tbuckley/cabot-search huggingface dataset:
Structural Differences Produced in Mammalian Cells by Changes in Their Environment
Authors: Max G. Menefee, Virginia J. Evans
Journal: JNCI Journal of the National Cancer Institute (1960)

Epidermal cells assume a different form and internal structure when they are cultured in tissue-culture medium containing protein or in medium without protein. They grow as flattened sheets of cells on the flask walls in a medium containing protein and in free-floating, rounded clumps in medium without protein. If they are cultured in protein-free medium in the presence of a Millipore filter, they attach themselves to it and grow in flattened sheets just as they do in medium containing protein. Cells grown in protein medium produce characteristic lamellar bodies which appear to be derived from mitochondria. The Golgi complex is highly developed in epidermal cells grown in any of the tissue-culture media in contrast to its vestigial nature in epidermal cells in situ. This is consistent with a possible osmoregulatory function, since the cells in vitro are in a water-rich tissue-culture medium. Cells growing in suspension exhibit an ability to reduce osmium tetroxide on postosmication of their mitochondria, which does not occur when they are grown in flat sheets. This is independent of the medium in which they grow. It is postulated that the surface configuration of the cell may influence the chemistry of its mitochondria.
Review identifies five themes for addressing disparities in surgical care
Authors: Michael McCarthy
Journal: BMJ (2016)

A systematic review of research into disparities in surgical care in the United States has identified five themes to help guide research into variations in the quality of care and outcomes among patients.1

The reviewers said that surgical mortality among black and Hispanic patients in the US has been shown to be significantly higher compared with white patients for numerous procedures, including abdominal aortic aneurysm repair, coronary artery bypass, trauma care, spine surgery, and bariatric surgery. Black and Hispanic patients were also more likely to experience post-operative complications and had higher readmission rates.

The researchers reviewed 328 US studies on disparities in surgical care …
AB0237 Patient Reported General Health Associated with Amino Acid Metabolism in Patients with Early Untreated Rheumatoid Arthritis:
Authors: A. Kononoff, L. Arstila, H. Kautiainen, P. Elfving, E. Savolainen, H. Niinisalo, O. Kaipiainen-Seppänen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Aromatic and branched-chain amino acids and alanine have correlated positively, and valine, histidine and glutamine negatively with increasing levels of glucose. Those changes were at leat in part explained by insulin resistance. Insulin resistance is increased in inflammatory conditions like RA. <h3>Objectives</h3> To investigate amino acid metabolism (isoleucine, tyrosine, alanine, phenylalanine, leucine, valine, histidine, glutamine) among patients with newly diagnosed rheumatoid arthritis (RA) in a population based cohort. <h3>Methods</h3> For quantification of amino acids serum nuclear magnetic resonance platform operating at 500 MHz was used in native serum samples from patients with RA participating in Northern Savo 2010 Study. Correlations between age- and BMI-adjusted amino acid concentrations and patient reported general health (GH, VAS) were evaluated. The 95% confidence intervals for the correlations were obtained by bias-corrected bootstrapping (5,000 replications). <h3>Results</h3> Serum samples from 63 patients, 34 females and 29 males, with RA satisfying the ACR/Eular 2010 classification criteria were studied. The mean age (SD) of patients was 59.1 (12.0) years and the BMI (SD) 27.3 (5.4) kg/m<sup>2</sup>. 69.8% had anti-CCP antibodies. The mean DAS28 was 4.4 (1.3) and GH 52.7 (25.7). Correlations between age- and BMI-djusted amino acid concentrations and patient reported GH are shown in table. Phenylalanine, histidine and glutamine concentrations also correlated with CRP r=0.71, p&lt;0.001, r=-0.50, p&lt;0.001, and r=-0.33, p=0.013, respectively. <h3>Conclusions</h3> In untreated RA phenylalanine correlated positively with patient reported GH (higher disease burden) and CRP, whereas histidine and glutamine correlated negatively with them. In diabetes phenylalanine increased and histidine and glutamine decreased along with disturbances in glucose metabolism and in inflammation they may reflect inflammation associated insulin resistance. <h3>References</h3> Svenson KLG et al. Metabolism 1987;36:940–3. Soininen P et al. Analyst 2009;134:1781-5. Stančáková A et al. Diabetes 2012;61:1895-902. <h3>Disclosure of Interest</h3> None declared
OC-058 A survey of surgeon specific outcome data and their potential impact on surgical training
Authors: OS Al-Taan, S Satheesan, R Williams
Journal: Gut (2015)

<h3>Introduction</h3> The publication of surgeon specific data (SSD) for general surgeons at the end of 2013 started a new era in surgery in the UK. It is not known if and how this will impact surgical practice and training particularly with respect to high-risk cases. We aimed to explore the consultants’ perception and their potential changes in their practice as a result of SSD publication. <h3>Method</h3> A cross sectional on-line survey was sent to a sample of General Surgeons with an interest in Upper GI surgery. Details of their current surgical practice and their opinions on the changes they would make in clinical practice and training were collected. Questions were themed and data analysed both qualitatively and quantitatively. <h3>Results</h3> Eighty nine surgeons responded to the questionnaire. Of those 61 (68.5%) were cancer surgeons and 28 (31.5%) described themselves as a benign (including bariatric) surgeon. Thirty six (40%) surgeons considered SSD to be of no benefit at all to surgical training while 21 (23.5%) thought there will be some useful effect. Asked whether there was any negative effect on training, 33 surgeons (37%) thought there will be a detrimental effect on surgical training in general, and 25 (75%) of those thought this effect will be mainly on complex cases. However, when asked to specify the negative effects on surgical training 55 (73%) of the group said the number of complex operations done by trainees will drop and 35 (46%) thought the number of all operation done by trainees will drop. A significant point was the attitude toward trainees where 32 (36%) surgeons said they will perform major or complex cases themselves with 13 (14%) choosing the option of performing all cases themself. Upon asking about any general changes to practice, 11 (12.5%) said they will give up or reduce high risk surgery and 32 (36%) thought their practice will not change. Regarding the patients’ outcome 49 (55%) thought that SSD will improve outcomes while 40 (45%) answered that they will not change outcomes. Qualitative assessment, using content analysis technique, showed a minority of the surgeons will either avoid training their trainees in high risk patients and/or avoid high risk cases in order to maintain their SSD data reputation. <h3>Conclusion</h3> The publication of surgeons’ specific data will result in some changes to general surgical practice. It is too early to decide whether these effects are good for training, however, if these initial opinions are applied to routine practice then trainees may be faced with large scale reductions in training cases particularly those of a complex nature that would have major ramifications on surgical training. As the shape of surgical training continues to be developed it is important that the implications of SSD on surgical training are considered. <h3>Disclosure of interest</h3> None Declared.
PTU-247 Does enhanced recovery after colorectal surgery increase the incidence of parastomal hernias?
Authors: NR Houghton, J Lauder, J Alldis, C Craig
Journal: Gut (2015)

<h3>Introduction</h3> Evidence supporting the benefits of enhanced recovery after surgery (ERAS) protocols is abundant; however there is no published data on how ERAS may affect the incidence of parastomal hernias. <h3>Method</h3> Retrospective, observational, single centre cohort study of patients who underwent elective or emergency operations with stoma formation from January 2006 until March 2013. The cohort was split into ERAS and traditional recovery, and a review of case-notes and stoma nurse records allowed identification of those who developed parastomal hernias at any time point post-operatively. <h3>Results</h3> 208 patients were included; 95 underwent a traditional recovery, and 113 underwent ERAS. The demographics of these 2 groups were comparable. 14.74% non-ERAS patients (n = 14) developed parastomal hernias compared to 34.51% (n = 39) in the Enhanced Recovery group (p = 0.0011). <h3>Conclusion</h3> This study demonstrated a significantly increased incidence of parastomal hernias in those undergoing enhanced recovery, consistent with the earlier postoperative mobilisation. While the other benefits of ERAS outweigh this risk, this reality of modern post-operative care should reinvigorate the use of scrupulous surgical technique, and consideration of stoma site reinforcement options. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Gravante G, Elmussareh M. Enhanced recovery for colorectal surgery: practical hints, results and future challenges. World J Gastrointest Surg. 2012;4(8):190–8 Chestovich PJ, Lin AY, Yoo J. Fast-track pathways in colorectal surgery. Surg Clin North Am. 2013;93(1):21–32 Lv L, Shao YF, Zhou YB. The enhanced recovery after surgery (ERAS) pathway for patients undergoing colorectal surgery: an update of meta-analysis of randomized controlled trials. Int J Colorectal Dis. 2012;27(12):1549–54 Abraham N, Albayati S. Enhanced recovery after surgery programs hastens recovery after colorectal resections. World J Gastrointest Surg. 2011;3(1):1–6 Godbout JP. Glaser R. Review Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancer. J Neuroimmune Pharmacol. 2006;1(4):421–7 Boyapati L, Wang H. Review the role of stress in periodontal disease and wound healing. Periodontol 2000. 2007;44:195–210 Hotouras A, Murphy J, Thaha M, Chan CL. The persistent challenge of parastomal herniation: a review of the literature and future developments. Colorectal Dis 2013;15(5):e202–14 Sohn YJ, Moon SM, Shin US, Jee SH. Incidence and risk factors of parastomal hernia. J Korean Soc Coloproctol 2012;28(5):241–6
Limited role for transforming growth factor–β pathway activation-mediated escape from VEGF inhibition in murine glioma models
Authors: Davide Mangani, Michael Weller, Emad Seyed Sadr, Edith Willscher, Katharina Seystahl, Guido Reifenberger, Ghazaleh Tabatabai, Hans Binder, Hannah Schneider
Journal: Neuro-Oncology (2016)

Abstract Background The vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)–β pathways regulate key biological features of glioblastoma. Here we explore whether the TGF-β pathway, which promotes angiogenesis, invasiveness, and immunosuppression, acts as an escape pathway from VEGF inhibition. Methods The role of the TGF-β pathway in escape from VEGF inhibition was assessed in vitro and in vivo and by gene expression profiling in syngeneic mouse glioma models. Results We found that TGF-β is an upstream regulator of VEGF, whereas VEGF pathway activity does not alter the TGF-β pathway in vitro. In vivo, single-agent activity was observed for the VEGF antibody B20-4.1.1 in 3 and for the TGF-β receptor 1 antagonist LY2157299 in 2 of 4 models. Reduction of tumor volume and blood vessel density, but not induction of hypoxia, correlated with benefit from B20-4.1.1. Reduction of phosphorylated (p)SMAD2 by LY2157299 was seen in all models but did not predict survival. Resistance to B20 was associated with anti-angiogenesis escape pathway gene expression, whereas resistance to LY2157299 was associated with different immune response gene signatures in SMA-497 and GL-261 on transcriptomic profiling. The combination of B20 with LY2157299 was ineffective in SMA-497 but provided prolongation of survival in GL-261, associated with early suppression of pSMAD2 in tumor and host immune cells, prolonged suppression of angiogenesis, and delayed accumulation of tumor infiltrating microglia/macrophages. Conclusions Our study highlights the biological heterogeneity of murine glioma models and illustrates that cotargeting of the VEGF and TGF-β pathways might lead to improved tumor control only in subsets of glioblastoma.
Model-based analysis of the relationship between pembrolizumab (MK-3475) exposure and efficacy in patients with advanced or metastatic melanoma.
Authors: Richard Wayne Joseph, Tara C. Gangadhar, Igor Puzanov, Caroline Robert, Omid Hamid, Reinhard Dummer, Antoni Ribas, Janice M. Mehnert, Adil Daud, Kellie Ann Celentano, Jill Ann Lindia, Manash Shankar Chatterjee, David C. Turner, Kapil Mayawala, Jeroen Elassaiss-Schaap, Dinesh Prasad de Alwis, Xiaoyun Nicole Li, Scot Ebbinghaus, Soonmo Peter Kang, Richard Kefford
Journal: Journal of Clinical Oncology (2015)

3068 Background: Optimization of antibody dosing in oncology drug development is an area of growing interest. We have previously demonstrated that the dose and schedule of pembrolizumab does not correlate with clinical outcomes in melanoma. Here, we assess the relationship between steady state plasma exposure and tumor growth dynamics in patients enrolled in the KEYNOTE-001 and KEYNOTE-002 studies. Methods: Patients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) to 10 mg/kg Q2W or Q3W. Exposure was defined as the area under the serum concentration curve (AUC) over 6 weeks. Response was defined as the change in tumor size per standard rules for measuring target lesions (ie, sum of the longest diameters). We assessed the extent of tumor growth and its reduction under pembrolizumab treatment using nonlinear mixed effects modeling; specifically, we tested whether individual exposures predict patterns of tumor response. Results: In this initial analysis, we found that reduction in tumor growth was best characterized by an exponential decline, with an estimated halving time of approximately 4 months. The 90th percentile of pembrolizumab exposures ranged from 0.8 to 14 g×day/L. In agreement with the flat dose-efficacy relationship observed per objective response criteria, the observed individual pembrolizumab exposures do not significantly correlate with extent of tumor reduction or overall growth patterns over time. Conclusions: The significant and prolonged reductions in tumor size under pembrolizumab treatment were well characterized by the tumor size dynamics model. Tumor size reductions were independent of a wide (15-fold) range of exposure to pembrolizumab, supporting 2 mg/kg Q3W as an effective dosage that achieves a level of exposure sufficient to saturate tumor response. This examination of a wide exposure range and analysis via dynamic tumor size modeling demonstrates a framework for identifying an optimally efficacious dose in oncology. Clinical trial information: NCT01295827 and NCT01704287.
316P Nonrandomized comparison between docetaxel, CDDP and 5-FU (TPF) and docetaxel, CDDP and S-1 (TPS) in locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: A. Nakanome, S. Okano, T. Wakasugi, T. Enokida, T. Yamazaki, M. Tahara
Journal: Annals of Oncology (2015)
The history of multiple personality in the United States: I: The beginnings
Authors: E T Carlson
Journal: American Journal of Psychiatry (1981)

The origins of the history of multiple personality in the United States may be found in the lectures and writings of Benjamin Rush. Although the case of Mary Reynolds in 1811 has been thought to be the first known case of multiple personality. Rush described three earlier cases of dissociation and attempted to explain these strange phenomena.
PTH-160 Laparoscopic repair of giant hiatus hernia significantly improves quality of life – a single centre experience
Authors: YM Goh, YL Goh, N Krishnamohan, VD Shetty, PD Turner, JB Ward, KG Pursnani, RS Date
Journal: Gut (2015)

<h3>Introduction</h3> Centralisation of Upper Gastrointestinal cancer services has been associated with increase in number of referrals of giant hiatus hernia (GHH) over last 5 years. Laparoscopic repair (LR) of GHH is associated with recurrence rate of up to 30% and high mortality and morbidity. Therefore, we offer surgery only to symptomatic patients presenting with reflux, dysphagia, chest symptoms and intermittent gastric volvulus. The aim of this study is to evaluate quality of life (QoL) of these patients after LR of GHH. <h3>Method</h3> This is a postal questionnaire study of all the patients undergoing GHH repair between 2010 to 2014 in a tertiary referral centre. Patients were sent 2 questionnaires, 1. The Quality of Life in Reflux and Dyspepsia (QOLRAD) and 2. Our own short questionnaire. The QOLRAD questionnaire was made up of 25 questions; each scored out of 7 with 7 representing a high quality of life and 1 representing a low quality of life. A combination of these questions made up 5 dimensions namely emotional distress, sleep disturbance, food/drink problems, physical/social functioning and vitality. The second questionnaire assessed improvement in patient’s individual symptoms namely heartburn/reflux, weight loss, abdominal or chest pain/discomfort, vomiting, shortness of breath, nausea, bloating, difficulty swallowing and also overall improvement in health and QoL on a scale of 0 to 10, 0 being no improvement and 10 being excellent results. <h3>Results</h3> From a total of 68 patients, 2 died post-operatively (1 was an emergency and the other was an elective case). The other 2 died of unrelated causes. Of the remaining 64 patients, 27 (42.2%) responded. Mean score for each dimension in QOLRAD (out of 7) were as follows-emotional distress (6.15), sleep disturbance (6.22), food/drink problems (6.07), physical/social functioning (6.43) and vitality (6.02). In the second questionnaire, patients scored overall improvement of their symptoms out of 10. Of the 27 patients, 1 (3.7%) scored 1–3, 5 (18.5%) scored 4–6, 3 (11.1%) scored 7–8 and 18 (66.7%) scored 9–10. Similar findings were reported for improvement in QoL. <h3>Conclusion</h3> Our case series showed acceptable operative mortality of 2.9%; with a significant improvement in QoL in approximately two thirds of patients. Patient selection and standardisation of operation may be responsible for these results. <h3>Disclosure of interest</h3> None Declared.
PTU-198 Systematic review of the assessment and management of anal intraepithelial neoplasia grade iii
Authors: NN Alam, D White, SK Narang, IR Daniels, NJ Smart
Journal: Gut (2015)

<h3>Introduction</h3> Anal Intraepithelial Neoplasia (AIN) is dysplasia in the squamous epithelium of the anus and is a precursor for anal squamous cell carcinoma. AIN is associated with many risk factors particularly infection with the Human Papilloma Virus (HPV), which is found in 90% of cases. There is ambiguity with regards to the optimal management of AIN III and there are significant variations in the published guidelines produced by official bodies. Therefore the optimal treatment and long term management of AIN III is yet to be standardised. The aim of this review is to assess the evidence behind national society guidelines currently available in the literature available on AIN III management, surveillance and treatment. <h3>Method</h3> An electronic search of Pubmed was performed using the search terms <i>‘anal intraepithelial neoplasia’, ‘AIN’, ‘anal cancer’, ‘guidelines’, ‘surveillance’ and ‘management’.</i>Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1<sup>st</sup>January 2000 to 31<sup>st</sup>December 2014, assessing the treatment, surveillance or management of patients with AIN related to HPV were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. <h3>Results</h3> The database search identified 4473 articles and 2 guidelines were sourced from official body guidelines (ACPGBI and ASCRS). After inclusion criteria were applied, 22 abstracts were reviewed and 10 were excluded as they were not relevant to AIN III or anal cancer, and a further 6 were excluded as they were earlier versions of current guidelines. Three guidelines (American College of Radiology, NCCN and the European Society for Medical Oncology) were excluded as they were recommendations for anal cancer leaving three guidelines for review. Guidelines published by ACPGBI, ASCRS Italian Society of Colorectal Surgery (SICCR) were included for the systematic review. <h3>Conclusion</h3> All 3 guidelines agree that a high index of clinical suspicion is necessary for diagnosing AIN III. A disease specific history focussing on signs, symptoms and predisposing risk factors as well as a perianal examination, digital rectal examination and anal cytology is essential for assessment. However, there is significant variation amongst the guidelines with regards to surveillance, medical treatment, surgical excision and follow-up of patients with AIN III. The quality of evidence used to form the guidelines is of a low level with the majority based on Level 3 or 4 evidence. This review highlights that the current guidelines available are based on out-dated evidence of low quality and standardised registry data is needed to standardise assessment, treatment and surveillance to improve overall outcome. <h3>Disclosure of interest</h3> None Declared.