tbuckley/cabot-search huggingface dataset:
Monoclonal Antibodies for Migraine Prevention
Authors: Elizabeth W. Loder, Matthew S. Robbins
Journal: JAMA (2018)

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
Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in the USA
Authors: Imre Noth, David Oelberg, Manika Kaul, Craig S. Conoscenti, Ganesh Raghu
Journal: European Respiratory Journal (2018)

Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in more than 60 countries, including the USA [1]. In the two phase III INPULSIS trials, nintedanib reduced disease progression by reducing decline in forced vital capacity [2]. Most patients were able to manage the side-effects of nintedanib, with 19.3% of patients treated with nintedanib versus 13.0% treated with placebo permanently discontinuing the study medication due to adverse events. The most frequent adverse events were gastrointestinal, particularly diarrhoea. The proportion of patients who had one or more serious adverse events was similar between nintedanib and placebo (30.4% versus 30.0%). The safety and tolerability profile of nintedanib in patients with IPF in the clinical setting is consistent with the product label <http://ow.ly/Nulb30jPAld> The authors would like to acknowledge the contribution of Alexandar Allinger, Boehringer Ingelheim Pharma GmbH & Co. KG (Ingelheim am Rhein, Germany) to the acquisition and analysis of the data. Medical writing assistance was provided by Julie Fleming and Wendy Morris of FleishmanHillard Fishburn (London, UK), which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. All authors were involved in the interpretation of the data and writing of this letter and have approved the final version.
Health Care Utilization and Burden of Diabetic Ketoacidosis in the U.S. Over the Past Decade: A Nationwide Analysis
Authors: Dimpi Desai, Dhruv Mehta, Priyanka Mathias, Gopal Menon, Ulrich K. Schubart
Journal: Diabetes Care (2018)

OBJECTIVE Diabetes is one of the most common chronic diseases and a leading cause of morbidity and mortality in the U.S. Although our ability to treat diabetes and its associated complications has significantly improved, presentation with uncontrolled diabetes leading to ketoacidosis remains a significant problem. RESEARCH DESIGN AND METHODS We aimed to determine the incidence and costs of hospital admissions associated with diabetic ketoacidosis (DKA). We reviewed the National Inpatient Sample database for all hospitalizations in which DKA (ICD-9 codes 250.10, 250.11, 250.12, and 250.13) was the principal discharge diagnosis during 2003–2014 and calculated the population incidence by using U.S. census data. Patients with ICD-9 codes for diabetic coma were excluded because the codes do not distinguish between hypoglycemic and DKA-related coma. We then analyzed changes in temporal trends of incidence, length of stay, costs, and in-hospital mortality by using the Cochrane-Armitage test. RESULTS There were 1,760,101 primary admissions for DKA during the study period. In-hospital mortality for the cohort was 0.4% (n = 7,031). The total number of hospital discharges with the principal diagnosis of DKA increased from 118,808 in 2003 to 188,965 in 2014 (P &amp;lt; 0.0001). The length of stay significantly decreased from an average of 3.64 days in 2003 to 3.24 days in 2014 (P &amp;lt; 0.01). During this period, the mean hospital charges increased significantly from $18,987 (after adjusting for inflation) per admission in 2003 to $26,566 per admission in 2014. The resulting aggregate charges (i.e., national bill) for diabetes with ketoacidosis increased dramatically from $2.2 billion (after adjusting for inflation) in 2003 to $ 5.1 billion in 2014 (P &amp;lt; 0.001). However, there was a significant reduction in mortality from 611 (0.51%) in 2003 to 620 (0.3%) in 2014 (P &amp;lt; 0.01). CONCLUSIONS Our analysis shows that the population incidence for DKA hospitalizations in the U.S. continues to increase, but the mortality from this condition has significantly decreased, indicating advances in early diagnosis and better inpatient care. Despite decreases in the length of stay, the costs of hospitalizations have increased significantly, indicating opportunities for value-based care intervention in this vulnerable population.
Clinical Implications of Slower Cognitive Growth in the Psychosis Spectrum
Authors: Michele Poletti, Andrea Raballo
Journal: JAMA Psychiatry (2018)

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 Psychiatry 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 Psychiatry journal
A transgenic mouse model for HLA-B*57:01–linked abacavir drug tolerance and reactivity
Authors: Marco Cardone, Karla Garcia, Mulualem E. Tilahun, Lisa F. Boyd, Sintayehu Gebreyohannes, Masahide Yano, Gregory Roderiquez, Adovi D. Akue, Leslie Juengst, Elliot Mattson, Suryatheja Ananthula, Kannan Natarajan, Montserrat Puig, David H. Margulies, Michael A. Norcross
Journal: Journal of Clinical Investigation (2018)

Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo. In immunocompetent Tg animals, ABC induced CD8+ T cells with an anergy-like phenotype that did not lead to ADRs. In contrast, in vivo depletion of CD4+ T cells prior to ABC administration enhanced DC maturation to induce systemic ABC-reactive CD8+ T cells with an effector-like and skin-homing phenotype along with CD8+ infiltration and inflammation in drug-sensitized skin. B7 costimulatory molecule blockade prevented CD8+ T cell activation. These Tg mice provide a model for ABC tolerance and for the generation of HLA-B*57:01-restricted, ABC-reactive CD8+ T cells dependent on both HLA genetic risk and immunoregulatory host factors.
Correction to: PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse
Authors: Bingxin Zheng, Tingting Ren, Yi Huang, Kunkun Sun, Shidong Wang, Xing Bao, Kuisheng Liu, Wei Guo
Journal: Journal of Hematology & Oncology (2018)

The original article [1] contained an error in Table 1 whereby the 'Positive' column in the 'PD-L1' Tumor type group of columns was mistakenly included at the beginning of the 'PD-L2' Tumor type group of columns.
Phenotypic subtypes and risk of local recurrence after radical resection for rectal cancer.
Authors: Katrina Knight, Antonia K. Roseweir, James Hugh Park, Joanne Edwards, Donald C McMillan, Paul G. Horgan, Campbell SD Roxburgh
Journal: Journal of Clinical Oncology (2018)

637 Background: Phenotypic subtypes for CRC are reported to stratify outcomes. The four subtypes are based on features within the consensus molecular subtypes (CMS): immune, canonical, latent and stromal. In 81 pts, we recently reported concordance between CMS and phenotypic subtypes. Of note, the stromal subtype matched the CMS4 subtype in 84%. Local recurrence (LR) after rectal cancer surgery remains a problem. Identifying those at risk determines who should receive neoadjuvant therapy (NT) and guides surgery. We evaluated whether phenotypic subtypes are associated with LR after radical treatment of rectal cancer. Methods: From a CRC database, pts with rectal cancer and phenotypic subtyping available were identified. Subtyping was performed based on immune cell infiltrate, stromal volume and tumor proliferation. LR was considered pelvic or peritoneal. Results: Between 1997-2007, 260 pts had surgery for rectal cancer. Most were &gt; 65yrs (63%), male (58%) and TNM stage II (39%) or III (37%). 32 (13%) received NT. For phenotypic subtypes, 88 (35%) were Immune, 47 (19%) Canonical, 48 (19%) Latent and 67 (27%) Stromal. Median FU was 138 months (min 88). 70 pts (27%) developed recurrence: LR in 23 (8.8%) and systemic in 44 (16.9%). LR was associated with higher T stage (pT1-3 7% vs pT4 17%, p = 0.024), presence of vascular invasion (15% vs 6%, p = 0.018), serosal involvement (21% vs 6%, p = 0.001), margin involvement (22% vs 7%, p = 0.010), &gt; 50% tumor stroma (18% vs 3%, p = 0.002) and phenotypic subtype (immune 5%, canonical 6%, latent 4% and stromal = 21%, p = 0.002). Similar LR rates were obtained after excluding pts who had NT: Immune (4%), canonical (4%), latent (5%) and stromal (23%). Of the 23 LRs, most were Stromal subtype (n = 14) vs Immune (n = 4), Canonical (n = 3) and Latent (n = 2). Apart from increased node positivity (50% vs 30-44% p &lt; 0.05), there were no differences in rates of pT4 disease, tumor grade, vascular invasion, serosal involvement and margin positivity between stromal subtype and other groups. Conclusions: LR after rectal cancer surgery was associated with the stromal subtype. Validation is needed but pre-treatment tumor subtyping may identify subsets at risk of LR and have implications for patient selection for neoadjuvant therapy.
Effect of tumor progression on colon cancer stem cell plasticity.
Authors: Vi Kien Chiu, Rama Gallupalli, Diaa Osman, Zhaoshi Zeng, Jinru Shia, Philip Paty, Anne-France Le Rolle
Journal: Journal of Clinical Oncology (2018)

688 Background: Stage I colon cancer initiation is optimized through the activation of the embryonic stem cell (SC)-like program in colon adenoma cells (Le Rolle AF, et al., 2016). This malignant transformation requires cellular dedifferentiation since the embryonic SC-like program does not exist a priori in colon cells. High initial tumor plasticity provides a competitive advantage as the tumor has more intrinsic phenotypic flexibility to survive environmental challenges. Inhibition of the embryonic SC-like program represents a novel therapeutic strategy. Herein, we examine the evolution this high tumor plasticity in stage I-IV colon cancer. Methods: Human colon cancer tissues were collected prospectively under an MSKCC IRB protocol (Jan 1990-Dec 2000). RNA in situ hybridization of LGR5, a colon SC marker, was carried out on human colon tumors before and after therapeutic interventions. We performed Gene Set Enrichment Analysis (GSEA 2.0 Broad Institute software) using Affymetrix U133A expression profiles from normal colon mucosa (n = 33) and colon cancer epithelia from stage I (n = 17), II (n = 35), III (n= 39) and IV (n= 46) tumors. Statistical analyses were conducted with GraphPad Prism 5 and Microsoft Excel. Results: Putative colon SC markers and differentiation markers are increased and decreased, respectively, in stage I-IV colon cancer in comparison to normal colon. Although colon adenoma originates from LGR5 + colon SC, LGR5 + overexpression per se correlates with good prognosis stage IV colon cancer and is not a colon cancer stem cell biomarker. Maximal embryonic SC-like program enrichment occurs in stage I colon cancer. GSEA comparisons of moderately differentiated stages II-IV versus stage I colon cancer reveal progressive tumor differentiation from the stage I embryonic SC-like program toward the intestinal SC program at more advanced tumor stages. Notably, poorly differentiated stage IV colon cancer retains an embryonic SC-like program. Conclusions: We conclude that except for poorly differentiated tumors, colon cancer progression from stage I to IV involves a heterogeneous tumor differentiation process from an embryonic SC-like program towards the intestinal SC or more differentiated intestinal cell programs.
Letter by Rodriguez-Granillo et al Regarding Article, “Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015”
Authors: Gastón A. Rodriguez-Granillo, Alfredo E. Rodriguez, José Milei
Journal: Circulation (2018)
Association Between Groundwater Lithium and the Diagnosis of Bipolar Disorder and Dementia in the United States
Authors: William F. Parker, Rebecca J. Gorges, Y. Nina Gao, Yudong Zhang, Kwan Hur, Robert D. Gibbons
Journal: JAMA Psychiatry (2018)

This study examines the association between groundwater lithium and diagnoses of bipolar disorder and dementia in the United States, adjusting for local health care resources and demographics.
Five-Year Outcomes with PCI Guided by Fractional Flow Reserve
Authors: Panagiotis Xaplanteris, Stephane Fournier, Nico H.J. Pijls, William F. Fearon, Emanuele Barbato, Pim A.L. Tonino, Thomas Engstrøm, Stefan Kääb, Jan-Henk Dambrink, Gilles Rioufol, Gabor G. Toth, Zsolt Piroth, Nils Witt, Ole Fröbert, Petr Kala, Axel Linke, Nicola Jagic, Martin Mates, Kreton Mavromatis, Habib Samady, Anand Irimpen, Keith Oldroyd, Gianluca Campo, Martina Rothenbühler, Peter Jüni, Bernard De Bruyne
Journal: New England Journal of Medicine (2018)

We hypothesized that fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease.
Metabolic and Physiologic Imaging Biomarkers of the Tumor Microenvironment Predict Treatment Outcome with Radiation or a Hypoxia-Activated Prodrug in Mice
Authors: Shingo Matsumoto, Shun Kishimoto, Keita Saito, Yoichi Takakusagi, Jeeva P. Munasinghe, Nallathamby Devasahayam, Charles P. Hart, Robert J. Gillies, James B. Mitchell, Murali C. Krishna
Journal: Cancer Research (2018)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxic niches that lead to treatment resistance. Therefore, studies of tumor oxygenation and metabolic profiling should contribute to improved treatment strategies. Here, we define two imaging biomarkers that predict differences in tumor response to therapy: (i) partial oxygen pressure (pO2), measured by EPR imaging; and (ii) [1-13C] pyruvate metabolism rate, measured by hyperpolarized 13C MRI. Three human PDAC xenografts with varying treatment sensitivity (Hs766t, MiaPaCa2, and Su.86.86) were grown in mice. The median pO2 of the mature Hs766t, MiaPaCa2, and Su.86.86 tumors was 9.1 ± 1.7, 11.1 ± 2.2, and 17.6 ± 2.6 mm Hg, and the rate of pyruvate-to-lactate conversion was 2.72 ± 0.48, 2.28 ± 0.26, and 1.98 ± 0.51 per minute, respectively (n = 6, each). These results are in agreement with steady-state data of matabolites quantified by mass spectroscopy and histologic analysis, indicating glycolytic and hypoxia profile in Hs766t, MiaPaca2, and Su.86.86 tumors. Fractionated radiotherapy (5 Gy × 5) resulted in a tumor growth delay of 16.7 ± 1.6 and 18.0 ± 2.7 days in MiaPaca2 and Su.86.86 tumors, respectively, compared with 6.3 ± 2.7 days in hypoxic Hs766t tumors. Treatment with gemcitabine, a first-line chemotherapeutic agent, or the hypoxia-activated prodrug TH-302 was more effective against Hs766t tumors (20.0 ± 3.5 and 25.0 ± 7.7 days increase in survival time, respectively) than MiaPaCa2 (2.7 ± 0.4 and 6.7 ± 0.7 days) and Su.86.86 (4.7 ± 0.6 and 0.7 ± 0.6 days) tumors. Collectively, these results demonstrate the ability of molecular imaging biomarkers to predict the response of PDAC to treatment with radiotherapy and TH-302.Significance: pO2 imaging data and clinically available metabolic imaging data provide useful insight into predicting the treatment efficacy of chemotherapy, radiation, and a hypoxia-activated prodrug as monotherapies and combination therapies in PDAC tumor xenograft models. Cancer Res; 78(14); 3783-92. ©2018 AACR.
Abstract 17796: Toll-like Receptor 9 Signaling Pathway Ameliorates Cardiac Rupture After Myocardial Infarction by Promoting the Proliferation of Myofibroblasts
Authors: Shigemiki Omiya, Yosuke Omori, Kazuhiko Nishida, Ajay Shah, Kinya Otsu
Journal: Circulation (2015)

Background: Toll-like receptor (TLR) 9 signaling pathway plays an important role in inflammatory responses in failing hearts in response to pressure overload and in the pathogenesis of heart failure. However, the role of the signaling pathway in left ventricular (LV) remodeling after myocardial infarction, where necrotic cardiomyocyte death is prominent, has not been elucidated. Methods and Results: Wild-type (WT) (n=9) and TLR9 knockout (KO) mice (n=11) were subjected to the left coronary artery ligation to induce myocardial infarction (MI). The survival ratio 7 days after MI was significantly reduced in KO mice (36.4%) than in WT mice (88.9%) (p&lt;0.05). All of dead mice in both groups exhibited cardiac rupture. The peak time occurring rupture was 4 days after MI. The ischemia area at risk, identified by a lack of Evans blue staining were not significantly different between the WT and KO hearts (29.7% and 28.9%). Cardiovascular MRI imaging perfomed at 3 days post MI showed no difference in infarct size, LV volume and ejection fraction between WT and KO mice. The mRNA expression levels of inflammatory cytokines including IL-6 and TNFα were not significantly different in KO mice compared with WT mice. Immunohistochemical analysis did not show the significant difference in the extent of neutrophilic infiltration (CD45 positive cells) and macrophage accumulation (CD68 positive cells) in the infarct region between WT and KO mice. The number of myofibroblasts (αsmooth muscle action-positive cells), one of the cellular components in the formation of granulation tissue, was significantly reduced in KO mice (346 cells /mm2) compared to WT mice (1547 cells /mm2) (p&lt;0.05). The number of myofibroblasts exhibiting Ki-67 immunoreactivity was also markedly lower in KO mice (113 cells /mm2) than in WT mice (789 cells /mm2) (p&lt;0.05), indicating that the proliferative activity of myofibroblasts was significantly decreased in the infarcted regions of KO hearts. Conclusions: TLR9 signaling pathway is not involved in inflammatory responses in the infarcted regions of MI hearts but ameliorates cardiac rupture after MI by promoting the proliferation of myofibroblasts.
Epithelial barrier dysfunctions in atopic dermatitis: a skin-gut-lung model linking microbiome alteration and immune dysregulation
Authors: T.H. Zhu, T.R. Zhu, K.A. Tran, R.K. Sivamani, V.Y. Shi
Journal: British Journal of Dermatology (2018)

Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated. This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march. A literature search was conducted using the PubMed database for relevant articles with the keywords 'atopic dermatitis', 'epithelial barrier', 'skin', 'gut', 'lung', 'microbiome' and 'immune dysregulation'. Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin-mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract. As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long-term outcomes and reduce allergen sensitization in the airway and gut.
Prevention, diagnosis and management of paediatric ACL injuries
Authors: Clare L Ardern, Guri Ranum Ekås, Hege Grindem, Håvard Moksnes, Allen Anderson, Franck Chotel, Moises Cohen, Magnus Forssblad, Theodore J Ganley, Julian A Feller, Jón Karlsson, Mininder S Kocher, Robert F LaPrade, Michael McNamee, Bert Mandelbaum, Lyle Micheli, Nicholas G H Mohtadi, Bruce Reider, Justin P Roe, Romain Seil, Rainer Siebold, Holly J Silvers-Granelli, Torbjørn Soligard, Erik Witvrouw, Lars Engebretsen
Journal: British Journal of Sports Medicine (2018)