tbuckley/cabot-search huggingface dataset:
Abstract 18749: On Pump Beating Maze Procedure For Non-valvular Atrial Fibrillation Via Left Atrial Appendage
Authors: Miwa Ishioka, Akira Katayama, Masamichi Ozawa, Hitoshi Tachibana, Hiroshi Kodama, Keigo Dote
Journal: Circulation (2012)

BACKGROUND: The Cox maze procedure is the most effective surgical procedure for atrial fibrillation (AF). In recent years a number of different surgical ablation devices were introduced and new surgical ablation to treat AF are presented. OBJECTIVE The purpose of this article was to present a new surgical ablation approach; on pump beating maze procedure via left atrial appendage (LAA) for nonvalvular AF (NVAF). METHODS: Between February 2006 and October 2012, 31 patientswith persistent and paroxysmal atrial fibrillation undergoing non valvular heart disease and great vessel surgery using cardiopulmonary bypass (11 with large thrombus of left atrial appendage, 6 with graft replacement for aortic aneurysm, 9 with aortic valve replacement, 1 with ventricular septal defect, and 4 with coronary artery bypass grafting) were underwent the on pump beating maze procedure via left atrial appendage (LAA) using bipolarradiofrequency ablation concomitantly. The average age of patientswas 70 ± 8 years. The mean diameter of left atrium was 48 ± 7 mm. Six patients had paroxysmal atrialfibrillation and the other had permanent. The ablation line of our modification consisted of pulmonary box isolation and isthmus ablation. Pulmonary box isolation was made by right pulmonary epicardial clamp and LA roof and inferior clamp ablation via left atrial appendage. Left isthmus ablation between the line of pulmonary box isolation and mitral annulus was made by bipolar or monopolar pen epicardially. No further atriotomy was performed on the atrial septum or right atrium. After completion of these procedures, the combined surgery was performed. All patients in this series were operated on by the same surgical team. Results: No perioperative morality, cerebrovascular accidents, transient ischemic attacks, or both were documented in this series. One patient required a pacemaker implantation because of sinus node dysfunction. In a mean follow-up of 26±19 months, and 77.8 % of the patients are free from atrial fibrillation. CONCLUSION: The LAA maze procedure could be an attractive treatment for atrial fibrillation in non-mitral cardiac surgery without the need for atriotomies.
Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study
Authors: Rakhi Maiwall, Samba Siva Rao Pasupuleti, Chhagan Bihari, Archana Rastogi, Pawan Kumar Singh, Vini Naik, Akanksha Singh, Priyanka Jain, Awinash Kumar, Amar Mukund, R.P. Mathur, Guresh Kumar, Shiv Kumar Sarin
Journal: Hepatology (2019)

Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. We studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development. Of 818 patients with cirrhosis (age, 50.4 ± 11.8 years; 84% males; Model for End‐Stage Liver Disease [MELD], 19.9 ± 9.9), 36% had AKI at enrollment, 27% had previous AKI, and 61% developed new episodes of AKI during the follow‐up period. CKD developed in 269 (33%) patients. Serum cystatin C (CysC; subdistribution hazard ratio [SHR], 1.58; 1.07‐2.33), episodes of previous AKI (SHR, 1.26; 1.02‐1.56), and AKI stage at enrollment (no AKI [SHR, 1] vs. stage 1 [SHR, 3.28; 1.30‐8.25] vs. stage 2 [SHR, 4.33; 1.76‐10.66] vs. stage 3 [SHR, 4.5; 1.59‐12.73]) were identified as baseline risk factors for CKD development. On time‐varying competing risk analysis, MELD (SHR, 1.01; 1.00‐1.03), number of AKI episodes (SHR, 1.25; 1.15‐1.37), and CysC (SHR, 1.38; 1.01‐1.89) predicted CKD development. Development of CKD was associated with higher risk of death. Reduction in glomerular filtration rate (GFR) not meeting CKD criteria was observed in 66% of patients with cirrhosis, more so in those with previous AKI episodes and a high CysC level and MELD score. Renal histology, available in 55 patients, showed tubulointerstitial injury in 86%, cholemic nephrosis in 29%, and glomerular changes in 38%. Conclusion: Almost two‐thirds of patients with cirrhosis develop episodes of AKI and reduction in GFR; one‐third progress to CKD, resulting in adverse outcomes. Higher MELD and CysC levels and number of AKI episodes predict development of CKD in patients with cirrhosis.
Loureirin B suppresses RANKL-induced osteoclastogenesis and ovariectomized osteoporosis via attenuating NFATc1 and ROS activities
Authors: Yuhao Liu, Chao Wang, Gang Wang, Youqiang Sun, Zhangrong Deng, Leilei Chen, Kai Chen, Jennifer Tickner, Jacob Kenny, Dezhi Song, Qingwen Zhang, Haibin Wang, Zhenqiu Chen, Chi Zhou, Wei He, Jiake Xu
Journal: Theranostics (2019)

Rationale: Osteoporosis is a severe bone disorder that is a threat to our aging population. Excessive osteoclast formation and bone resorption lead to changes in trabecular bone volume and architecture, leaving the bones vulnerable to fracture. Therapeutic approaches of inhibiting osteoclastogenesis and bone resorption have been proven to be an efficient approach to prevent osteoporosis. In our study, we have demonstrated for the first time that Loureirin B (LrB) inhibits ovariectomized osteoporosis and explored its underlying mechanisms of action in vitro. Methods: We examined the effects of LrB on RANKL-induced osteoclast differentiation and bone resorption, and its impacts on RANKL-induced NFATc1 activation, calcium oscillations and reactive oxygen species (ROS) production in osteoclasts in vitro. We assessed the in vivo efficacy of LrB using an ovariectomy (OVX)-induced osteoporosis model, which was analyzed using micro-computed tomography (micro-CT) and bone histomorphometry. Results: We found that LrB represses osteoclastogenesis, bone resorption, F-actin belts formation, osteoclast specific gene expressions, ROS activity and calcium oscillations through preventing NFATc1 translocation and expression as well as affecting MAPK-NFAT signaling pathways in vitro. Our in vivo study indicated that LrB prevents OVX-induced osteoporosis and preserves bone volume by repressing osteoclast activity and function. Conclusions: Our findings confirm that LrB can attenuate osteoclast formation and OVX-induced osteoporosis. This novel and exciting discovery could pave the way for the development of LrB as a potential therapeutic treatment for osteoporosis.
A Most Reckless Proposal — A Plan to Continue Asbestos Use in the United States
Authors: Philip J. Landrigan, Richard A. Lemen
Journal: New England Journal of Medicine (2019)

Contrary to common belief among health professionals and the public, asbestos has never been permanently banned in the United States. A significant new use rule issued by the EPA creates loopholes that will permit continued and potentially expanded use of asbestos.
Cell proliferation as a biomarker for response to immune checkpoint inhibitors in highly inflamed renal cell carcinoma.
Authors: Sarabjot Pabla, Jason Zhu, Matthew Labriola, Rajan Gupta, Daniel J. George, Shannon McCall, Edwin Yau, Jeffrey M. Conroy, Sean T. Glenn, Mary Nesline, Antonios Papanicolau-Sengos, Blake Burgher, Felicia L. Lenzo, Tian Zhang, Carl Morrison
Journal: Journal of Clinical Oncology (2019)

61 Background: Cell proliferation is an important marker of survival in many tumors and we hypothesized that this attribute could be related to response to immune checkpoint inhibitors in RCC. Previously we reported (SITC 2018) moderately proliferative lung cancer has a much higher response rate than either poorly or highly proliferative tumors. Methods: 69 FFPE tumor samples of RCC were evaluated by RNA-seq to measure transcript levels of 394 immune related genes, including 10 related to cell proliferation (BUB1, CCNB2, CDK1, CDKN3, FOXM1, KIAA0101, MAD2L1, MELK, MKI67, TOP2A). Cell proliferation, defined as the mean mRNA expression of these 10 genes was evaluated for association with ORR to ICIs by RECIST v1.1 criteria for both PD-L1 IHC positive and negative cases. Cell proliferation for each case was split into 3 tertiles of poorly ( &lt; 33), moderately (33-66) and highly ( &gt; 66) proliferative compared to a reference population. Poorly and highly proliferative were grouped for comparison to moderately proliferative tumors. Tumors were inflamed or non-inflamed based upon RNA‐seq analysis of CD8 compared to a reference population of more than 500 cases of multiple tumors. Non-inflamed, or immune desert tumors, defined as the lower 25 th percentile of rank for CD8 + T-cells, and greater than 75 th percentile of rank as inflamed. Results: In our cohort of 69 patient the overall ORR was 18.8%. 15.9% of tumors were non-inflamed with an ORR of 9.1%. For 36.2% inflamed tumor the ORR was 32%. For cell proliferation 62.2% were poorly proliferative, 8.7% were highly proliferative, and 29% were moderately. ORR in moderately proliferative tumors was 30% versus 14.2% in poorly/highly proliferative tumors. In inflamed tumors, ORR in moderately proliferative tumors was 37.5% as opposed to 17.6% in poorly/highly proliferative tumors. In 11 non-inflamed tumors, there was only one responder, which was a poorly/highly proliferative tumor. Conclusions: Cell proliferation may play a crucial role in distinguishing RCC patients who may have a clinical benefit to ICI, including the important subgroup of inflamed tumors. Moderately proliferative tumors have a higher ORR than their poorly/highly counterparts.
Characterizing the T cell repertoire in lung squamous cell premalignancy and its association with lesion outcome.
Authors: Asaf Maoz, Carter Merenstein, Sarah Mazzilli, Joshua Campbell, Gang Liu, Sherry Zhang, Samjot S. Dhillon, Christopher Stevenson, Mary E. Reid, Marc Lenburg, Spira Avi, Jennifer Beane
Journal: Journal of Clinical Oncology (2019)

102 Background: The immune response to frank malignancy has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical, pathological and molecular features. Methods: Endobronchial biopsies (n=294) and brushings (n=137) from high-risk subjects (n=50), undergoing lung cancer screening at approximately 1-year intervals via auto fluorescence bronchoscopy and CT, were profiled by RNA-Seq as part of the Pre-Cancer Genome Atlas (PCGA). We applied the TCR Repertoire Utilities for Solid Tissue/Tumor (TRUST) tool to identify TCR CDR3 sequences in the RNA-Seq data. We quantified the ratio of private (i.e., found in one patient only) and public (i.e. found in two or more patients) TCRs that are found in curated databases with known antigen specificities. We measured the correlation of TCR diversity with previously derived PML transcriptional signatures and molecular subtypes; and with mutational burden among a subset of biopsies (n=115) also profiled with whole exome sequencing. Results: We detected 40,421 unique TCR sequences, of which 3,396 (8.4%) were found in more than one sample and 1,057 (2.6%) were found in two or more patients (i.e. Public). TCRs with known antigen specificities were enriched among public TCRs (p &lt; 0.001). In PMLs with a proliferative molecular subtype reflective of dysplasia (n=80), TCR diversity was decreased in PMLs that regressed versus PMLs that progressed (p=0.045). TCR diversity was negatively associated with a transcriptional signature of T-cell mediated immune activation (Spearman’s rho -0.26, p &lt; 0.001) but was not associated with mutational burden. Conclusions: To our knowledge, this is the first characterization of the TCR repertoire associated with bronchial premalignant lesions. TCR diversity may help predict the efficacy of the host immune response to PMLs but it is not associated with mutational burden. Further studies are needed to leverage these findings and explore the potential for immunoprevention of PMLs.
The Detrimental Effect of RA Pacing on LA Function and Clinical Outcome in Cardiac Resynchronization Therapy
Authors: Pieter Martens, Sébastien Deferm, Philippe B. Bertrand, Frederik H. Verbrugge, Jobbe Ramaekers, David Verhaert, Matthias Dupont, Pieter M. Vandervoort, Wilfried Mullens
Journal: JACC. Cardiovascular imaging (2019)
Detection of Uterine Leiomyosarcoma Peritoneal Lesions by SPECT/CT and ROLL Technique
Authors: Gianpiero Manca, Ludovico Maria Garau, Antonella Romanini, Domenico Rubello, Amedeo Nuzzo, Linda Barbarello, Lorenzo Fantechi, Patrick M. Colletti, Ugo Boggi, Duccio Volterrani
Journal: Clinical Nuclear Medicine (2019)

Abstract We reported the preoperative radio-guided localization of 4 peritoneal metastatic nodules in the case of a 45-year-old woman with uterine leiomyosarcoma. Three lines of chemotherapy were tried, but cardiotoxicity occurred. Within the context of so-called GOSTT (guided intraoperative scintigraphic tumor targeting), preoperative radio-guided localization of peritoneal metastases enabled their subsequent radio-guided excisional biopsy. SPECT/CT allowed for anatomical localization of the hot lesions and generated a 3-dimensional volume-rendering roadmap, facilitating a surgical approach.
Impact and influence of PET on imaging related endpoints in patients with Lymphoma using IWG-NHL or Lugano classification.
Authors: Manish Sharma, Oliver Bohnsack, Daniel Clark, Michael O'Connor, Anitha Singareddy, Jayant Narang, Rudresh Jarecha
Journal: Journal of Clinical Oncology (2019)

e19061 Background: Positron Emission Tomography (PET) scans were applied to lymphoma as early as in 1990s. Revised criteria for lymphoma assessment was published in 2007 by International Working Group (IWG). The criteria for PET into response assessment were added due to better sensitivity and superiority of PET over CT and its ability to distinguish between viable tumor and necrosis or fibrosis in residual mass after treatment. PET was primarily recommended for patients with FDG avid curable lymphomas such as Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) and later for the post-treatment assessment of DLBCL and HL. The Lugano Classification 2014 regarded FDG PET/CT to be the standard for staging and assessment of all FDG-avid histologies. Methods: A retrospective review of 10 Lymphoma studies with a total of 1,537 subjects and 17,394 time points was carried out using PET in addition to CT as per imaging schedule. There were 5 clinical trials with a total of 1,169 subjects with 15,480 time points using IWG-NHL classification 2007 while 5 clinical trials with a total of 729 subjects and 1,914 time points using Lugano classification 2014. The number of subjects and time points with PET where PET had an impact on the overall assessment was calculated. Results: PET was available for a total of 1,159 subjects (out of 1,537) and 4,688 time points (out of 17,394) across all 10 studies. Out of 4,688 visits with PET, 956 (20.4%) visits had an impact on overall assessment due to additional metabolic findings. Out of 1,159 subjects with PET, 462 (39.9%) subjects had an impact on overall assessment and study endpoints due to additional uptake related findings. The impact across different studies was between 7% to 59% possibly due to difference in indication, line of therapy and blinded independent review design. The most common impact due to PET was related to complete response and disease progression. Conclusions: It can be concluded that PET significantly impacts assessments and imaging endpoints for lymphoma clinical trials using IWG-NHL classification or Lugano classification. Thus, addition of PET improves the outcome of the response not only in lymphoma treatment and diagnosis, but also clinical trial outcomes. [Table: see text]
Regorafenib plus nivolumab in patients with advanced colorectal or gastric cancer: an open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603)
Authors: H. Hara, S. Fukuoka, N. Takahashi, T. Kojima, A. Kawazoe, M. Asayama, T. Yoshii, D. Kotani, H. Tamura, Y. Mikamoto, A. Sugama, M. Wakabayashi, S. Nomura, A. Sato, Y. Togashi, H. Nishikawa, K. Shitara
Journal: Annals of Oncology (2019)
JAVELIN ovarian PARP 100 study design: Phase III trial of avelumab + chemotherapy followed by avelumab + talazoparib maintenance in previously untreated epithelial ovarian cancer.
Authors: Ramez Nassef Eskander, Jonathan A. Ledermann, Michael J. Birrer, Keiichi Fujiwara, Stephanie Gaillard, Gary Edward Richardson, Caimiao Wei, Mahadi Ali Baig, Fabian Zohren, Bradley J. Monk
Journal: Journal of Clinical Oncology (2019)

TPS9 Background: Preclinical studies suggest that chemotherapy (CTX) and PARP inhibitors may increase tumor antigenicity, providing a rationale for combined treatment with checkpoint inhibitors in patients (pts) with ovarian cancer (OC). Talazoparib is a potent, orally bioavailable PARP inhibitor with a dual mechanism (PARP trapping and enzyme inhibition) that has shown clinical activity in BRCA-mutated OC and is a US-approved treatment for BRCA-mutated HER2– breast cancer. Avelumab is an anti–PD-L1 checkpoint inhibitor approved for the treatment of metastatic Merkel cell carcinoma and advanced platinum-treated urothelial carcinoma. In phase 1b studies, avelumab showed antitumor activity and acceptable safety in pts with platinum-resistant OC. The JAVELIN Ovarian PARP 100 trial is evaluating the efficacy of avelumab + CTX followed by avelumab + talazoparib maintenance compared with CTX + bevacizumab followed by bevacizumab maintenance in pts with previously untreated epithelial OC. Methods: JAVELIN Ovarian PARP 100 is a phase 3, randomized, open-label, multicenter trial. Eligible pts have previously untreated Stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer; are candidates for platinum-based CTX + bevacizumab; and have completed primary debulking surgery or are candidates for neoadjuvant CTX with planned interval debulking surgery. Approximately 720 pts will be randomized in a 2.5:1:2.5 ratio to receive: CTX (paclitaxel 175 mg/m 2 + carboplatin AUC 5/6 IV Q3W for 6 cycles) + avelumab (800 mg IV Q3W) followed by avelumab (800 mg Q2W) + talazoparib (0.75 mg QD orally) maintenance for up to 24 months (Arm A); CTX followed by talazoparib (0.75 mg QD) maintenance for up to 24 months (Arm B); or CTX + bevacizumab (15 mg/kg IV Q3W) followed by bevacizumab (15 mg/kg Q3W) maintenance for up to 21 doses or 22 per local approval (Arm C). Pts are stratified by germline BRCA1/2 mutation and resection status. The primary endpoint is progression-free survival (PFS) by blinded independent central review per RECIST v1.1. Other endpoints include overall survival, PFS2, health-related quality of life, and PK. Clinical trial information: NCT03642132.
Platinum-containing regimens as front-line treatment of advanced non-small cell lung cancer in two groups of elderly (≥ 70 year old) patients of different age.
Authors: Jacopo Giuliani, Andrea Bonetti, Anna Mercanti, Lara Furini, Emilia Durante, Filippo Greco, Anna Rita Trolese, Paolo Piacentini, Giacomo Moratello, Michele Tognetto
Journal: Journal of Clinical Oncology (2013)

e20617 Background: Elderly patients with advanced Non-Small Cell Lung Cancer (NSCLC) are underrepresented in clinical trials. Therefore we sought to evaluate the impact of a platinum-based doublet, given as a front-line chemotherapy, in two groups of elderly patients of different age with advanced NSCLC. Methods: A retrospective analysis of all consecutives elderly patients ( ≥70 year old) with advanced NSCLC who received a platinum based doublet as front line therapy at our Medical Oncology Unit from February 2005 to September 2011 was performed. The general case study was divided in two groups of patients of different age: “young-old” patients (70-74 year-old) and “old-old” patients (75-81 year-old). Results: Sixty-two consecutive elderly patients with advanced NSCLC were included in this study. Forty patients (65%) were “young-old” patients (group 1, median age 72 years) and 22 (35%) were “old-old” patients (group 2, median age 77 years). Overall, a total of 249 cycles were administered to the 62 patients; 164 cycles were administered to patients in group 1 and 85 cycles were given to patients in group 2; median number of administered cycles per patient was 4 (range 1-6) in both groups. Relevant clincal variables such as sex, stage, ECOG PS, Charlson score and histology were evenly distributed between the two subgroups. Regarding the type of first line chemotherapy, the great majority (92%) was treated with a carboplatin-containing regimen while only five patients (8%) received a cisplatin-based doublet: notably, all these patients are in group 1. Toxicity was mild, with grade 3-4 neutropenia in 17% of group 1 patients and in 9% of group 2 patients. Median OS was 9.8 months in both groups. Conclusions: This retrospective evaluation shows the safety and efficacy of a platinum-based doublet given as first-line chemotherapy in elderly advanced NSCLC patients. For several reasons, including the ease of administration, carboplatin is the preferred platinum analogue. The combination with vinorelbine or gemcitabine is associated with a very good toxicity profile that does not seem to have a detrimental effect on efficacy.
Efficacy of precutting endoscopic mucosal resection with full or partial circumferential incision using a snare tip for difficult colorectal lesions
Authors: Naohisa Yoshida, Ken Inoue, Osamu Dohi, Ritsu Yasuda, Ryohei Hirose, Yuji Naito, Takaaki Murakami, Kiyoshi Ogiso, Yutaka Inada, Yoshikazu Inagaki, Yukiko Morinaga, Mitsuo Kishimoto, Yoshito Itoh
Journal: Endoscopy (2019)

Abstract Background We analyzed the efficacy of precutting endoscopic mucosal resection (EMR), which is a method of making a full or partial circumferential mucosal incision around a tumor with a snare tip for en bloc resection. Methods We reviewed cases from 2011 to 2018 in which precutting EMR (n = 167) and standard EMR (n = 557) were performed for lesions of 10 – 30 mm. Precutting EMR was indicated for benign lesions of 20 – 30 mm or lesions of &lt; 20 mm for which standard EMR was difficult. Through propensity score matching of the two groups, the therapeutic outcomes for 35 lesions of ≥ 20 mm and 98 lesions of &lt; 20 mm in each group were analyzed. Results In the two sizes of lesion, there were significant differences between the precutting and standard groups in the en bloc resection rate (≥ 20 mm 88.6 % vs. 48.5 %, P &lt; 0.001; &lt; 20 mm 98.0 % vs. 85.7 %, P = 0.004) and the histological complete resection rate (≥ 20 mm 71.4 % vs. 42.9 %, P = 0.02; &lt; 20 mm 87.8 % vs. 67.3 %, P &lt; 0.001). Conclusion Precutting EMR enabled high en bloc resection rates in cases involving difficult lesions.
Role and therapeutic potential of dietary ketone bodies in lymph vessel growth
Authors: Melissa García-Caballero, Annalisa Zecchin, Joris Souffreau, Anh-Co Khanh Truong, Laure-Anne Teuwen, Wesley Vermaelen, Rosa Martín-Pérez, Pauline de Zeeuw, Ann Bouché, Stefan Vinckier, Ivo Cornelissen, Guy Eelen, Bart Ghesquière, Massimiliano Mazzone, Mieke Dewerchin, Peter Carmeliet
Journal: Nature Metabolism (2019)
Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy
Authors: Heng-Huan Lee, Ying-Nai Wang, Weiya Xia, Chia-Hung Chen, Kun-Ming Rau, Leiguang Ye, Yongkun Wei, Chao-Kai Chou, Shao-Chun Wang, Meisi Yan, Chih-Yen Tu, Te-Chun Hsia, Shu-Fen Chiang, K.S. Clifford Chao, Ignacio I. Wistuba, Jennifer L. Hsu, Gabriel N. Hortobagyi, Mien-Chie Hung
Journal: Cancer Cell (2019)