tbuckley/cabot-search huggingface dataset:
Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W)
Authors: Maxime Dougados, James Cheng-Chung Wei, Robert Landewé, Joachim Sieper, Xenofon Baraliakos, Filip Van den Bosch, Walter P Maksymowych, Joerg Ermann, Jessica A Walsh, Tetsuya Tomita, Atul Deodhar, Désirée van der Heijde, Xiaoqi Li, Fangyi Zhao, Clinton C Bertram, Gaia Gallo, Hilde Carlier, Lianne S Gensler
Journal: Annals of the Rheumatic Diseases (2019)

Objectives To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W). Methods Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52. Results In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks. Conclusion The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab. Trial registration number NCT02696785 / NCT02696798 .
TMOD-02. IN VITRO &amp; IN VIVO CULTURE OF PATIENT DERIVED (PD) CSF-CTCS IN LEPTOMENINGEAL DISEASE (LMD) FROM MELANOMA TO IDENTIFY NOVEL TREATMENT STRATEGIES
Authors: Vincent Law, Brittany Evernden, John Puskas, Gisela Caceres, Elena Ryzhova, Inna Smalley, Nam Tran, Arnold Etame, Anthony Magliocco, Keiran Smalley, Peter Forsyth
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Approx. 5% of melanoma pts develop LMD. There are essentially no models of LMD available for therapeutic development. A significant barrier to the development of effective therapies against LMD has been the inability to culture and expand LMD cells. Here we report our strategies to in vitro &amp; in vivo culturing of CSF-CTCs. As a proof of concept, we assessed response to Ceritinib (Cer), a non-canonical IGF1R inhibitor) in combination with MEK inhibitor. METHODS We collected CSF from 11 patients (pts) from various sources (ie: LPs, Ommayas, autopsies). 3 pts CSF were collected at autopsies. PD-CSF-CTCs were expanded in vitro in conditioned media and in vivo using CDX model. scRNAseq analysis was performed to assess expression profiles of PD-CSF-CTCs. RESULTS AND DISCUSSION Of the total 61 PD-CSF-CTCs collected from 11 pts (avg: 4.07 CSF collections/patient), we successfully cultured PD-CSF-CTCs from 3 pts (20%) and were able to grow them in vivo from 2 pts (18%). scRNAseq analysis identified MLANA, IGF1R, SOX9 and ErbB3 were among genes highly expressed in our PD-CSF-CTCs. We evaluated the responses of the combination Cer with MEKi (Tra) in vitro and in vivo and found that these agents produced therapeutic effects to both established melanoma cell lines and our PD-CSF-CTCs. For example, in vivo testing showed a median survival (MS): 18, 35, and 27 days in WM164, WM164R and the PD-CSF-CTCs, respectively, in control groups. Whereas treatment with Cer + Tra produced significantly better MS in all three in vivo models and was not reached in WM164, WM164R (p&amp;lt; 0.001 &amp; p&amp;lt; 0.047, respectively) and 38.5 days in PD-CSF-CTCs (p&amp;lt; 0.032). CONCLUSIONS Though the sample size is small, this is the first report of the successful in vitro &amp; in vivo culture of CSF-CTCs from pts with LMD.
Skeletal Muscle Loss during Tyrosine Kinase Inhibitor Treatment for Advanced Hepatocellular Carcinoma Patients
Authors: Shinsuke Uchikawa, Tomokazu Kawaoka, Maiko Namba, Kenichiro Kodama, Kazuki Ohya, Kei Morio, Takashi Nakahara, Eisuke Murakami, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Shoichi Takahashi, Kazuaki Chayama, Hiroshi Aikata
Journal: Liver Cancer (2019)

The measurement of body composition such as the skeletal muscle index (SMI) has been reported to be useful for predicting prognosis in hepatocellular carcinoma (HCC). In this study, we analyzed skeletal muscle change during sorafenib and lenvatinib therapy and the association between SMI and prognosis.A total of 67 patients with advanced HCC and Child-Pugh grade A status treated with tyrosine kinase inhibitors (TKIs) at Hiroshima University between September 2009 and December 2018 were enrolled in this retrospective cohort study. Patients underwent computed tomography (CT) imaging before starting sorafenib treatment and 1-3 months after treatment initiation.In all patients, the median SMI was 45.3 cm2/m2 before TKI treatment and 42.1 cm2/m2 after treatment; 54 of 67 (80.6%) patients experienced SMI loss. The median ΔSMI was -1.5 cm2/m2/months, and no difference in ΔSMI was observed between patients receiving sorafenib and lenvatinib. No significant differences were observed in median ΔSMI between patients with and without progressive disease (-2.35 and -1.1 cm2/m2/months, respectively), albumin-bilirubin grade 1 and 2 group disease (-1.7 and -1.5 cm2/m2/months, respectively), and relative dose intensity ≤80 and >80 (-1.8 and -1.2 cm2/m2/months, respectively).This report demonstrated that patients receiving TKI treatment experienced a significant loss of skeletal muscle mass regardless of disease progression, hepatic reserve, or which TKI (sorafenib or lenvatinib) they received.
Safety with Parathion
Authors: J. S. Dodge
Journal: BMJ (1964)

BJORNAL 1593 only one survivor has been reported from haemorrhage into the peritoneal cavity.Several surgical operations have been tried for this condition,3 such as excision of the aneurysm followed either by end-to-end suture of the hepatic artery or by anastomosis of the proximal end of the splenic artery (after splenectomy) with the distal end of the hepatic artery.We are grateful to Mr. J.
Efficacy and Safety of Subcutaneous Prophylaxis with Concizumab in Patients with Hemophilia a or B with Inhibitors: Results from explorer4, a Phase 2, Randomized, Open-Label, Controlled Trial
Authors: Amy Shapiro, Giancarlo Castaman, Katarina Cepo, Lone Hvitfeldt Poulsen, Christian Hollensen, Tadashi Matsushita, Guy Young, Silva Zupancic-Salek, Victor Jimenez-Yuste
Journal: Blood (2019)
Modeling Tumor Evolutionary Dynamics to Predict Clinical Outcomes for Patients with Metastatic Colorectal Cancer: A Retrospective Analysis
Authors: Jiawei Zhou, Yutong Liu, Yubo Zhang, Quefeng Li, Yanguang Cao
Journal: Cancer Research (2019)

Over 50% of colorectal cancer patients develop resistance after a transient response to therapy. Understanding tumor resistance from an evolutionary perspective leads to better predictions of treatment outcomes. The objectives of this study were to develop a computational framework to analyze tumor longitudinal measurements and recapitulate the individual evolutionary dynamics in metastatic colorectal cancer (mCRC) patients. A stochastic modeling framework was developed to depict the whole spectrum of tumor evolution prior to diagnosis and during and after therapy. The evolutionary model was optimized using a nonlinear mixed effect (NLME) method based on the longitudinal measurements of liver metastatic lesions from 599 mCRC patients. The deterministic limits in the NLME model were applied to optimize the stochastic model for each patient. Cox proportional hazards models coupled with the least absolute shrinkage and selection operator (LASSO) algorithm were applied to predict patients' progression-free survival (PFS) and overall survival (OS). The stochastic evolutionary model well described the longitudinal profiles of tumor sizes. The evolutionary parameters optimized for each patient indicated substantial interpatient variability. The number of resistant subclones at diagnosis was found to be a significant predictor to survival, and the hazard ratios with 95% CI were 1.09 (0.79-1.49) and 1.54 (1.01-2.34) for patients with three or more resistant subclones. Coupled with several patient characteristics, evolutionary parameters strongly predict patients' PFS and OS. A stochastic computational framework was successfully developed to recapitulate individual patient evolutionary dynamics, which could predict clinical survival outcomes in mCRC patients. SIGNIFICANCE: A data analysis framework depicts the individual evolutionary dynamics of mCRC patients and can be generalized to project patient survival outcomes.
Allogeneic Hematopoietic Stem Cell Transplantation for Therapy-Related Myelodysplastic Syndromes and Acute Myeloid Leukemia
Authors: Leland Metheny, Wael Saber, Daniel J. Weisdorf, Marcos de Lima, Natalie Scott Callander, Mark Litzow, Partow Kebriaei, Aric C. Hall, Brenda M Sandmaier, Mei-Jie Zhang, Hai-Lin Wang, Khalid Bo-Subait
Journal: Blood (2019)
Achieving Early Remission By Induction Therapy Predicts a Favorable Outcome in Patients with Acute Myeloid Leukemia and an Intermediate Risk Karyotype Undergoing Allogeneic Stem Cell Transplantation in First Complete Remission
Authors: Philipp G. Hemmati, Theis H. Terwey, Il-Kang Na, Philipp le Coutre, Christian F. Jehn, Lam G. Vuong, Bernd Dörken, Renate Arnold
Journal: Blood (2014)
NIMG-67. DEVELOPMENT OF VERSATILE MACHINE-LEARNING APPROACHES FOR RADIOGENOMICS OF GLIOMA IN DIFFERENT COHORTS
Authors: Masamichi Takahashi, Risa Kawaguchi, Satoshi Takahashi, Mototaka Miyake, Manabu Kinoshita, Koichi Ichimura, Ryuji Hamamoto, Yoshitaka Narita, Jun Sese
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Radiogenomics aims to analyze clinical images and information, and to predict key molecular profiles of tumors. However, imaging protocol is usually different in facilities, and it has been rarely examined whether the performance of developed methods in a dataset is robustly sustained even in other independent datasets. We explored machine learning and matrix decomposition methods using preoperative magnetic resonance images (MRIs) of glioma patients to establish versatile platform regardless of the heterogeneity of the datasets. METHODS Preoperative glioma MRIs and clinical information were obtained from public dataset of The Cancer Imaging Archive (TCIA, N=159) and National Cancer Center Hospital (NCC, N=166). More than 16,000 radiomic features were applied for the prediction of tumor grading and IDH mutation status. Accuracy of prediction was evaluated by AUROC (area under the receiver operating characteristic curves). RESULTS The performances were comparable between the image features regardless of dimension reduction methods (the best accuracy for tumor grading and IDH status prediction was 0.91 and 0.88, respectively), but they were drastically decreased in the transfer learning (0.70 and 0.69). On the other hand, they were successfully improved by applying matrix decomposition and brain embedding (0.86 and 0.79). CONCLUSION Our result and pipeline can be a global benchmark for future studies in heterogeneous datasets. Further evaluation in larger cohorts are planned.
Synergistic effects of interleukin-1 beta and interleukin-3 on the expansion of human hematopoietic progenitor cells in liquid cultures
Authors: M Kobayashi, M Imamura, Y Gotohda, S Maeda, H Iwasaki, K Sakurada, M Kasai, AJ Hapel, T Miyazaki
Journal: Blood (1991)
Identification of Optimal Thalassemia Screening Strategies for Migrant Populations in Thailand: A Mixed-Methods Approach
Authors: Julia Z. Xu, Meghan Foe, Wilaslak Tanongsaksakul, Thidarat Suksangpleng, Supachai Ekwattanakit, Suchada Riolueang, Marilyn J. Telen, Bonnie N. Kaiser, Vip Viprakasit
Journal: Blood (2019)
More mental health beds are needed to reduce out-of-area treatment, says royal college
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The Royal College of Psychiatrists has called for hundreds more NHS mental health beds in England to end the “shameful” practice of sending severely ill patients far from their home for treatment.

“Out of area” placements are necessary when no local hospital bed is available to admit the patient. The government has pledged to end all inappropriate out-of-area placements for acutely ill adult patients by 2021.

But the college warned that progress towards this target had been too slow. …
Clinical Outcomes of Patients (pts) with TP53-Mutated Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS): A Single Center Experience
Authors: Jan Philipp Bewersdorf, Rory M Shallis, Lohith Gowda, Karl Hager, Nikolai A. Podoltsev, Steven D. Gore, Thomas Prebet, Stephanie Halene, Iris Isufi, Francine M. Foss, Scott F. Huntington, Tae Kon Kim, Manoj M Pillai, Terri L Parker, Natalia Neparidze, Noffar Bar, Stuart Seropian, Alexa J. Siddon, Amer M. Zeidan
Journal: Blood (2019)
Cancer-Related Distress and Unmet Needs Among Acute Myeloid Leukemia Survivors
Authors: Alexandra K Zaleta, Pierre Gardan, Shauna McManus, Melissa F. Miller, Kelly Clark, Nicole E Nicksic, Hildy Dillon, Tara Albrecht, Areej El-Jawahri, Clare Karten, Thomas W. LeBlanc, Jane L. Liesveld, Elizabeth Muenks, Barbara B. Rogers, Kristin Scheeler, Linda House
Journal: Blood (2019)
Procarbazine-Free Escalated Beacopdac in Frontline Therapy of Advanced Hodgkin Lymphoma Reduces Red Cell Transfusion Requirements and May Shorten Time to Menstrual Period Recovery Compared to Escalated Beacopp and Appears to be As Efficacious
Authors: Anna Santarsieri, Katherine Sturgess, Pauline Brice, Tobias F Menne, Wendy Osborne, Thomas Creasey, Kirit M. Ardeshna, Sarah Behan, Stephen Booth, Graham P. Collins, Kate Cwynarski, Sunil Iyengar, Stephen G Jones, Deirdre O'Mahony, Nicolas Martinez-Calle, Pamela McKay, Sateesh K Nagumantry, John Rudge, Nimish Shah, Gwyneth Stafford, Alexander Sternberg, Benjamin J Uttenthal, Andrew K McMillan, George A Follows
Journal: Blood (2019)
SCIDOT-17. UNDERSTANDING THE EFFECTS OF MOLECULAR SIZE ON VOLUME OF DISTRIBUTION IN CONVECTION-ENHANCED DELIVERY
Authors: Julian S Rechberger, Erica A Power, Liang Zhang, Ian Olson, Victor M Lu, David J Daniels
Journal: Neuro-Oncology (2019)

Abstract Diffuse midline gliomas harboring the H3K27M mutation, previously known as diffuse intrinsic pontine gliomas (DIPG), are rare and aggressive pediatric brain tumors without cure. One of the major challenge sin DIPG treatment is the effective delivery of therapeutic agents across the blood-brain barrier (BBB) to the tumor and surrounding infiltrating cells. Therefore, strategies that enhance drug delivery to the brain are of great interest. Convection-enhanced delivery (CED) is a technique that bypasses the BBB and increases drug distribution by applying hydraulic pressure to deliver compounds directly and evenly into a target region. However, knowledge in CED pharmacology and convective kinetics is still lacking. In an effort to characterize the feasibility, safety, and distribution in the brain based on molecular size of the delivered agent, we performed infusions of FITC-dextran (range 3,000 Da–150,000 Da) comparing CED and osmotic pump-based delivery into the brainstem of rodents. We calculated the area and volume of distribution (Vd) of the FITC-dextran throughout the brain. Our data showed that the Vd decreased exponentially with increased molecular weight of the FITC-dextran. Interestingly, the Vdcan maintain linearity at lower molecular weights. Maximal cross-sectional area and craniocaudal extension of fluorescence also decreased when lowering the infusate size. In addition, we developed a patient-derived DIPG orthotopic xenograft model and performed an image-guided CED cannula installation in the tumor bed. Using 3D bioluminescence imaging and computed tomography, we determined the tumor volume and the positioning of the cannula in the bulk tumor. The summation of these results supports CED as a promising technique for treating DIPG tumors. A better understanding of how drugs distribute by convection will allow us to optimize treatment regimens and, ultimately, offers hope to patients and families with this devastating disease.
Return to work after critical illness: a systematic review and meta-analysis
Authors: Biren B Kamdar, Rajat Suri, Mary R Suchyta, Kyle F Digrande, Kyla D Sherwood, Elizabeth Colantuoni, Victor D Dinglas, Dale M Needham, Ramona O Hopkins
Journal: Thorax (2019)

Background Survivors of critical illness often experience poor outcomes after hospitalisation, including delayed return to work, which carries substantial economic consequences. Objective To conduct a systematic review and meta-analysis of return to work after critical illness. Methods We searched PubMed, Embase, PsycINFO, CINAHL and Cochrane Library from 1970 to February 2018. Data were extracted, in duplicate, and random-effects meta-regression used to obtain pooled estimates. Results Fifty-two studies evaluated return to work in 10 015 previously employed survivors of critical illness, over a median (IQR) follow-up of 12 (6.25–38.5) months. By 1–3, 12 and 42–60 months’ follow-up, pooled return to work prevalence (95% CI) was 36% (23% to 49%), 60% (50% to 69%) and 68% (51% to 85%), respectively ( τ 2 =0.55, I 2 =87%, p=0.03). No significant difference was observed based on diagnosis (acute respiratory distress syndrome (ARDS) vs non-ARDS) or region (Europe vs North America vs Australia/New Zealand), but was observed when comparing mode of employment evaluation (in-person vs telephone vs mail). Following return to work, 20%–36% of survivors experienced job loss, 17%–66% occupation change and 5%–84% worsening employment status (eg, fewer work hours). Potential risk factors for delayed return to work include pre-existing comorbidities and post-hospital impairments (eg, mental health). Conclusion Approximately two-thirds, two-fifths and one-third of previously employed intensive care unit survivors are jobless up to 3, 12 and 60 months following hospital discharge. Survivors returning to work often experience job loss, occupation change or worse employment status. Interventions should be designed and evaluated to reduce the burden of this common and important problem for survivors of critical illness. Trial registration number PROSPERO CRD42018093135.
EXTH-20. HYPERPOLARIZED [2-13C] PYRUVATE TO [5-13C] GLUTAMATE AS BIOMARKERS OF IDH1 MUTANT GLIOMA RESPONSE TO TEMOZOLOMIDE THERAPY
Authors: Elavarasan Subramani, Chloe Najac, Georgios Batsios, Pavithra Viswanath, Marina Radoul, Anne Marie Gillespie, Russell O Pieper, Sabrina Ronen
Journal: Neuro-Oncology (2019)

Abstract Low-grade gliomas, driven by mutations in the cytosolic isocitrate dehydrogenase 1 (IDH1) gene, are less aggressive than primary glioblastoma, but nonetheless always recur and ultimately lead to patient death. The treatment of IDH1 mutant patients with Temozolomide (TMZ) improves survival, but there remains a need for complementary imaging methods to assess response to therapy at an early time point. The goal of this study was, therefore, to determine the value of magnetic resonance spectroscopy (MRS)-based metabolic imaging biomarkers for detection of response to treatment. To this end we investigated NHA and U87 cells expressing IDH1 R132H mutant gene (NHAIDHmut and U87IDHmut) and first used 1H MRS combined with chemometrics to examined the metabolic alterations that occurred following treatment with the IC50 value of TMZ. We observed a significant increase in 2-hydroxyglutarate (2-HG), glutamate, and glutamine, and metabolic pathway analysis showed tricarboxylic acid (TCA) cycle and pyruvate metabolism to be significantly altered pathways following TMZ treatment compared to DMSO control. To confirm changes in TCA cycle flux and to assess the metabolic pathways contributing to the increase in 2-HG and glutamate/glutamine, cells were then labelled with [1-13C] glucose and [3-13C] glutamine. Our data indicated that both glucose flux via the TCA to glutamate and 2HG, and the contribution of glutamine to glutamate and 2HG were increased following TMZ treatment. Finally, we used hyperpolarized 13C-MRS to dynamically probe the metabolism of hyperpolarized [2-13C] pyruvate and its conversion to hyperpolarized [5-13C] glutamate via the TCA cycle. Consistent with our previous findings, we observed that hyperpolarized [5-13C] glutamate synthesis was significantly higher in TMZ-treated cells compared to controls. Collectively, our findings identify 1H MRS-detectable elevation of 2-HG and glutamate/glutamine as well as hyperpolarized 13C-MRS-detectable [5-13C] glutamate production from [2-13C] pyruvate as potentially translatable metabolic biomarkers of response to TMZ therapy in mutant IDH1 glioma.
Reevaluating the Use of the Nationwide Inpatient Sample to Identify Incident Cases of Atrial Fibrillation After Aortic Valve Replacement—Reply
Authors: Rajat Kalra, Nirav Patel, Pankaj Arora
Journal: JAMA Internal Medicine (2019)

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Individualized Prediction of Follicular Lymphoma Risk Using a Combination of Blood t(14;18) Frequency Years before Diagnosis and a Polygenic Risk Score (PRS) of 9 SNPs Associated with Follicular Lymphoma Susceptibility
Authors: Herve Ghesquieres, Youenn Drouet, Manon Zala, Paolo Vineis, Gilles A. Salles, Bertrand Nadel, Sandrine Roulland
Journal: Blood (2019)