31 results on '"Leavis, Helen L"'
Search Results
2. Clinical Symptoms, Laboratory Parameters and Long-Term Follow-up in a National DADA2 Cohort
- Author
-
Andriessen, Marie Valérie E., Legger, G. Elizabeth, Bredius, Robbert G. M., van Gijn, Marielle E., Hak, A. Elisabeth, Muller, Petra C. E. Hissink, Kamphuis, Sylvia, Klouwer, Femke C. C., Kuijpers, Taco W., Leavis, Helen L., Nierkens, Stefan, Rutgers, Abraham, van der Veken, Lars T., van Well, Gijs T. J., Mulders-Manders, Catharina M., and van Montfrans, Joris M.
- Published
- 2023
- Full Text
- View/download PDF
3. Pulmonary Computed Tomography Screening Frequency in Primary Antibody Deficiency
- Author
-
Smits, Bas M., Boland, Sharisa L., Hol, Marjolein E., Dandis, Rana, Leavis, Helen L., de Jong, Pim A., Prevaes, Sabine M.P.J., Mohamed Hoesein, Firdaus A.A., van Montfrans, Joris M., and Ellerbroek, Pauline M.
- Published
- 2024
- Full Text
- View/download PDF
4. YajC, a predicted membrane protein, promotes Enterococcus faecium biofilm Formation in vitro and in a rat endocarditis model
- Author
-
Top, Janetta, primary, Zhang, Xinglin, additional, Hendrickx, Antoni P A, additional, Boeren, Sjef, additional, van Schaik, Willem, additional, Huebner, Johannes, additional, Willems, Rob J L, additional, Leavis, Helen L, additional, and Paganelli, Fernanda L, additional
- Published
- 2024
- Full Text
- View/download PDF
5. Management of adult-onset Still's disease: evidence- and consensus-based recommendations by experts.
- Author
-
Leavis, Helen L, Daele, Paul L A van, Mulders-Manders, Catharina, Michels, Renée, Rutgers, Abraham, Legger, Elizabeth, Bijl, Marc, Hak, Elisabeth A, Lam-Tse, Wai-Kwan, Bonte-Mineur, Femke, Fretter, Peter, Simon, Anna, Paassen, Pieter van, Goes, Marlies C van der, Flendrie, Marcel, Vercoutere, Ward, Lieshout, Antoine W T van, Leek, Arjen, Vastert, Sebastiaan J, and Tas, Sander W
- Subjects
- *
RHEUMATOID arthritis diagnosis , *BIOTHERAPY , *RHEUMATOID arthritis treatment , *CONSENSUS (Social sciences) , *WORLD Wide Web , *RESEARCH funding , *QUESTIONNAIRES , *METHOTREXATE , *TREATMENT effectiveness , *DESCRIPTIVE statistics , *EVIDENCE-based medicine , *DELPHI method , *RHEUMATOLOGISTS , *GLUCOCORTICOIDS , *EVALUATION - Abstract
Objectives Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis; most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. The objectives of this study were to conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. Methods The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of three rounds. In the first two rounds, online lists of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. Results Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side effects, and preferred the use of biologics over conventional treatment. The role of IL-1 and IL-6 blocking agents was considered important in the treatment of AOSD. Conclusion In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Chronically Activated T-cells Retain Their Inflammatory Properties in Common Variable Immunodeficiency
- Author
-
Berbers, Roos-Marijn, van der Wal, M. Marlot, van Montfrans, Joris M., Ellerbroek, Pauline M., Dalm, Virgil A. S. H., van Hagen, P. Martin, Leavis, Helen L., and van Wijk, Femke
- Published
- 2021
- Full Text
- View/download PDF
7. Management of adult-onset Still's disease: evidence- and consensus-based recommendations by experts
- Author
-
Leavis, Helen L, primary, van Daele, Paul L A, additional, Mulders-Manders, Catharina, additional, Michels, Renée, additional, Rutgers, Abraham, additional, Legger, Elizabeth, additional, Bijl, Marc, additional, Hak, Elisabeth A, additional, Lam-Tse, Wai-Kwan, additional, Bonte-Mineur, Femke, additional, Fretter, Peter, additional, Simon, Anna, additional, van Paassen, Pieter, additional, van der Goes, Marlies, additional, Flendrie, Marcel, additional, Vercoutere, Ward, additional, van Lieshout, Antoine W T, additional, Leek, Arjen, additional, Vastert, Sebastiaan J, additional, and Tas, Sander W, additional
- Published
- 2023
- Full Text
- View/download PDF
8. Neurological phenotype of adenosine deaminase 2 deficient patients: a cohort study.
- Author
-
Verschoof, Merelijne A., van Meenen, Laura C. C., Andriessen, M. Valérie E., Brinkman, Daniëlle M. C., Kamphuis, Sylvia, Kuijpers, Taco W., Leavis, Helen L., Legger, G. Elizabeth, Mulders‐Manders, Catharina M., de Pagter, Anne P. J., Rutgers, Abraham, van Well, Gijs T. J., Coutinho, Jonathan M., Hak, A. Elisabeth, van Montfrans, Joris M., and Klouwer, Femke C. C.
- Subjects
ADENOSINE deaminase ,TRANSIENT ischemic attack ,ISCHEMIC stroke ,HEMORRHAGIC stroke ,TUMOR necrosis factors ,STROKE - Abstract
Background and purpose: Patients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischaemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported. Methods: In this cohort study, patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands were included. The frequency and recurrence rates of neurological manifestations before and after initiation of tumor necrosis factor α (TNF‐α) inhibiting therapy were analyzed. Results: Twenty‐nine patients were included with a median age at presentation of 5 years (interquartile range 1–17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. Transient ischaemic attack (TIA)/ischaemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischaemic strokes occurred in 12 patients, one after initiation of TNF‐α inhibiting therapy and one whilst switching between TNF‐α inhibitors. None was large‐vessel occlusion stroke. Two hemorrhagic strokes occurred: one aneurysmatic subarachnoid hemorrhage and one spontaneous intracerebral hemorrhage. Most neurological symptoms, including cranial nerve deficits, vertigo, ataxia and seizures, were caused by TIAs/ischaemic strokes and seldom recurred after initiation of TNF‐α inhibiting therapy. Conclusions: Neurological manifestations, especially TIA/ischaemic stroke, are common in patients with ADA2 deficiency and frequently are the presenting symptom. Because it is a treatable cause of young stroke, for which antiplatelet and anticoagulant therapy are considered contraindicated, awareness amongst neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small‐vessel ischaemic stroke without an identified cause should be considered. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
9. Neurological phenotype of adenosine deaminase 2 deficient patients: a cohort study
- Author
-
Verschoof, Merelijne A., primary, van Meenen, Laura C. C., additional, Andriessen, M. Valérie E., additional, Brinkman, Daniëlle M. C., additional, Kamphuis, Sylvia, additional, Kuijpers, Taco W., additional, Leavis, Helen L., additional, Legger, G. Elizabeth, additional, Mulders‐Manders, Catharina M., additional, de Pagter, Anne P. J., additional, Rutgers, Abraham, additional, van Well, Gijs T. J., additional, Coutinho, Jonathan M., additional, Hak, A. Elisabeth, additional, van Montfrans, Joris M., additional, and Klouwer, Femke C. C., additional
- Published
- 2023
- Full Text
- View/download PDF
10. Leflunomide/hydroxychloroquine combination therapy targets type I IFN-associated proteins in patients with Sjögren’s syndrome that show potential to predict and monitor clinical response
- Author
-
Hamkour, Safae, primary, van der Heijden, Eefje HM, additional, Lopes, Ana P, additional, Blokland, Sofie L M, additional, Bekker, Cornelis P J, additional, Van Helden-Meeuwsen, Cornelia G, additional, Versnel, Marjan A, additional, Kruize, Aike A, additional, Radstake, Timothy RDJ, additional, Leavis, Helen L, additional, Hillen, Maarten R, additional, and van Roon, Joel AG, additional
- Published
- 2023
- Full Text
- View/download PDF
11. CCR9/CXCR5 Co-Expressing CD4 T Cells Are Increased in Primary Sjögren’s Syndrome and Are Enriched in PD-1/ICOS-Expressing Effector T Cells
- Author
-
Hinrichs, Anneline C., primary, Kruize, Aike A., additional, Lafeber, Floris P. J. G., additional, Leavis, Helen L., additional, and van Roon, Joel A. G., additional
- Published
- 2023
- Full Text
- View/download PDF
12. Chronische anemie en onverklaarde ontsteking
- Author
-
van Daele, Paul L.A., van der Made, Caspar I., Leavis, Helen L., Hak, A. E.Liesbeth, Potjewijd, Judith, Rutgers, Abraham Bram, Transplantation Immunology Groningen, Internal Medicine, and Immunology
- Subjects
Male ,Inflammation ,Anemia/diagnosis ,Mutation ,Humans ,Anemia, Macrocytic ,Middle Aged ,Aged - Abstract
Achtergrond Het VEXAS-syndroom is een auto-inflammatoire ziekte die ontstaat door een verworven of somatische mutatie in het UBA1-gen. Deze X-gebonden aandoening komt vrijwel alleen voor bij mannen en openbaart zich pas op oudere leeftijd. Casus Wij beschrijven een patiënt met het VEXAS-syndroom bij wie in eerste instantie niet de juiste diagnose werd gesteld. Nadat de diagnose was gesteld op basis van genetisch onderzoek, behandelden wij de patiënt met prednisolon en de IL-6-remmer tocilizumab. Conclusie Bij mannen vanaf de middelbare leeftijd die een multisystemisch inflammatoir ziektebeeld laten zien zonder infectie, moet de diagnose ‘VEXAS-syndroom’ worden overwogen, zeker wanneer er sprake is van een bijkomende macrocytaire anemie. De diagnose kan eenvoudig worden gesteld op basis van gericht onderzoek naar mutaties in UBA1. De behandeling bestaat vooral uit toediening van immunosuppressiva. De mortaliteit is hoog.
- Published
- 2023
13. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19
- Author
-
Bradbury, Charlotte A., Lawler, Patrick R., Stanworth, Simon J., McVerry, Bryan J., McQuilten, Zoe, Higgins, Alisa M., Mouncey, Paul R., Al-Beidh, Farah, Rowan, Kathryn M., Berry, Lindsay R., Lorenzi, Elizabeth, Zarychanski, Ryan, Arabi, Yaseen M., Annane, Djillali, Beane, Abi, Van Bentum-Puijk, Wilma, Bhimani, Zahra, Bihari, Shailesh, Bonten, Marc J. M., Brunkhorst, Frank M., Buzgau, Adrian, Buxton, Meredith, Carrier, Marc, Cheng, Allen C., Cove, Matthew, Detry, Michelle A., Estcourt, Lise J., Fitzgerald, Mark, Girard, Timothy D., Goligher, Ewan C., Goossens, Herman, Haniffa, Rashan, Hills, Thomas, Huang, David T., Horvat, Christopher M., Hunt, Beverley J., Ichihara, Nao, Lamontagne, Francois, Leavis, Helen L., Linstrum, Kelsey M., Litton, Edward, Marshall, John C., McAuley, Daniel F., McGlothlin, Anna, McGuinness, Shay P., Middeldorp, Saskia, Montgomery, Stephanie K., Morpeth, Susan C., Murthy, Srinivas, Neal, Matthew D., Nichol, Alistair D., Parke, Rachael L., Parker, Jane C., Reyes, Luis, Saito, Hiroki, Santos, Marlene S., Saunders, Christina T., Serpa-Neto, Ary, Seymour, Christopher W., Shankar-Hari, Manu, Singh, Vanessa, Tolppa, Timo, Turgeon, Alexis F., Turner, Anne M., van de Veerdonk, Frank L., Green, Cameron, Lewis, Roger J., Angus, Derek C., McArthur, Colin J., Berry, Scott, Derde, Lennie P. G., Webb, Steve A., Gordon, Anthony C., Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Vermassen, Joris, REMAP-CAP Investigators, University of Bristol [Bristol], University Health Network, University of Toronto, University of Oxford, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Monash University [Melbourne], Imperial College London, University of Manitoba [Winnipeg], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University Medical Center [Utrecht], St. Michael's Hospital, 215522, CS-2016-16-011, RP-2015-06-18, National Institutes of Health, NIH, U.S. Department of Defense, DOD, National Institute of General Medical Sciences, NIGMS, National Institute of Neurological Disorders and Stroke, NINDS, Gordon and Betty Moore Foundation, GBMF, Medtronic, Baxter International, Medical Center, University of Pittsburgh, CancerCare Manitoba Foundation, CCMF, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD, Wellcome Trust, WT, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, LAM Therapeutics, Canadian Institutes of Health Research, IRSC: 158584, Medical Research Council, MRC, National Institute for Health and Care Research, NIHR, European Commission, EC, National Heart and Lung Institute, NHLI, Queen's University Belfast, QUB: US8962032, National Health and Medical Research Council, NHMRC: APP1101719, National Medical Research Council, NMRC, Health Research Council of New Zealand, HRC: 16/631, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Swedish Orphan Biovitrum, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support: This study was funded by the following: the Platform for European Preparedness Against (Re-)Emerging Epidemics (PREPARE) consortium of the European Union, FP7-HEALTH-2013-INNOVATION-1 (grant 602525), the Rapid European COVID-19 Emergency Research Response (RECOVER) consortium of the European Union’s Horizon 2020 Research and Innovation Programme (grant 101003589), the Australian National Health and Medical Research Council (grant APP1101719), the Health Research Council of New Zealand (grant 16/631), the Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program (grant 158584), the NIHR and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (grant CTN 2014-012), the University of Pittsburgh Medical Center (UPMC) Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (grant PHRC-20-0147), the Minderoo Foundation, and the Wellcome Trust Innovations Project (grant 215522). Dr Shankar-Hari is funded by an NIHR clinician scientist fellowship (grant CS-2016-16-011) and Dr Gordon is funded by an NIHR research professorship (grant RP-2015-06-18)., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Clinical Trials Group, the Irish Critical Care Clinical Trials Network, the UK Critical Care Research Group and the International Forum of Acute Care Trialists., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands, reported receipt of personal fees from Lilly, BMS-Pfizer, Bayer, Amgen, Novartis, Janssen, Portola, Ablynx, and Grifols. Dr Lawler reported receipt of personal fees from Novartis, CorEvitas, and Brigham and Women’s Hospital and royalties from McGraw-Hill Publishing. Dr McVerry reported receipt of grants from the National Heart, Lung, and Blood Institute and Bayer Pharmaceuticals and personal fees from Boehringer Ingelheim. Dr L. Berry reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Lorenzi reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Zarychanski reported receipt of grants from the Canadian Institutes of Health Research, LifeArc, Research Manitoba, the CancerCare Manitoba Foundation, Peter Munk Cardiac Centre, and the Thistledown Foundation and research operating support as the Lyonel G. Israels Research Chair in Hematology. Dr Bonten reported membership in international study steering committees, advisory boards, and independent data safety and monitoring committees funded by Janssen Vaccines, Merck Sharp & Dohme, AstraZeneca, Pfizer, and Sanofi Pasteur (all reimbursements to UMC Utrecht). Dr Brunkhorst reported receipt of grants from Jena University Hospital. Dr Buxton reported receipt of a gift from the Breast Cancer Research Foundation and contracts with Amgen and Eisai. Dr Carrier reported receipt of grants from BMS-Pfizer and personal fees from Bayer, Sanofi, Servier, Leo Phama, and BMS-Pfizer to his institution. Dr Cove reported receipt of grants from the National Medical Research Council and personal fees from Baxter and Medtronic. Dr Estcourt reported receipt of grants from the UK National Institute for Health Research (NIHR) and the European Union Horizon 2020 Research and Innovation Programme. Dr Haniffa reported receipt of grants from the UK Research and Innovation/Medical Research Council African Critical Care Registry Network. Dr Horvat reported receipt of grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Dr Ichihara reported being affiliated with the Department of Healthcare Quality Assessment, University of Tokyo, which is a social collaboration supported by the National Clinical Database, Johnson & Johnson, and Nipro Corporation. Dr Marshall reported receipt of personal fees from AM Pharma and Critical Care Medicine. Dr McAuley reported receipt of personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Lilly, Vir Biotechnology, Faron Pharmaceutical, and SOBI and grants from the NIHR, the Wellcome Trust, Innovate UK, the UK Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, in addition, Dr McAuley had a Queen’s University Belfast patent for novel treatment for inflammatory disease (US8962032), was co-director of research at the Intensive Care Society until June 2021, and was director of the Efficacy and Mechanisms Evaluation Program for the UK Medical Research Council/NIHR. Dr Middeldorp reported receipt of personal fees from Daiichi Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Portola/Alexion, AbbVie, BMS-Pfizer, Sanofi, and Viatris, all paid to his institution, and grants from Daiichi Sankyo, Bayer, Pfizer, and Boehringer Ingelheim. Dr Neal reported equity in Haima Therapeutics, receipt of personal fees from Janssen Pharma and Haemonetics, and receipt of grants from Instrumentation Laboratory, the National Institutes of Health, and the Department of Defense. Dr Nichol reported receipt of personal fees from AM Pharma, paid to his university, and grants from Baxter. Dr Parke reported receipt of grants from Fisher and Paykel Healthcare NZ. Dr Serpa-Neto reported receipt of personal fees from Drager and Endpoint Health. Dr Seymour reported receipt of grants from the Gordon and Betty Moore Foundation and the National Institutes of Health/National Institute of General Medical Sciences. Dr Lewis reported being senior medical scientist at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr S. Berry reported being an employee with an ownership role at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Derde reported being a coordinating committee member for the European Clinical Research Alliance on Infectious Diseases, a member of the Dutch Intensivists Task Force on Acute Infectious Threats, a member of the International Scientific Advisory Board for Sepsis Canada, and a member of the Dutch Academy of Sciences’ Pandemic Preparedness Plan committee. Dr Gordon reported receipt of personal fees from 30 Respiratory, paid to his institution. No other disclosures were reported., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), Investigators, REMAP-CAP Writing Committee for the REMAP-CAP, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, and Intensive Care Medicine
- Subjects
Adult ,Male ,Platelet Aggregation Inhibitors/adverse effects ,Critical Illness ,[SDV]Life Sciences [q-bio] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Hemorrhage ,Aspirin/adverse effects ,Hemorrhage/chemically induced ,INFECTION ,Humans ,COAGULOPATHY ,Aspirin ,Anticoagulants ,COVID-19 ,Bayes Theorem ,Venous Thromboembolism ,General Medicine ,Middle Aged ,Respiration, Artificial ,COVID-19 Drug Treatment ,Critical Illness/mortality ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Purinergic P2Y Receptor Antagonists/adverse effects ,Purinergic P2Y Receptor Antagonists ,COVID-19/complications ,Female ,Human medicine ,Anticoagulants/adverse effects ,Platelet Aggregation Inhibitors ,Venous Thromboembolism/drug therapy - Abstract
Contains fulltext : 248713.pdf (Publisher’s version ) (Closed access) IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). CONCLUSIONS AND RELEVANCE: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.
- Published
- 2022
14. Soluble Signal Inhibitory Receptor on Leukocytes-1 Is Released from Activated Neutrophils by Proteinase 3 Cleavage
- Author
-
von Richthofen, Helen J., primary, Westerlaken, Geertje H.A., additional, Gollnast, Doron, additional, Besteman, Sjanna, additional, Delemarre, Eveline M., additional, Rodenburg, Karlijn, additional, Moerer, Petra, additional, Stapels, Daphne A.C., additional, Andiappan, Anand K., additional, Rötzschke, Olaf, additional, Nierkens, Stefan, additional, Leavis, Helen L., additional, Bont, Louis J., additional, Rooijakkers, Suzan H.M., additional, and Meyaard, Linde, additional
- Published
- 2023
- Full Text
- View/download PDF
15. In patients with primary Sjögren’s syndrome innate-like MAIT cells display upregulated IL-7R, IFN-γ, and IL-21 expression and have increased proportions of CCR9 and CXCR5-expressing cells
- Author
-
Hinrichs, Anneline C., primary, Kruize, Aike A., additional, Leavis, Helen L., additional, and van Roon, Joel A. G., additional
- Published
- 2022
- Full Text
- View/download PDF
16. Air pollution from livestock farms and the oropharyngeal microbiome of COPD patients and controls
- Author
-
van Kersen, Warner, primary, Bossers, Alex, additional, de Steenhuijsen Piters, Wouter A.A., additional, de Rooij, Myrna M.T., additional, Bonten, Marc, additional, Fluit, Ad C., additional, Heederik, Dick, additional, Paganelli, Fernanda L., additional, Rogers, Malbert, additional, Viveen, Marco, additional, Bogaert, Debby, additional, Leavis, Helen L., additional, and Smit, Lidwien A.M., additional
- Published
- 2022
- Full Text
- View/download PDF
17. Heterozygous Variants in the DNA-binding Domain of c-Myb May Affect Normal B/T Cell Development
- Author
-
Smits, Bas M., primary, Hartley, Taila, additional, Dünnebach, Ester, additional, Bartels, Marije, additional, Boycott, Kim M., additional, Kernohan, Kirstin D., additional, Dyment, David A., additional, Giltay, Jacques C., additional, Haddad, Elie, additional, Jarinova, Olga, additional, van Montfrans, Joris, additional, van Royen-Kerkhof, Annet, additional, van der Veken, Lars T., additional, de Witte, Moniek, additional, Nierkens, Stefan, additional, Pham-Huy, Anne, additional, and Leavis, Helen L., additional
- Published
- 2022
- Full Text
- View/download PDF
18. Case report: Up‐front allogeneic stem cell transplantation in a patient with the VEXAS syndrome
- Author
-
van Leeuwen‐Kerkhoff, Nathalie, primary, de Witte, Moniek A., additional, Heijstek, Marloes W., additional, and Leavis, Helen L., additional
- Published
- 2022
- Full Text
- View/download PDF
19. Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin
- Author
-
Spaan, András N., primary, Neehus, Anna-Lena, additional, Laplantine, Emmanuel, additional, Staels, Frederik, additional, Ogishi, Masato, additional, Seeleuthner, Yoann, additional, Rapaport, Franck, additional, Lacey, Keenan A., additional, Van Nieuwenhove, Erika, additional, Chrabieh, Maya, additional, Hum, David, additional, Migaud, Mélanie, additional, Izmiryan, Araksya, additional, Lorenzo, Lazaro, additional, Kochetkov, Tatiana, additional, Heesterbeek, Dani A. C., additional, Bardoel, Bart W., additional, DuMont, Ashley L., additional, Dobbs, Kerry, additional, Chardonnet, Solenne, additional, Heissel, Søren, additional, Baslan, Timour, additional, Zhang, Peng, additional, Yang, Rui, additional, Bogunovic, Dusan, additional, Wunderink, Herman F., additional, Haas, Pieter-Jan A., additional, Molina, Henrik, additional, Van Buggenhout, Griet, additional, Lyonnet, Stanislas, additional, Notarangelo, Luigi D., additional, Seppänen, Mikko R. J., additional, Weil, Robert, additional, Seminario, Gisela, additional, Gomez-Tello, Héctor, additional, Wouters, Carine, additional, Mesdaghi, Mehrnaz, additional, Shahrooei, Mohammad, additional, Bossuyt, Xavier, additional, Sag, Erdal, additional, Topaloglu, Rezan, additional, Ozen, Seza, additional, Leavis, Helen L., additional, van Eijk, Maarten M. J., additional, Bezrodnik, Liliana, additional, Blancas Galicia, Lizbeth, additional, Hovnanian, Alain, additional, Nassif, Aude, additional, Bader-Meunier, Brigitte, additional, Neven, Bénédicte, additional, Meyts, Isabelle, additional, Schrijvers, Rik, additional, Puel, Anne, additional, Bustamante, Jacinta, additional, Aksentijevich, Ivona, additional, Kastner, Daniel L., additional, Torres, Victor J., additional, Humblet-Baron, Stéphanie, additional, Liston, Adrian, additional, Abel, Laurent, additional, Boisson, Bertrand, additional, and Casanova, Jean-Laurent, additional
- Published
- 2022
- Full Text
- View/download PDF
20. CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome
- Author
-
Hinrichs, Anneline C., primary, Blokland, Sofie L. M., additional, Kruize, Aike A., additional, Lafeber, Floris P. J., additional, Leavis, Helen L., additional, and van Roon, Joel A. G., additional
- Published
- 2022
- Full Text
- View/download PDF
21. Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity
- Author
-
van Leeuwen, Leanne P.M., primary, GeurtsvanKessel, Corine H., additional, Ellerbroek, Pauline M., additional, de Bree, Godelieve J., additional, Potjewijd, Judith, additional, Rutgers, Abraham, additional, Jolink, Hetty, additional, van de Veerdonk, Frank, additional, van Gorp, Eric C.M., additional, de Wilt, Faye, additional, Bogers, Susanne, additional, Gommers, Lennert, additional, Geers, Daryl, additional, Bruns, Anke H.W., additional, Leavis, Helen L., additional, van Haga, Jelle W., additional, Lemkes, Bregtje A., additional, van der Veen, Annelou, additional, de Kruijf-Bazen, S.F.J., additional, van Paassen, Pieter, additional, de Leeuw, Karina, additional, van de Ven, Annick A.J.M., additional, Verbeek-Menken, Petra H., additional, van Wengen, Annelies, additional, Arend, Sandra M., additional, Ruten-Budde, Anja J., additional, van der Ent, Marianne W., additional, van Hagen, P. Martin, additional, Sanders, Rogier W., additional, Grobben, Marloes, additional, van der Straten, Karlijn, additional, Burger, Judith A., additional, Poniman, Meliawati, additional, Nierkens, Stefan, additional, van Gils, Marit J., additional, de Vries, Rory D., additional, and Dalm, Virgil A.S.H., additional
- Published
- 2022
- Full Text
- View/download PDF
22. Soluble signal inhibitory receptor on leukocytes-1 is released from activated neutrophils by proteinase 3 cleavage
- Author
-
von Richthofen, Helen J., primary, Westerlaken, Geertje H.A., additional, Gollnast, Doron, additional, Besteman, Sjanna, additional, Delemarre, Eveline M., additional, Rodenburg, Karlijn, additional, Moerer, Petra, additional, Stapels, Daphne A.C., additional, Andiappan, Anand K., additional, Rötzschke, Olaf, additional, Nierkens, Stefan, additional, Leavis, Helen L., additional, Bont, Louis J., additional, Rooijakkers, Suzan H.M., additional, and Meyaard, Linde, additional
- Published
- 2022
- Full Text
- View/download PDF
23. Stimulating severe COVID-19: the potential role of GM-CSF antagonism
- Author
-
Leavis, Helen L, primary, van de Veerdonk, Frank L, additional, and Murthy, Srinivas, additional
- Published
- 2022
- Full Text
- View/download PDF
24. Clinical features and immune-related protein patterns of anti-MDA5 positive clinically amyopathic dermatomyositis Dutch patients
- Author
-
Hensgens, Marjolein P M, primary, Delemarre, Eveline M, additional, Drylewicz, Julia, additional, Voortman, Mareye, additional, Krol, Roline M, additional, Dalm, Virgil A S H, additional, Miedema, Jelle R, additional, Wiertz, Ivo, additional, Grutters, Jan, additional, Limper, Maarten, additional, Nierkens, Stefan, additional, and Leavis, Helen L, additional
- Published
- 2022
- Full Text
- View/download PDF
25. Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS
- Author
-
van der Made, Caspar I., primary, Potjewijd, Judith, additional, Hoogstins, Annemiek, additional, Willems, Huub P.J., additional, Kwakernaak, Arjan J., additional, de Sevaux, Ruud G.L., additional, van Daele, Paul L.A., additional, Simons, Annet, additional, Heijstek, Marloes, additional, Beck, David B., additional, Netea, Mihai G., additional, van Paassen, Pieter, additional, Elizabeth Hak, A., additional, van der Veken, Lars T., additional, van Gijn, Marielle E., additional, Hoischen, Alexander, additional, van de Veerdonk, Frank L., additional, Leavis, Helen L., additional, and Rutgers, Abraham, additional
- Published
- 2022
- Full Text
- View/download PDF
26. Repetitive Immune-Mediated Noninfectious Endocarditis Necessitating 5 Mitral Valve Replacements
- Author
-
Muller, Steven A., primary, Leavis, Helen L., additional, Taha, Karim, additional, Koenderman, Leo, additional, Chamuleau, Steven A.J., additional, Suyker, Willem J.L., additional, and Cramer, Maarten J., additional
- Published
- 2021
- Full Text
- View/download PDF
27. The oropharyngeal microbiome of COPD patients and controls in a livestock dense area
- Author
-
van Kersen, Warner, primary, Bossers, Alex, additional, De Steenhuijsen Piters, Wouter A.A., additional, De Rooij, Myrna M.T., additional, Oldenwening, Marieke, additional, Bonten, Marc, additional, Fluit, Ad C., additional, Heederik, Dick, additional, Paganelli, Fernanda L., additional, Rogers, Malbert, additional, Viveen, Marco, additional, Willems, Rob, additional, Bogaert, Debby, additional, Leavis, Helen L., additional, and Smit, Lidwien A.M., additional
- Published
- 2021
- Full Text
- View/download PDF
28. Implementation of Early Next-Generation Sequencing for Inborn Errors of Immunity: A Prospective Observational Cohort Study of Diagnostic Yield and Clinical Implications in Dutch Genome Diagnostic Centers.
- Author
-
Elsink, Kim, Huibers, Manon M. H., Hollink, Iris H. I. M., Simons, Annet, Zonneveld-Huijssoon, Evelien, van der Veken, Lars T., Leavis, Helen L., Henriet, Stefanie S. V., van Deuren, Marcel, van de Veerdonk, Frank L., Potjewijd, Judith, Berghuis, Dagmar, Dalm, Virgil A. S. H., Vermont, Clementien L., van de Ven, Annick A. J. M., Lambeck, Annechien J. A., Abbott, Kristin M., van Hagen, P. Martin, de Bree, Godelieve J., and Kuijpers, Taco W.
- Subjects
NUCLEOTIDE sequencing ,CHILD patients ,COHORT analysis ,IMMUNOLOGIC diseases ,GENETIC testing ,GENETIC disorder diagnosis ,MOLECULAR diagnosis - Abstract
Objective: Inborn errors of immunity (IEI) are a heterogeneous group of disorders, affecting different components of the immune system. Over 450 IEI related genes have been identified, with new genes continually being recognized. This makes the early application of next-generation sequencing (NGS) as a diagnostic method in the evaluation of IEI a promising development. We aimed to provide an overview of the diagnostic yield and time to diagnosis in a cohort of patients suspected of IEI and evaluated by an NGS based IEI panel early in the diagnostic trajectory in a multicenter setting in the Netherlands. Study Design: We performed a prospective observational cohort study. We collected data of 165 patients with a clinical suspicion of IEI without prior NGS based panel evaluation that were referred for early NGS using a uniform IEI gene panel. The diagnostic yield was assessed in terms of definitive genetic diagnoses, inconclusive diagnoses and patients without abnormalities in the IEI gene panel. We also assessed time to diagnosis and clinical implications. Results: For children, the median time from first consultation to diagnosis was 119 days versus 124 days for adult patients (U=2323; p=0.644). The median turn-around time (TAT) of genetic testing was 56 days in pediatric patients and 60 days in adult patients (U=1892; p=0.191). A definitive molecular diagnosis was made in 25/65 (24.6%) of pediatric patients and 9/100 (9%) of adults. Most diagnosed disorders were identified in the categories of immune dysregulation (n=10/25; 40%), antibody deficiencies (n=5/25; 20%), and phagocyte diseases (n=5/25; 20%). Inconclusive outcomes were found in 76/165 (46.1%) patients. Within the patient group with a genetic diagnosis, a change in disease management occurred in 76% of patients. Conclusion: In this cohort, the highest yields of NGS based evaluation for IEI early in the diagnostic trajectory were found in pediatric patients, and in the disease categories immune dysregulation and phagocyte diseases. In cases where a definitive diagnosis was made, this led to important disease management implications in a large majority of patients. More research is needed to establish a uniform diagnostic pathway for cases with inconclusive diagnoses, including variants of unknown significance. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
29. Severe thrombotic microangiopathy after autologous stem cell transplantation in systemic sclerosis: a case report.
- Author
-
Sharif, Maryam O., Leavis, Helen L., Paassen, Pieter van, Rhenen, Anna van, Timmermans, Sjoerd A. M. E. G., Ton, Evelien, Laar, Jacob M. van, and Spierings, Julia
- Subjects
- *
GLUCOCORTICOIDS , *HISPANIC Americans , *HEMOLYSIS & hemolysins , *SYSTEMIC scleroderma , *SEVERITY of illness index , *CARDIAC tamponade , *LACTATE dehydrogenase , *THROMBOCYTOPENIA , *HEMATOPOIETIC stem cell transplantation - Abstract
The article describes the case of a 64-year-old White female who presented experienced severe thrombotic microangiopathy following autologous stem cell transplantation in systemic sclerosis (SSc). Topics covered include the medical history of the patient, the diagnostic challenges and dramatic course of haematopoietic stem cell transplantation-thrombotic microangiopathy (HSCT-TMA) in SSc as illustrated by the case, and patient outcome following treatment.
- Published
- 2021
- Full Text
- View/download PDF
30. Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus.
- Author
-
Kaan ED, Brunekreef TE, Drylewicz J, van den Hoogen LL, van der Linden M, Leavis HL, van Laar JM, van der Vlist M, Otten HG, and Limper M
- Abstract
Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of disease symptoms and an unpredictable clinical course. To improve treatment outcome, stratification based on immunological manifestations commonly seen in patients with SLE such as autoantibodies, type I interferon (IFN) signature and neutrophil extracellular trap (NET) release may help. It is assumed that there is an association between these immunological phenomena, since NET release induces IFN production and IFN induces autoantibody formation via B-cell activation. Here we studied the association between autoantibodies, the IFN signature, NET release, and clinical manifestations in patients with SLE., Methods: We performed principal component analysis (PCA) and hierarchical clustering of 57 SLE-related autoantibodies in 25 patients with SLE. We correlated each autoantibody to the IFN signature and NET inducing capacity., Results: We observed two distinct clusters: one cluster contained mostly patients with a high IFN signature. Patients in this cluster often present with cutaneous lupus, and have higher anti-dsDNA concentrations. Another cluster contained a mix of patients with a high and low IFN signature. Patients with high and low NET inducing capacity were equally distributed between the clusters. Variance between the clusters is mainly driven by antibodies against histones, RibP2, RibP0, EphB2, RibP1, PCNA, dsDNA, and nucleosome. In addition, we found a trend towards increased concentrations of autoantibodies against EphB2, RibP1, and RNP70 in patients with an IFN signature. We found a negative correlation of NET inducing capacity with anti-FcER (r = -0.530; p = 0.007) and anti-PmScl100 (r = -0.445; p = 0.03)., Conclusion: We identified a subgroup of patients with an IFN signature that express increased concentrations of antibodies against DNA and RNA-binding proteins, which can be useful for further patient stratification and a more targeted therapy. We did not find positive associations between autoantibodies and NET inducing capacity. Our study further strengthens the evidence of a correlation between RNA-binding autoantibodies and the IFN signature., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
- Published
- 2024
- Full Text
- View/download PDF
31. [Chronic anemia and unexplained inflammation: think of VEXAS syndrome].
- Author
-
van Daele PLA, van der Made CI, Leavis HL, Hak AEL, Potjewijd J, and Rutgers AB
- Subjects
- Male, Middle Aged, Humans, Aged, Inflammation, Mutation, Anemia diagnosis, Anemia etiology, Anemia, Macrocytic
- Abstract
Background: VEXAS-syndrome is an X-linked acquired multisystemic autoinflammatory disease caused by a somatic mutation in UBA1., Case Description: In this manuscript we describe a 79-year-old male suffering from skin lesions, macrocytic anemia and lab results showing inflammation in which, based on finding a mutation in UBA1, VEXAS was diagnosed. He was treated with a combination of high dose corticosteroids and anti-IL-6 with good response., Conclusion: In middle aged males presenting with multisystemic inflammation without evidence of infection a diagnosis of VEXAS should be considered, especially if there is evidence of a macrocytic anemia. Early testing for UBA1 mutations helps in making the diagnosis. Despite treatment with intensive immunosuppression mortality remains high.
- Published
- 2023
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.