tbuckley/cabot-search huggingface dataset:
Vemurafenib (V) in BRAF V600E metastatic melanoma (mM): Analysis of 507 patients (pts) enrolled in the French temporary authorization for use (ATU).
Authors: Celeste Lebbe, Caroline Robert, Brigitte Dreno, Luc Thomas, Jean Jacques Grob, Nicolas Meyer, Elodie Regnier-Rosencher, Philippe Saiag, Laurent Mortier, Valerie Hospital, Anne Benedicte Duval-Modeste, Sophie Dalac-Rat, Thierry Lesimple, Bernard Guillot, Marie Thérèse Leccia, Laurence Bitoun, Luz Bobadilla, Thomas Jouary
Journal: Journal of Clinical Oncology (2012)

8591 Background: V, a selective BRAF inhibitor, significantly improves OS in BRAF mutated mM. ATU is an exceptional measure making available drugs that have not yet been granted a Marketing Authorisation. We provide demographic data of pts treated by V in the ATU. Methods: V 960 mg BID was given to pts with unresectable stage IIIC or IV BRAF V600E mM. Genotyping was done on the national network of molecular genetics platforms funded by the Institut National du Cancer. Data were prospectively collected. Results: From Apr 2011 to Jan 2012, 83 sites enrolled 507 pts. 80% were treated by oncodermatologists. Pts characteristics at baseline are summarized below. Safety and efficacy data are being evaluated. Conclusions: Around 2 out of 3 patients with a BRAF mutated mM were enrolled in France in the ATU highlighting a large access to BRAF genotyping and to V. Demographic data differs from literature and clinical trials for: site of primary melanoma (reverse trunk/extremity ratio) and inclusion of pts with brain metastasis or PS&gt;2 (excluded in CT). A high number of pts had risk factors for NMSC emphasizing the importance of the communication between oncologists and dermatologists for managing V therapy. [Table: see text]
Endoscopy in eosinophilic esophagitis: within or beyond the reach of the endoscope?
Authors: Alex Straumann
Journal: Endoscopy (2016)

Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus. In order to establish the diagnosis of EoE, the following criteria should be met: presence of symptoms of esophageal dysfunction and predominantly eosinophilic inflammation of the esophagus [1]. Unlike the clinical manifestations and histologic findings, the diagnostic yield of endoscopy has been regarded as limited, because initially visible mucosal alterations were reported as being either unremarkable or even absent [2] [3]. However, in recent years it has become evident that the majority of patients with EoE present with a number of mucosal alterations that are clearly visible on endoscopy [4]. Subsequently, a grading and classification system assessing the five major EoE-associated endoscopic signs (edema, rings, exudates, furrows, strictures, [EREFS]) was developed [5]. Three of these signs – edema, white exudates, and furrows – were attributed to inflammatory changes, whereas the remaining two – rings and strictures – were thought to represent the features of remodeling.
Ambient Temperature and Early Delivery of Singleton Pregnancies
Authors: Sandie Ha, Danping Liu, Yeyi Zhu, Sung Soo Kim, Seth Sherman, Pauline Mendola
Journal: Environmental Health Perspectives (2016)

Background:Extreme temperature is associated with adverse birth outcomes but it is unclear whether it increases early delivery risk.Objectives:We aimed to determine the association between ambient temperature and early delivery.Methods:Medical records from 223,375 singleton deliveries from 12 U.S. sites were linked to local ambient temperature. Exposure to hot (&gt; 90th percentile) or cold (&lt; 10th percentile) using site-specific and window-specific temperature distributions were defined for 3-months preconception, 7-week periods during the first two trimesters, 1 week preceding delivery, and whole pregnancy. Poisson regression with generalized estimating equations calculated the relative risk (RR) and 95% confidence interval for early deliveries associated with hot/cold exposures, adjusting for conception month, humidity, site, sex, maternal demographics, parity, insurance, prepregnancy body mass index, pregnancy complications, and smoking or drinking during pregnancy. Acute temperature associations were estimated separately for warm (May–September) and cold season (October–April) in a case-crossover analysis using conditional logistic regression.Results:Compared with mild temperature (10–90th percentile), exposure to hot or cold during weeks 1–7 increased risk for early preterm (&lt; 34 weeks) [RRhot: 1.11 (95% CI: 1.01, 1.21); RRcold: 1.20 (95% CI: 1.11, 1.30)], late preterm (34–36 weeks) [RRcold: 1.09 (95% CI: 1.04, 1.15)], and early term (37–38 weeks) [RRhot: 1.04 (95% CI: 1.02, 1.07); RRcold: 1.03 (95% CI: 1.00, 1.05)] delivery. Findings were similar for hot exposures during weeks 15–21. Examining deliveries at each week from 23 through 38, whole-pregnancy hot exposures increased delivery risk by 6–21% at weeks 34 and 36–38. In the case-crossover analysis, a 5°F increase during the week preceding delivery was associated with 12–16% higher and 4–5% lower early delivery risk during warm and cold season, respectively.Conclusions:Both acute and chronic ambient temperature extremes may affect early delivery risk.Citation:Ha S, Liu D, Zhu Y, Kim SS, Sherman S, Mendola P. 2017. Ambient temperature and early delivery of singleton pregnancies. Environ Health Perspect 125:453–459; http://dx.doi.org/10.1289/EHP97Citation: Ha S, Liu D, Zhu Y, Kim SS, Sherman S, Mendola P. 2017. Ambient temperature and early delivery of singleton pregnancies. Environ Health Perspect 125:453–459; http://dx.doi.org/10.1289/EHP97
The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway
Authors: Rojo A Ratsimandresy, Mohanalaxmi Indramohan, Andrea Dorfleutner, Christian Stehlik
Journal: Cellular and Molecular Immunology (2016)

Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease (IBD) and increases the risk for colorectal cancer. Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice. However, the inflammasome sensor absent in melanoma 2 (AIM2) protects against colorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways. Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined. Here we show that the AIM2 inflammasome has a protective role in the intestine. During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein (IL-22BP) in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides (AMPs) Reg3β and Reg3γ, which promotes dysbiosis-linked colitis. During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2-/- mice promotes excessive IL-22 production and elevated STAT3 activation. Aim2-/- mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression. This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2-/- mice to colorectal cancer. Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.
Sampling Serum in Patients With Vitiligo to Measure Disease Activity in the Skin
Authors: Mehdi Rashighi, John E. Harris
Journal: JAMA Dermatology (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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Cost-effectiveness analysis of hepatic resection after chemotherapy in the management of patients with initially unresectable colorectal liver metastases.
Authors: N. Hayashi, N. Satoh, A. Chikamoto, O. Ikeda, K. Horino, M. Watanabe, T. Ishiko, H. Takamori, T. Beppu, H. Baba
Journal: Journal of Clinical Oncology (2010)

e16554 Background: Approximately 75% of patients with colorectal liver metastases (CLM) present with unresectable disease at diagnosis. For patients who do not undergo resection, survival rates are poor. The introduction of novel chemotherapeutic regimens including molecular-targeted drugs enabled us to increase the resection rate and the median survival of these patients. However, these chemotherapeutic drugs are extremely expensive and lead to rising health care costs. The aim of this study is to measure and describe the survival outcomes and health care cost in patients with initially unresectable CLM. Methods: 73 patients with primarily unresectable CLM who were started chemotherapy between May 2005 and March 2009 in our institute were included. We evaluated survival outcomes and health care cost in patients treated with chemotherapy with or without hepatic resection. Results: 28 of 73 patients with primarily unresectable CLM were performed curative hepatic resection after chemotherapy (Group A), while the other 45 patients continued to be treated by chemotherapy without resection (Group B). In Group A vs. Group B median survival after initiation of chemotherapy was > 42 vs. 21 months (p < 0.0001), 2-year survival rate was 100% vs. 36.3% (p < 0.0001), at a median follow-up of 56 months. The mean cost of chemotherapy per person in Group A and B was yen 3,780,000 ($US 40,824) and yen 3,090,000 ($US 33,372), respectively (N.S.). The average of hepatic resection-related cost per person was yen 1,600,000 ($US 17,280). The incremental cost-effectiveness ratio (ICER) for hepatic resection was yen 1,350,000 ($US14,580)/LYG(life- year gained) within the range of $50,000/LYG, an accepted threshold in oncology. Conclusions: Hepatic resection is a cost-effective option for selected patients with primarily unresectable CLM, downsizing of the lesions by chemotherapy permitted a subsequent curative resection. No significant financial relationships to disclose.
Biomarkers defining the metabolic age of red blood cells during cold storage
Authors: Giuseppe Paglia, Angelo D’Alessandro, Óttar Rolfsson, Ólafur E. Sigurjónsson, Aarash Bordbar, Sirus Palsson, Travis Nemkov, Kirk C. Hansen, Sveinn Gudmundsson, Bernhard O. Palsson
Journal: Blood (2016)
Tumor Monocyte Cross Talk Promotes Chemotherapy Resistance In Lymphoma
Authors: Zhe Zhang, Matthew J Maurer, Peggy A Bulur, Gustafson P Michael, Thomas M Habermann, Curtis L Olswold, James R Cerhan, Brian K Link, Dennis A. Gastineau, Thomas E Witzig, Stephen M Ansell, Allan B Dietz, Yi Lin
Journal: Blood (2013)
Sixty seconds on . . . the childhood obesity strategy
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Indeed. After facing more delays than you could shake a stick of rock at, the UK government’s long awaited menu for tackling one of the biggest public health challenges of our times was finally snuck out in mid-August during parliamentary recess.1

We couldn’t possibly comment. But the glut of criticism that the document received from …
The accuracy of pleural ultrasonography in diagnosing complicated parapneumonic pleural effusions: Table 1
Authors: Philip Z Svigals, Amit Chopra, James G Ravenel, Paul J Nietert, John T Huggins
Journal: Thorax (2016)

We compared the accuracy of pleural ultrasound versus chest CT versus chest radiograph (CXR) to determine radiographic complexity in predicting a complicated parapneumonic effusion (CPPE) defined by pleural fluid analysis. 66 patients with parapneumonic effusions were identified with complete data. Pleural ultrasound had a sensitivity of 69.2% (95% CI 48.2% to 85.7%) and specificity of 90.0% (95% CI 76.3% to 97.2%). Chest CT had a sensitivity of 76.9% (95% CI 56.3% to 91.0%) and specificity of 65.0% (95% CI 48.3% to 79.4%). CXR had a sensitivity of 61.5% (95% CI 40.6% to 79.8%) and specificity of 60.0% (95% CI 43.3% to 75.1%). Pleural ultrasound appears to be a superior modality to rule in a CPPE when compared with chest CT and CXR.
Accelerating Lead Compound Optimization
Authors: Alissa Poh
Journal: Cancer Discovery (2016)

Chemists at The Scripps Research Institute in La Jolla, CA, and Pfizer's La Jolla Laboratories have devised a new way to rapidly synthesize strained-ring structures, which are increasingly favored to optimize potential drugs. With this method, strain-release amination, Pfizer researchers were able to produce sufficient quantities of a particular structure they needed to evaluate a promising cancer drug candidate.
Early Response Evaluation with 18FDG-PET Scanning, but Not Phenotypic Profile, Are Predictive of Outcome in Diffuse Large B-Cell Lymphoma.
Authors: Jehan Dupuis, Philippe Gaulard, Emmanuel Itti, Alain Rahmouni, François Hemery, Josette Brière, Bettina Fabiani, Christiane Copie-Bergman, Christian Gisselbrecht, Michel Meignan, Félix Reyes, Corinne Haioun
Journal: Blood (2005)
External validation of prognostic models to predict risk of gestational diabetes mellitus in one Dutch cohort: prospective multicentre cohort study
Authors: Marije Lamain-de Ruiter, Anneke Kwee, Christiana A Naaktgeboren, Inge de Groot, Inge M Evers, Floris Groenendaal, Yolanda R Hering, Anjoke J M Huisjes, Cornel Kirpestein, Wilma M Monincx, Jacqueline E Siljee, Annewil Van ’t Zelfde, Charlotte M van Oirschot, Simone A Vankan-Buitelaar, Mariska A A W Vonk, Therese A Wiegers, Joost J Zwart, Arie Franx, Karel G M Moons, Maria P H Koster
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To perform an external validation and direct comparison of published prognostic models for early prediction of the risk of gestational diabetes mellitus, including predictors applicable in the first trimester of pregnancy. <b>Design</b>&nbsp;External validation of all published prognostic models in large scale, prospective, multicentre cohort study. <b>Setting</b>&nbsp;31 independent midwifery practices and six hospitals in the Netherlands. <b>Participants</b>&nbsp;Women recruited in their first trimester (&lt;14 weeks) of pregnancy between December 2012 and January 2014, at their initial prenatal visit. Women with pre-existing diabetes mellitus of any type were excluded. <b>Main outcome measures</b>&nbsp;Discrimination of the prognostic models was assessed by the C statistic, and calibration assessed by calibration plots. <b>Results</b>&nbsp;3723 women were included for analysis, of whom 181 (4.9%) developed gestational diabetes mellitus in pregnancy. 12 prognostic models for the disorder could be validated in the cohort. C statistics ranged from 0.67 to 0.78. Calibration plots showed that eight of the 12 models were well calibrated. The four models with the highest C statistics included almost all of the following predictors: maternal age, maternal body mass index, history of gestational diabetes mellitus, ethnicity, and family history of diabetes. Prognostic models had a similar performance in a subgroup of nulliparous women only. Decision curve analysis showed that the use of these four models always had a positive net benefit. <b>Conclusions</b>&nbsp;In this external validation study, most of the published prognostic models for gestational diabetes mellitus show acceptable discrimination and calibration. The four models with the highest discriminative abilities in this study cohort, which also perform well in a subgroup of nulliparous women, are easy models to apply in clinical practice and therefore deserve further evaluation regarding their clinical impact.
Phase II Trial of Dose-Dense R-CHOP Followed by Risk-Adapted Consolidation with Either ICE or ICE and ASCT, Based upon the Results of Biopsy Confirmed Abnormal Interim Restaging PET Scan, Improves Outcome in Patients with Advanced Stage DLBCL.
Authors: Craig Moskowitz, Paul A. Hamlin, Steven M. Horwitz, Ariela Noy, Owen A. O’Connor, M. Lia Palomba, Carol S. Portlock, David J. Straus, Simone Chennin-Lessac, Alandra Weaver, Julie Teruva-Feldstein, Heiko Schoder, Andrew D. Zelenetz
Journal: Blood (2006)
Interim and End-of-Treatment 18F-FDG-PET Evaluation of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 6 Cycles of Dose-Dense R-CHOP-14 Immunochemotherapy Plus Pegfilgrastim for First-Line Treatment: An Open-Label Clinical Trial in Spain.
Authors: Eva Gonzalez-Barca, Miguel Canales, Antonio Salar, Albert Oriol, María Jesús Vidal, Joan Bargay, Montse Cortés, J. Coya, Jose Francisco Tomas, Andrés López, José Javier Sánchez, Eva Donato, Andrés Llorente, Secundino Ferrer, Dolores Caballero
Journal: Blood (2009)
MAPK Pathway Inhibitors Sensitize BRAF-Mutant Melanoma to an Antibody-Drug Conjugate Targeting GPNMB
Authors: April A.N. Rose, Matthew G. Annis, Dennie T. Frederick, Marco Biondini, Zhifeng Dong, Lawrence Kwong, Lynda Chin, Tibor Keler, Thomas Hawthorne, Ian R. Watson, Keith T. Flaherty, Peter M. Siegel
Journal: Clinical Cancer Research (2016)

To determine if BRAF and/or MEK inhibitor-induced GPNMB expression renders melanomas sensitive to CDX-011, an antibody-drug conjugate targeting GPNMB.The Cancer Genome Atlas melanoma dataset was interrogated for a panel of MITF-regulated melanosomal differentiation antigens, including GPNMB. BRAF-mutant melanoma cell lines treated with BRAF or MEK inhibitors were assessed for GPNMB expression by RT-qPCR, immunoblot, and FACS analyses. Transient siRNA-mediated knockdown approaches were used to determine if MITF is requirement for treatment-induced GPNMB upregulation. GPNMB expression was analyzed in serial biopsies and serum samples from patients with melanoma taken before, during, and after disease progression on MAPK inhibitor treatment. Subcutaneous injections were performed to test the efficacy of MAPK inhibitors alone, CDX-011 alone, or their combination in suppressing melanoma growth.A MITF-dependent melanosomal differentiation signature is associated with poor prognosis in patients with this disease. MITF is increased following BRAF and MEK inhibitor treatment and induces the expression of melanosomal differentiation genes, including GPNMB. GPNMB is expressed at the cell surface in MAPK inhibitor-treated melanoma cells and is also elevated in on-treatment versus pretreatment biopsies from melanoma patients receiving MAPK pathway inhibitors. Combining BRAF and/or MEK inhibitors with CDX-011, an antibody-drug conjugate targeting GPNMB, is effective in causing melanoma regression in preclinical animal models and delays the recurrent melanoma growth observed with MEK or BRAF/MEK inhibitor treatment alone.The combination of MAPK pathway inhibitors with an antibody-drug conjugate targeting GPNMB is an effective therapeutic option for patients with melanoma. Clin Cancer Res; 22(24); 6088-98. ©2016 AACR.
P0847 : Malachite-II: Phase 3b trial of ombitasvir/paritaprevir/r and dasabuvir + ribavirin or telaprevir + peginterferon/ribavirin in peginterferon/ribavirin treatment-experienced adults with HCV genotype 1
Authors: G. Dore, B. Knysz, Y. Luo, E. Janczewska, A. Streinu-Cercel, F.A. Caruntu, A. Motoc, W. Mazur, D. Shaw, I. Tornai, J. Sasadeusz, R. Skoien, D. Sullivan, X. Liu, T. Podsadecki
Journal: Journal of Hepatology (2015)
Improving the Performance of Somatic Mutation Identification by Recovering Circulating Tumor DNA Mutations
Authors: Yu Fu, Cécile Jovelet, Thomas Filleron, Marion Pedrero, Nelly Motté, Yannick Boursin, Yufei Luo, Christophe Massard, Mario Campone, Christelle Levy, Véronique Diéras, Thomas Bachelot, Julie Garrabey, Jean-Charles Soria, Ludovic Lacroix, Fabrice André, Celine Lefebvre
Journal: Cancer Research (2016)

DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers. In a cohort of 93 breast cancer metastatic patients, cmDetect identified ctDNA mutations in 54% of the patients and recovered somatic mutations in cancer genes EGFR, PIK3CA, and TP53 We further showed that cmDetect detected ctDNA in 89% of patients with confirmed mutated cell-free tumor DNA by plasma analyses (n = 9) within 46 pan-cancer patients. Our results prompt immediate consideration of the use of this method as an additional step in somatic mutation calling using whole-exome sequencing data with blood samples as controls. Cancer Res; 76(20); 5954-61. ©2016 AACR.