tbuckley/cabot-search huggingface dataset:
US Food and Drug Administration Approval of New Drugs Based on Noninferiority Trials in Oncology
Authors: Bishal Gyawali, Aaron S. Kesselheim
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
Highly efficient therapeutic gene editing of human hematopoietic stem cells
Authors: Yuxuan Wu, Jing Zeng, Benjamin P. Roscoe, Pengpeng Liu, Qiuming Yao, Cicera R. Lazzarotto, Kendell Clement, Mitchel A. Cole, Kevin Luk, Cristina Baricordi, Anne H. Shen, Chunyan Ren, Erica B. Esrick, John P. Manis, David M. Dorfman, David A. Williams, Alessandra Biffi, Carlo Brugnara, Luca Biasco, Christian Brendel, Luca Pinello, Shengdar Q. Tsai, Scot A. Wolfe, Daniel E. Bauer
Journal: Nature Medicine (2019)
Child poverty in Scotland set to worsen despite targets set in 2017
Authors: Bryan Christie
Journal: BMJ (2019)

Child poverty in Scotland is projected to hit a 20 year high in the next few years, despite ambitious targets set by the Scottish government to reduce the problem.

This warning comes from the Resolution Foundation, which says that radical action will be needed if politicians are serious about meeting their targets.

Their report Wrong Direction 1 blames welfare policies introduced in 2015 by the UK government for the projected increase. These include a four year freeze on working …
The Effect of Liquid Meal Replacements on Cardiometabolic Risk Factors in Overweight/Obese Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Jarvis C. Noronha, Stephanie K. Nishi, Catherine R. Braunstein, Tauseef A. Khan, Sonia Blanco Mejia, Cyril W.C. Kendall, Hana Kahleová, Dario Rahelić, Jordi Salas-Salvadó, Lawrence A. Leiter, John L. Sievenpiper
Journal: Diabetes Care (2019)

The evidence for liquid meal replacements in diabetes has not been summarized. Our objective was to synthesize the evidence of the effect of liquid meal replacements on cardiometabolic risk factors in overweight/obese individuals with type 2 diabetes.Data sources included MEDLINE, EMBASE, and the Cochrane Library through 10 December 2018. We included randomized trials of ≥2 weeks assessing the effect of liquid meal replacements in weight loss diets compared with traditional weight loss diets on cardiometabolic risk factors in overweight/obese subjects with type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation).Nine trial comparisons (N = 961 [median follow-up 24 weeks]) met eligibility criteria. Mean differences were for body weight -2.37 kg (95% CI -3.30 to -1.44), BMI -0.87 kg/m2 (-1.31 to -0.42), body fat -1.66% (-2.17 to -1.15), waist circumference -2.24 cm (-3.72 to -0.77), HbA1c -0.43% (-0.66 to -0.19) (-4.7 mmol/mol [-7.2 to -2.1]), fasting glucose -0.63 mmol/L (-0.99 to -0.27), fasting insulin -11.83 pmol/L (-23.11 to -0.54), systolic blood pressure -4.97mmHg (-7.32 to -2.62), and diastolic blood pressure -1.98 mmHg (-3.05 to -0.91). There was no effect on blood lipids. The overall certainty of the evidence was low to moderate owing to imprecision and/or inconsistency.Liquid meal replacements in weight loss diets lead to modest reductions in body weight, BMI, and systolic blood pressure, and reductions of marginal clinical significance in body fat, waist circumference, HbA1c, fasting glucose, fasting insulin, and diastolic blood pressure. More high-quality trials are needed to improve the certainty in our estimates.
Abstract 249: Primary Ventricular Fibrillation in ST-Elevation Myocardial Infarction Remains the Major Early Complication
Authors: Fernando Rosell-Ortiz, Francisco J Mellado-Vergel, Manuel Ruiz-bailén
Journal: Circulation (2011)

Some data from in-hospital cohorts show that Primary Ventricular Fibrillation (pVF) is declining in patients with ST-Elevation Myocardial Infarction (STEMI). Our objective is to assess the current incidence, associated factors and early mortality of pVF in a pre-hospital cohort of STEMI patients. Methods Prospective cohort of unselected STEMI patients cared for by pre-hospital emergency teams in Andalusia. We analyzed the documented pVF episodes either as initial rhythm or as a complication before in-hospital admission. Univariate and multivariate analysis. Results Of 5529 patients included, 412(7.45%) had at least one pVF episode. All patients were treated, 383(92.9%) were admitted and 288(69.9%) were discharged alive. Univariate analysis: pVF patients are: younger (56.7vs64.1,p&lt;0.0001), male (8.2% vs 5.%,p=0.001), no diabetes (4.8% vs 8.5%,p&lt; 0.0001), no hypertension (6.2% vs 8.9%, p&lt;0.0001), no dyslipidemia (5.7% vs 8.5%,p&lt;0.0001), no prior myocardial infarction (5.6% vs 7.7%,p=0.04), shorter interval from onset-symptoms to call-EMS (63.6 vs 169.8,p&lt;0.0001, median in minutes, p&lt;0.0001), larger infarctions (≥5 leads, 7.9% vs 6.3%,p=0.03), hypotension (95.4 vs 125 mmHG,p&lt;0.0001), higher early mortality: on scene (36,3% vs 7%,p&lt;0.0001) and in-hospital(13.5% vs 6.6%,p&lt;0.0001). 1-month and 1-year mortality were not associated to pVF. pVF patients received more rescue PCI (12.6% vs 7.2%,p&lt;0.0001) but no other reperfusion treatments. Multivariate analysis: pVF was associated to younger patients (OR:0.978;CI 0969-0.987,p&lt;0.0001), neither diabetes (OR:1.063;CI 1.150-2.234,p=0.005) nor dyslipidemia (OR:1.429;CI:1.091-1.872,p=0.01), hypotension (OR:0.986;CI 0983-0.989,p&lt;0.0001), shorter interval symptoms (OR:0.998;CI:0997-0.999,p&lt;0.0001) and early mortality (OR:2.390;CI 1.673-3.415,p&lt;0.0001). They receive more rescue-PCI (OR:1.938;CI 1.362-2.759,p&lt;0.0001). Conclusions. The incidence of pVF in STEMI remains high when testing a pre-hospital cohort. It's an early complication, in younger patients without traditional risk factors, with hypotension during the episode and with high early mortality. Nevertheless, after discharge, the prognosis is as good as in no pVF patients.
CLO19-061: Clinical Features and Prognosis of Head and Neck Cancer in Patients With Esophagus Cancer
Authors: Weihui Zheng, Weimin Mao, Jianlin Lou
Journal: Journal of the National Comprehensive Cancer Network (2019)

Objective: This study investigated the clinical and prognostic characteristics of head and neck cancer in patients with esophagus cancer. Methods: Information on 124 patients with head and neck cancer with esophagus cancer was collected from head and neck and thoracic surgery departments between January 2007 and December 2016 in Zhejiang Cancer Hospital. The incidence of synchronous and metachronous cancer was described. The clinical characteristics and prognosis were also compared in synchronous and metachronous cancer. The number of hospitalization and different treatments were analyzed the affection on the survival time. Results: 32 cases were synchronous cancer and 72 cases were metachronous cancer. The rate of surgery and the number of hospitalization were significantly different in synchronous and metachronous cancer (χ 2 =4.661; P &lt;.05). The 1-year, 3-year, and 5-year survival rates were 39.9%, 19.9%, and15.2%, respectively in patients with synchronous cancer and the mean survival time was 18.4±6.2 months. In contrast, the survival rates were 78.7%, 77.8%, and 59.1% respectively in metachronous cancer and the mean survival time was 122.2±17.2 months. There was a significant difference between the 2 groups (χ 2 =10.934; P =.001). The number of hospitalizations greater than or equal to 5 times were significantly different from those with less than 5 times (χ 2 =10.574; P =.001). There was no statistically significant difference in the improvement of OS by single operation, chemotherapy, and target treatment. The P value was only slightly less than .05 in the radiation therapy. Conclusions: Head and neck cancer in patients with esophagus cancer have a high survival rate through active combined-modality therapies, especially in metachronous carcinoma.
Unseen Trauma—Our Responsibility to Discover
Authors: Michael B. Foote
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study
Authors: Michael R Savona, Olatoyosi Odenike, Philip C Amrein, David P Steensma, Amy E DeZern, Laura C Michaelis, Stefan Faderl, Wael Harb, Hagop Kantarjian, James Lowder, Aram Oganesian, Mohammad Azab, Guillermo Garcia-Manero
Journal: The Lancet Haematology (2019)
Tolerizing CTL by Sustained Hepatic PD-L1 Expression Provides a New Therapy Approach in Mouse Sepsis
Authors: Andreas von Knethen, Anne Schäfer, Laura Kuchler, Tilo Knape, Urs Christen, Edith Hintermann, Beate Fißlthaler, Katrin Schröder, Ralf P. Brandes, Berit Genz, Kerstin Abshagen, Brigitte M. Pützer, Lisa K. Sha, Andreas Weigert, Shahzad N. Syed, Martin Schulz, Ajay M. Shah, Andreas Ernst, Mateusz Putyrski, Fabian Finkelmeier, Marina Pesic, Florian Greten, Michael Hogardt, Volkhard A. J. Kempf, Sandra Gunne, Michael J. Parnham, Bernhard Brüne
Journal: Theranostics (2019)

Cytotoxic T lymphocyte (CTL) activation contributes to liver damage during sepsis, but the mechanisms involved are largely unknown.Understanding the underlying principle will permit interference with CTL activation and thus, provide a new therapeutic option.Methods: To elucidate the mechanism leading to CTL activation we used the Hepa1-6 cell line in vitro and the mouse model of in vivo polymicrobial sepsis, following cecal-ligation and -puncture (CLP) in wildtype, myeloid specific NOX-2, global NOX2 and NOX4 knockout mice, and their survival as a final readout.In this in vivo setting, we also determined hepatic mRNA and protein expression as well as clinical parameters of liver damage -aspartate-and alanine amino-transaminases.Hepatocyte specific overexpression of PD-L1 was achieved in vivo by adenoviral infection and transposon-based gene transfer using hydrodynamic injection.Results: We observed downregulation of PD-L1 on hepatocytes in the murine sepsis model.Adenoviral and transposon-based gene transfer to restore PD-L1 expression, significantly improved survival and reduced the release of liver damage, as PD-L1 is a co-receptor that negatively regulates T cell function.Similar protection was observed during pharmacological intervention using recombinant PD-L1-Fc.N-acetylcysteine blocked the downregulation of PD-L1 suggesting the involvement of reactive oxygen species.This was confirmed in vivo, as we observed significant upregulation of PD-L1 expression in NOX4 knockout mice, following sham operation, whereas its expression in global as well as myeloid lineage NOX2 knockout mice was comparable to that in the wild type animals.PD-L1 expression remained high following CLP only in total NOX2 knockouts, resulting in significantly reduced release of liver damage markers. Conclusion:These results suggest that, contrary to common assumption, maintaining PD-L1 expression on hepatocytes improves liver damage and survival of mice during sepsis.We conclude that administering recombinant PD-L1 or inhibiting NOX2 activity might offer a new therapeutic option in sepsis.
Stromal Tumor-infiltrating Lymphocytes in NRG Oncology/NSABP B-31 Adjuvant Trial for Early-Stage HER2-Positive Breast Cancer
Authors: Rim S Kim, Nan Song, Patrick G Gavin, Roberto Salgado, Hanna Bandos, Zuzana Kos, Giuseppe Floris, Gert G G M Van den Eynden, Sunil Badve, Sandra Demaria, Priya Rastogi, Louis Fehrenbacher, Eleftherios P Mamounas, Sandra M Swain, D Lawrence Wickerham, Joseph P Costantino, Soonmyung Paik, Norman Wolmark, Charles E Geyer, Peter C Lucas, Katherine L Pogue-Geile
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract We retrospectively assessed association of stromal tumor-infiltrating lymphocytes (sTILs) with clinical outcomes and molecular variables reportedly predictive of trastuzumab-benefit in National Surgical Adjuvant Breast and Bowel Project B-31 (N = 2130). sTILs were assessed in 1581 eligible B-31 cases utilizing all available hematoxylin and eosin slides. Mean concordance between main reviewer and six other pathologists was 90.8% in 100 cases. Cox regressions were used to calculate hazard ratios (HRs). In chemotherapy and trastuzumab added to chemotherapy arms, increases in sTILs, as a semicontinuous variable (combined arms HR = 0.42, 95% confidence interval = 0.27 to 0.64, two-sided P &lt; .001) or as lymphocyte-predominant breast cancer with more than 50% sTILs (combined arms HR = 0.65, 95% confidence interval = 0.49 to 0.86, two-sided P = .003) were statistically significantly associated with improved disease-free survival. There was no association of sTILs with trastuzumab benefit. However, higher sTILs were statistically significantly associated with higher trastuzumab benefit groups by 8-gene prediction model (two-sided P &lt; .001). Neither PIK3CA mutations nor Fc-gamma-receptor polymorphisms were associated with sTILs. sTILs may have utility as a prognostic biomarker identifying HER2-positive early breast cancer at low recurrence risk.
Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair
Authors: Anubhav N. Mathur, Bahar Zirak, Ian C. Boothby, Madge Tan, Jarish N. Cohen, Thea M. Mauro, Pooja Mehta, Margaret M. Lowe, Abul K. Abbas, Niwa Ali, Michael D. Rosenblum
Journal: Immunity (2019)
Reclassifying cannabis based drugs has not made accessing them easier, MPs hear
Authors: Ingrid Torjesen
Journal: BMJ (2019)

Patients are struggling to access cannabis based medicinal products despite a law change last November allowing specialist doctors to prescribe them,1 MPs on the Commons Health and Social Care Committee have been told at an evidence gathering session for its inquiry into medicinal cannabis.

This even includes patients such as Alfie Dingley2—a child with intractable epilepsy whose case was instrumental in changing the law, who was granted access to a cannabis based medicinal product through special licensing arrangements.3 That licence was revoked after the law change, and Peter Carroll, director of the campaign group End of Pain, said he was “shocked and horrified” that the local trust refused to prescribe the product.

Sally Davies, chief medical officer …
Executive functions are cognitive gadgets
Authors: Senne Braem, Bernhard Hommel
Journal: Behavioral and Brain Sciences (2019)

Many psychologists and neuroscientists still see executive functions as independent, domain-general, supervisory functions that are often dissociated from more "low-level" associative learning. Here, we suggest that executive functions very much build on associative learning, and argue that executive functions might be better understood as culture-sensitive cognitive gadgets, rather than as ready-made cognitive instincts.
Letter by El-Battrawy et al Regarding Article, “Female Sex Is a Risk Modifier Rather Than a Risk Factor for Stroke in Atrial Fibrillation: Should We Use a CHA <sub>2</sub> DS <sub>2</sub> -VASc-VA Score Rather Than CHA <sub>2</sub> DS <sub>2</sub> -VASc?”
Authors: Ibrahim El-Battrawy, Martin Borggrefe, Ibrahim Akin
Journal: Circulation (2018)
Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study
Authors: Suzanne Trudel, Nikoletta Lendvai, Rakesh Popat, Peter M. Voorhees, Brandi Reeves, Edward N. Libby, Paul G. Richardson, Axel Hoos, Ira Gupta, Veronique Bragulat, Zangdong He, Joanna B. Opalinska, Adam D. Cohen
Journal: Blood Cancer Journal (2019)

Abstract Interim analyses of a phase I study with GSK2857916, an antibody–drug conjugate against B cell maturation antigen, have previously reported a 60% overall response and 7.9 months progression-free survival in relapsed/refractory multiple myeloma (MM). We provide updated safety and efficacy results of the BMA117159 trial following an additional 14 months' follow-up. This open-label, first-in-human, phase I study was conducted at nine centres in the USA, Canada and the UK, and included adults with MM and progressive disease after stem cell transplantation, alkylators, proteasome inhibitors, and immunomodulators. In part 1, the recommended dose of 3.4 mg/kg was identified; in part 2, patients received GSK2857916 3.4 mg/kg once every 3 weeks. Selected part 2 safety/tolerability and efficacy endpoints are reported. Twenty-one (60.0%; 95% confidence interval (CI) 42.1–76.1) of 35 patients achieved partial response or better, including two stringent complete responses and three complete responses. The median progression-free survival was 12 months and median duration of response was 14.3 months. Thrombocytopenia and corneal events were commonly reported; no new safety signals were identified. GSK2857916 was well tolerated and demonstrated a rapid, deep and durable response in heavily pre-treated patients with relapsed/refractory MM, consolidating the interim analyses conclusions that GSK2857916 is a promising treatment for these patients.
CD47-Targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer
Authors: Bernhard Kiss, Nynke S. van den Berg, Robert Ertsey, Kelly McKenna, Kathleen E. Mach, Chiyuan Amy Zhang, Jens-Peter Volkmer, Irving L. Weissman, Eben L. Rosenthal, Joseph C. Liao
Journal: Clinical Cancer Research (2019)

Near-infrared photoimmunotherapy (NIR-PIT) is a localized molecular cancer therapy combining a photosensitizer-conjugated mAb and light energy. CD47 is an innate immune checkpoint widely expressed on bladder cancer cells, but absent from luminal normal urothelium. Targeting CD47 for NIR-PIT has the potential to selectively induce cancer cell death and minimize damage to normal urothelium.The cytotoxic effect of NIR-PIT with anti-CD47-IR700 was investigated in human bladder cancer cell lines and primary human bladder cancer cells derived from fresh surgical samples. Phagocytosis assays were performed to evaluate macrophage activity after NIR-PIT. Anti-CD47-IR700 was administered to murine xenograft tumor models of human bladder cancer for in vivo molecular imaging and NIR-PIT.Cytotoxicity in cell lines and primary bladder cancer cells significantly increased in a light-dose-dependent manner with CD47-targeted NIR-PIT. Phagocytosis of cancer cells significantly increased with NIR-PIT compared with antibody alone (P = 0.0002). In vivo fluorescence intensity of anti-CD47-IR700 in tumors reached a peak 24-hour postinjection and was detectable for at least 14 days. After a single round of CD47-targeted NIR-PIT, treated animals showed significantly slower tumor growth compared with controls (P < 0.0001). Repeated CD47-targeted NIR-PIT treatment further slowed tumor growth (P = 0.0104) and improved survival compared with controls.CD47-targeted NIR-PIT increased direct cancer cell death and phagocytosis resulting in inhibited tumor growth and improved survival in a murine xenograft model of human bladder cancer.
Management of ocular allergy
Authors: Andrea Leonardi, Diana Silva, Daniel Perez Formigo, Banu Bozkurt, Vibha Sharma, Pia Allegri, Carmen Rondon, Virginia Calder, Dermot Ryan, Marek L. Kowalski, Luis Delgado, Serge Doan, Jean L. Fauquert
Journal: Allergy (2019)

The treatment and management of ocular allergy (OA) remain a major concern for different specialties, including allergists, ophthalmologists, primary care physicians, rhinologists, pediatricians, dermatologists, clinical immunologists, and pharmacists. We performed a systematic review of all relevant publications in MEDLINE, Scopus, and Web Science including systematic reviews and meta-analysis. Publications were considered relevant if they addressed treatments, or management strategies of OA. A further wider systematic literature search was performed if no evidence or good quality evidence was found. There are effective drugs for the treatment of OA; however, there is a lack an optimal treatment for the perennial and severe forms. Topical antihistamines, mast cell stabilizers, or double-action drugs are the first choice of treatment. All of them are effective in reducing signs and symptoms of OA. The safety and optimal dosing regimen of the most effective topical anti-inflammatory drugs, corticosteroids, are still a major concern. Topical calcineurin inhibitors may be used in steroid-dependent/resistant cases of severe allergic keratoconjunctivitis. Allergen-specific immunotherapy may be considered in cases of failure of first-line treatments or to modify the natural course of OA disease. Based on the current wealth of publications and on the collective experience, recommendations on management of OA have been proposed.
Biochemical Characterization of GS-4059 As a Potent and Selective Covalent Irreversible Inhibitor of Bruton's Tyrosine Kinase
Authors: Albert Liclican, Weimei Xing, Loredana Serafini, Ting Wang, Kathy Brendza, Justin Lutz, Adrian S. Ray, Brian Schultz, Roman Sakowicz, Joy Y. Feng
Journal: Blood (2016)