tbuckley/cabot-search huggingface dataset:
Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease
Authors: Matthew J. Crowley, Clarissa J. Diamantidis, Jennifer R. McDuffie, C. Blake Cameron, John W. Stanifer, Clare K. Mock, Xianwei Wang, Shuang Tang, Avishek Nagi, Andrzej S. Kosinski, John W. Williams
Journal: Annals of Internal Medicine (2017)

Background: Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. Purpose: To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment. Data Sources: MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Study Selection: English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. Data Extraction: 2 reviewers abstracted data and independently rated study quality and strength of evidence. Data Synthesis: On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF. Limitations: Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. Conclusion: Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support the recent changes in metformin labeling. Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016027708)
A Decade of Reduced-Intensity Conditioned Allogeneic Haematopoietic Stem Cell Transplantation for Myelodysplastic Syndromes Following Conditioning with Fludarabine, Busulphan and Alemtuzumab.
Authors: Aloysius YL Ho, Pramila Krishnamurthy, ZiYi Lim, Michelle Kenyon, Aleksander Mijovic, Stephen Devereux, Antonio Pagliuca, Ghulam J Mufti
Journal: Blood (2009)
Fatal Cerebral Infarction in an Asymptomatic Young Patient With Primary Antiphospholipid Syndrome.
Authors: Shinjiro Muneta, Eisuke Yokota, Seiichiro Watanabe, Isao Matsumoto, Yoriaki Yamashita
Journal: Circulation (1995)

An 18-year-old woman with primary antiphospholipid syndrome developed a major cerebral infarction leading to brain death despite intensive treatment with steroids, urokinase, glyceol and heparin. Fatal strokes associated with this syndrome are rare. A computed tomographic scan of the brain suggested occlusion of the main trunk of the right middle cerebral artery. The titer of antibodies against cardiolipin/ beta 2-glycoprotein I complex in serum was extremely high.
P210 Implementation of electronic copd discharge care bundles: a quality improvement project
Authors: S Santharam, ST Lugg, G Packer, R Colclough, S Gompertz
Journal: Thorax (2016)

<h3>Background and aims</h3> Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are responsible for 115,000 emergency admissions to hospital <i>p.a.</i>; one-third of patients are re-admitted within 90 days. COPD discharge care bundles reduce re-admission rate.<sup>1</sup> Paper-based COPD discharge bundles were implemented in our trust (a large tertiary centre in the West Midlands) in 2013, with disappointing completion rates. In order to improve compliance, an electronic bundle (e-bundle) was introduced This uses a novel system (Figure 1) that electronically alerts our multidisciplinary respiratory support team to potential AECOPD patients when medications for AECOPD are electronically prescribed (e-prescribed). The aim of this audit was to see whether completion of COPD discharge bundles in this trust has improved since the e-prescribing alert system and e-bundle implementation in 2015. <h3>Methods</h3> Admissions coded as AECOPD were retrospectively identified using ICD-10 codes for a three-month continuous period in 2015. Discharge summaries and e-bundles for each patient were accessed via online records, and in patients who were bundle-appropriate, data were collected on the presence or absence of a bundle, and completion of its 10 individual elements. <h3>Results</h3> In 2015, 125 admissions coded as AECOPD were identified; 93 were bundle-appropriate. 80% of these had a COPD discharge bundle in the electronic record; a significant improvement on the 38% bundle completion in bundle-appropriate patients in 2013 (<i>p</i> &lt; 0.0001). Percentage completion was &gt;90% for seven of the ten elements included in the 2015 e-bundle. Direct comparison of the six points included in both the 2013 paper bundle and the 2015 e-bundle, revealed that more patients were assessed for pulmonary rehabilitation in 2013 (100% vs 92%, <i>p</i> = 0.0417); all other elements had no significant change in completion rates. <h3>Conclusions</h3> Introduction of an e-bundle and e-prescribing alerts to respiratory support team members more than doubled completion of COPD discharge bundles. This clearly shows the benefit conferred by use of an electronic system for prescribing, referrals and bundle proformas. We advocate the increased use of e-bundles as electronic prescribing and information systems are introduced across trusts. <h3>Reference</h3> Hopkinson NS, <i>et al</i>. Designing and implementing a COPD care discharge bundle. <i>Thorax</i> 2012;<b>67</b>:90–92.
Abnormality on a skull radiograph
Authors: Janice Ser Huey Tan, Timothy Shao Ern Tan
Journal: BMJ (2017)

A 65 year old woman presented with a four week history of increased fatigue, intermittent chest pain, dyspnoea, and frequent constipation. Biochemistry showed haemoglobin of 95 g/L (baseline 130 g/L) and an estimated glomerular filtration rate of 5 ml/min/1.73m2 (baseline 50 ml/min/1.73m2). Initial chest radiography revealed multiple unexplained rib fractures, which prompted a further skeletal survey, including a radiograph of the skull (fig 1⇓).



Fig 1  Radiograph of the skull



What does the skull radiograph show?

Lytic bone lesions caused by myeloma bone disease (fig 2).

The skull radiograph (fig 2) shows widespread mottled lytic punched out deposits in the skull vault, which creates a “pepper pot” …
M5 The correlation between satisfaction with information about medicines and clinical outcomes in an ethnically diverse difficult asthma cohort
Authors: H Dhruve, H Khachi
Journal: Thorax (2016)

<h3>Introduction</h3> It is thought that a common cause of poor asthma control is lack of information about medication and their use. This study aims to investigate the influence of satisfaction with information about medicines and its associated clinical outcomes in patients in a difficult asthma cohort. <h3>Methodology</h3> Ethics approval was granted. All patients attending a difficult asthma clinic in a large tertiary centre were invited to participate. The Satisfaction with Information about Medicines Scale (SIMS) questionnaire was used.<sup>1</sup> This validated 17 item questionnaire, explores various aspects of medication information with preventer inhalers and the associated patient satisfaction with this. Demographic and adherence information from the GP were also collected. SPSS version 22.0 was used to analyse the data. <h3>Results</h3> The table shows that patients from non-Caucasian backgrounds had statistically significantly lower reported satisfaction with information about medicines. There was also a statistically significant correlation between low satisfaction with information and increased salbutamol use and rates of asthma exacerbations. <h3>Discussion</h3> This study shows the importance of ethnicity to the level of satisfaction with information about medicines. Language barriers, lack of understanding or health beliefs could be contributing factors. Our study found no statistical significance found between GP prescription refill rates (adherence) and associated exacerbations and salbutamol use. However, it is worth noting that our study did not investigate whether patients who picked up their preventer inhalers were indeed using them as intended by their clinician, nor did it assess inhaler technique. <h3>Conclusion</h3> We have shown that using a validated questionnaire can help identify patients who are at risk of having a lower satisfaction with their medicines and in turn a greater likelihood of having poorer clinical outcomes. Eliciting satisfaction with information about medication can help tailor interventions to support clinical outcomes in patients from ethnic minorities. <h3>Reference</h3> Horne R, Hankins M, <i>et al</i>. The Satisfaction with Information about Medicines Scale (SIMS): a new measurement tool for audit and research. <i>Qual Health Care</i> 2001;<b>10</b>(3):135–140.
OA01.05 The Impact of Lung Age on Postoperative Complications in Patients with Lung Cancer Combined with Pulmonary Fibrosis and Emphysema
Authors: Masahito Naito, Yasuto Kondo, Hirotsugu Yamazaki, Hiroyasu Nakashima, Yoshio Matsui, Kazu Shiomi, Yukitoshi Satoh
Journal: Journal of Thoracic Oncology (2017)
Lymphoma Symptoms: Data from a Phase 3, International, Randomized, Open-Label, Multicenter Study in Patients with Previously Treated Mantle Cell Lymphoma (MCL) Treated with Ibrutinib Vs. Temsirolimus
Authors: Georg Hess, Simon Rule, Wojciech Jurczak, Mats Jerkeman, Rodrigo Santucci, Chiara Rusconi, Dolores Caballero, Cristina M. Joao, Mathias Witzens-Harig, Isabelle Bence-Bruckler, Seok-Goo Cho, Nibedita Bandyopadhyay, Jenna Goldberg, John Bothos, Christopher Enny, Jessica Vermeulen, Shana Traina, Martin H. Dreyling
Journal: Blood (2015)
Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV
Authors: Bence György, Cyrille Sage, Artur A. Indzhykulian, Deborah I. Scheffer, Alain R. Brisson, Sisareuth Tan, Xudong Wu, Adrienn Volak, Dakai Mu, Panos I. Tamvakologos, Yaqiao Li, Zachary Fitzpatrick, Maria Ericsson, Xandra O. Breakefield, David P. Corey, Casey A. Maguire
Journal: Molecular Therapy (2017)

Adeno-associated virus (AAV) is a safe and effective vector for gene therapy for retinal disorders. Gene therapy for hearing disorders is not as advanced, in part because gene delivery to sensory hair cells of the inner ear is inefficient. Although AAV transduces the inner hair cells of the mouse cochlea, outer hair cells remain refractory to transduction. Here, we demonstrate that a vector, exosome-associated AAV (exo-AAV), is a potent carrier of transgenes to all inner ear hair cells. Exo-AAV1-GFP is more efficient than conventional AAV1-GFP, both in mouse cochlear explants in vitro and with direct cochlear injection in vivo. Exo-AAV shows no toxicity in vivo, as assayed by tests of auditory and vestibular function. Finally, exo-AAV1 gene therapy partially rescues hearing in a mouse model of hereditary deafness (lipoma HMGIC fusion partner-like 5/tetraspan membrane protein of hair cell stereocilia [Lhfpl5/Tmhs-/-]). Exo-AAV is a powerful gene delivery system for hair cell research and may be useful for gene therapy for deafness.
Constitutive Lymphoid Expression of the Nuclear Form of RNase H1 Is Associated with Development of Immature B Cell Lymphomas.
Authors: Kiran B Sakhuja, Lina A Gugliotti, Yutaka Suzuki, Alexander L Kovalchuk, Hongsheng Wang, Dong-Mi Shin, Susana M Cerritelli, Herbert C Morse, Robert J Crouch
Journal: Blood (2009)
No Evidence That PTEN Abnormalities Impact on Outcome in Pediatric Patients with T-Cell Acute Lymphoblastic Leukemia (T-ALL) Treated on the MRC UKALL2003 Trial
Authors: Sarah Jenkinson, Amy A Kirkwood, Nicholas Goulden, Ajay J. Vora, Chris Mitchell, Rachel Wade, Jeremy Hancock, Anthony V. Moorman, David C Linch, Rosemary E Gale
Journal: Blood (2014)
Up-Front Treatment of Diffuse Large-B Cell Lymphoma (DLBCL) in Elderly Patients with Rituximab in Combination with CHOP-Like Chemotherapy: A Multicenter Study on the Current Clinical Management.
Authors: Miguel A. Canales, Javier de la Serna, Pilar Sabin, Joaquin Diaz-Mediavilla, Mariano Provencio, Rosa Ayala, Ricardo Perez, Ana Alvarez, Antonio Sanchez, Raquel Gil, Fernando Hernandez-Navarro
Journal: Blood (2005)
Mechanism of thymic renewal after infusion of suicide gene-modified donor T cells after hematopoietic stem cell transplantation (HSCT) in adult patients.
Authors: C. Bordignon, L. Vago, G. Oliveira, M. Noviello, C. Soldati, D. Ghio, I. Brigida, A. Aiuti, M. T. Lupo-Stanghellini, J. Peccatori, A. Lambiase, A. Bondanza, A. Del Maschio, F. Ciceri, C. Bonini
Journal: Journal of Clinical Oncology (2011)

6526 Background: In haploidentical HSCT, the infusion of donor T cells genetically modified to express the Herpes Simplex Virus Thymidine kinase (HSV-Tk) suicide gene allows GvHD control, while rapidly providing effective and polyclonal T cell repertoire against pathogens and underlying tumors (Ciceri, Bonini, Lancet Oncol 2009). Methods: In phase I/II trial, 28 pts with hematologic tumors received purified HSV-Tk transduced cells after T cell depleted HSCT and 22/28 had rapid and stable T cell immune reconstitution (IR). Though HSV-Tk+ cell infusions are needed to achieve these effects, HSV-Tk+ cells represent the minority of lymphocytes circulating in treated pts. Therefore, we hypothesized an indirect role of HSV-Tk+ cells in prompting T cell development from graft progenitors by a thymus-dependent pathway. Results: Treated pts showed early recovery of naïve T cells, mostly negative for the HSV-Tk transgene. Newly reconstituted CD4+ naïve T cells were almost entirely comprised by CD31+ recent thymic emigrants. Accordingly, CT scans showed increased thymic volume and single joint T cell Receptor Excision Circles counts rose following HSV-Tk cell add backs. Comparison with a cohort of pts subject to T-cell replete HSCT further suggested a unique direct role of HSV-Tk+ cells in promoting thymopoiesis. Once HSV-Tkneg T cells appeared, full immune competence against infections was obtained, and was not compromised in those pts in whom the suicide gene was activated to control GvHD. Notably, serum IL-7 markedly rose after Tk cell add backs, suggesting that the genetically manipulated T cells may mediate the release of this stromal cytokine, in turn supporting the generation and maturation of T cells. Notably, in absence of HSV-Tk cell engraftment, neither increase in IL-7 levels nor appearance of HSV-Tkneg T cells were noted. Conclusions: The infusion of suicide gene-modified T cells induces IL-7 release, boosts the function of adult thymus and prompts recovery of a polyclonal, fully competent, T cell repertoire. A phase III trial (TK008) with HSV-Tk+ cells in haploidentical HSCT for leukemia, already ongoing in Italy, is expanding in EU.
Erythrocyte membrane-coated nanogel for combinatorial antivirulence and responsive antimicrobial delivery against Staphylococcus aureus infection
Authors: Yue Zhang, Jianhua Zhang, Wansong Chen, Pavimol Angsantikul, Kevin A Spiekermann, Ronnie H. Fang, Weiwei Gao, Liangfang Zhang
Journal: Journal of Controlled Release (2017)
P3.02a-025 PROs With Ceritinib Versus Chemotherapy in Patients With Previously Untreated ALK-rearranged Nonsquamous NSCLC (ASCEND-4)
Authors: Daniel Shao-Weng Tan, Jean-Charles Soria, Gilberto De Castro, Yi Long Wu, Luis Paz-Ares, Jürgen Wolf, Sarayut Geater, Sergey Orlov, Diego Cortinovis, Chong-Jen Yu, Maximilian Hochmair, Alexis Cortot, Chun-Ming Tsai, Denis Moro-Sibilot, Rosario García Campelo, Fabrice Branle, Paramita Sen, Gero Struebbe, Tracey Mcculloch, Lucio Crinò
Journal: Journal of Thoracic Oncology (2017)
Evidence for Differential Regulation of Transferrin Receptor 1 in Normal vs. Malignant B Cells.
Authors: Ioanna Chiotoglou, Tatjana Smilevska, Kostas Stamatopoulos, Maria Samara, Sophia Likousi, Chrysoula Belessi, Nikolaos Laoutaris, Athanasios Fassas, Nikolaos Stathakis, Panagoula Kollia
Journal: Blood (2005)
Development of Myelodysplastic Syndrome and Acute Leukemias in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS): A Population-Based Study of 17,315 Patients
Authors: Lindsey E. Roeker, Dirk Larson, Robert A. Kyle, Shaji K. Kumar, Angela Dispenzieri, S. Vincent Rajkumar
Journal: Blood (2012)
Nitric oxide metabolism in COPD comorbidities
Authors: Svetlana Soodaeva, Timur Li, Igor Klimanov, Lidiya Nikitina, Natalia Kubysheva, Larisa Postnikova, Olga Mironova, Anatoly Fedin
Journal: European Respiratory Journal (2014)

Chronic cerebral ischemia (CCI) is the most common comorbidity in COPD. Impaired Nitric Oxide (NO) metabolism is considered to be a key point in the pathogenesis of these diseases.  The study was aimed to investigate NO metabolism in patients with COPD, CCI and in those with combination of both diseases.  The investigation included 110 patients aged 51-76 years: 27 stable COPD patients (II and III stages according to the Global Initiative for Obstructive Lung Disease); 58 patients with CCI (II and III stages); 25 – with both diseases. The control group included 20 healthy non-smokers of the same age. Serum levels of NO 2  - , NO 3  - , total NO 2  - /NO 3  -  and 3-nitrotyrosine (3-NT) were measured.  In all groups serum 3-NT levels were under the lower threshold of method sensitivity (3.2 ng/ml). Significant increase in total NO 2 -/NO 3 - was observed in CCI, COPD and COPD+CCI groups compared to healthy controls (1,7-fold, 1,9-fold and 2,5-fold respectively). Increase in serum NO 3 - level was also found in CCI, COPD and COPD+CCI groups compared to control group (21.3 ± 2.0 µM, p  3 - level in COPD+CCI patients was significantly higher than in CCI group.  Serum NO 2 - was a significantly increase in stable COPD compared to the control group (3.7±1.0 µM and 1.6±0.8 µM, respectively, p=0.03), in COPD+CCI the same difference was noticed, p  2 - level was higher in COPD and COPD+CCI patients compared to CCI group (p 2 - level was revealed in COPD+CCI patients (p  These data suggest that COPD and CCI are characterized by different mechanisms of NO cycle impairments.
Combination of the Proteasome Inhibitor Bortezomib and a Histone Deacetylase Inhibitor PXD101 Results in Synergistic Inhibition of Osteoclastogenesis and Significantly Stronger Inhibition of Multiple Myeloma Growth In Vitro and In Vivo.
Authors: Rentian Feng, Ana B. Oton, Kenneth Patrene, Gulsum Anderson, Markus Y. Mapara, Chandra Belani, David Roodman, Suzanne Lentzsch
Journal: Blood (2006)
High Dose Therapy Improves Survival in Systemic Light Chain Amyloidosis: 14 Year Follow up
Authors: Simrit Parmar, Joshua Howell, Michael Wang, Mubeen A Khan, Qaiser Bashir, Jatin J. Shah, Nina Shah, Uday R. Popat, Sergio A Giralt, Robert Z. Orlowski, Muzaffar Qazilbash
Journal: Blood (2012)
P2.01-076 Drebrin: A New Targetable Molecular Marker of Lung Adenocarcinoma
Authors: Shinji Iyama, Masao Ono, Hitomi Kawai-Nakahara, Ryan Husni, Tomoko Dai, Toshihiro Shiozawa, Akiko Sakata, Masayuki Noguchi
Journal: Journal of Thoracic Oncology (2017)
MA13.01 Markerless Tumor Tracking during Lung Radiotherapy Using Intrafraction X-Ray Imaging
Authors: Chun-Chien (Andy) Shieh, Vincent Caillet, Michelle Dunbar, Paul Keall, Nicholas Hardcastle, Jeremy Booth, Chen-Yu Huang, Carol Haddad, Thomas Eade, Ilana Feain
Journal: Journal of Thoracic Oncology (2017)
Why and Where do We Miss Significant Prostate Cancer with Multi-parametric Magnetic Resonance Imaging followed by Magnetic Resonance-guided and Transrectal Ultrasound-guided Biopsy in Biopsy-naïve Men?
Authors: Martijn G. Schouten, Marloes van der Leest, Morgan Pokorny, Martijn Hoogenboom, Jelle O. Barentsz, Les C. Thompson, Jurgen J. Fütterer
Journal: European Urology (2017)
Hypomethylating Agent Therapy for Acute Myelogenous Leukemia (AML) Can Induce Sustained Responses with Low Induction Mortality.
Authors: Jasleen K Randhawa, Christopher Bredeson, Timothy S. Fenske, Ayman Saad, Jeanne Palmer, Parameswaran N Hari, Horatiu Olteanu, Ehab Atallah
Journal: Blood (2009)
P1.05-062 Is Lung Microwave Thermoablation a Valid Alternative to Surgery in High Risk Patients? A Propensity Match Analysis
Authors: Paolo Mendogni, Davide Tosi, Alessandro Palleschi, Lorenzo Rosso, Ilaria Righi, Matteo Montoli, Francesco Damarco, Claudia Bareggi, Cristina Marenghi, Mario Nosotti
Journal: Journal of Thoracic Oncology (2017)
Hyperamylinemia Contributes to Cardiac Dysfunction in Obesity and Diabetes
Authors: Sanda Despa, Kenneth B. Margulies, Le Chen, Anne A. Knowlton, Peter J. Havel, Heinrich Taegtmeyer, Donald M. Bers, Florin Despa
Journal: Circulation Research (2012)

Rationale: Hyperamylinemia is common in patients with obesity and insulin resistance, coincides with hyperinsulinemia, and results in amyloid deposition. Amylin amyloids are generally considered a pancreatic disorder in type 2 diabetes. However, elevated circulating levels of amylin may also lead to amylin accumulation and proteotoxicity in peripheral organs, including the heart. Objective: To test whether amylin accumulates in the heart of obese and type 2 diabetic patients and to uncover the effects of amylin accumulation on cardiac morphology and function. Methods and Results: We compared amylin deposition in failing and nonfailing hearts from lean, obese, and type 2 diabetic humans using immunohistochemistry and Western blots. We found significant accumulation of large amylin oligomers, fibrils, and plaques in failing hearts from obese and diabetic patients but not in normal hearts and failing hearts from lean, nondiabetic humans. Small amylin oligomers were even elevated in nonfailing hearts from overweight/obese patients, suggesting an early state of accumulation. Using a rat model of hyperamylinemia transgenic for human amylin, we observed that amylin oligomers attach to the sarcolemma, leading to myocyte Ca 2+ dysregulation, pathological myocyte remodeling, and diastolic dysfunction, starting from prediabetes. In contrast, prediabetic rats expressing the same level of wild-type rat amylin, a nonamyloidogenic isoform, exhibited normal heart structure and function. Conclusions: Hyperamylinemia promotes amylin deposition in the heart, causing alterations of cardiac myocyte structure and function. We propose that detection and disruption of cardiac amylin buildup may be both a predictor of heart dysfunction and a novel therapeutic strategy in diabetic cardiomyopathy.