tbuckley/cabot-search huggingface dataset:
PB2180 EXPERIENCE VRD‐PACE‐LIKE REGIMEN IN PATIENTS WITH PRIMARY REFRACTORY MYELOMA FOR PERIPHERAL STEM CELL MOBILIZATION
Authors: I. Nakastoev, V. Ryzhko, A. Novikova, Y. Balzhanova, A. Grachev, T. Abramova, M. Samtcova, P. Vasilchenkova, A. Danilina, M. Kanaeva, E. Gribanova
Journal: HemaSphere (2019)

Background: High‐dose chemotherapy followed by autologous stem‐cell transplant (ASCT) is the current treatment in patients with multiple myeloma (MM). To obtain the effect of ASCT it is necessary to achieve a response to induction therapy. Lenalidomide‐based regimens as the second‐line therapy failed peripheral blood mobilization of CD34+ cells and increase the risk of its inadequate collection. Thus, intensive chemotherapy regimens as VRD‐PACE and its modifications are used to enhance treatment response and effective mobilization. Aims: To estimate safety and efficacy of VRD‐PACE‐like regimens for peripheral stem cell mobilization. Methods A total of 7 patients with primary refractory multiple myeloma were enrolled in the study. All patients received VRD‐PACE‐like regimens in conventional doses followed by granulocyte colony‐stimulating factor (G‐CSF 10 μg/kg/day) started after reducing leukocytes count ≤ 1.0 × 10 9 /L. As mobilizing regimen in 3 patients was administred VRD‐PACE, 3–RD‐PACE and 1–KRD‐PACE. Results: A total of 7 patients with primary refractory myeloma were enrolled in the study. The median age was 51 (range 40–56 years), of them 3 were men. These patients didn’t receive suboptimal response to bortezomib‐based regimens. Therefore, administration of second‐line therapy was required. Patients received in average 6 cycles of chemotherapy (6–10) and three lines of therapy. At initiation treatment with VRD‐PACE only 1 patient had very good partial response (VGPR), 3–partial response (PR), 3–disease progression. One patient with VGPR had adverse cytogenetic abnormalities and for this reason was treated with VRD‐PACE. All patients who received VRD‐PACE‐like regimens achieved decline of serum monoclonal protein, of them 2 obtained VGPR. Mobilization failure was in 2 patients due to inadequate collection of CD34+ cells. Before mobilization each of these patients received only 2 lenalidomide‐based cycles. Afterwards, high‐dose cyclophosphamide‐based mobilization was performed and sufficient amount of CD34+ cells was received. In the others 5 patients CD34+ cells were collected enough for tandem ASCT (6–12.4 × 10 6 /kg). VRD‐PACE‐like regimens were not associated with severe complications. Only 1 patient was diagnosed with parietal thrombosis of the common femoral vein and 1 patient had Herpes labialis. One patient needed packed red cell and platelet transfusion. Summary/Conclusion: VRD‐PACE‐like regimens are an effective option for treatment of refractory/relapse MM. We concluded that VRD‐PACE‐like regimens are well‐tolerated and effective option for mobilization of CD34+ cells in patients with suboptimal treatment response or aggressive MM. image
Association of changes in red meat consumption with total and cause specific mortality among US women and men: two prospective cohort studies
Authors: Yan Zheng, Yanping Li, Ambika Satija, An Pan, Mercedes Sotos-Prieto, Eric Rimm, Walter C Willett, Frank B Hu
Journal: BMJ (2019)

To evaluate the association of changes in red meat consumption with total and cause specific mortality in women and men.Two prospective cohort studies with repeated measures of diet and lifestyle factors.Nurses' Health Study and the Health Professionals Follow-up Study, United States.53 553 women and 27 916 men without cardiovascular disease or cancer at baseline.Death confirmed by state vital statistics records, the national death index, or reported by families and the postal system.14 019 deaths occurred during 1.2 million person years of follow-up. Increases in red meat consumption over eight years were associated with a higher mortality risk in the subsequent eight years among women and men (both P for trend<0.05, P for heterogeneity=0.97). An increase in total red meat consumption of at least half a serving per day was associated with a 10% higher mortality risk (pooled hazard ratio 1.10, 95% confidence interval 1.04 to 1.17). For processed and unprocessed red meat consumption, an increase of at least half a serving per day was associated with a 13% higher mortality risk (1.13, 1.04 to 1.23) and a 9% higher mortality risk (1.09, 1.02 to 1.17), respectively. A decrease in consumption of processed or unprocessed red meat of at least half a serving per day was not associated with mortality risk. The association between increased red meat consumption and mortality risk was consistent across subgroups defined by age, physical activity, dietary quality, smoking status, or alcohol consumption.Increases in red meat consumption, especially processed meat, were associated with higher overall mortality rates.
Abstract 20509: Impact of Pulmonary Vein Isolation During Atrial Flutter Ablation: A Meta-Analysis
Authors: Scott M Koerber, Mohit Turagam, Frank Cuoco, Marcus Wharton, Dhanunjaya Lakkireddy, Sandeep Gautam
Journal: Circulation (2017)

Introduction: Atrial arrhythmias (AA), including atrial fibrillation (AF), have been reported in patients after undergoing a cavotricuspid isthmus ablation (CTI) for atrial flutter (AFL). Various s...
Abstract 224: Repeat Coronary Artery Bypass Grafting in an Adult Case of Kawasaki Disease
Authors: Yuka Sakurai, Masahide Chikada, Hirotoshi Suzuki, Masanori Sagane, Daijyun Ro, Kiyoshi Chiba, Hirokuni Ono, Makoto Oono, Yousuke Kitanaka, Hiroshi Nishimaki, Takeshi Miyairi
Journal: Circulation (2015)

Background: The incidence of giant coronary artery aneurysm as a complication of Kawasaki disease is approximately 0.35%. Kawasaki disease was first described in 1967. However, only a few studies have reported on adult cases of cardiovascular sequelae in Kawasaki disease. Adult cases of coronary stenosis due to Kawasaki disease shows a predilection for the age range of late teens to the twenties; elderly onset, such as around the age of 60 years, is rare. Case report: A 62-year-old woman with a history of coronary artery bypass grafting (two-vessel bypass) was diagnosed with a coronary artery aneurysm and concomitant Kawasaki disease at another hospital at the age of 48 years. A reoperation was recommended owing to re-strangulation, but the patient opted for progress observation. At the age of 53 years, the patient experienced respiratory pain during laborious work, and coronary angiography was indicated. We therefore performed coronary artery bypass grafting (four-vessel bypass) for there to base Kawasaki disease, calcification of advanced, restenosis, coronary flow was observed. The postoperative course was good, and the patient has remained without restenosis for 9 years after the surgery. Conclusion: The progress of patients with a history of Kawasaki disease in adulthood has not been established; these patients therefore require periodical follow-up examinations. Moreover, because coronary artery involvement in Kawasaki disease is a risk factor for myocardial infarction, careful attention should be paid to lifestyle-related diseases.
AB1094 ARTERIOSCLEROSIS MAY AFFECT PERIAORTIC/PERIARTERIAL LESIONS AND THEIR ANEURYSMAL CHANGES IN PATIENTS WITH IGG4-RELATED PERIAORTITIS/PERIARTERITIS
Authors: Ichiro Mizushima, Masahiro Konishi, Hajime Sanada, Kazuyuki Suzuki, Akari Takeji, Satoshi Hara, Kiyoaki Ito, Hiroshi Fujii, Kazunori Yamada, Mitsuhiro Kawano
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> IgG4-related periaortitis/periarteritis (IgG4-PA) is a major organ manifestation of IgG4-related disease (IgG4-RD) [1]. In the affected aorta/artery, arteriosclerotic changes are frequently observed [2]. However, the influence of arteriosclerosis on IgG4-PA and aneurysmal changes of the affected lesions has not been well evaluated. <h3>Objectives</h3> This study aimed to clarify the relationship of arteriosclerosis with periaortic/periarterial lesions and their aneurysmal changes. <h3>Methods</h3> We retrospectively investigated the medical data, including the presence of IgG4-PA at diagnosis, new development of IgG4-PA during the clinical course, arteriosclerotic and aneurysmal changes of the affected lesions, and classic risk factors for arteriosclerosis in 130 patients with IgG4-RD at a single center in Japan. The relationship of arteriosclerosis with the periaortic/periarterial lesions and their aneurysmal changes was statistically analyzed. <h3>Results</h3> Of the 130 patients with IgG4-RD, 44 comprising 39 men and 5 women (mean age 67.4 years) were diagnosed with IgG4-PA. The mean follow-up period was 72.8 months, and the mean serum IgG4 level at diagnosis was 851 mg/dL. The proportions of males (88.6% vs. 55.8%, <i>P</i>&lt;0.001), positive smoking history (81.4% vs. 47.6%, <i>P</i>&lt;0.001), and history of malignancy (36.4% vs. 14.0%, <i>P</i>=0.006) were significantly higher in the 44 patients with IgG4-PA than in the 86 without it. Arterial wall calcification and/or mural thrombus in the affected lesions were detected in 86.0% of the IgG4-PA patients, some of whom had had these arteriosclerotic changes before the development of periaortic/periarterial lesions. Of the 44 with IgG4-PA, 9 had aneurysmal changes of the affected lesions at the time of the first diagnosis of IgG4-RD. Notably, these 9 patients with aneurysmal changes had a significantly higher incidence of hypertension (77.8% vs. 34.3%, <i>P</i>=0.027) and mural thrombus in the affected lesions (100% vs. 64.7%, <i>P</i>=0.044) than the remaining 35 without aneurysmal changes. However, diabetes mellitus, dyslipidemia, smoking history, C-reactive protein level elevation, or arterial wall calcification of the affected lesions did not differ significantly between the two groups. <h3>Conclusion</h3> The present study suggests that arteriosclerotic changes and the classic risk factors for arteriosclerosis may be related to periaortic/periarterial lesions and their aneurysmal changes in IgG4-PA. <h3>References</h3> [1] Stone JH, et al. IgG4-related disease. N Engl J Med. 2012 Feb 9;366(6):539-51. [2] Inoue D, et al. Immunoglobulin G4-related periaortitis and periarteritis: CT findings in 17 patients. Radiology. 2011 Nov;261(2):625-33. <h3>Disclosure of Interests</h3> None declared
Genetic identification of brain cell types underlying schizophrenia
Authors: Nathan G. Skene, Julien Bryois, Trygve E. Bakken, Gerome Breen, James J. Crowley, Héléna A. Gaspar, Paola Giusti-Rodriguez, Rebecca D. Hodge, Jeremy A. Miller, Ana B. Muñoz-Manchado, Michael C. O’Donovan, Michael J. Owen, Antonio F. Pardiñas, Jesper Ryge, James T. R. Walters, Sten Linnarsson, Ed S. Lein, Patrick F. Sullivan, Jens Hjerling-Leffler
Journal: Nature Genetics (2018)
Metagenome-assembled genomes uncover a global brackish microbiome
Authors: Luisa W. Hugerth, John Larsson, Johannes Alneberg, Markus V. Lindh, Catherine Legrand, Jarone Pinhassi, Anders F. Andersson
Journal: Genome biology (2015)

Microbes are main drivers of biogeochemical cycles in oceans and lakes. Although the genome is a foundation for understanding the metabolism, ecology and evolution of an organism, few bacterioplankton genomes have been sequenced, partly due to difficulties in cultivating them. We use automatic binning to reconstruct a large number of bacterioplankton genomes from a metagenomic time-series from the Baltic Sea, one of world's largest brackish water bodies. These genomes represent novel species within typical freshwater and marine clades, including clades not previously sequenced. The genomes' seasonal dynamics follow phylogenetic patterns, but with fine-grained lineage-specific variations, reflected in gene-content. Signs of streamlining are evident in most genomes, and estimated genome sizes correlate with abundance variation across filter size fractions. Comparing the genomes with globally distributed metagenomes reveals significant fragment recruitment at high sequence identity from brackish waters in North America, but little from lakes or oceans. This suggests the existence of a global brackish metacommunity whose populations diverged from freshwater and marine relatives over 100,000 years ago, long before the Baltic Sea was formed (8000 years ago). This markedly contrasts to most Baltic Sea multicellular organisms, which are locally adapted populations of freshwater or marine counterparts. We describe the gene content, temporal dynamics and biogeography of a large set of new bacterioplankton genomes assembled from metagenomes. We propose that brackish environments exert such strong selection that lineages adapted to them flourish globally with limited influence from surrounding aquatic communities.
THU0309 NONLINEAR PHARMACOKINETICS OF RITUXIMAB IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY ASSOCIATED VASCULITIS
Authors: Denis Mulleman, Amina Bensalem, David Ternant, Gilles Paintaud, Divi Cornec, Ulrich Specks
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rituximab (RTX) was approved in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). <h3>Objectives:</h3> To describe the pharmacokinetics of rituximab in AAV patients and to explore its sources of variability <h3>Methods:</h3> Rituximab pharmacokinetics was described in 92 AAV patients from the RAVE trial (rituximab for ANCA- associated vasculitis) using a population modeling approach. A semi-mechanistic model including a latent target antigen turnover allowed the estimation of specific target-mediated elimination of rituximab in addition to its non-specific elimination. Sex, body surface area (BSA), BVAS/WG score, and status newly diagnosed on pharmacokinetic parameters were investigated as covariates. <h3>Results:</h3> A two compartments model including target mediated elimination best described rituximab pharmacokinetics. The mean (interindividual standard deviation) estimated central volume of distribution was 3.06 L (2.61%), systemic clearance was 0.135 L days<sup>−1</sup> (6.43%), and target-mediated elimination rate constant was 19.13 x 10<sup>-6</sup> nmol<sup>-1</sup> days<sup>−1</sup>(fixed to 0). The initial activity of the disease was higher in male than in female (p=4.09 x 10<sup>-14</sup>), and in patients newly diagnosed at inclusion (p=7.91 x 10<sup>-5</sup>). Moreover, systemic clearance was slightly lower in granulomatosis with polyangiitis group than in other AAV groups (p=3.6 x 10<sup>-3</sup>). Neither BVAS/WG score nor BSA were significant covariates in a multivariate analysis. <h3>Conclusion:</h3> We report a nonlinear target-mediated elimination of rituximab in AAV patients. Granulomatosis with polyangiitis patients have a lower global clearance of rituximab than other AAV groups. Our study not support the utility of BSA based individualized dosing protocols, as previously reported (1). <h3>Reference:</h3> [1] Cornec D, et al. Pharmacokinetics of rituximab and clinical outcomes in patients with anti-neutrophil cytoplasmic antibody associated vasculitis. Rheumatology. 2018;57:639-50. <h3>Disclosure of Interests:</h3> Denis Mulleman Speakers bureau: Pfizer, Novartis, Grifols, Amina Bensalem: None declared, David Ternant Speakers bureau: Sanofi, Amgen, Gilles Paintaud Grant/research support from: Novartis, Roche Pharma, Sanofi-Genzyme, Chugai, Pfizer and Shire, Divi Cornec: None declared, Ulrich Specks: None declared
PB1846 ANTHROPOMETRIC AND HORMONAL PARAMETERS IN COMPARISON WITH BONE MINERAL DENSITY IN MEN WITH HAEMOPHILIA FROM LOWER SILESIA ‐ PRELIMINARY REPORT
Authors: M.M. Biernat, D. Jędrzejuk, D. Urbaniak‐Kujda, I. Prajs, M. Podolak‐Dawidziak, T. Wróbel
Journal: HemaSphere (2019)

Background: In patients with haemophilia, recurrent episodes of bleeding lead to joint deterioration and bone resorption. To date, the effect of various risk factors on the bone mineral density (BMD) reduction have found conflicting results. Aims: The aim of the study was to analyze the impact of certain parameters, such as: viral status of patients, estradiol, testosteron, parathormone and vitamin D levels in relation to bone density. Methods: 24 men with moderate and severe haemophilia, aged 18‐35 were enrolled. BMD at the lumbar spine, trabecular bone score (TBS) and total body densitometry were measured using dual X ray absorptiometry method (DXA) (densitometer Horizon, Hologic, 2017). Blood analyses were performed for morphology parameters, liver and kidney function parameters, HCV, HBV, HIV viral status, estradiol, testosteron, DHEA‐S, TSH, parathormone and Vitamin D levels. Results: The study population included 24 men with haemophilia A, who had been receiving prophylactic factor replacement therapy. HCV seropositivity was found in 6/24 patients (25%), whereas HBV seropositivity was detected in 4 patients (16,7%). There was no patient infected with HIV virus. No statistical correlation was found between BMD and viral serological status. It was found that in 15/24 patients BMD was normal with a Z‐score of &gt; ‐1 (62,5%), whereas in 9/24 patients (37,55%), BMD was decreased. In hemophilic patients with normal BMD Z‐score, the increased BMI, androidal fat deposit (AFD), gynoidal fat deposit (GFD), fat mass index (FMI), free fat mass index (FFMI), Estimated visceral adipose tissue (Est VAT) mass were detected. Among all analyzed hormones, only serum estradiol concentration was statistically higher in patients with normal BMD. In 17/24 examined patients Vitamin D deficiency (&lt;20 ng/ml) was detected (71%), although Vitamin D insufficiency (&lt;30 ng/ml) was found in 4/24 patients (16,7%). Three patients (12,5%) had a normal Vitamin D concentration. Summary/Conclusion: The higher BMD in haemophilic patients is related with certain anthropometric parameters, such as body‐fat‐, free‐fat‐mass indexes and visceral fat tissue. BMD negatively correlated with % body fat, androidal fat mass and PTH, whereas TBS negatively related with androidal/visceral fat mass. We found that Vitamin D deficiency is very common in haemophilic patients, however there was no correlation between Vitamin D levels and BMD.
PB1649 EXOSOMES‐MEDIATED DELIVERY OF RNA OLIGOS DIRECTED TO CHE‐1/AATF IMPAIRS BCP‐ALL VITALITY
Authors: M. Caforio, C. Sorino, V. Bertaina, A. Pitisci, G. Battafarano, A. Del Fattore, M. Fanciulli, V. Folgiero, F. Locatelli
Journal: HemaSphere (2019)

Background: Precursor B cell acute lymphoblastic leukemia (BCP‐ALL) is the most common childhood malignancy and represents the leading cause of cancer‐related death in children and young adults. BCP‐ALL arises from a monoclonal or oligoclonal expansion of malignant B cell precursors in the bone marrow and despite the overall progress in treatment relapse occurs across the whole spectrum of all subtypes with an overall survival of 30%. We recently found that Che‐1/AATF, an important RNA polymerase II binding protein involved in the regulation of gene transcription with anti‐apoptotic activity in different tumour contests, exerts a pivotal role in BCP‐ALL. Che‐1 is highly expressed in a cohort of BCP‐ALL patients at the onset of disease and at time of relapse, irrespective of genetic heterogeneity, but were barely detectable when patients obtained leukemia remission. Notably, Che‐1 depletion strongly affected growth of BCP‐ALL cells and sensitized to Adriamycin. Aims: With the aim to therapeutically inhibit Che‐1 expression, overcoming the difficulty of the nuclear localization, and to find a technical approach available in in vivo models we focused on exosome‐mediated delivery of RNA oligos. Methods: To test this hypothesis, peripheral blood obtained from healthy donors was used for monocytes isolation and differentiation to immature dendritic cells. Supernatants were harvested and submitted to exosomes extraction procedure. Vesicles were electroporated with FITC‐conjugated oligos to set up experimental conditions. We observed high oligos loading and a 100% efficiency of oligo delivery in BCP‐ALL cell lines and in primary blast cells upon cellular co‐culture. In the same experimental conditions, we tested the efficacy of a panel of FITC‐conjugate oligo targeting Che‐1. Results: The exosome‐mediated delivery of combination of two oligos resulted in downregulation of Che‐1 expression in BCP‐ALL cell lines. The obtained result produced also an increase in PARP cleavage and an higher amount of cells in subG0‐1 phase. Summary/Conclusion: Since part of this procedure is an already approved GMP‐grade procedure, we will test the cooperation between exosome‐mediated Che‐1 downregulation and the current therapeutic treatments with the aim to develop a new applicable clinical approach, particularly in BCP‐ALL relapsed patients.
Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading
Authors: Aristeidis H. Katsanos, George A. Alexiou, Andreas D. Fotopoulos, Pascal Jabbour, Athanasios P. Kyritsis, Chrissa Sioka
Journal: Clinical Nuclear Medicine (2019)

Purpose Gliomas constitute the most frequent primary brain tumors. Glioblastoma, the most common and malignant glioma in adults, has dismal prognosis with any current therapy. On the other hand, low-grade gliomas, the second most common type of gliomas, are potentially curative with appropriate treatment. Methods We conducted a meta-analysis to assess the performance of PET tracers with the best available evidence, namely, fluorodeoxyglucose (FDG), 11 C-methionine (MET), and 18 F-fluoroethyltyrosine (FET), in differentiating low- from high-grade gliomas. Results Twenty-three studies with a total of 994 participants were included in this meta-analysis. The pooled sensitivities of both MET PET and FET PET were found to be significantly higher than of FDG PET (94%, 88%, and 63% respectively, P &lt; 0.001). The pooled specificity of FDG PET was found to be significantly greater compared with both MET PET and FET PET (89%, 55%, and 57%, respectively; P = 0.002). Fluorodeoxyglucose PET was superior in terms of higher positive likelihood ratio values compared with both FET PET and MET PET. Conclusions This meta-analysis indicated that both MET and FET were superior to FDG in terms of sensitivity for identifying glioma grade.
Subsets of ILC3−ILC1-like cells generate a diversity spectrum of innate lymphoid cells in human mucosal tissues
Authors: Marina Cella, Ramya Gamini, Cristiane Sécca, Patrick L. Collins, Shanrong Zhao, Vincent Peng, Michelle L. Robinette, Jorge Schettini, Konstantin Zaitsev, William Gordon, Jennifer K. Bando, Kentaro Yomogida, Victor Cortez, Catrina Fronick, Robert Fulton, Lih-Ling Lin, Susan Gilfillan, Richard A. Flavell, Liang Shan, Maxim N. Artyomov, Michael Bowman, Eugene M. Oltz, Scott A. Jelinsky, Marco Colonna
Journal: Nature Immunology (2019)