tbuckley/cabot-search huggingface dataset:
The Rise of Pseudomedicine for Dementia and Brain Health
Authors: Joanna Hellmuth, Gil D. Rabinovici, Bruce L. Miller
Journal: JAMA (2019)

This Viewpoint discusses the growing market for complementary interventions to prevent cognitive impairment and promote brain health, and urges health care professionals to partner with patients to address their health concerns and help them understand the market forces behind unproven treatments.
IDH1 Mutant AML Is Susceptible to Targeting De Novo Lipid Synthesis Independent of 2-Hydroxyglutarate and Has a Distinct Metabolic Profile from IDH2 Mutant AML
Authors: Daniel Thomas, Yusuke Nakauchi, Manhong Wu, Ming Zheng, Subarna Sinha, David Dill, Gary Peltz, Ravindra Majeti
Journal: Blood (2018)
Real-world experience of trifluridine/tipiracil in patients with metastatic colorectal cancer: A multicenter United Kingdom study.
Authors: Chara Stavraka, Athanasios Pouptsis, Paul Kabuubi, Vasileios Angelis, Alicja Synowiec, Mark Baxter, Ainsley Barrie, Amparo Andres Costa, Alia Nizam, Julien De Naurois, Christos Mikropoulos, Mark Hill, Janet Shirley Graham, Victoria Harris, John A. Bridgewater, Paul J. Ross
Journal: Journal of Clinical Oncology (2019)

668 Background: TAS-102 is an orally administered combination of the thymidine-based nucleic acid analogue, trifluridine and the thymidine phosphorylase inhibitor, tipiracil hydrochloride. Following the phase III RECOURSE study, it received approval as third line treatment for metastatic colorectal cancer showing significant improvement in overall and progression free survival and an acceptable toxicity profile. Methods: We performed a multicenter retrospective observational study of patients with metastatic colorectal cancer receiving TAS-102 as third line treatment between 2016 and 2018 in Cancer centers across the UK. Results: A total of 143 patients were included (94 men, 49 women). Median age was 68 years (35-82). All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 90% of patients had ECOG ≥ 1. Median duration of treatment was 2.9 months (0.5-22.9), with a response rate of 1.6% and stable disease achieved in 24%. Median OS was 7 months (95% CI 5.84-8.15) and median PFS 2.6 months (95% CI 2.2-3.36). A dose reduction was required in 28% of patients, while 8% discontinued treatment due to toxicity. AEs reported included fatigue 81.3% (G3 16.8%), nausea 34.5% (G3 4.5%) and diarrhoea 25.5% (G3 1.8%). Neutropenia was common 50.4%, (≥ G3: 25.4%) with 4.2% cases of neutropenic fever while thrombocytopenia was less frequent 8.7% (≥ G3 1.8%). Conclusions: The OS, PFS and ORR observed in our real-world experience were consistent with the RECOURSE trial, though we noted a lower disease control rate. Overall, TAS-102 was well tolerated and the most prevalent adverse events seen in our patients were in keeping with those reported in the trial. Although severe toxicities were less frequent than the trial, we experienced higher rates of toxicity induced dose reductions and treatment cessations, which could reflect the differences between trial and real world populations. Further validation is warranted.
Abstract 13333: Mechanism of Termination of Random Wave Propagation by Ablation of Complex Fractionated Atrial Electrogram Region in Persistent Atrial Fibrillation: Three-dimensional Analysis Using Non-contact Mapping
Authors: Junjiroh Koyama, Hiroshige Yamabe, Miwa Ito, Tadashi Hoshiyama, Hisanori Kanazawa, Hisao Ogawa
Journal: Circulation (2013)

Background: Catheter ablation of complex fractionated atrial electrogram (CFAE) region has been shown to be effective for the termination of persistent atrial fibrillation (PeAF). However, the mech...
T Cells Play a Causal Role in Diastolic Dysfunction during Uremic Cardiomyopathy
Authors: Pamela D. Winterberg, Jennifer M. Robertson, Michael S. Kelleman, Roshan P. George, Mandy L. Ford
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Uremic cardiomyopathy, which features left ventricular hypertrophy, diastolic dysfunction, and impaired myocardial strain, predicts mortality in patients with CKD. In this study, the authors present findings supporting emerging evidence that T cells play a causal role in diastolic dysfunction during CKD. In a mouse model of CKD, they demonstrate that T cells infiltrate the heart and lead to diastolic dysfunction and impaired ventricular strain, whereas depletion of T cells improves diastolic function and myocardial strain. They also show that in children with CKD, increasing frequency of T cells bearing markers of sustained activation (PD-1 and CD57) is associated with echocardiographic indications of worsening diastolic function. Future research may inform novel therapies that target T cell function to mitigate early subclinical myocardial dysfunction during CKD. Background Uremic cardiomyopathy, characterized by left ventricular hypertrophy, diastolic dysfunction, and impaired myocardial strain, contributes to increased cardiovascular mortality in patients with CKD. Emerging evidence suggests a pathogenic role for T cells during chronic heart failure. Methods To determine whether T cells contribute to uremic cardiomyopathy pathogenesis, we modeled this condition by inducing CKD via 5/6th nephrectomy in mice. We used flow cytometry to assess expression of markers of T cell memory or activation by lymphocytes from CKD mice and controls, as well as lymphocyte capacity for cytokine production. Flow cytometry was also used to quantify immune cells isolated from heart tissue. To test effects of T cell depletion on cardiac function, we gave CKD mice anti-CD3 antibody injections to deplete T cells and compared heart function (assessed by echocardiography) with that of controls. Finally, we correlated T cell phenotypes with structural and functional measures on clinically acquired echocardiograms in children with CKD. Results Mice with CKD accumulated T cells bearing markers of memory differentiation (CD44 hi ) and activation (PD-1, KLRG1, OX40), as reported previously in human CKD. In addition, mice with CKD showed T cells infiltrating the heart. T cell depletion significantly improved both diastolic function and myocardial strain in CKD mice without altering hypertension or degree of renal dysfunction. In children with CKD, increasing frequency of T cells bearing activation markers PD-1 and/or CD57 was associated with worsening diastolic function on echocardiogram. Conclusions CKD results in an accumulation of proinflammatory T cells that appears to contribute to myocardial dysfunction.
Concept of disposable duodenoscope: at what cost?
Authors: Ji Young Bang, Bryce Sutton, Robert Hawes, Shyam Varadarajulu
Journal: Gut (2019)

Although most postendoscopic retrograde cholangiopancreatography (ERCP) biliary tract infections are attributed to suboptimal ductal drainage, transmission of infection by contaminated reusable duodenoscopes has been reported. To overcome this limitation, a disposable duodenoscope has been recently developed. However, given the widespread use and large volume of ERCPs being performed worldwide, the financial viability of this novel concept is unclear. Utilising an activity-based costing and financial model, we estimated that the per-procedure cost of a disposable duodenoscope in the United States can vary from $797 to $1547 for centres performing at the 75th percentile of ERCP procedure volume and from $1318 to $2068 for centres performing at the 25th percentile of procedure volume, based on infection rates of 0.4% to 1%, respectively. However, when infection was not factored, the per-procedure cost decreased to $818 and $297 for centres performing at the 25th and 75th percentiles, respectively.

Given the recent reports on infection outbreaks, including carbapenem-resistant Enterobacteriaceae (CRE), caused by contaminated duodenoscopes used at ERCP,1–4 a disposable duodenoscope (ExaltTM, Single-Use Duodenoscope, Boston Scientific Corporation, Natick, Massachusetts, USA) has been developed to circumvent this problem.5 To determine the adaptability of this innovation in clinical practice, we estimated the per-procedure cost of ERCP using a reusable duodenoscope in order to assess the break-even costs for transitioning to disposable duodenoscopes. An activity-based costing and financial model was constructed based on the current clinical practice of ERCP at a tertiary medical centre in the USA.

The annual procedure volume was 1752 ERCPs in 2018. Nine duodenoscopes with lifetime usage of 3 years and a reprocessing turn-over time of 40 min per scope were required to meet the clinical needs. The cost of an individual duodenoscope was $35 000 ($11 667/year) with annual maintenance and repair costs of $1451 per scope. The annual cost …
Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma
Authors: Alex J. Bell, Brody H. Foy, Matthew Richardson, Amisha Singapuri, Evgeny Mirkes, Maarten van den Berge, David Kay, Chris Brightling, Alexander N. Gorban, Craig J. Galbán, Salman Siddiqui
Journal: Journal of Allergy and Clinical Immunology (2019)
The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer
Authors: Jong Woo Lee, Yu Zhang, Kyung Jin Eoh, Roshan Sharma, Miguel F. Sanmamed, Jenny Wu, Justin Choi, Hee Sun Park, Akiko Iwasaki, Edward Kaftan, Lieping Chen, Vali Papadimitrakopoulou, Roy S. Herbst, Ja Seok Koo
Journal: Journal of Thoracic Oncology (2019)

IntroductionThis study aimed to characterize the tumor-infiltrating immune cells population in Kras/tumor protein 53 (Trp53)-driven lung tumors and to evaluate the combinatorial antitumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed death -1 (PD-1) or programmed cell death ligand 1 (PD-L1) in vivo.MethodsTrp53FloxFlox;KrasG12D/+;Rosa26LSL-Luciferase/LSL-Luciferase (PKL) genetically engineered mice were used to develop autochthonous lung tumors with intratracheal delivery of adenoviral Cre recombinase. Using these tumor-bearing lungs, tumor-infiltrating immune cells were characterized by both mass cytometry and flow cytometry. PKL-mediated immunocompetent syngeneic and transgenic lung cancer mouse models were treated with MEKi alone as well as in combination with either anti–PD-1 or anti–PD-L1 mAbs. Tumor growth and survival outcome were assessed. Finally, immune cell populations within spleens and tumors were evaluated by flow cytometry and immunohistochemistry.ResultsMyeloid-derived suppressor cells (MDSCs) were significantly augmented in PKL-driven lung tumors compared to normal lungs of tumor-free mice. PD-L1 expression appeared to be highly positive in both lung tumor cells and, particularly MDSCs. The combinatory administration of MEKi with either anti–PD-1 or anti–PD-L1 mAbs synergistically increased antitumor response and survival outcome compared with single-agent therapy in both the PKL-mediated syngeneic and transgenic lung cancer models. Theses combinational treatments resulted in significant increases of tumor-infiltrating CD8+ and CD4+ T cells, whereas attenuation of CD11b+/Gr-1high MDSCs, in particular, Ly6Ghigh polymorphonuclear-MDSCs in the syngeneic model.ConclusionsThese findings suggest a potential therapeutic approach for untargetable Kras/p53-driven lung cancers with synergy between targeted therapy using MEKi and immunotherapies.
Comparative effectiveness of nivolumab (NIVO) relative to standard of care (SOC) for advanced/metastatic (adv/met) gastric or gastroesophageal junction cancer (GC/GEJC): A simulated treatment comparison (STC).
Authors: Ian Chau, Dieter Ayers, Sarah Goring, Sam Keeping, Rebecca Goulding, Shannon Cope, Eric Chamot, Hannah Le, Yanqing Xu, Pranav Abraham, Beata Korytowsky
Journal: Journal of Clinical Oncology (2019)

128 Background: The prognosis of adv/met GC/GEJC among patients receiving third and later lines (L) of therapy is poor, and effective treatment options are limited. The study objective was to estimate the relative effect of NIVO versus SOC for overall survival (OS), in the US among adv/met GC/GEJC patients who received ≥ 3L therapy. Methods: A STC was performed using individual patient data from the single-arm CheckMate 032 (CM032) trial, and the Flatiron Health (FH) database. Eligible patients had adv/met GC/GEJC and received NIVO (CM032) or SOC (FH) as ≥ 3L therapy; all patients met CM032 eligibility criteria. A regression model of OS was fit to CM032 data using prognostic factors and treatment effect modifiers identified through a systematic literature review. The regression model was used to predict OS for NIVO, using Flatiron patient characteristics as covariates, and to estimate the expected outcome if NIVO had been available in the Flatiron population. The observed and predicted OS for NIVO was compared against the observed OS for SOC to generate naïve and adjusted hazard ratio comparisons of NIVO vs SOC. Results: In total, 42 and 43 patients were included from CM032 and Flatiron, respectively. In the Cox model, 19 prognostic factors were considered and the final model adjusted for 6, based on data availability across the two sources: ECOG, alkaline phosphatase (ALP) and hemoglobin, sex, prior surgery, and tumor location. Median OS was 8.97 months in the NIVO group and 5.61 months in the SOC group. The STC adjustment yielded a hazard ratio of 0.66 (95% CI: 0.41 to 1.06) for NIVO vs SOC compared to the naïve estimate of 0.64 (0.40 to 1.03). Sensitivity analyses confirm this result. Conclusions: In the absence of head-to-head data, this study suggests that NIVO may confer a benefit in terms of OS versus SOC for patients with GC/GEJC in ≥ 3L therapy in the US setting. Despite the inherent limitations of using non-randomized comparisons of clinical trial data and real-world evidence, these findings provide insight into the potential benefit of novel agents such as NIVO.
Extranodal Natural Killer/T-Cell Lymphoma Nasal Type in 87 Cases from Spain: Clinical Presentation, Treatment and Prognostic Factors. Study from the Geltamo Group
Authors: Eva González-Barca, Alejandro Martín, Jose Luis Bello, Juan Miguel Miguel Bergua Burgues, Carlos Panizo, Maite Encuentra, Ana Monter Rovira, Raul Cordoba, Mariana Bastos, Jose Javier Sanchez Blanco, Pilar Gomez, Ana Marin Niebla, Sonia González de Villambrosia, Maria Jose Sayas, Hugo Daniel Luzardo Henriquez, Maria De La Cruz Viguria Alegria, Blanca Sanchez-Gonzalez, Monica Roig, Jaime Perez De Oteyza, Elena Cabezudo, Lourdes Escoda, Raquel de Oña, Josë Antonio Queizan, Maria Stefania Infante, Ana Muntañola Prat, Andres Lopez
Journal: Blood (2018)
Structural Factors Shape the Effects of the Opioid Epidemic on Pregnant Women and Infants
Authors: Katy B. Kozhimannil, Lindsay K. Admon
Journal: JAMA (2019)

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
Zwitterionic near-infrared fluorophore-conjugated epidermal growth factor for fast, real-time, and target-cell-specific cancer imaging
Authors: Hyunjin Kim, Mi Hyeon Cho, Hak Soo Choi, Byung Il Lee, Yongdoo Choi
Journal: Theranostics (2019)

Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, which is associated with metastatic potential and poor prognosis in cancer patients.Therefore, development of EGFR-targeted sensitive imaging probes has been a challenge in tumor targeting, image-guided cancer surgery, patient-selective anti-EGFR therapy, and efficient targeted therapies.Methods: We synthesized a zwitterionic near-infrared fluorophore (ATTO655)-conjugated epidermal growth factor (EGF) as a novel activatable molecular probe.Fluorescence OFF/ON property and EGFR-targeting specificity of EGF-ATTO655 as well as its utility in real-time near-infrared (NIR) fluorescence imaging of EGFR-positive cancers were evaluated using in vitro and in vivo studies.Results: When conjugated to EGF, the fluorescence of ATTO655 quenched efficiently by photo-induced electron transfer (PET) mechanism between the conjugated dyes and nearby amino acid quenchers (tryptophan/tyrosine residues), which was stably maintained at physiological pH and in the presence of serum for at least 17 h.The fluorescence of EGF-ATTO655 turned on by receptor-mediated endocytosis and subsequent disintegration of EGF in EGFR-positive A431 cancer cells, thereby enabling specific and real-time fluorescence imaging of EGFR-positive cancer cells.Consequently, EGFR-positive tumors could be clearly visualized 3 h post-injection with a significantly high tumor-to-background ratio (TBR = 6.37).Conclusion: This PET mechanism-based OFF/ON type of EGF probe showed great potential for rapid, real-time, and target-cell-specific imaging of EGFR-overexpressing cancers in vitro and in vivo.
Dutch hospital gets €5m from lottery to develop drug for rare condition after price hike
Authors: Tony Sheldon
Journal: BMJ (2019)

A Dutch university hospital has been awarded €5m (£4.4m; $5.6m) of lottery funding to help develop its plans to supply its own cost price version of the orphan drug chenodeoxycholic acid (CDCA).

Last year Amsterdam University Medical Center began work on a small scale magistral preparation of CDCA—a primary bile acid used in treating a rare hereditary metabolic disorder, cerebrotendinous xanthomatosis (CTX). This followed health insurers’ refusal to meet the more than fivefold price increase, from €30 000 to around …
Recent Advances in Polymeric Nanomedicines for Cancer Immunotherapy
Authors: Eun Sook Lee, Jung Min Shin, Soyoung Son, Hyewon Ko, Wooram Um, Seok Ho Song, Jae Ah Lee, Jae Hyung Park
Journal: Advanced Healthcare Materials (2019)

Abstract Immunotherapy has emerged as a promising approach to treat cancer, since it facilitates eradication of cancer by enhancing innate and/or adaptive immunity without using cytotoxic drugs. Of the immunotherapeutic approaches, significant clinical potentials are shown in cancer vaccination, immune checkpoint therapy, and adoptive cell transfer. Nevertheless, conventional immunotherapies often involve immune‐related adverse effects, such as liver dysfunction, hypophysitis, type I diabetes, and neuropathy. In an attempt to address these issues, polymeric nanomedicines are extensively investigated in recent years. In this review, recent advances in polymeric nanomedicines for cancer immunotherapy are highlighted and thoroughly discussed in terms of 1) antigen presentation, 2) activation of antigen‐presenting cells and T cells, and 3) promotion of effector cells. Also, the future perspectives to develop ideal nanomedicines for cancer immunotherapy are provided.
Abstract 14149: Clinical Practice Gap Analysis of ACS Management: A Comparison of Physicians in the US and Outside of the US
Authors: Amy Larkin, Michael LaCouture, Philippe Guedj, Thomas O’Neil, Suzanne Hughes
Journal: Circulation (2017)

Introduction: Understanding clinical practice gaps for cardiologists and primary care physicians (PCPs) both in the United States (US) and outside the US (OUS) related to ACS management can inform ...
Punishment-Predictive Cues Guide Avoidance through Potentiation of Hypothalamus-to-Habenula Synapses
Authors: Massimo Trusel, Alvaro Nuno-Perez, Salvatore Lecca, Harumi Harada, Arnaud L. Lalive, Mauro Congiu, Kiwamu Takemoto, Takuya Takahashi, Francesco Ferraguti, Manuel Mameli
Journal: Neuron (2019)
Abstract 18510: Cardiac Atrial Appendage Stem Cells Restore Cardiac Function in Chronic Myocardial Infarction
Authors: Valerie Dekoninck, Maarten Hendrickx, Luc Jamaer, Jasperina Dubois, Jeroen Declercq, Annick Daniels, Ingrid Arijs, Eric Bijnens, Nick Heuts, Filip Hendrikx, Virginie Bito, Jean-Luc Rummens, Marc Hendrikx
Journal: Circulation (2017)

Introduction: Cardiac atrial appendage stem cells have been shown to preserve cardiac function in the setting of acute myocardial infarction (MI) in the minipig model : this application takes advantage of preserved extracellular tissue architecture, although it is subject to the inflammatory hostility of the milieu. Hypothesis: Whether this treatment is also applicable to a chronic ischemia model remains unknown. Methods: Autologous CASCs were isolated from atrial appendages of Gottingen minipigs based on high aldehyde dehydrogenase activity and expanded. MI was induced by 2 h snare ligation of the left anterior descending artery. Two months (M) after MI induction, CASCs were intramyocardially injected under NOGA guidance (MI-CASC, n=6). Non-transplanted pigs (MI, n= 8) received sham treatment. 3D electromechanical mapping (EMM) and cardiac MRI were performed to assess left ventricular (LV) function. Results: Global LV ejection fraction was preserved 2M post-injection in the MI-CASC group (57±13% pre vs 6...
Expanding the repertoire of miRNAs and miRNA-offset RNAs expressed in multiple myeloma by small RNA deep sequencing
Authors: Luca Agnelli, Andrea Bisognin, Katia Todoerti, Martina Manzoni, Elisa Taiana, Serena Galletti, Giovanna Cutrona, Enrico Gaffo, Stefania Bortoluzzi, Antonino Neri
Journal: Blood Cancer Journal (2019)

Abstract Microarray analysis of the multiple myeloma (MM) miRNome has unraveled the differential expression of miRNAs in cytogenetic subgroups, their involvement in the tumor biology and their effectiveness in prognostic models. Herein, the small RNA transcriptional landscape in MM has been investigated exploiting the possibilities offered by small RNA-seq, including accurate quantification of known mature species, discovery and characterization of isomiRs, and miRNA-offset RNAs (moRNAs). Matched small RNA-seq and miRNA GeneChip ® microarray expression profiles were obtained in a representative panel of 30 primary MM tumors, fully characterized for genomic aberrations and mutations. RNA-seq and microarray gave concordant estimations of known species. Enhanced analysis of RNA-seq data with the miR&amp;moRe pipeline led to the characterization of 655 known and 17 new mature miRNAs and of 74 moRNAs expressed in the considered cohort, 5 of which (moR-150-3p, moR-24-2-5p, moR-421-5p, moR-21-5p, and moR-6724-5p) at high level. Ectopic expression of miR-135a-3p in t(4;14) patients, upregulation of moR-150-3p and moR-21-5p in t(14;16)/t(14;20) samples, and of moR-6724-1-5p in patients overexpressing CCND1 were uncovered and validated by qRT-PCR. Overall, RNA-seq offered a more complete overview of small non-coding RNA in MM tumors, indicating specific moRNAs that demand further investigations to explore their role in MM biology.
Prediction of Leukemia-Free Survival Following Haploidentical Stem Cell Transplantation in Acute Myeloid Leukemia: A Study from the Acute Leukemia Working Party of the EBMT
Authors: Roni Shouval, Joshua A Fein, Myriam Labopin, Fabio Ciceri, Emanuele Angelucci, Didier Blaise, Johanna Tischer, William Arcese, Koc Yener, Benedetto Bruno, José Luís Díez Martín, Stella Santarone, Simona Sica, Mohamad Mohty, Arnon Nagler
Journal: Blood (2018)