tbuckley/cabot-search huggingface dataset:
OC-038 Making The Change: Switching to Infliximab Biosimilars for IBD at North Bristol NHS Trust
Authors: L Chung, B Arnold, R Johnson, MJ Lockett
Journal: Gut (2016)

<h3>Introduction</h3> Infliximab biosimilars have been available since February 2015, however at the time there was limited guidance on how to introduce the products. The PLANETRA and PLANETAS studies demonstrate that biosimilars are equivalent in clinical efficacy when compared to Remicade®. From the 1<sup>st</sup> July 2015, the gastroenterology department at NBT introduced biosimilar infliximab making cost savings of £200,000. A 50:50 gain share agreement was negotiated with the local Clinical Commissioning Groups and these savings will be re-invested into Gastroenterology services. Here we describe how a multidisciplinary approach led to a safe transition to biosimilar infliximab. <h3>Methods</h3> An additional pharmacist was funded to implement the switch using projected savings from the gain share. Patients who were established on Remicade® were sent a letter with details of the proposed switch and given the opportunity to raise any concerns in a consultation with the specialist pharmacists in Gastroenterology. Verbal consent was obtained prior to switching to Inflectra®. Practical guidance for the prescribing and dispensing of biosimilar infliximab was circulated to clinicians and pharmacy staff. Educational sessions were provided to the Medical Day Case Unit nurses. Adverse events were reported via the Yellow card<sup>® </sup>Scheme and the Biologics Therapy Audit. From December 2015, patients were asked to complete a survey to explore their experiences leading up to and during the switch. We decided not to study clinical outcomes as the sample size is misrepresentative and the follow-up period too short to draw meaningful conclusions. <h3>Results</h3> In total, 64/65 patients consented to the switch. Following the switch, 7 patients discontinued treatment (2 post-surgery; 5 switched to alternative biologic). We received a 46% response rate to the survey. Patient feedback was largely positive. 83% of patients received the written correspondence; 93% reported that they understood the information leaflet in part (23%) or in full (70%). 96% had the opportunity to speak to pharmacist before their first infusion. Overall, 97% of patients were satisfied with the changeover process. <h3>Conclusion</h3> We have demonstrated how a multidisciplinary approach allowed the successful switch to a biosimilar within 3 months and the potential benefits to be had. The additional pharmacist post, funded by the projected gain share, will be made a substantive this year allowing for closer monitoring and optimisation of biologic treatment. This will lead to further cost savings through discontinuation of these drugs where appropriate. Since the completion of this project, the BSG has revised their statement to acknowledge that there is sufficient evidence to recommend use of biosimilar infliximab in IBD. <h3>Disclosure of Interest</h3> L. Chung: None Declared, B. Arnold: None Declared, R. Johnson: None Declared, M. Lockett Conflict with: sponsored by MSD to attend conference in 2016
An unusual and unpleasant experience with ERCP: nasal septum damage
Authors: Serkan Torun, Ufuk Kuzu, Bülent Ödemiş
Journal: Endoscopy (2016)

Endoscopic retrograde cholangiopancreatography (ERCP) has evolved into a largely therapeutic procedure for the management of a variety of benign and malignant pancreaticobiliary disorders. Although the most commonly related adverse events include pancreatitis, bleeding, perforation, cholangitis, and cardiopulmonary issues [1] [2] [3], a range of rare and often underappreciated complications can occur. Here we report on a case of nasal septum damage caused by an endoscopic nasobiliary drain (ENBD).
Treatment of Consecutive Patients with Chronic Myeloid Leukemia In the Cooperating Centers From the Slovak Republic After 2000 – A Report From the Population Based CAMELIA Registry
Authors: Eva Demeckova, Martin Mistrik, Ludmila Demitrovicova, Juraj Chudej, Imrich Markuliak, Elena Tothova, Jan Muzik, Ladislav Dusek
Journal: Blood (2011)
Stopping antibiotics after 5 days in clinically stable community-acquired pneumonia was noninferior to usual care
Authors: Thomas Fekete
Journal: Annals of Internal Medicine (2016)

Source Citation Uranga A, España PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia: a multicenter randomized clinical trial. JAMA Intern Med. 2016;176:1257-65. 27455166
Bone Marrow Neutralizes Human Regulatory T-Cells to Permit Graft-Versus-Tumor Immunity In Humanized Mice
Authors: Teun Guichelaar, Henk Rozemuller, Maarten Emmelot, Bianka Martini, Gert Storm, Henk M Lokhorst, Anton Martens, Tuna Mutis
Journal: Blood (2010)
Blood Antioxidant Defenses and Sickle Cell Disease: Analyzing Cytochrome b Reductase 1 Protein Levels and Structure in Erythrocyte Membranes
Authors: Richard J Kulmacz, Wen Liu, Vladimir Berka, Mohammad H. Rahbar, Modupe Idowu, Alex George, Harinder S. Juneja
Journal: Blood (2015)
A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer
Authors: H. Yoshioka, N. Katakami, H. Okamoto, Y. Iwamoto, T. Seto, T. Takahashi, N. Sunaga, S. Kudoh, K. Chikamori, M. Harada, H. Tanaka, H. Saito, H. Saka, K. Takeda, N. Nogami, N. Masuda, T. Harada, H. Kitagawa, H. Horio, T. Yamanaka, M. Fukuoka, N. Yamamoto, K. Nakagawa
Journal: Annals of Oncology (2016)
PTU-068 Dose Optimisation Using Drug and Antibody Levels Can Benefit 50% Patients Prescribed Anti TNF Therapy Compared to Empiric Dose Adjustment: Abstract PTU-068 Table 1
Authors: P Harrow, C Skinner, T Hoque, A Ibarra, J Lindsay
Journal: Gut (2016)

<h3>Introduction</h3> In 2014 therapeutic drug monitoring (TDM) for antiTNF was introduced to the Royal London Hospital. Approximately 170 IBD patients per month receive infliximab or adalimumab. Previous data have shown TDM and optimised antiTNF prescribing improves clinical outcomes.<sup>1</sup> We audited the impact of TDM on cost-effectiveness and clinical outcome after 9 months compared to predictions we made prior to the introduction of this service.<sup>2</sup> <h3>Methods</h3> All IBD patients on antiTNF who had TDM between November 2014 and July 2015 were identified retrospectively using pathology records. Ideal standards of care were defined prospectively for different drug and antibody results. Actual clinical actions and outcomes 3 months after TDM were recorded and compared with the defined ideal standards of care. <h3>Results</h3> 160 tests on 133 patients were identified in the study period including 74 patients on infliximab and 59 patients on adalimumab. 88% patients had Crohn’s disease and 10% had ulcerative colitis. Escalated dosing regimens (increased dose or frequency) were prescribed in 48% patients. In patients on escalated doses, 13% IFX and 33% ADA had unrecordably high drug levels. A further 8% IFX patients on escalated doses were in deep clinical remission (CRP &lt; 5 and HBI or Mayo score 0–1). Reducing these prescriptions to standard dosing alone could have saved £166800 over 12 months. However, only 3/19 patients had dose reductions within 3 months, saving £27980. Neutralising antibodies were identified in 12% IFX and 9% ADA patients. Appropriate cessation of antiTNF took place in 75% IFX and 20% ADA patients. Appropriate dose escalation only took place in 36% IFX and 6% ADA patients with low levels and no antibodies. <h3>Conclusion</h3> Empiric prescribing based on clinical assessment alone leads to sub-optimal drug levels in around 50% patients. The introduction of antiTNF TDM has allowed rational dose optimisation with immediate savings and clinical benefits. In routine practice, delays in interpreting TDM impacted on dose optimisation and wasted resources. These data have led to local changes in practice to ensure all results are acted on promptly. <h3>References</h3> 1 Vaughn BP, Sandborn WJ, Cheifetz AS. Biologic concentration testing in IBD<i>. Inflamm Bowel Dis</i> 2015;<b>21</b>(6):1435–1442. 2 Tandiari T, <i>et al</i>. PTH-083 Selective monitoring of antiTNF drug levels and antibodies will reduce short-term prescribing costs and provide early personalised tailoring of antiTNF therapy in routine IBD practice. <i>Gut</i> 2015;<b>64</b>(Suppl 1): A443. <h3>Disclosure of Interest</h3> P. Harrow: None Declared, C. Skinner: None Declared, T. Hoque: None Declared, A. Ibarra: None Declared, J. Lindsay Grant/research support from: MSD, Takeda and Hospira, Consultant for: MSD, Takeda, Abbvie, Napp, Hospira and Celltrion
Ten-Year Follow-up Data of Diffuse Large B-Cell Lymphoma Patients: Single Center Experience
Authors: Murat Ozbalak, M. Cem Ar, Ayse Salihoglu, Emine Gulturk, Ahmet Emre Eskazan, Seniz Ongoren Aydin, Zafer Baslar, Teoman Soysal, Yildiz Aydin, Nukhet Tuzuner, A. Burhan Ferhanoglu
Journal: Blood (2011)
P0346 : Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma
Authors: P. Reichl, M. Fang, P. Starlinger, K. Staufer, R. Nenutil, P. Muller, K. Greplova, D. Valik, S. Dooley, C. Brostjan, T. Gruenberger, J. Shen, K. Man, M. Trauner, J. Yu, C.F. Gao, W. Mikulits
Journal: Journal of Hepatology (2015)
THU0509 Optical Coherence Tomography Description of Tophi in Gout Shows that Irregular Tophus Morphology, Oedema and Absence of Capsule Are Associated with Symptomatic Disease
Authors: G. Abignano, F. Del Galdo, D. McGonagle
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The basis as to why chronic gout related tophi may be completely asymptomatic is not understood. In experimental settings coating of gouty crystals may be associated with the prevention of inflammatory responses (1). <h3>Objectives</h3> We used optical coherence tomography (OCT) in patients with gout to test the hypothesis that tophus related pain was due to the disruption of tophus capsule. <h3>Methods</h3> Eight consecutive patients with tophaceous gout were recruited. Each patient received detailed clinical assessment by a Rheumatologist including physical examination, history, current therapy, presence, number and site of tophi and whether or not each tophus was symptomatic. Tophi were photographed and scanned using Vivosight OCT scan (Michelson Diagnostics, Kent, UK). OCT of corresponding regions of the opposite side were undertaken for comparison and for subclinical tophi evaluation. One hundred slices OCT scans allowed post-processing 3D reconstructions of the visualized superficial tophus morphology (smooth or irregular) and presence or absence of tophus capsule were assessed. VAS pain scores for individual tophi were subsequently collected and correlated with imaging. <h3>Results</h3> Thirty seven tophi from eight patients with tophaceous gout were scanned. Four patients had tophi located at fingers, one at toes, two at both sites. Two patients of the third group had additional sites involved in form of multiple aggregates located at knees, heels, elbows. VAS score ranged from 0 to 9 (median=2). Eleven of the 37 tophi were symptomatic (VAS score range: 4–9), the remaining 26 were mildly or not symptomatic (VAS score 0–3). Most of the tophi (28/37) had a smooth border, 9 had an irregular aspect. Tophi with smooth border seemed to be surrounded by a “pseudo-capsule” (p&lt;0.05). Tophi with irregular aspect were associated with optical density changes possibly consistent with oedema (p&lt;0.05). A relationship between irregular tophi and pain was evident (p=0.0025). On the contrary, presence of smooth tophi with capsules were not associated with significant pain. <h3>Conclusions</h3> These findings suggest that non-painful tophi in patients with tophaceous gout have a different morphology and a capsule which provides support for the idea that a capsule prevents pain and inflammation. Capsular disruption is linked to flares and the hypothesis that initial serum urate lowering therapy may lead to capsule disruption should be further investigated. <h3>References</h3> Schauer C et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014;20:511–7 <h3>Disclosure of Interest</h3> None declared
Gastrointestinal and Hepatic Involvement in Chronic Gvhd: An Analysis From the Chronic Gvhd Consortium
Authors: Joseph Pidala, Xiaoyu Chai, Brenda Kurland, Mukta Arora, Corey Cutler, Mary E.D. Flowers, Yoshi Inamoto, Madan Jagasia, Nandita Khera, Jeanne Palmer, Georgia Vogelsang, Stephanie J Lee
Journal: Blood (2012)
SAT0304 Coagulation Factor XIII Might Be A Promising Marker for Predicting Atherosclerosis in SLE
Authors: I. Matsuura, E. Lourenco, J. Grossman, B. Skaggs, M. McMahon
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Several traditional and non-traditional risk have been implicated in the development of atherosclerosis in systemic lupus erythematosus (SLE). However, while growing evidence demonstrates that blood coagulation factor XIII (FXIII) may play an essential role in atherothrombotic disease in patients with primary antiphospholipid syndrome, the role of this coagulation factor in atherothrombotic disease and overall disease activity in patients with SLE is still poorly understood. Plasma FXIII cross-links fibrin with itself and with the endothelium, making clots resistant to fibrinolysis. Intracellular FXIII in monocytes also cross-links Type I angiotensin receptor dimer, which increases monocyte adhesion to endothelial cells and accelerates atherosclerosis. We investigated whether FXIII was associated with intima media thickness (IMT) of carotid arteries or disease activity in patients with SLE. <h3>Objectives</h3> to evaluate clinical significance of FXIII in SLE. <h3>Methods</h3> the study involved 50 consecutive patients with SLE enrolled in a longitudinal study on atherosclerosis biomarker from 2008 through 2015 at UCLA. Plasma FXIII activity (FXIIIa) was measured in the blood samples by ELISA. B-mode and Doppler Scanning was performed to measure IMT at baseline and 24–36 month. <h3>Results</h3> Table1 shows the correlation with plasma level of FXIIIa and variables that were independently associated with SLE activity and atherosclerosis. There was a strong inverse correlation with the SLE Disease Activity Index (SLEDAI), physician global assessment (PGA), and dsDNA antibody, whereas there was a significant positive correlation between FXIIIa and C3 and IMT at the follow-up ultrasound (Figure1). In patients with high plasma FXIIIa (&gt;143%), the mean SLEDAI was significantly lower, (2.17± 3.7 vs. 4.1 ± 3.2, p=0.009) and IMT at follow-up was significantly higher (0.61 ± 0.17 vs. 0.51 ± 0.14, p=0.009). <h3>Conclusions</h3> Although further confirmatory testing is underway, FXIII might be a novel marker for increased IMT in SLE. <h3>References</h3> McMahon M, Skaggs BJ, Grossman JM, Sahakian L, Fitzgerald J, Wong WK, et al. A panel of biomarkers is associated with increased risk of the presence and progression of atherosclerosis in women with systemic lupus erythematosus. Arthritis Rheumatol. 2014;66(1):130–9. Ames PR, Iannaccone L, Alves JD, Margarita A, Lopez LR, Brancaccio V. Factor XIII in primary antiphospholipid syndrome. The Journal of rheumatology. 2005;32(6):1058–62. Muszbek L, Bereczky Z, Bagoly Z, Shemirani AH, Katona E. Factor XIII and atherothrombotic diseases. Seminars in thrombosis and hemostasis. 2010;36(1):18–33. <h3>Disclosure of Interest</h3> None declared
Genetic Bases of Fungal White Rot Wood Decay Predicted by Phylogenomic Analysis of Correlated Gene-Phenotype Evolution
Authors: László G. Nagy, Robert Riley, Philip J. Bergmann, Krisztina Krizsán, Francis M. Martin, Igor V. Grigoriev, Dan Cullen, David S. Hibbett
Journal: Molecular Biology and Evolution (2016)

Fungal decomposition of plant cell walls (PCW) is a complex process that has diverse industrial applications and huge impacts on the carbon cycle. White rot (WR) is a powerful mode of PCW decay in which lignin and carbohydrates are both degraded. Mechanistic studies of decay coupled with comparative genomic analyses have provided clues to the enzymatic components of WR systems and their evolutionary origins, but the complete suite of genes necessary for WR remains undetermined. Here, we use phylogenomic comparative methods, which we validate through simulations, to identify shifts in gene family diversification rates that are correlated with evolution of WR, using data from 62 fungal genomes. We detected 409 gene families that appear to be evolutionarily correlated with WR. The identified gene families encode well-characterized decay enzymes, e.g., fungal class II peroxidases and cellobiohydrolases, and enzymes involved in import and detoxification pathways, as well as 73 gene families that have no functional annotation. About 310 of the 409 identified gene families are present in the genome of the model WR fungus Phanerochaete chrysosporium and 192 of these (62%) have been shown to be upregulated under ligninolytic culture conditions, which corroborates the phylogeny-based functional inferences. These results illuminate the complexity of WR and suggest that its evolution has involved a general elaboration of the decay apparatus, including numerous gene families with as-yet unknown exact functions.
A Role of JAK/STAT Pathway in Cutaneous T-Cell Lymphomas: Exploring Its Effects for Targeted Therapy
Authors: Cristina Pérez, Julia Gonzalez-Rincon, Carmen Almaraz, Soraya Curiel, Nuria Garcia, Helena Pisonero, Sagrario Gomez, Laura Cereceda, Arantza Onaindia, Rebeca Madureira, Alicia Leon, Carmen González-Vela, Pablo L Ortiz-Romero, Nerea Martinez, Margarita Sanchez-Beato, Jose Pedro Vaqué, Miguel Angel A. Piris
Journal: Blood (2014)
HLA Haploidentical Stem Cell Transplantation After Removal of αβ+ T Lymphocytes and B Lymphocytes Is an Effective Treatment for Children with Life-Threatening, Non-Malignant Disorders
Authors: Alice Bertaina, Mariateresa Romano, Sergio Rutella, Giuseppe Palumbo, Daria Pagliara, Stefano Ceccarelli, Letizia P Brescia, Giuseppina Li Pira, Francesca Cocca, Maria Ester Bernardo, Giuseppe M Milano, Daniela Pende, Michela Falco, Lorenzo Moretta, Franco Locatelli
Journal: Blood (2012)
Clonal Tracking of the Geographic Distribution of Hematopoiesis in Nonhuman Primates Provides New Insights into HSPC Migration and Differentiation
Authors: Chuanfeng Wu, Samson J Koelle, Brian Li, Diego Espinoza, Rong Lu, Allen E Krouse, Mark Metzger, Robert Donahue, Cynthia E. Dunbar
Journal: Blood (2015)
Huntington's disease
Authors: M. J. U. Novak, S. J. Tabrizi
Journal: BMJ (2010)

#### Summary points

Huntington’s disease is a devastating inherited neurodegenerative disease characterised by progressive motor, cognitive, and psychiatric symptoms. Patients may present with any of these symptoms, and familiarity with the phenotype is therefore important. Chorea and loss of balance are early symptoms that patients notice, although families often notice cognitive or personality changes before this.

#### Sources and selection criteria

This review is based on our experience of leading (SJT) and working in (MJUN) the multidisciplinary Huntington’s disease clinic at the National Hospital for Neurology and Neurosurgery, supported by an up to date literature review performed using PubMed and a review of the Cochrane database.

The disease occurs in all racial groups but is most common in people of northern European origin. Its prevalence in the Western hemisphere is 7-10/100 000.w1 The mean age of onset of symptoms is 40 years, but juvenile onset ( 70 years) forms are well recognised. The Huntington’s Disease Association (HDA) has records of 6161 adults with symptomatic Huntington’s disease and 541 children with juvenile Huntington’s disease (in England and Wales) at the time of writing. This is a conservative estimate of prevalence because it includes only those people in contact with the HDA, and it suggests that the true prevalence of the disease is higher than previously thought.1

Although relatively uncommon, Huntington’s disease can be devastating for patients and their families. People who are at risk of developing the disease because of a family history face difficult decisions about genetic testing. We review …
Persistence of Imiglucerase in Cell Compartment Explains Dosing Frequency of Every Two Weeks in Type 1 Gaucher Disease
Authors: Juliette Berger, Marie Vigan, Jérôme Stirnemann, Céline Bourgne, Alexandre Janel, Nadia Belmatoug, Christian Rose, Monia Bengherbia, Bruno Pereira, France Mentré, Marc G Berger
Journal: Blood (2014)
In Patients Newly Diagnosed with Chronic Lymphocytic Leukemia the Absolute Monocyte Count At Presentation Is Directly Associated with Disease Progression Independently From Rai Staging or Cytogenetics
Authors: Ryan A. Wilcox, Kari Rabe, Neil Kay, Timothy G. Call, Svetomir N. Markovic, Luis F. Porrata, Susan Schwager, Clive S. Zent, Curtis A. Hanson, Tait D. Shanafelt
Journal: Blood (2011)
THU0082 Medication Impact on The Risk of Incident Diabetes Mellitus in Patients with Rheumatoid Arthritis: Hydroxychloroquine and Abatacept Protect while Glucocorticoids and Statins Worsen: Table 1.
Authors: G. Ozen, S. Pedro, M. Holmqvist, K. Michaud
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Chronic inflammation and some anti-inflammatory medications in rheumatoid arthritis (RA) are not only responsible for accelerated atherosclerosis but also have effects on the development of traditional risk factors, among which type 2 diabetes mellitus (DM) is the most important. Although hydroxychloroquine (HCQ) and TNF inhibitors have been reported to decrease incident DM risk in RA, there are still a number of unanswered questions regarding the impact of newer biologics, statins, and the timing, dosing, and sustainability of this effect. <h3>Objectives</h3> To investigate the impact of specific DMARDs and statins on the risk of incident DM in patients with RA. <h3>Methods</h3> Study patients were participants without baseline DM and at least 1 year in the National Data Bank for Rheumatic Diseases (NDB) from 2000 through 2015. DM was determined by patient self-report or use of DM-specific medication. Multivariable Cox proportional hazard models were adjusted for age, sex, ethnicity, socioeconomic and smoking status, comorbidities, body mass index (BMI), and RA severity while examining the time-dependent association of HCQ, other DMARDs, glucocorticoids (GC), and statins. <h3>Results</h3> During the 71,668 person-year followup of 13,669 RA patients, 1,139 developed DM. Adjusted HR (95% CI) for DM were 0.67 (0.57–0.80) for HCQ, 0.52 (0.31–0.89) for abatacept, 1.31 (1.15–1.49) for GC, and 1.56 (1.36–1.78) for statins <i>(Table)</i>. There was no evidence of risk change through MTX, other synthetic and biological DMARDs. Although the risk reduction was significantly associated with higher HCQ doses and longer (&gt;4 years) treatment durations, HCQ dose of &lt;400mg/day, HR 0.71 (0.52–0.96), and ≥2-year duration, HR 0.72 (0.56–0.91), were also protective. DM-free survival of the patients who discontinued HCQ were quite similar to the patients who started HCQ and kept receiving the drug. Concomitant use of GC did not adversely affect the protective effect of HCQ, HR 0.69 (0.51–0.93). However, there was significant increased risk with statins and GC, HR 2.03 (1.65–2.50). In concomitant use of HCQ and statins, the protective effect of HCQ and increased risk with statins disappeared, HR 0.92 (0.68, 1.25). <h3>Conclusions</h3> The risk of incident DM in RA was reduced with HCQ and abatacept and increased with GC and statins. HCQ not only confers a sustainable, dose and treatment duration-dependent protective effect but also abolishes the increased risk of DM as a consequence of GC or statins. <h3>Disclosure of Interest</h3> None declared