tbuckley/cabot-search huggingface dataset:
2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty
Authors: Susan M. Goodman, Bryan Springer, Gordon Guyatt, Matthew P. Abdel, Vinod Dasa, Michael George, Ora Gewurz‐Singer, Jon T. Giles, Beverly Johnson, Steve Lee, Lisa A. Mandl, Michael A. Mont, Peter Sculco, Scott Sporer, Louis Stryker, Marat Turgunbaev, Barry Brause, Antonia F. Chen, Jeremy Gililland, Mark Goodman, Arlene Hurley‐Rosenblatt, Kyriakos Kirou, Elena Losina, Ronald MacKenzie, Kaleb Michaud, Ted Mikuls, Linda Russell, Alexander Sah, Amy S. Miller, Jasvinder A. Singh, Adolph Yates
Journal: Arthritis & Rheumatology (2017)

Objective This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence‐based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). Methods A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi‐step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. Results The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease‐modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low‐ or moderate‐quality evidence. Conclusion This guideline should help decision‐making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high‐quality direct randomized controlled trial data.
Impact of tricyclic antidepressants (TCAs), SSRIs, and other antidepressants on overall survival in patients with advanced lung cancer.
Authors: Nabeela Iffat Siddiqi, Mahender Yellu, Shuchi Gulati, Changchun Xie, Jane Pruemer, Nagla Fawzy Abdel Karim
Journal: Journal of Clinical Oncology (2015)

e22237 Background: Recent preclinical data through a systematic drug-repurposing computational approach querying a large number of gene expression datasets identified TCAs as having a survival benefit in patients with lung cancer. TCAs were found to induce apoptosis in both chemo-naïve and chemo-resistant tumor cells in human small cell lung cancer (SCLC) tumor cells. However, the clinical effects are unclear. We conducted a study to investigate the impact of antidepressants on overall survival in advanced lung cancer. Methods: We retrospectively identified patients with advanced lung cancers (stage IIIA, IIIB and IV) with non-small cell lung cancers, small cell lung cancers and rare histopathologic types at our institute between 2004 and 2014. Patients with early stage lung cancer and partial data were excluded from analysis. Data was collected on patient demographics (age, gender), diagnosis (histopathology), antidepressants used, and date of death. Other antidepressants including duloxetine, trazodone, and mirtazapine were grouped together. Patients taking antidepressants were identified and those not taking them were used as the control group. Death was the end point. Kaplan-Meier method was used to calculate median overall survival with 95% CI. Cox model was used to test the treatment effect. Data was analyzed using the SAS (Version 9.4). Results: Of the 197 patients reviewed, 45 were on antidepressants. Median overall survival (OS) for patients on TCAs was 307 days (CI 95%) compared to 560 days in the control group (hazard ratio (HR) of 1.943, p = 0.1627). The SSRI group had a median OS of 436 days compared to 539 days (HR 0.836; p = 0.598); however, the cox model showed that patients taking SSRIs had a potential trend to live longer. The other antidepressants group had a median OS of 805 days compared to 531 days (CI 95%: 353 – 839; HR 0. 6602 p = 0.6602). Conclusions: Patients taking TCAs had a negative impact on OS which is contrary to what was suggested by preclinical trials. SSRIs and other antidepressants had no statistical impact on survival; however, the data on SSRIs showed a trend toward improved survival. Further studies in a larger population will help further explore our results.
SAT-307-A direct comparative study among magnetic resonance elastography, vibration controlled transient elastography and shear wave elastography in patients with non-alcoholic fatty liver disease
Authors: Kento Imajo, Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Masato Yoneda, Hiroyuki Kirikoshi, Satoru Saito, Atsushi Nakajima
Journal: Journal of Hepatology (2019)
THU-446-AMPK/PGC-1α-mediated metabolic reprogramming of hepatic stellate cells promote stemness of hepatocellular carcinoma via metabolite lactate shuttle
Authors: Jia Yao, Jianye Cai, Qing Yang, Jun Zheng, Liang Chen, Tongyu Lu, Yingcai Zhang, Yang Yang
Journal: Journal of Hepatology (2019)
Abstract 16694: Cardiomyocyte-derived D-dopachrome Tautomerase Maintains Calcium Homeostasis and Contractility During LV Pressure Overload
Authors: Yina Ma, Kevin N Su, Jiasheng Zhang, Daniel Pfau, Xiaohong Wu, Xiaoyue Hu, Richard Bucala, Lawrence Young
Journal: Circulation (2017)

Background: The mechanisms modulating the transition of LV hypertrophy to heart failure (HF) remain incompletely understood. D-dopachrome tautomerase (DDT) is a newly discovered protein that is hig...
The prognostic impact of the international association for the study of lung cancer (IASLC) definitions on completeness of surgical resection for non-small cell lung cancer (NSCLC)
Authors: M. Gagliasso, C.F. Cartia, A. Maraschi, R. Rapanà, S. Sobrero, A. Sandri, G. Migliaretti, F. Ardissone
Journal: Annals of Oncology (2019)

Background: To reappraise the prognostic significance of the IASLC definitions of complete, uncertain, and incomplete resection in NSCLC surgery. Methods: Single-institution retrospective review of 1052 consecutive patients surgically treated for NSCLC between 2008 and 2017. Complete resection was defined by absence of residual disease; systematic nodal dissection; no extracapsular extension in lymph nodes removed separately or those at lung specimen margin; negativity of distal mediastinal lymph nodes. An uncertain resection was defined by free resection margins, but one of the following applied: inadequate lymph node assessment; positivity of distal mediastinal lymph nodes; presence of carcinoma in situ at bronchial margin; positive pleural lavage cytology. A resection was defined incomplete by presence of residual disease; extracapsular extension in distal mediastinal lymph nodes or those at lung specimen margin; positive cytology of pleural or pericardial effusions. Follow-up was complete and overall survival (OS) was assessed using the Kaplan-Meier method and Cox proportional hazard modeling. Results: Eight hundred eighty-six (84.2%) patients had a complete resection, 131 (12.5%) an uncertain resection, and 35 (3.3%) an incomplete resection. Median follow-up was 44.9 months (range, 0.1 to 132.3). Complete resection was associated with significantly better survival compared to uncertain and incomplete resection (adjusted hazard ratio, 1.84 and 2.31, respectively; both p = 0.0001). Median OS and 5-year survival rate were 102.3, 32.9, 23.3 months and 62.3%, 33.5%, 24.3% in patients undergoing complete, uncertain, and incomplete resection, respectively. Additional significant predictors for OS in the multivariable Cox model were patient age and Charlson Comorbidity Index; tumor diameter, histology and pathologic TNM stage; and the occurrence of postoperative adverse events. Conclusions: Our current experience confirms that in NSCLC surgery, significant differences exist in long-term survival following complete, uncertain, and incomplete resection, as defined by the IASLC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
<i>XPC, XPF, TP53</i> and <i>GSTP1</i> polymorphisms in prognosis of cutaneous melanoma patients.
Authors: Carmen Silvia Passos Lima, Gabriela Vilas Boas Gomez, Cristiane Oliveira, Gustavo Jacob Lourenco, José Augusto Rinck, Aparecida Machado Moraes
Journal: Journal of Clinical Oncology (2015)

9038 Background: XPC, XPF, TP53 and GSTP1 genes act on repair and detoxification of ultraviolet (UV) radiation-induced DNA damage, which are related to cutaneous melanoma (CM) development and progression. The DNA repair ability is variable in humans, since the genes enrolled in the process are polymorphic. This study aimed to evaluate whether XPC c.2815A > C, XPF c.2505T > C, TP53 c.215G > C and GSTP1 c.313A > G polymorphisms are associated with survival of CM patients. Methods: We analyzed 237 CM patients diagnosed from 2000 to 2014 at the University of Campinas. Genomic DNA of patients was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays, for discrimination of pertinent genotypes. Relapse-free survival (RFS) and overall survival (OS) times were calculated using Kaplan-Meier estimate probabilities and differences between survival curves were analyzed by the log-rank test. The prognostic impact of genotypes was examined using univariate and multivariate Cox regression analyses. Results: The median follow-up time of all patients enrolled in this study was 52 months (range: 0.9-175.1 months). At 60 months of follow-up, patients with XPC CC genotype presented shorter RFS (59.6% vs. 74.0%, P= 0.03), and patients with XPF CC genotype presented a tendency for short RFS (48.0% vs. 73.5%, P= 0.06) and a shorter OS (71.8% vs. 85.6%, P< 0.001) than those with other genotypes (Kaplan-Meier estimates). Patients with XPC CC genotype (HR: 1.85, P = 0.03) and XPF CC genotype (HR: 3.59, P= 0.01) had more chance to recurrence than those with other genotypes in univariate and multivariate Cox regression analyses, respectively. Patients with XPF CC (HR: 3.52, P= 0.001) and XPF TC+CC (HR: 9.40, P= 0.02) genotypes were associated with greater risk of progressing to death than other genotypes in univariate and multivariate Cox regression analyses, respectively. Conclusions: The data suggest, for the first time, that inherited abnormality in DNA repair pathway related to XPC and XPF polymorphisms influence prognosis of CM patients. These findings, once validated in additional studies, will contribute to individualize high-risk patients, who deserve to receive a closer follow-up and/or adjuvant therapy.
Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial
Authors: Haruhiro Saito, Tatsuro Fukuhara, Naoki Furuya, Kana Watanabe, Shunichi Sugawara, Shunichiro Iwasawa, Yoshio Tsunezuka, Ou Yamaguchi, Morihito Okada, Kozo Yoshimori, Ichiro Nakachi, Akihiko Gemma, Koichi Azuma, Futoshi Kurimoto, Yukari Tsubata, Yuka Fujita, Hiromi Nagashima, Gyo Asai, Satoshi Watanabe, Masaki Miyazaki, Koichi Hagiwara, Toshihiro Nukiwa, Satoshi Morita, Kunihiko Kobayashi, Makoto Maemondo
Journal: The Lancet Oncology (2019)
Conventional Cytogenetic and Flow Cytometry Analysis in Pediatric Patients with Acute Lymphoblastic Leukemia (ALL) in a Brazilian Population
Authors: Erica Aires Gil, Gioconda Dr Leão, Andrea Lac Fernandes, Roberto C Vasconcelos, Aldair Paiva, Gabriela Va Alves, Marcos Dias Leão, Edvis Santos Soares Serafim, Frank Bahia, Rodrigo Villar Freitas, Geraldo Barroso Cavalcanti
Journal: Blood (2017)
Nontranslational function of leucyl-tRNA synthetase regulates myogenic differentiation and skeletal muscle regeneration
Authors: Kook Son, Jae-Sung You, Mee-Sup Yoon, Chong Dai, Jong Hyun Kim, Nidhi Khanna, Aditi Banerjee, Susan A. Martinis, Gyoonhee Han, Jung Min Han, Sunghoon Kim, Jie Chen
Journal: Journal of Clinical Investigation (2019)

Aside from its catalytic function in protein synthesis, leucyl-tRNA synthetase (LRS) has a nontranslational function in regulating cell growth via the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) pathway by sensing amino acid availability. mTOR also regulates skeletal myogenesis, but the signaling mechanism is distinct from that in cell growth regulation. A role of LRS in myogenesis has not been reported. Here we report that LRS negatively regulated myoblast differentiation in vitro. This function of LRS was independent of its regulation of protein synthesis, and it required leucine-binding but not tRNA charging activity of LRS. Local knock down of LRS accelerated muscle regeneration in a mouse injury model, and so did the knock down of Rag or Raptor. Further in vitro studies established a Rag-mTORC1 pathway, which inhibits the IRS1-PI3K-Akt pathway, to be the mediator of the nontranslational function of LRS in myogenesis. BC-LI-0186, an inhibitor reported to disrupt LRS-Rag interaction, promoted robust muscle regeneration with enhanced functional recovery, and this effect was abolished by cotreatment with an Akt inhibitor. Taken together, our findings revealed what we believe is a novel function for LRS in controlling the homeostasis of myogenesis, and suggested a potential therapeutic strategy to target a noncanonical function of a housekeeping protein.
FRI-120-Structural liver disease rather than portal hypertension is the predominant factor for hepatic macrophage activation in patients with cirrhosis, portal vein thrombosis and idiopathic portal hypertension
Authors: Nikolaj Worm Orntoft, Michel Blé, Anna Baiges, Claudia Berbel, Virginia Hernández-Gea, Fanny Turon, Søren Møller, Holger Jon Møller, Juan Carlos Garcia-Pagan, Henning Grønbæk
Journal: Journal of Hepatology (2019)
A study evaluating the different treatment modalities for EGFR mutation positive advanced NSCLC patients that acquire c-MET amplification after EGFR TKI therapy resistant
Authors: J. Qu, L. Liu, J. Heng, C. Zhou, Y. Xiong, W. Jiang, N. Yang
Journal: Annals of Oncology (2019)

Background: c-MET amplification was one of the major important mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Whereas, once the patient acquired c-MET amplification combined with EGFR mutation after EGFR-TKI resistant, the most optimal treatment strategy is remains controversial. Our study proposed an optimal treatment strategy for EGFR mutant NSCLC patients who acquired c-MET amplification after EGFR TKI resistance. Methods: Patients with EGFR mutant NSCLC acquiring c-MET amplification, detected from a re-biopsy performed after progression on EGFR-TKI, were identified in Hunan Cancer Hospital. Clinical data were retrospectively collected. Results: Between March 2015 and July 2018, 393 patients were screened and 30 of them were enrolled. EGFR status prior to the initiation of first line therapy was not associated with sex, age and smoking status. After patients developed resistance to EGFR-TKI, the re-biopsy was performed. 30 patients with c-MET amplification and EGFR mutation and received different treatment. The median PFS between c-MET inhibitors(c-METi) combined EGFR-TKI versus c-MET inhibitors were 4.0 months and 1.5 months (HR:0.07; 95% CI, 0.01 to 0.35; P = 0.003), respectively. The PFS in the chemotherapy group was 3.0m and without significance compared to c-METi combined EGFR-TKI group or c-METi monotherapy group. The objective response rates for patients treated with a combination of c-METi and EGFR-TKI, chemotherapy alone and c-METi alone were 58.8%, 14.3% and 16.7%, respectively. Conclusions: This study, comparing the ORR and PFS of EGFR-mutant patients after acquiring c-MET as the major resistance of EGFR-TKI, suggests that a combination of c-METi and EGFR-TKI maybe the best optimal treatment. Legal entity responsible for the study: Hunan Provincial Tumor Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
SAT-461-HCC recurrence after DAA treatment in HCV patients
Authors: Maria Guarino, Dario Bruzzese, Giovan Giuseppe Di Costanzo, Marco Guarracino, Federica Morando, Anna Sessa, Luca Rinaldi, Marcello Persico, Angelo Salomone Megna, Coppola Nicola, Valentina Cossiga, Nicola Caporaso, Filomena Morisco
Journal: Journal of Hepatology (2019)
SAT-315-Clinical utility and application of non-invasive tests of fibrosis in the selection of patients with advanced fibrosis due to NASH in the Phase 2 ATLAS trial
Authors: Rohit Loomba, Naim Alkhouri, Simone Strasser, Vincent Wai-Sun Wong, Raul Aguilar Schall, Bryan Mccolgan, Mani Subramanian, Stephen Djedjos, Robert Myers, Zachary Goodman, Aasim Sheikh, Guy Neff, Bal Bhandari, Nadege Gunn, Kris V. Kowdley
Journal: Journal of Hepatology (2019)
TCTAP A-039 Gastrointestinal Bleeding Events with or Without Proton Pump Inhibitors Among Patients Post Primary Percutaneous Coronary Intervention
Authors: Mark Resty Baldoz Rivera, Ma. Louise Dianne Sasoy, Joyce Pooi Wan Lee, Serene Chiew Peng Lim, Michael Mao-Chen Liang, Syed Saqib Imran, Zhan Yun Lim
Journal: Journal of the American College of Cardiology (2019)
Sensitivity of pretargeted <sup>68</sup>Ga PET-CT to detect colorectal carcinoma liver metastases in a mouse model: Comparison with <sup>18</sup>FDG PET-CT.
Authors: Fanny Foubert, Michel Cherel, Alain Faivre-Chauvet, Sebastien Gouard, Catherine Maurel, Yann Touchefeu, Eric Frampas
Journal: Journal of Clinical Oncology (2015)

e22128 Background: The aim of our study was to compare the performances of a pretargeted PET (pPET) imaging with anti-CEA (carcinoembryonic antigen) and anti-HSG (histamine-succinyl-glycine) recombinant humanized bispecific monoclonal antibody (TF2) and 68Ga-labeled HSG peptide (IMP288) to conventional 18FDG PET in an orthotopic murine model of colorectal cancer liver metastases. Methods: CEA expression of colorectal cancer cells (LS174T Luc) was assessed in vitro by flow cytometry and in vivo by CEA staining. Hepatic tumors were grafted by intraportal injection and tumor burden was confirmed using bioluminescence. One group was pretargeted with TF2 and IMP288-68Ga 24 hours later (n = 8). One group received 18FDG (n = 8). One group had both imaging modalities (n = 7). PET acquisitions started 1 hour after radionuclide injection. Biodistributions of the 68Ga labeled peptide and 18FDG in tumors and normal tissues were assessed one hour after imaging. Results: LS174T Luc cells expressed CEA. Considering tissues uptakes, Tumor/Organ ratio with 68Ga-PETp were statistically significantly higher compared to 18FDG PET (p < 0.05) with both imaging and biodistribution data. 68Ga-PETp sensitivity for tumor detection was 67% versus 31% with 18FDG PET (p = 0.049). For smaller tumors less than 200 mg, the sensitivity was 44% with 68Ga-PETp versus 0% with 18FDG PET (p = 0.031). A strong correlation was demonstrated between signals measured on PET images and biodistribution analyzes (r2= 0.85). Conclusions: 68Ga-PETp was more sensitive than 18FDG-PET for the detection of colorectal liver metastases in an orthotopic murine model. Improved Tumor/Organ ratio allows imaging and therapeutic considerations.
National data on sorafenib therapy adherence for veterans with hepatocellular carcinoma.
Authors: Sheetal Malhotra, David Ping-Hsin Wu, Yeun-Hee Anna Park
Journal: Journal of Clinical Oncology (2015)

9593 Background: Medication adherence can help improve disease progression and survival. One way to improve adherence is to facilitate ease of administration, i.e., oral vs. intravenous. Our study of veterans with hepatocellular cancer (HCC) on Sorafenib therapy aimed to assess the factors that affect adherence and overall survival. Methods: A retrospective analysis of national level data from 2007 to 2013 collected by 120 VA medical centers across the country on diagnosing and treating patients with cancer was used for the study. Data on age at diagnosis, gender, race, marital status, comorbidities concurrent medication use, days from diagnosis to treatment, days medication was supplied for, and medication refills were obtained. Chemotherapy adherence was calculated from the medication supply and refill information. Survival till time of death or endpoint was also calculated. Data were analyzed through descriptive analysis, Chi Square tests, t-tests, Pearson correlations and Regression analysis to assess factors related to adherence and survival as well as differences in adherence and survival. Results: In our study, about 2,778 were prescribed Sorafenib. Most veterans were males (99%) with a mean age of 62 years. Of these, 2006 (72%) were adherent to the treatment in some way. Adherence was associated significantly with ethnicity (P < 0.001). Those adherent to their therapy were older at time of diagnosis compared to those who were not adherent (62.4 years vs. 61.4 years, t = 3.041, P < 0.01). There were no significant associations with marital status, gender, or presence of comorbidities. Increased adherence percentage was negatively related to cost of treatment (r = -0.14, P < 0.001) and positively related to overall survival (r = 0.353, P < 0.001). The number of concurrent medications (OR 0.969, 95% CI = 0.95- 0.99, P < 0.01) and total number of treatment days were (OR 0.997, 95% CI = 0.997- 0.998, P < 0.001) significantly related to chemotherapy adherence. In regression analysis, overall survival was also related to total treatment days (r2= 0.503, P < 0.001). Conclusions: Understanding and targeting factors that affect chemotherapy adherence can affect disease outcomes, including survival.
Increased Risk of Death in First Year After Liver Transplantation Among Patients With Nonalcoholic Steatohepatitis vs Liver Disease of Other Etiologies
Authors: Shunji Nagai, Kelly Collins, Lucy C. Chau, Mohamed Safwan, Michael Rizzari, Atsushi Yoshida, Marwan S. Abouljoud, Dilip Moonka
Journal: Clinical Gastroenterology and Hepatology (2019)