Role of ctDNA to predict risk of recurrence following potentially curative resection of biliary tract and pancreatic malignancies.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 336-336
Author(s):  
Angela Lamarca ◽  
Mairead Geraldine McNamara ◽  
Richard Hubner ◽  
Juan W. Valle

336 Background: The potential role of ctDNA to identify residual disease after potentially curative resection has been suggested in some malignancies; its role in resected pancreatico(P)-biliary(B) malignancies is unknown. Methods: Patients diagnosed with PB malignancies underwent molecular profiling (ctDNA) using FoundationMedicine Liquid (72 cancer-related genes) following potentially curative resection. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. Primary objective: prevalence of ctDNA identification and its correlation with recurrence (relapse-free survival (RFS) and relapse rate). Results: Total of 11 individuals had ctDNA analysed following potentially curative resection for PB malignancies: 8 B (4 extra-hepatic cholangiocarcinoma (eCCA), 2 ampulla, 1 intrahepatic cholangiocarcinoma (iCCA), 1 gallbladder cancer (GBC)) and 3 P. Baseline characteristics: 6 female (54.55%), median age 71.59 years (range 39.98-81.19). Most were pT2 (45.45%), pN0 (54.55%) and R0 (63.64%). Following surgery, 6 patients were started on adjuvant chemotherapy; at the end of follow-up (data cut-off 25/6/2020; median follow-up 11.15 months (range 5.45-13.52); 5 relapsed (45.45%) and 2 died (18.18%). Estimated median RFS was 11.43 months (95% CI 2.28-not reached); median overall survival was not reached. No sample failed ctDNA analysis; presence of ctDNA was identified in 3/11 (27.27%) of the samples; 2 and 1 samples had 2 and 1 pathological alterations identified, respectively: ALK fusion (1 sample; GBC), TP53 mutation (2 samples; eCCA and GBC), CHEK2 mutation (1 sample; pancreas), IDH2 mutation (1 sample; eCCA). Mean maximum MAF was 1.47 (2 in biliary; 0.43 in pancreas). Variants of unknown significance were identified in 72.73% of the samples (87.5% in B; 33.33% in P; p-value 0.152). None of the baseline characteristics explored correlated with presence of ctDNA. There was a trend towards increased relapse risk in the patients with ctDNA present following potentially curative surgery; Cox regression for RFS [HR 2.64 (95% CI 0.36-19.31); median RFS 11.44 months (95% CI 2.28-not reached) vs 10.87 (95% CI 2.21-not reached)]; relapse rate 37.5% (ctDNA absent) vs 66.67% (ctDNA present); statistical significance was not reached (p-value 0.340 and p-value 0.545, respectively). Conclusions: This pilot study demonstrates the feasibility of testing for ctDNA following potentially curative resection in PB malignancies. Presence of ctDNA may be associated with increased relapse risk; further studies are required to increase sample size and assess clinical implications.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1986-1986
Author(s):  
Jiong Hu ◽  
han-Bo Dou ◽  
Ling Wang ◽  
Wei Tang

Abstract Abstract 1986 For adult patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donor (MSD) is recommended for standard and high-risk patients. The role of unrelated donor transplantation (URD) is not fully determined. In this single-center retrospective analysis, we included all consecutive adult patients with high-risk ALL in 1st complete remission (CR) without sibling donor between Jan 2007 to June 2012. Overall, 74 patients were included in the analysis in which 32 patients received URD allo-HSCT during 1st CR with busulfan-cyclophophamide preparation regimen and in vivo T cell depletion with anti-T-lymphoglobulin (ATG). The median time from remission to transplantation was 4.5 months (3∼13). Forty-two patients in the chemotherapy group with 1st CR more than 6 months received consolidation chemotherapy alone either due to lack of suitable URD (n=21), refuse to URD search (n=14), unwillingness to undergo transplantation with available URD (n=5) and donor refuse to donate (n=2). Salvage allo-HSCT was allowed after relapse and actually 5 patients in the chemotherapy group received transplantation from URD donor (n=2) or haplo-identical donor (n=2) in the subsequent remission. The clinical characteristics such age, sex, initial WBC, and Philadelphia chromosome are all distributed equally in the two groups. With a median follow-up of 18 months for the whole group, 30 patients relapsed with estimated 3-year relapse rate (RR) at 58.1±8.5%. The 3-year event-free survival (LFS), non-relapse mortality (NRM) and overall survival (OS) were 38.0±7.9%, 11.1±4.4% and 46.0±9.0% respectively. In the URD allo-HSCT group, RR was 30.6±11.4% which was significantly lower than chemotherapy group (80.5±10.1%, p<0.001) while NRM was higher (16.4±6.7% vs. 0, p=0.028). Overall, 3-year LFS was superior in URD allo-HSCT group compared to chemotherapy (57.8±10.6% vs. 19.5±10.5%; median not reached vs. 13 months, p=0.002) and 3-year OS was also improved in URD allo-HSCT group (63.5±13.3%, median not reached versus 31.6±10.6%, median 24 months, p=0.016). Based on our data, URD allo-HSCT significantly reduced the relapse rate in high-risk ALL and the benefit translated into improvement in both LFS and OS. Prospective randomized study based on availability of HLA matched URD is warranted to confirm the exact role of URD transplantation in adult ALL. Table 1. Patient's characteristics Chemotherapy URD-allo-HSCT P value No of patients N=42 N=32 Median Follow-up (months) 15 (7.7∼48) 22 (8.2∼49) Sex (M/F) 19/23 21/11 0.08 Age 24.5 (16∼60) 25 (16∼57) 0.10     >35 14 9 0.61     <=35 28 23 Initial WBC (×109/L) 80.3 (15.3∼97.9) 61.5 (3.2∼98.4) 0.12 Cytogenetics     Ph+ 8 10 0.33     Ph− 33 22 Table 2. Clinical outcome in different treatment strategies Chemotherapy URD-allo-HSCT P value No of patients N=42 N=32 OS 31.6 ± 10.6% 63.5 ± 13.3% 0.016     median 24.9 months not reached LFS 19.5 ± 10.5% 57.8 ± 10.6% 0.002     median 13.2 months not reached Relapse rate 80.5 ± 10.1% 30.6 ± 11.4% <0.001 NRM 0% 16.4 ± 6.7% 0.028 Disclosures: No relevant conflicts of interest to declare.


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
V Varnavas ◽  
M Terasawa ◽  
J Sieira ◽  
J P Abugattas ◽  
E Stroker ◽  
...  

Abstract Introduction The purpose of this study was to analyze and compare the electrophysiological findings in redo radiofrequency (RF)-ablation of AF in a series of patients with durable PV isolation (PVI) and with PV reconnection after index procedure with the second-generation cryoballon (CB). Methods and results A total of 132 patients (81 males, 60.7 ± 12.4 years) who underwent CB-A for paroxysmal AF (PAF) were enrolled. Indication for the redo procedure was symptomatic (PAF) in 83 (63%) and persistent AF (PeAF) or persistent regular atrial tachycardia (RAT) in 49 (37%). Seventy-five (57%) patients presented a PV reconnection (PV group), whereas 57 (43%) no PV reconnection (non-PV group). The non-PV group exhibited significantly more atrial flutters and non-PV foci than the PV group after induction protocol (67% vs. 36%, p = 0.003 and 51% vs. 24% p = 0.002, respectively) (Table 1). Twenty-two (29.3%) patients of the PV group and 20 (35%) patients of the non-PV group had AF/RAT recurrence after a mean follow-up of 12.5 ± 8 months. The survival analysis demonstrated no statistical significance in recurrence between the two groups (log rank p = 0.358). In the cox regression analysis only the AF/RAT recurrence in the blanking period could predict independently an AF/RAT relapse. Conclusions AF/RAT recurrence in patients after CB-A with durable PVI is significantly associated to atrial flutters and non-PV foci. No statistically different success rate regarding AF/RAT freedom was detected between PV and non-PV Group after redo RF-CA. Table 1. Electrophysiological findings PV Groupn = 75 non-PV Groupn = 57 p-value PV trigger (n of patients) 75(100) 0(0) &lt;0.001 LSPV 29 (39) 0 (0) &lt;0.001 LIPV 15 (20) 0 (0) &lt;0.001 RSPV 27 (36) 0 (0) &lt;0.001 RIPV 33 (44) 0 (0) &lt;0.001 Atrial flutters (n of patients) 27 (36) 38 (67) 0.003 Roof-flutter 13 (17) 34 (60) 0.0001 Peri-mitral-flutter 9 (12) 20 (35) 0.003 Right flutter 13 (17) 5 (9) 0.2 Non-PV foci (n of patients) 18 (24) 29 (51) 0.002 Categorical variables are expressed as absolute and percentage (in brackets). LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; PV, pulmonary vein; RSPV, right superior pulmonary vein; RIPV, right inferior pulmonary vein.


2020 ◽  
Vol 11 (3) ◽  
pp. 4061-4067
Author(s):  
Alpesh ◽  
Jumale V P

In the present study follow up kept on immediate post-operative day and at one week to evaluate pain, bleeding and inflammation. Final follow up at two months for assessment of aesthetic score by three independent personnel. Pain and inflammation were more associated with Group B compared to Group A, but there are no statistical significance differences among this groups (P value- 0.074 and 0.136 for pain and inflammation respectively on immediate post-operative day. Chi-square test). Final follow up assessment of aesthetic scores at two months calculated by Chi- square test and comparisons of two groups for aesthetic scores done by Independent t-Test. All three personnel gave higher aesthetic score to Group B but statistically this was not significant (P-value 0.287, 0.129 and 0.400 by Observer 1, 2 and patients respectively. Chi-square test). The mean aesthetic score given by Observer 1, 2 and patient was higher associated to Group B but statistically this was not significant (P=0.526, 0.055 and 0.232 independent t-Test).


Perfusion ◽  
2021 ◽  
pp. 026765912199599
Author(s):  
Esther Dreier ◽  
Maximilian Valentin Malfertheiner ◽  
Thomas Dienemann ◽  
Christoph Fisser ◽  
Maik Foltan ◽  
...  

Background: The role of venovenous extracorporeal membrane oxygenation (VV ECMO) in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) still remains unclear. Our aim was to investigate the clinical course and outcome of those patients and to identify factors associated with the need for prolonged ECMO therapy. Methods: A retrospective single-center study on patients with VV ECMO for COVID-19-associated ARDS was performed. Baseline characteristics, ventilatory and ECMO parameters, and laboratory and virological results were evaluated over time. Six months follow-up was assessed. Results: Eleven of 16 patients (68.8%) survived to 6 months follow-up with four patients requiring short-term (<28 days) and seven requiring prolonged (⩾28 days) ECMO support. Lung compliance before ECMO was higher in the prolonged than in the short-term group (28.1 (28.8–32.1) ml/cmH2O vs 18.7 (17.7–25.0) ml/cmH2O, p = 0.030). Mechanical ventilation before ECMO was longer (19 (16–23) days vs 5 (5–9) days, p = 0.002) and SOFA score was higher (12.0 (10.5–17.0) vs 10.0 (9.0–10.0), p = 0.002) in non-survivors compared to survivors. Low viral load during the first days on ECMO tended to indicate worse outcomes. Seroconversion against SARS-CoV-2 occurred in all patients, but did not affect outcome. Conclusions: VV ECMO support for COVID-19-induced ARDS is justified if initiated early and at an experienced ECMO center. Prolonged ECMO therapy might be required in those patients. Although no relevant predictive factors for the duration of ECMO support were found, the decision to stop therapy should not be made dependent of the length of ECMO treatment.


Author(s):  
Kemar J Brown ◽  
Njambi Mathenge ◽  
Daniela Crousillat ◽  
Jaclyn Pagliaro ◽  
Connor Grady ◽  
...  

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in the rapid uptake of telemedicine (TM) for routine cardiovascular care. Objectives To examine the predictors of TM utilization among ambulatory cardiology patients during the COVID-19 pandemic. Methods In this single centre retrospective study, all ambulatory cardiovascular encounters occurring between March 16th - June 19th, 2020 were assessed. Baseline characteristics by visit type (in-person, TM-phone, TM-video) were compared using Chi-square and student t-tests, with statistical significance defined by p value &lt; 0.05. Multivariate logistic regression was used to explore the predictors of TM versus in-person care. Results 8446 patients (86% Non-Hispanic White, 42% female, median age 66.8 +/- 15.2 years) completed an ambulatory cardiovascular visit during the study period. TM-phone (n = 4,981, 61.5%) was the primary mode of ambulatory care followed by TM-video (n = 2693, 33.2%). Non-Hispanic Black race (OR 0.56; 95% CI: 0.35 - 0.94, p-value=0.02), Hispanic ethnicity (OR 0.53; 95% CI: 0.29 - 0.98, p = 0.04), public insurance (Medicaid OR 0.50; 95% CI:0.32 – 0.79, p = 0.003, Medicare OR 0.65; 95% CI: 0.47– 0.89, p = 0.009), zip-code linked median household income (MHI) of &lt;$75,000, age &gt;85 years, and patients with a diagnosis of heart failure were associated with reduced access to TM-video encounters and a higher likelihood of in-person care. Conclusions Significant disparities in TM-video access for ambulatory cardiovascular care exist among the elderly, lower income, as well as Black and Hispanic racial/ethnic groups.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 689.1-690
Author(s):  
S. Monti ◽  
L. Dagna ◽  
C. Campochiaro ◽  
A. Tomelleri ◽  
G. Zanframundo ◽  
...  

Background:Giant cell arteritis (GCA) is the most frequent systemic vasculitis after the age of 50 years old. Recent interest in the processes of immune and vascular aging have been proposed as a disease risk factor. Data on the impact of age at diagnosis of GCA on the clinical course of the disease are scarceObjectives:To assess the role of age at diagnosis of GCA on the risk and time to relapseMethods:Centres participating in the Italian Society of Rheumatology Vasculitis Study Group retrospectively enrolled patients with a diagnosis of GCA until December 2019. The cohort was divided in tertiles according to age at diagnosis (≤ 72; 73-79; > 79 years old). Negative binomial regression was used to assess the relapse rate according to age groups, and Cox regression for time to first relapse.Results:Of 720 patients enrolled in 14 Italian reference centres, 711 had complete follow-up data (female 50%; mean age 75±7). Median follow-up duration was 34 months (IQR 16;70). Patients in the older group at diagnosis (> 79 years) had more frequent visual loss compared to the 73-79 and ≤ 72 age groups (31% vs 20% vs 7%; p<0.001), but lower rates of general symptoms (56% vs 70% vs 77%; p<0.001). Large-vessel (LV)-GCA was less frequent in the older group (18% vs 22% vs 43%; p<0.001). At least one relapse occurred in 47% of patients. Median time to relapse was 12 months (IQR 6;23). Age did not influence the rate of relapses [18 per 100 persons/years (95%CI 15;21) vs 19 (95% CI 17;22) vs 19 (95%CI 17;22)], nor the time to first relapse (Figure 1). LV-GCA, presentation with significantly elevated c-reactive protein (> 50 mg/L) and general symptoms were independent predictors of relapse.Conclusion:Age at diagnosis of GCA influenced the clinical presentation and risk of ischaemic complications, but did not affect the relapse rate during follow-up. LV-GCA occurred more frequently in younger patients and was an independent predictor of relapse risk, highlighting the need for a correct characterization of the clinical subtype at the early stages of disease.Disclosure of Interests:Sara Monti: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Giovanni Zanframundo: None declared, Catherine Klersy: None declared, Francesco Muratore: None declared, Luigi Boiardi: None declared, Roberto Padoan: None declared, Mara Felicetti: None declared, Franco Schiavon: None declared, Milena Bond: None declared, Alvise Berti: None declared, Roberto Bortolotti: None declared, Carlotta Nannini: None declared, Fabrizio Cantini: None declared, Alessandro Giollo: None declared, Edoardo Conticini: None declared, angelica gattamelata: None declared, Roberta Priori: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Giacomo Emmi: None declared, Martina Finocchi: None declared, Giulia Cassone: None declared, Ariela Hoxha Speakers bureau: Celgene, UCB, Novartis, Sanofi, Werfen, Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Michele Colaci: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Carlo Salvarani: None declared, Carlomaurizio Montecucco: None declared


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Fassikaw Kebede ◽  
Birhanu Kebede ◽  
Tsehay Kebede ◽  
Melaku Agmasu

The human immune deficiency virus (HIV) is the strongest risk factor for the incidence of tuberculosis (TB) by way of reactivation of latent or new infection. The provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB. To date, there have been limited clinical data regarding the effectiveness of isoniazid preventive therapy (IPT) on TB incidence. This study aimed to assess the effect of isoniazid preventive therapy on the incidence of tuberculosis for seropositive children in Northwest Ethiopia. Methods. A facility-based retrospective follow-up was employed for reviewing 421 files from 1 January 2015 up to 30 December 2019. EpiData version 3.2 and Stata/14 software were used for data entry and analysis, respectively. Categorical variables at bivariable Cox regression were assessed for candidates transferred at P value <0.25 for multivariable Cox regression to claiming predictors associated with TB incidence rate at 95% CI at P < 0.005 . Result. The overall incidence of TB was found to be 4.99 cases per 100 person-years at 95% CI (3.89–6.53). Missed IPT (AHR = 7.45, 95% CI: 2.96, 18.74, P < 0.001 ), missed cotrimoxazole preventive therapy (CPT) (AHR = 2.4, 95% CI: 1.84–4.74, P < 0.022 ), age ≥ 11 years (AHR = 4.2, 95% CI: 1.04–7.03, P < 0.048 ), MUAC ≤ 11.5 cm (AHR = 4.36, 95% CI: 1.97–9.97, P < 0.001 ), WHO stages III and IV (AHR = 2.04, 95% CI: 1.12–3.74, P < 0.022 ), and CD4 count ≤100 cells/μl (AHR = 3.96, 95% CI: 1.52–10.34, P < 0.005 ) were significantly associated with TB incidence. Conclusion. Concomitant administration of ART with IPT had demoted more than ninety-six percent of new TB incidences for this report. Undertaking in-depth TB screening and frequent follow-up among all these children is critical in order to prevent and control tuberculosis.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Mackenzie Steck ◽  
Omar Saeed ◽  
Balaji Krishnaiah ◽  
Samarth Shah ◽  
Jaclyn Stoffel ◽  
...  

Presentation Objective: Does glycemic variability worsen Modified Rankin Score (mRS) following ischemic stroke in patients treated with thrombolytics (tPA)? Background/Purpose: Acute hyperglycemia and strict glucose control have been identified as predictors of hemorrhage, increased length of stay and hypoglycemia following ischemic stroke. However, the role of glucose variability in patients with ischemic stroke treated with tPA is largely unknown. The aim of this study was to evaluate the role of glycemic variability on discharge outcomes in patients treated with tPA for ischemic stroke. Methodology: A retrospective review of adults with ischemic stroke who received tPA was completed. Patients hospitalized for at least 48 hours with image-confirmed ischemic stroke and symptom onset within 4.5 hours of presentation were included. Glycemic variability was measured using the J-index calculation and groups were defined as patients with normal or abnormal J-indices. Logistic regression models were developed to determine odds ratios for defined outcomes including NIHSS score, mRS and disposition at discharge. Statistical significance was a p-value of <0.05. Results: Of the 229 patients included, 132 (58%) had a normal J-index (4.7 – 23.6). In the univariate analysis, abnormal J-index was associated with higher rates of hypertension (94% vs 73%), type 2 diabetes mellitus (74% vs 12%), chronic kidney disease (34% vs 11%), higher initial blood glucose values (220 ±172 vs 111 ±20) and HbA1c, and worse outcomes in terms of NIHSS score, mRS and disposition at discharge. In the multivariate analysis, patients with an abnormal J-index had higher odds of unfavorable outcomes in terms of discharge mRS (OR 2.1; 95% CI 1.0 – 4.3, p=0.045) and hemorrhagic transformation (OR 4.1; 95% CI 1.7 – 10.2, p=0.002). There was no difference in discharge disposition (OR 1.4; 95% CI 0.7 – 3.0 p=0.4). Conclusion: Glycemic variability, following ischemic stroke, may result in unfavorable patient outcomes in patients treated with tPA. Additional studies are needed to determine the appropriate glucose management strategy.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 425-425
Author(s):  
Angela Lamarca ◽  
Mairead Geraldine McNamara ◽  
Richard Hubner ◽  
Juan W. Valle

425 Background: Molecular profiling of tumour samples and circulating tumour DNA (ctDNA) may inform treatment of advanced cancer; the role of ctDNA to predict progression-free-survival (PFS) and overall survival (OS) in advanced PDAC is not fully understood. Methods: Eligible patients: those diagnosed with advanced PDAC undergoing molecular profiling [tumour (Foundation Medicine CDx/Caris) or ctDNA (FoundationMedicine Liquid (72 cancer-related genes))]. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. The primary aim was to assess the impact of presence of ctDNA at time of systemic chemotherapy initiation on PFS and OS. Results: Total of 26 samples (ctDNA 18 samples and 8 tumour samples) from 25 patients diagnosed with advanced PDAC underwent molecular profiling. When the whole population was analysed, the rate of sample analysis failure seemed to be higher when tumour tissue was tested (37.5%) compared to ctDNA (5.56%); p-value 0.072. The overall rate of identification of pathological findings was 72.73%, with 18.18% of patients having targetable findings [EGFRmut (1 patient), KRAS G12C mut (1 patient), FGFR2 fusion (1 patient), RNF43 mut (1 patient)]; these findings impacted treatment management in one patient only (RNF43 mutation; Wnt inhibitor). Variants of unknown significance were identified in 63.64% of samples. Patients with ctDNA analysis at time of palliative chemotherapy initiation (16 samples; 15 patients) were analysed [6 female (40.00%), median age 69.57 years (range 51.61-81.49), metastatic disease (66.67%), 80% first-line (80%), 20% second-line]. Pathological mutations were identified in 9/15 (60.00%) of these patients (KRAS mutation identified in 6/9). After median follow-up of 8.33 months from sample acquisition, 80% and 53.33% of patients had progressed and died, respectively. Median estimated PFS and OS were 5.65 months (95% CI 1.59-8.17) and 7.80 months (95% CI 4.13-not reached). Presence (vs absence) of pathological alterations in ctDNA showed a trend towards shorter PFS (2.91 vs 6.51 months; HR 1.38 (95% CI 0.40-4.77)) and OS (6.12 vs 9.72 months; HR 2.03 (95% CI 0.60-6.82)). Conclusions: This pilot study demonstrates the feasibility of ctDNA analysis in patients with advanced PDAC prior to initiation of palliative therapy. The presence of pathological alterations in ctDNA may prognosticate for worse PFS and OS. Larger studies are required to confirm these findings.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Nora Krau ◽  
Sandra Freitag-Wolf ◽  
Doreen Brehm ◽  
Rainer Petzina ◽  
Georg Lutter ◽  
...  

Background: GDF15 belongs to the transforming growth factor superfamily and has a significant role in regulating inflammatory and apoptotic pathways. GDF15 is an emerging biomarker for risk stratification in cardiovascular disease. Here we analyze its prognostic value in patients with severe symptomatic aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI). Methods and Results: We prospectively enrolled 217 patients undergoing TAVI (using Edwards Sapien XT prostheses) at our institution over a continuous period of 35 month (2/2011-12/2013). All patients were available for complete follow up. Clinical parameters were determined before the procedure, biomarkers (GDF15 & NTproBNP) were measured before, 3 and 7 days after TAVI. The primary endpoint was survival time, all available prognostic factors were studied by Cox regression analysis with backward selection based on the likelihood ratio criteria. At median follow-up of 349 d (Q1-Q3 106-660d), a total of n=66 deaths occurred. 30d mortality was 6.9%. Mean age was 81.8 years (± 6.0 y) and 55.8% were females. Mean log. Euroscore (ES) was 25.4% (± 17.2%). Median preprocedural GDF15 values were 2256 pg/ml (Q1-Q3 1585.5-3082.0). In univariate analyses, increased GDF15 levels (upper quartile compared to lower three quartiles) revealed a HR of 2.4 (CI 1.5-3.9, p<0.001) for adverse outcome. In addition, also log. ES (p= 0.001), log. ES II (p=0.018), STS-Score (p=0.019), NTproBNP (p=0.037) and atrial fibrillation (p=0.02) demonstrated statistical significance for negative outcome. A multivariate Cox regression analysis including these factors and postprocedural aortic regurgitation, demonstrated that elevated GDF15 had a HR of 2.104 (CI 1.3-3.5; p=0.003) for negative outcome in patients undergoing TAVI, while elevated NTproBNP had HR of 1.412 (CI 0.8-2.4; p=0.212). Moreover, this analysis also revealed the log. ES as an independent risk factor (HR of 2.211, CI 1.3-3.7; p= 0.002). Conclusion: Increased GDF15 levels are associated with a poor prognosis in patients undergoing TAVI. Furthermore, GDF15 showed to be superior to the established biomarker NTproBNP in risk stratification of patients undergoing TAVI providing additional prognostic information.


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