tbuckley/cabot-search huggingface dataset:
2 Use of “assessment for retreatment with tace (ART)” score to ensure appropriate patient selection: a retrospective review of tace re-treatment in the northern ireland regional tace service
Authors: L McNeill, L Stratton, PT Kennedy, IS Cadden, WJ Cash, R McCorry, NI McDougall
Journal: Gut (2017)

Background  The “Assessment for Retreatment with TACE (transarterial chemoembolization)” (ART) score was developed to determine suitability for additional TACE treatment in patients with hepatocellular cancer - it utilises AST, absence of radiological response and Child-Pugh score following initial procedure. Those with a score of   Aim  To determine whether the ART score successfully predicted those patients who did and did not have repeat TACE for HCC.  Method  Retrospective application of ART score to all patients undergoing TACE at the Royal Victoria Hospital, Belfast from March 2011 until July 2016.  Results  99 patients had TACE during the study period of whom 64 had a second TACE. The ART score was >2.5 in 22 of the 64 and therefore ART score would have excluded one third of retreatments. Of the 35 patients who just had a single TACE treatment, further TACE was not required in 11 (disease was stable in 8 patients, 2 underwent alternative treatments (1 transplant, 1 segmentectomy) and 1 refused). Of the remaining 24 patients not offered repeat TACE, 18 (75%) had an ART score of ≥2.5 and 6 were deemed unfit for other reasons (2 demonstrated disease progression not accounted for by ART score, 2 had significant comorbidities and 2 experienced complications following the initial procedure).  Conclusions  The ART score successfully identified three quarters of patients deemed unsuitable for repeat TACE treatment. However, if applied ART would have excluded one third of patients who had a successful second TACE.
Hepatocytes contribute to residual glucose production in a mouse model for glycogen storage disease type Ia
Authors: Brenda S. Hijmans, Andreas Boss, Theo H. van Dijk, Maud Soty, Henk Wolters, Elodie Mutel, Albert K. Groen, Terry G.J. Derks, Gilles Mithieux, Arend Heerschap, Dirk‐Jan Reijngoud, Fabienne Rajas, Maaike H. Oosterveer
Journal: Hepatology (2017)

It is a long‐standing enigma how glycogen storage disease (GSD) type I patients retain a limited capacity for endogenous glucose production despite the loss of glucose‐6‐phosphatase activity. Insight into the source of residual endogenous glucose production is of clinical importance given the risk of sudden death in these patients, but so far contradictory mechanisms have been proposed. We investigated glucose‐6‐phosphatase–independent endogenous glucose production in hepatocytes isolated from a liver‐specific GSD Ia mouse model (L‐ G6pc –/– mice) and performed real‐time analysis of hepatic glucose fluxes and glycogen metabolism in L‐ G6pc –/– mice using state‐of‐the‐art stable isotope methodologies. Here we show that G6pc ‐deficient hepatocytes are capable of producing glucose. In vivo analysis of hepatic glucose metabolism revealed that the hepatic glucokinase flux was decreased by 95% in L‐ G6pc –/– mice. It also showed increased glycogen phosphorylase flux in L‐ G6pc –/– mice, which is coupled to the release of free glucose through glycogen debranching. Although the ex vivo activities of debranching enzyme and lysosomal acid maltase, two major hepatic α‐glucosidases, were unaltered in L‐ G6pc −/− mice, pharmacological inhibition of α‐glucosidase activity almost completely abolished residual glucose production by G6pc ‐deficient hepatocytes. Conclusion : Our data indicate that hepatocytes contribute to residual glucose production in GSD Ia. We show that α‐glucosidase activity, i.e. glycogen debranching and/or lysosomal glycogen breakdown, contributes to residual glucose production by GSD Ia hepatocytes. A strong reduction in hepatic GCK flux in L‐ G6pc‐/‐ mice furthermore limits the phosphorylation of free glucose synthesized by G6pc ‐deficient hepatocytes, allowing the release of glucose into the circulation. The almost complete abrogation of GCK flux in G6pc ‐deficient liver also explains the contradictory reports on residual glucose production in GSD Ia patients. (H epatology 2017;66:2042–2054)
Role of thrombin receptors in ovarian cancer invasion and metastasis
Authors: Anika Agarwal, L. Covic, G. Azabdaftari, A. Kuliopulos
Journal: Cancer Research (2004)

4916  Of all gynecological malignancies, ovarian cancer presents the greatest clinical challenge requiring intensive and complex therapies. In ovarian cancer, as in other solid tumors, the metastatic phase of the disease is often the cause of death and the treatment options and prognosis for women with late stage ovarian cancer remain poor. We and others have shown that the class of receptors known as protease-activated receptors (PAR1-4) play an important role in the invasion and metastasis of solid tumors derived from breast, lung, colon and prostate tissues. Interestingly, ovarian cancer cell lines have been shown to have very high levels of PAR1 mRNA expression. The aim of these studies was to determine whether PAR1 or the other PARs play a role in the invasive process of ovarian cancer. We characterized the cell surface and functional expression of the four known PARs in three ovarian cancer cell lines (SKOV-3, OVCAR-4 and IGROV-1) selected from the NCI-60 panel. We found that all the three cell lines had high levels of PAR1 expression on the cell surface by FACS and gave a robust Ca 2+ signal upon addition of a PAR1-specific ligand or thrombin. Cell surface expression of PAR2 was low but OVCAR-4 and SKOV-3 cells gave strong Ca 2+ signals in response to the PAR2 ligand. PAR3 and PAR4 were not expressed or functionally active in the three cell types. We then examined the effect of activation of PAR1 on cell migration of SKOV-3 cells. Both thrombin and the PAR1-specific ligand, TFLLRN, enhanced migration of SKOV-3 cells by 24-37%. PAR2 and PAR4-specific ligands SLIGKV and AYPGKF did not affect migration of SKOV-3 cells. Therefore, our in vitro data suggest that PAR1 plays a proinvasive role in SKOV-3 ovarian cancer cells. Studies using a nude mice invasion and metastasis model are currently in progress to investigate whether inhibition of PAR1 might affect the progression of SKOV-3 ovarian cancer in vivo.
Nontraditional Diagnoses in Minority Populations
Authors: Isra Ahmad
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study
Authors: Benjamin O Wolthers, Thomas L Frandsen, André Baruchel, Andishe Attarbaschi, Shlomit Barzilai, Antonella Colombini, Gabriele Escherich, Kathrine Grell, Hiroto Inaba, Gábor Kovacs, Der-Cherng Liang, Marion Mateos, Veerle Mondelaers, Anja Möricke, Tomasz Ociepa, Sujith Samarasinghe, Lewis B Silverman, Inge M van der Sluis, Martin Stanulla, Lynda M Vrooman, Michihiro Yano, Ester Zapotocka, Kjeld Schmiegelow
Journal: The Lancet Oncology (2017)
Converting Bystanders to Immediate Responders
Authors: Adil H. Haider, Elliott R. Haut, George C. Velmahos
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Abstract 20: Fatty Liver is Associated with Greater Incidence of Cardiovascular Risk Factors
Authors: Jiantao Ma, Shih-Jen Hwang, Udo Hoffmann, Caroline S Fox, Michelle T Long
Journal: Circulation (2016)

Introduction: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk for cardiovascular (CV) related-death. Prior studies have demonstrated a cross-sectional association between NAFLD and CV risk factors including hypertension, hyperlipidemia, and insulin resistance. Little is known about the relationship between NAFLD and incident CV risk factors in the American adult population. We hypothesized that, independent of overall adiposity, NAFLD is associated with incident CV risk factors. Methods: We conducted a longitudinal study of 1,645 Framingham Heart Study Third Generation Cohort participants (median age 44.0 years, 46.1% women) who attended examination 1 (2002-2005) and examination 2 (2008-2011) and participated in the multi-detector computed tomography (MDCT) sub-study (2002-2005). The median follow up duration was 6.2 years. We excluded participants with heavy alcohol use or with prevalent myocardial infarction and stroke at baseline. Liver fat was assessed using MDCT at the baseline examination. Odds ratios (OR) of incident CV risk factors per standard deviation increase of liver fat were estimated using logistic regression models with adjustment for multiple baseline covariates including BMI. Results: The prevalence of NAFLD was 16.6% in the present sample. In multivariable-adjusted models, liver fat was not associated with incident metabolic syndrome (OR 1.10, 95%CI: 0.88, 1.37), hypertriglyceridemia (OR 0.93, 95%CI: 0.75, 1.16), low high-density lipoprotein (OR 1.21, 95%CI: 0.88, 1.66), or prediabetes (OR 1.15, 95%CI: 0.95, 1.40). However, per standard deviation increase of liver fat, we observed a greater risk of incident hypertension (OR 1.22, 95%CI: 1.02-1.46, P-value=0.03) and incident type 2 diabetes (OR 1.45, 95%CI: 1.15-1.84, P-value=0.002). The association with liver fat and incident type 2 diabetes remained after additional adjustment for visceral adipose tissue volume (OR 1.42, 95%CI: 1.10-1.82, P-value=0.006). Conclusions: The present study demonstrates that higher level of liver fat is associated with increased incidence of hypertension and type 2 diabetes over 6 years. Future studies are needed to determine if interventions targeting individuals with NAFLD may reduce incident CV risk factors burden.
Health Aspects of Family Planning.
Journal: Annals of Internal Medicine (1970)

Family planning practices can have broad effects on health which may be life long.  Family planning can prevent aggravation of severe hypertension recurrent toxemia of pregnancy hemolytic disease marked anemia and malnutrition as well as other conditions which are contraindications to pregnancy (e.g. cardiovascular  disease diabetes epilepsy and mental disease).  Maternal health is often related to interpregnancy intervals.  Infant mortality often increases with parity fertility; regulation can improve the health of the remainder of the family by reducing the ultimate size of the family.  Family planning programs should be incorporated into general health care programs for greater acceptance.
Management of Acute Diverticulitis
Authors: Sachin D. Shah, Adam S. Cifu
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Tumor Evolution as a Therapeutic Target
Authors: Nabil Amirouchene-Angelozzi, Charles Swanton, Alberto Bardelli
Journal: Cancer Discovery (2017)

Recent technological advances in the field of molecular diagnostics (including blood-based tumor genotyping) allow the measurement of clonal evolution in patients with cancer, thus adding a new dimension to precision medicine: time. The translation of this new knowledge into clinical benefit implies rethinking therapeutic strategies. In essence, it means considering as a target not only individual oncogenes but also the evolving nature of human tumors. Here, we analyze the limitations of targeted therapies and propose approaches for treatment within an evolutionary framework.
Response to Comment on Harlan. Islet Transplantation for Hypoglycemia Unawareness/Severe Hypoglycemia: Caveat Emptor. Diabetes Care 2016;39:1072–1074
Authors: David M. Harlan
Journal: Diabetes Care (2017)

Hering et al. (1) frame their comments around solitary islet transplant’s benefit for some of the Clinical Islet Transplantation Consortium phase 3 trial (CIT-07) study’s 48 patients with long-standing type 1 diabetes (T1D) and severe hypoglycemic episodes (SHE) (2). I endorsed their assertion that some patients benefited (3).

I framed my commentary (3) in a different light, however. Quoting from the study report (2), CIT-07 was performed “to serve as a license-enabling study” for the U.S. Food and Drug Administration (FDA) as it weighs licensing isolated pancreatic islets as an appropriate therapy for some individuals with T1D. Such licensing decisions are adjudicated by the FDA’s Center for Biologics Evaluation and Research, Office of Cellular, Tissue and …
Adefovir-Induced Hypophosphatemic Osteomalacia Mimicking Bone Metastases From Primary Hepatocarcinoma
Authors: Wei-Jun Wei, Zhen-Kui Sun, Chen-Tian Shen, Zhong-Ling Qiu, Quan-Yong Luo
Journal: Clinical Nuclear Medicine (2017)

Adefovir-induced hypophosphatemic osteomalacia in the context of hepatocarcinoma is rare and needs to be differentiated from metastatic hepatocarcinoma. We here report a case of severe osteomalacia whose focal uptakes of radiotracer on the Tc-MDP SPECT/CT images mimicked that of metastatic hepatocarcinoma.
89Zr-Lumretuzumab PET Imaging before and during HER3 Antibody Lumretuzumab Treatment in Patients with Solid Tumors
Authors: Frederike Bensch, Laetitia E. Lamberts, Michaël M. Smeenk, Annelies Jorritsma-Smit, Marjolijn N. Lub-de Hooge, Anton G.T. Terwisscha van Scheltinga, Johan R. de Jong, Jourik A. Gietema, Carolien P. Schröder, Marlene Thomas, Wolfgang Jacob, Keelara Abiraj, Celine Adessi, Georgina Meneses-Lorente, Ian James, Martin Weisser, Adrienne H. Brouwers, Elisabeth G.E. de Vries
Journal: Clinical Cancer Research (2017)

Abstract Purpose: We evaluated biodistribution and tumor targeting of 89Zr-lumretuzumab before and during treatment with lumretuzumab, a human epidermal growth factor receptor 3 (HER3)–targeting monoclonal antibody. Experimental Design: Twenty patients with histologically confirmed HER3-expressing tumors received 89Zr-lumretuzumab and underwent positron emission tomography (PET). In part A, 89Zr-lumretuzumab was given with additional, escalating doses of unlabeled lumretuzumab, and scans were performed 2, 4, and 7 days after injection to determine optimal imaging conditions. In part B, patients were scanned following tracer injection before (baseline) and after a pharmacodynamic (PD)-active lumretuzumab dose for saturation analysis. HER3 expression was determined immunohistochemically in skin biopsies. Tracer uptake was calculated as standardized uptake value (SUV). Results: Optimal PET conditions were found to be 4 and 7 days after administration of 89Zr-lumretuzumab with 100-mg unlabeled lumretuzumab. At baseline using 100-mg unlabeled lumretuzumab, the tumor SUVmax was 3.4 (±1.9) at 4 days after injection. SUVmean values for normal blood, liver, lung, and brain tissues were 4.9, 6.4, 0.9 and 0.2, respectively. Saturation analysis (n = 7) showed that 4 days after lumretuzumab administration, tumor uptake decreased by 11.9% (±8.2), 10.0% (±16.5), and 24.6% (±20.9) at PD-active doses of 400, 800, and 1,600 mg, respectively, when compared with baseline. Membranous HER3 was completely downregulated in paired skin biopsies already at and above 400-mg lumretuzumab. Conclusions: PET imaging showed biodistribution and tumor-specific 89Zr-lumretuzumab uptake. Although, PD-active lumretuzumab doses decreased 89Zr-lumretuzumab uptake, there was no clear evidence of tumor saturation by PET imaging as the tumor SUV did not plateau with increasing doses. Clin Cancer Res; 23(20); 6128–37. ©2017 AACR.
Redundant and diverse intranodal pacemakers and conduction pathways protect the human sinoatrial node from failure
Authors: Ning Li, Brian J. Hansen, Thomas A. Csepe, Jichao Zhao, Anthony J. Ignozzi, Lidiya V. Sul, Stanislav O. Zakharkin, Anuradha Kalyanasundaram, Jonathan P. Davis, Brandon J. Biesiadecki, Ahmet Kilic, Paul M. L. Janssen, Peter J. Mohler, Raul Weiss, John D. Hummel, Vadim V. Fedorov
Journal: Science Translational Medicine (2017)

The human sinoatrial node (SAN) efficiently maintains heart rhythm even under adverse conditions. However, the specific mechanisms involved in the human SAN's ability to prevent rhythm failure, also referred to as its robustness, are unknown. Challenges exist because the three-dimensional (3D) intramural structure of the human SAN differs from well-studied animal models, and clinical electrode recordings are limited to only surface atrial activation. Hence, to innovate the translational study of human SAN structural and functional robustness, we integrated intramural optical mapping, 3D histology reconstruction, and molecular mapping of the ex vivo human heart. When challenged with adenosine or atrial pacing, redundant intranodal pacemakers within the human SAN maintained automaticity and delivered electrical impulses to the atria through sinoatrial conduction pathways (SACPs), thereby ensuring a fail-safe mechanism for robust maintenance of sinus rhythm. During adenosine perturbation, the primary central SAN pacemaker was suppressed, whereas previously inactive superior or inferior intranodal pacemakers took over automaticity maintenance. Sinus rhythm was also rescued by activation of another SACP when the preferential SACP was suppressed, suggesting two independent fail-safe mechanisms for automaticity and conduction. The fail-safe mechanism in response to adenosine challenge is orchestrated by heterogeneous differences in adenosine A1 receptors and downstream GIRK4 channel protein expressions across the SAN complex. Only failure of all pacemakers and/or SACPs resulted in SAN arrest or conduction block. Our results unmasked reserve mechanisms that protect the human SAN pacemaker and conduction complex from rhythm failure, which may contribute to treatment of SAN arrhythmias.
Identifying sources of distress in patients with breast cancer.
Authors: Karina I. Halilova, Gabrielle Betty Rocque, Elizabeth Ann Kvale, Kerri S. Bevis, Richard A. Taylor, Aras Acemgil, Michelle Martin, Wendy Demark-Wahnefried, Yufeng Li, Karen Meneses, Mona Fouad, Edward Partridge, Maria Pisu
Journal: Journal of Clinical Oncology (2015)

e17707 Background: Multiple factors can contribute to distress experienced after a diagnosis of breast cancer; tools are needed to identify the concerns of this population. Lay navigators can use distress screening results to characterize concerns of individual patients and the population. Methods: The Patient Care Connect Program established in 2012 includes 12 cancer centers in AL, MS, FL, GA, and TN, which navigate cancer patients ≥ 65 years old. Navigators documented distress levels (0-10), sources of distress, and requests for navigator assistance using Distress Tools (DT) during the period of 3/2013 to 1/2015. Results: Out of 1338 breast cancer patients screened for distress, 14% were African American and 11% had advanced disease. Twenty five percent of patients reported distress scores ≥ 4 (moderate distress) and 6% reported scores ≥ 8 (severe distress). Although physical symptoms were the most frequently reported cause of distress (24%), other sources of distress included information needs (19%), emotional problems (15%), practical concerns (7%) and cognitive difficulties (6%). African Americans reported distress caused by physical symptoms (29%), information needs (17%), emotional needs (19%), and practical problems (15%). Patients with advanced disease reported distress from physical symptoms (30%) and information needs (26%) frequently. Overall, patients were more likely to request navigator assistance with distress items related to knowledge, concerns about treatment (66%) and diagnosis (57%) than they were for symptoms such as pain (27%). Conclusions: Distress screening results of breast cancer patients using simple DTs by lay navigators demonstrate a diverse set of needs that extend beyond physical symptoms-based concerns. Routine distress screening can be utilized to identify potential sources of distress and might become the focus of tailored-interventions and additional support services. Navigators are well positioned to identify and triage patients to such services. This publication was made possible by Grant Number 1C1CMS331023 from the Department of Health and Human Services, Centers for Medicare & Medicaid Services.
A novel model of autosomal recessive polycystic kidney questions the role of the fibrocystin C-terminus in disease mechanism
Authors: Patricia Outeda, Luis Menezes, Erum A. Hartung, Stacey Bridges, Fang Zhou, Xianjun Zhu, Hangxue Xu, Qiong Huang, Qin Yao, Feng Qian, Gregory G. Germino, Terry Watnick
Journal: Kidney International (2017)