tbuckley/cabot-search huggingface dataset:
The invariant natural killer T cell–mediated chemokine X-C motif chemokine ligand 1–X-C motif chemokine receptor 1 axis promotes allergic airway hyperresponsiveness by recruiting CD103+ dendritic cells
Authors: Yeon Duk Woo, Jaemoon Koh, Hye-Ryun Kang, Hye Young Kim, Doo Hyun Chung
Journal: Journal of Allergy and Clinical Immunology (2018)
Inhibition of thioredoxin activates mitophagy and overcomes adaptive bortezomib resistance in multiple myeloma
Authors: Zhihong Zheng, Shengjun Fan, Jing Zheng, Wei Huang, Cristina Gasparetto, Nelson J. Chao, Jianda Hu, Yubin Kang
Journal: Journal of Hematology & Oncology (2018)

Although current chemotherapy using bortezomib (Velcade) against multiple myeloma in adults has achieved significant responses and even remission, a majority of patients will develop acquired resistance to bortezomib. Increased thioredoxin level has been reported to be associated with carcinogenesis; however, the role of thioredoxin in bortezomib drug resistance of myeloma remains unclear. We generated several bortezomib-resistant myeloma cell lines by serially passaging with increased concentrations of bortezomib over a period of 1.5 years. Thioredoxin expression was measured by real-time PCR and western blot. The role of thioredoxin in the survival of bortezomib-resistant myeloma cells was determined by specific shRNA knockdown in vitro and in vivo. Thioredoxin inhibitor (PX12) was used to determine the effectiveness of thioredoxin inhibition in the treatment of bortezomib-resistant myeloma cells. The effect of thioredoxin inhibition on mitophagy induction was examined. The correlation of thioredoxin expression with patient overall survival was interrogated. Thioredoxin expression was significantly upregulated in bortezomib-resistant myeloma cells and the change correlated with the increase of bortezomib concentration. Thioredoxin gene knockdown using specific shRNA sensitized bortezomib-resistant myeloma cells to bortezomib efficiency in vitro and in vivo. Similarly, pharmacological inhibition with PX12 inhibited the growth of bortezomib-resistant myeloma cells and overcame bortezomib resistance in vitro and in vivo. Furthermore, inhibition of thioredoxin resulted in the activation of mitophagy and blockage of mitophagy prevented the effects of PX12 on bortezomib-resistant myeloma cells, indicating that mitophagy is the important molecular mechanism for the induction of cell death in bortezomib-resistant myeloma cells by PX12. Moreover, inhibition of thioredoxin resulted in downregulation of phosphorylated mTOR and ERK1/2. Finally, thioredoxin was overexpressed in primary myeloma cells isolated from bortezomib-resistant myeloma patients and overexpression of thioredoxin correlated with poor overall survival in patients with multiple myeloma. Our findings demonstrated that increased thioredoxin plays a critical role in bortezomib resistance in multiple myeloma through mitophagy inactivation and increased mTOR and ERK1/2 phosphorylation. Thioredoxin provides a potential target for clinical therapeutics against multiple myeloma, particularly for bortezomib-resistant/refractory myeloma patients.
A molecular and clinico-pathological model for predicting abiraterone acetate/prednisone (AA/P) efficacy in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Manish Kohli, Rui Qin, Liguo Wang, Hugues Sicotte, Rachel Carlson, Winston Tan, Rafael E. Jimenez, Liewei Wang, Jeanette Eckel-Passow, Brian Addis Costello, Henry C. Pitot, Fernando Quevedo, Roxana Stefania Dronca, Kevin Wu, Timothy Jerome Moynihan, Thai Huu Ho, Alan Haruo Bryce, Thomas D Atwell, Brendan P McMenomy, Scott Dehm
Journal: Journal of Clinical Oncology (2015)

5056 Background: There are no known markers for predicting AA/P efficacy in chemo-naïve mCRPC stage. We explored a model for predicting the 12-week efficacy outcome after initiation of AA/P in a prospective clinical trial (NCT# 01953640). Methods: mCRPC patients initiating AA/P underwent biopsy of metastases at baseline (pre AA/P) and at week 12. Somatic whole exome DNA sequencing; gene expression for AR full length (ARFL) and splice variants (ARVs) was performed of baseline metastases. Composite progression on AA/P at week 12, (primary endpoint) was evaluated with PSA, RECIST, bone scan and symptoms (based on PCWG2 criteria). Candidate molecular factors (RNA expression of ARFL, ARV3, ARV7, ARV9, ARV23, ARV45, Chromogranin-A (CGA)) were explored in a multivariate Cox Proportional Hazard Regression (CPHR) model. Additionally, PSA/testosterone levels, Gleason Score (GS:2-6;7;8-10) at initial diagnosis; time from starting hormone therapy to mCRPC stage (years), serum CGA levels were also included. A final CPHR model fitted only those factors which exceeded an entry threshold in univariate analysis or were considered clinically relevant. Results: Between 6/2013 and 11/2014, 56/70 patients enrolled had disease assessed at the 12-week time point. The CPHR model includes 56 patients with complete sequencing and 12 week clinical outcomes. The median follow up for the cohort was 170 days (41-502 days). Progression at 12-weeks was observed in 23/56 patients. The final CPHR model included baseline expression of ARV45 (HR = 13.107, p-value = 0.017); CGA levels (HR = 0.998, p-value = 0.004); time from hormone therapy to mCRPC stage (HR = 0.782, p-value = 0.008); GS at initial diagnosis (HR = 0.004, p-value < 0.001 for GS group 7 and HR = 0.008 p-value < 0.001 for GS group 8-10) and ARFL, ARV3, ARV7, ARV9, ARV23. A C-statistic for the model was observed at 0.76 with an adjusted R2 of 0.47 (likelihood ratio p-value < 0.001). Conclusions: Clinical prediction rules are needed for developing precision medicine in mCRPC. An initial attempt to incorporate molecular and clinico-pathological factors appears feasible. Evaluation for model stability remains ongoing. Clinical trial information: NCT# 01953640.
Adalimumab for childhood onset uveitis
Authors: A V Ramanan, Catherine Guly
Journal: Annals of the Rheumatic Diseases (2018)

Juvenile idiopathic arthritis (JIA)-associated uveitis is the most common cause of paediatric uveitis and is associated with significant visual morbidity.1 Despite considerable improvements in the treatment of JIA, most trials of biological agents in JIA excluded children with uveitis for methodological reasons. This has meant a limited evidence base and availability of biological therapies for paediatric uveitis. The ADJUVITE study2 published in this journal and the recently published SYCAMORE study3 both provide much needed evidence for use of biologics in children with uveitis.

The ADJUVITE study2 randomised 32 patients with childhood onset anterior uveitis and an inadequate response to topical steroid and methotrexate (MTX), based on a laser flare photometry (LFP) reading of ≥30 photon units/ms, to fortnightly adalimumab or placebo. The primary outcome was response to treatment at the end of month 2, defined as a reduction of at least 30% of ocular inflammation on LFP with no worsening of anterior chamber cells or flare according to Standardised Uveitis Nomenclature (SUN) criteria.4 In the adalimumab group, 9/16 patients had a 30% reduction in flare on LFP compared with 3/15 in the placebo group, which was statistically significant, but as the authors acknowledge should be interpreted with some caution as the CI included 1. There was no significant reduction in anterior chamber cell scores.

This small study, following on from the SYCAMORE trial,3 which was stopped early due to evidence of efficacy of adalimumab for JIA-associated uveitis, provides further support for the use of adalimumab in childhood uveitis.

However, there are striking differences between the ADJUVITE …
Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial
Authors: Irene L. Wapnir, Karen N. Price, Stewart J. Anderson, André Robidoux, Miguel Martín, Johan W.R. Nortier, Alexander H.G. Paterson, Mothaffar F. Rimawi, István Láng, José Manuel Baena-Cañada, Beat Thürlimann, Eleftherios P. Mamounas, Charles E. Geyer, Shari Gelber, Alan S. Coates, Richard D. Gelber, Priya Rastogi, Meredith M. Regan, Norman Wolmark, Stefan Aebi
Journal: Journal of Clinical Oncology (2018)

Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)-negative ILRR, but additional follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomly assigned to receive CT or no CT and stratified by prior CT, hormone receptor status, and location of ILRR. Patients with hormone receptor-positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti-human epidermal growth factor receptor 2 therapy was optional. End points were disease-free survival (DFS), overall survival, and breast cancer-free interval. Results From August 2003 to January 2010, 162 patients were enrolled: 58 with ER-negative and 104 with ER-positive ILRR. At 9 years of median follow-up, 27 DFS events were observed in the ER-negative group and 40 in the ER-positive group. The hazard ratios (HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v 34%, CT v no CT, respectively) in patients with ER-negative ILRR and 1.07 (95% CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively) in patients with ER-positive ILRR ( P
Pertinence de l'indication de la fibroscopie oeso-gastroduodénale selon les critères de l'EPAGE
Authors: EH Ould Mahfoud, Y Thiyfa, M Tahiri Joutei Hassani, F Haddad, W Hliwa, A Bellabah, W Badre
Journal: Endoscopy (2018)

La pratique de la fibroscopie oeso-gastroduodénale (FOGD) est en augmentation constante. Sa prescription doit être rationalisée tenant compte du rapport cout/bénéfice/risque. Des critères évaluant la pertinence des indications de la FOGD ont été élabores par un panel d'experts Européens l'EPAGE (European Panel on Appropriateness of GastrointestinalEndoscopy). Les objectifs de notre étude étaient d'évaluer l'application en pratique clinique des critères de l'EPAGE II, de tester la pertinence des indications de la FOGD et de rechercher une éventuelle corrélation entre la pertinence de cet examen et le résultat endoscopique.
Role of Preoperative Variables in Reducing the Rate of Occult Invasive Disease for Women Considering Active Surveillance for Ductal Carcinoma In Situ
Authors: Lars J. Grimm, Marc D. Ryser, Terry Hyslop
Journal: JAMA Surgery (2018)

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 Surgery 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 Surgery journal
Inconsistent Hypertension Guidelines: We Need a Little Help Here
Authors: Neil Skolnik
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
SCN5A: the greatest HITS collection
Authors: David S. Park, Glenn I. Fishman
Journal: Journal of Clinical Investigation (2018)

Heart failure (HF) has been referred to as the cardiovascular epidemic of our time. Understanding the molecular determinants of HF disease progression and mortality risk is of utmost importance. In this issue of the JCI, Zhang et al. uncover an important link between clinical HF mortality risk and a common variant that regulates SCN5A expression through microRNA-dependent (miR-dependent)mechanisms. They also demonstrate that haploinsufficiency of SCN5A is associated with increased accumulation of reactive oxygen species (ROS) in a genetically engineered murine model. Their data suggest that even modest depression of SCN5A expression may promote pathologic cardiac remodeling and progression of HF.
Early Resuscitation for Adults With Sepsis in a Low-Income Country
Authors: Wagner Luis Nedel, Caroline Deutschendorf
Journal: JAMA (2018)

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
Risk Factors for Anaphylactoid Reaction to Low Osmolar Contrast During Cardiac Catheterization
Authors: Martin A. Smith, Lisanne P. Newton, David Newton, Leslie Cho, Maria A. Barcena Blanch, Lyda Cuervo Pardo, Xiaofeng Wang, Manshi Li, David M. Lang
Journal: Journal of Allergy and Clinical Immunology (2018)
Efficiency of different control measures for preventing carbapenemase-producing enterobacteria and glycopeptide-resistant Enterococcus faecium outbreaks: a 6-year prospective study in a French multihospital institution, January 2010 to December 2015
Authors: Sandra Fournier, Laure Desenfant, Catherine Monteil, Michèle Nion-Huang, Christian Richard, Vincent Jarlier
Journal: Eurosurveillance (2018)

An infection control programme was implemented in a 21,000-bed multihospital institution for controlling the spread of carbapenemase-producing Enterobacteriaceae (CPE) and glycopeptide-resistant Enterococcus faecium (GRE), classified as 'emergent extensively drug-resistant bacteria' (eXDR) in France. We evaluated factors associated with outbreaks occurrence (n = 103), which followed 901 eXDR introductions (index case followed or not by secondary cases) from 2010 to 2015. In univariate analysis, knowing that patients had been hospitalised abroad, bacterial species (GRE vs CPE, as well as the CPE Klebsiella pneumoniae compared with the other Enterobacteriaceae species) and type of measures implemented within the first 2 days of hospitalisation were associated with outbreaks occurrence, but not the type of wards where carriers were hospitalised, nor the eXDR colonisation or infection status. In multivariate analysis, occurrence of outbreaks was significantly lower when contact precautions (odds ratio (OR): 0.34; 95% confidence interval (CI): 0.22-0.54) and even more when dedicated nursing staff (OR: 0.09; 95% CI: 0.02-0.39) were implemented around eXDR index cases within the first 2 days of hospitalisation (p < 10 - 3). GRE introductions were more frequently associated with occurrence of outbreaks than CPE (OR: 3.58; 95% CI: 2.32-5.51, p < 10 - 3). A sustained and coordinated strategy is efficient to limit the spread of eXDR at the scale of a large health institution.
Consensus guidelines on the optimal management in interventional EUS procedures: results from the Asian EUS group RAND/UCLA expert panel
Authors: Anthony Y B Teoh, Vinay Dhir, Mitsuhiro Kida, Ichiro Yasuda, Zhen Dong Jin, Dong Wan Seo, Majid Almadi, Tiing Leong Ang, Kazuo Hara, Ida Hilmi, Takao Itoi, Sundeep Lakhtakia, Koji Matsuda, Nonthalee Pausawasdi, Rajesh Puri, Raymond S Tang, Hsiu-Po Wang, Ai Ming Yang, Robert Hawes, Shyam Varadarajulu, Kenjiro Yasuda, Lawrence Khek Yu Ho
Journal: Gut (2018)

Objectives Interventional endoscopic ultrasonography (EUS) procedures are gaining popularity and the most commonly performed procedures include EUS-guided drainage of pancreatic pseudocyst, EUS-guided biliary drainage, EUS-guided pancreatic duct drainage and EUS-guided celiac plexus ablation. The aim of this paper is to formulate a set of practice guidelines addressing various aspects of the above procedures. Methods Formulation of the guidelines was based on the best scientific evidence available. The RAND/UCLA appropriateness methodology (RAM) was used. Panellists recruited comprised experts in surgery, interventional EUS, interventional radiology and oncology from 11 countries. Between June 2014 and October 2016, the panellists met in meetings to discuss and vote on the clinical scenarios for each of the interventional EUS procedures in question. Results A total of 15 statements on EUS-guided drainage of pancreatic pseudocyst, 15 statements on EUS-guided biliary drainage, 12 statements on EUS-guided pancreatic duct drainage and 14 statements on EUS-guided celiac plexus ablation were formulated. The statements addressed the indications for the procedures, technical aspects, pre- and post-procedural management, management of complications, and competency and training in the procedures. All statements except one were found to be appropriate. Randomised studies to address clinical questions in a number of aspects of the procedures are urgently required. Conclusions The current guidelines on interventional EUS procedures are the first published by an endoscopic society. These guidelines provide an in-depth review of the current evidence and standardise the management of the procedures.
Mieux choisir le moment de la procédure diminue la morbidité de la Gastrostomie Percutanée Endoscopique (GPE)
Authors: C Yazbeck, E Aoude, Y Yazbeck, B Akiki
Journal: Endoscopy (2018)

La gastrostomie percutanée endoscopique est devenue la technique de préférence d'alimentation assistée chez les patients incapables de suppléer à leurs besoins par la seule voie orale et ayant une intégrité du tractus digestif. Cette technique est de réalisation rapide et facile entre les mains expérimentées, elle est moins couteuse et moins morbide que la voie chirurgicale. Le taux de réussite est de 94 – 98%. Les complications graves sont rares (hémorragie, fistule gastro colique, perforation ou lacération viscérale), les infections représentent un souci essentiel et fréquent pouvant rarement mettre en danger la vie du patient.
Korean Version of Test for Respiratory and Asthma Control in Kids (TRACK): Reliability and Validity
Authors: Dong In Suh, Yun Jung Choi, Kwang-Cheon Jang, Hyeon-Jong Jong Yang, Hyo Bin Kim, Mee-Yong Shin, Young Yull Koh
Journal: Journal of Allergy and Clinical Immunology (2018)
Activity and Safety of Cetuximab Plus Modified FOLFOXIRI Followed by Maintenance With Cetuximab or Bevacizumab for <i>RAS</i> and <i>BRAF</i> Wild-type Metastatic Colorectal Cancer
Authors: Chiara Cremolini, Carlotta Antoniotti, Sara Lonardi, Giuseppe Aprile, Francesca Bergamo, Gianluca Masi, Roberta Grande, Giuseppe Tonini, Claudia Mescoli, Giovanni Gerardo Cardellino, Luigi Coltelli, Lisa Salvatore, Domenico Cristiano Corsi, Cristiana Lupi, Donatello Gemma, Monica Ronzoni, Emanuela Dell’Aquila, Federica Marmorino, Francesca Di Fabio, Maria Laura Mancini, Lorenzo Marcucci, Gabriella Fontanini, Vittorina Zagonel, Luca Boni, Alfredo Falcone
Journal: JAMA Oncology (2018)

The combination of a triple-drug chemotherapy regimen with an anti-epidermal growth factor receptor (EGFR) agent as a first-line treatment of metastatic colorectal cancer (mCRC) showed promising activity along with safety concerns in single-arm phase 2 trials. The role of maintenance following chemotherapy and anti-EGFR and the optimal regimen to be adopted are not established.To evaluate the activity and safety of cetuximab plus modified FOLFOXIRI (mFOLFOXIRI) and explore the role of maintenance with cetuximab or bevacizumab in RAS and BRAF wild-type mCRC.In a prospective, noncomparative, open-label, multicenter, randomized phase 2 trial, patients aged 18 to 75 years with unresectable, previously untreated RAS and BRAF wild-type (before amendment, KRAS wild-type) mCRC were recruited from 21 oncology units in Italy from October 19, 2011, to March 1, 2015 (followed up through May 31, 2017). In total, 323 patients were screened and 143 were randomized to 2 treatment arms to receive as a first-line induction a regimen of mFOLFOXIRI plus cetuximab followed by cetuximab (arm A) or bevacizumab (arm B) until disease progression. Primary analyses were conducted in a modified intention-to-treat population.mFOLFOXIRI plus cetuximab repeated every 2 weeks for up to 8 cycles, followed by maintenance with cetuximab or bevacizumab until disease progression.The primary end point was the 10-month progression-free rate (PFR); secondary end points included progression-free and overall survival, response rate, rate of metastases resection, and adverse events.Of 143 patients randomized, 116 (81.1%) (median [interquartile range (IQR)] age, 59.5 [53-67] years; 34 [29.3%] women) had RAS and BRAF wild-type mCRC. At a median (IQR) follow-up of 44.0 (30.5-52.1) months, 10-month PFRs were 50.8% (90% CI, 39.5%-62.2%) in arm A and 40.4% (90% CI, 29.4%-52.1%) in arm B. The overall response rate was 71.6% (95% CI, 62.4%-79.5%). Main grade 3/4 adverse events were neutropenia (occurring in 36 patients [31%]), diarrhea (in 21 patients [18%]), skin toxic effects (in 18 patients [16%]), asthenia (in 11 patients [9%]), stomatitis (in 7 patients [6%]), and febrile neutropenia (in 3 patients [3%]).Although neither of the 2 arms met the primary end point, the findings indicate that a 4-month induction regimen of mFOLFOXIRI plus cetuximab is feasible and provides relevant activity results, leading to a high surgical resection rate.clinicaltrials.gov Identifier: NCT02295930.