tbuckley/cabot-search huggingface dataset:
A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-associated and non-HPV–associated head and neck (H/N) cancer.
Authors: Tanguy Y. Seiwert, Barbara Burtness, Jared Weiss, Iris Gluck, Joseph Paul Eder, Sara I Pai, Marisa Dolled-Filhart, Kenneth Emancipator, Kumudu Pathiraja, Christine Gause, Robert Iannone, Holly Brown, Jennifer Houp, Jonathan D. Cheng, Laura Quan Man Chow
Journal: Journal of Clinical Oncology (2014)

6011 Background: The PD-1 receptor-ligand pathway can be used by tumors to evade immune surveillance, thereby allowing neoplastic growth. MK-3475 is a highly selective, humanized IgG4/kappa isotype mAb designed to block PD-1 interaction with its ligands PD-L1 and PD-L2, to reactivate the immune system to eradicate the host tumor. Methods: Pts with recurrent/metastatic H/N cancer were enrolled in this multi-center, non-randomized trial in two cohorts (HPV and non-HPV associated). Pts were prescreened for PD-L1 expression by immunohistochemistry (22C3), and if positive allowed to proceed with treatment of single agent MK-3475 given intravenously at 10 mg/kg every 2 wks. Primary objectives are to determine (1) safety and tolerability and (2) anti-tumor activity of MK-3475 assessed by RECIST 1.1. Secondary objectives include progression-free survival, overall survival and response duration. Results: All results are based on preliminary, unaudited data as of Jan. 27, 2014. 77.9% of patients expressed PD-L1, defined as ≥1% of stained cells in the tumor microenvironment (Table). Of 60 patients (11 female, 49 male) enrolled in the study, 19 had an ECOG status of 0, and 40 had an ECOG status of 1 (1 unknown); 23 were HPV+ and 37 were HPV-; 9 had no prior systemic treatment, 10 had 1, 16 had 2, 13 had 3, and 7 had ≥4 prior regimens of treatment (5 unknown). Of the patients treated with MK-3475, 78.3% experienced ≥1 AE, and 46.7% reported a drug-related (DR) AE. The most common DR AEs reported were pruritis (6, 10%), fatigue (4, 7%), rash (4, 7%), and diarrhea (3, 5%). At least one Grade 3-5 AE was reported in 55.0% of patients, with 13.3% reporting a DR Gr 3-5 AE. Grade 3-5 AEs considered DR were hyponatremia, lymphopenia, rash, diarrhea, musculoskeletal pain, abscess (neck), and atrial fibrillation. Tumor shrinkage was observed in several patients, but protocol-specified efficacy analyses are not yet available. Conclusions: To date, treatment with MK-3475 has been well tolerated overall, with few serious DR AEs. Protocol-specified efficacy analyses are not yet available. Clinical trial information: NCT01848834.PD-L1 staining in tumors of screened patients (n=104). Staining (%) 0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100 n 50 8 9 3 2 2 4 3 2 21
Fish oil supplementation for primary prevention of atrial fibrillation after coronary artery bypass graft surgery: A randomized clinical trial
Authors: Ali Vasheghani Farahani, Awat Yousefi Azar, Hamid Reza Goodarzynejad, Elnaz Khorrami, Mohammad Javad Hosseinzadeh-Attar, Sima Oshnouei, Alireza Alizadeh Ghavidel, Elham Golfeshan, Fateme Ghourban Pour
Journal: International Journal of Surgery (2017)
EGFR-targeted micelles containing near-infrared dye for enhanced photothermal therapy in colorectal cancer
Authors: Ying-Hsia Shih, Tsai-Yueh Luo, Ping-Fang Chiang, Cheng-Jung Yao, Wuu-Jyh Lin, Cheng-Liang Peng, Ming-Jium Shieh
Journal: Journal of Controlled Release (2017)
Functional study of naturally occurring human antibodies in breast cancer
Authors: Yue-Jin Wen, Anne T. Mancino, Thomas Kieber-Emmons
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1753 

Introduction: Naturally occurring B–cell responses in the form of serum auto-antibodies to tumor-associated antigens are frequently observed in sera of patients with malignancies. Autoimmune responses in cancer patients may reflect molecular events that lead to tumorigenesis or disease progression. The purpose of this research was to study the role of auto-antibodies to promote human breast cancer cell growth and its potential mechanism by excessive activation of signal transduction pathways. Methods: Human antibody clones were screened from a human IgG Fab cDNA library that was constructed for a patient with breast cancer. The antibody binding to tumor antigen was tested by Western blot. The human breast cancer cell lines were treated with some of the Fab clones and the cell growth was measured by 3H-Thymidine uptake and MTT assay. Signal transduction pathways was evaluated by cell proliferation assay, in which three commonly used inhibitors including PD98059, Wortmannin, and PP1 were used. The potential signal pathway was further confirmed by Western blot. Results: Western blot performed on two selected antibodies showed that both clones’ product have stronger binding ability to the breast cancer antigen than the one from the normal breast tissues, indicating that the immune recognition of tested Fabs were breast cancer specific. The antigens recognized by the two tested clone products were of the similar size, a protein of molecular about 30-35 kDa, although the amino acid sequence of two clones varied by three residues in the CDR2 domain. The functional study showed that one IgG Fab (referred as Fab1) could stimulate both MCF-7 and MDA-MB-231 breast cancer cell lines growth in vitro. Pretreatment with either PD98059, a specific inhibitor of MEK1, or PP1, a specific inhibitor of Src, remarkably inhibited Fab1-induced breast cancer cell growth. In contrast, pretreatment with of wortmannin, a specific inhibitor of PI-3 kinase, did not show any inhibition effect to the Fab1-induced tumor growth. Western blot showed that Fab1 rapidly and transiently increased the phosphorylation of ERKs in both MCF-7 and MDA-MB-231 cells, with a maximal effect seen at 15 min and a return to baseline by 30 min. In agreement with the data from the cell proliferation assay, the induction of ERK phosphorylation by Fab1 was blocked by PD98059 and PP1, indicating that ERK phosphorylation and Src kinase activity are required for the clone 1 Fab-induced tumor growth. Conclusion: Our studies indicated the possible role of human antibody to promote tumor cell growth by directly binding of IgG Fab to breast tumor antigen and the involvement of ERK signal transduction in this Fab-induced tumor cell growth. These findings provide for further speculation as to the role of auto-antibodies in activating signaling pathways that regulate tumor growth as a basis for disease progression.
Pulmonary Perfusion Scan Mimicking Hepatobiliary Scintigraphy in a Patient With an Uncommon Manifestation of Granulomatosis With Polyangiitis
Authors: Michelle D. Hopstone, Evan A. Raff, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2017)

A 36-year-old man with known granulomatosis with polyangiitis underwent quantitative ventilation-perfusion pulmonary scintigraphy as part of an initial evaluation for lung transplant candidacy. Radiotracer uptake on the perfusion study has the appearance of the hepatic silhouette, drawing initial concern that there may have been a misadministration of 99mTc with a hepatobiliary agent. Comparison CT reveals extensive cystic bronchiectasis, parenchymal destruction, and volume loss involving the entire left lung and basal portions of the right lung, with the residual portions of functional lung parenchyma conforming to a shape similar to the liver.
TCTAP A-148 Drug Eluting Stents Versus Drug Eluting Balloons in the Treatment of Very Small De Novo Coronary Artery Disease
Authors: Hui Wen Sim, Rajiv Ananthakrishna, Poay-Huan Loh, Edgar Lik-Wui Tay, Koo Hui Chan, Mark Chan, Ronald Chi-Hang Lee, Adrian Low, Huay Cheem Tan, Joshua P. Loh
Journal: Journal of the American College of Cardiology (2017)
Evaluation of Experimental Retreatment and Prolonged Therapy with Subcutaneous (SC) Bortezomib in Patients (Pts) with Multiple Myeloma in First or Second Relapse, a Randomized, Controlled, Phase 3 Study
Authors: Michele Cavo, Marco Gobbi, Anna Potamianou, Marjolein Lahaye, Catherine Couturier, Evangelos Terpos
Journal: Blood (2016)
Disentangling Maternal Depression and Antidepressant Use During Pregnancy as Risks for Autism in Children
Authors: Tim F. Oberlander, Lonnie Zwaigenbaum
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
Permanent Leadless Cardiac Pacemaker Therapy
Authors: Fleur V.Y. Tjong, Vivek Y. Reddy
Journal: Circulation (2017)

A new technology, leadless pacemaker therapy, was recently introduced clinically to address lead- and pocket-related complications in conventional transvenous pacemaker therapy. These leadless devices are self-contained right ventricular single-chamber pacemakers implanted by using a femoral percutaneous approach. In this review of available clinical data on leadless pacemakers, early results with leadless devices are compared with historical results with conventional single-chamber pacing. Both presently manufactured leadless pacemakers show similar complications, which are mostly related to the implant procedure: cardiac perforation, device dislocation, and femoral vascular access site complications. In comparison with conventional transvenous single-chamber pacemakers, slightly higher short-term complication rates have been observed: 4.8% for leadless pacemakers versus 4.1% for conventional pacemakers. The complication rate of the leadless pacemakers is influenced by the implanter learning curve for this new procedure. No long-term outcome data are yet available for the leadless pacemakers. Larger leadless pacing trials, with long-term follow-up and direct randomized comparison with conventional pacing systems, will be required to define the proper clinical role of these leadless systems. Although current leadless pacemakers are limited to right ventricular pacing, future advanced, communicating, multicomponent systems are expected to expand the potential benefits of leadless therapy to a larger patient population.
TCTAP A-018 Rapid Inhibition of Platelet Aggregation with Loading Doses of 20 mg Prasugrel Versus 300 mg Clopidogrel in Japanese Acute Myocardial Infarction Patients
Authors: Ryo Yoshioka, Atsushi Hirohata, Keizo Yamamoto, Kiyotaka Tohgi, Toshinobu Yoshida, Toru Yoshioka
Journal: Journal of the American College of Cardiology (2017)
Early Post-Transplant Epigenetic Therapy By Panobinostat and Decitabine Followed By Donor Lymphocyte Infusion (DLI): Interim Results of the HOVON-116 Phase I/II Feasibility Study in Poor-Risk AML Recipients of Allogeneic Stem Cell Transplantation (alloHSCT)
Authors: Jan J. Cornelissen, Yvette van Norden, Michel van Gelder, Dimitri A. Breems, Johan Maertens, Mojca Jongen-Lavrencic, Annoek Broers, Sacha S. Zeerleder, Lucien Noens, Gert Ossenkoppele, Ellen Meijer
Journal: Blood (2016)
Factors associated with high-volume providers of stereotactic radiation therapy for Medicare beneficiaries in 2012.
Authors: Sean Maroongroge, Henry S. Park, Charles E. Rutter, Roy H. Decker, James B. Yu
Journal: Journal of Clinical Oncology (2015)

e17578 Background: Stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS are highly effective methods of radiation delivery that have gained increasing attention for multiple clinical indications. We used 2012 Medicare billing data to characterize the prevalence of SBRT/SRS utilization by radiation oncologists for Medicare patients and to determine the relative effect of provider and county characteristics on SBRT/SRS utilization. Methods: We performed a cross-sectional study of providers listed as Radiation Oncologists in the 2012 Centers for Medicare & Medicaid Provider Utilization and Payment database. We linked this dataset with provider-level covariates from the 2014 Physician Compare dataset and county-level covariates from the Area Health Resources File. Our outcome of interest was whether a provider billed for a SBRT/SRS-specific CPT code on > 10 Medicare Part B beneficiaries during 2012. Covariates included provider-level characteristics such as gender, years of experience, and county-level sociodemographic and competition measures. We performed summary statistics and a logistic regression to determine odds ratios for characteristics affecting SBRT/SRS use at the provider level. Results: Of the 3,785 radiation oncologists in our sample, 547 (14.5%) billed for SBRT/SRS on > 10 Medicare Part B patients in 2012. The number of decades since residency graduation (OR 0.80 [95% CI 0.74-0.88], p < 0.001), male gender (OR 1.84, [95% CI 1.45-2.34], p < 0.001) and practicing in a metro county (OR 2.75 [95% CI 1.53-4.93], p = 0.001) were all significantly associated with high-volume SBRT/SRS. Conclusions: Our findings suggest that a small minority of radiation oncologists are performing > 10 stereotactic radiation therapy procedures in the Medicare population. High-volume SBRT/SRS is more likely to be performed by physicians who finished training more recently, are male, and are working in metro counties. We hypothesize that graduation year may be associated with SBRT/SRS adoption due to cost and training barriers of adopting new modalities. Further studies should focus on the accessibility of stereotactic radiation therapy for Medicare beneficiaries.
Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025
Authors: Bernard Escudier, Robert J. Motzer, Padmanee Sharma, John Wagstaff, Elizabeth R. Plimack, Hans J. Hammers, Frede Donskov, Howard Gurney, Jeffrey A. Sosman, Pawel G. Zalewski, Ulrika Harmenberg, David F. McDermott, Toni K. Choueiri, Martin Richardet, Yoshihiko Tomita, Alain Ravaud, Justin Doan, Huanyu Zhao, Helene Hardy, Saby George
Journal: European Urology (2017)
Cutaneous Toxicity Induced by Hibiscus Tea in a Patient Treated with Erlotinib
Authors: Claire Jacquin-Porretaz, Charlée Nardin, Dominique Blanc, François Aubin, Blandine Gérard, Christine Drobacheff-Thiebaut, Pascale Jacoulet, Virginie Westeel
Journal: Journal of Thoracic Oncology (2017)
LAV-BPIFB4 isoform modulates eNOS signalling through Ca2+/PKC-alpha-dependent mechanism
Authors: Chiara Carmela Spinelli, Albino Carrizzo, Anna Ferrario, Francesco Villa, Antonio Damato, Mariateresa Ambrosio, Michele Madonna, Giacomo Frati, Sergio Fucile, Miriam Sciaccaluga, Mario Capunzo, Gaetano Calì, Luciano Milanesi, Anna Maciag, Annibale Alessandro Puca, Carmine Vecchione
Journal: Cardiovascular Research (2017)

Ageing is associated with impairment of endothelial nitric oxide synthase (eNOS) and progressive reduction in endothelial function. A genetic study on long-living individuals—who are characterized by delays in ageing and in the onset of cardiovascular disease—previously revealed I229V (rs2070325) in bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) as a longevity-associated variant (LAV); the LAV protein enhanced endothelial NO production and vasorelaxation through a protein kinase R–like endoplasmic reticulum kinase/14-3-3/heat shock protein 90 signal. Here, we further characterize the molecular mechanisms underlying LAV-BPIFB4-dependent enhancement of vascular function. LAV-BPIFB4 upregulated eNOS function via mobilization of Ca2+ and activation of protein kinase C alpha (PKCα). Indeed, the overexpression of LAV-BPIFB4 in human endothelial cells enhanced ATP-induced Ca2+ mobilization and the translocation of PKCα to the plasma membrane. Coherently, pharmacological inhibition of PKCα blunted the positive effect of LAV-BPIFB4 on eNOS and endothelial function. In addition, although LAV-BPIFB4 lost the ability to activate PKCα and eNOS in ex vivo vessels studied in an external Ca2+-free medium and in vessels from eNOS−/− mice, it still potentiated endothelial activity, recruiting an alternative mechanism dependent upon endothelium-derived hyperpolarizing factor (EDHF). We have identified novel molecular determinants of the beneficial effects of LAV-BPIFB4 on endothelial function, showing the roles of Ca2+ mobilization and PKCα in eNOS activation and of EDHF when eNOS is inhibited. These results highlight the role LAV-BPIFB4 can have in restoring signals that are lost during ageing.
Analysis of an electrical impedance spectroscopy system in short‐term digital dermoscopy imaging of melanocytic lesions
Authors: L. Rocha, S.W. Menzies, S. Lo, M. Avramidis, R. Khoury, L. Jackett, P. Guitera
Journal: British Journal of Dermatology (2017)

Electrical impedance spectroscopy (EIS) is a noninvasive diagnostic technique that measures tissue impedance. To evaluate the effect of adding an EIS measurement at baseline to suspicious melanocytic lesions undergoing routine short‐term sequential digital dermoscopy imaging (SDDI). Patients presented with suspicious melanocytic lesions that were eligible for short‐term SDDI (with no clear feature of melanoma on dermoscopy). EIS measurement was performed at the first visit following dermoscopic photography. Normally, an EIS score of ≥ 4 is considered positive; however, this protocol investigated a higher cut‐off in combination with SDDI. When the EIS score was ≥ 7 the lesion was excised immediately owing to the high risk of melanoma. Lesions with a score < 7 were monitored with standard SDDI over a 3‐month period. From a total of 160 lesions analysed, 128 of 154 benign lesions received an EIS score of 0–6, giving a specificity of the EIS method for the diagnosis of melanoma of 83·1% [95% confidence interval (CI) 76·3–88·7]. Five of the six melanomas found in this study had an EIS score ≥ 7, with a sensitivity for melanoma diagnosis of 83·3% (95% CI 35·9–99·6). When EIS 0–6 lesions were subsequently followed up with SDDI, one additional melanoma was detected (EIS = 6) giving a sensitivity for the diagnosis of melanoma overall of 100% (95% CI 54·1–100; six of six malignant melanomas excised) and a specificity of 69·5% (95% CI 61·5–76·6; 107 of 154 benign lesions not excised). If utilizing a protocol where an EIS score ≤ 3 requires no SDDI and ≥ 7 requires immediate excision, it reduced the need for SDDI by 46·9% (n = 75/160; 95% CI 39·0–54·9).
TCTAP C-054 Endovascular Entry Closure of Aortic Dissection with Amplatzer Vascular Plug 2
Authors: Yosuke Hata, Osamu Iida, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Takuya Tsujimura, Shota Okuno, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2017)
National approach to OTC prescribing is needed
Authors: David Phizackerley
Journal: BMJ (2017)

Iacobucci’s article highlights the challenges facing clinical commissioning groups (CCGs) as they attempt to save money by restricting GP prescribing of over-the-counter (OTC) medicines.1 Concerns over this piecemeal approach to cost saving were also highlighted in an editorial in the Drug and Therapeutics Bulletin .2

For commissioning new medicines, national guidance …
Registry of implants for the reconstruction of pelvic floor in males and females: A feasibility case series
Authors: Dimitri Barski, Holger Gerullis, Thorsten Ecke, Jennifer Kranz, Laila Schneidewind, Nadine Leistner, Fabian Queissert, Sandra Mühlstädt, Markus Grabbert, Rana Tahbaz, Alexandre Egon Pelzer, Ralf Joukhadar, Uwe Klinge, Mihaly Boros, Werner Bader, Gert Naumann, Frank Puppe, Thomas Otto
Journal: International Journal of Surgery (2017)
Determinants of reflux-induced chronic cough
Authors: Thomas V K Herregods, Ans Pauwels, Jafar Jafari, Daniel Sifrim, Albert J Bredenoord, Jan Tack, André J P M Smout
Journal: Gut (2017)

Objective Gastro-oesophageal reflux is considered to be an important contributing factor in chronic unexplained cough. It remains unclear why some reflux episodes in the same patient causes cough while others do not. To understand more about the mechanism by which reflux induces cough, we aimed to identify factors which are important in triggering cough. Design In this multicentre study, 49 patients with reflux-associated chronic cough were analysed using 24-hour pH-impedance-pressure monitoring. The characteristics of reflux episodes that were followed by cough were compared with reflux episodes not associated with cough. Results The majority (72.4%) of the reflux episodes were acidic (pH&lt;4). Compared with reflux episodes that were not followed by cough, reflux episodes that were followed by a cough burst were associated with a higher proximal extent (p=0.0001), a higher volume clearance time (p=0.002) and a higher acid burden in the preceding 15 min window (p=0.019) and higher reflux burden in the preceding 30 min window (p=0.044). No significant difference was found between the two groups when looking at the nadir pH, the pH drop, the acid clearance time or the percentage of reflux episodes which were acidic. Conclusions The presence of a larger volume of refluxate and oesophageal exposure to reflux for a longer period of time seems to play an important role in inducing cough, while the acidity of the refluxate seems to be less relevant. This helps explain the observation that most patients with chronic cough tend not to benefit from acid inhibitory treatment.
A Critical Role of MyD88 Signaling in Donor T Cells for Graft-Versus-Host Disease (GVHD) and Graft-Versus-Leukemia Effect (GVL) After Experimental Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)
Authors: Ji-Young Lim, Dae-Chul Jeong, Hyewon Youn, Eun-Young Choi, Chang-Ki Min
Journal: Blood (2012)
A new cascade of HIV care for the era of “treat all”
Authors: Matthew P. Fox, Sydney Rosen
Journal: PLoS Medicine (2017)

Now that the World Health Organization has recommended antiretroviral therapy for all people infected with HIV regardless of their CD4 count, millions more people will become eligible for HIV treatment.• We and others have previously described the cascade of care for HIV treatment for monitoring retention in care and targeting interventions to improve retention to areas of greatest need.• To inform research and track progress, we propose a new cascade for the "treat all" policy that effectively removes the pretreatment waiting period.• Current data on retention through each stage of care will have limited value under this new cascade, as some stages will no longer exist while others will include patients who were previously not eligible.• New data are needed to parameterize the care cascade under the "treat all" policy, and new interventions will be needed to improve retention across the new cascade.
TCTAP C-113 Not All Those Who Wander Are Lost
Authors: Dharmaraj Karthikesan, Kantha Rao Narasamuloo, Kai Soon Liew, Ahmad Faiz Mohd Ezanee, Gerard Jason Mathews, Yi Zhi Cheng, Ahmad Shukri Saad, Wan Faizal Bin Wan Rahimi Shah, Huan Yean Kang, Saravanan Krishinan, Chee Tat Liew
Journal: Journal of the American College of Cardiology (2017)