tbuckley/cabot-search huggingface dataset:
PS1537 CO‐TRANSPLANTATION OF MESENCHYMAL STEM CELLS CAN AMELIORATES ACUTE GVHD AND VIREMIA AFTER ALLO‐HSCT FOR APLASTIC ANEMIA: A MULTI‐CENTER RETROSPECTIVE STUDY OF 75PATIENTS
Authors: M. Chen, Z. Zheng, J. Hu, T. Yang
Journal: HemaSphere (2019)

Background: Mesenchymal stem cells (MSCs) are known to exhibit immunomodulatory, anti‐inflammatory, and pro‐angiogenic properties, and therefore have the potential to improve the outcome of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for severe aplastic anemia (AA). Aims: To explore the efficacy and safety of allo‐HSCT by co‐transplantation with MSCs in AA patients Methods: We conducted a multi‐center retrospective study to comparing the incidence and severity of acute GvHD, transplant‐related complication and overall survival (OS) of allo‐HSCT with or without co‐injection of MSCs in AA patients. A total of 75 consecutive severe AA patients (43males/32 females) undergoing allo‐HSCT at 4 hospitals from January 2012 to February 2018 were analyzed. 45 patients transplanted with donor HSCs only,and 30 patients transplanted with HSCs and MSCs. MSCs infusion dose was 0.5–3.0 × 10 6 /kg, at day0/+1 following HSCs infusion. Results: All patients achieved successful engraftment within one month post transplant. There was no difference in time to leukocyte and platelet engraftment in the two groups. There was a trend to a lower incidence of aGVHD in the MSC group (13.3% versus 26.7%,χ 2 = 2.066 P = 0.151). Moreover, a lower incidence of CMV replication in the MSC group was observed (CMV:26.7% vs 64.4 %,P = 0.003). With a median follow‐up time of 615 days (range:29–2315ays),the 2‐yr OS was similar in both groups (76.2% vs 77.3%,P = 0.883). A combination of bone marrow and peripheral blood as the sources of stem cells co‐transplanted with MSCs (n = 9) demonstrated an improved survival benefit (2‐yr OS = 100%). Summary/Conclusion: These data support that co‐transplantation with MSCs could ameliorate the challenges of aGVHD and viremia and facilitate survival in allo‐HSCT for AA patients.
Temporal changes within the (bladder) tumor microenvironment that accompany the therapeutic effects of the immunocytokine NHS-IL12
Authors: Y. Maurice Morillon, Zhen Su, Jeffrey Schlom, John W. Greiner
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> While significant strides in the treatment of metastatic bladder cancer have been made with immune checkpoint inhibitors, the treatment of carcinoma in situ and non-muscle invasive, non-metastatic (superficial) human urothelial carcinoma, also termed non-muscle invasive bladder cancer (NMIBC), remains intractable with bacillus Calmette-Guerin (BCG) employed as the standard of care. In this study, an immunocytokine, NHS-muIL12, which consists of two molecules of murine IL-12 fused to NHS76, a tumor necrosis-targeting human IgG1, was examined as an immunotherapeutic in an orthotopic MB49<sup>luc</sup> bladder tumor model. <h3>Methods</h3> The antitumor activity of systemic administration of NHS-muIL12 was investigated on MB49<sup>luc</sup> tumors, an aggressive, bioluminescent orthotopic bladder cancer model. Temporal studies were carried out on MB49<sup>luc</sup> bladder tumors harvested during various time points during NHS-muIL12 treatment and cellular changes associated with the reduction in tumor burden following NHS-muIL12 were determined by flow cytometry. Effects of those changes on the proliferation/activation of lymphoid cells were also determined. <h3>Results</h3> Studies revealed a significant reduction in MB49<sup>luc</sup> bladder tumor burden occurring between days 3 and 6 after the third and final systemic administration of NHS-muIL12. Temporal analyses of the MB49<sup>luc</sup> bladder tumor microenvironment (TME) initially revealed a large accumulation of myeloid-derived suppressor cells (MDSCs) and macrophages that elicited potent immunosuppression. Immunosuppression was characterized by the inability of CD4<sup>+</sup> and CD8<sup>+</sup> T cells to respond to broad-based immune stimulants. NHS-muIL12 administration resulted in temporal-dependent reductions in the number of MDSCs, macrophages and tumor-associated TGF<b>-</b>β, which culminated in a re-ignition of CD4<sup>+</sup> and CD8<sup>+</sup> T cells to elicit potent antitumor responses against MB49<sup>luc</sup> bladder tumors. <h3>Conclusions</h3> These findings provide strong evidence that the systemic administration of an immunocytokine consisting of a tumor-targeting Ig through recognition of DNA and DNA-histone complexes coupled to muIL-12 can effectively target the bladder TME; this significantly reduces the myeloid cellular compartment and reverts an immunosuppressive to an immunopermissive TME, ultimately resulting in antitumor effects. These studies provide further rationale for the employment of NHS-IL12 as an immunomodulator and clinical immunotherapeutic for NMIBC.
AB1144 ULTRA HIGH FIELD MRI MICROARCHITECTURE ANALYSIS IMPROVES THE PREDICTION OF PROXIMAL FEMUR FRACTURE: A COMBINED STUDY WITH EX VIVO BIOMECHANICAL TESTS
Authors: Daphne Guenoun, Martine Pithioux, Jean-Christophe Souplet, Sandrine Guis, Thomas Le Corroller, Alaxandre Fouré, Vanessa Pauly, Jean-Pierre Mattei, Monique Bernard, Maxime Guye, Patrick Chabrand, Pierre Champsaur, David Bendahan
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The purpose of this study was to assess cadaveric proximal femurs from the points of view of bone microarchitecture using ultra-high field (UHF) 7 Tesla magnetic resonance imaging (MRI), bone strength using biomechanical tests and bone mineral density (BMD) using Dual-energy X-ray absorptiometry (DXA). <h3>Objectives</h3> We aimed at determining whether bone microarchitecture parameters were related to bone strength and BMD and whether UHF MRI can provide additional information regarding bone strength. <h3>Methods</h3> BMD of ten proximal femurs from five cadavers were investigated using DXA and the bone volume fraction (BVF), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp), fractal dimension (FD), Euler characteristics (Euler Ch.), Connectivity density (Conn. D) and Degree of anisotropy (DA) of each femur was quantified using UHF MRI. The whole set of specimens underwent mechanical compression tests to failure. <h3>Results</h3> BMD and all the microarchitecture parameters except ConnD were significantly correlated with failure load (p &lt; 0.05). The microarchitecture parameters were correlated to each other but not correlated with BMD. Multiple regression analysis demonstrated that the combination of the microarchitecture parameters and BMD improved the prediction of the failure load with for example an improved fracture risk prediction from R<sup>2</sup> = 0.418 to 0.688 when combining BMD and Euler Ch. Overall, femur bone microarchitecture assessed with UHF MRI was significantly correlated with biomechanical parameters. The multimodal assessment of BMD and trabecular bone microarchitecture using UHF MRI improved the fracture risk prediction of femoral bone and might be of interest for the future investigation of selected osteoporotic patients. <h3>Conclusion</h3> We demonstrated that femur bone microarchitecture assessed with UHF MRI was significantly correlated with biomechanical parameters. The multimodal assessment of bone mineral density and trabecular bone microarchitecture using UHF MRI improved the fracture risk prediction of femoral bone and might be of interest for the future investigation of selected osteoporotic patients. <h3>Disclosure of Interests</h3> None declared
Integrative Analysis of Zika Virus Genome RNA Structure Reveals Critical Determinants of Viral Infectivity
Authors: Pan Li, Yifan Wei, Miao Mei, Lei Tang, Lei Sun, Wenze Huang, Jianyu Zhou, Chunlin Zou, Shaojun Zhang, Cheng-Feng Qin, Tao Jiang, Jianfeng Dai, Xu Tan, Qiangfeng Cliff Zhang
Journal: Cell Host & Microbe (2018)
Abstract P332: Socio-environmental Influences on Youth Total Sedentary Time: Results From the Hispanic Community Health Study / Study of Latino Youth
Authors: Melawhy L Garcia, Sheila F Castaneda, Linda C Gallo, Maria Lopez-Gurrola, Krista M Perreira, Daniela Sotres-Alvarez, Carmen R Isasi, Earle C Chambers, Martha L Daviglus, Linda Van Horn, Kelly R Everson, Jordan A Carlson, Gregory A Talavera
Journal: Circulation (2018)

Introduction: Sedentary behavior (SED) is associated with higher obesity and cardiometabolic risk in youth, independent of physical activity. Studies showing the association between screen time and SED among Hispanics/Latinos, have primarily focused on Mexican-origin Hispanics. Additional research is needed to examine other socio-environmental factors that can influence SED among diverse Hispanics/Latinos. This cross-sectional study examined the home-, neighborhood-, and school- environment to identify factors associated with total sedentary time among youth. Methods: Data from 1,104 youth ages 8-16 years and 728 caregivers (mean age 43.1 ± 8.2 years) from four U.S. cities, who participated in the Study of Latino Youth (2012-2014), were examined. Associations between socio-environmental factors (measured by self-report) and total sedentary time (measured by one-week Actical accelerometry) were examined in linear regression models that included MVPA minutes/day, demographic covariates, and accounted for the complex survey design and sampling weights. Results: Mean sedentary time was 10.1 ± 1.8 hours/day. Home environment factors, such as electronics in the bedroom and parent limit setting, were not associated with total sedentary time. Presence of barriers to physical activity in the neighborhood (e.g., muggings, gangs) was associated with 13.4 more minutes of sedentary time per day. Attending a school that never/rarely compared to sometimes offered after school physical activity opportunities was associated with more sedentary time (B=38.0 minutes/day; 95% Confidence Interval: 13.5-62.4). Conclusions: The study findings highlight the need for future research to investigate other sources of sedentary behavior in the home for interventionist to focus on specific SED-based strategies to decrease sedentary time among youth. Minimizing barriers by identifying safe places to be active in participant’s neighborhoods may also support youth to spend less time indoors where sedentary time is prevalent.
PB1682 ADULT ACUTE LEUKEMIA AND SEASONALITY: A SINGLE CENTER EXPERIENCE
Authors: D. Sahin, T. N. Yigenoglu, O. Saygılı, S. Bascı, B. Uncu Ulu, T. Darcın, M. Bakırtas, D. Iskender, M. Kızıl Cakar, M. S. Dal, F. Altuntas
Journal: HemaSphere (2019)

Background: Etiology of acute leukemias have been investigated for a long time. Although the exact causes are not known, both genetic and environmental factors are thought to play an important role. Some infectious agents underlie etiology of many haematological malignancies. Evidence suggests antigenic stimulation consequent to community – acquired infections may stimulate oncogens or may disrupt tumor supressor genes. Therefore seasonal changes in incidence of acute leukemia have been studied over the last 2 decades with mixed results. Aims: The aim of this study was to investigate seasonal changes in the incidence of acute leukemia in adults. Methods: Data from Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Stem Cell Transplantation Unit database were retrospectively analyzed. Results: A total of 252 patients with acute leukemia had received allogeneic bone marrow transplantation at our center between March 2009 and December 2018. Their data were retrospectively analyzed. 152 patients had acute myeloid leukemia (AML, n = 152) and 100 patients had acute lymphoblastic leukemia (ALL, n = 100). No relation was found between season of first diagnose date and incidence of AML and ALL(p = 0.900, p = 0.206,respectively) Summary/Conclusion: Environmental factors including infections have long been suspected as a probable factor in the etiology of leukemias. If there is a seasonal variation in the onset of leukemia, this may be interpreted as supportive evidence of infectious etiology but in our study, we found no seasonal effect related to date of diagnosis.
THU0131 EFFECT OF METABOLIC SYNDROME ON THE COURSE OF RHEUMATOID ARTHRITIS AND CARDIOVASCULAR RISK
Authors: Svetlana Lapshina, Liutsiia Feiskhanova, Luciya Kupkenova, Ridiya Sharafutdinova, Aigul Akhmetzianova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Both rheumatoid arthritis (RA) and metabolic syndrome (MS) have an inflammatory component in the pathogenesis and both aggravate cardiovascular risks. <h3>Objectives</h3> <b>The aim</b> is to study the effect of MS on the course of RA and the increase in cardiovascular risk in these patients. <h3>Methods</h3> 100 patients (men 7%, women 93%) aged 21 to 81 years (average age 55±12.4) with reliable RA were examined. High activity in DAS28 scale was observed in 68%, moderate - in 30%, low - in 2%, rheumatoid factor (RF) positivity - in 88%, ACCP - 81%. Disease-modifying antirheumatic drugs received 78%, glucocorticosteroids 60% of patients. Arterial hypertension (AH) was present in 45% of patients. MS according to NCEP/ATPIII criteria was identified in 59 patients, according to its presence, patients were divided into 2 groups (MS+ and MS-). Patients were examined in standard laboratory tests, all of them had echocardiogram. <h3>Results</h3> In the presence of MS, RA activity was significantly higher (DAS28 4.2±0.5) compared with patients without it (DAS28 3.5±0.6) most of all because of pain syndrome (p&lt;0.01). A correlation was observed between the presence of MS and pain on a visual analogue scale and the number of painful joints (p&lt;0.05). However, there was no significant difference according to the level of the ESR, CRP, the presence of the RF, the X-ray stage of RA. There were no differences in the range of received therapy, but the dose of prednisone was higher in the MS+ group (7.8±3.5 vs 6.4±3.69, p&lt;0.05). Systolic blood pressure (BP) was higher in the MS+ group (128.3±17.3) vs MS- (119.3±15.9). The level of BP correlated (p&lt;0.05) with the severity of pain. The verified AH was present in 42 (71.2%) patients of the MS+ group (1 stage -2, 2 stage -24, 3 stage -16 patients) and in 3 (7.3%) patients of the MS- group (1 stage in 1 patient, 2 stages in 2 patients). The cholesterol level was higher in the MS+ group 5.1±1.1 compared with the MS- group 4.6±0.6 (p&lt;0.01). There was observed a persistent tendency (p&lt;0.01) in increasing of the mass index of the left ventricle myocardium according to echocardiogram. In patients with MS+, hypertrophy of the left ventricular myocardium was detected according to echocardiogram even with a normal level of BP. <h3>Conclusion</h3> The presence of MS in patients with RA is associated with a higher activity of RA most of all because of pain syndrome. At the same time, pain syndrome correlates with the level of blood pressure. The combination of MS and RA leads to an increase of cardiovascular risk factors: cholesterol level and myocardial hypertrophy, which causes the need of using the echocardiography for this group of patients. <h3>Reference</h3> [1] rheumatoid arthritis, metabolic syndrome. <h3>Disclosure of Interests</h3> None declared
Abstract 19917: Symptom Clusters Predictive of Treatment Seeking Delay in Older Adults With Acute Decompensated Heart Failure
Authors: Kristen A Sethares, Brian Ayotte, Corrine Y Jurgens
Journal: Circulation (2016)

Introduction: Older heart failure (HF) patients have difficulty recognizing and correctly interpreting symptoms, which can lead to delay in seeking treatment. Although symptoms rarely occur in isol...
Abstract 14592: Trends in Systolic Blood Pressure and High-Sensitivity Troponin-T With Cardiovascular Disease: The Cardiovascular Health Study
Authors: David M Tehrani, Wenjun Fan, Vijay Nambi, Julius Gardin, Ezra Amsterdam, Calvin Hirsch, Christopher R deFilippi, Tamar Polonsky, Nathan D Wong
Journal: Circulation (2017)

Background: High-sensitivity troponin (hs-TnT) is individually associated with incident hypertension (HTN) and cardiovascular disease (CVD) events. The association of changes in both hs-TnT and blo...
PB2063 HAIRY CELL VARIANT–LABORATORY FINDINGS OF A CASE SERIES
Authors: A. Chereghini, M. Gonclaves, D. Daniel, R. Silva, Y. Maekawa, F. Muramoto, N. Tamashiro, T. Takao, A. Sandes, M. Silva
Journal: HemaSphere (2019)

Background: Hairy cell leukemias are rare mature B‐cell neoplasms that morphologically present cytoplasmatic projections. According to the most recent World Health Organization Classification, they can be Classic (HCL) or Variant (HCLv). These two diseases present important clinical and laboratory differences. HCLv is the rarest of them with an incidence of less than 1 case:1.000.000 inhabitants/year. Unlike HCL, HCLv generally presents with elevated blood counts, there is no monocytopenia and the abnormal cells present an identifiable nucleolus. HCLv cells do not express CD25 or present BRAF mutation mutations, findings that are almost universally present in HCL. Aims: The aim of this study was to describe the laboratory findings of all HCLv cases diagnosed at Grupo Fleury from 2015 to 2018. Methods A retrospective descriptive study of the laboratory findings of all HCLv cases diagnosed at Grupo Fleury from 2015 to 2018. Complete blood counts were obtained with a Sysmex XE 5000 counter and submitted to morphology review. Blood or bone marrow immunophenotypic prophiles were obtained using an 8‐color FACS Canto II cytometer for acquisition and Inifinicyt for analysis. Antibodies against CD3, CD4, CD5, CD8, CD10, CD11c, CD19, CD20, CD22, CD23, CD25, CD38, CD45, CD56, CD79b, CD103, CD123, CD200, KAPPA, LAMBDA, FMC7, IgM, IgD, IgG and IgA were used. Results: 7 cases were diagnosed during this period (0.04% of all of suspected oncological cases submitted immunophenotyping). Median age was 86 years old (range: 58‐89), and 3 were males. Median CBC values were [median (range)]: hemoglobin = 10.1 g/dL (8.8‐12.7); lymphocytes = 2.4 × 10 9 /L (1.4‐16.5); monocytes = 0.53 × 10 9 /L (0.2‐3.1); platelets = 91 × 10 9 /L (76‐97, and an outlier of 1.106 × 10 9 /L). No cases presented monocytopenia Flow cytometry (5 of peripheral blood and 2 of bone marrow aspirate), demonstrated universal positivity for CD19, CD20, FMC‐7, CD103, and CD11c (partial expression in one case). No case demonstrated CD5, CD10, CD25, CD38 or CD123. Of note, CD200 expression was negative or mild in all cases. Five cases were IgM+/IgD+, one IgM+, and the other was IgG+. Two demonstrated kappa expression and 5 were lambda light chain restricted. Karyotype was normal in all of the 3 cases analyzed. Summary/Conclusion: Flow cytometry, along with morphology, was the main sources of diagnosis, as no specific genetic alteration is known. The presence of CD103 and CD11c in the absence of CD123 and CD25 suggest HCLv, excluding classical HCL. CD200, classically strongly expressed in classical HCL was negative or only weakly expressed in HCLv and may help on diagnosis.
Diverse Behavior in 18F-Fluorocholine PET/CT of Brain Tumors in Patients With Neurofibromatosis Type 1
Authors: Francisco José Pena Pardo, José María Borrás Moreno, Fátima Jiménez Aragón, Jesús González García, Ana María García Vicente
Journal: Clinical Nuclear Medicine (2019)

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that causes CNS tumors in around 20% of patients, being pilocytic astrocytomas (PA), and particularly optic pathway gliomas (OPG), the most common. We present three cases of NF1 patients referred for F-fluorocholine PET/CT because of suspected glioma in the setting of ongoing FUMEGA (Functional and Metabolic Glioma Analysis) trial. One case turned out to be a WHO grade I ganglioglioma; the second was a high grade glioma; and the last one (negative in PET) a probable low-grade glioma.
PB1877 DISSECTION OF THE EFFECTS OF JAK AND BTK INHIBITORS ON THE FUNCTIONALITY OF HEALTHY AND MALIGNANT LYMPHOCYTES
Authors: T. Hofland, I. de Weerdt, H. ter Burg, R. de Boer, S. Tannheimer, S. Tonino, A. Kater, E. Eldering
Journal: HemaSphere (2019)

Background: Despite the emergence of small molecule inhibitors, current treatment modalities for chronic lymphocytic leukemia (CLL) are not curative, and the search for new therapeutic strategies continues. Pro-survival signaling derived from the micro-environment is often mediated via JAK signaling. However, whether JAK inhibitors are useful in CLL therapy has not been studied extensively. JAK inhibitors are valuable therapeutic agents in myelofibrosis and show promising results in graft-versus-host-disease, but are associated with an increased infection risk, presumably due to their effect on other immune cells. Other kinase inhibitors used for CLL treatment, like the BTK inhibitor ibrutinib and PI3Kδ inhibitor idelalisib, have similar off-tumor effects. Aims: We compared functional effects of the JAK inhibitors momelotinib and ruxolitinib, BTK inhibitors ibrutinib and tirabrutinib and PI3Kδ inhibitor idelalisib on malignant CLL cells, but also healthy T, B and NK lymphocytes. Methods: Immune modulation of CLL cells and healthy lymphocytes by kinase inhibitors was studied using in vitro stimulation assays that activate either B cells, NK cells or T cells. Results: We found several interesting differences among the inhibitors, apart from expected and well–known effects. Momelotinib but not ruxolitinib blocked cytokine-induced proliferation of CLL cells. Momelotinib also reduced B cell receptor (BCR) signaling in contrast to ruxolitinib, indicating that these JAK inhibitors in fact have a distinct target spectrum. In contrast to tirabrutinib, ibrutinib had inhibitory effects on T cell activation, probably due to ITK inhibition. Remarkably, both BTK inhibitors stimulated IFN-γ production in a mixed lymphocyte reaction. Summary/Conclusion: Collectively, our results demonstrate that kinase inhibitors directed at identical targets may have differential effects on lymphocyte function, and their unique profile could be strategically employed to balance desired versus unwanted lymphocyte inhibition in cancer- or autoimmune therapies.