tbuckley/cabot-search huggingface dataset:
Modulation of Inflammatory Arthritis in Mice by Gut Microbiota Through Mucosal Inflammation and Autoantibody Generation
Authors: Widian K. Jubair, Jason D. Hendrickson, Erin L. Severs, Hanna M. Schulz, Sumitra Adhikari, Diana Ir, Jose D. Pagan, Robert M. Anthony, Charles E. Robertson, Daniel N. Frank, Nirmal K. Banda, Kristine A. Kuhn
Journal: Arthritis & Rheumatology (2018)

Objective Observations of microbial dysbiosis in patients with rheumatoid arthritis (RA) have raised interest in studying microbial–mucosal interactions as a potential trigger of RA. Using the murine collagen‐induced arthritis (CIA) model, we undertook this study to test our hypothesis that microbiota modulate immune responses leading to autoimmune arthritis. Methods CIA was induced by immunization of mice with type II collagen (CII) in adjuvant on days 0 and 21, with arthritis appearing on days 23 and 24. Intestinal microbiota were profiled by 16S ribosomal RNA sequencing every 7 days during the course of CIA, and intestinal mucosal changes were evaluated on days 14 and 35. Then, microbiota were depleted either early (7 days before immunization) or late (day 21 after immunization) by administration of broad‐spectrum antibiotics. Disease severity, autoantibody and systemic cytokine production, and intestinal mucosal responses were monitored in the setting of microbial reduction. Results Significant dysbiosis and mucosal inflammation occurred early in CIA, prior to visible arthritis, and continued to evolve during the course of disease. Depletion of the microbiota prior to the induction of CIA resulted in an ~40% reduction in disease severity and in significantly reduced levels of serum inflammatory cytokines and anti‐CII antibodies. In intestinal tissue, production of interleukin‐17A (IL‐17A) and IL‐22 was delayed. Unexpectedly, microbial depletion during the late phase of CIA resulted in a &gt;50% decrease in disease severity. Anti‐CII antibodies were mildly reduced but were significantly impaired in their ability to activate complement, likely due to altered glycosylation profiles. Conclusion These data support a model in which intestinal dysbiosis triggers mucosal immune responses that stimulate T and B cells that are key for the development of inflammatory arthritis.
Bawa-Garba to appeal High Court ruling and may challenge manslaughter conviction
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The trainee paediatrician Hazida Bawa-Garba is to appeal the High Court’s ruling to strike her from the UK medical register.1

Bawa-Garba has instructed the barristers James Laddie QC, who specialises in employment and discrimination law, and Sarah Hannett to represent her. She may also appeal her 2015 conviction for gross negligence manslaughter over the death of …
Combined PET/DCE-MRI in a Rabbit Model of Atherosclerosis
Authors: Claudia Calcagno, Olivier Lairez, Julie Hawkins, Steven W. Kerr, Melanie S. Dugas, Thomas Simpson, Jelle Epskamp, Philip M. Robson, Mootaz Eldib, Ilda Bander, Purushothaman K-Raman, Sarayu Ramachandran, Alison Pruzan, Audrey Kaufman, Venkatesh Mani, Alexander Ehlgen, Heiko G. Niessen, John Broadwater, Zahi A. Fayad
Journal: JACC. Cardiovascular imaging (2018)
What is the most important predictor of renal function after opened and robotic partial nephrectomy? A propensity score matched study.
Authors: Ngoc Ha Nguyen, Jae Young Joung, Sangchul Lee, Hakmin Lee, Young Dong Yu, Chang Wook Jeong, Sung Kyu Hong, Sang Eun Lee, Seok-Soo Byun
Journal: Journal of Clinical Oncology (2018)

701 Background: This study was designed to investigate the parameters that predict the short term and long term renal function after opened partial nephrectomy (OPN) and robot-assisted partial nephrectomy (RPN). Methods: Medical records of 896 patients who underwent OPN and RPN between Feb 2004 to Apr 2017 at our institution were retrospectively reviewed. The propensity scores matching between of OPN and RPN group were performed with a ratio of 1:1. Postoperative outcomes were compared and multivariate logistic regression was performed to identify the parameters influencing acute kidney injury (AKI) and chronic kidney disease (CKD) progression. Results: No significant differences of preoperative characteristics were observed between two study groups after propensity score matching. RPN was significantly associated with longer warm ischemic time (WIT) (p &lt; 0.001); yet, estimated blood loss (EBL), positive surgical margin (PSM) rate, major postoperative complication and CKD progression were significantly lower in RPN group (p values were &lt; 0.001; 0.033; &lt; 0.001; &lt; 0.001 and 0.005 respectively). Multivariate analysis exhibited RPN is more favorable than OPN in terms of preserving renal function. Patients with a higher baseline estimated glomerular filtration rate (eGFR) were significantly associated with greater risk of AKI (OR = 1.036; 95% CI of OR 1.021-1.052; p &lt; 0.001), but reduced risk of CKD progression (OR = 0.975; 95% CI of OR 0.955-0.994; p = 0.011). Other independent predictors of CKD progression included WIT (p = 0.025), age (p = 0.035), higher BMI (0.041) and diabetes mellitus history (p = 0.035). Conclusions: Age, BMI, diabetes mellitus history, baseline eGFR and WIT were the independent predictors of CKD progression after PN. RPN is more favorable than OPN for reducing EBL, PSM, major postoperative complication and renal function preservation.
Loss of Pax5 Exploits Sca1-BCR-ABLp190 Susceptibility to Confer the Metabolic Shift Essential for pB-ALL
Authors: Alberto Martín-Lorenzo, Franziska Auer, Lai N. Chan, Idoia García-Ramírez, Inés González-Herrero, Guillermo Rodríguez-Hernández, Christoph Bartenhagen, Martin Dugas, Michael Gombert, Sebastian Ginzel, Oscar Blanco, Alberto Orfao, Diego Alonso-López, Javier De Las Rivas, Maria B. García-Cenador, Francisco J. García-Criado, Markus Müschen, Isidro Sánchez-García, Arndt Borkhardt, Carolina Vicente-Dueñas, Julia Hauer
Journal: Cancer Research (2018)

Preleukemic clones carrying
Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation
Authors: Heike Pfeifer, Katharina Raum, Sandra Markovic, Verena Nowak, Stephanie Fey, Julia Obländer, Jovita Pressler, Verena Böhm, Monika Brüggemann, Lydia Wunderle, Andreas Hüttmann, Ralph Wäsch, Joachim Beck, Matthias Stelljes, Andreas Viardot, Fabian Lang, Dieter Hoelzer, Wolf-Karsten Hofmann, Hubert Serve, Christel Weiss, Nicola Goekbuget, Oliver G. Ottmann, Daniel Nowak
Journal: Blood (2018)
Novel phytopeptide osmotin mimics preventive effects of adiponectin on vascular inflammation and atherosclerosis
Authors: Yui Takahashi, Rena Watanabe, Yuki Sato, Nana Ozawa, Miho Kojima, Kaho Watanabe-Kominato, Remina Shirai, Kengo Sato, Tsutomu Hirano, Takuya Watanabe
Journal: Metabolism (2018)
Randomized phase II study to compare docetaxel plus S-1 with cisplatin plus S-1 in advanced gastric cancer without measurable lesions (HERBIS-3).
Authors: Jin Matsuyama, Yukinori Kurokawa, Kazuhiro Nishikawa, Yutaka Kimura, Atsushi Takeno, Junji Kawada, Ryohei Kawabata, Youichi Makari, Shigeyuki Tamura, Yuichiro Doki, Daisuke Sakai, Toshio Shimokawa, Taroh Satoh
Journal: Journal of Clinical Oncology (2018)

119 Background: Cisplatin and S-1 (CS) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. Docetaxel is a well-known agent with high anti-tumor effect for peritoneal metastasis from gastric cancer. A previous phase III study showed docetaxel plus S-1 (DS) regimen was recommended especially for advanced gastric cancer without measurable lesions. However, there was no study comparing the efficacy and safety of these two regimens. Methods: Eligibility criteria included HER2-negative unresectable or recurrent gastric adenocarcinoma, no measurable lesion according to RECIST v1.1, no massive peritoneal metastasis, no prior chemotherapy or radiotherapy, age ≤75, PS 0-2, adequate oral intake, and preserved organ functions. Patients were randomized to receive CS (cisplatin 60 mg/m² on day 8, S-1 40–60 mg twice a day for 3 weeks, every 5 weeks) or DS (docetaxel 40 mg/m² on day 1, S-1 40–60 mg twice a day for 2 weeks, every 3 weeks). Primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse events. Results: Sixty-one patients were randomly allocated the CS group (n = 31) or the DS group (n = 30) between Aug 2011 and Sep 2015. All were unresectable primary cases, and baseline characteristics were well balanced between the two groups. One patient was ineligible due to HER2-positive. There was no treatment-related death. The main grade 3 or worse adverse events were neutropenia (27% in CS vs. 40% in DS), anemia (10% in CS vs. 10% in DS), fatigue (13% in CS vs. 7% in DS), anorexia (10% in CS vs. 3% in DS), and diarrhea (10% in CS vs. 3% in DS). The median OS time were 15.8 months in CS and 20.0 months in DS, respectively (log-rank P = 0.113). Hazard ratio for OS was 0.617 (95%CI, 0.337 – 1.128). The median PFS time were 9.6 months in CS and 11.2 months in DS, respectively (log-rank P = 0.196). Hazard ratio for PFS was 0.698 (95%CI, 0.404 – 1.208). Conclusions: DS showed less toxic and more active profiles than CS for treatment of advanced gastric cancer without measurable lesions. The clinical benefit of DS regimen should be demonstrated in a phase III study. Clinical trial information: UMIN000006179.
Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy
Authors: Y.-K. Kang, M.-H. Ryu, S.H. Park, J.G. Kim, J.W. Kim, S.-H. Cho, Y.-I. Park, S.R. Park, S.Y. Rha, M.J. Kang, J.Y. Cho, S.Y. Kang, S.Y. Roh, B.-Y. Ryoo, B.-H. Nam, Y.-W. Jo, K.-E. Yoon, S.C. Oh
Journal: Annals of Oncology (2018)
Systematic review: Gut microbiota in fecal samples and detection of colorectal neoplasms
Authors: Efrat L. Amitay, Agne Krilaviciute, Hermann Brenner
Journal: Gut Microbes (2018)

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. Dysbiosis in the gut microbiota may be associated with CRC. This systematic review focuses on differences in gut microbial community between people diagnosed with CRC or adenoma and healthy individuals using fecal samples, emphasizing non-invasive fecal microbiome models for CRC early diagnosis.Nineteen studies were identified in a systematic literature search of Pubmed, Web of Science and ScienceDirect. Several bacteria were reported to differ in abundance between CRC and adenoma cases and healthy controls, with Fusobacterium the most common. Fecal multi-bacterial predictive models used to distinguish CRC patients from healthy controls had reported areas under the receiver operating curve (AUCs) in external validation populations of 0.68–0.77.Though advanced sequencing techniques could in the future complement current non-invasive methods for CRC early detection, more studies with high statistical power, comparable and reproducible methods and external validation of predictive models are needed.
Procalcitonin Testing to Guide Antibiotic Therapy in Acute Upper and Lower Respiratory Tract Infections
Authors: Philipp Schuetz, Yannick Wirz, Beat Mueller
Journal: JAMA (2018)

<h3>Clinical Question</h3> Is the use of procalcitonin for guiding antibiotic decisions in patients with acute upper and lower respiratory tract infections associated with improved clinical outcomes compared with usual care? <h3>Bottom Line</h3> Among patients with varying types and severity of acute respiratory infection, using procalcitonin to guide decisions about antibiotics is associated with lower rates of antibiotic exposure, antibiotic-related adverse effects, and mortality.
Impact of Body Weight Loss From Maximum Weight on Fragility Bone Fractures in Japanese Patients With Type 2 Diabetes: The Fukuoka Diabetes Registry
Authors: Yuji Komorita, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Akiko Sumi, Masahito Yoshinari, Udai Nakamura, Dongchon Kang, Takanari Kitazono
Journal: Diabetes Care (2018)

OBJECTIVE There is growing evidence that weight loss is associated with increased fracture risk in the general population. As patients with diabetes often lose weight intentionally or unintentionally, we aimed to investigate prospectively the relationship between weight loss from maximum body weight and fracture risk. RESEARCH DESIGN AND METHODS A total of 4,706 Japanese participants with type 2 diabetes (mean age 66 years), including 2,755 men and 1,951 postmenopausal women, were followed for a median of 5.3 years and were divided according to weight loss from maximum weight: &amp;lt;10%, 10% to &amp;lt;20%, 20% to &amp;lt;30%, and ≥30%. The primary outcomes were fragility fractures defined as fractures at sites of hip and spine. RESULTS During the follow-up period, fragility fractures occurred in 198 participants. The age- and sex-adjusted incidence rates per 1,000 person-years in all participants were 6.4 (&amp;lt;10% weight loss from maximum body weight), 7.8 (10% to &amp;lt;20%), 11.7 (20% to &amp;lt;30%), and 19.2 (≥30%) (P for trend &amp;lt;0.001). Multivariate-adjusted hazard ratios for fragility fractures compared with reference (&amp;lt;10% weight loss) were 1.48 (95% CI 0.79–2.77) in the 10% to &amp;lt;20% group, 2.23 (1.08–4.64) in 20% to &amp;lt;30%, and 5.20 (2.15–12.57) in ≥30% in men, and 1.19 (0.78–1.82) in 10% to &amp;lt;20%, 1.62 (0.96–2.73) in 20% to &amp;lt;30%, and 1.97 (0.84–4.62) in ≥30% in postmenopausal women. CONCLUSIONS The current study demonstrates that ≥20% body weight loss from maximum weight is a significant risk factor for fragility fractures in patients with type 2 diabetes, especially in men.
Are inhaled corticosteroids prescribed rationally in primary ciliary dyskinesia?
Authors: Eleonora Dehlink, Charlotte Richardson, Gemma Marsh, Kiralie Lee, Angela Jamalzadeh, Andrew Bush, Claire Hogg, Siobhán B. Carr
Journal: European Respiratory Journal (2018)

Primary ciliary dyskinesia (PCD) is a chronic suppurative lung disease characterised by abnormal mucociliary clearance due to genetic defects of motile cilia. PCD patients often present with wheeze and many are prescribed inhaled corticosteroids (ICS). However, ICS are not recommended by international treatment guidelines unless patients have co-existing asthma or airway reactivity [1], or asthma/wheeze with reversible bronchial obstruction (BDR) [2]. The aim of this cross-sectional single-centre study was to determine whether ICS prescriptions were targeted appropriately in PCD [3]. ICS are prescribed irrationally in PCD because diagnosing airway eosinophilia and asthma in this setting is difficult <http://ow.ly/nrcB30id7Be>
Many CCGs are failing to boost mental health funding, BMA warns
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Many clinical commissioning groups (CCGs) in England are failing to increase spending on mental health services in line with national policy commitments, a report from the BMA has found.1

The government has made repeated commitments to increase funding for mental health services over recent years. But in light of concerns that the money is not reaching the frontline, the BMA examined recent spending trends across England.

Using data obtained from freedom of information requests, it found …
Fewer foundation doctors are going straight into specialty training, says GMC
Authors: Abi Rimmer
Journal: BMJ (2016)

Fewer junior doctors are entering further specialty training directly after completing their second year of foundation training (F2), the General Medical Council has found.

On 21 July the GMC published research and data on doctors’ progression through exams and recruitment.1

It found that 66% of F2 doctors who completed foundation training in the summer of 2015 applied in round one to enter specialty training in August 2015. This compares with 78% of F2 doctors who completed their foundation training in the summer of 2012.

The GMC said that, although the number of F2 doctors had increased since 2012, the lower proportion …
TEMPORAL TRENDS, DETERMINANTS AND IMPACT OF HIGH-INTENSITY LIPID LOWERING THERAPY IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Roxana Mehran, Serdar Farhan, Usman Baber, Michela Faggioni, Melissa Aquino, Jaya Chandrasekhar, Sabato Sorrentino, Birgit Vogel, George Dangas, Annaporna Kini, Samin K. Sharma
Journal: Journal of the American College of Cardiology (2018)
CLINICAL OUTCOMES AND SAFETY OF TRANSCATHETER AORTIC VALVE REPLACEMENT WITH AND WITHOUT ROUTINE USE OF TRANSESOPHAGEAL ECHOCARDIOGRAPHY
Authors: Udit Bhatnagar, Terezia Petraskova, Maheedhar Gedela, Chirag Desai, Tomasz Stys, Adam Stys
Journal: Journal of the American College of Cardiology (2018)
Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients
Authors: Pauline Depuydt, Valentina Boeva, Toby D Hocking, Robrecht Cannoodt, Inge M Ambros, Peter F Ambros, Shahab Asgharzadeh, Edward F Attiyeh, Valérie Combaret, Raffaella Defferrari, Matthias Fischer, Barbara Hero, Michael D Hogarty, Meredith S Irwin, Jan Koster, Susan Kreissman, Ruth Ladenstein, Eve Lapouble, Geneviève Laureys, Wendy B London, Katia Mazzocco, Akira Nakagawara, Rosa Noguera, Miki Ohira, Julie R Park, Ulrike Pötschger, Jessica Theissen, Gian Paolo Tonini, Dominique Valteau-Couanet, Luigi Varesio, Rogier Versteeg, Frank Speleman, John M Maris, Gudrun Schleiermacher, Katleen De Preter
Journal: JNCI Journal of the National Cancer Institute (2018)

Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblastoma patients. To improve outcome prediction in high-risk neuroblastoma, we aimed to design a prognostic classification method based on copy number aberrations.In an international collaboration, normalized high-resolution DNA copy number data (arrayCGH and SNP arrays) from 556 high-risk neuroblastomas obtained at diagnosis were collected from nine collaborative groups and segmented using the same method. We applied logistic and Cox proportional hazard regression to identify genomic aberrations associated with poor outcome.In this study, we identified two types of copy number aberrations that are associated with extremely poor outcome. Distal 6q losses were detected in 5.9% of patients and were associated with a 10-year survival probability of only 3.4% (95% confidence interval [CI] = 0.5% to 23.3%, two-sided P = .002). Amplifications of regions not encompassing the MYCN locus were detected in 18.1% of patients and were associated with a 10-year survival probability of only 5.8% (95% CI = 1.5% to 22.2%, two-sided P < .001).Using a unique large copy number data set of high-risk neuroblastoma cases, we identified a small subset of high-risk neuroblastoma patients with extremely low survival probability that might be eligible for inclusion in clinical trials of new therapeutics. The amplicons may also nominate alternative treatments that target the amplified genes.
Escalating Inhaled Glucocorticoids to Prevent Asthma Exacerbations
Authors: Philip G. Bardin
Journal: New England Journal of Medicine (2018)

Inhaled glucocorticoids are pivotal to achieve asthma control and disease stability in both children and adults; despite their use, with or without other treatments, many patients with asthma have ongoing episodic disease exacerbations.1 Often, these are linked to provocative factors such as viral or bacterial infections, nonadherence to treatment, allergen exposure, and environmental air pollution.2 Although the clinical presentation varies widely, exacerbations are frequently heralded by slowly declining lung function and increasing asthma symptoms. These acute flares of asthma are detrimental because they adversely affect quality of life, lung function, and health care costs and have the potential to end . . .
A novel Immunoscore signature to predict survival in patients with gastric cancer: Implications for immunotherapy.
Authors: Dongqiang Zeng, Yunfang Yu, Rui Zhou, Wangjun Liao
Journal: Journal of Clinical Oncology (2018)

84 Background: Immunotherapies are transforming the treatment of gastric cancer (GC). Unfortunately, the majority of patients do not respond to immunotherapy. Thus, a novel risk score is needed to estimate tumor-infiltrating immune cells in predicting survival of GC and guide of more effective immunotherapy strategies. Methods: In total, 700 patients with GC from Gene Expression Ominus were sorted by training (490 patients) and validation (210 patients) cohorts.Immune risk score (IRS) signature based on the association between the expression of every immune cell and the duration of individual patients' survival was constructed using the LASSO Cox regression model. The relation between immunomodulatory genes, microsatellite instability and IRS value in GC was explored. Results: We established an IRS signature consisting of 11 types of immune cell fractions selected by the LASSO model, an IRS signature for GC was significantly different developed to classify patients into high- and low-risk groups in three cohorts. In the initial training cohort of patients, an IRS signature for GC was developed to classify patients into high- and low-risk groups in 8-year overall survival (hazard ratio [HR] = 2.93, P &lt; 0.0001). The performance of IRS was validated in the validation cohort (HR = 1.77, P = 0.011) and in the entire cohort (HR = 2.54, P &lt; 0.0001). In an ad-hoc analysis, we found the IRS value was substantially correlated with the expression of immunomodulatory genes including PD-1, PD-L1 and PD-L2, a prominent lower IRS was observed in microsatellite-instable (MSI) tumors compare with the microsatellite-stable (MSS) tumors. We developed nomograms for clinical use that integrated IRS signature and four clinicopathological risk factors was generated to predict which patients might have better survival with GC, and it performed well in the three cohorts (concordance index: 0.775, 0.682, and 0.752, respectively). Conclusions: These findings indicate that the assessment of the immune status via Immunoscore provides a potent predictor of survival in patients with GC and this resource may help facilitate the development of precision immunotherapy.
LETTER OF THE MONTH Building a safer NHS—September rather than August?
Authors: Richard C Worth
Journal: BMJ (2007)

We welcome your rapid responses, whether in direct response to an article in Career Focus or as a way of sharing your own ideas. As long as it isn9t libellous or offensive, we9ll post it on our website. We print a selection of rapid reponses here and the writer of the best each month wins an <i>Oxford Handbook</i> of their choice. Letter of the month prize is donated by OUP.