11 results on '"Kaplanski, G."'
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2. Hypophysite, aussi une affaire d’interniste : étude rétrospective monocentrique de 60 cas
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Miquel, L., primary, Testud, B., additional, Albarel, F., additional, Sahakian, N., additional, Cuny, T., additional, Brue, T., additional, Schleinitz, N., additional, Kaplanski, G., additional, Ebbo, M., additional, and Castinetti, F., additional
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- 2024
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3. Hypophysite : la nécéssité d’une collaboration entre endocrinologue et interniste
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Miquel, L., Testud, B., Albarel, F., Sahakian, N., Cuny, T., Brue, T., Schleinitz, N., Kaplanski, G., Ebbo, M., and Castinetti, F.
- Abstract
L’hypophysite est une atteinte inflammatoire de l’hypophyse et/ou de l’infundibulum, pouvant entraîner des séquelles cliniques, radiologiques et hormonales. Sa caractérisation est limitée dans la littérature.
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- 2024
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4. Vascular endothelial-cadherin is involved in endothelial cell detachment during thrombotic thrombocytopenic purpura.
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Cauchois R, Lagarde M, Muller R, Faccini J, Leroyer A, Arnaud L, Poullin P, Dignat-George F, Kaplanski G, and Tellier E
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- Humans, Animals, Phosphorylation, Male, Middle Aged, Female, Case-Control Studies, Adult, Calcium metabolism, Calcium blood, Endothelial Cells metabolism, ADAMTS13 Protein blood, ADAMTS13 Protein metabolism, Cells, Cultured, Mice, Mice, Inbred C57BL, Severity of Illness Index, Aged, Cadherins metabolism, Purpura, Thrombotic Thrombocytopenic blood, Human Umbilical Vein Endothelial Cells metabolism, Antigens, CD metabolism, Capillary Permeability, Cell Adhesion
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Background: Immune thrombotic thrombocytopenic purpura (i-TTP) is a life-threatening thrombotic microangiopathy linked to ADAMTS-13 deficiency. It has long been assumed that the activation of endothelial cells is the triggering factor for the thrombotic thrombocytopenic purpura crisis. Circulating endothelial cells (CECs) have been shown to be a biomarker of vascular damage and are associated with the clinical severity of i-TTP. However, the mechanisms leading to endothelial cell detachment remain unclear., Objectives: We investigated junctional destabilization the mechanisms underlying cell detachment in thrombotic thrombocytopenic purpura., Methods: We quantified CECs in i-TTP patients and investigated the effect of plasmas in vitro by measuring phosphorylation and internalization of vascular endothelial (VE)-Cadherin and in vivo in a vascular permeability model., Results: In plasma from i-TTP patients, we show that CEC count is associated with severity and correlated to intracellular calcium influx (P < .01). In vitro, serum from i-TTP patients induced stronger detachment of human umbilical vein endothelial cells than serum from control patients (P < .001). Plasma from i-TTP patients induced a higher calcium-dependent phosphorylation (P < .05) and internalization (P < .05) of VE-cadherin compared with plasma from control patients. This effect could be reproduced by immunoglobulin (Ig)G fraction isolated from patient plasma and, in particular, by the F(ab)'2 fragments of the corresponding IgG. In addition, subcutaneous injection of i-TTP plasma into mice resulted in higher vascular permeability than plasma from control patients. An inhibitor of endothelial calcium influx, ITF1697, normalized this increase in permeability., Conclusion: Our results suggest that plasma-induced endothelial activation also leads to an increase in vascular permeability. They contribute to the understanding of the mechanisms behind the presence of elevated CECs in patients' blood by linking endothelial activation to endothelial injury., Competing Interests: Declaration of competing interests P.P. is a member of the scientific advisory boards of Ablynx-Sanofi. The other authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)
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- 2024
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5. Deciphering the Presentation and Etiologies of Hypophysitis Highlights the Need for Repeated Systematical Investigation.
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Miquel L, Testud B, Albarel F, Sahakian N, Cuny T, Graillon T, Brue T, Dufour H, Schleinitz N, Kaplanski G, Ebbo M, and Castinetti F
- Abstract
Aims: Hypophysitis is defined as an inflammation of the pituitary gland and/or infundibulum. Our aim was to characterize the initial course and evolution of patients with hypophysitis according to the different etiologies., Patients and Methods: Retrospective observational study conducted in a universitary referral hospital center. Patients over 15 years of age were included if they had a diagnosis of hypophysitis between January 2014 and October 2023, with the exclusion of hypophysitis secondary to immune checkpoint inhibitors., Results: Sixty-one patients (64% women; median age, 34 years) were included. Polyuria-polydipsia, headache and asthenia were present in 64%, 48% and 44% of cases respectively. At diagnosis, at least one anterior pituitary deficiency was present in 91.5% of cases and vasopressin deficiency in 56%. MRI was abnormal in 97% of cases. Secondary hypophysitis was found in 46% of cases (n=28), including sarcoidosis in 28% (n=17) and L-group histiocytoses in 13.1% (n=8). Among patients with secondary hypophysitis, pituitary deficiency preceded systemic manifestations in 23% and occurred concomitantly in 23% of cases. Patients were treated in 36% of cases (glucocorticoids, surgery…), without improvement of pituitary hormone deficits., Conclusions: A systemic etiology of hypophysitis was found in almost half of the patients. Pituitary disorders preceded the systemic disease in a quarter of the cases. This emphasizes the importance of a systematic repeated workup looking for a secondary etiology of hypophysitis in these patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
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- 2024
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6. [Role of university hospital doctors specialized in internal medicine in health professions training and institutions in France: Survey of the National College of Teachers of Internal Medicine (CEMI)].
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Rauzy O, Bouillet L, Chevalier K, Cohen-Aubart F, Delacroix I, Hanslik T, Kaplanski G, Lazaro E, Le Moigne E, Pottier P, Riviere E, and Mouthon L
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Rationale: On the occasion of the General stage meeting of Internal Medicine, the National College of Internal Medicine Teachers (CEMI) conducted a survey on teaching activity among all French university hospital (HU) internal medicine specialists., Method: The survey was carried out in September 2023 by sending an email to 101 hospital practitioners university professors (PU-PH) and 18 hospital practitioners assistant professors (MCU-PH) of internal medicine in subsection 53-01 of the National council of universities (CNU), as well as to the 11 HU internists working in immunology (subsection 47-01) or therapeutics (subsection 48-04)., Results: Seventy-three HUs (56.1%) responded to the survey, including 65 PU-PH, 7 MCU-PH and 1 university hospital practitioner (PHU). Internal medicine HUs participate in faculty teaching: 80% are responsible for teaching, 30% are responsible for the year or cycle or lead committees and 40% have had or have an elected mandate at the faculty or at university. Internal medicine HU are involved in the teaching of semiology during the first cycle of medical studies, but also in pharmaceutical sciences, dentistry, midwifery and in paramedical training. They are very invested in the implementation of the second cycle reform and 80% are involved in the preparation of Objective Structured Clinical Examinations (ECOS), mainly as examiners (90%). They also participate in teaching using simulation (60%), teaching advanced practice nurses (IPA) (25%), and writing CEMI books (75%). For ECOS, 90% participate as examiners, 60% participate in teaching using simulation, 25% are involved in teaching advanced practice nurses (IPA), 75% participated in the writing of CEMI works. Eight (12%) internal medicine HUs co-facilitate training with patients and 26 (38%) participate in master's courses at the Faculty of Sciences. Finally, 94% are affiliated with a research unit and 48% supervise university theses students., Conclusion: Internal medicine universities teachers have a strong educational commitment, particularly in semiology and in the reform of the second cycle of medical studies with ECOS and simulation., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)
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- 2024
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7. Tell-tale immune-related neurological syndromes: Should we look for and underlying low-grade B-cell lymphoma? A retrospective study on 12 cases.
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Coen M, Benyamine A, Delmont E, Kaplanski G, Bouabdallah R, Xerri L, Attarian S, and Serratrice J
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- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Adult, Lymphoma, B-Cell pathology, Lymphoma, B-Cell immunology
- Abstract
Introduction: Immune-related neurological syndromes (affecting both the central and peripheral nervous system, as well as the neuromuscular junction) can associate with low-grade B-cell lymphomas., Methods: We conducted a retrospective study on the records of patients with miscellaneous immune-related neuropathies followed by the "Referral Centre for Neuromuscular Diseases and ALS" in collaboration with the Services of Internal Medicine and Hematology (La Timone Hospital, and the Paoli Calmettes-Insitute, Marseille, France; Geneva University Hospitals, Geneva, Switzerland). Clinical, biological, immunological and histological work-up was carried out and data collected., Results: We identified 12 patients with neurological syndromes and atypical presentation/course. In all these patients multiple autoantibodies were found. This prompted us to perform thorough hematologic investigations, that led to the diagnosis of different type of Low-Grade B-Cell lymphomas [i.e. marginal zone lymphomas with lymphoplasmacytic differentiation (n=3), splenic marginal area lymphoma with secondary lymph node invasion (n=1), unclassified marginal area lymphomas (n=8)]. Treatment of the underling lymphoma resulted in an improvement (n=8) or stabilization (n=4) of neurological disease., Conclusion: Atypical presentation of immune-related neurological syndromes, as well as the presence of antibodies with different antigenic targets should be regarded as "warning signs" and raise the suspicion of a paraneoplastic origin sustained by an underlying low-grade B-cell lymphoma that should be actively sought and treated. Close collaboration between internists, neurologists and hematologists allows for the appropriate management of each case., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2024. Published by Elsevier GmbH.)
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- 2024
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8. Diagnosis of thrombotic thrombocytopenic purpura: easy-to-use fiber optic surface plasmon resonance immunoassays for automated ADAMTS-13 antigen and conformation evaluation.
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Bonnez Q, Dekimpe C, Bekaert T, Tellier E, Kaplanski G, Joly BS, Veyradier A, Coppo P, Lammertyn J, Tersteeg C, De Meyer SF, and Vanhoorelbeke K
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- Humans, Case-Control Studies, Biomarkers blood, Reproducibility of Results, Protein Conformation, Predictive Value of Tests, Immunoassay methods, Automation, Laboratory, Female, Male, ADAMTS13 Protein blood, ADAMTS13 Protein immunology, Purpura, Thrombotic Thrombocytopenic diagnosis, Purpura, Thrombotic Thrombocytopenic blood, Purpura, Thrombotic Thrombocytopenic immunology, Surface Plasmon Resonance, Enzyme-Linked Immunosorbent Assay methods
- Abstract
Background: Laboratory diagnosis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains challenging when ADAMTS-13 activity ranges between 10% and 20%. To prevent misdiagnosis, open ADAMTS-13 conformation gained clinical attention as a novel biomarker, especially to diagnose acute iTTP in patients with diagnostic undecisive ADAMTS-13 activity. Plasma ADAMTS-13 conformation analysis corrects for ADAMTS-13 antigen, with both parameters being characterized in enzyme-linked immunosorbent assay (ELISA)-based reference assays requiring expert technicians., Objectives: To design ADAMTS-13 antigen and conformation assays on automated, easy-to-use fiber optic surface plasmon resonance (FO-SPR) technology to promote assay accessibility and diagnose challenging iTTP patients., Methods: ADAMTS-13 antigen and conformation assays were designed on FO-SPR technology. Plasma of 20 healthy donors and 20 acute iTTP patients were quantified, and data from FO-SPR and ELISA reference assays were compared., Results: Following assay design, both antigen and conformation FO-SPR assays were optimized and characterized, presenting strong analytical sensitivity (detection limit of 0.001 μg/mL) and repeatability (interassay variation of 14.4%). Comparative analysis suggested positive correlation (Spearman r of 0.92) and good agreement between FO-SPR and ELISA assays. As expected, FO-SPR assays showed a closed or open ADAMTS-13 conformation in healthy donors and acute iTTP patients, respectively., Conclusion: Both ADAMTS-13 antigen and conformation assays were transferred onto automated, easy-to-use FO-SPR technology, displaying potent analytical sensitivity and reproducibility. ADAMTS-13 antigen and conformation were determined for healthy donors and acute iTTP patients showing strong correlation with ELISA reference. Introducing FO-SPR technology in clinical context could support routine diagnosis of acute iTTP patients, notably when ADAMTS-13 activity fluctuates between 10% and 20%., Competing Interests: Declaration of competing interests J.L. is a member of the Board of Directors of FOx Biosystems. Q.B., C.D., T.B., E.T., G.K., B.S.J., A.V., P.C., C.T., S.F.D.M., and K.V. have no conflicts of interest to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)
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- 2024
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9. Reduction of mortality, cardiac damage, and cerebral damage by IL-1 inhibition in a murine model of TTP.
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Muller R, Cauchois R, Lagarde M, Roffino S, Genovesio C, Fernandez S, Hache G, Guillet B, Kara Y, Marlinge M, Lenting P, Poullin P, Dignat-George F, Tellier E, and Kaplanski G
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- Animals, Male, Mice, ADAMTS13 Protein metabolism, Disease Models, Animal, Interleukin-1alpha metabolism, Interleukin-1beta metabolism, Interleukin-1beta blood, Mice, Inbred C57BL, Retrospective Studies, von Willebrand Factor metabolism, von Willebrand Factor antagonists & inhibitors, Interleukin 1 Receptor Antagonist Protein pharmacology, Interleukin 1 Receptor Antagonist Protein therapeutic use, Purpura, Thrombotic Thrombocytopenic drug therapy, Purpura, Thrombotic Thrombocytopenic pathology, Purpura, Thrombotic Thrombocytopenic mortality
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Abstract: Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in von Willebrand factor cleavage resulting in capillary microthrombus formation and ischemic organ damage. Interleukin-1 (IL-1) has been shown to drive sterile inflammation after ischemia and could play an essential contribution to postischemic organ damage in TTP. Our objectives were to evaluate IL-1 involvement during TTP and to test the efficacy of the recombinant IL-1 receptor antagonist, anakinra, in a murine TTP model. We retrospectively measured plasma IL-1 concentrations in patients with TTP and controls. Patients with TTP exhibited elevated plasma IL-1α and -1β concentrations, which correlated with disease course and survival. In a mouse model of TTP, we administered anakinra (IL-1 inhibitor) or placebo for 5 days and evaluated the efficacy of this treatment. Anakinra significantly reduced mortality of mice (P < .001). Anakinra significantly decreased TTP-induced cardiac damage as assessed by blood troponin concentrations, evaluation of left ventricular function by echocardiography, [18F]fluorodeoxyglucose positron emission tomography of myocardial glucose metabolism, and cardiac histology. Anakinra also significantly reduced brain TTP-induced damage evaluated through blood PS100b concentrations, nuclear imaging, and histology. We finally showed that IL-1α and -1β trigger endothelial degranulation in vitro, leading to the release of von Willebrand factor. In conclusion, anakinra significantly reduced TTP mortality in a preclinical model of the disease by inhibiting both endothelial degranulation and postischemic inflammation, supporting further evaluations in humans., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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10. Molecular B-cell clonality assay in minor salivary glands as a useful tool for the lymphoma risk assessment in Sjögren's syndrome.
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Benyamine A, Poulet A, Belenotti P, Nihous H, Ene N, Jarrot PA, Swiader L, Mancini J, Beaufils N, Essaydi A, Gabert J, Weiller PJ, and Kaplanski G
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- Humans, Female, Middle Aged, Risk Assessment methods, Male, Aged, Adult, Lymphoma, Non-Hodgkin pathology, Lymphoma, Non-Hodgkin diagnosis, Lymphoma, Non-Hodgkin genetics, Lymphoma, Non-Hodgkin immunology, Salivary Gland Neoplasms genetics, Salivary Gland Neoplasms pathology, Salivary Gland Neoplasms immunology, Aged, 80 and over, Sjogren's Syndrome immunology, Sjogren's Syndrome diagnosis, Sjogren's Syndrome genetics, B-Lymphocytes immunology, Salivary Glands, Minor pathology
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Objectives: Non-Hodgkin's lymphoma (NHL) risk assessment is crucial in Sjögren's syndrome (SS). We studied the prevalence of clonal immunoglobulin gene rearrangements in minor salivary glands (MSG) and their correlations with lymphoma occurrence and with previously established NHL predictors., Methods: Molecular B-cell expansion was studied in fresh-frozen MSG of 207 patients with either suspected SS or with suspected lymphoma during SS, using a standardised multiplex PCR assay combined with heteroduplex analysis by microcapillary electrophoresis. The assignation of clonal cases was based on EuroClonality consortium guidelines., Results: Among 207 studied patients, 31 (15%) had MSG monoclonal B-cell infiltration. Monoclonality was significantly more frequent in patients with SS (28/123, 22.8%) compared with patients without SS (3/84, 3.6%, P<0.001). Monoclonal B-cell infiltration in MSG of SS patients correlated significantly with ongoing salivary gland NHL, salivary gland swelling, CD4
+ T-cell lymphopenia, rheumatoid factor (RF) activity, low complement levels and type 2 mixed cryoglobulinemia. The accumulation of biological risk factors was associated with a higher rate of MSG B-cell monoclonality given that patients with only positive RF had no probability of MSG B-cell monoclonality, RF-positive patients with 1 or 2 other risk factors had a 25.0% and 85.7% probability of MSG B-cell monoclonality, respectively., Conclusion: The detection of MSG monoclonal B-cell expansion by this easy-to-perform molecular assay is useful, both at the time of diagnosis and during the course of SS. Monoclonal B-cell expansion is associated with a subset of SS patients presenting either ongoing lymphoma or other established lymphoma predictive factors., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)- Published
- 2024
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11. [High anti-topoisomerase-1 autoantibodies levels are associated with the extension of skin fibrosis and vascular progression in patients with systemic sclerosis].
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Dol C, Granel B, Resseguier N, Kaplanski G, Reynaud-Gaubert M, Schleinitz N, Grob JJ, Delaporte E, Lafforgue P, Rossi P, Bardin N, and Benyamine A
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- Humans, Female, Male, Sclerosis complications, Prognosis, Fibrosis, Autoantibodies analysis, Scleroderma, Systemic complications, Scleroderma, Systemic diagnosis
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Background: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients., Methods: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant., Results: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495)., Conclusion: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)
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- 2024
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