tbuckley/cabot-search huggingface dataset:
TCTAP C-219 Combined Percutaneous Procedure in Patient with Lutembacher Syndrome: A Case Report and Real-world Practice
Authors: Quang Phan Tan, Lan Hieu Nguyen, Tai Duc Le, Truong Quang Nguyen, Hoyoun Won, Wangsoo Lee, Sang Wook Kim
Journal: Journal of the American College of Cardiology (2019)
Analysis of outcomes based on response for patients with relapsed or relapsed and refractory multiple myeloma in the phase 3 PANORAMA 1 study.
Authors: Vania T.M. Hungria, Jesus F. San Miguel, Sung-Soo Yoon, Meral Beksac, Meletios A. Dimopoulos, Ashraf Elghandour, Wieslaw W. Jedrzejczak, Andreas Guenther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Robert L. Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae Hoon Lee, Hermann Einsele, Monika Sopala, Bourras-Rezki Bengoudifa, Claudia Corrado, Paul G. Richardson
Journal: Journal of Clinical Oncology (2015)

8575 Background: Panobinostat (PAN) is the first pan-deacetylase inhibitor (pan-DACi) to demonstrate a statistically significant and clinically relevant increase in median progression-free survival (PFS) in patients (pts) with relapsed or relapsed and refractory multiple myeloma (MM) in a phase 3 clinical trial. In the PANORAMA 1 trial, pts randomized to receive PAN + bortezomib (BTZ) and dexamethasone (Dex; PAN-BTZ-Dex) demonstrated a median PFS of 12.0 months vs 8.1 months for pts who received placebo + BTZ and Dex (Pbo-BTZ-Dex; HR, 0.63; P < .0001). Here, we present a detailed analysis of the effect of response on clinical outcomes. Methods: Response outcomes, including rate of near complete/complete response (nCR/CR) and duration of response (DOR), were analyzed. A landmarkanalysis at 6, 12, 18, and 24 weeks using a Cox regression model was conducted to determine PFS in pts who achieved nCR/CR or partial response (PR) per mEBMT and IMWG criteria. Results: The nCR/CR rate was significantly higher with PAN-BTZ-Dex vs Pbo-BTZ-Dex (27.6% vs 15.7%; P = .00006 post hoc testing).The DOR for pts with nCR/CR and PR was 18.4 and 9.0 months, respectively, in the PAN-BTZ-Dex arm and 14.5 and 8.8 months, respectively, in the Pbo-BTZ-Dex arm. The landmark analysis by mEBMT criteria at 12 weeks demonstrated a median PFS of 16.5 months for pts with CR/nCR and 10.3 months for pts with PR in the PAN-BTZ-Dex arm (HR, 0.40; 95%CI, 0.25-0.65) and a median PFS of 14.1 months for pts with CR/nCR and 9.7 months for pts with PR in the Pbo-BTZ-Dex arm (HR, 0.62; 95%CI, 0.36-1.07). By IMWG criteria, the landmark analysis at 12 weeks demonstrated a median PFS of 15.9 months for pts with ≥ very good PR (VGPR) and 8.1 months for pts with PR in the PAN-BTZ-Dex arm (HR, 0.36; 95%CI, 0.21-0.62) and a median PFS of 14.4 months for pts with ≥ VGPR and 7.6 months for pts with PR in the Pbo-BTZ-Dex arm (HR, 0.39; 95% CI, 0.22-0.68). Similar results were observed the other landmarks tested. Conclusions: A higher proportion of pts in the PAN-BTZ-Dex arm achieved higher-quality responses, which are associated with longer PFS. Overall, these data support achievement of higher-quality responses as a treatment goal in relapsed/refractory MM. Clinical trial information: NCT01023308.
Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits
Authors: Andrew D. Grotzinger, Mijke Rhemtulla, Ronald de Vlaming, Stuart J. Ritchie, Travis T. Mallard, W. David Hill, Hill F. Ip, Riccardo E. Marioni, Andrew M. McIntosh, Ian J. Deary, Philipp D. Koellinger, K. Paige Harden, Michel G. Nivard, Elliot M. Tucker-Drob
Journal: Nature Human Behaviour (2019)
FRI-296-Interaction between the soluble guanylate cyclase and the NLRP3 inflammasome in Kupffer cells: Implications for the anti-inflammatory actions of sGC stimulation in liver
Authors: Roger Flores-Costa, Marta Duran-Güell, Mireia Casulleras, Cristina López-Vicario, Esther Titos, Joan Clària
Journal: Journal of Hepatology (2019)
THU-316-Cognitive impairment or hepatic encephalopathy? A prospective cross-sectional study in patients with non-alcoholic fatty liver disease
Authors: Nir Bar, Shira Deri, Muriel Webb, Jenny Rutenburg, Fadi Younes, Oren Shibolet, Shira Zelber-Sagi, Helena Katchman
Journal: Journal of Hepatology (2019)
PS-135-MSDC-0602 K, a PPAR-gamma sparing modulator of the mitochondrial pyruvate carrier, improves NASH outcome in a diet-induced animal model of non-alcoholic steatohepatitis
Authors: Rebecca Caffrey, Jonathon Marioneaux, Jerry Colca, Pierre Bedossa, Arun Sanyal
Journal: Journal of Hepatology (2019)
Benzo(a)pyrene facilitates dermatophagoides group 1 (Der f 1)‐induced epithelial cytokine release through aryl hydrocarbon receptor in asthma
Authors: Eryi Wang, Xiaoyu Liu, Wei Tu, Danh C. Do, Haiqiong Yu, Liteng Yang, Yufeng Zhou, Damo Xu, Shau‐Ku Huang, Pingchang Yang, Pixin Ran, Pei‐Song Gao, Zhigang Liu
Journal: Allergy (2019)

Abstract Background Environmental pollutants, which coexist with allergens, have been associated with the exacerbation of asthma. However, the underlying molecular mechanisms remain elusive. We sought to determine whether benzo(a)pyrene (BaP) co‐exposure with dermatophagoides group 1 allergen (Der f 1) can potentiate Der f 1‐induced asthma and its underlying mechanisms. Methods The effect of BaP was investigated in Der f 1‐induced mouse model of asthma, including airway hyper‐responsiveness, allergic inflammation, and epithelial‐derived cytokines. The impact of BaP on Der f 1‐induced airway epithelial cell oxidative stress (ROS) and cytokine release was further analyzed. The role of aryl hydrocarbon receptor (AhR) signaling in BaP‐promoted Der f 1‐induced ROS, cytokine production, and allergic inflammation was also investigated. Results Compared with Der f 1, BaP co‐exposure with Der f 1 led to airway hyper‐responsiveness and increased lung inflammation in mouse model of asthma. Increased expression of TSLP, IL‐33, and IL‐25 was also found in the airways of these mice. Moreover, BaP co‐exposure with Der f 1 activated AhR signaling with increased expression of AhR and CYP1A1 and promoted airway epithelial ROS generation and TSLP and IL‐33, but not IL‐25, expression. Interestingly, AhR antagonist CH223191 or cells with AhR knockdown abrogated the increased expression of ROS, TSLP, and IL‐33. Furthermore, ROS inhibitor N‐acetyl‐L‐cysteine (NAC) also suppressed BaP co‐exposure‐induced expression of epithelial TSLP, IL‐33, and IL‐25. Finally, AhR antagonist CH223191 and NAC inhibited BaP co‐exposure with Der f 1‐induced lung inflammation. Conclusions Our findings suggest that BaP facilitates Der f 1‐induced epithelial cytokine release through the AhR‐ROS axis.
Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management
Authors: Preetesh Jain, Michael Wang
Journal: American Journal of Hematology (2019)

Abstract Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX‐11 expression. Cyclin‐D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki‐67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53 , BIRC3 , CDKN2A , MAP3K14 , NOTCH2 , NSD2 , and SMARCA4 genes. In therapy, long‐term follow‐up on chemo‐immunotherapy studies has demonstrated durable remissions in some patients; however, long‐term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy‐free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine‐microenvironmental milieu, incorporation of positron emission tomography‐computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next‐generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.
Abstract 20223: Responses to Acetylcholine in Stented Target Vessel in Comparison to Non-Target Vessel in Patients After Percutaneous Coronary Intervention
Authors: Yusuke Akiyama, Tetsuya Matoba, Yasushi Mukai, Daisuke Furukawa, Keiji Oi, Shunji Hayashidani, Toyokazu Uwatoku, Hiroyuki Tsutsui
Journal: Circulation (2017)

Introduction: Several studies have reported the relationship between 1st generation drug-eluting stent (DES) implantation and coronary endothelial dysfunction (CED). However, no study has examined coronary responses to acetylcholine in stented target vessel (TV) in comparison to non-TV in each subject with 2nd generation DES. Methods: From 2011 to 2013, a total of 115 patients underwent coronary angiogram at 6 to 8 months after percutaneous coronary intervention (PCI) with stent implantation in one branch of the left coronary artery (LCA) (BMS: n=53, 2nd generation DES: n=60). We compared maximum coronary vasoconstriction to incremental doses of intracoronary acetylcholine (low 10 μg, middle 30 μg, and high 100 μg) in both stented TV and non-TV in LCA. Results: Acetylcholine-induced vasoconstriction was equivalent between TV and non-TV in patients treated with 2nd generation DES (45% vs. 44%, P=0.71 by paired T-test, Figure). Interestingly, acetylcholine-induced vasoconstriction in the TV was significantl...
FRI-458-Response evaluation using modified RECIST criteria predict outcomes better than RECIST 1.1 criteria in patients with HCC treated with Yttrium-90 radioembolization
Authors: HongJun Choi, Tae Seop Lim, Mi Young Jeon, In Rae Cho, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seung Up Kim, Jae Seung Lee
Journal: Journal of Hepatology (2019)
SAT-221-Autoantibodies to apolipoprotein A1 (apoA-1): A new prognostic biomarker in HCV infection
Authors: Margaret Bassendine, Sabrina Pagano, Simon Bridge, David Sheridan, Isaac Shawa, Matthew Cramp, Simon Taylor-Robinson, Dermot Neely, Nicolas Vuilleumier
Journal: Journal of Hepatology (2019)
PS-003-Activation of the miR-34a/SIRT1:AMPK axis contributes for insulin resistance and mitochondrial dysfunction in the NAFLD muscle
Authors: André L. Simão, Marta B. Afonso, Pedro Miguel Rodrigues, Margarida Gama-Carvalho, Mariana V. Machado, Helena Cortez-Pinto, Cecília M.P. Rodrigues, Rui E. Castro
Journal: Journal of Hepatology (2019)
Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule
Authors: Julian M Yabut, Justin D Crane, Alexander E Green, Damien J Keating, Waliul I Khan, Gregory R Steinberg
Journal: Endocrine Reviews (2019)

Abstract Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).
Immunoglobulin light chains generate proinflammatory and profibrotic kidney injury
Authors: Wei-Zhong Ying, Xingsheng Li, Sunil Rangarajan, Wenguang Feng, Lisa M. Curtis, Paul W. Sanders
Journal: Journal of Clinical Investigation (2019)

Because of the less-than-robust response to therapy and impact on choice of optimal chemotherapy and prognosis, chronic kidney disease has drawn attention in the treatment of multiple myeloma, a malignant hematologic disorder that can produce significant amounts of monoclonal immunoglobulin free light chains (FLCs). These low-molecular-weight proteins are relatively freely filtered through the glomerulus and are reabsorbed by the proximal tubule. The present study demonstrated that during the process of metabolism of immunoglobulin FLCs, ROS activated the STAT1 pathway in proximal tubule epithelium. STAT1 activation served as the seminal signaling molecule that produced the proinflammatory molecule IL-1β, as well as the profibrotic agent TGF-β by this portion of the nephron. These effects occurred in vivo and were produced specifically by the generation of hydrogen peroxide by the VL domain of the light chain. To the extent that the experiments reflect the human condition, these studies offer insights into the pathogenesis of progressive kidney failure in the setting of lymphoproliferative disorders, such as multiple myeloma, that feature increased circulating levels of monoclonal immunoglobulin fragments that require metabolism by the kidney.
Lymphoid stress-surveillance in prostate cancer.
Authors: Deborah Enting, Maria Luisa Iannitto, Fidelma Cahill, Aida Santaolalla, Simon Chowdhury, Mieke Van Hemelrijck, Adrian C Hayday
Journal: Journal of Clinical Oncology (2015)

e22097 Background: Prostate cancer (PCa) remains a significant health burden. There is evidence that PCa development is substantially controlled by the immune system. The body harbours a natural mechanism, termed Lymphoid Stress-Surveillance (LSS), whereby γδ T cells and NK cells eradicate DNA-damaged cells. The prospect of LSS acting as a natural regulator of PCa would provide a novel means to assess a patient’s condition and form a basis for proposing potential therapies to promote it. However, the status of LSS in PCa remains largely unexplored and it is likely that there is significant inter-individual heterogeneity in LSS responses as has been demonstrated in healthy subjects. This might explain the diversity in anti-tumour immune responses observed in patients. Methods: We have developed a longitudinal prospective cohort study to periodically monitor LSS profiles via peripheral blood in various PCa cohorts including patients with advanced and localised PCa and various treatment cohorts. In depth immune phenotyping will be correlated with clinical characteristics. The aim of this study is to identify patterns of LSS that may predict individual PCa-specific mortality and responses to therapy. Results: At present 140 patients have been recruited and over 360 blood samples collected for peripheral blood mononuclear cell and plasma isolation. First observations indicate that patients with advanced PCa display more variable and higher monocyte fraction. Furthermore this cohort shows trends towards a more unfavourable chemokine receptor profile with decreased percentage of CCR2+ γδ T cells and increased frequency of CXCR4+ γδ T cells. Conclusions: We are able to perform in depth immune monitoring on a large number of PCa patients in a routine clinical setting. First results indicate a possible adverse LSS response for patients with advanced PCa which will be explored in additional analyses. The first results of this ongoing project will be presented.
Correlation among different KRAS alterations, genetic co-mutations and PD-L1 expression in patients treated with immunotherapy in metastatic NSCLC
Authors: L. Gianoncelli, G. Spitaleri, A. Passaro, C. Fumagalli, P. Trillo Aliaga, E. Del Signore, V. Stati, E. Ferraro, E. Guerini-Rocco, C.M. Catania, M. Barberis, F. de Marinis
Journal: Annals of Oncology (2019)

Background: No molecularly driven strategy against KRAS demonstrated convincing activity in clinical trials. The introduction of immune checkpoints inhibitors (IO) represents a paradigm shift in treatment of NSCLC without gene target. Considering the association with smoke, the high mutational burden, the high PDL1 expression and the abundance of T-cell infiltrating lymphocyte, KRAS mutant tumors have been considered an attractive target for IO. Methods: Patients (pts) with stage IV NSCLC harboring KRAS mutation treated with IO in our Institution between 2016 and 2018 were retrospectively identified by electronic medical record review. All pts provided written informed consent for the collection of clinical, demographic and molecular data. Results: A total number of 328 consecutive pts with KRAS mutant NSCLC were identified, of them 32 received IO. All eligible pts had PDL1 testing and in 21 cases (65.6%) NGS was available. Median age was 63 (range 44-78). Male/female were 17/15. Most pts had an adequate ECOG PS (0/1 18.7%/65.6% respectively). 29 pts (90.6%) were smokers. According to the setting, 10 pts were treated in 1st-line, 9 in 2nd-line and 13 in further lines. Between the 9 subtypes of KRAS mutation identified in our cohort, G12C was the commonest (14, 43.8%). 15 pts (46.9%) had PDL1≥50%, 10 (31.2%) had PD-L1 between 1-49%, and 7 (21.9%) were negative. 8 pts (25%) had co-occurring gene mutations. With a median follow-up of 5.1 mos (0.4-28.6), the mPFS and mOS for ITT population were 4.47 (95% CI 2.5-6.4) and 7.73 (95% CI 6-14.5) mos. Conclusions: Our preliminary results, contrary to findings in other oncogene driven NSCLC, showed that the presence of KRAS mutations seems to be irrelevant for the selection of patients for IO. Furthermore, neither the association of co-mutation (found in the 25% of cases) nor the type of KRAS variant or the treatment setting (1st vs further lines) seems to have an impact on the effectiveness of IO in KRAS NSCLC pts. Data about clinical efficacy according to PD-L1 expression will be presented at the meeting. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 3108: Prevalence, Referral Patterns, Testing and Surgery in Aortic Stenosis: Leaving Women and Elderly Patients Behind?
Authors: Jasmina Radeva, Howard Birnbaum, Edward Tuttle, Sara Filipek, David S Bach
Journal: Circulation (2006)

Objective. This study describes the prevalence of aortic stenosis (AS) using a privately insured employer claims database and extrapolates the estimates to the adult U.S. population. Differences as...
Ureteral Stone Mimicking Abnormal Sacral Uptake on 99mTc MDP Bone Scintigraphy
Authors: Renjie Wang, Gege Zhao, Bin Chen, Bin Ji
Journal: Clinical Nuclear Medicine (2019)

Abstract Bone tracer uptake related to ureteral stones has been reported several times before. We present a right ureteral stone mimicking abnormal focal sacral uptake on planar scan in a patient with rectal cancer. This case highlights the necessity of performing SPECT/CT to ascertain the origin of abnormal focal sacral uptake on planar scan, especially in patients with a history of kidney stones.
Abstract 18009: Clinical-officer Led Echocardiographic Screening is Sensitive for Diagnosing Rheumatic Heart Disease in Malawi, Africa
Authors: Amy E Sims, Craig A Sable, Mina Hosseinipour, Melissa Karlsten, Peter N Kazembe, Charles G Minard, Daniel J Penny
Journal: Circulation (2015)

Malawi, Africa has a high prevalence of rheumatic heart disease (RHD). Echocardiographic (echo) screening for RHD in asymptomatic children may enable early diagnosis and treatment in order to prevent progression of RHD. Malawi has few physicians, and no pediatric cardiologists in the country. Therefore, physician-led RHD screening is not feasible. Clinical officers (CO’s) are mid-level providers who may be able to perform RHD echo screening. Hypothesis: After training, CO’s will have similar results in identifying RHD by echocardiography as a pediatric cardiologist. Methods: 8 CO’s with no previous echo experience completed 3 half-days of didactic and computer-module based training as well as 2 days of clinical attachments at a local school. On the attachments, CO’s completed an average of 60 mentored RHD screening echos with a Philips portable CX50 echo machine. CO’s were evaluated by performing screening echos on 20 children with and without RHD who were screened in the previous year. They indicated whether the children should be referred for follow-up. Screening protocol called for referral if a mitral regurgitation jet measured more than 1.5 cm or an aortic regurgitation jet measured more than 1 cm. Kappa statistic was calculated based on agreement with a pediatric cardiologist’s screening result (referral vs. no referral). Sensitivity and specificity were estimated using a generalized linear mixed model. Results: The mean kappa statistic comparing CO reads to the pediatric cardiologist was 0.72 (95% CI: 0.62, 0.82). Kappa ranged from a minimum of 0.57 to a maximum of 0.90. Overall, sensitivity was 0.92 (95% CI: 0.86, 0.95), and specificity was 0.80 (95% CI: 0.68, 0.88). Conclusion: There is substantial agreement between the CO and pediatric cardiologist diagnoses. In addition, CO’s had a high sensitivity in detecting RHD. With short-course training, CO-led echo screening for RHD is a viable alternative to physician-led screening in resource-limited settings.
SAT-495-Incidence and risk factors of hepatocellular carcinoma in patients with hepatitis C in China and the US
Authors: Ming Yang, Neehar D. Parikh, Huixin Liu, Elizabeth Wu, Sherry Fu, Huiying Rao, Bo Feng, Andy Lin, Ran Fei, Lai Wei, Anna S. Lok
Journal: Journal of Hepatology (2019)
Dozens of device companies implicated in $1.2bn scam, say US prosecutors
Authors: Owen Dyer
Journal: BMJ (2019)

In what US authorities are calling one of the largest healthcare frauds in history, 130 medical device makers have seen their Medicare payments suspended, suspected of being willing participants in a complex kickback scheme that saw hundreds of thousands of patients sold medically unnecessary back, shoulder, wrist, and knee braces at US taxpayers’ expense.

Three physicians and the senior executives of five telemedicine companies were among 24 people charged as a result of Operation Brace Yourself, a collaboration between the FBI and investigators from the Department of Health and Human Services. Most of the others accused are owners of medical device companies.

The scam allegedly began, prosecutors said, with international call centres in the Philippines and Latin America that recruited US …
SAT-277-Screening diabetic patients at risk for complications of nonalcoholic fatty liver disease: Prospective evaluation of national and international guideline recommendations
Authors: Valentin Blank, Volker Keim, David Petroff, Maria Heni, Thomas Berg, Yvonne Bausback, Arne Dietrich, Anke Toenjes, Martin Bauer, Beer Sebastian, Marcus Hollenbach, Yvonne Kupplich, Matthias Blüher, Udo Thrandorf, Johannes Wiegand, Thomas Karlas
Journal: Journal of Hepatology (2019)