tbuckley/cabot-search huggingface dataset:
Efficacy of Combined VEGFR1-3, PDGFα/β, and FGFR1-3 Blockade Using Nintedanib for Esophagogastric Cancer
Authors: Elizabeth Won, Azfar Basunia, Walid K. Chatila, Jaclyn F. Hechtman, Joanne F. Chou, Geoffrey Y. Ku, Sree B. Chalasani, Michelle S. Boyar, Zoe Goldberg, Avni M. Desai, Yaelle Tuvy, Michael F. Berger, Laura Tang, David P. Kelsen, Mark Schattner, David H. Ilson, Marinela Capanu, David B. Solit, Nikolaus Schultz, Yelena Y. Janjigian
Journal: Clinical Cancer Research (2019)

Abstract Purpose: VEGFR2-directed therapy is commonly used to treat metastatic esophagogastric cancer, but disease progresses in most patients within months. Therapeutic resistance is likely mediated in part by co-occurring amplifications of the genes for multiple oncogenic receptor tyrosine kinases (RTK). We therefore tested the efficacy of combined inhibition of VEGFR1-3, PDGFα/β, and FGFR1-3 using nintedanib. Patients and Methods: Patients with metastatic esophagogastric adenocarcinoma and disease progression on first-line chemotherapy were treated with nintedanib 200 mg twice daily. The primary endpoint was progression-free survival (PFS) at 6 months; secondary endpoints included tumor response and safety. Tumor biopsies were profiled by targeted capture next-generation sequencing (NGS) to identify molecular predictors of drug response. Results: The study achieved its primary endpoint; 6 of 32 patients (19%) were progression-free at 6 months. With a median follow-up of 14.5 months among survivors, median overall survival (OS) was 14.2 months [95% confidence interval (CI), 10.8 months–NR]. Nintedanib was well tolerated; grade ≥ 3 toxicities were uncommon and included grade 3 hypertension (15%) and liver enzyme elevation (4%). FGFR2 alterations were identified in 18% of patients but were not predictive of clinical outcome on nintedanib therapy. Alterations in cell-cycle pathway genes were associated with worse median PFS (1.61 months for patients with cell-cycle pathway alterations vs. 2.66 months for patients without, P = 0.019). Conclusions: Nintedanib treatment resulted in modest disease stabilization in patients with metastatic esophagogastric cancer. Alterations in cell-cycle pathway genes and increased global copy-number alteration (CNA) burden warrant further study as prognostic or predictive biomarkers.
NHS commissioners will decide whether to tender large contracts under new proposals
Authors: Matthew Limb
Journal: BMJ (2019)

The NHS will have “discretion” over whether to put services out to competitive tender under new reform proposals that should cut transaction costs, health officials have told MPs.

But the use of procurement will not end for good, and NHS bodies will still be free to purchase services from the private sector, the Commons Health and Social Care Committee heard.

Simon Stevens, NHS England chief executive, said that the NHS would not revert to a “closed shop” under the NHS long term plan. He and other officials, including NHS Improvement’s chief executive, Ian Dalton, were questioned on 2 April about how the NHS long term plan,1 published …
Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder
Authors: Bipasha Mukherjee-Clavin, Ruifa Mi, Barbara Kern, In Young Choi, Hotae Lim, Yohan Oh, Benjamin Lannon, Kevin J. Kim, Shaughn Bell, Junho K. Hur, Woochang Hwang, Young Hyun Che, Omer Habib, Robert H. Baloh, Kevin Eggan, Gerald Brandacher, Ahmet Hoke, Lorenz Studer, Yong Jun Kim, Gabsang Lee
Journal: Nature Biomedical Engineering (2019)
Risk of severe herpes simplex virus infection in systemic lupus erythematosus: analysis of epidemiology and risk factors analysis in Taiwan
Authors: Tzu-Hao Li, Chien-Chih Lai, Wen-Hsiu Wang, Wei-Sheng Chen, Yen-Po Tsao, Chang-Youh Tsai, Yu-Sheng Chang
Journal: Annals of the Rheumatic Diseases (2019)

Patients with systemic lupus erythematosus (SLE) are susceptible to herpes simplex virus (HSV) infection, which occasionally leads to severe complications including meningoencephalitis and keratitis. However, few attempts to analyse the associated incidence and risk factors have been made.We enrolled patients with SLE recorded between 1997 and 2012 and compared the incidence rate (IR) of severe HSV infection, including meningoencephalitis, septicaemia, ocular and visceral involvement, and other specific complications demanding hospitalisation, with that of a non-SLE cohort. A Cox multivariate proportional hazards model was applied to analyse the risk factors of severe HSV infection in patients with SLE.A total of 122 520 subjects (24 504 patients with SLE and 98 016 age-matched and sex-matched non-SLE controls) were included, and a higher IR of severe HSV infection was revealed in the SLE group (IR ratio=3.93, p<0.001). In patients with SLE, previous oral and genital infection (HR=2.29, p=0.049), intravenous steroid pulse therapy (HR=5.32, p<0.001) and daily oral dose of over 7.5 mg of prednisolone (HR=1.59, p=0.024) were independent risk factors for severe HSV infection, whereas age of ≤18 (HR=0.45, p=0.029) was a protective factor.Patients with SLE are at higher risk of severe HSV infection, and related risk factors include being older than 18 years, having a history of HSV mucocutaneous infection, recent receipt of steroid pulse therapy and a daily oral dose of steroid over 7.5 mg prednisolone.
Treatment of cancer-associated venous thromboembolism in the age of direct oral anticoagulants
Authors: C. Ay, J. Beyer-Westendorf, I. Pabinger
Journal: Annals of Oncology (2019)

Anticoagulation for cancer-associated venous thromboembolism (VTE) can be challenging due to complications-including bleeding and potential drug-drug interactions with chemotherapy-associated with vitamin K antagonists and inconvenience of low-molecular-weight heparin (LMWH). Direct oral anticoagulants (DOACs) could partially overcome these issues, but until recently there were no large clinical trials assessing their efficacy and safety in cancer patients. This review summarizes clinical treatment guidelines, prior clinical and real-world evidence for anticoagulant choice, recent clinical trials assessing DOACs for cancer-associated VTE (i.e. Hokusai-VTE Cancer, SELECT-D, CARAVAGGIO, and ADAM VTE), and special considerations for DOAC use. Based on established data, clinical guidelines recommend patients with cancer-associated VTE receive LMWH treatment of at least 3-6 months. Nevertheless, LMWH is underused and associated with poor compliance and persistence in these patients relative to oral anticoagulants. Clinical data supporting DOAC use in cancer patients are becoming available. In Hokusai-VTE Cancer, edoxaban was noninferior to dalteparin for the composite of recurrent VTE and major bleeding (12.8% versus 13.5%), with numerically lower recurrent VTE (7.9% versus 11.3%) and significantly higher major bleeding (6.9% versus 4.0%); only patients with gastrointestinal cancer had significantly higher risk of bleeding with edoxaban. In SELECT-D, rivaroxaban had numerically lower VTE recurrence (4% versus 11%), comparable major bleeding (6% versus 4%), and numerically higher clinically relevant nonmajor bleeding (13% versus 4%) versus dalteparin. Most bleeding events were gastrointestinal or urologic; patients with esophageal/gastroesophageal cancer had higher rates of major bleeding with rivaroxaban (36% versus 11%). For comparison of apixaban versus dalteparin, CARAVAGGIO is ongoing, and preliminary results from ADAM VTE are favorable. This review concludes that DOACs appear to be reasonable alternatives to LMWH for treatment of cancer-associated VTE. In patients with gastrointestinal cancer, DOAC use should be considered on a case-by-case basis with consideration of the relative risks and benefits.
Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis
Authors: Patricia Santofimia-Castaño, Yi Xia, Wenjun Lan, Zhengwei Zhou, Can Huang, Ling Peng, Philippe Soubeyran, Adrián Velázquez-Campoy, Olga Abián, Bruno Rizzuti, José L. Neira, Juan Iovanna
Journal: Journal of Clinical Investigation (2019)

Intrinsically disordered proteins (IDPs) are emerging as attractive drug targets by virtue of their prevalence in various diseases including cancer. Drug development targeting IDPs is challenging because they have dynamical structure features and conventional drug design is not applicable. NUPR1 is an IDP playing an important role in pancreatic cancer. We previously reported that Trifluoperazine (TFP), an antipsychotic agent, was capable of binding to NUPR1 and inhibiting tumors growth. Unfortunately, TFP showed strong central nervous system side-effects. In this work, we undertook a multidisciplinary approach to optimize TFP, based on the synergy of computer modeling, chemical synthesis, and a variety of biophysical, biochemical and biological evaluations. A family of TFP-derived compounds was produced and the most active one, named ZZW-115, showed a dose-dependent tumor regression with no neurological effects and induced cell death mainly by necroptosis. This study opens a new perspective for drug development against IDPs, demonstrating the possibility of successful ligand-based drug design for such challenging targets.
Malignant Peripheral Nerve Sheath Tumor With Bilateral Adrenal Metastases
Authors: Sarthak Tripathy, Averilicia Passah, Abhinav Singhal, Arun Prashanth, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2019)

MPNSTs (malignant peripheral nerve sheath tumors) are a highly malignant group of soft tissue sarcomas and carry a very poor prognosis. Metastasis to bilateral adrenal glands is very rare in such group of neoplasms. We discuss a case of 85-year-old man who was diagnosed with MPNST from prevertebral mass with metastases to bilateral adrenal glands and bone marrow from the beginning and role of serial F-FDG PET/CT scans in response assessment first to sunitinib (tyrosine kinase inhibitor) and then to liposomal doxorubicin.
Risk Factors
Authors: Steven D. Helgerson
Journal: JAMA (2003)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
EZH2 Inhibitors: Take It EZy, It Is All About Context
Authors: Vamsidhar Velcheti, Kwok-Kin Wong, Yogen Saunthararajah
Journal: Cancer Discovery (2019)

Even in diffuse large B-cell lymphoma (DLBCL), a cancer of professional antigen-presenting cells, response rates to immune checkpoint blockade therapy have been limited. One reason for DLBCL immune evasion is epigenetic repression instead of activation of the antigen-presenting MHC-a dissection of mechanisms underlying this repression suggests an opening for restoring B-cell maturation and, along the way, MHC expression as a novel modality of cytoreducing DLBCL and simultaneously augmenting possibilities for immunotherapy.See related article by Ennishi et al., p. 546.
The oral Janus kinase/spleen tyrosine kinase inhibitor<scp>ASN</scp>002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate‐to‐severe atopic dermatitis: results from a randomized double‐blind placebo‐controlled study
Authors: R. Bissonnette, C. Maari, S. Forman, N. Bhatia, M. Lee, J. Fowler, S. Tyring, D. Pariser, H. Sofen, S. Dhawan, M. Zook, D.J. Zammit, H. Usansky, L. Denis, N. Rao, T. Song, A.B. Pavel, E. Guttman‐Yassky
Journal: British Journal of Dermatology (2019)

ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways. The objectives of this study were to evaluate the efficacy, safety, pharmacokinetics and effects on systemic biomarkers of ASN002 in patients with moderate‐to‐severe AD. Methods A total of 36 patients with moderate‐to‐severe AD were randomized (3 : 1) to ASN002 or placebo in the phase Ib study. Three dosage cohorts were studied over a 28‑day period (20 mg, 40 mg and 80 mg once daily). ASN002 was superior to placebo for the proportion of patients achieving Eczema Area and Severity Index (EASI) 50 (20 mg 20%, P = 0·93; 40 mg 100%, P = 0·003; 80 mg 83%, P = 0·03; placebo 22%), EASI 75 (20 mg 0%, P = 0·27; 40 mg 71%, P = 0·06; 80 mg 33%, P = 0·65; placebo 22%) and in change from baseline in pruritus (20 mg −1·3 ± 2·1, P = 0·81; 40 mg −3·1 ± 2·7, P = 0·27; 80 mg −4·7 ± 2·1, P = 0·01; placebo −1·6 ± 1·8). Adverse events were generally mild and similar across all groups. ASN002 showed dose‐dependent plasma exposure with low interpatient variability, significantly downregulated several serum biomarkers involved in Th1, Th2 and Th17/Th22 immunity, and decreased the atherosclerosis‐associated biomarker E selectin/SELE. In patients with moderate‐to‐severe AD, ASN002 showed strong efficacy with rapid onset of action and associated improvements in systemic inflammation.
<scp>CCL</scp> 2 serves as a downstream effector of interleukin‐1β and tumour necrosis factor‐α signalling in Schnitzler syndrome
Authors: N. Kambe, C. T. H. Nguyen
Journal: British Journal of Dermatology (2019)

Linked Article: Krause et al. Br J Dermatol 2019; 180:859–868.
Friend or foe: an unusual case of small intestinal mass
Authors: Yu-jen Tseng, Wei-qun Ding, Liang Zhong, Zhong-guang Luo
Journal: Endoscopy (2019)

A previously healthy 72-year-old woman presented with a 2-year history of recurrent abdominal pain and bloating. The abdominal symptoms were often associated with food ingestion. No changes in defecation habits were noted. A local hospital diagnosed the patient with a mass in the small intestine and instructed regular follow-ups. The patient decided to seek further treatment at our facility and was scheduled for a small-intestine computed tomography (CT) scan with contrast.
Incidence of hepatocellular carcinoma in HIV/HBV-coinfected patients on tenofovir therapy: Relevance for screening strategies
Authors: Gilles Wandeler, Etienne Mauron, Andrew Atkinson, Jean-François Dufour, David Kraus, Peter Reiss, Lars Peters, François Dabis, Jan Fehr, Enos Bernasconi, Marc van der Valk, Colette Smit, Lars K. Gjærde, Jürgen Rockstroh, Didier Neau, Fabrice Bonnet, Andri Rauch
Journal: Journal of Hepatology (2019)
Accelerated partial breast irradiation using a strut-based brachytherapy device: A multi-institutional initial report on acute and late toxicity with greater than 24-month follow-up.
Authors: Jon F. Strasser, Dayee Jacob, Christoper D. Koprowski, Deanna J. Attai, Ernest Butler, Steven E. Finkelstein, Ben Han, Robert Hong, Lydia T. Komarnicky, Robert R. Kuske, Maureen Lyden, Sudha B. Mahalingam, Constantine Mantz, Serban Morcovescu, Stephen S. Nigh, Kerri Perry, Jondavid Pollock, Jay E. Reiff, Daniel Scanderbeg, Catheryn M. Yashar
Journal: Journal of Clinical Oncology (2012)

149 Background: Accelerated partial breast irradiation (APBI) is commonly used in early-stage breast cancer. The SAVI Collaborative Research Group is a multi-institutional group created to study outcomes in patients who received APBI utilizing strut-based brachytherapy. This analysis reports the acute and late toxicities for patients with greater than 2-year follow-up (F/U) from this study. Methods: 904 APBI patients (ductal carcinoma in situ [n=267] or invasive breast cancer [n=637]), received HDR brachytherapy (34 Gy in 10 fractions) using the SAVI device (Cianna Medical). Patients with dosimetry and documented follow-up were evaluated within 6 weeks of treatment for early adverse events (AEs), and at 1 year, 2 years, and beyond for late AEs. Dosimetric parameters were evaluated with respect to toxicity and will be presented. Results: In 212 patients (median age 62.9 years, range 40-88) all with follow-up greater than 24 months, the median tumor size was 12mm. As of last follow-up (&gt;24 months) cumulative rates of erythema and hyperpigmentation of grade 2 or higher were 1.4% and 0.5%. The incidence of grade 2 or higher telangiectasia, seroma and fat necrosis were 2.8%, 2.8%, and 0.5% respectively. Conclusions: Adverse events for APBI with SAVI are low in incidence, low in grade and compare favorably to other HDR APBI methods.
Colonic Abrikossoff tumor: fortuitous discovery at colonoscopy for serrated adenomas polyposis, and resection by endoscopic submucosal dissection
Authors: Margot Biscay, Edouard Chabrun, Sarah Menguy, Elodie Cesbron-Métivier, Marc Barthet, Marion Marty, Mathieu Pioche
Journal: Endoscopy (2019)

Granular cell tumors (GCTs) are a type of submucosal tumor, with an overall soft tissue tumor incidence of 0.03 % [1]. They are benign neural tumors presenting typically in the dermis or subcutis, in adults, and more frequently in women.
The polarity protein Scrib limits atherosclerosis development in mice
Authors: Christoph Schürmann, Franziska L Dienst, Katalin Pálfi, Andrea E Vasconez, James A Oo, ShengPeng Wang, Giulia K Buchmann, Stefan Offermanns, Bart van de Sluis, Matthias S Leisegang, Stefan Günther, Patrick O Humbert, Eunjee Lee, Jun Zhu, Andreas Weigert, Praveen Mathoor, Ilka Wittig, Christoph Kruse, Ralf P Brandes
Journal: Cardiovascular Research (2019)

The protein Scrib (Scribble 1) is known to control apico-basal polarity in epithelial cells. The role of polarity proteins in the vascular system remains poorly characterized; however, we previously reported that Scrib maintains the endothelial phenotype and directed migration. On this basis, we hypothesized that Scrib has anti-atherosclerotic functions.Tamoxifen-induced Scrib-knockout mice were crossed with ApoE-/- knockout mice and spontaneous atherosclerosis under high-fat diet (HFD), as well as accelerated atherosclerosis in response to partial carotid artery ligation and HFD, was induced. Deletion of Scrib resulted in increased atherosclerosis development in both models. Mechanistically, flow- as well as acetylcholine-induced endothelium-dependent relaxation and AKT phosphorylation was reduced by deletion of Scrib, whereas vascular permeability and leucocyte extravasation were increased after Scrib knockout. Scrib immune pull down in primary carotid endothelial cells and mass spectrometry identified Arhgef7 (Rho Guanine Nucleotide Exchange Factor 7, βPix) as interaction partner. Scrib or Arhgef7 down-regulation by siRNA reduced the endothelial barrier function in human umbilical vein endothelial cells. Gene expression analysis from murine samples and from human biobank material of carotid endarterectomies indicated that loss of Scrib resulted in endothelial dedifferentiation with a decreased expression of endothelial signature genes.By maintaining a quiescent endothelial phenotype, the polarity protein Scrib elicits anti-atherosclerotic functions.
Abstract 15995: Etiology and Outcomes Associated With Endothelial Dysfunction in Post Cardiac Arrest Patients
Authors: Hitesh V Gidwani, Patrick Coppler, Rohit Rattan, Riaz Rahman, Shiva Shashidharan, Andrew Darwin, Peter Adams, Maia Taft, Hannah Airgood, Jonathan Elmer, Cameron Dezfulian
Journal: Circulation (2015)

Background: Endothelial dysfunction (ED) may occur after cardiac arrest (CA) both due to the underlying patient comorbidities which result in CA and the global ischemia-reperfusion which results. The prevalence of ED after CA is poorly characterized as is any association with outcomes. Hypothesis: ED will be more common in asphyxial arrests, after prolonged CPR times and in subjects with multiple coronary artery risk factors. ED will associate with worsened outcomes. Methods: Prospective, observational study of 23 CA with return of spontaneous circulation (ROSC) expected to live &gt;48 h. ED was assessed at 0-6 hours and at 36-48 hours after ROSC using measurements of plasma nitrite (n=14) or laser speckle contrast imaging (LSCI) (n=13) before and after 6 min vaso-occlusion (VO) of forearm blood flow. VO was achieved using a blood pressure cuff inflated at 200 mm Hg. LSCI quantified blood flow at baseline (pre-VO), during ischemia (trough), upon reperfusion (hyperemia peak) and 5 min later (nadir). LSCI values were all normalized to pre-VO baseline. Plasma nitrite was measured before after VO. Plasma nitrite was quantified by reductive chemiluminescence. ED is known to result in lower plasma nitrite and reduced post-VO hyperemia and nadir. Data was gathered on patient comorbidities, CA characteristics and outcomes and means compared by Mann Whitney U for dichotomous variables and Spearman correlation for continuous variables. Results: Lower ischemic trough and reperfusion nadir were associated with unfavorable features and outcomes ( Table ). No patient factors were associated ED. LSCI nadir at 0-6 hrs correlated with CPR duration (r = -0.7, p =0.01) and trough correlated with number of CPR epinephrine doses (r= -0.7, p = 0.01). Plasma nitrite levels were similar in all comparisons. Conclusions: LSCI features characteristic of ED were more often noted with prolonged and asphyxial, non-VF CA rather than patient factors and were associated with worsened outcome.
Spontaneous atopic dermatitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL‐1β
Authors: Christian Schwartz, Tara Moran, Sean P. Saunders, Agnieszka Kaszlikowska, Achilleas Floudas, Joana Bom, Gabriel Nunez, Yoichiro Iwakura, Luke O’Neill, Alan D. Irvine, Andrew N. J. McKenzie, Graham Ogg, Patrick T. Walsh, Jocelyne Demengeot, Padraic G. Fallon
Journal: Allergy (2019)

Atopic dermatitis (AD) is one of the most common skin diseases with a multifactorial etiology. Mutations leading to loss of skin barrier function are associated with the development of AD with group 2 innate lymphoid cells (ILC2) promoting acute skin inflammation. Filaggrin-mutant (Flg