tbuckley/cabot-search huggingface dataset:
A Constitutional Activating <i>MET</i> Mutation Makes the Genetic Link between Malignancies and Chronic Inflammatory Diseases
Authors: Morad El Bouchtaoui, Marcio Do Cruzeiro, Christophe Leboeuf, Irmine Loisel-Ferreira, Carèle Fedronie, Chrystophe Ferreira, Rachida Ait El Far, Marianne Ziol, Marc Espié, Géraldine Falgarone, Bruno Cassinat, Jean-Jacques Kiladjian, Jean-Paul Feugeas, Anne Janin, Guilhem Bousquet
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The genesis of all cancers results from an accumulation of mutations, constitutional and/or acquired when induced by external mutagenic factors. High-speed technologies for genome sequencing have completely changed the study of disease genetics, but with limited knowledge of the functional value of most genetic changes. Experimental Design: Here, we proposed an innovative individual approach by studying tissue samples from a young woman with an unusual association of breast cancer, polycythemia vera, and rheumatoid arthritis. We performed genomic analyses for copy number variations and point mutations on laser-microdissected tumor cells from the breast cancer, and on CD34+ cells sorted from bone marrow aspiration, to identify gene abnormalities common to these two types of cell populations. Results: Using ONCOSCAN technology, we identified a constitutional pR988C, c2962C&amp;gt;T mutation of MET. Using CRISPR-Cas9 technology, we established pR988C MET-mutated transgenic mice, which reproduced the autoimmune diseases and myeloproliferation found in our index-case; one of the transgenic mice spontaneously developed a skin squamous cell carcinoma. We also showed that additional mutagenic factors were required to induce cancers, including skin squamous cell carcinoma and thyroid cancer. Using an anti-MET drug, cabozantinib, we demonstrated for the first time the functional role of this mutation in the maintenance of myeloproliferation and rheumatoid arthritis, and in cancer genesis. Conclusions: Our study opens a considerable field of application in the domain of constitutional genetics, to establish genetic links between cancers and other very different severe diseases.
THU-088-Serum markers of interstitial matrix formation (PRO-C3) and basement membrane remodeling (PRO-C4 and C4M) predict recurrence of fibrosis and survival in post-liver transplanted patients
Authors: Mette Juul Nielsen, Ida Villesen, Natasja Gudmann, Diana Leeming, Aleksander Krag, Morten Karsdal, Rambabu Surabattula, Tim Zimmermann, Detlef Schuppan
Journal: Journal of Hepatology (2019)
Lenalidomide and low-dose dexamethasone (Ld) is equivalent to Ld plus autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM): Results of a randomized, phase III trial.
Authors: Suzanne Lentzsch, Susanna Miao, Jordan Mark Schecter, Kent A. Griffith, Daniel Paul Normolle, Markus Y Mapara, Robert L Redner, Nicolas Villanueva
Journal: Journal of Clinical Oncology (2015)

8530 Background: Upfront ASCT is the current standard of care for transplant-eligible NDMM. However, its use has come into question with the emergence of novel agents such as lenalidomide. This randomized phase III study evaluated the role of upfront ASCT in NDMM, with Ld administered as induction therapy. Methods: Patients aged 18–75 years with transplant-eligible, previously untreated, NDMM were randomized to four 28-day cycles of lenalidomide (25 mg days 1–21) plus low-dose dexamethasone (40mg days 1, 8, 15, 22) followed by stem-cell mobilization and: ASCT conditioned with 200 mg/m2melphalan (Arm A; Ld+ASCT); or Ld for 4 additional cycles (Arm B; Ld). Patients subsequently received maintenance lenalidomide (10–15 mg) for ≤ 2 years or until disease progression. Patients with stable disease prior to stem-cell collection, or with progressive disease at any time, went off study. The primary objective was to compare best response in Arm A versus Arm B. Secondary objectives were comparisons of the duration of response, progression-free survival (PFS), and overall survival (OS). Results: Sixty patients were randomized between February 2009 and August 2014: 31 into Arm A, and 29 into Arm B. Baseline characteristics were similar in the two arms. The mean age was 62 years (range 48–75), and 43.3% of patients had International Staging System stage 1 disease. In an intention-to-treat analysis, neither the overall response ( ≥ partial response) rate (83.9% vs. 72.4%; p = 0.28) nor the complete response rate (21.9 vs. 19.3%; p = 0.28) differed significantly between Arm A and Arm B. The median follow-up time for the entire study population was 53.5 months (95% confidence interval [CI]: 49.5–58.3). OS and PFS at 4 years were estimated at 79.0% (95% CI: 56.2–90.8) vs. 86.5% (95% CI: 63.7–95.4) (p = 0.31) and 69.3% (95% CI: 47.6–83.4) vs. 56.8% (95% CI: 34.3–74.2) (p = 0.30) in Arm A vs. Arm B, respectively. Conclusions: Ld without upfront ASCT appears to provide similar treatment response, OS, and PFS benefits to Ld plus ASCT in NDMM. Clinical trial information: NCT01731886.
Treatment of Metastatic Urothelial Cancer in 2018
Authors: Joaquim Bellmunt, Alejo Rodriguez-Vida
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Previous exposure to bevacizumab indicated inferior benefits from PD-1/PD-L1 inhibitors in nonsquamous NSCLC
Authors: F. Zhou, Y. Pan, C. Zhou
Journal: Annals of Oncology (2019)

Background: Bevacizumab is known to enhance the effects of immunotherapy. The landmark IMPOWER150 has demonstrated that the addition of atezolizumab to bevacizumab plus chemotherapy significantly improved survival outcomes among patients with metastatic nonsquamous NSCLC. However, the impact of previous use of bevacizumab on the efficacy of PD-1/PD-L1 inhibitors remained unclear. Methods: Between Oct 2016 to Sep 2019, 113 patients who were treated with PD-1/PD-L1 inhibitors either as a standard of care or on a clinical trial at Shanghai Pulmonary Hospital were identified. Patients who had prior exposure to immunotherapeutic agents, or death within 4 weeks from the first dose of ICIs treatment were excluded from the analysis. The information regarding previous exposure to bevacizumab was reviewed in electronic medical record. Results: The median age of enrolled patients was 63 years (range, 29 to 82). Regarding histology, 59.2% (67/113) had nonsquamous NSCLC and 40.8% (46/113) had squamous cell carcinoma. Overall, 16 patients (14.2%) previously received bevacizumab therapy, all of whom had nonsquamous NSCLC. Interestingly, patients who were previous exposure to bevacizumab had shorter PFS than those who were not (1.9 versus 4.3 months, p = 0.017). We then divided patients into 3 groups: arm 1 (16 patients, previous exposure to bevacizumab), arm 2 (51 patients, nonsquamous NSCLC who were not previous exposure to bevacizumab), arm 3 (46 patients, squamous cell carcinoma). The PFS was significantly different between arm 1 and arm 2 (1.9 versus 4.3 months, p = 0.023) or arm 3 (1.9 versus 4.2 months, p = 0.045), but not arm 2 and arm 3 (4.3 versus 4.2 months, p = 0.736). Patients in arm 1 also had inferior ORR (14.3% versus 29.4% versus 29.5%, p = 0.342) and DCR (42.9% versus 70.6% versus 68.2%, p = 0.05) compared with arm 2 and arm 3. Multivariate analysis identified previous exposure to bevacizumab as being independently associated with poorer PFS (HR = 1.9, 95%CI, 1.01-3.59, p = 0.048). Conclusions: Previous use of bevacizumab indicated inferior benefits from PD-1/PD-L1 inhibitors in nonsquamous NSCLC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Universal varicella vaccination in the Sicilian paediatric population: rapid uptake of the vaccination programme and morbidity trends over five years
Authors: G Giammanco, S Ciriminna, I Barberi, L Titone, M Lo Giudice, L R Biasio
Journal: Eurosurveillance (2009)

Following the licensure of the Oka/Merck varicella vaccine in Italy in January 2003, the Sicilian health authorities launched a universal vaccination programme in all nine Local Health Units. A two-cohort vaccination strategy was adopted to minimise the shift of the mean age of varicella occurrence to older age groups, with the goal of vaccinating with one dose at least 80% of children in their second year of life and 50% of susceptible adolescents in their 12th year of life. Two studies were implemented in parallel to closely monitor vaccination coverage as well as varicella incidence. Overall, the programme achieved its target, with 87.5% vaccine coverage for the birth cohort 2005 and 90.2% for adolescents born in 1995 and 1996. Varicella surveillance data obtained from a total of 28,188 children (0-14 years-old) monitored by family paediatricians showed a decline in incidence rates from 95.7 (95% confidence interval (CI): 72.2-126.8) for 1,000 person-years (PY) in 2004 to 9.0 (95% CI: 6.4-12.6) for 1,000 PY in 2007. In Europe, the only similar experience is the routine childhood varicella vaccination programme in Germany that started in 2004 with a single dose at the age of 11-14 months. The two-cohort universal vaccination programme implemented in Sicily, as well as the network for the surveillance study, can offer a model to other European countries that are considering introducing universal childhood varicella vaccination.
Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non–small Cell Lung Cancer
Authors: Natasha B. Leighl, Ray D. Page, Victoria M. Raymond, Davey B. Daniel, Stephen G. Divers, Karen L. Reckamp, Miguel A. Villalona-Calero, Daniel Dix, Justin I. Odegaard, Richard B. Lanman, Vassiliki A. Papadimitrakopoulou
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Complete and timely tissue genotyping is challenging, leading to significant numbers of patients with newly diagnosed metastatic non–small cell lung cancer (mNSCLC) being undergenotyped for all eight genomic biomarkers recommended by professional guidelines. We aimed to demonstrate noninferiority of comprehensive cell-free DNA (cfDNA) relative to physician discretion standard-of-care (SOC) tissue genotyping to identify guideline-recommended biomarkers in patients with mNSCLC. Patients and Methods: Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretion SOC tissue genotyping submitted a pretreatment blood sample for comprehensive cfDNA analysis (Guardant360). Results: Among 282 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 60 patients versus 77 cfDNA identified patients (21.3% vs. 27.3%; P &amp;lt; 0.0001 for noninferiority). In tissue-positive patients, the biomarker was identified alone (12/60) or concordant with cfDNA (48/60), an 80% cfDNA clinical sensitivity for any guideline-recommended biomarker. For FDA-approved targets (EGFR, ALK, ROS1, BRAF) concordance was &amp;gt;98.2% with 100% positive predictive value for cfDNA versus tissue (34/34 EGFR-, ALK-, or BRAF-positive patients). Utilizing cfDNA, in addition to tissue, increased detection by 48%, from 60 to 89 patients, including those with negative, not assessed, or insufficient tissue results. cfDNA median turnaround time was significantly faster than tissue (9 vs. 15 days; P &amp;lt; 0.0001). Guideline-complete genotyping was significantly more likely (268 vs. 51; P &amp;lt; 0.0001). Conclusions: In the largest cfDNA study in previously untreated mNSCLC, a validated comprehensive cfDNA test identifies guideline-recommended biomarkers at a rate at least as high as SOC tissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping. See related commentary by Meador and Oxnard, p. 4583
Abstract 206: Coronary Artery Thrombosis in an Infant with Kawasaki Disease without Giant Coronary Aneurysm and Iron Deficiency Anemia: a Case Report
Authors: Rungrote Natesirinilkul, Pimlak Charoenkwan, Rekwan Sittiwangkul, Suchaya Silvilairat, Yupada Prongpot
Journal: Circulation (2015)

The major complication of Kawasaki disease is coronary aneurysm which can cause acute coronary disease in early adulthood. There are some reports of coronary artery thrombosis during the period of active Kawasaki disease in infants with giant coronary aneurysm. This report demonstrated a 5-month-old male infant who presented high-grade fever for 7 days. He was treated as urinary tract infection for 6 days before referral. At admission, he had fever, red lips and swelling of both feet, then was diagnosed Kawasaki disease. His EKG showed ST elevation at lead II, III and AVF. His initial echocardiogram revealed coronary dilatation with perivascular brightness; RCA 2.7 mm (Z-score 4.38), LMCA 2.88 mm (Z-score 2.83) and LAD 2.7 mm (Z-score 5.79). There was a clot 2.5 X 2.5 mm in LAD. However, his LV systolic function was normal (EF 76%). His blood test showed low hemoglobin as 8.9 g/dL and MCV as 61.9 fL, high white cell count 20,400/mm3 and platelet count as 606,000/mm3. His initial ESR and CRP elevated at 91 mm/hr and 52 mg/L, respectively. The cardiac enzymes were normal; CKMBmass 2.9 ng/mL (0-3) and troponin-T 0.004 ng/mL (&lt; 0.4). He received IVIG 2.3 g/kg and aspirin 79 mg/kg/day and was closely monitored the vital signs and cardiac enzymes. His fever completely disappeared within 24 hours after treatment, then aspirin was decreased to 6 mg/kg/day. Also, he received intravenous heparin for 4 days, and then was switched to Enoxaparin. He was discharged uneventfully on day 22 of admission. Further blood test confirmed the diagnosis of iron deficiency anemia as follow; serum iron 30 [[Unable to Display Character: &amp;#613;]]g/dL, transferrin-iron binding capacity 446 [[Unable to Display Character: &amp;#613;]]g/dL and transferrin saturation 6.7% (&lt; 16). He received iron supplement for 4 months. The clot in coronary artery gradually decreased in size and finally disappeared in seven months after diagnosis. So, the Enoxaparin was discontinued. He received low-dose aspirin for total course 15 months. His thrombophilia work up was unremarkable. Anemia which is one of the supplementary criteria for atypical Kawasaki disease should be properly evaluated for the cause. The study to find the association between iron deficiency anemia, which was reported as a risk for thromboembolic events, and severity of Kawasaki disease should be further investigated.
FRI-299-Transcriptomic and epigenetic characterization of a NAFLD murine model
Authors: Antonio Gil-Gomez, Ángela Rojas, Rocio Munoz hernandez, Rocío Gallego-Durán, Sheila Gato, Rocío Montero-Vallejo, Douglas Maya-Miles, Javier Ampuero, Manuel Romero Gomez
Journal: Journal of Hepatology (2019)
PS-179-Analysis of long-term persistence of HCV resistance-associated substitutions within NS, NS5A and NS5B in genotype 1 and 3 after DAA treatment failure
Authors: Julia Dietz, Johannes Vermehren, Tania Welzel, Beat Müllhaupt, Peter Buggisch, Matschenz Kathrin, PD Dr. Schattenberg Jörn, Christoph Antoni, Stefan Mauss, Elena Durmashkina, Claus Niederau, Thomas Discher, Janina Trauth, Julian Schulze zur Wiesch, Felix Piecha, Tobias Müller, Thomas Berg, Christoph Neumann-Haefelin, Christoph Berg, Stefan Zeuzem, Christoph Sarrazin
Journal: Journal of Hepatology (2019)
Inhibition of LSD1 by small molecule inhibitors stimulates fetal hemoglobin synthesis
Authors: Cuong Quang Le, Greggory Myers, Alawi Habara, Natee Jearawiriyapaisarn, George J. Murphy, David H. K. Chui, Martin H. Steinberg, James Douglas Engel, Shuaiying Cui
Journal: Blood (2019)
<i>Notes from the Field:</i> Hepatitis A Outbreak Associated with Drug Use and Homelessness — West Virginia, 2018
Authors: Erica Wilson, Megan G. Hofmeister, Shannon McBee, Janet Briscoe, Erica Thomasson, R. Henry Olaisen, Ryan Augustine, Eliana Duncan, Sapna Bamrah Morris, Loretta Haddy
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
PS-141-CyTOF-based immune monitoring of HBV-HCC patients receiving autologous anti-tumour T-cell therapy
Authors: Anthony Tan, Nina Le Bert, Thinesh Krishnamoorthy, Alicia Chua, Xinyuan Zhao, Huisi Tan, Adeline Chia, Hiang Keat Tan, Rajneesh Kumar, Farah Irani, Zi Zong Ho, Lu-en Wai, Sarene Koh, Evan Newell, William Hwang, Wan Cheng Chow, Antonio Bertoletti
Journal: Journal of Hepatology (2019)
Monster 2015-2016 El Niño Event Triggered Infectious Diseases
Authors: M.J. Friedrich
Journal: JAMA (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 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
Aortic dilatation in a patient with Takayasu arteritis treated with tocilizumab
Authors: Francesco Muratore, Carlo Salvarani
Journal: Annals of the Rheumatic Diseases (2019)

In recent years there has been growing interest in the use of tocilizumab for the treatment of large vessel vasculitis. Although the primary endpoint (time to relapse) was not met in the first randomised, placebo-controlled trial evaluating the efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis, the results suggested favour for tocilizumab over placebo without new safety concerns.1 In this journal, three cases of Takayasu arteritis progression during tocilizumab treatment have been described.2 3 We report one additional patient with disease progression despite tocilizumab therapy.

A 25-year-old woman presented with constitutional …
Salvage treatment with irinotecan/cisplatin versus pemetrexed/cisplatin in patients with non-small cell lung cancer pretreated with a non-platinum-based regimen in the first-line setting: A randomized phase II study of the Hellenic Oncology Research Group (HORG).
Authors: Nikolaos K. Kentepozidis, Panagiota Economopoulou, Charalampos Christophyllakis, Leonidas Chelis, Aristidis Polyzos, Nikolaos Vardakis, Filippos Koinis, Christos Nikolaou, Vassilis Georgoulias, Athanasios Kotsakis
Journal: Journal of Clinical Oncology (2015)

e19044 Background: Platinum-based chemotherapy is the standard front-line treatment for patients with advanced Non Small Cell Lung Cancer (NSCLC). However, third generation non-platinum combinations are considered an alternative therapeutic option for patients who cannot tolerate toxic effects of platinum compounds. The objective of this study was to compare the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) against pemetrexed plus cisplatin (PC) in platinum-naïve patients with advanced NSCLC previously treated with a taxane plus gemcitabine regimen. Methods: A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m2 on day 1 and 100 mg/m2 on day 8 plus cisplatin 80 mg/m2 on day 8 every 3 weeks (arm IC) or pemetrexed 500 mg/m2 plus cisplatin 80 mg/m2 on day 1 every 3 weeks (arm B) with dexamethasone, folic acid and vitamin B12 being co-administered. The primary endpoint was the comparison of the overall response rate (ORR) between the two regimens. Results: The ORR and the median progression free survival (PFS) were 18% and 3.3 months in IC arm and 19% and 4.2 months in the PC arm (p= ns). However, patients treated with PC had a better median overall survival compared to patients treated with IC (6.9 vs.10.9 months, p= 0.013), which might be related to the increased number of deaths occurring early or during follow-up in the IC arm. PC had a better toxicity profile than IC, with statistically significant lower incidence of grade 3/4 neutropenia (3% vs. 31%; p= 0.0001) and diarrhea (1.6 % vs.14.7%, p= 0.018). Conclusions: In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin has a better overall survival and tolerance than irinotecan/cisplatin and is a valid therapeutic option in this setting. Clinical trial information: NCT00614965.
Abstract 12525: No Effect of Glycoprotein Platelet Inhibitors Administered During Primary PCI in Patients Included in the Norwegian Coronary Stent Trial
Authors: Dennis W Nilsen, Kaare Bonaa, Alf Inge Larsen, Harry Staines, Jan Erik Nordrehaug
Journal: Circulation (2018)

Introduction: In the NORSTENT (Norwegian Coronary Stent Trial), 9013 patients with stable or unstable coronary artery disease were randomized to undergo percutaneous coronary intervention (PCI) wit...