tbuckley/cabot-search huggingface dataset:
PS1125 LINKING MICROENVIRONMENTAL SIGNALS TO METABOLIC SWITCHES AND IBRUTINIB RESPONSE IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Z. Chen, H. ter Burg, G. Andrejeva, J.C. Rathmell, F. Forconi, A.P. Kater, G.J. van der Windt, E. Eldering
Journal: HemaSphere (2019)

Background: Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous B cell malignancy, with accumulation of clonal CD5+ B cells in blood, lymph nodes (LN) and bone marrow. CLL has become a paradigm for a cancer that depends on signals from the microenvironment. This is evidenced by the clinical success of the Btk inhibitor ibrutinib, which drives CLL cells out of the LN to eventually die by neglect. In peripheral blood, CLL cells are quiescent, non‐cycling, with low metabolic activity. In contrast, in LN CLL cells receive various signals from surrounding cells, crucial for proliferation, and protection from chemotherapeutic drugs. These acquired advantages are possibly linked with altered metabolism, but it is unclear if and how CLL cells change their metabolism in the LN environment. Aims: We aimed to investigate the altered metabolism of CLL cells in the tumor microenvironment, and what signals determine these changes. Methods: Glucose uptake, glycolysis, mitochondrial mass, oxidative phosphorylation and lipid uptake were measured by flow cytometer or Seahorse XF96 analyzer, and 90 metabolites were analyzed by LC mass‐spectrometry. Results: We first established that the metabolic activity profile of circulating recent LN emigrants (CXCR4 high /CD5 dim PB lymphocytes) resembled that of actual LN residents (obtained by a core biopsy), which showed both higher mitochondrial mass and glucose uptake than paired peripheral blood CLL cells. In vitro stimulation of isolated blood‐derived CLL samples demonstrated that CD40 but not BCR signaling recapitulate these metabolic changes. Next, 10 patient samples were stimulated with/without CD40L for 48 hours and analyzed by mass‐spec for metabolic intermediates. To draw a further parallel with the situation in LN, metabolomics was performed on 13 patients sampled before and after 3 months of ibrutinib treatment. Combined, the data shows that various metabolic pathways are activated in the tumor microenvironment, particularly TCA cycle, pyruvate metabolism, glycolysis, and fatty acid metabolism. Apart from these overall changes, the highest ranking shifts in metabolites point to involvement of amino acids to fuel the TCA cycle. Moreover, aberrant patterns in metabolic changes after ibrutinib were noted in some patients, possibly linked with clinical response. Summary/Conclusion: CD40 signaling leads to increased oxidative phosphorylation and glycolysis in the CLL microenvironment. Opposite changes were observed in ibrutinib treated samples, together providing indirect insight into the metabolism in the CLL LN.
PB1828 PRIMARY PROPHYLAXIS OF CHEMOTHERAPY‐INDUCED FEBRILE NEUTROPENIA IN ADULT PATIENTS WITH LYMPHOPROLIFERATIVE DISORDERS ‐ CLINICAL EXPERIENCE IN UNIVERSITY HOSPITAL SPLIT
Authors: M. Petrić, L. Vicelić Čutura, V. Blaslov, A. Miljak, D. Galušić
Journal: HemaSphere (2019)

Background: Febrile neutropenia (FN) is the development of fever in a patient with an abnormally low number of neutrophil granulocytes. It can be associated with other signs of infection and is often consequence of chemotherapy treatment. Granulocyte colony‐stimulating factors (G‐CSF) are used for prophylaxis of FN. We analyzed data of adult patients with lymphoproliferative disorders who were treated with chemotherapy regimens of high or intermediate risk for developing FN, according to guidelines of European organization for research and treatment of cancer (EORTC). Aims: To investigate the benefit of primary prophylaxis of chemotherapy‐induced FN in patients with lymphoproliferative disoders. To evaluate the incidence of FN following chemotherapy regimens of high or intermediate risk for developing FN. Methods: We analyzed medical history of all 97 adult patients (M = 55; F = 42, aged 21 – 81 (mean, 54) years) with lymphoproliferative disorders who were treated with chemotherapy regimens of high or intermediate risk for developing FN in the period from 1 st November 2017 till 1 st November 2018. Incidence of FN was analyzed according to type of chemotherapy regimen and administration of primary prophylaxis. Results: Primary prophylaxis with G‐CSF was administered to all (N = 12) patients who were treated with high risk chemotherapy regimens, in compare to only 24 (28%) patients who received intermediate risk regimens. FN was registered in total of 24 (25%) patients, of whom 20 were treated with intermediate risk regimens. Among patients who received primary prophylaxis after intermediate risk regimens, only 4 (17%) of them developed FN, in compare to 16 (26%) of patients who previously did not receive primary prophylaxis after same regimens. Incidence of FN was higher in females (N = 14) and after the first cycle of chemotherapy regimen (N = 15). Summary/Conclusion: Primary prophylaxis with G‐CSF reduces the risk of developing FN, so it is recommended to administer primary prophylaxis to all patients who are treated with high risk chemotherapy regimens. Primary prophylaxis in patients receiving intermediate risk regimens should be carefully considered because of the high incidence of FN in those who did not receive prophylaxis. In those circumstances, other risk factors (such as comorbidities, age of patient, history of previous infections and FN, stage of the disease and others) should be evaluated before the decision whether to administer primary prophylaxis or not. In our patients, low incidence of FN was observed in the group who received primary prophylaxis after intermediate risk regimens.
Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomised trial
Authors: Ofri Mosenzon, Stephen D Wiviott, Avivit Cahn, Aliza Rozenberg, Ilan Yanuv, Erica L Goodrich, Sabina A Murphy, Hiddo J L Heerspink, Thomas A Zelniker, Jamie P Dwyer, Deepak L Bhatt, Lawrence A Leiter, Darren K McGuire, John P H Wilding, Eri T Kato, Ingrid A M Gause-Nilsson, Martin Fredriksson, Peter A Johansson, Anna Maria Langkilde, Marc S Sabatine, Itamar Raz
Journal: The Lancet Diabetes & Endocrinology (2019)
Stroke After Transcatheter Aortic Valve Replacement
Authors: Steven R. Messé, Gorav Ailawadi
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
AB0759 BIOLOGICS IMPROVES ARTERIAL STIFFNESS WITH CS DMARDS-RESISTANT ACTIVE PSORIATIC ARTHRITIS. A COHORT STUDY
Authors: Kensuke Kume, Kanzo Amano, Toshikatsu Kanazawa, Kazuhiko Hatta, Naohiko Matsumoto
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patients with psoriatic arthritis (PsA) have an increased cardiovascular (CV) risk. We should have strategies for primary cardiovascular prevention in PSA<sup>1)</sup>. But there is no evidence of CV risk management and arterial stiffness about biologics in patients with PsA <h3>Objectives:</h3> To examine the effect of biologics plus conventional synthetic (cs) DMARDs on arterial stiffness in cs DMARDs resistant PsA patients in a cohort study design. <h3>Methods:</h3> 38 PSA and patients with moderate to severe active disease despite cs DMARDs treatment (disease activity score: DAPSA<sup>2)</sup> score&gt;14) were received Biologics plus cs DMARDs. All patients have no previous history of CV. Arterial stiffness was assessed with cardio-ankle vascular index (CAVI, modified pulse wave velocity(PWV)) and augmentation index corrected for a heart rate of 75 beats per minute (AIx@75) at baseline and 24 weeks follow-up. Clinical data were collected at regular visits. CAVI is very similar to pulse wave velocity (PWV), and CAVI measures arterial wall stiffness independent of blood pressure and it is superior to brachial ankle PWV as an index of arterial stiffness<sup>2</sup>. <h3>Results:</h3> 35 PsA patients(18 patients adalimumab,13 patients infliximab, and 4 patients ustekinumab, respectively) completed this study, Treatment with biologics(10.88 ± 1.86 and 9.46± 1.14%; p = 0.006), attenuated the CAVI significantly from baseline to 24 weeks follow up. Treatment with biologics(36.4 ± 8.6, 32.1 ± 3.8%; p = 0.008) attenuated the aix@75 significantly from baseline to 24 weeks follow up. DAPSA score improved significantly from baseline to 24 weeks(17.45±6.33, 5.44±3.43: p=0.01). There are no significant differences among biologics about CAVI and aix@75. Surprisingly, improvement of CAVI and aIx@75 were not correlated disease activity at 24 weeks of biologics treatment (CAVI: p=0.91, aIx@75: p=0.88). Biologics improves arterial stiffness independently of its effects on disease activity, since even in high disease activity (4 cases; DAPSA score&gt;28) is halted. <h3>Conclusion:</h3> These findings suggest that combination therapy, biologics with cs DMARDs not only reduced PsA disease activity but also limited vascular damage in patients with cs DMARDS resistant active PsA <h3>References</h3> [1] Søren Lund Kristensen, et al. Psoriasis, psoriatic arthritis and cardiovascular risk: are we closer to a clinical recommendation?Ann Rheum Dis. 2015; 74: 321-2. [2] Schoels MM, et al. Disease activity in psoriatic arthritis (PsA): defining remission and treatment success using the DAPSA score. Ann Rheum Dis, 2016; 75: 811-8. <h3>Acknowledgement:</h3> Thank you for all paitents and colleagues. <h3>Disclosure of interests:</h3> None declared
Abstract 15006: Marked Practice Variation in Antithrombotic Care With the Berlin EXCOR VAD
Authors: Lindsay J May, Angela Lorts, Christina VanderPluym, Jennifer Conway, Patti Massicotte, Morgan Millar, Marie E Steiner, David N Rosenthal
Journal: Circulation (2017)

Introduction: The Berlin EXCOR remains the only FDA-approved pediatric VAD. Unfortunately antithrombotic therapy (ATT) on this device is challenging: stroke occurs in 28% of patients and 50% have m...
Human Tissue-Resident Mucosal-Associated Invariant T (MAIT) Cells in Renal Fibrosis and CKD
Authors: Becker M. P. Law, Ray Wilkinson, Xiangju Wang, Katrina Kildey, Kurt Giuliani, Kenneth W. Beagley, Jacobus Ungerer, Helen Healy, Andrew J. Kassianos
Journal: Journal of the American Society of Nephrology (2019)

Mucosal-associated invariant T (MAIT) cells represent a specialized lymphocyte population associated with chronic inflammatory disorders. Little is known, however, about MAIT cells in diseases of the kidney, including CKD.To evaluate MAIT cells in human native kidneys with tubulointerstitial fibrosis, the hallmark of CKD, we used multicolor flow cytometry to identify, enumerate, and phenotype such cells from human kidney tissue biopsy samples, and immunofluorescence microscopy to localize these cells. We cocultured MAIT cells and human primary proximal tubular epithelial cells (PTECs) under hypoxic (1% oxygen) conditions to enable examination of mechanistic tubulointerstitial interactions.We identified MAIT cells (CD3+ TCR Vα7.2+ CD161hi) in healthy and diseased kidney tissues, detecting expression of tissue-resident markers (CD103/CD69) on MAIT cells in both states. Tissue samples from kidneys with tubulointerstitial fibrosis had significantly elevated numbers of MAIT cells compared with either nonfibrotic samples from diseased kidneys or tissue samples from healthy kidneys. Furthermore, CD69 expression levels, also an established marker of lymphocyte activation, were significantly increased on MAIT cells from fibrotic tissue samples. Immunofluorescent analyses of fibrotic kidney tissue identified MAIT cells accumulating adjacent to PTECs. Notably, MAIT cells activated in the presence of human PTECs under hypoxic conditions (modeling the fibrotic microenvironment) displayed significantly upregulated expression of CD69 and cytotoxic molecules perforin and granzyme B; we also observed a corresponding significant increase in PTEC necrosis in these cocultures.Our findings indicate that human tissue-resident MAIT cells in the kidney may contribute to the fibrotic process of CKD via complex interactions with PTECs.
Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases
Authors: Amandine Chaix, Emily N.C. Manoogian, Girish C. Melkani, Satchidananda Panda
Journal: Annual Review of Nutrition (2019)

Molecular clocks are present in almost every cell to anticipate daily recurring and predictable changes, such as rhythmic nutrient availability, and to adapt cellular functions accordingly. At the same time, nutrient-sensing pathways can respond to acute nutrient imbalance and modulate and orient metabolism so cells can adapt optimally to a declining or increasing availability of nutrients. Organismal circadian rhythms are coordinated by behavioral rhythms such as activity-rest and feeding-fasting cycles to temporally orchestrate a sequence of physiological processes to optimize metabolism. Basic research in circadian rhythms has largely focused on the functioning of the self-sustaining molecular circadian oscillator, while research in nutrition science has yielded insights into physiological responses to caloric deprivation or to specific macronutrients. Integration of these two fields into actionable new concepts in the timing of food intake has led to the emerging practice of time-restricted eating. In this paradigm, daily caloric intake is restricted to a consistent window of 8-12 h. This paradigm has pervasive benefits on multiple organ systems.
PS1073 PRELIMINARY RESULTS OF ASTX660, A NOVEL NON‐PEPTIDOMIMETIC CIAP1/2 AND XIAP ANTAGONIST, IN RELAPSED/REFRACTORY PERIPHERAL T‐CELL LYMPHOMA AND CUTANEOUS T CELL LYMPHOMA
Authors: A. Mehta, A. Hollebecque, F. Foss, J. Lister, M. Mita, N. Wagner‐Johnston, M.J. Dyer, B. You, A. Prica, F. Hernandez‐Llizaliturri, R. Ferraldeschi, D. Chan, J. Zhang, F. Samaniego
Journal: HemaSphere (2019)

Background: ASTX660 is an oral, novel non‐peptidomimetic, small‐molecule antagonist of cellular/X‐linked inhibitors of apoptosis proteins (cIAP1/2 and XIAP). ASTX660 is currently being evaluated in a first‐in‐human phase 1‐2 study in patients (pts) with advanced solid tumors and lymphoma (ClinicalTrials.gov NCT02503423). In the phase 1 part of the study, the recommended phase 2 dose (RP2D) was identified with a favorable safety profile and initial evidence of clinical activity in a pt with mycoses fungoides (Mita et al, presented at the AACR‐NCI‐EORTC Conference 2017, abs #A091). Aims: Herein, we report preliminary efficacy and safety results from the ongoing relapsed/refractory (r/r) peripheral T‐cell lymphoma (PTCL) and cutaneous T‐cell lymphoma (CTCL) Phase 2 cohorts. Methods: Pts receive treatment with ASXT660 at the RP2D 180 mg/day on Days 1 to 7, and 15 to 22 in a 28‐day cycle. The primary endpoint is response rate as assessed by the investigator according to either the Lugano criteria (PTCL) or Global Assessment (CTCL). Adverse events (AEs) are assessed per CTCAE V4.03. Results: As of 15 January 2019, 16 PTCL pts and 13 CTCL pts have received ASTX660. Pt characteristics: median (range) age: PTCL: 59 (39–81) years and CTCL: 57 (23–75) years; median number of prior therapies: PTCL: 3 (1–7) and CTCL: 3 (1–9). In the PTCL cohort the ORR is 28% (4/14); 2 pts have yet to reach their first assessment. Three responding pts remain on study drug for 7–10 months. Responses have been observed in pts with AITL and PTCL‐NOS. In the CTCL cohort the global response is 25% (3/12); 1 pt has yet to reach their first assessment. Two responding pts remain on study drug for 4–6 months. Responses have been seen in pts with large cell transformation, sezary syndrome and visceral metastases. Among all pts, the most common related AEs of any grade (≥ 15%) were lipase elevation (38%), amylase elevation (34%), ALT elevation (28%), elevation (24%) and rash (24%). Related AEs ≥ Grade 3 occurring in ≥3 pts were rash (n = 5) and lipase elevation (n = 4). Accrual continues; updated efficacy and safety results will be presented at the meeting. Summary/Conclusion: In the ongoing Phase 2 cohorts ASTX660 has shown activity against PTCL and CTCL with manageable safety profile. These early data support continued development of ASXT660 for the treatment of r/r PTCL and CTCL. Correlative studies are aimed at identifying predictors of response.
AB0991 PRELIMINARY RESULTS OF REFERRALS TO A TERTIARY PEDIATRIC RHEUMATOLOGY OUTPATIENT CLINIC: A YEAR IN REVIEW
Authors: Şerife Gül Karadağ, Ayşe Tanatar, Hafize Emine Sonmez, Nuray Aktay Ayaz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Previously, the profile of pediatric rheumatology practice was demonstrated from several countries(1,2). However, there is not a documented data about the pediatric rheumatology clinic population in our country. <h3>Objectives</h3> To evaluate and define the patient population referred to a tertiary pediatric rheumatology outpatient clinic in Turkey <h3>Methods</h3> We prospectively evaluated the patients who were initially referred to our department with suspicion of rheumatic diseases in a year period. These findings cover only ten months results as a preliminary study. <h3>Results</h3> A total of 2317 new patients(1142 male/1175 female) were seen. Among them, most of patients(n=1455) were referred from pediatric outpatient clinics, pediatric emergency units(n=168) and orthopedic surgeons(n:91). Of these 48.9% had a final diagnosis of a rheumatic disease, 37.9% had non-rheumatic conditions, and 13.2% had no definitive diagnosis yet. Most of them were periodic fever syndromes(n=553), juvenile idiopathic arthritis(n=207) and vasculitis(n=160)(Table 1). Other than rheumatological diseases, non-rheumatic conditions were mostly vitamin d deficiency, infections, mechanic-orthopedic conditions, and growing pains(Table 2). <h3>Conclusion</h3> Both in our country and all over the world, there are limited number of pediatric rheumatology centers and experienced pediatric rheumatologists, and it is clearly known that diagnosing a rheumatic disease requires a careful evaluation and a high index of suspicion. As our study implies, a vast majority of referrals are composed of non-rheumatic conditions, so specifying the algorithms before referring the patients to pediatric rheumatology centers will be cost-effective and time for evaluation of patients with rheumatic diseases will be satisfactory. <h3>References</h3> [1] Hashkes PJ, Profile of a pediatric rheumatology practice in Israel, Clin Exp Rheumatol. 2003Jan-Feb;21(1):123-8. [2] Rosenberg AM, Analysis of a pediatric rheumatology clinic population. J Rheumatol. 1990Jun;17(6):827-30. <h3>Disclosure of Interests</h3> None declared
Fecal Microbiota Transplantation for Ulcerative Colitis
Authors: Nicolas Benech, Nathalie Kapel, Harry Sokol
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
SP0013 GROWTH FACTORS AND CARTILAGE: FROM MECHANISMS TO DMOADS
Authors: Marc Hochberg
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Growth factors are biologically active molecules that can stimulate cellular division, growth and differentiation and, in articular cartilage, can regulate development, homeostasis and regeneration of matrix. These anabolic factors can stimulate synthesis of proteoglycans, aggrecan and type II collagen, induce mesenchymal stem cell (MSC) proliferation and drive differentiation of MSCs into chondrocytes and decrease catabolic effects of cytokines and matrix metalloproteinases (MMPs). Growth factors would not, however, be expected to have a direct analgesic effect in patients with symptomatic knee osteoarthritis. <h3>Objectives:</h3> To review the role of growth factors in articular cartilage, identify specific growth factors and review data from phase 1 and 2 studies of selected growth factors in subjects with knee osteoarthritis. <h3>Methods:</h3> A PubMed search was performed using key words "cartilage or chondrocyte" and "growth factor". The search included both original manuscripts and review articles as well as clinical trials but was limited to English language. From these searches, I selected review articles and clinical trials and excluded articles that solely examined molecular mechanisms of action of growth factors on chondrocytes. <h3>Results:</h3> Growth factors for articular cartilage include molecules in the transforming growth factor-β (TGF-ββ superfamily (including TGF-β1, bone morphogenic protein [BMP]-2 and BMP-7), insulin-like growth factor-I, fibroblast growth factor (FGF) family (including FGF-2 and FGF-18), platelet-derived growth factor (PDGF) and Wnt ligands as well as platelet rich plasma (PRP). <h3>Conclusion:</h3> Data will be presented from phase 1 and 2 studies of rhFGF-18 and SM-04690, a Wnt signaling inhibitor, that demonstrate proof-of-concept and early efficacy of these growth factors for structure modifying effects in subjects with knee osteoarthritis (OA). <h3>References:</h3> [1] Boehme KA, Rolauffs B: Onset and progression of human osteoarthritis - can growth factors, inflammatory cytokines, or differential miRNA expression concomitantly induce proliferation, ECM degradation, and inflammation in articular cartilage? Int J Mol Sci 2018;19:2282;doi:10.3390/ijms19082282. [2] Zhu Z, Li J, Ruan G, Wang G, Huang C, Ding C: Investigational drugs for the treatment of osteoarthritis, an update on recent developments. Expert Opin Invest Drugs 2018. doi.org/10.1080/13543784.2018.1539075. <h3>Disclosure of Interests:</h3> Marc Hochberg Shareholder of: BriOri Biotech, Theralogix LLC., Consultant for: Bristol Myers Squibb, Eli Lilly, EMD Serono, Novartis Pharma AG, Pfizer Inc., Samumed LLC, Symic Bio Inc., Theralogix LLC, TissueGene Inc., TLC Biopharmaceuticals, Inc., Zynerba, Galapagos, IQVIA, Hoffman LaRoche.