tbuckley/cabot-search huggingface dataset:
Obesity and the Risk of New-Onset Atrial Fibrillation
Authors: Harpreet S Bajaj, Steven D Hillson
Journal: JAMA (2005)

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
Re: Marlon Perera, Nathan Papa, Daniel Christidis, et al. Sensitivity, Specificity, and Predictors of Positive 68 Ga–Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol 2016;70:926–37
Authors: Fabio Zattoni, Filiberto Zattoni, Laura Evangelista
Journal: European Urology (2016)
High efficacy and continued tumor shrinkage with cyclophosphamide, vincristine, and dacarbazine (CVD) in patients (Pts) with malignant pheochromocytoma/paraganglioma harboring succinate dehydrogenase subunit B (SDHB) mutations.
Authors: I. Jawed, L. Amiri-Kordestani, M. Velarde, K. Adams, S. Balasubramaniam, J. Reynolds, K. Pacak, A. T. Fojo
Journal: Journal of Clinical Oncology (2011)

2526 Background: Pheochromocytomas and paragangliomas are rare tumors of the adrenals and paraganglia, respectively. As many as 30% of pts harbor a mutation in the VHL, RET, NF1, SDHB, SDHC, or SDHD genes. Pts with SDHB mutations have the highest rate of malignancy, with more aggressive tumors occurring earlier in life and often in extra-adrenal locations. We report on 10 patients with pheochromocytoma or paraganglioma and mutations/polymorphisms in the SDHB gene treated with CVD. Methods: After controlling symptoms of catecholamine excess, all patients received cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 on day 1 and dacarbazine 600 mg/m2 on days 1 and 2, every 21 - 28 days. Results: SDHB mutations (8) or polymorphisms (2) were confirmed in all pts. A median of 18.5 cycles (range 7 - 41) was administered. Reductions in vincristine for neuropathy (median 10 cycles) and dacarbazine (median 6 cycles) for delayed marrow recovery were made in 6 pts. Tumor shrinkage was observed in all pts (12% - 100% by RECIST) resulting in one CR, 7 PR, and one yet to be confirmed PR. Responses were observed at all sites of disease including liver, lungs, retroperitoneal nodes, and bones. Median time to response was 338 days. Median duration of response was >299 days (range 30 - 1092 days). One pt who had received radiation therapy and had an undefined congenital disease developed a secondary leukemia and died in a PR. FDG PET/CT imaging demonstrated continued reduction in SUVmax values in 26/30 lesions from a median SUV >25 to <6 over a median time >825 days as treatment was administered providing evidence of continued drug efficacy during prolonged administration. Conclusions: CVD therapy has a very high level of activity in pts with pheochromocytoma/paraganglioma harboring SDHB mutations/polymorphism. Chronic therapy over prolonged periods of time resulted in continued tumor shrinkage. These results suggest that in pts with metastatic SDHB-related pheochromocytoma/paraganglioma CVD, an effective therapy with continued tumor shrinkage over a prolonged time, should be a part of their initial management.
Microarray study reveals a transforming growth factor-β-dependent mechanism of fibrosis in discoid lupus erythematosus
Authors: C. Solé, M. Gimenez-Barcons, B. Ferrer, J. Ordi-Ros, J. Cortés-Hernández
Journal: British Journal of Dermatology (2016)

Discoid lupus erythematosus (DLE) is characterized by scarring lesions that develop and perpetuate fibrotic lesions. These are not observed in subacute cutaneous lupus erythematosus (SCLE). The pathophysiological basis of this is currently unknown. To identify contradistinctive signalling pathways and cellular signatures between the two type of lupus, with a focus on the molecular mechanisms leading to fibrosis. We conducted a gene expression microarray analysis in lesional and nonlesional skin biopsy specimens of patients with DLE (n = 10) and SCLE (n = 10). Confirmatory reverse‐transcriptase quantitative polymerase chain reaction (RT‐qPCR) and immunohistochemistry were performed on selected transcripts in a new cohort of paraffin‐embedded skin biopsies (n = 20). Changes over time of a group of selected inflammatory and fibrotic genes were also evaluated in a second biopsy taken 12 weeks later. In vitro functional studies were performed in primary isolated fibroblasts. Compared with nonlesional skin, DLE samples expressed a distinctive T‐cell gene signature. DLE samples displayed a significant CD4 T‐cell enrichment with an imbalance towards T helper 1 cytokine predominance and a relative increased forkhead box (FOX)P3 response. RT‐qPCR and immunochemical analysis over time showed a progressive increment of fibrotic markers and persistent FOXP3 recruitment. Ex vivo upregulation of SERPINE1, MMP9, TGFBR1, phosphorylated SMAD3 and TGFB1 suggested a transforming growth factor (TGF)‐β‐dependent mechanism of fibrosis in DLE, also confirmed by the results observed following in vitro stimulation with TGF‐β. These results highlight major pathogenic pathways in DLE and provide novel molecular targets for the development of new therapies. The data suggest the existence of a TGF‐β‐dependent pathway inducing fibrosis in DLE.
The relationship of presenting symptom burden and survival in patients with head and neck cancer (HNC).
Authors: G. B. Gunn, T. R. Mendoza, X. S. Wang, A. S. Garden, J. S. Lewin, W. H. Morrison, S. J. Frank, M. S. Chambers, C. S. Cleeland, D. I. Rosenthal
Journal: Journal of Clinical Oncology (2010)

5600 Background: Previous studies have shown that patient-reported outcomes with QOL instruments are predictive of survival. We investigate the relationship between HNC patient-reported symptoms and survival in addition to clinician ratings of ECOG performance status (PS). Methods: 129 patients with HNC participated in the study. Patients completed the M. D. Anderson Symptom Inventory - Head and Neck module (MDASI-HN) prior to radiotherapy or chemoradiotherapy. Cluster analysis was used to identify those who were symptomatic due to their disease prior to treatment. Cox regression was used to examine differences in survival between symptom burden groups with PS as covariate. Logistic regression was used to determine the relationship of overall survival status with symptom burden and performance status. Results: 46% (60/129) of HNC patients were identified to have symptoms prior to therapy. The top symptoms at presentation were fatigue, emotional distress, pain, disturbed sleep, drowsiness and sadness. Under Cox regression, symptom burden (OR=2.3, 95% CI: 1.1, 4.9, p<0.032) and performance status (OR=4.4, 95% CI: 2.1, 9.0, p<0.001) are significant predictors of survival. Under logistic regression, symptom burden (OR=3.2, 95% CI: 1.3, 7.9, p<0.011) and performance status (OR=7.0, 95% CI: 2.4, 20.4, p<0.001) are significant predictors of survival status. The logistic model with both performance status and symptom burden as predictors of survival showed better model fit than either predictor alone. Conclusions: Half of HNC patients are symptomatic prior to radiation therapy, but most have mild symptom severity. However, patients with high pretreatment symptom burden have poorer survival outcomes, and the combination of PS and symptom burden is a better predictor than either alone. No significant financial relationships to disclose.
Comprehensive genomic profiling in colorectal cancer (CRC) to identify differing frequencies of clinically relevant genomic alterations (CRGA) in tumors of patients (pts) less than age 50 as compared to those of pts over age 65.
Authors: Mark Bailey, Edith P. Mitchell, Deborah Morosini, Doron Lipson, Jeffrey S. Ross, Vincent A. Miller, Jie He, Phil Stephens
Journal: Journal of Clinical Oncology (2016)

570 Background: CRC is increasing in young pts and are believed to have worse pathological features than older pts. Mutational profiles may differ in pts. The objective of this study was to compare and describe the genomic complexity of CRC in pts &lt; 50 to &gt; 65 in the FoundationOne database. Methods: DNA was extracted from 2,267 FFPE clinical specimens with colorectal cancer (CRC) (&lt; 50 yo, n=1280; &gt; 65 yo, n = 987). CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 603X for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. All classes of genomic alterations (GA) were identified. Clinically relevant genomic alterations (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Among the 50 genes analyzed, the &gt; differences were noted in BRAF and FAM123B in pts &gt; 65. KRAS mutations occurred in 50.5% vs 51.3%; NRAS, 2.6% vs 4.8%, BRAF, 5.5% vs 11.9% in younger pts vs older pts, respectively. Few differences in genomic complexity were observed, although a trend toward increase frequency of BRAF mutations were observed in pts &gt; 65. Conclusions: While some differences in tumor genomic profiles and complexity were observed in CRC pts &lt; 50 vs &gt; 65, changes in BRAF and FAM123B were more frequent in the &gt; 65. Ongoing studies will assess differences in molecular and genomic features between younger and older CRC pts. [Table: see text]
Sorafenib, gamma-secretase inhibitor, and bortezomib as potential therapeutic agents for hepatoblastoma.
Authors: P. C. Sanchez-Diaz, T. L. Chen, R. Meyers, M. H. Malogolowkin, J. Y. Hung, G. E. Tomlinson
Journal: Journal of Clinical Oncology (2010)

9550 Background: Older children with hepatoblastoma (HB) as well as liver tumors with features of hepatocellular carcinoma (HCC) often have more aggressive features and are resistant to the conventional agents used in the treatment of hepatoblastoma. These aggressive tumors have been classified as "transitional cell liver tumors" (TCLT). We undertook an in-vitro analysis of the effect of the following three agents: sorafenib, bortezomib and the gamma-secretase inhibitors (GSI), Compound E, using cell lines derived from aggressive pediatric liver tumors. Though these agents have been shown to be effective in other malignancies, however, their use in pediatric liver tumors has not yet been explored. Methods: Two cell lines were utilized: HepG2 and Hep293TT. HepG2 was derived from a 16-year-old and although previously thought to be HCC, has recently been shown to have features of HB. Hep293TT is derived from a 5-year-old child with an aggressive HB exhibiting TCLT features. HepG2 and Hep293TT cells were incubated in the presence of different concentrations of the GSI Compound E and the cell cycle distribution measured. The IC50 for bortezomib and sorafenib was determined in both cell lines. To investigate the effect on the stem-like cell component, cells were incubated in the presence of Compound E, bortezomib or sorafenib and the percentage of CD133 and/or aldehyde dehydrogenase (ALDH) positive cells was determined by flow cytometry. Cells incubated with drug vehicle (DMSO) were included as control in all experiments. Results: Compound E induced a G1 arrest in HepG2 cells and both cell lines were sensitive to bortezomib and sorafenib. In addition, a 20% to 50% reduction in the CD133 and ALDH positive fractions was observed after exposure to these drugs in both cell lines. Conclusions: This study using tumor cell lines from aggressive pediatric liver tumors demonstrated that sorafenib, bortezomib and GSI have activity both in decreasing tumor cell proliferation and also in targeting the stem-like cell fractions. Our observations thus may provide the basis for novel and potentially highly effective approaches to treat these aggressive childhood tumors. No significant financial relationships to disclose.
Long-Term Survival in Adult Patients with Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL) Who Achieved Minimal Residual Disease (MRD) Response Following Anti-CD19 BiTE® Blinatumomab
Authors: Gerhard Zugmaier, Nicola Goekbuget, Andreas Viardot, Matthias Stelljes, Svenja Neumann, Heinz A. Horst, Albrecht Reichle, Reinhard Marks, Christoph Faul, Monika Brueggemann, Chris Holland, Margit Schmidt, Noemi Mergen, Marie-Elisabeth Goebeler, Hermann Einsele, Ralf C. Bargou, Max S. Topp
Journal: Blood (2014)
EGFR overexpression in invasive squamous cell carcinoma of the penis.
Authors: A. K. Bahl, M. Sohail, E. Johnson, D. N. Church, A. Aziz, R. Persad
Journal: Journal of Clinical Oncology (2010)

e15078 Background: Squamous cell carcinoma of penis (SCCP) is an uncommon malignancy. The published literature on its biology and treatment is limited. Traditional treatments like standard chemotherapy drug combinations have been poorly studied and there is dearth of recent advances in systemic therapy. The use of novel targeted agents in this area has not been reported. Over the past years evidence has accumulated that EGFR overexpression correlates with a relatively unfavourable clinical outcome in several malignancies, including head and neck cancers. EGFR antagonists have shown promising results with improved outcomes in these settings. This study was designed to examine EGFR overexpression in invasive SCC of the penis with confirmed lymph nodal spread. Methods: 13 tumour samples of histologically proven squamous cell carcinoma with confirmed nodal spread were retrospectively analysed. EGFR expression was evaluated and graded (0, 1+, 2+, 3+) using anti-EGFR monoclonal antibody (clone H11, DakoCytomation Ltd, Cambridgeshire, UK) for EGFR1. Overexpression of EGFR was defined as any immunohistologic staining of tumor cell membranes above background level whether complete or incomplete circumferential staining. Results: 12 cases (92%) overexpressed EGFR (11 cases 3+, 1 case 2+). Of the specimens examined only 1 case showed weak receptor expression scoring 1+. In all cases, adjacent normal squamous epithelium demonstrated normal background EGFR expression. Conclusions: EGFR was overexpressed in more than 90% of the studied cases of invasive penile SCC with confirmed lymph nodal involvement. Given this high rate of overexpression, EGFR targeted therapy may represent a novel therapeutic target in managing penile cancer with the potential for improved survival outcome. No significant financial relationships to disclose.
Eicosanoids in non-small cell lung cancer (NSCLC).
Authors: D. H. Johnson, L. Horn, Z. Zhao, G. Milne, J. Morrow, A. Sandler, Y. Shyr, D. P. Carbone
Journal: Journal of Clinical Oncology (2010)

7613 Background: COX-2 is frequently upregulated in NSCLC leading to high PGE2 levels that may play a role in NSCLC pathogenesis. PGE-M, the main urine metabolite of PGE2, accurately reflects changes in systemic and intratumoral PGE2 levels [CCR 11:6634, 2005]. A ≥ 70% decline in PGE-M in NSCLC pts treated with docetaxel (D) + celecoxib (C) 400 mg bid was associated with a possible survival benefit. In an ongoing trial, study pts are prospectively selected using a change in PGE-M levels before and after C 600 mg bid which is the dose needed to effect maximum COX-2 inhibition [CCR 12:3381, 2006]. Methods: Previously treated NSCLC pts, PS 0-2, evaluable/measurable disease, adequate marrow, renal and hepatic function, no current NSAID or sulfa allergy are eligible. Screened pts with ≥ 70% decline in PGE-M receive D 75 mg/m2 or pemetrexed 500 mg/m2 q3wk + continued C 600 mg bid × 4 cycles followed by C 400 mg bid until PD or excess toxicity. Results: Through 12/0930 pts (F = 13, M = 17) enrolled. At baseline men had higher PGE-M (median: 34.7 vs. 16.9 ng/mg Cr) and lower LTE4 levels (78.6 vs. 101.4 pg/mg Cr) (LTE4 is main leukotriene metabolite). Median PGE-M levels decreased from 21.4 to 8.1 ng/mg Cr (p = 0.000) pre- and post-C; LTE4 was unchanged (97.7 to 82.3 pg/mg Cr; p = 0.92); and PGI-M decreased from 119 to 47.5 pg/mg Cr (p = 0.004). In men PGE-M decreased post C whereas LTE4 increased (78.6 to 93.4 ng/mg Cr; p = 0.017) suggesting a possible shunting to the 5-LO/leukotriene pathway. Both PGE-M and LTE4 decreased in women. 13 pts received C + chemo; 10 evaluable; 6 SD and 4 PD. Treatment was well tolerated; no cardiac toxicities noted. Conclusions: These preliminary data indicate C 600 mg bid effectively inhibits intratumoral COX-2 in > 40% NSCLC pts. The effect is greatest in current smokers and males compared to never smokers and females. Post C, LTE4 increased in males (former smokers primarily). These data may have implications for chemoprevention trials. [Lung Cancer SPORE CA90949] No significant financial relationships to disclose.
Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group
Authors: Inéz Frerichs, Marcelo B P Amato, Anton H van Kaam, David G Tingay, Zhanqi Zhao, Bartłomiej Grychtol, Marc Bodenstein, Hervé Gagnon, Stephan H Böhm, Eckhard Teschner, Ola Stenqvist, Tommaso Mauri, Vinicius Torsani, Luigi Camporota, Andreas Schibler, Gerhard K Wolf, Diederik Gommers, Steffen Leonhardt, Andy Adler
Journal: Thorax (2016)

Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.
Necrotic Cell Sensor Clec4e Promotes a Proatherogenic Macrophage Phenotype Through Activation of the Unfolded Protein Response
Authors: Marc Clément, Gemma Basatemur, Leanne Masters, Lauren Baker, Patrick Bruneval, Takao Iwawaki, Manfred Kneilling, Sho Yamasaki, Jane Goodall, Ziad Mallat
Journal: Circulation (2016)

Background: Atherosclerotic lesion expansion is characterized by the development of a lipid-rich necrotic core known to be associated with the occurrence of complications. Abnormal lipid handling, inflammation, and alteration of cell survival or proliferation contribute to necrotic core formation, but the molecular mechanisms involved in this process are not properly understood. C-type lectin receptor 4e (Clec4e) recognizes the cord factor of Mycobacterium tuberculosis but also senses molecular patterns released by necrotic cells and drives inflammation. Methods: We hypothesized that activation of Clec4e signaling by necrosis is causally involved in atherogenesis. We addressed the impact of Clec4e activation on macrophage functions in vitro and on the development of atherosclerosis using low-density lipoprotein receptor–deficient ( Ldlr −/− ) mice in vivo. Results: We show that Clec4e is expressed within human and mouse atherosclerotic lesions and is activated by necrotic lesion extracts. Clec4e signaling in macrophages inhibits cholesterol efflux and induces a Syk-mediated endoplasmic reticulum stress response, leading to the induction of proinflammatory mediators and growth factors. Chop and Ire1a deficiencies significantly limit Clec4e-dependent effects, whereas Atf3 deficiency aggravates Clec4e-mediated inflammation and alteration of cholesterol efflux. Repopulation of Ldlr −/− mice with Clec4e −/− bone marrow reduces lipid accumulation, endoplasmic reticulum stress, and macrophage inflammation and proliferation within the developing arterial lesions and significantly limits atherosclerosis. Conclusions: Our results identify a nonredundant role for Clec4e in coordinating major biological pathways involved in atherosclerosis and suggest that it may play similar roles in other chronic inflammatory diseases.
The Outlook of Digital Health for Cardiovascular Medicine
Authors: Mintu P. Turakhia, Sumbul A. Desai, Robert A. Harrington
Journal: JAMA Cardiology (2016)

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