tbuckley/cabot-search huggingface dataset:
Calreticulin Ins5 and Del52 Mutations Impair Unfolded Protein and Oxidative Stress Responses in Hematopoietic Cells
Authors: Simona Salati, Elena Genovese, Zelia Prudente, Chiara Carretta, Niccolò Bartalucci, Valentina Pennucci, Samantha Ruberti, Chiara Rossi, Sebastiano Rontauroli, Carmela Mannarelli, Roberta Zini, Elisa Bianchi, Paola Guglielmelli, Enrico Tagliafico, Alessandro M. Vannucchi, Rossella Manfredini
Journal: Blood (2018)
Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology
Authors: Kathryn Oakland, Georgina Chadwick, James E East, Richard Guy, Adam Humphries, Vipul Jairath, Simon McPherson, Magdalena Metzner, A John Morris, Mike F Murphy, Tony Tham, Raman Uberoi, Andrew McCulloch Veitch, James Wheeler, Cuthbert Regan, Jonathan Hoare
Journal: Gut (2019)

This is the first UK national guideline to concentrate on acute lower gastrointestinal bleeding (LGIB) and has been commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). The Guidelines Development Group consisted of representatives from the BSG Endoscopy Committee, the Association of Coloproctology of Great Britain and Ireland, the British Society of Interventional Radiology, the Royal College of Radiologists, NHS Blood and Transplant and a patient representative. A systematic search of the literature was undertaken and the quality of evidence and grading of recommendations appraised according to the GRADE(Grading of Recommendations Assessment, Development and Evaluation) methodology. These guidelines focus on the diagnosis and management of acute LGIB in adults, including methods of risk assessment and interventions to diagnose and treat bleeding (colonoscopy, computed tomography, mesenteric angiography, endoscopic therapy, embolisation and surgery). Recommendations are included on the management of patients who develop LGIB while receiving anticoagulants (including direct oral anticoagulants) or antiplatelet drugs. The appropriate use of blood transfusion is also discussed, including haemoglobin triggers and targets.
Suboptimal dosing of common heart failure treatments in newly diagnosed patients with heart failure : a retrospective population-based cohort study in Sweden
Authors: G. Wikstrom, Kurt Boman, Mona Olofsson, J. Stalhammar, G. J. Bergman, M. Tornblom, V. Wintzell, B. Balas, S. Corda, Karl Lindmark
Journal: European Journal of Heart Failure (2017)
GP contract: £2.8bn deal gives English practices core funding boost for five years
Authors: Gareth Iacobucci
Journal: BMJ (2019)

General practices in England will be able to give all staff a 2% pay uplift this year, after a landmark £2.8bn (€3.2bn; $3.7bn) five year contract deal was agreed by the BMA’s General Practitioners Committee and NHS England.

The deal, described as the most significant change to the GP contract since 2004, will increase core practice funding by almost £1bn over the next five years. This will be supplemented by an extra £1.8bn over the same five years to support primary care networks, in which practices will work together to provide care to 30 000 to 50 000 patients across a wider geographic area.

The agreement will provide upfront investment of £405m this year, delivered through a combination of a 1.4% increase to core funding and a new network contract (delivered through a directed enhanced service (DES)) that will operate alongside practices’ standard contracts.

It also delivers a state backed indemnity scheme for all GPs. This means that, from April 2019, GPs (including those who work out of hours) and practice staff will no longer have to personally fund clinical …
Abstract 19658: Physicians on Cardiac Arrest Teams are Most Often Non-specialists With Limited Clinical Experience
Authors: Kasper G Lauridsen, Anders S Schmidt, Philip Caap, Rasmus S Aagaard, Bo Løfgren
Journal: Circulation (2015)

Introduction: The quality of in-hospital resuscitation is poor and may be affected by clinical experience and cardiopulmonary resuscitation (CPR) training. This study aimed to investigate the clinical experience, self-perceived skills, CPR training, and knowledge of guidelines on when to abandon resuscitation among physicians on cardiac arrest teams. Methods: This is a nationwide cross-sectional study in Denmark. Telephone interviews were performed with physicians on cardiac arrest teams in public somatic hospitals. Telephone interviews were performed using a structured questionnaire. Results: In total, 93 physicians (53% male) from 45 hospitals participated. Median age was 34 interquartile range (30-39) years. Participants were medical students working as locum physicians (5%), residents and fellows (79%), chief physicians (16%), and median postgraduate clinical experience was 48 (19-87) months. Most physicians (92%) felt confident in treating a cardiac arrest, while less felt confident in performing intubation (41%) and focused cardiac ultrasound (39%) during cardiac arrest. Median time since last CPR training was 4 months (2-10) and 48% had attended a European Resuscitation Council (ERC) Advanced Life Support (ALS) course. The majority (84%) felt confident in terminating resuscitation however only 9% were able to state ERC guidelines on when to abandon resuscitation. Conclusions: Physicians on Danish cardiac arrest teams are most often non-specialists with four or less years of clinical experience. Several physicians are not able to perform important clinical skills during resuscitation. Less than half of physicians have attended an ERC ALS course. Only very few physicians know the ERC guidelines on when to abandon resuscitation.
Feasibility of using a fitness tracker to assess activity level and toxicity in colorectal cancer patients.
Authors: William Harrell Ward, Caitlin R. Meeker, Maureen Hill, Elizabeth A. Handorf, Michael J. Hall, Elin R. Sigurdson, Igor A. Astsaturov, Crystal S. Denlinger, Sanjay S. Reddy, Joshua E. Meyer, Matthew R. Zibelman, David Madnick, Matthew Moccia, Efrat Dotan, Jeffrey M. Farma, Namrata Vijayvergia
Journal: Journal of Clinical Oncology (2019)

684 Background: Performance status (PS) is traditionally used to predict tolerance and morbidity associated with colorectal cancer (CRC) treatment. Monitoring activity level at the start of therapy using a wearable fitness tracker (Fitbit) may provide a more accurate estimate of overall patient (pt) PS and help predict treatment-related toxicity. Methods: With IRB approval, we prospectively enrolled CRC pts undergoing therapy into two cohorts: medical (M) and surgical (S). Our primary aim was to assess the feasibility of using Fitbit to assess activity level and toxicity. After documenting baseline ECOG PS, M and S pts wore Fitbit for four days while receiving chemotherapy or prior to surgery, respectively. Pts’ mean steps per day (SPD) were calculated, excluding days Fitbit was worn &lt; 12 hours. To stratify the prediction of toxicity risk, a cutoff of 5,000 SPD was selected and any post-operative complication (S pts) or ≥ grade 3 toxicity (M pts) was counted as toxicity. The study is ongoing to accrue 80 pts. Results: On interim analysis, 43 pts were evaluated for the primary aim. Seventy nine percent (34/43) of pts had at least 3 days with ≥ 12 hours of Fitbit usage, meeting the 75% feasibility endpoint. Forty pts (25 M, 15 S) had at least 1 day with ≥ 12 hours of Fitbit usage and had data available for analysis. Mean SPD for PS 0 and PS 1 pts was 7,183 and 3,214, respectively (p=0.01), and overall was 6,290 (SD 4,416). Eight M pts and 2 S pts experienced toxicity (Table). The rate of toxicity was 23% (7/30) in pts with PS 0 and 33% (3/10) in pts with PS 1. With SPD as cutoff, the toxicity rate was 11% (2/19) in pts with &gt; 5000, compared to 38% (8/21) in pts with &lt; 5000. Conclusions: We observed high rates of compliance with a fitness tracker in CRC pts. SPD serves as a useful identifier for toxicity and may be a better predictor than traditional PS. These findings provide rationale to study SPD in lieu of PS for risk stratification of patients undergoing therapy and possibly incorporate pre-habilitation programs in high-risk groups, though validation in larger studies is needed. [Table: see text]
Mitochondria-Responsive Drug Release along with Heat Shock Mediated by Multifunctional Glycolipid Micelles for Precise Cancer Chemo-Phototherapy
Authors: Yanan Tan, Yun Zhu, Lijuan Wen, Xiqin Yang, Xuan Liu, Tingting Meng, Suhuan Dai, Yuan Ping, Hong Yuan, Fuqiang Hu
Journal: Theranostics (2019)

Responsive drug release in tumor mitochondria is a pre-requisite for mitochondria-targeted drug delivery systems to improve the efficacy of this promising therapeutic modality. To this end, a photothermal stimulation strategy for mitochondria-responsive drug release along with heat shock is developed to maximize the antitumor effects with minimal side effects. Methods: This strategy relies on mitochondrial-targeted delivery of doxorubicin (DOX) through a photothermal and lipophilic agent IR-780 iodide (IR780)-modified glycolipid conjugates (CSOSA), which can synergistically triggers high-level reactive oxygen species (ROS) to kill tumor cells. Results: Specifically, upon laser irradiation, the photothermal conversion by IR780-CSOSA can not only weaken the hydrophobic interaction between the core of micelles and DOX and trigger unexpected micelle swelling to release DOX in mitochondria for the amplification of ROS, but also induce mitochondria-specific heat shock to promote the fast evolution of ROS at the same locus to eradicate cancer cells in a more effective way. Furthermore, IR780-CSOSA micelles may independently realize the real-time diagnosis and imaging on multiple tumor models. Deep penetration into tumors by IR780-CSOSA/DOX micelles can be manipulated under laser irradiation. Conclusion: Such multifunctional IR780-CSOSA/DOX micelles with integration of mitochondria-responsive drug release and heat shock are demonstrated to be superior to the non-mitochondria-responsive therapy. This study opens up new avenues for the future cancer diagnosis and treatment.
Association between Quality of Response and Outcome in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib
Authors: Paolo Strati, Mariela Sivina, Ekaterina Kim, Michael J. Keating, William G. Wierda, Alessandra Ferrajoli, Hagop M. Kantarjian, Zeev E. Estrov, Nitin Jain, Philip A. Thompson, Jan A. Burger
Journal: Blood (2018)
Combinatorial interactions of genetic variants in human cardiomyopathy
Authors: Dekker C. Deacon, Cassandra L. Happe, Chao Chen, Neil Tedeschi, Ana Maria Manso, Ting Li, Nancy D. Dalton, Qian Peng, Elie N. Farah, Yusu Gu, Kevin P. Tenerelli, Vivien D. Tran, Ju Chen, Kirk L. Peterson, Nicholas J. Schork, Eric D. Adler, Adam J. Engler, Robert S. Ross, Neil C. Chi
Journal: Nature Biomedical Engineering (2019)
Ebola in the Democratic Republic of the Congo: time to sound a global alert?
Authors: Lawrence Gostin, Alexandra Phelan, Alex Godwin Coutinho, Mark Eccleston-Turner, Ngozi Erondu, Oyebanji Filani, Tom Inglesby, Rebecca Katz, Allan Maleche, Jennifer B Nuzzo, Oyewale Tomori, Matthew Kavanagh
Journal: The Lancet (2019)
Histone Deacetylase Inhibitors with or without AKT Inhibition Potentially Increase the Efficacy of Daratumumab in Multiple Myeloma By Enhancing the Antibody-Dependent Cell-Mediated and Complement-Dependent Cytotoxicity As Well As Apoptosis
Authors: Mitsuhito Hirano, Yoichi Imai, Weng-Chit Ung, Kota Sato, Muneyoshi Futami, Arinobu Tojo
Journal: Blood (2018)
Incidence of a first venous thrombotic event in people with HIV in the Netherlands: a retrospective cohort study
Authors: Jaime F Borjas Howard, Casper Rokx, Colette Smit, Ferdinand W N M Wit, Elise D Pieterman, Karina Meijer, Bart Rijnders, Wouter F W Bierman, Y I G Vladimir Tichelaar, M. Van der Valk, M.E.E. Van Kasteren, E.F. Schippers, E.M.S. Leyten, F.P. Kroon, J.G. Den Hollander, S.H. Lowe, J.W. Mulder, K. Brinkman, E.H. Gisolf, P. Reiss, S. Zaheri, M. Hillebregt, M.E. van der Ende
Journal: The Lancet HIV (2019)
The Devil Is in the Details
Authors: Eli Ben-Chetrit, Linda Shavit, Ariella Tvito, Maya Korem, Alon Bnaya
Journal: New England Journal of Medicine (2019)

A 75-year-old woman was admitted to the hospital with a 4-month history of weight loss (total weight loss, 8 kg) and night sweats. She reported no fever, arthralgias, cough, abdominal pain, or diarrhea.
Abstract O.01: Epidemiology of Kawasaki disease in South Korea, 2009-2011
Authors: Gi Beom Kim, Ji Whan Han, Yong Won Park, Min Seob Song, Young Mi Hong, Sung Ho Cha, Dong Soo Kim
Journal: Circulation (2015)

We assessed the recent epidemiologic features of Kawasaki disease in South Korea from the nationwide survey conducted between 2009 and 2011. We collected data regarding the incidence, symptoms, treatment, and coronary complications associated with acute Kawasaki disease by sending questionnaires to the 100 hospitals that have pediatric residency programs. We received complete responses from 73 hospitals and partial responses from 14 hospitals. A total of 13,031 cases of Kawasaki disease were reported from the 87 hospitals (3,941 in 2009, 4,635 in 2010, and 4,455 in 2011). The male to female ratio was 1.44:1, and the median age at diagnosis was 28 months. From the questionnaires with complete responses, we noted that the incidence of Kawasaki disease per 100,000 children less than 5 years of age was 115.4 in 2009, 132.9 in 2010, and 134.4 in 2011 (average rate, 127.7). Kawasaki disease occurred more frequently during summer (June, July, and August) and during winter (December and January). The recurrence rate was 3.83% (387 of 10,100). The mean total duration of fever was 5.6 ± 2.4 days. The most common symptom was conjunctival injection (88.2%). The standard dose of intravenous immunoglobulin was administered to 93.6% (9,453 of 10,097), and non-responder rate was 11.6%. Coronary aneurysm occurred in 1.9% (180 of 9,028) though giant aneurysm developed in 0.26% (26 of 9,882) of patients over 3 years. Two patients had myocardial infarction. No mortality was reported during this period. In conclusion, the average annual incidence of Kawasaki disease in South Korea has continuously increased to 134.4 per 100,000 children less than 5 years of age in 2011, which is the second highest incidence of Kawasaki disease worldwide, following its incidence in Japan.
Treatment for <i>Helicobacter pylori</i> appears to reduce the incidence of gastric cancer: eradication effect or screening effect?
Authors: Yutaka Yamaji, Yoshihiro Hirata
Journal: Gut (2019)

We read with interest the report by Doorakkers et al describing the effect of Helicobacter pylori eradication in preventing the development of non-cardia gastric adenocarcinoma in a population-based Swedish cohort.1 The authors used nationwide Swedish registries to investigate the incidence of gastric adenocarcinoma after H. pylori eradication treatment. Specifically, standardised incidence ratios (SIRs) were used to examine the incidence of gastric adenocarcinoma in individuals treated for H. pylori compared with a background population of corresponding age, sex and calendar year distribution. The time trend of the SIRs after H. pylori eradication was assessed for up to 7.5 years.

The results showed that the risk of non-cardia gastric adenocarcinoma sharply decreased over time after …
Differential Association of Mitochondrial DNA Haplogroups J and H With the Methylation Status of Articular Cartilage: Potential Role in Apoptosis and Metabolic and Developmental Processes
Authors: Estefanía Cortés‐Pereira, Juan Fernández‐Tajes, Mercedes Fernández‐Moreno, María E. Vázquez‐Mosquera, Sara Relaño, Paula Ramos‐Louro, Alejandro Durán‐Sotuela, Andrea Dalmao‐Fernández, Natividad Oreiro, Francisco J. Blanco, Ignacio Rego‐Pérez
Journal: Arthritis & Rheumatology (2019)

To analyze the influence of mitochondrial genome variation on the DNA methylome of articular cartilage.DNA methylation profiling was performed using data deposited in the NCBI Gene Expression Omnibus database (accession no. GSE43269). Data were obtained for 14 cartilage samples from subjects with haplogroup J and 20 cartilage samples from subjects with haplogroup H. Subsequent validation was performed in an independent subset of 7 subjects with haplogroup J and 9 with haplogroup H by RNA-seq. Correlated genes were validated by real-time polymerase chain reaction in an independent cohort of 12 subjects with haplogroup J and 12 with haplogroup H. Appropriate analyses were performed using R Bioconductor and qBasePlus software, and gene ontology analysis was conducted using DAVID version 6.8.DNA methylation profiling revealed 538 differentially methylated loci, while whole-transcriptome profiling identified 2,384 differentially expressed genes, between cartilage samples from subjects with haplogroup H and those with haplogroup J. Seventeen genes showed an inverse correlation between methylation and expression. In terms of gene ontology, differences in correlations between methylation and expression were also detected between cartilage from subjects with haplogroup H and those with haplogroup J, highlighting a significantly enhanced apoptotic process in cartilage from subjects with haplogroup H (P = 0.007 for methylation and P = 0.019 for expression) and repressed apoptotic process in cartilage from subjects with haplogroup J (P = 0.021 for methylation), as well as a significant enrichment of genes related to metabolic processes (P = 1.93 × 10-4 for methylation and P = 6.79 x 10-4 for expression) and regulation of gene expression (P = 0.012 for methylation) in cartilage from subjects with haplogroup H, and to developmental processes (P = 0.015 for methylation and P = 8.25 x 10-12 for expression) in cartilage from subjects with haplogroup J.Mitochondrial DNA variation differentially associates with the methylation status of articular cartilage by acting on key mechanisms involved in osteoarthritis, such as apoptosis and metabolic and developmental processes.
Abstract P2-13-06: Long term clinical follow up of real world HER2-positive patients since the introduction of trastuzumab
Authors: S Ellegard, M Asowed, K Engvall, A-L Hallbeck, N Elander, O Stål
Journal: Cancer Research (2019)

Abstract Background: The prognosis for patients with HER2-positive early breast cancer (EBC) has improved dramatically since the introduction of adjuvant trastuzumab therapy. With the addition of pertuzumab the prognosis has improved further. However, there is a need to study how these results from clinical controlled trials are transferred to the real-world clinical setting. In this study we aim to investigate all patients with early HER2-positive breast cancer in our region since the introduction of adjuvant trastuzumab to evaluate the implementation of trastuzumab treatment regarding treatment coverage, prognosis and survival. Method: All patients with HER2-positve EBC, diagnosed between 2006 and 2014 in South-east Sweden were included in the study. The patients were identified using the Swedish national breast cancer register and then cross-referenced with data from the pathology department at each hospital in order to obtain complete coverage in a retrospective clinical follow up. In addition, data were collected from medical records for each patient to verify the actual given treatments and survival data. Results: Preliminary data is available. 611 patients were included with a median follow-up time of 5 years. During the follow-up period the number of patients diagnosed with HER2-positive EBC cancer doubled. 73% of all patients received trastuzumab treatment; however the coverage increased successively from 56% in 2006 to 83% in 2013. ER-positive patients did receive trastuzumab therapy to the same extent as ER-negative patients. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS) and breast cancer specific survival (BCSS) at 5 years were 85%, 76%, and 75% for patients not receiving trastuzumab. In the trastuzumab treated group LRFS, DRFS and BCSS was 95%, 85% and 83% respectively. The group not receiving trastuzumab was significantly older, had more frequently node negative disease and was not treated with chemotherapy to the same extent. Conclusion: A significant amount of early HER2-positive breast cancer patients did not receive adjuvant trastuzumab therapy between 2006 and 2014. In this group fewer patients received chemotherapy and despite less nodal involvement LRFS, DRFS and BCSS were poor for these patients. Citation Format: Ellegard S, Asowed M, Engvall K, Hallbeck A-L, Elander N, Stål O. Long term clinical follow up of real world HER2-positive patients since the introduction of trastuzumab [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-13-06.
Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase III KEYNOTE-181 study.
Authors: Takashi Kojima, Kei Muro, Eric Francois, Chih-Hung Hsu, Toshikazu Moriwaki, Sung-Bae Kim, Se-Hoon Lee, Jaafar Bennouna, Ken Kato, Shen Lin, Shi-Qui Qin, Paula Ferreira, Toshihiko Doi, Antoine Adenis, Peter C. Enzinger, Manish A. Shah, Ruixue Wang, Pooja Bhagia, S. Peter Kang, Jean-Philippe Metges
Journal: Journal of Clinical Oncology (2019)

2 Background: Patients with advanced esophageal cancer after first-line chemotherapy (chemo) have a poor prognosis and limited treatment options. We present results of the phase 3 KEYNOTE-181 study of pembrolizumab vs investigator’s choice chemo as second-line therapy for patients (pts) with advanced/metastatic squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ (NCT02564263). Methods: Eligible pts were randomized 1:1 to pembrolizumab 200 mg Q3W for up to 2 years or investigator’s choice chemo of paclitaxel, docetaxel, or irinotecan. Randomization was stratified by histology (SCC vs adenocarcinoma) and region (Asia vs rest of world). Primary end points were OS in the SCC, PD-L1 combined positive score (CPS) ≥10, and ITT populations. Results: 628 pts were randomized including 401 with SCC, and 222 with CPS ≥10. As of October 15, 2018, the median follow-up was 7.1 mo (pembrolizumab) vs 6.9 mo (chemo). Pembrolizumab was superior to chemo for OS in CPS ≥10 (N=222; median 9.3 vs 6.7 mo; HR 0.69; 95% CI 0.52-0.93; P=0.0074). The 12-mo OS rate in pts with CPS ≥10 was 43% vs 20%. There was clinically meaningful improvement in OS with pembrolizumab vs chemo in pts with SCC, but this was not statistically significant per prespecified boundaries (N=401; 8.2 mo vs 7.1 mo; HR 0.78; 95% CI 0.63-0.96; P=0.0095). In the ITT population, while directionally favorable, the difference in OS was not statistically significant (N=628; 7.1 mo vs 7.1 mo; HR 0.89; 95% CI 0.75-1.05; P=0.0560). Fewer pts had any-grade (64% vs 86%) or grade 3-5 (18% vs 41%) drug-related AEs with pembrolizumab vs chemo. Conclusion: Pembrolizumab significantly improved OS compared with chemo as second-line therapy for advanced esophageal cancer with PD-L1 CPS ≥10, with a more favorable safety profile. These data support pembrolizumab as a new second-line standard of care for esophageal cancer with PD-L1 CPS ≥10. The phase 3 KEYNOTE-590 study of pembrolizumab plus chemo as first-line therapy for advanced esophageal cancer is ongoing (NCT03189719). Clinical trial information: NCT02564263.
Efficacy Of 100 Mg SC Mepolizumab For Severe Eosinophilic Asthma (SEA) Across Blood Eosinophil Counts: Meta-Analysis
Authors: Steven W. Yancey, Frank Albers, Daniel J. Bratton, Eric S. Bradford, Namhee Kwon, Pascal Chanez, Christopher Licskai, Santiago Quirce
Journal: Journal of Allergy and Clinical Immunology (2019)