tbuckley/cabot-search huggingface dataset:
Safety and efficacy of <i>nab</i>-paclitaxel (<i>nab</i>-P) in patients (pts) with metastatic breast cancer (MBC): Real-world results from a U.S. health insurance database.
Authors: Debra A. Patt, Caihua Liang, Ling Li, Amy Ko, Cindy Duval Fraser, Deyanira Corzo, Cheryl Enger
Journal: Journal of Clinical Oncology (2014)

1075 Background: nab-P is an albumin-bound formulation of paclitaxel approved in 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy, based on an international phase 3 trial comparing nab-P with paclitaxel on an every 3 week (q3w) schedule. The objective of this study was to characterize safety and efficacy outcomes of nab-P in MBC in the United States using health insurance claims data. Methods: A retrospective claims analysis was conductedusing the Optum Research Database (United Health affiliate). The analysis included women aged ≥ 18 years diagnosed with MBC (≥ 2 claims of BC diagnosis separated by ≥ 30 days and ≥ 2 claims of metastatic spread) prior to nab-P initiation. Pts had ≥ 6 months of continuous enrollment in a US health insurance plan from January 2005 through September 2012, complete medical coverage and pharmacy benefits, no other primary malignancy, and no prior nab-P. Data were supplemented by Social Security Death Index sources. Cohorts were determined by line of therapy, nab-P regimen, and schedule. Descriptive statistics were used to characterize outcomes. Endpoints included treatment patterns, time to treatment discontinuation (TTD), overall survival (OS), and safety. Results: Of the 664 eligible pts, most were between 40-69 years of age (88%) and had received nab-P as ≥ second-line therapy (74%), monotherapy (61%), and weekly dosing (71%). Agents used in combination with nab-P included bevacizumab (22%) and HER2-targeted therapies (9%). Median TTD and OS were 6.1 and 17.4 months, respectively. By line of therapy (first, second, and ≥ third), TTD was 7.1, 6.6, and 5.3 months and OS was 22.7, 17.4, and 15.1 months. In a subgroup of pts with aggressive disease (≤ 50 years of age or having ≥ 3 metastases), median OS was 15.6 months, similar to the overall cohort. No new safety signals were observed. Conclusions: Consistent with clinical trial data, outcomes in this real-world population confirm the effectiveness and manageable safety profile of nab-P in pts with MBC. This analysis will also help evaluate the benefit of nab-P in pts aged ≥ 70 years.
AB0075 Aortitis syndrome (takayasu’s arteritis) associated with systemic lupus erythematosus
Authors: C Korkmaz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Aortitis syndrome (Takayasu’s arteritis) associated with various autoimmune diseases have been reported. <h3>Objectives</h3> We report the rare association of aortitis syndrome with SLE in two patients. <h3>Methods</h3> Case report. <h3>Results</h3> Case 1. A 49-year-old woman admitted with Raynaud’s phenomenon, right upper extremity claudication, malar rash, and oral ulcerations. Examination showed that her right radial pulse was not palpable. A systolic bruit was heard over her right carotid artery. Laboratory results were as follows: erythrocyte sedimentation rate 89 mm/h, leukopenia, thrombocytopenia, positive ANA, positive anti-ds-DNA. An artogram demonstrated a complete obstruction of the right subclavian artery near its origin. The patient was diagnosed as having SLE and TA based on ACR criteries for both diseases. She was treated with prednisolone and azathioprine. 6 months later, her right radial pulse was weakly present. Case 2. A 30-year-old man was diagnosed in 1985 as having SLE based on malar rash, arthritis, positive ANA, positive anti-ds-DNA, hematologic abnormalities. He was treated with prednisolone (P) and azathioprine. He was readmitted in 1992 with progressive difficulty walking and symptoms of lower extremity claudication. Aortogram revealed occlusion of the abdominal aorta below the renal arteries. In 1994, he developed renal and cerebral involvement and superior vena cava syndrome (SVCS). He was again treated with P and cyclophosphamide (C). In 2000, A computed tomogram of the thorax confirmed SVCS due to mediastinal fibrosis. He has been using P and tamoxifen for 1 month. <h3>Conclusion</h3> Our experience with these cases suggests that all patients with SLE be followed carefully for the development of occlusive arterial involvement.
The FUTURE Trial: A Multicenter Randomised Controlled Trial on Target Biopsy Techniques Based on Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer in Patients with Prior Negative Biopsies
Authors: Olivier Wegelin, Leonie Exterkate, Marloes van der Leest, Jean A. Kummer, Willem Vreuls, Peter C. de Bruin, J.L.H.Ruud Bosch, Jelle O. Barentsz, Diederik M. Somford, Harm H.E. van Melick
Journal: European Urology (2018)
Inactivation of the Intestinal Apical Sodium Bile Acid Transporter Profoundly Inhibits Cholesterol Absorption.
Authors: Ivo P. Van De Peppel, Anna Bertolini, Theo H. Van Dijk, A. (Bert) K. Groen, Johan W. Jonker, Henkian J. Verkade
Journal: Hepatology (2018)
Disparities in length of goals of care conversations between oncologists and patients with advanced cancer.
Authors: Cardinale B. Smith, Sofya Pintova, Kerin B. Adelson, Jason Parker Gonsky, Natalia Egorova, Nina A. Bickell
Journal: Journal of Clinical Oncology (2018)

19 Background: Studies show minority patients have inadequate discussions about treatment, prognosis, and goals of care (GoC) which translate into substandard treatment, worse quality of life, and poorer survival than whites. However, there is a paucity of data on the quality of communication among minority patients with advanced cancer. We studied factors impacting the oncologists’ time spent during GoC discussion visits with their minority and non-minority patients. Methods: At community, academic, municipal, and rural hospitals, we recruited and randomized solid tumor oncologists and their newly diagnosed advanced cancer patients with &lt;2-year prognosis to participate in a RCT, testing a coaching model of communication skills training. Patients were surveyed after post-imaging visits. These visits were audiotaped and median encounter time recorded. We define GoC discussions as patients report that their doctor talked about preferences for cancer treatment and clarified things most important to them given their illness. Comparisons were made using non-parametric tests. We used mix-effect models for risk adjustment. Results: For 22 randomized oncologists in the study,142 post-imaging encounters were audiotaped. Of these, 38% were non-Hispanic White, 32% non-Hispanic Black and 19% Hispanic. The median face to face time oncologists spent during a GoC encounter with an advanced cancer minority patient was 12 minutes compared to 17 minutes for non-minorities (p=0.002). Median encounter times varied between the four sites, ranging from 10 minutes to 18 minutes, p=0.009. For visits that took place after progression of disease, duration of visit was 18 minutes versus 13 minutes if there were no progression, p=0.007. After controlling for clustering of the patients within the hospitals and progression of disease, time spent with minority patients remained less than with non-minority patients (15 min vs. 18 min, p=0.02). Conclusions: Oncologists' time spent conducting GoC conversations with minority cancer patients is significantly less than with non-minority patients. Evaluating factors that contribute to this disparity is critically important to ensure minority patients receive high-quality cancer care. Clinical trial information: NCT02374255.
Risk of Appendiceal Neoplasm in Periappendicular Abscess in Patients Treated With Interval Appendectomy vs Follow-up With Magnetic Resonance Imaging
Authors: Jari Mällinen, Tero Rautio, Juha Grönroos, Tuomo Rantanen, Pia Nordström, Heini Savolainen, Pasi Ohtonen, Saija Hurme, Paulina Salminen
Journal: JAMA Surgery (2018)

<h3>Importance</h3> The step after conservative treatment of periappendicular abscess arouses controversy, ranging from recommendations to abandon interval appendectomy based on low recurrence rates of the precipitating diagnosis to performing routine interval appendectomy owing to novel findings of increased neoplasm risk at interval appendectomy. To our knowledge, there are no randomized clinical trials with sufficient patient numbers comparing these treatments. <h3>Objective</h3> To compare interval appendectomy and follow-up with magnetic resonance imaging after initial successful nonoperative treatment of periappendicular abscess. <h3>Design, Setting, and Participants</h3> The Peri–Appendicitis Acuta randomized clinical trial was a multicenter, noninferiority trial conducted in 5 hospitals in Finland. All patients between age 18 and 60 years with periappendicular abscess diagnosed by computed tomography and successful initial nonoperative treatment from January 2013 to April 2016 were included. Data analysis occurred from April 2016 to September 2017. <h3>Interventions</h3> Patients were randomized either to interval appendectomy or follow-up with magnetic resonance imaging; all patients underwent colonoscopy. <h3>Main Outcomes and Measures</h3> The primary end point was treatment success, defined as an absence of postoperative morbidity in the appendectomy group and appendicitis recurrence in the follow-up group. Secondary predefined end points included neoplasm incidence, inflammatory bowel disease, length of hospital stay, and days of sick leave. <h3>Results</h3> A total of 60 patients were included (36 men [60%]; median [interquartile range] age: interval appendectomy group, 49 [18-60] years; follow-up group, 47 [22-61] years). An interim analysis in April 2016 showed a high rate of neoplasm (10 of 60 [17%]), with all neoplasms in patients older than 40 years. The trial was prematurely terminated owing to ethical concerns. Two more neoplasms were diagnosed after study termination, resulting in an overall neoplasm incidence of 20% (12 of 60). On study termination, the overall morbidity rate of interval appendectomy was 10% (3 of 30), and 10 of the patients in the follow-up group (33%) had undergone appendectomy. <h3>Conclusions and Relevance</h3> The neoplasm rate after periappendicular abscess in this small study population was high, especially in patients older than 40 years. If this considerable rate of neoplasms after periappendicular abscess is validated by future studies, it would argue for routine interval appendectomy in this setting. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT03013686
Development of PARP and Immune-Checkpoint Inhibitor Combinations
Authors: Ross A Stewart, Patrick G Pilié, Timothy A Yap
Journal: Cancer Research (2018)

Abstract PARP inhibitors drive increased DNA damage, particularly in tumors with existing defects in DNA repair. This damage not only promotes immune priming through a range of molecular mechanisms, but also leads to adaptive upregulation of programmed death ligand 1 (PD-L1) expression. In this context, PARP inhibition and programmed cell death 1(PD-1)/PD-L1–targeting antibodies represent a rationale combination. In this review, we detail the basic and translational science underpinning this promising new combination, summarize available clinical data, and discuss the key questions that remain to be addressed during future development.
Stat3 enhances Progesterone Receptor (PR)-mediated transcriptional activity through Sp-1 in the p21 promoter in breast cancer cells.
Authors: Cecilia Proietti, Cinthia Rosemblit, Wendy Beguelin, Victoria Sundblad, Maria Diaz Flaque, Martin Rivas, Romina Carnevale, Eduardo Charreau, Roxana Schillaci, Patricia Elizalde
Journal: Cancer Research (2008)

3021   We have previously demonstrated that the synthetic progestin medroxyprogesterone acetate (MPA) is able to induce Stat3 transcriptional activation, which is in turn an absolute requirement for progestin stimulation of  in vitro  and  in vivo  breast cancer growth, both in C4HD cells from an experimental model of hormonal carcinogenesis in which MPA induced mammary adenocarcinomas in Balb/c mice, and in the human breast cancer cell line T47D (Mol Cell Biol, 25: 4826, 2005). We have also shown that Stat3, acting as a coactivator, modulates PR function when binding to specific progesterone response elements (PRE) in the promoter regions of target genes, such as  bcl-X  (Proc Amer Assoc Cancer Res 2007;48:1029). It is known that progesterone induces the cyclin-dependent kinase inhibitor p21 expression through a transcriptional mechanism which involves interaction between progesterone-bound PR and the transcription factor Sp1 at proximal Sp1-binding sites. Here, we studied whether Stat3 could modulate PR activation when regulating the transcription of the p21 gene, which lacks canonical PREs in its promoter region. Assessment of the expression of the progestin-regulated p21 gene showed that MPA treatment of C4HD or T47D cells induced an increase in the levels of these proteins, which was further enhanced in a dose-dependent manner in the presence of a plasmid expressing a constitutively activated Stat3 mutant, Stat3-C. This effect was inhibited when the cells were transfected with Stat3 siRNA. To study the effect of Stat3 on PR-mediated transcriptional activity through this indirect mechanism, C4HD or T47D cells were transiently transfected with a p21 promoter reporter construct, together with increasing amounts of Stat3-C. We found that Stat3-C enhanced progestin-induced PR transcriptional activity in a dose-dependent manner. This effect was completely abolished when Stat3 expression was silenced using an siRNA strategy. We assessed the specific association of Stat3 and PR to the Sp-1 binding site in the p21 promoter in the context of living cells by performing Chromatin Immunoprecipitation Assays. We found that MPA treatment of T47D cells induced Sp-1, PR and Stat3 recruitment to the p21 promoter. These data identify, for the first time, Stat3 as a coactivator of progestin-activated PR when regulating p21 transcription by tethering to DNA-bound trans-acting factor Sp1.
Dissemination of Misinformative and Biased Information about Prostate Cancer on YouTube
Authors: Stacy Loeb, Shomik Sengupta, Mohit Butaney, Joseph N. Macaluso, Stefan W. Czarniecki, Rebecca Robbins, R. Scott Braithwaite, Lingshan Gao, Nataliya Byrne, Dawn Walter, Aisha Langford
Journal: European Urology (2018)
Revealing the Effects of Zika—Detection of Brain Abnormalities and Other Disabilities Associated With Congenital Infection
Authors: Margaret A. Honein, Denise J. Jamieson
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
Phase-1 Study of PF-114 Mesylate in CML Failing Prior Tyrosine Kinase-Inhibitor Therapy
Authors: Anna G Turkina, Olga Vinogradova, Elza Lomaia, Evgeniya Shatokhina, Oleg Shukhov, Ekaterina Chelysheva, Irina Nemchenko, Anna Petrova, Anastasiya Bykova, Andrey Zaritskey, Nadia Siordia, Dzhariyat Shikhbabaeva, Vasily Shuvaev, Jorge E. Cortes, Robert Peter Gale, Michele Baccarani, Oliver G. Ottmann, Ilya Mikhailov, Fedor Novikov, Veronika Shulgina, Ghermes Chilov
Journal: Blood (2018)
Addressing Clinical Significance—Reply
Authors: Molly P. Jarman, Adil H. Haider
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Hippo Deficiency Leads to Cardiac Dysfunction Accompanied by Cardiomyocyte Dedifferentiation During Pressure Overload
Authors: Shohei Ikeda, Wataru Mizushima, Sebastiano Sciarretta, Maha Abdellatif, Peiyong Zhai, Risa Mukai, Nadezhda Fefelova, Shin-ichi Oka, Michinari Nakamura, Dominic P. Del Re, Iain Farrance, Ji Yeon Park, Bin Tian, Lai-Hua Xie, Mohit Kumar, Chiao-Po Hsu, Sakthivel Sadayappan, Hiroaki Shimokawa, Dae-Sik Lim, Junichi Sadoshima
Journal: Circulation Research (2019)

Rationale: The Hippo pathway plays an important role in determining organ size through regulation of cell proliferation and apoptosis. Hippo inactivation and consequent activation of YAP (Yes-associated protein), a transcription cofactor, have been proposed as a strategy to promote myocardial regeneration after myocardial infarction. However, the long-term effects of Hippo deficiency on cardiac function under stress remain unknown. Objective: We investigated the long-term effect of Hippo deficiency on cardiac function in the presence of pressure overload (PO). Methods and Results: We used mice with cardiac-specific homozygous knockout of WW45 (WW45cKO), in which activation of Mst1 (Mammalian sterile 20-like 1) and Lats2 (large tumor suppressor kinase 2), the upstream kinases of the Hippo pathway, is effectively suppressed because of the absence of the scaffolding protein. We used male mice at 3 to 4 month of age in all animal experiments. We subjected WW45cKO mice to transverse aortic constriction for up to 12 weeks. WW45cKO mice exhibited higher levels of nuclear YAP in cardiomyocytes during PO. Unexpectedly, the progression of cardiac dysfunction induced by PO was exacerbated in WW45cKO mice, despite decreased apoptosis and activated cardiomyocyte cell cycle reentry. WW45cKO mice exhibited cardiomyocyte sarcomere disarray and upregulation of TEAD1 (transcriptional enhancer factor) target genes involved in cardiomyocyte dedifferentiation during PO. Genetic and pharmacological inactivation of the YAP-TEAD1 pathway reduced the PO-induced cardiac dysfunction in WW45cKO mice and attenuated cardiomyocyte dedifferentiation. Furthermore, the YAP-TEAD1 pathway upregulated OSM (oncostatin M) and OSM receptors, which played an essential role in mediating cardiomyocyte dedifferentiation. OSM also upregulated YAP and TEAD1 and promoted cardiomyocyte dedifferentiation, indicating the existence of a positive feedback mechanism consisting of YAP, TEAD1, and OSM. Conclusions: Although activation of YAP promotes cardiomyocyte regeneration after cardiac injury, it induces cardiomyocyte dedifferentiation and heart failure in the long-term in the presence of PO through activation of the YAP-TEAD1-OSM positive feedback mechanism.
#8 Introducing innovative invasive procedures and devices into clinical practice: an in-depth analysis of NHS Trusts’ New Invasive Procedure governance (oral presentation)
Authors: S. Cousins, H. Richards, J. Zahra, D. Elliott, K. Avery, H. Robertson, S. Paramasivan, N. Wilson, J. Mathews, Z. Tolkein, B. Main, N.S. Blencowe, R. Hinchliffe, J.M. Blazeby
Journal: International Journal of Surgery (2018)
Clinical Features at Baseline Cannot Predict Symptom Response to Placebo in Patients With Eosinophilic Esophagitis
Authors: Ikuo Hirano, Evan S. Dellon, Margaret H. Collins, James Williams, Lan Lan, David A. Katzka
Journal: Clinical Gastroenterology and Hepatology (2018)

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by ≥15 eosinophils per high-power field (eos/hpf) and esophageal dysfunction.1 One confounder in the assessment of drug efficacy in clinical trials for EoE2 and other gastrointestinal diseases3,4 has been the symptomatic response to placebo. In placebo-controlled, randomized trials of EoE therapies, placebo response rates as high as 78% have been reported.2 To mitigate placebo effect, a phase 2, randomized, double-blind, placebo-controlled trial of budesonide oral suspension (BOS) was designed with a single-blind, placebo run-in to attempt to screen out placebo responders before randomization.5 The aim of this post hoc analysis was to identify clinical factors associated with a symptom response during the placebo run-in.
Reprint of: Positive Psychological Well-Being and Cardiovascular Disease
Authors: Laura D. Kubzansky, Jeff C. Huffman, Julia K. Boehm, Rosalba Hernandez, Eric S. Kim, Hayami K. Koga, Emily H. Feig, Donald M. Lloyd-Jones, Martin E.P. Seligman, Darwin R. Labarthe
Journal: Journal of the American College of Cardiology (2018)
Non–Vitamin K Antagonist Oral Anticoagulants in the Treatment of Atrial Fibrillation
Authors: Alexander C. Fanaroff, E. Magnus Ohman
Journal: Annual Review of Medicine (2018)

Atrial fibrillation (AF) increases a patient's stroke risk four- to five-fold. Anticoagulation with the vitamin K antagonist (VKA) warfarin reduces the risk of stroke by 67%, but warfarin carries a significant risk of major bleeding and has unpredictable pharmacodynamics with a narrow therapeutic window, necessitating frequent monitoring of its anticoagulant effect. The non–vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban provide more predictable anticoagulant activity than warfarin with a lower risk of major bleeding, and each is noninferior to warfarin for the prevention of stroke. All have earned regulatory approval in the past eight years. At least one of the NOACs is approved for use in all patients with AF, except those with mechanical valves and rheumatic mitral valve disease, for whom warfarin remains the only option. Recent clinical trials have shown that antithrombotic regimens including NOACs are safe and effective in patients with AF who need potent antiplatelet therapy.