tbuckley/cabot-search huggingface dataset:
Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study
Authors: P Emery, C O Bingham, G R Burmester, V P Bykerk, D E Furst, X Mariette, D van der Heijde, R van Vollenhoven, C Arendt, I Mountian, O Purcaru, D Tatla, B VanLunen, M E Weinblatt
Journal: Annals of the Rheumatic Diseases (2016)

Objectives To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks. Methods DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)&lt;2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints. Results Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p&lt;0.001) and sLDA (43.8% vs 28.6%, p&lt;0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p&lt;0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p&lt;0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): −1.00 vs −0.82, p&lt;0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY). Conclusions CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX. Trial registration number NCT01519791.
Genetic Gradients in Epileptic Brain Malformations
Authors: Juan M. Pascual
Journal: JAMA Neurology (2016)

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 Neurology 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 Neurology journal
Pakistan is hit by a shortage of anti-tuberculosis drugs
Authors: Abdul Nafey Kazi, Hafsa Mohiuddin
Journal: BMJ (2016)

Pakistan is facing a severe shortage of drugs to treat tuberculosis (TB)—most notably ethambutol and pyrazinamide which are used to treat complex cases—because the government and the pharmaceutical industry have not been able to come to an agreement over pricing.

Most patients with TB are treated with a fixed dose combination available free under the Directly Observed Treatment, Short Course (DOTS) programme, but more complex cases need treatment …
FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis
Authors: Mustafa Suker, Berend R Beumer, Eran Sadot, Lysiane Marthey, Jason E Faris, Eric A Mellon, Bassel F El-Rayes, Andrea Wang-Gillam, Jill Lacy, Peter J Hosein, Sing Yu Moorcraft, Thierry Conroy, Florian Hohla, Peter Allen, Julien Taieb, Theodore S Hong, Ravi Shridhar, Ian Chau, Casper H van Eijck, Bas Groot Koerkamp
Journal: The Lancet Oncology (2016)
South Dakota illegally placed disabled people in nursing homes, federal investigation finds
Authors: Michael McCarthy
Journal: BMJ (2016)

In violation of federal law, the state of South Dakota unnecessarily placed elderly people and people with disabilities in nursing facilities when they could have stayed in their homes and communities with appropriate support, a US Department of Justice investigation has found.

Under the 1990 Americans with Disabilities Act (ADA) and a subsequent Supreme Court ruling, states must provide people with disabilities services in the most integrated community setting appropriate to their needs, regardless of age or type of disability.

In a 2 May letter to South Dakota governor, Dennis Daugaard, the head of the Justice Department’s Civil Rights Division, Vanita Gupta said that many of the state’s elderly and disabled people were being sent to long term care facilities despite their preference for …
An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation
Authors: George P Souroullas, William R Jeck, Joel S Parker, Jeremy M Simon, Jie-Yu Liu, Joshiawa Paulk, Jessie Xiong, Kelly S Clark, Yuri Fedoriw, Jun Qi, Christin E Burd, James E Bradner, Norman E Sharpless
Journal: Nature Medicine (2016)
Reduction in late mortality among 5-year survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Gregory T. Armstrong, Yutaka Yasui, Yan Chen, Wendy M. Leisenring, Todd M. Gibson, Ann Mertens, Marilyn Stovall, Melissa M. Hudson, Kevin C. Oeffinger, Smita Bhatia, Kevin R. Krull, Paul C. Nathan, Joseph Philip Neglia, Daniel M. Green, Leslie L. Robison
Journal: Journal of Clinical Oncology (2015)

LBA2 Background: Over the past four decades, treatment of many childhood cancers has been modified with the aim of achieving high survival rates while reducing the risk of life-threatening late-effects, and promoting risk-based follow-up care of survivors. Methods: Late mortality was evaluated in 34,033 5-year survivors (diagnosed &lt; 21 years of age from 1970-1999, median follow-up 21 years, range 5-38) using cumulative incidence and Poisson regression models adjusted for demographic and disease factors to calculate relative risk (RR) and 95% confidence intervals (CI). Mortality due to non-recurrence/non-external (NR/NE) causes, which includes deaths that reflect late-effects of cancer therapy, was evaluated. Results: 1,622 (41%) of the 3,958 deaths were attributable to NR/NE causes, including 751 subsequent neoplasm (SN), 243 cardiac, and 136 pulmonary deaths. Changes in therapy by decade included reduced rates of: cranial radiotherapy (RT) for acute lymphoblastic leukemia (ALL, 86%, 54%, 22%), RT for Wilms tumor (WT, 77%, 54%, 49%) and RT for Hodgkin lymphoma (HL, 96%, 88%, 77%). Reductions in 15 year cumulative NR/NE mortality were observed across treatment eras for ALL (p &lt; .001), HL (p = .005), and WT (p = .005). Cardiac deaths decreased in ALL (p = .002), HL (p = .06), and WT (p = .04), and SN deaths decreased in WT (p &lt; .001). Year of diagnosis (adjusted for age, sex, diagnosis, follow-up time) was significantly associated with a reduced risk of all-cause mortality (RR = 0.85, CI 0.83-0.87), NR/NE death (RR = 0.87, CI 0.84-0.91), death from SN (RR = 0.84, CI 0.80-0.89), cardiac death (RR = 0.78, CI 0.69-0.87) and pulmonary death (RR = 0.79, CI 0.68-0.91). Conclusions: The CCSS cohort provides evidence that the strategy of modifying therapy to reduce the occurrence of late-effects, and promotion of early detection, is successfully translating into a significant reduction in observed late mortality. [Table: see text]
Couples having IVF should be asked their wishes about spare embryos before egg retrieval
Authors: R. P Dickey, J. B. Krentel
Journal: BMJ (1996)

Storage of sperm and embryosCryopreservation of sperm should be offered to men with testicular cancer EDrroR,-Patients with testicular cancer often become infertile as a result of the disease and its treatment.It has been argued that all such patients should be offered cryopreservation of semen,' but in 1980 Braken and Smith reported that only 4% of patients had semen of suitable quality for a fertility programme.2The advent of intracytoplasmic sperm injection now allows even low quality sperm to be used successfully,3 but many clinicians are unaware of recent advances and the facilities available.To determine the awareness and availability of this service we sent a questionnaire to 292 consultant urologists, of whom 197 (67%) replied; we also contacted the 41 cryopreserva- tion centres in the United Kingdom.We found that 71 urologists routinely used cryopreservation facilities, while 123 left the oncologists to organise this.Of the 71 who routinely used the services, most (48) recommended storage of semen samples obtained after unilateral orchidectomy that was performed within one week of diagnosis; only a minority (23) thought that a short delay between diagnosis and orchidectomy would have an adverse effect on the clinical outcome.Of the 41 cryopreservation centres, only five offered storage on the NHS, but a further 10 had contracts with oncology services at preferential rates.All of the centres offered immediate access to facilities, so that the treatment of patients with cancer would not be greatly delayed.Cryopreservation of semen has been availablefor over 20 years in the United Kingdom but is still used by a minority of urologists.Infertility after the treatment of testicular cancer may be a cause of litigation, and this will become an increasingly important issue.Low cost storage of sperm is readily available in most of the United Kingdom and should be offered to patients with testicular cancer at the start of their treatment.
Evaluation of the relationship between patient factors and the reduction in clearance of pegylated liposomal doxorubicin
Authors: N. M. La-Beck, B. A. Zamboni, D. Tzemach, H. Schmeeda, R. Sapir, A. Gabizon, W. C. Zamboni
Journal: Journal of Clinical Oncology (2009)

2548 Background: The reticuloendothelial system (RES), which includes monocytes, may have a key role in clearance (CL) of nanoparticle sized pegylated liposomes. However, the factors affecting the CL of liposomes are unclear. Age, body composition, and monocyte count have been related to CL of liposomal agents (Zamboni, ASCO '07; Maruca, ASCO '07; Sidone, AACR- NCI-EORTC '07). The CL of pegylated liposomal doxorubicin (PLD) decreases significantly from cycle 1 to 3 (Gabizon, Cancer Chemother Pharmacol 2008). The objectives of this study were to evaluate factors associated with decreases in PLD CL. Methods: Patients (pts) with various solid tumors were randomized to PLD administered IV every 28 days at 30, 60 and 45 mg/m 2 (n = 6) or 60, 30 and 45 mg/m 2 (n = 6) on cycles 1, 2 and 3 respectively. Serial plasma samples for PLD pharmacokinetic (PK) analysis were obtained prior to and at 1 h, 24 h, 72 to 96 h, 7 d, 14 d, 21 d, and 28 d after PLD infusion on cycles 1, 2, and 3. Samples were processed to measure sum total (encapsulated + released) doxorubicin by HPLC with fluorescence. PLD CL was calculated by noncompartmental methods. Precycle monocyte count, age, and ratio of total body weight to ideal body weight were compared to PLD CL. Results: Mean + SD PLD CL on cycles 1 and 3 were 23.7 + 7.7 mL/h and 16.4 + 5.4 mL/h, (P &lt; 0.0001). Pts with a reduction as compared with an increase in precycle monocyte count from cycle 1 to 3 had a mean + SD change in PLD CL of -11.5 + -3.5 mL/h and -5.3 + -3.0 mL/h, respectively (P = 0.09). Median age was 61 years old (yo). Pts &gt; 61 yo and &lt; 61 yo had a mean + SD change in PLD CL from cycles 1 to 3 of - 8.7 + -4.3 mL/h and -5.2 + -5.4 mL/h, respectively (P = 0.16). Conclusions: PLD CL decreased significantly from cycle 1 to 3. Decreased precycle monocyte count was associated with a larger decrease in PLD CL compared to increased monocyte count. Pts &gt; 61 yo had a larger decrease in CL compared to pts &lt; 61 yo. These results suggest monocytes are involved in the CL of PLD and that older pts may have less RES reserve and thus may be more likely to have a larger decrease in PLD CL with subsequent treatment cycles. Statistical significance was not met due to small sample size; however, further investigation of the association between changes in PLD CL and patient age and monocyte count is warranted. [Table: see text]
O-008 Phase II study of tivantinib (ARQ 197) in combination with Cetuximab in EGFR Inhibitor-resistant, MET-High, KRAS Wild-Type (KRASwt) Metastatic Colorectal Cancer (mCRC)
Authors: L. Rimassa, S. Bozzarelli, S. Cordio, L. Toppo, S. Lonardi, A. Zaniboni, R. Bordonaro, W. Liguigli, V. Zagonel, M.C. Tronconi, L. Di Tommaso, L. Giordano, A. Santoro
Journal: Annals of Oncology (2015)
TMIC-03LOSS OF DAMAGE-ASSOCIATED MOLECULAR PATTERN SENSING IN CANCER STEM CELLS PROMOTES GLIOBLASTOMA MAINTENANCE
Authors: Alvaro Alvarado, James Hale, Erin Mulkearns-Hubert, Daniel Silver, Justin Lathia
Journal: Neuro-Oncology (2015)

TMIC-03. LOSS OF DAMAGE-ASSOCIATED MOLECULAR PATTERN SENSING IN CANCER STEM CELLS PROMOTES GLIOBLASTOMA MAINTENANCE Alvaro Alvarado1,2, James Hale1, Erin Mulkearns-Hubert1, Daniel Silver1, and Justin Lathia1,2; Cleveland Clinic, Cleveland, OH, USA; Case Western Reserve University, Cleveland, OH, USA Glioblastoma (GBM) is composed of heterogeneous cellular populations, including self-renewing, tumorigenic cancer stem cells (CSCs). Discrete anatomical niches have been described where CSCs communicate with their surroundings to promote their self-renewal, tumor maintenance and increased resistance to conventional therapies. A hallmark of GBM is necrosis and the tumor microenvironment also contains many damage-associated molecular pattern molecules (DAMPs) that elicit an immune response and trigger cell death. These DAMPs are sensed by receptors such as those from the toll-like receptor (TLR) family, which have well-established roles in non-immune cells within the brain. The mechanisms by which CSCs but not other tumors cells can thrive despite DAMPs have yet to be elucidated. We analyzed the expression of TLR family members in patient-derived cells and found TLR4 was significantly decreased inCSCs comparedwith non-CSC. Bioinformatics analyses of patient datasets confirmed lower TLR4 expression is associated with poor prognosis. Stimulation of TLR4 induced a decrease in proliferation in non-CSCs, which was not observed in CSCs. Overexpression of TLR4 in CSCs decreased proliferation and self-renewal as well as expression of the stem cell markers SOX2, OCT4, NANOG, and OLIG2. We analyzed the promoter region of these critical genes and identified common transcription factors that were further validated by comparing their expression in CSCs vs. non-CSCs in a RNA-seq dataset. The expression of the top ten candidates was analyzed in the context of TLR4 overexpression. We identified Retinoblastoma binding protein 5 (RbBP5) as a potential key player in this signaling pathway. Mechanistic studies are in progress to determine how RbBP5 and TLR4 interact to regulate stem cell and self-renewal pathways. Our results link a damage-sensing receptor to a CSC-specific transcription factor that is upregulated in GBM and allows cells to tolerate hostile environmental cues. Neuro-Oncology 17:v221–v225, 2015. doi:10.1093/neuonc/nov236.3 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.
Critical and direct involvement of the CD23 stalk region in IgE binding
Authors: Regina Selb, Julia Eckl-Dorna, Teresa E. Twaroch, Christian Lupinek, Andrea Teufelberger, Gerhard Hofer, Margarete Focke-Tejkl, Barbara Gepp, Birgit Linhart, Heimo Breiteneder, Adolf Ellinger, Walter Keller, Kenneth H. Roux, Rudolf Valenta, Verena Niederberger
Journal: Journal of Allergy and Clinical Immunology (2016)

The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.We expressed 4 CD23 variants. One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated. The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism. By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23. Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23.Our results provide a new model for the CD23-IgE interaction. We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
Allograft T-Cell, T-Regs, NK-Cell and B-Cell Content Influence Distinct Clinical Outcomes Following G-CSF Mobilized Hematopoietic Stem Cell Transplantation
Authors: Sumithira Vasu, Anissa Bingman, Susan Geyer, Patrick Elder, Rhonda Kitzler, Hillary Bradbury, Lynn Odonnell, William Blum, Samantha M. Jaglowski, Leslie A. Andritsos, Rebecca B. Klisovic, Sam Penza, Yvonne A Efebera, Craig C. Hofmeister, Don M. Benson, Natarajan Muthusamy, Gerard Lozanski, Steven M. Devine
Journal: Blood (2014)
Virus of Avian Myeloblastosis. XXII. Influence of Folic Acid and Other Factors on Growth of Myeloblasts and Virus Synthesis in Tissue Culture&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: C BECKER, G S BEAUDREAU, W CASTLE, B W GIBSON, D BEARD, J W BEARD
Journal: JNCI Journal of the National Cancer Institute (1962)
Cytotoxic Responses Induced by Peptidoglycans With or Without In Vivo Antitumor Activity<xref ref-type="fn" rid="FN2">2</xref>
Authors: A F Goguel, B Payelle, G Lespinats, C Nauciel
Journal: JNCI Journal of the National Cancer Institute (1983)

Cytotoxic responses mediated by effector cells stimulated in vivo were studied after ip injection in mice of peptidoglycans extracted from gram-positive bacteria. A comparison was done between Staphylococcus aureus peptidoglycan (PGS), which possessed an antitumor effect, and Micrococcus lysodeikticus peptidoglycan, which was ineffective against tumors. Both peptidoglycans induced similar effects on the modulation of T-cell cytotoxic response. Both were able to stimulate splenic and peritoneal nonspecific cytotoxicity against YAC-1 lymphoid tumor cells, but only PGS could induce cytotoxicity and cytostasis against solid tumor target cells.
ATNT-08CB-017: A PHASE 1/2 TRIAL OF BEVACIZUMAB PLUS TPI 287, A NOVEL BRAIN PENETRABLE ANTI-MICROTUBULE AGENT, IN PATIENTS WITH RECURRENT GLIOBLASTOMA NAÏVE TO ANTI-ANGIOGENIC THERAPY
Authors: Samuel Goldlust, L. Burt Nabors, J. Paul Duic, Nimish Mohile, Tara Benkers, Sigmund Hsu, Sandra Silberman, Samuel Singer, George Farmer
Journal: Neuro-Oncology (2015)

BACKGROUND: TPI 287, a third-generation taxane that readily penetrates the blood brain barrier, is under investigation for the treatment of recurrent glioblastoma (GBM). CB-017 is a dose-escalation phase 1/2 multi-center trial designed to determine the maximum tolerated dose (MTD) and efficacy of TPI 287 in combination with bevacizumab (BEV) in patients without prior exposure to angiogenesis inhibitors. Interim results from the dose escalation stage of the trial are reported here. METHODS: Patients with GBM at first relapse after standard therapy without prior exposure to anti-angiogenic agents are eligible for enrollment. BEV is administered at 10 mg/kg as an IV infusion once every 2 weeks. TPI 287 is administered as a 1-hour IV infusion every 3 weeks. Dose escalation of TPI 287 is planned until a dose-limiting toxicity (DLT) is observed in order to select the recommended phase 2 dose. MRIs are obtained at the end of every six-week cycle with response assessment via RANO. RESULTS: As of June 2015, 21 patients have been enrolled in 6 dose-escalation cohorts (140-200 mg/sq m). No DLTs have been observed to date, with myelosuppression (n = 2) as the only drug-related grade 3/4 adverse event reported. Among the 17 patients evaluable for response, 9 (53%) achieved objective response (2 CR, 7 PR) and 7 had stable disease. Median and 6-month PFS are 5.5 months [95% C.I. 4.1-10.7] and 38%, respectively. Median overall survival is 12.9 months [95% C.I. 12.2-NR] and 1-year survival is 73% after a median follow-up of 12.4 mo. CONCLUSION: TPI 287 is safe and potentially efficacious in combination with bevacizumab for the treatment of recurrent GBM. Updated safety and efficacy results will be presented.
Case 39-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, M. Flint Beal, Judith A. Ferry
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 66-year-old woman was admitted to the hospital in early November because of fever and neurologic problems.She was in a stable state of health until eight months earlier, when fever developed after a trip to New Jersey, and the temperature ranged as high as 38.3°C, with fatigue, headache, nausea, and vomiting. A physician found that the hematocrit was 30 percent and the erythrocyte sedimentation rate was elevated. A test for antinuclear antibodies was positive in a titer of 1:32. A computed tomographic (CT) scan of the abdomen was reported to be negative. No specific diagnosis was . . .