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1.
Stem Cell Res Ther ; 11(1): 404, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948252

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) pandemic is quickly spreading all over the world. This virus, which is called SARS-CoV-2, has infected tens of thousands of people. Based on symptoms, the pathogenesis of acute respiratory illness is responsible for highly homogenous coronaviruses as well as other pathogens. Evidence suggests that high inflammation rates, oxidation, and overwhelming immune response probably contribute to pathology of COVID-19. COVID-19 causes cytokine storm, which subsequently leads to acute respiratory distress syndrome (ARDS), often ending up in the death of patients. Mesenchymal stem cells (MSCs) are multipotential stem cells that are recognized via self-renewal capacity, generation of clonal populations, and multilineage differentiation. MSCs are present in nearly all tissues of the body, playing an essential role in repair and generation of tissues. Furthermore, MSCs have broad immunoregulatory properties through the interaction of immune cells in both innate and adaptive immune systems, leading to immunosuppression of many effector activities. MSCs can reduce the cytokine storm produced by coronavirus infection. In a number of studies, the administration of these cells has been beneficial for COVID-19 patients. Also, MSCs may be able to improve pulmonary fibrosis and lung function. In this review, we will review the newest research findings regarding MSC-based immunomodulation in patients with COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Citocinas/imunologia , Imunossupressão/métodos , Células-Tronco Mesenquimais/metabolismo , Pneumonia Viral/terapia , Animais , Infecções por Coronavirus/imunologia , Citocinas/efeitos adversos , Humanos , Pandemias , Pneumonia Viral/imunologia
2.
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
3.
ESMO Open ; 5(5)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32958531

RESUMO

BACKGROUND: Immunosuppression induced by anticancer therapy in a COVID-19-positive asymptomatic patient with cancer may have a devastating effect and, eventually, be lethal. To identify asymptomatic cases among patients receiving active cancer treatment, the Federico II University Hospital in Naples performs rapid serological tests in addition to hospital standard clinical triage for COVID-19 infection. METHODS: From 6 to 17 April 2020, all candidates for chemotherapy, radiotherapy or target/immunotherapy, if negative at the standard clinical triage on the day scheduled for anticancer treatment, received a rapid serological test on peripheral blood for COVID-19 IgM and IgG detection. In case of COVID-19 IgM and/or IgG positivity, patients underwent a real-time PCR (RT-PCR) SARS-CoV-2 test to confirm infection, and active cancer treatment was delayed. RESULTS: Overall 466 patients, negative for COVID-19 symptoms, underwent serological testing in addition to standard clinical triage. The average age was 61 years (range 25-88 years). Most patients (190, 40.8%) had breast cancer, and chemotherapy with or without immunotherapy was administered in 323 (69.3%) patients. Overall 433 (92.9%) patients were IgG-negative and IgM-negative, and 33 (7.1%) were IgM-positive and/or IgG-positive. Among the latter patients, 18 (3.9%), 11 (2.4%) and 4 (0.9%) were IgM-negative/IgG-positive, IgM-positive/IgG-negative and IgM-positive/IgG-positive, respectively. All 33 patients with a positive serological test, tested negative for RT-PCR SARS-CoV-2 test. No patient in our cohort developed symptoms suggestive of active COVID-19 infection. CONCLUSION: Rapid serological testing at hospital admission failed to detect active asymptomatic COVID-19 infection. Moreover, it entailed additional economic and human resources, delayed therapy administrationand increased hospital accesses.


Assuntos
Infecções Assintomáticas , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Imunossupressão/efeitos adversos , Neoplasias/terapia , Pneumonia Viral/diagnóstico , Triagem/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antineoplásicos Imunológicos/efeitos adversos , Betacoronavirus/genética , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Técnicas de Laboratório Clínico/economia , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/economia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Testes Diagnósticos de Rotina/economia , Testes Diagnósticos de Rotina/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Humanos , Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Pandemias , Admissão do Paciente/economia , Admissão do Paciente/estatística & dados numéricos , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Guias de Prática Clínica como Assunto , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/economia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos , Sensibilidade e Especificidade
5.
Curr Opin Rheumatol ; 32(5): 429-433, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32744823

RESUMO

PURPOSE OF REVIEW: There are currently many unanswered questions surrounding the management of patients with immune-mediated inflammatory diseases during the COVID-19 pandemic and several 'rapid' guidelines have been released, although are subject to be updated and changed in the near future. The purpose of this review is to discuss the approach to management of patients with immune-mediated diseases during the COVID-19 pandemic. RECENT FINDINGS: At present, there is little evidence to suggest an increased risk of COVID-19 infection or its complications in patients with immune-mediated diseases or associated with conventional or biologic disease modifying antirheumatic drugs; however, glucocorticoid use does appear to have negative associations. SUMMARY: Currently, conventional and biologic disease modifying antirheumatic drugs can be continued in the absence of SARS-CoV-2 exposure. In the case of exposure, with the exception of hydroxyhcloroquine and sulfasalazine, immunosuppression should be held for 2 weeks. Our recommendations and the guidelines we discuss here are based on C-level recommendations but help provide a framework for how to counsel our patients during this pandemic.


Assuntos
Antirreumáticos/uso terapêutico , Betacoronavirus , Competência Clínica , Infecções por Coronavirus/epidemiologia , Imunossupressão/métodos , Pneumonia Viral/epidemiologia , Doenças Reumáticas/tratamento farmacológico , Reumatologistas/normas , Comorbidade , Humanos , Pandemias , Doenças Reumáticas/complicações , Doenças Reumáticas/epidemiologia
6.
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
7.
Ann Transplant ; 25: e925755, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32703929

RESUMO

Kidney transplantation at the time of the COVID-19 pandemic is challenging. Modifying the immunosuppression protocols is controversial and not evidence based. In this study, we aim to review the published literature of kidney transplant recipients who encountered COVID-19. A literature review was performed using PubMed, ScienceDirect, and World Health Organization databases to identify relevant English-language articles published up to May 7, 2020. There were 24 articles that reported 129 kidney transplant recipients who encountered COVID-19. The age mean was 54.2 years with 73.7% as males. The most commonly reported presentations in order were fever (82.3%), cough (58%), shortness of breath (33.2%), and fatigue (30.7%). Acute kidney injury was observed in 34.1% of patients. Kidney transplant patients encountered COVID-19 were maintained on tacrolimus (Tac, 92%), mycophenolate mofetil (MMF, 78.8%), and prednisone (Pred, 77%) and were manage by holding MMF in 79.1% of patients and holding Tac in 34.4% of patients. In all, 20% of patients needed Intensive Care Unit (ICU) admission and 24.6% of patients required mechanical ventilation. In all, 18.8% of patients had died compared to the reported general population COVID-19 mortality of 3.4%. The clinical presentation of COVID-19 in kidney transplant recipients may be different from the general population with a higher rate of severe disease, complications including renal failure, and mortality.


Assuntos
Causas de Morte , Infecções por Coronavirus/epidemiologia , Saúde Global , Controle de Infecções/métodos , Transplante de Rim/estatística & dados numéricos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/cirurgia , Adulto , Bases de Dados Factuais , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressão/métodos , Incidência , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , Medição de Risco , Análise de Sobrevida , Organização Mundial da Saúde
8.
Nephrol Dial Transplant ; 35(7): 1250-1261, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32678882

RESUMO

BACKGROUND: Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies. METHODS: We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate. RESULTS: Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients. CONCLUSIONS: Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Rejeição de Enxerto/terapia , Hidroxicloroquina/uso terapêutico , Imunossupressão/métodos , Transplante de Rim , Ácido Micofenólico/uso terapêutico , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Antimaláricos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Rejeição de Enxerto/complicações , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Transplantados
9.
Front Immunol ; 11: 1059, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-468036

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic keeps the world in suspense. In addition to the fundamental challenges for the health care system, the individual departments must decide how to deal with patients at risk. Neurologists are confronted with the question, how they should advise their patients regarding immunosuppressive treatment. In particular, the large number of different disease-modifying therapies (DMTs) in the treatment of neuroimmunological diseases such as multiple sclerosis poses a challenge. To a limited extent, it might be useful to transfer knowledge from previous SARS- and Middle East respiratory syndrome (MERS) coronavirus outbreaks in 2002/2003 and 2012 to the current situation. Overall, immunosuppressive therapy does neither seem to have a major impact on infection with SARS- and MERS-CoV nor does it seem to lead to a severe disease course in many cases. Considering the immunological responses against infections with novel coronaviruses in humans, interferons, glatiramer acetate, and teriflunomide appear to be safe. As lymphopenia seems to be associated with a more severe disease course, all DMTs causing lymphopenia, such as cladribine, alemtuzumab, and dimethyl fumarate, need to be reviewed more thoroughly. As they are, in general, associated with a higher risk of infection, depleting anti-CD20 antibodies may be problematic drugs. However, it has to be differentiated between the depletion phase and the phase of immune reconstitution. In summary, previous coronavirus outbreaks have not shown an increased risk for immunocompromised patients. Patients with severe neuroimmunological diseases should be kept from hasty discontinuation of immunotherapy.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Esclerose Múltipla/terapia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Fatores Etários , Infecções por Coronavirus/virologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Masculino , Pandemias , Pneumonia Viral/virologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/virologia , Fatores Sexuais
10.
Front Immunol ; 11: 1059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477373

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic keeps the world in suspense. In addition to the fundamental challenges for the health care system, the individual departments must decide how to deal with patients at risk. Neurologists are confronted with the question, how they should advise their patients regarding immunosuppressive treatment. In particular, the large number of different disease-modifying therapies (DMTs) in the treatment of neuroimmunological diseases such as multiple sclerosis poses a challenge. To a limited extent, it might be useful to transfer knowledge from previous SARS- and Middle East respiratory syndrome (MERS) coronavirus outbreaks in 2002/2003 and 2012 to the current situation. Overall, immunosuppressive therapy does neither seem to have a major impact on infection with SARS- and MERS-CoV nor does it seem to lead to a severe disease course in many cases. Considering the immunological responses against infections with novel coronaviruses in humans, interferons, glatiramer acetate, and teriflunomide appear to be safe. As lymphopenia seems to be associated with a more severe disease course, all DMTs causing lymphopenia, such as cladribine, alemtuzumab, and dimethyl fumarate, need to be reviewed more thoroughly. As they are, in general, associated with a higher risk of infection, depleting anti-CD20 antibodies may be problematic drugs. However, it has to be differentiated between the depletion phase and the phase of immune reconstitution. In summary, previous coronavirus outbreaks have not shown an increased risk for immunocompromised patients. Patients with severe neuroimmunological diseases should be kept from hasty discontinuation of immunotherapy.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Esclerose Múltipla/terapia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Fatores Etários , Infecções por Coronavirus/virologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Masculino , Pandemias , Pneumonia Viral/virologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/virologia , Fatores Sexuais
11.
PLoS One ; 15(6): e0234867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569300

RESUMO

Different modes of exogenous electrical stimulation at physiological strength has been applied to various diseases. Previously, we extensively demonstrated the usability of mild electrical stimulation (MES) with low frequency pulse current at 55 pulses per second (MES55) for several disease conditions. Here we found that MES with high frequency pulse-current (5500 pulse per second; MES5500) suppressed the overproduction of pro-inflammatory cytokines induced by phorbol myristate acetate/ionomycin in Jurkat T cells and primary splenocytes. MES5500 also suppressed the overproduction of inflammatory cytokines, improved liver damage and reduced mouse spleen enlargement in concanavalin-A-treated BALB/c mice. The molecular mechanism underlying these effects included the ability of MES5500 to induce modest amount of hydrogen peroxide and control multiple signaling pathways important for immune regulation, such as NF-κB, NFAT and NRF2. In the treatment of various inflammatory and immune-related diseases, suppression of excessive inflammatory cytokines is key, but because immunosuppressive drugs used in the clinical setting have serious side effects, development of safer methods of inhibiting cytokines is required. Our finding provides evidence that physical medicine in the form of MES5500 may be considered as a novel therapeutic tool or as adjunctive therapy for inflammatory and immune-related diseases.


Assuntos
Citocinas/imunologia , Terapia por Estimulação Elétrica/métodos , Peróxido de Hidrogênio/imunologia , Imunossupressão/métodos , Inflamação/imunologia , Inflamação/terapia , Animais , Concanavalina A , Feminino , Humanos , Inflamação/induzido quimicamente , Células Jurkat , Fígado/imunologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Baço/patologia
12.
Ann Hematol ; 99(7): 1485-1491, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32488602

RESUMO

No agreement had been reached on the treatment of patients with pure red cell aplasia (PRCA) secondary to indolent malignancies. Data was collected from patients with acquired PRCA from May, 2014 to May, 2018 in Peking Union Medical College Hospital. Tumor-associated PRCA and primary PRCA patients were matched at a ratio of 1:2 with compatible baseline characteristics. All patients had been treated with CsA or sirolimus for at least 6 months with the efficacy and adverse events recorded. Twelve tumor-associated PRCA patients (3 thymoma, 8 lymphoproliferative disorders, and 1 smoldering multiple myeloma) with stable underling disease and 24 acquired primary PRCA patients were selected. 83.3% tumor-associated PRCA patients and 100% primary PRCA patients (P = 0.436) responded to immunosuppression therapy (IST) at a median of 2.5 and 3.5 months (P = 0.137), respectively. No different was found in side effects. The ORR at the end of a median of 21.5-month follow-up was 75% and 70.8% (P = 0.795), respectively. No tumor progression was reported except one secondary patient had lymphoma relapse after 2 years of IST and was given chemotherapy again. These results suggested IST had similar effect, safety on patients with tumor-associated, and primary PRCA patients when the tumors were stable.


Assuntos
Imunossupressão , Imunossupressores/uso terapêutico , Neoplasias/complicações , Aplasia Pura de Série Vermelha/tratamento farmacológico , Aplasia Pura de Série Vermelha/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Linfoma/complicações , Linfoma/tratamento farmacológico , Linfoma/patologia , Transtornos Linfoproliferativos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Timoma/complicações , Timoma/tratamento farmacológico , Timoma/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/patologia , Resultado do Tratamento
14.
J Am Acad Dermatol ; 83(4): 1150-1159, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32569797

RESUMO

Dermatologists treating immune-mediated skin disease must now contend with the uncertainties associated with immunosuppressive use in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Although the risk of infection with many commonly used immunosuppressive agents remains low, direct data evaluating the safety of such agents in coronavirus disease 2019 (COVID-19) are scarce. This article reviews and offers guidance based on currently available safety data and the most recent COVID-19 outcome data in patients with immune-mediated dermatologic disease. The interdisciplinary panel of experts emphasizes a stepwise, shared decision-making approach in the management of immunosuppressive therapy. The goal of this article is to help providers minimize the risk of disease flares while simultaneously minimizing the risk of iatrogenic harm during an evolving pandemic.


Assuntos
Infecções por Coronavirus/prevenção & controle , Dermatologia/normas , Imunossupressão/normas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , Dermatopatias/terapia , Comitês Consultivos/normas , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Tomada de Decisão Clínica , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Tomada de Decisão Compartilhada , Dermatologistas/normas , Dermatologia/métodos , Suscetibilidade a Doenças/imunologia , Médicos Hospitalares/normas , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Comunicação Interdisciplinar , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Dermatopatias/imunologia , Sociedades Médicas/normas , Exacerbação dos Sintomas
15.
Br J Cancer ; 123(5): 691-693, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32546835
16.
Scand J Immunol ; 92(4): e12921, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32594540

RESUMO

Antibodies forming a complex with antigen in vivo can dramatically change the antibody response to this antigen. In some situations, the response will be a 100-fold stronger than in animals immunized with antigen alone, and in other situations, the response will be completely suppressed. IgG is known to suppress the antibody response, for example to erythrocytes, and this is used clinically in Rhesus prophylaxis. The mechanism behind IgG-mediated immune suppression is still not understood. Here, we will review studies performed in experimental animal models and discuss the various hypotheses put forward to explain the profound suppressive effect of IgG. We conclude that an exclusive role for negative regulation of B cells through FcγRIIB, increased clearance of erythrocytes from the circulation or complement-mediated lysis is unlikely. Epitope masking, where IgG hides the epitope from B cells, or trogocytosis, where IgG removes the epitope from the erythrocyte, is compatible with many observations. These two mechanisms are not mutually exclusive. Moreover, it cannot be ruled out that clearance, in combination with other mechanisms, plays a role.


Assuntos
Formação de Anticorpos/imunologia , Epitopos/imunologia , Imunoglobulina G/imunologia , Imunossupressão , Ativação Linfocitária/imunologia , Animais , Imunossupressão/métodos
18.
Am J Transplant ; 20(9): 2599-2601, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32400099

RESUMO

The COVID-19 pandemic is spreading worldwide and the impact of the disease in transplant patients is evolving. In this case report, we presented a 63-year-old female kidney transplant recipient who presented with dyspnea and cough and was diagnosed with COVID-19 pneumonia. On the fourth day of admission, the patient's condition worsened. Therefore, the immunosuppressive medications were discontinued, and hydrocortisone was started. The patient died on the fifth day.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Rejeição de Enxerto/prevenção & controle , Falência Renal Crônica/complicações , Transplante de Rim/métodos , Pneumonia Viral/complicações , Transplantados , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Imunossupressão/métodos , Falência Renal Crônica/cirurgia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia
19.
Future Oncol ; 16(20): 1455-1461, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32412310

RESUMO

During the ongoing global pandemic of coronavirus disease 2019 (COVID-19), the benefit of treating patients with cancer must be weighed against the COVID-19 infection risks to patients, staff and society. Prostate cancer is one of the most common cancers among men and raises particular interest during the pandemic as recent reports show that the TMPRSS2 (and other serine proteases), which facilitate the entry, replication and budding of the virion from a cell, can be inhibited using androgen deprivation therapy. Nevertheless, patients with metastatic prostate cancer commonly receive chemotherapy which may compromise their immune system. This paper aims to address the current status of the COVID-19 in patients with cancer overall and suggests an optimal approach to patients with metastatic prostate cancer.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Comorbidade , Humanos , Imunossupressão/métodos , Masculino , Neoplasias de Próstata Resistentes à Castração/patologia , Serina Endopeptidases/efeitos dos fármacos
20.
Lancet ; 395(10237): 1627-1639, 2020 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-32446407

RESUMO

BACKGROUND: Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. METHODS: The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232. FINDINGS: The seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3·2-18·0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT. INTERPRETATION: Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression. FUNDING: The 7th EU Framework Programme.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Rejeição de Enxerto/prevenção & controle , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Células Dendríticas/imunologia , Rejeição de Enxerto/imunologia , Humanos , Imunossupressão/efeitos adversos , Macrófagos/imunologia , Linfócitos T Reguladores/imunologia
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