tbuckley/cabot-search huggingface dataset:
Association of Longitudinal Trajectory of Albuminuria in Young Adulthood With Myocardial Structure and Function in Later Life
Authors: Ravi B. Patel, Laura A. Colangelo, Jared P. Reis, Joao A. C. Lima, Sanjiv J. Shah, Donald M. Lloyd-Jones
Journal: JAMA Cardiology (2019)

Albuminuria, as measured by single urine albumin-to-creatinine ratio (UACR) levels, is associated with cardiac remodeling and adverse clinical outcomes. The longitudinal patterns of change in UACR through young adulthood and their associations with myocardial structure and function later in life remain unclear.To describe the trajectory of albuminuria as measured by UACR across a 20-year span and evaluate the association of albuminuria trajectory with echocardiographic indices of structure and function in middle age.In the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of black and white participants aged 18 to 30 years at baseline (March 1985 to June 1986) were evaluated over 30 years. Participants underwent evaluations at 4 urban US sites. Data were collected from March 1985 to May 2016, and data were analyzed from September 2018 to April 2019.Trajectories of UACR from the year 10 examination to the year 30 examination as determined by latent class modeling.Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 30 examination.Of the 2647 included participants, 1441 (54.4%) were white, 1206 (45.6%) were black, and the mean (SD) age was 35.2 (3.6) years. A total of 5 trajectory groups of UACR were identified, including 1718 participants (64.9%) in the low-stable group, 682 (25.8%) in the moderate-stable group, 116 (4.4%) in the high-stable group, 88 (3.3%) in the moderate-increasing group, and 43 (1.6%) in the high-increasing group. Apart from the high-increasing cohort, the remaining 4 groups had median baseline UACR levels less than 30 mg/g. Male sex, current smoking, diabetes, and elevated blood pressure were more common in the moderate-increasing and high-increasing UACR groups. After adjustment for clinical variables and baseline UACR levels, there were significant differences in left ventricular (LV) mass by trajectory group (mean [SE] LV mass: high-increasing, 98.4 [3.4] g/m2; moderate-increasing, 91.7 [2.2] g/m2; high-stable, 86.0 [2.1] g/m2; moderate-stable, 82.3 [0.8] g/m2; low-stable, 78.6 [0.5] g/m2; P < .001). Significant differences by trajectory group were also noted in LV longitudinal strain, e' tissue velocities, and estimated LV filling pressures, even after adjustment for clinical variables and baseline UACR level. The association of trajectory group with indices of myocardial structure and function remained significant after adjustment for clinical variables and cumulative UACR from the year 10 to year 25 examinations.There are distinct patterns of change in albuminuria among young adults over a 20-year span, and these trajectory groups cannot be identified by baseline UACR level alone. Dynamic changes in albuminuria are independently associated with adverse alterations to cardiac structure, LV systolic function, and LV diastolic function.
18F-Fluorodeoxyglucose Positron Emission Tomography Versus Bone Marrow Biopsy for the Evaluation of Bone Marrow Infiltration in Newly Diagnosed Lymphoma Patients: Real-World Clinical Management of Patients at the National Cancer Institute, México
Authors: Tania Aguado, Antonio Olivas-Martinez, Uvi Cancino-Ramos, Diego Zúñiga, Carmen Lome, Silvia Rivas-Vera, Myrna Candelaria
Journal: Blood (2019)
Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells
Authors: Valentina Bonanni, Fabrizio Antonangeli, Angela Santoni, Giovanni Bernardini
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The peculiar multiple myeloma microenvironment, characterized by up-regulated levels of several inflammatory chemokines, including the CXCR3 receptor ligands CXCL9 and CXCL10, limits NK cell positioning into the bone marrow by interfering with CXCR4 function. It is still unclear if the consequent reduced influx of transferred cells into the tumor represents a potential limiting factor for the success of NK cell-based adoptive therapy. We hypothesize that inhibition of CXCR3 function on NK cells will result in increased tumor clearance, due to higher NK cell bone marrow infiltration. <h3>Methods</h3> Since different activation protocols differently affect expression and function of homing receptors, we analyzed the bone marrow homing properties and anti-tumor efficacy of NK cells stimulated in vitro with two independent protocols. NK cells were purified from wild-type or <i>Cxcr3</i><sup><i>−/−</i></sup> mice and incubated with IL-15 alone or with a combination of IL-12, IL-15, IL-18 (IL-12/15/18). Alternatively, CXCR3 function was neutralized in vivo using a specific blocking antibody. NK cell functional behavior and tumor growth were analyzed in bone marrow samples by FACS analysis. <h3>Results</h3> Both activation protocols promoted degranulation and IFN-γ production by donor NK cells infiltrating the bone marrow of tumor-bearing mice, although IL-15 promoted a faster but more transient acquisition of functional capacities. In addition, IL-15-activated cells accumulated more in the bone marrow in a short time but showed lower persistence in vivo. Targeting of CXCR3 increased the bone marrow homing capacity of IL-15 but not IL12/15/18 activated NK cells. This effect correlated with a superior and durable myeloma clearance capacity of transferred cells in vivo. <h3>Conclusions</h3> Our results demonstrate that in vitro activation affects NK cell anti-myeloma activity in vivo by regulating their BM infiltration. Furthermore, we provided direct evidence that CXCR3 restrains NK cell anti-tumor capacity in vivo according to the activation protocol used, and that the effects of NK cell-based adoptive immunotherapy for multiple myeloma can be improved by increasing their bone marrow homing through CXCR3 inhibition.
PDTM-34. RADIOSENSITIZATION BY BRD4 INHIBITION IN DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Takahiro Sasaki, Hiroaki Katagi, Dusten Unruh, Stewart Goldman, Lihua Zou, Ali Shilatifard, Rintaro Hashizume
Journal: Neuro-Oncology (2019)

Abstract Diffuse intrinsic pontine glioma (DIPG), the most frequent brainstem tumor in pediatrics, is one of the devastating childhood cancers, and virtually all patients die within two years after diagnosis. Since these tumors occur in the brainstem which is vital area, there are no surgical options for providing relief to patients, and conventional chemotherapy as well as radiation therapy provides palliative relief at best. DIPG shows increased H3 K27 acetylation (H3K27ac), which binds to BET bromodomain protein 4 (BRD4) and they are strongly associated with active transcription. Here we tested the hypothesis that BRD4 inhibition by JQ1 enhances radiation-induced DNA damage, making it a potential radiosensitizer in the treatment of DIPG. We evaluated the effects of JQ1 on genes expression using RNA sequence. Radiation-induced DNA double-strand break (DSB) repair was analyzed by immunocytochemistry and western blotting of DSB markers γH2AX and 53BP1, and DSB repair markers pRad50 and Rad51. Clonogenic survival assay was used to determine the effect of JQ1 on radiation response of DIPG cells. In vivo response to radiation monotherapy and combination therapy of RT and JQ1 were evaluated in patient-derived DIPG xenografts. JQ1 significantly reduced the expression of DNA DSB repair genes in DIPG cells. JQ1 sustained high levels of γH2AX and 53BP1 and reduced the levels of pRad50 and Rad51 in irradiated DIPG cells. JQ1 reduced clonogenic survival and enhanced radiation effect in DIPG cells. In vivo studies revealed increased survival of animals treated with combination therapy of RT and JQ1 in compared to either monotherapy. Together, these results highlight JQ1 as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG.
BMT CTN 1803: Haploidentical Natural Killer Cells (K-NK002) to Prevent Post-Transplant Relapse in AML and MDS (NK-REALM)
Authors: Sumithra Vasu, Nelli Bejanyan, Steven M Devine, Elizabeth O. Hexner, Brent Logan, Leo Luznik, Brittany K. Ragon, Andrew Sandler, Elizabeth F Krakow, Michael Fitzgerald, Lorraine Tracey, Richard E. Champlin
Journal: Blood (2020)
DNA Repair Genes' Expression Abnormalities in De Novo Acute Myelogenous Leukemia (AML): Implications for Targeted Treatment
Authors: Frieda Kontsioti, Eirini Maratou, Anthi Bouhla, Vassiliki Mpakou, Konstantinos Gkodopoulos, Georgia Stavroulaki, Eirini Glezou, Thomas Thomopoulos, Efthimia Bazani, Sotirios Papageorgiou, Argiris Symeonidis, George Dimitriadis, Vassiliki Pappa
Journal: Blood (2019)
CSIG-09. PROTEOMIC ANALYSIS OF MENINGIOMA CELL-DERIVED EXTRACELLULAR VESICLES: FIRST OF A KIND
Authors: Franz Ricklefs, Manka Fuh, Cecile Maire, Mareike Holz, Katharina Kolbe, Manfred Westphal, Hartmut Schlüter, Katrin Lamszus
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Extracellular vesicles (EVs) play an important role in cell-cell communication in different types of tumors, carrying multiple layers of biological functional molecules, including proteins, RNA, DNA and lipids. Their implication as biomarkers in tumor disease is under current investigation. We previously showed that EVs in glioblastoma reflect the tumor subtype and that glioblastoma patients have elevated circulating particle counts. Regarding to meningioma, it is not known to what extent these usually benign tumors secrete EVs and how these EVs reflect the tumor. Here we report the first study that analyzed meningioma cell-derived EVs. METHODS Meningioma tissue, short-term cell cultures and cell culture-derived EVs (menEVs), (n=4) were analyzed by global mass-spectromety, immunoblotting and imaging flow cytometry and compared to EVs from glioblastoma short-term cell cultures (gEVs), (n=4). Plasma EVs from meningioma patients (n = 12) were analyzed for their tetraspanin marker expression (CD9, CD81 and CD63). EVs were further analyzed by nanoparticle analysis (NTA) and electron microscopy. RESULTS menEVs were 110-140nm in size and exhibited vesicular structures by electron microscopy. We identified 269 proteins in menEVs through mass spectometry. 45 proteins were upregulated in menEVs compared to short-term cell culture and original tumor tissue. 99 proteins were exclusively found in menEVs compared to gEVs, with osteopontin being the top highly expressed protein within the mEV fraction. Both meningioma and glioblastoma patients have elevated circulating plasma EV counts (p&lt; 0.01), as measured by NTA. CONCLUSION The increase in circulating plasma EVs in meningioma patients suggests that tumor cell-derived EVs augment the pool of circulating EVs and could be utilized to obtain information on the tumor by liquid biopsy. Osteopontin is known to be expressed at high levels in meningiomas and its association with menEVs may facilitate isolation of circulating meningioma-specific EVs for analysis.
AUTO1, a Novel Fast Off CD19CAR Delivers Durable Remissions and Prolonged CAR T Cell Persistence with Low CRS or Neurotoxicity in Adult ALL
Authors: Claire Roddie, Maeve A O'Reilly, Maria A V Marzolini, Leigh Wood, Juliana Dias Alves Pinto, Mahnaz Abbasian, Ketki Vispute, Mark W. Lowdell, Graham Wheeler, Joanna Olejnik, Bilyana Popova, Kim Champion, Alexia Gali, Yashma Pathak, Victoria Spanswick, Helen Lowe, John A. Hartley, Farzin Farzaneh, David C. Linch, Martin Pule, Karl S Peggs
Journal: Blood (2019)
A Novel Targeted Approach to Achieve Immune System Reset: CD45-Targeted Antibody Drug Conjugates Enable Autologous HSCT, Ameliorate Disease in Autoimmune Models, Potently Kill Human Immune Cells from Normal Donors and MS Patients, and Achieve Immune Depletion in Non-Human Primates (NHP)
Authors: Geoff O Gillard, Jennifer L Proctor, Melissa L. Brooks, Tahirih L Lamothe, Sharon L. Hyzy, Oliver Mikse, Sean McDonough, Rahul Palchaudhuri, Anjali Bhat, Ganapathy N. Sarma, Prashant Bhattarai, Pranoti Sawant, Bradley R Pearse, Charlotte F. Mcdonough, Anthony E. Boitano, Michael P. Cooke
Journal: Blood (2019)
Estimated Life Expectancy and Income of Patients With Sickle Cell Disease Compared With Those Without Sickle Cell Disease
Authors: Deborah Lubeck, Irene Agodoa, Nickhill Bhakta, Mark Danese, Kartik Pappu, Robin Howard, Michelle Gleeson, Marc Halperin, Sophie Lanzkron
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Individuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD. <h3>Objective</h3> To estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD. <h3>Design, Setting, and Participants</h3> Cohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018. <h3>Main Outcomes and Measures</h3> Life expectancy, quality-adjusted life expectancy, and projected lifetime income. <h3>Results</h3> The estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates. <h3>Conclusions and Relevance</h3> In this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.
Night Transplantation and Catecholamine Exposure Accelerates In Vivo Leukemia Development By Enhancing Bone Marrow Homing Capacity in Leukemic Cells
Authors: Pauline Hanns, Anna M Paczulla, Martina Konantz, Marcelle Baer, Pontus Lundberg, Stefan Dirnhofer, Claudia Lengerke
Journal: Blood (2019)
CBFA2T3-GLIS2 Fusion Gene Cause Dismal Clinical Course in Acute Megakaryocytic Leukemia of Down Syndrome
Authors: Nao Takasugi, Kenichi Amano, Yasuo Kubota, Shota Kato, Yuichi Mitani, Junya Fujimura, Junko Takita, Mitsuteru Hiwatari
Journal: Blood (2019)
CMET-03. MANAGEMENT OF MULTIPLE BRAIN METASTASES BY STAGED SRS FOCUSING ON UTMOST RISK LESIONS
Authors: Junjie Zhen, Shaoqun Li, Mingyao Lai, lei wen, linbo cai
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Patients with multiple large brain metastases (LBMs) are subject to cause intracranial hypertension, which remains a clinical difficulty so far. The present study is to investigate whether staged stereotactic radiosurgery (SRS) is a feasible solution to improve clinical symptoms and life quality in palliative management. METHODS Patients with brain metastases treated between 1 January 2016 and 30 March 2019 were retrospectively studied. The patients inclusion criteria included were: 1) metastatic lesions ≥ 3; 2) tumor lesions with a supratentorial invasion ≥ 3 cm or a subtentorial invasion ≥ 2 cm; 3) with neurological impairment or with a high risk for intracranial hypertension. The first stage of SRS dose regimens for utmost risk supratentorial lesions were 20-24Gy within 2-fractions (fx); whereas 24Gy/3-fx for subtentorial lesions. For the 2nd stage, the rest metastatic lesions with relatively lower risk were treated with 16-18Gy/1-fx one week after that. RESULTS A total of 30 patients were enrolled included in this study. The neurological symptoms were significantly relieved following 1st stage of SRS, with a median period of 3 days (2–14 days). 13 out of 30 patients were randomly selected for MR imaging two weeks after SRS. It suggested that 84.6% (11/13) of the patients were observed with a clear reduction of tumor volume. The median reduced diameter was 0.38 (0.17–0.83) cm and a median volume reduction was 3.22 (0.01–9.08) mm3. According to RANO-BM, the objective remission rate of utmost risk lesions was 100%, whereas the less critical lesions was 95.16% (59/62). One patient (3.33%) was identified with acute adverse reaction (&gt; grade 3). CONCLUSIONS Staged SRS with a priority for utmost risk lesions was indicated to be an effective approach for multiple large brain metastases. Further prospective study is highly warranted.
Myopathy with Spina Bifida
Authors: R. G. Paley
Journal: BMJ (1947)

MYOPATHY WITH SPINA BIFIDA B treatment are the keynotes to success in this very serious abdominal emergency. SummaryThe anatomy, pathology, and aetiology of mesenteric vascular occlusion are described, and some of the literature is reviewed.Symptomatology and diagnosis are considered, and a plea is made for the earlier recognition of the disease.The importance of signs of cardiac, vascular, or blood disease, or of any evidence of haemorrhage from the bowel, is stressed.Two personal cases, with recovery, are presented.Treatment is discussed and the possibilities of the use of heparin are considered.I wish to express my thanks to Surg.Lieut.C.
The Frequency of Calr and MPL Gene Mutations in Jak2 V617F - Positive Chronic Myeloproliferative Neoplasms in Russia
Authors: Tatiana V Makarik, Adhamjon O Abdullaev, Sergei M. Kulikov, Elena E Nikulina, Svetlana A Treglazova, Irina N Subortseva, Alla M. Kovrigina, Anait L. Melikyan, Andrey B Sudarikov, Valery G. Savchenko
Journal: Blood (2019)
Management Algorithms for Gaucher Disease Type 1 in Saudi Arabia: A Consensus Result from a National Meeting
Authors: Ayman Alhejazi, Abdul Kareem Almomen, Ahmad M Tarawah, Ahmed M AlSuliman, Hussain H. Al Saeed, Mahsen AlSaleh, Ohoud F Kashari, Marwan Elbagoury, Omar Hussein
Journal: Blood (2019)
A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome
Authors: Amer M. Zeidan, Daniel A Pollyea, Jacqueline S Garcia, Andrew Brunner, Fernando Roncolato, Uma Borate, Olatoyosi Odenike, Ashish R. Bajel, Anne Marie Watson, Katharina Götze, Florian Nolte, Peter T. Tan, Wan-Jen Hong, Martin Dunbar, Ying Zhou, Lori Gressick, William Ainsworth, Jason Harb, Ahmed Hamed Salem, John Hayslip, Ronan Swords, Guillermo Garcia-Manero
Journal: Blood (2019)
2017-2018 Hematology Drug Approvals at the Food and Drug Administration (FDA): Communication of Patient-Reported Outcomes (PRO) Information in FDA Clinical Reviews and Prescribing Information (PI)
Authors: Janice Kim, Bindu Kanapuru, Jessica K Roydhouse, Ann T. Farrell, Najat Bouchkouj, Hussein Ezzeldin, Paul Kluetz
Journal: Blood (2019)
Lipidomic Profiling of Plasma Samples in Patients with Newly Diagnosed Multiple Myeloma; A Biomarker Study for Predicting the Response and Toxicities of Melphalan, Prednisolone and Bortezomib (MPB) Regimen : An Ancillary Study of the JCOG1105 (JCOG1105A1)
Authors: Masaki Ri, Shinsuke Iida, Dai Maruyama, Kosuke Saito, Yoshiro Saito, Satoshi Osaga, Masahiro Tohkin, Naoki Miyata, Kensei Tobinai, Noriko Fukuhara, Kana Miyazaki, Yosuke Minami, Norifumi Tsukamoto, Hideki Tsujimura, Makoto Yoshimitsu, Kenichi Miyamoto, Kunihiro Tsukasaki, Hirokazu Nagai
Journal: Blood (2019)
Once-Daily versus Twice-Daily Tacrolimus in Kidney Transplantation: A Systematic Review and Meta-analysis of Observational Studies
Authors: Somratai Vadcharavivad, Warangkana Saengram, Annop Phupradit, Nalinee Poolsup, Wiwat Chancharoenthana
Journal: Drugs (2019)

Tacrolimus is the most commonly prescribed medication in initial immunosuppressive regimens to prevent acute rejection in kidney transplant recipients (KTRs). Tacrolimus was originally available as an immediate-release formulation (IR-Tac) given twice daily. Extended-release tacrolimus (ER-Tac) given once daily was later developed with the expectation of improved medication adherence. Data from observational studies, which compared outcomes between ER-Tac and IR-Tac in different populations of KTRs including those who are unlikely to be enrolled in randomized clinical trials, have been reported.To evaluate the incidence of biopsy-proven acute rejection (BPAR) at 12 months together with other outcomes reported in observational studies among adult KTRs who received ER-Tac compared to IR-Tac.In accordance with the recommendations of the Cochrane Collaboration and the Meta-analysis of Observational Studies in Epidemiology, we systematically reviewed all observational studies that compared clinical outcomes between ER-Tac and IR-Tac in KTRs. The systematic searches were conducted on PubMed, EMBASE, Scopus, and Web of Science without language restriction. Reference lists were also searched and reviewed. Data were extracted for BPAR, graft survival, patient survival, estimated glomerular filtration rate (eGFR), serum creatinine (Scr), creatinine clearance (CrCl), at different times after kidney transplantation (KT). A meta-analysis was performed to integrate the results from the eligible studies. This study is registered with PROSPERO, number CRD42019135705.From the 1401 articles screened, 10 observational studies in KTRs who received tacrolimus were included. The pooled results showed significantly lower BPAR with ER-Tac than with IR-Tac at 12 months post-KT (5 studies, n = 659; RR, 0.69; 95% CI 0.51-0.95; p = 0.02; I2 = 0%). No significant differences in BPAR at other time points after KT were found. Graft survival, patient survival, Scr, and eGFR were comparable between groups at different times over approximately 1 year after transplantation.Based upon currently available evidence in observational studies, 30% lower risk of BPAR was observed in ER-Tac group compared with IR-Tac group at 12 months post-KT, while there was no significant difference in BPAR risk at any other studied time points. No differences in graft- and patient-survival rates and kidney function were found. Given the limitations of observational studies to make causal inference, as well as quality limitations among the included studies, caution should be exercised in interpreting these findings.
Novel Evidence That the Nlrp3 Inflammasome Plays a Role in Bone Marrow As a "Cogwheel" Connecting Purinergic Signaling with Activation of the Complement Cascade to Induce "Sterile Inflammation", Which Is Required for Optimal Mobilization of Hematopoietic Stem/Progenitor Cells
Authors: Mateusz Adamiak, Anna Lenkiewicz, Kamila Bujko, Arjun Thapa, Magdalena Kucia, Ahmed Abdel-Latif, Janina Ratajczak, Mariusz Z Ratajczak
Journal: Blood (2019)