tbuckley/cabot-search huggingface dataset:
Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis
Authors: Bianca Tesi, Kristina Lagerstedt-Robinson, Samuel C C Chiang, Eya Ben Bdira, Miguel Abboud, Burcu Belen, Omer Devecioglu, Zehra Fadoo, Allen E J Yeoh, Hans Christian Erichsen, Merja Möttönen, Himmet Haluk Akar, Johanna Hästbacka, Zuhre Kaya, Susana Nunes, Turkan Patiroglu, Magnus Sabel, Ebru Tugrul Saribeyoglu, Tor Henrik Tvedt, Ekrem Unal, Sule Unal, Aysegul Unuvar, Marie Meeths, Jan-Inge Henter, Magnus Nordenskjöld, Yenan T Bryceson
Journal: Genome Medicine (2015)
Phase II clinical study of STI571 in Japanese (Jpn) patients (pts) with malignant gastrointestinal stromal tumors (GIST): results of the B 1201 study
Authors: T. Doi, T. Nishida, S. Hirota, T. Sugiyama, K. Yamao, M. Koseki, T. Okamura, K. Shirao, A. Ohtsu
Journal: Journal of Clinical Oncology (2004)

4078 Background: STI 571, (Gleevec), is a specific inhibitor of BCR-ABL, c-kit, and PDGFR tyrosine kinases. After demonstration of efficacy against KIT- positive GISTs, STI571 was approved for the treatment of GISTs in the US and the EU. This Phase II open-labelled, multicenter trial investigated the efficacy, tolerability, and PK of STI571 in Japanese pts with unresectable and/or metastatic malignant GISTs. Methods:The inclusion criteria were KIT-positive and unresectable and/or metastatic GISTs with measurable lesions, adequate organ function, PS (ECOG)of 0–2, and a life expectancy >2 months. Pts were randomized to either 400 or 600 mg/day of STI571. For PD, the dose was increased. Efficacy was assessed by SWOG criteria, and toxicity was reported by NCI-CTC v2.0. PK was examined in 21 patients. Results: 74 pts were enrolled (400 mg /600 mg = 28/46, M/F = 48/26, PS 0/1/2=57/14/3, median age=56 years (range 24–74)). C-kit mutations in exon 11 was the most common mutational abnormality (79.7 %) and mutation in exon 9 was the next most common (10.3 %). The overall response rate was 55.4% (CR/PR/SD/PD = 0/41/30/1).The percentage of pts with PR was higher in the 600 mg dose group than in the 400 mg dose group (60.9% vs 46.4%) however this was not statistically significant. All pts experienced AE with a suspected relationship to STI571, 90 % of which were grade 1 or 2 (nausea, vomiting, diarrhoea, facial edema, etc). A relatively high number (>5% of incidents) of grade 3/4 toxicities were observed including neutropenia (17.6%) and dermatitis (6.8%), which were higher in the 600 mg dose group (21.7 % vs.10.9 %) than in the 400 mg dose group (10.7 % vs. 0 %). More patients in the 600 mg dose group required dose interruptions (39% vs. 67%) and reductions(39% vs.70%). PK analysis revealed a dose-proportional increase of Cmax and AUC0–24 as similarly reported in previous studies. Conclusions: STI571 has substantial objective effects against unresectable and/or metastatic GISTs in Jpn pts, with considerable safety and tolerability. An optimal dose of 400 mg daily is recommended for pts with malignant GIST based on the results of this study. No significant financial relationships to disclose.
Immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine in infants: a comparative, observer-blind, randomised, controlled trial
Authors: Xavier Sáez-Llorens, Ralf Clemens, Geert Leroux-Roels, José Jimeno, Sue Ann Costa Clemens, William C Weldon, M Steven Oberste, Natanael Molina, Ananda S Bandyopadhyay
Journal: The Lancet Infectious Diseases (2015)
Interleukin-15 (IL-15) Can Replace the IL-2 Signal in IL-2–Dependent Adult T-Cell Leukemia (ATL) Cell Lines: Expression of IL-15 Receptor α on ATL Cells
Authors: Yasuaki Yamada, Kazuyuki Sugawara, Tomoko Hata, Kazuto Tsuruta, Ryozo Moriuchi, Takahiro Maeda, Sunao Atogami, Ken Murata, Kenshi Fujimoto, Tomoko Kohno, Kunihiro Tsukasaki, Masao Tomonaga, Yo-ichi Hirakata, Shimeru Kamihira
Journal: Blood (1998)
Comparison of Antihypertensive Efficacy of Carvedilol, a New Vasodilating β-Blocker, versus Atenolol
Authors: R. De Cesaris, G. Ranieri, R. Chiarappa, R. Assereto, P. Garanzelli, U. Martignoni, P. Nazzaron, A. Pettroccione, D. Bedoschi
Journal: Drugs (1988)
Clonic Perseveration vs Stereotypy Phenomenology
Authors: Yi-cheng Tai, Michael Wang Keong Fong, Victor S. C. Fung
Journal: JAMA Neurology (2015)

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
Phase I trial of LBY135, a monoclonal antibody agonist to DR5, alone and in combination with capecitabine in advanced solid tumors
Authors: S. Sharma, E. G. de Vries, J. R. Infante, C. Oldenhuis, L. Chiang, S. Bilic, M. Goldbrunner, J. W. Scott, H. A. Burris
Journal: Journal of Clinical Oncology (2008)

3538 Background: LBY135 is a chimeric (mouse/human) IgG1 monoclonal antibody agonist that binds with high specificity to the DR5 receptor and mimics the action of TRAIL. LBY135 has shown activity in mouse xenograft tumor models of colon, breast, lung, pancreas and prostate. Methods: LBY135 has been administered once every 21-days either alone (Arm 1) or in combination with capecitabine (1,000 mg/m2 bid 2 weeks on 1 week off, Arm 2) to adult patients (pts) with advanced solid tumors. A Bayesian logistic regression model with overdose control guided dose escalation. Results: A total of 56 pts, 30 male, 26 female, median age 61, have been enrolled to the following arms and dose levels (mg/kg): Arm 1, 32 pts at 0.3 (4 pts), 1 (3 pts), 3 (3 pts), 10 (5 pts), 15 (9 pts), 20 (8 pts); Arm 2, 24 pts at 1 (4 pts), 3 (7 pts), 10 (4 pts), 15 (1 pt), 20 (8 pts). Most common tumor types enrolled were: mesothelioma (10 pts), colon (8 pts) in Arm 1, and colon (11 pts), breast (5 pts) in Arm 2. No DLTs were observed in Arm 1. Two grade 3 DLTs, mucositis (1 mg/kg) and colitis (20 mg/kg) were observed in Arm 2. Frequent adverse events (AE) (≥ 25%) mostly grade 1 or 2, included: hypotension, fatigue, nausea, (Arms 1 and 2), and vomiting, pyrexia, dyspnea, diarrhea, abdominal pain, constipation, (Arm 2). Frequent AE (15%) considered possibly treatment related, included hypotension, nausea, (Arms 1 and 2), and anemia, fatigue, diarrhea, hand foot syndrome, mucositis, vomiting (Arm 2). Grade 3 AE considered possibly treatment related, included anemia (Arm 1) and anemia, colitis, diarrhea, fatigue, mucositis (Arm 2). LBY135 exposure (AUC) appeared dose proportional with t1/2 of ∼10 days. Saturation of antigen sink was reached at dose levels > 3. 0 mg/kg. Immunogenicity was detected in 13/51 (25%) pts, and 5 of those pts appeared to have reduced exposure on repeat dosing. In Arm 1, 14/32 pts, including 6/10 mesothelioma pts, received ≥ 4 cycles of treatment (range 4–23), 1 pt (sarcoma) had a minor response and 2 pts (1 NSCLC, 1 prostate) had decreases in tumor markers of 50% and 40% respectively. In Arm 2, 1 pt (CRC) had a PR, 1 pt (ovarian) had metabolic (PET) PR, and 4 pts (2 ovarian, 1 CRC, 1 pancreatic) had decreases in tumor markers of 60–73%. Conclusions: LBY135 is well tolerated and has shown signs of clinical activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
The management of dysphagia in esophageal cancer patients undergoing neoadjuvant chemotherapy: Is invasive tube feeding required?
Authors: M. Rousseau, P. Guevremont, M. Chasen, J. Spicer, E. Eckert, T. Alcindor, S. Ades, L. E. Ferri
Journal: Journal of Clinical Oncology (2009)

9613 Background: The dysphagia commonly associated with esophageal cancer often interferes with patient tolerance of neo-adjuvant chemotherapy. Surgical or endoscopic invasive tube feeding (ITF - gastroscopy/jejunostomy/stent) is a commonly employed strategy to maintain nutritional support however it can cause significant morbidity in its own right. We sought to determine if a strategy of careful dietary counseling and appropriately-timed neoadjuvant chemotherapy can obviate the need for ITF. Methods: Pts undergoing neoadjuvant chemotherapy (TAX/CDDP/5FU Q3 weeks x3) for esophageal or GEJ adenocarcinoma at a single institution from 3/07–7/08 were identified from a prospective database. All received dietary counseling and were closely monitored for signs/ symptoms of malnutrition with serial (baseline, after 1 st cycle, pre-surgery) Body Mass Index (BMI), albumin, dysphagia scores (0 best - 4 worse), and quality of life (FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant treatment and the need for ITF. Data presented as median (range) or mean (±SD), paired t-test or Wilcoxon signed ranks test determined significance. Results: 25 pts received neoadjuvant chemotherapy and significant dysphagia (score 2–4) was found in 14. Dysphagia scores improved in all 14 (all results in Table 1 ), and 10/13 improved after the first cycle. No patient required ITF. QoL as assessed by the FACT-E improved in 13/14 patients. A small decrease in BMI was noted, however serum albumin did not significantly decrease. Conclusions: Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for ITF in patients with significant dysphagia from esophageal adenocarcinoma. [Table: see text] No significant financial relationships to disclose.
The Teaching of Clinical Medicine
Authors: R R STRUTHERS
Journal: JAMA (2020)

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
Preoperative Serum AFP is a Non-ideal Prognostic Marker for Hepatitis B Virus-associated Hepatocellular Carcinoma After Hepatectomy
Authors: S.L. Yang, L. Liu, S. Yang, L.P. Liu, J.W. Ren, X. Fang, G.G. Chen, P.B.S. Lai
Journal: Clinical Gastroenterology and Hepatology (2015)
Medicare’s New Bundled Payments
Authors: Matthew J. Press, Rahul Rajkumar, Patrick H. Conway
Journal: JAMA (2015)

The Centers for Medicare & Medicaid Services (CMS) is increasingly paying for health care through alternative payment models (APMs) that reward value and quality. Currently, more than 20% of Medicare fee-for-service payments flow through APMs, putting the Administration’s goals of 30% by 2016 and 50% by 2018 within reach.1 These APMs include accountable care organizations (ACOs), bundled payments, and advanced primary care medical homes. In this Viewpoint, we discuss the role of bundled payments.
Prevalence and trends in overweight and obesity among Chinese adults in 2004–10: data from three nationwide surveys in China
Authors: Yong Jiang, Yu Xu, Yufang Bi, Limin Wang, Mei Zhang, Maigeng Zhou, Yichong Li, Min Xu, Jieli Lu, Tiange Wang, Meng Dai, Di Zhang, Weiqing Wang, Guang Ning, Linhong Wang, Wenhua Zhao
Journal: The Lancet (2015)
Phase II pharmacodynamic trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy: FISH results
Authors: E. Felip, F. Rojo, M. Reck, A. Heller, B. Klughammer, H. Maacke, J. Möcks, U. Brennscheidt, U. Gatzemeier, J. Baselga
Journal: Journal of Clinical Oncology (2006)

7160 Background: The HER1/EGFR inhibitor erlotinib significantly prolongs survival of patients with previously-treated advanced NSCLC. Methods for selecting patients most likely to derive clinical benefit from erlotinib are not established. Increased HER1/EGFR gene copy number has been suggested as a potential predictive biomarker of clinical benefit, and was investigated in this phase II study. Methods: Advanced NSCLC patients who failed first line chemotherapy were treated with erlotinib monotherapy, 150 mg/d p.o. Each patient underwent tumor biopsy before start of treatment. Tumor HER1/EGFR gene amplification status was assessed using FISH, and classified as positive (amplification, polysomy, high polysomy) or negative (disomy, trisomy). Results: 83 patients were included: median age 56 (range 35–78); sex: male 72%, female 28%; histology: adenocarcinoma 43%, large cell 31%, squamous cell 19%, others 7%; smoking status: 44 current smokers, 28 former smokers, 11 never smokers. Of 73 evaluable patients, 7 (10%) achieved partial response (PR), 28 (38%) had stable disease (SD) and 38 (52%) had disease progression. PRs were observed in 4 males / 3 females; in 5 adenocarcinomas / 1 large cell/ 1 squamous cell; in 2 current / 3 former / 2 never smokers. Erlotinib was well tolerated and no unexpected toxicities were seen. HER1/EGFR gene copy number was evaluated in 53 patients. 15 patients were FISH +, 10 of whom achieved clinical benefit (PR, or SD for ≥12 weeks). Only 5 of 38 FISH - patients had clinical benefit. FISH + patients achieved a longer median time to progression (137 vs 43 days; p = 0.00011; HR 0.35) as well as overall survival (226 vs 115 days; p = 0.3221, HR 0.722). Conclusion: In this study, increased HER1/EGFR gene copy number was associated with a better outcome on erlotinib therapy. [Table: see text] [Table: see text]
Association of <i>SLCO2B1</i> Genotypes With Time to Progression and Overall Survival in Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer
Authors: Xiaodong Wang, Lauren C. Harshman, Wanling Xie, Mari Nakabayashi, Fangfang Qu, Mark M. Pomerantz, Gwo-Shu Mary Lee, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2015)

To validate the association of three previously demonstrated SLCO2B1 germline variants with time to progression (TTP) in patients receiving androgen-deprivation therapy (ADT), and to evaluate if the SLCO2B1 genetic variants impacted overall survival (OS) for prostate cancer (PC).
Bristol Cup Posters: Summaries of Posters
Authors: J. Schofield, S. Jackson, A. Irvine, T. Padlard, S. Gunn, N. Evans
Journal: British Journal of Dermatology (2005)

The definitive version can be found at: http://onlinelibrary.wiley.com/ Copyright British Association of Dermatologists & Blackwell [Full text of this article is not available in the UHRA]
Citrullinated Vimentin Presented on MHC-II in Tumor Cells Is a Target for CD4+ T-Cell–Mediated Antitumor Immunity
Authors: Victoria A. Brentville, Rachael L. Metheringham, Barbara Gunn, Peter Symonds, Ian Daniels, Mohamed Gijon, Katherine Cook, Wei Xue, Lindy G. Durrant
Journal: Cancer Research (2016)

Abstract Stressful conditions in the harsh tumor microenvironment induce autophagy in cancer cells as a mechanism to promote their survival. However, autophagy also causes post-translational modification of proteins that are recognized by the immune system. In particular, modified self-antigens can trigger CD4+ T-cell responses that might be exploited to boost antitumor immune defenses. In this study, we investigated the ability of CD4 cells to target tumor-specific self-antigens modified by citrullination, which converts arginine residues in proteins to citrulline. Focusing on the intermediate filament protein vimentin, which is frequently citrullinated in cells during epithelial-to-mesenchymal transition of metastasizing epithelial tumors, we generated citrullinated vimentin peptides for immunization experiments in mice. Immunization with these peptides induced IFNγ- and granzyme B-secreting CD4 T cells in response to autophagic tumor targets. Remarkably, a single immunization with modified peptide, up to 14 days after tumor implant, resulted in long-term survival in 60% to 90% of animals with no associated toxicity. This antitumor response was dependent on CD4 cells and not CD8+ T cells. These results show how CD4 cells can mediate potent antitumor responses against modified self-epitopes presented on tumor cells, and they illustrate for the first time how the citrullinated peptides may offer especially attractive vaccine targets for cancer therapy. Cancer Res; 76(3); 548–60. ©2015 AACR.
Fractionated administration of topotecan and cisplatin in elderly patients with small-cell lung cancer: A phase I study
Authors: S. Umemura, K. Fujiwara, S. Harita, H. Kamei, N. Takigawa, T. Shibayama, M. Tabata, K. Kiura, H. Ueoka, M. Tanimoto
Journal: Journal of Clinical Oncology (2005)

7245 Background: This phase I study was designed to determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a fractionated regimen of topotecan and cisplatin in elderly patients with small-cell lung cancer (SCLC). Methods: The eligibility criteria were: histologically or cytologically proven SCLC, patients 76 years of age or older, no previous chemotherapy, performance status 0–2, and adequate reserve of organ function. The patients received both cisplatin and topotecan on days 1 to 3. Cisplatin was administered at a fixed dose of 20 mg/m2, while topotecan was administered at escalating doses, with a starting dose of 0.5 mg/m2. Therapy was repeated every 3 weeks up to 4 cycles, and patients with limited disease (LD) also received thoracic radiotherapy at the dose of 45 Gy (30 fractions) after completion of the chemotherapy course. Results: The characteristics of the 21 patients enrolled in this study were as follows. Male/female: 19/2, median age (range): 78 (76–82), and LD/ED: 10/11. The MTD of topotecan was 1.2 mg/m2. The DLTs were grade 4 neutropenia lasting for 4 days, febrile neutropenia, and grade 4 hyponatremia. No treatment-related death was encountered. The recommended doses of cisplatin and topotecan for a phase II study are 20 mg/m2 and 1.0 mg/m2, respectively. The overall response rate was 60% in patients with LD and 55% in patients with extensive disease. Conclusions: The results of this study indicate that fractionated administration of cisplatin and topotecan may be a well-tolerated and effective regimen for elderly patients with SCLC, warranting a phase II study. No significant financial relationships to disclose.
American College of Cardiology/American Heart Association 2006 Update of the Clinical Competence Statement on Invasive ElectrophysiologyStudies,CatheterAblation,andCardioversion
Authors: Cynthia M. Tracy, Masood Akhtar, John P. DiMarco, Douglas L. Packer, Howard H. Weitz, Mark A. Creager, David R. Holmes, Geno Merli, George P. Rodgers, Cynthia M. Tracy, Howard H. Weitz
Journal: Journal of the American College of Cardiology (2006)
Benefits and Harms of Once-Weekly Glucagon-like Peptide-1 Receptor Agonist Treatments
Authors: Francesco Zaccardi, Zin Zin Htike, David R. Webb, Kamlesh Khunti, Melanie J. Davies
Journal: Annals of Internal Medicine (2015)

Background: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of type 2 diabetes. Purpose: To summarize evidence for the cardiometabolic efficacy and adverse effects of once-weekly GLP-1RAs in adults with type 2 diabetes. Data Sources: Electronic databases (PubMed, Web of Science, Cochrane Central Register of Controlled Trials, U.S. Food and Drug Administration, European Medicines Agency, ClinicalTrials.gov) and congress abstracts from inception through 26 September 2015. Study Selection: Randomized, controlled trials (≥24 weeks of follow-up) studying albiglutide, dulaglutide, once-weekly exenatide, semaglutide, and taspoglutide and reporting a cardiometabolic (primary outcome, hemoglobin A1c [HbA1c]) or safety outcome. Data Extraction: Extraction was done in duplicate, and risk of bias was assessed. No language restriction was applied. Data Synthesis: 34 trials (21 126 participants) were included. Compared with placebo, all once-weekly GLP-1RAs reduced HbA1c and fasting plasma glucose; taspoglutide, 20 mg, once-weekly exenatide, and dulaglutide, 1.5 mg, reduced body weight. Among once-weekly GLP-1RAs, the greatest differences were found between dulaglutide, 1.5 mg, and taspoglutide, 10 mg, for HbA1c (–0.4% [95% CI, –0.7% to –0.2%]), once-weekly exenatide and albiglutide for fasting plasma glucose (–0.7 mmol/L [CI, –1.1 to –0.2 mmol/L]; –12.6 mg/dL [CI, –19.8 to –3.6 mg/dL]), and taspoglutide, 20 mg, and dulaglutide, 0.75 mg, for body weight (–1.5 kg [CI, –2.2 to –0.8]). Clinically marginal or no differences were found for blood pressure, blood lipid levels, and C-reactive protein levels. Once-weekly exenatide increased heart rate compared with albiglutide and dulaglutide (1.4 to 3.2 beats/min). Among once-weekly GLP-1RAs, the risk for hypoglycemia was similar, whereas taspoglutide, 20 mg, had the greatest risk for nausea (odds ratios, 1.9 to 5.9). Limitation: Data were unavailable for semaglutide, definitions of outcomes were heterogeneous, the last-observation-carried-forward imputation method was used in 73% of trials, and publication bias is possible. Conclusion: Compared with other once-weekly GLP-1RAs, dulaglutide, 1.5 mg; once-weekly exenatide; and taspoglutide, 20 mg, showed a greater reduction of HbA1c, fasting plasma glucose, and body weight. Taspoglutide, 20 mg, had the highest risk for nausea; risk for hypoglycemia among once-weekly GLP-1RAs was similar. Primary Funding Source: Sanofi Aventis (grant to the University of Leicester).