A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension

2020 ◽  
Vol 56 (3) ◽  
pp. 2000513
Author(s):  
Stefano Ghio ◽  
Valentina Mercurio ◽  
Federico Fortuni ◽  
Paul R. Forfia ◽  
Henning Gall ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Value ◽  
Survival Rates ◽  
Intermediate Risk ◽  
Chi Squared ◽  
Risk Patients ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Question addressedEchocardiography is not currently considered as providing sufficient prognostic information to serve as an integral part of treatment goals in pulmonary arterial hypertension (PAH). We tested the hypothesis that incorporation of multiple parameters reflecting right heart function would improve the prognostic value of this imaging modality.Methods and main resultsWe pooled individual patient data from a total of 517 patients (mean age 52±15 years, 64.8% females) included in seven observational studies conducted at five European and United States academic centres. Patients were subdivided into three groups representing progressive degrees of right ventricular dysfunction based on a combination of echocardiographic measurements, as follows. Group 1 (low risk): normal tricuspid annular plane systolic excursion (TAPSE) and nonsignificant tricuspid regurgitation (TR) (n=129); group 2 (intermediate risk): normal TAPSE and significant TR or impaired TAPSE and nondilated inferior vena cava (IVC) (n=256); group 3 (high risk): impaired TAPSE and dilated IVC (n=132). The 5-year cumulative survival rate was 82% in group 1, 63% in group 2 and 43% in group 3. Low-risk patients had better survival rates than intermediate-risk patients (log-rank Chi-squared 12.25; p<0.001) and intermediate-risk patients had better survival rates than high-risk patients (log-rank Chi-squared 26.25; p<0.001). Inclusion of other parameters such as right atrial area and pericardial effusion did not provide added prognostic value.Answer to the questionThe proposed echocardiographic approach integrating the evaluation of TAPSE, TR grade and IVC is effective in stratifying the risk for all-cause mortality in PAH patients, outperforming the prognostic parameters suggested by current guidelines.

scholarly journals Appropriate secondary prevention and clinical outcomes after acute myocardial infarction according to atherothrombotic risk stratification: The FAST-MI 2010 registry

2018 ◽  
Vol 26 (4) ◽  
pp. 411-419 ◽  
Author(s):  
Victoria Tea ◽  
Marc Bonaca ◽  
Chekrallah Chamandi ◽  
Marie-Christine Iliou ◽  
Thibaut Lhermusier ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
High Risk ◽  
Secondary Prevention ◽  
High Risk Patients ◽  
Risk Patients ◽  
St Elevation ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background Full secondary prevention medication regimen is often under-prescribed after acute myocardial infarction. Design The purpose of this study was to analyse the relationship between prescription of appropriate secondary prevention treatment at discharge and long-term clinical outcomes according to risk level defined by the Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS-2P) after acute myocardial infarction. Methods We used data from the 2010 French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction (FAST-MI) registry, including 4169 consecutive acute myocardial infarction patients admitted to cardiac intensive care units in France. Level of risk was stratified in three groups using the TRS-2P score: group 1 (low-risk; TRS-2P=0/1); group 2 (intermediate-risk; TRS-2P=2); and group 3 (high-risk; TRS-2P≥3). Appropriate secondary prevention treatment was defined according to the latest guidelines (dual antiplatelet therapy and moderate/high dose statins for all; new-P2Y12 inhibitors, angiotensin-converting-enzyme inhibitor/angiotensin-receptor-blockers and beta-blockers as indicated). Results Prevalence of groups 1, 2 and 3 was 46%, 25% and 29% respectively. Appropriate secondary prevention treatment at discharge was used in 39.5%, 37% and 28% of each group, respectively. After multivariate adjustment, evidence-based treatments at discharge were associated with lower rates of major adverse cardiovascular events (death, re-myocardial infarction or stroke) at five years especially in high-risk patients: hazard ratio = 0.82 (95% confidence interval: 0.59–1.12, p = 0.21) in group 1, 0.74 (0.54–1.01; p = 0.06) in group 2, and 0.64 (0.52–0.79, p < 0.001) in group 3. Conclusions Use of appropriate secondary prevention treatment at discharge was inversely correlated with patient risk. The increased hazard related to lack of prescription of recommended medications was much larger in high-risk patients. Specific efforts should be directed at better prescription of recommended treatment, particularly in high-risk patients.

Survival of Patients with High-Risk Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

2021 ◽  
Vol 104 (6) ◽  
pp. 895-901
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
High Risk ◽  
Congenital Heart ◽  
First Year ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD) with uncorrected left-to-right shunts. Currently, no consensus guideline exists on the management of PAH-CHD in children, especially those who do not meet operability criteria. Objective: To compare survival between three groups of high-risk PAH-CHD, group 1: total correction including both surgical and percutaneous intervention, group 2: palliative treatment, and group 3: conservative with medical treatment group. Materials and Methods: All pediatric patients with PAH-CHD that underwent cardiac catheterization between January 1, 2008 and December 31, 2017 were retrospectively reviewed. Inclusion criteria were high risk PAH-CHD patients who had pulmonary vascular resistance (PVR) greater than 6 Wood unit·m² and PVR-to-SVR ratio greater than 0.3 evaluated in room air. Exclusion criteria were younger than three months of age, severe left side heart disease with pulmonary capillary wedge pressure greater than 15 mmHg, obstructive total pulmonary venous return, and single ventricle physiology. The Kaplan-Meier analysis was performed from the date of PAH diagnosis to the date of all-cause mortality or to censored date at last follow-up. Results: Seventy-six patients with a median age at diagnosis of 27.5 months (IQR 14.5 to 69.0 months) were included in this study. The patients were divided into three subgroups and included 38 patients (50.0%) in group 1, six patients (7.9%) in group 2, and 32 patients (42.1%) in group 3. The median follow-up time was 554 days (IQR 103 to 2,133 days). The overall mortality was 21.7%. One-year survival in patients with simple lesion in group 1 and 3 were 79.5% and 87.5% and patients with complex lesions in group 1, 2, and 3 were 93.8%, 83.3%, and 73.1%, respectively. The results showed that most mortalities occurred in the first year. There were no statistically significant differences in survival among difference types of treatment (log rank test, p=0.522). Conclusion: The mortality of high-risk PAH-CHD patients were not different among those who underwent corrective surgery, palliative, or conservative treatment. The mortality was high in the first year after PAH diagnosis and remain stable afterward. Management decision for an individual with high-risk PAH-CHD patients requires comprehensive clinical assessment to balance the risks and benefits before making individualized clinical judgment. Keywords: Pulmonary hypertension; Congenital heart disease; High-risk patients

scholarly journals Results of neuroblastoma treatment in Lithuania: a single centre experience

2017 ◽  
Vol 24 (2) ◽  
pp. 128-137 ◽  
Author(s):  
Austėja Juškaitė ◽  
Indrė Tamulienė ◽  
Jelena Rascon
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Age At Diagnosis ◽  
Mycn Amplification ◽  
Disease Group ◽  
High Risk Patients ◽  
Risk Patients ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background. Neuroblastoma (NB) is the most common extracranial solid tumour in children. This is a very rare disease with heterogeneous biology varying from complete spontaneous regression to a highly aggressive tumour responsible for 15% of malignancy-related death in early childhood. Analyses of survival rates in Europe have shown a considerable difference between Northern/Western and Eastern European countries. Treatment results of NB in Lithuania have never been analyzed. Aim. To assess the survival rate of children with NB according to initial spread of the disease, age at diagnosis, the MYCN amplification, risk group, and treatment period. Patients and methods. A retrospective single-centre analysis of patients’ records was performed. Children diagnosed and treated for NB between 2000 and 2015 at the Centre of Paediatric Oncology and Haematology of the Children’s Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos were included. The patients were divided into three groups according to the spread of the disease: group 1 – patients with local NB older than 12 years of age; group 2 – stage IV patients, also called the M stage; group 3 – infants with stages 4S and MS. The patients were stratified into three risk groups – low, intermediate and high risk. Estimates of five-year overall survival (OS5y) were calculated using the Kaplan-Meier method comparing survival probability according to spread of the disease, age at diagnosis, the MYCN amplification, risk group and treatment period (2000–2007 vs 2008–2015). Results. Overall 60 children (31 girls and 29 boys) with NB were included. The median age at diagnosis was 1.87 years (ranged from 4 days to 15 years). Seventy-eight percent of cases were found to be differentiated or undifferentiated NB, 22% – ganglioneuroblastoma. The local form of the disease was predominant: 57% (34/60) of patients were allocated to the group 1, 37% (22/60) with initial metastatic disease were assigned to group 2, and infants with 4S or MS stage comprising 7% (4/60) allocated to group 3, respectively. The probability of OS5y for the entire cohort was 71% with the median follow-up of 8.8 ± 4.8 years. The probability of OS5y for local disease (group 1) was significantly higher compared to metastatic disease (group 2) (94% vs. 34%, p = 0.001, respectively) as well as for infants compared to children older than 12 months at the time of diagnosis (90% vs 60%, p = 0.009, respectively). The MYCN gene amplification had a negative influence on OS5y, with 78% of MYCN-negative patients surviving in comparison to 40% of MYCN-positive patients who did not survive (p = 0.153). The high-risk patients had significantly worse OS5y than children with intermediated or low risk (35% vs. 82% vs. 100%, respectively, p = 0.001). Comparison of OS5y between two treatment periods in the entire patient population revealed a non-significant increase in survival from 66% in the 2000–2007 period to 82% in the 2008–2015 period (p = 0.291), mostly due to a dramatic improvement achieved for high-risk patients whose survival rate increased from 9% in the 2000–2007 period to 70% in the 2008–2015 period (p = 0.009). Conclusions. There was a slight predominance of low-risk patients, probably due to a higher number of infants. A better probability of OS5y was confirmed in infants with local disease and in MYCN-negative patients. The OS5y for children treated for NB at our institution over 16 years increased from 66% in the 2000–2007 period to 82% in the 2008–2015 period with the most significant improvement achieved for high risk patients. The current survival rate of children treated for NB at our institution is in line with the reported numbers in Northern and Western European countries.

scholarly journals Mean arterial pressure within 24 hours of admission predicts short-term prognosis in patients with intermediate-risk and high-risk pulmonary embolism

2020 ◽  
Author(s):  
Jialong Chen ◽  
Jing Lin ◽  
Dansen Wu ◽  
XiaoLan Guo ◽  
XiuHua Li ◽  
...  
Keyword(s):  
High Risk ◽  
Cox Regression ◽  
Hospital Death ◽  
Intermediate Risk ◽  
Short Term ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

Abstract Objective: Pulmonary embolism is a terrible cardiovascular condition with considerable morbidity and mortality. Previous studies have investigated systolic blood pressure (systolic BP) and diastolic blood pressure (diastolic BP) as being related to 30-day and in-hospital mortality. We aimed to determine whether the average mean arterial pressure (aMAP) in the first 24 hours of hospital admission is useful in predicting short-term outcomes of intermediate-risk and high-risk PE patients. Method: We conducted a single-center retrospective study. From May 2012 to April 2019, 122 intermediate-risk and high-risk PE patients were included. The primary outcome was in-hospital mortality. The secondary outcome was adverse events. ROC curves and cut-off values for aMAP predicting in-hospital death were computed. According to cut-off values, we categorized five groups defined as follows: group 1: aMAP<70 mmHg; group 2: 70 mmHg≤aMAP<80 mmHg; group 3: 80 mmHg≤aMAP<90 mmHg; group 4: 90 mmHg≤aMAP<100 mmHg; and group 5: aMAP≥100 mmHg. Cox regression models were calculated to investigate associations between aMAP and in-hospital death. Results: In the study group of 122 patients, 15 patients (12.30%) died in the hospital due to PE. ROC analysis for MAP predicting in-hospital death revealed an AUC of 0.729 with a cut-off value of 79.4 mmHg. Cox regression models showed a significant association between in-hospital death and aMAP group 1 (ref), aMAP group 2 (OR 1.680, 95% CI 0.020-140.335), aMAP group 3 (OR 0.003, 95% CI 0.0001-0.343), aMAP group 4 (OR 0.006, 95% CI 0.0001-1.671), and aMAP group 5 (OR 0.003, 95% CI 0.0001-9.744). In particular, those with an aMAP of 80-90 mmHg suffer from minimum adverse events. Conclusion: The prognostic role of MAP during the first 24 hours of hospital admission should be emphasized in patients with PE. The optimal range of MAP for intermediate-risk and high-risk PE patients may be 80 to 90 mmHg.

Coalescence of the German-Austrian and IMRAW Cytogenetic MDS Databases: Modification of Patient Risk Groups.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2468-2468 ◽  
Author(s):  
Christian Steidl ◽  
Julie Schanz ◽  
Michelle M. Le Beau ◽  
John M. Bennett ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Risk Stratification ◽  
Risk Group ◽  
Intermediate Risk ◽  
Risk Patients ◽  
Group 3 ◽  
Group 2 ◽  
Stratification System ◽  
Risk Stratification System ◽  
Group 1

Abstract Introduction The International Prognostic Scoring System (IPSS) for evaluating prognosis in myelodysplastic syndromes (MDS) has been the standard for risk assessment in this disease for the past ten years. Based on a patient cohort comprising 816 primary MDS patients from the IMRAW, a refined bone marrow cytogenetic classification system was introduced. Recently, the GACMSG published cytogenetic data including 1155 primary MDS patients treated with supportive care only. Coalescence of these two large databases offered the opportunity to analyze the cytogenetic data jointly and to propose a modified cytogenetic risk stratification system. Patients and Methods 1971 patients with karyotype and survival data originating from the IMRAW and the GACMSG cohorts were included in this study. The collectives comprised patients with primary MDS treated with supportive care, only allowing short courses of low dose oral chemotherapy or hemopoietic growth factors. By reviewing the ISCN karyotypes, the patients were grouped into cytogenetic categories defined by median survival (MS) (Haase et al, Blood in press). The categories comprised karyotypes with the respective abnormality alone or in combination with one additional anomaly. Karyotypes with 3, or more than 3 abnormalities were considered separate categories. Results We found 15 cytogenetic categories each comprising 10 or more patients. These categories could be combined into 4 prognostic groups according to the MS: Group 1 (MS&gt;3 years): normal karyotype, del(5q), del(12p), del(20q), +21, −Y, −X; Group 2 (1.5–3 years): +1/+1q/t(1q), add(3q)/inv(3q)/del(3q)/t(3q), +8, del(11q); Group 3 (1–1.5 years): 3 anomalies, −7, del(7q); Group 4 (MS&lt;1 year): &gt;3 anomalies. Further stratification of these categories led to a system with 4 distinct risk strata (number of patients): good (1374), int-1 (160), int-2 (99), and poor (166). Only 172 patients (9% of all patients) could not be classified according to this system. Survival analysis of these 4 groups showed distinct MS (Log-rank test: p&lt;0.0001): good, 50 months; int-1, 24 months; int-2, 15 months; poor, 6 months. When combining the non-classified patients into one group MS was 31 months. When comparing this new classification system with the original system defined by the IPSS, 66 formerly intermediate risk patients shifted into the good risk group and 114 poor risk patients into the intermediate risk group. Discussion Combined examination of the two databases introduces 7 new cytogenetic categories with distinct survival times as compared to the IPSS; Group 1: del(12p), +21, −X; Group 2: +1/+1q/t(1q), add(3q)/inv(3q)/del(3q)/t(3q), del(11q); Group 3: 3 anomalies. Based on previously published data, the proposed system combines non-complex karyotypes in one category and distinguishes karyotypes with 3 or more than 3 abnormalities. With respect to future refined integrative scoring in MDS we present an approach that distinguishes groups of intermediate risk and a heterogeneous group of as yet unclassified rare cases harboring uncertain prognoses. In the latter cases, risk assessment should be based on other prognostic parameters rather than assigning an intermediate risk to this group. This new cytogenetic risk stratification system needs to be validated and tested using multivariate approaches.

Clinical outcomes of single-dose cardioplegia in high-risk coronary bypass

2020 ◽  
pp. 021849232096643
Author(s):  
Serdar Gunaydin ◽  
Orhan Eren Gunertem ◽  
Seyhan Babaroglu ◽  
Atike Tekeli Kunt ◽  
Kevin McCusker ◽  
...  
Keyword(s):  
Single Dose ◽  
Coronary Artery ◽  
High Risk ◽  
Myocardial Protection ◽  
Artery Bypass ◽  
Bypass Grafting ◽  
Risk Patients ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background Despite the increasing popularity of single-dose cardioplegia techniques in coronary artery bypass grafting, the time window for successful reperfusion remains unclear. This study aimed to compare different cardioplegic techniques based on early and 30-day clinical outcomes via thorough monitoring. Methods This prospective cohort study included high-risk patients undergoing coronary artery bypass grafting and receiving 3 different types of cardioplegia between January 2017 and June 2019. Group 1 ( n = 101) had a single dose of del Nido cardioplegia, group 2 ( n = 92) had a single dose of histidine-tryptophane-ketoglutarate, and group 3 ( n = 119) had cold blood cardioplegia. Patients were examined perioperatively by memory loop recording and auto-triggered memory loop recording for 30 days, with documentation of predefined events. Results Interleukin-6 and cardiac troponin levels in group 1 were significantly higher than those in groups 2 and 3. The incidence of predefined events as markers of inadequate myocardial protection was significantly higher group 1, with more frequent atrial fibrillation attacks and more hospital readmissions. The readmission rate was 17.6% in group 1, 9% in group 2, and 8% in group 3. Conclusions Our data demonstrate the long-term efficacy of cardioplegic techniques, which may become more crucial in high-risk patients who genuinely have a chance to benefit from adjunct myocardial protection. Patients given del Nido cardioplegia had a significantly more prominent inflammatory response and higher troponin levels after cardiopulmonary bypass. This group had issues in the longer term with significantly more cardiac events and a higher rehospitalization rate.

P823Clinical benefits of high dose statins according to the atherothrombotic risk stratification after acute myocardial infarction. The FAST-MI registries

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Puymirat ◽  
V Tea ◽  
F Schiele ◽  
C Baixas ◽  
X Lamit ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
High Risk ◽  
Risk Stratification ◽  
High Dose ◽  
Intermediate Risk ◽  
Group 3 ◽  
Baseline Characteristics ◽  
Group 2 ◽  
Group 1

Abstract Background High dose statins prescription are strongly recommended in patients after acute myocardial infarction (AMI) in current guidelines. Aim We aimed to assess the clinical impact on major cardiovascular events (MACE) of high dose statins prescription at discharge according to the atherothrombotic risk stratification in a routine-practice population of AMI patients, and to determine the relative efficacy of currently recommended high dose statins according to risk level. Methods We used data from the 2005, and 2010 FAST-MI nationwide registries, including 7,839 patients with AMI (54% STEMI) admitted to cardiac intensive care units in France. Atherothrombotic risk stratification was performed using the TIMI Risk Score for Secondary Prevention (TRS-2P). Patients were defined in 3 categories: Group 1 (Low-risk; TRS-2P=0/1); Group 2 (Intermediate-risk; TRS-2P=2); and, Group 3 (High-risk; TRS-2P≥3). Baseline characteristics and the rate of MACE (defined as death, stroke or re-MI) at 5-years were analyzed according to TRS-2P categories, and the impact of high dose statins (i.e. atorvastatin 80mg/day or rosuvastatin 20mg/day) at discharge was compared using Cox multivariate analysis among the different risk groups. Results A total of 7,348 patients discharge alive and in whom TRS-2P was available. Prevalence of Groups 1, 2, and Group 3 was 41.5%, 25% and 33.5% respectively. Over the 5-year period, the overall risk of patients admitted for AMI decreased in Group 3 from 41% to 27% (P<0.001). Optimal medical therapy at discharge (defined by the use of dual antiplatelets therapy, statins for all; and, beta-blocker, ACE-I or ARB when appropriate) was 53% in Group 3, 67% in Group 2, and 80% in Group 1 (P<0.001). High dose statins prescription at discharge was 18.5% (Group 3), 31.3% (Group 2), and 41.3%% (Group 1). High dose statins prescription was associated with lower MACE at five-year in the overall population compared to patients with intermediate/low dose statins or without statin prescription (14.3% vs. 29.6%; Δ absolute risk= 15.3%; HR adjusted on baseline characteristics and management: 0.86, 0.76–0.97, P=0.018). The decrease in MACE at five-year was observed in all TRS-2P categories (Group 1: 8.1% vs. 10.7%, Δ= 2.6%; Group 2: 14.8% vs. 21.6%, Δ= 6.8%; Group 3: 30.8% vs. 51.6%, Δ= 20.8%). Finally, the benefits of high dose statins in low- and intermediate-risk was lower (HR=0.97; 95% CI, 0.74–1.26; P=0.81 and HR=1.06; 95% CI, 0.81–1.38; P=0.81) compared to high-risk patients (HR=0.78; 95% CI, 0.65–0.94; P=0.008). Five-year events-free survival Conclusions High dose statins prescription at discharge after AMI was associated with lower MACE at five-year regardless of the atherothrombotic risk stratification, although the highest absolute reduction was found in the high risk TRS2P class. Acknowledgement/Funding The FAST-MI 2010 registry is a registry of the French Society of Cardiology, supported by unrestricted grants from: Merck, the Eli-Lilly-Daiichi-Sanky

scholarly journals Can we safely reduce the administration of 131-iodine in patients with differentiated thyroid cancer? – experience of the Brugmann hospital in Brussels

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Laura Iconaru ◽  
Felicia Baleanu ◽  
Georgiana Taujan ◽  
Ruth Duttmann ◽  
Linda Spinato ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
High Risk ◽  
Differentiated Thyroid Cancer ◽  
Low Risk ◽  
Response To Treatment ◽  
Intermediate Risk ◽  
Risk Of Recurrence ◽  
Risk Patients ◽  
Group 2 ◽  
Group 1

Abstract Background 131-iodine (131I) administration after surgery remains a standard practice in differentiated thyroid cancer (DTC). In 2014, the American Thyroid Association presented new guidelines for the staging and management of DTC, including no systematic 131I in patients at low-risk of recurrence and a reduced 131I activity in intermediate risk. The present study aims at evaluating the rate of response to treatment following this new therapeutic management compared to our previous treatment strategy in patients with DTC of different risks of recurrence. Methods Patients treated and followed up for DTC according to the 2014-ATA guidelines (Group 2) were compared to those treated between 2007 and 2014 (Group 1) in terms of general characteristics, risk of recurrence (based on the 2015-ATA recommendations), preparation to 131I administration, cumulative administered 131I activity and response to treatment. Results In total, 136 patients were included: 78 in Group 1 and 58 in Group 2. The two groups were not statistically different in terms of clinical characteristics nor risk stratification: 42.3% in Group 1 and 31% in Group 2 were classified as low risk, 38.5 and 48.3% as intermediate risk and 19.2 and 20.7% as high risk (P = 0.38). Two patients (one in each group) with distant metastases were excluded from the analysis. Preparation to 131I administration consisted in rhTSH stimulation in 23.4% of the patients in Group 1 and 100% in Group 2 (p < 0.001). 131I was administered to 46/77 patients (59.7%) in Group 1 (5 at low risk of recurrence) and 38/57 patients (66.7%) in Group 2 (0 with a low risk). Among the patients treated by 131I, median cumulative activity was significantly higher in Group 1 (3.70GBq [100 mCi] range 1.11–11.1 GBq [30–300 mCi]) than in Group 2 (1.11 GBq [30 mCi], range 1.11–7.4 GBq [30–200 mCi], P < 0.001). Complete response was found in 90.9% in Group 1 vs. 96.5% in Group 2 (P = 0.20). Conclusions Using the 2015-ATA evidence-based guidelines for the management of DTC, meaning no 131I administration in low-risk patients, a low activity in intermediate and even high risk patients, and a systematic use of rhTSH stimulation before 131I therapy allowed us to reduce significantly the median administered 131I activity, with a similar rate of complete therapeutic response.

scholarly journals Combined Infusion of Anti-CD19 and Anti-Bcma CART Cells after Early or Later Transplantation in the Front Line Was Superior to Salvage Therapy for High Risk MM

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1949-1949 ◽  
Author(s):  
Xiaolan Shi ◽  
Lingzhi Yan ◽  
Jingjing Shang ◽  
Liqing Kang ◽  
Song Jin ◽  
...  
Keyword(s):  
High Risk ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Front Line ◽  
Risk Patients ◽  
Group 3 ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

Background: Multiple myeloma (MM) is an incurable plasma cell malignancies despite the advent of numerously new drugs especially for high risk patients. Our previous study showed good response for the de novo high risk patients who received CD19 and BCMA-specific CART cell therapy after ASCT in the front line with mild CRS and other side effects (reported on the 2018 ASH meeting). To determine the best time to do ASCT and CART cell treatment for those patients, we retrospectively analyzed the patients' outcome according to their time to do autologous transplantation (NCT 03455972). Methods:The high risk MM patients defined in this study were in R-ISS stage III, IgD/IgE type, or with measurable EMD,or who only achieved PR or less after 4 cycles of triplet induction or relapsed. Lymphocytes were collected from PBSCs and cultured with an anti-CD3 monoclonal antibody to activate T-cell proliferation after stem cell collection. The cells were transduced with recombinant lentiviral verctors which respectively contained the anti-BCMA or anti-CD19 single chain variable fragment (scFv), the cytoplasmic portion of the OX40 and CD28 costimulatory moiety, and the CD3z T-cell activation domain. This is the new third generation CAR technique applied in clinic. BuCy or Melphalan were used as conditioning, followed by infusion of autologous stem cells. CART-19 (1×107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused directly on d14 to d20 after transplantation. The cytokine release syndrome (CRS) was graded according to the UPen cytokine release syndrome grading system. Neurotoxic side effects and other toxicities were assessed according to the CARTOX and CTCAE v 4.03. Plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-17A proteins were determined with a cytokine kit. IMiDs alone were given as maintenance therapy. Responses were assessed by IMWG criteria. 10-color flow cytometry was used to monitor MRD regularly after CART treatment. The median of follow-up was 13 (1~23) months. Results: To date, 32 patients have completed the CART cells infusion (Table 1). The median age was 53 years with 24 male and 8 female. CRS occurred in 31 patients (97%) with grade 1 or 2 and just 1 patient (3%) with grade 3. Tocilizumab was used to treating only one patient with grade 3 CRS. Six patients needed to use low-dose vascular active drugs. Other acute and chronic toxicities were slight and reversible. The ORR was 100% (32/32) in this study, with 72% of patients achieved CR or above. There was no TRM or neurologic complications or administration of corticosteroid. All patients were divided into three groups according to their time to transplant. Group 1 underwent ASCT and CART cell treatment as first line therapy; Group 2 underwent ASCT and CART cell treatment at second line because of induction failure or re-induction after PD or relapse; Group 3 underwent salvage ASCT and CART treatment at third line or more after disease progress or relapse.With a median follow-up of 13 months, the latest response of CR and above were 78% in group 1, 100% in group 2 and 44% in group 3. Except the group 3 patients, MRD negativity in BM of the other two groups increased continuously after CART therapy, and some patients achieved MRD negativity at the level 10-6 (shown in Table 1). Patients in group 1 and 2 were in continuous response but 5/9 (56%) patients relapsed in group 3 and 2 patients died of disease. The median PFS and OS of the patients in three groups were all not reached but 1-year PFS was 100%, 100%, 68% for group1, 2, 3 respectively (p<0.05); 2-year OS was 100%, 100%, 64% for each group (p<0.05) (Figure 1). Conclusions: Combined infusion of anti-CD19 and anti-BCMA CART cells after ASCT for high risk MM was safe and effective, especially as conjunction therapy to early or later transplant at front line even with primary resistant disease or early disease progress. For those RRMM patients, CART cell therapy followed by ASCT seems to be better to prolong patients' PFS than CART treatment alone with FC chemotherapy reported in our another study (NCT 03196414). Disclosures No relevant conflicts of interest to declare.

scholarly journals FRI0276 EARLY TREATMENT WITH ANTI-TNF IS ASSOCIATED WITH HIGHER RESPONSE RATES IN PATIENTS WITH ACTIVE AXSPA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 725.2-725
Author(s):  
S. Gulle ◽  
İ. Sari ◽  
E. Durak Ediboglu ◽  
H. Candan ◽  
F. Onen ◽  
...  
Keyword(s):  
Survival Rates ◽  
Response Rates ◽  
Retention Rates ◽  
Symptom Duration ◽  
Early Disease ◽  
Drug Retention ◽  
Predictors Of Response ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background:Treatment options for axial spondyloarthritis (axSpA) is currently limited, and up to 40% of the patients require biologic therapies to control symptoms. Early commencement of biologics suggested to have higher response rates but data regarding this subject is limited.Objectives:The primary aim was to investigate tumor necrosis factor inhibitor (TNFi) response and retention rates in axSpA patients who were treated in the early disease period (symptom duration (≤5 years). Our secondary aim was to identify factors predicting response to TNFi.Methods:Adult axial SpA patients who started TNFi treatments within the five years of their symptoms were identified and defined as “Group 1”. Patients whose TNFi treatments started five years after their initial symptoms served as a control group (Group 2: 5-10 years and Group3: ≥10 years). Response and survival rates at 6, 12, and 24 months were calculated. Predictors of response on TNFi survival at 24 months were also analyzed.Results:There was a total of 364 axiSpA (Group 1: 95, Group 2: 82 and Group 3: 187) patients in the study (69.8% male, 46.8±12.6 years). Group 1 patients tended to be younger, with a lower baseline CRP titers and lower HLA–B27 rate compared to the other groups. Drug survival rates were similar between the groups. This finding also remained similar when AS and nraxSpA patients analyzed separately. However, regardless of symptom duration, the drug retention rates were significantly higher in the AS group than in nraxSpA (Table 2). ASAS40 responses were higher in Group 1 than in Group 3 both at 12 and 24 months. Predictors of response based on ASAS40 at 24 months were treatment within the five years of the symptoms (OR:2.2) and age at baseline (OR:0.97) in univariate analysis. However, baseline ASDAS (OR:1.4) was the only factor in multiple regression.Conclusion:In this study we showed the following: 1) TNFi started in the early disease course resulted in a better ASAS40 response at both 12 and 24 months, 2) TNFi timing (started in the early or late disease period) seems not affecting drug retention rates, and 3) baseline disease activity is the most important predictor in achieving ASAS40 response at 24 months.Disclosure of Interests:None declared

Sign in / Sign up

Export Citation Format

Share Document