tbuckley/cabot-search huggingface dataset:
Evaluation of progression-free survival by blinded independent central review in patients with progressive, well-differentiated pancreatic neuroendocrine tumors treated with sunitinib or placebo.
Authors: E. Van Cutsem, J. F. Seitz, J. Raoul, J. W. Valle, S. J. Faivre, S. Patyna, D. Klademenos, D. Lu, R. C. Chao, E. Raymond
Journal: Journal of Clinical Oncology (2011)

249 Background: Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor with antiangiogenic activity. In a phase III, double-blind, placebo-controlled, randomized trial in patients with advanced, well-differentiated progressive pancreatic neuroendocrine tumors (NET), sunitinib 37.5 mg continuous daily dosing significantly improved investigator-assessed progression-free survival (PFS) compared with placebo (median, 11.4 months vs. 5.5 months; hazard ratio [HR] 0.418; 95% CI: 0.263, 0.662; P=0.0001). To evaluate the possibility that recognizable treatment- associated adverse events (AEs) might have impacted the efficacy results by unblinding the investigators, we conducted a retrospective blinded independent central review (BICR) of the tumor imaging scans. Methods: PFS was defined as the time from randomization to the first objective progression of disease or death due to any cause, whichever occurred first. Baseline and on-study CT/MRI scans were evaluated independently according to a two-reader, two-time point lock, followed by a sequential locked read, batch mode paradigm, by independent, third party radiologists. Reading radiologists were blinded to investigator tumor assessments and AEs; discrepancies were adjudicated by a similarly blinded and independent third radiologist. Results: Overall, 171 patients were randomized to treatment (sunitinib, n=86, placebo, n=85). Scans were collected retrospectively for 170 (99.4%) patients. Complete scan sets/time points were available for 160 patients (93.6%). Median PFS based on BICR of scans was 12.6 months for sunitinib and 5.8 months for placebo with an HR of 0.315 (95% CI: 0.181, 0.546; p=0.000015), consistent with the investigator- assessed PFS results. Conclusions: This BICR of tumor scans confirms the investigator-assessed, clinically meaningful PFS benefit of sunitinib in patients with pancreatic NET, and provides evidence against the presence of any systematic bias favoring sunitinib. [Table: see text]
Clonal and Subclonal Cytogenetic Aberrations: Association with D-Type Cyclin Expression and Event-Free Survival (EFS) in Multiple Myeloma (MM).
Authors: Dirk Hose, John DeVos, Nadine Müller, Jean-Francois Rossi, Christiane Heiß, Karène Mahtouk, Michael Hundemer, Thierry X. Reme, Axel Benner, Jérôme Moreaux, Véronique Pantesco, Thomas Möhler, Eric Jourdan, Anna Jauch, Bernard Klein, Hartmut Goldschmidt
Journal: Blood (2006)
Interleukin 23–Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris
Authors: Laurence Feldmeyer, Alessio Mylonas, Olivier Demaria, Anna Mennella, Nikhil Yawalkar, Emmanuel Laffitte, Daniel Hohl, Michel Gilliet, Curdin Conrad
Journal: JAMA Dermatology (2017)

<h3>Importance</h3> Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. <h3>Objective</h3> To determine whether blockade of the interleukin 23–helper T cell 17 (IL-23–T<sub>H</sub>17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP. <h3>Design, Setting, and Participants</h3> In this case report, a patient with PRP received outpatient treatment at a university hospital department of dermatology with ustekinumab according to the dosing regimen approved for psoriasis. Lesional skin biopsy samples were taken from this patient and 2 others with refractory PRP. Messenger RNA (mRNA) expression of proinflammatory innate and T-cell–derived cytokines were measured and compared with skin samples from patients with psoriasis and healthy donors. From 1 patient, lesional skin samples were taken before ustekinumab treatment and 4 and 28 weeks after treatment initiation. Follow-up was completed after 6 months. <h3>Intervention</h3> Subcutaneous ustekinumab, 45 mg, at weeks 0 and 4 and quarterly thereafter. <h3>Main Outcomes and Measures</h3> The primary outcome was to determine the changes in expression of proinflammatory innate and T-cell–derived cytokines during ustekinumab therapy. The secondary objective was to evaluate the clinical and histopathologic phenotype in relation to the mRNA expression profile of proinflammatory cytokines. <h3>Results</h3> In lesional PRP skin samples from a single patient, upregulated expression levels were found for most proinflammatory innate cytokines, including tumor necrosis factor (TNF), IL-6, IL-12, IL-23, and IL-1β. Among adaptive T-cell cytokines, an increase of T<sub>H</sub>1 cytokines and, in particular, T<sub>H</sub>17 cytokines IL-17A, IL-17F, and IL-22 was seen in PRP. The patient with PRP who received ustekinumab showed regression of skin lesions after 2 weeks and almost complete resolution after 1 month. Clinical and histopathologic improvement paralleled the expression levels of T<sub>H</sub>17 cytokines but not of interferon-γ and TNF, which lagged behind the amelioration. <h3>Conclusions and Relevance</h3> In this case report, a role of the IL-23–T<sub>H</sub>17-axis in PRP was identified, suggesting a shared pathogenic inflammatory pathway with psoriasis, despite evident clinical and histopathologic differences. In addition, this report provides a rationale for targeting the IL-23–T<sub>H</sub>17-pathway as a treatment option for refractory PRP.
Organization of the dermal matrix impacts the biomechanical properties of skin
Authors: A.K. Langton, H.K. Graham, J.C. McConnell, M.J. Sherratt, C.E.M. Griffiths, R.E.B. Watson
Journal: British Journal of Dermatology (2017)

Human skin has the crucial roles of maintaining homeostasis and protecting against the external environment. Skin offers protection against mechanical trauma due to the reversible deformation of its structure; these biomechanical properties are amenable to dynamic testing using noninvasive devices.To characterize the biomechanical properties of young, black African/African-Caribbean and white Northern European skin from different anatomical sites, and to relate underlying skin architecture to biomechanical function.Using cutometry and ballistometry, the biomechanical properties of buttock and dorsal forearm skin were determined in black African/African-Caribbean (n = 18) and white Northern European (n = 20) individuals aged 18-30 years. Skin biopsies were obtained from a subset of the volunteers (black African/African-Caribbean, n = 5; white Northern European, n = 6) and processed for histological and immunohistochemical detection of the major elastic fibre components and fibrillar collagens.We have determined that healthy skin from young African and white Northern European individuals has similar biomechanical properties (F3): the skin is resilient (capable of returning to its original position following deformation, R1), exhibits minimal fatigue (R4) and is highly elastic (R2, R5 and R7). At the histological level, skin with these biomechanical properties is imbued with strong interdigitation of the rete ridges at the dermoepidermal junction (DEJ) and candelabra-like arrays of elastic fibres throughout the papillary dermis. Dramatic disruption to this highly organized arrangement of elastic fibres, effacement of the rete ridges and alterations to the alignment of the fibrillar collagens is apparent in the white Northern European forearm and coincides with a marked decline in biomechanical function.Maintenance of skin architecture - both epidermal morphology and elastic fibre arrangement - is essential for optimal skin biomechanical properties. Disruption to underlying skin architecture, as observed in the young white Northern European forearm, compromises biomechanical function.
Randomized Phase II Study of BLP25 Liposome Vaccine (L-BLP25) in Patients with Multiple Myeloma
Authors: Eva Rossmann, Anders Österborg, Eva Löfvenberg, Aniruddha Choudhury, Ulf Forssmann, Stefanie Senger, Andreas Schröder, Håkan Mellstedt
Journal: Blood (2011)
FURTHER NEW ZOOPARASITES OF MAN
Journal: JAMA (1920)

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
Review of Donald W. Light and Antonio F. Maturo, <i>Good Pharma: The Public-Health Model of the Mario Negri Institute</i><sup>1</sup>
Authors: Jill A. Fisher
Journal: The American Journal of Bioethics (2017)

"Review of Donald W. Light and Antonio F. Maturo, Good Pharma: The Public-Health Model of the Mario Negri Institute11." The American Journal of Bioethics, 17(2), pp. W9–W10
More non-opiate users complete treatment but heroin users’ health worsens, review finds
Authors: Susan Mayor
Journal: BMJ (2017)

The number of non-opiate drug users who completed drug misuse treatment programmes in England has more than doubled in the past 10 years, but success rates are lower in people misusing opiates and their health problems are increasing, a wide ranging review has found.

The review, carried out by Public Health England,1 analysed data from locally commissioned drug misuse treatment services providing structured intervention services in the community and prisons around the country. It was overseen by an expert reference group and informed by focus groups of service users.

Results showed that the proportion of people using non-opiate drugs (such as cannabis, cocaine, …
The Linear ubiquitin chain assembly complex acts as a liver tumor suppressor and inhibits hepatocyte apoptosis and hepatitis
Authors: Yutaka Shimizu, Nieves Peltzer, Alexandra Sevko, Elodie Lafont, Aida Sarr, Helena Draberova, Henning Walczak
Journal: Hepatology (2017)

Linear ubiquitination is a key posttranslational modification that regulates immune signaling and cell death pathways, notably tumor necrosis factor receptor 1 (TNFR1) signaling. The only known enzyme complex capable of forming linear ubiquitin chains under native conditions to date is the linear ubiquitin chain assembly complex, of which the catalytic core component is heme‐oxidized iron regulatory protein 2 ubiquitin ligase‐1–interacting protein (HOIP). To understand the underlying mechanisms of maintenance of liver homeostasis and the role of linear ubiquitination specifically in liver parenchymal cells, we investigated the physiological role of HOIP in the liver parenchyma. To do so, we created mice harboring liver parenchymal cell–specific deletion of HOIP ( HoipΔhep mice) by crossing Hoip ‐floxed mice with albumin–Cre mice. HOIP deficiency in liver parenchymal cells triggered tumorigenesis at 18 months of age preceded by spontaneous hepatocyte apoptosis and liver inflammation within the first month of life. In line with the emergence of inflammation, HoipΔhep mice displayed enhanced liver regeneration and DNA damage. In addition, consistent with increased apoptosis, HOIP‐deficient hepatocytes showed enhanced caspase activation and endogenous formation of a death‐inducing signaling complex which activated caspase‐8. Unexpectedly, exacerbated caspase activation and apoptosis were not dependent on TNFR1, whereas ensuing liver inflammation and tumorigenesis were promoted by TNFR1 signaling. Conclusion : The linear ubiquitin chain assembly complex serves as a previously undescribed tumor suppressor in the liver, restraining TNFR1‐independent apoptosis in hepatocytes which, in its absence, is causative of TNFR1‐mediated inflammation, resulting in hepatocarcinogenesis. (H epatology 2017;65:1963‐1978).
Combination Therapy of a Defucosylated Anti-HM1.24 Monoclonal Antibody Plus Lenalidomide Significantly Enhances Myeloma Cell Cytotoxicity Via Antibody-Dependent Cellular Cytotoxicity
Authors: Takeshi Harada, Shuji Ozaki, Asuka Oda, Hiroe Amou, Shiro Fujii, Shingen Nakamura, Hirokazu Miki, Ayako Nakano, Kumiko Kagawa, Kyoko Takeuchi, Masahiro Abe, Hironobu Shibata, Shigeto Kawai, Hisafumi Yamada-Okabe, Toshio Matsumoto
Journal: Blood (2011)
Mantle Cell Lymphoma Cells Express B7 Family Molecules and B7-H1 Expression Are up-Regulated After LPS Exposure Via MEK-Dependent and PI3K/Akt-Dependent Pathways In Mantle Cell Lymphoma Cells
Authors: Lijuan Wang, Hanying Bao, Yang Yang, Yi Zhao, Donghua He, Peilin Lu, Yi Li, Li Yang, Qing Yi, Michael Wang, Zhen Cai
Journal: Blood (2010)
Clinical Outcomes of R-CHOP Chemotherapy Alone Compared with R-CHOP Plus Radiotherapy in Patients with Localized, Non-Bulky Diffuse Large B-Cell Lymphoma
Authors: Ji Hyun Park, Dok Hyun Yoon, Shin Kim, Jung Sun Park, Sang-wook Lee, Chan-Sik Park, Jooryung Huh, Seok Jin Kim, Myung Hee Chang, Hyeon Seok Eom, Yong Park, Jin Seok Kim, Soon Il Lee, Min Kyoung Kim, Young Rok Do, Jong-Ho Won, Yeung-Chul Mun, Won Sik Lee, Hye Jin Kang, Hyo Jung Kim, Jung Hye Kwon, Jeong-A Kim, Jae-Yong Kwak, Jee Hyun Kong, Sung Yong Oh, Sun Ah Lee, Jae Hoon Lee, Eun Kyung Park, Sung Hwa Bae, Je-Jung Lee, Hyun Jung Jun, Yang Soo Kim, Hwan-Jung Yun, Won Seog Kim, Cheolwon Suh
Journal: Blood (2014)
Target regimen profiles for treatment of tuberculosis: a WHO document
Authors: Christian Lienhardt, Payam Nahid, Michael L. Rich, Cathy Bansbach, Emily A. Kendall, Gavin Churchyard, Lice González-Angulo, Lia D'Ambrosio, Giovanni Battista Migliori, Mario Raviglione
Journal: European Respiratory Journal (2017)

Treatment of tuberculosis (TB) relies on a combination of bactericidal and sterilising drugs administered for an adequate duration of time to ensure synergy of action in order to achieve definitive cure and prevent the selection of drug-resistant mutants [1]. Current treatment regimens are, however, not ideal, due to long duration and some toxicity. Particularly unsatisfactory are regimens recommended for the treatment of multidrug-resistant (MDR) (a form of tuberculosis with strains resistant to at least rifampicin and isoniazid) or extensively drug-resistant (XDR)-TB that have lower efficacy, significant toxicity, longer duration and high costs [2–5]. New TB drugs and regimens are needed to improve cure rates, lessen toxicity, and shorten the treatment of both drug-susceptible (DS) and drug-resistant TB (currently at least 6 and 9–20 months, respectively) [6, 7]. Two TB drugs (bedaquiline and delamanid) [8, 9] have become available and are recommended by the World Health Organization (WHO) for the treatment of MDR-TB under certain conditions [10, 11]. Newly launched WHO target regimen profiles for new anti-TB regimens: process and results of this initiative <http://ow.ly/TOUO307po08>
Potential Therapeutic Role of the Selective Adhesion Molecule (SAM) Inhibitor Natalizumab in Multiple Myeloma.
Authors: Klaus Podar, Alexander Zimmerhackl, Ursula Hainz, Mariateresa Fulciniti, Sonia Vallet, Dian Olsen, Yu-Tzu Tai, Teru Hideshima, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood (2009)
Copy Fees and Limitation of Patients’ Access to Their Own Medical Records
Authors: Austin W. Jaspers, Jennifer L. Cox, Harlan M. Krumholz
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
MPs condemn “arbitrary” decisions on infertility treatment
Authors: Matthew Limb
Journal: BMJ (2017)

MPs have called on ministers to end “devastating” disparities in access to infertility services across England.

They said that “crude, discriminatory, and arbitrary” funding decisions by clinical commissioning groups (CCGs) were causing suffering to people denied treatments, including stress, anxiety, depression, and the breakdown of relationships.

In a cross party debate on 19 January MPs said that wide variations in service provision should be investigated and a national tariff introduced to end anomalies in treatment costs.

Steve McCabe, Labour MP for Birmingham, Selly Oak, said that some CCGs were withdrawing fertility services altogether because of budgetary pressures. Many other CCGs were funding fewer treatment cycles than recommended by national guidelines or changing local eligibility …
Identification of Prognostic Factors in Early Unfavorable Stage Hodgkin’s Lymphoma (HL): An Individual Patient Data Meta-Analysis.
Authors: Julia Bohlius, Heinz Haverkamp, Volker Diehl, Houchingue Eghbali, Christopher Ferme, Jeremy Franklin, Beate Pfistner, Petra Schiller, John Raemaekers, Andreas Engert, Michel Henry-Amar
Journal: Blood (2006)
Incidence of Bone Marrow (BM) Fibrosis in Multiple Myeloma (MM) Patients and Its Relationship to Cytogenetic (CG) Abnormalities in a Minority Population
Authors: Gurinder Sidhu, Rabia Latif, Jinli Liu, Constantine Axiotis, Ratesh Khillan, Albert S. Braverman
Journal: Blood (2011)
Phase II Study of Melphalan, Prednisone and Lenalidomide Combination for Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation
Authors: Vivek Roy, A. Keith Stewart, P. Leif Bergsagel, Angela Dispenzieri, Kristina Laumann, Jake Allred, Martha Q. Lacy, Rafael Fonseca, Craig B. Reeder, Shaji Kumar, Candido E. Rivera, Morie A. Gertz, Philip R. Greipp, Francis K. Buadi, Suzanne R. Hayman, S. Vincent Rajkumar
Journal: Blood (2008)
Complete or Partial Deletions of IKZF1 Occur In 28% of Blast Crisis CML and Are the Only Recurrent Submicroscopic Alteration Associated with Disease Progression: An Analysis of 43 Cases Using High-Resolution Genome-Wide Copy Number DNA Arrays and Molecular Assays
Authors: Vera Grossmann, Melanie Zenger, Alexander Kohlmann, Susanne Schnittger, Wolfgang Kern, Martin C Mueller, Andreas Hochhaus, Torsten Haferlach, Claudia Haferlach
Journal: Blood (2010)
Optimal prediction of atrial fibrillation recurrence after ablation: A computational anatomy study
Authors: Marta Varela, Felipe Bisbal, Ernesto Zacur, Esther Guiu, Antonio Berruezo, Marta Sitges, Susana Prat, Oleg Aslanidi, Lluis Mont, Pablo Lamata de la Orden
Journal: Circulation (2015)
Abstract 16914: On-treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF
Authors: Christopher B Fordyce, Anne S Hellkamp, Yuliya Lokhnygina, Samuel M Lindner, Jonathan P Piccini, Richard C Becker, Scott D Berkowitz, Guenter Breithardt, Keith A Fox, Jonathan L Halperin, Graeme J Hankey, Kenneth W Mahaffey, Christopher C Nessel, Daniel E Singer, Manesh R Patel
Journal: Circulation (2015)

Introduction: ROCKET AF demonstrated the noninferiority of rivaroxaban vs. warfarin in preventing stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (AF). It is unknown whether outcomes differ among patients with worsening renal function (WRF) on rivaroxaban compared with warfarin. Methods: After excluding patients with insufficient data to calculate creatinine clearance (CrCl, Cockcroft-Gault; n=1624), we included all remaining patients (n=12,612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. The primary efficacy endpoint was the composite of stroke or SE; the primary safety endpoint was the composite of major bleeding and clinically relevant non-major bleeding. On-treatment WRF, as defined in recent cardiovascular studies as a decrease of ≥20% from screening CrCl, was evaluated as a time-dependent covariate in Cox proportional hazards models. Results: Baseline characteristics were generally similar between patients who maintained stable renal function (SRF) (n=9292) and patients with WRF (n=3320). Overall rates of stroke or SE, myocardial infarction, and bleeding were also similar, but WRF patients had an increase in vascular death (1.41 events/100 pt-years for SRF to 2.21 for WRF p=0.026). WRF patients on rivaroxaban had a reduction in stroke or SE compared with WRF patients on warfarin (1.54 events/100 pt-years for rivaroxaban to 3.25 for warfarin) that was not seen in SRF patients (p=0.050 for interaction; Figure). WRF patients on rivaroxaban had a greater incidence of hemoglobin fall ≥2 g/dL (3.56 events/100 pt-years for rivaroxaban to 1.85 for warfarin), that was not seen in SRF patients (p=0.047 for interaction). However, there was no difference in major or clinically relevant non-major bleeding. Conclusions: Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and SE compared with warfarin without an increase in the composite bleeding endpoint.