tbuckley/cabot-search huggingface dataset:
FRI0010 Pharmacokinetics, Safety and Tolerance of BCD-085, A Novel IL-17 Inhibitor, Based on The Results of Phase 1 Clinical Study in Healthy Volunteers
Authors: E. Chernyaeva, A. Eremeeva, A. Galustyan, R. Ivanov
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> BCD-085 is an innovative humanized monoclonal antibody against interleukin-17 with genetically modified Fc- and CDR-regions, aimed to improve treatment outcomes in patients with several autoimmune disorders. <h3>Objectives</h3> To study pharmacokinetics and safety of a single SC injection of BCD-085 in ascending doses in healthy male volunteers. <h3>Methods</h3> A standard "3+3" first-in-human dose escalation phase 1 clinical study design was used. Different cohorts of healthy male volunteers 18 to 45 years of age received a single subcutaneous injection of BCD-085 in ascending doses (0.05 mg/kg, 0.025 mg/kg, 0.0825 mg/kg, 1.25 mg/kg, 1.75 mg/kg, 2.25 mg/kg and 3.0 mg/kg). After injection all participants underwent 57 days of observation which included assessment of the tolerance, safety, pharmacokinetics and immunogenicity of the studied medicine. <h3>Results</h3> 22 healthy male volunteers received a single SC injection of BCD-085. <i>Pharmacokinetics:</i> Pharmacokinetic data were available from 21 volunteers with median body weights of 73.6 kg (range; 65.2–84.8). 1 volunteer withdrew from the study due to SAE that was not related to study drug (car accident). Regardless of the cohort changes of BCD-085 concentration were linear: after SC injection it slowly increased and reached the maximum value at the end of the first week. Thus, dose dependency was observed, while the half-life was not dependent on the dose and was 15–22 days. Mean C<sub>max</sub> of BCD-085 amounted to 12,232.5 ng/ml (median – 10937.0 ng/ml), T<sub>max</sub> – 156.6 hours (median 168.0), AUC<sub>0-t</sub> – 8780483.5 (ng/ml)*h (median – 8169096.2 (ng/ml)*hr), AUC<sub>0-inf</sub> – 4786108616.7 (ng/ml)*h (median – 4275500952.5 (ng/ml)*h), the half-life – 387.9 hours (median – 383.7 hours). <i>Safety:</i> In total, 6 adverse events were registered during the study, the toxicity in all these cases was mild (grade 1 in accordance with CTCAE v.4.03). Transaminases increase was more common (9.09%); grade 1 neutropenia occurred just in one volunteer. Single SC injections of BCD-085 were well tolerated with no signs of any local reactions. Immunogenicity assessment did not detect occurrence of anti-drug antibodies. <h3>Conclusions</h3> BCD-085 is safe when administered SC in a wide range of doses from 0.05 to 3.0 mg/kg. Pharmacokinetics of a novel IL-17 blocker is standard for therapeutic monoclonal antibodies. Further clinical evaluation of BCD-085 is underway. <h3>References</h3> final study report on phase 1 clinical study of BCD-085 in healthy volunteers. <h3>Disclosure of Interest</h3> E. Chernyaeva Employee of: BIOCAD, A. Eremeeva Employee of: BIOCAD, A. Galustyan Grant/research support from: BIOCAD, R. Ivanov Employee of: BIOCAD
PI3 kinase pathway regulated miRNome in glioblastoma: identification of miR-326 as a tumour suppressor miRNA
Authors: Zahid Nawaz, Vikas Patil, Yashna Paul, Alangar S. Hegde, Arimappamagan Arivazhagan, Vani Santosh, Kumaravel Somasundaram
Journal: Molecular Cancer (2016)

Glioblastomas (GBM) continue to remain one of the most dreaded tumours that are highly infiltrative in nature and easily preclude comprehensive surgical resection. GBMs pose an intricate etiology as they are being associated with a plethora of genetic and epigenetic lesions. Misregulation of the PI3 kinase pathway is one of the most familiar events in GBM. While the PI3 kinase signalling regulated pathways and genes have been comprehensively studied, its impact on the miRNome is yet to be explored. The objective of this study was to elucidate the PI3 kinase pathway regulated miRNAs in GBM. miRNA expression profiling was conducted to monitor the differentially regulated miRNAs upon PI3 kinase pathway abrogation. qRT-PCR was used to measure the abundance of miR-326 and its host gene encoded transcript. Proliferation assay, colony suppression assay and wound healing assay were carried out in pre-miR transfected cells to investigate its role in malignant transformation. Potential targets of miR-326 were identified by transcriptome analysis of miR-326 overexpressing cells by whole RNA sequencing and selected targets were validated. Several publically available data sets were used for various investigations described above. We identified several miRNA that were regulated by PI3 kinase pathway. miR-326, a GBM downregulated miRNA, was validated as one of the miRNAs whose expression was alleviated upon abrogation of the PI3 kinase pathway. Overexpression of miR-326 resulted in reduced proliferation, colony suppression and hindered the migration capacity of glioma cells. Arrestin, Beta 1 (ARRB1), the host gene of miR-326, was also downregulated in GBM and interestingly, the expression of ARRB1 was also alleviated upon inhibition of the PI3 kinase pathway, indicating similar regulation pattern. More importantly, miR-326 exhibited a significant positive correlation with ARRB1 in terms of its expression. Transcriptome analysis upon miR-326 overexpression coupled with integrative bioinformatics approach identified several putative targets of miR-326. Selected targets were validated and interestingly found to be upregulated in GBM. Taken together, our study uncovered the PI3 kinase regulated miRNome in GBM. miR-326, a PI3 kinase pathway inhibited miRNA, was demonstrated as a tumour suppressor miRNA in GBM.
Post-Renal Transplant De Novo Non-Skin Malignancies in Mycophenolate Mofetil- and Calcineurin Inhibitor-Based Immunosuppression.
Authors: Lohith Bachegowda, Diptesh Gupta, Ajoy Bharadwaj, Karthik Ranganna, TIM Adamowicz, Anil Kumar
Journal: Blood (2009)
Fludarabine and Melphalan Conditioning Regimen in Young Patients with Acute Myeloid Leukemia in CR1 Undergoing a Matched Related Allogeneic Stem Cell Transplant: A Single Center Experience.
Authors: Mammen Chandy, Vikram Mathews, T. Rajasekar, Kavitha M. Lakshmi, Auro Viswabandya, Joseph M. John, Biju George, Alok Srivastava
Journal: Blood (2007)
Dendritic and T Cell Subsets Correlate with the Development and Site of Acute GVHD Following Unrelated Cord Blood Transplantation. A Multivariate Analysis of Host, Graft, and Day+50 Immune Profile.
Authors: Paul Szabolcs, Kyung-Duk Park, Luciana Marti, Young-Ah Lee, Melissa Reese, Linda Sanders, Donna Niedzwiecki, Joanne Kurtzberg
Journal: Blood (2004)
Apoptosis of Leukemic Cells by Using tRNase ZL Under the Direction of Oncogene-Targeting Small Guide RNA.
Authors: Norihiro Watanabe, Miwako Narita, Akie Yamahira, Tomoyo Taniguchi, Tatsuo Furukawa, Tetsuo Yoshida, Tatsuya Miyazawa, Masayuki Nashimoto, Masuhiro Takahashi
Journal: Blood (2010)
Donor milk is no better than formula for very low birthweight infants, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Donor milk does not seem to improve neurodevelopment in very low birthweight infants any more than preterm formula, a study published in JAMA has found.1

Giving donor milk to very low birthweight infants has increased in the past 10 years despite a lack of information about associated outcomes. This study is the largest randomised blinded trial of donor human milk in very low birthweight infants to date and the only one …
Eloquent-2 Update: A Phase 3, Randomized, Open-Label Study of Elotuzumab in Combination with Lenalidomide/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma - 3-Year Safety and Efficacy Follow-up
Authors: Meletios A. Dimopoulos, Sagar Lonial, Darrell White, Philippe Moreau, Antonio Palumbo, Jesus San Miguel, Ofer Shpilberg, Kenneth C. Anderson, Sebastian Grosicki, Ivan Spicka, Adam Walter-Croneck, Hila Magen-Nativ, Maria-Victoria Mateos, Andrew Belch, Donna Reece, Meral Beksac, Eric Bleickhardt, Valerie Poulart, Jessica Katz, Anil K. Singhal, Paul G. Richardson
Journal: Blood (2015)
Sensitivity and Specificity of Laboratory Parameters to Detect Early/Prefibrotic Myelofibrosis in 857 Patients with Essential Thrombocythemia. A Diagnostic Algorithm
Authors: Alessandra Carobbio, Guido Finazzi, Juergen Thiele, Hans-Michael Kvasnicka, Francesco Passamonti, Elisa Rumi, Marco Ruggeri, Francesco Rodeghiero, Maria Luigia Randi, Irene Bertozzi, Alessandro M. Vannucchi, Elisabetta Antonioli, Heinz Gisslinger, Veronika Buxhofer-Ausch, Naseema Gangat, Alessandro Rambaldi, Ayalew Tefferi, Tiziano Barbui
Journal: Blood (2011)
Neurotrophin Receptors and Ligands Are Highly Expressed in Acute Leukemia and Promote Leukemogenesis.
Authors: Zhixiong Li, Gernot Beutel, Johann Meyer, Christian Koenecke, Thomas Neumann, Min Yang, Juergen Krauter, Mathias Rhein, Nils von Neuhoff, Michael Heuser, Helmut Diedrich, Ludwig Wilkens, Brigitte Schlegelberger, Arnold Ganser, Christopher Baum
Journal: Blood (2007)
Fluzone® High-Dose Influenza Vaccine with a Booster Is Associated with Low Rates of Influenza Infection in Patients with Plasma Cell Disorders
Authors: Andrew R Branagan, Eamon Duffy, Chandra Sekhar Boddupall, Randy A Albrecht, Lin Zhang, Rakesh Verma, Dennis L Cooper, Stuart Seropian, Terri L Parker, Xiaopan Yao, Thomas M Ferencz, Madhav V Dhodapkar
Journal: Blood (2015)
Notes from the Field: Fungal Bloodstream Infections Associated with a Compounded Intravenous Medication at an Outpatient Oncology Clinic — New York City, 2016
Authors: Amber M. Vasquez, Jason Lake, Stephanie Ngai, Megan Halbrook, Snigdha Vallabhaneni, M. Shannon Keckler, Heather Moulton-Meissner, Shawn R. Lockhart, Christopher T. Lee, Kiran Perkins, Joseph F. Perz, Mike Antwi, Miranda S. Moore, Jane Greenko, Eleanor Adams, Janet Haas, Sandra Elkind, Marjorie Berman, Dani Zavasky, Tom Chiller, Joel Ackelsberg
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On May 24, 2016, the New York City Department of Health and Mental Hygiene notified CDC of two cases of Exophiala dermatitidis bloodstream infections among patients with malignancies who had received care from a single physician at an outpatient oncology facility (clinic A). Review of January 1-May 31, 2016 microbiology records identified E. dermatitidis bloodstream infections in two additional patients who also had received care at clinic A. All four patients had implanted vascular access ports and had received intravenous (IV) medications, including a compounded IV flush solution containing saline, heparin, vancomycin, and ceftazidime, compounded and administered at clinic A.
Fully Implanted Brain–Computer Interface in a Locked-In Patient with ALS
Authors: Mariska J. Vansteensel, Elmar G.M. Pels, Martin G. Bleichner, Mariana P. Branco, Timothy Denison, Zachary V. Freudenburg, Peter Gosselaar, Sacha Leinders, Thomas H. Ottens, Max A. Van Den Boom, Peter C. Van Rijen, Erik J. Aarnoutse, Nick F. Ramsey
Journal: New England Journal of Medicine (2016)

Options for people with severe paralysis who have lost the ability to communicate orally are limited. We describe a method for communication in a patient with late-stage amyotrophic lateral sclerosis (ALS), involving a fully implanted brain-computer interface that consists of subdural electrodes placed over the motor cortex and a transmitter placed subcutaneously in the left side of the thorax. By attempting to move the hand on the side opposite the implanted electrodes, the patient accurately and independently controlled a computer typing program 28 weeks after electrode placement, at the equivalent of two letters per minute. The brain-computer interface offered autonomous communication that supplemented and at times supplanted the patient's eye-tracking device. (Funded by the Government of the Netherlands and the European Union; ClinicalTrials.gov number, NCT02224469 .).
THU0640-HPR Provision of Care Services for Rheumatic and Musculoskeletal Diseases-Related Foot and Ankle Problems: A Survey from Sixteen European Countries: Table 1.
Authors: B.A.-P. Alcacer-Pitarch, M. Backhouse, G. Gijon-Nogeron, D. Biscontini, S. Bonafede, A. Ferreira, A. Gatt, Y. Lescure, T.N. Nava, A. Redmond
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The increased prevalence of foot and ankle pathologies in Rheumatic and Musculoskeletal diseases (RMDs) is well documented<sup>1</sup>, however the provision of foot &amp; ankle (F&amp;A) healthcare services for people with RMDs in Europe has not been evaluated. <h3>Objectives</h3> To assess the current healthcare systems for providing foot &amp; ankle healthcare services for people with RMDs in Europe. <h3>Methods</h3> A survey was undertaken to evaluate current provision of F&amp;A health care services for people with RMDs across Europe. A questionnaire was distributed to all 22 country presidents representing HP associations within EULAR. The questionnaire used was developed and piloted (in 7 countries) by the EULAR F&amp;A Study Group, and structured to capture the provision and type of F&amp;A services for people with RMDs. When the HP presidents felt unable to answer specific questions they were encouraged to consult a colleague who may be better placed to provide the answers. <h3>Results</h3> Sixteen questionnaires were completed (Norway, Ireland, Sweden, Hungary, Netherlands, UK, Denmark, Portugal, Italy, Switzerland, Austria, France, Czech Republic, Spain, Belgium, Malta). Of the 16, 13 respondents indicated provision of F&amp;A health care services in their country, but only three countries had services specialising in RMD-related F&amp;A problems (Netherlands, UK, Malta). The professions providing the care for patients with RMD-related F&amp;A problems were different depending on the pathology and the country (Table1). Podiatrists provided care for F&amp;A pain and deformity problems in 11 countries, but provided F&amp;A ulcer care in only 8 countries. <h3>Conclusions</h3> Only 3 countries have F&amp;A health care services specialised to the needs of people with RMDs. The professions providing the care varied between countries, and also depended on the F&amp;A pathology. Interestingly, F&amp;A healthcare services were provided by professions that do not solely specialised in F&amp;A care. Further research is needed to assess the variation of F&amp;A healthcare services between and within European countries and the impact on healthcare of various F&amp;A healthcare service designs. <h3>References</h3> Woodburn, J. &amp; Helliwell, P. Foot problems in rheumatology. Rheumatology 36, 932–934 (1997). <h3>Disclosure of Interest</h3> None declared
Zero‐Order Antibiotic Release from Multilayer Contact Lenses: Nonuniform Drug and Diffusivity Distributions Produce Constant‐Rate Drug Delivery
Authors: Gustavo Guzman, Siamak Shams Es‐haghi, Turgut Nugay, Mukerrem Cakmak
Journal: Advanced Healthcare Materials (2016)

A novel approach to zero-order constant-rate drug delivery from contact lenses is presented. Quasi-Case II non-Fickian transport is achieved by nonuniform drug and diffusivity distributions within three-layer bimodal amphiphilic conetworks (β-APCNs). The center layer is a highly oxygen permeable β-APCN matrix, which contains the drug and exhibits a high drug diffusivity. The outer β-APCN layers contain no-drug and are loaded with vitamin E, which slows diffusion. In contrast to single-layer neat-polymer and vitamin E-loaded films that display first-order "burst" kinetics, it is demonstrated experimentally and by modeling that the combined effect of nonuniform distribution of drug loading and diffusion constants within the three-layer lens maintains low local drug concentration at the lens-fluid interface and yields zero-order drug delivery. The release rates of topical antibiotics provide constant-rate therapeutic-level delivery with appropriate oxygen permeability for at least 30 h, at which time ≈25% of the drug was released.
THU0057 Validation of The Baseline ADAMTS5 mRNA Levels as A Prediction Biomarker for The Efficacy of Infliximab; A Multicenter Clinical Trial
Authors: K. Tsuzaka, M. Nagata, K. Amano, T. Mimura, S. Kagami, Y. Miwa, K. Ikeda, T. Mitsuka, H. Kanai, I. Sekigawa
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) has been reported to play a key role in aggrecan degradation in cartilage. Lower level of the baseline blood ADAMTS5 mRNA level has been also reported to predict the better response to infliximab (IFX) in RA patients using a single-center study. <h3>Objectives</h3> In this study, we performed a prospective, multicenter, and observational study to derive and validate the baseline blood ADAMTS5 mRNA that would be predictive of the efficacy of IFX in RA patients. <h3>Methods</h3> Forty-one RA patients (Age, 54.1±12.3 y/o; Disease duration, 4.5±7.1 years; DAS28_ESR, 5.07±1.07; SDAI 23.5±1.03; Bio naïve, 91.7%) were enrolled and treated with IFX. Peripheral blood samples were collected at baseline and ADAMTS5 mRNA was quantified using real-time PCR as the ratio of b-actin mRNA (Index as BiologicMate®). <h3>Results</h3> Five patients dropped out of this study while 44.1%, 14.7%, 29.4%, 41.1%, 23.5%, and 23.5% of the remaining patients achieved good responder, none responder, DAS_ESR remission, DAS_CRP remission, SDAI remission, and Boolean remission at 14 weeks9 treatment with IFX, respectively. Baseline ADAMTS5 mRNA levels in the SDAI remission group was significantly (p=0.049) lower than that in the non-SDAI remission group at 14 weeks9 treatment with IFX. Area under curve (AUC) of the ROC curve for predicting the SDAI remission (SDAI ≤3.3) using the baseline ADAMTS5 mRNA at 14 weeks was 0.67, and the cut-off value of ADAMTS5 mRNA was calculated as 2.1 Index. There observed no difference in the general patient backgrounds (average age, disease duration, dose of MTX, dose of steroid, baseline SDAI, etc) between Low-ADAMTS5 (&lt;2.1 Index) group and High-ADAMTS5d group. However, DAS28, CDAI, and SDAI at 14 weeks after treatment were significantly (p=0.031) lower in Low-ADAMTS5 group than those in High-ADAMTS5 group. The accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the baseline Low-ADAMTS5 (&lt;2.1 Index) for predicting the SDAI remission (SDAI ≤3.3) at 14 weeks after treatment with IFX were 76.5%, 66.7%, and 85.7%, respectively. Interestingly, we observed positive correlation between baseline ADAMTS5 mRNA and SDAI score at 14 weeks after treatment with IFX. <h3>Conclusions</h3> The baseline blood ADAMTS5 mRNA level was validated as a biomarker for the prediction of the response to IFX in RA patients using the multicenter clinical trial. <h3>Disclosure of Interest</h3> K. Tsuzaka Shareholder of: Kaytee Bio, Co.&amp;Ltd., M. Nagata: None declared, K. Amano: None declared, T. Mimura: None declared, S. Kagami: None declared, Y. Miwa: None declared, K. Ikeda: None declared, T. Mitsuka: None declared, H. Kanai: None declared, I. Sekigawa: None declared
AB0040 Antioxidant Potential and Free Radical Potential of Synovial Fluid (SF) in Rheumatoid Arthritis (RA) and Osteoarthritis (OA):
Authors: G. Kudriavtseva, Y.A. Malencov, V.V. Shishkin, V.I. Shishkin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Intra-articular dynamics of free radical processes in RA and OA reflects the degree of cellular destruction and the depth of the membrane pathological changes. Multi-component antioxidant system hinders the development of these negative phenomena. <h3>Objectives</h3> We studied the dynamics of free radical processes (the rate of lipid peroxidation (LPO - the level of malondialdehyde - MDA), activity of phospholipase (PHL-A2) and phospholipids - PHL) and the antioxidant defense system (activity superoxiddismutase (SOD), catalase (CAT), glutathione-S-transferase (G-S-T), tocopherols (TF) and ceruloplasmin (CP) in SF of patients with RA and OA. The data were compared with the levels of inflammation cytokines. <h3>Methods</h3> Investigated the SG of the knee in 15 patients with RA and 15 patients with OA, female, age 50±12 years. Besides the well-known methods of biochemistry and enzymology, for determining the activity of PHL-A2 used immunoassay method and reagent kits of company "Cayman chemical", analysis of cytokines was performed enzymelinked immunosorbent method. <h3>Results</h3> In OA, and especially in RA in SF, with the intensification of free radical processes (intensified the breakdown of phospholipids, increases the level MDA – secondary product of LPO and marker of degradation of membrane structures). Against this background, the observed inhibition of the antioxidant defense system (decreased activity of SOD, CAT, G-ST – enzyme conjugates with glutathione toxic products LPO and promotes their excretion; reduced level TF, designed to stabilize the lipid composition of membranes and protect them from degradation caused PHL-A2, and also block the damaging effect of singlet oxygen; also dramatically reduced the level of CP, which neutralizes free radicals). These changes are consistent with activation in SF with RA and OA proinflammatory cytokines and TNF-α. Table 1.Free radicals, antioxidant defense system and cytokine status of SF with RA and OA <h3>Conclusions</h3> Intensification of free radical processes, generation of reactive oxygen species as a result of suppression of antioxidant protection is a cause of metabolic disorders of proteins and lipids in LF with RA and OA, the cause of the inflammatory process that causes apoptosis and cell destruction. The current strategy for the treatment of RA and OA is focused on reducing pain and preventing progressive degeneration of articular cartilage and subchondral bone, based on identified pathogenetic mechanisms, such as the development of inflammation and tissue destruction caused by the activation of free radical processes, suppression of antioxidant protection, dynamics of proinflammatory cytokines and TNF-α. <h3>Disclosure of Interest</h3> None declared