tbuckley/cabot-search huggingface dataset:
PS-185-Magnetic resonance risk score and liver stiffness by transient elastography have complementary prognostic values in patients with primary sclerosing cholangitis
Authors: Nora Cazzagon, Sanaa El Mouhadi, Sara Lemoinne, Palak J. Trivedi, Farid Gaouar, Astrid Donald Kemgang Fankem, Karima Ben Belkacem, Annarosa Floreani, Gideon Hirschfield, Yves Chretien, Chantal Housset, Raffaella Motta, Francesco Paolo Russo, Olivier Chazouillères, Lionel Arrivé, Christophe Corpechot
Journal: Journal of Hepatology (2019)
Assessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes
Authors: Elvira D’Andrea, Spencer P. Hey, Cherie L. Ramirez, Aaron S. Kesselheim
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Niacin remains a therapeutic option for patients with cardiovascular disease, but recent studies have called into question the effectiveness of other drugs that increase high-density lipoprotein cholesterol levels. <h3>Objective</h3> To systematically review and evaluate the evidence supporting current US Food and Drug Administration–approved uses of niacin in cardiovascular disease prevention settings. <h3>Data Sources</h3> MEDLINE, Embase, Cochrane Controlled Clinical Trial Register (Central), ClinicalTrials.gov, and TrialResults-center, from database inception to October 2017. <h3>Study Selection</h3> The systematic review included clinical trials involving niacin as a treatment for cardiovascular disease. The meta-analysis included randomized clinical trials reporting niacin's effect, as exposure, on at least 1 long-term cardiovascular disease outcome. <h3>Data Extraction and Synthesis</h3> Aggregate study-level data were extracted between November 2017 and January 2018 by 3 independent reviewers, and the analysis was performed in February 2018. Inverse-variance weighted methods were used to produce pooled risk ratios using random-effects models for between-study heterogeneity. Random effects–weighted metaregression analysis was used to assess the association of change in high-density lipoprotein cholesterol levels with the log risk ratio of the pooled results. <h3>Main Outcomes and Measures</h3> Cardiovascular disease, coronary heart disease mortality, and other cardiovascular events, including acute coronary syndrome, fatal and nonfatal stroke, revascularization, and major adverse cardiac events. <h3>Results</h3> Of 119 clinical trials, 17 documented niacin's effect on at least 1 cardiovascular disease outcome. The meta-analysis included 35 760 patients with histories of cardiovascular disease or dyslipidemia. Cumulative evidence found no preventive association of niacin with cardiovascular outcomes in secondary prevention. Stratified meta-analysis showed an association of niacin monotherapy with reduction of some cardiovascular events among patients without statin treatment (acute coronary syndrome: relative risk, 0.74; 95% CI, 0.58-0.96; stroke: relative risk, 0.74; 95% CI, 0.59-0.94; revascularization: relative risk, 0.51; 95% CI, 0.37-0.72). These results were mainly derived from 2 trials conducted in the 1970s and 1980s. <h3>Conclusions and Relevance</h3> Niacin may have some use in lipid control for secondary prevention as monotherapy, perhaps in patients intolerant to statins, but evidence is from older studies on a population potentially not representative of current-day patients.
Thrombospondin Type 1 Domain–Containing 7A Localizes to the Slit Diaphragm and Stabilizes Membrane Dynamics of Fully Differentiated Podocytes
Authors: Johanna Herwig, Sinah Skuza, Wiebke Sachs, Marlies Sachs, Antonio Virgilio Failla, Gabriele Rune, Tobias N. Meyer, Lars Fester, Catherine Meyer-Schwesinger
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Among adults with membranous nephropathy, about 3%–5% have autoantibodies directed against thrombospondin type 1 domain–containing 7A (THSD7A), a podocyte-expressed transmembrane protein. To better understand the effects of THSD7A autoantibodies in this disease, the authors investigated THSD7A’s temporal expression, spatial expression, and biological function in podocytes. They found that embryonic THSD7A expression begins on glomerular vascularization and slit diaphragm formation and that THSD7A and THSD7A autoantibodies localize to the slit diaphragm domain of foot processes. Expression of THSD7A in cultured human podocytes was associated with enhanced adhesion and decreased ability to migrate, suggesting that THSD7A may be involved in stabilizing the slit diaphragm and that autoantibodies to THSD7A might structurally and functionally alter the slit diaphragm’s permeability to protein. Background About 3%–5% of adults with membranous nephropathy have autoantibodies directed against thrombospondin type 1 domain–containing 7A (THSD7A), a podocyte-expressed transmembrane protein. However, the temporal and spatial expression of THSD7A and its biologic function for podocytes are unknown, information that is needed to understand the effects of THSD7A autoantibodies in this disease. Methods Using a variety of microscopic techniques, we analyzed THSD7A localization in postnatal, adult, and autoantibody-injected mice as well as in human podocytes. We also analyzed THSD7A function in human podocytes using confocal microscopy; Western blotting; and adhesion and migration assays. Results We found that THSD7A expression begins on glomerular vascularization with slit diaphragm formation in development. THSD7A localizes to the basal aspect of foot processes, closely following the meanders of the slit diaphragm in human and mice. Autoantibodies binding to THSD7A localize to the slit diaphragm. In human podocytes, THSD7A expression is accentuated at filopodia and thin arborized protrusions, an expression pattern associated with decreased membrane activity of cytoskeletal regulators. We also found that, phenotypically, THSD7A expression in human podocytes is associated not only with increases in cell size, enhanced adhesion, and reduced detachment from collagen type IV–coated plates but also, with decreased ability to migrate. Conclusions Our findings suggest that THSD7A functions as a foot process protein involved in the stabilization of the slit diaphragm of mature podocytes and that autoantibodies to THSD7A, on the basis of their localization, might structurally and functionally alter the slit diaphragm’s permeability to protein.
SAT-204-Hepatitis E virus antigen in urine as a useful diagnostic Background and aims: for monitoring infection and detection of recent infection
Authors: Bernhard Schlevogt, Stahl Yannick, Iyad Kabar, Hauke Heinzow, Benjamin Maasoumy, Birgit Bremer, Daniel Todt, Markus Cornberg, Heiner Wedemeyer, Thomas Pietschmann, Michael P. Manns, Steinmann Eike, Patrick Behrendt
Journal: Journal of Hepatology (2019)
Circulating tumor cells (CTCs) kinetics as a useful tool to evaluate clinical evolution of metastatic colorectal cancer (mCCR) patients.
Authors: Virgilio Souza e Silva, Marcello Ferretti Fanelli, Celso Abdon Lopes de Melo, Solange Moraes Sanches, Marcelo Calil Machado Netto, Aldo Lourenço Abbade Dettino, Milena Shizue Tariki, Aline Damascena, Vanessa da Silva Alves, Juliana Valim Romero, Emne Ali Abdallah, Ludmilla Thome Domingos Chinen
Journal: Journal of Clinical Oncology (2015)

e22036 Background: CTCs have demonstrated promising results as a prognostic tool in patients with mCCR. The purpose of our study was to prospectively correlate CTCs counting with clinical outcomes and therapeutic responses accessed by conventional imaging. We also aimed to evaluate bevacizumab use and the KRAS status and their correlation with CTCs kinetics over time. Methods: A prospective study of 54 patients with mCRC. Blood samples were collected at baseline and at two follow-up visits every two months. We used the ISET system (Isolation by Size of Epithelial Tumor Cells) for analysis and characterization of CTCs. Responses were evaluated mainly with CT scans, using RECIST criteria. Defined of cut-off as a median value of CTC counts.The cut-off for CTC1 was 2.0 (0-31 CTCs/mL), CTC2 was 3.0 (0-47 CTCs/mL). Results: : All patients had metastatic disease and 60% (n = 32) were KRAS wild type (wt). During follow-up 54% (n = 29) of the patients were exposed to monoclonal antibodies along with systemic treatment (anti-VEGF (n = 19) and anti-EGFR (n = 10)). Comparing the baseline CTC level (CTC1) with the level at CTC 2 (first follow-up), CTC1 positive (+) patients who became negative (-) were classified with a favorable evolution (n = 14), and had a progression-free survival (PFS) median of 14.7 months. This was higher than patients with an unfavorable evolution (CTC1 – and CTC2 +) (n = 13), who were CTC1(-) and became CTC2 (+), with a median PFS of 6.9 months (p = 0.06). Patients that used anti-VEGF who presented a favorable CTC kinetic (n = 6) had a PFS of 18,2 months, higher than those with a unfavorable kinetic (n = 5; PFS = 5,6 months; p = 0.007). Patients with KRAS wt with a favorable CTC kinetic had a PFS of 14,7 months, higher than those KRAS wt with a unfavorable kinetic of 9.4 months (p = 0.02). Conclusions: Reinforced the notion that the evaluation of CTC kinetics could be promising in the prognostic correlation during the follow-up of patients with mCRC. Also, we were able to demonstrate that the use of anti-VEGF did not interfere in the kinetics of CTC, unlike previous studies. In the KRAS wt patients, we may have a new tool capable of identifying a population that is genuinely responsive to anti-EGFR therapy.
Medical Algorithms: Diagnosis and treatment of Hymenoptera venom allergy
Authors: Gunter J. Sturm, Lisa Arzt‐Gradwohl, Eva‐ M. Varga
Journal: Allergy (2019)

Diagnosis of Hymenoptera venom allergy (HVA) is straightforward in the majority of patients, but can be challenging in double positive and test negative patients. Test results sometimes can be confusing as patients with high skin test reactivity and high specific IgE (sIgE) levels are not at risk for severe systemic sting reactions (SSR), and conversely, patients with weakly positive or even negative tests can experience severe SSR. Venom immunotherapy (VIT) is safe, highly effective, and recommended in patients with moderate to severe SSR and in patients with SSR confined to generalized skin symptoms if quality of life is impaired.
Progression Risk Stratification of Asymptomatic Waldenström Macroglobulinemia
Authors: Mark Bustoros, Romanos Sklavenitis-Pistofidis, Prashant Kapoor, Chia-Jen Liu, Efstathios Kastritis, Saurabh Zanwar, Geoffrey Fell, Jithma P. Abeykoon, Kalvis Hornburg, Carl Jannes Neuse, Catherine R. Marinac, David Liu, Jenny Soiffer, Maria Gavriatopoulou, Cody Boehner, Joseph M. Cappuccio, Henry Dumke, Kaitlen Reyes, Robert J. Soiffer, Robert A. Kyle, Steven P. Treon, Jorge J. Castillo, Meletios A. Dimopoulos, Stephen M. Ansell, Lorenzo Trippa, Irene M. Ghobrial
Journal: Journal of Clinical Oncology (2019)

Waldenström macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease is not well defined.We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 and 2014.During the 23-year study period, with a median follow-up of 7.8 years, 317 patients progressed to symptomatic WM (72%). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70% or greater, β2-microglobulin 4.0 mg/dL or greater, and albumin 3.5 g/dL or less were all identified as independent predictors of disease progression. To assess progression risk in patients with AWM, we trained and cross-validated a proportional hazards model using bone marrow infiltration, immunoglobulin M, albumin, and beta-2 microglobulin values as continuous measures. The model divided the cohort into three distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.8 years, an intermediate-risk group with a median TTP of 4.8 years, and a low-risk group with a median TTP of 9.3 years. We validated this model in two external cohorts, demonstrating robustness and generalizability. For clinical applicability, we made the model available as a Web page application ( www.awmrisk.com ). By combining two cohorts, we were powered to identify wild type MYD88 as an independent predictor of progression (hazard ratio, 2.7).This classification system is positioned to inform patient monitoring and care and, for the first time to our knowledge, to identify patients with high-risk AWM who may need closer follow-up or benefit from early intervention.
Correlation of various clinical, imaging and laboratory parameters with outcome in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs): Results from a prospective, observational, single institution study
Authors: K. Rounis, C. Papadaki, D. Makrakis, A. Monastirioti, L. Vamvakas, K. Kalbakis, D. Mavroudis, S. Aggelaki
Journal: Annals of Oncology (2019)

Background: PDL1 expression in the tumor is used as a biomarker predictive of benefit from ICIs in NSCLC. We prospectively evaluated clinical, imaging and laboratory parameters to identify additional factors that could be used for patient (pt) selection. Methods: Pt and disease characteristics, sites (brain, liver, bones) and extent (1 vs ≥ 2) of metastases, concomitant use of steroids, antibiotics, or chronic use of proton pump inhibitors, neutrophil to lymphocyte ratio and LDH were prospectively collected from pts with NSCLC treated with ICIs in the 2nd or 3rd line. Response rate (RR), Progression free survival (PFS) and overall survival (OS) data were prospectively recorded. Results: Forty-four pts, median age 69 years, 50% squamous, 50% non-squamous, were included in the analysis. Performance status was 0-1 in 75% and 2 in 25% of pts, 92.7% were active/former smokers and PDL1 was ≥1% in 62% of pts with available PDL1 status. Partial response was recorded in 20% of pts, 30% had stable and 50% progressive disease. Median PFS and OS were 2.7 and 7.6 months, respectively. Prolonged (≥14d, either within 30d pre- or during treatment) use of antibiotics (p = 0,007) and concurrent steroids (p = 0,047) were inversely correlated with response. In multivariate analysis, liver metastases [HR = 4 (CI: 1,6 – 9,9; p = 0.003)], prolonged antibiotic use [HR = 2,76 (CI: 1,8 – 6,4; p = 0,02)] and concurrent steroids [HR = 3,3 (CI: 1,4 – 8,1; p = 0,009)] were independent predictors of shorter PFS, whereas, only antibiotics had a negative impact on OS [HR 4,6 (CI: 1,7-12, p = 0,003)]. Conclusions: To our knowledge this is the first prospective evaluation of routine clinical parameters potentially associated with outcome from ICIs in NSCLC. Our data are in accordance with previous retrospective reports regarding the adverse effect of antibiotics and steroids in the outcome of pts. Moreover, we show that in these pts liver metastases are predictive for inferior outcomes. Legal entity responsible for the study: University Hospital of Heraklion, Crete, Greece. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
FRI-223-Contribution of HBV and HCV infection in mortality of B-NHL subjects
Authors: Myagmarjav Budeebazar, Delgerbat Boldbaatar, Sukhbaatar Myadagsuren, Tungalag Saruul, Uurtsaikh Baatarsuren, khishigjargal Batsukh, Erdeenetsogt Dungubat, Andreas Bungert, Altankhuu Mordorjyn, Dahgwahdorj Yagaanbuyant, Duger Davaadorj, Naranbaatar Dashdorj, Naranjargal Dashdorj
Journal: Journal of Hepatology (2019)
Disseminated subcutaneous nodules and destructive polyarthritis
Authors: Nobuya Abe, Yuichiro Fujieda, Olga Amengual, Tatsuya Atsumi
Journal: BMJ (2019)

A 56 year old man presented with multiple subcutaneous nodules over his body and deformities of both hands and feet. He had a seven year history of chronic peripheral polyarthritis (suspected to be rheumatoid arthritis) but had been reluctant to take antirheumatic therapy and did not attend clinic appointments. He consumed 40-60 g (5-7 units) of alcohol a day.

Examination revealed asymmetrical elastic, hard, painless, and partly ulcerated subcutaneous nodules around articular structures, tendons, and bursas (fig 1). The nodules restricted extension of the left forefinger and left knee.



Fig 1 
Multiple subcutaneous nodules and deformities of both hands



Plain joint radiography of the fingers and toes showed widespread destructive arthritis with joint dislocation, ankylosis, and well defined, punched …
Abstract P183: Minimal Impact of JAMA 2014 Guidelines on Blood Pressure Control in a Large Health System
Authors: Alex R Chang, J E Hartle, Lawrence Appel, Morgan Grams
Journal: Circulation (2017)

Background: JAMA 2014 blood pressure (BP) guidelines raised BP goals for adults older than 60 years (from &lt;140/90 to &lt;150/90) and adults with chronic kidney disease (CKD) or diabetes (from &lt; 130/80 to &lt;140/90). It is unknown whether there were changes in BP control at the health system level after guideline publication. Methods: Using data from 288,962 adults receiving primary care in the Geisinger Health System, we compared blood pressure control over 1-year time periods before and after the February 2014 publication of the JAMA 2014 BP guidelines (i.e. Aug 2012-July 2013 vs Aug 2014-July 2015). Mixed effects models were used, allowing intercepts to vary by individual, adjusted for age, gender, and race. Results: Mean age was 49.2 ± 18.3 y, 56.7% were female, and 2.5% were black. Prevalence of diagnoses for hypertension, diabetes, and CKD were 40.0%, 15.1%, and 11.4%, respectively. Overall, distributions of systolic BP were similar before and after JAMA 2014 BP guidelines (Figure). BP control &lt;140/90 was also similar between the two periods for adults 18-59 y (90.9% vs. 90.3%; OR 1.01, 95% CI: 0.99-1.02; p=0.3), adults ≥ 60 y (81.8% vs 82.2%; OR 1.01, 95% CI: 1.00-1.03; p=0.05), and adults with diabetes (83.2% vs. 82.7%; OR 1.00, 95% CI: 0.99-1.02; p=0.7) whereas BP control &lt;140/90 improved slightly for adults with CKD (81.7% vs. 82.1%; OR 1.06, 95% CI: 1.04-1.08; p&lt;0.001). BP control &lt;130/80 was marginally worse after JAMA 2014 BP guidelines in patients with diabetes (53.5% vs. 51.8%; OR 0.98, 95% CI: 0.96-0.99; p=0.01). Trends were similar in analyses only including patients with hypertension diagnoses (overall 78.6% vs. 78.2%, OR 1.00, 95% CI: 0.99-1.02; p=0.5), and when using a goal of &lt; 130/80 for patients with CKD (53.3% vs. 53.5%; OR 1.06, 95% CI: 1.04-1.08; p&lt;0.001). Conclusion: There was little change in blood pressure control in a large integrated health system after publication of the JAMA 2014 BP guidelines. These findings are reassuring given recent findings from the SPRINT trial supporting lower BP goals.
Motion, frames of reference, dead horses, and metaphysics
Authors: A. H. Wertheim
Journal: Behavioral and Brain Sciences (2001)

Various annoyingly incorrect statements of Stoffregen &amp; Bardy are corrected, for example, that perception researchers commonly use the term “absolute motion” to denote motion without any frame of reference, confuse earth-relative and gravity-relative motion, err with respect to the frame of reference implied by their subject is motion responses, believe in sense specific motion percepts, and do not investigate sensory interactions at neurophysiological levels. In addition, much of the target article seems to concern metaphysics rather than empirical science.
FRI-010-Bezafibrate add-on therapy in high-risk primary biliary cholangitis is associated with an improvement of fibrometer and fibrometer-VCTE, two high-accuracy non-invasive fibrosis tests extensively validated in frequent chronic liver diseases
Authors: Christophe Corpechot, Alexandra Rousseau, Sara Lemoinne, Gaouar Farid, Karima Ben Belkacem, Raoul Poupon, Olivier Chazouillères, Paul Cales
Journal: Journal of Hepatology (2019)
Successful endoscopic submucosal dissection of a large cavernous hemangioma in the colon
Authors: Kan Chen, Min Yan, Feng Liu
Journal: Endoscopy (2019)

Endoscopic submucosal dissection (ESD) is regarded as a common treatment for complete resection of early gastrointestinal neoplasms [1]. However, few cases have been reported on ESD for resection of cavernous hemangioma in the digestive tract. Here we present a patient with a globular, pedunculated, cavernous hemangioma in the descending colon that was removed successfully en bloc by ESD without any bleeding ([Video 1]).
Overall survival of pediatric patients enrolled on phase 1 oncology trials.
Authors: Stuart Cramer, Julia M Adams, Joseph Gerald Pressey
Journal: Journal of Clinical Oncology (2015)

e21017 Background: There are few effective therapeutic options for many metastatic or recurrent pediatric malignancies. Phase I trials are a critical step in the development of new agents for such cancers. Given that phase I therapy candidates have exhausted known curative options, they may generally be assumed to face a short life expectancy with little prospect for meaningful quality of life. While previous reviews of pediatric phase I trials have tabulated safety, efficiency, and patient characteristics, no prior studies have measured outcomes extending beyond participation in the phase I trial. Methods: A retrospective review of patients enrolled on Children's Oncology Group (COG) or investigator initiated phase I trials at the University of Alabama at Birmingham from 2006 to 2014. Results: Seventy-four enrollments occurred on phase I trials from a total of fifty-four patients. Demographically, phase I patients mirrored that of newly diagnosed patients at our institution. Thirty-two percent of patients carried a diagnosis of sarcoma while neuroblastoma and central nervous system (CNS) tumors accounted for 26% and 17% of patients, respectively. Overall survival (OS) for all patients was 39%, 25%, and 15% at 1, 3, and 5 years, respectively. Patients with neuroblastoma had an OS at 1 year of 70% versus sarcoma and CNS tumors who had an OS of 22% and 28% at 1 year, respectively. While RECIST response rates were low, 22% of patients had stabilization of their disease for a minimum of 3 months. Only 18% of patients were taken off study due to toxicity and no toxic deaths were recorded. Finally, 17% of patients were enrolled on multiple phase I trials. Conclusions: Early phase clinical trials are a critical step in the development of new anti-cancer therapies; yet, surveys demonstrate that referring physicians and nurses often express misconceptions about the tolerability and outcomes of patients on phase 1 trials. Our institutional data suggests that phase I patients tolerate therapy well with few severe toxicities and that for a substantial subset of patients, survival may be longer than otherwise expected. These findings are highlighted by a subset of patients enrolling on multiple phase 1 trials.
FRI-468-Identifying optimal candidates for combining transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma: A multicenter observational study
Authors: Enxin Wang, Wei Bai, Zhexuan Wang, Dongdong Xia, Qiuhe Wang, Ming Huang, Junhui Sun, Wei Mu, Hui Zhao, Xingnan Pan, Guoliang Shao, Xiaoli Zhu, Guowen Yin, Haibin Shi, Jianbing Wu, Jiaping Li, Zhengyu Lin, Shufa Yang, Jueshi Liu, Wenhui Wang, Xu Zhu, Rong Ding, Yong Lv, Hui Chen, Kai Li, Jing Niu, Zhanxin Yin, Jielai Xia, Daiming Fan, Guohong Han
Journal: Journal of Hepatology (2019)
THU-104-New fibroblast activation protein inhibitor, CPD, attenuates fibrosis and chronic liver disease progresion in CCL4 induced liver fibrosis, but not in MDR2-/- mice
Authors: Ai Ting Yang, Yong Ook Kim, Misbah Aslam, Mariacristina Giardino, Hiroyuki Abe, Kyoung Sook Park, Muhammad Ashfaq Khan, Hong You, Ji Dong Jia, Thomas Klein, Detlef Schuppan
Journal: Journal of Hepatology (2019)