tbuckley/cabot-search huggingface dataset:
AB1240-HPR Patients' dogma, number of swollen joints and physicians' and patients' age predict non-adherence to medicines and non-pharmacological interventions in rheumatoid arthritis – a mixed methods study
Authors: V Ritschl, A Lackner, C Boström, M Kundi, P Studenic, J Smolen, T Stamm
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In rheumatoid arthritis (RA), up to 80% of patients were found to be non-adherent to prescribed medication and non-pharmacological recommendations. These patients do not achieve an optimal clinical outcome. <h3>Objectives</h3> In the present study, we therefore explored predictors that may lead to non-adherence to both medicines and/or non-pharmacological recommendations. <h3>Methods</h3> In a mixed methods study, retrospective observational data from patients meeting the ACR/EULAR criteria for RA who were non-attenders/missed the routine check up visits for at least 9 months to the rheumatology clinic and had had an initial DMARD therapy were queried of the databases of two rheumatology centers in Austria (Graz, Vienna). Subsequently, we invited all patients to take part in a qualitative semi-structured interview study with a meaning condensation data analysis. In the interviews, patients were assigned to the subgroups "adherent" (e.g. having regular rheumatology visits in another clinic) or "non-adherent" (e.g. having stopped taking the prescribed medication). Possible predictors derived from the qualitative analysis and the retrospective observational data were then tested in a logistic regression model. <h3>Results</h3> In total, data of 459 patients (346 [75.4%] females; mean age 63.0 [SD± 14.8]) were extracted out of the databases. 131 patients (109 [83.2%] females; mean age 64.8 [SD± 14.1]) participated in the qualitative interviews. In addition to already known themes, new topics arose from the analysis: (i) patient9s dogma inhibited adherent behavior, in that patients felt that pain was an important part of life and attributed to having had a high manual workload during life of which patients were proud; (ii) patients had less trust in physicians when they were seeking support from other physicians, because they appeared to be "young or unexperienced"; (iii) Some patients did not feel properly understood if physicians only prescribed medication without giving advice on non-pharmacological aspects of treatment. Two clinical variables were found to be predictors for non-adherent behavior (table 1): swollen joint count (patients with higher numbers of swollen joints were less adherent) and age (younger patients were less adherent). <h3>Conclusions</h3> In order to achieve a good clinical outcome, it is important to provide evidence based treatment recommendations, but also to ensure adherence to these. The predictors found in our study could be used to enhance patient adherence and therefore improve clinical outcome. <h3>Acknowledgements</h3> This project was partially funded by AbbVie Inc. <h3>Disclosure of Interest</h3> None declared
Abstract 031: Predictors and Cardiovascular Outcomes Associated with ECG-Evident Left Ventricular Hypertrophy in a Large Population
Authors: Carlos Iribarren, Alfred D Round, Meng Lu, Peter M Okin, Edward J McNulty
Journal: Circulation (2013)

Left ventricular hypertrophy that is evident on the electrocardiogram (ECG LVH) is a common condition affecting 1-5% of the general population and up to one third of patients with hypertension. However, there have been no studies examining the prevalence, correlates and associated cardiovascular disease (CVD) outcomes associated with ECG LVH in a very large and ethnically diverse population. In this study, we aimed to determine the prevalence of ECG LVH, its demographic and clinical correlates as well as its association with longitudinal CVD outcomes among members of Kaiser Permanente of Northern California. We performed a retrospective observational cohort study using an existing database of randomly selected, single ECGs taken on 1.4 million persons over age 30 as part of routine medical care between 1995 and 2009. We linked the index ECG data with other health plan databases, including hospitalizations and vital status through 8/31/12. The total accumulated follow-up time was 9.8 million person-years. ECG LVH was defined by sex-specific Cornell voltage Criteria (for men: S in V3 plus R in aVL &gt;2.8 mV [28 mm]; for women: S in V3 + R in aVL &gt;2.0 mV [20 mm] derived by processing raw ECG measurements from these two leads. The overall prevalence of ECG LVH was 5.1% (71,745 / 1,398,524), it was higher among women (7.4%; 55,296 / 743,466) than in men (2.5%; 16,449 / 655,058); in blacks (10%; 11,258 / 112,230) compared to whites (4.9%; 37,692 / 763,445), Asians (4.6%; 7,014 / 153,780) and Latinos (4.3%; 7,253 / 168,686); in persons over age 65 (9.3 %; 37,071 / 398,666) and in patients with a history of hypertension (9.2%; 46,415 / 502,462). In Cox regression, after excluding persons with prior cardiovascular events and after adjusting for age, gender, race/ethnicity, smoking status, obesity, diabetes, hypertension and hyperlipidemia, ECG LVH was independently associated with subsequent acute coronary syndrome (n=38,239; HR [hazard ratio]=1.66; 95% CI 1.60 to 1.73), cardiac arrest (n=12,144; HR=2.02; 95% CI 1.90 to 2.14), total stroke (n=49,518; HR=1.67; 95% CI 1.62 to 1.72), heart failure (n=47,294; HR=2.43; 95% CI, 2.37 to 2.50) and all cause-mortality (n=127,036; HR=1.78; 95% CI, 1.74 to 1.81). In conclusion ECG LVH is a relatively common ECG finding and a robust independent predictor of cardiovascular events and all-cause mortality in the largest population yet examined.
Maternal Antidepressant Use and Pregnancy Outcomes
Authors: Kimberly Ann Yonkers, Ariadna Forray, Megan V. Smith
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
Combination Therapy with Bispecific Antibodies and PD-1 Blockade Enhances the Antitumor Potency of T Cells
Authors: Chien-Hsing Chang, Yang Wang, Rongxiu Li, Diane L. Rossi, Donglin Liu, Edmund A. Rossi, Thomas M. Cardillo, David M. Goldenberg
Journal: Cancer Research (2017)

The DOCK-AND-LOCK (DNL) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL to generate a novel class of trivalent bispecific antibodies (bsAb), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different antitumor Fabs. Here, we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2- and CEACAM5-expressing cancer cells, respectively. (E1)-3s and (14)-3s, in the presence of human T cells, killed target cells grown as monolayers at subnanomolar concentrations, with a similar potency observed for drug-resistant cells. Antitumor efficacy was demonstrated for (E1)-3s coadministered with human peripheral blood mononuclear cells (PBMC) in NOD/SCID mice harboring xenografts of MDA-MB-231, a triple-negative breast cancer line constitutively expressing Trop-2 and PD-L1. Growth inhibition was observed following treatment with (E1)-3s or (14)-3s combined with human PBMC in 3D spheroids generated from target cell lines to mimic the in vivo behavior and microenvironment of these tumors. Moreover, addition of an antagonistic anti-PD-1 antibody increased cell death in 3D spheroids and extended survival of MDA-MB-231-bearing mice. These preclinical results emphasize the potential of combining T-cell-redirecting bsAbs with antagonists or agonists that mitigate T-cell inhibition within the tumor microenvironment to improve immunotherapy of solid cancers in patients. They also support the use of 3D spheroids as a predictive alternative to in vivo models for evaluating T-cell functions. Cancer Res; 77(19); 5384-94. ©2017 AACR.
Expansion of blood IgG 4 + B, T H 2, and regulatory T cells in patients with IgG 4 -related disease
Authors: Jorn J. Heeringa, A. Faiz Karim, Jan A.M. van Laar, Robert M. Verdijk, Dion Paridaens, P. Martin van Hagen, Menno C. van Zelm
Journal: Journal of Allergy and Clinical Immunology (2017)
Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40
Authors: David J. Messenheimer, Shawn M. Jensen, Michael E. Afentoulis, Keith W. Wegmann, Zipei Feng, David J. Friedman, Michael J. Gough, Walter J. Urba, Bernard A. Fox
Journal: Clinical Cancer Research (2017)

Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 followed by anti-PD-1.Results: The concurrent addition of anti-PD-1 significantly attenuated the therapeutic effect of anti-OX40 alone. Combination-treated mice had considerable increases in type I and type II serum cytokines and significantly augmented expression of inhibitory receptors or exhaustion markers CTLA-4 and TIM-3 on T cells. Combination treatment increased intratumoral CD4+ T-cell proliferation at day 13, but at day 19, both CD4+ and CD8+ T-cell proliferation was significantly reduced compared with untreated mice. In two tumor models, sequential combination of anti-OX40 followed by anti-PD-1 (but not the reverse order) resulted in significant increases in therapeutic efficacy. Against MMTV-PyMT tumors, sequential combination was dependent on both CD4+ and CD8+ T cells and completely regressed tumors in approximately 30% of treated animals.Conclusions: These results highlight the importance of timing for optimized therapeutic effect with combination immunotherapies and suggest the testing of sequencing in combination immunotherapy clinical trials. Clin Cancer Res; 23(20); 6165-77. ©2017 AACRSee related commentary by Colombo, p. 5999.
Characteristics of Clinical Studies Used for US Food and Drug Administration Approval of High-Risk Medical Device Supplements
Authors: Sarah Y. Zheng, Sanket S. Dhruva, Rita F. Redberg
Journal: JAMA (2017)

<h3>Importance</h3> High-risk medical devices often undergo modifications, which are approved by the US Food and Drug Administration (FDA) through various kinds of premarket approval (PMA) supplements. There have been multiple high-profile recalls of devices approved as PMA supplements. <h3>Objective</h3> To characterize the quality of the clinical studies and data (strength of evidence) used to support FDA approval of panel-track supplements (a type of PMA supplement pathway that is used for significant changes in a device or indication for use and always requires clinical data). <h3>Design and Setting</h3> Descriptive study of clinical studies supporting panel-track supplements approved by the FDA between April 19, 2006, and October 9, 2015. <h3>Exposure</h3> Panel-track supplement approval. <h3>Main Outcomes and Measures</h3> Methodological quality of studies including randomization, blinding, type of controls, clinical vs surrogate primary end points, use of post hoc analyses, and reporting of age and sex. <h3>Results</h3> Eighty-three clinical studies supported the approval of 78 panel-track supplements, with 71 panel-track supplements (91%) supported by a single study. Of the 83 studies, 37 (45%) were randomized clinical trials and 25 (30%) were blinded. The median number of patients per study was 185 (interquartile range, 75-305), and the median follow-up duration was 180 days (interquartile range, 84-270 days). There were a total of 150 primary end points (mean [SD], 1.8 [1.2] per study), and 57 primary end points (38%) were compared with controls. Of primary end points with controls, 6 (11%) were retrospective controls and 51 (89%) were active controls. One hundred twenty-one primary end points (81%) were surrogate end points. Thirty-three studies (40%) did not report age and 25 (30%) did not report sex for all enrolled patients. The FDA required postapproval studies for 29 of 78 (37%) panel-track supplements. <h3>Conclusions and Relevance</h3> Among clinical studies used to support FDA approval of high-risk medical device modifications, fewer than half were randomized, blinded, or controlled, and most primary outcomes were based on surrogate end points. These findings suggest that the quality of studies and data evaluated to support approval by the FDA of modifications of high-risk devices should be improved.
14 Medications that affect the lower oesophageal sphincter and risk of oesophageal cancer: a cohort study of 465,768 uk biobank participants
Authors: A Spence, A Kunzmann, U McMenamin, H Coleman, B Johnston, L Murray, C Cardwell
Journal: Gut (2017)

Background  Medications that relax the lower oesophageal sphincter may promote acid reflux, a known contributor to oesophageal adenocarcinoma development.  Aim  We investigated the association between lower oesophageal sphincter relaxing medications and oesophageal cancer (OC) risk.  Method  A retrospective cohort study of participants within the UK Biobank from 2006 and 2014 was performed. Age-dependent Cox-regression analysis was used to calculate adjusted HR and 95% CI for OC risk in individuals prescribed benzodiazepines, calcium channel blockers, nitrates, respiratory sympathomimetics and xanthines.  Results  Of 4 75 768 study participants, 409 were diagnosed with OC during 8 years of follow-up. There was a significant direct association with OC in participants using respiratory sympathomimetics (HR 1.71, 95% CI 1.20–2.42), with similar increased risk of oesophageal adenocarcinoma with use of these respiratory medications (HR 1.68, 95% CI 1.10–2.54) and xanthines (HR 4.82, 95% CI 1.16–20.10). Participants taking respiratory sympathomimetics or any lower oesophageal sphincter relaxing medication were also at greater risk of oesophageal squamous cell cancer (HR 2.51, 95% CI 1.29–4.87 and HR 2.03, 95% CI 1.01–4.09, respectively). There was no significant association between OC and the other medications investigated.  Conclusions  Respiratory sympathomimetics were associated with greater risk of OC overall, and both adenocarcinoma and squamous cell carcinoma subtypes. Individuals using lower oesophageal sphincter relaxing medications are at increased risk of squamous cell carcinoma, and as this tumour is not associated with excessive acid reflux, an alternative pathway to this cancer with these medications may exist.
Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche
Authors: Ioannis Mitroulis, Lan-Sun Chen, Rashim Pal Singh, Ioannis Kourtzelis, Matina Economopoulou, Tetsuhiro Kajikawa, Maria Troullinaki, Athanasios Ziogas, Klara Ruppova, Kavita Hosur, Tomoki Maekawa, Baomei Wang, Pallavi Subramanian, Torsten Tonn, Panayotis Verginis, Malte von Bonin, Manja Wobus, Martin Bornhäuser, Tatyana Grinenko, Marianna Di Scala, Andres Hidalgo, Ben Wielockx, George Hajishengallis, Triantafyllos Chavakis
Journal: Journal of Clinical Investigation (2017)

Hematopoietic stem cells (HSCs) remain mostly quiescent under steady-state conditions but switch to a proliferative state following hematopoietic stress, e.g., bone marrow (BM) injury, transplantation, or systemic infection and inflammation. The homeostatic balance between quiescence, self-renewal, and differentiation of HSCs is strongly dependent on their interactions with cells that constitute a specialized microanatomical environment in the BM known as the HSC niche. Here, we identified the secreted extracellular matrix protein Del-1 as a component and regulator of the HSC niche. Specifically, we found that Del-1 was expressed by several cellular components of the HSC niche, including arteriolar endothelial cells, CXCL12-abundant reticular (CAR) cells, and cells of the osteoblastic lineage. Del-1 promoted critical functions of the HSC niche, as it regulated long-term HSC (LT-HSC) proliferation and differentiation toward the myeloid lineage. Del-1 deficiency in mice resulted in reduced LT-HSC proliferation and infringed preferentially upon myelopoiesis under both steady-state and stressful conditions, such as hematopoietic cell transplantation and G-CSF- or inflammation-induced stress myelopoiesis. Del-1-induced HSC proliferation and myeloid lineage commitment were mediated by β3 integrin on hematopoietic progenitors. This hitherto unknown Del-1 function in the HSC niche represents a juxtacrine homeostatic adaptation of the hematopoietic system in stress myelopoiesis.
Endoscopic submucosal dissection of colitis-related dysplasia
Authors: Noriko Suzuki, Takashi Toyonaga, James East
Journal: Endoscopy (2017)

Background and study aims Endoscopic submucosal dissection (ESD) offers en bloc resection of lesions, allowing precise pathological assessment. Although possible in ulcerative colitis (UC) patients, the chronic inflammation may increase the procedural risks and reduce the complete resection rate. The aim of this study was to assess the feasibility of ESD for UC and to consider the factors contributing to its technical difficulty. Patients and methods Multicenter experiences of ESD for UC were retrospectively analyzed by reviewing endoscopic videos, pictures, reports, and clinical notes. Results A total of 32 dysplastic lesions were included (23 in British patients, 9 in Japanese patients). The lesions were macroscopically flat or with subtle extension macroscopically in 30 patients (94 %), with a median size of 33 mm (range 12 - 73 mm), and were located in the distal colon, including one on a pouch anastomosis. Submucosal fibrosis and adipose deposition were observed in 31 (97 %) and 13 lesions (41 %), respectively. En bloc resection was possible in 29/32 lesions (91 %). One patient had delayed bleeding. Advanced pathology was observed in 11 lesions (35 %). Recurrence was observed in only one patient (after a median of 33 months [range 6 - 76 months]); however, three patients developed metachronous lesions. Conclusions ESD is feasible for UC dysplasia without an increased rate of complications. Submucosal fibrosis and fat deposition were frequently observed and contributed to the technical complexity. Careful and intensive follow-up should be organized to detect metachronous lesions.
Abstract P281: Bcl-2 Limits Ischemia-Reperfusion Injury of the Naive Myocardium by Preserving Mitochondrial Integrity and Respiratory Complex Functionality and Is Modulated by PKCε
Authors: David A Liem, Jun Zhang, Christopher Lotz, Ding Wang, Peipei Ping
Journal: Circulation Research (2011)

Over-expression of Bcl-2 protects against myocardial ischemia/reperfusion (I/R) injury. Nevertheless, the participation of Bcl-2 in basal myocardium, and its subcellular targets under such conditions, remains elusive. Using a mouse line with an ablation of the Bcl-2 gene, we found that myocardial infarct size (IS) was exacerbated vs. wild type (WT) mice, demonstrating that Bcl-2 limit IS in basal I/R injury. The exacerbated IS in Bcl-2 KO was abolished by in vivo treatment with the selective Mitochondrial Permeability Transition (MPT) inhibitor cyclosporine A (10 mg/kg, iv) , while isolated cardiac mitochondria from Bcl-2 null mice exhibited increased matrix swelling in response to CaCl 2 , showing an increased susceptibility to MPT. However, recombinant Bcl-2 or PKCε were both sufficient to attenuate the increased susceptibility to MPT. Interestingly, spectrophotometric analysis of baseline activities of Mitochondrial Electron Transport Chain Complexes (ETC) I and V (but not of ETC II, III and IV), were increased in cardiac mitochondria from Bcl-2 null mice as compared to mitochondria from normal WT mice, demonstrating an altered mitochondrial respiratory complex functionality. In addition, immunoprecipitation with PKCε in AE-PKCε mouse hearts (i.e. mice with an increased activity of PKCε) followed by immunoblotting for Bcl-2, showed an 2-fold increased interaction between PKCε and Bcl-2. Similarly, immunoprecipitation with Phospho-Serine followed by immunoblotting for Bcl-2 indicated a 2-fold increased Serine residue phosphorylation of Bcl-2. Mass spectrometry analysis further showed that PKCε can phosporylate Bcl-2 at its Serine24 residue site in vitro, indicating that PKCε can directly interact and phosphorylate Bcl-2. These data suggest that Bcl-2 is pivotal in limiting IS in basal I/R injury by counteracting MPT and preserving mitochondrial respiratory complex functionality, and implicate a direct interaction and phosphorylation of Bcl-2 by PKCε in this process.
Improving the Appropriate Use of Transthoracic Echocardiography
Authors: R. Sacha Bhatia, Noah M. Ivers, X. Cindy Yin, Dorothy Myers, Gillian C. Nesbitt, Jeremy Edwards, Kibar Yared, Rishi K. Wadhera, Justina C. Wu, Aaron P. Kithcart, Brian M. Wong, Mark S. Hansen, Adina S. Weinerman, Steven Shadowitz, Debra Elman, Michael E. Farkouh, Paaladinesh Thavendiranathan, Jacob A. Udell, Amer M. Johri, Chi-Ming Chow, Judith Hall, Zachary Bouck, Ashley Cohen, Kevin E. Thorpe, Harry Rakowski, Michael H. Picard, Rory B. Weiner
Journal: Journal of the American College of Cardiology (2017)