RESUMO
OBJECTIVES: The gastrointestinal tract (GIT) is frequently involved in systemic sclerosis (SSc) and is responsible for alteration of quality of life. Many complications can occur, including chronic intestinal pseudo-obstruction, digestive haemorrhage and small-intestinal bacterial overgrowth. Since early development of organ failure is associated with poor prognosis, we need to identify risk factors associated with severe GIT involvement to prevent severe forms of the disease. METHODS: We conducted an observational prospective study, which included 90 SSc patients from December 2019 to September 2021. We collected questionnaires about digestive manifestations and quality of life, blood and stool samples, and performed imaging. At inclusion and throughout the study we assessed the occurrence of malnutrition and severe GIT disorders. We performed statistical analysis to highlight eventual risk factors associated with digestive manifestations, including hierarchical cluster analysis. RESULTS: A majority of our patients had gastro-oesophageal manifestations (93.3%), followed by intestinal manifestations (67.8%) and anorectal manifestations (18.9%). We found a correlation between anorectal disorders and cardiac disease, and between gastro-oesophageal involvement and impaired pulmonary function tests. Smoking was significantly associated with occurrence of severe GIT disorders. Malnutrition was frequent and associated with more cardiac and pulmonary disease. Cluster analysis identified three groups of patients, including one cluster with cardiac and digestive involvement. CONCLUSIONS: GIT manifestations are frequent and severe in SSc. Smoking appears to be associated with severe disease. Anorectal manifestations may be associated with cardiac disease, but we need more studies to validate these results.
Assuntos
Gastroenteropatias , Qualidade de Vida , Escleroderma Sistêmico , Humanos , Feminino , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Estudos Prospectivos , Masculino , Pessoa de Meia-Idade , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Gastroenteropatias/diagnóstico , Prognóstico , França/epidemiologia , Fatores de Risco , Idoso , Análise por Conglomerados , Adulto , Índice de Gravidade de Doença , Fumar/efeitos adversos , Fumar/epidemiologia , Desnutrição/epidemiologia , Desnutrição/diagnósticoRESUMO
Hematopoietic stem cell transplant (HSCT) recipients may be at high risk of mortality from coronavirus disease 2019 (COVID-19). However, specific data on COVID-19 after treatment with HSCT in patients affected by autoimmune diseases (ADs) are still lacking. In this multicenter observational study of the European Society for Blood and Marrow Transplantation (EBMT), clinical data on COVID-19 in 11 patients affected by severe ADs treated with HSCT (n = 3 allogeneic transplant; n = 8 autologous transplant) are reported. All patients were symptomatic during the initial phase of the SARS-CoV-2 infection. At screening, 5 patients reported upper respiratory symptoms, 3 patients had cough without oxygen requirement, and 6 patients exhibited extra-pulmonary symptoms. Four cases developed a lower respiratory tract disease (LRTD). Hospitalization was required in 6 cases, without necessity of intensive care unit (ICU) admission and/or ventilation/supplemental oxygen. Different interventions were adopted: remdesivir (n = 1), nirmatrelvir/ritonavir (n = 1), sotrovimab (n = 1), immunoglobulins (n = 1). At last follow-up, all patients are alive and had resolution of the infection. The current analysis describing the mild-moderate course of COVID-19 in transplant recipients affected by ADs, similar to the course observed in ADs under standard treatments, provides useful information to support the delivery of HSCT programs in this field. Vaccination and new treatments available for SARS-CoV-2 may be useful to further minimize the risk of infection.
Assuntos
Doenças Autoimunes , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , SARS-CoV-2 , RNA Viral , Transplantados , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/terapiaRESUMO
Acute cerebrovascular ischemic events are a rare and severe complication of giant cell arteritis (GCA). We aimed to determine the prevalence of GCA-related stroke, the overall survival and the relapse-free survival in patients with GCA. A multicentric retrospective analysis was performed on 129 patients with GCA diagnosed between September 2010 and October 2018 in two University Hospitals. Among 129 GCA patients, 18 (16%) presented an acute ischemic cerebrovascular event. Patients with stroke were older (83 [67-96] years versus 76 [58-96]; pâ¯=â¯0.014) and more frequently males (61% versus 30%; pâ¯=â¯0.014) than those without stroke. The frequency of anterior ischemic optic neuropathy was higher in patients with stroke (nâ¯=â¯6, 33%) than patients without stroke (nâ¯=â¯12, 11%)(pâ¯=â¯0.02). Overall survival was significantly decreased in GCA patients with stroke (4.4 months), comparatively to patients without stroke (221.7 months; log rank testâ¯=â¯0.006). The 3-years relapse-free survival was decreased in patients with stroke (8.42 versus78.0 months; log rankâ¯=â¯0.0001), as well as the time with sustained remission (78 versus 139 months; log rank testâ¯=â¯0.0004). This study shows the prevalence and risk factors of ischemic stroke in GCA.
Assuntos
Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Estudos RetrospectivosRESUMO
Conditioning regimen prior to hematopoietic stem cell transplantation have an impact on patient fertility through the use of gonadal irradiation and/or bifunctional alkylating agents. Their impact on fertility depends mainly on the dose used and, in women, on age at the time of treatment. All patients should benefit before treatment from a consultation informing them of the potential impact on fertility and of fertility preservation techniques. In the absence of contraindications, the major toxicity of myeloablative conditioning regimen justifies fertility preservation. There are few data concerning fertility after reduced-intensity conditioning. Despite lower theoretical gonadotoxicity, we also recommend fertility preservation, if possible before transplantation. The fertility preservation techniques used depend on the patient's age, pathology and conditioning. In the event of subsequent use of harvested gonadal tissue in the context of acute leukemia or aggressive lymphoma, it is advisable to assess the risk of reintroduction of tumor cells. Finally, it is recommended to assess gonadal function after transplant, especially after reduced conditioning. If there is persistent residual gonadal function, post-treatment fertility preservation should be discuss.
RESUMO
BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2LD) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc. OBJECTIVE: We aimed to assess the safety and biological efficacy of IL-2LD in patients with SSc. METHODS: As part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)/day of IL-2 for 5 days, followed by fortnightly injections for 6 months. Laboratory and clinical evaluations were performed between baseline and month 6. RESULTS: At day 8, the primary endpoint (Treg frequency) was reached with a 1.8±0.5-fold increase of Treg levels among CD4+ T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2LD was well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period. CONCLUSION: IL-2LD at a dosage of 1 MIU/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2LD therapeutic efficacy in SSc.
Assuntos
Interleucina-2 , Escleroderma Sistêmico , Linfócitos T Reguladores , Humanos , Doenças Autoimunes/tratamento farmacológico , Interleucina-2/efeitos adversos , Interleucina-2/uso terapêutico , Qualidade de Vida , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/imunologia , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 13th workshop on hematopoietic stem cell transplantation clinical practices harmonization procedures in September 2022 in Lille, France. The aim of this workshop is to update the mobilization and conditioning protocols for autologous hematopoietic stem cell transplantation for autoimmune diseases, and to specify contraindications for transplant, conditioning regimen selection, immunosuppressive treatment discontinuation before mobilization and disease-specific surveillance.
Assuntos
Doenças Autoimunes , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Autólogo , Transplante de Medula Óssea , Doenças Autoimunes/terapia , Imunossupressores/uso terapêutico , França , Sociedades Médicas , Condicionamento Pré-TransplanteRESUMO
Systemic sclerosis (SSc) is a rare autoimmune disease (AD), characterised by early diffuse vasculopathy, activation of the immune response and progressive skin and internal organ fibrosis. In severe progressive diffuse SSc (dSSc), autologous hematopoietic stem cell transplantation (aHSCT) improves survival, despite its own risk of complications and transplant related mortality (TRM). We present herein the case of a dSSc patient undergoing aHSCT with low dose cyclophosphamide conditioning and sudden acute myopericarditis and cardiogenic shock, four weeks after a second mRNA SARS-CoV-2 vaccine (Pfizer) injection. Four days of extracorporeal membrane oxygenation (ECMO) support during the aplasia period, allowed to observe full cardiac function recovery and progressive SSc rehabilitation with sustained disease response at 30 months follow-up. This report illustrates, for the first time to our knowledge, that ECMO can be indicated despite aplasia during aHSCT and successfully used as a bridge towards heart function recovery in highly selected and fragile AD patients. We review the factors that may contribute to endothelial and myocardial stunning and acute reversible cardiac failure in SSc and aggravate intrinsic endothelial injury during the aHSCT procedure. These classically include: cyclophosphamide drug toxicity, viral infections and autoimmune activation with disease flair per se. In the COVID-19 pandemic times, acute myocarditis due to recent viral infection or mRNA vaccine per se, must also be considered.
RESUMO
Current evidence-based clinical practice guidelines recommend the use of both low-molecular-weight heparin (LMWH) and direct factor Xa inhibitors (apixapan, edoxaban and rivaroxaban) as first-line options for the treatment of venous thromboembolism (VTE) in patients with cancer. However, most of these guidelines refer to the general cancer patient population and provide limited guidance for specific subgroups of patients at particularly high risk of bleeding, such as those with gastrointestinal cancers, primary or metastatic brain tumors, thrombocytopenia, or renal impairment. In these complex populations, the management of cancer-associated thrombosis (CAT) poses unique challenges and requires a nuanced approach based on the primum non nocere principle. This comprehensive review critically examines the relevant literature and discusses the therapeutic options currently available for the management of CAT in these special situations.
Assuntos
Neoplasias , Trombose , Tromboembolia Venosa , Humanos , Heparina de Baixo Peso Molecular/uso terapêutico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Rivaroxabana/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Trombose/tratamento farmacológicoRESUMO
Breast cancer is the most common cancer in women. Patients with breast cancer have a 4-fold increased risk of venous thromboembolism (VTE) compared to age- and sex-matched controls without cancer. VTE remains the second leading cause of death in cancer patients and an independent risk factor for mortality. In women with breast cancer, the main risk factors for developing VTE are increasing age, obesity, disease stage, central catheter placement and cancer treatments, including surgery, chemotherapy, hormonotherapy and cyclin-dependent kinase 4/6 inhibitors. In women receiving tamoxifen, the risk of VTE is particularly increased within the first 6 months after initiation of hormonotherapy, although some evidence suggests that this risk may persist through the first 2 years of treatment. The risk of VTE appears to be lower in patients receiving aromatase inhibitors. In breast cancer patients receiving cyclin-dependent kinase 4/6 inhibitors, the rate of VTE is approximately 6%. Current clinical practice guidelines for the treatment and prevention of VTE in patients with cancer suggest that thromboprophylaxis should not be used routinely in ambulatory cancer patients receiving chemotherapy or hormonotherapy. The risk-benefit ratio of thromboprophylaxis should be assessed on a case-by-case basis and be the subject of multidisciplinary discussion.
Assuntos
Neoplasias da Mama , Tromboembolia Venosa , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/tratamento farmacológico , Quinase 4 Dependente de Ciclina , Tamoxifeno/efeitos adversos , Fatores de RiscoRESUMO
Introduction: We aimed to analyze patients with acute and chronic joint involvements in sarcoidosis. Methods: This is a retrospective multicenter analysis of patients with proven sarcoidosis, as defined by clinical, radiological, and histological criteria, with at least one clinical and/or ultrasonographic synovitis. Results: Thirty-nine patients with sarcoid arthropathy were included, and among them 19 had acute sarcoidosis (Lofgren's syndrome). Joint involvement and DAS44-CRP were not significantly different in acute and chronic sarcoid arthropathies. Acute forms were more frequent than chronic sarcoid arthropathy in Caucasians, without any difference of sex or age between these 2 forms. Joint involvement was frequently more symmetrical in acute than chronic forms (100 vs. 70%; p < 0.05), with a more frequent involvement in wrists and ankles in acute forms, whereas the tender and swollen joint counts and the DAS44-CRP were similar between the 2 groups. Skin lesions were significantly more frequent in patients with acute forms [17 (89%) vs. 5 (25%); p < 0.05] and were erythema nodosum in all patients with Löfgren's syndrome and sarcoid skin lesions in those with chronic sarcoidosis. Among 20 patients with chronic sarcoidosis, treatment was used in 17 (85%) cases, and consisted in NSAIDs alone (n = 5; 25%), steroids alone (n = 5; 25%), hydroxychloroquine (n = 2; 20%), methotrexate (n = 3; 15%), and TNF inhibitors (n = 2; 10%). A complete/partial joint response was noted in 14 (70%) cases with a DAS44-CRP reduction of 2.07 [1.85-2.44] (from 3.13 [2.76-3.42] to 1.06 [0.9-1.17]; p < 0.05). Conclusion: Sarcoid arthropathies have different clinical phenotypes in acute and chronic forms and various treatment regimens such as hydroxychloroquine and methotrexate could be used in chronic forms.