tbuckley/cabot-search huggingface dataset:
Ketamine based drug should be available for treatment resistant depression, says FDA panel
Authors: Joanne Silberner
Journal: BMJ (2019)

An advisory committee to the US Food and Drug Administration (FDA) has strongly endorsed esketamine, a derivative of the anaesthetic drug ketamine, for treatment resistant depression. The recommendation makes it likely that the agency will approve the drug for marketing in the US.

Injectable and oral ketamine is used for pain relief and sedation, and can cause amnesia. It is also used to sedate horses, and has illicit popularity as a “club drug” to induce hallucinations and calmness, or in the words of the website Vice, “to get wobbly.”1

If approved by the FDA, esketamine would be the first new treatment for major depression in decades. Some clinics in the …
Diminished Renal Pathology in a Mouse Model of Sickle Cell Anemia in Which Fibrinogen Binding to Mac-1 Is Inhibited
Authors: Md Nasimuzzaman, Paritha I. Arumugam, Eric S. Mullins, Jeanne M James, Katherine VandenHeuvel, Marilou Narciso, Maureen A. Shaw, Sarah McGraw, Bruce J. Aronow, Matthew J. Flick, Punam Malik
Journal: Blood (2018)
Achieving remission in psoriatic arthritis by early initiation of TNF inhibition: a double-blind, randomised, placebo-controlled trial of golimumab plus methotrexate versus placebo plus methotrexate
Authors: Leonieke J J van Mens, Henriëtte M de Jong, Inka Fluri, Michael T Nurmohamed, Marleen G H van de Sande, Marc Kok, Arno W R van Kuijk, Dominique Baeten
Journal: Annals of the Rheumatic Diseases (2019)

Early initiation of effective treatment favours remission in rheumatoid arthritis, but it remains unknown if the same concept applies to psoriatic arthritis (PsA). Therefore, this study investigated whether the combination of golimumab plus methotrexate (MTX) as a first-line treatment is superior to MTX alone in inducing remission in PsA.This investigator-initiated, multicentre, double-blind, randomised, placebo-controlled trial included 51 MTX and bDMARD-naive patients with PsA fulfilling the CASPAR criteria and with active disease at baseline (≥3 swollen joint count/tender joint count). Patients were randomised to golimumab (50 mg SC monthly)+MTX (n=26) (TNFi arm) or matched placebo+MTX (n=25) (MTX arm). MTX was started 15 mg/week and increased to 25 mg/week over 8 weeks. The primary endpoint was percentage of patients achieving Disease Activity Score (DAS) remission (<1.6) at week 22. Safety was assessed throughout the study.The primary efficacy endpoint was achieved by 81% in the TNFi arm versus 42 % in the MTX arm (p=0.004). This difference in DAS remission was already observed at week 8. A significant difference in favour of the golimumab+MTX arm at week 22 was also observed for other response criteria such as MDA, ACR20/50/70, disease measures and patient-reported outcomes. The occurrence rates of adverse event and treatment-emergent adverse event were similar in both arms.In patients with early PsA, DAS remission at week 22 was almost doubled with golimumab+MTX versus MTX alone. This double-blind, randomised, placebo-controlled study supports the concept that early initiation of TNFi in patients with PsA favours remission.NCT01871649.
West German Study PlanB Trial: Adjuvant Four Cycles of Epirubicin and Cyclophosphamide Plus Docetaxel Versus Six Cycles of Docetaxel and Cyclophosphamide in HER2-Negative Early Breast Cancer
Authors: Ulrike Nitz, Oleg Gluz, Michael Clemens, Wolfram Malter, Toralf Reimer, Benno Nuding, Bahriye Aktas, Andrea Stefek, Anke Pollmanns, Fatemeh Lorenz-Salehi, Christoph Uleer, Petra Krabisch, Sherko Kuemmel, Cornelia Liedtke, Steven Shak, Rachel Wuerstlein, Matthias Christgen, Ronald E. Kates, Hans H. Kreipe, Nadia Harbeck
Journal: Journal of Clinical Oncology (2019)

PURPOSE The West German Study Group PlanB trial evaluated an anthracycline-free chemotherapy standard (six cycles of docetaxel and cyclophosphamide [TC]) in the routine treatment of human epidermal growth factor receptor 2–negative early breast cancer (EBC). PATIENTS AND METHODS Patients with pT1 to pT4c, all pN+, and pN0/high-risk EBC were eligible. High-risk pN0 was defined by one or more of the following: pT greater than 2, grade 2 to 3, high urokinase-type plasminogen activator/plasminogen activator inhibitor-1, hormone receptor (HR) negativity, and less than 35 years of age. After an early amendment, all HR-positive tumors underwent recurrence score (RS) testing, with chemotherapy omission recommended in RS less than or equal to 11 pN0 to pN1 disease. Patients were randomly assigned to four cycles of epirubicin (E) 90 /cyclophoshamide (C) 600 followed by four cycles of docetaxel (T) 100 or six cycles of T 75 C 600 (administered once every 3 weeks). The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The protocol specified P = .05 for a noninferiority margin of 4.4% for all patients combined. RESULTS Of the 3,198 registered patients, 348 (RS ≤ 11) omitted chemotherapy, and 401 were not randomly assigned. The intention-to-treat population included 2,449 patients (1,227 EC-T v 1,222 TC: postmenopausal, 62.2% v 60.8%; pN0, 58.2% v 59.5%; pT1, 57.6% v 52.3%; HR positive, 81.4% v 82.2%; RS greater than 25 [in HR-positive patients], 26.2% v 27.5%). Within the safety population (1,167 v 1,178 patients), 87.5% v 93.0% completed therapy. After a 60-month median follow-up, 5-year outcomes were similar in the EC-T and TC arms (DFS, 89.6% [95% CI, 87.9% to 91.5%] v 89.9% [95% CI, 88.1% to 91.8%]; OS, 94.5% [95% CI, 93.1% to 95.9%] v 94.7% [95% CI, 93.3% to 96.1%]). The DFS difference was within the noninferiority margin of the original trial design. Five treatment-related deaths were reported for TC (one for EC-T), despite a trend toward more-severe adverse events in the latter. Interaction analysis revealed no predictive trends with respect to key factors, including triple-negative, luminal A/B-like, pN, age, and RS status. CONCLUSION In the West German Study Group PlanB trial, 5-year outcomes for TC and EC-T were equally excellent. Six cycles of TC is an effective/safe option in human epidermal growth factor receptor 2–negative EBC with pN0 high genomic risk or pN1 EBC with genomically intermediate- to high-risk disease.
Restrictive FDA Requirements and the Development of Generic Topical Medications
Authors: Nicholas K. Mollanazar
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Case 63-1964
Authors: K. Frank Austen, Wallace H. Clark
Journal: New England Journal of Medicine (1964)

Presentation of Case First admission. A seventy-year-old woman entered the hospital because of a skin rash.Nine months previously headaches and a brownish nasal discharge developed, and examination of the nose several months later revealed a friable mucous membrane covered with bloody crusts. Treatment with syrup of hydriodic acid and a spray containing iodide caused improvement. A few months before admission numbness, pain and swelling of the feet and ankles began, and red spots appeared over the lower portions of the legs. During the month before entry the spots spread to involve all four extremities, and the swelling and pain . . .
Abstract SY25-01: Genome regulation by long noncoding RNAs
Authors: Howard Y. Chang
Journal: Cancer Research (2018)

Abstract The discovery of extensive transcription of long noncoding RNAs (lncRNAs) provides an important new perspective on the centrality of RNA in gene regulation. I will discuss genome-scale strategies to discover and characterize lncRNAs. An emerging theme from multiple model systems is that LncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators, and target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, long noncoding RNAs can function as modular scaffolds to specify higher-order organization in RNP complexes and in chromatin states. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs in human diseases. Citation Format: Howard Y. Chang. Genome regulation by long noncoding RNAs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY25-01.
CD70 and ganglioside expression by GBM induce T-cell apoptosis which is protected by desferoxamine
Authors: Ali Chahlavi, Patricia Rayman, Amy L. Richmond, Charlie Tannenbaum, Kaushik Biswas, Michael A. Vogelbaum, Gene H. Barnett, James Finke
Journal: Cancer Research (2005)

6027  Immunotherapy is an attractive approach to the treatment of Glioblastoma multiforme (GBM), however, immunosuppression mediated by the tumor microenvironment may impair T cell based immunotherapy. The goal here was to examine the role of gangliosides and CD70 in GBM-induced apoptosis of T cells. Seven GBM lines were co-cultured with peripheral blood T-cells to prior to assessing T cell death. The relevance of GBM-derived gangliosides in T-cell killing was assessed by testing whether blocking ganglioside expression by GBM lines using glucosylceramide synthase inhibitor, PPPP would reduce the apoptogenic activity of the GBM lines. Gangliosides isolated from these cell lines were also tested for their ability to induce T cell death. Two apoptogenic GBM gangliosides were separated by HPLC, and individual fractions tested for their ability to induce T cell death. The GBM cell lines also were evaluated for the expression of CD70. The role of CD70 in stimulating T-cell death was determined using CD70 antibody. Cyclosporine-a, Bongkrekic-acid (BA) and Desferoxamine were used with gangliosides and GBM tumors in the presence of T-cells to assess their protective effects on these lymphocytes. Four cell lines induced T-cell death in resting T cells and five in activated T cells. Three of the apoptogenic cell lines (U87, CCF52 and D54) had a high percentage of CD70 expression, while CCF4 and two non-apoptogenic GBM lines (CCF3 and U138) had minimal detectable CD70 surface expression. High expression of CD70 is involved in tumor-induced T cell death since the addition of CD70 antibody to the co-cultures partially reduced T cell apoptosis by the CD70 expressing GBM lines but not the CD70 negative line (CCF4). Gangliosides expressed by the four apoptogenic GBM lines also participated in T-cell apoptosis. Blocking ganglioside expression by GBM lines with PPPP partially prevented T cell apoptosis. Furthermore, gangliosides isolated from these four GBM lines induced apoptosis of T lymphocytes. HPLC analysis of gangliosides revealed enhanced expression of GM1, GM2 and GD1a by the apoptogenic tumors compared to the non-apoptogenic lines. HPLC separation of GBM derived ganglisodies revealed two major peaks of apoptogenic activity against T cells, one with the elution time of GM2 and the other with an elution time near GD1a. All three drugs achieved some protection; however, desferoxamine, an iron chelator, was most effective against T-cell killing by GBM cell-lines and their purified gangliosides. These findings demonstrate that CD70 and gangliosides expressed by GBM lines participate in mediating T cell death and that the antioxidant desferoxamine may be useful in promoting T cell survival and function.
Risk Stratification Integrating Deauville Score on Interim PET-CT Scan and Baseline International Prognostic Index in Diffuse Large B-Cell Lymphoma Patients
Authors: Ho-Young Yhim, Sung Kyun Yim, So Yeon Jeon, Yeon-Hee Han, Myung-Hee Sohn, Na-Ri Lee, Eun-Kee Song, Chang-Yeol Yim, Hee Sun Kim, Jae-Yong Kwak
Journal: Blood (2018)
Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics
Authors: Sayuri Miyauchi, Sangwoo S. Kim, John Pang, Kathryn A. Gold, J. Silvio Gutkind, Joseph A. Califano, Loren K. Mell, Ezra E.W. Cohen, Andrew B. Sharabi
Journal: Clinical Cancer Research (2019)

Head and neck squamous cell carcinoma (HNSCC) accounts for more than 600,000 cases and 380,000 deaths annually worldwide. Although human papillomavirus (HPV)-associated HNSCCs have better overall survival compared with HPV-negative HNSCC, loco-regional recurrence remains a significant cause of mortality and additional combinatorial strategies are needed to improve outcomes. The primary conventional therapies to treat HNSCC are surgery, radiation, and chemotherapies; however, multiple other targeted systemic options are used and being tested including cetuximab, bevacizumab, mTOR inhibitors, and metformin. In 2016, the first checkpoint blockade immunotherapy was approved for recurrent or metastatic HNSCC refractory to platinum-based chemotherapy. This immunotherapy approval confirmed the critical importance of the immune system and immunomodulation in HNSCC pathogenesis, response to treatment, and disease control. However, although immuno-oncology agents are rapidly expanding, the role that the immune system plays in the mechanism of action and clinical efficacy of standard conventional therapies is likely underappreciated. In this article, we focus on how conventional and targeted therapies may directly modulate the immune system and the tumor microenvironment to better understand the effects and combinatorial potential of these therapies in the context and era of immunotherapy.
P010 Characterization of distinct dendritic cell subsets in the context of chronic inflammation
Authors: F Coutant, J Zhang, P Miossec
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Assistant. <h3>Introduction</h3> Dendritic cells (DCs) are central regulators of the balance between immunity and tolerance, and alteration of the specialized DCs system is a common feature in chronic inflammatory diseases, such as rheumatoid arthritis (RA). In RA, synovial tissues are characterized by aberrant distribution of DCs populations, with altered phenotype. However, an in-depth characterization of the altered phenotype and functions of DCs in RA has been hampered by a lack of specific DCs markers and relevant <i>in vitro</i> culture model. <h3>Objectives</h3> To perform an in-depth phenotypic characterization of DCs found in RA joints with an extensive panel of monoclonal antibodies specific of DCs, and to establish a relevant <i>in vitro</i> culture model to generate DCs resembling to those found in joints. <h3>Methods</h3> Flow cytometry was used for analysis of cell surface molecules expressed on DCs found in RA synovial fluid (SF). Staining was performed with a panel of 100 mouse monoclonal antibodies specific of DCs, generated by immunization with different subsets of human DCs. Phenotype of DCs from synovial fluid was then compared to the phenotype of monocytes co-cultured <i>in vitro</i> with synoviocytes from RA patients, in presence or not of synovial fluid, or cytokines. <h3>Results</h3> In RA SF patients, two main DCs subsets were identified, with distinct surface protein phenotypes. One subset was characterized by markers of plasmacytoid DCs (CD303, CD123), whereas the other subset expressed markers of myeloid/conventional DCs (CD11c, DCIR). This last subset of DCs expressed some markers found on inflammatory DCs, the main inducers of Th17 cells in RA joints. Surprisingly, the two subsets of DCs expressed also surface proteins shared by synoviocytes. Culture of human monocytes with synoviocytes and/or combination of pro-inflammatory cytokines (TNF, M-CSF, IL-4) yielded DCs with a phenotype close to the phenotype of conventional DCs found in RA synovial fluid. <h3>Conclusions</h3> We uncovered previously unreported phenotypic heterogeneity of DCs in a chronic inflammatory context, and characterized two main subsets of DCs. The next steps will be to understand the consequences of this heterogeneity on the pathogenicity of the disease. This will be facilitated by our relevant <i>in vitro</i> culture model that allows the generation of DCs, closely resembling those found in joints of patients with RA. <h3>Disclosure of Interest</h3> None declared.
Longitudinal Multilevel Omic Analysis of Pediatric T-ALL Reveals Distinct Mechanisms for Disease Progression in Type 1 and in Type 2 Relapses
Authors: Paulina Richter-Pechanska, Joachim B. Kunz, Tobias Rausch, Busra Erarslan-Uysal, Beat Bornhauser, Viktoras Frismantas, Maria Pamela Dobay, Caroline Von Knebel Doeberitz, Martin Zimmermann, Stephan Fuhrmann, Martin Stanulla, Martin Schrappe, Gunnar Cario, Gabriele Escherich, Kseniya Bakharevich, Renate Kirschner-Schwabe, Cornelia Eckert, Stefan Pfister, Martina U. Muckenthaler, Jean-Pierre Bourquin, Jan O. Korbel, Andreas E. Kulozik
Journal: Blood (2018)
Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology
Authors: Douglas E. Wood, Ella A. Kazerooni, Scott L. Baum, George A. Eapen, David S. Ettinger, Lifang Hou, David M. Jackman, Donald Klippenstein, Rohit Kumar, Rudy P. Lackner, Lorriana E. Leard, Inga T. Lennes, Ann N.C. Leung, Samir S. Makani, Pierre P. Massion, Peter Mazzone, Robert E. Merritt, Bryan F. Meyers, David E. Midthun, Sudhakar Pipavath, Christie Pratt, Chakravarthy Reddy, Mary E. Reid, Arnold J. Rotter, Peter B. Sachs, Matthew B. Schabath, Mark L. Schiebler, Betty C. Tong, William D. Travis, Benjamin Wei, Stephen C. Yang, Kristina M. Gregory, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2018)

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.
Clinical Testing of Hemechip in Nigeria for Point-of-Care Screening of Sickle Cell Disease
Authors: Muhammad Noman Hasan, Arwa Fraiwan, Priyaleela Thota, Tolulope Oginni, Grace Mfon Olanipekun, Fatimah Hassan-Hanga, Jane Little, Stephen K. Obaro, Umut A. Gurkan
Journal: Blood (2018)
Short survival and frequent transformation in extranodal marginal zone lymphoma with multiple mucosal sites presentation
Authors: Juan Pablo Alderuccio, Wei Zhao, Amrita Desai, Jeremy Ramdial, Nicolas Gallastegui, Erik Kimble, Macarena I. de la Fuente, Muhammad Husnain, Joseph D. Rosenblatt, Alvaro J. Alencar, Jonathan H. Schatz, Craig H. Moskowitz, Jennifer R. Chapman, Francisco Vega, Isildinha M. Reis, Izidore S. Lossos
Journal: American Journal of Hematology (2019)

Between 11 and 37% of extranodal marginal zone lymphoma (EMZL) patients present with disease involvement in multiple mucosal sites (MMS). We analyzed 405 EMZL patients seen between 1995 and 2017: 265 (65.4%) patients presented with stage I disease, 49 of 309 (15.8%) patients with bone marrow involvement, and 35 of 328 (10.7%) patients with monoclonal gammopathy (MG). Forty-three (10.6%) patients had MMS presentation, which was more frequently seen in patients aged >60 years (55.8%). Five (17.9%) of 28 MMS patients had MG. MMS patients commonly exhibited the International Prognostic Index (IPI) >2 (79.1%), Follicular Lymphoma International Prognostic Index (FLIPI) >2 (39.5%), and Mucosa-Associated Lymphoid Tissue Lymphoma International Prognostic Index (MALT-IPI) 2-3 (60.5%). Both MMS presentation and MG were associated with shorter survival univariately. In multivariable Cox regression models, shorter progression-free survival (PFS) and overall survival (OS) were observed in patients with MMS (hazard ratio [HR] = 3.08 and 2.92, respectively), age ≥60 years (HR = 1.52 and 2.45, respectively), and in patients who failed to attain a complete remission following initial therapy (HR = 3.27 and 2.13, respectively). Elevated lactate dehydrogenase was associated with shorter PFS (HR = 1.92), while anemia (HR = 2.46) was associated with shortened OS. MALT-IPI ≥2 (HR = 2.47 and 4.75), FLIPI >2 (HR = 1.65 and 2.09), and IPI >2 (HR = 2.09 and 1.73) were associated with shorter PFS and OS, respectively. Higher grade transformation (HGT) occurred in 11 (25.6%) MMS patients with a 5-year cumulative incidence of 13.2% (95% CI 4.7-26.1%). EMZL patients with MMS presentation represent a novel clinical subset associated with shorter PFS, OS, and higher incidence of HGT that needs novel therapeutic approaches.
Abstract 18850: Use of High Sensitivity Troponin Levels for Prediction of Myocardial Ischemia During Stress Testing
Authors: Bryan Kindya, Muhammad Hammadah, Ayman Alkhoder, Ibhar Al Mheid, Kobina Wilmost, Wesley O'Neal, Samaah Sullivan, Ayman Samman Tahhan, Alaeldine Hammoud, Naser Abdulhadi, Heval Mohamed Kelli, Ronnie Ramadan, Pratik Pimple, Pratik Sandesara, Amit Shah, Malik Obideen, Laura Ward, Yi-An Ko, Yan Sun, Brad Pearce, Ernest Garcia, Michael Kutner, J. Douglas Bremmer, Fabio Esteves, David Sheps, Paolo Raggi, Viola Vaccarino, Arshed Quyyumi
Journal: Circulation (2017)

Introduction: Stress tests are routinely used for the detection of reversible myocardial ischemia. We determined the relationship between resting high sensitivity cardiac troponin I (hs-cTnI) levels and stress-induced myocardial ischemia (SMI) in patients with known coronary artery disease (CAD). Hypothesis: Patients with low hs-cTnI levels will not have reversible ischemia during stress. Methods: A discovery cohort of 581 patients and a validation cohort of 103 patients with stable CAD underwent 99mTc-SPECT myocardial perfusion imaging during treadmill exercise or pharmacologic stress testing and had pre-stress hs-cTnI levels measured (Abbott Labs). SMI was defined as a new or worsening impairment in myocardial perfusion using a 17-segment model. Sensitivity, specificity, and negative predictive value (NPV) were calculated. Results: The 34.9% of patients who developed SMI in the discovery cohort had higher hs-cTnI levels (5.4 [3.9-9.2] vs 3.9 [2.5-6.5] pg/mL, p<0.001). Low resting levels of hs-cTnI had a...