tbuckley/cabot-search huggingface dataset:
Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Colorado Children, 2010–2017
Authors: G. Todd Alonso, Alex Coakley, Laura Pyle, Katherine Manseau, Sarah Thomas, Arleta Rewers
Journal: Diabetes Care (2019)

OBJECTIVE We examined trends in diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes at a large pediatric diabetes center between 2010 and 2017, overlapping with the Affordable Care Act’s overhaul of U.S. health care. RESEARCH DESIGN AND METHODS Colorado residents &amp;lt;18 years old who were diagnosed with type 1 diabetes from 2010 to 2017 and subsequently followed at the Barbara Davis Center for Diabetes were included. Logistic regression models were used to test associations among age, sex, race/ethnicity, insurance, language, year of diagnosis, and rural/nonrural residence and DKA at diagnosis. Linear regression models were used to test the association of each predictor with HbA1c at diagnosis. RESULTS There were 2,429 subjects who met the inclusion criteria. From 2010 to 2017, the rate of DKA increased from 41 to 58%. It increased from 35.3 to 59.6% among patients with private insurance (odds ratio 1.10 [95% CI 1.05–1.15]; P &amp;lt; 0.0001) but remained unchanged (52.2–58.8%) among children with public insurance (1.03 [0.97–1.09]; P = 0.36). In the multivariable model, public insurance (1.33 [1.08–1.64]; P = 0.007), rural address (1.42 [1.08–1.86]; P = 0.013), and HbA1c (1.32 [1.26–1.38]; P &amp;lt; 0.0001) were positively associated with DKA, whereas age, race/ethnicity, sex, and primary language were not. CONCLUSIONS The increase in the rate of DKA in patients with newly diagnosed type 1 diabetes was driven by patients with private insurance. This paradoxically occurred during a time of increasing health insurance coverage. More study is needed to understand the factors driving these changes.
Characteristics and treatment regimens across ERS SHARP severe asthma registries
Authors: Job J.M.H. van Bragt, Ian M. Adcock, Elisabeth H.D. Bel, Gert-Jan Braunstahl, Anneke ten Brinke, John Busby, Giorgio W. Canonica, Hui Cao, Kian Fan Chung, Zsuzsanna Csoma, Barbro Dahlén, Elizabeth Davin, Susanne Hansen, Enrico Heffler, Ildiko Horvath, Stephanie Korn, Maxim Kots, Piotr Kuna, Namhee Kwon, Renaud Louis, Vicente Plaza, Celeste Porsbjerg, David Ramos-Barbon, Levi B. Richards, Sabina Škrgat, Jacob K. Sont, Susanne J.H. Vijverberg, Els J.M. Weersink, Valentyna Yasinska, Scott S. Wagers, Ratko Djukanovic, Anke H. Maitland-van der Zee
Journal: European Respiratory Journal (2019)

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals. This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases. Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m −2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day −1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day −1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively. The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
Validation of the International Scale for Measurement of BCR-ABL by RQ-PCR Based on Deriving Laboratory-Specific Conversion Factors.
Authors: Susan Branford, Linda Fletcher, Nicolas C.P. Cross, Andreas Hochhaus, Martin C. Mueller, Dong-Wook Kim, Jerald Radich, Giuseppe Saglio, Fabrizio Pane, Kevin Lynch, John M. Goldman, Timothy Hughes
Journal: Blood (2007)
Factors that could potentially impact on the initiation time of oncology clinical trials at investigational sites
Authors: Ayaka Sano, Hiromi Sasamoto, Mitsuyoshi Nakamura, Koji Ando, Naomi Shimada, Yayoi Kondo, Junichiro Sawa, Ryuichi Ebisawa, Hajime Suzuki, Akihiro Maruhashi, Takanori Tsuda, Xinbin Qiu, Nobuyuki Shiga, Jotaro Shinagawa
Journal: Annals of Oncology (2019)
Significantly Increased Accumulation of 18F-FDG Throughout the Left Middle Cerebral Artery Territory Corresponding to Acute-Phase Infarction
Authors: Chio Okuyama, Takuro Nakae, Satoshi Oka, Jun Nohara, Hiroshi Yamauchi
Journal: Clinical Nuclear Medicine (2019)

A 70-year-old woman had spontaneous resolution of an embolism in her right middle cerebral artery (MCA) (day 1); another embolism occurred in her left MCA (day 3), which was promptly removed. On day 5, F-FDG PET/CT performed for staging mediastinal lymphoma showed marked FDG accumulation in the left MCA territory, whereas a defect was seen in the right insular region. Eventually, bilateral lesions developed irreversible infarction. Anaerobic metabolism and/or inflammation in acute-phase infarction were the supposed mechanism for the increased accumulation of FDG in her left MCA territory.
Expression of B7-H1 in Mantle Cell Lymphoma Leads to Inhibition of T Cell Response to Tumor Cells
Authors: Lijuan Wang, Jianfei Qian, Yong Lu, Haiyan Li, Sungyoul Hong, Hanying Bao, Donghua He, Zhiqiang Liu, Yuhuan Zheng, Jin He, Yongsheng Lan, Yi Li, Sattva Neelapu, Jing Yang, Michael Wang, Cai Zhen, Qing Yi
Journal: Blood (2011)
Oligosaccharide Expression and Modification Defines Novel Targets within the Vascular Tree: Selective Chondroitin Sulfate C Expression in the Tumor Microenvironment Generates a Novel Target of Otherwise Constitutive Receptors.
Authors: Amr El-Sheikh, Gourab Bhattacharjee, Per Borgstrom, Mattias Belting, Thomas Edgington
Journal: Blood (2004)
Human Monoclonal Antibody Targeting IL-17A (AIN457) Down-Regulates MM Cell-Growth and Survival and Inhibits Osteoclast Development In Vitro and In Vivo: A Potential Novel Therapeutic Application In Myeloma
Authors: Rao H Prabhala, Mariateresa Fulciniti, Dheeraj Pelluru, Puru Nanjappa, Christine Pai, Saem Lee, Nithya Prabhala, Weihua Song, Constantine S. Mitsiades, Konstantinos Lefkimmiatis, Yu-Tzu Tai, Irene Ghobrial, Paul Richardson, John Daley, Kenneth C. Anderson, Seth Ettenberg, Franco Di Padova, Nikhil C. Munshi
Journal: Blood (2010)
On-Going Evolution Of IGH In B-Cell Precursor Acute Lymphoblastic Leukemia Does Not Substantially Affect Day 29, Post-Treatment MRD Quantification By High-Throughput Sequencing
Authors: David Wu, Ryan O Emerson, Anna Sherwood, Mignon L. Loh, Anne Angiolillo, Ilan Kirsch, Christopher S Carlson, David Williamson, Brent L. Wood, Harlan Robins
Journal: Blood (2013)
Dose Dependent Enhancement Of Neutrophil Recovery By Infusion Of Notch Ligand Ex Vivo Expanded Cord Blood Progenitors: Results Of a Multi-Center Phase I Trial
Authors: Colleen Delaney, Filippo Milano, Ian Nicoud, Shelly Heimfeld, Chatchada Karanes, Jonathan A Gutman, John E. Wagner, Frederick R. Appelbaum, Irwin D. Bernstein
Journal: Blood (2013)
Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing in Transgenic Mice
Authors: Cara Lunn Shirai, James N Ley, Brian S. White, Justin Tibbitts, Jin Shao, Matthew Ndonwi, Sanghyun Kim, Brian Wadugu, Theresa Okeyo-Owuor, Timothy A. Graubert, Matthew J. Walter
Journal: Blood (2014)
Investigation of the Molecular Basis of High Oxygen Affinity Hemoglobin Brigham (α2Aβ2100 Pro→Leu) In a Subject with Familial Erythrocytosis
Authors: Bindu Abraham, Yiping Jia, Francine Wood, Chad Reiter, Jay Nelson Lozier, Jeffery L. Miller, Abdu Alayash
Journal: Blood (2010)
Impact of Surgical Resection on Survival Outcomes After Chemoradiotherapy in Anal Adenocarcinoma
Authors: Richard Li, Ashwin Shinde, Marwan Fakih, Stephen Sentovich, Kurt Melstrom, Rebecca Nelson, Scott Glaser, Yi-Jen Chen, Karyn Goodman, Arya Amini
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Anal adenocarcinoma is a rare malignancy with a poor prognosis, and no randomized data are available to guide management. Prior retrospective analyses offer differing conclusions on the benefit of surgical resection after chemoradiotherapy (CRT) in these patients. We used the National Cancer Database (NCDB) to analyze survival outcomes in patients undergoing CRT with and without subsequent surgical resection. Methods: Patients with adenocarcinoma of the anus diagnosed in 2004 through 2015 were identified using the NCDB. Patients with metastatic disease and survival &lt;90 days were excluded. We analyzed patients receiving CRT and stratified by receipt of surgical resection. Logistic regression was used to evaluate predictors of use of surgery and to form a propensity score–matched cohort. Overall survival (OS) was compared between treatment strategies using Cox proportional hazards regression. Results: We identified 1,747 patients with anal adenocarcinoma receiving CRT, of whom 1,005 (58%) received surgery. Predictors of increased receipt of surgery included age &lt;65 years, private insurance, overlapping involvement of the anus and rectum, N0 disease, and external-beam radiation dose ≥4,000 cGy. With a median follow-up of 3.5 years, 5-year OS was 61.1% in patients receiving CRT plus surgery compared with 39.8% in patients receiving CRT alone (log-rank P &lt;.001). In multivariate analysis, surgery was associated with significantly improved OS (hazard ratio, −0.59; 95% CI, 0.50–0.68; P &lt;.001). This survival benefit persisted in a propensity score–matched cohort (log-rank P &lt;.001). Conclusions: In the largest series of anal adenocarcinoma cases to date, treatment with CRT followed by surgery was associated with a significant survival benefit compared with CRT alone in propensity score–matching analysis. Our findings support national guideline recommendations of neoadjuvant CRT followed by resection for patients with anal adenocarcinoma.
Kinetics of Immune Responses and Tumor Burden in Patients with Indolent B Cell Lymphomas Receiving Recombinant Idiotype Vaccination as the Sole Treatment.
Authors: Cristina Bertinetti, Frank Schueler, Kristina Heining-Mikesch, Katja Zirlik, Tina Tomann, Brigitte Franke, Gottfried Dolken, Hendrik Veelken
Journal: Blood (2006)
Physiologic Frailty Among Hematopoietic Cell Transplantation (HCT) Survivors Suggests Accelerated Aging and Is a Predictor for Premature Mortality: A Report from the Bone Marrow Transplant Survivor Study (BMTSS)
Authors: Mukta Arora, Can-Lan Sun, Kirsten K. Ness, Jennifer Berano Teh, Jessica Wu, Liton F. Francisco, Saro Armenian, Amy Schad, Golnaz Namdar, Alysia Bosworth, Linus Kuo, Daniel Weisdorf, Stephen J. Forman, Smita Bhatia
Journal: Blood (2015)
Differential Induction of Apoptosis in Human Leukemia Cells (ML-1, ML-2, CTV-1 and KASUMI-1) Exposed to the Proteasome Inhibitor Bortezomib and the Effect of Transforming Growth Factor-beta Signaling Pathway.
Authors: Ota Fuchs, Dana Provaznikova, Gabriela Peslova, Marcela Kocova, Iuri Marinov, Ivan Spicka
Journal: Blood (2006)
Clinic Staff Time and Labor Costs Associated with Administering Pegfilgrastim as Compared with Filgrastim to Patients Receiving Myelosuppressive Chemotherapy: Results of a Health Economic Model
Authors: Douglas C.A. Taylor, Michelle Skornecki, Gregory Hill, Richard Barron, Chris Anstead, Barry Fortner, Seval Ozer-Deniz
Journal: Blood (2010)
Ras Pathway Activation in Childhood B-Lineage Acute Lymphoblastic Leukemia: Ras, Ptpn11, and Flt3 Mutations.
Authors: Hélène Cavé, Sami Saba, Nathalie Philippe, Nathalie Grardel, Brigitte Nelken, Lucilia Norton, Alain Robert, Karima Yacouben, Etienne Vilmer, Yves Bertrand, Claude Preudhomme
Journal: Blood (2004)
Significant Ex-Vivo Expansion and Functional Activation of Cord Blood (CB) Natural Killer (NK) Cells with A Concomittant Significant Decrease in CB T Cells Following Stimulation with Genetically Engineered K562 Cells (K562-mb15-41BBL).
Authors: Jessica Hochberg, Janet Ayello, Carmella VandeVen, Jeremy Gold, Evan Cairo, Frances Zhao, Mitchell S. Cairo
Journal: Blood (2009)
Comprehensive Evaluation of Time-to-Response Parameter as a Predictor of Long-Term Outcomes Following Imatinib Therapy in Chronic Phase Chronic Myeloid Leukemia.
Authors: Dong Hwan (Dennis) Kim, Jung A. Kim, Jina Yun, Lakshmi Sriharsha, Jun Ho Jang, Kihyun Kim, Chul Won Jung, Suzanne Kamel-Reid, Jerald Radich, Jeffrey H. Lipton
Journal: Blood (2009)
Epidermal hepcidin is required for neutrophil response to bacterial infection
Authors: Mariangela Malerba, Sabine Louis, Sylvain Cuvellier, Srikanth Mairpady Shambat, Camille Hua, Camille Gomart, Agnès Fouet, Nicolas Ortonne, Jean-Winoc Decousser, Annelies S. Zinkernagel, Jacques R.R. Mathieu, Carole Peyssonnaux
Journal: Journal of Clinical Investigation (2019)

Novel approaches for adjunctive therapy are urgently needed for complicated infections and patients with compromised immunity. Necrotizing fasciitis (NF) is a destructive skin and soft tissue infection. Despite treatment with systemic antibiotics and radical debridement of necrotic tissue, lethality remains high. The key iron regulatory hormone hepcidin was originally identified as a cationic antimicrobial peptide (AMP), but its putative expression and role in the skin, a major site of AMP production, have never been investigated. We report here that hepcidin production is induced in the skin of patients with group A Streptococcus (GAS) NF. In a GAS-induced NF model, mice lacking hepcidin in keratinocytes failed to restrict systemic spread of infection from an initial tissue focus. Unexpectedly, this effect was due to its ability to promote production of the CXCL1 chemokine by keratinocytes, resulting in neutrophil recruitment. Unlike CXCL1, hepcidin is resistant to degradation by major GAS proteases and could therefore serve as a reservoir to maintain steady-state levels of CXCL1 in infected tissue. Finally, injection of synthetic hepcidin at the site of infection can limit or completely prevent systemic spread of GAS infection, suggesting that hepcidin agonists could have a therapeutic role in NF.
Sixty seconds on . . . <i>Sesame Street</i> and opioids
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The letter “O” for opioid and the number 5.7 million. Shockingly, that’s the estimated number of US children under the age of 11 who live in households with a parent with a substance use disorder.

America’s opioid crisis has inspired the iconic US kids’ TV show Sesame Street to introduce a new character whose mother is battling addiction. …
High Aurora Kinase and Low Dido Levels Characterizes a Sub-Group of Chronic Lymphocytic Leukemia with Chromosomal Gains and High White Blood Cell Counts: Potential Inter-Regulatory Role of E2F1 and Mir-17-92 Cluster
Authors: Felipe C Souza, Josiane L Schiavinato, Antonio R. Lucena-Araujo, Fabio M Oliveira, Amelia G Araújo, Dimas Tadeu Covas, Carlos Martínez-A, Marco A Zago, Rodrigo A Panepucci
Journal: Blood (2016)
The Efficacy and Safety of Continued Hydroxyurea Therapy Versus Switching to Ruxolitinib in Patients with Polycythemia Vera: A Randomized, Double-Blind, Double-Dummy, Symptom Study (RELIEF)
Authors: Ruben Mesa, Alessandro M. Vannucchi, Abdulraheem Yacoub, Pierre Zachee, Mamta Garg, Roger Lyons, Silwan Chedid, Steffen Koschmieder, Ciro Rinaldi, Jennifer Byrne, Yasmin Hasan, Francesco Passamonti, Srdan Verstovsek, Deborah Hunter, Mark M Jones, Shui He, Alex Morozov, Bruno Martino
Journal: Blood (2014)
Genetic Variation in NFATC2 Is Associated with a Higher Risk of Asparaginase Allergy
Authors: Christian A. Fernandez, Colton Smith, Wenjian Yang, Charles G. Mullighan, Chunxu Qu, Eric C. Larsen, William Paul Bowman, Chengcheng Liu, Laura B. Ramsey, Tamara Chang, Seth E. Karol, Mignon L. Loh, Elizabeth A. Raetz, Naomi J. Winick, Stephen Hunger, William L. Carroll, Sima Jeha, Ching-Hon Pui, William E. Evans, Meenakshi Devidas, Mary V. Relling
Journal: Blood (2014)
Navitoclax (ABT-263) Plus Fludarabine/Cyclophosphamide/Rituximab (FCR) or Bendamustine/Rituximab (BR): A Phase 1 Study in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL),
Authors: Thomas J. Kipps, Lode J. Swinnen, William G. Wierda, Jeffrey Alan Jones, Steven E. Coutre, Mitchell R Smith, Jianning Yang, Yue Cui, Todd Busman, Sari Enschede, Rod Humerickhouse
Journal: Blood (2011)
Moving Ahead with a New NEJM.org
Authors: Edward W. Campion, Lisa A. Scott, John E. Muenning, Kathy L. Stern, Maro A. Gartside, Kirsti M. Frazier, Nancy S. Burns, Allison J. Lawlor, Jacqueline M. Prince, Robert J. Stuart, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2018)
Cross Sectional Study to Evaluate the Utility of Screening Tools to Identify Low Von Willebrand Factor Levels In Women with Menorrhagia (ZPMCB-VWD).
Authors: Sweta Gupta, Megan A. Lemanczyk, Pamela A. Christopherson, Ke Yan, Raymond G Hoffmann, Michael R Lund, Robert R. Montgomery, Joan Cox Gill
Journal: Blood (2010)
Machine Learning Prediction of Mortality and Hospitalization in Heart Failure With Preserved Ejection Fraction
Authors: Suveen Angraal, Bobak J. Mortazavi, Aakriti Gupta, Rohan Khera, Tariq Ahmad, Nihar R. Desai, Daniel L. Jacoby, Frederick A. Masoudi, John A. Spertus, Harlan M. Krumholz
Journal: JACC Heart Failure (2019)

This study sought to develop models for predicting mortality and heart failure (HF) hospitalization for outpatients with HF with preserved ejection fraction (HFpEF) in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial.Although risk assessment models are available for patients with HF with reduced ejection fraction, few have assessed the risks of death and hospitalization in patients with HFpEF.The following 5 methods: logistic regression with a forward selection of variables; logistic regression with a lasso regularization for variable selection; random forest (RF); gradient descent boosting; and support vector machine, were used to train models for assessing risks of mortality and HF hospitalization through 3 years of follow-up and were validated using 5-fold cross-validation. Model discrimination and calibration were estimated using receiver-operating characteristic curves and Brier scores, respectively. The top prediction variables were assessed by using the best performing models, using the incremental improvement of each variable in 5-fold cross-validation.The RF was the best performing model with a mean C-statistic of 0.72 (95% confidence interval [CI]: 0.69 to 0.75) for predicting mortality (Brier score: 0.17), and 0.76 (95% CI: 0.71 to 0.81) for HF hospitalization (Brier score: 0.19). Blood urea nitrogen levels, body mass index, and Kansas City Cardiomyopathy Questionnaire (KCCQ) subscale scores were strongly associated with mortality, whereas hemoglobin level, blood urea nitrogen, time since previous HF hospitalization, and KCCQ scores were the most significant predictors of HF hospitalization.These models predict the risks of mortality and HF hospitalization in patients with HFpEF and emphasize the importance of health status data in determining prognosis. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302).
Prognostic CMR Parameters For Cardiac Complications In Large Cohort Of Well Treated Thalssemia Major Patients
Authors: Antonella Meloni, Cristina Tassi, Maria Grazia Batzella, Francesca Valeria Commendatore, Giorgio Giannotti, Giuseppe Serra, Petra Keilberg, Aurelio Maggio, Gianluca Valeri, Vincenzo Positano, Massimo Lombardi, Alessia Pepe
Journal: Blood (2013)
No Impact of Adverse Karyotype on Outcome after Allogeneic Stem Cell Transplantation in Patients with High-Risk Acute Lymphoblastic Leukemia.
Authors: Ingo Tamm, Gero Massenkeil, Mandy Wagner, Theis Terwey, Christoph Lutz, Stefan Neuburger, Christiane Bommert, Bernd Dörken, Renate Arnold
Journal: Blood (2006)
The Efficacy of Oral Elemental Diet in Patients with Hematopoietic Stem Cell Transplantation
Authors: Takanobu Morishita, Natsuko Tsushita, Kanae Imai, Toshiyasu Sakai, Kotaro Miyao, Reona Sakemura, Tomonori Kato, Keiko Niimi, Yoshitaka Ono, Masashi Sawa
Journal: Blood (2014)
In vivo VEGF imaging with 89Zr-bevacizumab in a human ovarian tumor xenograft model using MicroPET and MicroCT.
Authors: Wouter Nagengast, Elisabeth de Vries, Geke Hospers, Nanno Mulder, Johan de Jong, Adrienne Brouwers, Marjolijn de Hooge
Journal: Cancer Research (2007)

5508  VEGF, released by tumor cells, is an important growth factor in tumor angiogenesis as it induces tumor neovascularization. VEGF leads to paracrine effects and results in abundant presence of VEGF in the tumor micro-environment. Non-invasive measurement of VEGF in the tumor might give insight in the available target for VEGF dependent anti-angiogenic therapy. Bevacizumab is a humanized monoclonal antibody which blocks the biological pathways of VEGF induced tumor angiogenesis by binding to VEGF, most likely in the micro-environment of the tumor. For that reason, we developed radiolabeled bevacizumab for in vivo VEGF imaging using the relatively new long-lived PET isotope 89Zirconium (89Zr) (T1/2 3.27d) allowing high resolution (Micro)PET imaging. Methods: Labeling, stability and in-vitro immunoreactivity studies were performed. Thereafter, nude mice were inoculated subcutaneously with VEGF producing human SKOV-3 ovarian tumor cells. After tumor size reached 7-9 mm in diameter, mice were injected with 100 μg ( ± 3.5 MBq) of 89Zr-bevacizumab or human 89Zr-IgG. Human 89Zr-IgG served as an aspecific control antibody. MicroPET images, MicroCT images and biodistribution studies were obtained at 24, 72 and 168 h post injection. MicroPET and MicroCT images were fused to calculate uptake of 89Zr-bevacizumab and Zr89-IgG in the micro-environment of the tumor. Results:89Zr-bevacizumab labeling efficiency was >95%. The tracer was stable > 168 h at 37°C in serum. The immunoreactive fraction determined by ELISA was >0.50. MicroPET images showed uptake in well perfused organs after 24 h and clear tumor localization after 72 h post injection. Tumor uptake determined by quantification of MicroPET images was higher for 89Zr-bevacizumab 168 h post injection, namely 7.38% ± 2.06 injected dose (ID)cm-3 compared to 3.39% ± 1.16 IDcm-3 for human 89Zr-IgG (p=0.011). These data were confirmed by ex-vivo biodistribution studies. Uptake in other organs was mainly seen in liver and spleen. Discussion: The labeling of bevacizumab with the PET isotope 89Zr allows imaging matching the pharmacokinetic half life of bevacizumab. (Micro)PET imaging permits not only excellent visualization, but also dynamic quantification of 89Zr-bevacizumab in the micro-environment of the tumor. Tumor uptake of 89Zr-bevacizumab was significantly higher compared to control 89Zr-IgG, signifying that 89Zr-bevacizumab could potentially be used to visualize VEGF-levels in the micro-environment of the tumor.
Ischemia-Reperfusion Injury with Pringle's Maneuver Induces Increasing of Unusually Large Von Willebrand Factor Multimers after Hepatectomy
Authors: Takahiro Yoshikawa, Takeo Nomi, Kazuya Sakai, Masaki Hayakawa, Daisuke Hokuto, Satoshi Yasuda, Masayuki Sho, Masanori Matsumoto
Journal: Blood (2017)