tbuckley/cabot-search huggingface dataset:
PB2199 MESENCHYMAL STEM CELLS IN PH‐NEGATIVE MYELOPROLIFERATIVE NEOPLASMS: IDLE OBSERVERS OR PART OF THE DISEASE?
Authors: M. Santoro, A. B. Di Stefano, F. Di Piazza, J. Lo Re, V. Accurso, S. Mancuso, A. Russo, A. Cordova, S. Siragusa
Journal: HemaSphere (2019)

Background: Pathogenesis in Philadelphia‐negative Myeloproliferative Neoplasms (MPNs) is surely linked to genomic alterations in Hematopoietic Stem Cells (HSCs), most of all on genes which can carry mutations referred to as driver mutations : JAK2, CALR and MPL. Inflammation, neoangiogenesis and fibrosis are part of the clinical and biological picture of MPNs. Recent studies have hypotized a possible HSC‐independent, active role of the Mesenchymal Stem Cells (MSCs) in the pathogenesis of these diseases. Aims: Our aim is to characterize the molecular profile of bone marrow MSCs (BM‐MSCs) of patients with diagnosis of MPNs to explore their possible contribution in the pathogenesis of the disease. In particular, we focused on the study of specific miRNA and mRNA already known in literature to be involved in processes of inflammation, neoangiogenesis and fibrosis in MPNs. Methods Primary cultures of BM‐MSCs were obtained from bone marrow samples of patients with diagnosis of MPNs. Genic expression profile was evaluated with Real‐Time Polymerase Chain Reaction compared to mesenchymal human healthy cell line. Results: We found that some markers known to be involved in angiogenesis, as miR221, miR20a, HIF‐1a and VEGF, are upregulated in BM‐MSCs of MPNs patients. Regarding bone marrow fibrosis, expression analysis of THSB1, TGF‐beta mRNAs and miR21 in BM‐MSCs highlighted sensible upregulation in all samples, strongly suggesting a possible role of the MSCs in the mediation or induction of the fibrosis process in the bone marrow, in these diseases. Summary/Conclusion: Our data suggest a possible role of the BM‐MSCs in fibrosis and neoangiogenesis in MPNs. In subgroup analysis, no significant differences were found between specific diseases (polychythemia vera, essential thrombocytemia, myelfibrosis and MPN‐unclassifiable). Being driver mutations not enough to explain different clinical and histological presentations, it maybe that the study of the pathological MSCs will help comprehend the complex machine of pathogenesis in MPNs and possibly find new targets to develop drugs that may change the natural history of these diseases.
In AF, ABC scores predicted stroke or major bleeding better than CHA<sub>2</sub>DS<sub>2</sub>-VASc and HAS-BLED scores, respectively
Authors: Clive Kearon
Journal: Annals of Internal Medicine (2019)

Source Citation Berg DD, Ruff CT, Jarolim P, et al. Performance of the ABC scores for assessing the risk of stroke or systemic embolism and bleeding in patients with atrial fibrillation in ENGAGE AF-TIMI 48. Circulation. 2019;139:760-71. 30586727
Abstract P018: Circulating Levels of Endostatin are Related to Future Cardiovascular Mortality in Elderly subjects
Authors: Lars Lind, Toralph Rughe, Johan Sundström, Erik Ingelsson, Anders Larsson, Johan Ärnlöv
Journal: Circulation (2012)

Background: Endostatin, a biological active fragment of the extracellular matrix protein collagen XVIII, is known to be involved in angiogenesis. We evaluated if circulating lvels of this compound was related to future mortality in two different cohorts of elderly subjects. Methods: In the PIVUS cohort of 931 subjects all aged 70 years at baseline, 90 individuals died during a median follow-up of 7.9 years. In the ULSAM cohort of 748 men aged 77 years at baseline, 261 individuals died during a median follow-up of 8.1 years. Results: Circulating levels of endostatin were related to future all-cause mortality in both samples following adjustment for age, gender, education, exercise habits, smoking BMI, blood pressure, lipids, diabetes and prior cardiovascular disease (HR 1.54 for a 1 SD change, 95%CI 1.26-1.90, p&lt;0.0001 in PIVUS and HR 1.35, 95%CI 1.18-1.54 in ULSAM, both p&lt;0.0001). In ULSAM, in which the cause of death was known, the HR was higher for cardiovascular mortality (HR 1.47, 95%CI 1.22- 1.780, p&lt;0.0001). Conclusion: Endostatin was related to future mortality in two elderly Swedish sohorts independently of life-style factors and cardiovascular risk factors. The fact that the HR for cardiovascular mortality was higher than for all-cause mortality indicates a role of endostatin in the pathogenesis of cardiovascular diseases.
PB2082 PHENOTYPIC ALTERATIONS IN CHRONIC MYELOMONOCYTIC LEUKEMIA: SIMILARITIES AND DIFFERENCES MYELODYSPLASTIC SYNDROMES
Authors: J. R. Marques, F. G. Pereira‐Cunha, G. B. O. Duarte, I. Lorand‐Metze
Journal: HemaSphere (2019)

Background: Recently, 3 types of monocytes have been characterized by immunophenotyping in chronic myelomonocytic leukemia (CMML). Increase in monocytes in bone marrow (BM) may also be found in myelodysplastic syndromes (MDS). In a previous study using multiparameter flow cytometry to study BM myeloid precursors in MDS we found monocyte increase in 21% of the patients, with similar frequencies in RAEB and low risk MDS, but this was associated with a worse overall survival. Aims: to study the phenotypic characteristics of BM myelomonocytic precursors and CD34 + progenitors in CMML and compare them with findings observed in MDS. Methods we studied cases of CMML and low risk MDS entering our Laboratory in 2018. Bone marrow (BM) was collected at the diagnostic work‐up. Diagnosis and classification of the cases was made by WHO 2016 criteria based on peripheral blood counts, BM morphology and cytogenetics. Cases of transitory peripheral cytopenias presenting normal results were used as controls. Immunophenotyping of BM cells was made with and 8‐color platform according to Euroflow. A minimum 300000 cells were acquired. Results: We examined 24 cases of MDS (age 27‐88 years), and 19 CMMLs (age 55‐90 years) which were compared with 12 controls (age 25‐79 years). Concerning immunophenotypic features, SSC of granulocytic precursors/SSC of lymphocytes &lt;6 was seen in 10 MDS and in 9 LMMC cases. Abnormal antigen expression in granulocytic precursors was observed in 11/23 MDS (0 alterations = 12, 1 = 5 and 2 = 6) and 11/17 CMML (0 alterations = 7, 1 = 7 and 2 = 5). Total monocytes were increased in all CMMLs but also in 15 cases of MDS, with similar proportions of classical monocytes (median 94.7% and 93.1% respectively), but increase in monocytes in CMML was mostly dependent on increase in classical monocytes, while in MDS both classical and non‐classical forms increased. Myeloid CD34 + progenitors were &gt;2% in 4 cases of CMML but in none of the MDS cases. Total lymphocytes increased in MDS, but decreased in CMML. In these later, the decrease was more prominent in mature B‐cells, but occurred also in T CD4 + cells. Summary/Conclusion: Immunophenotyping of BM in CMML discloses several abnormalities of monocytic but also of granulocytic precursors, similar to MDS. Besides, decrease in lymphoid cells is similar to what has been described in juvenile myelomonocytic leukemia but different from those seen in low risk MDS.
Giant Secondary Overgrowth of Type-1 Pulmonary Cystic Airway Malformation Upon Development of Anaplastic Lymphoma Kinase–Rearranged Adenocarcinoma
Authors: Giuseppe Pelosi, Andrea Vandoni, Alberto Meroni, Elisabetta Uslenghi, Fabio Callipo, Nikolaos Papanikolaou, Maria Cannone, Emanuela Balladore, Maria Emilia D’Amico, Sergio Harari, Maurizio Zompatori, Matteo Incarbone
Journal: Journal of Thoracic Oncology (2019)
Response to Comment on Scholtens et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism. Diabetes Care 2019;42:381–392
Authors: Denise M. Scholtens, Boyd E. Metzger
Journal: Diabetes Care (2019)

As described in our article (1), the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and HAPO Follow-up Study (HAPO FUS) allowed examination of associations between maternal glucose levels during a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks’ gestation, across the continuum, with child glucose metabolism at ages 10–14 years. The comment by Hulman (2) on our article (1) raises questions about exploratory trajectory analyses that complemented main regression analyses of these secondary predictors and outcomes.

First, regarding exploration of a cubic model, after the fasting blood draw, the HAPO protocol specified recording the number of minutes following glucose consumption for two subsequent blood draws: times ranged 50–70 min and 110–130 min. Using times in minutes as reported, cubic fits were explored, along with linear and quadratic models that included both fixed and random effects. …
Dramatic but suspensive effect of interleukin-1 inhibitors for persistent urticarial vasculitis: a French multicentre retrospective study
Authors: Thomas Bettuzzi, Alban Deroux, Marie Jachiet, Meryem-Maud Farhat, julien wipff, Marc Fabre, Laurence Bouillet, Nora Kramkimel, Selim Aractingi, Nicolas Dupin, Benjamin Terrier
Journal: Annals of the Rheumatic Diseases (2019)

Urticarial vasculitis (UV) is rare systemic disease characterised by a dermal capillary inflammation responsible of long-lasting urticarial lesions, and sometimes some systemic manifestations.1 2 UV can be separated into two different entities: hypocomplementemic UV (HUV) and normocomplementemic UV (NUV). Treatment of UV depends on the severity of the disease and the occurrence of relapses. In patients refractory to colchicine or dapsone, glucocorticoids (GCs), conventional immunosuppressive agents or rituximab (RTX) can be used,1 2 leading to significant morbidity. Interleukin-1β (IL-1β) inhibitors are biologics mainly used in autoinflammatory diseases.3 We report here a French retrospective multicentr study of patients treated with IL-1β inhibitors for persistent disease despite GCs and/or immunosuppressive agents.

This French retrospective multicentre study was conducted in four departments of Dermatology and Internal Medicine. We included patients with persistent UV to at …
Use of Directly Observed Therapy to Assess Treatment Adherence in Patients With Apparent Treatment-Resistant Hypertension
Authors: Marcel Ruzicka, Frans H. H. Leenen, Tim Ramsay, Ann Bugeja, Cedric Edwards, Brendan McCormick, Swapnil Hiremath
Journal: JAMA Internal Medicine (2019)

to nurse practitioners and physician assistants, prescribing decisions may involve pharmacists; registered nurses who may supervise treatment of chronic disease, implement standing orders, and educate patients about new therapies; and procedural nurses who may arrange visits from medical device representatives and oversee purchasing.In Australia, Karanges et al found that many nonphysicians received speaking fees, highlighting their influential role. 3 The expansion of the Sunshine Act in the United States to include additional prescribing clinicians is a welcome development, although still several years away.The Australian experience with broader reporting of industry payments to health care professionals suggests that the forthcoming data should be illuminating.The next steps are to move from greater transparency to reforms that address the high costs of medical care and diminish the incentives for industry payments to health care professionals in the first place.
Risk factors and indicators of severe systemic insect sting reactions
Authors: Johanna Stoevesandt, Gunter J. Sturm, Patrizia Bonadonna, Joanna N.G. Oude Elberink, Axel Trautmann
Journal: Allergy (2019)

Abstract Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one‐quarter of sting‐induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long‐term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta‐blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline‐directed antihypertensive treatment. The absence of urticaria/angioedema during sting‐induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom‐allergic patients. Measurement of platelet‐activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.
PB2113 IMPACT OF CLONAL HETEROGENEITY IN COMPLEX KARYOTYPES OF MULTIPLE MYELOMA PATIENTS WITH FIRST LINE BORTEZOMIB‐BASED THERAPY: A SINGLE‐INSTITUTION EXPERIENCE IN BULGARIA
Authors: S. Angelova, K. Ignatova, P. Ganeva, S. Lozenov, M. Jagurinoski, G. Balatzenko, B. Spassov
Journal: HemaSphere (2019)

Background: Multiple myeloma (MM) is genetically heterogeneous with varied clinical outcomes, primarily due to the coexistence of diverse numerical and structural cytogenetic abnormalities (CA). The data about prognostic significance of clonal evolution and cumulative effect of multiple high‐risk (HR) CA in complex karyotypes (CK) of MM patience (pts) is controversially. Aims: 1) to make cytogenetics profiling of CK in our MM pts with first line bortezomib‐based therapy (BBT); 2) to find relationship between clonal heterogeneity in CK and therapeutic response and OS of our MM pts. Methods We examined the cytogenetic features in 78 pts with newly diagnosed MM using conventional cytogenetics and molecular‐genetics (for t(4;14)/MMSET‐IgH) analysis for 5 years (2014‐2018) in SBALHZ–Sofia, Bulgaria. The followed CA were considered as clinically relevant: hyperdiploidy, hypodiploidy, gap 1q, ‐13/13q‐, ‐17/17p‐, t(4;14), t(11;14). OS was calculated using Kaplan‐Meier estimates. Results: The CK was occurred in about 38% (30/78) of our pts: in 77% (23/30) with hyperdiploidy and in 23% (7/30) without it. The features of clonal evolution (2 or more aberrant cell clones) were defined in 57% (17/30) CK and predominantly were connected with hyperdiploidy (15/17). The coexistence of 2 or more adverse prognostic CA was defined in 60% (18/30) CK. The proportion of pts with normal karyotype (NK) who achieved CR and VGPR was two and half times more than in pts with CK (16,7% vs 41,7%). The autologous stem cell transplantation (ASCT) was applied at 26,7% (8/30) pts with CK and 31% (15/48) pts with NK. We have not found a statistically significant difference in the OS of our pts with signs of clonal evolution or multiple HR CA in CK compared to other CK pts. Although the mean OS of pts with HR CA or clonal heterogeneity in CK without ASCT was lower than OS of CK pts treated with ASCT, the difference in OS wasn’t statistically significant (19.0 mths vs 25.2 mths, p = 0.419). Only groups that stratified according to Mayo Stratification of Myeloma (with HR CA, intermediate‐risk CA and standard‐risk CA) had a statistically significant OS difference (p &lt; 0,006). Summary/Conclusion: We have not found cumulative adverse effect of multiple HR CA or signs of clonal evolution in CK on OS of our MM pts.
Abstract 10103: Cell Cycle Activation of Hypertrophic Cardiomyopathy: Insights From Research of Patient-Specific Induced Pluripotent Stem Cells-Derived Cardiomyocytes
Authors: Shunsuke Funakoshi, Takeru Makiyama, Takeshi Kimura, Shinya Yamanaka, Yoshinori Yoshida
Journal: Circulation (2013)

Backgrounds: Hypertrophic Cardiomyopathy (HCM) is a popular inherited disease which leads to heart failure, arrhythmia and sudden cardiac death. Although several genetic mutations causing HCM have ...
FRI0629 APPLICATION OF AN ADVANCED NOISE REDUCTION ALGORITHM FOR IMAGING OF HANDS IN RHEUMATIC DISEASES – EVALUATION OF IMAGE QUALITY COMPARED TO STANDARD DOSE IMAGES
Authors: Katharina Ziegeler, Stefan Siepmann, Alexander Beck, Alexander Lembcke, Bernd Hamm, Kay Geert A. Hermann
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> X-ray is the fundamental imaging technique in diagnosis and follow up of rheumatic diseases. As patients often require sequential X-rays, dose reduction is of great importance. New advanced noise reduction algorithms allow for a dose reduction of up to 50%. <h3>Objectives</h3> The aim of this study was to evaluate, whether the application of an advanced noise reduction algorithms is feasible in the context of imaging of rheumatic diseases. <h3>Methods</h3> A total of 298 patients were enrolled prospectively into three tiers: 80%, 64% and 50% dose reduction groups. All patients received imaging of one hand (laterality randomly assigned) with low-dose technique and of the contralateral side with standard protocol. All images were evaluated by two blinded independent readers who scored (on a scale of 1 to 5) the visualisation of bony cortex, trabeculae and joint spaces of fingers and wrist separately as well as soft tissue and overall contrast. Score values were analysed using T-tests for paired samples. <h3>Results</h3> Overall image quality (expressed by mean sum scores out of 40) of the 50% low-dose images was 31.52 (SD 1.94) vs. 31.66 (SD 1.82) for standard images (p=0.217). Bony contours as well as trabeculae was equally well visualized in both image sets. An image example is given in Fig. 1 (Left hand: 50%-dose image; right hand: standard-dose image). Soft tissue visualization was slightly lower for low-dose compared to standard images (mean score of 3.81 vs. 3.88; p=0.001). <h3>Conclusion</h3> Overall image quality of low dose images was not inferior to standard dose images. Therefore, application of low-dose technology based on advanced noise estimation algorithms in the context of imaging of rheumatic diseases is feasible. <h3>Disclosure of Interests</h3> Katharina Ziegeler: None declared, Stefan Siepmann: None declared, Alexander Beck: None declared, Alexander Lembcke: None declared, Bernd Hamm Grant/research support from: Siemens, GE, Bayer, Samsung, Canon, Guerbet, Kay Geert A. Hermann Speakers bureau: AbbVie, MSD, Pfizer, UCB, Samsung
Structure, function, and regulation of renal organic anion transporters
Authors: Guofeng You
Journal: Medicinal Research Reviews (2002)

Abstract Renal elimination of anionic drugs, xenobiotics, and toxins is necessary for the survival of mammalian species. This process is mediated by vectorial transport from blood to urine through the cooperative functions of specific transporters in the basolateral and apical membranes of the proximal tubule epithelium. The first step of this process is the extraction of organic anions from the peritubular blood plasma into proximal tubule cells largely through the organic anion transporter (OAT) pathway. Therefore, the OAT pathway is one of the major sites for body drug clearance/detoxification. As a result, it is also the site for drug–drug interaction and drug‐induced nephrotoxicity. To maximize therapeutic efficacy and minimize toxicity, the structure‐function relationships of OATs and their regulation must be defined. The recent cloning and identification of OATs have paved the way for such investigations. This review summarizes the available data on the general properties of OATs, focusing in particular on the recent progress made from the author's laboratory as well as from other's, on the molecular characterization of the structure‐function relationships of OATs and their regulatory mechanisms. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 6, 602–616, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/med.10019
Effectiveness and Cost of Organized Outreach for Colorectal Cancer Screening: A Randomized, Controlled Trial
Authors: Ma Somsouk, Carly Rachocki, Ajitha Mannalithara, Dianne Garcia, Victoria Laleau, Barbara Grimes, Rachel B Issaka, Ellen Chen, Eric Vittinghoff, Jean A Shapiro, Uri Ladabaum
Journal: JNCI Journal of the National Cancer Institute (2019)

Colorectal cancer (CRC) screening remains underused, especially in safety-net systems. The objective of this study was to determine the effectiveness, costs, and cost-effectiveness of organized outreach using fecal immunochemical tests (FITs) compared with usual care.Patients age 50-75 years eligible for CRC screening from eight participating primary care safety-net clinics were randomly assigned to outreach intervention with usual care vs usual care alone. The intervention included a mailed postcard and call, followed by a mailed FIT kit, and a reminder phone call if the FIT kit was not returned. The primary outcome was screening participation at 1 year and a microcosting analysis of the outreach activities with embedded long-term cost-effectiveness of outreach. All statistical tests were two-sided.A total of 5386 patients were randomly assigned to the intervention group and 5434 to usual care. FIT screening was statistically significantly higher in the intervention group than in the control group (57.9% vs 37.4%, P < .001; difference = 20.5%, 95% confidence interval = 18.6% to 22.4%). In the intervention group, FIT completion rate was higher in patients who had previously completed a FIT vs those who had not (71.9% vs 35.7%, P < .001). There was evidence of effect modification of the intervention by language, and clinic. Outreach cost approximately $23 per patient and $112 per additional patient screened. Projecting long-term outcomes, outreach was estimated to cost $9200 per quality-adjusted life-year gained vs usual care.Population-based management with organized FIT outreach statistically significantly increased CRC screening and was cost-effective in a safety-net system. The sustainability of the program and any impact of economies of scale remain to be determined.