tbuckley/cabot-search huggingface dataset:
Tolerability of sorafenib in the treatment of hepatocellular carcinoma (HCC) in patients with Child A and B liver cirrhosis
Authors: K. Schuette, L. Zimmermann, J. Bornschein, D. Huster, A. Csepregi, P. Malfertheiner
Journal: Journal of Clinical Oncology (2009)

e15593 Background: Sorafenib (S) is the only drug that prolongs overall survival in patients (pts) with advanced HCC by nearly 3 months in pts with Child A liver cirrhosis (LC). This study aims to evaluate tolerability of S in pts with Child B LC. Methods: Pts with HCC not suitable for curative therapy were treated with S since it became available for clinical use. 50 of 139 consecutive patients diagnosed with HCC were treated with S (8 f, 42 m; median age 67 (18–86) yrs). Initial dose was 400 mg/day and increased in case of good tolerability stepwise up to 800mg/day. Pts were stratified according to the stage of LC and analyzed for treatment toxicity based on the National Cancer Institute Common Toxicity System. Results: 41 pts with HCC had LC, 17 in Child A and 24 in Child B stadium. Due to side effects a dose escalation to 800mg was possible in 9 pts (22.0%) only, 3 with Child A and 6 with Child B LC. Grade 1/2 toxicity was observed in 15 pts with initial Child A (88.2%) and in 11 pts with initial Child B LC (45.8%), grade 3/4 toxicity occurred in 2 pts with Child A (11.8%) and 3 pts with Child B LC (12.5%). After 12 weeks of follow-up, 12 pts with Child A (70.6%) and 10 pts with Child B LC (41.7%) at entry were still under treatment. A deterioration of liver function from Child A to Child B was observed in 5 of 17 pts (29.4%) and from Child B to Child C in 1 patient (4.2%). In 5 pts (29.4%) with Child A LC and 14 pts with Child B LC at entry treatment had been discontinued in advance. Survival in patients with LC Child A was better than in patients with LC Child B (median overall survival 327 (60–495) vs 138 (10–560) days resp., ns). Conclusions: Systemic therapy of advanced HCC with S appears to be a safe treatment option in pts with Child B LC. However, tolerability is an important limitation in the use of S independently of the stage of LC. Whether pts with advanced HCC benefit from a systemic treatment with smaller doses than 800mg/day needs to be addressed in further studies. [Table: see text]
Youth Involvement in the Decision to Start CGM Predicts Subsequent CGM Use
Authors: Victoria A. Miller, Rui Xiao, Nathalie Slick, Chris Feudtner, Steven M. Willi
Journal: Diabetes Care (2020)

OBJECTIVE The ability of continuous glucose monitoring (CGM) to improve diabetes outcomes depends upon consistent use. To identify factors that facilitate long-term use of CGM, this study tested the hypothesis that youth involvement in the decision to initiate this therapy would influence subsequent CGM use and that CGM self-efficacy and satisfaction mediate this relationship. RESEARCH DESIGN AND METHODS Before initiating CGM, parent-youth dyads (i.e., pairs) from an academic endocrinology clinic completed assessments, including a measure of the child’s involvement in the decision to start CGM. Two months into CGM use, youth completed measures of CGM self-efficacy and satisfaction. Fidelity of CGM use between weeks 5 and 12 was accessed via a cloud-based data repository. Hypotheses were tested with linear mixed-effects models, accounting for patients clustered within provider and repeated measures within patients. RESULTS CGM use in 108 dyads (youth mean age 13.4 ± 2.7 years; 73% White) was positively predicted by baseline parent report of youth involvement in the CGM decision (P &amp;lt; 0.0001), and this relationship was mediated by youth’s perceptions of CGM self-efficacy (P &amp;lt; 0.0001) and hassle (P = 0.014). So, when the youth shared their opinions about CGM with parents and participated in the decision to start, they perceived higher self-efficacy and lower hassle at 2-month follow-up, which predicted more days of use. This pattern held in models adjusting for youth race and sex and family income. CONCLUSIONS To achieve maximum clinical benefit from CGM use, providers should facilitate youth involvement in the decision to initiate the device.
Declining Use of Primary Care Among Commercially Insured Adults in the United States
Authors: Dawn E. DeWitt
Journal: Annals of Internal Medicine (2020)

Letters21 July 2020Declining Use of Primary Care Among Commercially Insured Adults in the United StatesDawn E. DeWitt, MDDawn E. DeWitt, MDElson S. Floyd College of Medicine, Washington State University, Spokane, Washington (D.E.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0481 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Ganguli and colleagues' (1) finding that Americans are receiving less care from primary care providers (PCPs) may presage another hit to primary care as a career choice. Several medical students recently relayed disappointing experiences in ambulatory primary care that factored into their preferences for hospital-based careers. Our students are not seeing the joy of continuity in primary care. When you know your patients, ambulatory practice is much more rewarding and the daily “work” is fundamentally different.Knowing my patients has led me to make diagnoses that have saved lives or avoided illness and has guided treatment on ...References1. Ganguli I, Shi Z, Orav EJ, et al. Declining use of primary care among commercially insured adults in the United States, 2008–2016. Ann Intern Med. 2020;172:240-247. [PMID: 32016285]. doi:10.7326/M19-1834 LinkGoogle Scholar2. Rask K. Pricing patients out of primary care. Ann Intern Med. 2020;172:283-284. [PMID: 32016281]. doi:10.7326/M19-4000 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington (D.E.D.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-0481. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDeclining Use of Primary Care Among Commercially Insured Adults in the United States, 2008–2016 Ishani Ganguli , Zhuo Shi , E. John Orav , Aarti Rao , Kristin N. Ray , and Ateev Mehrotra Metrics 21 July 2020Volume 173, Issue 2Page: 166KeywordsAlgorithmsComputersDisclosureHealth care qualityPopulation statisticsPrimary care physicians ePublished: 21 July 2020 Issue Published: 21 July 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Reply to Nannini and to Lipworth <i>et al.</i>
Authors: Michael C. Peters, John V. Fahy, Loren C. Denlinger
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Peters et al  reply to Nannini and to Lipworth et al  Dr  Nannini is concerned that IL-6 could be upregulated by overuse of β2-agonists  This is unlikely because the SARP-III (Severe Asthma Research Program III) protocol included a bronchodilator medication hold for the blood collection visits  Lipworth et al  provide important commentary on the links between IL-6 biology and airway viral infections, including coronavirus disease (COVID-19)
Surgical Jacket and Bouffant Use and Surgical Site Infection Risk
Authors: Adel Elkbuli, Saamia Shaikh, Shaikh Hai
Journal: JAMA Surgery (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 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
Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial
Authors: Kenneth H Mayer, Jean-Michel Molina, Melanie A Thompson, Peter L Anderson, Karam C Mounzer, Joss J De Wet, Edwin DeJesus, Heiko Jessen, Robert M Grant, Peter J Ruane, Pamela Wong, Ramin Ebrahimi, Lijie Zhong, Anita Mathias, Christian Callebaut, Sean E Collins, Moupali Das, Scott McCallister, Diana M Brainard, Cynthia Brinson, Amanda Clarke, Pep Coll, Frank A Post, C Bradley Hare
Journal: The Lancet (2020)
HSPA12A unstabilizes CD147 to inhibit lactate export and migration in human renal cell carcinoma
Authors: Xinxu Min, Xiaojin Zhang, Yunfan Li, Xiaofei Cao, Hao Cheng, Yuehua Li, Chuanfu Li, Qiuyue Kong, Qian Mao, Peipei Peng, Yan Ni, Jingjin Li, Yulian Duan, Li Liu, Zhengnian Ding
Journal: Theranostics (2020)

Background: Metastasis accounts for 90% of cancer-associated mortality in patients with renal cell carcinoma (RCC). However, the clinical management of RCC metastasis is challenging. Lactate export is known to play an important role in cancer cell migration. This study investigated the role of heat shock protein A12A (HSPA12A) in RCC migration. Methods: HSPA12A expression was examined in 82 pairs of matched RCC tumors and corresponding normal kidney tissues from patients by immunoblotting and immunofluorescence analyses. The proliferation of RCC cells was analyzed using MTT and EdU incorporation assays. The migration of RCC cells was evaluated by wound healing and Transwell migration assays. Extracellular acidification was examined using Seahorse technology. Protein stability was determined following treatment with protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132. Mass spectrometry, immunoprecipitation, and immunoblotting were employed to examine protein-protein interactions. Results: RCC tumors from patients showed downregulation of HSPA12A, which was associated with advanced tumor node metastasis stage. Intriguingly, overexpression of HSPA12A in RCC cells inhibited migration, whereas HSPA12A knockdown had the opposite effect. Lactate export, glycolysis rate, and CD147 protein abundance were also inhibited by HSPA12A overexpression but promoted by HSPA12A knockdown. An interaction of HSPA12A with HRD1 ubiquitin E3 ligase was detected in RCC cells. Further studies demonstrated that CD147 ubiquitination and proteasomal degradation were promoted by HSPA12A overexpression whereas inhibited by HSPA12A knockdown. Notably, the HSPA12A overexpression-induced inhibition of lactate export and migration were abolished by CD147 overexpression. Conclusion: Human RCC shows downregulation of HSPA12A. Overexpression of HSPA12A in RCC cells unstabilizes CD147 through increasing its ubiquitin-proteasome degradation, thereby inhibits lactate export and glycolysis, and ultimately suppresses RCC cell migration. Our results demonstrate that overexpression of HSPA12A might represent a viable strategy for managing RCC metastasis.
Pancreatic Cancer detection via Galectin-1-targeted Thermoacoustic Imaging: validation in an <i>in vivo</i> heterozygosity model
Authors: Huan Qin, Baohua Qin, Chang Yuan, Qun Chen, Da Xing
Journal: Theranostics (2020)

Purpose: To investigate the feasibility of microwave-induced thermoacoustic imaging (MTAI) in detecting small pancreatic tumors (< 10 mm in diameter) and to complement the limitation of current clinical imaging methods. Methods: A home-made MTAI system composed of a portable antenna and pulsed microwave generator was developed. The thermoacoustic nanoparticles were composed of the galectin-1 antibody for targeting pancreatic tumors and Fe3O4 nanoparticles as microwave absorbers (anti-Gal1-Fe3O4 nanoparticles). The microwave absorption properties of the nanoparticles were measured with a vector network analyzer and the resolving power of MTAI was investigated by imaging excised pancreatic tumors of different sizes (diameters of 1.0 mm, 3.1 mm, 5.0 mm, 7.2 mm). To simulate actual imaging scenarios, an in vivo heterozygosity model was constructed by covering the pancreatic tumors (~ 3 mm in diameter) in BALB/c nude mice with biologic tissue (~ 5 cm in depth). MTAI images of the heterozygosity model were acquired with/without the injection of the anti-Gal1-Fe3O4 nanoparticles and the thermoacoustic contrast from pancreatic tumors was evaluated with Student's paired t test. The data were analyzed with analysis of variance and nonparametric statistics. Results: Following intravenous infusion, anti-Gal1-Fe3O4 nanoparticles efficiently accumulated in the tumor. The MTAI contrast enhancement in pancreatic tumors with anti-Gal1-Fe3O4 nanoparticles was verified in vitro and in vivo. The pancreatic tumors were visible in nude mice examined with MTAI with a mean contrast enhancement ratio of 2.3 ± 0.15 (standard error of the mean) (P =. 001) at 6 h post-injection of the nanoparticles. MTAI identified tiny pancreatic tumors in deep tissues with high fidelity. Conclusion: MTAI offers deep imaging depth and high contrast when used with anti-Gal1-Fe3O4 nanoparticles. It can identify pancreatic tumors smaller than 5 mm, which is beyond the identification limit size (~10 mm) of other nondestructive clinical imaging methods. Thus, MTAI has great potential as an alternative imaging modality for early pancreatic cancer detection.
Growth and the Microbiome — Integrating Global Health with Basic Science
Authors: Ramnik J. Xavier
Journal: New England Journal of Medicine (2020)

Linear growth failure, or stunting, is a prevalent condition arising from undernutrition that has been identified as a major global health problem.1 Stunting is strongly associated with economic, health, and neurocognitive sequelae, making linear growth a major nutrition priority. Interventions that have focused on the supplementation of macronutrients and micronutrients2,3 and targeted efforts to improve water quality, sanitation, and hygiene have shown limited efficacy in combating growth failure.4 One potential causative factor that numerous studies have associated with stunting is environmental enteropathy (also called environmental enteric dysfunction [EED]), a subclinical syndrome that was first described in the 1960s. This disorder, . . .
Abstract GMM-032: UNRAVELLING THE STEROID METABOLOME IN EPITHELIAL OVARIAN CANCER
Authors: David N. Jeevan, Wiebke Arlt, Paul A. Foster, Sudha Sundar
Journal: Clinical Cancer Research (2019)

Abstract INTRODUCTION: Ovarian tissue possesses the capacity for steroidogenesis from as early as seven weeks gestation. Perturbations in the steroidogenic pathways have been implicated in the development and progression of epithelial ovarian carcinoma in adulthood but the evidence has been limited. Analysis of RNA-seq data from ovarian tissue now allows the genes involved in these pathways to be studied comprehensively helping direct future investigations and highlighting possible mechanisms of the disease. METHODS: RNA-seq data from 293 serous epithelial ovarian carcinomas from The Cancer Genome Atlas were extracted and the genes involved in steroidogenesis were systematically interrogated for high and low expression. Pathway analysis was employed to confirm significant findings. Comparison was made with novel RNA-seq data from first trimester fetal ovary and healthy adult ovary. RESULTS: Genes involved in the synthesis of androgens (HSD17B1, SRD5A1, AKR1C3, AR and STS) were all significantly upregulated in the high grade serous ovarian carcinoma group when compared to normal healthy ovary (p&amp;lt;0.05). Expression of several steroidogenic genes in malignancy appeared to mimic increased fetal expression with relative quiescence noted in the healthy ovary group. CONCLUSIONS: Transcriptome analysis shows upregulated gene expression of the androgen synthesis pathway is associated with epithelial ovarian cancer. This is supported by immunohistochemistry findings in recent studies. Investigation of the androgen pathway does remain a valid opportunity for mechanistic insight into this disease and potentially diagnostic and therapeutic exploitation. Ovarian steroidogenic gene expression in the first trimester appears to correlate with neoplastic growth in serous ovarian cancer but the significance of this is uncertain. Citation Format: David N. Jeevan, Wiebke Arlt, Paul A. Foster and Sudha Sundar. UNRAVELLING THE STEROID METABOLOME IN EPITHELIAL OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-032.
Checkpoint inhibitor-related renal vasculitis and use of rituximab
Authors: Omar Mamlouk, Jamie S Lin, Maen Abdelrahim, Amanda S Tchakarov, William F Glass, Umut Selamet, Maryam Buni, Noha Abdel-Wahab, Ala Abudayyeh
Journal: Journal for ImmunoTherapy of Cancer (2020)

The percentage of patients with cancer eligible for checkpoint inhibitor (CPI) therapy has increased rapidly over the past few years and approaches 45%. As a result, more cases of CPI-related nephrotoxicity, including a rare subset with vasculitis, are being reported. To elucidate the clinical presentation of CPI-associated renal vasculitis and its possible mechanisms, treatment options and prognosis, we describe cases from a comprehensive cancer center and reviewed the literature for similar cases. We retrospectively reviewed the charts of all patients with cancer from 2014 to 2020 who were diagnosed with CPI-related nephrotoxicity and underwent a kidney biopsy. We identified five cases of renal vasculitis: three patients were diagnosed with seronegative antineutrophil cytoplasm antibody (ANCA)-associated vasculitis, one case with seropositive ANCA-associated vasculitis and one case was diagnosed with IgA vasculitis. Of these cases, four patients were receiving nivolumab, and one patient was receiving tremelimumab. All patients had microscopic hematuria, four out of five patients had negative ANCA serology, one patient had concurrent lung involvement and positive ANCA serology, and all had severe acute kidney injury with creatinine &gt;4.50 mg/dL on diagnosis. All patients were treated by discontinuing CPI and initiating corticosteroids and rituximab. Three patients received plasmapheresis; two of these required renal replacement therapy including the patient with lung involvement. All patients after rituximab had a partial or complete renal response. Two patients died within 8 months of diagnosis due to malignancy progression. None of the patients had a relapse of vasculitis. We demonstrated that CPI can be associated with different types of renal vasculitis that are predominantly ANCA negative and manifest as severe acute kidney injury. Despite the lack of strong evidence, treatment similar to treatment of primary seropositive ANCA-associated vasculitis with corticosteroids and rituximab is well tolerated with favorable renal outcomes.
AB0320 BDMARDS SURVIVAL: THE TUNISIAN DATA
Authors: K. Saadaoui, H. Sahli, S. Boussaid, S. Jemmali, S. Rekik, E. Cheour, M. Elleuch
Journal: Annals of the Rheumatic Diseases (2020)

Background: The advent of biotherapies in the late 90s radically changed the face of inflammatory diseases including rheumatoid arthritis. The survival of these innovative therapies is an indicator, in clinical practice, of their long-term efficacy and safety. Objectives: The objective of this study was to assess their use in Tunisia through their survival during rheumatoid arthritis as well as to determine the factors that may influence their therapeutic maintenance in real life. Methods: This is a retrospective study including RA patients (ACR/EULAR 2010 criteria) and putted on biotherapy between 01-01-2014 and 12-31-2016. They were followed until 12-31-2018. The therapeutic maintenance rate at 12, 24, 36 and 48 months as well as the survival curves of biotherapies were analyzed using the Kaplan-Meier survival curves and compared by the Log-rank test. Reasons for interruption and patterns of biological change have been reported. Finally, an analysis of factors influencing survival was performed using Cox regression. A p&lt;0.05 was considered statistically significant. Results: Three hundred seventy-four patients were included in the study; sex ratio was 0,147. The baseline age was 55 ± 12.5 years [20 – 90] and the average disease duration was 11.7 ± 6.7 years [2 – 41]. Rheumatoid factor and ACPA were positive respectively in 79% and 71% cases. After failure of cDMARD, the first biotherapy prescribed was etanercept in 54% of cases, adalimumab in 14% of cases, certolizumab pegol 13%, infliximab 6%, tocilizumab 6% and rituximab in 7% of cases, with an average DAS28 at baseline 6.01 ± 0.89 [5,37 – 6,50]. Association with methotrexate was observed in 59,6% case and with corticosteroid in 57.2% case. Drug persistency rate at 12 months was 85.8%; at 24 months, 69.9%; at 36 months, 60.6% and at 48 months, 55.9%. Survival was on average 41.7 months with 95% CI (39.47 - 43.91). The presence of rheumatoid factors, the co-prescription of methotrexate as well as good initial therapeutic response were predictor of a better survival of biologicals at a statistically significant level p&lt;0.01 (Hazard Ratios for pursuit of biotherapy were respectively 1.79, 1.91 and 2,3). The use of glucocorticoids was a negative predictor of retention (Hazard Ratio for therapy pursuit was 0.47 p &lt; 0.001). This first biotherapy was stopped in 39% of cases and ineffectiveness was the major reason of interruption (52.7%). The anti-TNFα cycling was the most adopted therapeutic strategy with 64.6% of cases. The survival rates of the second biotherapy at 12, 24 and 36 months were 91%, 76.4% and 72.1%, respectively. Conclusion: Our study provides information about biotherapy prescription practices in Tunisia and their effectiveness in “real life”. It informs us about the use of these new therapies in our country and has shown an efficacy and a tolerance profile close to those reported in international registers. Disclosure of Interests: None declared