tbuckley/cabot-search huggingface dataset:
Evaluating Evolving Technologies in a Time of Rapid Change
Authors: Robert M. Califf
Journal: JAMA Cardiology (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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Cardiology journal
Enhanced Natural Killer and Cytotoxic T Lymphocyte Responses, with Decreased Monocytic Myeloid Derived Suppressor Cells May Promote Treatment Free Remission in Chronic Myeloid Leukaemia Patients Following Tyrosine Kinase Inhibitor Cessation
Authors: Amy Hughes, Jade Clarson, Deborah L White, David M. Ross, Timothy P. Hughes, Agnes S Yong
Journal: Blood (2016)
Under Our Noses
Authors: Ian Wicks
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 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
Prevalence of hereditary cancer susceptibility syndromes in children: A report from the Saudi Arabian Pediatric Hematology Oncology Society.
Authors: Wasil Jastaniah, Abdullah Aljefri, Mouhab Ayas, Musa Alharbi, Nawaf Alkhayat, Faisal Alanzi, Fawwaz Yassin, Fawaz Al-Kasim, Shaker Abdullah, Mohammed Burhan Abrar, Abdulrahman S. Alsultan
Journal: Journal of Clinical Oncology (2016)

e13086 Background: Hereditary cancer susceptibility syndromes (HCSS) contribute to the cause of up to 29% of childhood cancer. The Saudi population has high rate of consanguineous marriages and this might increase the prevalence of HCSS. Methods: Our study is a cross sectional multi-center study of children less than age 14 years who were diagnosed with cancer between January 2011 and December 2014. Data collected were: demographics, number of primary cancers, and cancer details. Parents were interviewed about consanguinity and the occurrence of cancer in 1st, 2nd, and 3rddegree relatives. HCSS risk assessment was based on the ACMG 2015 practice guidelines. The study was funded by Sanad children's cancer support association. Results: A total of 1291 patients (leukemia 49%, lymphoma 11%, brain tumors 10%, non-Ewings sarcoma 7.3%, Wilms tumor 6.1%, and others 16.6%) were enrolled as of December 2015. The median age at diagnosis was 5.1 years, male:female ratio was 1.3:1, and median sibship size was 4 (range, 0-12). Parental consanguinity was reported in 38%, mostly first degree. The number of patients with criteria that warrants HCSS work up is shown in the Table. A total of 486 (37.6%) met those criteria (leukemia 58%, non-Ewings sarcoma 19.4%, brain 12.8%, retinoblastoma 4.9%, hepatoblastoma 4.5%, and adrenocortical carcinoma 0.4%). Conclusions: Nearly 4 out of 10 children with cancer in Saudi Arabia met criteria for HCSS, most often due to parental consanguinity. The use of consanguinity solely as a risk factor for HCSS in our population needs to be determined. Genetic testing of at risk patients is on-going. Criteria Number of patients 1. Leukemia 282 A. Parental consanguinity 176 B. 2nd primary in the patient 4 C. Sibling with childhood cancer 0 D. Relative with LFS associated tumor ≤ 45 years 55 E. > 1 criteria 47 2. Non-Ewing Sarcoma 94 3. Brain tumor 62 A. Parental consanguinity 43 B. 2nd primary in the patient 0 C. Sibling with childhood cancer 1 D. Relative with Lynch syndrome associated cancer 1 E. Relative with LFS associated tumor ≤ 45 years 6 F. > 1 criteria 11 4. Retinoblastoma 24 5. Hepatoblastoma < 5 years 22 6. Adrenocortical carcinoma 2 Total 486 LFS, Li-Fraumeni syndrome.
Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer at high risk of disease recurrence (D-CARE): An international, placebo-controlled, randomized, double-blind phase III clinical trial.
Authors: Paul E. Goss, Carlos H. Barrios, Arlene Chan, Dianne M. Finkelstein, Hiroji Iwata, Miguel Martin, Ada Braun, Beiying Ding, Tapan Maniar, Robert E. Coleman
Journal: Journal of Clinical Oncology (2013)

TPS662 Background: In women with early-stage breast cancer, bone is a common site of distant recurrence and represents approximately 40% of all first recurrences. Preclinical studies demonstrated that inhibition of RANKL significantly delays skeletal tumor formation, reduces skeletal tumor burden, and prolongs survival of tumor-bearing mice. Denosumab is approved for the prevention of skeletal-related events (SREs) in patients with established bone metastases from solid tumors. The D-CARE trial is designed to assess if denosumab treatment prolongs bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. The primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Additional endpoints include safety, breast density, time to first on-study SRE (following the development of bone metastasis), patient reported outcomes, and biomarkers. Methods: In this international, randomized, double-blind, and placebo-controlled phase 3 trial, 4509 women with stage II or III breast cancer at high risk for recurrence and with known hormone and HERE2 receptor status were randomized. High risk was defined as biopsy evidence of breast cancer in regional lymph nodes, tumor size &gt; 5 cm (T3), or locally advanced disease (T4). Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination, must be planned. Patients with a prior history of breast cancer (except DCIS or LCIS) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization, or any intravenous BP use, were not eligible. Patients were randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. Supplemental vitamin D (≥ 400 IU) and calcium (≥ 500 mg) were required. The trial, sponsored by Amgen Inc., began enrolling patients in June 2010 and completed enrollment in late 2012. Clinical trial information: NCT01077154.
Enhanced Functional Genomic Screening Identifies Novel Mediators of Dual Leucine Zipper Kinase-Dependent Injury Signaling in Neurons
Authors: Derek S. Welsbie, Katherine L. Mitchell, Vinod Jaskula-Ranga, Valentin M. Sluch, Zhiyong Yang, Jessica Kim, Eugen Buehler, Amit Patel, Scott E. Martin, Ping-Wu Zhang, Yan Ge, Yukan Duan, John Fuller, Byung-Jin Kim, Eman Hamed, Xitiz Chamling, Lei Lei, Iain D.C. Fraser, Ze’ev A. Ronai, Cynthia A. Berlinicke, Donald J. Zack
Journal: Neuron (2017)
Give a voice to the voiceless
Authors: Kamran Abbasi
Journal: BMJ (2017)

Rudolf Virchow’s investigation of a typhus epidemic in 1848 identified a root cause: “The power of the aristocracy, propped up by the church.” Big business is today’s aristocracy, politicians and the state today’s church. In society’s pursuit of wealth and profit, it is poor people who carry the greatest burden of disease, whose deaths are most likely when fire engulfs a tower block, the levees break in New Orleans, or a Titanic sinks.

After last week’s fire in London’s Grenfell Tower Martin McKee recalls Virchow to urge us not to ignore …
Combien de temps dure une endoscopie digestive?
Authors: M Lagneau
Journal: Endoscopy (2006)

Considérer la durée d'une endoscopie sur le seul temps de l'acte technique est une vision partielle de l'organisation d'un plateau d'endoscopie. En pratique, il faut tenir compte de la durée réelle consacrée à une endoscopie, comprenant temps d'attente, entrée et sortie de salle, anesthésie, tenue des données administratives, lavage en salle.... L'étude entreprise avait pour objectif de répondre à 2 questions organisationnelles: 1- quel est le temps global nécessaire à la réalisation d'un acte d'endoscopie avec anesthésie. 2- quelles sont les disparités des durées d'endoscopie selon les opérateurs.
Fibrous scaffolds potentiate the paracrine function of mesenchymal stem cells: A new dimension in cell-material interaction
Authors: Ni Su, Peng-Lai Gao, Kai Wang, Jin-Yang Wang, Yi Zhong, Ying Luo
Journal: Biomaterials (2017)

While the studies on the material interaction with mesenchymal stem cells (MSCs) have been mainly focused on the ability of materials to provide environment to regulate cell viability, proliferation or differentiation, the therapeutic effects of MSC-material constructs may result from the secretion of immunomodulatory and angiogenic cytokines from MSCs. Here, electrospun scaffolds composed of fibers in random, aligned and mesh-like patterns were fabricated, and the paracrine behavior of adipose-derived MSCs (Ad-MSCs) on the scaffolds were investigated in comparison to the cell culture via conventional microplates. It was found that the Ad-MSCs on the electrospun fibers produced significantly higher levels of anti-inflammatory and pro-angiogenic cytokines compared to those cultured on microplates. The enhanced modulatory effects of the secreted products of Ad-MSCs on fibrous electrospun scaffolds were also proven in the cultures of endothelial cells and the LPS-stimulated macrophages, with three types of scaffolds showing distinct influences on the paracrine function of Ad-MSCs. In a skin excisional wound-healing model in rat, the conditioned medium collected from the MSC-scaffold system accelerated the wound closure, promoted the macrophage recruitment and enhanced the polarization of macrophages toward the pro-healing phenotype in the wound bed. Our study demonstrates that the fibrous topography of scaffolds is a key material property that modulates the paracrine function of cells. The discovery elucidates a new aspect of material functions, laying the foundation for developing scaffold materials to promote tissue regeneration/repair through guiding the paracrine signaling network.
Disease-free survival (DFS) as a surrogate for overall survival (OS) in localized prostate cancer (CaP).
Authors: Christopher Sweeney, Wanling Xie, Meredith M. Regan, Mari Nakabayashi, Marc E. Buyse, Noel W. Clarke, Laurence Collette, James J. Dignam, Karim Fizazi, Muriel Habibian, Susan Halabi, Philip W. Kantoff, Wendy R. Parulekar, Howard M. Sandler, Oliver Sartor, Howard R. Soule, Matthew Robert Sydes, Bertrand F. Tombal, Scott G. Williams
Journal: Journal of Clinical Oncology (2016)

5023 Background: Advances in the treatment of localized CaP have led to decreased recurrences and improved OS. The Intermediate Clinical Endpoints in CaP (ICECaP) Working Group is conducting an individual patient data (IPD) meta-analysis of possible surrogate endpoints for localized CaP trials. We hypothesized that DFS is a surrogate for OS. Methods: By June 2013, we systematically identified 102 eligible randomized trials (completed or ongoing) comparing treatments in localized CaP and collected IPD from trialists. DFS was defined from randomization (R) to the first evidence of clinical recurrence (loco-regional or distant) or death from any cause; or was censored at the date of last follow-up. OS was defined from R to death from any cause. We evaluated the surrogacy of DFS with OS using a meta-analytic 2-stage validation model where 2 conditions must hold to claim DFS is a surrogate for OS (Buyse et al, 2000 & 2011 - table). The secondary objective evaluated surrogacy of time to disease recurrence (TDR) with disease specific survival (DSS), defined analogously to DFS and OS but with non-CaP deaths censored. Results: By January 2016, IPD from 16,999 men randomized in 20 mature trials were available for analysis. 32% of the men were from prostatectomy trials, about 30% of the men had intermediate and 50% high-risk disease and 86% were < 74 yo. With median follow-up of 10.2 years, 32% (N = 5,370) men had died and 30% of these deaths (N = 1,592) were due to CaP. Conclusions: DFS can be used as a surrogate of OS and TDR as a surrogate of DSS. Meta-analytic 2-stage validation Model Condition 1: Correlation between the ICE and true endpoint Condition 2: Correlation between study specific treatment effect on endpoints R2 from weighted linear regression of t-year Kaplan Meier estimates (95% CI) Plackett's copula model estimate of Kendall Tau correlation (95% CI) R2 from weighted linear regression of treatment effects (log HR) (95% CI) DFS as a surrogate for OS 10y OS vs 5y DFS 0.80 (0.67,0.86) 8y OS vs 5y DFS 0.85 (0.76,0.90) 0.85(0.85,0.86) 0.80(0.60,0.87) TDR as surrogate for DSS 10y DSS vs 5y TDR 0.73 (0.56,0.81) 8y DSS vs 5y TDR 0.79 (0.67,0.85) 0.71(0.70,0.72) 0.61(0.29,0.75)
Association of atypia in ductal lavage and breast cancer risk.
Authors: Andrea De Censi, Massimiliano Cazzaniga, Chiara Casadio, Laura Chiapparini, Sara Gandini, Aliana Guerrieri-Gonzaga, Debora Macis, Paolo Veronesi, Bernardo Bonanni
Journal: Journal of Clinical Oncology (2017)

e13040 Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early detection of breast cancer and to provide individualized breast cancer risk assessment will greatly benefit from sampling cellular material from the target tissue. Ductal lavage (DL) is a minimally invasive technique which provides adequate material to detect atypical cells in mammary ducts. However, long term data of the association between atypia from and BC risk are lacking .We studied the prevalence of atypia in DL and its ability to predict BC development in women at risk. Methods: From March 2000 to July 2012 we performed DL in a consecutive series of 348 women with median age of 45 (range 19-74) at increased BC risk based on the following characteristics: 5 yrs Gail model &gt; 1.66% or &gt; 10% probability of BRCA mutation (n = 155), history of contralateral BC (CBC, n = 161), presence of a BRCA pathogenic variant (n = 32). We analyzed the presence of atypical cells in the baseline specimens and observed their evolution during follow-up. Results: The procedure was safe and well tolerated in most women, with pain and disconfort preventing the procedure in 5.4% of subjects. Overall, 126 (36%) women had atypia, with a prevalence of 32%, 39%, and 41% in the Gail, CBC and BRCA groups, respectively (p = 0.38). The overall prevalence of atypia considering all visits was 44% (range 36-51). After a median follow up of 6 years, cumulative BC events were 8% in women without atypia versus 14% in those with atypia (log-rank p = 0.08). In the highest risk groups (CBC and BRCA pathogenic variants), the number of BC events was 16 vs 11 in women with or without atypia (21% vs 10%; log-rank p = 0.05, Cox model adjusted for age p = 0.02). Conclusions: Our findings suggest that cytologic atypia in the fluid obtained by DL may predict the onset of BC in high-risk women. The reversal of atypia in DL as a surrogate biomarker of BC risk reduction warrants investigation.
Dose escalation results from a first-in-human, phase 1 study of the glucocorticoid-induced TNF receptor-related protein (GITR) agonist AMG 228 in patients (Pts) with advanced solid tumors.
Authors: Ben Tran, Richard D. Carvajal, Aurelien Marabelle, Sandip P. Patel, Patricia LoRusso, Erik Rasmussen, Gloria Juan, Vijay V. Upreti, Gataree Ngarmchamnanrith, Patrick Schöffski
Journal: Journal of Clinical Oncology (2017)

2521 Background: AMG 228 is an agonistic human IgG1 monoclonal antibody that binds to GITR (CD357), a TNFSFR costimulatory molecule expressed by effector/regulatory T cells. Dose escalation of this open label, first in human, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and maximum tolerated dose (MTD) and recommended phase 2 dose of AMG 228 in pts with advanced solid tumors. Methods: Pts with refractory advanced colorectal cancer (n = 13), squamous cell carcinoma of head and neck (n = 10), non–small cell lung cancer (n = 2), urothelial transitional cell carcinoma (n = 4), and melanoma (n = 1) received AMG 228 IV Q3W. Dose escalation was in two stages: single-pt cohorts until AMG 228-related grade &gt; 2 adverse events (AEs), efficacy, or 90 mg dose reached (4 cohorts: 3, 9, 30, and 90 mg), followed by rolling six design (n = 2 to 6) until MTD or highest planned dose of 1200 mg reached (5 cohorts: 180, 360, 600, 900, and 1200 mg). Primary endpoints included incidence of dose-limiting toxicities (DLTs) and AEs and PK. Additional endpoints were objective response (RECIST 1.1) and evidence of biological activity. Results: In total, 30 pts (median age 63 y) were treated (3, 9, 30, and 90 mg, n = 1; 180 mg, n = 6; 360 mg, n = 4; 600 mg, n = 6; 900 mg, n = 4; 1200 mg, n = 6). Twenty-seven (90%) pts had treatment-emergent AEs; the most common were hypophosphatemia (23%), fatigue (23%), anemia (23%), nausea (20%), and pyrexia (20%). No DLTs occurred; the MTD was not reached. AMG 228 exposure was dose-related, with PK profiles at low doses (3 to 90 mg) consistent with target mediated drug disposition; doses &gt; 360 mg achieved serum levels needed for 95% receptor occupancy on activated PBMCs. No evidence of T cell activation was observed despite complete target coverage in both tumor and peripheral blood. Among 29 evaluable pts, none had an objective response. Conclusions: In this population of pts with advanced solid tumors, AMG 228 Q3W was tolerable up to the highest tested dose (1200 mg), showing favorable PK. However, no clinical or immunological activity was observed in this limited number of pts. Clinical trial information: NCT02437916.
Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice
Authors: Zhen Sun, Wenyu Gou, Do-sung Kim, Xiao Dong, Charlie Strange, Yu Tan, David B. Adams, Hongjun Wang
Journal: Molecular Therapy (2017)

The objective of this study was to assess the capacity of adipose-derived mesenchymal stem cells (ASCs) to mitigate disease progression in an experimental chronic pancreatitis mouse model. Chronic pancreatitis (CP) was induced in C57BL/6 mice by repeated ethanol and cerulein injection, and mice were then infused with 4 × 105 or 1 × 106 GFP+ ASCs. Pancreas morphology, fibrosis, inflammation, and presence of GFP+ ASCs in pancreases were assessed 2 weeks after treatment. We found that ASC infusion attenuated pancreatic damage, preserved pancreas morphology, and reduced pancreatic fibrosis and cell death. GFP+ ASCs migrated to pancreas and differentiated into amylase+ cells. In further confirmation of the plasticity of ASCs, ASCs co-cultured with acinar cells in a Transwell system differentiated into amylase+ cells with increased expression of acinar cell-specific genes including amylase and chymoB1. Furthermore, culture of acinar or pancreatic stellate cell lines in ASC-conditioned medium attenuated ethanol and cerulein-induced pro-inflammatory cytokine production in vitro. Our data show that a single intravenous injection of ASCs ameliorated CP progression, likely by directly differentiating into acinar-like cells and by suppressing inflammation, fibrosis, and pancreatic tissue damage. These results suggest that ASC cell therapy has the potential to be a valuable treatment for patients with pancreatitis. The objective of this study was to assess the capacity of adipose-derived mesenchymal stem cells (ASCs) to mitigate disease progression in an experimental chronic pancreatitis mouse model. Chronic pancreatitis (CP) was induced in C57BL/6 mice by repeated ethanol and cerulein injection, and mice were then infused with 4 × 105 or 1 × 106 GFP+ ASCs. Pancreas morphology, fibrosis, inflammation, and presence of GFP+ ASCs in pancreases were assessed 2 weeks after treatment. We found that ASC infusion attenuated pancreatic damage, preserved pancreas morphology, and reduced pancreatic fibrosis and cell death. GFP+ ASCs migrated to pancreas and differentiated into amylase+ cells. In further confirmation of the plasticity of ASCs, ASCs co-cultured with acinar cells in a Transwell system differentiated into amylase+ cells with increased expression of acinar cell-specific genes including amylase and chymoB1. Furthermore, culture of acinar or pancreatic stellate cell lines in ASC-conditioned medium attenuated ethanol and cerulein-induced pro-inflammatory cytokine production in vitro. Our data show that a single intravenous injection of ASCs ameliorated CP progression, likely by directly differentiating into acinar-like cells and by suppressing inflammation, fibrosis, and pancreatic tissue damage. These results suggest that ASC cell therapy has the potential to be a valuable treatment for patients with pancreatitis.