المؤلفون: Colussi, Marco, Civitarese, Gabriele, Ahmetovic, Dragan, Bettini, Claudio, Gualtierotti, Roberta, Peyvandi, Flora, Mascetti, Sergio

مصطلحات موضوعية: Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition

الوصف: Joint bleeding is a common condition for people with hemophilia and, if untreated, can result in hemophilic arthropathy. Ultrasound imaging has recently emerged as an effective tool to diagnose joint recess distension caused by joint bleeding. However, no computer-aided diagnosis tool exists to support the practitioner in the diagnosis process. This paper addresses the problem of automatically detecting the recess and assessing whether it is distended in knee ultrasound images collected in patients with hemophilia. After framing the problem, we propose two different approaches: the first one adopts a one-stage object detection algorithm, while the second one is a multi-task approach with a classification and a detection branch. The experimental evaluation, conducted with $483$ annotated images, shows that the solution based on object detection alone has a balanced accuracy score of $0.74$ with a mean IoU value of $0.66$, while the multi-task approach has a higher balanced accuracy value ($0.78$) at the cost of a slightly lower mean IoU value.

الوصول الحر: http://arxiv.org/abs/2211.12089Test

المؤلفون: Klamroth, Robert, Hayes, Gregory, Andreeva, Tatiana, Gregg, Keith, Suzuki, Takashi, Mitha, Ismail Haroon, Hardesty, Brandon, Shima, Midori, Pollock, Toni, Slev, Patricia, Oldenburg, Johannes, Ozelo, Margareth C, Stieltjes, Natalie, Castet, Sabine-Marie, Mahlangu, Johnny, Peyvandi, Flora, Kazmi, Rashid, Schved, Jean-François, Leavitt, Andrew D, Callaghan, Michael, Pan-Petesch, Brigitte, Quon, Doris V, Andrews, Jayson, Trinh, Alex, Li, Mingjin, Wong, Yen

المصدر: Human Gene Therapy. 33(7-8)

مصطلحات موضوعية: Medical Biotechnology, Biomedical and Clinical Sciences, Genetics, Prevention, Antibodies, Neutralizing, Antibodies, Viral, Dependovirus, Genetic Vectors, Hemophilia A, Humans, Prospective Studies, Seroepidemiologic Studies, Serogroup, gene therapy, hemophilia A, adeno-associated virus, antibody, seropositivity, Clinical Sciences, Biotechnology, Medical biotechnology

الوصف: Adeno-associated virus (AAV)-mediated gene therapy may provide durable protection from bleeding events and reduce treatment burden for people with hemophilia A (HA). However, pre-existing immunity against AAV may limit transduction efficiency and hence treatment success. Global data on the prevalence of AAV serotypes are limited. In this global, prospective, noninterventional study, we determined the prevalence of pre-existing immunity against AAV2, AAV5, AAV6, AAV8, and AAVrh10 among people ≥12 years of age with HA and residual FVIII levels ≤2 IU/dL. Antibodies against each serotype were detected using validated, electrochemiluminescent-based enzyme-linked immunosorbent assays. To evaluate changes in antibody titers over time, 20% of participants were retested at 3 and 6 months. In total, 546 participants with HA were enrolled at 19 sites in 9 countries. Mean (standard deviation) age at enrollment was 36.0 (14.87) years, including 12.5% younger than 18 years, and 20.0% 50 years of age and older. On day 1, global seroprevalence was 58.5% for AAV2, 34.8% for AAV5, 48.7% for AAV6, 45.6% for AAV8, and 46.0% for AAVrh10. Considerable geographic variability was observed in the prevalence of pre-existing antibodies against each serotype, but AAV5 consistently had the lowest seroprevalence across the countries studied. AAV5 seropositivity rates were 51.8% in South Africa (n = 56), 46.2% in Russia (n = 91), 40% in Italy (n = 20), 37.2% in France (n = 86), 26.8% in the United States (n = 71), 26.9% in Brazil (n = 26), 28.1% in Germany (n = 89), 29.8% in Japan (n = 84), and 5.9% in the United Kingdom (n = 17). For all serotypes, seropositivity tended to increase with age. Serostatus and antibody titer were generally stable over the 6-month sampling period. As clinical trials of AAV-mediated gene therapies progress, data on the natural prevalence of antibodies against various AAV serotypes may become increasingly important.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4fd5t2tvTest

المؤلفون: Lombardi, Andrea, Villa, Simone, Colaneri, Marta, Scaglione, Giovanni, Bai, Francesca, Varisco, Benedetta, Bono, Valeria, Vena, Antonio, Dentone, Chiara, Russo, Chiara, Tettamanti, Mauro, Renisi, Giulia, Viero, Giulia, Azzarà, Cecilia, Mantero, Marco, Peyvandi, Flora, Bassetti, Matteo, Marchetti, Giulia, Muscatello, Antonio, Nobili, Alessandro, Gori, Andrea, Bandera, Alessandra, Bosari, Silvano, Scudeller, Luigia, Fusetti, Giuliana, Rusconi, Laura, Dell’Orto, Silvia, Prati, Daniele, Valenti, Luca, Giovannelli, Silvia, Manunta, Maria, Lamorte, Giuseppe, Ferarri, Francesca, Gori. , Andrea, Mangioni, Davide, Alagna, Laura, Bozzi, Giorgio, Lombardi. , Andrea, Ungaro, Riccardo, Ancona, Giuseppe, Mussa, Marco, Mariani, Bianca Veronica, Bolis, Matteo, Iannotti, Nathalie, Ludovisi, Serena, Comelli, Agnese, Biscarini, Simona, Castelli, Valeria, Palomba, Emanuele, Fava, Marco, Peri, Carlo Alberto, Saltini, Paola, Itri, Teresa, Ferroni, Valentina, Pastore, Valeria, Massafra, Roberta, Liparoti, Arianna, Muheberimana, Toussaint, Giommi, Alessandro, Bianco, Rosaria, Chitani, Grazia Eliana, Bobbio, Chiara, De Matteis, Irene, Bonomi, Angelo Bianchi, Gualtierotti, Roberta, Ferrari, Barbara, Rossio, Raffaella, Boasi, Nadia, Pagliaro, Erica, Massimo, Costanza, De Caro, Michele, Giachi, Andrea, Montano, Nicola, Vigone, Barbara, Bellocchi, Chiara, Carandina, Angelica, Fiorelli, Elisa, Melli, Valerie, Tobaldini, Eleonora, Blasi, Francesco, Aliberti, Stefano, Spotti, Maura, Terranova, Leonardo, Misuraca, Sofia, D’Adda, Alice, Della Fiore, Silvia, Di Pasquale, Marta, Mantero. , Marco, Contarini, Martina, Ori, Margherita, Morlacchi, Letizia, Rossetti, Valeria, Gramegna, Andrea, Pappalettera, Maria, Cavallini, Mirta, Buscemi, Agata, Vicenzi, Marco, Rota, Irena, Costantino, Giorgio, Solbiati, Monica, Furlan, Ludovico, Mancarella, Marta, Colombo, Giulia, Colombo, Giorgio, Fanin, Alice, Passarella, Mariele, Monzani, Valter, Canetta, Ciro, Rovellini, Angelo, Barbetta, Laura, Billi, Filippo, Folli, Christian, Accordino, Silvia, Maira, Diletta, Hu, Cinzia Maria, Motta, Irene, Scaramellini, Natalia, Fracanzani, Anna Ludovica, Lombardi, Rosa, Cespiati, Annalisa, Cesari, Matteo, Lucchi, Tiziano, Proietti, Marco, Calcaterra, Laura, Mandelli, Clara, Coppola, Carlotta, Cerizza, Arturo, Pesenti, Antonio Maria, Grasselli, Giacomo, Galazzi, Alessandro, Nobili. , Alessandro, Monti, Igor, Galbussera, Alessia Antonella, Crisafulli, Ernesto, Girelli, Domenico, Maroccia, Alessio, Gabbiani, Daniele, Busti, Fabiana, Vianello, Alice, Biondan, Marta, Sartori, Filippo, Faverio, Paola, Pesci, Alberto, Zucchetti, Stefano, Bonfanti, Paolo, Rossi, Marianna, Beretta, Ilaria, Spolti, Anna, Harari, Sergio, Elia, Davide, Cassandro, Roberto, Caminati, Antonella, Cipollone, Francesco, Guagnano, Maria Teresa, D’Ardes, Damiano, Rossi, Ilaria, Vezzani, Francesca, Spanevello, Antonio, Cherubino, Francesca, Visca, Dina, Contoli, Marco, Papi, Alberto, Morandi, Luca, Battistini, Nicholas, Moreo, Guido Luigi, Iannuzzi, Pasqualina, Fumagalla, Daniele, Leone, Sara

المساهمون: A. Lombardi, S. Villa, M. Colaneri, G. Scaglione, F. Bai, B. Varisco, V. Bono, A. Vena, C. Dentone, C. Russo, M. Tettamanti, G. Renisi, G. Viero, C. Azzarà, M. Mantero, F. Peyvandi, M. Bassetti, G. Marchetti, A. Muscatello, A. Nobili, A. Gori, A. Bandera, S. Bosari, L. Scudeller, G. Fusetti, L. Rusconi, S. Dell’Orto, D. Prati, L. Valenti, S. Giovannelli, M. Manunta, G. Lamorte, F. Ferarri, A. Gori., D. Mangioni, L. Alagna, G. Bozzi, A. Lombardi., R. Ungaro, G. Ancona, M. Mussa, B.V. Mariani, M. Boli, N. Iannotti, S. Ludovisi, A. Comelli, S. Biscarini, V. Castelli, E. Palomba, M. Fava, C.A. Peri, P. Saltini, T. Itri, V. Ferroni, V. Pastore, R. Massafra, A. Liparoti, T. Muheberimana, A. Giommi, R. Bianco, G.E. Chitani, C. Bobbio, I. De Mattei, A.B. Bonomi, R. Gualtierotti, B. Ferrari, R. Rossio, N. Boasi, E. Pagliaro, C. Massimo, M. De Caro, A. Giachi, N. Montano, B. Vigone, C. Bellocchi, A. Carandina, E. Fiorelli, V. Melli, E. Tobaldini, F. Blasi, S. Aliberti, M. Spotti, L. Terranova, S. Misuraca, A. D’Adda, S. Della Fiore, M. Di Pasquale, M. Mantero., M. Contarini, M. Ori, L. Morlacchi, V. Rossetti, A. Gramegna, M. Pappalettera, M. Cavallini

مصطلحات موضوعية: Vaccination, Breakthrough infection, SARS-COV-2, Settore MED/17 - Malattie Infettive

الوصف: Background Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p=0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p=0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039-0.542, p=0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582-1.703, p=0.987). Conclusions This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that ...

العلاقة: firstpage:1; lastpage:14; numberofpages:14; journal:JOURNAL OF INFECTION AND PUBLIC HEALTH; https://hdl.handle.net/2434/1024372Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85183136322

الإتاحة: https://doi.org/10.1016/j.jiph.2023.12.026Test
https://hdl.handle.net/2434/1024372Test

المؤلفون: EUHASS and CHESS participants, Fischer, Kathelijn, Lassila, Riitta, Peyvandi, Flora, Gatt, Alexander, Hollingsworth, Rob, Lambert, Thierry, Kaczmarek, Radek, Bettle, Amanda, Samji, Nasrin, Rivard, Georges Étienne, Carcao, Manuel, Iorio, Alfonso, Makris, Mike

المساهمون: HUS Comprehensive Cancer Center, Clinicum, Department of Clinical Chemistry and Hematology, Hematologian yksikkö

مصطلحات موضوعية: antibodies, factor VIII, hemophilia A, hemophilia B, neutralizing, registries, 3121 General medicine, internal medicine and other clinical medicine

الوصف: Background: Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant. Objectives: To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B. Methods: The European Haemophilia Safety Surveillance (EUHASS) and Canadian Bleeding Disorders Registry (CBDR) have been monitoring adverse events overall and according to concentrate for 11 and 8 years, respectively. Inhibitors were reported quarterly, and PUPs completed 50 exposure days without inhibitor development annually. Cumulative inhibitor incidences and 95% confidence intervals (CIs) were compared without adjustment for other risk factors. Results: Fifty-six European and 23 Canadian centers reported inhibitor development in 312 of 1219 (26%; CI, 23%-28%) PUPs with severe hemophilia A and 14 of 173 (8%; CI, 5%-13%) PUPs with severe hemophilia B. Inhibitor development was lower on plasma-derived factor (F)VIII (pdFVIII, 20%; CI, 14%-26%) than on standard half-life recombinant FVIII (SHL-rFVIII, 27%; CI, 24%-30% and odds ratio, 0.67; CI, 0.45%-0.98%; P = .04). Extended half-life recombinant FVIII (EHL-rFVIII, 22%; CI, 12%-36%) showed an intermediate inhibitor rate, while inhibitor rates for Advate (26%; CI, 22%-31%) and Kogenate/Helixate (30%; CI, 24%-36%) overlapped. For other SHL-rFVIII concentrates, inhibitor rates varied from 3% to 43%. Inhibitor development was similar for pdFIX (11%; CI, 3%-25%), SHL-rFIX (8%; CI, 3%-15%), and EHL-rFIX (7%; CI, 1%-22%). Conclusion: While confirming expected rates of inhibitors in PUPs, inhibitor development was lower in pdFVIII than in SHL-rFVIII. Preliminary data suggest variation in inhibitor development among different SHL-rFVIII and EHL-rFVIII concentrates. ; Peer reviewed

وصف الملف: application/pdf

العلاقة: The CBDR, owned by the AHCDC, is funded by the Provinces and Territories of Canada. Funds flow to AHCDC via CBS and the Ministère de la Santé et des Services Sociaux du Québec responsible for Héma-Québec, the blood and blood product provider in Quebec.; EUHASS and CHESS participants , Fischer , K , Lassila , R , Peyvandi , F , Gatt , A , Hollingsworth , R , Lambert , T , Kaczmarek , R , Bettle , A , Samji , N , Rivard , G É , Carcao , M , Iorio , A & Makris , M 2023 , ' Inhibitor development according to concentrate in severe hemophilia : reporting on 1392 Previously Untreated Patients from Europe and Canada ' , Research and practice in thrombosis and haemostasis , vol. 7 , no. 8 , 102265 . https://doi.org/10.1016/j.rpth.2023.102265Test; 85179013164; 5668759e-650e-4731-9ea9-9b2d33eb406d; http://hdl.handle.net/10138/569304Test; 001138752500001

الإتاحة: http://hdl.handle.net/10138/569304Test

المؤلفون: Mohsenian, Samin, Palla, Roberta, Menegatti, Marzia, Cairo, Andrea, Lecchi, Anna, Casini, Alessandro, Neerman Arbez, Marguerite, Asselta, Rosanna, Scardo, Sara, Siboni, Simona Maria, Blatny, Jan, Zapletal, Ondrej, Schved, Jean-Francois, Giansily-Blaizot, Muriel, Halimeh, Susan, Daoud, Mohamad Ayman, Platokouki, Helen, Pergantou, Helen, Schutgens, Roger E G, Van Haaften-Spoor, Monique, Brons, Paul, Laros-van Gorkom, Britta, Van Pinxten, Elise, Borhany, Munira, Fatima, Naveena, Mikovic, Danijela, Saracevic, Marko, Özdemir, Gül Nihal, Ay, Yılmaz, Makris, Michael, Lockley, Caryl, Mumford, Andrew, Harvey, Andrew, Austin, Steve, Shapiro, Amy, Williamson, Adrianna, McGuinn, Catherine, Goldberg, Ilene, De Moerloose, Philippe, Peyvandi, Flora

المصدر: ISSN: 2473-9529 ; Blood advances, vol. 8, no. 6 (2024) p. 1392-1404.

مصطلحات موضوعية: info:eu-repo/classification/ddc/616, info:eu-repo/classification/ddc/576.5, Humans, Female, Fibrinogen / genetics, Afibrinogenemia / epidemiology, Afibrinogenemia / genetics, Afibrinogenemia / complications, Prospective Studies, Retrospective Studies, Hemorrhage / genetics, Hemostatics

الوصف: Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA , FGB , and FGG . We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA , FGB , and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants ( FGG , p.Arg301Cys/His and FGA , p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38286442; https://archive-ouverte.unige.ch/unige:176815Test; unige:176815

الإتاحة: https://doi.org/10.1182/bloodadvances.2023012186Test
https://archive-ouverte.unige.ch/unige:176815Test

المؤلفون: Casini, Alessandro, Al-Samkari, Hanny, Hayward, Catherine, Peyvandi, Flora

المصدر: ISSN: 1351-8216 ; Haemophilia, vol. 30, no. S3 (2024) p. 60-69.

مصطلحات موضوعية: info:eu-repo/classification/ddc/616, Fibrinogen deficiency, Hereditary haemorrhagic telangiectasia, Inherited platelet dysfunction, Rare bleeding disorders, Afibrinogenemia / diagnosis, Antifibrinolytic Agents / therapeutic use, Blood Coagulation Disorders / drug therapy, Blood Coagulation Factors / therapeutic use, Female, Fibrinogen / therapeutic use, Hemorrhage / etiology, Hemorrhage / prevention & control, Humans, Pregnancy

الوصف: Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT). In the last decades, there have been large increases in knowledge on the epidemiology, genetics, physiopathology, clinical features, and diagnosis of RBDs, but improvements in management have been more limited and remain challenging. The treatment mainstay of RBDs is based only on replacement of a few available coagulation factor concentrates or cryoprecipitates. There is growing interest in therapeutic agents that enhance coagulation or inhibiting anticoagulant pathways in RBDs. In severe IPFD, the optimal platelet transfusion strategy is not yet established. Moreover, data is scarce on the effectiveness and safety of desmopressin and/or antifibrinolytic drugs often used for milder IPFD treatment. The best fibrinogen replacement strategy (prophylaxis vs. on demand) in afibrinogenemia is still debated. Similarly, the optimal trough fibrinogen target level for treatment of acute bleeding, and the role of fibrinogen replacement during pregnancy in mild hypofibrinogenemia and dysfibrinogenemia, have not been properly evaluated. The therapeutic arsenal in HHT includes antifibrinolytics and a series of antiangiogenic agents whose potential efficacy has been tested in small studies or are under investigation for treatment of bleeding. However, there is need to address several issues, including the optimal dosing strategies, the potential emergent toxicity of longer-term use, and the impact of systemic antiangiogenic treatment on visceral arteriovenous malformations.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38494995; https://archive-ouverte.unige.ch/unige:176812Test; unige:176812

الإتاحة: https://doi.org/10.1111/hae.14986Test
https://archive-ouverte.unige.ch/unige:176812Test

المؤلفون: Pipe, Steven W., Collins, Peter W., Dhalluin, Christophe, Kenet, Gili, Schmitt, Christophe, Buri, Muriel, Jiménez-Yuste, Victor, Peyvandi, Flora, Young, Guy, Oldenburg, Johannes, Mancuso, Maria Elisa, Kavakli, Kaan, Kiialainen, Anna, Deb, Sonia, Niggli, Markus, Chang, Tiffany, Lehle, Michaela, Fijnvandraat, Karin

الوصف: Subcutaneous emicizumab enables prophylaxis for people with hemophilia A (HA) from birth, potentially reducing risk of bleeding and intracranial hemorrhage (ICH). HAVEN 7 (NCT04431726) is the first clinical trial of emicizumab dedicated to infants, designed to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab in those aged ≤12 months with severe HA without factor VIII (FVIII) inhibitors. Participants in this phase 3b trial received emicizumab 3 mg/kg maintenance dose every 2 weeks for 52 weeks and are continuing emicizumab during the 7-year long-term follow-up. Efficacy end points included annualized bleed rate (ABR): treated, all, treated spontaneous, and treated joint bleeds. Safety end points included adverse events (AEs), thromboembolic events (TEs), thrombotic microangiopathies (TMAs), and immunogenicity (anti-emicizumab antibodies [ADAs] and FVIII inhibitors). At primary analysis, 55 male participants had received emicizumab (median treatment duration: 100.3; range, 52-118 weeks). Median age at informed consent was 4.0 months (range, 9 days to 11 months 30 days). Model-based ABR for treated bleeds was 0.4 (95% confidence interval, 0.30–0.63), with 54.5% of participants (n = 30) having zero treated bleeds. No ICH occurred. All 42 treated bleeds in 25 participants (45.5%) were traumatic. Nine participants (16.4%) had ≥1 emicizumab-related AE (all grade 1 injection-site reactions). No AE led to treatment changes. No deaths, TEs, or TMAs occurred. No participant tested positive for ADAs. Two participants were confirmed positive for FVIII inhibitors. This primary analysis of HAVEN 7 indicates that emicizumab is efficacious and well tolerated in infants with severe HA without FVIII inhibitors.

وصف الملف: application/pdf

العلاقة: https://orca.cardiff.ac.uk/id/eprint/165809/1/blood.2023021832.pdfTest; Pipe, Steven W., Collins, Peter W. https://orca.cardiff.ac.uk/view/cardiffauthors/A070283V.htmlTest orcid:0000-0002-6410-1324 orcid:0000-0002-6410-1324, Dhalluin, Christophe, Kenet, Gili, Schmitt, Christophe, Buri, Muriel, Jiménez-Yuste, Victor, Peyvandi, Flora, Young, Guy, Oldenburg, Johannes, Mancuso, Maria Elisa, Kavakli, Kaan, Kiialainen, Anna, Deb, Sonia, Niggli, Markus, Chang, Tiffany, Lehle, Michaela and Fijnvandraat, Karin 2024. Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b, open-label trial. Blood 14 , pp. 1355-1364. 10.1182/blood.2023021832 https://doi.org/10.1182/blood.2023021832Test file https://orca.cardiff.ac.uk/id/eprint/165809/1/blood.2023021832.pdfTest

الإتاحة: https://doi.org/10.1182/blood.2023021832Test
https://orca.cardiff.ac.uk/id/eprint/165809Test/
https://orca.cardiff.ac.uk/id/eprint/165809/1/blood.2023021832.pdfTest

المؤلفون: Castaman, Giancarlo, Peyvandi, Flora, Kremer Hovinga, Johanna A, Schutgens, Roger E G, Robson, Susan, Moreno, Katya, Jiménez-Yuste, Víctor

المصدر: Castaman, Giancarlo; Peyvandi, Flora; Kremer Hovinga, Johanna A; Schutgens, Roger E G; Robson, Susan; Moreno, Katya; Jiménez-Yuste, Víctor (2024). Surgical Experience from the STASEY Study of Emicizumab Prophylaxis in People with Hemophilia A with Factor VIII Inhibitors. TH open, 8(1), e42-e54. Thieme 10.1055/s-0043-1777766

مصطلحات موضوعية: 610 Medicine & health

الوصف: Background Guidelines surrounding emicizumab prophylaxis and perioperative treatment for people with hemophilia A (PwHA) with factor (F)VIII inhibitors undergoing surgeries are limited. The phase IIIb multicenter, single-arm STASEY study evaluated safety and tolerability of emicizumab prophylaxis in PwHA aged ≥12 years with FVIII inhibitors. This analysis assesses surgeries during study conduct, associated hemophilia medications, and postoperative bleeds (treated and untreated). Methods PwHA with FVIII inhibitors received emicizumab 3.0 mg/kg/week for 4 weeks, then 1.5 mg/kg/week until 2 years. Surgeries were managed and documented by treating physicians. Bleeds and treatments were recorded by physicians and participants. Results Forty-six participants had ≥1 on-study surgery, 37 underwent 56 minor surgeries, and 13 underwent 22 major surgeries. Four participants underwent both minor and major surgeries. Of 18 (81.8%) and 4 (18.2%) major surgeries managed with/without additional hemostatic medication, 33.3 and 25.0% were associated with a treated postoperative bleed, respectively. Of 24 (42.9%) and 32 (57.1%) minor surgeries managed with/without additional hemostatic medication, 15.6 and 25.0% were associated with a treated postoperative bleed, respectively. Recombinant activated FVII was the most common medication for prophylaxis and bleed treatment. There were no thrombotic microangiopathies (TMAs). One hypertrophic clot, considered unrelated to emicizumab, occurred following tooth extraction. Conclusion In this challenging population with a high bleeding risk, major surgeries were performed in PwHA receiving emicizumab with/without additional hemostatic medication. Postoperative bleeds occurred following 59.1% of major surgeries; 53.8% were treated. No arterial/venous thrombotic events or TMAs occurred due to concomitant emicizumab and bypassing agents. Trial registration This trial is registered at ClinicalTrials.gov (NCT03191799).

وصف الملف: application/pdf

العلاقة: https://boris.unibe.ch/191641Test/

الإتاحة: https://doi.org/10.1055/s-0043-1777766Test
https://boris.unibe.ch/191641/1/s-0043-1777766.pdfTest
https://boris.unibe.ch/191641Test/

المؤلفون: Agarwal, Suresh, Hermans, Cedric, Miesbach, Wolfgang, Peyvandi, Flora, Sidonio, Robert, Osmond, Dane, Newman, Vanessa, Henshaw, Josh, Pipe, Steven

المساهمون: BioMarin Pharmaceutical

المصدر: Haemophilia ; ISSN 1351-8216 1365-2516

الوصف: Introduction Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8‐1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8‐1 enrolment since emicizumab was an investigational therapy at the time of trial initiation. Aim Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec. Methods To estimate bleeding risk at weekly intervals following valoctocogene roxaparvovec infusion, a published emicizumab pharmacokinetic model was used to simulate emicizumab concentrations and merged with FVIII activity time‐course data for participants in GENEr8‐1. The analysis investigated three approved emicizumab dosing regimens for two transition scenarios that varied whether the last dose of emicizumab was administered on the same day or 4 weeks after valoctocogene roxaparvovec infusion. Results Simulations demonstrated administering the last emicizumab dose the day of valoctocogene roxaparvovec infusion and 4 weeks after offered similar levels of haemostatic control, and bleeding risk was similar for all emicizumab dosing regimens. An algorithm was developed to provide guidance for discontinuation of emicizumab. Theoretical cases based on GENEr8‐1 participants are presented to illustrate how decisions may vary among individuals. Conclusion Pharmacokinetic simulations demonstrated no clinically meaningful difference in bleeding risk caused by decaying emicizumab levels and rising gene therapy‐derived endogenous FVIII for all examined emicizumab doses and dosing regimens. Therefore, multiple approaches can safely transition individuals from emicizumab prophylaxis to valoctocogene roxaparvovec.

الإتاحة: https://doi.org/10.1111/hae.15025Test

المؤلفون: Giordano, Paola, Pollio, Berardino, Sottilotta, Gianluca, Biasoli, Chiara, Daniele, Filomena, De Cristofaro, Raimondo, Peyvandi, Flora, Villa, Maria Rosaria, Castaman, Giancarlo

المصدر: European Journal of Haematology ; volume 112, issue 5, page 765-775 ; ISSN 0902-4441 1600-0609

الوصف: Objectives To evaluate pattern of use and clinical outcomes in pediatric/adolescent patients enrolled in the IDEAL study. Methods This post‐hoc analysis of IDEAL retrospective‐prospective observational study focused on patients <18 years, 100% on prophylaxis during the entire observation period. Results Thirteen subjects (median age 10.0 years; 61.5% ≤ 11 years) were analyzed. The infusion frequency changed from 2/week in 84.6% ( N = 11) of patients with previous rFIX, to less than 1/weekly in 76.9% ( N = 9) with rIX‐FP and the annualized number of infusions reduced of 57% ( p = .002), from a mean ± SD of 95.1 ± 22.77 to 40.4 ± 6.79, respectively. Annualized mean consumption decreased of about 56% ( p = .001), from 3748.4 ± 1155.40 IU/kg with previous rFIX, to 1656.8 ± 456.63 IU/kg of rIX‐FP. Mean FIX trough level changed from 3.0% ± 1.98% to 10.92% ± 3.6%. Low mean Annualized Bleeding Rate was maintained across all prophylaxis regimens (0.8 ± 1.69 vs. 0.3 ± 0.89) and zero bleeding patients moved from 69.2% ( N = 9) with previous rFIX to 84.6% ( N = 11) with rIX‐FP ( p = .63). Two adverse events, none related to rIX‐FP, occurred in two patients. No inhibitors development was reported. Conclusions The results in this pediatric/adolescent subgroup support rIX‐FP prophylaxis may reduce infusion frequency, while providing high FIX trough levels, stable annualized bleeding rate and a good safety profile.

الإتاحة: https://doi.org/10.1111/ejh.14168Test