tbuckley/cabot-search huggingface dataset:
Abstract B09: IL6 and CXCL8 mediate redundant tumor-host signaling pathways that facilitate osteosarcoma lung metastasis
Authors: Ryan D. Roberts, Hakan Cam, Amy C. Gross, Sarah Winget, Doris Phelps, Peter J. Houghton
Journal: Cancer Research (2018)

Abstract Osteosarcoma (OS) kills patients through aggressive metastatic spread, primarily to lung tissues. Our lab has sought to understand that tumor-host interactions that mediate this propensity for OS cells to colonize and grow in the lung. We identified two factors, IL6 and CXCL8, that become overexpressed in metastatic OS nodules relative to the same patient’s primary lesions. Expression of these factors correlates strongly with capacity to colonize lung tissue in murine models of OS metastasis. Aberrant expression of ΔNp63 drives production of IL6 and CXCL8 and can endow poorly metastatic OS tumors with increased metastatic potential. This effect can be completely reversed by blocking IL6 and CXCL8. Treating mice inoculated with circulating OS cells with inhibitors of IL6 and CXCL8 signaling reduces lung metastasis. This effect completely blocks lung colonization in some models, but only when used in combination. The effects of IL6 and CXCL8 inhibition endure for many months beyond discontinuation of therapy. Genetic manipulation studies confirm that these effects result from on-target effects of the drugs. Clinical studies performed in canine patients will help determine whether these treatments might be effective adjuvants for the treatment of patients with OS. Citation Format: Ryan D. Roberts, Hakan Cam, Amy C. Gross, Sarah Winget, Doris Phelps, Peter J. Houghton. IL6 and CXCL8 mediate redundant tumor-host signaling pathways that facilitate osteosarcoma lung metastasis [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B09.
Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation
Authors: Victor Chiu, Rachel Hogen, Linda Sher, Niquelle Wadé, David Conti, Anastasia Martynova, Hongtao Li, Gangning Liang, Casey O'Connell
Journal: Hepatology (2019)

Telomeres are repetitive DNA sequences that protect the ends of linear chromosomes, and they are maintained by a ribonucleoprotein complex called telomerase. Variants in genes encoding for telomerase components have been associated with a spectrum of disease in the lung, skin, bone marrow, and liver. Mutations in the telomerase reverse transcriptase and telomerase RNA component genes have been observed at a higher prevalence in patients with liver disease compared with the general population; however, the presence of variants in other components of the telomerase complex and their impact on clinical outcomes has not been explored. We evaluated 86 patients with end‐stage liver disease for variants in an expanded panel of eight genes, and found that 17 patients (20%) had likely deleterious variants by in silico analysis. Seven unique likely deleterious variants were identified in the regulator of telomere elongation helicase 1 ( RTEL1 ) gene that encodes for a DNA helicase important in telomere maintenance and genomic stability. In gene burden association analysis of their clinical data, the presence of any RTEL1 variant was associated with a 29% lower baseline white blood cell count (95% confidence interval [CI], ‐7% to ‐46%; P Value = 0.01) compared with patients without RTEL1 variants, and the presence of any exonic missense RTEL1 variant was associated with a 42% lower baseline platelet count (95% CI, ‐5% to ‐65%: P Value = 0.03). The presence of any telomerase variant was associated with an increased number of readmissions within 1 year after transplantation demonstrated by an incident rate ratio (IRR) of 3.15 (95% CI, 1.22 to 8.57). No association with survival was observed. Conclusion : Among patients who underwent liver transplantation, the presence of any exonic missense variant was associated with a longer postoperative length of stay with an IRR of 2.16 (95% CI, 1.31 to 3.68).
Medical Misinformation
Authors: Joseph A. Hill, Stefan Agewall, Adrian Baranchuk, George W. Booz, Jeffrey S. Borer, Paolo G. Camici, Peng-Sheng Chen, Anna F. Dominiczak, Çetin Erol, Cindy L. Grines, Robert Gropler, Tomasz J. Guzik, Markus K. Heinemann, Ami E. Iskandrian, Bradley P. Knight, Barry London, Thomas F. Lüscher, Marco Metra, Kiran Musunuru, Brahmajee K. Nallamothu, Andrea Natale, Sanjeev Saksena, Michael H. Picard, Sunil V. Rao, Willem J. Remme, Robert S. Rosenson, Nancy K. Sweitzer, Adam Timmis, Christiaan Vrints
Journal: Circulation (2019)
Precision medicine and the cursed dimensions
Authors: Dennis L. Barbour
Journal: npj Digital Medicine (2019)

Our intuition regarding "average" is rooted in one-dimensional thinking, such as the distribution of height across a population. This intuition breaks down in higher dimensions when multiple measurements are combined: fewer individuals are close to average for many measurements simultaneously than for any single measurement alone. This phenomenon is known as the curse of dimensionality. In medicine, diagnostic sophistication generally increases through the addition of more predictive factors. Disease classes themselves become more dissimilar as a result, increasing the difficulty of incorporating (i.e., averaging) multiple patients into a single class for guiding treatment of new patients. Failure to consider the curse of dimensionality will ultimately lead to inherent limits on the degree to which precision medicine can extend the advances of evidence-based medicine for selecting suitable treatments. One strategy to compensate for the curse of dimensionality involves incorporating predictive observation models into the patient workup.
Patterns in Outpatient Benzodiazepine Prescribing in the United States
Authors: Sumit D. Agarwal, Bruce E. Landon
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Benzodiazepines are implicated in a growing number of overdose-related deaths. <h3>Objectives</h3> To quantify patterns in outpatient benzodiazepine prescribing and to compare them across specialties and indications. <h3>Design, Setting, and Participants</h3> This serial cross-sectional study (January 1, 2003, through December 31, 2015) used nationally representative National Ambulatory Medical Care Survey data. The yearly population-based sample of outpatient visits among adults, ranging from 20 884 visits in 2003 (representing 737 million visits) to 24 273 visits in 2015 (representing 841 million visits) was analyzed. Prescribing patterns were examined by specialty and indication and used to calculate the annual coprescribing rate of benzodiazepines with other sedating medications. Data were analyzed from July 1, 2017, through November 30, 2018. <h3>Main Outcomes and Measures</h3> Annual benzodiazepine visit rate. <h3>Results</h3> Among the 386 457 ambulatory care visits from 2003 through 2015, a total of 919 benzodiazepine visits occurred in 2003 and 1672 in 2015, nationally representing 27.6 million and 62.6 million visits, respectively. The benzodiazepine visit rate doubled from 3.8% (95% CI, 3.2%-4.4%) to 7.4% (95% CI, 6.4%-8.6%;<i>P</i> &lt; .001) of visits. Visits to primary care physicians accounted for approximately half of all benzodiazepine visits (52.3% [95% CI, 50.0%-54.6%]). The benzodiazepine visit rate did not change among visits to psychiatrists (29.6% [95% CI, 23.3%-36.7%] in 2003 to 30.2% [95% CI, 25.6%-35.2%] in 2015;<i>P</i> = .90), but increased among all other physicians, including primary care physicians (3.6% [95% CI, 2.9%-4.4%] to 7.5% [95% CI, 6.0%-9.5%];<i>P</i> &lt; .001). The benzodiazepine visit rate increased slightly for anxiety and depression (26.6% [95% CI, 22.6%-31.0%] to 33.5% [95% CI, 28.8%-38.6%];<i>P</i> = .003) and neurologic conditions (6.8% [95% CI, 4.8%-9.5%] to 8.7% [95% CI, 6.2%-12.1%];<i>P</i> &lt; .001), but more so for back and/or chronic pain (3.6% [95% CI, 2.6%-4.9%] to 8.5% [95% CI, 6.0%-11.9%];<i>P</i> &lt; .001) and other conditions (1.8% [95% CI, 1.4%-2.2%] to 4.4% [95% CI, 3.7%-5.2%];<i>P</i> &lt; .001); use did not change for insomnia (26.9% [95% CI, 19.3%-36.0%] to 25.6% [95% CI, 15.3%-39.6%];<i>P</i> = .72). The coprescribing rate of benzodiazepines with opioids quadrupled from 0.5% (95% CI, 0.3%-0.7%) in 2003 to 2.0% (95% CI, 1.4%-2.7%) in 2015 (<i>P</i> &lt; .001); the coprescribing rate with other sedating medications doubled from 0.7% (95% CI, 0.5%-0.9%) to 1.5% (95% CI, 1.1%-1.9%) (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The outpatient use of benzodiazepines has increased substantially. In light of increasing rates of overdose deaths involving benzodiazepines, understanding and addressing prescribing patterns may help curb the growing use of benzodiazepines.
Abstract P3-06-18: Comprehensive genomic profiling of carcinosarcomas of the breast
Authors: LM Gay, JA Elvin, J-A Vergilio, JK Killian, S Ramkissoon, E Severson, S Daniel, A Hammerich, E Sokol, G Frampton, J Chung, S Trabucco, S Ali, P Reddy, AB Schrock, VA Miller, JS Ross
Journal: Cancer Research (2019)

Abstract Background: Carcinosarcomas of the breast (BCSC) are exceptionally rare and the underlying genomic drivers are still being elucidated. Comprehensive genomic profiling (CGP) determines the tumor mutation burden (TMB) and identifies all four classes of genomic alterations (GA) that have potential to direct personalized treatment strategies. Methods: CGP by hybridization capture of exons from up to 315 cancer-related genes and select introns of 28 genes commonly rearranged in cancer was applied to ≥ 50ng of DNA extracted from 9 consecutive BCSC and sequenced to high, uniform median coverage (&amp;gt;500X). Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined by principal components analysis of optimized loci. Results: The 9 BCSC patients had a median age of 57 yrs (range 49-78 yrs). CGP was performed on the primary BCSC in 4 cases and on metastasis biopsies in 5 cases (4 lung and 1 lymph node). The mean GA/tumor was 6.6 and clinically relevant GA (CRGA)/tumor was 1.3. The most frequent non-CRGA were in TP53 (89%), MYC (56%) and LYN (40%). The most frequent CRGA were in PIK3CA (33%), and NF1, BRCA1, PTEN, RICTOR, FGFR1, AKT2 and STK11 (all at 11%). The median TMB for all BCSC was 2.4 mut/Mb with 1 (11%) tumor with a TMB &amp;gt; 20 mut/Mb and 8 BCSC (88%) with TMB &amp;lt; 5 mut/Mb. Five of 5 BCSC (100%) that were available for MSI status testing were microsatellite stable. Conclusions: On CGP, BCSC feature a high frequency of GA, but only a modest frequency of CRGA and high TMB. However, when the CRGA and TMB positive cases are combined (77.8% overall in this series), the opportunity for personalized targeted and immunotherapies are significant. Thus, further investigation of precision therapies for BCSC in the clinical trial setting appear warranted. Citation Format: Gay LM, Elvin JA, Vergilio J-A, Killian JK, Ramkissoon S, Severson E, Daniel S, Hammerich A, Sokol E, Frampton G, Chung J, Trabucco S, Ali S, Reddy P, Schrock AB, Miller VA, Ross JS. Comprehensive genomic profiling of carcinosarcomas of the breast [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-06-18.
Women and Children First: Promoting Empowerment Through Resistance Education—Reply
Authors: Rebecca C. Thurston, Karen A. Matthews
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Abstract P075: Oncologists’ Perceptions of the Usability of SPHERE: an Electronic Health Record Application Based on Life’s Simple 7™
Authors: Randi E Foraker, Marjorie M Kelley, Wilkister Tangasi, En-Ju Lin, Kathryn E Weaver
Journal: Circulation (2016)

Background: We developed SPHERE, an electronic health record (EHR) data visualization application, to automatically populate with EHR data on the American Heart Association’s cardiovascular health (CVH) behaviors and factors. SPHERE was designed to increase patient-provider communication around Life’s Simple 7™, and utilized a stoplight color scheme as part of the visualization to indicate “ideal” (green), “intermediate” (yellow), and “poor” (red) CVH. Results from the SPHERE Study showed improvements in body mass index and diabetes status among eligible patients seen in the intervention clinic as compared to the control clinic. It remains unknown whether the use of SPHERE would be acceptable to oncologists in the survivorship care setting, even though cancer survivors are at high risk for developing cardiovascular disease. Methods: We conducted one-on-one interviews, using a think-aloud protocol, with 14 oncologists (10 community practice, 4 academic) who were practicing in the NCI Community Oncology Research Program (NCORP). During the 30-minute interview period, we asked each oncologist to use SPHERE and we obtained user feedback on the SPHERE application. Results: Half of the oncologists were male, and most (78%) were medical oncologists; 2 were gynecologic oncologists, and 1 was a radiation oncologist. When asked about discussing CVH with post-treatment, good-prognosis patients, no oncologists indicated that they “never” talked to patients about CVH or initiated those discussions. Eleven oncologists responded that discussing CVH was either “somewhat important” or “very important”, and 9 oncologists indicated they were “somewhat comfortable” or “very comfortable” discussing CVH with patients. Themes identified from transcripts of the 7 hours of interviews suggest 1) strong interest in the tool, 2) high perceived importance of discussing CVH with patients who had a good prognosis, 3) high usability, and 4) a belief that the tool would be helpful and not overly burdensome in practice. Duplication of preventative health efforts with the primary care provider as well as workflow and time constraints were identified as barriers by several oncology providers. Conclusions: Overall, these preliminary data demonstrate acceptability and feasibility of implementing the SPHERE application tool within NCORP community oncology practices. These qualitative data suggest great potential for automated EHR-based applications such as SPHERE to impact the CVH of cancer patients in survivorship care.
Statins Work, but Only in People Who Take Them
Authors: Ann Marie Navar
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology 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 Cardiology journal
Prognostic value of genomic alterations (GA) on overall survival in appendiceal adenocarcinoma (AA).
Authors: Alexandre A Jacome, Kanwal Pratap Singh Raghav, Kenna Rael Shaw, Keith F. Fournier, Richard Eldon Royal, Melissa Taggart, Wai Chin Foo, Aurelio Aurelio Matamoros, Shahab U. Ahmed, Jennifer L. Guerra, Michael J. Overman, Cathy Eng
Journal: Journal of Clinical Oncology (2019)

554 Background: AA are extremely rare tumors, with potentially aggressive clinical behavior. The characterization of the molecular alterations of the disease is poorly described, as well as its association with clinical outcomes. The present study aims to evaluate the prognostic influence of GA on overall survival (OS) of AA patients (pts). Methods: We performed a retrospective study involving AA pts at MD Anderson Cancer Center between October 2012 and April 2017 who underwent next-generation sequencing (NGS) (at least 45 genes), using either tumor tissue specimens or peripheral blood for cell-free DNA (cfDNA). GA identified by NGS and clinicopathological variables were correlated with OS. Survival curves were performed by the Kaplan-Meier method and compared with log-rank test. Multivariate analysis of prognostic factors was performed by the Cox model. Results: A total of 78 pts were identified, of which 35 had died (45%) in a median follow-up time of 4.8 y. The majority of pts presented with stage IV disease (72%); 46% underwent cytoreductive surgery (CRS) + HIPEC. Tissue-based and cfDNA-based sequencing were performed on 73% and 23% of the pts, respectively, and 4% had both. The most frequent GA were KRAS (62%), TP53 (36%), GNAS (28%), SMAD4 (18%), PIK3CA (16%), and APC (15%). By univariate analysis, stage, tumor grade, and CRS + HIPEC demonstrated prognostic value (p &lt; 0.05). Multivariate subset analysis of stage IV pts adjusting for age, tumor grade (TG), CRS + HIPEC, KRAS, GNAS, and p53, demonstrated that poorly differentiated tumors and a KRAS mutated tumor resulted in worse OS (HR: 12.1 and HR: 3.9, respectively, both with p &lt; 0.05) and CRS + HIPEC resulted in an improved OS (HR: 0.32, p &lt; 0.05). Conclusions: Our analysis indicates that TG and the presence of the KRAS mutation are poor prognostic factors in the OS of pts with AA. CRS + HIPEC offers survival advantage . Molecular characterization and prognostication of these rare tumors may help guide therapy. These findings need validation, thereby continued evaluation in a larger population and utilizing a wider molecular platform is ongoing.
TCT-155 Transfemoral aortic valve replacement with the repositionable Lotus valve compared with the balloon-expandable Edwards Sapien 3 valve
Authors: Julia Seeger, Birgid Gonska, Christoph Rodewald, Dominik Scharnbeck, Wolfgang Rottbauer, Jochen Wöhrle
Journal: Journal of the American College of Cardiology (2015)
Modeling radiation dose to circulating lymphocytes during brain tumor treatment: Effects of target volume, dose rate, and treatment technique.
Authors: Susannah G. Yovino, Stuart A. Grossman, Lawrence Kleinberg, Eric C Ford
Journal: Journal of Clinical Oncology (2012)

2017 Background: Severe treatment-related lymphopenia (TRL) occurs in 40% of glioblastoma patients despite minimal radiation (RT) doses to bone marrow or nodal sites. In glioblastoma, TRL is associated with decreased survival. To explain the lymphopenia, we sought to estimate radiation doses received by circulating lymphocytes during partial brain RT. Methods: An in-house computer program linked to treatment planning software was used to calculate the mean radiation dose to circulating blood (DCB) and the fraction of blood receiving &gt;0.5 Gy. The model also studied the impact of different target volumes (PTV), dose rates (DR), and delivery techniques (IMRT, 3D-CRT). Results: The mean DCB for a 60-Gy course (8-cm diameter PTV, dose rate 600 MU/minute) was 2.2 Gy. With this the entire blood pool receives a lymphotoxic dose of &gt;0.5 Gy. DCB is correlated with fraction number, PTV size, and DR. Regardless of dose rate or delivery technique, the percent of circulating blood receiving &gt;0.5 Gy approached 100% as the number of fractions increased. Changing dose rate had minimal effects on mean DCB (3.1Gy for 300 MU/min vs 2.2 Gy for 1200 MU/min). Smaller PTV size reduced the percent of blood receiving &gt;0.5 Gy (15% for 2-cm diameter PTV vs 100% for 8-cm PTV). Conclusions: Standard RT for brain tumors delivers a lymphotoxic radiation dose to circulating blood. Altering dose rate may initially affect DCB, but advantages disappear over the course of 30 fractions. Marked reductions in target size appear to be the best way to avoid radiation injury to normal circulating lymphocytes. Other novel approaches are needed to limit radiation exposure to circulating lymphocytes given evidence associating lymphopenia with poorer outcomes in cancer patients.
Combined Elevated Anti-Adamts-13 Antibody Level and Low Adamts-13 Activity during Remission Highly Predicts Disease Relapse in a Prospective Cohort of Patients with Autoimmune Thrombotic Thrombocytopenic Purpura (TTP)
Authors: Francesca Schieppati, Laura Russo, Marina Marchetti, Gloria Caldara, Shenaz Brevi, Maria Testa, Luca Barcella, Monica Carpenedo, Mariella D'Adda, Giuseppe Rossi, Chiara Savignano, Atto Billio, Massimiliano Bruno Franco, Vincenzo Toschi, Anna Falanga
Journal: Blood (2018)