Neutrophil PRV-1 mRNA Overexpression in Chronic Idiopathic Myelofibrosis May Be Associated with Poor Prognosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4762-4762
Author(s):  
Heinz Gisslinger ◽  
Steffen Klippel ◽  
Hermann Heimpel ◽  
Mathias Kees ◽  
Alexandra Kaider ◽  
...  
Keyword(s):  
Risk Score ◽  
Statistical Power ◽  
Clinical Symptoms ◽  
Clinical Course ◽  
Significant Proportion ◽  
Small Sample ◽  
Risk Scores ◽  
Idiopathic Myelofibrosis ◽  
Chronic Idiopathic Myelofibrosis

Abstract Neutrophil PRV-1 mRNA is overexpressed in nearly all patients with polycythemia vera (PV) and discriminates PV from secondary polycythemia. In addition, 40– 50% of patients with essential thrombocythemia (ET) and chronic idiopathic myelofibrosis (cIMF) overexpress PRV-1. PRV-1 positive ET patients carry a significantly higher risk of thromboembolic complications compared to PRV-1 negative patients. In addition, PRV-1 overexpression and the growth of endogenous erythroid colonies (EECs) are closely correlated in ET patients. A significant proportion of PRV-1 positive/EEC positive ET patients develop PV during follow up, while this has not been observed in PRV-1/EEC negative patients. In contrast, PRV-1 and EEC expression in cIMF has not been analysed in the context of clinical course. We therefore determined PRV-1 expression and EEC formation in a cohort of 21 cIMF patients and compared clinical parameters and risk scores between PRV-1 positive and negative patients. Blood samples were drawn from 21 patients (m/f: 12/9; age: 72, 39–79 years); peripheral blood MNCs and granulocytes were purified concurrently. The former were assayed for EEC growth while the latter were used to measure PRV-1 expression. Diagnosis of cIMF according to the WHO criteria was confirmed by histopathology. The median time from diagnosis was 3 years (0,5–16,5 years). At the time of investigation six patients were receiving imatinib in the setting of a phase II trial and four received hydroxyurea. The nonparametric Wilcoxon rank sum test was used to compare hematocrit, WBC and platelet counts, LDH-levels, age as well as the Cologne risk score between groups. Fourteen of the 21 patients (67%) overexpressed PRV-1. Eight of these also showed autonomous EEC growth. Three of the remaining PRV-1 positive patients were receiving imatinib at the time of analysis and colony growth was suppressed both in the presence and absence of Epo. In the remaining three PRV-1 positive patients EEC growth was not evaluable due to lack of growth with Epo. Of the seven PRV-1 negative IMF patients six did not give rise to EECs, and one was not evaluable due to lack of growth in the presence of Epo. Hence, as previously reported in ET and in five cIMF patients, we find a close correlation between PRV-1 overexpression and EEC formation in our cohort of cIMF patients. These data support the hypothesis that two distinct molecular alterations, one leading to PRV-1 overexpression and EEC formation, the other not, can give rise to the clinical symptoms of cIMF. Because the EEC assay was informative in fewer patients than the PRV-1 assay and because the parameters are closely correlated, patients were classified by PRV-1 expression and the clinical course compared between the two groups. There was no difference between PRV-1 positive and negative patients with respect to WBC- and PLT counts, LDH-levels or highest hematocrit recorded during follow up. In contrast, PRV-1 positive cIMF patients displayed a trend to a poorer Cologne risk score (P=0.095). Thus, PRV-1 overexpressing CIMF may comprise a subgroup of patients with a poorer risk profile. Due to the relatively small sample size the statistical power of our study is limited and verification of the results in a larger sample is required.

scholarly journals AB0571 IS RITUXIMAB AN ADEQUATE GLUCOCORTICOID SPARING AGENT IN IDIOPATHIC INFLAMMATORY MYOPATHIES?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1582.1-1582
Author(s):  
B. H. Egeli ◽  
S. Ergun ◽  
Y. K. Gursoy ◽  
A. Cetin ◽  
S. Ugurlu
Keyword(s):  
Disease Activity ◽  
Alternative Treatment ◽  
Statistical Power ◽  
Signs And Symptoms ◽  
Small Sample ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Treatment Methods ◽  
Before And After

Background:Idiopathic inflammatory myopathies (IIM) are essentially treated aiming improvement of muscle function and extra muscular disease manifestations. The backbone of the treatment is corticosteroids enhancing the survival and patient quality of life. The lack of consensus on target-specific immunosuppressive treatment highlights the need for further studies evaluating alternative treatment methods. Rituximab is potentially a glucocorticoid-sparing agent which was reviewed in multiple studies with small sample sizes due to the rarity of the disease.Objectives:Higher statistical power can enhance the trustworthiness of alternative treatment methods yielding the main objective of this study.Methods:This retrospective study was conducted at a tertiary rheumatology center. Patients were diagnosed with an idiopathic inflammatory myopathy (dermatomyositis [DM], polymyositis [PM]) and were treated with rituximab in order to be included in this study. Clinical signs and symptoms of the presentation were noted during the first patient encounter as well as the follow-up. Parameters of disease activity including acute phase reactants, muscle enzyme levels, and disease-specific autoantibodies were analyzed.Results:The study includes 28 patients (20 DM, 8 PM). The age of diagnosis was 43.44 ± 15.77 years, follow-up duration was 60.7 ± 70.7 months. The presenting signs and symptoms of the patients are shown in Figure 1. The parameters of disease activity before and after treatment are summarized in Table 1. The mean corticosteroid dose decreased from 31.429 ±23.934 mg to 10.278 ±12.001 (p=0.001). Other treatment methods were methotrexate (n=18), Intravenous Immunoglobulin (IVIG) (n=7), and cyclophosphamide (n=2). There were not any deaths during the follow-up. Two patients were lost to follow-up.Table 1.The Parameters of Disease Activity Before and After TreatmentBefore TreatmentAfter TreatmentP ValueCPK, mean ± std (U/L)1426 ± 2049.92263.44 ± 265.630.004LDH, mean ± std (U/L)557.5 ± 365379.78 ± 192.10.03AST, mean ± std (U/L)62.52 ± 5930.16 ± 27.590.01ALT, mean ± std (U/L)56.48 ± 49.2127.64 ± 24.520.008ESR, mean ± std (mm/hour)26.38 ± 28.9820.39 ± 18.760.36CRP, mean ± std (mg/L)19.23 ± 46.1512.53 ± 26.670.5RF, mean ± std (U/mL)0 (0)N/AN/AANA, n (%)3 (10.71)N/AN/AFigure 1.The Presenting Signs and Symptoms of the PatientsConclusion:Rituximab is shown to be effective in treating myositis along with corticosteroids as well as a corticosteroid-sparing agent in retrospective studies and open-label clinical trials; however, lack of statistical power should be underlined. Long term decrease in steroid use and decrease in disease activity markers hints the effective use of rituximab as a glucocorticoid sparing agent as well as its safety with minimal side effects.Disclosure of Interests:None declared

Abstract 16541: Clinical and Imaging Phenotypes From a Registry of Segmental Arterial Mediolysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Arvind K Pandey ◽  
Marie Gerhard-Herman
Keyword(s):  
Risk Score ◽  
Clinical Laboratory ◽  
Clinical Symptoms ◽  
Intramural Hematoma ◽  
Arterial Dissection ◽  
Aged Patients ◽  
Male Predominance ◽  
Imaging Characteristics ◽  
Vascular Segment

Background: Segmental arterial mediolsyis (SAM) is a non-inflammatory arteriopathy that is increasingly being recognized; however, its clinical characteristics and natural history remain poorly defined. Methods: A retrospective, single-institution review of 20 patients presenting with arterial dissection, intramural hematoma, aneurysm, or occlusion between 2015 and 2020 was performed. To establish a non-invasive diagnosis of SAM, patients with FMD, inflammatory, or genetic arteriopathy were excluded by clinical, laboratory, and imaging criteria according to multidisciplinary guidelines. Patient demographics, clinical features, imaging findings, and management were assessed. Results: The average age of patients was 56 years; 75% were male. CAD was present in 15% of patients and 45% had hypertension; 55% were current or prior smokers. In patients without diagnosed CAD, the 10-year ASCVD risk score was 8.7% and the Framingham risk score was 6.8%. The average hemoglobin A1c was 5.6%. Acute onset abdominal pain (70%) was the most frequent presenting symptom. On average, two different arterial beds were affected at the time of diagnosis, most often in the abdomen. Arterial dissection was present in 75% of patients, and intramural hematoma was seen in 35% of cases. The most affected vessel was the superior mesenteric artery (50%), followed by the celiac, renal, and iliac arteries (35% each). Over a mean follow-up period of 20 months, all patients survived; two patients required intervention due to worsening clinical symptoms. Anticoagulation (AC) was utilized in 50% of cases, most commonly for one month. Long-term follow-up imaging was available in 11 patients; 3 patients (27%) had progression in lesion size over the first month. By 1 year, only 1 patient continued to show enlargement, with all others showing regression. Conclusions: This cohort provides longitudinal follow-up on both clinical and imaging characteristics of non-invasively diagnosed SAM. The condition shows a male predominance, typically manifesting in middle-aged patients with low to intermediate cardiovascular risk. While a subset of patients shows growth in size of the affected vascular segment over the first month, longer follow-up imaging demonstrates regression.

Host Immunogenetic Single Nucleotide Polymorphisms (SNPs) Predict Overall Survival in Small Lymphocytic Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2396-2396
Author(s):  
Carrie A. Thompson ◽  
Sophia Wang ◽  
Matthew J. Maurer ◽  
Thomas M. Habermann ◽  
Richard K. Severson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Los Angeles ◽  
Risk Score ◽  
Prognostic Biomarkers ◽  
Risk Scores ◽  
Tnf Alpha ◽  
Small Lymphocytic Lymphoma ◽  
Risk Of Death ◽  
Individual Snps

Abstract Small lymphocytic lymphoma (SLL) is an incurable indolent lymphoma, and there are relatively few prognostic biomarkers for this important NHL subtype. We evaluated the hypothesis that inherited variability in cytokine and immune-related genes was associated with overall survival in SLL. We genotyped 73 SNPs in 44 candidate genes in 140 SLL patients aged 20–70 years who participated in a population-based case-control study conducted from 1998–2000 through the Surveillance, Epidemiology, and End Results (SEER) cancer registries in Detroit, Seattle, Iowa, and Los Angeles. DNA was extracted from a venous blood sample or mouthwash buccal cell sample. All genotyping was conducted at the National Cancer Institute Core Genotyping Facility using the Taqman platform. Histology, stage, presence of B-symptoms, first course of therapy, date of last follow-up, and vital status were derived from linkage to registry databases at each study site in the spring of 2005. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) and 95% confidence interval for the association between individual SNPs and overall survival, adjusted for age, demographic and clinical factors. Multiple simultaneous modeling strategies were used to identify the best summary multi-SNP risk score to predict survival. At last follow-up, there were 45 deaths in 140 patients (32%). The median follow-up of the 95 surviving patients was 58 months (range 24–75 months). In multivariate modeling, SNPs in IL13 (rs1800925; HRCC=2.36, 1.24–4.49), IL7R (rs1494555; HRGG =2.20, 0.84–5.76), and TNF-alpha (rs1800630; HRAC/AA=1.73, 0.95–3.17) were the strongest and most robust predictors of survival. Two or more deleterious genotypes from these three SNPs increased the risk of death (HR=2.2, 1.2–4.1) compared with one or fewer deleterious genotypes (p=0.009). Three groups (low, intermediate, and high risk) were defined by combining the SNP score and a clinical/demographic score. The 5-year Kaplan-Meier survival estimates for these groups were 85%, 65%, and 11%, respectively. Compared to patients with a low risk score, patients with intermediate (HR=2.5, 1.2–5.1) or high (HR=11, 4.3–27.7) risk scores had poorer overall survival (p=3.9 x 10−8). Our preliminary results suggest that SNPs in IL13, IL7R, and TNF-alpha alone and in combination predict overall survival in SLL, lending support to the hypothesis that host genetic background is a promising class of prognostic biomarkers in SLL.

scholarly journals Autoimmune encephalitis associated with antibodies against the metabotropic glutamate receptor type 1: case report and review of the literature

2019 ◽  
Vol 12 ◽  
pp. 175628641984741 ◽  
Author(s):  
Monika Christ ◽  
Torsten Müller ◽  
Corinna Bien ◽  
Thomas Hagen ◽  
Markus Naumann ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Clinical Symptoms ◽  
Clinical Course ◽  
Autoimmune Encephalitis ◽  
Receptor Type ◽  
Metabotropic Glutamate

Autoimmune encephalitis associated with antibodies against the metabotropic glutamate receptor type 1 is a rare autoimmune disease with only 18 cases being described in the literature so far. Most patients present with subacute cerebellar ataxia. In more than one third of cases a paraneoplastic aetiology has been suspected. Here we report a case of a 45-year-old man without known malignancy, who presented with progressive dysarthria and subsequently developed subacute cerebellar ataxia. Immunotherapy with glucocorticoids, i.v. immunoglobulins and rituximab improved clinical symptoms and resulted in a stable disease course up to the present. The article describes the clinical course of the patient with a follow-up-period of approximately 24 months and reviews the cases reported in the literature so far.

Predictors of Survival and Time to Progression to Myeloid Neoplasm in Patients with Clonal Cytopenias

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Ahmad Nanaa ◽  
Rama Nana ◽  
Zhuoer Xie ◽  
Dragan Jevremovic ◽  
Phuong L. Nguyen ◽  
...  
Keyword(s):  
Risk Score ◽  
Risk Scores ◽  
Intermediate Risk ◽  
Mutation Status ◽  
Myeloid Neoplasm ◽  
Hla Dr ◽  
Risk Of Progression ◽  
Immune Phenotyping ◽  
Undetermined Significance

Background: Clonal cytopenias of Undetermined Significance (CCUS) have a higher risk of progression to myeloid neoplasm (MN) compared to idiopathic cytopenias of undetermined significance (ICUS) (Malcovati et al., Blood, 2017). The implementation of flow cytometric (FC) immune-phenotyping and next generation sequencing (NGS) in clinical practice has improved the diagnosis of these entities but the clinical significance and interaction of these abnormal results are still unknown. In this study we investigated predictive factors that play role in survival and progression to MN in patients with ICUS/CCUS. Methods: Patients (Pts) who had undergone evaluation for unexplained cytopenia and had undergone FC and bone marrow morphological assessment between 3/2015-3/2020 at Mayo Clinic Rochester were included. Pts were excluded if a malignant hematological disorder was diagnosed prior to the time of FC. FC included evaluation of the following parameters: Abnormal expression of HLA-DR/CD13, CD2, CD7, CD45, and CD56 on blasts; and abnormal CD13/CD16 expression and side scatter on granulocytic cells. NGS panel up to 2018 included 34 genes, ASXL1, BCOR, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA1, GATA2, IDH1, IDH2, JAK2, KIT, KRAS, MPL, MYD88, NOTCH1, NPM1, NRAS, PHF6, PTPN11, RUNX1, SETBP1, SF3B1, TERT, TET2, TP53, U2AF1, WT1, and ZRSR2; in 2018, BRAF was omitted and 12 genes were added, ANRD26, DDX41, ELANE, ETNK1, KDM6A, MYD88, NOTCH1, RAD21, SH2B3, SRP72, SMC3, and STAG2. Results: Characteristics: Of 490 consecutive pts, 238 (median age 69 years (range 19-92), 66% males) met our inclusion criteria as ICUS. 86 (36%) pts had CCUS (abnormal cytogenetics and/or tested positive for pathogenic mutations on NGS). After a median follow-up of 28 months (95% CI: 20 to 31 months), 21 (25%) patients developed MN and 23 (27%) died during follow-up. Comparing ICUS vs CCUS: upon comparing CCUS pts to ICUS, several factors were found to be significantly different: CCUS pts were older (p= .02); majority male (p= .04), had more abnormal HLA-DR/CD13 (p <.0001), more side-scattered light by FC (p <.0001), more pancytopenia on follow up (p= .02) and more morphologic atypia (<.0001). Overall survival (OS) outcomes in CCUS: Several covariates were significant in univariate models, and model selection was used to generate a risk score based on abnormal CD7, abnormal CD13/CD16, abnormal HLA-DR/CD13, splenomegaly and history of prior chemotherapy or radiotherapy (range: 0 - 4; HR=2.58, [95 CI: 1.69 - 3.94], p<.0001). Risk scores were grouped as low risk (score=0), intermediate risk (score=1), and high risk (score=2+), with estimated 2-yr-OS of 95%, 84%, 40%, respectively (Figure 1). An extended risk score model including NGS factors added ASXL1 and IDH1 mutation status to the previous model (range: 0 - 6; HR=2.72, [95 CI 1.82 - 4.06], p<0.0001). MN-free survival (MNFS) in CCUS: 37 pts either progressed to MN and/or died with a median follow up time for MNFS of 22.4 months. Similar for OS, model selection approaches yielded a composite risk score: splenomegaly, BCOR mutation status, mutation in RAS signaling pathway, abnormal expression of flow markers CD13/CD16, HLA-DR/CD13 or CD7 (HR=3.23, [95 CI: 1.90 - 5.49], p=<0.0001). Risk scores were grouped as low risk (score=0), intermediate risk (score=1), and high risk (score ≥ 2), with estimated 1-yr MNFS of 84%, 74%, and 31%, respectively (Figure 2). Conclusion: CCUS has unique features compared to ICUS. Several factors, including clinical characteristics, immune-phenotyping by FC, and somatic mutations have important impact on risk of progression to MN and on overall survival. Our findings serve as proof-of-concept that such integrated models could help identify CCUS patients at higher risks for progression to MN or death. They can guide treatment accordingly and should be evaluated further. Disclosures Shah: Dren Bio: Consultancy.

Mapping the genetic architecture of suicide attempt and suicide death using polygenic risk scores for clinically-related psychiatric disorders and traits

2021 ◽  
pp. 1-9
Author(s):  
Ikuo Otsuka ◽  
Hanga Galfalvy ◽  
Jia Guo ◽  
Masato Akiyama ◽  
Dan Rujescu ◽  
...  
Keyword(s):  
Suicide Attempt ◽  
Psychiatric Disorders ◽  
Suicidal Behavior ◽  
Statistical Power ◽  
Small Sample ◽  
European Ancestry ◽  
Risk Scores ◽  
Suicide Attempters ◽  
Polygenic Risk ◽  
Suicide Death

Abstract Background Suicidal behavior is moderately heritable and a consequence of a combination of the diathesis traits for suicidal behavior and suicide-related major psychiatric disorders. Here, we sought to examine shared polygenic effects between various psychiatric disorders/traits and suicidal behavior and to compare the shared polygenic effects of various psychiatric disorders/traits on non-fatal suicide attempt and suicide death. Methods We used our genotyped European ancestry sample of 260 non-fatal suicide attempters, 317 suicide decedents and 874 non-psychiatric controls to test whether polygenic risk scores (PRSs) obtained from large GWASs for 22 suicide-related psychiatric disorders/traits were associated with suicidal behavior. Results were compared between non-fatal suicide attempt and suicide death in a sensitivity analysis. Results PRSs for major depressive disorder, bipolar disorder, schizophrenia, ADHD, alcohol dependence, sensitivity to environmental stress and adversity, educational attainment, cognitive performance, and IQ were associated with suicidal behavior (Bonferroni-corrected p < 2.5 × 10−4). The polygenic effects of all 22 psychiatric disorders/traits had the same direction (p for binomial tests = 4.8 × 10−7) and were correlated (Spearman's ρ = 0.85) between non-fatal suicide attempters and suicide decedents. Conclusions We found that polygenic effects for major psychiatric disorders and diathesis-related traits including stress responsiveness and intellect/cognitive function contributed to suicidal behavior. While we found comparable polygenic architecture between non-fatal suicide attempters and suicide decedents based on correlations with PRSs of suicide-related psychiatric disorders/traits, our analyses are limited by small sample size resulting in low statistical power to detect difference between non-fatal suicide attempt and suicide death.

Abstract 19496: A New Exercise Testing Model Performs Better than the Duke Treadmill Score to Identify Patients at Increased Risk for All-cause Mortality

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Paul C Cremer ◽  
Yuping Wu ◽  
Lee Pierson ◽  
Danielle Brennan ◽  
Leslie Cho
Keyword(s):  
Risk Score ◽  
Exercise Testing ◽  
Risk Scores ◽  
Men And Women ◽  
Net Reclassification Improvement ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Duke Treadmill Score ◽  
Better Than

Background: Cardiovascular mortality has declined with advances in primary and secondary prevention, yet risk assessment for patients undergoing exercise treadmill testing is generally still based upon the Duke Treadmill Score (DTS). We hypothesized that a new risk score would perform better than the DTS. Methods: We studied 59,877 consecutive patients who had exercise testing between Januray 1, 2000 and October 27, 2011 with the sample divided equally into derivation and validation cohorts. The primary outcome was all-cause mortality. Risk scores for men and women were developed from Cox proportional hazards models. The DTS was compared to new risk scores in the validation cohort with C-statistics, category-free net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: Over a median follow-up of 8 years, there were 2,521 deaths. In the multivariable model, age, exercise capacity, heart rate recovery, weight, and renal disease were associated with mortality in men and women. Diabetes mellitus and history of smoking were associated with mortality in women whereas heart failure, current smoking, and hypertension were associated with mortality in men. C-statistics, NRI, and IDI were all improved with the new risk scores (Table). In particular, the new risk scores correctly reclassified patients with events, especially in women. Patients in the highest tertile of risk score also had substantial mortality during follow-up (Figure). Conclusions: We have developed new risk scores for men and women that perform better than the DTS, particularly in patients at the highest risk for all-cause mortality.

Use of a novel convolutional neural network-based mammographic evaluation to assess response to adjuvant endocrine therapy in women with early-stage breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 530-530
Author(s):  
Julia Elizabeth McGuinness ◽  
Vicky Ro ◽  
Simukayi Mutasa ◽  
Richard Ha ◽  
Katherine D. Crew
Keyword(s):  
Breast Cancer ◽  
Neural Network ◽  
Prognostic Factors ◽  
Convolutional Neural Network ◽  
Endocrine Therapy ◽  
Risk Score ◽  
Early Stage ◽  
Stage I ◽  
Risk Scores

530 Background: The standard of care for early-stage hormone receptor (HR)-positive breast cancer (BC) is 5-10 years of adjuvant endocrine therapy (ET), which leads to a 50-60% relative risk reduction in BC recurrence. However, 10-40% of patients may relapse up to 20 years (y) after diagnosis, and there is a need for biomarkers of response to ET. We developed a novel, fully-automated convolutional neural network (CNN)-based mammographic evaluation that accurately predicts BC risk, which is being evaluated as a pharmacodynamic response biomarker to adjuvant ET. Methods: We conducted a retrospective cohort study among women with HR-positive stage I-III unilateral BC diagnosed at Columbia University Irving Medical Center from 2007-2017, who received adjuvant ET and had at least 2 mammograms of the contralateral breast (baseline and annual follow-up). Demographics, clinical characteristics, BC treatments, and relapse status were extracted from the electronic health record and New York-Presbyterian Hospital Tumor Registry. We performed CNN analysis of mammograms at baseline (start of ET) and annual follow-up. Our primary endpoint was change in CNN risk score, expressed as a continuous variable (range, 0-1). We used two-sample t-tests to assess for differences in mean CNN scores between patients who relapsed or remained in remission. We evaluated if CNN score at baseline and change from baseline were associated with relapse using logistic regression, with adjustment for known prognostic factors. Results: Among 870 evaluable women, mean age at diagnosis was 59.5y (standard deviation [SD], 12.4); 60.3% had stage I tumors, 72.6% underwent lumpectomy, and 45.8% received chemotherapy. With a median follow-up of 4.9y, there were 68 (7.9%) breast cancer relapses (36 distant, 26 local, 6 new primary). Median number of evaluable mammograms per patient was 5 (range, 2-13). Mean baseline CNN risk scores were significantly higher among women who relapsed compared to those in remission (0.258 vs 0.237, p = 0.022), which remained significant after adjustment for known prognostic factors. There was a significant difference in mean absolute change in CNN risk score from baseline to 1y follow-up between those who relapsed vs. remained in remission (0.001 vs. -0.022, p = 0.027), but this was no longer significant in multivariable analysis. Conclusions: We demonstrated that higher baseline CNN risk score was an independent predictor of BC relapse. A greater decrease in mean CNN risk scores at 1-year follow-up after initiating adjuvant ET was seen among BC patients who remained in remission compared to those who relapsed. Therefore, baseline CNN risk scores may identify patients at high-risk for breast cancer recurrence to target for more intensive adjuvant treatment. Early changes in CNN risk scores may be used to predict response to long-term ET in the adjuvant setting.

P1110Role of an extensive diagnostic work-up in the detection of concealed cardiomyopathies in athletes with complex ventricular arrhythmias and implications for sports" eligibility assessment

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Dello Russo ◽  
M Casella ◽  
F Guerra ◽  
P Compagnucci ◽  
A Gasperetti ◽  
...  
Keyword(s):  
Risk Score ◽  
Ventricular Arrhythmias ◽  
Heart Diseases ◽  
Risk Scores ◽  
Competitive Sports ◽  
Non Invasive ◽  
Structural Heart Diseases ◽  
Eligibility Assessment ◽  
Work Up

Abstract Background ventricular Arrhythmias (VAs) are a common clinical problem and a critical issue with regards to sports" eligibility in athletes. Although VAs can be considered a benign feature of the athlete’s heart adaptive phenotype, they may also be the only clinical manifestation of a concealed cardiomyopathy, potentially heralding sudden cardiac death (SCD) during sports activity. Purpose to evaluate the diagnostic contribution and the implications for sports eligibility assessment of a thorough non-invasive and invasive work-up including electrophysiology study (EPS), electroanatomical mapping (EAM) and endomyocardial biopsy (EMB) in athletes with complex VAs and to derive a multiparametric risk score in order to easily predict structural heart diseases’ diagnosis. Methods we conducted a prospective, single-arm, open-label single center, observational study. All consecutive athletes presenting for evaluation at our institution after being disqualified from participating in sports due to complex VAs were enrolled. The athletes underwent a baseline non-invasive diagnostic protocol with transthoracic echocardiogram and gadolinium enhanced cardiac magnetic resonance imaging (cMRI). Subsequently EPS, EAM and EAM-guided EMB were performed if deemed necessary. Sports eligibility status was re-assessed at 6 months’ follow-up. A multivariable logistic regression model was built, considering cMRI as the gold standard exam. Results after diagnostic evaluation, 55 subjects (26.4%) had a diagnosis of heart disease, most commonly myocarditis (n = 27) and arrhythmogenic right ventricular cardiomyopathy (ARVC, n = 16). After 6 months, 100 athletes (48.1%) were judged eligible to participate in competitive sports and 46 subjects (22.1%) were deemed eligible to participate in non-competitive sports. On multivariable logistic-regression analysis, abnormalities on ECG (OR 5.3) or on echocardiogram (OR 3.7), sustained VA inducibility on EPS (OR 17.7) and low-voltage areas on EAM (OR 7.7) proved all predictive of concealed structural heart diseases’ diagnosis. We derived two simple risk scores: a 40-points risk score and an 8-points risk score (obtained by weighing each variable according to the regression model’s ORs). Both these risk scores’ performance proved very good (AUC = 0.856 for the 40-points score and AUC = 0.852 for the 8-points score, figure 1). Conclusions approximately 1/4 of athletes presenting with complex VAs have a concealed heart disease, most commonly myocarditis or ARVC. ECG, echocardiogram and EAM abnormalities and sustained VAs inducibility on EPS are predictive of structural heart diseases’ detection. Therefore, these diagnostic tests should be routinely included in the evaluation of athletes with complex VAs. A risk score including the results of these tests can greatly help in the prediction of concealed structural heart diseases’ diagnosis. More than 2/3 of subjects were judged eligible to participate in sports at 6 months’ follow-up. Abstract Figure 1. ROC curves for diagnosis

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