tbuckley/cabot-search huggingface dataset:
PTU-020 Endoscopy-related litigation in UK: causes, costs and outcome
Authors: K Sheikh, G Webster
Journal: Gut (2010)

<h3>Introduction</h3> When endoscopy-related complications occur, patients may seek legal redress. Although the majority of complaints in the UK are resolved locally by NHS Trusts, since its inception in 1995 approx 4% of cases referred to the NHS litigation authority (NHSLA) required settlement in the court. <h3>Aims</h3> To investigate the annual frequency of endoscopy-related claims, the endoscopic procedures and complications that result, and the outcome of claims handled by NHSLA. To assess how these claims may inform risk management strategies. <h3>Methods</h3> A search of the computerised NHSLA database was undertaken to extract the endoscopy related claims handled between 1995 and 2008. Search keywords used were “endoscopy”, “ERCP”, “colonoscopy”, “gastroscopy” and “PEG”. Details available included year of incident and claim, incident summary, clinical outcome, success/failure of claim, and financial settlement. <h3>Results</h3> 418 endoscopy-related negligence claims submitted to NHSLA during this period, which comprised 17% of total NHSLA claims requiring settlement in court. Of 353 claims that have been settled to date, 175 (49.6%) were successful, resulting in total costs of £6 773 686 and 178 (51.4%) were unsuccessful but still incurred legal costs of £258 656. Claims reached a peak in 2002–2003. Upper GI endoscopy and colonoscopy were associated with 65% of settled claims, but ERCP was the procedure most frequently linked to the 74/353 (21%) of claims related to a fatal outcome. Factors underlying claims following fatal complications included: inappropriate endoscopic treatment/direct complication (51%); delay in recognising complication±its management (39%); consent issues (6%); and medication issues (4%), including incorrect management of anticoagulation. <h3>Conclusion</h3> As &gt;500 000 endoscopies/year are performed in UK, the proportion of endoscopies that result in court proceedings through the NHSLA is tiny but the relative human and financial cost is high. Although the data suggest that claims are falling this may be misrepresentative, as claims can be made several years after the incident and the NHSLA has recently revised policies. Although successful claims resulted from direct endoscopic complications (eg, perforation, haemorrhage), many related to delays in the diagnosis and appropriate management of endoscopic complications, with adverse, and sometimes fatal, consequences. The findings may further inform the need for robust systems within endoscopy units to identify early and in particular late endoscopic complications.
Do all patients with advanced HER2 positive breast cancer need upfront-chemo when receiving trastuzumab? Randomized phase III trial SAKK 22/99
Authors: O. Pagani, D. Klingbiel, T. Ruhstaller, F. Nolè, S. Eppenberger, C. Oehlschlegel, J. Bernhard, P. Brauchli, D. Hess, C. Mamot, E. Munzone, B. Pestalozzi, M. Rabaglio, S. Aebi, K. Ribi, C. Rochlitz, K. Rothgiesser, B. Thürlimann, R. von Moos, K. Zaman, A. Goldhirsch
Journal: Annals of Oncology (2016)
Abstract 3224: Molecular Response LLC tumor bank and patient-derived tumor xenograft models: a powerful translational engine for discovery and development of novel oncology therapeutics
Authors: Thomas Broudy, Jill Ricono, Colleen Scott, Praveen Nair, Jayant Thatte, Cyrus Mirsaidi
Journal: Cancer Research (2015)

Abstract Patient-derived xenograft (PDX) models have been established from the world's largest living tumor bank at Molecular Response and used to mimic clinical trial settings with patients with heterogeneous populations and heterogeneous disease within oncology indications for a faster and less expensive path to test novel compounds in a more predictive preclinical setting. Overall, the collection is comprised of 144 000 tumor samples corresponding to 70 000 unique patients and continues to grow with new patient samples added routinely. For several patients, multiple samples were collected at different times (before and after treatment) or at different locations (primary/ metastatic). This allows evaluation of drug efficiency in pre and post treatment application which mimics a clinical setting as well the ability to monitor the effect of drug on the primary tumor and a matched metastatic tumor. For banked tumors, we have histo-pathological and molecular data as well as FFPE slides, DNA, RNA and chemosensitivity data from the original patient. MRL currently has over 350 PDX models in progress and has established &amp;gt;300 unique PDX models in multiple indications. Many established PDX models have confirmed histology and mutational profiling (Next-Gen sequencing) to demonstrate preservation of the biological characteristics of these models to the original patient sample as well as between passages within the model. MRL's vast collection of patient samples allows clients the ability to focus on unique subsets of patients for a custom model build or the ability to choose from our extensive list of established PDX models to further drug discovery of novel compounds. Citation Format: Thomas Broudy, Jill Ricono, Colleen Scott, Praveen Nair, Jayant Thatte, Cyrus Mirsaidi. Molecular Response LLC tumor bank and patient-derived tumor xenograft models: a powerful translational engine for discovery and development of novel oncology therapeutics. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3224. doi:10.1158/1538-7445.AM2015-3224
Abstract 3558: uPAR mediated endothelial targeting by oncolytic measles virus
Authors: Marcela M. Toro Bejarano, Yuqi Jing, Krisztina Kovacs, Jaime Merchan
Journal: Cancer Research (2015)

Abstract Background: The urokinase receptor (uPAR) is over-expressed in tumor cells as well as in tumor endothelium and plays a critical role in tumor neovascularization. We have recently rescued an oncolytic measles virus fully retargeted against human uPAR (MV-h-uPA). The aim of this study was to further characterize the endothelial targeting capabilities of MV-h-uPA over MV-GFP. Methods: In vitro cytotoxicity assays were performed in unstimulated and stimulated HUVEC, and the effects of both viruses were analyzed. The effects of MV-GFP and MV-h-uPA on actively forming vs. established capillaries was investigated using the matrigel tube formation assay. Endothelial to tumor transfer of MV-uPA or MV-GFP was investigated in breast, colon cnd kidney cancer cell lines expressing RFP by overlaying infected HUVEC on tumor cell monolayers. The mechanisms/kinetics of viral transfer from HUVEC to tumor cells was characterized. Microvessel density of tumors treated with MV-h-uPA was quantitated by immunohistochemistry using an antibody against CD31. Results: MV-h-uPA and MV-GFP induced cytotoxicity at 24, 48 and 72 hours in stimulated HUVECs. MV-h-uPA replicated more efficiently in growth factor stimulated, compared to resting HUVECs. Interestingly, MV-h-uPA, but not MV-GFP successfully infected actively forming (angiogenic) HUVEC capillaries, as assessed by mean fluorescence quantification of GFP expression of infected capillaries. On the other hand, the non-targeted MV-GFP predominantly infected already established HUVEC capillaries (infected 24 hours after tubes were formed), an effect not observed with MV-h-uPA. Importantly, MV-h-uPA did not induce vascular disrupting effects in HUVEC capillaries. MV-h-uPA was successfully transferred from infected endothelial cells to tumor cells. This effect was mediated by heterofusion, as chemical inhibition of virus induced fusion at different time points during co-culture completely blocked EC to TC transfer. Heterofusion occurred as early as 4 hours after endothelial cell overlay into tumor cell cultures. EC to TC viral transfer resulted in significant tumor cell cytotoxicity. Conclusion: The above results demonstrate the improved ability of uPAR retargeted oncolytic measles virus to infect, replicate and successfully infect angiogenic endothelial cells, as well as successful EC to TC transfer in vitro, resulting in tumor cell cytotoxicity. Vascular targeting by oncolytic MVs may result in improved tumor cell delivery in vivo, and enhanced antitumor effects. Citation Format: Marcela M. Toro Bejarano, Yuqi Jing, Krisztina Kovacs, Jaime Merchan. uPAR mediated endothelial targeting by oncolytic measles virus. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3558. doi:10.1158/1538-7445.AM2015-3558
The 20-Year Longitudinal Trajectories of Social Functioning in Individuals With Psychotic Disorders
Authors: Eva Velthorst, Anne-Kathrin J. Fett, Avraham Reichenberg, Greg Perlman, Jim van Os, Evelyn J. Bromet, Roman Kotov
Journal: American Journal of Psychiatry (2016)

Social impairment is a long-recognized core feature of schizophrenia and is common in other psychotic disorders. Still, to date the long-term trajectories of social impairment in psychotic disorders have rarely been studied systematically.Data came from the Suffolk County Mental Health Project, a 20-year prospective study of first-admission patients with psychotic disorders. A never-psychotic comparison group was also assessed. Latent class growth analysis was applied to longitudinal data on social functioning from 485 respondents with schizophrenia spectrum disorders and psychotic mood disorders, and associations of the empirically derived trajectories with premorbid social adjustment, diagnosis, and 20-year outcomes were examined.Four mostly stable trajectories of preserved (N=82; 59th percentile of comparison group sample distribution), moderately impaired (N=148; 17th percentile), severely impaired (N=181; 3rd percentile), and profoundly impaired (N=74; 1st percentile) functioning best described the 20-year course of social functioning across diagnoses. The outcome in the group with preserved functioning did not differ from that of never-psychotic individuals at 20 years, but the other groups functioned significantly worse. Differences among trajectories were already evident in childhood. The two most impaired trajectories started to diverge in early adolescence. Poorer social functioning trajectories were strongly associated with other real-world outcomes at 20 years. Multiple trajectories were represented within each disorder. However, more participants with schizophrenia spectrum disorders had impaired trajectories, and more with mood disorders had better functioning trajectories.The results highlight substantial variability of social outcomes within diagnoses-albeit overall worse social outcomes in schizophrenia spectrum disorders-and show remarkably stable long-term impairments in social functioning after illness onset across all diagnoses.
PWE-005 Initial experience of spyglass per-oral cholangioscopy in a UK centre
Authors: M Aljabiri, A Lerman, E Kalaitzakis, A Winstanley, M Noveli, S Pereira, A Hatfield, G Webster
Journal: Gut (2010)

<h3>Introduction</h3> Endoscopic retrograde cholangiopancreatography (ERCP) and biliary brush cytology fail to definitively diagnose the cause of biliary strictures and other intraductal lesions in the majority of cases. Recent advances in cholangioscopy allow direct mucosal visualisation and directed tissue sampling, which may improve diagnostic yield in these cases. <h3>Aim</h3> To evaluate initial experience of Spyglass cholangioscopy in our tertiary centre. <h3>Methods</h3> We retrospectively analysed patient demographics, indications for use, technical success, complications, and diagnostic yield in all cases of Spyglass cholangioscopy performed over the first year of use. <h3>Results</h3> Cholangioscopy was performed in 30 patients (21M:9F) in 2008–9, representing 30/723 (4%) of total ERCPs. 22 (73%) patients had undergone ERCP prior to referral. Indications for cholangioscopy included: indeterminate strictures (n=14 (47%)); intraductal mass lesion / filling defects (n=15 (50%)); suspected intraductal papillary mucinous neoplasm (n=1 (3%)). Cholangioscope insertion and mucosal visualisation was achieved in 97% (cholangioscope insertion was failed technically in one patient). One patient (3%) developed mild pancreatitis, and three (10%) developed pain during procedure due to water flushing above strictures, but without subsequent complication. Directed Spybite biopsies were taken in 12/30 (40%) of cases, with sufficient tissue for histological analysis in 10/12 (83%). A definitive histological diagnoses was reached in 8/10 (80%) with adequate tissue witha 67% sensitivity, and included: intraductal carcinoid (n=1), poorly differentiated adenocarcinoma (n=2), low grade dysplasia of the duct (n=2), IgG4 associated cholangitis (IAC) (n=2), intrahepatic papillary mucinous tumour (n=1). In conjunction with other diagnostic modalities (ERCP, CT, MRCP, EUS, percutaneous biopsy), the following final diagnoses were made: bile duct tumour (various types) (n=10), strictures (n=12) bnign secondary to CBD stone disease out of these 12 patients primary sclerosing cholangitis (n=5), common bile duct stones (n=3) these referrals were for therapy, IAC (n=1), pancreatic IPMN (n=1), common bile duct stones (n=1), peridochal varices (n=1), Liver mets resulting in compression of CBD (n=1). <h3>Conclusion</h3> To date, Spyglass cholangioscopy has been used in our practice to “trouble shoot”, where standard diagnostics have failed to achieve diagnosis. In small patient cohort safety profile appears good. Despite small tissue samples, directed biopsies have allowed definitive histological diagnoses to be made, which have significantly changed patient management. Further studies will better define role of cholangioscopy in diagnostic algorithm.
KRAS and Ki-67 in Non Small Cell Lung Cancer
Authors: M. Macerelli, G. De Maglio, L. Porcu, S. Bolzonello, S. Rizzato, C. Rossetto, V. Merlo, A. Follador, L. Pagani, V. Torri, M.C. Garassino, S. Pizzolitto, F. Puglisi, G. Fasola
Journal: Annals of Oncology (2015)
Pulmonary Hypertension in Thalassemia Assessed by Echocardiography: A Report From Baseline Data of the Thalassemia Clinical Research Network Longitudinal Cohort Study.
Authors: Claudia R. Morris, Hae-Young Kim, Felicia Trachtenberg, Charles T. Quinn, Nancy F Olivieri, Nancy Sweeters, Patricia J Giardina, Janet L Kwiatkowski, Alexis A. Thompson, Jeanne Boudreaux, Ellis J Neufeld, Elliott P Vichinsky
Journal: Blood (2009)
Phase I Trial: SABR and Ipilimumab—Response
Authors: Chad Tang, James W. Welsh, David Hong
Journal: Clinical Cancer Research (2017)

We thank Hiniker and colleagues for their interest in our work (1). We are delighted to hear that their patient continues to maintain a prolonged disease-free interval for now >5 years (2). We have also read with great interest their recent article reporting on the combination of ipilimumab and radiation to treat melanoma (3). We would like to highlight the observed activation of peripheral CD8+ T cells observed both by Hiniker and colleagues and others (4, 5) as a marker of systemic disease response. These data are in alignment with the data reported in our study, where greater CD8+ peripheral T-cell activation and numbers were associated with achievement of clinical benefit (1).Given the increasing number and variety of immunotherapy agents, greater and more effective salvage systemic options are becoming available. These options coupled with the utilization of more traditional modalities, including salvage radiation (as demonstrated by Hiniker and colleagues; ref. 2), may allow for the conversion of immunotherapy-refractory patients to long-term responders. We are currently conducting a phase II clinical trial investigating this phenomenon further (NCT02710253). In this trial, patients who progress on immunotherapy agents, including standard-of-care or experimental immunotherapy agents, are treated with salvage radiation at the time of progression.We therefore believe that it is important to identify biomarkers that facilitate early detection of patients unlikely to mount an effective systemic response. We hope that the utilization of such biomarkers with effective salvage options can help to create more cases like your patient with >5-year disease-free survival (2).See the original Letter to the Editor, p. 320J.W. Welsh reports receiving a commercial research grant from and is a consultant/advisory board member for Bristol-Myers Squibb. No potential conflicts of interest were disclosed by the other authors.
Abstract 826: DNA adducts induced by <i>in vitro</i> activation of diesel and biodiesel exhaust extracts
Authors: Jeffrey A. Ross, Garret B. Nelson, Esrta Mutlu, Sarah H. Warren, Matthews P. Peggy, M. Ian Gilmour, David M. DeMarini
Journal: Cancer Research (2015)

Abstract Petroleum diesel exhaust is a complex mixture containing many probable and known carcinogens. The development of biodiesel and biodiesel blends offers a renewable alternative to petroleum diesel, but few data are available concerning the carcinogenic potential of biodiesel exhausts. We compared the formation of covalent DNA adducts by the in vitro metabolic activation of organic extracts of diesel exhaust particles (DEP)from petroleum diesel and biodiesel. Two different petroleum diesel DEPs were examined (C-DEP and B0), as well as one biodiesel DEP (B100), and DEP resulting from combustion of a blend of 20% B100 and 80% B0 (B20), which is representative of commercially available biodiesel. Oxidative activation was performed in the presence of calf thymus DNA (ctDNA) using rat liver microsomal fractions with required cofactors (S9), and nitroreductive activation was performed using xanthine oxidase (XO) and hypoxanthine in the presence of ctDNA. The modified DNA was hydrolyzed and analyzed by 32P-postlabeling using either butanol extraction or nuclease P1 pre-enrichment. Multiple DNA adducts were produced with chromatographic mobilities consistent with polycyclic aromatic hydrocarbon (PAH) and nitro-PAH adducts. The types and quantities of DNA adducts produced from two independent petroleum diesel DEPs were similar, with evidence of formation of both PAH- and nitroPAH- derived adducts. In contrast, the biodiesel DEP B100 induced higher total levels of DNA adducts in both activation systems. The lowest levels of DNA adduct formation were observed with B20 DEP. These results suggest that the DEP from available biodiesel blends (B20) pose lower risk for induction of DNA damage than petroleum diesel. This is an abstract or a proposed presentation and does not necessarily reflect EPA policy. Citation Format: Jeffrey A. Ross, Garret B. Nelson, Esrta Mutlu, Sarah H. Warren, Matthews P. Peggy, M. Ian Gilmour, David M. DeMarini. DNA adducts induced by in vitro activation of diesel and biodiesel exhaust extracts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 826. doi:10.1158/1538-7445.AM2015-826
Screening for Social Determinants of Health
Authors: Laura Gottlieb, Caroline Fichtenberg, Nancy Adler
Journal: JAMA (2016)

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Concurrent split course hyperfractionated radiotherapy (Hfx RT) with biweekly cisplatin (DDP) and paclitaxel (P) in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck (SCCHN): The MUSC experience
Authors: R. Sawhney, A. Dragun, R. K. Stuart, U. B. Chaudhary, T. Day, M. B. Gillespie, A. Sharma
Journal: Journal of Clinical Oncology (2006)

5578 Background: Locally recurrent disease (RD) contributes to the majority of SCCHN-related deaths. In addition, second primary tumors (SPT) develop in approximately 30% of patients (pts) who were cured of their primary malignancy. For pts with disease (RD or SPT) in a previously irradiated region, therapeutic options are limited. Approaches utilizing reirradiation with concurrent chemotherapy (CT) have been investigated, with promising initial results. We retrospectively report the clinical outcome &amp; toxicity of such a regimen. Methods: A cohort of pts with locally recurrent or second primary SCCHN within previous radiation portals were treated with concurrent chemoradiotherapy (CRT). Pts received HFx RT (1.5 Gy/Fx BID × 5 every 2 wks × 4), in combination with DDP 15 mg/m 2 IV QD × 5 and P 20 mg/m 2 IV QD × 5 q 2 wks × 4. Filgrastim was given on days 6–13 of each 2 wk cycle. Results: Nineteen pts were treated (median age 61; 84% with RD at median of 22 mos, 16% SPT; primary site: oropharynx-32%, larynx-32%, oral cavity 21%). Two pts had treatment discontinued early (due to hemoptysis &amp; declining performance status, respectively). Seventeen pts were evaluable at a median f/u of 13 mos. Acute skin &amp; mucous membrane toxicity (Grade ≥ 2) was seen in 11% and 5% of pt’s, respectively, and 32% of pts developed skin fibrosis as a late radiation toxicity. Most pts (82%) received all 4 scheduled cycles of CT. Grade ≥ 3 hematologic toxicity occurred in 29% of pts (anemia 24%, neutropenia 24%, &amp; thrombocytopenia 12%). Infection was the primary non-hematologic toxicity, with Grade ≥ 3 infection in 29% (4 pneumonia, 1 vascular catheter). There was 1 treatment-related death (hypotension with CVA). Of the 16 pts who completed treatment, 4 had initial surgery, and thus had no measurable disease upon commencing CRT. Objective responses to CRT were noted in all of the remaining 12 pts and 50% achieved a CR. One-year OS rate was 65%, with median survival not yet reached. Conclusions: RD and SPT pts who are not surgical candidates have limited treatment options. Aggressive reirradiation with biweekly CT produces excellent response rates, with acceptable local and systemic toxicities. No significant financial relationships to disclose.
Quality of Life Assessment at Diagnosis and after Different Treatment Phases in Multiple Myeloma Brazilian Patients
Authors: Vanderleia Costa Silva, Manuella Sampaio Almeida, Vania T. M. Hungria, Leina Yukari Etto, José Salvador Rodrigues de Oliveira, José Carlos Barros, Rozana Ciconelli, Gisele W.B. Colleoni
Journal: Blood (2008)