tbuckley/cabot-search huggingface dataset:
PS1106 A RETROSPECTIVE ANALYSIS OF IMMUNE THROMBOCYTOPENIA PATIENTS TREATMENT RESULTS AFTER SEQUENTIAL SWITCHING OF THROMBOPOIETIC RECEPTOR‐AGONISTS
Authors: V. Ptushkin, O. Vinogradova, N. Tkachenko, M. Pankrashkina, M. Chernikov, V. Perova, D. Shikhbabaeva
Journal: HemaSphere (2019)

Background: Immune thrombocytopenia (ITP) is an immune‐mediated disease characterized by increased platelet destruction and impaired platelet production with transient or persistent decrease in the platelet count and increased risk of bleeding. Romiplostim (R) and Eltrombopag (E) are the first thrombopoietic receptor‐agonists (TPO‐ra) with demonstrated efficacy against ITP. So far, very few data are available about the potential contribution of switching from romiplostim to eltrombopag or vice versa in terms of efficacy or tolerance. Aims: To evaluate the reasons for and result of TPO‐ra switching in adult ITP patients Methods: We retrospectively analyzed all patients who received sequential treatment with both TPO‐RA between 2014 and 2018 in Moscow city hematology center (Botkin hospital). Results: Thirty‐three pts with primary ITP were included; 19 received first Romiplostim and 15 received first Eltrombopag. Reasons for switching were inefficacy (n = 30) and adverse events (n = 3). All patients (33) had previously received multiple courses of corticosteroids and IV Ig infusions, four (10%) received immunosuppression (rituximab), and five (14%) performed splenectomy. The median platelet count at the administration of the second TPO‐ra was 17x10 9 /l (range 3–25x10 9 /l). Twenty‐five (76%) patients had bleeding symptoms before the second TPO‐ra administration. From 33 included patients partial response (&gt; 50x10 9 /l without platelet transfusions and bleeding) was achieved in 16 (70%). PR was seen in sixteen from 19 (84%) in E to R group and seven from 15 (47%) in R to E group. Complete response (&gt;100x10 9 /l without pl. transfusions and bleeding) were achieve in 17 from 33 (52%). Twelve pts from 19 (63%) achieve CR in E to R group and five from 15 (30%) in R to E group. Two of 17 (10%) pts achieved a CR within 1–3 months, 11 (67%) pts in 3–12 months, and four (23%) pts later than 1 year from the start of switching to second TPO‐ra therapy. Three pts (2 in E group due to repeated thrombosis, and 1 in R group due to persistent increased liver enzymes) with recommendation of switching to second TPO‐ra due to adverse events resolved rapidly and maintained remission on alternative drug. In nine pts (28%) the switching to second TPO‐ra therapy was ineffective (blood platelet level was less than 30x10 9 /l pl). All of them were resistant to first TPO‐ra. Summary/Conclusion: Our results confirmed that switching from one thrombopoietic receptor‐agonist to another could be beneficial for patients with chronic immune thrombopenia who failed to respond. Yet longer follow‐up and larger number of pts enrolled are required to fully assess the potential benefits of such therapy change.
SP0186 WHAT DO GP”S KNOW ABOUT RMD”S? #CONNECTTODAY IN MALTA
Authors: Mary Vella
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The Arthritis and Rheumatism Association Malta known as ARAM has been established these last eleven years since 2007. Through this experience as a support group working very closely with RMDs patients through various talks and seminars, and participating on Live Radio and Television to bring awareness on RMDs, ARAM became aware that there is Lack of Knowledge on the subject by the GPs and this needed to be addressed. Patients were being given the idea that once one develops arthritis there was nothing that can be done to embrace an independent and good quality of life. Obviously, with so much research and studies, this is not so! I can confirm this myself being a patient who developed Rheumatoid Arthritis sixteen years ago. It was then that ARAM was established and being the President of the Association I advocated strongly for RMD Patients throughout the island. I believed that education and Knowledge on Arthritis should be a basic step both for the Patients as well as for the GPS and the General Public. <h3>Objectives:</h3> When Eular announced the award for national campaign Don"t delay Connect today" for early signs and symptoms and early referral, ARAM applied for the award in collaboration with the College of Family Doctors to educate the GPs on arthritis. This was possible after a number of meetings and discussion. <h3>Methods:</h3> ARAM approached the Synapse which is an E-platform led by a medical doctor for Health Professionals based on sharing academic research and other articles to people that matter. With such a professional body ARAM produced four videos by Rheumatologist specialist on RMDs focusing on different aspects of these chronic conditions. General Rheumatology Introduction –Dr Michaela Frendo Juvenile Arthritis – Dr Cecilia Mercieca Scleroderma– Dr Bernard Coleiro Fibromyalgia– Prof Andrew Borg Another two educational Talks for GPs led by Prof Andrew Borg, Head of Rheumatology Department of Mater Dei Hospital were held in a specific venue and were well attended. Topics delivered focused on: Management of Inflammatory Joints Management of Metabolic Bone diseases <h3>Conclusion:</h3> To this effect, ARAM believes that GPs are now better informed and educated and more aware of possible early interventions that could mitigate the seriousness on the condition. The general outcome of these talks include: GPs became more educated and informed which will translate into Better outcomes for the patients. <h3>Results:</h3> <b>Evaluation</b> was carried out following both interventions by asking GPs for their feedback on both the Synapse e-platform and the two seminars. <h3>Conclusion:</h3> To this effect, ARAM believes that GPs are now better informed and educated and more aware of possible early interventions that could mitigate the seriousness on the condition. <h3>Disclosure of Interests:</h3> None declared
TRANSCRIPTIONAL ALTERATIONS OF HEMATOPOIETIC STEM CELLS IN MYELODYSPLASTIC SYNDROMES
Authors: T. Ezponda, J. P. Romero, M. Ainciburu, A. Alfonso, A. Vilas, P. San Martín, L. Castro, T. Jiménez, F. López, J. Hernández, A. Molero, J. Montoro, B. Tazón, B. Paiva, M. Díez-Campelo, D. Valcárcel, J. San Miguel, D. Lara, F. Prósper
Journal: HemaSphere (2019)
Red blood cell dysfunction: a new player in cardiovascular disease
Authors: John Pernow, Ali Mahdi, Jiangning Yang, Zhichao Zhou
Journal: Cardiovascular Research (2019)

Abstract The primary role of red blood cells (RBCs) is to transport oxygen to the tissues and carbon dioxide to the lungs. However, emerging evidence suggests an important role of the RBC beyond being just a passive carrier of the respiratory gases. The RBCs are of importance for redox balance and are actively involved in the regulation of vascular tone, especially during hypoxic and ischaemic conditions by the release of nitric oxide (NO) bioactivity and adenosine triphosphate. The role of the RBC has gained further interest after recent discoveries demonstrating a markedly altered function of the cell in several pathological conditions. Such alterations include increased adhesion capability, increased formation of reactive oxygen species as well as altered protein content and enzymatic activities. Beyond signalling increased oxidative stress, the altered function of RBCs is characterized by reduced export of NO bioactivity regulated by increased arginase activity. Of further importance, the altered function of RBCs has important implications for several cardiovascular disease conditions. RBCs have been shown to induce endothelial dysfunction and to increase cardiac injury during ischaemia-reperfusion in diabetes mellitus. Finally, this new knowledge has led to novel therapeutic possibilities to intervene against cardiovascular disease by targeting signalling in the RBC. These novel data open up an entirely new view on the underlying pathophysiological mechanisms behind the cardiovascular disease processes in diabetes mellitus mediated by the RBC. This review highlights the current knowledge regarding the role of RBCs in cardiovascular regulation with focus on their importance for cardiovascular dysfunction in pathological conditions and therapeutic possibilities for targeting RBCs in cardiovascular disease.
Impact of zoledronic acid (Z) on pain in prostate cancer patients with bone metastases in a randomised placebo-control trial
Authors: L. Abetz, V. Barghout, R. Arbuckle, V. Bosch, N. Shirina, F. Saad
Journal: Journal of Clinical Oncology (2006)

4638 Background: Bone metastases occur in up to 80% of advanced prostate cancer patients and can results in painful Skeletal-Related Events (SREs). Z is the only biphosphonate approved for metastatic prostate cancer that decreases the occurrence of SREs which include pathologic fractures, severe bone pain requiring radiation therapy, spinal cord compression, surgery to bone and hypercalcemia of malignancy which may lead to daily activity limitations. We performed retrospective analyses on data from a placebo-controlled study of Z to investigate which items of the Brief Pain Inventory (BPI) were most sensitive to changes in patient’s pain due to treatment. Methods: Prostate cancer patients with bone metastases received Zoledronate 4 mg (n = 201) or placebo (n = 201). The BPI was administered at baseline (visit 2), and visits 3 (weeks 3–4), 4 (weeks 6–8), and then every second visit (every 6 weeks) until study end. Changes in BPI individual item scores and the Pain Severity and Pain Interference scale scores were compared between Z and placebo groups. Post-baseline missing data was replaced by Last Observation Carried Forward (LOCF). Results: Z was statistically significantly better than placebo for changes in BPI items ‘pain at its worst’, ‘pain at its least’, ‘pain on average’, and the BPI pain severity scale (p &lt; 0.05) at visit 4 (weeks 6–8), and visit 6 (week 12). For ‘pain right now’ there were statistically significant differences at visit 4, but not visit 6. Z was also superior to placebo for ‘pain right now’ and the Pain Severity and Interference scales at visit 12 (week 30–32) (p &lt; 0.05). Finally Z was superior to placebo for ‘interference with general activities’ at visits 12 (week 30–32), 16 (weeks 42–44), and LOCF (p &lt; 0.05). Conclusion: Our findings suggest that Z significantly reduces bone pain and general activity limitations in prostate cancer patients with bone metastases. Several items in the BPI are more sensitive to Z treatment including ‘pain at its worst’, ‘pain at its least’, ‘pain on average’, and the BPI Pain Severity scale. [Table: see text]
Abstract 14136: Protective Effects of Estradiol on Multiple Organ Injury Following Hemorrhagic Shock and Resuscitation and the Involvement of Inflammatory Pathways
Authors: Mona M Soliman, Maha Arafah
Journal: Circulation (2017)

Introduction: Resuscitation can promote inflammatory responses. Clinical and experimental studies have shown that females are more tolerant to injuries than males. Estrogens exhibit protective effe...
PS1049 COMPARATIVE RANDOMIZED STUDY OF PROTOCOL HAM VERSUS PROTOCOL FLAG IN RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA
Authors: A.R. elsergany, M.I. ismaeel, M.A. ibrahim, H.F. Ghazy, D.A. aladle
Journal: HemaSphere (2019)

Background: Acute myeloid leukemia (AML) is the commonest type of acute leukemias in adults resulting from clonal proliferation of bone marrow precursor cells with disruption of hemostasis. Patients initially respond to induction therapy but the majority of patients suffer relapse and refractoriness with very poor subsequent prognosis. Aims: To compare two widely used salvage regimens in treatment of relapsed/refractory AML, HAM (cytarabine, Mitoxantrone, Colony stimulating factor) versus FLAG (cytarabine, fludarabine, Colony stimulating factor) protocols. Methods: Prospective randomized study included 90 patient diagnosed as relapsed/refractory AML were selected from Oncology Center, Mansoura University, Egypt, from January 2014 to December 2017. Patients received salvage therapy either HAM or FLAG protocol, then outcomes regarding to efficacy, side effects and overall survival were assessed. Results: Ninety patients were included in our study, 43 patients received HAM protocol versus 47 received FLAG protocol. Complete remission (CR) was 42.6% in HAM group versus 48.8% in FLAG group (p = 0.5). On the other hand, hepatic impairment was 46.8% in HAM group versus 30.3% in FLAG group (p = 0.2). Also, renal impairment was 6.4% in HAM group versus 18.6% in FLAG group (p = 0.07). In addition, Event free survival (EFS) was higher in FLAG vs. HAM arms (9 versus 4 months, p = 0.2). Lastly, overall survival (OS) in HAM group was shorter than in FLAG group (3 vs. 5 months, P = 0.09) Summary/Conclusion: Both HAM and FLAG protocols are adequate salvage chemotherapy in relapsed/refractory AML, with different toxicity profile as HAM has more hepatotoxicity while FLAG is more nephrotoxic, CR was slightly higher with FLAG with more survival benefit compared with HAM protocol.
Circulating HER2/ErbB2 Levels Are Associated With Increased Incidence of Diabetes: A Population-Based Cohort Study
Authors: Iram Faqir Muhammad, Yan Borné, Xue Bao, Olle Melander, Marju Orho-Melander, Peter M. Nilsson, Jan Nilsson, Gunnar Engström
Journal: Diabetes Care (2019)

HER2/ErbB2 is a member of the epidermal growth factor receptor family. It is widely used as a tumor marker, but it also has recently been associated with insulin resistance. Both ErbB2 and diabetes have been associated with cancer; however, the relationship between ErbB2 and diabetes has not been well explored. The aim of this population-based cohort study was to assess the association between plasma ErbB2 and incidence of diabetes.The study population included participants from the Malmö Diet and Cancer-Cardiovascular Cohort (age range 46-68 years). After excluding participants with a history of diabetes and those missing data for ErbB2 and other covariates, the final study population consisted of 4,220 individuals. Incidence of diabetes was followed through linkages to local and national registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to quartiles of ErbB2, adjusted for potential confounders.Plasma ErbB2 was significantly and positively associated with glucose, insulin, and HbA1c after being adjusted for potential confounding factors. During a mean ± SD follow-up period of 20.20 ± 5.90 years, 615 participants (14.6%) were diagnosed with new-onset diabetes. Individuals with high levels of ErbB2 had a significantly higher risk of diabetes than those with low levels of ErbB2. The multivariable-adjusted hazard ratio was 1.31 (95% CI 1.03-1.66; P < 0.05) for the highest versus the lowest quartile of ErbB2 and was 1.15 (95% CI 1.05-1.25; P < 0.05) per 1-SD increase in ErbB2.Elevated levels of ErbB2 are associated with increased incidence of diabetes.
FGFR3 protein expression and gene mutation in primary and metastatic urothelial carcinoma (UC) tumors.
Authors: Jonathan E. Rosenberg, Lillian Werner, Aristotelis Bamias, Toni K. Choueiri, Fabio A. B. Schutz, Rachel S. Park, Robert O'Brien, Elizabeth Ann Guancial, Robert W Ross, David M. Berman, Markus Riester, Rosina Lis, Massimo F. Loda, Edward C. Stack, Franziska Michor, Nabil Chehab, Joaquim Bellmunt Molins
Journal: Journal of Clinical Oncology (2012)

4577 Background: FGFR3 protein expression may represent a valid therapeutic target in metastatic UC. The prevalence of both mutation and overexpression is unknown in metastatic UC. Methods: Tissue microarrays of formalin fixed paraffin-embedded urothelial carcinomas (UC) were stained for FGFR3 by immunohistochemistry (IHC) [primary (n=250); metastatic (n=31); of which (n=14) were paired]. FGFR3 immunostaining was scored as negative or positive based on previously reported scoring systems. FGFR3 mutation in primary tumors was assessed by iPlex and confirmed by hME sequencing (n=141) or Affymetrix OncoScan FFPE Express 2.0 (primary: n=17; metastases n=31). Results: FGFR3 IHC positivity was present in 48% of metastases (95% CI=32-65%) and 26% of primary tumors, (95%=CI 21-32%), though strong staining was rare (&lt;1%). Paired primary and metastatic tumors were both negative in 50% of cases, with 14% positive only in the metastasis, 14% positive only in the primary tumor, and 21% positive in both. If the primary tumor showed staining, 71% of the metastases showed staining. FGFR3 IHC staining did not impact overall survival (p=0.8). FGFR3 mutations were observed in 9.6% of metastatic tumors (95% CI=3.3-25%), compared to 3.5% of primary tumors (95% CI=1.5%-8%). Co-occurrence of mutation and FGFR3 DNA copy number gain was observed in one specimen. Conclusions: FGFR3 IHC staining is present 26 % of primary tumors of patients who go on to develop metastatic disease, and nearly half of metastatic tumor sites. FGFR3 mutation frequency in primary and metastatic tumor specimens is low. Further investigation of the frequency of FGFR3 protein expression in metastases is needed. The presence of FGFR3 protein by IHC staining in primary and metastatic specimens suggests that FGFR3 may represent a therapeutic target even in the absence of mutation. Further functional studies are needed.
PS1053 IMPACT OF CYTOMEGALOVIRUS REACTIVATION ON RELAPSE RATE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION IN PATIENTS WITH ACUTE MYELOBLASTIC LEUKEMIA
Authors: N. Ben Abdeljelil, M. Ben Hmida, R. Ouerghi, A. Lakhal, R. El Fatmi, L. Torjemane, D. Belloumi, S. Ladeb, W. Achour, T. Ben Othman
Journal: HemaSphere (2019)

Background: Cytomegalovirus (CMV) infection is a major complication after allogeneic stem cell transplantation (ASCT). Aims: The aim of the study was to evaluate the impact of CMV reactivation on the relapse rate after ASCT in patients with acute myeloid leukemia (AML). Methods: Retrospective study conducted in patients with AML who underwent ASCT from HLA identical sibling donor between January 2011 and December 2018. Conditioning regimen consisted of Busulfex and Cyclophosphamide (Bu/Cy) or Fludarabine and Busulfex (F/Bu). Graft‐versus‐host disease (GVHD) prophylaxis consisted of cyclosporine and a short course of methotrexate. Antiviral prophylaxis for CMV infection was assured by Acyclovir from day +1 to day +180. CMV detection was carried out once‐a‐week from engraftment to day +100 by either pp 65 antigenemia test or real‐time quantitative PCR. Results: Ninety‐three patients were enrolled (55 men and 38 women). Median age was 33 years (range, 5 ‐ 49 y). At the time of transplant, 73 patients (78.5%) were in CR1, 16 patients (17.2%) were in CR2 and 4 patients (4.3%) were in response failure. CMV serostatus for donor (D) and recipient (R) was available for 44 cases (47.3%). Serostatus of R+/D+ and R+/D− was observed in 38 patients (86.4%). Stem cell source were BM in 49 cases (52.7%) and PBSC in 44 cases (47.3%). No graft failure was observed. Acute GVHD grade II‐IV occurred in 19 patients (20.4%). Chronic GVHD was observed in 40 patients (45.4%). Twenty‐nine patients (31.2%) developed CMV reactivation. With a median follow‐up of 2 years (range 49 days – 7 years), the overall survival (OS) and the non‐relapse mortality (NRM) were not statistically significant between patients with CMV reactivation and those without CMV reactivation (74% vs 63%, p = 0.3 and 20.7% vs 7.8%, p = 0.08, respectively). Twenty‐four patients (25.8%) relapsed at a median of 6 months (range 2 ‐ 67 months). the rate of relapse among patients with CMV reactivation was significantly lower than in those without CMV reactivation (10.3% vs 32.8%, p = 0.02). In univariate analysis, the CMV reactivation was the only factor associated with a decreased risk of relapse (OR = 0.23, 95% CI: 0.06–0.87, p = 0.02). Summary/Conclusion: CMV reactivation was associated with decreased relapse risk after ASCT for patients with AML without a benefit in OS.
Abstract MP085: Cognitive Impairment Mediates the Impact of Short Sleep Duration on Mortality in Individuals with Cardiovascular or Cerebrovascular Disease
Authors: Julio Fernandez-Mendoza, Fan He, Alexandros N Vgontzas, Duanping Liao, Edward O Bixler
Journal: Circulation (2017)

Background: Cardiovascular disease (CVD) and cerebrovascular disease (CBV) have been associated with short sleep duration and mortality. Furthermore, short sleep duration has been associated with impaired cognition. Most studies have been limited by using self-report measures and treating sleep duration as a sole, independent predictor, thus, its role in predicting mortality is still not well-established. Hypothesis: We hypothesized that 1) short sleep duration increases the impact of CVD and CBV on mortality and 2) cognitive impairment mediates the association of short sleep duration with mortality in those with CVD or CBV. Methods: We addressed this question in the Penn State Adult Cohort, a random, general population sample of 1,741 men and women (48.7 ± 13.5 years) who were studied in the sleep laboratory and followed-up for 16.7 ± 4.6 years. CVD was defined by a history of heart disease, including hypertension or diabetes, and CBV by a history of stroke. Polysomnographic (PSG) total sleep time was classified as normal (≥ 6 hours) and short (&lt; 6 hours) sleep duration based on the median of the cohort. All individuals underwent a comprehensive neuropsychological evaluation, including Symbol Digit Modalities Test, Trail Making Test, Benton Visual Retention Test, Thurstone Word Fluency Test, and Mini-Mental State Examination. We tested the interaction between CVD, CBV and PSG sleep duration on mortality using Cox proportional hazard models controlling for multiple potential confounders. Results: The hazard ratios (95%CI) of mortality associated with CVD and CBV were 0.9 (0.6-1.3) and 1.3 (0.5-3.1) for individuals with normal sleep duration and 1.8 (1.3-2.5) and 2.4 (1.3-4.4) for individuals with short sleep duration (P-interaction &lt; .05). In individuals with CVD or CBV, short sleep duration was associated with impaired processing speed, executive attention, and short-term memory (all Ps &lt; .05). Cognitive impairment significantly mediated the impact of short sleep duration on mortality in those with CVD or CBV [proportion of mediation effects were 6.5% (1.4%-18.6%), 4.5% (0.4%-14.2%), and 6.2% (1.0%-18.4%) for processing speed, executive attention and short-term memory, respectively]. Conclusions: The risk of mortality associated with CVD and CBV is significantly increased in those with short sleep duration. Although cognitive impairment significantly mediated this association, its modest effect suggests that future studies should examine other underlying mechanisms linking short sleep duration with mortality in individuals with CVD or CBV.
Bypassing the bottleneck: intentional hepatitis C transmission with organ transplant
Authors: Christine M. Durand, Michael A. Chattergoon
Journal: Journal of Clinical Investigation (2019)

Solid organ transplantation from hepatitis C virus-positive (HCV-positive) deceased donors into HCV-negative recipients is a recent approach aimed to expand the donor organ pool in the setting of severe shortage. Good short-term outcomes have been reported with this approach in combination with direct-acting antivirals. In this issue of the JCI, Zahid and colleagues have characterized early viral kinetics and the genetic landscape of donor-to-recipient HCV transmission using single-genome sequencing. In seven HCV-negative recipients of four HCV-positive donor organs, productive infection with a highly diverse viral population was seen by day three after transplantation. The degree of genetic diversity seen in recipients of HCV-positive organs was unlike the narrow genetic bottleneck typically observed with acute HCV acquisition from intravenous drug use or sexual activity. All recipients achieved HCV cure with treatment. The consequences of acute infection with a genetically diverse HCV population are unknown; however, early clinical experience with this transplantation strategy is promising.