Assessment of Cardiovascular Events in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4031-4031
Author(s):  
Katia B.B. Pagnano ◽  
Paola Morelato Assunção ◽  
Roberto Zullli ◽  
Marcia T Delamain ◽  
Gislaine OLIVEIRA Duarte ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Cardiovascular Events ◽  
Kinase Inhibitors ◽  
Risk Groups ◽  
Arterial Disease ◽  
Baseline Risk ◽  
Advisory Committees ◽  
Coronary Arterial Disease ◽  
Very High

Abstract Introduction : Treatment with tyrosine kinase inhibitors (TKIs) has dramatically increased the overall survival of patients with chronic myeloid leukemia (CML) but second generation TKI has been associated with an increased risk of cardiovascular events. Objectives: The aim of this study was to evaluate the incidence of cardiovascular adverse events (CVE) in CML patients treated with TKIs and to correlate with the cardiovascular (CV) risk of the patients. Methods: this is a retrospective analysis of consecutive CML patients treated with TKIs between 2005 and 2013at our Institution. Baseline risk factors for CV diseases were collected at baseline and included age, arterial hypertension (AH), dyslipidemia, obesity, hypothireoidism, smoking, diabetes mellitus (DM), coronary artery disease and chronic renal failure. Cardiovascular events during TKI treatment were collected and included: myocardial infarction, unstable angina, peripheral arterial disease, stroke, arrythmia,hypertension and cardiac failure. Cardiovascular risk was calculated using the SCORE chart of the European Society of Cardiology and patients were classified in low, moderate, high and very high risk. Results: We analyzed CML patients treated with imatinib (n=117), dasatinib (n=91) and nilotinib (n=60). The median time of follow-up was 748, 519 and 851 days, respectively. Baseline risk factors: 90 patients (38,5%) had hypertension, 34 (14,5%) DM, 67 (28,6%) dyslipidemia, 51 (21,8%) obesity, 22 (9,4%) hypothyroidism, 14 (6%) coronary arterial disease, 21 (9%) systolic cardiac dysfunction, 4 (1,7%) stroke, 20 (8,5%) chronic kidney failure and 36 (15,4%) were smokers. SCORE chart classification: 106 patients (39,5%) were in the low-risk category, 70 (26%) in the moderate risk, 46 (17,2%) in the high risk, 46 (17,2%) in the very high risk group. Overall, the cumulative incidence of CVE was 4.1%. Five (5.5%) events occurred during dasatinib treatment (P=0.015), 6 (10%) events during nilotinib and no events during imatinib treatment (P=0.001). The incidence of CVE was 10.8% in the high and very high-risk groups and 0.52% in moderate and low risk group (P≤0.001). The incidence of arterial ischemic events (AIE) was 10% (n=6) in patients treated with nilotinib, 2.2% (n=2) with dasatinib and 0% with imatinib (P≤0.001). Arterial events were exclusively observed in high and very high-risk groups (8 events, 8.7%) (P≤0.001). The risk factors associated with a higher risk of CVE were hypertension (P≤0.001), dyslipidemia (P≤0.001), coronary arterial disease (P=0.003), congestive heart failure (P=0.002) and chronic renal failure (P=0.011). Disease progression was the main cause of death in all groups. Conclusions: CVE were more frequent in patients treated with second generation TKIs. AIE were more frequent in patients treated with nilotinib, in those having a high or very high risk SCORE. The CV risk stratification of CML patients before and during TKI therapy can help in TKI selection and to identify patients at high risk, in order to reduce the morbidity and mortality associated with CVE. Disclosures Pagnano: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Miers-Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Abstract P275: Demographic and Clinical Profile of Patients with Risk Factors for Coronary Heart Disease (CHD) Defined by National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III Guidelines

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
David M Kern ◽  
Sanjeev Balu ◽  
Ozgur Tunceli ◽  
Swetha Raparla ◽  
Deborah Anzalone
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Groups ◽  
Lipid Lowering ◽  
High Risk Patients ◽  
Low Hdl ◽  
Risk Patients ◽  
Artery Disease ◽  
Very High ◽  
Statin Use

Introduction: This study aimed to compare the demographic and clinical characteristics of patients with different risk factors for CHD as defined by NCEP ATP III guidelines. Methods: Dyslipidemia patients (≥1 medical claim for dyslipidemia, ≥1 pharmacy claim for a statin, or ≥1 LDL-C value ≥100 mg/dL [index date]) aged ≥18 y were identified from the HealthCore Integrated Research Environment from 1/1/2007-7/31/2012. Patients were classified as low risk (0 or 1 risk factor): hypertension, age ≥45 y [men] or ≥55 y [women], or low HDL-C), moderate/moderately high risk (≥2 risk factors), high risk (having CHD or CHD risk equivalent), or very high risk (having ACS or other established cardiovascular disease plus diabetes or metabolic syndrome). Demographics, comorbidities, medication use and lipid levels during the 12 months prior, and statin use during the 6 months post-index date were compared across risk groups (very high vs each other risk group). Results: There were 1,524,351 low-risk (mean age: 47 y; 45% men), 242,357 moderate-risk (mean age: 58 y; 59% men), 188,222 high-risk (mean age: 57 y; 52% men), and 57,469 very-high-risk (mean age: 63 y; 61% men) patients identified. Mean Deyo-Charlson comorbidity score differed greatly across risk strata: 0.20, 0.33, 1.26, and 2.22 from low to very high risk (p<.0001 for each). Compared with high-risk patients, very-high-risk patients had a higher rate of ischemic stroke: 5.4% vs 4.1%; peripheral artery disease: 17.1% vs 11.6%; coronary artery disease: 8.5% vs 8.2%; and abdominal aortic aneurysm: 2.3% vs 2.0% (p<.05 for each). Less than 1% of the total population had a prior prescription for each non-statin lipid-lowering medication (bile acid sequestrants, fibrates, ezetimibe, niacin, and omega-3). Very-high-risk patients had lower total cholesterol (very-high-risk mean: 194 mg/dL vs 207, 205, and 198 mg/dL for low-, moderate-/moderately-high-, and high-risk patients, respectively) and LDL-C (very-high-risk mean: 110 mg/dL vs 126, 126, and 116 mg/dL for the other risk groups; p<.0001 for each); higher triglycerides (TG) (very-high-risk mean: 206 mg/dL vs 123, 177, and 167 mg/dL for the other groups; p<.0001 for each); and lower HDL-C (very-high-risk mean: 45 mg/dL vs 57 [p<.0001], 45 [p=.006], and 51 mg/dL [p<.0001]). Statin use was low overall (15%), but higher in the very-high-risk group (45%) vs the high- (29%), moderate-/moderately-high- (18%), and low- (12%) risk groups (p<.0001 for each). Conclusions: Despite a large proportion of patients having high lipid levels, statin use after a dyslipidemia diagnosis was low: ≥80% of all patients (and more than half at very high risk) failed to receive a statin, indicating a potentially large population of patients who could benefit from statin treatment. Prior use of non-statin lipid-lowering medications was also low considering the high TG and low HDL-C levels among high-risk patients.

A Risk Score to Predict CMV Viremia within the First 100 Days after Allogeneic Stem Cell Transplantation Based on Pre-Transplant Parameters

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3877-3877
Author(s):  
Feras Alfraih ◽  
John Kuruvilla ◽  
Naheed Alam ◽  
Anna Lambie ◽  
Vikas Gupta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Cmv Infection ◽  
Allogeneic Hsct ◽  
Very High

Abstract Introduction: Cytomegalovirus (CMV) is a major infectious complication following allogeneic hematopoietic stem cell transplantation (HSCT). Risk of CMV infection varies between patients and individualized strategies for monitoring and therapy for CMV are needed. In this study, we attempted to establish a clinical score based on patient and transplant characteristics in order to predict the probability for early CMV viremia (CMV-V) within the first 100 days after HSCT. Methods: A total of 548 patients were evaluated after receiving HSCT between 2005 and 2012 at Princess Margaret Cancer Centre. CMV sero-negative recipients with CMV sero-negative donors (R-D-) were excluded. CMV-V was diagnosed in peripheral blood samples obtained on two occasions either by PCR (>200 IU/ml) or antigenemia testing (>2 positive cells/100000). A total of 378 patients were included into the study. Uni- and multivariable analyses were performed to identify risk factors for CMV-V. A weighted score was assigned to each factor based on the odds ratios determined by the multivariable analysis. A total score was calculated for each patient and used for assignment into one of 4 risk categories, the low risk (score 0-1), the intermediate (score 2-3), the high (score 4-5) and the very high (score 6-8). Median age for all patients was 51 years (range 17-71) and 173 (46%) were female. Matched related donors were used for two hundred fifteen patients (57%). Two hundred forty-three patients (64%) were transplanted for myeloid and 108 (29%) for lymphoid malignancies. One hundred thirteen patients (30%) were CMV sero-positive with a negative donor (R+D-) while 191 (51%) were recipient and donor CMV sero-positivity (R+D+). Graft versus host disease (GVHD) prophylaxis included CSA/MMF (n=200, 52%), and CSA/MTX (n=178, 48%). Myeloablative conditioning regimens were administered to 220 patients (58%), 158 patients (42%) were treated with a reduced intensity regimen. Three hundred-thirty seven patients (89%) received peripheral blood stem cells as a stem cell source. In vivo T cell depletion (TCD) with alemtuzumab was used in 138 (37%). Results: CMV-V occurred in 246 (64%) patients by day 100 post HSCT. The impact of patient and HSCT characteristics on the risk of CMV-V was assessed by multivariable analysis. The significant factors were CMV sero-status R+D- and R+D+, TCD, GVHD prophylaxis with MMF administration of myeloablative preparative regimens (Table 1). Table 1. Multivariate analysis for risk factors of CMV infection following allogeneic HSCT Table 1. Multivariate analysis for risk factors of CMV infection following allogeneic HSCT CMV-V rates on the 4 new risk categories amounted to 93% in the very high-risk, 78% in high-risk, 41% in intermediate-risk and 11% in low-risk group (Fig 1). The risk score was also predictive for the occurrence of multiple CMV-V reactivations with rates of 71%, 45%, 19% and 4% for the very high, high, intermediate and low-risk groups, respectively. The overall survival (OS) rate at 2 years was 33%(n=56) in the very high-risk group compared to 50% in other-risk groups (n=147) (P=0.01) (Fig 2). Non-relapse mortality (NRM) was 53% in the very high-risk versus 33% in other-risk groups (P<0.001). However, there was no difference on cumulative incidence of relapse between the groups (P=0.3). The cumulative incidence of grades 1-4 acute GVHD, grades 2-4, grades 3-4 at day 120 and overall chronic GVHD at 2 years was 68%, 47%, 25% and 39% in very high-risk group versus 65%, 52%, 21% and 52% in other-risk groups, suggesting slightly lower incidence of chronic GVHD in very high-risk vs other-risk groups. Conclusion: We present a new clinical scoring system to stratify the risk of early CMV viremia after allogeneic HSCT based on patients and HSCT characteristics. Identifying the risk for each patient would facilitate decision making with respect to strategies including CMV prophylaxis, pre-emptive treatment or inclusion into clinical trials, as well directing the CMV monitoring policy post-transplant. In addition, the risk score was associated with higher risk of overall mortality and NRM in the very high-risk versus other-risk groups. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Effect of Ethnicity on Preterm Birth and its Influence on the Risk Factors for Prematurity

2019 ◽  
pp. 180-192
Author(s):  
P Bachkangi ◽  
AH Taylor ◽  
JC Konje
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Preterm Birth ◽  
High Risk ◽  
Risk Groups ◽  
Individual Risk ◽  
Individual Risk Factor ◽  
Increased Risk ◽  
Gestational Age At Delivery ◽  
Very High

Preterm birth (PTB) affects 9.6% of pregnancies worldwide and is associated with a very high perinatal mortality that depends on the gestational age at delivery. As a result, PTB has a significant health and financial impact on health systems, families and societies. Its aetiology is not fully understood, but in most cases it is multifactorial, with several maternal, paternal, and epidemiological factors associated with increased risk. Other factors include parental ethnicity, maternal age and body mass index, socioeconomic status, and where the families live. This review examines the influence of ethnicity as an individual risk factor for PTB. It also explores its influence on the epidemiology of PTB and demonstrates that data on certain ethnicities are lacking, despite the fact that these ethnic clusters are within the very ‘high-risk groups’ that are adequately represented in some Western societies. This review examines the influence of ethnicity as an individual risk factor for PTB and also explores its influence on the different epidemiological aspects. A thorough revisit of the ethnic epidemiology unveiled other unnoticed risk factors that if addressed appropriately prematurity can be prevented. Moreover, certain ethnicities were not within the attention of researchers, despite the facts that they are very ‘high-risk groups’ and are also adequately represented in some Western societies.

Improved Outcome in High Risk and Very High Risk ALL by Risk Adapted SCT and in Standard Risk ALL by Intensive Chemotherapy in 713 Adult ALL Patients Treated According to the Prospective GMALL Study 07/2003.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 12-12 ◽  
Author(s):  
Nicola Gökbuget ◽  
Renate Arnold ◽  
Angelika Böhme ◽  
Rainer Fietkau ◽  
Mathias Freund ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Residual Disease ◽  
Univariate Analysis ◽  
Early Death ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Standard Risk ◽  
Very High ◽  
Improved Outcome

Abstract In 2003 the German Multicenter ALL Study Group (GMALL) initiated the trial GMALL 07/2003. Major aims were improvement of outcome by shortened, intensified induction, intensified consolidation, risk adapted and extended SCT indication and minimal residual disease (MRD) based treatment stratification. 8drug-induction was followed by uniform 1st consolidation based on HDARAC and HDMTX. Further treatment was stratified according to the following risk factors (RF): WBC > 30.000 in B-prec. ALL, late CR (>3wks), proB-, earlyT and mature T-ALL, Ph/BCR-ABL and t(4;11)/ALL1-AF4. The risk groups were defined as follows: standard risk (SR, no RF), high risk (HR,>= 1RF) and very high risk (VHR,Ph/BCR-ABL). HR and VHR pts were scheduled for SCT in CR1 with the following priorities: allo sibling, allo matched unrelated and autologous. VHR pts mostly received Imatinib according to different schedules. SR pts received 5 consolidation cycles (HDMTX/ASPx3, VP16/ARAC, CYCLO/ARAC) and reinduction. SR pts with high MRD after consolidation I were allocated to SCT. In the remaining SR pts decision on maintenance therapy was based on MRD. Between 04/03-12/06 713 evaluable (15–55 yrs) pts were included. The median age was 34 yrs. The CR rate after induction was 89% with 5% early death and 6% failure. 50%, 33% and 17% were allocated to SR (N=353), HR (N=235) and VHR (N=117) with similar CR rates of 92%, 88% and 85%. CR rate was not different in pts < vs > 35 yrs (90% vs 89%). 5 year overall survival (OS) was 54% and survival of CR (S-CR) pts was 59%. HR and VHR pts obtained 55% and 49% S-CR at 3 yrs resp. HR subgroups showed different S-CR for early T (58%), mature T (70%), pro B (66%) and other B-lineage ALL (37%). 68% and 71% of HR and VHR pts received SCT in CR1 as scheduled which thus contributed substantially to improved outcome. In SR- ALL S-CR was 69% (68% c/preB, 66% thymicT). The CCR probability was 52% at 3 yrs. CNS prophylaxis was very effective since only 2% of the CR pts had CNS involvement at relapse. Univariate analysis confirmed a significant prognostic impact of immunphenotype, WBC in B-lin ALL, time to CR and Ph/BCR-ABL. WBC was no prognostic factor in T-lin-ALL. Age was highly significant for survival with 64% survival < 35 yrs vs 48% above 35 yrs. In adolescents below 25 years the most favourable survival of 67% was achieved. In standard risk pts below 35 yrs the survival was 73% without SCT in CR1. Overall the study yielded improved CR rates (89%) and survival (54%). Risk adapted SCT indication was feasible (realised in 70% of HR/VHR pts) and lead to improved survival particularly in early/mature T-ALL and pro B-ALL. In standard risk (SR) the survival is favourable, even above 70% in young pts; however, the relapse rate is still high. Further intensification of therapy during the first year seems required. By definition of new risk factors additional SR patients could be allocated to SCT in CR1. There is however no intention to transfer all SR patients to SCT. Future improvement will be attempted by further inclusion of subtype specific and targeted therapies.

The Disease Risk Index Is a Robust Tool for Allogeneic Hematopoietic Stem Cell Transplantation Risk Stratification: An Independent Validation Study on a Large Cohort of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 988-988 ◽  
Author(s):  
Roni Shouval ◽  
Joshua Fein ◽  
Myriam Labopin ◽  
Nicolaus Kroger ◽  
Rafael F. Duarte ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Hematological Malignancies ◽  
Disease Risk ◽  
Risk Index ◽  
Risk Groups ◽  
Advisory Committees ◽  
Very High

Abstract Background: Allogeneic stem cell transplantation is a potentially curative procedure to a long list of hematological malignancies, but involves substantial risk of morbidity and mortality. Means for accurately predicting outcome and assessing risk are thus greatly needed. The Disease Risk Index (DRI) is a prognostic tool developed and validated by Armand et al. across a wide range of hematological malignancies (Blood 2012, Blood 2014) on cohorts of American patients. The Index stratifies patients into 4 distinct risk groups (low, intermediate, high, very high) and has yet to be validated in an international cohort. We sought to evaluate the validity of the DRI in a large cohort of European patients. Methods: This was a retrospective validation study on an independent cohort of patients undergoing allogeneic HSCT and reported the European Society for Blood and Marrow Transplantation (EBMT). Patients included had a hematological malignancy and underwent allogeneic transplantation between the years of 2000 and 2015. Risk groups were coded in accordance with the refined DRI (Blood, 2014). Outcomes were evaluated 4 years after the allogeneic HSCT. Overall survival (OS) was calculated with the Kaplan-Meier method. The log-rank test was used for comparisons of Kaplan-Meier curves. Cumulative incidence curves for nonrelapse mortality (NRM) and relapse with or without death were constructed reflecting time to relapse and time to NRM, respectively, as competing risks. The difference between cumulative incidence curves in the presence of a competing risk was tested with the Gray method. The prognostic effect of the DRI strata was estimated using a Cox proportional hazard model for OS and a Fine and Gray model for NRM and relapse. Results: A total of 89,061 patients from 423 transplantation centers were included in the analysis. Median age was 48.3 (IQR 36.2-57.5). The most frequent indication for transplantation was AML (39,530 patients) followed by ALL (16,206) and MDS (9,750); other indications spanned the spectrum of hematological malignancies. The majority of patients were in 1st or 2nd complete remission (54%). The median follow-up period was 3.6 years. Approximately 63% of patients were classified as intermediate risk by DRI, suggesting that this group could be further partitioned. The 4 year overall survival (95% CI) of the low, intermediate, high, and very high risk groups was 60.8% (59.9-61.8), 51.3% (50.8‐51.8), 27.0% (26.1‐27.8), 18.4% (17.1-19.8) (Figure 1). The same groups corresponded with increasing cumulative incidence of relapse; 8.9% (8.3-9.4), 19.3% (18.9-19.7), 39.0% (37.8-39.6), 45.1% (43.4-46.7), respectively. The DRI groups also showed increasing hazard between strata in the overall survival setting; intermediate risk was associated with a hazard ratio of 1.32, high risk 2.67 and very high risk 3.71 relative to low risk. Relapse showed a similar pattern. NRM was less strongly stratified by DRI (Table 1). The DRI groups maintained a similar risk, regardless of whether the transplantation was performed prior or after 2008. DRI was the strongest determinant of overall survival and relapse when introduced to a multivariable model with additional covariates. AUC for the index at 4 years was 62.5 for OS, 58.5 for NRM and 68.2 for relapse. Conclusions: We have validated the Disease Risk Index in a massive European data set. The groupings suggested by the DRI corresponded with distinct risk groups for overall mortality and relapse. Overall, our results indicate the international applicability of this robust prognostic tool. Figure 1. Kaplan-Meyer survival curves for overall survival, stratified by DRI Figure 1. Kaplan-Meyer survival curves for overall survival, stratified by DRI Table 1 Table 1. Disclosures Bader: Medac: Consultancy, Research Funding; Riemser: Research Funding; Neovii Biotech: Research Funding; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Bonini:Molmed SpA: Consultancy; TxCell: Membership on an entity's Board of Directors or advisory committees. Dreger:Gilead: Consultancy; Janssen: Consultancy; Novartis: Speakers Bureau; Gilead: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy. Kuball:Gadeta B.V,: Membership on an entity's Board of Directors or advisory committees. Montoto:Roche: Honoraria; Gilead: Research Funding.

scholarly journals High Incidence of Venous Thromboembolism in Patients with Chronic Graft-Versus-Host Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 44-46
Author(s):  
Najla El Jurdi ◽  
Heba Elhusseini ◽  
Todd E. DeFor ◽  
Grigori Okoev ◽  
Aleksandr Lazaryan ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Advisory Committees ◽  
High Incidence ◽  
Independent Association ◽  
Very High ◽  
Fund Research

Background: Limited studies report a wide range of venous thromboembolism (VTE) incidence among allogeneic hematopoietic cell transplant (alloHCT) recipients. Chronic GVHD (cGVHD) is an immune mediated complication after alloHCT associated with vascular endothelial damage and prolonged systemic inflammation. We hypothesized that patients developing cGVHD are a subgroup at particularly high risk for VTE. Aims: To assess VTE incidence, sites of involvement, and risk factors in patients with cGVHD and to examine the impact of VTE on clinical outcomes after alloHCT. Methods: We performed a retrospective cohort study of all 145 patients who developed cGVHD after a matched sibling (MSD) and umbilical cord blood (UCB) donor alloHCT from 2010 to 2018. VTE was defined as a new confirmed event by imaging at any time after cGVHD diagnosis. VTE sites were categorized as upper extremity (UE), lower extremity (LE) deep vein thrombosis (DVT) or pulmonary embolus (PE). We assessed the cumulative incidence of VTE treating non-VTE mortality as a competing risk. Multivariate regression was used to evaluate the independent association of risk factors with the incidence of VTE using predefined factors in our model including gender, age, DRI, cGVHD severity, days to cGVHD from transplant and platelet level. We accounted for multiple events of VTE using PWP regression. Cox and Fine and Gray regressions were used to evaluate the independent association of time-dependent VTE on overall survival (OS) and non-relapse mortality (NRM), respectively using propensity scoring to control for confounding.. Results: Median age at time of cGVHD diagnosis was 52 years (range 19-74). 104 (72%) patients received MSD and 41 (28%) UCB alloHCT. Of the 145 patients with cGVHD, 32 (22%) developed either 1 or 2 VTE events and 14 (10%) developed 2 VTE events. The first VTE events were PE (n=6, 19%), and DVT (n=26, 81%; n=17 LE, n= 8 UE and n=5 catheter related UE DVT); one patient developed an IVC thrombus. The second VTE events were PE (n=2, 14%), and DVT (n=12, 86%; n=5 LE, n= 7 UE and n=4 catheter related UE DVT). Most patients were on corticosteroids at the first (n=28, 88%) and second (n=10, 71%) VTE with a median dose of (0.3 and 0.2 mg/kg/day, respectively) ± additional immunosuppression therapies. The cumulative incidence of VTE through 5 years post cGVHD diagnosis was estimated at 22% (95% CI: 15-29%) with median time from cGVHD diagnosis to VTE of 234 days (IQR 85-599). Median time to the development of LE DVT or PE was shorter than UE DVT (107 vs 450 days, respectively). Incidence was higher in males (24% vs 18%), and was not significantly different by age (&lt; or ≥50), BMI (&lt; or ≥30), HCT- comorbidity index, donor type, conditioning regimen and GVHD prophylaxis. Cumulative incidence was higher (50%) in patients with high/very high risk DRI compared to 19% in those with low and intermediate risk DRI. VTE incidence was highest in patients with de novo cGVHD (25%) compared to quiescent (20%) and progressive type (17%). Cumulative incidence was 9%, 17% and 38% in those with mild, moderate and severe GVHD respectively. Patients with lung, gastrointestinal, genitourinary and liver cGVHD had a higher incidence of VTE. Patients developing cGVHD &gt;6 months from HCT had a higher incidence of VTE (24% vs 19%). In multivariate analysis, high/very high risk DRI was associated with higher risk of VTE (HR 2.5; 95% CI; 1.2-5.3) (Figure 2). VTE was not associated with a significantly higher 2-year NRM (HR 1.2; 95% CI; 0.4-3.6) or 5 year OS (HR 1.4; 95% CI; 0.7-3.0). Conclusion: Patients who develop cGVHD after alloHCT have a high incidence VTE. Identifying a subgroup at a particularly high risk for VTE could inform thromboprophylaxis and other supportive care strategies for prevention of such events. Disclosures Bachanova: Karyopharma: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; FATE: Research Funding; BMS: Research Funding; Incyte: Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Betts:Patent Pending: Patents & Royalties: Dr. Betts has a pending patent WO2017058950A1: Methods of treating transplant rejection. This includes the use of JAK inhibitors. Neither he nor his institution have received payment related to claims described in the patent.. Blazar:Tmunity: Other: Co-founder; Magenta Therapeutics: Consultancy; KidsFirst Fund: Research Funding; Fate Therapeutics Inc.: Research Funding; Childrens' Cancer Research Fund: Research Funding; BlueRock Therapeuetic: Consultancy; BlueRock Therapeutics: Research Funding. Brunstein:Astex: Research Funding; AlloVir: Other: Advisory board; Magenta: Research Funding; Gamida: Research Funding. Holtan:CSL Behring: Other: Clinical trial data adjudication; BMS: Consultancy; Generon: Consultancy; Incyte: Consultancy. Janakiram:Takeda, Fate, Nektar: Research Funding. Gangaraju:Sanofi Genzyme, Consultant for Cold Agglutinin Disease: Consultancy. MacMillan:Talaris Therapeutics, Inc: Consultancy; Angiocrine Biosciences, Inc.: Consultancy; Equillium, Inc.: Consultancy; Fate Therapeutics, Inc.: Consultancy; Mesoblast: Consultancy. Rashidi:Synthetic Biologics: Other: DSMC member (1 trial) and related honorarium. Weisdorf:Incyte: Research Funding; FATE Therapeutics: Consultancy. Arora:Pharmacyclics: Research Funding; Fate Therapeutics: Consultancy; Kadmon: Research Funding; Syndax: Research Funding.

scholarly journals p53 Mutant Independently Impacts Risk: Analysis of Deletion 5q, Lower-Risk Myelodysplastic Syndromes (MDS) Patients Treated with Lenalidomide (LEN) in the MDS-004 Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 414-414 ◽  
Author(s):  
Leonie Saft ◽  
Jack Shiansong Li ◽  
Peter L. Greenberg ◽  
Mikkael A. Sekeres ◽  
Guillermo F. Sanz ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Lower Risk ◽  
Research Funding ◽  
Risk Group ◽  
Risk Groups ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Very High

Abstract Introduction: Refined risk-classification of patients (pts) with MDS allows for improved treatment selection for individual pts. The Revised International Prognostic Scoring System (IPSS-R) has recently been validated as a prognostic tool in lower-risk MDS pts with deletion 5q [del(5q)], who were treated with LEN in the MDS-004 study (Sekeres et al. Blood Cancer J 2014; in press). P53 nuclear protein expression, as assessed by immunohistochemistry (IHC), predicted overall survival (OS) and risk of progression to acute myeloid leukemia (AML) in lower-risk MDS pts with del(5q) (Saft et al. Haematologica 2014;99:1041-9). This analysis evaluated the prognostic value of adding p53 IHC to IPSS-R to predict OS and AML progression in pts with lower-risk MDS with del(5q). Methods: In a subset of 85 pts from MDS-004 with bone marrow (BM) biopsies available, p53+ staining (≥ 1% IHC+++ BM cells) was visualized by IHC. Twenty-four pts had missing IPSS-R scores; 1 due to lack of baseline cytogenetic data and 23 because of missing exact BM blast percentage. Thus, 61 pts (42 initially treated with LEN and 19 with placebo) had IPSS-R and p53 IHC data available; 89% of pts in the placebo group crossed over to LEN 5 mg at Week 16. The IPSS-R Very Low and Very High risk groups with < 5 pts were combined with the Low and High risk groups, respectively. AML-free survival (AFS), OS, and time to AML progression within p53 IHC status (p53+ vs p53−), and IPSS-R risk groups were characterized by the Kaplan-Meier method with differences evaluated by the log-rank test. Results: Of 61 pts, 38% were p53+. There was a linear increasing trend in the proportion of pts with p53+ across IPSS-R risk groups from Very Low/Low, Intermediate to High/Very High (29%, 47% and 63%, respectively; Cochran-Armitage trend test P = 0.050). The 3 IPSS-R risk groups significantly predicted AFS and OS (log-rank P < 0.001 for both AFS and OS), but not time to AML progression (P = 0.335). Overall, AFS, OS, and time to AML progression differed significantly between p53+ versus p53− pts (23.9 vs 47.9 months for median AFS, P = 0.003; 27.0 vs 50.6 months for median OS, P = 0.005; and 44.3 months vs not reached [NR] for median time to AML progression,P = 0.003). In the IPSS-R Very Low/Low risk group (n = 38), AFS, OS, and time to AML progression were significantly worse in p53+ versus p53− pts (20.1 vs 63.1 months for median AFS, P = 0.011; 28.4 vs 76.8 months for median OS, P = 0.031; and 65.2 months vs NR for median time to AML progression, P = 0.014). Results for all IPSS-R risk groups in pts with p53 and IPSS-R data are presented in the Figure. The lack of significant differences between p53+ versus p53− pts in the Intermediate and High/Very High risk groups is likely due to the small sample size of these groups. Conclusions: In this exploratory subset analysis of lower-risk MDS pts with del(5q), p53 IHC status in the IPSS-R Very Low/Low risk group significantly impacted AFS, OS, and AML progression. These data support the addition of p53 mutational analysis to prognostic risk assessment which should help inform the selection of appropriate treatment for individual MDS pts with del(5q). These results need to be validated in a large sample set, which will be accomplished as part of the ongoing efforts to include prognostic molecular mutations in future updates of IPSS-R Figure 1 AFS (A), OS (B), and time to AML progression (C) in pts with p53 and IPSS-R data (N = 61) Figure 1. AFS (A), OS (B), and time to AML progression (C) in pts with p53 and IPSS-R data (N = 61) Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Shiansong Li: Celgene Corporation: Employment, Equity Ownership. Greenberg:Celgene: Research Funding; Onconova: Research Funding; GSK: Research Funding; Novartis: Research Funding; KaloBios: Research Funding. Sekeres:Amgen Corp.: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim Corp.: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Dreyfus:Novartis: Honoraria; Celgene: Honoraria. Fenaux:Novartis: Research Funding; Janssen: Research Funding; Celgene: Research Funding. Swern:Celgene: Employment, Equity Ownership. Sugrue:Celgene: Employment, Equity Ownership. Hellstrom-Lindberg:Celgene: Research Funding.

scholarly journals A Peri-Implant Disease Risk Score for Patients with Dental Implants: Validation and the Influence of the Interval between Maintenance Appointments

2019 ◽  
Vol 8 (2) ◽  
pp. 252 ◽  
Author(s):  
Miguel de Araújo Nobre ◽  
Francisco Salvado ◽  
Paulo Nogueira ◽  
Evangelista Rocha ◽  
Peter Ilg ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Disease Risk ◽  
Disease Incidence ◽  
Risk Groups ◽  
Risk Profile ◽  
Moderate Risk ◽  
C Statistic ◽  
Disease Risk Score ◽  
Very High

Background: There is a need for tools that provide prediction of peri-implant disease. The purpose of this study was to validate a risk score for peri-implant disease and to assess the influence of the recall regimen in disease incidence based on a five-year retrospective cohort. Methods: Three hundred and fifty-three patients with 1238 implants were observed. A risk score was calculated from eight predictors and risk groups were established. Relative risk (RR) was estimated using logistic regression, and the c-statistic was calculated. The effect/impact of the recall regimen (≤ six months; > six months) on the incidence of peri-implant disease was evaluated for a subset of cases and matched controls. The RR and the proportional attributable risk (PAR) were estimated. Results: At baseline, patients fell into the following risk profiles: low-risk (n = 102, 28.9%), moderate-risk (n = 68, 19.3%), high-risk (n = 77, 21.8%), and very high-risk (n = 106, 30%). The incidence of peri-implant disease over five years was 24.1% (n = 85 patients). The RR for the risk groups was 5.52 (c-statistic = 0.858). The RR for a longer recall regimen was 1.06, corresponding to a PAR of 5.87%. Conclusions: The risk score for estimating peri-implant disease was validated and showed very good performance. Maintenance appointments of < six months or > six months did not influence the incidence of peri-implant disease when considering the matching of cases and controls by risk profile.

scholarly journals Proposal for the use of echocardiography in bloodstream infections due to different streptococcal species

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sandra Chamat-Hedemand ◽  
Niels Eske Bruun ◽  
Lauge Østergaard ◽  
Magnus Arpi ◽  
Emil Fosbøl ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
High Risk ◽  
Blood Culture ◽  
Positive Blood Culture ◽  
Bloodstream Infections ◽  
Low Risk ◽  
Moderate Risk ◽  
Streptococcal Species ◽  
Very High

Abstract Background Infective endocarditis (IE) is diagnosed in 7–8% of streptococcal bloodstream infections (BSIs), yet it is unclear when to perform transthoracic (TTE) and transoesophageal echocardiography (TOE) according to different streptococcal species. The aim of this sub-study was to propose a flowchart for the use of echocardiography in streptococcal BSIs. Methods In a population-based setup, we investigated all patients admitted with streptococcal BSIs and crosslinked data with nationwide registries to identify comorbidities and concomitant hospitalization with IE. Streptococcal species were divided in four groups based on the crude risk of being diagnosed with IE (low-risk < 3%, moderate-risk 3–10%, high-risk 10–30% and very high-risk > 30%). Based on number of positive blood culture (BC) bottles and IE risk factors (prosthetic valve, previous IE, native valve disease, and cardiac device), we further stratified cases according to probability of concomitant IE diagnosis to create a flowchart suggesting TTE plus TOE (IE > 10%), TTE (IE 3–10%), or “wait & see” (IE < 3%). Results We included 6393 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men). BSIs with low-risk streptococci (S. pneumoniae, S. pyogenes, S. intermedius) are not initially recommended echocardiography, unless they have ≥3 positive BC bottles and an IE risk factor. Moderate-risk streptococci (S. agalactiae, S. anginosus, S. constellatus, S. dysgalactiae, S. salivarius, S. thermophilus) are guided to “wait & see” strategy if they neither have a risk factor nor ≥3 positive BC bottles, while a TTE is recommended if they have either ≥3 positive BC bottles or a risk factor. Further, a TTE and TOE are recommended if they present with both. High-risk streptococci (S. mitis/oralis, S. parasanguinis, G. adiacens) are directed to a TTE if they neither have a risk factor nor ≥3 positive BC bottles, but to TTE and TOE if they have either ≥3 positive BC bottles or a risk factor. Very high-risk streptococci (S. gordonii, S. gallolyticus, S. mutans, S. sanguinis) are guided directly to TTE and TOE due to a high baseline IE prevalence. Conclusion In addition to the clinical picture, this flowchart based on streptococcal species, number of positive blood culture bottles, and risk factors, can help guide the use of echocardiography in streptococcal bloodstream infections. Since echocardiography results are not available the findings should be confirmed prospectively with the use of systematic echocardiography.

scholarly journals Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Basilio Pintaudi ◽  
Alessia Scatena ◽  
Gabriella Piscitelli ◽  
Vera Frison ◽  
Salvatore Corrao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Quality Of Care ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Cardiovascular Risk Factors ◽  
High Cardiovascular Risk ◽  
Very High

Abstract Background The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. Methods The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. Results Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. Conclusions A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care.

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