tbuckley/cabot-search huggingface dataset:
The combination of DNA ploidy status and PTEN/6q15 deletions to provide strong and independent prognostic information in prostate cancer.
Authors: Maximilian Lennartz, Sarah Minner, Martina Kluth, Sophie Brasch, Hilko Wittmann, Leonard Paterna, Hans Heinzer, Ronald Simon, Guido Sauter, Thorsten Schlomm
Journal: Journal of Clinical Oncology (2015)

5027 Background: Aberrant DNA ploidy has been long discussed as a potential prognostic feature in prostate cancer. Methods: In this project, we analyzed the clinical significance of DNA ploidy in combination with the most frequent chromosomal deletions (PTEN, 6q15) with known prognostic impact in a contemporary series of 3,845 prostate cancers. Ploidy status was assessed in 3,845 cancers by using flow cytometry for which the 6q15 and PTEN deletion status was available from earlier projects. Results: The DNA status was diploid in 67.8%, tetraploid in 25.6% and aneuploid in 6.8% of tumors. Abnormal DNA content was significantly linked to high Gleason grade, advanced tumor stage, and positive nodal status (p < 0.0001 each). Deletions were seen for PTEN in 17.8% and for 6q15 in 20.3% of cases. Both deletions were significantly linked to high Gleason grade and advanced stage (p < 0.0001 each). Comparison with outcome data revealed, that the risk of PSA recurrence increased markedly from diploid to tetraploid tumors (p < 0.0001) and again from tetraploid to aneuploid cases. However, many patients with unfavorable tumor phenotype (39.9% of tumors with a Gleason grade of ≥ 4+4 = 8) or with PSA recurrence (55.2%) had a diploid DNA status. The fraction of unfavorable tumors with a normal DNA status decreased to 21.1% of Gleason ≥ 4+4 = 8 cancers and 29.0% of cancers with PSA recurrence, if DNA abnormality was defined as non-diploid and/or at least one of the two deletions. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Here, presence of deletions markedly increased the risk of PSA recurrence in diploid (p < 0.0001), tetraploid (p < 0.0001), and aneuploid cancers (p = 0.0049). Moreover, multiple models of multivariate analyses including preoperatively and postoperatively available parameters identified the “combined DNA status” as a strong independent predictor of poor patient outcome. Conclusions: It is concluded, that a combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) have the potential for clinical utility in prostate cancer.
Social and Behavioral Determinants of Spending
Authors: Karen E. Joynt Maddox
Journal: JAMA Internal Medicine (2017)

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02.32 Exploring the role of bcl-3 in cd4<sup>+</sup> t cells
Authors: Natasha L. West, Amy E. Anderson, Arthur G. Pratt, Nisha Nair, Andrew Skelton, Anne Barton, Ruaidhri J Carmody, Andrew D Rowan, John D Isaacs
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a disease of immune dysregulation whose pathogenesis remains incompletely understood. We previously identified an IL-6 mediated, STAT3 target gene-enriched 'signature' in circulating CD4<sup>+</sup> T cells of untreated arthritis patients that predicted progression to RA. BCL-3 was the most differentially expressed of these genes between RA patients and disease controls<sup>1</sup>. This atypical IκB molecular product appears to be important in murine T-cell biology. In this project we aim to explore the function of BCL-3 in human primary CD4<sup>+</sup> T cells, and its potential relevance to RA pathogenesis. <h3>Materials and methods</h3> Highly purified CD4<sup>+</sup> T-cells were isolated from human peripheral blood using magnetic beads. Phospho-STAT3 (pSTAT3) and paired BCL-3 gene expression were measured in cells from 161 untreated arthritis patients using flow cytometry and microarray technology, respectively. To study BCL-3 kinetics, CD4<sup>+</sup> T-cells isolated from healthy volunteers were stimulated with cytokines or TCR ligands; gene and protein expression were analysed by Taqman Real-Time PCR and Western Blotting respectively. To overexpress BCL-3 two methods were compared: use of our previously developed murine mimetic peptide, and lentiviral transduction. The phenotype of CD4<sup>+</sup> T-cells by means of proliferation, activation and intracellular cytokines were assessed by CFSE labelling, surface and intracellular flow cytometry respectively. <h3>Results</h3> Intracellular pSTAT3 correlates strongly with paired BCL-3 gene expression in circulating CD4<sup>+</sup> T-cells of early arthritis patients. <i>In vitro</i> kinetics experiments show its expression is induced by IL-6, but becomes maximal after TCR stimulation for 72 hours; protein peaks later at 5 days. A limited effect of the mimetic peptide on cultured CD4<sup>+</sup> T-cell phenotype likely reflects incomplete homology of murine and human peptides. Transduction of CD4<sup>+</sup> T-cells with rLV-hBCL3-IRES-ZsGreen1 lentivirus results in 6-fold upregulation of BCL-3 gene expression that remains detectable 6 days post transduction. <h3>Conclusions</h3> Enhanced STAT3 signalling accounts for increased BCL-3 expression in circulating CD4<sup>+</sup> T cells of early RA patients, and the kinetics of IL-6- and CD3/28-mediated BCL-3 induction in these cells have been defined, Having optimised a robust means of over-expressing BCL-3 by lentiviral transduction of primary human CD4<sup>+</sup> T cells, its specific functional role will now be explored.
SAT0310 Ultrasonographic scoring of the major salivary glands in sjogren's syndrome: a comparative study with disease activity indexes
Authors: N İnanç, Y Yalçınkaya, G Mumcu, Z Ertürk, AU Unal, P Atagündüz, H Direskeneli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Sjogren9s syndrome (SjS) is characterised by chronic autoimmune inflammation primarily affects the salivary and lacrimal glands. Recently, ultrasonography (USG) of major salivary glands (SG-USG) has been used to evaluate salivary glands in primary and secondary SjS. <h3>Objectives</h3> We aimed to investigate the association between the ultrasonographic scoring of major salivary glands and disease activity indexes in patientswith primary SjS. <h3>Methods</h3> Forty-two primary SjS patients fulfilling ACR-EULAR classification criteria (2002) were included. Disease activity indexes (Sjögren9s Syndrome Patients Reported Index (ESSPRI), Visual Analogue Scale (VAS), EULAR Sjögren9s Syndrome Disease Activity Index (ESSDAI)] were recorded. Major salivary glands (bilateral parotis and submandibular glands) were scored according to two different scoring system [Hocevar A. (0–48) ve Milic VD. (0–12)]. <h3>Results</h3> Demographics, clinical characteristics, disease activity indexes and SG-USG scores were summarised in table 1 and table 2. Twenty-four (57%) and25 (60%) patients had the cut-offvalues of ≥17 (Hocevar) and ≥6 (Milic USG).The patients with the scores of ≥17 (Hocevar)were found to have higher scores of ESSPRI-total (18±5 vs 14±5, p=0,01). Hocevar and Milic USG scores were shown to be higher in anti-Ro(+) SjS patients (25±10vs14±7and7±3vs4±2, p=0,01).USG scores were not found to be associated with the scores of ESSDAI, VAS and ESSPRI items. <h3>Conclusions</h3> Hocevar scoring system of major salivary glands was found to be related to patient reported activity in SjS. USG scores were associated with anti-Ro positivity. Evaluation of SG-USG might promote the diagnosis and follow-up of the SjS patients. <h3>Disclosure of Interest</h3> None declared
Intergroup randomized phase III study of postoperative irinotecan, 5-fluorouracil, and leucovorin versus oxaliplatin, 5-fluorouracil, and leucovorin versus 5-fluorouracil and leucovorin for patients with stage II or III rectal cancer receiving either preoperative radiation and 5-fluorouracil or postoperative radiation and 5-fluorouracil: ECOG E3201—An updated survival analysis.
Authors: Halla Sayed Nimeiri, Yang Feng, Paul J. Catalano, Neal J. Meropol, Bruce J. Giantonio, Elin R. Sigurdson, James A. Martenson, Robert P. Whitehead, Frank A. Sinicrope, Robert J. Mayer, Peter J. O'Dwyer, Al Bowen Benson
Journal: Journal of Clinical Oncology (2013)

e14711 Background: Postoperative adjuvant chemotherapy has been historically limited to single agent 5FU in stage II/III rectal cancer pts. This phase III trial evaluated differences between pts treated with adjuvant FOLFOX versus FOLFIRI versus FU alone in stage II/III rectal cancer. Methods: Eligibility: resectable (T3-4 N0,Tany N1-3) adenocarcinoma rectum ≤12cm from anal verge. Pts had the option to receive FU with pre or postoperative XRT (50.4Gy). Preoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm A), FOLFOX (arm B), FU/LV(arm C). Postoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm D), FOLFOX (arm E), FU/LV (arm F). Pts received 8 cycles. Overall survival (OS) was the primary endpoint. Secondary endpoints included toxicity, sphincter preservation and patterns of failure. Results: 225pts out of planned 3150 were enrolled (10/03 to 10/05). Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). 179 pts were randomized; (A:28, B:25, C:30, D:31, E:33, F:32). There was increased grade 3/4 toxicity, mainly diarrhea,in postoperative FU/XRT arms (D:39%), (E:28%), (F:48%). Twenty-two (12%) pts did not receive adjuvant therapy. At a median follow up of 7.4yrs, the five-year recurrence free rate was 69%. Median OS was 8.3 yrs. There was no statistical difference in OS between all randomized groups. Five-year OS in arms (A:B:C:D:E:F) were (73%, 83%, 83%, 73%, 78%, 73%) respectively. Conclusions: FOLFOX can be safely administered to rectal cancer pts following chemo radiation. Given limitations of early trial closure and small sample size, there was no difference in OS between pts who received FU alone, oxaliplatin based or irinotecan based adjuvant therapy. Clinical trial information: NCT00068692.
Asian Multinational Phase II Study of Darinaparsin in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma
Authors: Noriko Fukuhara, Won Seog Kim, Dok Hyun Yoon, Eiju Negoro, Kazuhito Yamamoto, Toshiki Uchida, Koji Izutsu, Yasuhito Terui, Hideaki Nakajima, Kiyoshi Ando, Youko Suehiro, Hye Jin Kang, Po-Shen Ko, Fumiko Nagahama, Yusuke Sonehara, Hirokazu Nagai, Hwei-Fang Tien, Yok-Lam Kwong, Kensei Tobinai
Journal: Blood (2021)
腫瘍特異的生分解性と増強された化学療法機能性を有する分子有機/無機ハイブリッド中空メソ多孔性有機シリカナノカプセル【Powered by NICT】
Authors: Huang Ping, Chen Yu, Lin Han, Yu Luodan, Zhang Linlin, Wang Liying, Zhu Yufang, Shi Jianlin
Journal: Biomaterials (2017)
Comparative efficacy and safety of second-line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network meta-analysis
Authors: Steve Kanters, Maria Eugenia Socias, Nicholas I Paton, Marco Vitoria, Meg Doherty, Dieter Ayers, Evan Popoff, Keith Chan, David A Cooper, Matthew O Wiens, Alexandra Calmy, Nathan Ford, Sabin Nsanzimana, Edward J Mills
Journal: The Lancet HIV (2017)
Comparaison du traitement par injection intra-sphinctérienne de toxine botulique de l’achalasie et des troubles moteurs oesophagiens atypiques
Authors: I Boytchev, M Gaudric, S Chaussad
Journal: Endoscopy (2004)

But: Comparer de façon rétrospective l’efficacité de l’injection intra-sphinctérienne de la toxine botulique (TB) dans le traitement de l’achalasie et des troubles moteurs oesophagiens atypiques dans une population de sujets à risque. Patients et Méthodes: De Janvier 1998 à Juillet 2003, 34 patients consécutifs ont reçu une injection intrasphinctérienne de 80 à 100 unités de TB. Les données cliniques (score d’Eckardt), manométriques et morphologiques ont été recueillies par consultation du dossier médical ou appel téléphonique du patient. Les patients ont été répartis: (groupe 1) achalasie; (groupe 2) troubles moteurs atypiques incluant des spasmes diffus et des troubles moteurs secondaires. Les indications de la TB étaient, pour l’ensemble des patients: l’âge, des comorbidités graves et, pour le groupe 1: l’échec de traitements antérieurs ou une contre indication à la dilatation pneumatique; pour le groupe 2: l’absence de traitement validé. Résultats (Tableau 1). Aucune complication en rapport avec la TB n’a été observée. Conclusion: 1) La réponse à l’injection intra-sphinctérienne de toxine botulique est satisfaisante dans l’achalasie malgré un taux de récidive très élevé. Chez les sujets à risque, elle constitue une alternative raisonnable aux traitements plus invasifs. Chez les patients en échec de traitement antérieur, elle permet de sélectionner des candidats à une éventuelle reprise chirurgicale. 2) La réponse tend à être moins nette et moins durable dans les troubles moteurs atypiques, l’absence d’autre traitement disponible et l’innocuité dela toxine botulique justifient néanmoins son utilisation.
PTU-060 Burden of liver disease in the west midlands: alcoholic liver disease hospital admissions increased
Authors: N Bhala, S Haroon, S Burwood, C Pennell, H Carter, A Daley, E Day, A El Sharkaway, J Ferguson, D Freshwater, V Gordon, A Holt, A Mittal, J Mukarati, I Perry, A Phillips, N Quann, M Tahir, R Thomson, E Unitt, C Bray, N Dennis, G Wrench
Journal: Gut (2017)

Introduction  Liver disease is a leading cause of premature death and a rising cause of hospital admissions in the UK. We sought to assess the clinical burden of common liver diseases in the West Midlands assessed by hospital admissions regionally.  Method  Routine data from PHE Alcohol and Liver Disease West Midlands Profiles from 2013–16 were assessed. Sources include the Office of National Statistics (ONS) and NHS Digital Hospital Episode Statistics (HES). Specific diseases assessed include: alcoholic liver disease (ALD); non-alcoholic fatty liver disease (NAFLD); chronic viral hepatitis B and C; and hepatocellular cancer (HCC).  Results  Age-standardised hospital admissions for all liver disease were lower than the national average, especially in males. However, hospital admission rates for ALD were higher (34.3 per 100,000) for both men and women compared to the national average (31.9). Coventry (54.9), Telford and Wrekin (53.7), Wolverhampton (43.5), Birmingham (41.9) and Worcestershire (41.8) were amongst the highest areas in the region. Solihull (12.3), Shropshire (25.0) and Staffordshire (26.0) were amongst the lowest areas. Hospital admission rates for chronic viral hepatitis related end-stage liver disease/HCC were similar to the national average, and those for NAFLD were lower than the national average.  Conclusion  Hospital admissions for alcoholic liver diseases are significantly higher in West Midlands compared to the rest of England. A collaborative liver health network in the West Midlands is required to help tackle the burden of preventable liver disease admissions.  References  . Chief Medical Officer Annual Report on Liver Disease2012  . Lancet Liver Commission Lancet2014  Disclosure of Interest  None Declared
SAT0198 Tocilizumab for the management of rheumatoid arthritis: discontinuation due to inefficacy and toxicity – experience from a large teaching hospital
Authors: E Byrne, P Mark, S Khalid, K-P Kuet, R Kilding, K Graves, J Maxwell, M Akil
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tocilizumab (TCZ) is a humanised anti interleukin-6 receptor antibody licensed for use for the treatment of moderate to severe Rheumatoid Arthritis (RA) as monotherapy or in combination with methotrexate (MTX). <h3>Objectives</h3> To describe the use of TCZ for RA in a large UK teaching centre and examine reasons for treatment discontinuation. <h3>Methods</h3> A retrospective case note review of all adult patients receiving TCZ either alone or in combination with DMARDS, for the treatment of RA between April 2009 and January 2017 in Sheffield, UK. <h3>Results</h3> 132 patients received TCZ for RA. 71% were female. 61% were CCP positive. Mean disease duration was 15.6 years (range 1.5–43). 46 (34.6%) received TCZ as monotherapy, 55 (42.1%) in combination with MTX and 31 (23.3%) other DMARDS. 23% of patients received concomitant oral prednisolone. Median duration of TCZ treatment was 27 months across the whole cohort, and 19 months in those who discontinued treatment. Overall 44 (33%) patients discontinued TCZ; 5 due to primary and 10 secondary inefficacy, 27 patients due to adverse events (8 recurrent infection, 5 abnormal LFT, 4 malignancy, 3 rash, 7 other including 1 death whilst on treatment). A logistic regression model, including gender, smoking status, disease duration, DMARD use, steroid treatment and number of prior biologics was constructed to examine association with treatment discontinuation. Of these factors, disease duration (p=0.05) and number of previous biologics (p=0.09) were weakly associated with persistence of TCZ and in particular there was no association of concomitant DMARD or steroid treatment with discontinuation either due to lack of efficacy or adverse events. Table 1 demonstrates the proportion of patients stopping treatment, and treatment duration according to previous biologic treatment received. We have not seen any cases of infusion reaction, diverticular perforation or reactivation of tuberculosis. <h3>Conclusions</h3> Our real world data on the use of TCZ in the treatment of adult patients with RA is consistent with clinical trial data for efficacy and safety and is similar to other biological drugs used in the treatment of RA. We have seen a relatively low rate of withdrawal due to primary and secondary treatment failure. <h3>Disclosure of Interest</h3> None declared
DEVELOPMENT OF A NEW SMART SURVEILLANCE SYSTEM FOR MONITORING SPORTS INJURIES
Authors: Mohsen Sadeghi, Mohammad Hossein Alizadeh
Journal: British Journal of Sports Medicine (2017)

Background There are several methods for monitoring sports injuries including simple questionnaires, text messaging and sophisticated surveillance systems. However, some problems related to inconsistency of injury definitions and classifications, high costs, data entry mistakes and lack of online technology usage may limit the efficacy of these methods and reduce validity of the recorded information. Objective To develop a new smart surveillance system for recording, reporting and analysing sports injuries. Design Common systems and methods for monitoring sports injuries were explored in the literature for identifying the potential problems and defects. Then, we searched for valid definitions and categories of sports injuries such as those available in consensus statements. Considering the popularity of smartphone amongst health care professionals, development of a connection between a special application and a computer software or another app was identified as the best way for designing a new surveillance system. Setting Mobile app and computer software. Interventions (or Assessment of Risk Factors) A mobile app was designed on an android platform for determining the characteristics of players, injuries and exposures. Another app and a computer software were also developed for data receiving unit of the system that was able to save information and to send data to the client's application. Main Outcome Measurements The data extracted from the smart surveillance system. Results The first version of the smart system that utilized recommendations of the consensus statement on football injuries had capability of recording injuries in an effective manner and sending them to the server software in which the data could be classified and analysed. Conclusions The new surveillance system for sports injuries is a technology-based system that links the medical staff of sports teams to organizations or researchers and speeds up recording and reporting the data of injuries.
ドナーCD19CAR T細胞は強力な移植片対リンパ腫活性を発揮するが,移植片対宿主活性は減弱する
Authors: Ghosh Arnab, Smith Melody, James Scott E, Velardi Enrico, Argyropoulos Kimon, Kreines Fabiana M, Levy Emily R, Lieberman Sophie, Jay Hillary, Tuckett Andrea Z, Tan Lisa, Young Lauren F, Takvorian Kate, Dudakov Jarrod A, Jenq Robert R, Hanash Alan M, Schietinger Andrea, Sadelain Michel, Van Den Brink Marcel R M, Davila Marco L, Gunset Gertrude, Perna Fabiana, Zakrzewski Johannes L, Motta Ana Carolina F, Murphy George F, Liu Chen
Journal: Nature Medicine (2017)
93 year old US doctor is sentenced to 10 years in prison for opioid distribution
Authors: Owen Dyer
Journal: BMJ (2017)

A Las Vegas doctor, aged 93, has been sentenced to 10 years in prison and fined $2.5m (£1.9m; €2.1m) for writing prescriptions for oxycodone, alprazolam (Xanax), and other drugs for no legitimate medical purpose.

Drugs prescribed by pain specialist Henri Wetselaar, a Dutch born veteran of the second world war, were distributed through a network of dealers and addicts to more than 230 people, the federal court heard.

Wetselaar’s medical …
Survival After Isolated Post-Operative Troponin Elevation
Authors: W. Scott Beattie, Duminda N. Wijeysundera, Matthew T.V. Chan, Philip J. Peyton, Kate Leslie, Michael J. Paech, P.J. Devereaux, Daniel I. Sessler, Sophie Wallace, Paul S. Myles
Journal: Journal of the American College of Cardiology (2017)