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1.
Blood ; 141(1): 11-21, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36054922

RESUMEN

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (<30 × 109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and the incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and nonpregnant women with ITP (53.4 per 100 person-years [95% confidence interval {CI}, 40.8-69.9] vs 37.1 [95% CI, 27.5-50.0]; hazard ratio {HR}, 1.35 [95% CI, 0.89-2.03], P = .16). Pregnant women with ITP were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95% CI, 1.41-5.23], P = .003; HR, 2.01 [95% CI, 1.14-3.57], P = .017, respectively). However, recurrence of severe bleeding events was not different between groups (P = .4). Nineteen (14%) neonates showed NITP <50 × 109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count <50 × 109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95% CI, 1.72-17.89], P = .004 and 4.07 [95% CI, 1.41-11.73], P = .009). To conclude, women with ITP do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling women with ITP.


Asunto(s)
Complicaciones Hematológicas del Embarazo , Púrpura Trombocitopénica Idiopática , Trombocitopenia Neonatal Aloinmune , Recién Nacido , Femenino , Humanos , Embarazo , Púrpura Trombocitopénica Idiopática/epidemiología , Púrpura Trombocitopénica Idiopática/terapia , Púrpura Trombocitopénica Idiopática/complicaciones , Estudios de Cohortes , Estudios Prospectivos , Complicaciones Hematológicas del Embarazo/epidemiología , Complicaciones Hematológicas del Embarazo/terapia , Trombocitopenia Neonatal Aloinmune/terapia , Estudios Retrospectivos
2.
Rev Infirm ; 72(289): 45-48, 2023 Mar.
Artículo en Francés | MEDLINE | ID: mdl-37024197

RESUMEN

The patient partnership is a new approach in which the patient, through his knowledge acquired from his experience with the disease, is a stakeholder in decisions about care, the organization of the health system and choices in terms of health policy. A team from the Blois hospital (41) was able to share the experience of a patient partnership during the analysis of a complex medical situation with a young man with sickle cell disease in a vaso-occlusive crisis. She reports here this new and enriching experience.


Asunto(s)
Anemia de Células Falciformes , Humanos , Masculino , Anemia de Células Falciformes/terapia
3.
Rheumatology (Oxford) ; 61(4): 1376-1384, 2022 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-34363461

RESUMEN

OBJECTIVE: To assess the safety and the efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK). METHODS: A total of 209 patients with TAK [median age 29 years (interquartile range 7-62)], 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)] or tocilizumab [n = 77 (37%) with 121 lines; i.v. and s.c. in 95 and 26 cases, respectively]. RESULTS: A complete response at 6 months was evidenced in 101/152 (66%) patients on TNF-α antagonists and 75/107 (70%) patients on tocilizumab. Age ≥30 years [odds ratio 2.09 (95% CI 1.09, 3.99)] was associated with complete response, whereas vascular signs [OR 0.26 (95% CI 0.1, 0.65)], baseline prednisone ≥20 mg/day [OR 0.51 (95% CI 0.28, 0.93)] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvement [HR 2.44 (95% CI 1.06, 5.65) and 3.66 (1.18, 11.4), respectively] and systemic signs at baseline [HR 2.01 (95% CI 1.30, 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNF-α antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biologic targeted therapies [37 (21%) on TNF-α antagonists and 21 (17%) on tocilizumab (P = 0.4), respectively]. CONCLUSION: This large multicentre study shows high efficacy of biologic targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.


Asunto(s)
Arteritis de Takayasu , Factor de Necrosis Tumoral alfa , Adulto , Anticuerpos Monoclonales Humanizados , Femenino , Humanos , Recurrencia , Estudios Retrospectivos , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/tratamiento farmacológico , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral
4.
Rheumatology (Oxford) ; 60(9): 4245-4251, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-33410479

RESUMEN

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.


Asunto(s)
Envejecimiento/inmunología , Inmunoglobulina A , Fallo Renal Crónico/etiología , Vasculitis/diagnóstico , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Fallo Renal Crónico/inmunología , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Estudios Retrospectivos , Vasculitis/inmunología
5.
Eur J Haematol ; 107(2): 190-201, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34288162

RESUMEN

BACKGROUND: A high prevalence of pulmonary embolism (PE) has been described during COVID-19. Our aim was to identify predictive factors of PE in non-ICU hospitalized COVID-19 patients. METHODS: Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID-19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. RESULTS: A total of 88 patients (median [IQR] age of 68 years [60-78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D-dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3-74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3-1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7-553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D-dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0-397.9], P = .004). CONCLUSION: The white blood count, the D-dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non-ICU COVID-19 patients.


Asunto(s)
COVID-19/complicaciones , Ferritinas/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Recuento de Leucocitos , Embolia Pulmonar/sangre , Embolia Pulmonar/complicaciones , COVID-19/virología , Francia , Humanos , Admisión del Paciente , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación
6.
Rheumatology (Oxford) ; 59(10): 3050-3057, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32211770

RESUMEN

OBJECTIVES: To describe the clinical presentation, treatments and prognosis of gastrointestinal (GI) involvement in adult IgA vasculitis (IgAV). METHODS: Data from 260 adults with IgAV included in a French multicentre retrospective survey were analysed. Presentation and outcomes of patients with (GI+) and without (GI-) GI involvement were compared. RESULTS: One hundred and thirty-seven (53%) patients had GI involvement. Initial manifestations were abdominal pain in 99%, intestinal bleeding in 31%, diarrhoea in 26% and acute surgical abdomen in only 4%. Abdominal imaging revealed thickening of intestinal wall in 61%, and endoscopies revealed abnormalities in 87%, mostly mucosal ulcerations. GI+ vs GI- patients were younger (46 ± 18 vs 54 ± 18 years; P = 0.0004), had more constitutional symptoms (43% vs 23%; P = 0.0005) and joint involvement (72 vs 50%; P = 0.0002), and higher CRP levels (3.7 vs 1.9 mg/dl; P = 0.001). Clinical response and relapse rates were comparable between groups, and all causes mortality (2 vs 4%) and IgAV-related mortality (1% vs 2%) as well. GI-related deaths were due to intestinal perforation and mesenteric ischaemia. CONCLUSION: GI involvement is frequent in adult IgAV. GI involvement is frequent in adult IgAV. Mortality is not uncommon but does not seem to be specifically related to GI. Immunosuppressants should not be preferred as first-line therapy for GI+ patients but may be required in case of acute surgical abdomen.


Asunto(s)
Enfermedades Gastrointestinales/etiología , Vasculitis por IgA/complicaciones , Abdomen Agudo/etiología , Dolor Abdominal/etiología , Adulto , Factores de Edad , Proteína C-Reactiva/análisis , Causas de Muerte , Diarrea/etiología , Francia , Enfermedades Gastrointestinales/diagnóstico por imagen , Enfermedades Gastrointestinales/mortalidad , Enfermedades Gastrointestinales/patología , Hemorragia Gastrointestinal/etiología , Humanos , Vasculitis por IgA/diagnóstico por imagen , Vasculitis por IgA/mortalidad , Vasculitis por IgA/patología , Inmunoglobulina A , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patología , Seudoobstrucción Intestinal/etiología , Intestinos/diagnóstico por imagen , Intestinos/patología , Persona de Mediana Edad , Náusea/etiología , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Vómitos/etiología
7.
J Pediatr ; 204: 225-233.e8, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30314658

RESUMEN

OBJECTIVES: To compare the efficacy and safety of intravenous immunoglobulins (IVIG) and anti-D immunoglobulin (anti-D) in pediatric immune thrombocytopenia (ITP). STUDY DESIGN: We conducted a systematic review and meta-analysis following PRISMA guidelines, including all randomized controlled trials that have assessed the efficacy and safety of anti-D and IVIG in children with ITP. We searched Medline, Embase, and Cochrane databases. Primary outcomes were the proportion of children achieving platelet count responses as defined in each study and bleeding response. Other safety outcomes included infusion reactions and hemolysis. RESULTS: Eleven studies with 558 children were included. Anti-D was significantly inferior to IVIG at increasing platelet counts, both for thresholds of >20 × 109/L at 24-72 hours (response rate ratio for anti-D vs IVIG: 0.85, 95% CI 0.78-0.94) and >50 × 109/L at 24-72 hours (response rate ratio for anti-D vs IVIG: 0.75, 95% CI 0.61-0.92). Bleeding response was assessed in 4 studies, but some heterogeneity in reporting leads to unclear conclusion. General symptoms after anti-D infusion were less frequent than after IVIG (Peto OR 0.39, 95% CI 0.25-0.62). Hemolysis was more frequent after anti-D. The overall quality of the studies was low. CONCLUSIONS: Compared with anti-D, IVIG led to a better response in terms of platelet count and may be preferred as a first-line treatment of ITP in children with acute hemorrhagic symptoms. However, the clinical significance of IVIG superiority on platelet count remains unclear.


Asunto(s)
Inmunoglobulinas Intravenosas/uso terapéutico , Púrpura Trombocitopénica Idiopática/terapia , Globulina Inmune rho(D)/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Hemorragia/etiología , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Lactante , Masculino , Recuento de Plaquetas , Ensayos Clínicos Controlados Aleatorios como Asunto , Globulina Inmune rho(D)/efectos adversos , Resultado del Tratamiento
8.
J Autoimmun ; 91: 55-60, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29678346

RESUMEN

OBJECTIVES: To assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA). METHODS: We conducted a retrospective multicenter study in 46 TA patients treated with tocilizumab. We analyzed factors associated with response to tocilizumab (assessed using NIH score). RESULTS: Forty-six patients with TA were included, with a median age of 43 years [29-54], and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 [2-3] at baseline to 0 [0-1] and 0 at 3 and 6 months, respectively; p < 0.0001). The daily prednisone dose also decreased from 15 mg [8-19] at baseline to 4 mg [5-21] and 5 mg [4.5-9] at 3 and 6 months, respectively (p < 0.0001) under tocilizumab. The overall tocilizumab failure free survival was 81% [CI 95%; 0.7-0.95], 72% [CI 95%; 0.55-0.95] and 48% [CI 95%; 0.2-0.1] at 12, 24 and 48 months, respectively. The presence of constitutional symptoms (HR 5.6 [CI 95%; 1.08-29], p = 0.041), and C-reactive protein level (HR 1.16 [CI 95%; 1.01-1.31], P = 0.003) at the time of tocilizumab initiation were significantly associated with tocilizumab event-free survival. The event-free survival was significantly better under tocilizumab therapy in comparison to DMARDs (p = 0.02). CONCLUSION: This large multicenter study shows that tocilizumab is efficient and may reduce the incidence of relapses in TA.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Inmunosupresores/uso terapéutico , Arteritis de Takayasu/tratamiento farmacológico , Adulto , Proteína C-Reactiva/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Estudios Retrospectivos , Análisis de Supervivencia , Arteritis de Takayasu/mortalidad , Resultado del Tratamiento
9.
Rheumatology (Oxford) ; 57(8): 1432-1438, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29757439

RESUMEN

OBJECTIVES: The use of thrombopoietin-receptor agonists (TPO-RAs) has increased as a second-line therapy in ITP, but the efficacy and safety of such drugs has not been evaluated in SLE-associated ITP. METHODS: This was a multicentre retrospective cohort study from 2009 to 2016. Participating centres (n = 11) were secondary- or tertiary-care hospitals belonging to the French national network for adult ITP. RESULTS: We included 18 patients with SLE-ITP treated with TPO-RAs; 10 (55%) had aPL, 5 (27%) showing definite APS. Except for one patient, all (94%) achieved response with TPO-RAs overall. After a median follow-up of 14.7 months with TPO-RAs, four arterial thrombosis events (including one catastrophic APS) occurred in four patients. Two venous thrombosis events occurred in a patient without APS or aPLs. CONCLUSION: Our results suggest that aPLs should be systematically screened before TPO-RA initiation in patients with SLE. With aPL positivity, alternative therapy should be discussed (if possible), especially in patients with definite APS or suboptimal adherence to anti-coagulation therapy.


Asunto(s)
Síndrome Antifosfolípido/tratamiento farmacológico , Benzoatos/efectos adversos , Hidrazinas/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Pirazoles/efectos adversos , Receptores de Trombopoyetina/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/efectos adversos , Trombopoyetina/efectos adversos , Trombosis/etiología , Adolescente , Adulto , Anciano , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Benzoatos/administración & dosificación , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Hidrazinas/administración & dosificación , Incidencia , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pronóstico , Pirazoles/administración & dosificación , Receptores Fc/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Estudios Retrospectivos , Trombopoyetina/administración & dosificación , Trombosis/inducido químicamente , Trombosis/epidemiología , Adulto Joven
10.
Am J Hematol ; 93(3): 424-429, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29247540

RESUMEN

The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)-associated immune cytopenias. This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE-associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions. In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31-48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6-11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%), and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow-up after the first injection of RTX was 26.4 months [14.3-71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX retreatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX-induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE-associated immune cytopenias.


Asunto(s)
Anemia Hemolítica Autoinmune/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/inmunología , Susceptibilidad a Enfermedades , Supervivencia sin Enfermedad , Evaluación de Medicamentos , Quimioterapia Combinada , Femenino , Fiebre/inducido químicamente , Estudios de Seguimiento , Humanos , Inmunosupresores/efectos adversos , Infecciones/etiología , Estimación de Kaplan-Meier , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/etiología , Púrpura Trombocitopénica Idiopática/inmunología , Aplasia Pura de Células Rojas/tratamiento farmacológico , Aplasia Pura de Células Rojas/etiología , Aplasia Pura de Células Rojas/inmunología , Estudios Retrospectivos , Rituximab/efectos adversos , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/etiología , Trombocitopenia/inmunología , Resultado del Tratamiento
13.
Br J Clin Pharmacol ; 83(8): 1773-1781, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28230269

RESUMEN

AIMS: Rituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target-antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RA patients. METHODS: In a cohort of 64 RA patients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area, sex and disease activity score in 28 joints on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis. RESULTS: A two-compartment model, with first-order distribution and elimination best described the data. The volume of distribution of central compartment and clearance of rituximab were estimated at 4.7 l and 0.56 l day-1 , respectively. Distribution and elimination half-lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with body surface area (P = 0.012) and was higher in male than in female (P = 0.004). We found that the elimination rate constant (k10 ) increased with CD19+ count (P = 0.00022) and IgG concentration (P = 7.4 × 10-8 ), and that k10 decreased with time (P = 0.00015), partly explained by a change in target-antigen amount. CONCLUSIONS: The association between CD19+ count and k10 may be explained by target-mediated drug disposition, while the association between IgG serum concentration and k10 may be explained by a saturation of the neonatal Fc receptor at high IgG concentrations, resulting in decreased recycling of rituximab.


Asunto(s)
Antígenos CD20/sangre , Antirreumáticos/farmacocinética , Artritis Reumatoide/tratamiento farmacológico , Linfocitos B/metabolismo , Inmunoglobulina G/sangre , Rituximab/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD19/metabolismo , Antígenos CD20/metabolismo , Antirreumáticos/uso terapéutico , Artritis Reumatoide/sangre , Superficie Corporal , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab/uso terapéutico , Factores Sexuales
14.
Rheumatology (Oxford) ; 55(2): 291-300, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26350487

RESUMEN

OBJECTIVE: We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study. METHODS: In this study, 123 patients with MDS and SIADs were analysed. RESULTS: Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P < 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P < 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5). CONCLUSION: The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent.


Asunto(s)
Autoinmunidad/inmunología , Azacitidina/uso terapéutico , Glucocorticoides/uso terapéutico , Inflamación/inmunología , Leucemia Mielomonocítica Crónica/inmunología , Síndromes Mielodisplásicos/inmunología , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Francia , Humanos , Inflamación/tratamiento farmacológico , Inflamación/etiología , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Masculino , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos
16.
Clin Exp Rheumatol ; 34(3 Suppl 97): S7-11, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26412031

RESUMEN

OBJECTIVES: Our objective was to describe the characteristics of posterior reversible encephalopathy syndrome (PRES) associated with systemic vasculitis. METHODS: A standardised questionnaire was used for a nationwide retrospective multicentre study in 2013 to collect clinical, radiological and outcome data about PRES associated with systemic vasculitis. RESULTS: We included six patients (all women; mean age 22.6±19.8 years (20-62)): two with polyarteritis nodosa and one case of each granulomatosis with polyangiitis, cryoglobulinaemic vasculitis, hypocomplementemic urticarial vasculitis, and Takayasu arteritis. PRES was the first manifestation of systemic vasculitis in three patients. Arterial hypertension was suspected to be the cause of PRES in five patients. Several other plausible causes including drugs, renal failure, and pneumonia were found in three patients. Clinical findings included headache, seizure, blurred or loss of vision, confusion, and altered cognition. Radiological study showed oedema in the occipital region in all patients, with a reversible state in MRIs performed one week to one month after the onset of PRES. Therapies used included antihypertensive therapy (n=5), immunosuppressive therapy (corticosteroids (n=5), cyclophosphamide (n=4), azathioprine (n=1), methotrexate (n=1), plasma exchange (n=1)), antibiotics (n=1), anticonvulsant therapy (n=2)), and analgesics. No relapse of PRES was reported during the follow-up period (mean: 47.5 ±29.9 months, 13-98); one patient continued to complain of vision loss. CONCLUSIONS: Our study indicates that PRES is a rare condition associated with systemic vasculitis; which may be present at the onset vasculitis symptoms. Antihypertensive drugs should be prescribed if blood pressure is elevated. The impact of immunosuppressive therapy remains unclear.


Asunto(s)
Síndrome de Leucoencefalopatía Posterior/etiología , Vasculitis Sistémica/complicaciones , Adulto , Antihipertensivos/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Síndrome de Leucoencefalopatía Posterior/tratamiento farmacológico
18.
Orphanet J Rare Dis ; 19(1): 65, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355710

RESUMEN

Inherited Metabolic Diseases (IMD) encompass a diverse group of rare genetic conditions that, despite their individual rarity, collectively affect a substantial proportion, estimated at as much as 1 in 784 live births. Among their wide-ranging clinical manifestations, cytopenia stands out as a prominent feature. Consequently, IMD should be considered a potential diagnosis when evaluating patients presenting with cytopenia. However, it is essential to note that the existing scientific literature pertaining to the link between IMD and cytopenia is limited, primarily comprising case reports and case series. This paucity of data may contribute to the inadequate recognition of the association between IMD and cytopenia, potentially leading to underdiagnosis. In this review, we synthesize our findings from a literature analysis along with our clinical expertise to offer a comprehensive insight into the clinical presentation of IMD cases associated with cytopenia. Furthermore, we introduce a structured diagnostic approach underpinned by decision-making algorithms, with the aim of enhancing the early identification and management of IMD-related cytopenia.


Asunto(s)
Citopenia , Enfermedades Metabólicas , Neutropenia , Humanos , Enfermedades Metabólicas/genética
19.
EClinicalMedicine ; 68: 102383, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38545090

RESUMEN

Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728). Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. Funding: Biophytis.

20.
RMD Open ; 9(2)2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37321669

RESUMEN

OBJECTIVES: In this large multicentre study, we compared the effectiveness and safety of tocilizumab intravenous versus subcutaneous (SC) in 109 Takayasu arteritis (TAK) patients. METHODS: We conducted a retrospective multicentre study in referral centres from France, Italy, Spain, Armenia, Israel, Japan, Tunisia and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019. RESULTS: A total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received intravenous and SC tocilizumab, respectively. A complete response (NIH <2 with less than 7.5 mg/day of prednisone) at 6 months was evidenced in 69% of TAK patients, of whom 57 (70%) and 11 (69%) patients were on intravenous and SC tocilizumab, respectively (p=0.95). The factors associated with complete response to tocilizumab at 6 months in multivariate analysis, only age <30 years (OR 2.85, 95% CI 1.14 to 7.12; p=0.027) and time between TAK diagnosis and tocilizumab initiation (OR 1.18, 95% CI 1.02 to 1.36; p=0.034). During the median follow-up of 30.1 months (0.4; 105.8) and 10.8 (0.1; 46.4) (p<0.0001) in patients who received tocilizumab in intravenous and SC forms, respectively, the risk of relapse was significantly higher in TAK patients on SC tocilizumab (HR=2.55, 95% CI 1.08 to 6.02; p=0.033). The overall cumulative incidence of relapse at 12 months in TAK patients was at 13.7% (95% CI 7.6% to 21.5%), with 10.3% (95% CI 4.8% to 18.4%) for those on intravenous tocilizumab vs 30.9% (95% CI 10.5% to 54.2%) for patients receiving SC tocilizumab. Adverse events occurred in 14 (15%) patients on intravenous route and in 2 (11%) on SC tocilizumab. CONCLUSION: In this study, we confirm that tocilizumab is effective in TAK, with complete remission being achieving by 70% of disease-modifying antirheumatic drugs-refractory TAK patients at 6 months.


Asunto(s)
Antirreumáticos , Arteritis de Takayasu , Humanos , Adulto , Estudios Retrospectivos , Arteritis de Takayasu/diagnóstico , Arteritis de Takayasu/tratamiento farmacológico , Resultado del Tratamiento , Antirreumáticos/uso terapéutico
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