tbuckley/cabot-search huggingface dataset:
P116 Multidrug-resistant tuberculosis (MDR-TB) monitoring in southeast london using current recommendations; does it prevent complications?
Authors: B Bradley, M Kamalanathan, AJ Shah, N Read, J Hall, M Belton, L Baker
Journal: Thorax (2016)

<h3>Background</h3> MDR-TB requires an intense treatment course with multiple drugs, many of which have significant recognised side effects. Frequency of monitoring to prevent long term complications is not fully established, but recent guidelines have gone some way to addressing this. In light of this we wanted to review the side effects of MDR-TB treatment in our population to identify whether our previous practice was in line with the current recommendations and if not, whether the currently recommended frequency could have identified these complications sooner. <h3>Methods</h3> 26 patients referred to our trust over 13 years (between 2002 and 2015) had a diagnosis of MDR-TB on a basis of isoniazid and rifampicin resistance on culture and/or PCR. Medical records were reviewed; diagnostic tests, resistance profiles, baseline investigations, treatment, drug monitoring tests and side effects were recorded on 21 of these patients. These were compared with current European Respiratory Society guidelines for MDR-TB management. <h3>Results</h3> All baseline tests were completed except for magnesium and electrocardiogram. 6 patients had care transferred elsewhere. Amikacin/cycloserine levels were performed in line with recommendations. Interval blood testing was not always undertaken as recommended, particularly near the end of treatment. 11/15 (73%) of patients experienced at least 1 complication to treatment. Most frequent were: amikacin induced ototoxicity in 5/15 (33%), PAS/prothionamide induced hypothyroidism in 3/15 (20%). Other complications included photosensitivity with pyrazinamide, clofazimine associated erythema, peripheral neuropathy secondary to linezolid/cycloserine, amikacin induced renal impairment and ureteric colic secondary to calculi. Audiometry revealed high frequency hearing loss prior to development of symptoms. One patient developed ototoxicity despite monthly audiometry testing. Hypothyroidism developed despite monthly thyroid function. <h3>Conclusions</h3> In our population there was a high incidence of significant side effects to MDR-TB regimes. Ototoxicity with amikacin is a significant concern. While frequent testing is advocated we found that complications were not necessarily negated by this. Frequency of testing was easier to achieve whilst an inpatient than an outpatient. With the advent of the World Health Organisation shorter MDR-TB regimen, the need for regular monitoring remains crucial, but the shorter duration of injectable drugs may also help decrease complication rates in the future.
Recovery of Viable MSCs Isolated From Fresh Umbilical Cord Tissue, Measured After Cryopreservation, Is on Average 8-Fold Higher when Compared to Recovery of Viable MSCs Isolated From Previously Cryopreserved Umbilical Cord Tissue
Authors: Robert Briddell, Frank Litkenhaus, Gail Foertsch, Angela Fuhrmann, Karen Foster, Kate Falcon Girard, Bruce Fiscus, Ann Boehm, Margaret Brown, Mystie Pettit, Asimena Rigas Bridges, Karen Nichols, William Fodor, Morey Kraus
Journal: Blood (2011)
P157 Seasonal variability of severe asthma exacerbations and clinical benefit from lebrikizumab
Authors: DF Choy, TL Staton, JR Arron, J Olsson, CTJ Holweg, S Grey, A Chai, JG Matthews
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Epidemiologic studies have implicated aeroallergens and respiratory infections as triggers underlying seasonal increases in asthma exacerbations in spring and autumn months. These seasonal factors may trigger or amplify airway inflammation in atopic, Type 2 high asthma patients that precipitates acute worsening of symptoms. Biologic therapies targeting Type 2 cytokine pathways have demonstrated efficacy in reducing the rate of severe asthma exacerbations, particularly in patients selected on the basis of Type 2 biomarkers. In children with asthma, increased inhaled corticosteroid or anti-IgE therapy has been found to reduce the rate of seasonal exacerbations. We hypothesised that lebrikizumab (anti-IL-13) therapy would likewise be effective in reducing seasonal exacerbations in adults with asthma. <h3>Methods</h3> We conducted <i>post-hoc</i> analyses of the Phase III LAVOLTA studies (NCT01867125 and NCT01868061) to assess the seasonal dependence of exacerbations and efficacy of lebrikizumab in 2,148 adults with moderate to severe asthma. We employed Poisson regression utilising linear mixed models to estimate the per-month (normalised by hemisphere) annualised exacerbation rate and treatment effect of lebrikizumab in reducing exacerbations (percent rate reduction). <h3>Results</h3> Per-month exacerbation rates in placebo treated eosinophil-low (&lt;300/µL) patients were lower and less variable (0.34 to 0.72 per year) than in eosinophil-high (≥300/µL) patients; (0.63/year in August to 1.43/year in September). The 95% confidence intervals for the per-month lebrikizumab treatment effect overlapped with zero in eosinophil-low patients for all calendar months. The maximum per-month treatment effects for eosinophil-high patients were observed during the autumn and spring months (62.7 [10.1, 84.5]% for September and 65.1 [8.6,86.7]% for May). The minimum per-month treatment effects were observed in the summer months (11.3[−148.7, 68.4]% for July and 6.6[−166.0, 67.2]% for August). <h3>Conclusions</h3> We conclude that seasonal spikes in exacerbations may be primarily dependent on Type 2 inflammatory processes. The molecular pathways underlying asthma exacerbations are heterogeneous and therapeutic strategies targeting Type 2 biology alone may have the greatest efficacy in limiting seasonal spikes in exacerbation rates. Overall, these data highlight that a significant proportion of asthma exacerbations may be independent of seasonal influences and/or Type 2 biology and that increased therapeutic efficacy may require targeting multiple distinct pathways in asthma.
RFP2 Modulates 20S Proteasome Activity, NF Kappa B Activation, and Tumor Cell Growth in Multiple Myeloma.
Authors: Moshe E Gatt, Mala Mani, Mikael Lerner, Teru Hideshima, Yunyu Zhang, Jui Dutta, Daniel E Carrasco, Alexei Protopopov, Olle Sangfelt, Dan Grander, Bart Barlogie, John D Shaughnessy, Kenneth C. Anderson, Daniel Ruben Carrasco
Journal: Blood (2009)
P1.05-004 Surfactant Protein C is a Prognostic Marker in Resected Non-Small Cell Lung Cancer
Authors: Ivan Macía, Juan Moya, Gemma Aiza, Ricard Ramos, Ignacio Escobar, Francisco Rivas, Anna Ureña, Gabriela Rosado, Pau Rodríguez-Taboada, Samantha Aso, Susana Padrones, Carlos Déniz, Ernest Nadal, Gabriel Capella
Journal: Journal of Thoracic Oncology (2017)
Autoimmunity in Patients (pts) with Chronic Myelomonocytic Leukemia (CMML): A Frequent Finding
Authors: Amer Swedeh, Mrinal Patnaik, Dima Alfakara, Aneel A Ashrani, Rajiv Pruthi, Michelle Elliott, Mark Litzow, Aref Al-Kali
Journal: Blood (2012)
P1.05-041 Dynamics of Brain Metastasis for Curatively Resected Stage I or II Non-Small Cell Lung Cancer Patients
Authors: Sumin Shin, Byung Jo Park, Jong Ho Cho, Hong Kwan Kim, Yong Soo Choi, Jae Ill Zo, Young Mog Shim, Jhingook Kim
Journal: Journal of Thoracic Oncology (2017)
P205 Improving long term oxygen prescribing at hospital discharge: a before and after study
Authors: S Forster, G Lowrey, S Smith
Journal: Thorax (2016)

<h3>Introduction</h3> Home oxygen costs the NHS approximately £120 million a year, with £13 million spent on oxygen that is never used.<sup>1</sup> Home oxygen teams require integration into the wider respiratory care pathway to ensure appropriate assessment of clinical need and risk, education and follow-up.<sup>2</sup> In Derbyshire, prescriptions initiated in the community had appropriate assessments in 90% of cases. In contrast, home oxygen initiated in secondary care at discharge was often prescribed on day of discharge, by junior doctors with no specialist training, without appropriate assessment and education, frequently necessitating early community input. Following two serious incidents post discharge, a study was implemented to evaluate the impact of a different approach to home oxygen prescription following acute hospital stay. The new service included an in-reach oxygen nurse and bespoke risk assessment for hospital discharges. <h3>Methods</h3> A before and after study was performed recording key outcomes, including number of prescriptions, cost, and input required post-discharge. This was carried out over a period of 12 months before and 12 months after implementation of the new service, assessing impact on compliance with guidelines and patient safety. <h3>Results</h3> In the pre-intervention period there were 278 home oxygen prescriptions resulting from the acute care setting, all performed by junior doctors, with 155 urgent (same day) prescriptions totalling £32,815. In the 12 months post-intervention there were 145 home oxygen prescriptions, 88 by in-reach nurses, including 56 urgent orders totalling £11,655. The previous need for 2 month post discharge visit for assessment and education reduced significantly, with associated dramatic reduction in phone-calls from patients with queries. <h3>Conclusion</h3> This study, though limited to single centre, shows significant cost and potential safety benefits. Introducing greater rigour to the in-hospital assessment process was thought to account for the overall fall in oxygen prescription, particularly high-cost urgent orders. With reduction in need for post-discharge intervention also reducing the burden in the community and suggesting greater patient understanding. <h3>References</h3> Directorate, N.M., COPD Commissioning toolkit. 2012. Hardinge M, <i>et al</i>. Guideline update: The British Thoracic Society Guidelines on home oxygen use in adults. <i>Thorax</i> 2015;<b>70</b>(6):589–91.
MA11.09 Progastrin-Releasing Peptide (ProGRP) to Rule out Progressive Disease in Patients with Small Cell Lung Carcinoma (SCLC)
Authors: Thomas Muley, Xiaotong Zhang, Stefan Holdenrieder, Catharina Korse, Xiuyi Zhi, Rafael Molina, Zhongjuan Liu, Gunther Hartmann, Michel Van Den Heuvel, Kun Qian, Ramon Marrades, Christine Engel, Ying He, Birgit Wehnl, Farshid Dayyani, Felix Jf Herth
Journal: Journal of Thoracic Oncology (2017)
OA03.05 Analysis of Early Survival in Patients with Advanced Non-Squamous NSCLC Treated with Nivolumab vs Docetaxel in CheckMate 057
Authors: Solange Peters, Frederico Cappuzzo, Leora Horn, Luis Paz-Ares, Hossein Borghaei, Fabrice Barlesi, Martin Steins, Enriqueta Felip, David Spigel, Cécile Dorange, Haolan Lu, Diane Healey, Teresa Kong Sanchez, Prabhu Bhagavatheeswaran, James Novotny, Brian Lestini, Julie Brahmer
Journal: Journal of Thoracic Oncology (2017)
S53 Effect of epigenetic inhibitors on lung fibroblast phenotype change in idiopathic pulmonary fibrosis
Authors: A Pasini, OJ Brand, G Jenkins, AJ Knox, L Pang
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Idiopathic Pulmonary Fibrosis (IFP) is a fatal interstitial lung disease with unknown aetiology. Lung myofibroblasts (activated fibrobalsts) are the major effector cells in the pathogenesis of IPF. Transforming growth factor-β (TGF-β1) is a potent activator of fibroblasts. Lack of effective treatment options necessitates novel therapeutic approaches. Epigenetic drugs, by inhibiting chromatin modifying enzymes involved in gene expression control, represent promising agents capable of modulating the cellular phenotype. We previously demonstrated that the cyclooxygenase-2 (<i>COX-2</i>) gene is epigenetically silenced in lung fibroblasts from IPF patients (F-IPF)<sup>1</sup> and epigenetic inhibitors and restore COX-2 expression. However, whether epigenetic inhibitors can alter fibroblast phenotype remains unknown. This study aimed to investigate the effect of four different epigenetic enzyme inhibitors on fibroblast phenotype change in IPF. <h3>Methods</h3> F-IPF and fibroblasts from non-fibrotic lung (F-NL) treated with TGF-β1 were cultured to test the effects of the epigenetic inhibitors BIX01294 (BIX, G9a histone methyltransferase inhibitor), 3-deazaneplanocin A (DZNep, EZH2 histone methyltransferase inhibitor), SAHA (histone deacetylases inhibitor) and Decitabine (DAC, DNA demethylating agent), in comparison with the COX-2 products prostaglandin E2 (PGE2). The expression of COX-2 and myofibroblast markers collagen 1 (COL1) and α-smooth muscle actin (α-SMA) was assessed. The <i>COX-2</i> DNA promoter methylation level was analysed by bisulfite sequencing. <h3>Results</h3> TGF-β1 induced a myofibroblast phenotype in F-NL characterised by COL1 and α-SMA upregulation and COX-2 downregulation, similar to F-IPF. PGE2 and SAHA were able to maintain/restore COX-2 expression in TGF-β1-induced myofibroblasts and F-IPF. DAC demonstrated similar effect in TGF-β1 treated F-NL only. SAHA also reduced COL1 and α-SMA expression. But DZNep and BIX showed no effect. No differences in the <i>COX-2</i> promoter methylation was detected between F-NL and F-IPF. <h3>Conclusions</h3> Among the epigenetic inhibitors tested, SAHA shows a promising antifibrotic effect by inhibiting fibroblast activation and the underlying molecular mechanisms are currently under investigation. <h3>Reference</h3> Coward WR, Feghali-Bostwick CA, Jenkins G, <i>et al</i>. A central role for G9a and EZH2 in the epigenetic silencing of cyclooxygenase-2 in idiopathic pulmonary fibrosis. <i>FASEB J</i> 2014; <b>28</b>(7):3183–96.
S124 The effectiveness of “in-clinic” smoking cessation support in the setting of secondary care respiratory outpatient services
Authors: I Valero-Sanchez, S Agrawal, S Brij, RA Evans, NJ Greening, M Perry, N Toms, E Wiggins, J Williams, MC Steiner
Journal: Thorax (2016)

<h3>Introduction and aims</h3> Although two thirds of smokers wish to quit, referral, uptake and engagement with smoking cessation (SC) services are frequently poor. In Leicester, uptake of smoking cessation referred from secondary care is approximately 20% with successful quit rate at four weeks of 10%. Provision of immediate support through smoking cessation specialist advice provided at the point of clinical assessment in outpatients might enhance referral uptake and quit rates. We assessed the value of this “in-clinic” approach in specialist respiratory outpatient clinics in two secondary care centres. <h3>Methods</h3> Provision of immediate smoking cessation advice was implemented in two outpatient clinic services providing specialist care for patients with complex, chronic obstructive pulmonary disease (COPD); an Acute General Hospital (Peterborough City Hospital, PCH) and a Tertiary Care Hospital (Glenfield Hospital, GH). All current smokers were referred to an on-site smoking cessation specialist advisor by the physician, or clinic nurse, as part of their outpatient review on the same day of their clinic visit. In the Glenfield service SC was provided by a smoking cessation specialist, using a harm reduction approach with a guided patient-led tailored programme and the possibility of direct supply treatment at the initial assessment. In the PCH service, SC using psychosocial and/or pharmacological therapy was undertaken by a dedicated smoking cessation officer Follow-up visits and telephone calls were arranged separately by the smoking service and data including demographics, treatment uptake and quit rates after 4 weeks were analysed. <h3>Results</h3> A population of 122 smokers with a diagnosis of COPD were assessed for in-clinic SC over a period of twelve months in both centres. Demographic details of both cohorts, outcomes of both SC strategies including treatment uptake and quit rates are disclosed in Table 1. <h3>Conclusions</h3> Providing “in-clinic”, expert smoking cessation advice results in favourable referral uptake and four week quit rates when compared with locally available data from paper based referral routes. Reinforcing physician delivered smoking cessation advice through immediate provision of proactive cessation support may be an effective means to enhance quit rates in secondary care.
Abstract 16338: Dna Hypomethylation in Long Non-coding Rna Promoter During Calcific Aortic Valve Stenosis: Implication for the Notch Pathway
Authors: Fayez Hadji, Marie-Chloé Boulanger, Émilie Lavoie-Charland, Nathalie Gaudreault, Sandra Guauque-Olarte, Rihab Bouchareb, Mohamed Nsaibia, Luigi Bouchard, Yohan Bossé, Patrick Mathieu
Journal: Circulation (2015)

Introduction:Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease. Transdifferentiation of valve interstitial cells of the aortic valve (VICs) into osteogenic cells is an important process in the pathology. However, the molecular mechanisms involved in gene expression during osteogenic transition are still poorly understood. Hypothesis:Long non-coding RNAs (lncRNAs) regulate gene expression pattern and may be involved in the osteogenic transdifferentiation during the development of the CAVS. Methods:Transcriptomic by RNA sequencing (RNA-seq) and DNA genome-wide methylation studies were performed in human aortic valves. In addition, the role of a lncRNA on the mineralization was explored and the molecular mechanisms by which it promotes osteogenic transdifferentiation was documented. Results:Transcriptomic profiling of CAVS and control valves revealed that a lncRNA was highly expressed in mineralized valves. The CpG islands in the promoter region of the gene coding this lncRNA were hypomethylated (n=23). These data were confirmed by q-PCR (n=152), fluorescence in situ hybridization (FISH) and pyrosequencing (n=60). Methylation status of the lncRNA promoter was inversely related to expression level and in isolated VICs a treatment with 5-aza-2’-deoxycytidine, which causes DNA demethylation, increased the expression of lncRNA by 2,5-fold. Knockdown or overexpression experiments showed that lncRNA play an important role in the osteogenic transdifferentiation via the Notch1 pathway. Promoter studies coupled with luciferase and chromatin immunoprecipitation (ChIP) revealed that this lncRNA interferes with the activity of Notch1 by physically interacting with the promoter. LncRNA-induced mineralization of VICs was rescued by a co-transfection of a vector encoding for the Notch intracellular domain (NICD). Conclusions:During CAVS the hypomethylation in the promoter region promotes the overexpression of a lncRNA. This lncRNA promotes the dysfunction of the Notch signaling pathway and induces the osteogenic transdifferentiation of VICs.
Bortezomib Plus Rituximab in Patients with Indolent Non-Hodgkin’s Lymphoma (NHL): A Phase 2 Study.
Authors: Sven de Vos, Shaker Dakhil, Peter McLaughlin, Mansoor Saleh, Robert Belt, Christopher Flowers, Mark Knapp, Lowell Hart, Dipti Patel-Donnelly, Martha Glenn, Stephanie A. Gregory, Charles Holladay, Anthony Boral, Tracy Zhang, André Goy
Journal: Blood (2005)
Clinical and Functional Relevance of Interactions Between the Bone Marrow Stormal Microenvironment and Primary Human Acute Myeloid Leukemia (AML) Cells
Authors: Soumit K. Basu, Sylvia Chien, Xin Zhao, Kenneth J. Kopecky, Frederick R. Appelbaum, Thalia Papayannopoulou, Elihu H. Estey, Pamela S. Becker
Journal: Blood (2010)
Key European guidelines for the diagnosis and management of patients with phenylketonuria
Authors: Francjan J van Spronsen, Annemiek MJ van Wegberg, Kirsten Ahring, Amaya Bélanger-Quintana, Nenad Blau, Annet M Bosch, Alberto Burlina, Jaime Campistol, Francois Feillet, Maria Giżewska, Stephan C Huijbregts, Shauna Kearney, Vincenzo Leuzzi, Francois Maillot, Ania C Muntau, Fritz K Trefz, Margreet van Rijn, John H Walter, Anita MacDonald
Journal: The Lancet Diabetes & Endocrinology (2017)
Progressive Purpura in a Long-term Care Patient
Authors: Jennifer M. E. Boggs, Catherine C. Foley, Mary E. Laing
Journal: JAMA Dermatology (2017)

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Abstract B01: Integrated genomic analysis identifies two subsets of cervical cancer with potentially distinct therapeutic profiles
Authors: Carolyn E. Banister, Lucia Pirisi, Kim E. Creek, Phillip J. Buckhaults
Journal: Clinical Cancer Research (2017)

Abstract Background and Significance: The continuous expression of HPV oncogenes is responsible for initiating and driving cervical cancer. Current treatments include radiation and Cisplatin-based chemotherapy. Targeted therapies can be directed to specific subset of tumors if they are known. Methods: Molecular genetic data generated by The Cancer Genome Atlas (TCGA) were analyzed. Results: We discovered and characterized a subset of HPV positive cervical cancers that do not express HPV transcripts, including the E6 and E7 oncogenes. These tumors more commonly appear in women with a median age of diagnosis 9 years later (54 vs. 45 years) (p-value = 0.023) and reveal worse survival (p-value 0.06). Gene expression profiles of HPV expressing tumors (HPV-active) are distinct from those tumors that do not express HPV (HPV-inactive). Gene Set Enrichment Analysis of the HPV-active tumors show enrichment for E2F target genes, as expected based on the activity of HPV E7. HPV-inactive tumors show enrichment for WNT/beta-catenin target genes. Additionally, this analysis reveals that the HPV-active tumors have increased AKT/MTOR signaling and HPV-inactive tumors have increased sonic hedgehog signaling indicating different potential therapeutic targets for these two classes of tumors. The majority of differentially expressed genes can be explained by DNA hyper methylation and silencing of expression. Somatic mutation landscapes are significantly different. HPV-inactive tumors are significantly enriched for non-synonymous somatic mutations (p-value &amp;lt;0.0000001) compared to HPV-active tumors. Conclusions: Many of the somatic mutations found in non-expressing tumors mimic the functions of the E6 and E7 viral oncoproteins, such as TP53, CTNNB1, EGFR and KRAS somatic mutations. Unexpectedly, BRCA1 and BRCA2 somatic mutations are more frequent in the HPV-inactive tumors. Therapeutic strategies based on PARP inhibition may be effective against this category of cervical cancers. Application of therapeutics routinely used in other cancer types could be used to exploit the weaknesses we discovered in the HPV-inactive tumors and may improve survival for these cervical cancer patients. Citation Format: Carolyn E. Banister, Lucia Pirisi, Kim E. Creek, Phillip J. Buckhaults. Integrated genomic analysis identifies two subsets of cervical cancer with potentially distinct therapeutic profiles. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B01.