tbuckley/cabot-search huggingface dataset:
Assessing the Long-term Safety of Endovascular Therapies—The Case of Peripheral Paclitaxel-Coated Devices
Authors: Jay Giri
Journal: JAMA Cardiology (2019)

Eric A. Secemsky, MD, MSc; Harun Kundi, MD; Ido Weinberg, MD; Michael R. Jaff, DO; Anna Krawisz, MD; Sahil A. Parikh, MD; Joshua A. Beckman, MD; Jihad Mustapha, MD; Kenneth Rosenfield, MD; Robert W. Yeh, MD
Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis
Authors: Priyanka Kachroo, Jesus M. Eraso, Stephen B. Beres, Randall J. Olsen, Luchang Zhu, Waleed Nasser, Paul E. Bernard, Concepcion C. Cantu, Matthew Ojeda Saavedra, María José Arredondo, Benjamin Strope, Hackwon Do, Muthiah Kumaraswami, Jaana Vuopio, Kirsi Gröndahl-Yli-Hannuksela, Karl G. Kristinsson, Magnus Gottfredsson, Maiju Pesonen, Johan Pensar, Emily R. Davenport, Andrew G. Clark, Jukka Corander, Dominique A. Caugant, Shahin Gaini, Marita Debess Magnussen, Samantha L. Kubiak, Hoang A. T. Nguyen, S. Wesley Long, Adeline R. Porter, Frank R. DeLeo, James M. Musser
Journal: Nature Genetics (2019)
Cyclophosphamide, Pomalidomide and Dexamethasone Significantly Improves Response over Poma/Dex in Relapsed/Refractory Myeloma Patients Previously Treated with Cyclophosphamide Combination Therapy - Initial Results of the Randomised Multicentre Mukseven Trial
Authors: James Croft, Andrew Hall, Katrina Walker, Amy L Sherborne, Sidra Ellis, Amy Price, Debbie Sherratt, Sadie Reed, Charlotte Pawlyn, Mamta Garg, Kevin Boyd, Gordon Cook, Sarah R Brown, Martin Kaiser
Journal: Blood (2018)
Donor IFNL4 Genotype Is Associated with Transplant-Related Mortality after Unrelated Donor Myeloablative Hematopoietic Cell Transplantation in Patients with Acute Leukemia
Authors: Shahinaz M Gadalla, Tao Wang, Olusegun Onabajo, Youjin Wang, Michael D. Haagenson, Jennifer A. Sees, Stephen R. Spellman, Hormuzd A. Katki, Stephanie J. Lee, Ludmila Prokunina-Olsson
Journal: Blood (2018)
Membrane-associated Mucin 1 (MUC1) Promotes Epidermal Growth Factor Receptor (EGFR)-mediated Mucin 5AC (MUC5AC) Overproduction in Chronic Airway Disease
Authors: Kosuk Kato, Eugene H. Chang, Yin Chen, Kwang Chul Kim
Journal: Journal of Allergy and Clinical Immunology (2019)
AAV9 Intracerebroventricular Gene Therapy Improves Lifespan and Normalises Long-Term Locomotor Behaviour in a Mouse Model of Niemann-Pick Type C1 Disease
Authors: M P Hughes, D A Smith, L Morris, C Fletcher, A Colaco, M Huebecker, G Massaro, J Tordo, N Palomar, E Henckaerts, S N Waddington, F M Platt, A A Rahim
Journal: Molecular Therapy (2018)
Preoperative factors predictive of pathologic upstaging in clinical stage I gastric cancer patients.
Authors: Hayavadhan Thuppal, Patricia Friedmann, John Christopher McAuliffe, Peter Muscarella, Haejin In
Journal: Journal of Clinical Oncology (2019)

39 Background: In patients with stage 1 gastric cancer, surgical resection without neoadjuvant therapy is offered as the first line treatment. However, some of these patients are found to have higher stage after resection and miss the opportunity for neoadjuvant therapy. Preoperative patient and tumor characteristics may be predictive of the likelihood of pathological upstaging in stage 1 gastric cancer patients who have not received neo-adjuvant therapy. Methods: The National Cancer Database was queried for patients diagnosed from 2004-2015 with clinical stage 1 gastric adenocarcinoma who had undergone surgical resection without neoadjuvant therapy. Univariate analysis and multivariable logistic regression were conducted to determine pre-operative factors associated with pathological upstaging. Candidate variables examined included age, sex, race, tumor size, histology, grade, tumor location, days to surgery, and lymphovascular invasion. Results: Analysis was conducted on 8,015 clinical stage 1 patients. Overall 1,981 (25%) patients were upstaged. On multivariable logistic regression analysis, significant predictors of upstaging included increasing tumor size [ref : size &lt; 1 cm, 1-2 cm aOR=3.8 (95% CI 2.3-6.1); 2-4 cm aOR=12.4 (7.9-19.5); &gt; = 4cm aOR=25.9 (22.9-56.4)], younger age [ref: &gt; = 75, &lt; 50 aOR=1.7 (1.4-2.1), 50-65 aOR=1.4 (1.2-1.6), 65-75 aOR=1.2 (1.1-1.5)], male gender [aOR=1.16 (1.0-1.3)], presence of diffuse type gastric cancer [aOR=2.3 (1.7-3.2)], mucinous type [aOR=1.7 (1.1-2.5)], or signet ring cell histology [aOR=1.6 (1.3-2.0)] compared to intestinal histology, presence of lymphovascular invasion [aOR=6.0 (5.0-7.1)], and increasing grade [ref: grade 1, grade 2 aOR=2.30 (1.7-3.5); grade 3 aOR=4.9 (3.6- 6.7)]. Conclusions: A quarter of all patients thought to have stage 1 gastric cancer prior to surgery had higher pathologic stage at time of resection. Patients with the above risk factors may be understaged with currently available diagnostic tools. The addition of neoadjuvant therapy should be considered when the above risk factors are present in clinical stage 1 patients.
Comment on Laiteerapong et al. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes &amp; Aging Study). Diabetes Care 2019;42: 416–426
Authors: Adam Hulman, Lasse Bjerg, Bendix Carstensen
Journal: Diabetes Care (2019)

We read with interest the article from Laiteerapong et al. (1) about the effect of early glycemic control on micro- and macrovascular complications and mortality in individuals with newly diagnosed type 2 diabetes. However, we have major concerns regarding their study.

First, we are concerned about the use of conditioning on the future when selecting the study sample, i.e., those still alive 10 years after diagnosis, while including this period in the follow-up time. The authors cautiously mentioned this as a limitation (lack of generalizability); however, we think that conditioning on the future makes the mortality figures erroneous and the interpretation of the complication results problematic with substantially limited clinical utility. The authors fitted a …
Targeting APLN/APLNR Improves Antiangiogenic Efficiency and Blunts Proinvasive Side Effects of VEGFA/VEGFR2 Blockade in Glioblastoma
Authors: Giorgia Mastrella, Mengzhuo Hou, Min Li, Veit M. Stoecklein, Nina Zdouc, Marie N.M. Volmar, Hrvoje Miletic, Sören Reinhard, Christel C. Herold-Mende, Susanne Kleber, Katharina Eisenhut, Gaetano Gargiulo, Michael Synowitz, Angelo L. Vescovi, Patrick N. Harter, Josef M. Penninger, Ernst Wagner, Michel Mittelbronn, Rolf Bjerkvig, Dolores Hambardzumyan, Ulrich Schüller, Jörg-Christian Tonn, Josefine Radke, Rainer Glass, Roland E. Kälin
Journal: Cancer Research (2019)

Abstract Antiangiogenic therapy of glioblastoma (GBM) with bevacizumab, a VEGFA-blocking antibody, may accelerate tumor cell invasion and induce alternative angiogenic pathways. Here we investigate the roles of the proangiogenic apelin receptor APLNR and its cognate ligand apelin in VEGFA/VEGFR2 antiangiogenic therapy against distinct subtypes of GBM. In proneural GBM, apelin levels were downregulated by VEGFA or VEGFR2 blockade. A central role for apelin/APLNR in controlling GBM vascularization was corroborated in a serial implantation model of the angiogenic switch that occurs in human GBM. Apelin and APLNR are broadly expressed in human GBM, and knockdown or knockout of APLN in orthotopic models of proneural or classical GBM subtypes significantly reduced GBM vascularization compared with controls. However, reduction in apelin expression led to accelerated GBM cell invasion. Analysis of stereotactic GBM biopsies from patients as well as from in vitro and in vivo experiments revealed increased dissemination of APLNR-positive tumor cells when apelin levels were reduced. Application of apelin-F13A, a mutant APLNR ligand, blocked tumor angiogenesis and GBM cell invasion. Furthermore, cotargeting VEGFR2 and APLNR synergistically improved survival of mice bearing proneural GBM. In summary, we show that apelin/APLNR signaling controls GBM angiogenesis and invasion and that both pathologic features are blunted by apelin-F13A. We suggest that apelin-F13A can improve the efficiency and reduce the side effects of established antiangiogenic treatments for distinct GBM subtypes. Significance: Pharmacologic targeting of the APLNR acts synergistically with established antiangiogenic treatments in glioblastoma and blunts therapy resistance to current strategies for antiangiogenesis. See related commentary by Amoozgar et al., p. 2104
Activity and Safety of Daratumumab Monotheray in Patients with Relapsed and Refractory Multiple Myeloma Requiring Dialysis: Preliminary Results of Spanish, Retrospective, Multicenter Trial
Authors: Maria José Cejalvo, Mario Legarda, Eugenia Abella, Elena Cabezudo, Cristina Encinas, Ana García-Feria, Belén Iñigo, Jesús Marín, Paz Ribas, M. Ángeles Ruíz, Javier de la Rubia
Journal: Blood (2017)
Phase II, Multiple-Dose Study of Anti-FcRn Antibody, Rozanolixizumab (UCB7665), in Patients with Primary Immune Thrombocytopenia: Interim Analysis
Authors: Tadeusz Robak, Isidro Jarque, Vasile Musteata, Peter Kiessling, Ute Massow, James Higginson, Rose Snipes, Stephen Jolles
Journal: Blood (2017)
Racial/ethnic differences in food sensitization and food allergy in a diverse multi-center cohort of U.S. infants
Authors: Anna J. Chen Arroyo, Lacey B. Robinson, Janice A. Espinola, Courtney N. Tierney, Ashley F. Sullivan, Susan A. Rudders, Carlos A. Camargo
Journal: Journal of Allergy and Clinical Immunology (2019)
A U.S. Food and Drug Administration Age Based Pooled Analysis of Cytokine Release Syndrome and Neurotoxicity in Subjects with Relapsed/Refractory Lymphoma Treated with Chimeric Antigen Receptor (CAR) T Cell Therapy
Authors: Poornima Sharma, Harpreet Singh, Najat Bouchkouj, Aviva C. Krauss, Bindu George
Journal: Blood (2018)
Patterns of Infection and Mortality Associated with Intensive AML Induction Therapy: 10 Year Experience from a Tertiary Cancer Centre in India
Authors: Hemanth Kumar, Nikita Mehra, Prasanth Ganesan, Venkatraman Radhakrishnan, Manikandan Dhanushkodi, Jayachandran P K, Trivadi S Ganesan, S Krupa Shankar, Tenali Gnana Sagar, Krishnarathinam Kannan
Journal: Blood (2018)
Respiratory Virus Detection in Nasal Lavage Fluid of Chronic Rhinosinusitis Patients During Acute Exacerbations
Authors: Jason Kwah, Mariel R. Benjamin, Stephanie Fischer, Assel Biyasheva, Amela Hadzic, Atsushi Kato, Whitney W. Stevens, Robert C. Kern, Stephanie S. Smith, Pedro C. Avila, Kevin C. Welch, David B. Conley, Bruce K. Tan, Leslie C. Grammer, Robert P. Schleimer, Anju T. Peters
Journal: Journal of Allergy and Clinical Immunology (2019)
Local recurrence of diminutive colorectal polyps after cold forceps polypectomy with jumbo forceps followed by magnified narrow-band imaging: a multicenter prospective study
Authors: Toshio Kuwai, Takuya Yamada, Tatsuya Toyokawa, Hiroaki Iwase, Tomohiro Kudo, Naoki Esaka, Hajime Ohta, Haruhiro Yamashita, Yasuo Hosoda, Noriko Watanabe, Naohiko Harada
Journal: Endoscopy (2019)

Background Cold polypectomy has been increasingly used to remove diminutive colorectal polyps. We evaluated the local recurrence rate of diminutive polyps at the 1-year follow-up after cold forceps polypectomy (CFP). Methods In a prospective, multicenter, observational cohort study, patients with diminutive colorectal polyps ( ≤ 5 mm) were treated by CFP using jumbo forceps followed by magnified narrow-band imaging (NBI). Patients were assessed for local recurrence at 1-year follow-up. Risk factors associated with local recurrence were analyzed using logistic regression analysis. Results Overall, 955 lesions were resected in 471 patients who completed the 1-year follow-up. The endoscopic complete resection rate was 99.4 %. Immediate and delayed bleeding occurred in 0.8 % and 0.2 % of cases, respectively, with no perforations observed. Local recurrence occurred in 2.1 % of cases at the 1-year follow-up. Univariable analyses indicated that polyps &gt; 3 mm (P &lt; 0.01) and immediate bleeding (P = 0.04) were significantly associated with local recurrence. A trend was observed for patients ≥ 65 years (P = 0.06) and fractional resection (P = 0.09). Multivariable analyses confirmed that lesions &gt; 3 mm were significantly associated with local recurrence (odds ratio 3.4, P = 0.02). Conclusions CFP with jumbo forceps followed by NBI-magnified observation had a low local recurrence rate and is an acceptable therapeutic option for diminutive colorectal polyps. Although we recommend limiting the use of CFP with jumbo forceps to polyps ≤ 3 mm in size, future comparative studies are needed to make recommendations on cold polypectomy using either forceps or snares as the preferred approach for diminutive polyp resection.
Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population
Authors: Jun Hirata, Kazuyoshi Hosomichi, Saori Sakaue, Masahiro Kanai, Hirofumi Nakaoka, Kazuyoshi Ishigaki, Ken Suzuki, Masato Akiyama, Toshihiro Kishikawa, Kotaro Ogawa, Tatsuo Masuda, Kenichi Yamamoto, Makoto Hirata, Koichi Matsuda, Yukihide Momozawa, Ituro Inoue, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada
Journal: Nature Genetics (2019)
Abstract P067: Early Exposure to PM <sub>2.5</sub> and Ozone During the Menopausal Transition as Predictor of Subclinical Atherosclerosis in Late Midlife Women: the Study of Women’s Health Across the Nation (SWAN)
Authors: Chunzhe Duan, Rachel Broadwin, Evelyn O Talbott, Maria M Brooks, Karren A Matthews, Emma Barinas-Mitchell
Journal: Circulation (2017)

Introduction: Long-term air pollution may be a risk factor for CVD mortality, but few studies have investigated its effect on subclinical atherosclerosis. Moreover, data among women transitioning the menopause are lacking. Hypothesis: We hypothesized that mid-life women exposed to higher levels of air pollution across a 5-year period may have a greater burden of subclinical atherosclerosis (higher common carotid intima-media thickness (CIMT), inter-adventitial diameter (AD) and plaque) 5 to 7 years later compared to women exposed to lower levels. Methods: This longitudinal study was conducted among 1,188 women from the Study of Women’s Health Across the Nation (SWAN) with available data on both air pollution exposure and CIMT. We excluded participants who had an MI and stroke before the carotid ultrasound scan. Yearly cumulative exposure levels of two air pollutants, particulate matter ≤2.5 μm (PM 2.5 ) and ozone (O 3 ), were collected from monitors 20km within the participant’s residential address at SWAN visit 3 – 7 (1999-2005). Corresponding years cumulative levels of continuous CVD risk factors were used as covariates. CIMT, AD and plaque presence were assessed at visits 12/13 (2010-2012). Linear regression models were used to estimate the effect of early exposure to PM 2.5 and O 3 on mean and maximum CIMT. Logistic regression was applied to assess the effects of air pollutants on plaque presence. Full models were adjusted for CVD risk factors, including BMI, smoking, cholesterol, triglyceride, HDL-C, menopause status, hormone use, fasting blood glucose, insulin, diabetic medication and hypertension, and the extended models were further adjusted for SBP and inflammatory biomarkers (tPA, PAI-1 and CRP). Results: At time of carotid scan, women were on average 59.6±2.7 years old and a majority were postmenopausal (88.4%). The women were White (48.4%), Black (31.2%), Chinese (13.3%) and Hispanic (7.1%). Cumulative PM 2.5 significantly predicted maximum CIMT adjusting for CVD risk factors such that 1 μg/m 3 higher cumulative exposure to PM 2.5 over 5 years was associated with a 7.4 μm (95% CI: 0.4 – 14.4) greater maximum CIMT. The association was not significant after adjusting for SBP but was not attenuated by adjusting for inflammatory biomarkers. PM 2.5 was related to mean CIMT and AD when adjusting for site, SES and age, but not after adjusting for other CVD risk factors. Ozone levels were not associated with any of the outcomes. No association was found between air pollution exposure and plaque presence. Conclusion: Early cumulative PM 2.5 exposure was associated with maximum CIMT later in the post-menopausal period. This association was largely explained by SBP suggesting that early exposure to air pollutants may relate to higher values of CIMT potentially by increasing SBP.
Three week versus six week immobilisation for stable Weber B type ankle fractures: randomised, multicentre, non-inferiority clinical trial
Authors: Tero Kortekangas, Heidi Haapasalo, Tapio Flinkkilä, Pasi Ohtonen, Simo Nortunen, Heikki-Jussi Laine, Teppo LN Järvinen, Harri Pakarinen
Journal: BMJ (2019)

To determine whether treatment of isolated stable Weber B type ankle fractures with a cast or a simple orthotic device for three weeks produces non-inferior outcomes compared with conventional immobilisation in a cast for six weeks.Randomised, pragmatic, non-inferiority, clinical trial with blinded outcome assessment.Two major trauma centres in Finland, 22 December 2012 to 6 June 2016.247 skeletally mature patients aged 16 years or older with an isolated Weber B type fibula fracture and congruent ankle mortise in static ankle radiographs.Participants were randomly allocated to conventional six week cast immobilisation (n=84) or three week treatment either in a cast (n=83) or in a simple orthosis (n=80).The primary, non-inferiority, intention-to-treat outcome was the Olerud-Molander Ankle Score at 12 months (OMAS; range 0-100; higher scores indicate better outcomes and fewer symptoms). The predefined non-inferiority margin for the primary outcome was -8.8 points. Secondary outcomes were ankle function, pain, quality of life, ankle motion, and radiographic outcome. Follow-up assessments were performed at 6, 12, and 52 weeks.212 of 247 randomised participants (86%) completed the study. At 52 weeks, the mean OMAS was 87.6 (SD 18.3) in the six week cast group, 91.7 (SD 12.9) in the three week cast group, and 89.8 (SD 18.4) in the three week orthosis group. The between group difference at 52 weeks for the three week cast versus six week cast was 3.6 points (95% confidence interval -1.9 to 9.1, P=0.20), and for the three week orthosis versus six week cast was 1.7 points (-4.0 to 7.3, P=0.56). In both comparisons, the confidence intervals did not include the predefined inferiority margin of -8.8 points. The only statistically significant between group differences observed in the secondary outcomes and harms in the two primary comparisons were slight improvement in ankle plantar flexion and incidence of deep vein thrombosis, both in the three week orthosis group versus six week cast group.Immobilisation for three weeks with a cast or orthosis was non-inferior to conventional cast immobilisation for six weeks in the treatment of an isolated stable Weber B type fracture.ClinicalTrials.gov NCT01758835.
Assessment of systemic and metastatic neutrophilic inflammation in synchronously resected colorectal cancer and liver metastases.
Authors: Colin William Steele, Campbell SD Roxburgh, Donald C McMillan, Paul G. Horgan, Owen J Samson
Journal: Journal of Clinical Oncology (2019)

534 Background: Immunotherapy has proven a largely ineffective treatment for MMR proficient colorectal cancer (CRC). Resistance to immunotherapy is due to the immunosuppressive microenvironment of colorectal cancer, with CMS4 disease proving most aggressive. Using a cohort of synchronously resected CRC and metastases we examine the relationships between common immune cells in the circulation and microenvironment of primary and secondary CRC to assess microenvironmental determinants of outcome in metastatic CRC. Methods: 46 patients that had synchronous resection of primary CRC and liver metastasis at Glasgow Royal Infirmary were included. The relationships between Neutrophil lymphocyte ratios (NLR), tissue MPO and CXCR2 positive neutrophils, CD68 positive macrophages, and CD8 positive effector T cells and Klintrup-Makinen (KM) scores were quantified. Results: There was correlation between MPO and CXCR2 positive neutrophils (r = 0.668, P = 0.014) within metastases and both of these factors were independently associated with poor outcome ( P &lt; 0.001, P = 0.002 respectively). High CD8+ T cells numbers and KM grade in both primary and metastatic niches were independently associated with better outcome following synchronous resection (P &lt; 0.01). High systemic neutrophil counts (NLR) were associated with poor outcome in patients having synchronous resection (P = 0.001) and correlated with neutrophil numbers in metastases (r = 0.329, P = 0.05). MPO (P &lt; 0.001) and CXCR2 (P = 0.004) positive neutrophils within the metastatic niche and KM grade of the primary tumour (P = 0.002) remained negative prognostic indicators on multivariate analysis. Conclusions: While CD8+ T cells impact positively on prognosis, the negative impact of neutrophils within the metastatic niche is the strongest determinant of outcome in synchronously resected CRC. This study raises questions as to the heterogeneity of neutrophils within primary and metastatic colorectal cancer and whether negatively prognostic neutrophils can be phenotyped and therapeutically targeted.
Impact of Age of Onset, Puberty, and Glycemic Control Followed From Diagnosis on Incidence of Retinopathy in Type 1 Diabetes: The VISS Study
Authors: Maria Nordwall, Mats Fredriksson, Johnny Ludvigsson, Hans J. Arnqvist
Journal: Diabetes Care (2019)

OBJECTIVE To evaluate sex, age at diabetes onset, puberty, and HbA1c, with subjects followed from diabetes diagnosis and during different time periods, as risk factors for developing diabetic simplex and proliferative retinopathy. RESEARCH DESIGN AND METHODS In a population-based observational study, HbA1c for 451 patients diagnosed with diabetes before 35 years of age during 1983–1987 in southeast Sweden was followed for up to 18–24 years from diagnosis. Long-term mean weighted HbA1c (wHbA1c) was calculated. Retinopathy was evaluated by fundus photography and analyzed in relation to wHbA1c levels. RESULTS Lower wHbA1c, diabetes onset ≤5 years of age, and diabetes onset before puberty, but not sex, were associated with longer time to appearance of simplex retinopathy. Proliferative retinopathy was associated only with wHbA1c. The time to first appearance of any retinopathy decreased with increasing wHbA1c. Lower wHbA1c after ≤5 years’ diabetes duration was associated with later onset of simplex retinopathy but not proliferative retinopathy. With time, most patients developed simplex retinopathy, except for those of the category wHbA1c ≤50 mmol/mol (6.7%), for which 20 of 36 patients were without any retinopathy at the end of the follow-up in contrast to none of 49 with wHbA1c &amp;gt;80 mmol/mol (9.5%). CONCLUSIONS Onset at ≤5 years of age and lower wHbA1c the first 5 years after diagnosis are associated with longer duration before development of simplex retinopathy. There is a strong positive association between long-term mean HbA1c measured from diagnosis and up to 20 years and appearance of both simplex and proliferative retinopathy.
Full Dose or Reduced Dose Melphalan (MEL) for Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM): A Single Center Analysis on 187 Consecutive Patients
Authors: Annamaria Brioli, vom Hofe Felix, Lars-Olof Mügge, Sebastian Scholl, Inken Hilgendorf, Herbert G. Sayer, Olaposi Yomade, Thomas Ernst, Andreas Hochhaus, Marie von Lilienfeld-Toal
Journal: Blood (2018)