tbuckley/cabot-search huggingface dataset:
Association of Midlife Cardiovascular Risk Profiles With Cerebral Perfusion at Older Ages
Authors: Sana Suri, Anya Topiwala, Michael A. Chappell, Thomas W. Okell, Eniko Zsoldos, Archana Singh-Manoux, Mika Kivimäki, Clare E. Mackay, Klaus P. Ebmeier
Journal: JAMA Network Open (2019)

Poor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults.To examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages.In this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included if they had no clinical diagnosis of dementia, had no gross brain structural abnormalities on magnetic resonance imaging scans, and had received pseudocontinuous arterial spin labeling magnetic resonance imaging. Cardiovascular risk was measured at 5-year intervals across 5 phases from September 1991 to October 2013. Arterial spin labeling scans were acquired between April 2014 and December 2014. Data analysis was performed from June 2016 to September 2018.Framingham Risk Score (FRS) for cardiovascular disease, comprising age, sex, high-density lipoprotein cholesterol level, total cholesterol level, systolic blood pressure, use of antihypertensive medications, cigarette smoking, and diabetes, was assessed at 5 visits.Cerebral blood flow (CBF; in milliliters per 100 g of tissue per minute) was quantified with pseudocontinuous arterial spin labeling magnetic resonance imaging.Of 116 adult participants, 99 (85.3%) were men. At the first examination, mean (SD) age was 47.1 (5.0) years; at the last examination, mean (SD) age was 67.4 (4.9) years. Mean (SD) age at MRI scan was 69.3 (5.0) years. Log-FRS increased with time (B = 0.058; 95% CI, 0.044 to 0.072; P < .001). Higher cumulative FRS over the 20-year period (measured as the integral of the rate of change of log-FRS) was associated with lower gray matter CBF (B = -0.513; 95% CI -0.802 to -0.224; P < .001) after adjustment for age, sex, education, socioeconomic status, cognitive status, arterial transit time, use of statins, and weekly alcohol consumption. Voxelwise analyses revealed that this association was significant in 39.6% of gray matter regions, including the posterior cingulate, precuneus, lateral parietal cortex, occipital cortex, hippocampi, and parahippocampal gyrus. The strength of the association of higher log-FRS with lower CBF decreased progressively from the first examination (R2 = 0.253; B = -10.816; 99% CI -18.375 to -3.257; P < .001) to the last (R2 = 0.188; B = -7.139; 99% CI -14.861 to 0.582; P = .02), such that the most recent FRS measurement at mean (SD) age 67.4 (4.9) years was not significantly associated with CBF with a Bonferroni-corrected P < .01 .Cardiovascular risk in midlife was significantly associated with lower gray matter perfusion at older ages, but this association was not significant for cardiovascular risk in later life. This finding could inform the timing of cardiovascular interventions so as to be optimally effective.
PF548 PROGNOSTIC MUTATIONS IN PATIENTS WITH MYELODYSPLASTIC SYNDROME TREATED WITH HEMATOPOIETIC STEM‐CELL TRANSPLANTATION
Authors: Z. Liu, S. Cao, F. Lou, Y. Sun, E. Jiang, M. Han
Journal: HemaSphere (2019)

Background: Genetic mutations in MDS patients are closely related with clinical phenotypes and prognosis in MDS patients. But whether mutations are prognostic for outcomes after allogeneic hematopoietic stem‐cell transplantation(allo‐HSCT) remains to be elaborated. Aims: This research was done to figure out whether genetic mutations help the risk‐stratification in MDS patients received transplantation. Methods: Targeted mutational analysis were performed on samples obtained before transplantation from 151 patients underwent HSCT. Overall‐survival(OS) was calculated from the date of transplantation to date of death, and surviving patients were censored at the date on which they were last known to be alive. Diease‐free survival(DFS) was calculated from the time of transplantation to date of relapse or death and was censored at the last date known to alive without relapse. We analyzed the relationship of mutations and clinical outcomes. Curves for OS and DFS were generated using the Kaplan‐Meier method and compared using log‐rank test.Cumulative incidence of nonrelapse death and relapse was assessed using competing risks from time of HSCT to nonrelapse death or relapse by the Gray test. Results: All 151 patients carried more than one mutations, most frequently in DNAH2(47.02%), KDM6B(42.38%), USH2A(41.06%), KMT2D(38.41%), PCLO(33.11%), CCDC168(32.45%), U2AF1(29.14%), TET2(27.81%), ASXL1(25.83%), ARID1B(23.18%). In univariable analyses, TP53 or PPM1D mutations, ANKRD26 mutations, FLT3 abnormalities(including FLT3‐ITD), PDGFRB mutations were associated with shorter OS(TP53 or PPM1D, P = 0.064; ANKRD26, P = 0.025, FLT3 abnormalities: P = 0.046; PDGFRB, P = 0.044) and DFS(TP53 or PPM1D, P = 0.019; ANKRD26, P = 0.058, FLT3 abnormalities: P = 0.047; PDGFRB, P = 0.048). In multivariable analysis including clinical variables, monosomal karyotype status, HCT‐CI, and candidate genes, PDGFRB mutations and FLT3 abnormalities were each independently associated with shorter OS(PDGFRB mutations, HR = 2.979, P = 0.021; FLT3 abnormalities, HR = 2.677, P = 0.018) and DFS(PDGFRB mutations, HR = 2.779, P = 0.019; FLT3 abnormalities, HR = 2.288, P = 0.03). PDGFRB mutations(P = 0.042), ANKRD26 mutations (P = 0.004) were associated with higher non‐relapse mortality rate. FLT3 abnormalities was associated with higher relapse rate in RAEB patients(P = 0.004). Summary/Conclusion: PDGFR mutations and FLT3 abnormalities are independently associated with shorter survival in MDS patients treated with allo‐HSCT.
Abstract 19235: Long Term Follow-up in Patients With Prior Electrical Storm Undergoing Ventricular Tachycardia Ablation
Authors: Breck C Sandvall, Ricardo Lugo, Jay Montgomery, Asad A Aboud, Pablo Saavedra, Juan C Estrada, Sharon Shen, Walter Clair, Robert Abraham, George Crossley, Christopher R Ellis, M. B Shoemaker, Arvindh N Kanagasundram
Journal: Circulation (2017)

Background: Electrical storm (ES) characterized by frequent arrhythmic episodes resulting in ICD shocks is associated with poor prognosis and can be treated with catheter ablation (CA). Patients wh...
Midgut NET With Orbital, Myocardial, Testicular, Lymph Nodal and Pulmonary Metastases Presenting With Bilateral Proptosis—Role of 68Ga-DOTANOC PET/CT
Authors: Raja Senthil, Thara Pratap, R Arun Visakh, Mathew Philip
Journal: Clinical Nuclear Medicine (2019)

Abstract Neuroendocrine tumors (NET) are rare neoplasms and commonly metastasize to liver, lymph nodes and less frequently to bones and lungs. Metastases to other organs are extremely rare and we report a case of NET clinically presenting with bilateral proptosis secondary to metastases in orbits. 68 Ga-DOTANOC PET/CT demonstrated somatostatin receptor overexpressing lesions in bilateral orbits, small intestine, lymph nodes, lungs, heart and testes in the absence of liver metastases.
AB0376 RESULTS OF A MANDATORY SWITCHING FROM ORIGINATOR TO BIOSIMILAR ETANERCEPT IN 117 PATIENTS WITH INFLAMMATORY ARTHRITIS FROM A SINGLE CENTER
Authors: Sabela Fernández, Senen Gonzalez, Carmen Ordas-Calvo, Edilia García-Fernández, Belén Rodríguez-De-Castro, Jesús Babío
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Currently available evidence indicates that a single switch from a bio-originator to one of its biosimilars is safe and effective and has cost benefits to the National Health Systems. However, there is some reluctance to switch patients due to lack of real-world data and differences between patients treated in the setting of real clinical practice and those of clinical trials <h3>Objectives</h3> We aimed to investigate the efficacy and safety of Etanercept-biosimilar (SB4), in a non-medical switch in patients with inflammatory arthritis (IA) <h3>Methods</h3> At Cabueñes Hospital a non-medical switch from Etanercept (ETN) to SB4 was carried out in March 2018. Inflammatory arthritis patients (rheumatoid arthritis (AR), psoriatic arthritis (APS), axial spondyloarthritis (AS), juvenile idiopathic arthritis (JIA)) were included in this single-center retrospective observational study from March 2018 to December 2018. Reasons for SB4 withdrawal were categorized as lack of effect (LOE), adverse events (AE) or others. <h3>Results</h3> A total of 117 patients were identified, 100% were switched to SB4 maintaining the same dose. Disease duration was 5 (2–8,5) years. 49 patients (41%) had basal optimized dose of ETN (dose down-titration or dose interval expansion). In most patients ETN was the first biologic. 31 patients (26%) stopped SB4 treatment during follow-up, mainly due to LOE (67%) or AE (25%), with median duration of SB4 3,5 months (1,9-5,9). Most AE that led to withdrawal were dermatological (injection-site reactions, skin rash). 11 patients switched back to ETN, 15 to others. Two patients died, both were APS (one sudden death and one aneurysmal subarachnoid hemorrhage). After switching to SB4, one stable patient with AS had recurrent acute anterior uveitis, and psoriasis worsening were noted in 2 patients with APS. 2 patients needed reinstatement of the full dose of biologic because of LOE. The clinical situation on ETN was stable in 23 of the 31 (74%) patients who stopped SB4 (no flares or changes in treatment in the last 6 months before switch). <b>Table 1 summarizes baseline characteristics and treatment outcomes</b>. <h3>Conclusion</h3> Biosimilar switch of SB4 was successful in over 74% of cases and was well tolerated. Most patients who stopped SB4 due to LOE had a clinical stable situation in this observational study. Some concerns regarding the safety profile and interchangeability have raised and further evidence on the efficacy of transitioning from reference ETN is needed. <h3>References</h3> [1] Kay J, Schoels MM, Dörner T, et al. Ann Rheum Dis2018;77:165-174 [2] Emery P, Vencovsky J, Sylwestrzak A, et al. Ann Rheum Dis2017;76:51–57 [3] Glintborg B, et al. Ann Rheum Dis2019Feb;78(2):192-200 <h3>Disclosure of Interests</h3> None declared
PS963 ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ADULT PHILADELPHIA‐POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA: DOES MINIMAL RESIDUAL DISEASE BEFORE TRANSPLANTATION MATTER FOR LONG TERM OUTCOME?
Authors: I. Ormazabal Velez, A. Figuera Alvarez, J.L. Steegmann Olmedillas, R. De la Cámara Llanza, A. García‐Noblejas Moya
Journal: HemaSphere (2019)

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is still the goal standard of care in Philadelphia‐positive acute lymphoblastic leukemia (Ph+ ALL) in adults with curative intention, though the introduction on tyrosin kinase inhibitors (TKI). Because some controversy on the importance of minimal residual disease (MRD) exists, we decided to evaluate our experience. Aims: The primary endpoint was evalute the impact of positive MRD on survival, as well as the incidence of disease‐free survival (DFS) and overall survival (OS). Secondary endpoints refined acute graft vs. host disease (aGvHD) and chronic GvHD (cGvHD) incidence, relapse incidence (RI), and non‐relapse mortality (NRM). Methods: Between 1993 and 2018, 45 HSCT were performed in 43 patients with Ph+ ALL in our hospital (2 double alloHSCT; 2,4%). Median age was 42 years (17–66), 55,8% of the patients were male and 44,2% were &lt;40 years. Disease status before transplant was divided in 74,4% CR1 (n = 32), 18,6% CR2 (n = 8) and 7% active disease (n = 3). MRD was available in 37 cases: 32,4% (n = 12) were positive and 54,1% (n = 20) negative by PCR, and 5,4% (n = 2) has positive and 8,1% (n = 3) negative cytogenetic, respectively. CNS was infiltrated in 8 cases (18,6%) and extramedular disease was detected in 13 cases (30,2%). TKI was employed in 24 cases (55,8%). Results: With a median follow up of 6 years (2 months‐23 years), the whole cohort DFS an OS rates were 51,2% and 55,8%, respectively. MRD positive before HSCT was related with worse outcome ( p &lt; 0,05%). The incidence of grade II‐IV aGvHD was 28,2% (n = 11) and cGvHD 30,8% (n = 12). Four patients (10,3%%) developed extensive cGvHD. Relapse incidence was 25,6% (n = 11) with a median time of 16 months (3–62). The incidence of NRM was 34,9% (n = 15). The causes in order of frequency were pneumonia or respiratory failure (n = 6; 31,6%) an septic shock (n = 3; 15,8%). Summary/Conclusion: In our cohort was highlghted the importance of achieving negative MRD before HSCT. An important goal in the near future should be the achievement of MRD negative before HSCT with the employment of current potent TKIs.
Abstract 17669: Severe Mitral Annular Calcification is Not an Independent Prohibitive Factor for Mitral Valve Replacement
Authors: Rayji S Tsutsui, Kinjal Banerjee, James D Thomas, Samir Kapadia, Zoran Popovic
Journal: Circulation (2017)

Background: Presence of severe mitral annular calcification (MAC) is considered a prohibitive risk factor for mitral valve repair and replacement (MVR). We sought to investigate if the presence of ...
Factors Predicting Poor Outcomes for Myeloma Patients at Different Ages: Results from 3894 Patients in the Myeloma XI Trial
Authors: Charlotte Pawlyn, Martin F Kaiser, David Cairns, Alina Striha, John R Jones, Vallari Shah, Matthew W Jenner, Mark T Drayson, Roger G Owen, Walter M Gregory, Gordon Cook, Graham Jackson, Gareth J. Morgan, Faith E Davies
Journal: Blood (2017)
Temporal inhibition of mouse mammary gland cancer metastasis by CORM-A1 and DETA/NO combination therapy
Authors: Kseniia Porshneva, Diana Papiernik, Mateusz Psurski, Agnieszka Łupicka-Słowik, Rafał Matkowski, Marcin Ekiert, Marcin Nowak, Joanna Jarosz, Joanna Banach, Magdalena Milczarek, Tomasz M Goszczyński, Marcin Sieńczyk, Joanna Wietrzyk
Journal: Theranostics (2019)

Carbon monoxide and nitric oxide are two of the most important vasoprotective mediators. Their downregulation observed during vascular dysfunction, which is associated with cancer progression, leads to uncontrolled platelet activation. Therefore, the aim of our studies was to improve vasoprotection and to decrease platelet activation during progression of mouse mammary gland cancer by concurrent use of CO and NO donors (CORM-A1 and DETA/NO, respectively).
Response to: ‘Mycophenolate mofetil: a step forward in the induction treatment of ANCA-associated vasculitis? Comment on the article by Jones et al’ by Vandergheynst et al
Authors: Rachel B Jones, Thomas F Hiemstra, Michael Walsh, David Jayne, Lorraine Harper
Journal: Annals of the Rheumatic Diseases (2019)

Response to: 'Mycophenolate mofetil: a step forward in the induction treatment of ANCAassociated vasculitis?Comment on the article by Jones et al ' by Vandergheynst et al We thank the authors for their interest in our publication.As stated in the commentary, 1 the MYCophenolate mofetil versus CYClophosphamide (MYCYC) trial was originally published in abstract form in 2013; the data published at that time was preliminary.The primary outcome events for the MYCYC trial, defined as remission with glucocorticoid compliance within 6 months, were adjudicated by blinded adjudicators.The differences in results as published 2 are due to the addition of glucocorticoid dose data made available after the publication of the 2013 abstract.The additional data resulted in a small change in the numbers of primary outcome events and, ultimately, the statistical inference of non-inferiority.These differences highlight the potential for even small, chance occurrences to alter the outcomes of trials and the need for large trials.We thank the authors for the comparison with the Rituximab for Antineutrophil cytoplasmic antibodies (ANCA)-associated Vasculitis trial, 3 which helps contextualise the study with other trials.Mycophenolate has never been compared directly to rituximab treatment for induction therapy in ANCA-associated vasculitis and it is difficult to make fair comparisons of therapies between different trials.We agree with the authors that mycophenolate must be used with caution in those at higher risk of relapse, as stated in the discussion.We also recognise that the use of concomitant therapies including intravenous glucocorticoids and plasma exchange may have facilitated early disease control in both groups.The higher relapses in the mycophenolate group suggest that cyclophosphamide may be preferable for patients at high risk of relapse.The current study does not suggest that mycophenolate should be the preferred choice for all but it does provide additional information on the potential risks and benefits of mycophenolate with glucocorticoids as induction therapy for those with nonlife-threatening disease.
p110 sEGFR, a 110-kD isoform of epidermal growth factor receptor, interacts with ErbB-2 in the presence of EGF
Authors: René Nieves-Alicea, José F. Rodríguez-Quiñones, Nita J. Maihle, Elsa M. Cora
Journal: Cancer Research (2005)

4505  The 110 kD isoform of epidermal growth factor receptor (p110 sEGFR) is an alternative-spliced variant of the 170 kD full-length epidermal growth factor receptor (EGFR/ErbB-1). This isoform has the same primary structure of the full-length receptor up to residue 603, thus having the same extracellular domain. The extracellular domain common to both proteins includes the ligand binding domain as well as residues involved in receptor dimerization with other members of the ErbB family: ErbB-2, ErbB-3 and ErbB-4. However, p110 sEGFR lacks the signal transduction capabilities of EGFR because the transmembrane, tyrosine kinase and regulatory domains are substituted by 78 unique amino acids in its c-terminal. Given that EGFR and p110 sEGFR have the same extracellular primary structure, we hypothesize that p110 sEGFR will interact with the same ligands and receptors as EGFR. To examine if p110 sEGFR interacts with ErbB-2, a co-immunoprecipitation assay was performed in the presence of the ligand of EGFR, epidermal growth factor (EGF). Equal amount of proteins in cell lysates from chinese hamster ovary (CHO) cells expressing p110 sEGFR or p170 EGFR, and SK-BR-3 cells were combined in the presence of EGF. After equilibration, the reactions were immunoprecipitated with either a monoclonal antibody against the extracellular domain of EGFR or with a polyclonal antibody against the intracellular domain of ErbB-2. The immunoprecipitated proteins were separated by SDS-PAGE and analyzed by immunoblot analysis. A band corresponding to ErbB-2 was observed by immunoblot analysis when p110 sEGFR was immunoprecipitated. Similarly, a band corresponding to p110 sEGFR was observed by immunoblot analysis when ErbB-2 was immunopreciptated. Together, these results suggest that p110 sEGFR interacts with ErbB-2. Future studies are directed to determine if this interaction is transduced to a cellular response. Supported by: NIH/NCI (CA73859 and CA8513), UPR-MSC MBRS RISE Program, NIH (COBRE P200RR016439).
PS1478 EVALUATION OF COMBINED MEASUREMENT OF IMMATURE PLATELET FRACTION AND SCHISTOCYTES IN PREGNANCY‐ASSOCIATED THROMBOTIC THROMBOCYTOPENIC PURPURA AND SEVERE PREECLAMPSIA/ HELLP SYNDROME
Authors: M. Fayek, M. Mekawy, R. El‐Gamal, A. Abdelkader, H. Abdelbary
Journal: HemaSphere (2019)

Background: The occurrence of thrombotic microangiopathy (TMA) in pregnancy is an unfortunate emergency condition. Proper diagnosis is mandatory which requires the consideration of two overlapping diagnoses: severe preeclampsia/ haemolysis, elevated liver enzymes, and low platelet syndrome (SPE/HELLP) and thrombotic thrombocytopenic purpura (TTP). The long turn‐around times of ADAMTS13 testing precludes the timely distinction between the two conditions. Aims: We aimed at evaluating schistocyte counts and immature platelet fraction (IPF%), as both increase in TMAs, to discriminate between TTP and SPE/HELLP of pregnancy. Methods: IPF% was measured using SysmexXE‐2100 automated hematology analyzer, and schistocyte counts were estimated microscopically as per the International Council for Standardization in Hematology (ICSH)‐Schistocyte Working Group guidelines. The study included 30 pregnant patients with SPE/HELLP, 13 pregnant patients with TTP, and 30 women with normal pregnancy. The discrimination between the two patient categories was based on clinical judgment and TTP cases were identified using the PLASMIC score. Results: TTP patients had higher values of IPF% than SPE/HELLP 19.5 (16.9–27.1) vs 13 (9.5 – 23.25); p &lt;0.001); similar results were revealed regarding schistocyte counts 6.5 (3.9–8.6) vs 2.1 (1.6 – 3.5); p &lt;0.001). IPF% and schistocyte counts were able to discriminate between TMA patients and normal pregnant women, and between and SPE/HELLP and TTP patients. Moreover, the discriminatory function of each was improved when the two parameters were used in combination. Summary/Conclusion: IPF% analysis should be used in conjunction with manual schistocyte counting in TMA cases to distinguish TTP pregnant patients from patients having SPE/HELLP.
THU0724-HPR RELIABILITY AND VALIDITY OF AN ACTIVITY LIMITATION MEASURE IN PERSONS WITH INCLUSION BODY MYOSITIS (IBM)
Authors: Malin Regardt
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Persons with Inclusion Body Myositis (IBM) are affected in their activities of daily living (1,2). <h3>Objectives:</h3> The aim of this study was to test validity and reliability of the questionnaire Disability in the Arm Shoulder and Hand (DASH) for patients with IBM. A second aim was to describe activity limitation measured by the Canadian occupational Performance measure (COPM). <h3>Methods:</h3> Persons diagnosed with IBM were identified through the Swedish Myositis Network (SweMyoNet) quality registry in Stockholm Sweden. A total of 36 persons with IBM were included in the registry and were invited to participate. A total of 17 men and 9 women agreed to participate. Median (Q1-Q3) age was 74 (70-79) years and the median (Q1-Q3) disease duration was 7 (3-8) years. Activity limitation were assessed by the questionnaire Disability of the Arm, Shoulder and Hand (DASH) and the The Canadian occupational performance measure (COPM) which investigate patient derived areas of daily activities. The data collection was performed at the Karolinska university hospital in Stockholm Sweden. At baseline both DASH and COPM were performed. The participants received a second DASH questionnaire to be answered within two weeks (Follow-up) and send back to the researcher. <h3>Results:</h3> There were good correlations between baseline measure and follow-up on DASH (rs 0.997; p=0.01) Indicating that the DASH is consistent over a short period of time. The results from COPM showed a variety of activities persons with IBM experienced problem with. Area with most activity limitations were basic self-care area such as dressing and grooming, fall, feeding, managing communication. Instrumental activities such as managing instruments, shopping and meal preparation. Leisure activities such as playing an instrument, run, paint and social activities such as visit friends, social engagements. Some of these activities were found in the DASH but not all. E.g. missing socializing with friends and family, problems swallowing or were environment dependent. <h3>Conclusion:</h3> The results indicate that DASH have a good test re-test reliability DASH includes some of the activities that persons with IBM experience difficulties with but not all. The participants experienced difficulties in all areas of life. <h3>References:</h3> [1] Eriksson M, Lindberg C. Hand function in 45 patients with sporadic inclusion body myositis. Occup Ther Int. 2012;19(2):108-16. [2] Cox FM, Titulaer MJ, Sont JK, Wintzen AR, Verschuuren JJ, Badrising UA. A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities. Brain. 2011;134(Pt 11):3167-75. <h3>Disclosure of Interests:</h3> None declared