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OBJECTIVES: To describe the characteristics, treatment and outcome of isolated ANCA-associated scleritis at diagnosis compared with idiopathic scleritis with negative ANCA tests. METHODS: This retrospective multicentre case-control study was performed within the French Vasculitis Study Group (FVSG) network and in three French tertiary ophthalmologic centres. Data from patients with scleritis without any systemic manifestation and with positive ANCA results were compared with those of a control group of patients with idiopathic scleritis with negative ANCA tests. RESULTS: A total of 120 patients, including 38 patients with ANCA-associated scleritis and 82 control patients, diagnosed between January 2007 and April 2022 were included. The median follow-up was 28 months (IQR 10-60). The median age at diagnosis was 48 years (IQR 33-60) and 75% were females. Scleromalacia was more frequent in ANCA-positive patients (P = 0.027) and 54% had associated ophthalmologic manifestations, without significant differences. ANCA-associated scleritis more frequently required systemic medications, including glucocorticoids (76% vs 34%; P < 0.001), and rituximab (P = 0.03) and had a lower remission rate after the first- and second-line treatment. Systemic ANCA-associated vasculitis (AAV) occurred in 30.7% of patients with PR3- or MPO-ANCA, after a median interval of 30 months (IQR 16.3-44). Increased CRP >5 mg/l at diagnosis was the only significant risk factor of progression to systemic AAV [adjusted hazard ratio 5.85 (95% CI 1.10, 31.01), P = 0.038]. CONCLUSION: Isolated ANCA-associated scleritis is mostly anterior scleritis with a higher risk of scleromalacia than ANCA-negative idiopathic scleritis and is more often difficult to treat. One-third of patients with PR3- or MPO-ANCA scleritis progressed to systemic AAV.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Esclerite , Feminino , Humanos , Masculino , Anticorpos Anticitoplasma de Neutrófilos , Esclerite/diagnóstico , Esclerite/tratamento farmacológico , Esclerite/etiologia , Estudos de Casos e Controles , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Rituximab/uso terapêutico , Estudos Retrospectivos , Peroxidase , MieloblastinaRESUMO
BACKGROUND: Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. METHODS: We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). RESULTS: No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (-15.9%; 95% CI, -29.4 to -2.5) compared with the PLEX not recommended group (-4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. CONCLUSIONS: PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making.
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Injúria Renal Aguda , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Injúria Renal Aguda/complicações , Injúria Renal Aguda/terapia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Anticorpos Anticitoplasma de Neutrófilos , Feminino , Humanos , Rim/patologia , Masculino , Troca Plasmática/efeitos adversos , Estudos RetrospectivosRESUMO
Long COVID-19 syndrome appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damage to microcapillaries, microthrombi, and endothelialitis. However, the mechanisms involved in these processes remain to be elucidated. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium, which provides a the major function is to prevent coagulation. A component of endothelial cell junctions is VE-cadherin, which is responsible for maintaining the integrity of the vessels through homophilic interactions of its Ca++-dependent adhesive extracellular domain. Here we provide the first evidence that VE-cadherin is a target in vitro for ACE2 cleavage because its extracellular domain (hrVE-ED) contains two amino acid sequences for ACE2 substrate recognition at the positions 256P-F257 and 321PMKP-325L. Indeed, incubation of hrVE-ED with the active ectopeptidase hrACE2 for 16 hrs in the presence of 10 µM ZnCl2 showed a dose-dependent (from 0.2 ng/µL to 2 ng/µL) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19 we detected a circulating form of ACE2 with an apparent molecular mass of 70 kDa, which was barely detectable in patients with mild COVID-19. Of importance, in the patients with severe COVID-19 disease, the presence of three soluble fragments of VE-cadherin (70, 62, 54 kDa) were detected using the antiEC1 antibody while only the 54 kDa fragment was present in patients with mild disease. Altogether, these data clearly support a role for ACE2 to cleave VE-cadherin, which leads to potential biomarkers of SARS-CoV-2 infection related with the vascular disease in "Long COVID-19".
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COVID-19 , Células Endoteliais , Humanos , Células Endoteliais/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2/metabolismo , Caderinas/metabolismo , Endotélio Vascular/metabolismoRESUMO
OBJECTIVES: To describe the characteristics, treatment and outcome of patients with immune thrombocytopenia with clinical significance (ITPCS) associated with SLE. METHODS: This retrospective multicentre study included SLE patients who experienced ≥1 ITPCS (defined as ITP with attributable bleeding disorders and/or a platelet count <30×109/l). Other causes of secondary thrombocytopenia were excluded. Major bleeding event (MBG) was defined as Khellaf score >8 and/or WHO score >2. RESULTS: A total of 90 patients were included, the median (range) follow-up duration was 80 (6-446) months. ITP was diagnosed before SLE in 25 patients. They presented a high rate of autoimmune haemolytic anaemia (15%), antiphospholipid antibody (62%) and antiphospholipid syndrome (19%). The 25 (28%) patients who experienced MBG had significantly more bleedings at ITP diagnosis and higher bleeding scores, and serositis and thrombosis during follow-up. They required significantly more treatment lines, transfusions and hospitalizations. The 11 (12%) patients who experienced no bleeding event presented a significantly more restricted SLE phenotype (cutaneous and/or articular). Patients received a mean (range) of 4.2 (1-11) treatment lines. Corticosteroids and HCQ allowed ITPCS overall response in one-third of patients. The median relapse-free survival of rituximab (n = 34), AZA (n = 19), MMF (n = 8), thrombopoietin-receptor agonists (n = 16) and splenectomy (n = 19) were 53, 31.5, 61, 24.5 and 78 months, respectively. Four patients experienced thrombotic events after splenectomy and one occurred under thrombopoietin-receptor agonist treatment. CONCLUSION: SLE-ITCS patients displayed a high rate of haematological abnormalities and MBG patients exhibited higher morbidity. Management of thrombocytopenia was highly heterogeneous and many options seem viable.
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Lúpus Eritematoso Sistêmico , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Trombose , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/terapia , Receptores de Trombopoetina/agonistas , Estudos Retrospectivos , Trombocitopenia/tratamento farmacológico , Trombose/tratamento farmacológicoRESUMO
OBJECTIVES: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV. METHODS: We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: <36, 36 ≤ age < 52; 52 ≤ age < 63 and ≥63 years. Comparison of presentation and outcome were performed according to age of disease onset. RESULTS: Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P < 0.0001) and gastrointestinal involvement (P = 0.001). In contrast, the oldest patients had more severe purpura with necrotic lesions (P = 0.001) and more frequent renal involvement (P < 0.0001), with more frequent haematuria, renal failure, higher urine protein excretion and more frequent tubulointerstitial lesions. Patients were treated similarly in all groups of age, and clinical response and relapse rates were similar between groups. In the 127 treated patients with follow-up data for >6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1-38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age. CONCLUSION: Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
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Envelhecimento/imunologia , Imunoglobulina A , Falência Renal Crônica/etiologia , Vasculite/diagnóstico , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Falência Renal Crônica/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Retrospectivos , Vasculite/imunologiaRESUMO
BACKGROUND: Vascular endothelial (VE)-cadherin is an endothelial cell-specific protein responsible for endothelium integrity. Its adhesive properties are regulated by post-translational processing, such as tyrosine phosphorylation at site Y685 in its cytoplasmic domain, and cleavage of its extracellular domain (sVE). In hormone-refractory metastatic breast cancer, we recently demonstrated that sVE levels correlate to poor survival. In the present study, we determine whether kidney cancer therapies had an effect on VE-cadherin structural modifications and their clinical interest to monitor patient outcome. METHODS: The effects of kidney cancer biotherapies were tested on an endothelial monolayer model mimicking the endothelium lining blood vessels and on a homotypic and heterotypic 3D cell model mimicking tumour growth. sVE was quantified by ELISA in renal cell carcinoma patients initiating sunitinib (48 patients) or bevacizumab (83 patients) in the first-line metastatic setting (SUVEGIL and TORAVA trials). RESULTS: Human VE-cadherin is a direct target for sunitinib which inhibits its VEGF-induced phosphorylation and cleavage on endothelial monolayer and endothelial cell migration in the 3D model. The tumour cell environment modulates VE-cadherin functions through MMPs and VEGF. We demonstrate the presence of soluble VE-cadherin in the sera of mRCC patients (n = 131) which level at baseline, is higher than in a healthy donor group (n = 96). Analysis of sVE level after 4 weeks of treatment showed that a decrease in sVE level discriminates the responders vs. non-responders to sunitinib, but not bevacizumab. CONCLUSIONS: These data highlight the interest for the sVE bioassay in future follow-up of cancer patients treated with targeted therapies such as tyrosine-kinase inhibitors.
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Antineoplásicos/uso terapêutico , Biomarcadores Farmacológicos , Caderinas/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Sunitinibe/uso terapêutico , Biomarcadores Farmacológicos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Células Cultivadas , Ensaios Clínicos como Assunto , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Terapia de Alvo Molecular/métodos , Metástase Neoplásica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: To describe extra-haematological manifestations associated with human parvovirus B19 (HPV-B19) infection. METHODS: We conducted a nationwide multicentre study to retrospectively describe the characteristics and outcome of extra-haematological manifestations in French adults. RESULTS: Data from 25 patients followed from 2001 to 2016 were analysed. Median age was 37.9 years (range: 22.7-83.4), with a female predominance (sex ratio: 4/1). Only 3 patients had an underlying predisposing condition (hemoglobinopathy or pregnancy). The most common manifestations were joint (80%) and skin (60%) involvement. Four patients (16%) had renal involvement (endocapillary proliferative or membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis). Three patients (12%) had peripheral nervous system involvement (mononeuritis, mononeuritis multiplex, Guillain-Barré syndrome) and 2 (8%) presented muscle involvement. Other manifestations included hemophagocytic lymphohistiocytosis (n = 1), myopericarditis and pleural effusion (n = 1), and lymphadenopathy and splenomegaly mimicking lymphoma with spleen infarcts (n = 1). Immunological abnormalities were frequent (56.5%). At 6 months, all patients were alive, and 54.2% were in complete remission. In 2 patients, joint involvement evolved into rheumatoid arthritis. Six patients (24%) received intravenous immunoglobulin (IVIg), with a good response in the 3 patients with peripheral nervous system involvement. CONCLUSIONS: HPV-B19 infection should be considered in a wide range of clinical manifestations. Although the prognosis is good, IVIg therapy should be discussed in patients with peripheral nerve involvement. However, its efficacy should be further investigated in prospective studies.
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Infecções por Parvoviridae/fisiopatologia , Parvovirus B19 Humano , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide , Feminino , Humanos , Imunoglobulinas Intravenosas , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Estudos Prospectivos , Estudos Retrospectivos , Adulto JovemRESUMO
Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease characterized by AE resistant to antihistamines and a chronic course. We report five new cases of InH-AAE (two women and three men) with a rapid and dramatic response to the anti-immunoglobulin-E antibody omalizumab. In our literature review, we found 13 other relevant cases with a good response to this treatment. Overall, in 6 out of 18 patients, the doses of omalizumab required to prevent recurrences of attacks were higher than the licensed dose for chronic urticaria. No significant adverse effects have been reported.
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Angioedema/tratamento farmacológico , Antialérgicos/uso terapêutico , Omalizumab/uso terapêutico , Adulto , Idoso de 80 Anos ou mais , Angioedema/diagnóstico , Angioedema/etiologia , Angioedema/metabolismo , Antialérgicos/administração & dosagem , Biomarcadores , Progressão da Doença , Feminino , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Omalizumab/administração & dosagem , Avaliação de Sintomas , Resultado do TratamentoRESUMO
BACKGROUND: The aetiology of angio-oedema (AE) is difficult to determine; however, it is essential in emergency situations when two major contexts may be present: mast cell-mediated AE and bradykinin-mediated AE. Different forms of AE are currently distinguished based on clinical criteria (spontaneous duration of the attack, presence of concomitant or late-appearing superficial urticaria, history of atopy, and others), but specific biomarkers could improve patient management. OBJECTIVE: In this prospective study, potential biomarkers have been identified, and their statistical characteristics were examined. METHODS: Samples were taken on day 0 (D0) and D7 for 3 patient groups (n = 11 each): bradykinin-mediated AE [peripheral site of attack, ear, nose, throat (ENT), and abdominal involvement], mast cell-mediated AE, and non-bradykinin-mediated abdominal pain. RESULTS: Assay of the potential biomarkers revealed no significant differences in C1 inhibitor and C4 levels. In contrast, D-dimer levels peaked during bradykinin-mediated AE attacks (median 2.2 mg/l at D0 vs. 0.52 mg/l at D7; p < 10-3) as well as during mast cell-mediated AE attacks (1.97 vs. 0.65 mg/l; p = 0.04) and were high in bradykinin-mediated AE compared to the control group (0.69 mg/l; p = 0.01). A threshold value of 0.62 mg/l was found to have a negative predictive value of 100% for bradykinin-mediated AE compared to other causes of abdominal pain (group 3). Circulating VE-cadherin levels were also increased during an attack (1,990 at D0 vs. 1,566 ng/ml at D7; p = 0.01), but could not distinguish between bradykinin-mediated and mast cell-mediated AE, like D-dimers. CONCLUSIONS: Exploration of changes in fibrinolysis-related markers (particularly D-dimers) is thus promising for the diagnosis of AE attacks in difficult-to-diagnose abdominal forms, although it was not able to differentiate between bradykinin and mast cell-mediated AE.
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Angioedema/diagnóstico , Angioedema/etiologia , Biomarcadores , Bradicinina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/sangue , Caderinas/sangue , Proteína Inibidora do Complemento C1 , Proteínas do Sistema Complemento , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Adulto JovemAssuntos
Produtos Biológicos/uso terapêutico , Interleucina-1/antagonistas & inibidores , Urticária/tratamento farmacológico , Vasculite/tratamento farmacológico , Adulto , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Sjögren's syndrome (SS) is a systemic autoimmune pathology manifested mainly by a dry syndrome, intense asthenia and arthromyalgia. Systemic manifestations may also occur. Since 2019, immunosuppressant agents (IS) or biotherapies are recommended only for patients with systemic involvement. However, before 2019, in some cases, paucisymptomatic patients had been treated with IS/biotherapies, often off-label. Objective: We propose to evaluate the benefit and safety of using IS/biotherapy in patients with SS without systemic involvement. Methods: We retrospectively collected the clinical records of all patients with SS diagnosed according to ACR/EULAR diagnostic criteria followed up between January 1980 and October 2023 at Grenoble University Hospital (France). Results: Eighty-three patients were included: 64 with an initially non-systemic form. Of these patients with an initially non-systemic form, 24 were treated with IS/biotherapy. None of them developed secondary systematization, whereas 11 out of 40 patients in the untreated group did (p < 0.05). On the other hand, IS/biotherapy did not appear to improve dry syndrome. There were no serious adverse events. Conclusion: Early introduction of an IS/biotherapy treatment appears to provide a benefit for the patient without side effects.
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OBJECTIVE: To evaluate tocilizumab (TCZ) efficacy in patients with refractory Behçet disease (BD). METHODS: This is a multicenter study of 30 patients fulfilling the international criteria for BD and treated with TCZ at different European referral centers. The clinical response was evaluated at 6 months from TCZ initiation. RESULTS: Ninety percent of patients with BD were refractory or intolerant to anti-tumor necrosis factor (anti-TNF) agents. Overall, TCZ was effective in 25 (83%) patients with BD of whom 18 (60%) and 7 (23%) were complete and partial responders, respectively. The complete response was 67%, 60%, and 42% in patients with uveitis (18/30), neurological manifestations (5/30), and mucocutaneous and/or articular (7/30) manifestations, respectively. TCZ had a significant steroid-sparing effect allowing patients to decrease their median daily prednisone dose from 20 (IQR 10-40) mg/day to 9 (IQR 5-13) mg at 6 months (P < 0.001). The number of patients with BD needing concomitant disease-modifying antirheumatic drug therapy fell from 7 (23%) to 4 (13%) at 6 months. Mild to moderate side effects were observed in 6 (20%) patients, and 3 (10%) presented with serious adverse events (pneumonia, intestinal perforation, and septicemia) requiring therapy discontinuation in 2 cases. CONCLUSION: TCZ seems to be an effective alternative to anti-TNF agents in treating BD-related uveitis and neurological manifestations.
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Antirreumáticos , Síndrome de Behçet , Uveíte , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Resultado do Tratamento , Uveíte/etiologia , Uveíte/complicações , Antirreumáticos/uso terapêutico , Fator de Necrose Tumoral alfa , Estudos RetrospectivosRESUMO
HBV reactivations are observed frequently in patients with past hepatitis B infection receiving cytotoxic and/or immunosuppressive chemotherapy for hemato-oncological malignancies or autoimmune diseases. Recent ischemic stroke was shown to induce immunodepression by misunderstood mechanisms. To our knowledge, the association between HBV reactivation and ischemic stroke has not been reported before. This study reports the case of an anti-HBs- and anti-HBc-positive patient who presented HBV reactivation in a context of recent ischemic stroke, with no other intercurrent iatrogenic phenomenon or usual immunosuppressive pathology.
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Isquemia Encefálica/patologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B/diagnóstico , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Substituição de Aminoácidos , DNA Viral/genética , Hepatite B/virologia , Vírus da Hepatite B/genética , Humanos , Fígado/patologia , Fígado/virologia , Masculino , Dados de Sequência Molecular , Ativação ViralRESUMO
Résumé Introduction. Une interprétation fiable de l'albuminémie est essentielle pour l'évaluation nutritionnelle biologique (ENB) de la personne âgée. L'objectif principal était d'évaluer si une formule de correction proposée en cas d'inflammation prolongée pouvait être extrapolée aux situations d'inflammation biologique aiguës : albuminémie corrigée = albuminémie dosée + protéine C réactive (CRP)/25. Méthode. Cette étude observationnelle prospective monocentrique incluait des patients âgés hospitalisés de manière non programmée au CHU Grenoble-Alpes. Un recueil clinique et biologique était réalisé à J1 et J8. Le critère de jugement principal était la comparaison de l'albuminémie corrigée par la formule à J1 avec l'albuminémie dosée à J8. Résultat. Parmi 175 patients analysés, la moyenne de la CRP était de 64 mg/L (3 ; 324) à J1 et 24 mg/L (3 ; 99) à J8. Entre l'albuminémie corrigée à J1 et l'albuminémie dosée à J8, la corrélation était de p = 0,58, [IC 95 % : 0,47 ; 0,67], p < 0,001, et la différence moyenne de 2,9 mg/L (-13,5 ; 18), IC 95 %[-3,68 ; -2,20], p < 0,001. Entre l'albuminémie dosée à J1 et l'albuminémie dosée à J8, la corrélation était de p = 0,74, IC 95 % [0,66 ; 0,80], p < 0,001, et la différence moyenne de 0,4 mg/L (-14 ; 11), IC 95 % [-0,24 ; 1,02], p = 0,23. DISCUSSION: La formule proposée ne peut pas être extrapolée aux situations d'inflammation biologique aiguës au cours desquelles l'albuminémie dosée semble être stable. L'albuminémie dosée pourrait servir telle quelle de référence à l'ENB, en s'intégrant dans une histoire clinique. Abstract Introduction. A reliable interpretation of albumin is essential for the elderly's biological nutritional assessment (BNA), but is complex because many parameters change it. The main objective was to evaluate the extrapolation of a correction formula proposed for prolonged inflammation to acute biological inflammation situations: corrected albuminemia = measured albuminemia + CRP/25. METHOD: This prospective, single-center observation study included patients over 65 years of age who were unexpectedly hospitalized in geriatrics and internal medicine at Grenoble University Hospital, excluding carriers of active neoplasia, hepatic insufficiency, nephrotic syndrome, and those for whom a ABI persisted on the eighth day. A clinical and biological collection was made on the first and eighth days. The primary endpoint was the comparison of albuminemia corrected by the formula on day 1 with measured albuminemia on day 8. RESULTS: One hundred and seventy-five patients were analyzed. The average CRP was 64 (3; 324) mg/L on day 1 and 24 (3; 99) mg/L on day 8. Between corrected albumin at day 1 and albumin at day 8, the correlation was ρ = 0.58, 95%CI [0.47; 0.67], P < 0.001, and the mean difference of 2.9 (-13,5; 18) mg/L, 95%CI [-3.68;-2.20], P < 0.001. Between D1 albumin and D8 albumin, the correlation was ρ = 0.74, 95%CI [0.66; 0.80], P < 0.001, and the mean difference of 0.4 (-14; 11) mg/L, 95%CI [-0.24; 1.02], P = 0.23. DISCUSSION: The proposed formula cannot be extrapolated to acute inflammatory situations. Measured albuminemia appears to be stable during acute biological inflammation situations. Measured albuminemia could be used as a reference for BNA, integrated into a clinical history.
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Hospitalização , Estado Nutricional , Idoso , Albuminas , Atenção à Saúde , Humanos , Estudos ProspectivosRESUMO
A reliable interpretation of albumin levels is essential when assessing nutrition in elderly people, but this is complex as it is affected by a number of parameters. The main objective of this study was to evaluate whether a correction formula proposed for prolonged inflammation could be extrapolated to acute biological inflammation situations: corrected albuminemia = measured albuminemia + CRP/25. This prospective, single-centre observation study included patients over 65 years of age who were the subject of an unscheduled hospitalisation in the geriatrics and internal medicine departments of Grenoble University Hospital, excluding carriers of active neoplasia, hepatic insufficiency, nephrotic syndrome and those who continued to present with an acute biological inflammation on the eighth day. Clinical and biological samples were taken on the first and eighth days. The primary objective was the comparison of albumin levels, corrected using the formula on day (d) 1, with albumin levels measured on d8. One hundred and seventy-five patients were analysed. Average CRP was 64 (3; 324) mg/L on d1 and 24 (3; 99) mg/L on d8. Between the corrected albumin levels on d1 and albumin levels measured on d8, the correlation was ρ = 0.58, 95% CI [0.47; 0.67], P < 0.001, with a mean difference of 2.9 (-13.5; 18) mg/L, 95% CI [-3.68-2.20], P < 0.001. Between the albumin levels measured on d1 and d8, the correlation was ρ = 0.74, 95%CI [0.66; 0.80], P < 0.001, with a mean difference of 0.4 (-14; 11) mg/L, 95%CI [-0.24; 1.02], P = 0.23. The proposed formula cannot be extrapolated to acute inflammatory situations. Albumin levels appear to be stable during acute biological inflammation. Albumin levels could be used as a reference for biological nutritional assessments and be integrated into the patient's clinical history.
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OBJECTIVE: Joint involvement can be observed during the course of adult IgA vasculitis (IgAV). However, clinical picture, prognosis, or pathophysiological data associated with this condition have been overlooked. We aimed to describe the clinical characteristics and outcome of IgAV patients with joint involvement and look to a specific cytokine profile. METHODS: We analyzed clinical and biological data from a nationwide study that included adult IgAV patients. Presentation and outcomes of patients with or without joint involvement were compared at baseline and during follow-up. Plasma cytokine measurements of IgAV patients included in a prospective study were also analyzed using multiplex assays. RESULTS: Among 260 patients, 62% had joint involvement. Among them, rheumatological manifestations included arthralgia (100%) or arthritis (16%), mostly involving the knees and ankles. In multivariate analysis, patients with joint involvement, compared to those without, were younger (p = 0.002; OR 0.87; 95% CI 0.80-0.95) and showed more frequent gastrointestinal tract involvement (p = 0.012; OR = 2.08; 95% CI 1.18-3.67). However, no difference in terms of clinical response, relapse, end-stage renal disease, or death was observed between groups. Among 13 cytokines measured, plasma interleukin (IL)-1ß level was higher in patients with joint involvement compared to those without (mean ± SEM IL-1ß, 3.5 ± 1.2 vs. 0.47 ± 0.1 pg/ml; p = 0.024) or healthy controls (vs. 1.2 ± 0.5 pg/ml; p = 0.076). CONCLUSION: Joint involvement is frequent in adult IgAV and is associated with more frequent gastrointestinal involvement. Increased plasma IL-1ß levels raise the question of targeting this cytokine in patients with chronic and/or refractory joint involvement. Key Points ⢠Joint involvement in adult IgAV is a frequent manifestation. ⢠Joint involvement is associated with more frequent gastrointestinal manifestations. ⢠Interleukin-1ß (IL-1ß) might orchestrate joint inflammation in adult IgAV. ⢠IL-1ß might be a therapeutic target in patients with chronic and/or refractory joint involvement.
Assuntos
Vasculite por IgA , Citocinas , Humanos , Imunoglobulina A , Fenótipo , Estudos ProspectivosRESUMO
BACKGROUND: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome. METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396. FINDINGS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030). INTERPRETATION: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies. FUNDING: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.