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1.
Exp Clin Transplant ; 18(5): 564-571, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33143601

RESUMO

OBJECTIVES: With the declaration of COVID-19 as a pandemic, many studies have indicated that elective surgeries should be postponed. However, postponement of transplants may cause diseases to get worse and increase the number in wait lists. We believe that, with precautions, transplant does not pose a risk during pandemic. Here, we aimed to evaluate our transplant results, which we safely performed during a 6-month pandemic period. MATERIALS AND METHODS: Until September 2020, 3140 kidney and 667 liver transplants have been performed in our centers. We evaluated 38 kidney transplants and 9 liver transplants procedures performed during the pandemic (March 1 to September 2, 2020). Recipient and donor candidates were screened for COVID-19 with polymerase chain reaction and thoracic computed tomography. All recipients had routine immunosuppressive protocol. During hospitalization at our COVID-19-free transplant facility, we restricted the interactions during multidisciplinary rounds. RESULTS: During the pandemic, 38 kidney transplants with an average length of hospital stay of 8.1 days were performed. Mean serum creatinine values of recipients were 0.91, 0.86, and 0.74 mg/dL on postoperative days 7, 30, and 90, respectively. During the pandemic, 9 living donor liver transplants (1 adult, 8 pediatric) were performed with an average length of hospital stay of 17.1 days. Mean serum total bilirubin levels were 0.9, 0.5, and 0.4 mg/dL on postoperative days 7, 30, and 90, respectively. Mean serum aspartate aminotransferase levels were 38.1, 28.3, and 22.3 U/L on postoperative days 7, 30, and 90, respectively. All recipients and donors were successfully discharged. Only 1 liver recipient died (on day 55 after discharge as a result of oxalosis-induced heart failure). CONCLUSIONS: According to our results, when precautions are taken, transplant does not pose a risk to patients during the pandemic period. We attribute the safety and success shown to our newly developed protocol in response to the COVID-19 pandemic.


Assuntos
Infecções por Coronavirus , Assistência à Saúde/tendências , Transplante de Rim/tendências , Transplante de Fígado/tendências , Avaliação de Processos e Resultados em Cuidados de Saúde/tendências , Pandemias , Pneumonia Viral , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Turquia , Listas de Espera , Adulto Jovem
2.
J Int Med Res ; 48(10): 300060520964009, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33100064

RESUMO

BACKGROUND: The causative virus of coronavirus disease 2019 (COVID-19) may cause severe fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to acute renal injury due to COVID-19 in patients who have undergone renal transplantation are scarce. We herein report two cases of COVID-19 along with acute kidney injury following kidney transplantation.Case presentation: Two patients with COVID-19 underwent renal transplantation and were subsequently diagnosed with acute kidney injury. The first patient presented with progressive respiratory symptoms and acute renal injury. He was treated with diuretics and suspension of immunosuppressive therapy; however, the patient died. The second patient presented with respiratory tract symptoms, hypoxemia, and progressive deterioration of renal function followed by improvement. Her mycophenolate mofetil was stopped after admission, and tacrolimus was discontinued 10 days later. Moxifloxacin and methylprednisolone were continued in combination with albumin and gamma globulin infusion. A diuretic was administered, and prednisone was gradually reduced along with tacrolimus. The patient exhibited a satisfactory clinical recovery. CONCLUSION: Patients who develop COVID-19 after kidney transplantation are at risk of acute kidney injury, and their prednisone, immunosuppressant, and gamma globulin treatment must be adjusted according to their condition.


Assuntos
Lesão Renal Aguda/patologia , Infecções por Coronavirus/patologia , Transplante de Rim/efeitos adversos , Rim/patologia , Pneumonia Viral/patologia , Lesão Renal Aguda/virologia , Adulto , Betacoronavirus , Esquema de Medicação , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Rim/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Transplantados , gama-Globulinas/administração & dosagem , gama-Globulinas/uso terapêutico
3.
Medicine (Baltimore) ; 99(43): e22926, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120848

RESUMO

RATIONALE: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies directed against the activity of factor VIII (FVIII) and presents with prolonged bleeding. 5.7% of systemic lupus erythematosus (SLE) patients are affected by AHA. PATIENT CONCERNS: A 51-year-old female patient with SLE presenting with the fatigue and spontaneous clinical bleeding symptoms such as hematuria and ecchymoses for 1 week. DIAGNOSIS: Laboratory examinations revealed prolongation of the activated partial thromboplastin time (APTT) (65.7 s), decreased FVIII activity (1.4%), and a titer of FVIII inhibitors of 8.5 Bethesda units/mL. INTERVENTIONS: Transfusion of recombinant human FVIII (ADVATE) in combination with intravenous methylprednisolone, cyclophosphamide, plasmapheresis, and fresh frozen plasma successfully stopped the bleeding and reduced the level of FVIII inhibitor. OUTCOMES: The size of the hematoma slowly decreased. The skin ecchymosis was gradually absorbed, the hemoglobin count increased, and the coagulation index gradually improved. There was no new bleeding or bleeding site. The patient was discharged and transferred to a local hospital for hospice care. LESSONS: AHA in a patient with SLE is rare. Once it occurs, it can be life-threatening. Clinicians should remain aware that because some cases of AHA may have features of SLE, appropriate distinction and diagnosis of these different but associated diseases is necessary.


Assuntos
Coagulantes/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/etiologia , Lúpus Eritematoso Sistêmico/complicações , Administração Intravenosa , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Testes de Coagulação Sanguínea/métodos , Coagulantes/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Equimose/diagnóstico , Equimose/etiologia , Fator VIII/administração & dosagem , Feminino , Hematúria/diagnóstico , Hematúria/etiologia , Hemofilia A/terapia , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/métodos , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Plasma , Plasmaferese/métodos , Resultado do Tratamento
5.
Int J Nanomedicine ; 15: 7937-7949, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116510

RESUMO

Background: Cyclosporine A (CsA) is an exceptional immunosuppressant used for the treatment of immune disorders. Niosomal vesicles are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. The objective of the study was to formulate combined nonionic surfactant based vesicles and to evaluate their in vitro characterization, release studies and in vivo studies. Materials and Methods: Five niosomal formulations (F7 to F11) were prepared using the thin film hydration method. The molar ratio of cholesterol and non-ionic surfactant taken was 1:1. In formulation F10, the combination of surfactants Span 20 and Brij 35 was used. The niosomes were characterized by zeta sizer and SEM for particle size analysis, in vitro drug release and stability studies. The pharmacokinetic studies were conducted on healthy albino rabbits. Results: The size of niosome was found in the range of 427.1 nm to 972.3 nm. SEM image of optimized formulations F10 exhibit the spherical nature of niosomal vesicles. DSC thermograms of niosomal formulations exhibited a broadened endothermic peak. The stability study exhibited that all formulations are stable and negligible change of vesicle size and entrapment was observed with time. The percentage drug release was significantly higher as compared to CsA plain dispersion for all niosomal formulations at pH 1.2 and 7.4. The release kinetic behavior showed that all preparations were best described by zero order and can release active ingredient in a sustained manner. The pharmacokinetic data showed the test formulation (F10) possessed greater bioavailability as compared to the reference formulation (CsA aqueous dispersion). Conclusion: The formulation F10 demonstrated a comparatively more delayed rate of release with enhanced dissolution as compared to a single surfactant scheme. The F10 formulation can be a remarkable nanotechnology for prolonged delivery of CsA orally with improved dissolution profile and bioavailability.


Assuntos
Portadores de Fármacos/química , Imunossupressores/química , Imunossupressores/farmacologia , Tensoativos/química , Animais , Disponibilidade Biológica , Colesterol/química , Ciclosporina/administração & dosagem , Ciclosporina/química , Ciclosporina/farmacocinética , Ciclosporina/farmacologia , Liberação Controlada de Fármacos , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Lipossomos , Tamanho da Partícula , Coelhos
6.
J Crohns Colitis ; 14(Supplement_3): S769-S773, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33085972

RESUMO

Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Infecções Assintomáticas , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Esquema de Medicação , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/imunologia , Pneumonia Viral/diagnóstico , Medição de Risco
7.
BMJ ; 371: m3734, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087345

RESUMO

OBJECTIVE: To assess whether reshaping of the immune balance by infusion of autologous natural regulatory T cells (nTregs) in patients after kidney transplantation is safe, feasible, and enables the tapering of lifelong high dose immunosuppression, with its limited efficacy, adverse effects, and high direct and indirect costs, along with addressing several key challenges of nTreg treatment, such as easy and robust manufacturing, danger of over immunosuppression, interaction with standard care drugs, and functional stability in an inflammatory environment in a useful proof-of-concept disease model. DESIGN: Investigator initiated, monocentre, nTreg dose escalation, phase I/IIa clinical trial (ONEnTreg13). SETTING: Charité-University Hospital, Berlin, Germany, within the ONE study consortium (funded by the European Union). PARTICIPANTS: Recipients of living donor kidney transplant (ONEnTreg13, n=11) and corresponding reference group trial (ONErgt11-CHA, n=9). INTERVENTIONS: CD4+ CD25+ FoxP3+ nTreg products were given seven days after kidney transplantation as one intravenous dose of 0.5, 1.0, or 2.5-3.0×106 cells/kg body weight, with subsequent stepwise tapering of triple immunosuppression to low dose tacrolimus monotherapy until week 48. MAIN OUTCOME MEASURES: The primary clinical and safety endpoints were assessed by a composite endpoint at week 60 with further three year follow-up. The assessment included incidence of biopsy confirmed acute rejection, assessment of nTreg infusion related adverse effects, and signs of over immunosuppression. Secondary endpoints addressed allograft functions. Accompanying research included a comprehensive exploratory biomarker portfolio. RESULTS: For all patients, nTreg products with sufficient yield, purity, and functionality could be generated from 40-50 mL of peripheral blood taken two weeks before kidney transplantation. None of the three nTreg dose escalation groups had dose limiting toxicity. The nTreg and reference groups had 100% three year allograft survival and similar clinical and safety profiles. Stable monotherapy immunosuppression was achieved in eight of 11 (73%) patients receiving nTregs, while the reference group remained on standard dual or triple drug immunosuppression (P=0.002). Mechanistically, the activation of conventional T cells was reduced and nTregs shifted in vivo from a polyclonal to an oligoclonal T cell receptor repertoire. CONCLUSIONS: The application of autologous nTregs was safe and feasible even in patients who had a kidney transplant and were immunosuppressed. These results warrant further evaluation of Treg efficacy and serve as the basis for the development of next generation nTreg approaches in transplantation and any immunopathologies. TRIAL REGISTRATION: NCT02371434 (ONEnTreg13) and EudraCT:2011-004301-24 (ONErgt11).


Assuntos
Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Linfócitos T Reguladores/transplante , Tacrolimo/administração & dosagem , Adulto , Aloenxertos/imunologia , Estudos de Viabilidade , Feminino , Alemanha , Sobrevivência de Enxerto/imunologia , Humanos , Infusões Intravenosas , Rim/imunologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do Tratamento , Suspensão de Tratamento
8.
Cochrane Database Syst Rev ; 9: CD008333, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990324

RESUMO

BACKGROUND: Anti-neutrophilic cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are a group of rare auto-inflammatory diseases that affects mainly small vessels. AAV includes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Anti-cytokine targeted therapy uses biological agents capable of specifically targeting and neutralising cytokine mediators of the inflammatory response. OBJECTIVES: To assess the benefits and harms of anti-cytokine targeted therapy for adults with AAV. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2019, Issue 7), MEDLINE and Embase up to 16 August 2019. We also examined reference lists of articles, clinical trial registries, websites of regulatory agencies and contacted manufacturers. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials of targeted anti-cytokine therapy in adults (18 years or older) with AAV compared with placebo, standard therapy or another modality and anti-cytokine therapy of different type or dose. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included four RCTs with a total of 440 participants (mean age 48 to 56 years). We analysed the studies in three groups: 1) mepolizumab (300 mg; three separate injections every four weeks for 52 weeks) versus placebo in participants with relapsing or refractory EGPA; 2) belimumab (10 mg/kg on days 0, 14, 28 and every 28 days thereafter until 12 months after the last participant was randomised) or etanercept (25 mg twice a week) with standard therapy (median 25 months) versus placebo with standard therapy (median 19 months) in participants with GPA/MPA; and 3) infliximab (3 mg/kg on days 1 and 14, before the response assessment on day 42) versus rituximab (0.375g/m2 on days 1, 8, 15 and 22) in participants with refractory GPA for up to 12 months. None of the studies were assessed as low risk of bias in all domains: one study did not report randomisation or blinding methods clearly. Three studies were at high risk and one study was at unclear risk of bias for selective outcome reporting. One trial with 136 participants with relapsing or refractory EGPA compared mepolizumab with placebo during 52 weeks of follow-up and observed one death in the mepolizumab group (1/68, 1.5%) and none in the placebo group (0/68, 0%) (Peto odds ratio (OR) 7.39, 95% confidence interval (CI) 0.15 to 372.38; low-certainty evidence). Low-certainty evidence suggests that more participants in the mepolizumab group had ≥ 24 weeks of accrued remission over 52 weeks compared to placebo (27.9% versus 2.9%; risk ratio (RR) 9.5, 95% CI 2.30 to 39.21), and durable remission within the first 24 weeks sustained until week 52 (19.1% mepolizumab versus 1.5% placebo; RR 13.0, 95% CI 1.75 to 96.63; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% Cl 4 to 13). Mepolizumab probably decreases risk of relapse (55.8% versus 82.4%; RR 0.68, 95% CI 0.53 to 0.86; NNTB 4, 95% CI 3 to 9; moderate-certainty evidence). There was low-certainty evidence regarding similar frequency of adverse events (AEs): total AEs (96.9% versus 94.1%; RR 1.03, 95% CI 0.96 to 1.11), serious AEs (17.7% versus 26.5%; RR 0.67, 95% CI 0.35 to 1.28) and withdrawals due to AEs (2.9% versus 1.5%; RR 2.00, 95% CI 0.19 to 21.54). Disease flares were not measured. Based on two trials with different follow-up periods (mean of 27 months for etanercept study; up to four years for belimumab study) including people with GPA (n = 263) and a small group of participants with MPA (n = 22) analysed together, we found low-certainty evidence suggesting that adding an active drug (etanercept or belimumab) to standard therapy does not increase or reduce mortality (3.4% versus 1.4%; Peto OR 2.45, 95% CI 0.55 to 10.97). Etanercept may have little or no effect on remission (92.3% versus 89.5%; RR 0.97, 95% CI 0.89 to 1.07), durable remission (70% versus 75.3%; RR 0.93, 95% CI 0.77 to 1.11; low-certainty evidence) and disease flares (56% versus 57.1%; RR 0.98, 95% CI 0.76 to 1.27; moderate-certainty evidence). Low-certainty evidence suggests that belimumab does not increase or reduce major relapse (1.9% versus 0%; RR 2.94, 95% CI 0.12 to 70.67) or any AE (92.5% versus 82.7%; RR 1.12, 95% CI 0.97 to 1.29). Low-certainty evidence suggests a similar frequency of serious or severe AEs (47.6% versus 47.6%; RR 1.00, 95% CI 0.80 to 1.27), but more frequent withdrawals due to AEs in the active drug group (11.2%) compared to the placebo group (4.2%), RR 2.66, 95% CI 1.07 to 6.59). One trial involving 17 participants with refractory GPA compared infliximab versus rituximab added to steroids and cytotoxic agents for 12 months. One participant died in each group (Peto OR 0.88, 95% CI, 0.05 to 15.51; 11% versus 12.5%). We have very low-certainty evidence for remission (22% versus 50%, RR 0.44, 95% Cl 0.11 to 1.81) and durable remission (11% versus 50%, RR 0.22, 95% CI 0.03 to 1.60), any severe AE (22.3% versus 12.5%; RR 1.78, 95% CI 0.2 to 16.1) and withdrawals due to AEs (0% versus 0%; RR 2.70, 95% CI 0.13 to 58.24). Disease flare/relapse and the frequency of any AE were not reported. AUTHORS' CONCLUSIONS: We found four studies but concerns about risk of bias and small sample sizes preclude firm conclusions. We found moderate-certainty evidence that in patients with relapsing or refractory EGPA, mepolizumab compared to placebo probably decreases disease relapse and low-certainty evidence that mepolizumab may increase the probability of accruing at least 24 weeks of disease remission. There were similar frequencies of total and serious AEs in both groups, but the study was too small to reliably assess these outcomes. Mepolizumab may result in little to no difference in mortality. However, there were very few events. In participants with GPA (and a small subgroup of participants with MPA), etanercept or belimumab may increase the probability of withdrawal due to AEs and may have little to no impact on serious AEs. Etanercept may have little or no impact on durable remission and probably does not reduce disease flare.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Imunossupressores/administração & dosagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome de Churg-Strauss/tratamento farmacológico , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Poliangiite Microscópica/tratamento farmacológico , Pessoa de Meia-Idade , Números Necessários para Tratar , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Prevenção Secundária , Esteroides/administração & dosagem
9.
Medicine (Baltimore) ; 99(39): e22180, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991411

RESUMO

BACKGROUND: Tacrolimus-based immunosuppression has resulted in enormous improvements on liver transplantation (LTx) outcomes. However, dose adjustment and medication adherence play a key role in post-transplant treatment success. The aim of the present study is to assess the trough levels and the need for adaptation of therapeutic doses in de novo LTx patients treated with Tacrolimus in the clinical routine, without any intervention to the treatment regimen. METHODS AND ANALYSIS: This is a pilot, prospective, exploratory, monocentric, non-interventional and non-randomized investigator-initiated study. Prospectively maintained data of 100 patients treated with various oral Tacrolimus-based immunosuppressants (Prograf or Envarsus) will be analyzed. The number of required dose adjustments of Tacrolimus formulations used in clinical routine for achieving the target trough level, Tacrolimus trough level, Tacrolimus dosing, concentration/dose ratio, routine laboratory tests, efficacy data (incl. survival, acute rejection, re-transplantation), patients therapy adherence, and infections requiring the need to reduce individual immunosuppressant dosing will be evaluated for each patient. RESULT: This study will evaluate the trough levels and the need for adaptation of therapeutic doses in de novo LTx patients treated with Tacrolimus in the clinical routine, without any intervention to the treatment regimen. CONCLUSION: The HDTACRO study will be the first study to systematically and prospectively evaluate various oral Tacrolimus-based immunosuppressants in de novo liver transplanted patients. If a difference between the therapy-subgroups is evident at the end of the trial, a randomized control trial will eventually be designed. Registration number: ClinicalTrials.gov: NCT04444817.


Assuntos
Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Fígado , Tacrolimo/administração & dosagem , Administração Oral , Relação Dose-Resposta a Droga , Humanos , Adesão à Medicação , Projetos Piloto , Estudos Prospectivos
10.
Medicine (Baltimore) ; 99(39): e22341, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991448

RESUMO

RATIONALE: The Goodpasture syndrome is an extremely rare disease, with renal and pulmonary manifestations, and is mediated by anti-glomerular basement membrane (anti-GBM) antibodies. Renal pathological changes are mainly characterized by glomerular crescent formation and linear immunofluorescent staining for immunoglobulin G on the GBM. There are few reports on the atypical course of the syndrome involving serum-negative anti-GBM antibodies. Therefore, we present a case of Goodpasture syndrome that presented with nephrotic-range proteinuria and was seronegative for anti-GBM antibodies. PATIENT CONCERNS: A 38-year-old Chinese man presented with a lung lesion that was discovered by physical examination a month prior to presentation. The chief concern was occasional hemoptysis without fever, cough, chest pain, and edema. DIAGNOSES: Laboratory testing revealed that the urinary protein level and urine erythrocyte count were 7.4 g/24 hours and 144/high-power field (HPF), respectively. Serological testing for anti-GBM antibodies was negative. Chest computed tomography revealed multiple exudative lesions in both lungs, indicating alveolar infiltration and hemorrhage. Electronic bronchoscopy and pathological examination of the alveolar lavage fluid indicated no abnormalities. However, kidney biopsy suggested cellular crescent formation and segmental necrosis of the globuli, with linear IgG and complement C3 deposition on the GBM. These findings were consistent with the diagnosis of anti-GBM antibody nephritis. INTERVENTIONS: The patient underwent 7 sessions of double filtration plasmapheresis. He was also administered with intravenous methylprednisolone and cyclophosphamide. After renal function stabilization, he was discharged under an immunosuppressive regimen comprising of glucocorticoids and cyclophosphamides. OUTCOMES: Three months later, follow-up examination revealed that the 24-hour urine protein had increased to 13 g. Furthermore, the urine erythrocyte count was 243/HPF. After a 6-month follow-up, the patient achieved partial remission, with a proteinuria level of 3.9 g/24 hours and a urine erythrocyte count of 187/HPF. LESSONS: This extremely rare case of Goodpasture syndrome manifested with seronegativity for anti-GBM antibodies and nephrotic-range proteinuria. Our findings emphasize the importance of renal biopsy for the clinical diagnosis of atypical cases. Furthermore, because renal involvement achieved only partial remission despite therapy, early detection and active treatment of the Goodpasture syndrome is necessary to improve the prognosis of patients.


Assuntos
Doença Antimembrana Basal Glomerular/complicações , Doença Antimembrana Basal Glomerular/imunologia , Autoanticorpos/sangue , Proteinúria/etiologia , Administração Intravenosa , Adulto , Assistência ao Convalescente , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/terapia , Grupo com Ancestrais do Continente Asiático/etnologia , Complemento C3/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hemoptise/diagnóstico , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Imunoglobulina G/metabolismo , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Rim/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Nefrite/diagnóstico , Nefrite/imunologia , Plasmaferese/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
11.
Transplantation ; 104(8): 1686-1694, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732848

RESUMO

BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.


Assuntos
Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Imunossupressores/efeitos adversos , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Resultado do Tratamento
12.
BMC Neurol ; 20(1): 319, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859168

RESUMO

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by antibodies that block or destroy nicotinic acetylcholine receptors at the neuromuscular junction. Most of MG patients need immunosuppression agents in addition to treatments that alleviate the symptoms. Intravenous immunoglobulin (IVIg) and plasma exchange are specific treatments given to patients with severe MG and myasthenia gravis crisis. IVIg therapy can cause an increase in serum viscosity; therefore, the risk for thromboembolic events, such as stroke, myocardial infarction, and pulmonary embolism, are reported after IVIg therapy. CASE PRESENTATION: An MG patient was treated with pyridostigmine bromide and prednisolone. The patient's symptoms worsened 26 days after the commencement of treatment and was presented with head drop and dyspnea. The patient was diagnosed with MG crisis and IVIg was initiated. However, the patient reported chest pain and dyspnea 3 days after IVIg had started. An electrocardiogram (ECG) revealed ST elevations in leads II, III, and aVF. A cardiac catheterization was performed and stenosis, obstruction, and sclerosis were ruled out. Glyceryl trinitrate relieved the patient's symptoms, suggesting coronary spastic angina (CSA). CONCLUSIONS: We report the first case of CSA after IVIg. Practitioners should be aware of the potential risks of CSA when administering IVIg for MG patients, in particular in old patients with vascular risk factors.


Assuntos
Vasoespasmo Coronário/etiologia , Imunoglobulinas Intravenosas/efeitos adversos , Miastenia Gravis/tratamento farmacológico , Idoso de 80 Anos ou mais , Anticorpos/sangue , Eletrocardiografia , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunossupressores/administração & dosagem , Miastenia Gravis/imunologia , Prednisolona/administração & dosagem , Brometo de Piridostigmina/administração & dosagem , Receptores Nicotínicos/imunologia
13.
Orv Hetil ; 161(31): 1293-1301, 2020 08.
Artigo em Húngaro | MEDLINE | ID: mdl-32750018

RESUMO

INTRODUCTION: Lupus nephritis is the most severe complication of systemic lupus erythematosus (SLE), its development and the effectiveness of immunosuppressive therapy substantially influence patients' quality of life and survival. AIM: In this retrospective observational investigation, the long term-outcome of patients with lupus nephritis, followed at the St. Margit Hospital Immunonephrological Outpatient Clinic, was evaluated. RESULTS: Between 1997 December 1 and 2019 April 30, 73 patients (age 33.7 ± 15 years, 82% female, 18% male) were under care with median observation of 119 [between 3-264] months. At diagnosis, eGFR showed 68 [7-120] ml/min, proteinuria was 2800 [23-16812] mg/day; 10 patients needed dialysis treatment acutely. Renal biopsy, performed in 68 patients, proved proliferative lupus nephritis in 55 and pure membranous lupus nephritis in 6 patients. Administering combined immunosuppressive therapy, complete remission was achieved in 50 and partial remission in 21 cases; one or repeated relapses developed in 28 subjects. Two patients, by the time they got under our care, had already required chronic dialysis, and in the long term, three more patients progressed to end-stage renal disease requiring renal replacement therapy. Renal function stabilized in all other participants, clinical activity of SLE, SLEDAI score, complement levels and immunserology results improved significantly. CONCLUSIONS: Lupus nephritis can be effectively treated by combined induction and prolonged maintenance immunosuppression, but to prevent progression of the disease, long-term care is necessary by co-operation of nephrologist and immunologist. To provide adequate prevention and therapy of the SLE's multiorgan involvement and also the potential complications of immunosuppression, multidisciplinary team is needed with all specialists who may facilitate these patients' complex care. For the long-term management of patients with lupus nephritis, the nephrologists have to be responsible, and the multidisciplinary teams also have to be under their direction. Orv Hetil. 2020; 161(31): 1293-1301.


Assuntos
Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Imunossupressores/administração & dosagem , Assistência de Longa Duração , Nefrite Lúpica/imunologia , Nefrite Lúpica/psicologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
14.
Neurología (Barc., Ed. impr.) ; 35(6): 57, jul.-ago. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-190278

RESUMO

INTRODUCCIÓN: La pandemia por SARS-CoV-2 está condicionando los abordajes diagnósticos, terapéuticos y asistenciales establecidos en esclerosis múltiple (EM). Durante las fases inicial y pico de la epidemia, los fármacos modificadores del curso de la EM caracterizados por ser inmunosupresores administrados en pulsos (TIP), vieron pospuesta su administración debido a la incertidumbre sobre su influencia en la infección, principalmente en contagiados/contagiosos asintomáticos/presintomáticos. El objetivo de este trabajo es presentar un algoritmo basado en criterios de seguridad que permita reanudar los TIP durante la fase de desescalado. MÉTODOS: Se elabora un algoritmo, cuya estructura se sustenta en la experiencia clínica en EM de los autores y en una revisión bibliográfica del conocimiento acumulado, que facilita la detección de contagiosos asintomáticos, presintomáticos o con síntomas leves de SARS-CoV-2, con el objetivo de evitar la administración de TIP y contagios por contacto prolongado en hospital de día (HdD). RESULTADOS: Algoritmo con doble filtro clínico-microbiológico consistente en la aplicación telemática de un listado de comprobación de síntomas y después realización de PCR para SARS-CoV-2 en exudado nasofaríngeo, a las 48 y 24 h antes del TIP programado respectivamente. CONCLUSIÓN: Considerando el balance beneficio-riesgo, la aplicación del algoritmo resultaría ventajosa pese a que no se conoce la proporción real de asintomáticos/presintomáticos contagiosos. La realización sistemática de PCR, como test con mayor sensibilidad en la fase presintomática de la infección, en combinación con un sistema de detección precoz de síntomas, reduciría contagios y favorecería la identificación de pacientes con riesgo antes de su exposición a TIP


INTRODUCTION: The COVID-19 pandemic is changing approaches to diagnosis, treatment, and care provision in multiple sclerosis (MS). During both the initial and peak phases of the epidemic, the administration of disease-modifying drugs, typically immunosuppressants administered in pulses, was suspended due to the uncertainty about their impact on SARS-CoV-2 infection, mainly in contagious asymptomatic/presymptomatic patients. The purpose of this study is to present a safety algorithm enabling patients to resume pulse immunosuppressive therapy (PIT) during the easing of lockdown measures. METHODS: We developed a safety algorithm based on our clinical experience with MS and the available published evidence; the algorithm assists in the detection of contagious asymptomatic/presymptomatic cases and of patients with mild symptoms of SARS-CoV-2 infection with a view to withdrawing PIT in these patients and preventing new infections at day hospitals. RESULTS: We developed a clinical/microbiological screening algorithm consisting of a symptom checklist, applied during a teleconsultation 48hours before the scheduled session of PIT, and PCR testing for SARS-CoV-2 in nasopharyngeal exudate 24hours before the procedure. CONCLUSION: The application of our safety algorithm presents a favourable risk-benefit ratio despite the fact that the actual proportion of asymptomatic and presymptomatic individuals is unknown. Systematic PCR testing, which provides the highest sensitivity for detecting presymptomatic cases, combined with early detection of symptoms of SARS-CoV-2 infection may reduce infections and improve detection of high-risk patients before they receive PIT


Assuntos
Humanos , Medidas de Segurança , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Betacoronavirus , Pandemias , Esclerose Múltipla/tratamento farmacológico , Imunossupressores/administração & dosagem , Pulsoterapia/normas , Medicina Baseada em Evidências , Equipamentos de Proteção/normas , Algoritmos
16.
PLoS One ; 15(8): e0234396, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756556

RESUMO

INTRODUCTION: Early conversion to a CNI-free immunosuppression with SRL was associated with an improved 1- and 3- yr renal function as compared with a CsA-based regimen in the SMART-Trial. Mixed results were reported on the occurrence of donor specific antibodies under mTOR-Is. Here, we present long-term results of the SMART-Trial. METHODS AND MATERIALS: N = 71 from 6 centers (n = 38 SRL and n = 33 CsA) of the original SMART-Trial (ITT n = 140) were enrolled in this observational, non-interventional extension study to collect retrospectively and prospectively follow-up data for the interval since baseline. Primary objective was the development of dnDSA. Blood samples were collected on average 8.7 years after transplantation. RESULTS: Development of dnDSA was not different (SRL 5/38, 13.2% vs. CsA 9/33, 27.3%; P = 0.097). GFR remained improved under SRL with 64.37 ml/min/1.73m2 vs. 53.19 ml/min/1.73m2 (p = 0.044). Patient survival did not differ between groups at 10 years. There was a trend towards a reduced graft failure rate (11.6% SRL vs. 23.9% CsA, p = 0.064) and less tumors under SRL (2.6% SRL vs. 15.2% CsA, p = 0.09). CONCLUSIONS: An early conversion to SRL did not result in an increased incidence of dnDSA nor increased long-term risk for the recipient. Transplant function remains improved with benefits for the graft survival.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim , Sirolimo/administração & dosagem , Adulto , Especificidade de Anticorpos , Esquema de Medicação , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fatores de Tempo , Doadores de Tecidos
17.
J Gastrointestin Liver Dis ; 29(3): 470, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32830825
18.
J Vet Sci ; 21(4): e47, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32735090

RESUMO

BACKGROUND: Homocysteine (HCY) was evaluated in healthy and chronic enteropathic dogs, however no studies on dogs with immunosuppressant-responsive enteropathy are available. OBJECTIVES: The aim was to evaluate serum HCY concentrations and its prognostic role in dogs with immunosuppressant-responsive enteropathy compared to healthy dogs. METHODS: Serum HCY concentration was statistically compared between 24 healthy dogs and 29 dogs with immunosuppressant-responsive enteropathy. Correlation analyses between serum total protein, albumin (ALB), C-reactive protein (CRP), folate and cobalamin, and serum HCY concentration were performed in immunosuppressant-responsive enteropathic dogs. RESULTS: The associations between serum HCY concentration and clinical, histological, endoscopic scores and follow-up were evaluated. Mean serum HCY concentration was higher in immunosuppressant-responsive enteropathic dogs compared to control dogs (30.22 ± 8.67 µmol/L vs. 5.26 ± 2.78 µmol/L; p < 0.0001). No association between serum HCY concentration and total protein, ALB, CRP, folate concentration as well as, clinical score, histological and endoscopic scores was found. A negative correlation between serum HCY concentration and cobalamin was noted (p = 0.0025, r = -0.54). No significant difference in HCY was found between responsive and non-responsive dogs or between survivors and non-survivors. CONCLUSIONS: Although, serum HCY concentration was higher in immunosuppressant-responsive enteropathy, its prognostic value remains unclear. However, further prospective, large-scale studies are warranted to better investigate the possible prognostic role of HCY in immunosuppressant-responsive enteropathic dogs.


Assuntos
Doenças do Cão/sangue , Enterite/tratamento farmacológico , Homocisteína/sangue , Imunossupressores/administração & dosagem , Animais , Doenças do Cão/diagnóstico , Cães , Enterite/diagnóstico , Feminino , Masculino , Prognóstico
19.
Dermatol Online J ; 26(5)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621697

RESUMO

We present a 53-year-old woman with severe lichenoid dermatitis secondary to pembrolizumab therapy that was refractory to both topical and oral steroids. After almost three months without improvement, the rash was effectively combated with a single 15mg dose of methotrexate. We hope this case will help guide the management of the cutaneous adverse effects of anti-PD1 immunotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Imunossupressores/administração & dosagem , Erupções Liquenoides/tratamento farmacológico , Metotrexato/administração & dosagem , Feminino , Humanos , Erupções Liquenoides/induzido quimicamente , Erupções Liquenoides/patologia , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade
20.
S Afr Med J ; 110(2): 159-166, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32657689

RESUMO

BACKGROUND: Tacrolimus forms the cornerstone for immunosuppression in solid-organ transplantation. It has a narrow therapeutic window with wide inter- and intra-patient variability (IPV). Cytochrome P-450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The rs776746A>G (i.e. CYP3A5*3) single-nucleotide polymorphism in CYP3A5 alters tacrolimus predose trough concentration (C0) and may also affect IPV, which may lead to immune- and/or drug-mediated allograft injury. CYP3A5*3 may result in absent (*3/*3), partial (*1/*3) or normal (*1/*1) CYP3A5 expression. The effect of CYP3A5*3 on tacrolimus exposure and variability has not been examined in South African (SA) transplant recipients. OBJECTIVES: To determine the frequencies and effect of CYP3A5 and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms on tacrolimus C0/dose ratios in different ethnic groups attending a tertiary renal transplant clinic in SA, and other factors that may explain inter- and IPV in tacrolimus C0. METHODS: All consenting stable renal transplant recipients on tacrolimus at the Livingstone Hospital Renal Unit in Port Elizabeth, SA, were included. Tacrolimus concentrations were obtained using a microparticle enzyme immunoassay method (ARCHITECT analyser, Abbott Laboratories). Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 and *6 allelic variants. RESULTS: There were 43 participants (35% black African, 44% mixed ancestry and 21% white), with a mean age of 44.5 years, median duration post-transplant of 47 months and median (interquartile range) creatinine and estimated glomerular filtration rate levels of 118 (92 - 140) µmol/L and 62 (49 - 76) mL/min at study inclusion. The mean tacrolimus C0 in the study was 6.7 ng/mL, with no difference across the different ethnic groups. However, the mean total daily dose of tacrolimus required was 9.1 mg (0.12 mg/kg), 7.2 mg (0.09 mg/kg) and 4.3 mg (0.06 mg/kg) in black, mixed-ancestry and white patients, respectively (p=0.017). The frequencies for CYP3A5 expressors (i.e. CYP3A5*1/*1 + CYP3A5*1/*3 genotypes) were 72%, 100%, 76% and 12% for all patients combined and black, mixed-ancestry and white patients, respectively. The frequencies for CYP3A5 non-expressors (i.e. CYP3A5*3/*3 genotypes) were 0%, 24% and 88% among the black, mixed-ancestry and white patients, respectively. None of the patients carried the CYP3A5*6 allele. CYP3A5*1/*1 and CYP3A5*1/*3 genotype carriers required a two-fold increase in dose compared with the non-expressor genotype carriers, CYP3A5*3/*3 (p<0.05). CYP3A5*3/*3 carriers also demonstrated higher IPV than CYP3A5*1/*1 and *1/*3 carriers (18.1% v. 14.2%; p=0.125). CONCLUSIONS: Compared with global transplant populations, SA renal transplant recipients demonstrated a very high rate of CYP3A5 expression, with a significant impact on tacrolimus pharmacokinetics. Genetic variation in CYP3A5 expression affects tacrolimus dosing requirements, and knowing the CYP3A5 genotype of transplant patients may allow better dose prediction compared with current standard dosing recommendations in a multi-ethnic population. Overall, black African patients required higher doses of tacrolimus than their white counterparts. While further prospective studies are needed to better evaluate dosing algorithms, it would appear that the starting dose of tacrolimus should be higher in black and mixed-race patients.


Assuntos
Citocromo P-450 CYP3A/genética , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Tacrolimo/administração & dosagem , Adulto , Estudos de Coortes , Grupos de Populações Continentais/genética , Relação Dose-Resposta a Droga , Feminino , Variação Genética , Genótipo , Humanos , Imunossupressores/farmacocinética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , África do Sul , Tacrolimo/farmacocinética
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