haemolytic anaemia, thalassaemia, osteoporosis and thrombocytopaenia. Median treatment initiation was at 17.0 weeks, at 24.0 weeks in group I, 14.5 weeks in group II and 16.0 weeks for group III. Mean daily dose was 66.2 ± 22.5 IU per kg (group I), 76.8 ± 24.1 IU per kg (group II) and 120.0 ± 49.1 IU per kg (group III). Objectively confirmed, symptomatic VTE occurred in 5 of 810 women (0.6%;0.2–1.5%). The rate of serious bleeding was 3.0% (1.9–4.4%), 0.9% (0.3–1.8%) occurred in the antepartum period, 2.1% (1.3–3.4%) peri-partum;1.1% (0.5–2.2%) was possibly heparin-related. There was no evidence of heparin-induced thrombocytopenia, and one case of osteoporosis (fracture of the saccygous bone during delivery). There were 94.4% successful pregnancies, 40 foetuses (4.9%; 3.6–6.7%) were lost due to miscarriage, 7 due to elective termination. Risk-stratified heparin prophylaxis was associated with a low incidence of symptomatic venous thromboembolism and few clinically important adverse events. Antepartum heparin prophylaxis is warranted in pregnant women with prior idiopathic thrombosis or symptomatic thrombophilia.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 394-394
Author(s):  
Lavanniya Kumar Palani Velu ◽  
Vishnuvardhan Chandrabalan ◽  
Ross Carter ◽  
Colin McKay ◽  
Donald McMillan ◽  
...  

394 Background: Pancreas-specific complications (PSC), comprising postoperative pancreatic fistula, post-pancreatectomy haemorrhage, and intra-abdominal collections, are drivers of morbidity following pancreaticoduodenectomy (PD). Intra-operatively derived pancreatic gland texture is a major determinant of postoperative PSC. We have previously demonstrated that a postoperative day 0 (PoD0) serum amylase ≥ 130 IU/L is an objective surrogate of pancreatic texture, and is associated with PSC. We sought to refine the PSC risk prediction model by including serial measurements of serum C-reactive protein (CRP). Methods: 230 consecutive patients undergoing PD between 2008 and 2014 were included in the study. Routine serum investigations, including amylase and CRP were performed from the pre-operative day. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP associated with clinically significant PSC. Results: 95 (41.3%) patients experienced a clinically significant PSC. ROC analysis identified post-operative day 2 (PoD2) serum CRP of 180 mg/L as the optimal threshold (P=0.005) associated with clinically significant PSC, a prolonged stay in critical care (P =0.032), and a relaparotomy (P = 0.045). Patients with a PoD0 serum amylase ≥ 130 IU/L who then developed a PoD2 serum CRP ≥ 180 mg/L had a higher incidence of postoperative complications. Patients were categorised into high, intermediate and low risk groups based on PoD0 serum amylase and PoD2 serum CRP. Patients in the high risk group (PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l) had significantly higher incidence of PSC, a return to theatre, prolonged lengths stay (all P≤ 0.05) and a four-fold increase in perioperative mortality compared patients in the intermediate and low risk groups (7 deaths in the high risk group versus 2 and nil in the intermediate and low risk groups respectively). Conclusions: A high risk profile, defined as PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l, should raise the clinician’s awareness of the increased risk of clinically significant PSC and a complicated postoperative course following pancreaticoduodenectomy.


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