tbuckley/cabot-search huggingface dataset:
S825 EVALUATION OF AMG 420, AN ANTI‐BCMA BISPECIFIC T‐CELL ENGAGER (BITE®) IMMUNOTHERAPY, IN R/R MULTIPLE MYELOMA (MM) PATIENTS: UPDATED RESULTS OF A FIRST‐IN‐HUMAN (FIH) PHASE 1 DOSE ESCALATION STUDY
Authors: M. Topp, J. Duell, G. Zugmaier, M. Attal, P. Moreau, C. Langer, J. Kroenke, T. Facon, A. Salnikov, R. Lesley, K. Beutner, J. Kalabus, E. Rasmussen, K. Riemann, A. Minella, G. Munzert, H. Einsele
Journal: HemaSphere (2019)

Background: BCMA, a member of the TNFR family, is expressed on MM and plasma cells (PC). Aims: Objectives of this study included assessing safety and activity of AMG 420/BI 836909, which binds BCMA (B‐Cell Maturation Antigen) on MM cells and CD3 on T cells, in relapsed and/or refractory (R/R) MM. Methods: In this FIH study (NCT02514239), 6‐week cycles of AMG 420 were given for ≤5 cycles or until disease progression (PD), toxicity, or consent withdrawal; 5 more cycles could be given for benefit. Eligible patients had progression after ≥2 lines (incl PI and IMiD). Excluded were PC leukemia, extramedullary relapse, CNS involvement, or prior allo‐SCT. MRD was defined as &lt;1 tumor cell / 10 4 bone marrow cells per flow cytometry. Results: As of Dec 10, 2018, 42 patients received AMG 420 (0.2–800 μg/d). Patients D/C for PD (n = 24), adverse events (AE, n = 7, incl 3 DLTs), death (4), completed 10 cycles (2), and consent (1). Median age was 65 y, median MM duration 5.2 y, and median # prior therapies 4. Patients were treated for a mean (SD) of 2.5 (2.6) cycles. There were 2 deaths from AEs (acute respiratory distress from flu / aspergillosis; fulminant hepatitis related to adenovirus infection); neither treatment related. Of those with serious AEs (SAEs, n = 21, 50%), 18 required hospitalization. SAEs occurring in &gt;1 patient were infections (n = 12) and polyneuropathy (PN, n = 2). Treatment‐related SAEs included 2 grade 3 PNs and 1 edema. Grade 2–3 CRS was seen in 3 patients. No anti‐AMG 420 Ab were detected. In this study, 800 μg/d was determined to not be tolerable as 2/3 patients had DLTs, 1 case of grade 3 CRS and 1 case of grade 3 PN; both required hospitalization and subsequently resolved. At 400 μg/d, there were 5 minimal residual disease (MRD)‐negative sCRs, 1 VGPR, and 1 PR, for a response rate of 7/10 (70%); at Dec datacut, responses lasted for 5.6–10.4 months with 4 patients ongoing on treatment. As of Feb 2019, some responses lasted &gt;1 year. Overall, there were 13/42 responders (6 sCRs, 3 CRs, 2 VGPRs, 2 PRs). Median time to any response was 1 month, with 9 of 13 patients responding in the first cycle. Summary/Conclusion: In this FIH study of AMG 420, a BiTE ® vs BCMA, in R/R MM, there was a 70% response rate (7/10) with 5 out of 7 responders achieving a sCR at 400 μg/d, a recommended dose for further investigation. image
Subacute progressive sensorimotor symptoms
Authors: Anna Francis, Robert Crossley, Stefen Brady
Journal: BMJ (2019)

A 24 year old woman presented with a three week history of numbness ascending from her ankles to her chest and affecting her hands.

She drank 20 units of alcohol at weekends, occasionally used cocaine, and had used recreational nitrous oxide (N2O) several times a month for the preceding four months. Her symptoms started following what she described as “excessive” N2O use three weeks earlier.

She had mild, symmetrical distal weakness of her upper and lower limbs, and needed assistance to walk. She had impaired sensitivity to pinprick and fine touch …
Abstract MP42: Reduction in Dietary Transfat Intake is Associated with Improved Lipid Particle Number in a Primary Prevention Population
Authors: Michael Garshick, Heidi Mochari-Greenberger, Lori Mosca
Journal: Circulation (2013)

Background: Recent public policy has focused on elimination of dietary transfats. The extent to which changes in transfat intake correlate with changes in cardiovascular disease (CVD) risk in real world settings is not established. Lipid Particle Number (LPN) is a novel marker of CVD risk and data from the Framingham Offspring Study indicate a doubling of CVD risk among those with LPN values in the highest versus lowest quartile. The purpose of this study was to determine if a decrease in transfat intake is associated with a decrease in LPN in a free living population at risk of CVD. Methods: This was a 1 year follow-up study of family members (n = 400, 33% male, 36% racial/ethnic minority, mean age 48 +/- 13) of patients hospitalized with CVD who participated in a 1 year NHLBI sponsored randomized controlled primary prevention lifestyle intervention trial and had complete dietary data and LPN measures at baseline and 1 year. Transfat (% of total kilocalories per day) was assessed by the validated Block Food Frequency Questionnaire and LPN (nmol/L) was measured at a central lab using NMR spectroscopy at baseline and 1 year. Traditional CVD risk factors and potential confounders were assessed by trained research personnel using standardized measures and questionnaires. Change in transfat as a percentage of total diet and mean absolute change in LPN at 1 year was assessed using multivariate adjusted linear regression models. Results: Over 1 year 57% (n = 226) of the study population decreased their transfat intake which did not vary significantly by group assignment. There was a significant positive correlation between baseline dietary transfat intake and LPN (p = 0.04). At baseline higher mean LPN was also associated with male sex (p &lt; 0.001), overweight/obesity (≥ 25 kg/m 2 , p &lt; 0.001), waist size (men ≥ 40 inches, women ≥ 35 inches, p &lt; 0.001), HgA1c (≥ 6.5%, p = 0.003), and current smoking (p = 0.01). Over 1 year, for every 1 percent change in transfat intake there was a 27 nmol/L change in LPN (p = 0.04). The association between the change in transfat intake and change in LPN was independent of baseline predictors, confounders, and group assignment (p = 0.03). Conclusion: In a free living population at risk of CVD, a reduction in transfat intake over 1 year was significantly associated with a reduction in LPN. These data suggest how improved LPN may be one potential mechanism by which elimination of transfat may confer CVD benefit, and provide insight into the potential for a decrease in transfat intake to decrease the burden of CVD.
Comprehensive viromewide antibody responses by systematic epitope scanning after hematopoietic cell transplantation
Authors: Rachel A. Bender Ignacio, Sayan Dasgupta, Terry Stevens-Ayers, Tomasz Kula, Joshua A. Hill, Stephanie J. Lee, Marco Mielcarek, Ann Duerr, Stephen J. Elledge, Michael Boeckh
Journal: Blood (2019)
PS1542 RESPIRATORY SYNCYTIAL VIRUS AND HUMAN METAPNEUMOVIRUS INFECTIONS AFTER ALLOGENEIC STEM CELL TRANSPLANTATION: IMPACT OF THE IMMUNODEFICIENCY SCORING INDEX AND RIBAVIRIN TREATMENT ON THE OUTCOMES
Authors: M. Akhmedov, V. Wais, E. Sala, A. Neagoie, A. Gantner, S. von Harsdorf, F. Kuchenbauer, A. Schubert, D. Michael, H. Döhner, D. Bunjes
Journal: HemaSphere (2019)

Background: Respiratory viral infections are a major cause of morbidity and mortality among allogeneic stem cell transplant recipients. In order to predict outcomes of the respiratory syncytial virus (RSV) infections in HSCT recipients, the immunodeficiency scoring index (ISI) was recently introduced. Aims: We decided to investigate the predictive role of the ISI in regards to progression to lower respiratory tract infection (LRTI) and mortality in an independent cohort of RSV and human metapneumovirus (hMPV) infected allogeneic stem cell transplant recipients. Methods: In total 71 patients were included in this study: 41 patients presented with upper respiratory tract infection (URTI) and 30 had primary LRTI. Patients were stratified as per ISI criteria into low, moderate and high-risk groups. Patients in the URTI cohort received treatment with either oral ribavirin (n = 20), intravenous ribavirin (n = 1) or with a combination of intravenous ribavirin and intravenous immunoglobulin (n = 1); 19 patients received no antiviral therapy. Patients in the LRTI cohort were treated either with intravenous ribavirin (n = 12), a combination of intravenous ribavirin and intravenous immunoglobulin (n = 16) or with oral ribavirin (n = 2). Results: Progression from URTI to LRTI was observed in 14% of the low-risk group, 20% of moderate and 75% of the high-risk group, p = 0,001. The trend of increased progression rate persisted after adjustment to received therapy, p < 0,0001. 21% of RSV-infected patients further progressed to LRTI compared to 29% of hMPV-infected patients, p = 0,524. In the LRTI cohort no (0%) virus-associated mortality was observed in the low-risk group compared to 16% in moderate and 43% in the high-risk group, p = 0,160. 17% deaths were observed among patients infected with RSV and 29% with hMPV, p = 0,517. With a median follow-up of 20 months, the median overall survival was not reached in both low and moderate-risk groups and was only 6 months in the high-risk group [95% CI: 0,23–11,77; p = 0,015]. Summary/Conclusion: ISI could predict progression from URTI to LRTI in a mixed cohort of RSV and hMPV infected allogeneic stem cell transplant recipients. The trend persisted after adjustment to received therapy. ISI was not able to predict mortality in the LRTI cohort but could predict overall survival in the entire cohort. No differences were observed in the outcomes of RSV and hMPV infected patients.
THU0402 CONTRIBUTION OF THE EOS IMAGING SYSTEM IN ASSESSING PELVIC AND SPINAL DEFORMITIES IN SPONDYLOARTHRITIS
Authors: Meriem Sellami, Wafa Hamdi, Hend Riahi, Kaouther Maatallah, Hanen Ferjani, Dhia Kaffel, Mohamed Montacer Kchir
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The severity of Spondyloarthritis (SA) lies mainly in the progressive ankylosis of the axial skeleton and the deformations generated. The means of assessing the spinal static disorders in SA are currently subjective and difficult to reproduce. Multidisciplinary collaboration has led to the development of a new biplane low dose radiology technology named EOS. It allows a simultaneous acquisition of the axial skeleton and the lower limbs in a standard standing position. <h3>Objectives:</h3> We aimed to assess pelvic and spinal parameters and spinal stature in patients with SA using the EOS system. <h3>Methods:</h3> This is a prospective cross-sectional study conducted over a 10-month period (January-October 2018) involving 50 patients with SA meeting the criteria of Assessment of SpondyloArthritis International Society. An entire body EOS examination of the vertebral column in a standardized standing position was performed in all patients. Pelvic parameters measured by the EOS system were pelvic incidence (PI: normal value: 48-55°), sacral slope (SS: normal value: 36-42°) and lateral pelvic tilt (LPT: normal value: 12-18°). Spinal stature parameters were thoracic kyphosis (normal value: 41-48°), lumbar lordosis (normal value: 43-61°), sagittal vertical axis (SVA: normal value: &lt;30mm) and spinosacred angle (SSA: normal value: &lt;132). <h3>Results:</h3> We enrolled 29 men (58%) and 21 women (42%) with an average age of 42.6 ± 11.09 years [20 -79]. The mean duration of SA was 12.4 ± 9.71 years [2-46]. SA was axial in 17 patients (34%), and axial and peripheral in 29 patients (58%). The median PI was 50.7 ± 11.81°. The median SS was 35.8 ± 11.64°. The median LPT was 14.9 ± 8.97°. The average value of thoracic kyphosis was 52.1± 12.1°. The average value of lumbar lordosis was 37.4 ± 16. The median SVA was 25.2 ± 55.88 mm and the median of SSA was 123.9 ± 16.64°. Thus, deformity of the thoracic spine was found in 40 patients (80%) with thoracic hypercyphosis type and thoracic rectitude in 12% and 68% of cases respectively. The deformity of the lumbar spine was found in 40 patients (80%) with lumbar hyperlordosis type and lumbar rectitude in 74% and 6% of cases respectively. From this construction and segmenting the SS values, we were able to classify the type of back according to Roussouly : the type 2 back was the most frequently found (40%), followed by type 3 back (34%), type 4 back (24%), and type 1 back (2%). Spinal deformities were more frequent in women (p=0.004) and associated with a longer duration of the disease (p&lt;0.0001) and a longer duration before initiation of treatment (p&lt;0.0001) (Table 1). <h3>Conclusion:</h3> Our study showed that the EOS system was a useful technique in assessing pelvic and spinal stature in patients with SA. <h3>Disclosure of Interests:</h3> None declared
PB2368 ONCE- VERSUS TWICE-DAILY FILGRASTIM FOR MOBILIZATION OF PERIPHERAL BLOOD STEM CELLS FROM HEALTHY DONORS: SINGLE CENTER EXPERIENCE
Authors: T. N. Yigenoglu, B. Uncu Ulu, S. Bascı, M. Bakırtas, T. Darcın, D. Sahin, D. Iskender, M. Kizil Cakar, M. S. Dal, F. Altuntas
Journal: HemaSphere (2019)

Background: Peripheral blood stem cell (PBSC) graft is widely used for allogeneic transplantation and produces faster neutrophil recovery than bone marrow cells[1]. Although the mobilization of peripheral blood stem cells from normal donors using filgrastim is widely used, the ideal schedule for the administration of filgrastim has not been determined. Aims: To compare the efficacy of peripheral blood stem cell mobilization on day 5 of filgrastim between once-daily(1∗10 mcg/kg) and twice-daily(2∗5 mcg/kg) administration, we performed a prospective study on our healthy donors. Methods: Healthy allogeneic donors whose PBSC mobilisation were done at Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Stem Cell Transplantation Unit, were separated to once-daily(1∗10 mcg/kg) and twice-daily(2∗5 mcg/kg) administration groups. 40 donors were randomly assigned to once-daily and twice-daily groups. Results: The number of CD34 cells collected on day 5 was not significantly different (9.6 ∗ 106 cells/kg in once-daily group and 9.1 ∗ 106 cells/kg in twice-daily group, P:0.620). The baseline white blood cell count,donor age and sex did not significantly affect the CD34 cell yield. Summary/Conclusion: Once-daily administration of filgrastim (1∗10 mcg/kg) appeared to be appropriate for the mobilization of CD34 cells in normal donors.
Transmission events and antimicrobial susceptibilities of methicillin-resistant Staphylococcus argenteus in Stockholm
Authors: C.G. Giske, F. Dyrkell, D. Arnellos, N. Vestberg, S. Hermansson Panna, I. Fröding, M. Ullberg, H. Fang
Journal: Clinical Microbiology and Infection (2019)
Disparities in Prevalence and Treatment of Mental Health Disorders in Children—Reply
Authors: Daniel G. Whitney, Mark D. Peterson
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Neuronally Enriched RUFY3 Is Required for Caspase-Mediated Axon Degeneration
Authors: Nicholas T. Hertz, Eliza L. Adams, Ross A. Weber, Rebecca J. Shen, Melanie K. O’Rourke, David J. Simon, Henry Zebroski, Olav Olsen, Charles W. Morgan, Trevor R. Mileur, Angela M. Hitchcock, Nicholas A. Sinnott Armstrong, Michael Wainberg, Michael C. Bassik, Henrik Molina, James A. Wells, Marc Tessier-Lavigne
Journal: Neuron (2019)
Modeling Structural Constraints on Protein Evolution via Side-Chain Conformational States
Authors: Umberto Perron, Alexey M Kozlov, Alexandros Stamatakis, Nick Goldman, Iain H Moal
Journal: Molecular Biology and Evolution (2019)

Few models of sequence evolution incorporate parameters describing protein structure, despite its high conservation, essential functional role and increasing availability. We present a structurally aware empirical substitution model for amino acid sequence evolution in which proteins are expressed using an expanded alphabet that relays both amino acid identity and structural information. Each character specifies an amino acid as well as information about the rotamer configuration of its side-chain: the discrete geometric pattern of permitted side-chain atomic positions, as defined by the dihedral angles between covalently linked atoms. By assigning rotamer states in 251,194 protein structures and identifying 4,508,390 substitutions between closely related sequences, we generate a 55-state "Dayhoff-like" model that shows that the evolutionary properties of amino acids depend strongly upon side-chain geometry. The model performs as well as or better than traditional 20-state models for divergence time estimation, tree inference, and ancestral state reconstruction. We conclude that not only is rotamer configuration a valuable source of information for phylogenetic studies, but that modeling the concomitant evolution of sequence and structure may have important implications for understanding protein folding and function.
SP0115 CASE 1 DISCUSSANT: IMMINENT FRACTURE RISK: ASSESSMENT AND DOES IT HELP CLINICAL MANAGEMENT
Authors: Cyrus Cooper
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> With an estimated 520,000 fragility fractures every year in the UK, delivering effective and efficient healthcare for this patient group has significant consequences for patients, families, the NHS, and society. A fragility fracture is a major risk factor for further fractures, and healthcare systems are now beginning to recognise the benefits of secondary fracture prevention. Despite this, less than 50% of patients receive effective secondary fracture prevention after a fragility fracture. This has led to national and international initiatives to improve clinical services by implementing fracture liaison services (FLSs). Successful funding of a new FLS is usually influenced by the number of fractures it is expected to prevent in the first few years after an index fracture. The expected number of fractures prevented is in turn determined by the baseline risk of subsequent fracture, the number of patients at high enough fracture risk to warrant anti-osteoporosis medication (AOM), and the degree of fracture risk reduction by AOMs. Underestimating fracture risk in the post-fracture period will lead to fewer expected fractures prevented and lower perceived benefit of the FLS by payers, and importantly also by patients, families, healthcare providers, and payers. Tools are available to determine the long-term risk of fracture based on patient factors, including previous fracture. Of these, FRAX and QFracture have been incorporated within UK NICE clinical guidance, and the FRAX-derived intervention threshold is used to guide recommendations for AOM in the NHS. <h3>Disclosure of Interests:</h3> Cyrus Cooper Consultant for: Personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB.
OP0248 THE IMPACT OF EXERCISE ON HAND FUNCTION AND QUALITY OF LIFE OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: A RANDOMIZED CONTROLLED TRIAL
Authors: Kyriaki Keramiotou, Christos Anagnostou, Antonis Galanos, Evaggelia Kataxaki, Petros Sfikakis, Maria Tektonidou
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) has a significant impact on the ability to perform daily activities and patients' quality of life. To date, no studies have examined the effect of exercise on hand function and quality of life of SLE patients. <h3>Objectives</h3> To determine the effect of exercise on hand strength, dexterity and performance of daily activities, and the quality of life of SLE patients. <h3>Methods</h3> A randomized, 24-week follow-up trial was designed. A total of 240 consecutive SLE patients fulfilling the SLICC classification criteria were evaluated. Sixty two patients who met the inclusion criteria [age&gt;18 years, upper limb arthralgias, DASH (Disabilities of the Arm, Shoulder, and Hand) score&gt;10 and stable drug regimen for ≥3 months], were randomly assigned to the exercise group (n=32) or the routine care (control) group (n=30). Patients in the exercise group received by the hand therapist a 30 min daily program at home of strengthening and stretching upper limb exercises for 12 weeks. Performance of daily activities was evaluated with the DASH and HAQ questionnaires, the grip and pinch strength with the Jamar dynamometer and pinch gauge tools respectively, the dexterity with the Purdue pegboard test, and the quality of life with the LUPUSQoL questionnaire, at 0, 6, 12 (end of the exercise program) and 24 weeks for both groups. SLE activity and cumulative organ damage were evaluated with the SLEDAI and SLICC/ACR-DI, respectively. <h3>Results</h3> There were no statistically significant differences between two groups in age (p=0.062), sex (p=0.346), disease duration (p=0.065), SLEDAI (p=0.937), SLICC/ACR-DI (p=0.242), number of tender joints (p=0.703), and use of corticosteroids (p=0.640), hydroxycloroquine (p=0.985) or immunosupressives (p=0.806). Thirty patients (93.75%) from the exercise group completed the 12-week exercise program and 28 (87.5%) were re-evaluated at 24 weeks; 30 patients (100%) of control group completed the 24-week study. The percent changes of DASH and HAQ scores were significantly lower (improvement) in the exercise group compared to control group at all-time points. Moreover, all percent changes of grip strength, pinch strength hand dexterity and the LupusQol score were significantly higher in the exercise group compared to control group at all-time points (Table 1). All values are presented as median (interquartile range). DASH=Disabilities of the Arm, Shoulder, and Hand), HAQ=Health Assessment Questionnaire, LUPUSQoL=Lupus Quality of Life, PH=physical health domain, DH=dominant hand, JAW=tripoid pinch, COM=combination. <h3>Conclusion</h3> Upper limb exercise, significantly improves hand function and quality of life in SLE patients. Clinicaltrials.gov Id: NCT03802578 <h3>Disclosure of Interests:&nbsp;</h3> None declared