tbuckley/cabot-search huggingface dataset:
Baseline total metabolic tumor volume assessed by 18FDG-PET/CT predicts outcome in advanced melanoma patients treated with pembrolizumab
Authors: G. Awada, I. Özdemir, J.K. Schwarze, E. Daeninck, O. Gondry, Y. Jansen, T. Seremet, M. Keyaerts, H. Everaert, B. Neyns
Journal: Annals of Oncology (2018)

Background: Pembrolizumab (PEMBRO) improves survival in patients (pts) with advanced melanoma (MEL). Baseline (BL) parameters that predict long-term benefit for PEMBRO treatment are under investigation. Methods: Outcome data of pts with advanced MEL treated with PEMBRO at our institution were collected as part of a prospective therapeutically non-interventional trial. Objective responses were evaluated using the immune-related response criteria. Total metabolic tumor volume (TMTV) was assessed by 18-fluorodeoxyglucose positron emission tomography (18FDG-PET/CT) using MIM Encore Software®. TMTV was defined as the sum of all tumor-associated voxels with a standardized uptake value (SUV) higher than the mean SUV measured in a reference region in normal liver tissue + 3 standard deviations. Results: BL 18FDG-PET/CT disease staging results were available for 69 pts. Median progression-free survival (mPFS) was 19 w (95% CI 9-29); median overall survival (mOS) was 130 w. A cut-off value of 90 mL of BL TMTV defined a subpopulation with significantly worse PFS (mPFS 7 w [95% CI 4-9] vs 56 w [95% CI 0-118]; HR 19.10, p < 0.001) and OS (mOS 21 w [95% CI 2-41] vs not reached; HR 46.14, p < 0.001). Additionally, a history of brain metastases (HBM), C-reactive protein (CRP) >5 times upper limit of normal (>5xULN), lactate dehydrogenase (LDH) >1xULN, WHO Performance Status (WHO PS) ≥1 and number of metastatic sites ≥2 were associated with significantly shorter PFS and OS in univariate analysis (log rank p < 0.05). In multivariate analysis (Cox multivariate logistic regression), a BL TMTV >90 mL (HR 3.70 [95% CI 1.79-7.69]), HBM (HR 2.08 [95% CI 1.11-3.85]) and WHO PS ≥ 1 (HR 2.08 [95% CI 1.12-3.85]) were significantly associated with shorter PFS; BL TMTV >90 mL (HR 14.29 [95% CI 5.26-33.33]) and HBM (HR 2.56 [95% CI 1.23-5.26]) were significantly associated with shorter OS. Conclusions: BL TMTV >90 mL and HBM independently correlate with worse PFS and OS in pts with advanced MEL treated with PEMBRO. Elevated BL CRP and LDH values overlap with, but are inferior to TMTV as predictive biomarkers for outcome of PEMBRO treatment. Confirmation of these results is under investigation in an independent second cohort. Legal entity responsible for the study: Universitair Ziekenhuis Brussel, Brussels, Belgium. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
A phase I study of ombrabulin (O) combined with bevacizumab (B) in patients with advanced solid tumors (NCT01193595).
Authors: Gianluca Del Conte, Rastilav Bahleda, Victor Moreno, Silvia Damian, Antonella Perotti, Nathalie Lassau, Françoise Farace, Michael Ong, Sarah Jane Stimpson, Nina Tunariu, Sandrine Micallef, Brigitte Demers, Corina Oprea, Giuseppe Capri, Jean-Charles Soria, Cristiana Sessa, L Rhoda Molife
Journal: Journal of Clinical Oncology (2012)

3080 Background: O is a vascular-disrupting agent derived from combretastatin A4-phosphate that induces rapid but transient tumor vascular shutdown. In experimental models, the combination of O with VEGF-blockade induced more regressions than O alone. This phase I study was performed to determine the maximum tolerated dose (MTD), and assess the overall safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity of O plus B. Trial is funded by sanofi. Methods: Patients (pt) with advanced solid tumors, ECOG PS ≤1, and adequate organ function were eligible. Increasing doses of O (mg/m²) was administered intravenously (IV) on day (d) 1; B (5 or 10mg/kg) was administered IV on d2, in 21d cycles (C). A Bayesian design was applied to determine dose escalation steps and MTD. PK sampling was performed in C1 and C2. PD sampling for circulating endothelial cells (CEC) and progenitors (CEP) were performed throughout. Dynamic contrast-enhanced ultrasound (DCE-US) to assess tumor perfusion was performed before and after C1 and C2 dosing. Results: 25 pts (M:F 6:19; median age 49 years [range 27-75]) have been treated at 8 dose levels of O/B: 8/5 (3), 11.5/5 (4), 11.5/10 (3), 15.5/10 (3), 20/10 (3), 25/10 (3); 35/10 (3) and 42/10 (3). Ovarian cancer was the most frequent tumor type (n=11). Median Cs received was 3 (1 to 14). No DLTs were observed during C1. Drug-related grade (g) 3-4 adverse events (AE) included hypertension in 2 pts (8/5; 11.5/5) and ileal perforation in 1 pt with peritoneal carcinomatosis at laparotomy (11.5/10). A case of duodenal perforation was unlikely related (25/10). Two pts with ovarian cancer (11.5/5; 20/10) had confirmed partial responses (4.4 months (mo) and 7+ mo). 13/23 (57%) pts with ≥ 1 tumor assessment had stable disease (n=8; median 4.3 mo [1.8-9.5]; 5 ongoing). Data from cohorts 1 and 2 demonstrated no evidence of a PK interaction.17/25 patients demonstrated a peak in CEC, and 7/9 patients a peak in CEP. 4/7 DCE-US evaluable pts had &gt;50% drop in tumor perfusion (AUC) at Day 8 of C1. Conclusions: O combined with B is well tolerated with early evidence of clinical activity. The MTD has not been reached (current dose level 50/10); cohorts of O combined with B at 15 mg/kg will be tested.
Rituximab/Bendamustine and Rituximab/Cytarabine (RB/RC) Induction Chemotherapy for Transplant-Eligible Patients with Mantle Cell Lymphoma: A Pooled Analysis of Two Phase 2 Clinical Trials and Off-Trial Experience
Authors: Reid W Merryman, Brad S Kahl, Robert A. Redd, Jad Bsat, Matthew Lewis Chase, Ann S. LaCasce, Arnold S. Freedman, Caron A. Jacobson, David C. Fisher, Samuel Y. Ng, Jennifer L Crombie, Austin I Kim, Oreofe O. Odejide, Matthew S. Davids, Jennifer R. Brown, Heather A. Jacene, Mehta-Shah Neha, Natasha Edwin, Amanda F Cashen, Nancy L. Bartlett, Armin Ghobadi, Philippe Armand, Robin M. Joyce, Eric D Jacobsen
Journal: Blood (2018)
Abstract 11548: Nanofibrous Collagen Scaffolds Seeded With Human Pluripotent Stem Cell-derived Cardiomyocytes Induce Cardiac Remodeling in Dilated Cardiomyopathy
Authors: Solene Boitard, Pierre Joanne, Maria Kitsara, Hany Nematalla, Valérie Vanneaux, Mathieu Pernot, Jerome Larghero, Patricia Forest, Yong Chen, Philippe Menasché, Onnik Agbulut
Journal: Circulation (2015)

Introduction: Limited data are available on the effect of stem cells in non-ischemic dilated cardiomyopathy (DCM). Hypothesis: Since the diffuse nature of DCM calls for a broad distribution of cells, we tested the scaffold-based delivery of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in a mouse model of DCM. Methods: (1) In vitro protocol: A clinical grade atelocollagen was electrospun and crosslinked under different conditions to optimize production of nanofibrous scaffolds. (2) In vivo protocol: The biocompatibility of acellular collagen scaffolds was first tested in C57BL6 (n=24) and αMHCMerCreMerSf/Sf (n=18) mice, a strain in which DCM is induced by a cardiac (αMHC)-specific and tamoxifen(T)-inducible invalidation of serum response factor (SRF). Scaffolds seeded with hiPSC-CM (obtained by a sequential activation/inhibition of the Wnt pathway) or kept acellular (controls) were then implanted in 8 and 6 αMHCMerCreMerSf/Sf mice, respectively. Results: As assessed by SEM and shear wave elastography, a 10% citric acid concentration and 150 min of baking at 150°C producing a scaffold with an average fiber thickness of 1400 nm, an average pore size of 2500 nm and an elasticity modulus of 10.1 kPa were associated with optimal hiPSC-CM differentiation and colonization of the scaffold. Seven and 14 days after implantation, the biocompatibility of cell-free scaffolds was confirmed by echocardiography and histology. Scaffolds seeded or not with hiPSC-CM were then grafted in DCM mice. After 14 days, heart function drastically decreased in hearts receiving cell-free scaffolds while it remained stable in the treated mice (p&lt;0.001 for LVEDV, LVESV and EF). This pattern was associated with (1) a significantly (p&lt;0.01) increased genomic and proteomic expression of SRF possibly reflecting an activation of resident stem cells (unaffected by T) and/or an increase in endothelial cells (also T-unaffected), in line with the greater vascularity of the scaffold, and (2) a reduced fibrosis consistent with the upregulation of several genes involved in extracellular matrix remodeling. Conclusion: These data suggest that a hiPSC-CM loaded electrospun collagen patch stabilizes function in DCM, most likely through paracrine signaling.
SAT0724-HPR Technological assisted rehabilitation following total knee joint replacement. a randomised controlled non-inferiority trial
Authors: H.H. Andersen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Supervised rehabilitation after total knee arthroplasty (TKA) has been suggested effective for quicker recovery. The effect of Technological Assisted Rehabilitation (TAR) in the participant's home compared to supervised rehabilitation has been investigated in trials and results suggest it being equal to supervised rehabilitation on short time follow-up (6 weeks to 4 months). No studies have been found that evaluate the effect of TAR on follow-ups longer than 4 months. <h3>Objectives</h3> The aim of this study was to evaluate the effect of TAR compared to supervised rehabilitation (usual care) on participants with TKA after 6 and 12 months. <h3>Methods</h3> This was a single-blinded, randomised controlled, non-inferiority study. 155 participants were randomised to either TAR (ICURA) or usual care. Intervention time was 6 weeks, follow-ups were after intervention, at 6 and 12 months. This study only concluded on 6 and 12 months. Primary outcome was 10 m walk test. Secondary outcomes were 2.45 m up and go, 30 s. Sit to Stand, active knee flexion and extension and the KOOS questionnaire. All outcomes were measured at all time points by a blinded assessor. Non-inferiority margin was no statistical significant- and less than 10% between group difference at 6 and 12 months, estimated by a repeated measurement analysis, adjusted for relevant baseline variables. <h3>Results</h3> Overall, the groups did not differ at baseline. No statistical between group difference was detected after 6 and 12 months for primary and secondary outcomes. A power analysis suggested severe lack of power to detect a statistical between group difference, due to high numbers of participants lost to follow-up after 6 and 12 months. The between group difference at 6 and 12 months was less than 10% for all outcomes except KOOS Quality of Life at 6 months, were a difference of 12.2% was detected, in favour of ICURA <h3>Conclusions</h3> The results show that the effect of ICURA is equal to usual care after 6 and 12 months. Because lack of power after 6 and 12 months, the statistical significance should be interpreted with caution, but overall between group difference after 6 and 12 months was less than 10% for primary and secondary outcomes. <h3>Disclosure of Interest</h3> None declared
Abstract 16770: The Road to Durable Pulmonary Vein Isolation by Means of Radiofrequency Ablation Annotation Algorithm
Authors: Nobuaki Tanaka, Koichi Inoue, Koji Tanaka, Yuko Toyoshima, Takafumi Oka, Masato Okada, Atsunori Okamura, Yasushi Koyama, Katsuomi Iwakura, Kenshi Fujii
Journal: Circulation (2015)

Background: Recurrence of atrial fibrillation (AF) after catheter ablation by means of circumferential pulmonary vein isolation (CPVI) is common and often related to the recovery of conduction pulmonary vein (PV) and left atrium (LA) following an initially successful CPVI. The ablation annotation system (CARTO3 System, VISITAG Module,) uses an algorithm for the automated annotation of RF ablation applications based on objective, predefined parameters. It could be helpful in accomplishing durable CPVI for AF. Objective: The objective of this study was to compare procedure parameters and outcomes between VISITAG-guided and non-guided CPVI. Methods: We include in this study 93 AF patients underwent CPVI. All ablations were performed by single operator using ThermoCool SmartTouch catheter. In 51 patients (group A, paroxysmal AF 29/51:56.8%), RF ablation was guided by an automated algorithm with predefined criteria of catheter stability range of motion ≤ 1.5mm ,catheter stability duration &gt;5 seconds, and force over time (contact force≧5g, time≧25%). When this condition is satisfied, new tag appears. Tag diameter was 6mm and we intended to move catheter to next position to appear the new tag where was overlapped with the former tag. When force time integral (FTI) of the tag becomes 100-150gs, the color of tag changed from white to red and we moved catheter to the next position. In 42 control patients (group B, paroxysmal AF 30/42:71.4%), ablations were performed by contact force guided ablation without automated algorithm. Results: CPVI at the initial anatomical line was achieved more often in group A than in group B (66.7% vs 36.9%; P=0.001). The frequency of time dependent conduction recovery was lower in group A (14 of 102 pairs of PVs [13.7%]) than in group B (26 of 84 pairs of PVs [30.9%] ; P=0.0055). During 6-month follow up with 3 month blanking period, 94.1% patients in group A and 76.2% patients in group B were free from any atrial tachyarrhythmias (P=0.019). Conclusion: In CPVI, automated ablation lesion annotation by optimal settings was effective in reducing the acute resumption of LA-PV conduction. Better durability of CPVI may improve long-term outcomes.
Mitochondrial DNA copy number in colorectal cancer cells is dependant of nuclear microsatellite instability status
Authors: Astrid Lièvre, Delphine Lecorre, Anne-Marie Bouvier, Caroline Chapusot, Françoise Piard, Jean Faivre, Pierre Laurent-Puig
Journal: Cancer Research (2006)

909   Frequent mitochondrial DNA (MtDNA) mutations have recently been described in colorectal cancer (CRC) cells. Most of these mutations are located in a polymorphic C-tract named D310 defining a hot spot of mutations in the non-coding D-Loop region. The consequences of these mutations are not well understood and need further investigations. As the D-loop plays a key role in the MtDNA replication, we investigated the role of D310 mutations on mtDNA copy number in CRC cells. We then correlated this MtDNA copy number with clinicopathologic parameters and microsatellite instability status (MSI or MSS) of 91 CRC patients (50 female, 41 male; mean age was 72.4±12.4 years). The tumor location was proximal, distal and rectal in 40, 41, and 10 cases respectively. Tumor stage was II in 40 cases and stage III in 51 cases. Twenty-three tumors were MSI-high. The mtDNA copy number was evaluated by quantitative real-time PCR using two specific Taqman DNA probes (Appliedbiosystems). The MTND2 mitochondrial gene probe measured the mtDNA copy number. The H1FX nuclear gene probe measured the nuclear DNA copy number (NuDNA). For each patient the copy number of MtDNA and NuDNA were measured on tumor and matched normal tissues in triplicate. DNA extracted from SW48 CRC cells was used as internal control. For each patient estimated ratio were calculated as follow: R Mt/Nu tumor : 2^(Ct NuDNA -Ct mtDNA ) tumor /2^(Ct NuDNA -Ct mtDNA ) SW48 ; R Mt/Nu Normal : 2^(Ct NuDNA -Ct mtDNA ) normal )/2^(Ct NuDNA -Ct mtDNA ) SW48 ; R Mt/Nu : (2^(Ct NuDNA -Ct mtDNA ) tumor  / 2^(Ct NuDNA -Ct mtDNA ) normal )/2^(Ct NuDNA -Ct mtDNA ) SW48. The latter ratio was used to compare patients between them. The D310 region was screened by direct sequencing and the presence of mutation was established by the comparison with matched non tumor tissues. The amount of MtDNA was significantly higher in tumor tissue compared with matched non-tumor tissue (0.87 vs 0.67; p Mt/Nu  according to the D310 mutation status (0.0043 vs 0.0033; ns). No significant difference was observed for the ratio R Mt/Nu  according to age, gender, tumor location, and tumor stage. However a significant difference in R Mt/Nu  was observed according to MSI status. MSI-H tumors showed a significant lower R Mt/Nu  than MSS tumors (0.0026 vs 0.0041; p Mt/Nu tumor  as compared to R Mt/Nu Normal  (0.97 vs 0.66; p
Neurodevelopment in Infants Exposed to Zika Virus In Utero
Authors: M Elisabeth Lopes Moreira, Karin Nielsen-Saines, Patricia Brasil, Tara Kerin, Luana Damasceno, Marcos Pone, Liege M A Carvalho, Sheila M Pone, Zilton Vasconcelos, Ieda P Ribeiro, Andrea A Zin, Irena Tsui, Kristina Adachi, Stephanie L Gaw, Umme-Aiman Halai, Tania S Salles, Denise C da Cunha, Myrna C Bonaldo, Claudia Raja Gabaglia, Leticia Guida, Jociele Malacarne, Roozemerie P Costa, S Clair Gomes, A Beatriz Reis, Fernanda V M Soares, Renata H Hasue, Carolina Y P Aizawa, Fernanda F Genovesi, Mitsue Aibe, Christa Einspieler, Peter B Marschik, J Paulo Pereira, Elyzabeth A Portari, Carla Janzen, James D Cherry
Journal: New England Journal of Medicine (2018)

Zika Virus and Neurodevelopment Exposure to Zika virus in utero has been associated with neurodevelopmental abnormalities. In this letter, the results of long-term follow-up of Brazilian children exposed to ZIKV in utero are reported.
FRI0060 Are older ra patients frail, or lonely and depressed?
Authors: F. Cleutjens, A. Boonen, M. van Onna
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The average rheumatoid arthritis (RA) patient has approximately 2 comorbidities, and this number increases with age. Both comorbidity and ageing are considered risk factors for frailty, a physiological syndrome characterised by reduced functional reserves and resistance to 'stressors' due to a cumulative decline of physiological and psychosocial systems. Frailty results in adverse health outcomes including hospitalisation and increased risk of mortality. The extent to which frailty is a relevant problem in elderly RA patients remains unknown. <h3>Objectives</h3> (1) To assess the prevalence of frailty and (2) to identify which factors are associated with frailty in elderly patients with RA. <h3>Methods</h3> Consecutive patients of the outpatient clinic where invited to participate in a study on ageing while ensuring equal representation of patients in three pre-defined age groups: 55–64, 65–74, and ≥75 years. Rheumatologists recorded the number of comorbidities. Patients rated their overall health on a visual analogue scale (0–100; 100 very bad health) and completed the validated Groningen Frailty Indicator (GFI), which contains 15 questions on the loss of functions and resources across 4 domains: physical (mobility functions, multiple health problems, physical fatigue, vision, hearing), cognitive (cognitive dysfunction), social (emotional isolation), and psychological (depressed mood and feelings of anxiety). Scores on items are dichotomized, "1"; indicating a problem or dependency. Prevalence of problems/dependency was compared among the 3 age-groups using a Kruskal-Wallis test. Characteristics of patients classified as frail (GFI score ≥4) or non-frail (GFI score &lt;4) were compared using a chi-square test for categorical data or the independent samples t-test for continuous data. <h3>Results</h3> The prevalence of frailty across age groups was respectively 43.3%. 40.0% and 43.4%. Frail RA patients were more often female, had a lower subjective health status. Remarkable, patients classified as frail identified problems in the social and psychosocial domains. Of interest, there were no differences regarding age, polypharmacy, number of comorbidities, and cognitive domain (figure 1). <h3>Conclusions</h3> Using validated questionnaires, frailty is highly prevalent in all RA patients older than 55 years and seems to be a distinctive health construct which is not necessarily related to increasing age, polypharmacy and comorbidity in patients with RA. An alternative explanation of our findings is that rheumatologists seem to miss symptoms of depression and loneliness among RA patients. <h3>Disclosure of Interest</h3> None declared
Abstract 15702: Association of Onset Season With Characteristics and Long-Term Outcomes in Acute Myocardial Patients: A Sub-Analysis of J-minuet Study
Authors: Taishi Okuno, Jiro Aoki, Kengo Tanabe, Koichi Nakao, Yukio Ozaki, Kazuo Kimura, Junya Ako, Teruo Noguchi, Satoshi Yasuda, Satoru Suwa, Kazuteru Fujimoto, Yasuharu Nakama, Takashi Morita, Wataru Shimizu, Yoshihiko Saito, Atsushi Hirohata, Yasuhiro Morita, Teruo Inoue, Atsunori Okamura, Toshiaki Mano, Kazuhito Hirata, Yoshisato Shibata, Mafumi Owa, Kenichi Tsujita, Hiroshi Funayama, Nobuaki Kokubu, Ken Kozuma, Shirou Uemura, Tetsuya Toubaru, Keijirou Saku, Shigeru Ohshima, Kunihiro Nishimura, Yoshihiro Miyamoto, Hisao Ogawa, Masaharu Ishihara
Journal: Circulation (2017)

Background: It is known that incidence of acute myocardial infarction (AMI) tend to be higher in cold season. However, the association of onset season with characteristics and long-term outcomes of...
P088 Distribution of Different HER2 Mutations and Their Impact on Clinical Responses to Afatinib in HER2-Mutant Lung Cancer
Authors: W. Fang, S. Zhao, Y. Liang, Y. Yang, L. Yang, X. Dong, L. Zhang, Y. Tang, S. Wang, Y. Yang, X. Ma, M. Wang, W. Wang, S. Zhao, K. Wang, S. Gao, L. Zhang
Journal: Journal of Thoracic Oncology (2018)