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1.
J Hematol Oncol ; 13(1): 131, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008453

RESUMO

SARS-CoV-2 has infected millions of people worldwide, but little is known at this time about second infections or reactivation. Here, we report a case of a 55-year-old female undergoing treatment for CD20+ B cell acute lymphoblastic leukemia who experienced a viral reactivation after receiving rituximab, cytarabine, and dasatinib. She was initially hospitalized with COVID-19 in April and developed a high antibody titer with two negative nasal polymerase chain reaction (PCR) swabs for SARS-CoV-2 on discharge. After recovery, she resumed treatment in June for her leukemia, which included rituximab, cytarabine, and dasatinib. She promptly lost her COVID-19 antibodies, and her nasal PCR turned positive in June. She developed a severe COVID-19 pneumonia with lymphopenia, high inflammatory markers, and characteristic bilateral ground-glass opacities on chest CT, requiring high-flow nasal cannula and transfer to the intensive care unit. She received steroids, anticoagulation, and convalescent plasma, and within 48 h she was off oxygen. She was discharged home in stable condition several days later. Given the short time frame from leukemia treatment to PCR positivity and the low case rate in mid-June in New York City, reinfection appears to have been unlikely and SARS-CoV-2 reactivation is a possible explanation. This case illustrates the risks of treating recently recovered COVID-19 patients with immunosuppressive therapy, particularly lymphocyte- and antibody-depleting therapy, and raises new questions about the potential of SARS-CoV-2 reactivation.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Citarabina/uso terapêutico , Imunossupressores/uso terapêutico , Pneumonia Viral/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Rituximab/uso terapêutico , Doença Aguda , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticoagulantes/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Citarabina/efeitos adversos , Feminino , Humanos , Imunização Passiva , Imunossupressores/efeitos adversos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase , Recidiva , Rituximab/efeitos adversos , Esteroides/uso terapêutico , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(40): e22596, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019479

RESUMO

BACKGROUND: The pathophysiologic of vascular malformations is still unclear, and the treatment of vascular malformations is a challenge. With improvement in the understanding of pathogenesis of vascular malformations, sirolimus has been a promising and effective treatment. As so far, there is absent convincing evidence to confirm the efficacy of sirolimus for vascular malformations. The purpose of this study was to evaluate the effectiveness and safety of sirolimus in the treatment of vascular malformations. METHODS: The literatures about the management of vascular malformations with sirolimus would be searched from databases of MEDLINE, EMBASE, PubMed, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine Database (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database. We will search each database from inception or 1995 to August 20, 2020. Two researchers worked independently on literature selection, data extraction and quality assessment. The efficacy and safety of sirolimus in the treatment of vascular malformations were the main outcomes. Adverse events after sirolimus were evaluated as the secondary outcomes. The included studies will be analyzed by Review Manager 5.3. If the results are applicable, meta-analysis would also be performed. RESULTS: The study will evaluate the efficacy and safety of sirolimus in the treatment of vascular malformations based on current evidence. CONCLUSION: The conclusion of this study will provide more reliable, evidence-based data for the use of sirolimus in the treatment of vascular malformations. PROSPERO REGISTRATION NUMBER: CRD42020167881.


Assuntos
Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico , Malformações Vasculares/tratamento farmacológico , Gerenciamento de Dados , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Projetos de Pesquisa , Segurança , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento , Malformações Vasculares/fisiopatologia
3.
Medicine (Baltimore) ; 99(40): e22639, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019487

RESUMO

INTRODUCTION: Tuberculous meningitis (TBM) is the most fatal type of tuberculosis in which corticosteroids are added with antitubercular therapy to prevent permanent brain damage. However, this treatment may produce paradoxical reactions. In such cases, thalidomide use might reduce central nervous system inflammation and improve the outcome. We present the case of a human immunodeficiency virus-negative patient with TBM who developed paradoxical reactions manifesting as multiple intracranial tuberculomas that were resistant to standard care (antitubercular drugs and corticosteroids) but responded well to thalidomide. PATIENT'S MAIN CONCERN AND CLINICAL FINDINGS: The patient was a 40-year-old Chinese female, who was admitted with a 10-day history of headaches, night sweats, and cough. She was healthy before contracting the infection and had no history of contact with tuberculosis patients. DIAGNOSES, INTERVENTION, AND OUTCOME: We diagnosed the patient with TBM complicated by the occurrence of pulmonary tuberculosis. Positive results were obtained from Gram and Ziehl-Neelsen staining of the sputum and acid-fast bacilli sputum culture. Standard treatment was initiated with antitubercular drugs (daily isoniazid, rifampicin, ethionamide, and pyrazinamide) and corticosteroids (dexamethasone). However, 3 months later the magnetic resonance imaging of the head revealed some new tuberculoma lesion. Thus, a specific therapy of antitubercular drugs and thalidomide was introduced. On completion of a 12-month course of antitubercular drugs with 2 months of thalidomide, the patient showed favorable outcomes without neurologic sequelae. Moreover, thalidomide appeared safe and well tolerated in the patient. CONCLUSION: In addition to the specific anti-tubercular and adjuvant corticosteroid therapies for TBM, thalidomide can be used as a "salvage" antitubercular drug in cases that are unresponsive to corticosteroids.


Assuntos
HIV/imunologia , Imunossupressores/uso terapêutico , Talidomida/uso terapêutico , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Pulmonar/complicações , Corticosteroides/uso terapêutico , Adulto , Antituberculosos/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Encéfalo/patologia , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Imagem por Ressonância Magnética/métodos , Terapia de Salvação , Resultado do Tratamento , Tuberculoma/diagnóstico por imagem , Tuberculose Meníngea/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
4.
Int Heart J ; 61(5): 1005-1013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999188

RESUMO

This study sought to evaluate clinical features, treatment patterns, and outcomes of patients with idiopathic inflammatory myopathy (IIM) complicated by heart failure (HF). Thirty-two patients with IIM-HF admitted to the Peking Union Medical College Hospital between January 1999 and January 2018 were retrospectively reviewed, including 14 patients with polymyositis, 11 with dermatomyositis, and 7 with overlap syndrome. Survivors and no-survivors were compared on clinical characteristics and treatment. Although systemic symptoms were variable, all patients presented with elevated troponin I. Rapid atrial arrhythmia was the most frequent arrhythmia. Systolic dysfunction and restrictive diastolic dysfunction were typical presentations in echocardiography. Twenty-nine patients were followed up for a median of 2.8 years (0.1 month to 11 years). We recorded 13 deaths of cardiogenic cause, 1 of serious IIM, and 3 of infective complications. The median survival time from diagnosis of IIM-HF to all-cause mortality was 8.4 months (range from 1 month to 5 years). Both all-cause deaths and cardiogenic deaths were more reported in the methotrexate-alone group than in the combination therapy group (6/7 versus 3/10, P = 0.050; 5/6 versus 2/9, P = 0.041). Combination therapy including methotrexate (HR = 0.188, 95%CI 0.040-0.871, P = 0.033) and taking ß-receptor blockers (HR = 0.249, 95%CI 0.086-0.719, P = 0.010) was associated with reduced risk of all-cause deaths. In conclusion, elevated troponin I, atrial arrhythmia, and systolic and restrictive diastolic dysfunction are typical characteristics of IIM-HF. Combined immunosuppression that includes methotrexate and ß-receptor blockers seems to be important to improve survival.


Assuntos
Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Miosite/tratamento farmacológico , Miosite/mortalidade , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , China/epidemiologia , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Insuficiência Cardíaca/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Miosite/complicações , Estudos Retrospectivos , Adulto Jovem
6.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32953089

RESUMO

Aplastic anemia (AA) in its severe form has historically been associated with high mortality. With limited supportive care and no effective strategy to reverse marrow failure, most patients diagnosed with severe AA (SAA) died of pancytopenia complications. Since the 1970s, hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have changed SAA's natural history by improving marrow function and pancytopenia. Standard IST with horse anti-thymocyte globulin plus cyclosporine produces a hematologic response rate of 60 to 70%. In the long term, about one-third of patients relapse, and 10 to 15% can develop cytogenetic abnormalities. Outcomes with either HSCT or IST are similar, and choosing between these modalities relies on age, availability of a histocompatible donor, comorbidities, and patient preference. The introduction of eltrombopag, a thrombopoietin receptor agonist, improved SAA outcomes as both salvage (second-line) and upfront therapy combined with IST. As a single agent, eltrombopag in doses up to 150 mg daily improved cytopenias in 40 to 50% in those who failed initial IST, which associated with higher marrow cellularity, suggesting a pan-stimulatory marrow effect. When eltrombopag was combined with IST as upfront therapy, overall (about 90%) and complete responses (about 50%) were higher than observed extensively with IST alone of 65% and 10%, respectively. Not surprisingly, given the strong correlation between hematologic response rates and survival in SAA, most (>90%) were alive after a median follow-up of 18 months. Longer follow-up and real-word data continue to confirm the activity of this agent in AA. The use of eltrombopag in different combinations and doses are currently being explored. The activity of another thrombopoietin receptor agonist in AA, romiplostim, suggests a class effect. In the coming years, the mechanisms of their activity and the most optimal regimen are likely to be elucidated.


Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Ciclosporina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Animais , Cavalos , Humanos , Terapia de Salvação
7.
BMJ ; 370: m2200, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873599

RESUMO

Hepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/virologia , Replicação Viral/imunologia , Animais , DNA Viral/sangue , Saúde Global , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Humanos , Imunossupressão , Imunossupressores/uso terapêutico , Fatores de Risco
8.
J Heart Lung Transplant ; 39(9): 894-903, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32891266

RESUMO

BACKGROUND: Orthotopic heart transplantation (OHT) recipients may be particularly vulnerable to coronavirus disease 2019 (COVID-19). OHT during the pandemic presents unique challenges in terms of feasibility and safety. METHODS: Chart review was performed for consecutive OHT recipients with COVID-19 and waitlisted patients who underwent OHT from March 1, 2020 to May 15, 2020. RESULTS: Of the approximately 400 OHT recipients followed at our institution, 22 acquired COVID-19. Clinical characteristics included median age 59 (range, 49-71) years, 14 (63.6%) were male, and median time from OHT to infection was 4.6 (2.5-20.6) years. Symptoms included fever (68.2%), gastrointestinal complaints (55%), and cough (46%). COVID-19 was severe or critical in 5 (23%). All patients had elevated inflammatory biomarkers. Immunosuppression was modified in 85% of patients. Most (n = 16, 86.4%) were hospitalized, 18% required intubation, and 14% required vasopressor support. Five patients (23%) expired. None of the patients requiring intubation survived. Five patients underwent OHT during the pandemic. They were all males, ranging from 30 to 59 years of age. Two were transplanted at United Network of Organ Sharing Status 1 or 2, 1 at Status 3, and 2 at Status 4. All were successfully discharged and are alive without allograft dysfunction or rejection. One contracted mild COVID-19 after the index hospitalization. CONCLUSION: OHT recipients with COVID-19 appear to have outcomes similar to the general population hospitalized with COVID-19. OHT during the pandemic is feasible when appropriate precautions are taken. Further study is needed to guide immunosuppression management in OHT recipients affected by COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Rejeição de Enxerto/prevenção & controle , Insuficiência Cardíaca/cirurgia , Transplante de Coração/métodos , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Pneumonia Viral/complicações , Idoso , Infecções por Coronavirus/epidemiologia , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento
9.
BMC Infect Dis ; 20(1): 707, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977764

RESUMO

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus-2 has spread rapidly worldwide and disease spread is currently increasing. Data on the clinical picture of transplant recipients and management of the anti-rejection immunosuppressive therapy on COVID-19 infection are lacking. CASE PRESENTATION: We report two cases of COVID-19 infection in renal transplant recipients with variable clinical presentations. The first patient presented with mild respiratory symptoms and a stable clinical course. The second patient had more severe clinical characteristics and presented with severe pneumonia and multi-organ failure. Both patients received a combination therapy including antiviral treatment and reduced immunosuppression therapy and finally recovered. CONCLUSIONS: We report COVID-19 infection in two renal transplant recipients with a favorable outcome but different clinical courses, which may provide a reference value for treating such patients.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Transplante de Rim , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Transplantados , Resultado do Tratamento
10.
Rheumatol Int ; 40(11): 1753-1762, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32930863

RESUMO

The novel coronavirus outbreak induces many concerns about the management of pregnancy, as well as rheumatic and musculoskeletal diseases. The very rapid spread of the infection throughout all inhabited continents leads to a fast-growing number of infected with SARS-CoV-2 and requires answers and special recommendations to the most vulnerable group of people: pregnant woman and patients on immunomodulatory or immunosuppressive treatment. A systematic literature search was performed in Embase, MEDLINE, and Scopus database for studies describing COVID-19 infection in pregnant women diagnosed with rheumatic and musculoskeletal diseases. From the 1,115 initially identified articles, we selected 29 publications in the English language, from which 18 were eligible according to the inclusion criteria. Limited number of cases and further researches are required to evaluate the risk of transmission of SARS-CoV-2 from mother to her infant as well as clinical features of infection in pregnant women. The conclusions of different authors, despite the small number of cases, suggest that there is no vertical transmission in women diagnosed with COVID-19 pneumonia. Although the World Health Organization recently reported that pregnant patients do not have a higher risk of infection than the rest of the population, Royal College of Obstetricians & Gynecologists and The Royal College of Midwives for COVID-19 infection in pregnancy published Guidelines for pregnant women with suspected SARS-CoV-2 infection.Considerations about patients with rheumatic diseases on the immunosuppressive treatment required European League Against Rheumatism, American College of Rheumatology, British Society for Rheumatology, and Australian Rheumatology Association to publish recommendations for patients with rheumatic diseases and COVID-19. These algorithms are very important to the medical society, but many concerns, absence of experience, and many questions are still unanswered and need time to be resolved and proceed successfully in this global pandemic situation.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez , Doenças Reumáticas/complicações , Infecções por Coronavirus/terapia , Feminino , Humanos , Imunossupressores/uso terapêutico , Transmissão Vertical de Doença Infecciosa , Pandemias , Pneumonia Viral/terapia , Gravidez , Complicações Infecciosas na Gravidez/terapia , Doenças Reumáticas/tratamento farmacológico
11.
Hautarzt ; 71(10): 762-771, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32886132

RESUMO

Hidradenitis suppurativa (HS) is a chronic, recurrent cutaneous disease of the terminal hair follicle which manifests with deep-seated, painful nodules, abscesses, and sinus tract formation. The pathophysiology of the disease includes among various factors also dermatoendocrinologic variables: Correlations with metabolic syndrome, obesity, sex steroid hormones, and the improvement after antiandrogen therapy are some of the key points presented in this review. Hormonal treatment of HS can be an effective and inexpensive alternative or add-on therapy to classic HS treatments, especially in cases where antibiotics and/or biologics are ineffective or contraindicated.


Assuntos
Abscesso/etiologia , Doenças do Sistema Endócrino/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Hidradenite Supurativa/fisiopatologia , Síndrome Metabólica/metabolismo , Antagonistas de Androgênios/uso terapêutico , Diabetes Mellitus/metabolismo , Dislipidemias/metabolismo , Folículo Piloso , Hidradenite Supurativa/tratamento farmacológico , Hidradenite Supurativa/metabolismo , Hormônios/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Obesidade/metabolismo
12.
Medicine (Baltimore) ; 99(38): e22216, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957358

RESUMO

The prevalence of Crohn disease (CD) is increasing in Asia, but data from Southeast Asian population are scarce.The databases of 2 university-based national tertiary referral centers located in Bangkok, Thailand, were retrospectively reviewed for adult patients diagnosed with CD during January 2000 to December 2017. Disease characteristics, diagnosis, treatment, and outcomes were described and compared between the 2000 to 2009 cohort (cohort A) and the 2010 to 2017 cohort (cohort B).One hundred eighty-two patients (mean age: 46.4 years, 50% male) with 993 patient-years of follow-up were included. Thirteen percent had a history of intestinal resection, but were not diagnosed until disease recurrence. Another 6% were diagnosed at the time of first surgery. There was no improvement in diagnostic proficiency between cohorts. Mesalamine, corticosteroids, thiopurines, and biologics were prescribed in 75.8%, 81.3%, 84.6%, and 13.7% of patients, respectively (P > .05 between cohorts). Notably, thiopurines were started earlier in cohort B. Median time to the start of thiopurines was 6.2 and 1.65 months in cohort A and B, respectively (P < .01). However, the cumulative 5-year rates of disease behavior progression (P = .43), hospitalization (P = .14), and bowel surgery (P = .29) were not significantly different between cohorts. Subgroup analysis including only patients who required thiopurines showed the early use of thiopurines to be associated with lower risk of intestinal surgery after diagnosis (hazard ratio: 0.30, 95% confidence interval: 0.11-0.85).Early disease recognition and early introduction of immunomodulators may prevent long-term complications and reduce unnecessary surgery in CD.


Assuntos
Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Mercaptopurina/uso terapêutico , Adulto , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tailândia/epidemiologia
14.
Medicine (Baltimore) ; 99(33): e21121, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871981

RESUMO

BACKGROUD: Mycophenolate mofetil (MMF) has been recommended for the treatment of lupus nephritis (LN). Although inter-racial differences exist regarding the appropriate dose and efficacy of MMF in patients with LN, no definitive meta-analysis has yet been conducted in Chinese patients. This analysis investigated the efficacy and safety of MMF in Chinese patients with proliferative LN. METHODS: A systematic literature search was conducted to select randomized controlled trials that reported at least one of the following: complete remission (CR), partial remission, total remission (TR; defined as complete remission + partial remission), relapse rate, serum creatinine, creatinine clearance, end-stage renal disease, death, infections, amenorrhea, leukopenia, alopecia, gastrointestinal symptoms, or liver damage. RESULTS: Eighteen trials (927 patients) were included; 14 (750 patients) reported CR, partial remission, and TR. Two trials (58 patients) reported relapse rates during maintenance treatment. MMF induction significantly improved CR and TR vs cyclophosphamide (relative risk 1.34, 95% confidence interval: 1.13-1.58; P < .001; relative risk 1.16, 95% confidence interval: 1.02-1.33; P = .03), and was associated with significantly lower risks of infection (P < .001), amenorrhea (P < .001), leukopenia, and alopecia. No significant difference in relapse rate was evident between the MMF and azathioprine groups (P = .66). CONCLUSION: According to this meta-analysis of 18 trials, MMF is significantly more effective than cyclophosphamide induction, and is associated with reduced incidences of infections, amenorrhea, leukopenia, and alopecia in Chinese patients with proliferative LN.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etnologia , Ácido Micofenólico/uso terapêutico , Grupo com Ancestrais do Continente Asiático , China , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Inibidores Enzimáticos/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Ácido Micofenólico/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
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
16.
Ann Hematol ; 99(11): 2463-2475, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32964342

RESUMO

TAFRO syndrome is a newly recognized disease entity characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The objective of this study was to investigate the effectiveness of tocilizumab, an anti-interleukin-6 receptor antibody, in patients with TAFRO syndrome. We performed a systematic literature review from inception to July 5, 2020, for articles reporting tocilizumab administration for the treatment of TAFRO syndrome. We identified 31 patients with TAFRO syndrome treated with tocilizumab. The mean age was 49.8 years, and 61.3% of the patients were male. The mean observation period was 12.6 months. Tocilizumab was used at the standard intravenous dose (8 mg/kg) weekly or every 2 weeks in combination with other immunosuppressive drugs, such as glucocorticoids, rituximab, cyclosporine, or cyclophosphamide, in most of the patients. Eighteen patients (58.1%) received tocilizumab as a first-line treatment, while it was a second-line or a third-line treatment for 13 patients with insufficient responses to the prior treatments. Sixteen patients (51.6%) obtained complete response to tocilizumab treatment, whereas 15 patients showed only partial or no response. Detailed factors of ineffectiveness included persistent thrombocytopenia (n = 7), persistent anasarca (n = 5), persistent renal dysfunction (n = 2), and persistent fever (n = 2). A total of four patients (12.9%) succumbed to the disease, while the remaining twenty-seven patients survived. Two patients achieved drug-free remission at last visit, and disease remission was maintained with tocilizumab monotherapy in five patients. No new safety signal was reported. Tocilizumab was effective in ~ 50% of the patients, suggesting it could serve as a treatment choice for TAFRO syndrome. Poor clinical response to tocilizumab observed in other patients highlights the need for the additional therapeutic treatment options.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
Front Immunol ; 11: 2086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983161

RESUMO

Immunosuppressive therapies increase the susceptibility of patients to infections. The current pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compels clinicians to develop recommendations for successful clinical management and surveillance of immunocompromised patients at high risk for severe disease progression. With only few case studies published on SARS-CoV-2 infection in patients with rheumatic diseases, we report a 25-year-old male who developed moderate coronavirus disease 2019 (COVID-19) with fever, mild dyspnea, and no major complications despite having received high-dose prednisolone, cyclophosphamide, and rituximab for the treatment of highly active, life-threatening eosinophilic granulomatosis with polyangiitis (EGPA).


Assuntos
Betacoronavirus/genética , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/tratamento farmacológico , Infecções por Coronavirus/complicações , Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Imunossupressores/uso terapêutico , Pneumonia Viral/complicações , Adulto , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Prednisolona/uso terapêutico , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rituximab/uso terapêutico , Resultado do Tratamento
18.
Medicine (Baltimore) ; 99(35): e21844, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871907

RESUMO

RATIONALE: The heart transplantation is the most important treatment for patients with end-stage severe heart disease who failed to conventional therapy. Post-transplant lymphoproliferative disorder is the second most common malignancy in heart transplant recipients. However, primary central nervous system lymphoma (PCNSL) after heart transplantation is an extremely rare condition. PATIENTS CONCERNS: This report described a 53-year-old male who was diagnosed as PCNSL 17 months after heart transplantation. DIAGNOSES: The patient was admitted to the local hospital presenting with dizziness, headache, and reduced left-sided power and sensation for 1 week. He had a medical history of heart transplantation because of the dilated cardiomyopathy 17 months ago and had a 17-month history of immunosuppressive therapy with tacrolimus. A computed tomography scan of the brain revealed a bulky mass in the right temporal lobe. The emergency intracranial mass resection and cerebral decompression were performed in our hospital. The histopathology of the brain lesions showed diffuse large B-cell lymphoma. A further FDG positron emission tomography-computed tomography scan of the whole body showed no significantly increased metabolic activity in other regions. The final diagnosis of this patient was PCNSL after heart transplantation. INTERVENTIONS: Given the poor health condition, with the patient's consent, the whole brain radiotherapy was performed with supportive care. OUTCOMES: The disease deteriorated rapidly during the period of receiving radiotherapy, and he died within 2 months from the diagnosis. LESSONS: PCNSL after heart transplantation is an extremely rare phenomenon with extremely poor prognosis. We should pay close attention to the heart recipients, especially when the patients present with neurological symptoms and signs. The available treatment options for PCNS-post-transplant lymphoproliferative disorder include the reduction of immunosuppressive drugs, immune-chemotherapy, operation, radiotherapy. However, individual treatments for heart transplant recipients with PCNSL should be based on the performance status and tolerance to treatment, combined with the doctor's experience and supportive care.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Transplante de Coração , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Tacrolimo/uso terapêutico , Tomografia Computadorizada por Raios X
19.
Am J Physiol Heart Circ Physiol ; 319(4): H793-H796, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32886002

RESUMO

The 60-kDa heat shock protein (HSP60) is a chaperone essential for mitochondrial proteostasis ensuring thus sufficient aerobic energy production. In pathological conditions, HSP60 can be translocated from the mitochondria and excreted from the cell. In turn, the extracellular HSP60 has a strong ability to trigger and enhance inflammatory response with marked proinflammatory cytokine induction, which is mainly mediated by Toll-like receptor binding. Previous studies have found increased circulating levels of HSP60 in hypertensive patients, as well as enhanced HSP60 expression and membrane translocation in the hypertrophic myocardium. These observations are of particular interest, since they could provide a possible pathophysiological explanation of the severe course and worse outcome of severe acute respiratory syndrome coronavirus 2 infection in hypertensive patients, repeatedly reported during the recent coronavirus disease 2019 (COVID-19) pandemic and related to hyperinflammatory response and cytokine storm development during the third phase of the disease. In this regard, pharmacological inhibition of HSP60 could attract attention to potentially ameliorate inappropriate inflammatory reaction in severe COVID-19 patients. Among HSP60 antagonizing drugs, mizoribine is the most intriguing, since it is clinically approved and exerts antiviral activity. However, this topic requires to be further scrutinized.


Assuntos
Betacoronavirus/patogenicidade , Chaperonina 60/metabolismo , Infecções por Coronavirus/metabolismo , Hipertensão/metabolismo , Mediadores da Inflamação/metabolismo , Pneumonia Viral/metabolismo , Animais , Chaperonina 60/antagonistas & inibidores , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Imunossupressores/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Ribonucleosídeos/uso terapêutico , Transdução de Sinais
20.
N Engl J Med ; 383(12): 1117-1128, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32937045

RESUMO

BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Azatioprina/uso terapêutico , Creatinina/urina , Ciclofosfamida/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Nefrite Lúpica/mortalidade , Masculino , Ácido Micofenólico/uso terapêutico , Indução de Remissão
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