tbuckley/cabot-search huggingface dataset:
Both Urgency and Balance Needed in Addressing Opioid Epidemic
Authors: Richard J. Bonnie, Aaron S. Kesselheim, David J. Clark
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
High-dose interleukin-2 therapy for metastatic renal cell carcinoma: A contemporary experience.
Authors: Ahmed A. Aboumohamed, Naveen Yarlagadda, Terrance Creighton, Diana Mehedint, Kristopher Attwood, Eric Kauffman, Saby George, Nikhil I. Khushalani, Roberto Pili, Thomas Schwaab
Journal: Journal of Clinical Oncology (2013)

e15604 Background: Despite recent advances in targeted treatment options, high dose interleukin-2 (HDIL-2) remains an important therapeutic option for metastatic renal cell carcinoma (mRCC). We present a contemporary experience of HDIL-2 in a high-volume, National Cancer Institute (NCI)-designated cancer center. Methods: Patients with mRCC who received HDIL-2 monotherapy as a first- or second-line therapy during 2004-2011 were identified. Patients’ demographics, pathologic variables, renal function, time until start of HDIL-2 therapy, number of cycles given (1-3), best responses (complete response; CR, partial response; PR, stable disease; SD, and progressive disease; PD), and primary RCC treatment were analyzed. Progression free survival (PFS) and overall survival (OS) were determined. Results: Of 176 mRCC patients, 91 patients were treated with HDIL-2 (59 as a primary treatment). Median age was 51 years and 73.9% were males. Median Follow-up was 44.9 months. Majority (92%) of tumors showed clear cell histology, and 14.8% had impaired renal function (creatinine &gt;1.5 mg/dL) prior to treatment. Patients with impaired initial renal function were more likely to get more treatment cycles (2-3) than those with adequate initial kidney function (92.3% vs.50.6%, respectively; p=0.002). Eighteen (20.5%) patients underwent cytoreductive nephrectomy. Lower tumor stage at diagnosis correlated with better treatment response (p=0.023), but with longer time from diagnosis to initiation of HDIL-2 (p=0.011). Prominent therapy complications included hypotension (67.4%), renal impairment (63%), impaired liver function (42.4%), and thrombocytopenia (31.5%). None needed hemodialysis for IL-2 induced renal toxicity, and all regained their pre-treatment baseline kidney functions after therapy. Four patients (4.5%) had CR, 11.4% had PR, and 31.8% had SD. Median PFS and OS were 8.6 and 35.5 months, respectively. Estimated 2-year OS rate was 60.6%. Conclusions: Incorporating HDIL-2 therapy in treatment strategies of patients with mRCC added to the patients’ survival in this contemporary series. HDIL-2 therapy appears to be well tolerated in patients with preexisting renal impairment with no long term renal toxicity.
Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation
Authors: Marta Wlodarska, Chengwei Luo, Raivo Kolde, Eva d’Hennezel, John W. Annand, Cortney E. Heim, Philipp Krastel, Esther K. Schmitt, Abdifatah S. Omar, Elizabeth A. Creasey, Ashley L. Garner, Sina Mohammadi, Daniel J. O’Connell, Sahar Abubucker, Timothy D. Arthur, Eric A. Franzosa, Curtis Huttenhower, Leon O. Murphy, Henry J. Haiser, Hera Vlamakis, Jeffrey A. Porter, Ramnik J. Xavier
Journal: Cell Host & Microbe (2017)
Mitochondrial Fission 1 Regulates GSK3 and AMPK Signaling to Sustain Leukemia Stem Cell Function in Acute Myelogenous Leukemia
Authors: Shanshan Pei, Mohammad Minhajuddin, Biniam Adane, Brett M Stevens, Nabilah Khan, Angelo D'alessandro, Travis Nemkov, Kirk C Hansen, Daniel A Pollyea, Craig T Jordan
Journal: Blood (2016)
SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans
Authors: E Kaitlynn Allen, Adrienne G Randolph, Tushar Bhangale, Pranay Dogra, Maikke Ohlson, Christine M Oshansky, Anthony E Zamora, John P Shannon, David Finkelstein, Amy Dressen, John DeVincenzo, Miguela Caniza, Ben Youngblood, Carrie M Rosenberger, Paul G Thomas
Journal: Nature Medicine (2017)
Cardiovascular Risk Factor Control for All
Authors: Philip Greenland, Valentin Fuster
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
Injurious Falls and Syncope in Older Community-Dwelling Adults Meeting Inclusion Criteria for SPRINT
Authors: Donal J. Sexton, Mark Canney, Matthew D. L. O’Connell, Patrick Moore, Mark A. Little, Conall M. O’Seaghdha, Rose-Anne Kenny
Journal: JAMA Internal Medicine (2017)

This study compares rates of injurious falls and syncope in community-dwelling older adults in the Irish Longitudinal Study on Ageing with rates in the Systolic Blood Pressure Intervention Trial.
Cardiac Metabolic Deregulation Induced by the Tyrosine Kinase Receptor Inhibitor Sunitinib is rescued by Endothelin Receptor Antagonism
Authors: Joevin Sourdon, Franck Lager, Thomas Viel, Daniel Balvay, Rebecca Moorhouse, Evangeline Bennana, Gilles Renault, Pierre-Louis Tharaux, Neeraj Dhaun, Bertrand Tavitian
Journal: Theranostics (2017)

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Development of PEGylated carboxylic acid-modified polyamidoamine dendrimers as bone-targeting carriers for the treatment of bone diseases
Authors: Shugo Yamashita, Hidemasa Katsumi, Nozomi Hibino, Yugo Isobe, Yumiko Yagi, Kosuke Kusamori, Toshiyasu Sakane, Akira Yamamoto
Journal: Journal of Controlled Release (2017)
Treatment through progression with ofranogene obadenovec (VB-111), an anti-cancer viral therapy, significantly attenuates tumor growth in recurrent GBM: Individual phase 2 patient data.
Authors: Andrew Jacob Brenner, Patrick Y. Wen, James J. Vredenburgh, Katherine B. Peters, Deborah T. Blumenthal, Laurence S Freedman, Bernice Oberman, Noa Lowenton-Spier, Michal Lavi, Dror Harats, Yael Chava Cohen
Journal: Journal of Clinical Oncology (2017)

2055 Background: Ofranergene obadenovec (VB-111) is a viral cancer-therapy with a dual mechanism: vascular disruption and induction of a tumor directed immune response. Prolongation of overall survival (OS) has been shown in recurrent glioblastoma (rGBM) patients treated through progression with VB-111 in combination with bevacizumab (BEV) compared to historical controls and to patients with limited exposure (LE) to VB-111. Here we present individual patient tumor growth data. Methods: VB-111 was administered at 1x10 13 viral particles bimonthly until progression, followed by BEV standard of care (LE cohort). The protocol was amended to allow treatment through progression (TThP) with VB-111 bimonthly, with the addition of BEV 10mg/Kg biweekly, until further progression (TThP cohort). Tumor dimensions were assessed q2 months by MRI locally and by an independent central lab. The slope of the log tumor measurement over time was calculated for each patient, average slopes were compared across therapy groups using the Wilcoxon Rank Sum test. Results: 46 patients received up to 13 doses of VB-111. All started with VB-111 monotherapy. 22 were included in the LE cohort; 24 in the TThP cohort. Cohorts were comparable by measures of age, performance status, prior lines of therapy, baseline tumor dimensions and progression-free-survival. Spider diagrams demonstrate similar rapid tumor growth in both LE and TThP cohorts during the VB-111 monotherapy period (local site data; median % increase (MPI) per 30d: 14.8 vs 14.1, p = 0.98). In the TThP cohort, growth was attenuated after the 1 st progression, compared to the preceding VB-111 monotherapy period (MPI: 0.6 vs 14.1, p = 0.0032); responses were seen, including 2 complete responses (CR), one patient remaining in CR over 3 years. A similar attenuation was seen in central lab tumor measurements. Conclusions: Treatment through progression with VB-111 in combination with BEV induced durable tumor growth attenuation, which was associated with prolonged OS of 15 months in patients with rGBM. The GLOBE phase 3 randomized controlled trial of VB-111 in rGBM is currently underway. Clinical trial information: NCT01260506.
Adverse Pathologic Findings for Men Electing Immediate Radical Prostatectomy
Authors: Hiten D. Patel, Jeffrey J. Tosoian, H. Ballentine Carter, Jonathan I. Epstein
Journal: JAMA Oncology (2017)

<h3>Importance</h3> Active surveillance is recommended for patients with very low-risk (VLR) and low-risk (LR) prostate cancer. Despite controversy, recent clinical guidelines state surveillance may be considered for men with low-volume intermediate-risk (LVIR) disease. <h3>Objective</h3> To compare rates of adverse pathologic findings among VLR, LR, and LVIR men electing immediate radical prostatectomy and evaluate criteria to define if a favorable intermediate-risk group minimizing risk exists. <h3>Design, Setting, and Participants</h3> This was a cohort study of men (2005-July 2016) with clinically localized VLR (1264 patients), LR (4849 patients), and LVIR (608 patients) (1-2 cores, Gleason 3 + 4 = 7, prostate-specific antigen [PSA] level &lt;20 ng/mL) prostate cancer undergoing radical prostatectomy evaluated retrospectively at Johns Hopkins Hospital. <h3>Interventions</h3> Radical prostatectomy. <h3>Main Outcomes and Measures</h3> The proportions of men found to have at least Gleason 4 + 3 = 7 disease and other adverse pathologic features were compared by risk group. Log-binomial regression calculated relative risk (RR) of adverse pathologic findings in the LVIR cohort compared with VLR and LR cohorts. Analyses were repeated in subgroups of the LVIR population who otherwise met criteria for VLR (T1c, PSA density [PSAD] &lt;0.15 ng/mL/cm<sup>3</sup>, ≤50% cancer in any core) and LR (≤T2a, PSA level &lt;10 ng/mL) disease. Rates of adverse pathologic findings within the LVIR group were calculated based on various clinical thresholds, and univariable and multivariable logistic regression analyses were performed to identify predictors of adverse pathologic findings. <h3>Results</h3> The rate of adverse pathologic findings was significantly higher for LVIR disease (150 of 608 patients [24.7%]; RR, 4.50; 95% CI, 3.73-5.43;<i>P</i> &lt; .001) compared with LR disease (280 of 4849 [5.8%]), and LVIR disease (RR, 5.14; 95% CI, 3.84-6.89;<i>P</i> &lt; .001) compared with men with VLR disease (60 of 1264 [4.7%]). Restriction of LVIR men to additional criteria did not significantly affect results. There were no preoperative clinical or pathologic criteria that could identify a subgroup of the LVIR population with rates of adverse pathologic findings comparable with those of the VLR and LR cohorts. PSAD was a significant predictor of adverse pathologic findings, but Gleason score had the largest effect (odds ratio, 4.30 (95% CI, 3.40-5.44;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Nearly 25% of men (150 of 608) electing immediate radical prostatectomy with low-volume, Gleason 3 + 4 prostate cancer on biopsy are found to harbor adverse surgical pathologic findings. These data do not support the presence of a "favorable" subgroup among included patients and could have important implications for active surveillance in similar patients with Gleason 3 + 4 = 7 prostate cancer.
Letter to the editor: Trends in tuberculosis notification rates by country of origin in the metropolitan area of Rome, 2010 to 2015
Authors: Monica Sañé Schepisi, Paola Scognamiglio, Maurizio D’Amato, Enrico Girardi, Vincenzo Puro
Journal: Eurosurveillance (2017)

Preview this article: Letter to the editor: Trends in tuberculosis notification rates by country of origin in the metropolitan area of Rome, 2010 to 2015, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/22/27/eurosurv-22-27-4-1.gif
Coordinate Regulation of NF-κB Subunit Expression In Pediatric Hodgkin Lymphoma Patients with Rapid Early Response to Therapy, but Not Slow Early Response to Therapy
Authors: Terzah M Horton, Andrea Sheehan, Dolores Lopez-Terrada, Robert Hutchison, Sonya Narendra, Meng-Fen Wu, Lu Chen, Hao Liu
Journal: Blood (2010)
Gut microbiome in multiple sclerosis: The players involved and the roles they play
Authors: Shailesh K. Shahi, Samantha N. Freedman, Ashutosh K. Mangalam
Journal: Gut Microbes (2017)

The human gut contains trillions of bacteria (microbiome) that play a major role in maintaining a healthy state for the host. Perturbation of this healthy gut microbiome might be an important environmental factor in the pathogenesis of inflammatory autoimmune diseases such as multiple sclerosis (MS). Others and we have recently reported that MS patients have gut microbial dysbiosis (altered microbiota) with the depletion of some and enrichment of other bacteria. However, the significance of gut bacteria that show lower or higher abundance in MS is unclear. The majority of gut bacteria are associated with certain metabolic pathways, which in turn help in the maintenance of immune homeostasis of the host. Here we discuss recent MS microbiome studies and the possible mechanisms through which gut microbiome might contribute to the pathogenesis of MS.
Early treatment utilization of palbociclib for metastatic breast cancer (MBC) in a U.S. community oncology network.
Authors: Debra A. Patt, Debanjali Mitra, Robyn K. Harrell, Janet L. Espirito, Julia Jane Perkins, Lynn McRoy, Bhakti Arondekar
Journal: Journal of Clinical Oncology (2016)

e18112 Background: Palbociclib was approved in Feb 2015 as initial endocrine-based treatment (tx) for postmenopausal women with ER+/HER2- MBC. Efficacy and safety were assessed in an open-label randomized phase 2 trial. This study evaluated early usage patterns of palbociclib in a real world community oncology network. Methods: This is a retrospective observational longitudinal rolling cohort study to assess adult MBC patients (pts) initiating tx with palbociclib from 02/2015 to 01/2016. Data is cumulatively extracted from The US Oncology Network/McKesson Specialty Health electronic health record (EHR) database every 2 months. Pts on clinical trial are excluded. Demographic and clinical characteristics, prior tx, dosing patterns, and duration of tx are characterized. Results: 1148 pts were identified as having newly started palbociclib from 02/2015 to 09/2015. Median age at initiation of tx was 63 years. Among pts with documented receptor status (n = 623), 94% were ER+/HER2-. Median Karnofsky performance status at time of tx was 90%. The majority of pts had prior exposure to chemo (58%) or endocrine tx (85%) prior to palbociclib. Documented visceral metastases were present in 32% of pts and bone only metastases in 18%. 92% of pts started at the full dose of 125mg. Palbociclib was most frequently used in combination with letrozole (53%). Among pts with ≥ 1 CBC (n = 984), 39% and 6% of pts had neutrophil counts < 1000 and < 500 (grade 3 and grade 4), respectively. Among pts with at least 6 months of follow-up (n = 260), 31% had a dose reduction at any time, and 15% had discontinued tx. Conclusions: Early utilization demonstrates the demographic characteristics of pts receiving palbociclib appear similar to the US registrational trial. A higher proportion of pts had prior exposure to chemotherapy or endocrine tx in this community network, however line of therapy was not well captured using structured data. Proportion of pts with reduction in neutrophil counts to < 500 was consistent with what was observed in the clinical trial. Majority of the pts are still being treated with palbociclib. Additional planned follow-up time will provide further insight into the real world outcomes of tx. (Funding: Pfizer)
Distinction of Risk Factors for Superficial vs Organ-Space Surgical Site Infections After Pancreatic Surgery
Authors: Irmina A. Elliott, Carmen Chan, Tara A. Russell, Amanda M. Dann, Jennifer L. Williams, Lauren Damato, Hallie Chung, Mark D. Girgis, O. Joe Hines, Howard A. Reber, Timothy R. Donahue
Journal: JAMA Surgery (2017)

Surgical site infection (SSI) rates are increasingly used as a quality metric. However, risk factors for SSI in pancreatic surgery remain undefined.To stratify superficial and organ-space SSIs after pancreatectomy and investigate their modifiable risk factors.This retrospective analysis included 201 patients undergoing pancreatic surgery at a university-based tertiary referral center from July 1, 2013, through June 30, 2015, and 10 371 patients from National Surgical Quality Improvement Program-Hepatopancreaticobiliary (NSQIP-HPB) Collaborative sites from January 1, 2014, through December 31, 2015.Superficial, deep-incisional, and organ-space SSIs, as defined by NSQIP.Among the 201 patients treated at the single center (108 men [53.7%] and 93 women [46.3%]; median age, 48.6 years [IQR, 41.4-57.3 years]), 58 had any SSI (28.9%); 28 (13.9%), superficial SSI; 8 (4%), deep-incisional SSI; and 24 (11.9%), organ-space SSI. Independent risk factors for superficial SSI were preoperative biliary stenting (odds ratio [OR], 4.81; 95% CI, 1.25-18.56; P = .02) and use of immunosuppressive corticosteroids (OR, 13.42; 95% CI, 1.64-109.72; P = .02), whereas soft gland texture was the only risk factor for organ-space SSI (OR, 4.45; 95% CI, 1.35-14.66; P = .01). Most patients with organ-space infections also had grades B/C fistulae (15 of 24 [62.5%] vs 4 of 143 [2.8%] in patients with no SSI; P < .001). Organ/space but not superficial SSI was associated with an increased rate of sepsis (7 of 24 [29.2%] vs 4 of 143 [2.8%]; P < .001) and prolonged length of hospital stay (12 vs 8 days; P = .04). Among patients in the NSQIP-HPB Collaborative, 2057 (19.8%) had any SSI; 719 (6.9%), superficial SSI; 207 (2%), deep-incisional SSI; and 1287 (12.4%), organ-space SSI. Preoperative biliary stenting was confirmed as an independent risk factor for superficial SSI (OR, 2.07; 95% CI, 1.58-2.71; P < .001). In this larger data set, soft gland texture was an independent risk factor for superficial SSI (OR, 1.45; 95% CI, 1.14-1.85; P = .002) but was more strongly and significantly associated with organ-space SSI (OR, 2.32; 95% CI, 1.88-2.85; P < .001).Preoperative biliary stenting and coriticosteroid use increase superficial SSI, even in patients receiving perioperative piperacillin-tazobactam. Additional measures, including extended broad-spectrum perioperative antibiotic treatment, should be considered in these patients. Organ/space SSIs appear to be related to pancreatic fistulae, which are not modifiable. Reporting these different subtypes as a single, overall rate may be misleading.
Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients
Authors: S Ruberti, E Bianchi, P Guglielmelli, S Rontauroli, G Barbieri, L Tavernari, T Fanelli, R Norfo, V Pennucci, G Corbizi Fattori, C Mannarelli, N Bartalucci, B Mora, L Elli, M A Avanzini, C Rossi, S Salmoiraghi, R Zini, S Salati, Z Prudente, V Rosti, F Passamonti, A Rambaldi, S Ferrari, E Tagliafico, A M Vannucchi, R Manfredini
Journal: Leukemia (2017)

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared with the essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. MAF overexpression and knockdown experiments shed some light into the role of MAF in PMF pathogenesis, by demonstrating that MAF favors the megakaryocyte and monocyte/macrophage commitment of HPCs and leads to the increased expression of proinflammatory and profibrotic mediators. Among them, we focused our further studies on SPP1 and LGALS3. We assessed SPP1 and LGALS3 protein levels in 115 PMF, 47 ET and 24 PV patients plasma samples and we found that SPP1 plasma levels are significantly higher in PMF compared with ET and PV patients. Furthermore, in vitro assays demonstrated that SPP1 promotes fibroblasts and mesenchymal stromal cells proliferation and collagen production. Strikingly, clinical correlation analyses uncovered that higher SPP1 plasma levels in PMF patients correlate with a more severe fibrosis degree and a shorter overall survival. Collectively our data unveil that MAF overexpression contributes to PMF pathogenesis by driving the deranged production of the profibrotic mediator SPP1.