tbuckley/cabot-search huggingface dataset:
Abstract P251: Association Between Different Measures of Obesity and Kidney Function Decline
Authors: Zhi Yu, Morgan E Grams, Chiadi E Ndumele, Lynne Wagenknecht, Eric Boerwinkle, Kari North, Casey M Rebholz, Edward L Giovannucci, Josef Coresh
Journal: Circulation (2019)

Introduction: Obesity has been related to increased risk of incident cardiovascular disease, diabetes, and mortality as well as chronic kidney disease (CKD). However, the effect of obesity on long-term kidney function and whether it differs by gender and race are not known. Hypothesis: Obesity status is associated with future decline in kidney function. Methods: Obesity was measured by baseline body mass index (BMI), waist to hip ratio (WHR), and predicted percent fat (PPF) among 14,020 White (W) and African-American (AA) men and women (M/F) in the Atherosclerosis Risk in Communities (ARIC) study who were diabetes-free, had BMI &gt; 18.5 kg/m 2 , and had estimated glomerular filtration rate (eGFR) &gt; 60 ml/min/1.73 m 2 at baseline. Obesity was categorized into tertiles within each race-sex group. PPF was derived using anthropometric prediction equations including information on age, race, weight, height, and waist circumference. Mixed models with random intercepts and random slopes were used to evaluate the association between baseline obesity status and eGFR trajectories (calculated from serum creatinine at 5 visits). Cox proportional hazards models were used to estimate the hazard ratios (HRs) of end-stage kidney disease (ESKD) associated with baseline obesity status. Results: At baseline, participants had a mean age of 54 years, median eGFR of 103 ml/min/1.73 m 2 , and median BMI of 27 kg/m 2 . Over 30 years follow-up, all obesity measures showed some associations with more rapid eGFR decline with PPF showing the most consistent associations across race-sex subgroups ( Table ). All obesity indicators were associated with increased risk of ESKD for all race-sex groups (p trend&lt;0.05). For example, the HRs (95% CI) of ESKD per SD of PPF were 1.20 (1.05, 1.37) for WM, 1.54 (1.31, 1.80) for WF, 1.67 (1.45, 1.92) for AAM, and 1.62 (1.42, 1.84) for AAF. Conclusion: In summary, obesity status is a risk factor for future decline in kidney function and development of ESKD in community-dwelling adults with PPF showing some advantages over BMI and WHR.
Genetic determinants of paediatric food allergy: A systematic review
Authors: Noor H. A. Suaini, Yichao Wang, Victoria X. Soriano, David J. Martino, Katrina J. Allen, Justine A. Ellis, Jennifer J. Koplin
Journal: Allergy (2019)

Abstract Background The genetic determinants of food allergy have not been systematically reviewed. We therefore systematically reviewed the literature on the genetic basis of food allergy, identifying areas for further investigation. Methods We searched three electronic databases (MEDLINE, EMBASE and PubMed) on 9 January 2018. Two authors screened retrieved articles for review according to inclusion criteria and extracted relevant information on study characteristics and measures of association. Eligible studies included those that reported an unaffected nonatopic control group, had genetic information and were carried out in children. Results Of the 2088 studies retrieved, 32 met our inclusion criteria. Five were genome‐wide association studies, and the remaining were candidate gene studies. Twenty‐two of the studies were carried out in a predominantly Caucasian population with the remaining 10 from Asian‐specific populations or unspecified ethnicity. We found FLG, HLA, IL10, IL13, as well as some evidence for other variants ( SPINK5, SERPINB and C11orf30 ) that are associated with food allergy. Conclusions Little genetic research has been carried out in food allergy, with FLG, HLA and IL13 being the most reproducible genes for an association with food allergy. Despite promising results, existing genetic studies on food allergy are inundated with issues such as inadequate sample size and absence of multiple testing correction. Few included replication analyses or population stratification measures. Studies addressing these limitations along with functional studies are therefore needed to unravel the mechanisms of action of the identified genes.
Phase I study of ontuxizumab, a humanized monoclonal antibody (mAb) recognizing endosialin in Japanese patients (pts) with hepatocellular carcinoma (HCC).
Authors: Masafumi Ikeda, Takeshi Aramaki, Yoshitaka Inaba, Kenya Nakai, Toshihiko Doi, Takuji Okusaka
Journal: Journal of Clinical Oncology (2015)

2521 Background: Endosialin is a cell surface glycoprotein that is expressed on cells involved in the development of tumor vasculature, primarily pericyte and stromal fibroblast. Ontuxizumab is a humanized IgG1κ mAb that is the first clinical stage agent to target Endosialin. Based on the safety profile obtained in the dose escalation portion of this study, 3 dosage cohorts were expanded to further characterize the safety, pharmacokinetics (PK), and preliminary efficacy of Ontuxizumab in advanced HCC pts. Methods: HCC pts with Child-Pugh (CP) A who have no other appropriate treatment were enrolled at 4 study sites to 3 dosage cohorts; 4 and 8 mg/kg weekly, and 12 mg/kg biweekly as 4 weeks a cycle. Primary objective was safety. Efficacy endpoints were Response rate by RECIST v.1.1, Disease Control Rate (DCR) and Time to Progression (TTP). Results: Fifteen pts with advanced HCC pre-treated at minimum with sorafenib have been enrolled. Of these, 11 and 4 pts presented with ECOG 0 and 1 respectively, while 10 and 5 pts presented with CP A5 and A6 respectively. The PK profile from the HCC cohort was consistent with those of the dose escalation cohorts with other solid tumors. There were no significant differences for Cmax and AUC of Ontuxizumab between HCC and other solid tumors. Mean t1/2was 99.0 - 216 hours after multiple administrations. Safety profile was mainly characterized by Gr 1-2 events. Treatment related adverse events (AEs) were observed in 10 of 15 pts. The most common AEs were hiccups (20%), ALT increased, AST increased, blood bilirubin increased, hypoalbuminaemia and malaise (each 13%). There were 3 treatment related Gr 3-4 AEs (ALT increased, AST increased and hyperglycaemia), and no treatment related serious AEs. No CRs or PRs were reported; DCR was 60% with TTP ranging 1.4 to 12.9 months. Five pts (33%) showed tumor shrinkage and durable (over 6 months) SD was observed in 3 pts (20%). Conclusions: Ontuxizumab appears generally well tolerated in this HCC population with a PK profile consistent with the profile in other solid tumors. Preliminary efficacy results suggest that Ontuxizumab at minimum 4 mg/kg weekly warrants further investigation for clinical activity in HCC. Clinical trial information: NCT01773434.
Final Results of a Prospective Randomized Multicenter Phase III Trial Comparing Treosulfan/Fludarabine to Reduced Intensity Conditioning with Busulfan/Fludarabine Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Elderly or Comorbid Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome
Authors: Dietrich W Beelen, Rudolf Trenschel, Matthias Stelljes, Tamás Masszi, Péter Reményi, Eva-Maria Maria Wagner-Drouet, Peter Dreger, Wolfgang Bethge, Fabio Ciceri, Friedrich Stoelzel, Christian Junghanss, Mauricette Michallet, Miroslaw Markiewicz
Journal: Blood (2017)
A phase I study to assess the safety and tolerability of intravesical pembrolizumab in recurrent non-muscle invasive bladder cancer (NMIBC).
Authors: Victoria K Woodcock, Karin Purshouse, Chrissie Butcher, Caroline Haddon, Gillian Verrall, Leena Elhussein, Mariolina Salio, Mark R. Middleton, Vincenzo Cerundolo, Jeremy Crew, Andrew Protheroe
Journal: Journal of Clinical Oncology (2019)

406 Background: Intravesical BCG has been the mainstay of therapy following TURBT for intermediate risk NMIBC for many years and is thought to act through activation of non-specific local immunity. With the recent success of checkpoint inhibitor treatment in metastatic bladder cancer, we sought to investigate the anti-PD1 inhibitor pembrolizumab as a potential agent for use in patients with intermediate risk NMIBC in a phase I/II study. The primary aim of the phase I safety run-in was to assess the safety and tolerability of intravesical pembrolizumab after TURBT in patients with intermediate risk NMIBC. Methods: Eligible patients had recurrent NMIBC for which adjuvant treatment post TURBT was a reasonable treatment option, ECOG PS 0-1 and adequate end organ function. Pembrolizumab was administered by intravesical instillation once weekly for a total of 6 doses. Intra-patient dose escalation was performed in three paired patient cohorts with doses starting at 50mg and increasing through 100mg to a maximum of 200mg. Adverse events (AEs) were assessed using CTCAE v4.03 with dose limiting toxicity (DLT) defined as a clinically significant, drug related, grade 4 haematological or ≥ grade 3 non-haematological toxicity occurring within 7 days of administration of the first treatment at a given dose for that patient. Results: In the first 4 patients treated, no DLTs were seen during dose escalation. Drug-related AEs included Grade 1 dysuria, fatigue and nausea. Grade 1-2 urinary tract infections, Grade 1 cystitis and Grade 3 urosepsis (SAE) were observed but assessed as probably not related to pembrolizumab. Recruitment of a final cohort of two patients at repeated doses of 200mg is ongoing to confirm safety and tolerability of this dose. Conclusions: Administration of intravesical pembrolizumab was safe and well tolerated in patients with NMIBC following TURBT. A randomised, parallel group, phase II marker-lesion study to assess the safety, efficacy and tolerability of either intravesical pembrolizumab or intravenous pembrolizumab in a larger cohort of patients with intermediate risk recurrent NMIBC is planned. Clinical trial information: NCT03167151.
Abstract P106: Genetically Determined Fibrinogen, Gamma Prime Fibrinogen and Risk of Venous Thromboembolism and Ischemic Stroke: Evidence From Mendelian Randomization
Authors: Jillian Maners, Dipender Gill, Nathan Pankratz, Weihong Tang, Nicholas L Smith, Alanna C Morrison, Abbas Dehghan, Paul S de Vries
Journal: Circulation (2019)

Introduction: Fibrinogen is a key component of the coagulation cascade, and variation in its circulating levels may contribute to thrombotic diseases, such as venous thromboembolism (VTE) and ischemic stroke. Methods: Two-sample Mendelian randomization (MR) was applied to estimate the causal effect of circulating fibrinogen and its isoform, gamma prime fibrinogen, on risk of VTE and ischemic stroke subtypes using summary statistics from published genome-wide association studies of fibrinogen, VTE, and ischemic stroke, and an unpublished study of gamma prime fibrinogen. Genetic instruments for fibrinogen and gamma prime fibrinogen were selected by pruning genome-wide significant variants to linkage disequilibrium r 2 &lt; 0.1. The inverse variance weighted MR approach was used to estimate effects in the main analysis, with additional approaches that are more robust to the inclusion of pleiotropic variants applied in sensitivity analyses, including MR-Egger, weighted median MR, and weighted mode MR. Results: The main inverse variance weighted MR estimates ( Table ) based on 85 genetic instruments for fibrinogen and 27 genetic instruments for gamma prime fibrinogen indicated a protective effect of both fibrinogen and gamma prime fibrinogen levels on VTE risk. Higher fibrinogen levels decreased the risk of cardioembolic stroke but increased the risk of large artery and small vessel stroke. Higher gamma prime fibrinogen levels decreased the risk of all ischemic stroke, cardioembolic stroke, and large artery stroke. Effect estimates were consistent across sensitivity analyses, indicating that the results are unlikely to be attributable to the inclusion of pleiotropic variants. Conclusion: Our results are consistent with effects of genetically determined fibrinogen and gamma prime fibrinogen on VTE and ischemic stroke. The identified protective effects may reflect the diverse roles of the fibrinogen, beyond the formation of fibrin clots, in thrombotic diseases with different etiologies.
BST-236, a Novel Cytarabine Prodrug, Is Safer and As Effective As Cytarabine in In Vivo Leukemia Models
Authors: Shoshi Tessler, Inbal Mishalian, Ronny Peri-Naor, Stela Gengrinovitch, Raphael Mayer, Ruth Ben Yakar, Amnon Peled, Liat Flaishon
Journal: Blood (2018)
Abstract P244: Serum Uric Acid Level is A Predictor of Nonalcoholic Fatty Liver Disease in an Apparently Healthy Population
Authors: Cristina P Baena, Grasiele L Martins, Mariana F Leite, Ariele B Haagsma, Clara I de Paiva, Guilherme R Kallaur, Andre M Nogueira, Camila C Simao, Camila Cavalli, Daniele R Goss, Paulo A Junior
Journal: Circulation (2019)

Background: Nonalcoholic Fatty Liver Disease (NAFLD) is the most frequent hepatic abnormality in the western countries and commonly asymptomatic. Known risk factors for the disease are obesity, type 2 diabetes, hypertension and dyslipidemia. Serum Uric Acid levels (SUA) has been associated with a variety of cardiometabolic disorders. Yet the relationship between NAFLD and SUA is less known. Hypothesis: We assessed the hypothesis that there is an association between SUA levels with NAFLD in an apparently healthy population in Brazil. Materials and Methods: A cross-sectional study was conducted among 2.660 adult Brazilians who underwent to a medical check-up at Marcelino Champagnat Hospital in Curitiba/PR. Sociodemographic, anthropometric and laboratory evaluations were conducted, including abdominal ultrasonography. NAFLD was diagnosed by abdominal ultrasound, with evidence of contrast between the liver and renal parenchyma. Individuals with history of significant alcohol consumption (intake superior to 140g/week for men and 70g/week for women) or using hipouricemic medications were excluded from the analysis. Binary logistic regression models were built to test the impact of SUA levels on NAFLD by sex. Adjustments were subsequently made by age, fasting glucose, body mass index, hypertension, dyslipidemia and smoking status to test the independence of SUA in association with NAFLD. Results: We included 1.329 men (46.1±8.5 years) and 351 women (46.3±8.2 years) in the final analysis. Prevalence of NAFLD were 35.6% and 38.7% for men and women, respectively (p&lt;0.001). Mean SUA levels were significantly higher in subjects with NAFLD (6.52±1.30mg/dL vs 5.51±1.41 mg/dL) in men and ( 6.36±1.34 mg/dL vs 5.53 ±1.28 mg/dL) in women (p&lt;0.001 for both). Crude models for NAFLD by unit of SUA yielded OR of 1.69 (CI 95% 1.53-1.86) and 1.61 (CI 95% 1.33-1.94) for men and women, respectively. Fully adjusted models showed OR of 1.43 (CI 95% 1.27-1.62) and 1.48 (CI 95% 1.17-1.88), for men and women, respectively. Conclusion: SUA levels are independently associated with NAFLD in an apparently healthy population. Future studies should explore the benefits of lowering SUA levels on NAFLD prevention and potential mechanisms of this association.
THE IMPACT OF SEDENTARY BEHAVIOR PATTERNS ON CAROTID ATHEROSCLEROTIC BURDEN: INFERENCES FROM THE CORINTHIA EPIDEMIOLOGICAL STUDY
Authors: Sotirios Tsalamandris, Evangelos Oikonomou, George Lazaros, Evangelia Christoforatou, Georgia Vogiatzi, Christos Chasikidis, Konstantinos Mourouzis, George-Angelo Papamikroulis, Athina Goliopoulou, Margienti Papakonstantinou, Maria Anastasiou, Evgenia Bourouki, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2019)
Abstract MP57: Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study
Authors: Nora Franceschini, Bridget M Lin
Journal: Circulation (2019)

Background: Chronic kidney disease (CKD) is common, disproportionally burdens ethnic minorities in the US, and is associated with increased cardiovascular mortality. Our prior trans-ethnic genetic research has identified approximately 100 loci for kidney function. We now extend this research to CKD stages in studies of diverse populations. To uncover genetic factors associated CKD stages, we performed genome-wide association studies in diverse populations within the Population Architecture using Genomics and Epidemiology (PAGE) study. Methods: We assembled multi-ethnic data on CKD non-overlapping cases (4,690 mild to moderate CKD, 1,105 advanced CKD [stage 5] including end-stage kidney disease) and non-CKD controls for up to 46,263 PAGE participants (African Americans, Hispanics/Latinos, East Asian, Native Hawaiian and American Indians). We implemented a generalized estimating equation approach for single test genome-wide association analyses using ancestry combined data and adjusting for age, sex, principal components, study and ethnicity. Results: The analyses identified two associated loci at p &lt; 5.3 x 10 -8 , including a novel association with mild to moderate CKD on chromosome 9, which is driven by an intronic variant of TYRP1 (rs186208070, allele frequency 0.01 in our combined sample, 1000 Genomes: 0.02 in AFR, 0.003 AMR, 0.001 EUR, p=4.4 x 10 -8 ). Several genome-wide associated variants at the APOL1 locus were associated with advanced CKD. The most significant finding was for APOL1 G1 rs73885319 (p=1.19 x 10 -9 ). Additional variants with suggestive associations at p&lt;10 -6 for advanced CKD included an intronic low frequency variant in FTO (rs7189997) and a variant nearby IRX3 (rs8050506). Both variants are more common in African ancestry and these loci were previously associated with obesity traits. Conclusions: Our study on the genetics of CKD identified a novel locus for mild to moderate CKD and showed for the first time strong associations of African-ancestry APOL1 variants with advanced CKD across multi-ethnic populations.
Real-world treatment patterns for platinum-sensitive recurrent serous ovarian cancer: Findings from a multinational medical record review.
Authors: Jerzy Tyczynski, Sarah Williams, Noolie Gregory, Mandy Garratt, Ilian Tchakov, Keith L. Davis, James A. Kaye, Jennifer Korsnes, Jan Lewis
Journal: Journal of Clinical Oncology (2015)

e16548 Background: Platinum-based chemotherapy is considered standard treatment for platinum-sensitive recurrent ovarian cancer (PSR OC). New targeted agents continue to be evaluated in this setting. Data on PSR OC treatment patterns in routine practice are needed to inform health–health technology and reimbursement assessments of standard and new treatments. Methods: We retrospectively reviewed a sample of medical records from three countries (United Kingdom [UK], Canada [CAN], and Netherlands [NL]) to assess PSR OC treatment patterns. Women determined to have serous PSR OC (progression-free interval of ≥ 6 months after 1st-line platinum completion) during 2009–2013 were selected, with the study index date defined as PSR OC diagnosis date. First-line treatments were evaluated as pre-index history, and 2nd-line or later treatments were assessed from index until death or last medical record. Results: In total, 421 patients were analyzed (n = 312 UK, 73 CAN, and 36 from the NL; median age at index: 61, 60, and 60 years). Germline BRCA testing was performed in 21%, 29%, and 20% of patients, respectively, with positive status (gBRCA1m/2m) identified in 29%, 29%, and 43% of those tested. Carboplatin + paclitaxel was the most common 1st-line regimen (78%, 89%, 83%). Maintenance following 1st-line occurred only in the UK (4%) and NL (3%), with bevacizumab used in all cases. The majority of patients (73%, 62%, 81%) received 2nd-line treatment (1st treatment for PSR OC), which involved a carboplatin-containing regimen in > 90% of cases; 7% received non-platinum regimens. Carboplatin + paclitaxel was most frequently used in 2nd-line (31%, 40%, 62%; median five cycles). Initiation of 3rd-line therapy occurred in 17%, 38%, and 38% of 2nd-line initiators. Conclusions: Platinum retreatment in the 2nd-line setting for PSR OC was the standard of care in this real-world review. Maintenance therapy was rarely employed as part of initial treatment, reflecting the current lack of an approved maintenance indication in CAN and only recent approval in the UK and NL.
The PAZOREAL non-interventional study to assess efficacy and safety of pazopanib and everolimus in the changing metastatic renal cell carcinoma (mRCC) treatment landscape
Authors: P. Goebell, C. Doehn, C. Grüllich, V. Grünwald, T. Steiner, R. Ehness, M. Welslau
Journal: Annals of Oncology (2016)
Annals Graphic Medicine - Progress Notes: Soapcalls
Authors: Michael Natter
Journal: Annals of Internal Medicine (2019)

Web Exclusives19 March 2019Annals Graphic Medicine - Progress Notes: SoapcallsFREEMichael Natter, MDMichael Natter, MDNYU School of Medicine, New York, New York (M.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0007 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: NYU School of Medicine, New York, New York (M.N.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0002.Author/Illustrator Information: Michael Natter, MD, is a current internal medicine resident at NYU School of Medicine and a graduate of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia. His artwork is inspired by his medical training, patient encounters, and the human condition. A type 1 diabetic, Dr. Natter views himself as a patient as well as a doctor and plans to pursue a fellowship in endocrinology to help others who also share his disease. You can find more of his illustrations, stories, and comics on Instagram (www.instagram.com/mike.natter) and Twitter (@mike_natter).About Progress Notes: Progress Notes explores the everyday emotional, clinical, humorous, and ethical challenges of the medical residency training process. As implied by the title of the series, these pieces act as a visual bildungsroman, graphically dissecting the subtext of what it means to be a young doctor in today's medical world. Progress Notes appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA Novel Graphic Medicine Curriculum for Resident Physicians: Boosting Empathy and Communication through Comics 19 March 2019Volume 170, Issue 6Page: W82-W83KeywordsConflicts of interestDisclosureEmotionsEndocrinologyFellowshipsGraduate medical educationResidency ePublished: 19 March 2019 Issue Published: 19 March 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...