tbuckley/cabot-search huggingface dataset:
CREST: Randomised phase III study of stenting as a bridge to surgery in obstructing colorectal cancer—Results of the UK ColoRectal Endoscopic Stenting Trial (CREST).
Authors: James Hill, Clive Kay, Dion Morton, Laura Magill, Kelly Handley, Richard G. Gray
Journal: Journal of Clinical Oncology (2016)

3507 Background: Uncertainty remains about the efficacy and safety of endoluminal stenting as an alternative to emergency surgery in patients with potentially curable obstructing left sided colorectal cancer. Emergency presentations still account for 20% of all colorectal cancer cases; obstruction is present in 80% of these. Methods: Patients presenting in the emergency setting with left-sided colonic obstruction needing urgent decompression and radiological features of a carcinoma were randomized to either: endoluminal stenting as a bridge to surgery or surgical decompression. Patients were stratified according to curative intent based on pre-operative staging investigations. A combined endoscopic/fluoroscopic technique was standardized in stent workshops with elective surgery performed 1-4 weeks later. Results: 246 patients from 39 units were randomized between 2009 and 2014 with 98% complying with allocated treatment. 92% were treated with curative intent. 30-day post-operative mortality (5.3% vs 4.4%) and length of hospital stay [15.5 days (IQR 10-26) vs 16 days (10-27)] were similar with stenting and surgery. Stenting achieved relief of obstruction in 82% of patients and reduced stoma formation; 69% emergency surgery v 45% with stenting as a bridge to surgery (p < 0.001). There were no significant differences in QoL at 3 and 12 months or critical care utilization. 1 year mortality for potentially curative patients did not differ by treatment group. Conclusions: CReST is the largest trial of endoluminal stenting in obstructing colorectal cancer. In patients fit enough to undergo surgery, stenting as a bridge to surgery reduced stoma formation without a detrimental effect on one-year survival. Post-operative mortality, length of hospital stay, critical care usage and Quality of Life were not different between the two treatment groups. Clinical trial information: 13846816.
More Precisely Targeting the Coal Mine of Social Adversity
Authors: Neal Halfon
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Response to Comment on Kovatchev and Cobelli. Glucose Variability: Timing, Risk Analysis, and Relationship to Hypoglycemia in Diabetes. Diabetes Care 2016;39:502–510
Authors: Boris Kovatchev, Claudio Cobelli
Journal: Diabetes Care (2016)

We thank Dr. Service (1) for critically reviewing our Perspective (2) on glucose variability (GV) in diabetes, and, in response, we would like to point out certain distinctions between our view of GV and the definition of the mean amplitude of glucose excursions (MAGE)—a widely used statistical metric of GV that Service introduced in 1970 (3). However, before explaining these distinctions, we must first address Service’s specific criticism of our mentioning of MAGE.

1.  The formula we presented for the calculation of MAGE is correct and so is our assessment that MAGE is “inherently biased toward hyperglycemia and has a relatively weak association with hypoglycemia” (2). This assessment has …
Anti-GP2 IgA: a biomarker for disease severity and/or cholangiocarcinoma in primary sclerosing cholangitis?
Authors: Sumera Rizvi, Ju Dong Yang, Gregory J Gores
Journal: Gut (2016)

Primary sclerosing cholangitis (PSC) is a heterogeneous and complex syndrome with highly variable disease progression and unknown etiopathogenesis, the latter perhaps influenced by the microbiome.1 ,2 Moreover, it is a premalignant disease in that it confers a significant risk for the development of cholangiocarcinoma (CCA) in a subset of patients.3 Detection of CCA in PSC poses a major diagnostic dilemma as inflammation-related dominant strictures in PSC may mimic malignant strictures.3 Contemporary diagnostic modalities for early detection of CCA in patients with PSC remain suboptimal although innovative approaches are emerging.4 Hence, there is a critical need for the development of a biomarker which may identify the subgroup of patients with PSC at risk for CCA. Such a biomarker would enable earlier CCA detection which in turn increases the likelihood of having curative treatment options. Biomarkers, in general, are analytes which can be detected in tissues, cells or body fluids, and signify either the presence of a disease or its outcome.5 The ideal biomarker should be readily detected in a non-invasive manner, and be highly sensitive and specific in its diagnostic, predictive and prognostic capability.5 

In this issue, Jendrek et al report a potential biomarker, antiglycoprotein 2 (anti-GP2), in PSC, CCA, as well as secondary sclerosing cholangitis (SSC).6 Autoantibodies against glycoproteins of the pancreatic acini (PABs) are reported to have a high specificity …
Lipid Screening in Children and Adolescents
Authors: Elaine M. Urbina, Sarah D. de Ferranti
Journal: JAMA (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 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
Myocardial Infarction-Associated Circular RNA Predicting Left Ventricular Dysfunction
Authors: Melanie Vausort, Antonio Salgado-Somoza, Lu Zhang, Przemyslaw Leszek, Markus Scholz, Andrej Teren, Ralph Burkhardt, Joachim Thiery, Daniel R. Wagner, Yvan Devaux
Journal: Journal of the American College of Cardiology (2016)
A first-in-human study of neural stem cells (NSCs) expressing cytosine deaminase (CD) in combination with 5-fluorocytosine (5-FC) in patients with recurrent high-grade glioma.
Authors: Jana Portnow, Behnam Badie, Timothy W. Synold, Alexander Annala, Bihong Chen, Joseph Frank, Rex A. Moats, John Wood, Massimo D'Apuzzo, Victoria Bedell, Paul Henry Frankel, Karen S. Aboody
Journal: Journal of Clinical Oncology (2013)

2018 Background: Human NSCs are inherently tumor-tropic, making them attractive drug delivery vehicles. This pilot-feasibility study assessed the safety of using genetically-modified NSCs for tumor selective enzyme/prodrug therapy. An immortalized, clonal NSC line was retrovirally-transduced to stably express CD, which converts the prodrug 5-FC to 5-fluorouracil (5-FU), producing chemotherapy locally at sites of tumor in the brain. Methods: Patients 18 years or older with recurrent high-grade glioma underwent intracranial administration of NSCs during tumor resection or biopsy. Four days later, 5-FC was administered orally every 6 hours for 7 days. Study treatment was given only once. A standard 3+3 dose escalation schema was used to increase doses of NSCs from 1 x 10 7 to 5 x 10 7 and 5-FC from 75 to 150 mg/kg/day. Intracerebral microdialysis was performed to measure brain levels of 5-FC and 5-FU; serial blood samples were obtained to assess systemic drug concentrations. Three patients received iron-labeled NSCs for MRI tracking. Brain autopsies were done on 2 patients. Results: Fifteen patients received study treatment. Three were inevaluable for toxicity and replaced. All patients tolerated the NSCs well. There was 1 dose-limiting toxicity (grade 3 transaminitis) possibly related to 5-FC. At the highest dose level of NSCs, the average steady-state concentration of 5-FU in the brain was 63.9±7.9 nM. The average maximum 5-FU level in brain was 104±88 nM compared to 24±36 nM in plasma, indicating local production of 5-FU in the brain by the NSCs. MR imaging of iron-labeled NSCs showed preliminary evidence of NSC migration. Autopsy data documented (by IHC, FISH, and PCR) NSCs at distant sites of tumor in the brain and no development of secondary tumors. Conclusions: This first-in-human study has demonstrated safety and proof-of-concept regarding NSC-mediated conversion of 5-FC to 5-FU and NSC tumor-tropism. NSCs have the potential to overcome obstacles of drug delivery that limit current gene therapy strategies. Results of this pilot study will serve as the foundation for future NSC studies. (Supported by NCI 1R21 CA137639-01A1, CIRM DR-01421). Clinical trial information: NCT01172964.
Sequencing-Based Detection of Circulating Tumor DNA in the Autologous Stem Cell Grafts of Patients with Diffuse Large B-Cell Lymphoma Undergoing Hematopoietic Stem Cell Transplantation
Authors: Alex F. Herrera, Reid W. Merryman, Katherine A. Kong, Heather Sun, Jennifer R. Brown, David C. Fisher, Matthew S. Davids, Eric D. Jacobsen, Caron A. Jacobson, Haesook T. Kim, Ann S. LaCasce, German A. Pihan, Aliyah R Sohani, Scott J. Rodig, Arnold S. Freedman, Jerome Ritz, Malek Faham, Philippe Armand
Journal: Blood (2015)
A new home for science
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Wellcome Trust

The Francis Crick Institute in London, which scientists start to move into this week, is a building that was designed with collaboration in mind.

Once the 1250 scientists are installed in Europe’s largest biomedical research space—of more than 120 000 square metres (or 17 football pitches) over eight floors—team work is likely to come naturally. The …
Translational Research on Incubation of Cocaine Craving
Authors: Xuan Li, Marco Venniro, Yavin Shaham
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Serine 421 regulates mutant huntingtin toxicity and clearance in mice
Authors: Ian H. Kratter, Hengameh Zahed, Alice Lau, Andrey S. Tsvetkov, Aaron C. Daub, Kurt F. Weiberth, Xiaofeng Gu, Frédéric Saudou, Sandrine Humbert, X. William Yang, Alex Osmand, Joan S. Steffan, Eliezer Masliah, Steven Finkbeiner
Journal: Journal of Clinical Investigation (2016)

Huntington's disease (HD) is a progressive, adult-onset neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the N-terminal region of the protein huntingtin (HTT). There are no cures or disease-modifying therapies for HD. HTT has a highly conserved Akt phosphorylation site at serine 421, and prior work in HD models found that phosphorylation at S421 (S421-P) diminishes the toxicity of mutant HTT (mHTT) fragments in neuronal cultures. However, whether S421-P affects the toxicity of mHTT in vivo remains unknown. In this work, we used murine models to investigate the role of S421-P in HTT-induced neurodegeneration. Specifically, we mutated the human mHTT gene within a BAC to express either an aspartic acid or an alanine at position 421, mimicking tonic phosphorylation (mHTT-S421D mice) or preventing phosphorylation (mHTT-S421A mice), respectively. Mimicking HTT phosphorylation strongly ameliorated mHTT-induced behavioral dysfunction and striatal neurodegeneration, whereas neuronal dysfunction persisted when S421 phosphorylation was blocked. We found that S421 phosphorylation mitigates neurodegeneration by increasing proteasome-dependent turnover of mHTT and reducing the presence of a toxic mHTT conformer. These data indicate that S421 is a potent modifier of mHTT toxicity and offer in vivo validation for S421 as a therapeutic target in HD.
High Prevalence of Concomitant Oncogene Mutations in Prospectively Identified Patients with ROS1-Positive Metastatic Lung Cancer
Authors: Marcel Wiesweg, Wilfried E.E. Eberhardt, Henning Reis, Saskia Ting, Nikoleta Savvidou, Charlotte Skiba, Thomas Herold, Daniel C. Christoph, Johannes Meiler, Karl Worm, Stefan Kasper, Dirk Theegarten, Jörg Hense, Thomas Hager, Kaid Darwiche, Filiz Oezkan, Clemens Aigner, Stefan Welter, Hilmar Kühl, Martin Stuschke, Kurt W. Schmid, Martin Schuler
Journal: Journal of Thoracic Oncology (2016)
Circulating tumor cell analysis in patients with non-small cell lung cancer
Authors: T. Kato, K. Yamada, H. Nokihara, T. Fukui, N. Yamamoto, I. Sekine, H. Kunitoh, Y. Ohe, F. Koizumi, T. Tamura
Journal: Journal of Clinical Oncology (2008)

19026 Background: The detection and quantification of tumor cells circulating in the blood may be helpful for clinical staging and estimating prognosis. We investigated the detectability and clinical significance of circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). Methods: NSCLC patients with locally advanced disease (stage IIIA/IIIB), advanced disease with pleural effusion (stage IIIB/IV), or recurrent disease with pleural effusion were eligible for enrollment. The number of CTCs in 7.5 mL of whole blood collected before treatment (baseline) were measured using the CellSearch System, which is based on immunomagnetic enrichment targeting CD326 (EpCAM) and staining for DAPI, cytokeratin 8, 18, 19, and CD45. The cell morphology was confirmed in all cases. Results: Thirty-six patients were eligible and analyzed. The median patient age was 60 years old; 30 patients had adenocarcinoma, 4 had squamous cell carcinoma and 2 had others. Fourteen patients (39%) had one or more CTCs at baseline. The positive rates and the range of CTC counts at baseline were 1/8 (13%) and 0 - 1 among patients with stage IIIA, 1/5 (20%) and 0 - 16 among patients with stage IIIB, 3/8 (38%) and 0 - 4 among patients with stage IV, and 9/15 (60%) and 0 - 67 among pretreated patients. Patients with one or more CTCs at baseline had a poorer outcome than patients with no CTCs (all patients: median overall survival, 60 vs. 377 days, respectively [log-rank test, p < .001]; pretreated patients: median overall survival, 31 vs. 250 days, respectively [log-rank test, p = .004]). Conclusion: The positive CTC rate increased with advancing disease stage. The CTC counts and positive rates were higher among pretreated patients than among untreated patients. The detection of CTCs at baseline may predict a poor prognosis, especially in pretreated NSCLC patients. No significant financial relationships to disclose.
Nurse-Led Titration of Angiotensin-Converting Enzyme Inhibitors, β-Adrenergic Blocking Agents, and Angiotensin Receptor Blockers in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Andrea Driscoll, Judy Currey, Andrew Maxwell Tonkin
Journal: JAMA Cardiology (2016)

Does nurse-led titration of β-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with heart failure with reduced ejection fraction improve outcomes?Participants whose treatment included nurse-led titration experienced fewer hospital admissions for any cause and an increase in survival, with more participants reaching target dose within a shorter period.
Clinical significance of homologous recombination deficiency (HRD) score testing in endometrial cancer patients.
Authors: Jean M. Hansen, Kari Lassen Ring, Keith A. Baggerly, Sherry Wu, Kirsten Timms, Christopher Neff, Elisha Hughes, Rebecca A. Previs, Russell Broaddus, Robert L. Coleman, Karen H. Lu, Anil Sood
Journal: Journal of Clinical Oncology (2016)

5584 Background: HRD score is related to chemotherapy response in both triple negative breast and high-grade serous ovarian cancers. The role of HRD is unknown in endometrial cancer. We examined the relationship between HRD score and survival in a cohort of endometrial cancer patients and with tumor growth using murine orthotopic models. Methods: 137 formalin-fixed paraffin-embedded endometrioid adenocarcinoma patient samples were tested for HRD score, microsatellite instability (MSI) and high mutation load (HML) using a next generation sequencing assay targeting the coding regions of 43 genes and 54,091 genome wide SNPs. The HRD score is the sum of three previously described scores (loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition) that quantitate genome rearrangement. Clinical records were obtained for all 137 patients. HRD scores were also generated on a panel of established endometrial cancer cell lines and their response to olaparib was assessed. Tumor growth and patterns of metastatic spread were assessed in orthotopic mouse models of endometrial cancer. Results: Median age at diagnosis was 62 years. The majority of patients presented with early stage disease (54%, 11%, 27%, 8% stage I, II, III, IV respectively), and FIGO grade 2 histology (1%, 73%, 26% grade 1, 2, 3). HRD scores were generated for 112 patient samples, MSI status was determined for 126 samples, and HML status determined for 137 samples. The median HRD score was 3. Patients with HRD score < 3 had significantly longer PFS and OS than patients with HRD score ≥ 3 (p = 0.024 and 0.0067, respectively). At the time of necropsy, mice injected with Hec1a (HRD score = 19) had significantly higher tumor burden than mice injected with Ishikawa (HRD score = 6). Within each group, treatment with olaparib significantly reduced tumor growth, but the effect was greater in the Hec1a group. Conclusions: Low HRD score was correlated with improved survival in endometrial cancer patients, and with decreased tumor growth in mouse models. The high HRD score model had increased response to olaparib treatment. Our findings support the use of HRD score in guiding the choice of adjuvant therapy for patients with endometrial cancer.
WP-1130 Induces Apoptosis in Multiple Myeloma Cells by Inactivation of Jak2 and Syk Tyrosine Kinases Via a Novel Mechanism of Selective Protein Trafficking
Authors: Daniel Lebovic, Vaibhav Kapuria, Malathi Hari, Moshe Talpaz, Andrzej Jakubowiak, Nicholas Donato
Journal: Blood (2008)
Outcomes of High Dose Steroid Treatment with or without Aminocaproic Acid in Critically Ill Stem Cell Transplant Recipients with Diffuse Alveolar Hemorrhage
Authors: Nisha Rathi, Andrew Dinh, Sajid A. Haque, Lei Feng, Suyu Liu, Wenli Dong, Joseph L Nates, Kristen J Price, Uday Popat
Journal: Blood (2011)
Incidence and survival patterns of primary central nervous system (CNS), systemic and concurrent diffuse large B-cell lymphoma (DLBCL).
Authors: Shiva Kumar Reddy Mukkamalla, Hussain M. Naseri, Tanmay Sahai, Todd F. Roberts, Mohsin Ilyas Malik
Journal: Journal of Clinical Oncology (2016)

e13512 Background: Concurrent CNS and systemic involvement with DLBCL is a rare presentation. To our knowledge there is no study looking at the incidence and survival patterns of concurrent CNS and systemic DLBCL lymphoma. Methods: DLBCL cases diagnosed between 2000 and 2008 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Further stratification was done using primary site of disease and Ann Arbor staging. Patients with non-CNS primary site from all stages were labeled as systemic and those with CNS as primary site belonging to stage I were categorized as primary CNS DLBCL. Concurrent disease included patients with CNS as primary site and belonging to stages II, III and IV at diagnosis. Overall survival (OS) and DLBCL specific survival (DSS) were analyzed using Chi-square test and Cox proportional hazards model. Results: Among 40774 patients with DLBCL, 95.7% had systemic, 3.4% had primary CNS and 0.9% had concurrent DLBCL. Majority of the population was > 50 years of age (79%) and Caucasian (84%) with near equal male to female distribution (53% vs 47%). 5-year overall survival (OS) and DLBCL specific survival (DSS) for systemic, primary CNS and concurrent diseases were 49%, 23%. 22%, and 63%, 34%, 33% respectively. Primary CNS DLBCL (HR 3.05) and concurrent DLBCL (HR 1.69) had poor prognosis compared to systemic DLBCL. Other poor prognostic factors included age > 50 years (HR 2.34), Black ethnicity (1.14), male gender (1.17), higher stage at diagnosis (HR 1.90), higher International Prognostic Index (HR 2.33), being single (HR 1.62) and lacking high school education (HR 1.14). On the other hand, higher income status (HR 0.91) and undergoing radiotherapy (HR 0.72) were associated with better outcomes. Conclusions: Our analysis showed majority of DLBCL cases to be systemic with only 4.3% being primary CNS and concurrent at diagnosis. However, this minority subset has a very poor prognosis. Additional studies are required to prospectively validate these findings and develop novel treatment approaches to improve outcomes in this patient subgroup.
Defective Peripheral Blood Endothelial Cell Progenitors in Patients with Scleroderma and Psoriatic Arthritis
Authors: Taxiarchis V Kourelis, Akrivi D Manola, Despoina Adamidou, Lazaros Sakkas, Eyagelia Mperou, George E Karras, George Vassilopoulos, Nikolaos E Stathakis, Michael G Alexandrakis, Despoina S Kyriakou
Journal: Blood (2008)
Dexmedetomidine to Reduce Intubation Time in Patients With Agitated Delirium
Authors: Mika Hamilton, Andre Amaral
Journal: JAMA (2016)

To the Editor Dr Reade and colleagues1 assessed the effect of dexmedetomidine on ventilator-free time in patients with agitated delirium. We have concerns about their definition of outcomes, potential clinician subconscious cognitive biases, and randomization imbalances.