tbuckley/cabot-search huggingface dataset:
Informed Consent and the Reasonable-Patient Standard—Reply
Authors: Erica S. Spatz, Harlan M. Krumholz, Benjamin W. Moulton
Journal: JAMA (2016)

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
Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma
Authors: Huan Liu, Zhiqiang Liu, Juan Du, Jin He, Pei Lin, Behrang Amini, Michael W. Starbuck, Nora Novane, Jatin J. Shah, Richard E. Davis, Jian Hou, Robert F. Gagel, Jing Yang
Journal: Science Translational Medicine (2016)

Myeloma-expressed thymidine phosphorylase enhances bone lesion formation by acting on osteoclasts and osteoblasts.
Breast cancer in very young Pakistani women at a cancer hospital in Lahore
Authors: N. Siddiqui, M. K. Siddique, I. A. Muazzam, R. Faiz, N. Anwar, F. Badar
Journal: Journal of Clinical Oncology (2008)

11596 Background: Young breast cancer patients reported to have more advanced disease presenting with larger tumor size, more lymph node involvement and higher local recurrence rates. We studied the tumor characteristics, treatment given, relapse rate in breast cancer patients of our institution. Methods: Between 1994 and 2002, 2,322 breast cancer patients were registered at Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore (Pakistan). Their records were reviewed from a retrospectively collected database. Patients were divided into two groups: those ≤35 years and those >35 years. Tumor characteristics measured were size, lymph node status and stage (TNM staging). Treatment given was also reviewed. Outcome measures included local and distant disease relapse. Results: At presentation, 1,883 breast cancer women were above 35 years of age while very young patients were 439 patients. Distribution of patient having tumor size ≤2cm (24% vs. 25%), node negative disease (30% vs. 32.0%) and stage I tumor (8% vs. 9%) were similar in both younger and older groups. Younger women underwent more lumpectomies (51% vs. 39%) while mastectomies were performed more frequently in older women (60.91% vs. 47.60%). Most patients younger than 35 years were treated with standard chemotherapy (91% vs. 81%) and radiation therapy (66% vs. 58%). Among 2,322 patients, 893 were lost to follow up. Both young and old patients had similar local relapse (20.55% vs. 17.08%) and recurrence with distant metastasis (20.14% vs. 17.82%). Death was recorded in 175 patients (19.3% young; 12.08% old). The survival distributions were not found to be significantly different between the age groups. Conclusions: In contrast to most studies, our hospital data shows no significant difference in baseline tumor characteristics, local disease relapse and distant metastasis in both younger and older breast cancer patients. Among our young and the older breast cancer patients treated, outcome measures were also similar in both groups of women. No significant financial relationships to disclose.
HIV Infection and Survival Among Women With Cervical Cancer
Authors: Scott Dryden-Peterson, Memory Bvochora-Nsingo, Gita Suneja, Jason A. Efstathiou, Surbhi Grover, Sebathu Chiyapo, Doreen Ramogola-Masire, Malebogo Kebabonye-Pusoentsi, Rebecca Clayman, Abigail C. Mapes, Neo Tapela, Aida Asmelash, Heluf Medhin, Akila N. Viswanathan, Anthony H. Russell, Lilie L. Lin, Mukendi K.A. Kayembe, Mompati Mmalane, Thomas C. Randall, Bruce Chabner, Shahin Lockman
Journal: Journal of Clinical Oncology (2016)

Purpose Cervical cancer is the leading cause of cancer death among the 20 million women with HIV worldwide. We sought to determine whether HIV infection affected survival in women with invasive cervical cancer. Patients and Methods We enrolled sequential patients with cervical cancer in Botswana from 2010 to 2015. Standard treatment included external beam radiation and brachytherapy with concurrent cisplatin chemotherapy. The effect of HIV on survival was estimated by using an inverse probability weighted marginal Cox model. Results A total of 348 women with cervical cancer were enrolled, including 231 (66.4%) with HIV and 96 (27.6%) without HIV. The majority (189 [81.8%]) of women with HIV received antiretroviral therapy before cancer diagnosis. The median CD4 cell count for women with HIV was 397 (interquartile range, 264 to 555). After a median follow-up of 19.7 months, 117 (50.7%) women with HIV and 40 (41.7%) without HIV died. One death was attributed to HIV and the remaining to cancer. Three-year survival for the women with HIV was 35% (95% CI, 27% to 44%) and 48% (95% CI, 35% to 60%) for those without HIV. In an adjusted analysis, HIV infection significantly increased the risk for death among all women (hazard ratio, 1.95; 95% CI, 1.20 to 3.17) and in the subset that received guideline-concordant curative treatment (hazard ratio, 2.63; 95% CI, 1.05 to 6.55). The adverse effect of HIV on survival was greater for women with a more-limited stage cancer ( P = .035), those treated with curative intent ( P = .003), and those with a lower CD4 cell count ( P = .036). Advanced stage and poor treatment completion contributed to high mortality overall. Conclusion In the context of good access to and use of antiretroviral treatment in Botswana, HIV infection significantly decreases cervical cancer survival.
Complementing T-cell Function: An Inhibitory Role of the Complement System in T-cell–Mediated Antitumor Immunity
Authors: Weiyi Peng, Jodi A. McKenzie, Patrick Hwu
Journal: Cancer Discovery (2016)

Abstract Summary: New data from Wang and colleagues show that complement C3 suppresses the function of CD8+ tumor-infiltrating T cells by inhibiting IL10 production, and targeting the complement receptors C3aR and C5aR enhances the antitumor activity of immune checkpoint blockade. Their results not only define a new role of complement receptors as T-cell coinhibitory receptors, but also are useful in the development of novel strategies to improve the effectiveness of cancer immunotherapy. Cancer Discov; 6(9); 953–5. ©2016 AACR. See related article by Wang et al., p. 1022.
Estrogen receptor (ER)β expression and worse outcome from melanoma in pregnant and perimenopausal women
Authors: Alessia Gori, Imma Savarese, Antonietta D'Errico, Marta Grazzini, Federica Papi, Vincenza Maio, Piero Covarelli, Daniela Massi, Sara Gandini, Vincenzo De Giorgi
Journal: Journal of the American Academy of Dermatology (2016)
NICE recommends ticagrelor with aspirin for three years post-MI
Authors: Jacqui Wise
Journal: BMJ (2016)

Patients who have had a myocardial infarction (MI) should be given a low dose of the anti-clotting drug ticagrelor (Brilique) together with aspirin for as long as three years, new draft guidance from the National Institute for Health and Care Excellence (NICE) says.1

Most centres in the United Kingdom already use a higher (90 mg) dose of ticagrelor in combination with aspirin for as long as 12 months as first line management …
P2X7 Receptor Activation By ATP As Target of Novel Therapies in Acute Myeloid Leukemia
Authors: Valentina Salvestrini, Stefania Orecchioni, Francesca Reggiani, Giovanna Talarico, Elisa Orioli, Elena Adinolfi, Francesco Bertolini, Francesco Di Virgilio, Michele Cavo, Roberto Massimo Lemoli, Antonio Curti
Journal: Blood (2015)
Cardiovascular and death risks are lower if parents live longer, show UK data
Authors: Susan Mayor
Journal: BMJ (2016)

Middle aged people whose parents lived beyond age 70 have a lower all cause mortality rate and lower risk of a wide range of cardiovascular conditions than people whose parents died younger, data from the UK Biobank have shown.

The analysis, reported in the Journal of the American College of Cardiology ,1 included 186 151 non-adopted people whose parents were deceased, who volunteered to take part in the UK Biobank, which collects data on a wide range of health …
Genomic analysis and 3-y efficacy and safety update of COMBI-d: A phase 3 study of dabrafenib (D) + trametinib (T) vs D monotherapy in patients (pts) with unresectable or metastatic <i>BRAF</i> V600E/K-mutant cutaneous melanoma.
Authors: Keith Flaherty, Michael A. Davies, Jean Jacques Grob, Georgina V. Long, Paul D. Nathan, Antoni Ribas, Caroline Robert, Dirk Schadendorf, Dennie T Frederick, Marc R Hammond, Judit Jane-Valbuena, Xinmeng Jasmine Mu, Matthew Squires, Savina A. Jaeger, Stephen R. Lane, Bijoyesh Mookerjee, Levi A. Garraway
Journal: Journal of Clinical Oncology (2016)

9502 Background: Previous analysis of COMBI-d (NCT01584648) showed that D+T compared with D monotherapy improved ORR (69% [95% CI, 62%-75%] vs 53% [95% CI, 46%-60%]; P = 0.0014), reduced risk of progression (HR, 0.67 [95% CI, 0.53-0.84]; P = 0.0004) and death (HR, 0.71 [95% CI, 0.55-0.92]; P = 0.0107), and increased 2-y OS rate (51% vs 42%) in BRAFV600–mutant melanoma. Methods: In this phase 3, randomized, double-blind study, pts with histologically confirmed unresectable stage IIIC or IV, BRAF V600E/K–mutant melanoma were randomized 1:1 to receive frontline D 150 mg twice daily (BID) + T 2 mg once daily or D 150 mg BID only. The primary endpoint was PFS; secondary endpoints were OS, ORR, duration of response, and safety. Whole-exome sequencing was used to assess somatic mutations and copy number changes in pretreatment tumor (mean target coverage [MTC], 170×) and matched normal blood samples (MTC, 100×) collected from > 140 pts to further characterize BRAF V600–mutant melanoma and explore whether individual gene changes or genetic profiles were associated with treatment benefit. Results: A total of 423 pts were randomized to D+T (n = 211) or D (n = 212). As expected, initial genetic analysis of 130 pts showed that BRAF was the most frequently mutated gene (V600E, 83%; V600K, 15%). Additional mutations were observed in genes related to tumor suppression (TP53, PTEN, CDKND2A) and resistance to MAPK pathway inhibition (MEK1, MEK2, NRAS, NF1, RAC1), and amplifications were observed in BRAF and MITF. Overall mutation rate was higher in V600K vs V600E pts (median mutations per sample, 1701 vs 419; P< 0.0001). Updated genomic analysis, including OS and mutation rate association, and efficacy and safety results, including 3-y OS, will be presented. Conclusions: Preliminary genetic analyses showed additional mutations related to tumor suppression and MAPK inhibitor resistance were present in pts with BRAF-mutant melanoma, with a higher overall mutation rate in V600K-mutant tumors. Updated genetic analysis and 3-y efficacy and safety analysis will be presented. Clinical trial information: NCT01584648.
In Patient with Chronic Lymphocytic Leukemia the Overall SURVIVAL Is NOT Different WHEN Analysed by Cause of Death, Related or NOT Related to the Disease
Authors: Luca Laurenti, Francesco Autore, Barbara Vannata, Idanna Innocenti, Francesco Santini, Nicola Piccirillo, Patrizia Chiusolo, Simona Sica, Giuseppe Leone
Journal: Blood (2012)
A pilot study of fosbretabulin with bevacizumab in recurrent high-grade gliomas.
Authors: R. Altaha, M. Almubarak, M. D. Newton, A. Torres-Trejo, G. Marano, G. Hobbs, L. Gibson, W. P. Petros, S. C. Remick
Journal: Journal of Clinical Oncology (2010)

TPS147 Background: Recurrent high-grade gliomas have a very poor prognosis. Bevacizumab, a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), has shown promising results in recent clinical trials and is currently FDA approved for recurrent high-grade gliomas. Fosbretabulin is a novel vascular disrupting agent (VDA) that causes acute occlusion of existing blood vessels, leading to intratumoral necrosis. However, VDA-treated tumors rapidly regrow from a characteristic rim of residual viable cells at the tumor periphery. Addition of bevacizumab will prevent VEGF signaling that restores tumor perfusion through new vessel formation. This combination has been used safely in a phase I study in subjects with advanced solid tumors (Nathan et al, 2007 AACR meeting, Abstract B7). Methods: The primary objective of this single-institution investigator-initiated study is to determine the feasibility and safety of combining fosbretabulin with bevacizumab in patients with high-grade recurrent gliomas after failing first-line treatment of temozolomide chemotherapy and radiation. Eligible patients will be assigned to one of two cohorts sequentially to determine effects on tumor blood flow and optimal sequencing. DCE–MRI brain and Neurolite SPECT will be done at pretreatment (day 0) and between 4-6 hours post fosbretabulin, and repeated 5 days post bevacizumab. The first cohort of 6 patients will receive fosbretabulin 60 mg/m2 IV (Day 1), followed by bevacizumab 10 mg/kg IV 24 hours later (Day 2). The second cohort of 6 patients will receive bevacizumab 10 mg/kg IV (Day 1), followed by fosbretabulin 60 mg/m2 IV 24 hours later (day 2). Additionally, fosbretabulin plasma pharmacokinetics on the two administration schedules and the prognostic value of the level of circulating endothelial progenitor cells (CEPs) in relation to tumor response will be assessed. A secondary objective would be to assess 6-months progression-free survival and objective tumor response in these patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OXiGENE
The Pathogenesis of Disseminated Intravascular Coagulation in Sepsis
Authors: Theodore F. Logan
Journal: JAMA (1994)

To the Editor.  —We read with interest the excellent article by Levi et al 1 reviewing the pathogenetic mechanisms of the activation of coagulation and fibrinolysis in sepsis. It is noted that plasminogen activator activity can result from the activation of the contact-activated (intrinsic) coagulation pathway. However, several studies are cited that suggest that the activation of fibrinolysis was independent of activation of the coagulation system in sepsis. The temporal relationship between the appearance of tumor necrosis factor-α (TNF-α) after endotoxin and the increase in fibrinolytic activity as well as the abolition of fibrinolytic activation in endotoxin-treated chimpanzees given pentoxifylline, suggested that TNF-α was the mediator of this effect. We would like to suggest further insight into the mechanism of TNF-induced fibrinolytic activation.  In a phase I (uncontrolled) study of TNF-α in human cancer patients, we have recently demonstrated the release of tissue-type plasminogen activator (t-PA, an endothelial product as
Preclinical Assessment of Young Blood Plasma for Alzheimer Disease
Authors: Jinte Middeldorp, Benoit Lehallier, Saul A. Villeda, Suzanne S. M. Miedema, Emily Evans, Eva Czirr, Hui Zhang, Jian Luo, Trisha Stan, Kira I. Mosher, Eliezer Masliah, Tony Wyss-Coray
Journal: JAMA Neurology (2016)

Alzheimer disease (AD) pathology starts long before clinical symptoms manifest, and there is no therapy to treat, delay, or prevent the disease. A shared blood circulation between 2 mice (aka parabiosis) or repeated injections of young blood plasma (plasma from 2- to 3-month-old mice) into old mice has revealed benefits of young plasma on synaptic function and behavior. However, to our knowledge, the potential benefit of young blood has not been tested in preclinical models of neurodegeneration or AD.To determine whether young blood plasma ameliorates pathology and cognition in a mouse model for AD and could be a possible future treatment for the disease.In this preclinical study, mice that harbor a human mutant APP gene, which causes familial AD, were aged to develop AD-like disease including accumulation of amyloid plaques, loss of synaptic and neuronal proteins, and behavioral deficits. The initial parabiosis studies were done in 2010, and the final studies were conducted in 2014. Alzheimer disease model mice were then treated either by surgically connecting them with a young healthy mouse, thus providing a shared blood circulation through parabiosis, or through repeated injections of plasma from young mice.Neuropathological parameters and changes in hippocampal gene expression in response to the treatment were assessed. In addition, cognition was tested in AD model mice intravenously injected with young blood plasma.Aged mutant amyloid precursor protein mice with established disease showed a near complete restoration in levels of synaptic and neuronal proteins after exposure to young blood in parabiosis (synaptophysin P = .02; calbindin P = .02) or following intravenous plasma administration (synaptophysin P < .001; calbindin P = .14). Amyloid plaques were not affected, but the beneficial effects in neurons in the hippocampus were accompanied by a reversal of abnormal extracellular receptor kinase signaling (P = .05), a kinase implicated in AD. Moreover, young plasma administration was associated with improved working memory (P = .01) and associative memory (P = .02) in amyloid precursor protein mice.Factors in young blood have the potential to ameliorate disease in a model of AD.
Soluble CD23 (sCD23): A Forgotten Indicator of Prognosis and Identifier of Outcome in Patients with Chronic Lymphocytic Leukemia Utilizing a Novel Cba Approach
Authors: Timothy William Farren, Fengting Liu, Magali Le Garff-Tavernier, Marika Sarfati, Frans Nauwelaers, Jim Keenan, Noel Warner, Helene Merle-Beral, Samir G. Agrawal
Journal: Blood (2014)
Human serum substitution by artificial sera of scalable allergen reactivity based on polyclonal antibodies and chimeras of human FcγRI and IgE domains
Authors: N. Offermann, M. Plum, U. Hübner, K. Rathloff, I. Braren, M. Fooke, E. Spillner
Journal: Allergy (2016)

Human sera are the first choice as controls for diagnostic applications such as immunoassays, but are limited regarding availability, varying quality, and high costs. In this study, we aimed to circumvent these limitations by the use of a chimeric adaptor molecule comprising the extracellular domains of the human FcγRI (CD64) fused with human IgE Fc domains (CD64-IgE Fc). Allergen-specific antibodies were produced in rabbits using eight different allergens, extracts, and allergen mixtures including mites, pollen, drugs, and food. Preincubation of polyclonal IgG with CD64-IgE Fc established allergen-specific artificial sera that showed comparable results for more than 20 allergens and allergen extracts in three diagnostic systems for the determination of specific IgE. The agreement for these artificial sera is within ±1 radioallergosorbent test (RAST) class. Hence, rabbit IgG complexed with the IgG-specific CD64-IgE Fc adaptor molecule could provide a substitute for human reference sera with specificity for virtually any protein of interest.
High risk vascular fingerprint in patients treated with cisplatin-based chemotherapy for testicular cancer.
Authors: Sjoukje Lubberts, Hink Boer, Renske Altena, Coby Meijer, Arie M. van Roon, Nynke Zwart, Sjoukje Oosting, Pieter W Kamphuisen, Janine Nuver, Andries J. Smit, André B. Mulder, Joop D. Lefrandt, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2015)

e15556 Background: Metastatic TC (mTC) can be cured with cisplatin-based chemotherapy (CT). This comes at the price of increased risk for premature cardiovascular disease (CVD). We investigated risk factors (RFs) and markers of early vascular damage. Methods: Prospective study in mTC patients (pts) treated with CT. A vascular fingerprint was established of RFs: BMI >25 kg/m2, smoking, tension >140/90 mmHg, dyslipidemia (total cholesterol >5.1 or LDL >3.4 mmol/L) or fasting glucose ≥7 mmol/L. High risk (HR) fingerprint was defined as ≥3 RFs. Intima media thickness (IMT), von Willebrand Factor (vWF) and factor VIII (FVIII) were measured before, during and 1 yr after CT. Vascular events up to 2 yrs after CT were assessed. Results: 73 pts (median age 30 yrs (18-46)) participated. 22% had a HR fingerprint and 23% had metabolic syndrome (NCEP 2004). Overall, IMT did not change. vWF increased and was at 1 yr still elevated: 18% had persistent vWF >150%. Changes in IMT and vWF did not differ between HR fingerprint pts and non-HR pts, however HR pts had higher pre-CT IMT and vWF (table). 8 pts (11%) had a vascular event: 4 arterial (2 strokes (1 plus renal infarction), splenal infarction, renal infarction) and 4 pulmonary embolisms. HR fingerprint pts had more often arterial events (table). 6 pts had pre-CT high FVIII level (>150%) of which 3 (50%) developed events versus 5/65 (8%) with normal FVIII pre-CT (p=.002). Conclusions: Many mTC pts have pre-CT already cardiovascular RFs. Estimation of a vascular fingerprint using traditional RFs and FVIII could be used in selection of pts who benefit from preventive strategies. HR fingerprint, n=16 No HR fingerprint, n=57 P* Median (range) Age pre-CT 31 (19-45) 30 (18-46) .256 IMT max (µm) Pre-CT 660 (550-872) 563 (435-1097) .010 1 yr 630 (492-855) 592 (400-1037) .121 vWF (%) Pre-CT 114 (51-297) 91 (42-176) .035 During CT 162 (100-379) 160 (51-299) .406 1 yr 118 (45-237) 108 (44-218) .572 FVIII (%) Pre-CT 105 (74-162) 100 (49-153) .186 During CT 152 (116-342) 150 (22-268) .171 1 yr 124 (43-188) 119 (34-197) .779 N (%) FVIII Pre-CT >150% 4/16 (25%) 2/55 (4%) .021 Vascular events 4/16 (25%) 4/57 (7%) .064 Arterial 3/16 (19%) 1/57 (2%) .031 Venous 1/16 (6%) 3/57 (5%) 1.000 *Mann Whitney U / Fisher exact test.