tbuckley/cabot-search huggingface dataset:
P240 Pneumothorax management in cystic fibrosis patients
Authors: J. Gallagher, S. Chandramouli, D. Nazareth, K. Mohan, M. Ledson, M. J. Walshaw, J. Greenwood
Journal: Thorax (2011)

<h3>Introduction</h3> Spontaneous pneumothorax is a well-recognised complication in cystic fibrosis and is associated with increased morbidity and mortality. Although chemical pleurodesis and surgery are successful in preventing recurrence in non-CF patients, there are few data regarding their efficacy in CF. <h3>Method</h3> To look at this further we reviewed the management and outcome of all 28 patients (mean age at first pneumothorax 26 years [range 18–54], mean FEV<sub>1</sub> 32% predicted [17–68], 18 female) in our centre who had developed a pneumothorax (58 episodes [1–7]) from 1993 to 2010. <h3>Results</h3> Nine sustained bilateral pneumothoraces (either at initial presentation or as a subsequent event) and 16 recurrence (mean interval 4 months [1–12]). The outcomes of the initial and second line treatments are shown in the Abstract P240 table 1. 14 patients (50%) died within 12 months and 20 (71%) within 2 years of their first pneumothorax, and five deaths occurred after surgery (mean 10 days [3–21]). The highest risk of recurrence occurred in the chest drain group (62%) followed by chemical pleurodesis (with 4 g talc) (57%), observation (40%) and the surgical group (20%). <h3>Conclusion</h3> Thus, we have confirmed that spontaneous pneumothorax is a poor prognostic factor in CF, with 57% of patients experiencing a recurrent pneumothorax within the first year and poor one and 2-year survival rates. Surgical treatment was associated with a lower risk of recurrence, but at the expense of an increase in mortality. Randomised controlled trials of treatment options and the formulation of guidelines are required to determine the timing and optimal management to prevent recurrent pneumothorax in CF patients.
Abstract 2315: Reversible disruption of mSWI/SNF-like BAF complexes by the SS18-SSX oncogenic fusion in synovial sarcoma.
Authors: Cigall Kadoch, Gerald R. Crabtree
Journal: Cancer Research (2013)

Abstract Recent exon sequencing studies have revealed frequent mutations in subunits of SWI/SNF or BAF complexes and implicated them as tumor suppressors. Indeed, we estimate that they are mutated in 15.8 percent of sequenced human cancers. Interestingly, the subunits most commonly mutated are not required for chromatin remodeling in vitro and thus may contribute to chromatin regulation in a novel way. One difficultly in understanding the role of these complexes in cancer is distinguishing primary driving mutations from passenger mutations. To investigate the underlying mechanism we studied human synovial sarcoma (SS), in which transformation results from a remarkably precise and uniform translocation of exactly 78 amino acids of SSX to the SS18 protein. In a proteomic study we discovered that SS18 is a dedicated, non-exchangeable subunit of BAF complexes. We demonstrate that the hallmark SS18-SSX fusion incorporates into BAF complexes, evicting both the wild-type SS18 protein and the tumor suppressor, hSNF5 (BAF47). The altered complex binds the Sox2 locus, reversing polycomb-mediated repression and results in Sox2 activation. Sox2 is uniformly expressed in SS tumors and is essential for their proliferation. Increasing the concentration of wild-type SS18 leads to reassembly of the wild-type complex, retargeting of BAF complexes away from the Sox2 locus, polycomb-mediated repression of Sox2 and cessation of proliferation. This mechanism of transformation depends on only two amino acids of SSX and hence provides a potential foundation for therapeutic intervention. Citation Format: Cigall Kadoch, Gerald R. Crabtree. Reversible disruption of mSWI/SNF-like BAF complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2315. doi:10.1158/1538-7445.AM2013-2315
Abstract 2077: MicroRNA signature of hyperplastic enlarged lobular units (HELU) from patients with high risk of breast cancer
Authors: Sofie Nilsson, Göran Landberg
Journal: Cancer Research (2010)

Abstract In order to detect early pathological changes in breast tissue, which could reveal the underlying mechanism to cancer progression, we investigated the microRNA (miRNA) expression profile in hyperplastic enlarged lobular units (HELUs). HELUs arise from normal terminal duct lobular units (TDLUs) and are potentially the earliest histologically identifiable alterations in the development of breast cancer. TDLUs and HELUs, from formalin-fixed paraffin embedded tissue from patients with high risk of developing breast cancer, were laser capture microdissected and the RNA was extracted. Expression profiles were obtained using a qRT-PCR-based array analyzing 667 human miRNAs. In the first set of miRNA array analyses of paired samples from four specimens with early HELUs, we obtained a list of 16 downregulated and 10 upregulated miRNAs with a significant change (p&amp;lt;0.05) in expression. Among the most pronounced altered miRNAs were miR-136, miR-301b, miR-302b and miR-576-5p. To validate these results, more paired samples of fully developed HELUs will be added to the study and candidate miRNAs will be further validated using qPCR and in situ hybridization of formalin fixed specimens using a selection material of 100 patients with high risk of breast cancer. These ongoing miRNA analyses will potentially reveal additional miRNAs that are linked to the development of TDLUs towards HELUs as well as substantiating the frequency of the various alterations observed. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2077.
The Regional Injection of Penicillin in Local Infections
Authors: David Rose, David Hurwitz
Journal: New England Journal of Medicine (1946)

THE advent of penicillin has opened up innumerable fields of exploration in the treatment of infection. Sufficient work has been done and enough reports have been published on the production, assaying and pharmacology of the drug to permit omission of their discussion. This report is mainly concerned with the administration and dosage of penicillin in local infections, with direct regional injection and without systemic injections or other local therapy.There have been many attempts to use penicillin locally. Peck1 reported 15 cases in which this drug was employed locally with good results. He, however, also used it systemically, and in . . .
REGIONAL CONTRACTION HETEROGENEITY IS ASSOCIATED WITH PERSISTENT MYOCARDIAL DYSFUNCTION AND UNFAVORABLE CLINICAL OUTCOMES IN PATIENTS WITH PERIPARTUM CARDIOMYOPATHY
Authors: Bhupendar Tayal, Dennis McNamara, Joan Briller, Julie Damp, James Fett, Eileen Hsich, Kalgi Modi, Navin Rajagopalan, John Gorcsan
Journal: Journal of the American College of Cardiology (2015)
P271 Impact of structured referral and follow-up pathways on access to ventilatory support for people with motor neurone disease (MND)
Authors: S. K. Banerjee, M. G. Davies, I. E. Smith
Journal: Thorax (2011)

<h3>Introduction</h3> Attitudes to surveillance for and treatment of ventilatory failure among people with MND have changed over several years. In the UK this culminated in the publication in July 2010 of National Institute of Clinical Excellence (NICE) guidance designed to increase access to non-invasive ventilation (NIV). The services offered in our respiratory unit have evolved on the basis of published evidence in advance of formal guidelines. We examined the impact of compliance with practice parameter recommendations in NICE to our referral numbers and uptake of NIV in East Anglia. <h3>Methods</h3> A retrospective review of number of referrals and new NIV starters from 1984 to 2010 in a regional respiratory support unit. Between 2001 and 2005 the MND Association helped to establish a care centre in Cambridge and closer working was established with the respiratory service. From 2006 the default position was to offer all patients newly diagnosed with MND a respiratory assessment and structured 3 monthly follow-up appointments in a fashion subsequently detailed in the NICE guidance. <h3>Results</h3> The numbers of new referrals and people starting NIV are shown in Abstract P271 figure 1. Between 1984 and 2000 there was slow growth but the mean annual values were just seven referrals and four new NIV starters (57%). With closer working between neurologists in the care centre and the respiratory unit between 2001 and 2005 mean referral numbers increased to 31 with 17 new NIV starters (55%) per year. With default referral and 3 monthly reviews the number referred grew to 44 with around 31 NIV starters per year (70%). <h3>Conclusion</h3> With an estimated population of 2.5 million in East Anglia, and an annual incidence of 2.8 per 100 000 we estimate 70 new cases of MND per year. Around 60% of patients are therefore being referred and 70% of these are starting NIV. Implementing the NICE guidance could have a similar impact across the UK, a great improvement on the position in 2000 when only around 3% of patients were being offered NIV.1
INTRAVASCULAR ULTRASOUND, BUT NOT OPTICAL COHERENCE TOMOGRAPHY, PREDICTS NO REFLOW PHENOMENON AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION CAUSED BY PLAQUE RUPTURE
Authors: Tsunenari Soeda, Takumi Higuma, Naoki Abe, Masahiro Yamada, Hiroaki Yokoyama, Shuji Shibutani, Haibo Jia, Jinwei Tian, Rocco Vergallo, Yoshiyasu Minami, Hang Lee, Ken Okumura, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2015)
Ebola in Freetown Area, Sierra Leone — A Case Study of 581 Patients
Authors: Rashid Ansumana, Kathryn H Jacobsen, Foday Sahr, M'baimba Idris, Henry Bangura, Mohamed Boie-Jalloh, Joseph M Lamin, Santigie Sesay
Journal: New England Journal of Medicine (2014)

Ebola virus continues to cause considerable disease in West Africa, with an initial 70% associated mortality. This report shows improving survival at one center in Sierra Leone.
Soluble Biodegradable Polymer-Based Cytokine Gene Delivery for Cancer Treatment
Authors: Anurag Maheshwari, Ram I. Mahato, John McGregor, Sang-oh Han, Wolfram E. Samlowski, Jong-Sang Park, Sung Wan Kim
Journal: Molecular Therapy (2000)

<h2>Abstract</h2> Transgene expression and tumor regression after direct injection of plasmid DNA encoding cytokine genes, such as mIL-12 and mIFN-γ, remain very low. The objective of this study is to develop nontoxic biodegradable polymer-based cytokine gene delivery systems, which should enhance mIL-12 expression, increasing the likelihood of complete tumor elimination. We synthesized poly[α-(4-aminobutyl)-l-glycolic acid] (PAGA), a biodegradable nontoxic polymer, by melting condensation. Plasmids used in this study encoded luciferase (pLuc) and murine interleukin-12 (pmIL-12) genes. PAGA/plasmid complexes were prepared at different (±) charge ratios and characterized in terms of particle size, zeta potential, osmolality, surface morphology, and cytotoxicity. Polyplexes prepared by complexing PAGA with pmIL-12 as well as pLuc were used for transfection into cultured CT-26 colon adenocarcinoma cells as well as into CT-26 tumor-bearing BALB/c mice. The <i>in vitro</i> and <i>in vivo</i> transfection efficiency was determined by luciferase assay (for pLuc), enzyme-linked immunosorbent assay (for mIL-12, p70, and p40), and reverse transcriptase–polymerase chain reaction (RT–PCR) (for Luc and mIL-12 p35). PAGA condensed and protected plasmids from nuclease degradation. The mean particle size and zeta potential of the polyplexes prepared in 5% (w/v) glucose at 3:1 (±) charge ratio were approximately 100 nm and 20 mV, respectively. The surface characterization of polyplexes as determined by atomic force microscopy showed complete condensation of DNA with an ellipsoidal structure in Z direction. The levels of mIL-12 p40, mIL-12 p70, and mIFN-γ were significantly higher for PAGA/pmIL-12 complexes compared to that of naked pmIL-12. This is in good agreement with RT–PCR data, which showed significant levels of mIL-12 p35 expression. The PAGA/pmIL-12 complexes did not induce any cytotoxicity in CT-26 cells as evidenced by 3-{4,5-dimethylthiazol-2-yl}-2,5-diphenyltetrazolium bromide assay and showed enhanced antitumor activity <i>in vivo</i> compared to naked pmIL-12. PAGA/pmIL-12 complexes are nontoxic and significantly enhance mIL-12 expression at mRNA and protein levels both <i>in vitro</i> and <i>in vivo</i>.
Emergency Thoracotomy for Massive Spontaneous Hemopneumothorax
Authors: Mark H. Williams, John C. Carmen, David M. Seymour
Journal: New England Journal of Medicine (1954)

MASSIVE intrapleural hemorrhage is a rare but frequently fatal complication of spontaneous pneumothorax for which surgical treatment has only recently been utilized. This article summarizes published data demonstrating that intrapleural hemorrhage in this condition frequently presents an indication for emergency thoracotomy. Preoperative management and the indications for and conduct of operation are briefly considered, and a typical case is briefly reported in which the hemorrhage did not assume serious proportions until four days after onset of the illness, when a positive pressure pneumothorax presumably developed and produced rupture of a vascular adhesion. By actual weight and measurement the intrapleural blood . . .
Abstract 4091: Epigenetic silencing of microRNA in the pathobiology of CLL
Authors: Deepa Sampath, Chaomei Liu, William G. Wierda, Michael J. Keating
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRs, miRNA) are a class of non-coding RNA that control gene expression at a post-transcriptional level. Specific and aberrant miRNA signatures distinguish indolent and relapsed forms of chronic lymphocytic leukemia (CLL). In this study, we focused on the expression and cellular targets of a set of microRNA (miR15a, miR-16, miR-29b and miR-101) that are differentially expressed in indolent and refractory disease. The tumor suppressor microRNAs, miR-15a and miR-16, are downregulated in 68% of all CLL and associated with an indolent course. These miRNA are located on an intron of the dleu2 gene within a genomic locus (chr13q) that is frequently deleted in leukemia. However, deletions in 13q usually involve only one allele and do not adequately account for the low expression levels of miR-15a and miR-16. We hypothesized that aberrant recruitment of the histone deacetylases could be a novel mechanism that drives the silencing of miR-15a and miR-16 in CLL. Correspondingly, exposure to a variety of small molecule histone deacetylase inhibitors led to the re-expression of miR-15a and miR-16 in 30% of samples that undergo silencing. We then evaluated the cellular targets of miR-15a and miR-16 in CLL. Ectopic expression of miR-15 and miR-16 in primary leukemia cells led to a loss of Bcl-2 and Mcl-1. However, pharmacological re-expression of these miRNA led to decreases in Mcl-1 protein, with no loss in Bcl-2. Losses in the levels of Mcl-1 were associated with induction of cell death in these leukemia cells. In contrast to miR-15a and miR-16, the microRNAs miR-29b and miR-101 are well expressed in indolent disease but become silenced in relapsed/refractory disease by unknown mechanisms. We identified that exposure to a variety of histone deacetylase inhibitors induced the re-expression of miR-29b and miR-101 in 30-50% of the downregulated samples. Chromatin immunoprecipitation experiments demonstrated that deacetylase inhibition led to an increase in permissive chromatin marks at the gene promoters for these miRNA. miR-29b is known to target Mcl-1, Tcl-1 as well as the DNA methyltransferases 3a and 3b. Ectopic expression of miR-29b in CLL cells led to the decrease of Mcl-1 protein. In parallel, expression of miR-101 led to the inhibition of EZH2 expression. Correspondingly, pharmacological re-expression of miR-29b and miR-101 was associated with losses in Mcl-1 and EZH2 in CLL cells and apoptotic death of these leukemia cells. These results identify a role for epigenetic mechanisms in the pathological silencing of miRNA in both indolent and relapsed CLL. They also offer a novel therapeutic strategy by which to reverse epigenetic silencing of miRNA for therapeutic benefit. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4091.
SAT0257 A Major Clinical Response to Anti-TNF Agents is Associated with a Reduced Development of Fatty Changes in the Spine of Patients with Ankylosing Spondylitis – New Analyses from the Easic Registry
Authors: X. Baraliakos, F. Heldmann, J. Callhoff, J. Listing, J. Braun
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fatty changes (FC) on T1-weighted magnetic resonance images (MRI) have been described in the spine of patients with ankylosing spondylitis (AS). Such lesions were recently found to be related to syndesmophyte development in AS patients treated with anti-TNF agents. While TNF blockers have been shown to reduce inflammatory changes seen on STIR MRI sequences, their effect on the course of FC has not been studied in detail to date. <h3>Objectives</h3> To study the course of FC in patients with AS under anti-TNF therapy and analyse which clinical parameters are associated with the occurrence of FC. <h3>Methods</h3> MRI of AS patients participating in the EASIC Registry who had received infliximab for 2 years were blindly for the time point of examination. Presence or absence of FC was recorded for all vertebral edges (VEs) at baseline, after 24 weeks and after 2 years of treatment. Spinal radiographs at baseline and 2 years were scored by the mSASSS. Relative risk (RR) calculations were performed based on generalized estimation equations (GEE model). Poisson variation and X2 test was used to compare MRI findings between time points. <h3>Results</h3> Complete sets of MRI were available of 73 patients (mean age 40.5±10.5 years, 86.3% male, HLA-B27+: 83.6%, mean BASDAI 6.5±1.4, mean disease duration 10.0±8.4 years) resulting in a total of 1,948 VEs at each time point. At baseline, FC were found in 619 VEs (31.8%). After 24 weeks of infliximab therapy, regression of FC was seen in 19 VEs (3.1%), while new FC had appeared in 133/1,329 VEs (10.0%). After 2 years, regression of FC was observed in 35/619 VEs (5.7%) and new FC were seen in 215 VEs (16.2%), while 4/1,948 VEs (0.3%) showed both regression and development to FDL at different time points. Increased inflammatory activity at baseline was significantly associated with development of FC: 34% of VEs with inflammation vs. 12.9% of VEs without (p&lt;0.0001). Baseline mSASSS scores increased the risk of FC: RR 1.03, 95% CI: 1.01-1.04 (p=0.0003), while a major treatment response (50% BASDAI improvement) was associated with lower risk: RR=0.85, 95% CI: 0.76-0.95 (p=0.005). Being female lowered the risk for FC by 22%: RR: 0.88, 95% CI: 0.59-1.32, p=0.544), and younger age also had some influence: RR: 0.97, 95% CI: 0.93-1.00 (p=0.0327). <h3>References</h3> This study confirms that FC develop in AS patients treated with TNF blockers and that inflammation may be one source of that. However, the most important finding of this analysis is that a good response to TNF blockers was associated with significantly lower risk to develop FC. Whether this leads to a decrease in new bone formation over time remains to be seen. <h3>Disclosure of Interest</h3> None Declared
PTU-129 The Role Of Primary Resection And Hepatic Resection In The Management Of Metastatic Pancreatic Neuroendocrine Tumours With Irresectable Liver Metastases
Authors: L Mills, R Srirajaskanthan, J Ramage, A Prachalias, P Srinivasan, K Menon, A Quaglia, N Heaton
Journal: Gut (2014)

<h3>Introduction</h3> More than 40% of pancreatic neuroendocrine tumour (PNET) patients have liver metastases (LM) at diagnosis. Whilst it is agreed that, where possible, curative surgery offers the best outcomes, the role of debulking surgery in the context of irresectable LM remains unclear. There is also no clear evidence to support resection of the pancreatic primary in the context of irresectable liver metastases. The aim of this study is to investigate the survival benefits of different surgical treatments of LM. <h3>Methods</h3> The notes of 111 PNET patients who had visited King’s since 2004 were reviewed. 53 had LM at diagnosis and were divided into 3 cohorts: No Resection (NR) n = 27, Pancreatic Resection (PR) n = 6 and Pancreatic and Liver Resection (PLR) n = 11. Median follow-up was 40.2 months. <h3>Results</h3> Median survival for all patients with liver metastases was 61.1 months. Survival was significantly worse for patients with no resection; NR (23 months) vs. PR (98 months) p = 0.047, NR (23 months) vs. PLR (n/a) p = 0.008, but there was no significant difference between PR and PLR. Of the 11 PLR patients, 6 received debulking rather than curative resection. Univariate analysis showed no significant survival difference between dubulking and curative liver resection; however, multivariate analysis showed that resectability of liver metastases was not a significant prognostic variable. <h3>Conclusion</h3> Resection of the primary significantly improves survival in the presence of irrespectable liver metastases. There may be a role for debulking surgery in patients with irresectable liver metastases, however, the data so far does not appear to suggest a survival benefit over primary resection alone; larger studies are needed. <h3>Disclosure of Interest</h3> None Declared.