ABSTRACT
Introdução:uma vez conhecidos os mecanismos de patogênese do SARS-CoV-2, vários métodos de tratamento para a COVID-19 foram desenvolvidos, dentre eles destaca-se o uso dos anticorpos monoclonais para o contexto de pacientes em estágios graves da doença. Objetivo: compreender se o uso dos anticorpos monoclonais para tratamento da COVID-19 grave interfere nos níveis séricos da angiotensina II. Metodologia:Para a realização dessa pesquisa foram selecionados através do DeCS e MeSH os descritores "COVID-19", "Angiotensin II" e "Antibodies, Monoclonal" e seus respectivos "entry terms" sugeridos pela base MeSH. Posteriormente,utilizando-se os operadores booleanos OR e AND, foi montada uma estratégia de busca, a qual foi utilizada nas bases de dados PUBMED, EMBASE, Web of Science, Cochrane Library e Scopus, sem restrição dedata de publicação ou idioma. Resultados:ao final do processo de seleção dos artigos, 29 foram selecionados para a leitura e análise completa. Nesta revisão, foram abordados diferentes tipos de anticorpos monoclonais, os quais foram oportunamente agrupados de acordo com o seu mecanismo de ação. Conclusão: foi possível concluir que das cinco classes de anticorpos monoclonais tratadas neste trabalho, três potencialmente podem causar alterações nos níveis séricos de angiotensina II (AU).
Introduction:once the mechanisms of pathogenesis of SARS-CoV-2 are known, several methods of treatment for COVID-19 have been developed, among them the use of monoclonal antibodies for the context of patients in severe stages of the disease. Purpose:to understand whether the use of monoclonal antibodies for the treatment of severe COVID-19 interferes with serum angiotensin II levels. Methodology:For this research were selected through DeCS and MeSH the descriptors "COVID-19", "Angiotensin II" and "Antibodies, Monoclonal" and their respective entry "Terms" suggested by the MeSH database. Subsequently, using the boolean operators OR and AND, a search strategy was set up, which was used in the databases PUBMED, EMBASE, Web of Science, Cochrane Library and Scopus, without restriction of publication date or language. Results:at the end of the article selection process, 29 were selected for reading and full analysis. In this review, different types of monoclonal antibodies were addressed, which were opportunely grouped according to their mechanism of action. Conclusion:it was possible to conclude that of the five classes of monoclonal antibodies treated in this study, three potentially can cause changes in serum levels of angiotensin II (AU).
Introducción:Una vez conocidos los mecanismos de patogénesis del SARSCoV-2, se desarrollaron variosmétodos de tratamiento para el COVID-19, entre ellos, el uso de anticuerpos monoclonales para el contexto de pacientes en fases graves de la enfermedad. Objetivo:Comprender si el uso de anticuerpos monoclonales para el tratamiento de la COVID-19 grave interfiere en los niveles séricos de angiotensina II. Metodología:Los descriptores "COVID-19", "Angiotensina II", "Anticuerpos, Monoclonales" y sus respectivos "entry terms" (términos de entrada) sugeridos por el MeSH fueron seleccionados a través de DeCS yMeSH. Posteriormente, utilizando los operadores booleanos OR y AND, se estableció una estrategia de búsqueda que se utilizó en las bases de datos PUBMED, EMBASE, Web of Science, Cochrane Library y Scopus, sin restricción de fecha de publicación ni de idioma. Resultados:Al final del proceso de selección de artículos, se seleccionaron 29 artículos para su lectura y análisis completos. En esta revisión se han abordado diferentes tipos de anticuerpos monoclonales, que se han agrupado oportunamente según su mecanismo de acción. Conclusión:Se pudo concluir que de las cinco clases de anticuerpos monoclonales tratados en este trabajo, tres pueden potencialmente causar alteraciones en los niveles séricos de angiotensina II (AU).
Subject(s)
Angiotensin II , COVID-19/drug therapy , Immunologic Factors/therapeutic use , Antibodies, Monoclonal/therapeutic use , SARS-CoV-2/enzymologyABSTRACT
El término miocarditis hace referencia a una inflamación del miocardio, que puede tener diversas causas (infecciones, tóxicos, enfermedades autoinmunes). Su diagnóstico es desafiante debido al gran espectro de presentaciones clínicas que puede adoptar, muchas veces imitando patologías más prevalentes como el infarto agudo de miocardio. La miocarditis asociada a enfermedades autoinmunes es poco frecuente, y la importancia de reconocerla radica en que el diagnóstico e inicio temprano del tratamiento son cruciales para mejorar su pronóstico. Presentamos aquí un caso clínico de una perimiocarditis lúpica.
Myocarditis refers to an inflammation of the myocardium, which can have various causes (infections, toxic substances, autoimmune diseases). Its diagnosis is challenging due to the wide spectrum of clinical presentations, often mimicking more prevalent pathologies such as acute myocardial infarction. Myocarditis associated with autoimmune diseases is rare, and the importance of recognizing is that early diagnosis and initiation of treatment are crucial to improve its prognosis. We present here a clinical case of lupus perimyocarditis.
O termo miocardite refere-se a uma inflamação do miocárdio, que pode ter várias causas (infecções, substâncias tóxicas, doenças autoimunes). Seu diagnóstico é desafiador devido ao amplo espectro de apresentações clínicas que pode ter, muitas vezes mimetizando patologias mais prevalentes como o infarto agudo do miocárdio. A miocardite associada a doenças autoimunes é rara, e a importância de reconhecê-la reside no fato de que o diagnóstico precoce e o início do tratamento são cruciais para melhorar seu prognóstico. Apresentamos aqui um caso clínico de perimiocardite lúpica.
Subject(s)
Humans , Female , Adult , Heart Failure/therapy , Myocarditis/diagnostic imaging , Chest Pain , Methylprednisolone/therapeutic use , Treatment Outcome , Immunoglobulins, Intravenous/therapeutic use , Cyclophosphamide/therapeutic use , Hydroxychloroquine/therapeutic use , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/complications , Myocarditis/etiology , Myocarditis/drug therapyABSTRACT
OBJECTIVES@#There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM.@*METHODS@#The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0.@*RESULTS@#Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%).@*CONCLUSIONS@#In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Immunologic Factors/therapeutic use , Male , Middle Aged , Multiple Myeloma/therapy , Neoplasm Staging , Pain , Prognosis , Proteasome Inhibitors/therapeutic useABSTRACT
Follicular lymphoma is an indolent malignant tumor originating from lymph nodes and lymphoid tissues, which may affect the patients' quality of survival due to the recurrence and progression. In recent years, with the deepening understand of the molecular biology and signaling pathways, many new targeted drugs for follicular lymphoma have been discovered, such as monoclonal antibodies, checkpoint inhibitors, epigenetic regulation related targeted therapies and signaling pathway inhibitors. In this review, the new progress of immunotherapy for follicular lymphoma is summarized briefly.
Subject(s)
Antineoplastic Agents/pharmacology , Epigenesis, Genetic , Humans , Immunologic Factors/therapeutic use , Immunotherapy , Lymphoma, Follicular/drug therapyABSTRACT
As lung cancer targeted therapy and immunotherapy drugs are the current hot spot in the research and development area of new anti-tumor drugs, the amount of clinical trial in this area is increasing year by year. On the basis of combing the on-site inspections of drug registration clinical trials from 2019 to 2021, combined with the characteristics of lung cancer targeted therapy and immunotherapy drugs, this paper discusses the focus of on-site inspection of clinical trials of such drugs, and puts forward suggestions for the compliant implementation of lung cancer clinical trials. .
Subject(s)
Antineoplastic Agents/therapeutic use , Humans , Immunologic Factors/therapeutic use , Immunotherapy , Lung Neoplasms/drug therapy , Molecular Targeted TherapyABSTRACT
Small cell lung cancer is a kind of malignant tumor with strong invasiveness and poor prognosis, and the classic therapeutic modality of the disease remains multidisciplinary and comprehensive treatment. Treatment options for small cell lung cancer have been stalled for a long time, and new opportunities have emerged in recent years due to the development and initial experience of immunotherapeutic drugs. Clinical trials of some selected immune checkpoint inhibitors have confirmed the efficacy and safety in small cell lung cancer. Based on the results of phase III clinical trials (Impower133 and CASPIAN), Atezolizumab or Durvalumab in combination with chemotherapy has been approved by the U.S. Food and Drug Administration for the first-line treatment of extensive-stage small cell lung cancer. Clinical trials involving immune checkpoint inhibitors are being actively carried out and provide different perspectives for the management of small cell lung cancer. This article aimed to review the clinical progress in immunotherapy of small cell lung cancer. .
Subject(s)
Clinical Trials, Phase III as Topic , Humans , Immune Checkpoint Inhibitors , Immunologic Factors/therapeutic use , Immunotherapy/methods , Lung Neoplasms/pathology , Small Cell Lung Carcinoma/pathologyABSTRACT
ABSTRACT For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.
RESUMO Pacientes com doenças autoimunes exigem uma constante preocupação com os riscos e benefícios do tratamento imunossupressor ou imunomodulador. O conhecimento das rotinas no uso de cada uma dessas drogas é fundamental para o bom desfecho clínico, evitando a piora da doença ou efeitos colaterais. As drogas imunossupressoras e imunomoduladoras agem em diferentes pontos da resposta imunológica a fim de controlar a doença para qual são indicadas. O conhecimento do mecanismo de ação, principais posologias, efeitos adversos e os riscos de infecções e neoplasias relacionadas ao uso dessas medicações são fundamentais para um tratamento seguro. Cada uma delas apresenta um perfil específico de complicações e o manejo deve ser individualizado em diferentes cenários ao longo do seguimento do paciente. O uso de medicações para profilaxia primária de infecções e a vacinação são pontos essenciais no planejamento do tratamento, prevenindo potenciais complicações infecciosas ao longo do acompanhamento. O uso de imunossupressores e imunomoduladores é uma frequente realidade no dia-a-dia do neurologista, e o conhecimento das características de cada droga é crucial para o sucesso do tratamento. A realização de uma rotina antes, durante e depois do uso dessas medicações evita complicações relacionadas com o tratamento e alcança um melhor controle da doença.
Subject(s)
Humans , Neurology , Immunologic Factors/therapeutic use , Immunosuppressive Agents/adverse effectsABSTRACT
Resumen El manejo de las reacciones adversas inducidas por los inhibidores del punto de control inmunitario (IPCI) en cáncer, demanda un trabajo multidisciplinario. Revisamos las causas y el curso clínico de las consultas e internaciones debidas a reacciones adversas de los IPCI entre septiembre de 2015 y julio de 2019 en el Instituto Alexander Fleming. Se registraron los datos demográficos, diagnóstico oncológico, reacción adversa y su grado, requerimiento de internación, tratamiento, mortalidad y evaluación de la reexposición. Se registraron 124 reacciones adversas por IPCI en 89 pacientes. Sesenta y ocho recibían monoterapia y 21 terapia combinada. Las manifestaciones cutáneas fueron las más frecuentes, seguidas de las generales, endocrinas (con mayor frecuencia hipotiroidismo), colitis, neumonitis, neurológicas y hepatitis. Fueron graves (grado ≥ 3), 26 toxicidades en 25 pacientes. Se internaron 15, y 6 de ellos requirieron terapia intensiva. Un caso fue fatal. Recibieron glucocorticoides 34 (12 de ellos por vía intravenosa). Un paciente recibió micofenolato y uno inmuno globulina endovenosa. En 20 se discontinuó el tratamiento. Ocho se reexpusieron y uno de ellos debió suspender definitivamente. Se presenta en esta serie de casos nuestra experiencia con el diagnóstico y tratamiento de las reacciones adversas de una familia de drogas cuya utilización ha crecido en los últimos años.
Abstract The management of patients with immune-related adverse events (irAEs) frequently demands a multidisciplinary approach. We reviewed the causes and clinical course of medical visits and admissions at the Instituto Alexander Fleming due to irAEs between September 2015 and July 2019. Demographic data, diagnosis, toxicity and its severity, requirement of admission, treatment, mortality, and evaluation of the re-administration of immunotherapy were collected. We found 124 irAEs in 89 patients. Sixty-eight of them received monotherapy (76.4%) and 21 (23.6%) combination of drugs. Cutaneous manifestations were the most frequent cause of irAEs, followed by general manifestations, endocrine dysfunctions (hypothyroidism the most frequent), colitis, pneumonitis, neurologic dis orders, and hepatitis. In 26 adverse events (in 25 patients), severity grade was ≥ 3. Fifteen were admitted and 6 required ICU admission. One patient died. Thirty-four received glucocorticoids, 12 of them by intravenous route. One patient received mycophenolate and one IVIG. In 20, the treatment was discontinued; 8 were re-exposed, with definitive discontinuation in one patient. In this case series we report our experience in the diagnosis and management of adverse reactions related to a family of drugs whose use has grown in recent years.
Subject(s)
Humans , Drug-Related Side Effects and Adverse Reactions , Neoplasms/drug therapy , Nervous System Diseases , Immune Checkpoint Inhibitors , Immunologic Factors/therapeutic use , ImmunotherapyABSTRACT
O vitiligo é uma desordem dermatológica complexa, cuja patogênese ainda não é totalmente esclarecida. Apesar de não apresentar complicações funcionais no organismo dos pacientes acometidos, o vitiligo pode resultar em um grande impacto psicossocial. Desse modo, é importante que os médicos saibam como conduzir o tratamento dessa patologia. O objetivo deste estudo foi documentar as terapias disponíveis para o tratamento do vitiligo, assim como apontar pesquisas que relataram a utilização dessas opções terapêuticas e os dados resultantes. As terapias abordadas foram corticoides tópicos e sistêmicos, fototerapia e fotoquimioterapias, antioxidantes, imunomoduladores, fenilalanina, despigmentação, procedimentos cirúrgicos e novas abordagens. A monoterapia parece ser menos eficaz no tratamento do vitiligo. A associação de medicação tópica e/ou sistêmica com o uso da fototerapia ultravioleta B de banda estreita parece ser o padrão-ouro para a repigmentação da pele dos pacientes. Medicamentos novos estão em estudo, porém sua eficácia e o estudo dos possíveis efeitos colaterais, principalmente a longo prazo, têm que ser melhores investigados. É necessário que o médico dermatologista, em conjunto com o paciente, escolha a melhor terapia dentre as disponíveis, de acordo com critérios clínicos e a possibilidade de acesso ao tratamento pelo portador. O acompanhamento e a abordagem por uma equipe multiprofissional também são importantes. (AU)
Vitiligo is a complex dermatological disorder, whose pathogenesis has not yet been fully elucidated. Although it does not present functional complications in the affected patients' body, vitiligo can result in a great psychosocial impact. Therefore, it is important that physicians know how to conduct its treatment. This study aimed at documenting the available therapies for the treatment of vitiligo, as well as pointing out studies reporting the use of these therapeutic options and their resulting data. The therapies addressed were topical and systemic corticosteroids, phototherapy, and photochemotherapies, antioxidants, immunomodulators, phenylalanine, depigmentation, surgical procedures, and new approaches. Monotherapy appears to be less effective in the treatment of vitiligo. The combination of topical and/or systemic medication with the use of narrowband ultraviolet B phototherapy seems to be the gold standard for the patients' skin repigmentation. New drugs are under study, but their effectiveness and study of possible side effects, especially in the long run, have to be better investigated. It is necessary that the dermatologist, together with the patient, choose the best therapy among those available, according to clinical criteria and the possibility of access to treatment by the patient. Monitoring and approach by a multiprofessional team is also important. (AU)
Subject(s)
Humans , Vitiligo/therapy , Phototherapy/methods , Phenylalanine/therapeutic use , Vitiligo/drug therapy , Vitiligo/radiotherapy , Adrenal Cortex Hormones/therapeutic use , Plant Preparations/therapeutic use , Polypodium , Immunologic Factors/therapeutic use , Phytotherapy , Antioxidants/therapeutic useABSTRACT
Doenças autoimunes são doenças universais, e os diagnósticos e tratamentos primários são habitualmente iniciados por clínicos em enfermarias ou ambulatórios, antes de serem encaminhados a especialistas. Além disso, pacientes em uso de biológicos internados em hospitais gerais têm sido cada vez mais frequentes na prática clínica. Conhecer o perfil de segurança, as indicações e os efeitos colaterais dessas drogas deve ser preocupação dos clínicos. Neste trabalho, foi realizada revisão de literatura sobre terapia biológica com rituximabe no tratamento das principais doenças autoimunes sistêmicas da prática clínica: artrite reumatoide, lúpus eritematoso sistêmico, vasculites relacionadas aos anticorpos anticitoplasma de neutrófilo, púrpura trombocitopênica imune e espondilite anquilosante. (AU)
AutoimmunAutoimmune diseases are universal diseases and primary diagnosis and treatment are typically initiated by internists in wards or outpatient clinics before being referred to specialists. In addition, patients on use of biologicals hospitalized in general hospitals have been increasingly common in clinical practice. Knowing the safety profile, the indications, and the side effects of these drugs should be a concern for the internists as well. In this study, the literature review was performed on biological therapy with Rituximab for treating the main systemic autoimmune diseases of clinical practice: rheumatoid arthritis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitides, immune thrombocytopenic purpura, and ankylosing spondylitis. (AU)
Subject(s)
Humans , Autoimmune Diseases/drug therapy , Rituximab/therapeutic use , Immunologic Factors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Spondylitis, Ankylosing/drug therapy , Immunoglobulins/drug effects , B-Lymphocytes/drug effects , Antigens, CD20/drug effects , Rituximab/pharmacologyABSTRACT
A vasculopatia livedoide é uma doença cutâneo-vascular que surge devido à oclusão trombogênica de vasos da derme. Apresenta-se por meio de máculas ou pápulas eritematosas e purpúricas, em membros inferiores, que podem levar à ulceração dolorosa crônica e recorrente. Com a evolução, pode haver cicatrização, o que leva ao aparecimento de áreas de fibrose e cicatrizes atróficas, irregulares e esbranquiçadas, dando nome à patologia. Relata-se o caso de uma paciente com vasculopatia livedoide de acometimento de membros inferiores. (AU)
Livedoid vasculopathy is a vascular skin disease resulting from thrombogenic occlusion of dermal blood vessels. It presents with erythematous, purpuric macules or papules on the lower limbs, which can lead to chronic and recurrent painful ulceration. With its progression, there may be scarring leading to the appearance of areas of fibrosis and atrophic, irregular, and whitish scars, which gave this name to the pathology. The case of a patient with livedoid vasculopathy affecting the lower limbs is reported. (AU)
Subject(s)
Humans , Female , Middle Aged , Livedoid Vasculopathy/diagnosis , Skin Ulcer/diagnosis , Immunoglobulins/therapeutic use , beta-Thalassemia/complications , Lower Extremity/pathology , Erythema/diagnosis , Immunologic Factors/therapeutic useABSTRACT
INTRODUCTION@#The use of drugs that modulate the immune system during paediatric severe sepsis and septic shock may alter the course of disease and is poorly studied. This study aims to characterise these children who received immunomodulators and describe their clinical outcomes.@*METHODS@#This is a retrospective chart review of patients with severe sepsis and septic shock admitted into the paediatric intensive care unit (PICU). Clinical, haematological and outcome characteristics of patients with or without exposure to immune-modulating drugs were compared. Primary outcome was PICU mortality; secondary outcomes were 28-day ventilator-free days (VFD) and intensive care unit-free days (IFD). Univariate and multivariable analyses were performed for these outcomes.@*RESULTS@#A total of 109 patients with paediatric severe sepsis or septic shock were identified. Of this number, 47 (43.1%), 16 (14.7%) and 3 (2.8%) patients received systemic corticosteroids, intravenous immunoglobulins and granulocyte colony stimulating factor, respectively. Patients who received immune-modulating drugs were more likely to require invasive ventilation (38/54 [70.4%] versus 26/55 [47.3%], @*CONCLUSION@#Immune-modulating drugs were frequently used in paediatric severe sepsis and septic shock. Patients who received these drugs seemed to require more PICU support. Further studies are required to examine this association thoroughly.
Subject(s)
Child , Humans , Immunologic Factors/therapeutic use , Intensive Care Units, Pediatric , Retrospective Studies , Sepsis/drug therapy , Shock, Septic/drug therapyABSTRACT
As of 31 October 2020 This is the tenth edition of this summary of rapid systematic reviews, which includes the results of a rapid systematic review of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 46 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/therapeutic useABSTRACT
As of 31 October 2020 This is the tenth edition of this summary of rapid systematic reviews, which includes the results of a rapid systematic review of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 46 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/therapeutic useABSTRACT
As of 31 October 2020 This is the tenth edition of this summary of rapid systematic reviews, which includes the results of a rapid systematic review of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 46 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/therapeutic useABSTRACT
ABSTRACT Purpose: To compare the benefits and side effects of pars plana vitrectomy with those of systemic immune modulator therapy for patients with complicated intermediate uveitis. Methods: This prospective clinical trial enrolled patients with recurrent intermediate uveitis who exhibited minimal improvement of visual acuity, despite injections of periocular steroids. Twenty patients were randomized to the pars plana vitrectomy group or oral steroid and cyclosporine-A group (10 eyes of 10 patients per group). Follow-up was performed for 24 months to study changes in visual acuity, binocular indirect ophthalmoscopy score, fluorescein angiography, and optical coherence tomography findings. Results: Visual acuity (logarithm of the minimal angle of resolution) significantly improved from 0.71 to 0.42 (p=0.001) in the surgical group, whereas it improved from 0.68 to 0.43 (p=0.001) in the immune modulator therapy group. Seven patients (70%) in the surgical group gained ≥2 lines, and six patients (60%) in the immune modulator therapy group gained ≥2 lines (p=0.970). Fluorescein angiography and optical coherence tomography studies showed that six of seven pars plana vitrectomy patients who had cystoid macular edema experienced improvement, whereas two patients with diffuse macular edema did not experience improvement. In the immune modulator therapy group, three of six patients with cystoid macular edema did not experience improvement, whereas two patients with diffuse macular edema experienced improvement. Conclusions: Pars plana vitrectomy and immune modulator therapy resulted in significant improvement in visual function in patients with persistent inflammation secondary to chronic intermediate uveitis. Despite this success, there remains a need for the determination of optimal indications for the use of each modality. Immune modulator therapy was successful for the treatment of diffuse macular edema associated with chronic intermediate uveitis, whereas pars plana vitrectomy was not.
RESUMO Objetivo: Comparar os benefícios e efeitos co laterais da vitrectomia via pars plana com os da terapia imunomo duladora sistêmica em pacientes com uveíte intermediária complicada. Métodos: Estudo clínico prospectivo incluiu pacientes com uveíte intermediária recorrente que apresentaram melhora minima da acuidade visual, apesar das injeções perioculares de esteroides. Vinte pacientes foram randomizados para o grupo de vitrectomia via pars plana ou esteróide oral e ciclosporina A (10 olhos de 10 pacientes por grupo). O acompanhamento foi de 24 meses para estudar al te rações na acuidade visual, o escore da oftalmoscopia binocular indireta, a angiofluoresceinografia e achados na to mográfica de coerência óptica. Resultados: A acuidade visual (logaritmo do ângulo mínimo de resolução) melhorou significativamente de 0,71 para 0,42 (p=0,001) no grupo cirúrgico, enquanto melhorou de 0,68 para 0,43 (p=0,001) no grupo da terapia imunomoduladora. Sete pacientes (70%) no grupo cirúrgico ganharam ≥2 linhas e seis pacientes (60%) no grupo da terapia imunomoduladora ganharam ≥2 linhas (p=0,970). Os estudos de angiofluoresceinografia e tomografia de coerência óptica mostraram que seis dos sete pacientes da vitrectomia via pars plana que apresentaram edema macular cistóide melhoraram, enquanto dois pacientes com edema macular difuso não apresentaram melhora. No grupo da terapia imunomoduladora, três dos seis pacientes com edema macular cistoide não apresentaram melhora, enquanto dois pacientes com edema macular difuso melhoraram. Conclusões: A vitrectomia via pars plana e a terapia imunomoduladora resultaram em melhora significative da função visual dos pacientes com inflamação persistente secundária a uveíte intermediária crônica. Apesar desse sucesso, continua sendo necessário determinar as melhores indicações para o uso de cada modalidade. A terapia imunomoduladora foi bem sucedida no tratamento do edema macular difuso associado à uveíte intermediária crônica, enquanto a vitrectomia via pars plana não foi.
Subject(s)
Humans , Vitrectomy , Uveitis, Intermediate , Macular Edema , Immunologic Factors , Visual Acuity , Uveitis, Intermediate/therapy , Prospective Studies , Retrospective Studies , Immunologic Factors/therapeutic useABSTRACT
More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review we examined 30 therapeutic options. Findings from the RECOVERY Trial showed that low doses of dexamethasone (6 mg of oral or intravenous preparation once daily for 10 days) significantly reduced mortality by one-third in ventilated patients and by one fifth in patients receiving oxygen only. The anticipated RECOVERY. Trial findings and WHO's SOLIDARITY Trial findings both show no benefit via use of hydroxychloroquine and lopinavir/ritonavir in terms of reducing 28-day mortality or reduced time to clinical improvement or reduced adverse events. Currently, there is no evidence of benefit in critical outcomes (i.e. reduction in mortality) from any therapeutic option (though remdesivir is revealing promise as one option based on 2 randomized controlled trials) and that conclusively allows for safe and effective use to mitigate or eliminate the causative agent of COVID-19. Currently, as to ivermectin, we found 1 in vitro study and 4 observational studies that were largely confounded (nonrandomized), and lacked the methodological rigor to allow much confidence in the results. They were pre-print and non-peer reviewed and were judged to be of high risk of bias and very low quality of evidence. The researchers concluded in large part that the findings could be considered hypothesis testing and urged the conduct of large sample sized RCTs to assess any clinical benefit. Currently, as to favipiravir, we found 1 RCT and 2 observational studies. The results were inconclusive for benefits of favipiravir, and sample sizes were small and results came via largely preprints and non-peer reviewed publications. The 2 nonrandomized observational designs revealed sub-optimal methods with no optimal adjustments, masking, or stratification. A recent release by Glenmark announced promising results from a Phase 3 Clinical Trial of favipiravir in patients with mild to moderate COVID-19. A Phase 3 RCT demonstrates statistically significant faster time to clinical improvement with favipiravir treatment compared to control (n=150 patients).
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/therapeutic useABSTRACT
Myasthenia gravis (MG) is a heterogeneous disease, and there is no unique therapeutic approach for all patients. In 2013 the Myasthenia Gravis American Foundation (MGFA) panel of experts defined refractory MG as the lack of change or deterioration after the use of corticosteroids and two immunosuppressive agents, in adequate doses and time. We report a 51-years-old female with MG of bulbar predominance, who presented four myasthenic crises in 17 months despite the use of corticosteroids, azathioprine and mycophenolate. The high costs associated with her hospitalizations, as well as severe caloric - protein malnutrition, the need for tracheostomy and gastrostomy support, led us to use rituximab. The patient evolved with an excellent response, free of crises after 30 months. She gained 12 kg of weight, without tracheostomy and gastrostomy, only using pyridostigmine support 4 times a day.
Subject(s)
Humans , Female , Middle Aged , Rituximab/therapeutic use , Myasthenia Gravis/drug therapy , Immunologic Factors/therapeutic use , Myasthenia Gravis/diagnosisABSTRACT
ABSTRACT Background: The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic. Objective: To discuss strategies to manage those patients. Methods: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. Conclusions: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.
RESUMO Introdução: A mais recente pandemia causada pelo coronavírus SARS-CoV-2 (COVID-19, do inglês coronavirus disease 2019) representa uma ameaça potencial para pacientes com doenças autoimunes, incluindo esclerose múltipla (EM) e transtorno do espectro de neuromielite óptica (NMOSD, do inglês neuromyelitis optica spectrum disorders). Esses pacientes são geralmente tratados com medicamentos imunomoduladores ou imunossupressores que podem alterar a resposta normal do organismo a infecções. Até o momento, não há consenso sobre como o manejo dos pacientes com EM e NMOSD deve ser realizado durante a pandemia. Objetivo: Discutir estratégias para manejar esses pacientes. Métodos: Focamos em como 1) reduzir o risco de infecção por COVID-19, como distanciamento social, telemedicina e exames laboratoriais e de imagem em intervalos mais amplos; 2) manejo de surtos, incluindo evitar tratamento de surto leve e uso de corticoide oral; 3) gerenciar terapias modificadoras de doença, como a preferência por medicamentos associados a menor risco de infecção (interferons, glatirâmer, teriflunomida e natalizumabe) e infusão em intervalo estendido de natalizumabe, quando seguro; 4) individualizar a escolha da terapia de indução para EM (anticorpos monoclonais anti-CD20, alentuzumabe e cladribina); 5) manejar terapias preventivas de NMOSD, incluindo seleção inicial de terapia e manutenção do tratamento atual; 6) manejar pacientes com EM/NMOSD que foram infectados por COVID-19. Conclusão: No futuro, séries de casos de pacientes com MS/NMOSD infectados com COVID-19 nos ajudará a definir as melhores estratégias de manejo. Por enquanto, contamos com a experiência e orientação especializadas.