scholarly journals Risk factors for recurrence amongst high intermediate risk patients with endometrioid adenocarcinoma

2012 ◽  
Vol 23 (4) ◽  
pp. 257 ◽  
Author(s):  
Agnes Y. Bahng ◽  
Christina Chu ◽  
Paul Wileyto ◽  
Stephen Rubin ◽  
Lilie L. Lin
Keyword(s):  
Risk Factors ◽  
Endometrioid Adenocarcinoma ◽  
Intermediate Risk ◽  
Risk Patients ◽  
Risk Factors For Recurrence

scholarly journals Risk factors of recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism: from the COMMAND VTE Registry

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y Yamashita ◽  
H Amano ◽  
T Morimoto ◽  
T Kimura ◽  
Keyword(s):  
Risk Factors ◽  
Major Bleeding ◽  
Independent Risk Factor ◽  
Anticoagulation Therapy ◽  
Intermediate Risk ◽  
Risk Patients ◽  
History Of ◽  
Independent Risk Factors ◽  
Recurrent Vte

Abstract Background/Introduction Patients with venous thromboembolism (VTE), including pulmonary embolism (PE), have a long-term risk of recurrence, and anticoagulation therapy is recommended for the prevention of recurrence. The latest 2019 European Society of Cardiology (ESC) guideline classified the risks of recurrence into low- (<3%/year), intermediate- (3–8%/year), and high- (>8%/year) risk, and recommended the extended anticoagulation therapy of indefinite duration for high-risk patients as well as intermediate-risk patients. However, extended anticoagulation therapy of indefinite duration for all of intermediate-risk patients have been a matter of active debate. Thus, additional risk assessment of recurrence in intermediate-risk patients might be clinically relevant in defining the optimal duration of anticoagulation therapy. Furthermore, bleeding risk during anticoagulation therapy should also be taken into consideration for optimal duration of anticoagulation therapy. However, there are limited data assessing the risk of recurrence as well as bleeding in patients with intermediate-risk for recurrence based on the classification in the latest 2019 ESC guideline. Purpose The current study aimed to identify the risk factors of recurrence as well as major bleeding in patients with intermediate-risk for recurrence, using a large observational database of VTE patients in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. Results In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97–14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56–7.50), while the independent risk factors for major bleeding were age ≥75 years (HR 2.04, 95% CI 1.36–3.07), men (HR 1.52, 95% CI 1.02–2.27), history of major bleeding (HR 3.48, 95% CI 1.82–6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04–6.37). Conclusions Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Venous Thromboembolism (VTE) Risk Assessment & Prophylaxis In Irish Hospitalized Obstetric Patients: A Nationwide Cross-Sectional Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1151-1151
Author(s):  
Caroline M Noone ◽  
Susan O'Shea ◽  
Maeve P Crowley ◽  
John Higgins
Keyword(s):  
Risk Factors ◽  
Risk Assessment ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Mode Of Delivery ◽  
Low Risk ◽  
Average Weight ◽  
Intermediate Risk ◽  
Cross Sectional ◽  
Risk Patients

Abstract Background Pulmonary embolism continues to be the second leading cause of mortality in pregnancy and the puerperium. VTE complicates 1 - 2/1000 pregnancies, and the risk increases with age, mode of delivery, and presence of co-morbidities. Literature has shown that the use of low molecular weight heparin (LMWH) is safe in this patient cohort. Aims Assessment of the prevalence of VTE risk in hospitalised women in both the antenatal and postnatal groups to determine the proportion of at-risk patients who receive LMWH prophylaxis appropriately. Methods The study period was September 2011 to November 2012. All inpatients in the participating hospitals on the day of investigation were assessed for risk of VTE on the basis of hospital chart review. Risk profile was assessed in accordance with the 2009 Royal College of Obstetricians and Gynaecologist Guidelines. Patients undergoing procedures or on the labour ward at the time of review were excluded. Ethical approval was obtained from the ethics committees governing all centres. Results 610 pregnancies were reviewed across 19 centres. The average age of was 31+/- 5.65yrs (Range 16-47), with 21.87% aged over 35. 22% had a parity of 3 or more. The average weight was 71.51kg (Range 42-134kg, SD 14.482kg). Data on BMI was available for 77% - 34% were overweight and 21% were obese. 1% had a BMI>40. 31% were antenatal and 69% were postnatal. 63% of antenatal patients were low risk (<2 risk factors), 35% were intermediate risk (2 or more risk factors, prophylaxis should be considered) and 2% were high risk. All the high risk patients were on prophylaxis at an appropriate dose. 4% of the low risk patients were on prophylaxis unnecessarily. Only 7% of the intermediate risk patients were on correctly dosed prophylaxis. Among postnatal patients, 41% were low risk (<2 risk factors), 58% were intermediate risk (2 or more risk factors, require prophylaxis) and <1% were high risk. 80% were appropriately risk stratified and put on LMWH if necessary. 59% of patients should have been on LMWH but only 42% were (92% Tinzaparin and 8% Enoxoparin). This included 8 patients who were on LMWH unnecessarily. 38% were on too low a dose. Conclusion VTE prophylaxis remains a central issue in obstetric care given its prominent role in maternal morbidity and mortality and the increasing prevalence of risk factors such as obesity and increasing maternal age. It is clear that while there is good awareness of the risk in the postnatal period, there is less emphasis on risk assessment in antenatal patients where prophylaxis is rarely used. Those on prophylaxis are also likely to be on an incorrect dose. There is a clear role for a national guideline to standardize care for all pregnant women. On the basis of these findings, we have authored a guideline and this is now in use as a reference in all Irish maternity units. Disclosures: No relevant conflicts of interest to declare.

Predicting Early Mortality in Diffuse Large B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5411-5411
Author(s):  
Jamie M Maddox
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Early Mortality ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Non Hodgkin Lymphoma ◽  
Risk Patients ◽  
Large B Cell

Abstract It is difficult to find figures for the expected rate of early mortality in diffuse large B-cell non-Hodgkin lymphoma (DLBCL) as many of the patients who are destined to die early do not enter clinical trials. Our own rate of early mortality (death within 100 days of the diagnostic test being performed) was higher than we had anticipated (23%). We undertook a study to look at risk factors for early mortality, and to see if there were any factors which could be improved by altering our investigation and initial management. Our haematology database has baseline demographic and prognostic information on all cases of haematological malignancy diagnosed in our centre. A two year period was chosen retrospectively from 1st January 2013 until 31st December 2014. This gave 97 registered patients with DLBCL. Early mortality was significantly related to the patient age, Eastern Cooperative Oncology Group (ECOG) performance status, lactase dehydrogenase value, presence of 2 or more sites of extranodal disease and the presence of B-symptoms. We did not see a significant relationship to the presence of marrow disease or the presence of disease bulk. As the majority of the relevant factors are already part of validated prognostic scoring systems, we evaluated the (International Prognostic Index) IPI, the R-IPI (revised International Prognostic Index) and the NCCN-IPI (enhanced International Prognostic Index) to see which was the best predictor of early mortality. The IPI gave the chance of 100 day mortality as 4% for low or low-intermediate risk patients, 16% for high-intermediate risk patients and 53% for high risk patients. The R-IPI gave the chance of 100 day mortality as 0% for low risk patients, 5% for intermediate risk patients and 48% for high risk patients. The NCCN-IPI gave the chance of 100 day mortality as 0% for low or low-intermediate risk patients, 13% for high-intermediate risk patients and 57% for high risk patients (figure 1). By six months, the mortality rate in high risk NCCN-IPI patients had reached 71% while the low and low-intermediate groups remained at 0%. Some patients were included who were not considered for potentially curative chemotherapy. Even with these patients excluded, the risk of 100 day mortality was still 50% in the high risk NCCN-IPI group. Some of the risk factors for mortality will likely worsen if the diagnosis or initial treatment are delayed. We therefore looked at the overall pathway from referral until first treatment. We found that those with early mortality tended to have a shorter time course until receiving their first treatment, likely reflecting the fact that they were more unwell when they first presented. Disclosures Maddox: Janssen: Other: Funding to attend ASH 2016 (travel, accommodation, registration); Boehringer-Ingelheim: Other: Funding to attend ASH 2014 (travel, accommodation, registration).

scholarly journals The Genes for Tissue Factor F3 and Nuclear Receptor 4A Are Down-Regulated in Early Death Acute Promyelocytic Leukemia Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3902-3902
Author(s):  
Miriam Frech ◽  
Kathleen Stabla ◽  
Andrea Nist ◽  
Marco Mernberger ◽  
Heidi Altmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Nuclear Receptor ◽  
Research Funding ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Intermediate Risk ◽  
Atra Treatment ◽  
Differentiation Therapy ◽  
Protein Levels ◽  
Risk Patients

Abstract Introduction: Acute promyelocytic leukemia (APL) patients are successfully treated via differentiation therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Attempts to apply ATRA-based differentiation therapy to non-APL acute myeloid leukemia (AML) patients have not been effective so far (Johnson & Redner, 2015). Furthermore, 10-30% of the APL patients suffer an early death (ED) within 30 days, due to hemorrhages, infections, differentiation syndrome and thrombosis. Different risk factors have been identified, but the underlying mechanisms and successful treatment of ED in APL patients still have not been established (Kwaan et al., 2014, Lehmann et al., 2017). Hence, it is highly important to identify novel risk factors to understand the mechanistic processes in APL ED patients. Methods: To identify target genes, 50 bp single-read RNA sequencing (RNAseq) of 6 ED and 9 APL controls (cohort #1; n=15) and 4 ED and 5 APL controls (cohort #2; n=9) was executed. Samples were taken from patients with confirmed diagnosis of APL before beginning of treatment. Cohort #1 consisted of 15 patients: median age 60 years (range 37-73 years), 10 high-risk patients and 5 low/intermediate-risk patients according to Sanz score. Patients of cohort #1 were treated according to the AIDA2000 protocol of the Study Alliance Leukemia (SAL) study group. Cohort #2 consisted of 9 patients: median age 55 years (range 36-79 years), 4 high-risk patients and 5 low/intermediate-risk patients. Most patients of cohort 2 were treated according to the AIDA2000 (SAL) or APL0406 protocol. Gene validation was performed via RT-qPCR. PML-RARα variants were determined by Mentype AMLplexQS (Biotype). Survival and RT-qPCR analyses were performed with 64 non-APL AML patients´ samples treated within the clinical trial of the AMLSG HD98B study (Schlenk et al., 2004). In this trial, all patients received ICE (idarubicin, cytarabine, etoposide) chemotherapy. The patients were randomly assigned to ATRA or no ATRA. In our cohort, 26 patients had received ICE-ATRA, whereas 38 only ICE. Amaxa nucleofector technology was used for overexpression of PML-RARα bcr1 or bcr3 variant in U937 cells. NB4 or AML cells treated with 1 µM ATRA up to 72 h or 1-2 µM ATO up to 48 h were analyzed via flow cytometry, CellTiter-Glo viability assay, RT-qPCR or Western blot. Results: RNAseq of cohorts 1 and 2 showed F3 (Tissue Factor) and members of nuclear receptor 4A family, NR4A1/2/3, significantly downregulated in ED compared to control APL cases. GSEA analysis further identified a gene family including F3 and members of nuclear receptor 4A family, NR4A1/2/3, co-regulated upon leukotriene and thrombin treatment. Downregulation of F3 was further validated by RT-qPCR. Analysis of PML-RARα variants in APL control and ED cases (n=38, Chi-square p < 0.041) showed a significant enrichment of the short variant bcr3 in ED APL. Artificial overexpression of the short bcr3 and long bcr1 PML/RARα variant in U937 further revealed a correlation between bcr3 and downregulation of NR4A2/3. Moreover, treatment of the APL NB4 cell line with ATRA or ATO induced further downregulation of F3 but upregulation of NR4A2/3 transcripts. ATRA treatment induced the same effects on F3 and NR4A3 protein levels, while ATO led not only to a decrease of F3 but also NR4A3 protein levels. We next sought to address the role of F3 and NR4A in non-APL AML. In 5 non-APL AML cell lines high F3 transcript and protein levels were positively correlated with a better response to ATRA treatment in vitro. Consistently, analyzing samples taken from the AMLSG HD98B trial, AML patients with high F3 but also NR4A3 transcript levels treated with ICE chemotherapy showed a significantly prolonged overall survival upon additional ATRA treatment in vivo (Log-rank p < 0.008). Conclusions: Expression of F3 and NR4A1/2/3 is downregulated in APL ED and decreased expression of NR4A2/3 is associated with short PML-RARα variant bcr3, which is significantly enriched in ED APL. Since NR4A members are associated with coagulation and inflammation, they may be important F3-related factors, contributing to the bcr3 ED APL phenotype. As ATRA and ATO treatment is known to further inhibit F3 expression, alternative therapies not inhibiting F3 expression could be worthwhile in APL ED patients. Moreover, F3 and NR4A3 expression levels seem to be highly relevant as marker for the prediction of ATRA response in non-APL AML patients. Figure. Figure. Disclosures Platzbecker: Celgene: Research Funding. Thiede:Novartis: Honoraria, Research Funding; AgenDix: Other: Ownership. Schlenk:Pfizer: Research Funding, Speakers Bureau.

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