tbuckley/cabot-search huggingface dataset:
Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma
Authors: Alissa A Thomas, Lauren E Abrey, Robert Terziev, Jeffrey Raizer, Nina L Martinez, Peter Forsyth, Nina Paleologos, Matthew Matasar, Craig S Sauter, Craig Moskowitz, Stephen D Nimer, Lisa M DeAngelis, Thomas Kaley, Sean Grimm, David N Louis, J. Gregory Cairncross, Katherine S Panageas, Samuel Briggs, Geraldine Faivre, Nimish A Mohile, Jayesh Mehta, Philip Jonsson, Debyani Chakravarty, Jianjiong Gao, Nikolaus Schultz, Cameron W Brennan, Jason T Huse, Antonio Omuro
Journal: Neuro-Oncology (2017)

Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy.Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 × 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day × 3 days, then busulfan 3.2 mg/kg/day × 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing.Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors.TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odg_msk_2017, accessed 6 January 2017.NCT00588523.
Type of surgery for early breast cancer and predictive factors an institutional review: A regression model.
Authors: Mahvish Muzaffar, Iman Mohamed, Colette Gaba, Sadik Khuder
Journal: Journal of Clinical Oncology (2013)

e12016 Background: Breast conserving surgery (BCS) is the preferred surgical management for most early-stage breast cancer, given the equivalent survival after BCS plus radiation and mastectomy (M). Clinical reports of an increasing trend in mastectomy from some institutional reviews have been published. The aim of this study was to assess correlation of type of surgery with different factors in our cancer registry database. Methods: We retrospectively reviewed the cancer registry data at UTMC for early breast cancer stage I/II from 2006-2010. Patient demographics, tumor characteristics, institution of surgery, academic versus private surgeon were identified and compared. We used univariate analysis to select factors for entry into a multivariate analysis. Multinomial logistic regression analysis was performed to predict the type of surgery (cancer side mastectomy (CSM) versus BCS, bilateral mastectomy (BM) versus BCS based on the above variables. A p-value of &lt; 0.05 was significant and comparisons were two tailed. Results: We identified 506 eligible patients with stage I/II breast cancer. 306(60.5%) had undergone breast conservative surgery (BCS), 91 (18%) patients had cancer side mastectomy (CSM) and 109 (21.5%) patients had bilateral mastectomy (BM). 298 (59%) patients were stage I and 208 (41%) had stage II, 218 (42%) had undergone surgery at academic center versus 298 (58%) at nonacademic institution. Predictors o CSM were stage II (p =0.0193), high-grade tumor (p=0.015), surgeon from academic institution (p=0.64), age (p=0.61). Predictors of BM were surgeon from academic institution (p=0.060), age (p=0.07). Conclusions: This study confirms some known factors like stage, surgeon expertise, as influencing factors in type of local surgery, while at the same time did not show impact of race and other tumor characteristics. Further research of these factors need to confirm the influence on decision making prospectively.
Submucosal tunneling endoscopic septum division for Zenker’s diverticulum: a reproducible procedure for endoscopists who perform peroral endoscopic myotomy
Authors: Bertrand Brieau, Sarah Leblanc, Benoit Bordacahar, Maximillien Barret, Romain Coriat, Frederic Prat, Stanislas Chaussade
Journal: Endoscopy (2017)

Zenker's diverticulum is a rare disease occurring in less than 0.5 % of the global population. Currently, the diverticuloscope-assisted diverticulotomy represents the traditional procedure, the diverticuloscope enabling better exposure of the muscular fibers. Although effective and safer than surgery, this technique could be complicated by perforation, which is reported in as many as 6.5 % of patients [1]. Recently, Li et al. reported a novel technique called the submucosal tunneling endoscopic septum division (STESD) [2], inspired by the peroral endoscopic myotomy (POEM) technique [3]. The theoretical advantage is to completely dissect the muscular septum without mucosal opening. This video case reports the second successful treatment of Zenker's diverticulum using this new procedure.
Pericytes impair capillary blood flow and motor function after chronic spinal cord injury
Authors: Yaqing Li, Ana M Lucas-Osma, Sophie Black, Mischa V Bandet, Marilee J Stephens, Romana Vavrek, Leo Sanelli, Keith K Fenrich, Antonio F Di Narzo, Stella Dracheva, Ian R Winship, Karim Fouad, David J Bennett
Journal: Nature Medicine (2017)
The Immunohistochemical Expression of p53 in Bone Marrow Biopsy Has Unfavorable Prognostic Impact in Higher Risk Myelodysplastic Syndromes If It Is at Least 10%
Authors: Alfredo Molteni, Emanuele Ravano, Laura Bandiera, Marta Riva, Michele Nichelatti, Silvia Cantoni, Mauro Truini, Roberto Cairoli
Journal: Blood (2016)
Reconsidering Physician–Pharmaceutical Industry Relationships
Authors: Colette DeJong, R. Adams Dudley
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
A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis
Authors: DanQi Deng, Peilian Zhang, Yun Guo, Teck Onn Lim
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objective</h3> We evaluate the efficacy of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) for the treatment of lupus nephritis (LN). Previous reports showed hUC-MSC could have dramatic treatment effect. <h3>Methods</h3> Eighteen patients with WHO class III or IV LN were randomly assigned to hUC-MSC (dose 2×10<sup>8</sup> cells) or placebo. All patients received standard immunosuppressive treatment, which consisted of intravenous methylprednisolone and cyclophosphamide, followed by maintenance oral prednisolone and mycophenolate mofetil. <h3>Results</h3> Remission occurred in 9 of 12 patients (75%) in the hUC-MSC group and 5 of 6 patients (83%) in the placebo group. Remission was defined as stabilisation or improvement in renal function, reduction in urinary red cells and protein. A similar proportion of patients on hUC-MSC and placebo achieved complete remission. Improvements in serum albumin, complement, renal function, Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group scores were similar in both groups. One patient on placebo had a stroke and another had ascites. One patient on hUC-MSC had leucopenia, pneumonia and subcutaneous abscess and another died of severe pneumonia. The trial was abandoned after 18 patients were enrolled when it had become obvious it would not demonstrate a positive treatment effect. <h3>Conclusion</h3> hUC-MSC has no apparent additional effect over and above standard immunosuppression. <h3>Trial registration number</h3> NCT01539902; Results.
Abstract 421: Nck Promotes Podosome Formation and Function in Vascular Endothelial Cells
Authors: Sankar P Chaki, Rola Barhoumi, Gonzalo M Rivera
Journal: Circulation Research (2015)

Podosomes are actin rich adhesion structures capable of extracellular matrix remodeling (ECM) and facilitate invasive cell migration. ECM remodeling and migration of endothelial cells (ECs) are prerequisites for angiogenesis, an important process in development and cardiovascular disease. In this study using a combination of molecular genetics and high resolution microscopy, we have demonstrated that adaptor proteins Nck1 and Nck2, that links signaling by tyrosine phosphorylation with actin dynamics, promote podosome formation and function. Expression of human Nck1-YFP or human Nck2-mCherry induces podosome formation in human umbilical vein endothelial cells. Silencing of Nck by retroviral expression of short hairpin RNA disrupted podosome formation in Src transformed endothelial cells. Both number of cells with podosomes and number of podosomes per cell decreased significantly (P&lt;0.05) compared with control and rescued cells. Functionally, Nck silenced cells were deficient in fluorescent gelatin matrix degradation, an effect that could be almost completely reversed by expression of siRNA-resistant Nck2. Further, overexpression of Nck in Src transformed endothelial cells induced an even higher (p&lt;0.05) index of matrix degradation when compared with Src transformed control cells. Overall, a high degree of colocalization between F-actin and areas of degradation was observed. However, areas of degradation without cellular/F-actin colocalization [[Unable to Display Character: &amp;#8211;]] presumably due to the highly motile nature of HUVEC [[Unable to Display Character: &amp;#8211;]] were also observed. Mechanistically we found that Nck promote podosome biogenesis through interaction with p62Dok. Collectively, these results provide strong support for a critical role of Nck adaptors in the invasive program of endothelial cells which is important in health and diseases.
Use of bone scans during initial prostate cancer (CaP) workup, downstream procedures, and associated Medicare costs.
Authors: Aaron David Falchook, Ramzi George Salloum, Laura H. Hendrix, Ronald C. Chen
Journal: Journal of Clinical Oncology (2013)

5040 Background: Bone scans are not recommended in the routine workup for patients with apparent low and intermediate risk CaP. We quantified the use of bone scans in low and intermediate risk patients, uses of other imaging and procedures after the bone scan, and costs to Medicare. Methods: Patients in the Surveillance Epidemiology and End Results (SEER)-Medicare database diagnosed with CaP from 2004 to 2007 were included. PSA, Gleason score and clinical T stage were used to define D’Amico risk categories. Patients with metastatic disease were included because the decision to order a staging bone scan for patients with apparent low and intermediate risk cancers occurs before knowledge about metastasis. We report use of bone scans from the date of diagnosis to the earlier of treatment or 12 months. In patients who received bone scans, we report use of X-ray, CT, MRI, and bone biopsy following bone scan to the earlier of treatment or 12 months. Cost was estimated using Medicare reimbursement rates. Results: 28% and 47% of patients with apparent low- and intermediate-risk prostate cancer received a bone scan (Table); &lt;1% of these patients were found to have metastatic disease after work-up. A high proportion of patients had other imaging studies or biopsies after bone scan. For low and intermediate risk patients, the combined cost to Medicare of bone scan, X-ray, and bone biopsy as part of initial workup is estimated at $11,000,000 per year. The cost from CT and MRI after bone scan costs Medicare approximately $15,400,000 per year. Conclusions: Overuse of bone scans is common in workup of apparent low and intermediate risk CaP, even with an almost 0% risk of metastatic disease. X-rays, bone biopsies, and perhaps additional scans such as CT and MRI may result from bone scan findings, which are mostly false positives for these patients. These unnecessary procedures are costly to Medicare. [Table: see text]
Cerebral Venous Thrombosis in Neonates, Children and Adolescents; Results from the German Pediatric Surveillance Unit for Rare Pediatric Diseases (ESPED)
Authors: Susanne Holzhauer, Christine Heller, Knöfler Ralf, Kentouche Karim, Krümpel Anne, Kurnik Karin, Ulrike Nowak-Gottl
Journal: Blood (2016)
Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis
Authors: William J. Sandborn, Chinyu Su, Bruce E. Sands, Geert R. D’Haens, Séverine Vermeire, Stefan Schreiber, Silvio Danese, Brian G. Feagan, Walter Reinisch, Wojciech Niezychowski, Gary Friedman, Nervin Lawendy, Dahong Yu, Deborah Woodworth, Arnab Mukherjee, Haiying Zhang, Paul Healey, Julian Panés
Journal: New England Journal of Medicine (2017)

Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy.
Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics
Authors: Toshihiro Tanaka, Weici Zhang, Ying Sun, Zongwen Shuai, Asiya Seema Chida, Thomas P. Kenny, Guo‐Xiang Yang, Ignacio Sanz, Aftab Ansari, Christopher L. Bowlus, Gregory C. Ippolito, Ross L. Coppel, Kazuichi Okazaki, Xiao‐Song He, Patrick S.C. Leung, M. Eric Gershwin
Journal: Hepatology (2017)

A major problem in autoimmunity has been identification of the earliest events that lead to breach of tolerance. Although there have been major advances in dissecting effector pathways and the multilineage immune responses to mitochondrial self-antigens in primary biliary cholangitis, the critical links between environmental factors and tolerance remain elusive. We hypothesized that environmental xenobiotic modification of the E2 subunit of the pyruvate dehydrogenase (PDC-E2) inner lipoyl domain can lead to loss of tolerance to genetically susceptible hosts. Previously we demonstrated that serum anti-PDC-E2 autoantibodies cross-react with the chemical xenobiotics 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid and further that there is a high frequency of PDC-E2-specific peripheral plasmablasts. Herein we generated 104 recombinant monoclonal antibodies (mAbs) based on paired heavy-chain and light-chain variable regions of individual plasmablasts derived from primary biliary cholangitis patients. We identified 32 mAbs reactive with native PDC-E2, including 20 specific for PDC-E2 and 12 cross-reactive with both PDC-E2 and 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid. A lower frequency of replacement somatic hypermutations, indicating a lower level of affinity maturation, was observed in the complementarity-determining regions of the cross-reactive mAbs in comparison to mAbs exclusively recognizing PDC-E2 or those for irrelevant antigens. In particular, when the highly mutated heavy-chain gene of a cross-reactive mAb was reverted to the germline sequence, the PDC-E2 reactivity was reduced dramatically, whereas the xenobiotic reactivity was retained. Importantly, cross-reactive mAbs also recognized lipoic acid, a mitochondrial fatty acid that is covalently bound to PDC-E2.Our data reflect that chemically modified lipoic acid or lipoic acid itself, through molecular mimicry, is the initial target that leads to the development of primary biliary cholangitis. (Hepatology 2017;66:885-895).
The future of asthma research and development: a roadmap from the European Asthma Research and Innovation Partnership (EARIP)
Authors: Sarah Masefield, Jessica Edwards, Kjeld Hansen, Dominique Hamerlijnck, Karin Lisspers, Marc van der Schee, Liliana Silva, John Matthews, Mina Gaga, Ian Adcock, Stephen Holgate, Samantha Walker, Pippa Powell
Journal: European Respiratory Journal (2017)

Asthma is highly prevalent and associated with high morbidity and mortality. It affects 30–50 million people in Europe, often starting in infancy and persisting throughout life. Asthma is a major global health challenge, affecting more than 300 million people worldwide and at least 10% of all Europeans [1]. People with asthma live at risk of life-threatening asthma attacks, leading to over 500 000 hospitalisations each year. Approximately 5–10% of asthma cases are so severe that current treatments do not work. Asthma outcomes will be transformed if the priorities in the EARIP research roadmap are addressed <http://ow.ly/9maP307TVNk> Thanks go to all EARIP partners: Sebastian Johnston, Sven-Erik Dahlen, Giuseppe De Carlo, Susanna Palkonen, Luis Garcia-Marcos, Nikos Papadopoulos, Aggeliki Androutsopoulou, Cezmi Akdis, Maciek Kupczyk, John Riley, David Myles, Mark Levick, Ratko Djukanovic, Piotr Kuna; and to the remaining workshop participants and PICO question developers: Guy Joos, Hilary Pinnock, Antonius Schneider, Liliana Silva, Jacky Smith, Otto Spranger, Peter Sterk, Phil Taverner, Ian Adcock, Peter Barnes, Elisabeth Bel, Breda Flood, Liliya Gentet, Christina Gratziou, Ian Hall, Rob Horne, Katherine Cowan, Leanne Metcalf, Erika Kennington, Courtney Coleman, Liam Heaney, Hector Ortega, Samantha Sonnappa, Rik Loijmans, Ildiko Horvath, John Riley, Sarah Kirby, Lucy Yardley, Ben Ainsworth, Paul Cullinan, Angela Simpson. The final thanks go to the EARIP Patient Advisory Group and all who completed the online surveys.
Safety and Efficacy of Donor-Derived Virus Specific Cytotoxic T Lymphocytes(CTL) Administered in Treatment for CMV/EBV Infections after Allogenetic Stem Cell Transplantation
Authors: Jingbo Wang, Xiaojun Huang, Ying Hu, Song Xue, Haoyu Cheng, Yuming Yin, Weijie Zhang, Jiangying Gu, Junbao He, Fan Yang
Journal: Blood (2016)
An evidence-based, point-of-care tool to guide completion of asthma action plans in practice
Authors: Andrew Kouri, Louis-Philippe Boulet, Alan Kaplan, Samir Gupta
Journal: European Respiratory Journal (2017)

Asthma action plans (AAPs) reduce healthcare utilisation, improve quality of life and are recommended across guidelines. However, fewer than 25% of patients receive an AAP, partly due to prescribers' inability to complete “yellow zone” instructions (how to intensify therapy for acute loss of control). We sought to review best evidence to develop a practical, evidence-based tool to facilitate yellow zone guidance in adults. We reviewed recent asthma guidelines and adult studies addressing acute loss of asthma control (January 2010 to March 2016). We developed evidence-based rules for yellow zone therapy and operational guidelines to maximise adherence and minimise errors. We reviewed three guidelines and 11 manuscripts (2486 abstracts screened). Recommendations were comparable but some areas lacked guidance. For 15/43 asthma regimens, the commonly recommended four- to five-fold yellow zone inhaled corticosteroid dose increase was problematic due to regulatory dose limits. We identified evidence-based alternatives for 8/15 regimens. Operational guidance included increasing to a maximum of four inhalations while maintaining baseline inhaler frequency and device in the yellow zone. We developed a practical implementation tool to facilitate AAP delivery at the point of care, addressing existing gaps and uncertainties. Our tool should be implemented as part of a multifaceted approach to augment AAP usage.
Intermittent glucocorticoid steroid dosing enhances muscle repair without eliciting muscle atrophy
Authors: Mattia Quattrocelli, David Y. Barefield, James L. Warner, Andy H. Vo, Michele Hadhazy, Judy U. Earley, Alexis R. Demonbreun, Elizabeth M. McNally
Journal: Journal of Clinical Investigation (2017)

Glucocorticoid steroids such as prednisone are prescribed for chronic muscle conditions such as Duchenne muscular dystrophy, where their use is associated with prolonged ambulation. The positive effects of chronic steroid treatment in muscular dystrophy are paradoxical because these steroids are also known to trigger muscle atrophy. Chronic steroid use usually involves once-daily dosing, although weekly dosing in children has been suggested for its reduced side effects on behavior. In this work, we tested steroid dosing in mice and found that a single pulse of glucocorticoid steroids improved sarcolemmal repair through increased expression of annexins A1 and A6, which mediate myofiber repair. This increased expression was dependent on glucocorticoid response elements upstream of annexins and was reinforced by the expression of forkhead box O1 (FOXO1). We compared weekly versus daily steroid treatment in mouse models of acute muscle injury and in muscular dystrophy and determined that both regimens provided comparable benefits in terms of annexin gene expression and muscle repair. However, daily dosing activated atrophic pathways, including F-box protein 32 (Fbxo32), which encodes atrogin-1. Conversely, weekly steroid treatment in mdx mice improved muscle function and histopathology and concomitantly induced the ergogenic transcription factor Krüppel-like factor 15 (Klf15) while decreasing Fbxo32. These findings suggest that intermittent, rather than daily, glucocorticoid steroid regimen promotes sarcolemmal repair and muscle recovery from injury while limiting atrophic remodeling.