tbuckley/cabot-search huggingface dataset:
Checkpoint inhibitors assessment in oropharynx carcinoma (CIAO).
Authors: Renata Ferrarotto, Bonnie S. Glisson, Diana Bell, Kate A. Hutcheson, Jack Phan, Hai T. Tran, Dyanne L Gibbs, J. Jack Lee, Maura L. Gillison, Andrew G. Sikora, Neil D. Gross
Journal: Journal of Clinical Oncology (2018)

TPS118 Background: Oropharyngeal squamous cell carcinoma (OPSCC) is classified by HPV status. Patients with HPV negative OPSCC have worse prognosis when compared to HPV positive. The epidemic of HPV associated OPSCC emphasizes the need to improve outcomes and reduce treatment related toxicities in this patient population. Taken together, there is an unmet need for novel treatment approaches to improve survival and/or quality of life in patients with OPSCC. Checkpoint inhibitors, particularly anti-PD-1/PD-L1, have shown encouraging activity in metastatic head and neck SCC. Targeting both PD-1 and CTLA-4 pathways may have additive or synergistic activity. Durvalumab and tremelimumab are immune checkpoint inhibitors that target, respectively, PD-L1 and CTLA-4. The optimal integration of novel therapeutics into clinical practice requires a thorough understanding of the molecular effects of treatment that is best evaluated by longitudinal tumor sampling. Minimally invasive transoral robotic surgery (TORS) provides opportunities to leverage standard-of-care surgery to interrogate the tumor microenvironment after neoadjuvant treatment. Methods: This is a randomized, window of opportunity trial evaluating durvalumab single agent or combined with tremelimumab in OPSCC patients amenable to curative intent surgery. The primary objective is to quantify differences in CD8+ TILs between pre- and post-treatment surgical specimens in patients treated with durvalumab vs. durvalumab plus tremelimumab. Secondary objectives include assessing the safety and toxicity of durvalumab plus or minus tremelimumab in the preoperative setting; objective response rate by RECIST at 8 weeks; percentage of patients undergoing surgery at 8 weeks; percentage of viable tumor cells in the surgical specimen; and patient-reported outcomes. Pre- and post- treatment tumor and blood based immune biomarkers will be evaluated and correlated with HPV status, outcomes, and toxicity. Eligible patients must be ≥ 18 years old, have surgically resectable stage II-IVA newly diagnosed OPSCC or loco-regional recurrence from an OPSCC primary ≥ 6 months after completion of curative intent treatment, and have a performance status ECOG 0-1. Enrollment is ongoing. Clinical trial information: NCT03144778.
Abstract MS2-2: Understanding the unique biology of ILC
Authors: S Oesterreich
Journal: Cancer Research (2018)

Abstract Invasive lobular breast cancer (ILC) is characterized by distinct etiological, pathological, and clinical features, yet the underlying biology is poorly understood. To extend the molecular determinants of ILC beyond the well-known loss of E-cadherin, we combined a plethora of in silico and wet-bench approaches, and comprehensively characterized ILC tumor models and clinical samples. In support of recent data from The Cancer Genome Atlas on differences in mutations in critical ER co-factors between invasive lobular and ductal cancers, we have identified distinct ER signaling pathways, and mechanisms of endocrine resistance in ILC. These include the acquisition of unique ER target genes, activation of IGF and FGFR signaling, and changes in metabolic pathways. As part of our efforts to elucidate mediators of ILC progression, transcriptomic analysis of primary tissue from patients with and without disease recurrence identified potential genetic drivers, including Cortactin, an actin binding protein with a known role in metastasis. To further identify genes that mediate the unique metastatic properties of ILC cells, we sequenced metastases to the ovary and the gastrointestinal tract, and uncovered pathways that might serve as critical vulnerabilities and therapeutic opportunities. In this lecture, I will review our progress, and discuss the potential clinical significance and implications of these findings. Citation Format: Oesterreich S. Understanding the unique biology of ILC [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr MS2-2.
Use of Oxyhemoglobin Saturation or Oxygen Tension—an Unsolved Question—Reply
Authors: John N. Kheir, Brian D. Polizzotti, James A. DiNardo
Journal: JAMA Pediatrics (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 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
Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans
Authors: Murray A. Raskind, Elaine R. Peskind, Bruce Chow, Crystal Harris, Anne Davis-Karim, Hollie A. Holmes, Kimberly L. Hart, Miles McFall, Thomas A. Mellman, Christopher Reist, Jennifer Romesser, Robert Rosenheck, Mei-Chiung Shih, Murray B. Stein, Robert Swift, Theresa Gleason, Ying Lu, Grant D. Huang
Journal: New England Journal of Medicine (2018)

In randomized trials, prazosin, an α1-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans.We recruited veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women. After week 10, participants continued to receive prazosin or placebo in a double-blind fashion for an additional 16 weeks. The three primary outcome measures were the change in score from baseline to 10 weeks on the Clinician-Administered PTSD Scale (CAPS) item B2 ("recurrent distressing dreams"; scores range from 0 to 8, with higher scores indicating more frequent and more distressing dreams); the change in score from baseline to 10 weeks on the Pittsburgh Sleep Quality Index (PSQI; scores range from 0 to 21, with higher scores indicating worse sleep quality); and the Clinical Global Impression of Change (CGIC) score at 10 weeks (scores range from 1 to 7, with lower scores indicating greater improvement and a score of 4 indicating no change).A total of 304 participants underwent randomization; 152 were assigned to prazosin, and 152 to placebo. At 10 weeks, there were no significant differences between the prazosin group and the placebo group in the mean change from baseline in the CAPS item B2 score (between-group difference, 0.2; 95% confidence interval [CI], -0.3 to 0.8; P=0.38), in the mean change in PSQI score (between-group difference, 0.1; 95% CI, -0.9 to 1.1; P=0.80), or in the CGIC score (between-group difference, 0; 95% CI, -0.3 to 0.3; P=0.96). There were no significant differences in these measures at 26 weeks (a secondary outcome) or in other secondary outcomes. At 10 weeks, the mean difference between the prazosin group and the placebo group in the change from baseline in supine systolic blood pressure was a decrease of 6.7 mm Hg. The adverse event of new or worsening suicidal ideation occurred in 8% of the participants assigned to prazosin versus 15% of those assigned to placebo.In this trial involving military veterans who had chronic PTSD, prazosin did not alleviate distressing dreams or improve sleep quality. (Funded by the Department of Veterans Affairs Cooperative Studies Program; PACT ClinicalTrials.gov number, NCT00532493 .).
The importance of the need for better systemic therapy in the definitive treatment of high-risk prostate cancer regardless of whether the initial treatment modality was external beam radiation, I-125 brachytherapy, or radical prostatectomy.
Authors: Jay P. Ciezki, Chandana A. Reddy, Omar Y. Mian, Jorge A. Garcia, Eric A. Klein, James Ulchaker, Kenneth Angermeier, Steven C. Campbell, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2018)

65 Background: While androgen deprivation therapy (ADT) is a common form of systemic therapy for treating high-risk prostate cancer (HRCaP), distant metastases development remains the predominate form of failure. We present a description of the sites of failure after treatment of HRCaP with External Beam Radiation (EBRT), I-125 Brachytherapy (PB), or Radical Prostatectomy (RP). This is accompanied by an analysis of prostate cancer-specific mortality (PCSM) after clinical failure. Methods: The study includes 2186 patients with HRCaP according to NCCN guidelines (684 EBRT, 409 PB, and 1093 RP). The association of PCSM with clinical and pathologic variables was assessed with Fine and Gray regression with non-PCSM mortality treated as a competing event. Results: The median f/u is 52 months. Overall, there were 323 clinical failures (sites of first failures: 287 distant (DM), 34 local (LF), 2 DM + LF). The median time to the diagnosis of DM was 44 months. ADT was used in 93% of EBRT, 53% of PB and 19% of RP patients. Further details regarding the development of DM is shown in Table 1. The type of initial treatment was not associated with PCSM after DM (Table 1). The only factor significantly associated with PCSM was Gleason Score (p = 0.0372). Conclusions: DM is the primary mode of failure after definitive treatment of HRCaP. The type of initial definitive treatment did not affect PCSM after DM. The cure rates of all forms of definitive treatment of HRCaP would benefit from better systemic therapy. [Table: see text]
P128 Analysis of DNA methylation patterns in rheumatoid arthritis patient: a system for prioritising meaningful difference
Authors: R Pitaksalee, AN Burska, J Rogers, X Xie, P Emery, R Hodgett, F Ponchel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Alterations in DNA methylation patterns have been related to several diseases, including Rheumatoid Arthritis (RA). <h3>Objectives</h3> To identify changes in DNA methylation pattern of naïve and memory CD4 +T cells and monocytes in early, drug naïve RA patients to help understand early event in disease pathology. <h3>Methods</h3> The methylation patterns of 480,000 CpGs were analysed in the 3 cell types from 6 healthy control (HC) and 10 RA patients using an Illumina genome-wide array. Standard t-tests were performed to associate p-value to individual CpG-probe. A scoring system was developed to select and prioritise differentially methylated CpGs with potential cumulative effect due to proximity with other significant CpGs. Rules for scoring were designed with respect to the significance of each CpGs and the distance (in bp) between them. Further filtering was applied to initially select the CpGs which highest significant (p-value≤0.0001) which have at least 2 proximal significant CpGs (p-value≤0.01). Rules were coded in R for systematic analysis. Lists of selected CpGs for all three cells for both hypo- and hyper-methylation were generated. Commonality was analysed using Venn diagram. <h3>Results</h3> Different changes in methylation patterns were observed between HC and RA in the 3 cell types and thresholds of significance were set at p-value 0.01, 0.001 and 0.0001. The total number of differentially methylated CpGs was enriched in naïve T-cells (18,020) compared to memory (14,197) and monocytes (6,490) (p-value≤0.01). Using our designed rules, we were able to prioritise cluster of differentially methylated CpGs which were then associated to 420, 7, and 48 hypomethylated genes, and 420, 719 and 21 hypermethylated genes respectively in naïve/memory T-cells and monocytes. Venn diagrams of hypermethylated gene showed only 1 genes (ABAT) in common to all 3 subsets. Hypomethylated gene showed no commonalities between the 3 cell subsets, and only 1 gene common between T-cell subsets (SLC43A2). Of note, the TNF gene was second on the priority list for naïve T-cell hypomethylation while no difference was observed in memory/monocytes. The IL-17 gene was de-methylated only in memory T-cells, hypermethylated in RA, but fully methylated in naïve/monocytes. Hypomethylation of socs3 was specific to monocytes. <h3>Conclusions</h3> These data suggest quite different types of changes in patterns of DNA methylation affecting the 3 subsets early in the RA disease process. Our scoring system to prioritise clusters of differential methylation highlighted genes known to be related to early RA pathogenesis. Further work remains to explore the relationship between these genes and the biological effect at the transcriptional/translational level resulting from these alterations in DNA methylation. <h3>Disclosure of interest</h3> None declared
Local Movement to Ban Menthol Tobacco Products as a Result of Federal Inaction
Authors: Stanton A. Glantz, Philip Gardiner
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
Chronic Urticaria Associated With Methylisothiazolinone Type IV Hypersensitivity
Authors: Tyler M. Bauman, David M. Sheinbein
Journal: JAMA Dermatology (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 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
Cell free circulating tumor DNA <i>ERBB2</i> amplifications are targetable in patients with pancreatic ductal adenocarcinoma.
Authors: Afsaneh Barzi, Victoria Raymond, Andrea Wang-Gillam, Richard B. Lanman
Journal: Journal of Clinical Oncology (2018)

282 Background: Molecularly targeted therapies have led to improved clinical benefit, however few targeted therapies exist in pancreatic ductal adenocarcinoma (PDAC). ERBB2 (HER2) amplifications (AMP) in PDAC have been described as potentially targetable, especially in KRAS wild type tumors. We describe the incidence of ERBB2 AMP in patients (pts) with PDAC who underwent cell-free circulating tumor DNA (cfDNA) testing with a CLIA/CAP/NYSDOH approved 73 gene assay. Methods: The Guardant Health Clinical Database was queried (March 2014-July 2017) for pts with a diagnosis of PDAC and an ERBB2 AMP identified on cfDNA (Guardant360). Copy number AMP ≥ 2.12 is reported. Pts with multiple cfDNA timepoints were included if an ERBB2 AMP was identified at any timepoint. Results: 30 pts met inclusion criteria (1.7% of pts with PDAC (1722)). Median age at test order was 63 years (range 24 to 92). 26 pts had one cfDNA timepoint, three pts had two, and one patient had three. In the pts with multiple timepoints, ERBB2 AMP was identified at one timepoint each for a total of 30 timepoints from 30 unique pts. In two pts, ERBB2 AMP was initially not detected (ND) and detected subsequently. In two pts, ERBB2 AMP was initially detected and subsequently ND. Median number of alterations per test was 6 (range 1 to 13). Median ERBB2 AMP was 2.47 copies (range 2.14 to 7.51). Concurrent KRAS single nucleotide variant was identified in 20 tests (66.7%); G12D(6), G12V(5), Q61H(1); G12D/ KRAS AMP(6), G12R/ KRAS AMP(2). Clinical follow-up was available for three pts, two of whom were treated with anti-HER2 therapy. One patient with a low ERBB2 AMP (2.20 copies) / KRAS wild type progressed on multiple lines of therapy. Following identification of cfDNA ERBB2 AMP, Traztuzumab was added to the FOLFOX regimen with clinical improvement and significant decline in CA19-9 (1,847 to 22 U/mL) over a four-month period. ERBB2 AMP decreased to undetected over the same period. For the past 8 months, patient has been on Trastuzumab alone with further decrease in CA19-9 (16 U/mL). Conclusions: cfDNA detects potentially targetable ERBB2 AMP in pts with PDAC, and targeted anti-HER2 therapy should be explored, even when these amplifications are detected at the lower range.
EVALUATION OF INTRACORONARY THROMBUS BY OPTICAL COHERENCE TOMOGRAPHY (OCT): CHARACTERIZATION, QUANTIFICATION AND PROGNOSTIC IMPACT IN PATIENTS WITH NON-ST-ELEVATION ACUTE CORONARY SYNDROME - A DOCTORS SUBSTUDY
Authors: Nicolas F. Meneveau, Mohamed-Chouaib Yahia, Nassim Braik, Benjamin Bonnet, Romain Chopard, Nicolas Amabile, Geraud Souteyrand, Patrick Ohlmann, Yoann Lefrançois, Johanne Silvain, Francois Schiele
Journal: Journal of the American College of Cardiology (2018)
Consultants support junior doctors’ “principled stance” over contract negotiations
Authors: Tom Moberly
Journal: BMJ (2016)

Consultants have supported junior doctors’ “principled stance” over contract negotiations and their decision to take further industrial action.

Delegates at the BMA’s annual UK consultants’ conference in London on 3 March unanimously passed a series of motions that expressed support for junior doctors.

One motion, which was passed unanimously, supported “the junior doctors’ principled stance in their dispute over their NHS contract negotiations.” Proposing the motion Nick Platt, …
Anaerobic 4-hydroxyproline utilization: Discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity
Authors: Yolanda Y. Huang, Ana Martínez-del Campo, Emily P. Balskus
Journal: Gut Microbes (2018)

The discovery of enzymes responsible for previously unappreciated microbial metabolic pathways furthers our understanding of host-microbe and microbe-microbe interactions. We recently identified and characterized a new gut microbial glycyl radical enzyme (GRE) responsible for anaerobic metabolism of trans-4-hydroxy-l-proline (Hyp). Hyp dehydratase (HypD) catalyzes the removal of water from Hyp to generate Δ1-pyrroline-5-carboxylate (P5C). This enzyme is encoded in the genomes of a diverse set of gut anaerobes and is prevalent and abundant in healthy human stool metagenomes. Here, we discuss the roles HypD may play in different microbial metabolic pathways as well as the potential implications of this activity for colonization resistance and pathogenesis within the human gut. Finally, we present evidence of anaerobic Hyp metabolism in sediments through enrichment culturing of Hyp-degrading bacteria, highlighting the wide distribution of this pathway in anoxic environments beyond the human gut.
Emergency medicine specialty training recruitment is “highest ever,” says HEE
Authors: Abi Rimmer
Journal: BMJ (2014)

More doctors than ever before have been recruited to the first year of acute care common stem emergency medicine specialty and core training (ACCS CT/ST1), Health Education England (HEE) has said.

Board papers published on the organisation’s website said, “ACCS CT/ST1 entry in 2014 has significantly improved and …
Abstract 13201: Increase in Bystander Cardiopulmonary Resuscitation in Sweden During the Last 15 Years is Mainly Attributed to Increased Rates of “Chest Compression Only” CPR
Authors: Gabriel Riva, Jacob Hollenberg, Leif Svensson, Mattias Ringh, Sten Rubertsson, Per Nordberg, Andreas Claesson, Therese Djärv, Johan Herlitz
Journal: Circulation (2016)

Introduction: Bystander cardiopulmonary resuscitation (CPR) traditionally consists of both ventilations and chest compressions. The concept of Compression Only CPR (CO-CPR) has emerged since rescue breaths are difficult to perform, potentially delay the start of CPR, and interrupt chest compressions. Since 2010 guidelines suggest CO-CPR for untrained bystanders and for trained bystanders unwilling or unable to perform rescue breaths. Aim: The aim was to describe changes in rates of bystander CPR, CO-CPR and survival during 3 different time-periods of CPR-guidelines on a national level. We hypothesized that dissemination of CO-CPR would be associated with increased CPR-rates and similar survival compared to standard CPR. Method: A registry based cohort study including all bystander witnessed cases of out-of-hospital cardiac arrests reported to the Swedish Cardiac Arrest Registry in 2000 - 2014. Exposure was categorized as bystander CPR or No-CPR. Bystander CPR was further categorized into Standard CPR (S-CPR) or CO-CPR. Primary outcome was 30-day survival. Results: 23169 patients were included. Total rates of bystander CPR increased from 38% in 2000-2005 to 70% in 2011-2014. CO-CPR increased from 5% in 2000-2005 to 28% in 2011-2014. There was no significant difference in survival among patients receiving CO-CPR or S-CPR (13,6% vs. 12,9% p=0,3). Conclusion: The increase in bystander CPR during the last 15 years in Sweden is mainly attributed to an increase in CO-CPR. Any form of bystander CPR was associated with increased 30-day survival compared to no CPR in all time periods studied. Overall 30-day survival was not different when comparing CO-CPR to S-CPR.