EMA/CO for High-Risk Gestational Trophoblastic Neoplasia: Good Outcomes With Induction Low-Dose Etoposide-Cisplatin and Genetic Analysis

2013 ◽  
Vol 31 (2) ◽  
pp. 280-286 ◽  
Author(s):  
Constantine Alifrangis ◽  
Roshan Agarwal ◽  
Delia Short ◽  
Rosemary A. Fisher ◽  
Neil J. Sebire ◽  
...  
Keyword(s):  
High Risk ◽  
Genetic Analysis ◽  
Low Dose ◽  
Significant Proportion ◽  
Genetic Diagnosis ◽  
Low Risk ◽  
Gestational Trophoblastic Neoplasia ◽  
High Risk Patients ◽  
Gynecology And Obstetrics ◽  
Risk Patients

Purpose Patients with high-risk (International Federation of Gynecology and Obstetrics score ≥ 7) gestational trophoblastic neoplasia (GTN) frequently receive etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine (EMA/CO). Between 1979 and 1995, overall survival (OS) with this regimen at our institute was 85.4% with a significant proportion of early deaths (< 4 weeks). Here, we determine whether survival rates have improved in a more recent patient cohort (1995 to 2010). Patients and Methods Patients receiving EMA/CO were identified using the Charing Cross GTN database. Genetic analysis identified nongestational trophoblastic tumors (nGTTs). The use of induction low-dose etoposide 100 mg/m2 and cisplatin 20 mg/m2 (EP; days 1 and 2 every 7 days) since 1995 to reduce early deaths before commencing EMA/CO was noted. Results Four hundred thirty-eight patients received EMA/CO between 1995 and 2010. Six patients had nGTTs, 140 had high-risk disease, and 250 had relapsed/resistant low-risk GTN. OS was 94.3% in high-risk patients (90.4% including nGTTs) and 99.6% in the low-risk group, with a median follow-up time of 4.2 years. All patients with nGTT and seven patients with high-risk GTNs died as a result of drug-resistant disease. EP induction chemotherapy was given to 23.1% of high-risk patients (33 of 140 patients) with a large disease burden, and the early death rate was only 0.7% (n = 1; 95% CI, 0.1% to 3.7%) compared with 7.2% (n = 11 of 151 patients; 95% CI, 4.1% to 12.6%) in the pre-1995 cohort. Conclusion OS after EMA/CO for high-risk GTN has increased by nearly 9%. This reflects a more accurate estimate of OS by excluding nGTTs (3.9%) in patients with atypical presentations using genetic diagnosis. Low-dose induction EP in selected individuals also allows near complete elimination of early deaths. The latter should be considered routinely in high-risk GTN.

The Effect Of Low Dose Intravenous Heparin On Anti-Factor Xa And Antithrombin III

1981 ◽  
Author(s):  
S A Jennings ◽  
B P Heather ◽  
R M Greenhalgh
Keyword(s):  
High Risk ◽  
Low Dose ◽  
Antithrombin Iii ◽  
Risk Group ◽  
Factor Xa ◽  
Low Risk ◽  
Heparin Infusion ◽  
High Risk Patients ◽  
Intravenous Heparin ◽  
Risk Patients

Preoperative blood samples from 17 patients undergoing major abdominal surgery were examined by the thrombelasto-graph saline dilution test, which has previously been shown to be a predictor of the risk of early postoperative deep vein thrombosis (DVT)(Heather et al 1980). By this test 8 patients were predicted to be at low risk of developing a DVT and received no special prophylaxis. 9 patients were considered to be at risk and were treated with a subcutaneous dose of 1000 units of heparin with the premedication together with a low dose of intravenous heparin infusion from the induction of anaesthesia until 2 hours after operation. Plasma antithrombin III (ATIII) concentration and anti-factor Xa activity were measured preoperatively, on day 1 and on day 3. No early DVT occurred, as assessed by I125 fibrinogen scanning, in either the untreated low risk patients or in the high risk patients receiving heparin infusion. The high risk patients had lower levels of ATIII before operation than the low risk patients (75±9%; 98±39%) and significantly lower levels on day 3 (64±25%; 106±34% p<0.02). However, these lowered levels of ATIII appeared in the high risk group to be augmented by the significant increase in anti-factor Xa activity 127±64%. before operation, 217±89%, on day 1 (p<0.02). Furthermore, on day 3 the high risk patients had significantly greater activity than those patients in the low risk group (212±76%; 106±34% p<0.02).These results show that those patients at risk of developing a postoperative DVT had a significantly enhanced activation of anti-factor Xa, as a result of intravenous low dose heparin with the subsequent abolition of early venous thrombosis.

scholarly journals Validation of the High-Risk Prognostic Score Defined By the Presence of Mutations in NRAS or TP53 in a Cohort of 497 Patients with Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-5
Author(s):  
Rosa Ayala ◽  
Pau Montesinos ◽  
Eva Barragán ◽  
Joaquin Martinez-Lopez ◽  
Miguel A. Sanz ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Low Dose ◽  
Prognostic Score ◽  
Low Risk ◽  
Hypomethylating Agents ◽  
Younger Patients ◽  
High Risk Patients ◽  
Risk Patients ◽  
Low Dose Cytarabine

INTRODUCTION Older AML patients have a different mutational landscape compared to younger patients. The prognostic classification of AML proposed by the European Leukemia Net (2017) is based on the presence of mutations in FLT3 (ITD), NPM1, CEBPA, RUNX1, ASXL1 and TP53. However, our group has identified a high-risk prognostic score in older patients with AML, who are undergoing treatment with azacitidine or low-dose cytarabine plus fludarabine, which predict a shorter survival. OBJECTIVE Validation of the previously identified high-risk prognostic score, defined by the presence of mutations in NRAS or TP53, in 3 cohorts of patients with AML who have been studied by NGS with a custom panel in the healthcare practice (Cohort 1: Intensive treatment; cohort 2: Hypomethylating agents and cohort 3: low-dose cytarabine) METHODS The study was conducted on a series of 535 patients diagnosed with AML (mean age 67). Patients evaluated for OS and RFS were 497 cases: intensive treatment (schemes 3+7 or similar; n=238), hypomethylating agents (azacitidine, decitabine; n=113) and treated with low-dose cytarabine (n=146). 38 patients on supportive therapy were excluded. Mutational profile was identified at diagnosis by NGS technique (Ion Torrent System), using a custom panel of 41 genes involved in myeloid pathologies: ASXL1, BCOR, BCORL1, CALR, CBL, CEBPA, DNMT3A, EPAS1, EPOR, ETV6, EZH2, FLT3, IDH1, IDH2, JAK2, KDM6A, KIT, KMT2A, KRAS, MPL, NF1, NPM1, NRAS, PHF6, PRPF40B, RAD21, RUNX1, SETBP1, SF3A1, SF3B1, SH2B3, SMC1A, SRSF2, STAG2, TET2, THPO, TP53, U2AF1, VHL, WT1 y ZRSR2. The mean OS and RFS were compared by means of Kaplan-Meier curves using the log-rank test. The bioinformatics analysis was performed with the SPSS software. RESULTS The median SG and RFS of this series was 10.8 months and 6.9 months respectively. The mutational profile in older patients was different from that analyzed in younger patients. We observed greater presence of mutations in NPM1 in younger patients (34.4 vs 18.6%, p=0.04), while in older than 65 years were identified more mutations in ASXL1 (3.9 vs 16.6%, p&lt;0.01) or RUNX1 (8.6 vs 18.4%, p=0.005). No differences were observed in TP53, NRAS, TET2, DNMT3A and FLT3-ITD. However, we detected differences in VAF distribution of variants with lower VAF in younger patients in NPM1 (0.9 vs 5%, p=0.001), RUNX1 (4.1 vs 9.1%, p=0.003), ASXL1 (1.5 vs 8.2%, p&lt;0.001) and TP53 (5.9 vs 14%, p&lt;0.001) The median OS for intensively treated patients with a low-risk prognostic score was 49.1 months (17.56, 80.60) vs. 18.9 (14.98, 22.79) for high-risk patients (p=0.015). The median RFS was 45.2 months (5.2; 85.14) for low-risk patients vs. 42.1 (18.35; 65.92) for high-risk patients (p=0.167). The median OS for low-risk patients treated with hypomethylating agents was 13.2 months (9.02, 17.47) vs. 4.8 (1.6, 7.9) for patients with a high-risk score (p=0.002). The median RFS was 9.9 months (7.4, 12.3) for low-risk patients vs. 14.9 (10.1, 19.8) for high-risk patients (p=0.682). The median OS for patients treated with low-dose cytarabine was 8.4 months (4.9, 12.1) for low risk vs. 3.1 (1.22, 4.94) for high risk (p&lt;0.001). The median RFS was 6.8 months (5.28, 8.42) for low-risk patients vs. 3.7 (2.75, 4.66) for those with a high-risk score (p=0.008). CONCLUSIONS We have confirm that exist differences in the mutational profile between older and younger AML patients and these differences have implications in the definition of risk of these patients. The prognostic score defined by the presence of mutations in the TP53 and NRAS genes, has been validated as an adverse prognostic factor across the three treatment groups studied (intensive treatment, hypomethylating agents and low-dose cytarabine) for OS, and this score no predict risk of relapse in the cohorts with intensive and hypomethylating treatments at difference to the low-dose cytarabine cohort. ML.M. enjoys a research grant from the Spanish Society of Hematology and Hemotherapy. This work has been financed thanks to the aid PI16/01225 and PI19/01518, from the Instituto de Salud Carlos III (Ministerio de Economía, Industria y Competitividad) and co-financed by the European Development Fund. Disclosures Montesinos: Astellas, Novartis, Janssen: Speakers Bureau; Celgene, Pfizer, Abbvie: Consultancy; Pfizer, Abbvie, Daiichi Sankyo: Research Funding. Martinez-Lopez:Incyte: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Janssen-cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; BMS: Consultancy, Research Funding. Sanz:Teva, Daiichi-Sankyo, Orsenix, AbbVie, Novartis, and Pfizer: Other: Consulting or Advisory Role.

scholarly journals Definition and Validation of a Risk-Stratification Model for Probable or Proven COVID-19 Patients in Emergency Departments: The Revised HOME-CoV Score.

2021 ◽  
Author(s):  
Douillet Delphine ◽  
Riou Jérémie ◽  
Morin Francois ◽  
Mahieu Rafaël ◽  
Chauvin Anthony ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Significant Proportion ◽  
Home Treatment ◽  
Low Risk ◽  
Clinical Criteria ◽  
High Risk Patients ◽  
Risk Patients ◽  
Definition Of ◽  
Original Rule

Abstract The HOME-CoV rule is a list of clinical criteria defined by experts’ consensus, qualifying patients with probable or proven COVID-19 for home treatment when negative. The aims were to define and validate a revised HOME-CoV score, optimizing the original rule. Definition of the revised HOME-CoV score using logistic regression in a prospective multicenter cohort and validation in another cohort of patients who presented to the emergency department with proven or probable COVID-19. The main outcome was non-invasive or invasive ventilation or all-cause death within the 7 days following inclusion. Two threshold values were defined using a sensitivity of > 0.9 and a specificity of > 0.9 to identify low-risk patients and high-risk patients, respectively. The revised HOME-CoV score included seven clinical criteria. In the definition cohort (n=1696), the AUC was 87.6 (95% CI 84.7 to 90.6). The cutoffs to define low-risk and high-risk patients were <2 and >3, respectively. In the validation cohort (n=1304), the AUC was 85.8 (95% CI 80.6 to 91.0) and 85.5 (95% CI 76.8 to 94.1) in the subgroup of patients with positive RT-PCR for SARS-CoV2. A score of < 2 qualified 73% of patients as low risk with a sensitivity of 0.84 (0.66-0.95) and a negative predictive value of 0.99 (0.99-1.00). The revised HOME-CoV score compared favorably with the original rule and other models. The revised HOME-CoV score may allow accurate risk stratification and safely qualify for home treatment, a significant proportion of patients with probable or proven COVID-19.

scholarly journals Individualization in the treatment of resistant forms of gestational trophoblastic neoplasia

2020 ◽  
Vol 66 (6) ◽  
pp. 667-672
Author(s):  
Елена Ульрих ◽  
Gulfiya Teletaeva ◽  
Anna Semenova ◽  
Evgenii Levchenko ◽  
Dariya Ulrikh ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
High Risk ◽  
Combined Treatment ◽  
Low Risk ◽  
Gestational Trophoblastic Neoplasia ◽  
High Risk Patients ◽  
Trophoblastic Tumor ◽  
Ultra High Risk ◽  
Risk Patients ◽  
Line Chemotherapy

Objective: to summarize the experience of treatment patients with resistant forms of gestational trophoblastic neoplasia (GTN). Materials and methods: results of treatment of 15 patients with resistant forms of GTN treated in the N.N. Petrov Research Institute of Oncology through the period 01.01.10-12.11.19 were analyzed. Results: In three out of the 15 patients the tumor was initially characterized as the low-risk (3/15, 20%), the remaining 12 women were from the high-risk group (12/15, 80%). Four out of 12 high-risk patients were ultra-high risk (> 12 points according to the FIGO classification). In low-risk patients with resistant GTN forms EMA-CO therapy proved to be effective as the second line chemotherapy. In eight high-risk patients the combined treatment included the surgical component (hysterectomy in 3 cases, thoracotomy with metastasectomy in 3 cases, hysterotomy with excision of the tumor in 1 case, excision of the tumor from the abdominal wall - in 1 case). In three cases of ultra-high risk GTN, the EMA-EP chemotherapy proved effectiveness, in one of them - without a combination with surgical treatment. Combined treatment was performed in two other cases: in one case with chemotherapy was followed by thoracotomy, metastasectomy, in another - by a gamma knife radiotherapy of brain metastasis. Conclusion: even in cases of low-risk GTN careful monitoring of patients is required, despite adequate treatment among resistant forms. After the failure of methotrexate monochemotherapy with low-risk GTN patients can be successfully treated with EMA-CO chemotherapy. Only rare histological forms (epithelioid trophoblastic tumor, placental site trophoblastic tumor) are not sensitive to drug therapy and require surgical treatment. In cases of ultrahigh-risk GTN with resistance to 1st-line chemotherapy an EMA-EP regimen is effective with or without surgical intervention. Residual “tumor nodes” after completion of treatment and normalization of the HCG level do not always require surgical removal, their dynamic observation is possible, because according to the results of observations, when they were nevertheless excised, no histologically viable tumor tissue was found.

scholarly journals Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Low Risk ◽  
Premalignant Lesions ◽  
High Risk Patients ◽  
European Guidelines ◽  
Progression Of Disease ◽  
Risk Patients ◽  
Progression Risk

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.

scholarly journals A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  
Keyword(s):  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Progression Free Survival ◽  
Low Risk ◽  
Functional Enrichment ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Of Progression ◽  
Risk Patients

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

scholarly journals Does socioeconomic status make a difference? A register-based study on the extent to which cardiovascular screening in patients with inflammatory arthritis leads to recommended follow-up in general practice

RMD Open ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. e000940
Author(s):  
Anette Hvenegaard Kjeldgaard ◽  
Kim Hørslev-Petersen ◽  
Sonja Wehberg ◽  
Jens Soendergaard ◽  
Jette Primdahl
Keyword(s):  
Blood Pressure ◽  
Socioeconomic Status ◽  
High Risk ◽  
Secondary Care ◽  
Inflammatory Arthritis ◽  
Low Risk ◽  
Risk Screening ◽  
High Risk Patients ◽  
Eular Recommendations ◽  
Risk Patients

ObjectiveTo investigate to what extent patients with inflammatory arthritis (IA) follow recommendations given in a secondary care nurse-led cardiovascular (CV) risk screening consultation to consult their general practitioner (GP) to reduce their CV risk and whether their socioeconomic status (SES) affects adherence.MethodsAdults with IA who had participated in a secondary care screening consultation from July 2012 to July 2015, based on the EULAR recommendations, were identified. Patients were considered to have high CV risk if they had risk Systematic COronary Risk Evaluation (SCORE) ≥5%, according to the European SCORE model or systolic blood pressure ≥145 mmHg, total cholesterol ≥8 mmol/L, LDL cholesterol ≥5 mmol/L, HbA1c ≥42 mmol/mol or fasting glucose ≥6 mmol/L. The primary outcome was a consultation with their GP and at least one action focusing on CV risk factors within 6 weeks after the screening consultation.ResultsThe study comprised 1265 patients, aged 18–85 years. Of these, 336/447 (75%) of the high-risk patients and 580/819 (71%) of the low-risk patients had a GP consultation. 127/336 (38%) of high-risk patients and 160/580 (28%) of low-risk patients received relevant actions related to their CV risk, for example, blood pressure home measurement or prescription for statins, antihypertensives or antidiabetics. Education ≥10 years increased the odds for non-adherence (OR 0.58, 95% CI 0.0.37 to 0.92, p=0.02).Conclusions75% of the high-risk patients consulted their GP after the secondary care CV risk screening, and 38% of these received an action relevant for their CV risk. Higher education decreased adherence.

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