tbuckley/cabot-search huggingface dataset:
Estimating Left Ventricular Filling Pressure by Echocardiography
Authors: Oyvind S. Andersen, Otto A. Smiseth, Hisham Dokainish, Muaz M. Abudiab, Robert C. Schutt, Arnav Kumar, Kimi Sato, Serge Harb, Einar Gude, Espen W. Remme, Arne K. Andreassen, Jong-Won Ha, Jiaqiong Xu, Allan L. Klein, Sherif F. Nagueh
Journal: Journal of the American College of Cardiology (2017)

The diagnosis of heart failure may be challenging because symptoms are rather nonspecific. Elevated left ventricular (LV) filling pressure may be used to confirm the diagnosis, but cardiac catheterization is often not practical. Echocardiographic indexes are therefore used as markers of filling pressure.This study investigated the feasibility and accuracy of comprehensive echocardiography in identifying patients with elevated LV filling pressure.We conducted a multicenter study of 450 patients with a wide spectrum of cardiac diseases referred for cardiac catheterization. Left atrial volume index, in combination with flow velocities and tissue Doppler velocities, was used to estimate LV filling pressure. Invasively measured pressure was used as the gold standard.Mean left ventricular ejection fraction (LVEF) was 47%, with 209 patients having an LVEF <50%. Invasive measurements showed elevated LV filling pressure in 58% of patients. Clinical assessment had an accuracy of 72% in identifying patients with elevated filling pressure, whereas echocardiography had an accuracy of 87% (p < 0.001 vs. clinical assessment). The combination of clinical and echocardiographic assessment was incremental, with a net reclassification improvement of 1.5 versus clinical assessment (p < 0.001).Echocardiographic assessment of LV filling pressure is feasible and accurate. When combined with clinical data, it leads to a more accurate diagnosis, regardless of LVEF.
Confirmatory open-label, single-arm, multicenter phase 2 study of the BiTE antibody blinatumomab in patients (pts) with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL).
Authors: Max S. Topp, Nicola Goekbuget, Anthony Selwyn Stein, Ralf C. Bargou, Hervé Dombret, Adele K. Fielding, Josep M. Ribera, Robin Foà, Gerhard Zugmaier, Chris Holland, Tapan Maniar, Birgit Huber, Dirk Nagorsen, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2014)

7005^ Background: Blinatumomab, an investigational bispecific T-cell engaging (BiTE) antibody that directs cytotoxic T-cells to CD19-expressing target cells, has shown antileukemia activity in an exploratory study in adult r/r B-precursor ALL. We evaluated blinatumomab efficacy and toxicity in a large confirmatory phase 2 study. Methods: Pts (≥18 yrs) with Ph-negative r/r ALL (refractory; 1st relapse <12 mo; relapse post HSCT <12 mo; ≥2ndsalvage) were eligible. Blinatumomab was given by continuous IV infusion (4 wks on/2 wks off) for up to 5 cycles (cycle 1 only: 9 μg/d days 1-7; then 28 μg/d). The primary endpoint was complete remission (CR) or CR with partial hematological recovery (CRh*) within the first 2 cycles. Results: 189 pts were enrolled and received blinatumomab for a median (range) of 2 (1–5) cycles. Median age was 39 (18–79) yrs. As of Jan 2014 (primary analysis in Feb 2014), 43% of pts achieved CR/CRh*; 80% of responses occurred within cycle 1. CRs/CRh* were seen in all subgroups (Table). Regardless of causality, the most frequent adverse events (AEs) were pyrexia (59%), headache (35%) and febrile neutropenia (29%). The most frequent gr ≥3 AEs were febrile neutropenia (26%), anemia (15%) and neutropenia (15%); 2% had gr ≥3 cytokine release syndrome. The most common gr ≥3 nervous system disorders were headache (4%), encephalopathy (3%) and ataxia (2%). 3 (2%) pts had gr 5 AEs considered treatment-related (sepsis, n=2; candida infection, n=1). Conclusions: This large phase 2 study confirmed the antileukemia activity of single-agent blinatumomab in a difficult-to-treat population with r/r ALL. Clinical trial information: NCT01466179. Endpoint All patients N=189 Primary CR/CRh*, n (%)a Prior aHSCT (n=64) No prior aHSCT: No prior salvage (n=25) 1 prior salvage (n=47) ≥2 prior salvages or primary refractory (n=53) 82 (43) 95% CI, 36%–51% 30 (47) 10 (40) 24 (51) 18 (34) Secondary CR, n (%)a 64 (34) CRh*, n (%)a 18 (10) Median relapse-free survival, mo (95% CI) 5.9 (5.0–8.4) Median OS, mo (95% CI) 6.1 (4.2–7.5) Exploratory Responders n=82 Minimal residual disease (MRD) response, n (%)a 61 (74) Abbreviation: aHSCT, allogeneic stem cell transplantation. a First two cycles (central review).
A Two-Biomarker Model Predicts Mortality in the Critically Ill with Sepsis
Authors: Carmen Mikacenic, Brenda L. Price, Susanna Harju-Baker, D. Shane O’Mahony, Cassianne Robinson-Cohen, Frank Radella, William O. Hahn, Ronit Katz, David C. Christiani, Jonathan Himmelfarb, W. Conrad Liles, Mark M. Wurfel
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Improving the prospective identification of patients with systemic inflammatory response syndrome (SIRS) and sepsis at low risk for organ dysfunction and death is a major clinical challenge.To develop and validate a multibiomarker-based prediction model for 28-day mortality in critically ill patients with SIRS and sepsis.A derivation cohort (n = 888) and internal test cohort (n = 278) were taken from a prospective study of critically ill intensive care unit (ICU) patients meeting two of four SIRS criteria at an academic medical center for whom plasma was obtained within 24 hours. The validation cohort (n = 759) was taken from a prospective cohort enrolled at another academic medical center ICU for whom plasma was obtained within 48 hours. We measured concentrations of angiopoietin-1, angiopoietin-2, IL-6, IL-8, soluble tumor necrosis factor receptor-1, soluble vascular cell adhesion molecule-1, granulocyte colony-stimulating factor, and soluble Fas.We identified a two-biomarker model in the derivation cohort that predicted mortality (area under the receiver operator characteristic curve [AUC], 0.79; 95% confidence interval [CI], 0.74-0.83). It performed well in the internal test cohort (AUC, 0.75; 95% CI, 0.65-0.85) and the external validation cohort (AUC, 0.77; 95% CI, 0.72-0.83). We determined a model score threshold demonstrating high negative predictive value (0.95) for death. In addition to a low risk of death, patients below this threshold had shorter ICU length of stay, lower incidence of acute kidney injury, acute respiratory distress syndrome, and need for vasopressors.We have developed a simple, robust biomarker-based model that identifies patients with SIRS/sepsis at low risk for death and organ dysfunction.
The Aptamer ARC1779 Potently and Specifically Inhibits the Excessive von Willebrand Factor (vWF) Activity and vWF-Mediated Ex Vivo Platelet Function of Patients with Thrombotic Thrombocytopenic Purpura (TTP).
Authors: Bernd Jilma, Florian B. Mayr, Paul Knoebl, Alexander O. Spiel, Patricia G. Merlino, Robert Schaub, James C. Gilbert
Journal: Blood (2007)
Validation of the Royal Marsden Hospital (RMH) prognostic score in 100 patients with advanced sarcoma enrolled in early phase clinical trials at a major cancer center.
Authors: Michael Wagner, Kenneth R. Hess, David S. Hong, Chad Tang, Aung Naing, Siqing Fu, Filip Janku, Sarina Anne Piha-Paul, Ralph Zinner, Jennifer J. Wheler, Apostolia Maria Tsimberidou, Shreyaskumar Patel, Neeta Somaiah, Vinod Ravi, Robert S. Benjamin, Funda Meric-Bernstam, Vivek Subbiah
Journal: Journal of Clinical Oncology (2015)

10558 Background: Standard therapy refractory, metastatic and advanced sarcoma patients (pts) have few therapeutic options, and may benefit from enrollment in early stage clinical trials. The Royal Marsden Hospital (RMH) score predicts survival in pts prior to enrollment in Phase I clinical trials. We sought to validate the RMH score as a predictive marker in this population, and to assess if the presence of chromosomal translocations would predict benefit in Phase I clinical trials with targeted agents. Methods: Data from medical records of pts referred for enrollment in predominantly VEGF/VEGFR/mTOR inhibitor based Phase I clinical trials at M.D. Anderson Cancer Center were systematically reviewed. Pts were stratified according to RMH score (albumin, LDH, and number of metastatic sites), and the presence or absence of chromosomal translocations. Results: Among the 100 sarcoma pts [soft tissue (STS) (n = 79); bone (n = 21)] analyzed, the median age at trial enrollment was 48 (range 14-80). 46 pts (46%) were male. 26 pts (26%) had identifiable chromosomal translocations (17 with EWSR1 rearrangements). Clinical trial enrollment included 31 pts on VEGF agent alone, 16 pts on mTOR inhibitor alone, 13 pts on VEGF+mTOR, 11 pts on VEGF+chemotherapy, 6 pts on VEGF+mTOR+chemotherapy and 23 pts on other targeted agents. Median OS of pts with an RMH score of 0, 1, or 2 or greater was 18.9 mos, 7.5 mos, and 4.0 mos, respectively [HR 2.1 (1.5, 2.9) p < 0.0001]. Median PFS in pts with a translocation was 3.8 mos, and without was 3.5 mos [HR 0.97 (0.60, 1.57), p = 0.89]. Median OS in pts with translocation was 9.5 mos and without was 10.1 mos [HR 1.19 (0.74-1.94), p = 0.48]. Median PFS in STS pts was 4.2 mos (2.8-6.3), and bone sarcoma pts was 2.8 mos (2.0-7.6). Median OS in STS pts was 10.2 mos (95%CI: 8.4-15), and in bone sarcoma pts 7.8 mos (95%CI: 6.5-29). Clinical benefit rate (CR+PR+SD > 6 mos) across all Phase I trials was 35 % (4 PR+ 31 SD > 6 mos). Conclusions: RMH score is a significant predictor of overall survival in metastatic sarcoma pts treated on Phase I therapies. The presence of a chromosomal translocation had no effect on outcomes on sarcoma pts enrolled in Phase I trials.
Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency
Authors: Julien Cottineau, Molly C. Kottemann, Francis P. Lach, Young-Hoon Kang, Frédéric Vély, Elissa K. Deenick, Tomi Lazarov, Laure Gineau, Yi Wang, Andrea Farina, Marie Chansel, Lazaro Lorenzo, Christelle Piperoglou, Cindy S. Ma, Patrick Nitschke, Aziz Belkadi, Yuval Itan, Bertrand Boisson, Fabienne Jabot-Hanin, Capucine Picard, Jacinta Bustamante, Céline Eidenschenk, Soraya Boucherit, Nathalie Aladjidi, Didier Lacombe, Pascal Barat, Waseem Qasim, Jane A. Hurst, Andrew J. Pollard, Holm H. Uhlig, Claire Fieschi, Jean Michon, Vladimir P. Bermudez, Laurent Abel, Jean-Pierre de Villartay, Frédéric Geissmann, Stuart G. Tangye, Jerard Hurwitz, Eric Vivier, Jean-Laurent Casanova, Agata Smogorzewska, Emmanuelle Jouanguy
Journal: Journal of Clinical Investigation (2017)

Inborn errors of DNA repair or replication underlie a variety of clinical phenotypes. We studied 5 patients from 4 kindreds, all of whom displayed intrauterine growth retardation, chronic neutropenia, and NK cell deficiency. Four of the 5 patients also had postnatal growth retardation. The association of neutropenia and NK cell deficiency, which is unusual among primary immunodeficiencies and bone marrow failures, was due to a blockade in the bone marrow and was mildly symptomatic. We discovered compound heterozygous rare mutations in Go-Ichi-Ni-San (GINS) complex subunit 1 (GINS1, also known as PSF1) in the 5 patients. The GINS complex is essential for eukaryotic DNA replication, and homozygous null mutations of GINS component-encoding genes are embryonic lethal in mice. The patients' fibroblasts displayed impaired GINS complex assembly, basal replication stress, impaired checkpoint signaling, defective cell cycle control, and genomic instability, which was rescued by WT GINS1. The residual levels of GINS1 activity reached 3% to 16% in patients' cells, depending on their GINS1 genotype, and correlated with the severity of growth retardation and the in vitro cellular phenotype. The levels of GINS1 activity did not influence the immunological phenotype, which was uniform. Autosomal recessive, partial GINS1 deficiency impairs DNA replication and underlies intra-uterine (and postnatal) growth retardation, chronic neutropenia, and NK cell deficiency.
Early treatment cuts disability in rheumatoid arthritis, UK study suggests
Authors: Susan Mayor
Journal: BMJ (2017)

Patients with rheumatoid arthritis treated with disease modifying therapy early after symptom onset showed less progression in disability over time than those treated later, show the results of a 20 year follow-up UK study.1

Researchers prospectively followed up 602 patients (median age 56) with rheumatoid arthritis who were included in the Norfolk Arthritis Register. Participants were recruited from 1990 to 1994 and had their symptoms and disease activity assessed at baseline and at one, two, three, five, seven, 10, 15, …
Peficitinib, a JAK Inhibitor, in the Treatment of Moderate‐to‐Severe Rheumatoid Arthritis in Patients With an Inadequate Response to Methotrexate
Authors: A. J. Kivitz, S. R. Gutierrez‐Ureña, J. Poiley, M. C. Genovese, R. Kristy, K. Shay, X. Wang, J. P. Garg, A. Zubrzycka‐Sienkiewicz
Journal: Arthritis & Rheumatology (2016)

To evaluate the efficacy and safety of orally administered once-daily peficitinib in combination with methotrexate (MTX) in patients with moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response to MTX.In this multinational, phase IIb, randomized, double-blind, placebo-controlled, dose-ranging trial, patients with RA (n = 378) were treated with peficitinib 25 mg, 50 mg, 100 mg, or 150 mg plus MTX, or matching placebo plus MTX once daily for 12 weeks. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 12.ACR20 response rates at week 12 were 43.9%, 61.5% (P < 0.05 versus placebo), 46.4%, 57.7%, and 44.4% in the peficitinib 25 mg, 50 mg, 100 mg, 150 mg, and placebo groups, respectively. Significant decreases from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level were seen in the peficitinib 50 mg (P < 0.05) and 150 mg (P < 0.01) groups compared with placebo at week 12. Overall, the incidence of adverse events (AEs) was similar between peficitinib and placebo. The most common AEs were urinary tract infection (n = 22 [6%]), upper respiratory tract infection (n = 16 [4%]), and diarrhea (n = 16 [4%]). There were 3 cases of herpes zoster infection (2 in the peficitinib 100 mg group and 1 in the 150 mg group) and 2 cases of serious infection (viral infection in the peficitinib 100 mg group and erysipelas in the 150 mg group).The ACR20 response rate in the group receiving peficitinib 50 mg plus MTX was significantly different compared with the rate in patients receiving placebo, but there were no apparent dose-dependent responses, and the placebo response rate was high. Peficitinib plus MTX in patients with moderate-to-severe RA was well tolerated, with limited safety signals emerging.
Ombitasvir, paritaprevir, and ritonavir plus dasabuvir for 8 weeks in previously untreated patients with hepatitis C virus genotype 1b infection without cirrhosis (GARNET): a single-arm, open-label, phase 3b trial
Authors: Tania M Welzel, Tarik Asselah, Emily O Dumas, Stefan Zeuzem, David Shaw, Rawi Hazzan, Xavier Forns, Tami Pilot-Matias, Wenjing Lu, Daniel E Cohen, Jordan J Feld
Journal: The Lancet. Gastroenterology & hepatology (2017)
Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort
Authors: Elin Org, Yuna Blum, Silva Kasela, Margarete Mehrabian, Johanna Kuusisto, Antti J. Kangas, Pasi Soininen, Zeneng Wang, Mika Ala-Korpela, Stanley L. Hazen, Markku Laakso, Aldons J. Lusis
Journal: Genome biology (2017)

The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota–metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state. Our study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host–gut microbiota relationships.
Rapid magnetic isolation of extracellular vesicles via lipid-based nanoprobes
Authors: Yuan Wan, Gong Cheng, Xin Liu, Si-Jie Hao, Merisa Nisic, Chuan-Dong Zhu, Yi-Qiu Xia, Wen-Qing Li, Zhi-Gang Wang, Wen-Long Zhang, Shawn J. Rice, Aswathy Sebastian, Istvan Albert, Chandra P. Belani, Si-Yang Zheng
Journal: Nature Biomedical Engineering (2017)
Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial
Authors: Judith A Aberg, Craig A Sponseller, Douglas J Ward, Vladimir A Kryzhanovski, Stuart E Campbell, Melanie A Thompson
Journal: The Lancet HIV (2017)
Physician Breast Cancer Screening Recommendations Following Guideline Changes
Authors: Archana Radhakrishnan, Sarah A. Nowak, Andrew M. Parker, Kala Visvanathan, Craig Evan Pollack
Journal: JAMA Internal Medicine (2017)

Joshua Demb, MPH; Philip Chu, MS; Thomas Nelson, PhD; David Hall, PhD; Anthony Seibert, PhD; Ramit Lamba, MD; John Boone, PhD; Mayil Krishnam, MD; Christopher Cagnon, PhD; Maryam Bostani, PhD; Robert Gould, DSc; Diana Miglioretti, PhD; Rebecca Smith-Bindman, MD
Glutathione Primes T Cell Metabolism for Inflammation
Authors: Tak W. Mak, Melanie Grusdat, Gordon S. Duncan, Catherine Dostert, Yannic Nonnenmacher, Maureen Cox, Carole Binsfeld, Zhenyue Hao, Anne Brüstle, Momoe Itsumi, Christian Jäger, Ying Chen, Olaf Pinkenburg, Bärbel Camara, Markus Ollert, Carsten Bindslev-Jensen, Vasilis Vasiliou, Chiara Gorrini, Philipp A. Lang, Michael Lohoff, Isaac S. Harris, Karsten Hiller, Dirk Brenner
Journal: Immunity (2017)
Comparison of Efficacy and Safety Between Propranolol and Steroid for Infantile Hemangioma
Authors: Kyu Han Kim, Tae Hyun Choi, Yunhee Choi, Young Woon Park, Ki Yong Hong, Dong Young Kim, Yun Seon Choe, Hyunjung Lee, Jung-Eun Cheon, Jung-Bin Park, Kyung Duk Park, Hyoung Jin Kang, Hee Young Shin, Jae Hoon Jeong
Journal: JAMA Dermatology (2017)

There are limited data from randomized clinical trials comparing propranolol and steroid medication for treatment of infantile hemangioma (IH).To determine the efficacy and safety of propranolol compared with steroid as a first-line treatment for IH.This randomized clinical noninferiority trial tested the efficacy and safety of propranolol vs steroid treatment for IH at a single academic hospital. All participants were diagnosed with IH between June 2013 and October 2014, had normal heart function, and had not been previously treated for IH.The participants were randomly assigned to either the propranolol group or the steroid group. In the propranolol group, the patients were admitted, observed for adverse effects for 3 days after treatment initiation, and then released and treated as outpatients for 16 weeks (2 mg/kg/d). In the steroid group, the patients were seen as outpatients from the beginning and were also treated for 16 weeks (2 mg/kg/d).The primary efficacy variable was the response to treatment at 16 weeks, which was evaluated by the hemangioma volume using magnetic resonance imaging before and at 16 weeks after treatment initiation. While comparing the effect of medication between the groups, we monitored the adverse effects of both drugs.A total of 34 patients (15 boys, 19 girls; mean age, 3.3 months; range, 0.3-8.2 months) were randomized to receive either propranolol or steroid treatment (17 in each treatment group). Guardians for 2 patients in the steroid group withdrew their consent, and 1 patient in the propranolol group did not complete the efficacy test. The intention-to-treat analysis, applying multiple imputations, found the treatment response rate in the propranolol group to be 95.65%, and that of the steroid group was 91.94%. Because the difference in response rate between the groups was 3.71%, propranolol was considered noninferior. We found that there was no difference between the groups in safety outcomes.Our trial demonstrated that propranolol was not inferior to steroid with respect to therapeutic effects in IH.clinicaltrials.gov Identifier: NCT01908972.
Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015
Authors: Aaron J Cohen, Michael Brauer, Richard Burnett, H Ross Anderson, Joseph Frostad, Kara Estep, Kalpana Balakrishnan, Bert Brunekreef, Lalit Dandona, Rakhi Dandona, Valery Feigin, Greg Freedman, Bryan Hubbell, Amelia Jobling, Haidong Kan, Luke Knibbs, Yang Liu, Randall Martin, Lidia Morawska, C Arden Pope, Hwashin Shin, Kurt Straif, Gavin Shaddick, Matthew Thomas, Rita van Dingenen, Aaron van Donkelaar, Theo Vos, Christopher J L Murray, Mohammad H Forouzanfar
Journal: The Lancet (2017)

Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels.
A heart–brain–kidney network controls adaptation to cardiac stress through tissue macrophage activation
Authors: Katsuhito Fujiu, Munehiko Shibata, Yukiteru Nakayama, Fusa Ogata, Sahohime Matsumoto, Koji Noshita, Shingo Iwami, Susumu Nakae, Issei Komuro, Ryozo Nagai, Ichiro Manabe
Journal: Nature Medicine (2017)
Therapeutic applications of BCI technologies
Authors: Dennis J. McFarland, Janis Daly, Chadwick Boulay, Muhammad A. Parvaz
Journal: Brain-Computer Interfaces (2017)

Brain-computer interface (BCI) technology can restore communication and control to people who are severely paralyzed. There has been speculation that this technology might also be useful for a variety of diverse therapeutic applications. This survey considers possible ways that BCI technology can be applied to motor rehabilitation following stroke, Parkinson's disease, and psychiatric disorders. We consider potential neural signals as well as the design and goals of BCI-based therapeutic applications. These diverse applications all share a reliance on neuroimaging and signal-processing technologies. At the same time, each of these potential applications presents a series of unique challenges.
(32) Porokeratosis of Mibelli
Authors: M.J. Cheesbrough, P.D.C. Kinmont
Journal: British Journal of Dermatology (1978)

Journal Article (32) Porokeratosis of Mibelli Get access M.J. Cheesbrough, M.J. Cheesbrough General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar P.D.C. Kinmont P.D.C. Kinmont General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue s16, 1 December 1978, Pages 62–63, https://doi.org/10.1111/j.1365-2133.1978.tb15254.x Published: 01 December 1978