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3. Effect of tranexamic acid by baseline risk of death in acute bleeding patients: a meta-analysis of individual patient-level data from 28 333 patients

Author

Kayani, Aasia, Geer, Amber, Ndungu, Bernard, Fawole, Bukola, Gilliam, Catherine, Adetayo, Cecelia, Barrow, Collette, Beaumont, Danielle, Prowse, Danielle, I'Anson, David, Balogun, Eni, Miah, Hakim, Shakur-Still, Haleema, Roberts, Ian, Brooks, Imogen, Onandia, Julio, Ker, Katharine, Javaid, Kiran, Suncuan, Laura, Frimley, Lauren, Reid, Mia, Arribas, Monica, Benyahia, Myriam, Okunade, Olujide, Edwards, Phil, Chaudhri, Rizwana, Kostrov, Sergey, Kansagra, Sneha, Pepple, Tracey, Ageron, Francois-Xavier, Gayet-Ageron, Angele, and Coats, Timothy J.

Published
2020
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5. Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial

Author

Brenner, Amy, Afolabi, Adefemi, Ahmad, Syed Masroor, Arribas, Monica, Chaudhri, Rizwana, Coats, Timothy, Cuzick, Jack, Gilmore, Ian, Hawkey, Christopher, Jairath, Vipul, Javaid, Kiran, Kayani, Aasia, Mutti, Muttiullah, Nadeem, Muhammad Arif, Shakur-Still, Haleema, Stanworth, Simon, Veitch, Andrew, Roberts, Ian, and HALT-IT Trial Collaborators

Published
2019
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10. A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT

Author

Roberts, Ian, primary, Shakur-Still, Haleema, additional, Afolabi, Adefemi, additional, Akere, Adegboyega, additional, Arribas, Monica, additional, Austin, Emma, additional, Bal, Kiran, additional, Bazeer, Nuha, additional, Beaumont, Danielle, additional, Brenner, Amy, additional, Carrington, Laura, additional, Chaudhri, Rizwana, additional, Coats, Timothy, additional, Gilmore, Ian, additional, Halligan, Kenneth, additional, Hussain, Irshad, additional, Jairath, Vipul, additional, Javaid, Kiran, additional, Kayani, Aasia, additional, Lisman, Ton, additional, Mansukhani, Raoul, additional, Miners, Alec, additional, Mutti, Muttiullah, additional, Nadeem, Muhammad Arif, additional, Pollok, Richard, additional, Prowse, Danielle, additional, Simmons, Jonathan, additional, Stanworth, Simon, additional, Veitch, Andrew, additional, and Williams, Jack, additional

Published
2021
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11. WOMAN-PharmacoTXA trial: Study protocol for a randomised controlled trial to assess the pharmacokinetics and pharmacodynamics of intramuscular, intravenous and oral administration of tranexamic acid in women giving birth by caesarean section

Author

Arribas, Monica, primary, Roberts, Ian, additional, Chaudhri, Rizwana, additional, Geer, Amber, additional, Prowse, Danielle, additional, Lubeya, Mwansa Ketty, additional, Kayani, Aasia, additional, Javaid, Kiran, additional, Grassin-Delyle, Stanislas, additional, and Shakur-Still, Haleema, additional

Published
2021
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12. Effect of tranexamic acid by baseline risk of death in acute bleeding patients: a meta-analysis of individual patient-level data from 28 333 patients

Author

Ageron, Francois-Xavier, primary, Gayet-Ageron, Angele, additional, Ker, Katharine, additional, Coats, Timothy J., additional, Shakur-Still, Haleema, additional, Roberts, Ian, additional, Kayani, Aasia, additional, Geer, Amber, additional, Ndungu, Bernard, additional, Fawole, Bukola, additional, Gilliam, Catherine, additional, Adetayo, Cecelia, additional, Barrow, Collette, additional, Beaumont, Danielle, additional, Prowse, Danielle, additional, I'Anson, David, additional, Balogun, Eni, additional, Miah, Hakim, additional, Brooks, Imogen, additional, Onandia, Julio, additional, Javaid, Kiran, additional, Suncuan, Laura, additional, Frimley, Lauren, additional, Reid, Mia, additional, Arribas, Monica, additional, Benyahia, Myriam, additional, Okunade, Olujide, additional, Edwards, Phil, additional, Chaudhri, Rizwana, additional, Kostrov, Sergey, additional, Kansagra, Sneha, additional, and Pepple, Tracey, additional

Published
2020
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13. Additional file 1 of Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial

Author

Brenner, Amy, Adefemi Afolabi, Ahmad, Syed, Arribas, Monica, Rizwana Chaudhri, Coats, Timothy, Cuzick, Jack, Gilmore, Ian, Hawkey, Christopher, Jairath, Vipul, Javaid, Kiran, Aasia Kayani, Muttiullah Mutti, Nadeem, Muhammad, Shakur-Still, Haleema, Stanworth, Simon, Veitch, Andrew, and Roberts, Ian

Abstract

Figure S1 Trial profile. Figure S2 Cumulative percentage of death due to bleeding in the tranexamic acid and placebo groups. Figure S3 Distribution of cause of death by days since randomisation. Table S1 Baseline characteristics of participants prior to randomisation. Table S2 Death due to bleeding and rebleeding. Table S3 Other causes of death and all-cause mortality. Table S4 Death due to bleeding by subgroups. Table S5 Need for surgical, endoscopic and radiological interventions and blood transfusion. Table S6 Thromboembolic events, complications and self-care capacity. Table S7 Adverse events. (DOC 355 kb)

Published
2019
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14. Expression of Concern

Author

Guerra, Carmen, Navarro, Paloma, Valverde, Angela M., Arribas, Monica, Bruning, Jens, Kozak, Leslie P., Kahn, C. Ronald, and Benito, Manuel

Subjects
Health care industry
Abstract

Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistanceOriginal citation: J Clin Invest. 2001;108(8):1205-1213. https://doi.org/10.1172/JCI13103.Citation for this Expression of Concern: J Clin Invest. 2019;129(1):437. https://doi.org/10.1172/JCI126191.A reader recently [...]

Published
2019
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17. Brown Adipose Tissue-Specific Insulin Receptor Knockout Mice Show a Lipoatrophic Diabetes Phenotype

Author

NAVARRO, PALOMA, GUERRA, CARMEN, ARRIBAS, MONICA, VALVERDE, ANGELA M., and BENITO, MANUEL

Subjects
Brown adipose tissue -- Physiological aspects, Insulin -- Receptors, Diabetes -- Development and progression, Health
Abstract

To define the role of brown adipose tissue in the whole body glucose disposal, we have generated mice with a brown adipose tissue-specific insulin receptor (IR) knockout (BATIRKO) using the [...]

Published
2000

25. Insulin-induced up-regulated uncoupling protein-1 expression is mediated by insulin receptor substrate 1 through the phosphatidylinositol 3-kinase/Akt signaling pathway in fetal brown adipocytes.

Author

Valverde AM, Arribas M, Mur C, Navarro P, Pons S, Cassard-Doulcier AM, Kahn CR, and Benito M

Subjects
Animals, CCAAT-Enhancer-Binding Protein-alpha genetics, DNA metabolism, Insulin Receptor Substrate Proteins, Ion Channels, Mice, Mitochondrial Proteins, Phosphorylation, Promoter Regions, Genetic, Proto-Oncogene Proteins c-akt, Receptors, Cytoplasmic and Nuclear genetics, Transcription Factors genetics, Transcriptional Activation, Uncoupling Protein 1, Up-Regulation, Adipocytes metabolism, Adipose Tissue, Brown metabolism, Carrier Proteins genetics, Gene Expression Regulation drug effects, Insulin pharmacology, Membrane Proteins genetics, Phosphatidylinositol 3-Kinases physiology, Phosphoproteins physiology, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins physiology
Abstract

To investigate the role of insulin receptor substrate-1 (IRS-1) and its downstream signaling in insulin-induced thermogenic differentiation of brown adipocytes, we have reconstituted IRS-1-deficient fetal brown adipocytes (IRS-1(-/-)) with wild-type IRS-1 (IRS-1(wt)). The lack of IRS-1 resulted in the inability of insulin to induce IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity and Akt phosphorylation in IRS-1(-/-) brown adipocytes. In addition, these cells showed an impairment in activating alpha-Akt, beta-Akt, and gamma-Akt isoforms upon insulin stimulation. Reconstitution of IRS-1(-/-) brown adipocytes with IRS-1(wt) restored the IRS-1/PI 3-kinase/Akt signaling pathway. Treatment of wild-type brown adipocytes with insulin for 24 h up-regulated uncoupling protein-1 (UCP-1) expression and transactivated the UCP-1 promoter; this effect was abolished in the absence of IRS-1 or in the presence of an Akt inhibitor and further recovered after IRS-1(wt) reconstitution. Neither UCP-2 nor UCP-3 was up-regulated by insulin in wild-type and IRS-1-deficient brown adipocytes. Insulin stimulated the expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) and its DNA binding activity in wild-type brown adipocytes but not in IRS-1(-/-) cells. However, insulin stimulation of both C/EBPalpha expression and binding activity was restored after IRS-1(wt) reconstitution of deficient cells. Retrovirus-mediated expression of C/EBPalpha and peroxisome proliferator-activated receptor gamma in IRS-1(-/-) brown adipocytes up-regulated UCP-1 protein content and transactivated UCP-1 promoter regardless of insulin stimulation. Both C/EBPalpha and peroxisome proliferator-activated receptor gamma reconstituted FAS mRNA expression, but only C/EBPalpha restored insulin sensitivity in the absence of IRS-1. Finally, reconstitution of IRS-1(-/-) brown adipocytes with the IRS-1 mutants IRS-1(Phe-895), which lacks IRS-1/growth factor receptor binding protein 2 binding but not IRS-1/p85-PI 3-kinase binding, or with IRS-1(Tyr-608/Tyr-628/Tyr-658), which only binds p85-PI 3-kinase, induced UCP-1 expression and transactivated the UCP-1 promoter. These data provide strong evidence for an essential role of IRS-1 through the PI 3-kinase/Akt signaling pathway inducing UCP-1 gene expression by insulin.

Published
2003
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