tbuckley/cabot-search huggingface dataset:
Annals Story Slam - Innovations: Practices That Build Trust - Relational Leadership Institute
Authors: Brian Park
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Innovations: Practices That Build Trust - Relational Leadership InstituteFREEBrian Park, MDBrian Park, MDOregon Health & Science University, Portland, Oregon (B.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0004 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Innovations: Practices That Build Trust - Relational Leadership Institute "Innovations: Practices That Build Trust - Relational Leadership Institute," by Brian Park, MD (Duration 5:03)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Oregon Health & Science University, Portland, Oregon (B.P.)Current Author Address: Brian Park, MD; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
The Contribution of Germline Predisposition Gene Mutations to Clinical Subtypes of Invasive Breast Cancer From a Clinical Genetic Testing Cohort
Authors: Chunling Hu, Eric C Polley, Siddhartha Yadav, Jenna Lilyquist, Hermela Shimelis, Jie Na, Steven N Hart, David E Goldgar, Swati Shah, Tina Pesaran, Jill S Dolinsky, Holly LaDuca, Fergus J Couch
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background The germline cancer predisposition genes associated with increased risk of each clinical subtype of breast cancer, defined by estrogen receptor (ER), progesterone receptor (PR), and HER2, are not well defined. Methods A total of 54 555 invasive breast cancer patients with 56 480 breast tumors were subjected to clinical hereditary cancer multigene panel testing. Heterogeneity for predisposition genes across clinical breast cancer subtypes was assessed by comparing mutation frequencies by gene among tumor subtypes and by association studies between each tumor subtype and reference controls. Results Mutations in 15 cancer predisposition genes were detected in 8.6% of patients with ER+/HER2-; 8.9% with ER+/HER2+; 7.7% with ER-/HER2+; and 14.4% of ER-/PR-/HER2- tumors. BRCA1, BRCA2, BARD1, and PALB2 mutations were enriched in ER- and HER2- tumors; RAD51C and RAD51D mutations were enriched in ER- tumors only; TP53 mutations were enriched in HER2+ tumors, and ATM and CHEK2 mutations were enriched in both ER+ and/or HER2+ tumors. All genes were associated with moderate (odds ratio &amp;gt; 2.00) or strong (odds ratio &amp;gt; 5.00) risks of at least one subtype of breast cancer in case-control analyses. Mutations in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53 had predicted lifetime absolute risks of at least 20.0% for breast cancer. Conclusions Germline mutations in hereditary cancer panel genes confer subtype-specific risks of breast cancer. Combined tumor subtype, age at breast cancer diagnosis, and family history of breast and/or ovarian cancer information provides refined categorical estimates of mutation prevalence for women considering genetic testing.
Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe: a CENTER-TBI analysis
Authors: Jilske A. Huijben, Eveline J. A. Wiegers, Hester F. Lingsma, Giuseppe Citerio, Andrew I. R. Maas, David K. Menon, Ari Ercole, David Nelson, Mathieu van der Jagt, Ewout W. Steyerberg, Raimund Helbok, Fiona Lecky, Wilco Peul, Tatiana Birg, Tommaso Zoerle, Marco Carbonara, Nino Stocchetti
Journal: Intensive Care Medicine (2020)

To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers.This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers.A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13-15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatments (MOR = 2.9, p < 0.001); and smaller in 6-month outcome (MOR = 1.2, p = 0.01).Half of contemporary TBI patients at the ICU have mild to moderate head injury. Substantial between-center variations exist in ICU stay and treatment policies, and less so in outcome. It remains unclear whether admission of short-stay patients represents appropriate prudence or inappropriate use of clinical resources.
Clinical Significance of Higher Cutoffs for Myositis Autoantibody Positivity Using the Euroimmun Research Line Blot: Comment on the Article by Mecoli et al
Authors: Evangelia Zampeli, Ilir I. Cinoku, Clio P. Mavragani, Fotini N. Skopouli, Haralampos M. Moutsopoulos
Journal: Arthritis & Rheumatology (2020)
Hyperbaric oxygen therapy for hematopoietic progenitor cell (HPC) collection in poor mobilizers.
Authors: Bijay Nair, Sarah Waheed, Gary Villines, Frits Van Rhee, Saad Zafar Usmani, Stephen Medlin, Elias J. Anaissie, Zeba Singh, Daohong Zhou, Bart Barlogie, Michele Cottler-Fox
Journal: Journal of Clinical Oncology (2012)

e18576 Background: Currently available agents such as cyclophosphamide or etoposide in combination with G-CSF and plerixafor are effective in mobilizing HPC in most patients with myeloma and refractory lymphoma needing autologous HPC transplant. Unfortunately, there are patients who are unable to mobilize HPC adequately because of prior radiation or stem cell toxic alkylating chemotherapy. As Thom et al. noted an increase in circulating CD34+ cells in patients undergoing hyperbaric oxygen therapy (HBOT) for osteoradionecrosis of the mandible, we examined this modality as a mobilizing agent in those who failed at least one other modality. Methods: A retrospective data review of all patients undergoing HPC mobilization from January 2009 to December 2011 identified 9 patients (7 male, 2 female), (8 multiple myeloma, 1 non-Hodgkin lymphoma) who underwent HBOT for mobilization of HPC after failing to collect at least 2 x 10e6 CD34+ cells/kg CD34 cells/kg body weight following standard mobilization using chemotherapy, G-CSF and/or plerixafor. Mean age was 61 (range 52-82 y). Four had previously undergone autologous transplant. Treatment was in hyperbaric oxygen chambers pressurized with 100% oxygen at 1.5 atmospheres of pressure for 90 minutes per day, with treatment ranging from 3 to 8 days. During this period patients also received growth factors and plerixafor. Results: Total CD34+ cells/kg collected ranged from 0.1 - 20.6 x 10e6 CD34+ cells/kg; 5 patients collected &gt; 2 x 10e6 CD34+ cells/kg, of which 3 collected &gt; 5 x 10e6 CD34+ cells/kg. All patients had failed prior mobilization and collection with G-CSF, and 8 had also previously received plerixafor. One of the patients who had undergone prior tandem transplant collected 8.23 x10e6 CD34+ cells/kg. No patient experienced toxicities known to be associated with use of HBOT such as barotrauma. Conclusions: HBOT appears to be an effective and safe modality to mobilize HPC in patients who are poor mobilizers, when used in conjunction with G-CSF and plerixafor.
lncRNA-PLACT1 sustains activation of NF-κB pathway through a positive feedback loop with IκBα/E2F1 axis in pancreatic cancer
Authors: Xiaofan Ren, Changhao Chen, Yuming Luo, Mingyang Liu, Yuting Li, Shangyou Zheng, Huilin Ye, Zhiqiang Fu, Min Li, Zhihua Li, Rufu Chen
Journal: Molecular Cancer (2020)

Abstract Background The activation of NF-κB signaling pathway is regarded as the dominant process that correlates with tumorigenesis. Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play crucial roles in sustaining the NF-κB signaling pathway. However, the underlying mechanisms have not yet been elucidated. Methods The expression and clinical features of PLACT1 were analyzed in a 166-case cohort of PDAC by qRT-PCR and in situ hybridization. The functional role of PLACT1 was evaluated by both in vitro and in vivo experiments. Chromatin isolation by RNA purification assays were utilized to examine the interaction of PLACT1 with IκBα promoter. Results We identified a novel lncRNA- PLACT1 , which was significantly upregulated in tumor tissues and correlated with progression and poor survival in PDAC patients. Moreover, PLACT1 promoted the proliferation and invasion of PDAC cells in vitro. Consistently, PLACT1 overexpression fostered the progression of PDAC both in orthotopic and lung metastasis mice models. Mechanistically, PLACT1 suppressed IκBα expression by recruiting hnRNPA1 to IκBα promoter, which led to increased H3K27me3 that decreased the transcriptional level of IκBα. Furthermore, E2F1-mediated overexpression of PLACT1 modulated the progression of PDAC by sustained activation of NF-κB signaling pathway through forming a positive feedback loop with IκBα. Importantly, administration of the NF-κB signaling pathway inhibitor significantly suppressed PLACT1 -induced sustained activation of NF-κB signaling pathway, leading to reduced tumorigenesis in vivo. Conclusions Our findings suggest that PLACT1 provides a novel epigenetic mechanism involved in constitutive activation of NF-κB signaling pathway and may represent a new therapeutic target of PDAC.
High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) for relapsed metastatic germ cell tumors (mGCTs): The Alberta experience from 2001 to 2018.
Authors: Hanbo Zhang, Nimira S. Alimohamed, Naveen S. Basappa, Tina Cheng, Michael Chu, Nanette Cox-Kennett, D. Scott Ernst, Amelie Fontaine, Sunita Ghosh, Daniel Yick Chin Heng, Richard Littleton, Scott A. North, Cindy Railton, Irwindeep Sandhu, Douglas Allan Stewart, Chris Venner, Peter M. Venner, Michael Paul Kolinsky
Journal: Journal of Clinical Oncology (2020)

406 Background: HDC-ASCT is a standard therapy for patients (pts) with mGCTs whose disease progresses on or after conventional dose chemotherapy. We conducted a retrospective review of HDC-ASCT in pts with relapsed mCGT in Alberta over the past two decades. Methods: Pts with mGCTs who received HDC-ASCT at two provincial referral cancer centers in Alberta, Canada from 2001-2018 were identified. Baseline clinical and treatment characteristics were collected as well as overall survival (OS) and disease-free survival (DFS). Relevant prognostic variables were analyzed. Results: Forty three pts were identified. Median age was 28 years (range 19 – 56). Majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty pts (47%) had poor risk disease as per IGCCC at start of first-line chemotherapy. HDC-ASCT was used as second-line therapy in 65% and 58% received tandem HDC-ASCT. Median follow-up from ASCT was 22 months (range 2 – 181). At last follow-up, 42% of pts are alive without disease, including 3/7 (43%) of pts with primary mediastinal disease. Two-year and 5-year DFS/OS were 44%/51% and 41%/43%, respectively. Median OS and DFS for all pts were 27.9 months (10.2 – NR) and 9.3 months (4.2 – 124), respectively. Conclusions: We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Pts appeared to benefit regardless of primary site. Though limited by small sample size, we found a numerical difference in DFS and OS between 2nd and 3rd line HDC-ASCT and single vs. tandem ASCT.[Table: see text]
Real-world data of cabozantinib in patients with VEGF-refractory metastatic renal cell carcinoma (mRCC): Results from the French Early Access Program (CABOREAL).
Authors: Marine Gross-Goupil, Aude Flechon, Christine Chevreau, Delphine Topart, Gwenaelle Gravis, Stephane Oudard, Jean-Marc Tourani, Lionnel Geoffrois, Emeline Meriaux, Antoine Thiery-Vuillemin, Philippe Barthelemy, Sylvain Ladoire, Brigitte Laguerre, Valérie Perrot, Anais Billard, Bernard Escudier, Laurence Albiges
Journal: Journal of Clinical Oncology (2020)

683 Background: Cabozantinib (Cabo) is approved in Europe for the treatment of mRCC in first line and after failure of tyrosine kinase inhibitors (TKI). We report the results from real-world use of Cabo in the French Early Access Program (EAP) (CABOREAL [NCT03744585]). Methods: Data were retrospectively collected from 26 centers. Patients (pts) were treated with Cabo during the Temporary Authorization for Use (ATU) period from Sep 12, 2016 to licensing in Feb 19, 2018. Pts were eligible after 2 prior VEGFR TKI unless clinical decision for 2nd line (L). The aim was to evaluate the use and activity of Cabo in real-life conditions. Overall survival (OS) was calculated from initiation of Cabo. Results: Overall, 410 pts were included. Median age was 63 years, 85% had clear-cell histology, 41% and 32% were intermediate/poor IMDC risk, respectively. Pts were mostly ECOG 1 (42%) or 2 (30%); 229 (56%) pts had bone metastasis (mets). Median follow-up was 14.4 months (m). Cabo was used as 2L, 3L and 4L or beyond for 101 (25%), 137 (33%) and 172 (41%) pts respectively; 204 pts (50%) were pretreated with nivolumab (Nivo). Activity results and dose reduction are summarized in the table. Starting dose was 60 mg (290 pts, 71%), 40 mg (109 pts, 27%) and 20 mg (8 pts, 2%). Treatment interruption occurred for 267 pts (65%), dose modification for 240 pts (59%) and schedule change for 64 pts (16%). Median daily dose was 40 mg/day. Treatment discontinuation occurred for 348 (85%) pts, with 86 (25%) due to adverse events. Notably, 184 (54%) pts received a subsequent systemic therapy. Conclusions: We report the largest real-world study of Cabo in mRCC to date. CABOREAL demonstrates that using dose modification, median Cabo duration was 7.6 m in a heavily pretreated population, with the longest treatment duration in patients with prior Nivo exposure. Clinical trial information: NCT03744585. [Table: see text]
Addressing Mistreatment in Medical Education
Authors: Anjali B. Thakkar, Colette Dejong, Mitchell H. Katz
Journal: JAMA Internal Medicine (2020)

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
Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis
Authors: Sonja Ständer, Gil Yosipovitch, Franz J. Legat, Jean-Philippe Lacour, Carle Paul, Joanna Narbutt, Thomas Bieber, Laurent Misery, Andreas Wollenberg, Adam Reich, Faiz Ahmad, Christophe Piketty
Journal: New England Journal of Medicine (2020)

Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis.
A Novel Strategy for Treating Inflammatory Bowel Disease by Targeting Delivery of Methotrexate through Glucan Particles
Authors: Ying Sun, Bingchao Duan, Huanhuan Chen, Xiaojuan Xu
Journal: Advanced Healthcare Materials (2020)

Abstract Therapy of inflammatory bowel disease (IBD) has been a difficult task in the medical field. There is a great clinical need for more effective treatments for IBD. Herein, a targeted oral delivery system of yeast glucan particles (YGPs) carrying a clinically used anti‐inflammatory drug methotrexate (MTX) to the inflamed sites in IBD mice for therapy is reported. In the findings, MTX is effectively loaded into YGPs through re‐precipitation followed by gelation reaction of alginate to obtain the composite YGPs/MTX, which are internalized into RAW264.7 macrophage cells through dectin‐1 and CR3 receptors. Furthermore, YGPs/MTX can suppress the proliferation of macrophage cells efficiently, leading to down‐regulation of pro‐inflammatory cytokines induced by lipopolysaccharides. Additionally, YGPs accumulate in the inflammation site of colitis mice, enabling YGPs/MTX to target the inflammatory site, significantly improve the efficacy of MTX, and reduce the cytotoxicity of MTX. Therefore, the YGPs‐based drug delivery system provides a new strategy for MTX application in the clinical treatment of IBD.
Local delivery of bone morphogenetic protein-2 from near infrared-responsive hydrogels for bone tissue regeneration
Authors: Silvia Sanchez-Casanova, Francisco M. Martin-Saavedra, Clara Escudero-Duch, Maria I. Falguera Uceda, Martin Prieto, Manuel Arruebo, Paloma Acebo, Mario L. Fabiilli, Renny T. Franceschi, Nuria Vilaboa
Journal: Biomaterials (2020)
Trends in PRO reporting in clinical trials leading to GU cancer drug approvals from 2007 to 2018.
Authors: Monica Tamil, Houssein Safa, Adele Semaan, Jad Chahoud
Journal: Journal of Clinical Oncology (2020)

641 Background: Having standardized and high quality reporting of patient reported outcomes (PRO), especially in clinical trials that establish standards of care in oncology is important for patient centered care. This study assessed the status of reporting and quality of analysis of PROs in FDA approved drugs for genitourinary malignancies. Methods: We conducted a systematic review of the FDA archives to identify urological cancer drugs approved between 2007-2018. We retrieved the clinical trials that led to these drug approvals from ClinicalTrials.gov and PubMed. We systematically screened for PROs and reviewed their analytic tools and interpretation methods reported in their published manuscripts and study protocols. A clinical trial was considered to include PROs if they were reported in either the primary or a subsequent manuscript. Results: We identified 22 clinical trials leading to FDA approval of urological cancer drugs between 2007-2018. Only 63% of trials had published PROs. PROs were reported in the primary clinical trial manuscripts for two drugs (9%), and in a secondary PRO manuscript for 12 drugs (54%). The median time between the primary and secondary papers was 12 months (IQR:7.5-26 months). Among the 14 published PRO papers, the hypothesis was broad in 79%, and not reported in 21%. PROs were never included as a primary endpoint of a study. Instead, PROs were reported as secondary endpoints in 5 (36%) and as exploratory endpoints in 7 (50%) studies, while two papers (14%) did not mention PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (64%) and FACT-P (50%). In 92% of PRO papers, statistical analyses were conducted to account for missing data. Control for type I error was needed but not done in 57% of the trials. Conclusions: Delays in publication of PROs occur regularly in trials leading to drug approval in GU malignancies. Our study highlights the need to enhance standardization of the analysis and interpretation of PROs to maximize the value of this data for drug development and approval.
Loss of <i>SNAI2</i> in prostate cancer and effect on patient response to androgen deprivation therapy.
Authors: Niall Corcoran, Marek Cmero, Natalie Kurganovs, Patrick McCoy, Anthony Costello, Andrew Ryan, Phillip Parente, Christopher Hovens
Journal: Journal of Clinical Oncology (2020)

338 Background: Androgen receptor (AR) signalling is important in prostate cancer progression, and therapies that specifically target this pathway are the mainstay of treatment for advanced disease. Treatment however is non-curative, and resistance develops inevitably with time. Although the mechanisms that drive castration resistant disease have been intensively analysed, how tumours survive and persist during the initial pathway inhibition is unclear. Methods: To track this process in detail we performed a Phase II neo-adjuvant study of a novel combination of AR targeting therapies (degarelix &amp; abiraterone &amp; bicalutamide) for 6 months prior to prostatectomy in men with high risk, localised disease. To determine what was driving tumour persistence in poorly responding patients, we comprehensively characterised pre- and post-treatment samples using both whole genome and RNA-sequencing, validating pertinent findings by qRT-PCR, IHC and FISH. Results: Despite universal ‘biochemical responses’, objective responses to treatment as measured by residual tumours volumes were highly variable. This state which we term ‘castration-persistence’, is molecularly distinct from ‘castration-resistance’, and is characterised by global transcriptional reprogramming leading to a transitional EMT state. Whole genome sequencing confirms tumour persistence is not associated with the emergence of a ‘driver’ lesion, rather treatment response is associated with regression of a ‘treatment sensitive’ subclonal population, defined by deletion of the EMT master regulator SNAI2. The extent of treatment response observed was determined by the prevalence of cells with loss of SNAI2 in pre-treatment biopsies. Conclusions: Cell plasticity with transition to a mesenchymal phenotype defines prostate cancer cell survival to acute AR signalling inhibition. Tumour response is determined by the proportion of cells present harbouring defects in this program.