tbuckley/cabot-search huggingface dataset:
Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction Intervals
Authors: Elizabeth L. Yanik, Christina A. Clarke, Jon J. Snyder, Ruth M. Pfeiffer, Eric A. Engels
Journal: Journal of the American Society of Nephrology (2015)

Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin’s lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin’s lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin’s lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention.
AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC)
Authors: B. Rini, O. Rixe, R. Bukowski, M. D. Michaelson, G. Wilding, G. Hudes, O. Bolte, H. Steinfeldt, S. D. Reich, R. Motzer
Journal: Journal of Clinical Oncology (2005)

4509 Background: Clear cell renal carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau tumor suppressor gene, which leads to overexpression of hypoxia-regulated genes including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). AG-013736 is an oral small molecule with potent inhibitory effects against the VEGF receptors 1 and 2 and PDGF-β receptor. A phase 2 trial was conducted to assess the safety and efficacy of AG-013736 in cytokine-refractory RCC. Methods: Patients (pts) with metastatic RCC were treated with repeat 4-week cycles of AG-013736 at 5 mg twice daily. Eligibility included measurable disease, ECOG performance status (PS) of 0 or 1 and failure of one prior cytokine-based therapy. A Simon 2 stage minimax design was used (α=0.05; β=0.2; null response rate (RR)=5%; alternative RR=15%). Results: The median age of 52 enrolled pts was 58.5 (35–85) years, 40 (77%) were men, 49 (94%) had prior nephrectomy and 31 (60%) had PS 0. Best response as assessed by RECIST criteria was PR in 21 pts. (40%) (95% confidence interval: 27.0–54.9%). With a median follow up of 1 year (235–387 days), 13 pts (25%) have progressed, 3 (6%) have discontinued for adverse events (AEs) and 36 (69%) remain on study with response or stable disease. Median time to progression has not been reached, and only 1 patient with PR has relapsed (after 232 days of therapy). Drug-related hypertension (htn), controlled by standard therapy, was observed in 17 pts (33%), and 1 pt was discontinued for worsening htn. Other related AEs were mostly grade 1/2 events including fatigue (29%), nausea (29%), diarrhea (27%), hoarseness (19%), anorexia (17%) and weight loss (15%). Grade 3/4 AEs related to AG-013736 in >1 pt. include htn (12%), aggravated htn (6%), diarrhea (6%), fatigue (6%), blister (4%) and limb pain (4%). There were no cases of neutropenia or thrombocytopenia above grade 1. Conclusions: AG-013736 has a substantial objective response rate in cytokine-refractory, metastatic RCC. Therapy was well tolerated with manageable toxicity. Additional investigation of AG-013736 in multiple solid tumor settings is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Children With Acute Lymphoblastic Leukemia Who Receive T-Cell–Depleted HLA Mismatched Marrow Allografts From Unrelated Donors Have an Increased Incidence of Primary Graft Failure but a Similar Overall Transplant Outcome
Authors: Ann Green, Emer Clarke, Linda Hunt, Andrew Canterbury, Alan Lankester, Geoff Hale, Herman Waldmann, Sally Goodman, Jacqueline M. Cornish, David I. Marks, Colin G. Steward, Anthony Oakhill, Derwood H. Pamphilon
Journal: Blood (1999)
Abstract 16151: Acute Kidney Injury is a Powerful and an Independent Determinant of In-Hospital Mortality in Patients Undergoing Percutaneous Coronary Interventions
Authors: Judith Kooiman, Milan Seth, Brahmajee K Nallamothu, Michael Heung, David Humes, Hitinder S Gurm
Journal: Circulation (2014)

Introduction: Acute kidney injury (AKI) is a common complication of percutaneous coronary intervention (PCI) and is associated with increased mortality. Previous studies analysing mortality risk in patients with AKI were hampered by common risk factors for both outcomes. The aim of our study was to analyse the association between AKI and in-hospital mortality post PCI after adjustment for confounding by common risk factors. Methods: This study was performed using data from a regional registry of patients undergoing PCI in the state of Michigan. The primary endpoints were AKI and all-cause in-hospital mortality. Propensity matching was performed, with each AKI patient matched to four controls. Attributive risk (AR) and the exposed impact number of AKI for mortality were calculated in the propensity-matched cohort. Results: Between January 2009 and June 2013, 92,317 patients were included, of whom 2,141(2.3%) developed AKI. We matched 1,371/2,141 patients with AKI to 5,484 controls. AKI was strongly associated with mortality (OR = 12.52, 95% CI 9.29 - 16.86, p &lt; 0.0001) after adjustment for baseline covariates in the propensity-matched cohort. The association between AKI and mortality was present in all subgroups and strata of baseline AKI-risk (Figure 1). The estimated AR for mortality of AKI was 31.4% (95% CI 26.8% - 37.5%). Among matched patients with AKI, one death could be prevented for every 9 cases of AKI successfully eliminated. Conclusion: Our results indicate that AKI attributes to nearly one-third of the in-hospital mortality post PCI. Preventing nine cases of AKI could potentially prevent one death. These study findings stress the need for highly effective AKI preventive strategies.
Five-Year Survival in EGFR -Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs
Authors: Jessica J. Lin, Stephanie Cardarella, Christine A. Lydon, Suzanne E. Dahlberg, David M. Jackman, Pasi A. Jänne, Bruce E. Johnson
Journal: Journal of Thoracic Oncology (2015)
Mandatory submission of patient identifiable information to third parties: FGM now, what next?
Authors: Susan Bewley, Brenda Kelly, Katrina Darke, Katrina Erskine, Clare Gerada, Patricia Lohr, Paquita de Zulueta
Journal: BMJ (2015)

The government has done much to tackle female genital mutilation (FGM),1 2 3 but the planned rollout of FGM Enhanced Data Collection across the NHS in October 2015 is ill considered. All healthcare professionals will be legally obliged to submit highly sensitive, patient identifiable information on every woman with FGM attending the NHS for whatever reason. A woeful consultation preceded the ministerial direction, which also says patient consent is not …
Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer
Authors: Bruce Montgomery, Mario A. Eisenberger, Matthew B. Rettig, Franklin Chu, Roberto Pili, Joseph J. Stephenson, Nicholas J. Vogelzang, Alan J. Koletsky, Luke T. Nordquist, William J. Edenfield, Khalid Mamlouk, Karen J. Ferrante, Mary-Ellen Taplin
Journal: Clinical Cancer Research (2015)

Galeterone is a selective, multitargeted agent that inhibits CYP17, antagonizes the androgen receptor (AR), and reduces AR expression in prostate cancer cells by causing an increase in AR protein degradation. These open-label phase I and II studies [Androgen Receptor Modulation Optimized for Response-1 (ARMOR1) and ARMOR2 part 1] evaluated the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC) and established a dose for further study.In ARMOR1, 49 patients received increasing doses (650-2,600 mg) of galeterone in capsule formulation; 28 patients in ARMOR2 part 1 received increasing doses (1,700-3,400 mg) of galeterone in tablet formulation for 12 weeks. Patients were evaluated biweekly for safety and efficacy, and pharmacokinetic parameters were assessed.In ARMOR1, across all doses, 49.0% (24/49) achieved a ≥30% decline in prostate-specific antigen (PSA; PSA30) and 22.4% (11/49) demonstrated a ≥50% PSA decline (PSA50). In ARMOR2 part 1, across all doses, PSA30 was 64.0% (16/25) and PSA50 was 48.0% (12/25). In the 2,550-mg dose cohort, PSA30 was 72.7% (8/11) and PSA50 was 54.5% (6/11). Galeterone was well tolerated; the most common adverse events were fatigue, increased liver enzymes, gastrointestinal events, and pruritus. Most were mild or moderate in severity and required no action and there were no apparent mineralocorticoid excess (AME) events.The efficacy and safety from ARMOR1 and ARMOR2 part 1 and the pharmacokinetic results support the galeterone tablet dose of 2,550 mg/d for further study. Galeterone was well tolerated and demonstrated pharmacodynamic changes consistent with its selective, multifunctional AR signaling inhibition.
Surgical Guidance in Prostate Cancer: “From Molecule to Man” Translations
Authors: Fijs W.B. van Leeuwen, Henk G. van der Poel
Journal: Clinical Cancer Research (2015)

Given the frequency of the disease and the difficulty of tumor resections, image-guided surgery technologies may aid the surgical management of prostate cancer patients. The "from molecule to man" translation of such approaches is, however, complex and depends on many different features, both from a technical and a practical perspective.
Redefining the issues in fetal experimentation
Authors: E. F. Diamond
Journal: JAMA (1976)

THERE has been a crisis of public confidence ( Marriage and Family Newsletter , January 1972, pp 1-8) in the medical profession generated in this country by the performance of vivisection-type experiments on live aborted fetuses 1 and highly questionable therapeutic trials involving institutionalized mentally defective children. 2,3 Very few investigators and a small number of studies are involved. Measures to prevent a recurrence of abuses are appropriate, but the response of the medical profession to attempts to establish guidelines has been hyperbolic, and overblown, and inconsistent with the profession's crucial responsibility to patient advocacy.  The issue has never been whether research would be conducted but how it would be conducted. Research is not necessarily deterred by restrictive guidelines. It is quite possible that research as a whole would be advanced if the public were reassured that no further abuses would be tolerated ( News & Comment 25:8, 1974).  Much of what has
Immunology of protection from Ebola virus infection
Authors: Philip R. Krause, Paula R. Bryant, Thomas Clark, Walla Dempsey, Erik Henchal, Nelson L. Michael, Jason A. Regules, Marion F. Gruber
Journal: Science Translational Medicine (2015)

A December 2014 meeting reviewed Ebola virus immunology relevant to vaccine development, including Ebola prevention, immunity, assay standardization, and regulatory considerations. Vaccinated humans appear to achieve immune responses comparable in magnitude with those associated with protection in nonhuman primates, suggesting that immunological data could be used to demonstrate vaccine efficacy.
Integrative miRNA and whole-genome analyses of epicardial adipose tissue in patients with coronary atherosclerosis
Authors: Michele Vacca, Marco Di Eusanio, Marica Cariello, Giusi Graziano, Simona D'Amore, Francesco Dimitri Petridis, Andria D'orazio, Lorena Salvatore, Antonio Tamburro, Gianluca Folesani, David Rutigliano, Fabio Pellegrini, Carlo Sabbà, Giuseppe Palasciano, Roberto Di Bartolomeo, Antonio Moschetta
Journal: Cardiovascular Research (2015)

BackgroundEpicardial adipose tissue (EAT) is an atypical fat depot surrounding the heart with a putative role in the development of atherosclerosis.
Abstract 16767: Exosomes Mediate Heat Shock Protein 27 Athero-Protective Signalling
Authors: Chunhua Shi, Yuan Zhang, Yongxiang Chen, Edward R O’Brien
Journal: Circulation (2014)

Introduction: Exosomes represent a discrete population of nano-vesicles secreted by a variety of cells and may contain unique protein cargo that play a role in inter-cellular signalling. We previously showed (ATVB 2009, JACC 2013) that membrane-like vesicles mediate the release of the novel biomarker and athero-protective agent, Heat Shock Protein 27 (HSP27), however did not explore downstream signalling effects of HSP27-laden exosomes. Hypothesis: Monocyte derived exosomes facilitate the transfer of HSP27 to human aortic endothelial cells (HAEC) and THP-1 MΦ to elicit athero-protective signalling effects. Methods: Exosome particles were purified from conditioned medium of THP-1 monocytes. As we previously showed that HSP27 athero-protection involves activation of NF-kB (e.g., with resultant changes in the expression of key athero-protective genes) we sought to determine if exosomes alter NF-kB signalling, as well as augment the internalization of HSP27 into cells as a cell membrane receptor for HSP27 is yet to be established. Results: Purified THP-1 derived exosomes express the classical exosome biomarkers CD81 and MHC-II. Flow cytometry revealed that 18% and 23% of these exosomes are positive for HSP27 immunolabeling with 10 and 40 μg/ml anti-Hsp27-FITC, respectively. The fraction of positive exosomes dropped to 3% when 40 μg/ml of recombinant HSP27 (rHSP27) was co-mixed with these samples and 10 μg/ml anti-HSP27-FITC, thereby confirming immunolabeling specificity. In contrast, a FITC labeled truncated form of the C-terminus of HSP27 (referred to as rC1-FITC) did not bind to exosomes. Indeed, exogenous rHSP27 bound to exosomes potentiated a ~50% increase of triggered NF-κB signalling (p&lt;0.001) in THP-1 MΦ containing an alkaline phosphatase NF-kB reporter construct, while the truncated form of HSP27 (or rC1) did not (p=0.56). In both THP-1 MΦ and HAEC internalization of rHSP27-FITC into cells improved dramatically after exosome binding (e.g., THP-1: 157% increase, p&lt;0.0001), while rC1-FITC had no effect. Conclusion: Exosomes contain HSP27 cargo that provide a novel inter-cellular signalling mechanism for the athero-protective effects of HSP27 by activating NF-kB and facilitating HSP27 internalization into cells.
Abstract OI-1: Origin of Metastatic Traits in Breast Cancer
Authors: Yibin Kang
Journal: Cancer Research (2015)

Abstract Metastasis represents the most devastating stage of cancer progression and is responsible for most of cancer-related death. How and when breast cancer cells acquire metastatic traits is a topic of intense investigation and debate in the field. It has become clear that the development of metastatic capability in cancer cells is a continuous process that is shaped by the tissue of origin of the primary tumor, early oncogenic events, as well as the stresses tumor cells endure when they encounter different microenvironments and therapeutic treatments. Many genes play multiple functions during primary tumorigenesis and metastatic progression, and may represent ideal targets for therapeutic intervention. In this lecture, I will discuss some latest findings in our understanding of the origin and evolution of metastasis traits in breast cancer, with emphasis on the connection of metastasis genes to early events of tumor initiation. Citation Format: Yibin Kang. Origin of Metastatic Traits in Breast Cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OI-1.
Assessing the Patient Care Implications of “Concierge” and Other Direct Patient Contracting Practices: A Policy Position Paper From the American College of Physicians
Authors: Robert Doherty
Journal: Annals of Internal Medicine (2015)

As physicians seek innovative practice models, one that is gaining ground is for practices to contract with patients to pay directly for some or all services—often called cash-only, retainer, boutique, concierge, or direct primary care or specialty care practices. Such descriptions do not reflect the variability found in practices. For the purposes of this paper, the American College of Physicians (ACP) defines a direct patient contracting practice (DPCP) as any practice that directly contracts with patients to pay out-of-pocket for some or all of the services provided by the practice, in lieu of or in addition to traditional insurance arrangements, and/or charges an administrative fee to patients, sometimes called a retainer or concierge fee, often in return for a promise of more personalized and accessible care. This definition encompasses the practice types previously described. The move to DPCPs is based on the premise that access and quality of care will be improved without third-party payers imposing themselves between the patient and the physician. Yet concerns have been raised that DPCPs may cause access issues for patients who cannot afford to pay directly for care. This ACP position paper, initiated and written by its Medical Practice and Quality Committee and approved by the Board of Regents on 25 July 2015, assesses the impact of DPCPs on access, cost, and quality; discusses principles from the ACP Ethics Manual, Sixth Edition, that should apply to all practice types; and makes recommendations to mitigate any adverse effect on underserved patients.
Obesity-Related Medical Care Costs Medicaid $8 Billion a Year
Authors: Julie A. Jacob
Journal: JAMA (2015)

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
Senate committee inquiry into drug price hikes will continue despite arrest of hedge fund manager Shkreli
Authors: Owen Dyer
Journal: BMJ (2015)

The arrest for securities fraud of Martin Shkreli, 32, who became the boyish face of drug industry greed this summer when his firm Turing Pharmaceuticals bought the generic toxoplasmosis treatment pyrimethamine (Daraprim) and raised the price by 5000% overnight,1 has been greeted with jubilation not just by the public but by an industry that had rapidly come to see Shkreli as a major public relations problem.

Shkreli is accused of embezzling $11m (£7.4m; €10.1m) from Retrophin Inc, a biotechnology firm that he founded in 2011, to pay back investors in “Ponzi-like schemes” involving his two hedge funds. He posted $5m bail and protested his innocence through a spokesman.

Under Shkreli’s leadership Retrophin had also engaged in generic drug price hiking, raising the cost …
Glycogen Synthase Kinase 3 Beta Predicts Survival in Resected Adenocarcinoma of the Pancreas
Authors: Edgar Ben-Josef, Asha George, William F. Regine, Ross Abrams, Meredith Morgan, Dafydd Thomas, Paul L. Schaefer, Thomas A. DiPetrillo, Mitchel Fromm, William Small, Samir Narayan, Kathryn Winter, Kent A. Griffith, Chandan Guha, Terence M. Williams
Journal: Clinical Cancer Research (2015)

GSK3β is a protein kinase that can suppress a number of key oncoproteins. We have previously shown in preclinical models of pancreatic ductal adenocarcinoma (PDAC) that inhibition of GSK3β causes stabilization and nuclear translocation of β-catenin, poor differentiation, proliferation, and resistance to radiation. The objective of this study was to determine its utility as a biomarker of clinical outcomes.Automated Quantitative Immunofluorescence Analysis (AQUA) of GSK3β was performed on a tissue microarray with samples from 163 patients treated on RTOG 9704. On the basis of findings in an exploratory cohort, GSK3β was analyzed as a categorical variable using its upper quartile (>Q3) as a cut point. Overall survival (OS) and disease-free survival (DFS) were estimated with the Kaplan-Meier method, and GSK3β groupings were compared using the log-rank test. Univariable and multivariable Cox proportional hazards models were used to determine associations between GSK3β and OS/DFS.The 3-year OS rates for GSK3β≤Q3 versus GSK3β >Q3 were 16% (95% confidence intervals; CI, 10%-23%) and 30% (95% CI, 17%-44%), respectively, P = 0.0082. The 3-year DFS rates were 9% (95% CI, 5%-15%) and 20% (95% CI, 9%-33%) respectively, P value = 0.0081. On multivariable analysis, GSK3β was a significant predictor of OS. Patients with GSK3β >Q3 had a 46% reduced risk of dying of pancreatic cancer (HR, 0.54; 95% CI, 0.31-0.96, P value = 0.034). The HR for DFS was 0.65 (95% CI, 0.39-1.07; P value = 0.092).GSK3β expression is a strong prognosticator in PDAC, independent of other known factors such as tumor (T) stage, nodal status, surgical margins and CA19-9. Clin Cancer Res; 21(24); 5612-8. ©2015 AACR.
Transfers from a general hospital psychiatric service to a state hospital
Authors: P G Cotton, A Bené-Kociemba, S Roses
Journal: American Journal of Psychiatry (1980)

The authors investigated the marked decline in the number of patients transferred from an inpatient service of a general hospital to a state hospital during a 30-month period. The major reasons for transfer were unmanageable behavior, high risk of suicide or homicide, administrative considerations, and unremitting or deteriorating course. They found that administrative concern about three factors--the many problems of patients likely to be transferred, staff anxiety, and the relationship between the general hospital and state hospital units--can facilitate the decline in the number of patients transferred to a state hospital.