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1.
N Engl J Med ; 386(1): 11-23, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34986284

RESUMO

BACKGROUND: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).


Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Benzoatos/uso terapêutico , Ciclosporina/uso terapêutico , Hidrazinas/uso terapêutico , Imunossupressores/uso terapêutico , Pirazóis/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/genética , Soro Antilinfocitário/efeitos adversos , Benzoatos/efeitos adversos , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Hidrazinas/efeitos adversos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Pirazóis/efeitos adversos , Receptores de Trombopoetina/agonistas , Indução de Remissão , Adulto Jovem
2.
Artigo em Inglês | MEDLINE | ID: mdl-34759018

RESUMO

BACKGROUND AND OBJECTIVES: To investigate whether children receiving immunosuppressive therapies for neuroimmunologic disorders had (1) increased susceptibility to SARS-CoV2 infection or to develop more severe forms of COVID-19; (2) increased relapses or autoimmune complications if infected; and (3) changes in health care delivery during the pandemic. METHODS: Patients with and without immunosuppressive treatment were recruited to participate in a retrospective survey evaluating the period from March 14, 2020, to March 30, 2021. Demographics, clinical features, type of immunosuppressive treatment, suspected or confirmed COVID-19 in the patients or cohabitants, and changes in care delivery were recorded. RESULTS: One hundred fifty-three children were included: 84 (55%) female, median age 13 years (interquartile range [8-16] years), 79 (52%) on immunosuppressive treatment. COVID-19 was suspected or confirmed in 17 (11%) (all mild), with a frequency similar in patients with and without immunosuppressive treatment (11/79 [14%] vs 6/74 [8%], p = 0.3085). The frequency of neurologic relapses was similar in patients with (18%) and without (21%) COVID-19. Factors associated with COVID-19 included having cohabitants with COVID-19 (p < 0.001) and lower blood levels of vitamin D (p = 0.039). Return to face-to-face schooling or mask type did not influence the risk of infection, although 43(28%) children had contact with a classmate with COVID-19. Clinic visits changed from face to face to remote for 120 (79%) patients; 110 (92%) were satisfied with the change. DISCUSSION: In this cohort of children with neuroimmunologic disorders, the frequency of COVID-19 was low and not affected by immunosuppressive therapies. The main risk factors for developing COVID-19 were having cohabitants with COVID-19 and low vitamin D levels.


Assuntos
COVID-19/complicações , COVID-19/imunologia , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/imunologia , SARS-CoV-2/imunologia , Adolescente , COVID-19/prevenção & controle , COVID-19/virologia , Criança , Atenção à Saúde/organização & administração , Atenção à Saúde/estatística & dados numéricos , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Máscaras/estatística & dados numéricos , Máscaras/virologia , Doenças do Sistema Nervoso/virologia , Pandemias , Recidiva , Estudos Retrospectivos , Vitamina D/sangue
5.
World J Gastroenterol ; 27(45): 7771-7783, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34963740

RESUMO

Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the "early" phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.


Assuntos
Transplante de Fígado , Ductos Biliares , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Transplante de Fígado/efeitos adversos
6.
Nihon Shokakibyo Gakkai Zasshi ; 118(11): 1038-1046, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34759100

RESUMO

We investigated the development of hepatits B virus (HBV) reactivation in patients receiving immunosuppressive therapy or chemotherapy at our hospital for 8 years. Using the automatic checking system for HBV reactivation coded using medical information that has been in operation in our hospital since October 2012, we prospectively observed the occurrence status of HBV reactivation in immunosuppressive/chemotherapy cases for 8 years. HBV reactivation occurred in 31 of 1516 patients with HBV infection. It occurred annually between 1 and 7 cases in multiple clinical departments, and in 8 of 59 patients treated with rituximab, 10 of 653 patients treated with antineoplastic agents, 10 of 399 patients treated with steroids, and 3 of 212 patients treated with direct-acting antivirals. The cumulative incidence of HBV reactivation was 1.2%, 2.3%, and 3.4% at 1, 2, and 3 years, respectively. The results of Cox regression analysis showed that the incidence of HBV reactivation was significantly higher in patients who received rituximab (odds ratio:12.841) or steroid (hazard ratio:4.264) or those who tested positive for HBc antibody alone (hazard ratio:11.005). We observed the occurrence of HBV reactivation in HBV-infected patients treated with immunosuppressive therapy or chemotherapy. HBV reactivation by immunosuppressive therapy or chemotherapy still occurs, and further safety management and caution are required in the hospital.


Assuntos
Hepatite C Crônica , Herpesvirus Cercopitecino 1 , Antivirais/uso terapêutico , Anticorpos Anti-Hepatite B/farmacologia , Antígenos de Superfície da Hepatite B/farmacologia , Vírus da Hepatite B , Hepatite C Crônica/tratamento farmacológico , Hospitais , Humanos , Imunossupressores/efeitos adversos , Rituximab/efeitos adversos , Ativação Viral
7.
BMC Neurol ; 21(1): 448, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781882

RESUMO

BACKGROUND: Tacrolimus is a macrolide immunosuppressant widely used to prevent rejection after solid organ transplantation. In general, adverse events of tacrolimus occur more often as the concentration of tacrolimus in the blood increases. We report the case of a 39-year-old man who developed a variety of adverse events despite in the therapeutic level of tacrolimus in the blood. CASE PRESENTATION: A 39-year-old man underwent liver transplantation for liver cirrhosis due to alcoholic liver disease. The postoperative immunosuppressant consisted of tacrolimus (5 mg) and mycophenolate (500 mg) twice daily. Five months after taking tacrolimus, he presented with talkativeness, which gradually worsened. Brain magnetic resonance imaging performed 10 months after tacrolimus administration revealed a hyperintense lesion affecting the middle of the pontine tegmentum on T2WI. The blood concentration of tacrolimus was 7.2 ng/mL (therapeutic range 5-20 ng/mL). After 21 months, he exhibited postural tremor in both the hands. Twenty-four months after taking tacrolimus, he showed drowsy mentality, intention tremor, and dysdiadochokinesia. Electroencephalography presented generalized high-voltage rhythmic delta waves; therefore, tacrolimus was discontinued in suspicion of tacrolimus-induced neurotoxicity, and anticonvulsive treatment was started. The level of consciousness gradually improved, and the patient was able to walk independently with mild ataxia. CONCLUSION: This case shows that tacrolimus-induced neurotoxicity can occur even at normal concentrations. Therefore, if a patient taking tacrolimus exhibits psychiatric or neurologic symptoms, neurotoxicity should be considered even when the blood tacrolimus is within the therapeutic range.


Assuntos
Transtorno Bipolar , Transplante de Fígado , Estado Epiléptico , Adulto , Transtorno Bipolar/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Masculino , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Tacrolimo/efeitos adversos
8.
Ann Transplant ; 26: e933001, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34697282

RESUMO

BACKGROUND There are many safety concerns regarding the use of antithymocyte globulin (ATG) in kidney transplant recipients (KTRs) during the ongoing COVID-19 pandemic. Hereby, we present our recent experience with ATG administration both as induction therapy and as an anti-rejection treatment. MATERIAL AND METHODS We retrospectively analyzed all patients transplanted during the first 12 months of the COVID-19 pandemic who were treated with thymoglobulin. The ATG dosing, lymphocyte number and percentage in blood smear, adverse effects (thrombocytopenia and infectious complications), and kidney graft function up to 12 months and patients' outcomes were analyzed and compared to KTRs who received basiliximab induction. RESULTS During pandemic, a total of 31 patients were treated with ATG and 59 received basiliximab. The median cumulative ATG doses were 275 (175-325) mg in the induction subgroup and 263 (200-275) mg in the anti-rejection treatment subgroup. Mild thrombocytopenia was noted in 7 (22.6%) and 13 (29.5%) patients, respectively. There were more infectious complications among patients treated with ATG as compared with the basiliximab subgroup (32.3 vs 10.2%, P<0.01), but there were similar incidence rates of thrombocytopenia. Kidney graft function up to 12 months after transplant was comparable (1.1 [1.0-1.9] vs 1.1 [1.0-1.4] mg/dl, respectively). CONCLUSIONS 1. ATG use in the induction protocol or as the anti-rejection treatment during the COVID-19 pandemic appears to be safe and the risk of adverse events is acceptable. 2. During the COVID-19 pandemic the necessary use of ATG should not be postponed, especially in KTRs with increased immunologic risk.


Assuntos
Soro Antilinfocitário , COVID-19 , Imunossupressores , Transplante de Rim , Soro Antilinfocitário/efeitos adversos , Soro Antilinfocitário/uso terapêutico , Basiliximab/uso terapêutico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Rim , Pandemias , Estudos Retrospectivos
9.
Transplant Proc ; 53(9): 2681-2684, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620498

RESUMO

BACKGROUND: The appearance of edema limits the use of everolimus de novo together with tacrolimus and steroids in kidney transplantation. We aimed to investigate the frequency and characteristics of patients with edema and compare them according to the type of immunosuppression. METHODS: We studied 150 kidney transplant recipients between 2015 and 2017 based on receiving everolimus de novo (group A) or mycophenolic acid derivatives (group B). RESULTS: We analyzed 50 patients in group A and 100 in group B. Follow-up was 26.2 ± 10 months. Fifty-six patients presented edema (37.3%): 54% in group A and 29% in group B (P = .003). Edema was mild in 74% of patients in group A and 57.1% in group B. The probability of edema was 10.1%, 22.4%, and 41% at 3, 6, and 12 months, respectively, in group A vs 10.1%, 20.3%, and 25.4% in group B (P = .006). Patients were treated mostly with diuretics (14.3% in group A vs 27.6% in group B) and discontinuation of calcium channel blockers (46.4% in group A vs 48.3% in group B). Improvement was 70.4% in group A vs 60.7% in group B; patient worsening was 0% in group A vs 10.7% in group B; and there was no change in 29.6% in group A vs 28.6% in group B. We did not find differences in patient or graft survival in those who presented edema, regardless of the treatment group. CONCLUSION: The use of everolimus and standard doses of tacrolimus caused edema in 54% of patients, with no impact on renal function or survival compared with mycophenolic acid derivatives. The edema was mostly of low intensity and improved in most patients.


Assuntos
Everolimo , Imunossupressores , Edema/induzido quimicamente , Everolimo/efeitos adversos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Tacrolimo
11.
PLoS One ; 16(10): e0258437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644366

RESUMO

OBJECTIVE: To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. METHODS: An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. RESULTS: Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. CONCLUSIONS: The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Feminino , Cloridrato de Fingolimode/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Sistema de Registros , Estudos Retrospectivos , Espanha , Resultado do Tratamento
12.
Transplant Rev (Orlando) ; 35(4): 100653, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34597943

RESUMO

There is growing evidence about the potential favorable effects that can be obtained from converting the administration of calcineurin inhibitors (CNIs) to Belatacept in kidney transplantation recipients. We conducted a meta-analysis to formulate strong evidence from the current literature about this effect on kidney functions, as measured by the estimated glomerular filtration rate (eGFR). Our search was conducted on the following databases: PubMed, Web of Science, Scopus, Embase, Google Scholar, Cochrane library, the clinical trials, and the International Standard Randomized Controlled Trial Number registries to obtain all studies that investigated the effect of post-transplantation CNIs conversion to Belatacept on kidney functions. Thirteen studies were finally included in the current study. The results showed a significant improvement in the eGFR following the conversion as compared to its value prior to it (MD = 10.41; 95% CI = 6.93, 13.90; P-value < 0.001). Although, there was no risk of bias among the pooled studies (P-value = 0.391), there was a significant heterogenity (I 2 = 80%; P value < 0.001). Serum creatinine levels showed no significant change following the conversion as compared to its value prior to it (MD = -1.22; 95% CI = -2.61, 0.16; P-value = 0.083). Nevertheless, a significant heterogeneity among the included studies was observed (I 2 = 87%; P-value = 0.005). Belatacept can be a good alternative to the CNI-based regimens following the kidney transplantation. The conversion to Belatacept resulted in an improvement in eGFR.


Assuntos
Rejeição de Enxerto , Imunossupressores , Abatacepte/uso terapêutico , Inibidores de Calcineurina , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Emerg Med Clin North Am ; 39(4): 807-820, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34600639

RESUMO

Abdominal pain in an immunocompromised patient represents a common clinical scenario that may have uncommon causes. Evaluation relies first on identifying the immunocompromise, whether due to congenital immunodeficiencies, malignancy, hematopoietic stem cell transplant, solid organ transplant, or human immunodeficiency virus/acquired immunodeficiency syndrome. Based on this determination, the emergency physician may then build a focused differential of pathophysiologic possibilities. Careful evaluation is necessary given the absence of classic physical examination findings, and liberal use of laboratory and cross-sectional imaging is prudent. Conservative evaluation and disposition of these high-risk patients is important to consider.


Assuntos
Dor Abdominal/etiologia , Hospedeiro Imunocomprometido , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por Citomegalovirus/complicações , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Enterocolite Neutropênica/complicações , Doença Enxerto-Hospedeiro/complicações , Infecções por HIV/complicações , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunossupressores/efeitos adversos , Obstrução Intestinal/complicações , Transtornos Linfoproliferativos/complicações , Anamnese , Mucosite/complicações , Neoplasias/complicações , Exame Físico
16.
Front Immunol ; 12: 708848, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659200

RESUMO

Impressive efforts have been made by researchers worldwide in the development of target vaccines against the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and in improving the management of immunomodulating agents. Currently, different vaccine formulations, such as viral vector, mRNA, and protein-based, almost all directed toward the spike protein that includes the domain for receptor binding, have been approved. Although data are not conclusive, patients affected by autoimmune rheumatic diseases (ARDs) seem to have a slightly higher disease prevalence, risk of hospitalization, and death from coronavirus disease-2019 (COVID-19) than the general population. Therefore, ARD patients, under immunosuppressive agents, have been included among the priority target groups for vaccine administration. However, specific cautions are needed to optimize vaccine safety and effectiveness in these patients, such as modification in some of the ongoing immunosuppressive therapies and the preferential use of mRNA other than vector-based vaccines. Immunomodulating agents can be a therapeutic opportunity for the management of COVID-19 patients; however, their clinical impact depends on how they are handled. To place in therapy immunomodulating agents in the correct window of opportunity throughout the identification of surrogate markers of disease progression and host immune response is mandatory to optimize patient's outcome.


Assuntos
Autoimunidade/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Hospedeiro Imunocomprometido/imunologia , Doenças Reumáticas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , SARS-CoV-2/imunologia , Vacinação
18.
Transplant Proc ; 53(9): 2743-2746, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34598811

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus that is affecting the entire world population. The objective of this study was to analyze the repercussion of the disease in a group of patients at risk such as heart transplant recipients. METHODS: From February 2020 to February 2021, heart transplant recipients diagnosed with COVID-19 were consecutively included. The total number of transplant recipients in outpatient follow-up at that time was 381. Three levels of infection were determined: group A: asymptomatic patients or with trivial symptoms without the need for hospital admission (6 patients); group B: patients admitted to the hospital for respiratory symptoms (12 patients); and group C: patients with severe symptoms and need for admission to the critical care unit (2 patients). At each risk level, medical performance was different: group A: close control, no therapeutic modification; group B: reduction of calcineurin inhibitor and substitution of mycophenolate mofetil for everolimus; group C: reduction of calcineurin inhibitor and withdrawal of mycophenolate mofetil. RESULTS: The prevalence of infection in the series was 5.2%. Most patients admitted had a pathologic chest x-ray with fever, cough, dyspnea, or vomiting. The change in immunosuppression performed in patients in group 2 was well tolerated and there was no graft rejection. Antiviral treatment was little used. However, boluses of steroids and some antibiotics were used frequently. The need for supplemental oxygen was 50% in group 2 and 100% in group 3. CONCLUSIONS: A significant number of transplant recipients will be affected by COVID-19 (5.3%). Management of the infection will depend on the severity of the infection and must be based on a balance between reduction and adjustment of immunosuppression, strict control of the cardiologic situation, and treatment of the infection.


Assuntos
COVID-19 , Transplante de Coração , Transplante de Rim , Transplante de Coração/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , SARS-CoV-2 , Centros de Atenção Terciária , Transplantados
19.
G Ital Nefrol ; 38(Suppl 77)2021 Sep 07.
Artigo em Italiano | MEDLINE | ID: mdl-34669312

RESUMO

Steroid minimization has always been one of the most desired goals regarding immunosuppressive therapy after renal transplantation. Following the introduction of cyclosporine different steroid-free protocols became available, but their implementation was limited due to the high risk of acute rejection. In the last few years, the use of a very low dose of prednisone (5 mg/day) has been deemed to guarantee a good balance between steroid toxicity and efficacy. However, high interpatient variability in prednisolone exposure prevented the standard low dose to be as safe as expected in all patients. Therefore, steroid side effects can still be observed in a variable percentage of patients. In this setting, the personalization of steroid dosage might prevent an over exposure to the drug, but this strategy is not available yet. Thus, steroid withdrawal remains the only available strategy to limit side effects. In the last 40 years, we learned that steroid free protocols are associated with a higher risk of acute rejection, but they do not reduce graft survival. Hence, patients at higher risk for acute rejection or recurrence of their primary renal disease are usually excluded from these protocols. Early steroid withdrawal (within 7 days after transplantation) has been widely used and also suggested by American guidelines. However, steroid withdrawal 3-4 months after transplantation has been preferred by many Authors and deemed equally efficient. In addition, early but not late steroid withdrawal should always be associated to induction therapy. Lastly, Tacrolimus plus Mycophenolic Acid has become the most used association in steroid minimization protocols.


Assuntos
Rejeição de Enxerto , Imunossupressores , Esteroides , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Ácido Micofenólico , Prednisona , Esteroides/efeitos adversos , Tacrolimo
20.
Int Heart J ; 62(5): 1096-1105, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544982

RESUMO

While cardiac imaging has improved the diagnosis and risk assessment for cardiac sarcoidosis (CS), treatment regimens have consisted of generalized heart failure therapies and non-specific anti-inflammatory regimens. The overall goal of this study was to perform high-sensitivity plasma profiling of specific inflammatory pathways in patients with sarcoidosis and with CS.Specific inflammatory/proteolytic cascades were upregulated in sarcoidosis patients, and certain profiles emerged for CS patients.Plasma samples were collected from patients with biopsy-confirmed sarcoidosis undergoing F-18 fluorodeoxyglucose positron emission tomography (n = 47) and compared to those of referent control subjects (n = 6). Using a high-sensitivity, automated multiplex array, cytokines, soluble cytokine receptor profiles (an index of cytokine activation), as well as matrix metalloproteinase (MMP), and endogenous MMP inhibitors (TIMPs) were examined.The plasma tumor necrosis factor (TNF) and soluble TNF receptors sCD30 and sTNFRI were increased using sarcoidosis, and sTNFRII increased in CS patients (n = 18). The soluble interleukin sIL-2R and vascular endothelial growth factor receptors (sVEGFR2 and sVEGFR3) increased to the greatest degree in CS patients. When computed as a function of referent control values, the majority of soluble cytokine receptors increased in both sarcoidosis and CS groups. Plasma MMP-9 levels increased in sarcoidosis but not in the CS subset. Plasma TIMP levels declined in both groups.The findings from this study were the identification of increased activation of a cluster of soluble cytokine receptors, which augment not only inflammatory cell maturation but also transmigration in patients with sarcoidosis and patients with cardiac involvement.


Assuntos
Citocinas/metabolismo , Cardiopatias/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Sarcoidose/diagnóstico , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos de Avaliação como Assunto , Feminino , Fluordesoxiglucose F18/administração & dosagem , Cardiopatias/sangue , Cardiopatias/complicações , Cardiopatias/patologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Inflamação/metabolismo , Masculino , Inibidores de Metaloproteinases de Matriz/metabolismo , Metaloproteinases da Matriz/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Receptores de Interleucina-2/metabolismo , Receptores do Fator de Necrose Tumoral/sangue , Medição de Risco , Sarcoidose/sangue , Sarcoidose/complicações , Sarcoidose/patologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
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