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  1. Article: Treatment of UTIs Due to

    Chapelle, Caroline / Gaborit, Benjamin / Dumont, Raphaëlle / Dinh, Aurélien / Vallée, Maxime

    Antibiotics (Basel, Switzerland)

    2021  Volume 10, Issue 11

    Abstract: Background: K. pneumoniae: Methods: this narrative review of the literature was performed according to the criteria of preferred reporting items for systematic review and meta-analyses statement (PRISMA) (2020).: Results and conclusions: KPCp-UTIs ...

    Abstract Background: K. pneumoniae
    Methods: this narrative review of the literature was performed according to the criteria of preferred reporting items for systematic review and meta-analyses statement (PRISMA) (2020).
    Results and conclusions: KPCp-UTIs are a real challenge for physicians. While cefiderocol, meropenem-vaborbactam, ceftazidim-avibactam, and imipenem-relebactam represent a major step forward in the treatment of these UTIs, no guidelines are currently available, in view of choosing the most appropriate treatment, in each specific case.
    Language English
    Publishing date 2021-11-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics10111332
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  2. Article ; Online: Susceptibility to mycobacterial infection in VEXAS syndrome.

    Riescher, Stanislas / Lecomte, Raphael / Danic, Gwenvael / Graveleau, Julie / Le Bris, Yannick / Hello, Muriel / Guillouzouic, Aurélie / Guardiolle, Vianney / Garnier, Alice / Grossi, Olivier / Gaborit, Benjamin / Néel, Antoine

    Rheumatology (Oxford, England)

    2024  

    Abstract: Objectives: VEXAS is a recently described acquired auto-inflammatory and hematologic syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency.: Patients and methods: Two of our 10 VEXAS ... ...

    Abstract Objectives: VEXAS is a recently described acquired auto-inflammatory and hematologic syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency.
    Patients and methods: Two of our 10 VEXAS patients developed a disseminated Mycobacterium avium infection. To shed light on this observation, we retrospectively studied all patients with disseminated non-tuberculous mycobacterial infections (NTMi) seen at our institution over 13 years. Inclusion criteria were a positive blood/bone marrow culture, or 2 positive cultures from distinct sites, or one positive culture with 2 involved sites.
    Results: patient 1 presented with fever, rash, orbital cellulitis and lung infiltrates. Patient 2 presented with fever and purpura. In both cases, Mycobacterium avium was identified on bone marrow culture. Twenty cases of disseminated NTMi were reviewed. Among 11 HIV-negative patients, three had chronic immune-mediated disease; three had untreated myeloid neoplasm; two had VEXAS; one had undergone kidney transplantation; one had GATA-2 deficiency; and one had no identified aetiology. None had lymphoid neoplasia or had undergone bone marrow transplantation. HIV-negative cases had higher CD4 counts than HIV-positive patients (median CD4: 515/mm3  vs 38/mm3, p< 0.001). Monocytopenia was present in seven cases. At 2 years, six patients had died, including both VEXAS patients.
    Discussion: VEXAS patients have an intrinsic susceptibility to disseminated NTMi, which may result from monocytic dysfunction. NTMi can mimic VEXAS flare. Clinicians should maintain a high suspicion for opportunistic infections before escalating immunosuppressive therapy. Further studies are needed to confirm and better decipher the herein reported observations.
    Language English
    Publishing date 2024-02-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keae087
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  3. Article ; Online: Comparative effectiveness of empirical antibiotic treatments in methicillin-susceptible Staphylococcus aureus infective endocarditis: A post hoc analysis of a prospective French cohort study.

    Lecomte, Raphaël / Deschanvres, Colin / Bourreau, Alexis / Ruffier d'Epenoux, Louise / Le Turnier, Paul / Gaborit, Benjamin / Chauveau, Marie / Michel, Magali / Le Tourneau, Thierry / Bémer, Pascale / Corvec, Stéphane / Boutoille, David

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

    2024  Volume 142, Page(s) 106989

    Abstract: Objectives: The empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible ... ...

    Abstract Objectives: The empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis.
    Methods: A post hoc analysis of a prospective cohort study of patients hospitalized in a French reference centre with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteraemia under treatment.
    Results: Of the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteraemia compared to other treatments (3.6 d vs. 4.6 d, P = 0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 d vs. 4.7 d, P < 0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteraemia ≤72 h (P = 0.02), whereas endocarditis on native valves (P = 0.01), and intracardiac abscess were associated with longer duration of bacteraemia (P = 0.01).
    Conclusions: Empirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides.
    MeSH term(s) Humans ; Cefazolin/therapeutic use ; Methicillin/pharmacology ; Methicillin/therapeutic use ; Prospective Studies ; Staphylococcus aureus ; Cohort Studies ; Staphylococcal Infections/drug therapy ; Anti-Bacterial Agents/therapeutic use ; Endocarditis, Bacterial/drug therapy ; Endocarditis/drug therapy ; Bacteremia/drug therapy
    Chemical Substances Cefazolin (IHS69L0Y4T) ; Methicillin (Q91FH1328A) ; Anti-Bacterial Agents
    Language English
    Publishing date 2024-02-28
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 1331197-9
    ISSN 1878-3511 ; 1201-9712
    ISSN (online) 1878-3511
    ISSN 1201-9712
    DOI 10.1016/j.ijid.2024.106989
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    Zs.A 4516: Show issues Location:
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  4. Article ; Online: Characteristics and Prognosis Factors of Pneumocystis jirovecii Pneumonia According to Underlying Disease: A Retrospective Multicenter Study.

    Lécuyer, Romain / Issa, Nahéma / Camou, Fabrice / Lavergne, Rose-Anne / Gabriel, Frederic / Morio, Florent / Canet, Emmanuel / Raffi, François / Boutoille, David / Cady, Anne / Gousseff, Marie / Crabol, Yoann / Néel, Antoine / Tessoulin, Benoît / Gaborit, Benjamin

    Chest

    2024  

    Abstract: Background: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated.!## ...

    Abstract Background: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated.
    Research question: Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease?
    Study design and methods: In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality.
    Results: Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010).
    Interpretation: Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1032552-9
    ISSN 1931-3543 ; 0012-3692
    ISSN (online) 1931-3543
    ISSN 0012-3692
    DOI 10.1016/j.chest.2024.01.015
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  5. Article ; Online: Nocardiosis in graft recipients of kidneys from extended-criteria donors following switch to belatacept complicated by acute rejection.

    Ville, Simon / Gaborit, Benjamin / Meyer, Jeremy / Masset, Christophe / Tanguy, Lescornet / Garandeau, Claire

    Transplant international : official journal of the European Society for Organ Transplantation

    2020  Volume 33, Issue 11, Page(s) 1565–1568

    MeSH term(s) Abatacept ; Graft Rejection ; Graft Survival ; Humans ; Immunosuppressive Agents ; Kidney ; Nocardia Infections/drug therapy ; Tissue Donors ; Transplant Recipients
    Chemical Substances Immunosuppressive Agents ; Abatacept (7D0YB67S97)
    Language English
    Publishing date 2020-09-16
    Publishing country England
    Document type Letter
    ZDB-ID 639435-8
    ISSN 1432-2277 ; 0934-0874
    ISSN (online) 1432-2277
    ISSN 0934-0874
    DOI 10.1111/tri.13722
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    Zs.A 2358: Show issues Location:
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  6. Article ; Online: A murine model of Staphylococcus aureus infected chronic diabetic wound: A new tool to develop alternative therapeutics.

    Huon, Jean-François / Gaborit, Benjamin / Caillon, Jocelyne / Boutoille, David / Navas, Dominique

    Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

    2020  Volume 28, Issue 3, Page(s) 400–408

    Abstract: Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically ... ...

    Abstract Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL-17A compared to control mice that resulted in an IL-17/IFN-γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL-10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL-10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL-10/IFN-γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.
    MeSH term(s) Animals ; Chronic Disease ; Diabetes Complications/complications ; Diabetes Complications/microbiology ; Diabetes Complications/pathology ; Disease Models, Animal ; Female ; Mice ; Skin Ulcer/etiology ; Skin Ulcer/pathology ; Skin Ulcer/therapy ; Staphylococcal Infections/etiology ; Staphylococcal Infections/pathology ; Staphylococcus aureus ; Time Factors ; Wound Healing ; Wound Infection/etiology ; Wound Infection/pathology
    Language English
    Publishing date 2020-03-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1174873-4
    ISSN 1524-475X ; 1067-1927
    ISSN (online) 1524-475X
    ISSN 1067-1927
    DOI 10.1111/wrr.12802
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    Zs.A 3890: Show issues Location:
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  7. Article ; Online: Corrigendum: XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2 spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants.

    Vanhove, Bernard / Marot, Stéphane / So, Ray T / Gaborit, Benjamin / Evanno, Gwénaëlle / Malet, Isabelle / Lafrogne, Guillaume / Mevel, Edwige / Ciron, Carine / Royer, Pierre-Joseph / Lheriteau, Elsa / Raffi, François / Bruzzone, Roberto / Mok, Chris Ka Pun / Duvaux, Odile / Marcelin, Anne-Geneviève / Calvez, Vincent

    Frontiers in immunology

    2023  Volume 14, Page(s) 1208705

    Abstract: This corrects the article DOI: 10.3389/fimmu.2021.761250.]. ...

    Abstract [This corrects the article DOI: 10.3389/fimmu.2021.761250.].
    Language English
    Publishing date 2023-04-28
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1208705
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  8. Article ; Online: Circulating Regulatory T Cells Expressing Tumor Necrosis Factor Receptor Type 2 Contribute to Sepsis-Induced Immunosuppression in Patients During Septic Shock.

    Gaborit, Benjamin Jean / Chaumette, Tanguy / Chauveau, Marie / Asquier-Khati, Antoine / Roquilly, Antoine / Boutoille, David / Josien, Régis / Salomon, Benoit L / Asehnoune, Karim

    The Journal of infectious diseases

    2021  Volume 224, Issue 12, Page(s) 2160–2169

    Abstract: Background: Septic shock remains a major cause of death that can be complicated by long-term impairment in immune function. Among regulatory T (Treg) cells, the tumor necrosis factor receptor 2 positive (TNFR2pos) Treg-cell subset endorses significant ... ...

    Abstract Background: Septic shock remains a major cause of death that can be complicated by long-term impairment in immune function. Among regulatory T (Treg) cells, the tumor necrosis factor receptor 2 positive (TNFR2pos) Treg-cell subset endorses significant immunosuppressive functions in human tumors and a sepsis mouse model but has not been investigated during septic shock in humans.
    Methods: We prospectively enrolled patients with septic shock hospitalized in intensive care units (ICU). We performed immunophenotyping and functional tests of CD4+ T cells, Treg cells, and TNFR2pos Treg cells on blood samples collected 1, 4, and 7 days after admission to ICU.
    Results: We investigated 10 patients with septic shock compared to 10 healthy controls. Although the proportions of circulating Treg cells and TNFR2pos Treg-cell subsets were not increased, their CTLA4 expression and suppressive functions in vitro were increased at 4 days of septic shock. Peripheral blood mononuclear cells from healthy donors cultured with serum from septic shock patients had increased CTLA4 expression in TNFR2pos Treg cells compared to TNFR2neg Treg cells.
    Conclusions: In patients with septic shock, CTLA4 expression and suppressive function were increased in circulating TNFR2pos Treg cells. We identify TNFR2pos Treg cells as a potential attractive target for therapeutic intervention.
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/metabolism ; CTLA-4 Antigen/metabolism ; Humans ; Immunosuppression Therapy ; Leukocytes, Mononuclear ; Mice ; Receptors, Tumor Necrosis Factor, Type II/metabolism ; Sepsis/metabolism ; Shock, Septic/immunology ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances CTLA-4 Antigen ; Receptors, Tumor Necrosis Factor, Type II
    Language English
    Publishing date 2021-05-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiab276
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  9. Article ; Online: Plea for multitargeted interventions for severe COVID-19.

    Gaborit, Benjamin Jean / Bergmann, Jean-François / Mussini, Cristina / Arribas, Jose Ramon / Behrens, Georg / Walmsley, Sharon / Pozniak, Anton / Raffi, François

    The Lancet. Infectious diseases

    2020  Volume 20, Issue 10, Page(s) 1122–1123

    MeSH term(s) Antiviral Agents/therapeutic use ; Betacoronavirus ; Coronavirus Infections/drug therapy ; Drug Therapy, Combination ; Humans ; Immunologic Factors/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Immunotherapy ; Pandemics ; Pneumonia, Viral/drug therapy
    Chemical Substances Antiviral Agents ; Immunologic Factors ; Immunosuppressive Agents
    Keywords covid19
    Language English
    Publishing date 2020-04-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2061641-7
    ISSN 1474-4457 ; 1473-3099
    ISSN (online) 1474-4457
    ISSN 1473-3099
    DOI 10.1016/S1473-3099(20)30312-1
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    Zs.A 5743: Show issues Location:
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  10. Article: Effect of Swine Glyco-humanized Polyclonal Neutralizing Antibody on Survival and Respiratory Failure in Patients Hospitalized With Severe COVID-19: A Randomized, Placebo-Controlled Trial.

    Gaborit, Benjamin / Vanhove, Bernard / Lacombe, Karine / Guimard, Thomas / Hocqueloux, Laurent / Perrier, Ludivine / Dubee, Vincent / Ferre, Virginie / Bressollette, Celine / Josien, Régis / Thuaut, Aurélie Le / Vibet, Marie-Anne / Jobert, Alexandra / Dailly, Eric / Ader, Florence / Brouard, Sophie / Duvaux, Odile / Raffi, François

    Open forum infectious diseases

    2023  Volume 10, Issue 11, Page(s) ofad525

    Abstract: Background: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19).: Methods: This phase 2b clinical trial enrolled ... ...

    Abstract Background: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19).
    Methods: This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15.
    Results: Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66;
    Conclusions: Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.
    Language English
    Publishing date 2023-10-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofad525
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