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1.
PLoS One ; 16(1): e0245025, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33411780

RESUMEN

PURPOSE: COVID-19 pandemic has multifaceted presentations with rising evidence of immune-mediated mechanisms underplay. We sought to explore the outcomes of severe COVID-19 patients treated with a multi-mechanism approach (MMA) in addition to standard-of-care (SC) versus patients who only received SC treatment. MATERIALS AND METHODS: Data were collected retrospectively for patients admitted to the intensive care unit (ICU). This observational cohort study was performed at five institutions, 3 in the United States and 2 in Honduras. Patients were stratified for MMA vs. SC treatment during ICU stay. MMA treatment consists of widely available medications started immediately upon hospitalization. These interventions target immunomodulation, anticoagulation, viral suppression, and oxygenation. Primary outcomes included in-hospital mortality and length of stay (LOS) for the index hospitalization and were measured using logistic regression. RESULTS: Of 86 patients admitted, 65 (76%) who had severe COVID-19 were included in the study; 30 (46%) patients were in SC group, compared with 35 (54%) patients treated with MMA group. Twelve (40%) patients in the SC group died, compared with 5 (14%) in the MMA group (p-value = 0.01, Chi squared test). After adjustment for gender, age, treatment group, Q-SOFA score, the MMA group had a mean length of stay 8.15 days, when compared with SC group with 13.55 days. ICU length of stay was reduced by a mean of 5.4 days (adjusted for a mean age of 54 years, p-value 0.03) and up to 9 days (unadjusted for mean age), with no significant reduction in overall adjusted mortality rate, where the strongest predictor of mortality was the use of mechanical ventilation. CONCLUSION: The finding that MMA decreases the average ICU length of stay by 5.4 days and up to 9 days in older patients suggests that implementation of this treatment protocol could allow a healthcare system to manage 60% more COVID-19 patients with the same number of ICU beds.


Asunto(s)
/terapia , Unidades de Cuidados Intensivos , Tiempo de Internación , Adulto , Anciano , Anciano de 80 o más Años , /epidemiología , Femenino , Honduras/epidemiología , Humanos , Factores Inmunológicos/administración & dosificación , Masculino , Persona de Mediana Edad , Respiración Artificial , Estudios Retrospectivos , Resultado del Tratamiento
2.
Mult Scler Relat Disord ; 48: 102734, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33429305

RESUMEN

BACKGROUND: . Teriflunomide is an immunomodulatory drug approved for Multiple Sclerosis (MS) treatment that inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in the de novo pyrimidine synthesis pathway. This mechanism can produce antiviral effects, thus teriflunomide has gained attention during COVID-19 pandemic. Moreover, in the last months, some case-reports have been published describing MS patients treated with teriflunomide who developed mild and self-limiting forms of COVID-19. METHODS: Here, we describe the case of a 57-year-old man affected by MS, and treated with teriflunomide, who developed a mild form of SARS-CoV-2 infection. Moreover, we provide a detailed literature review about the available cases of COVID-19 in MS patients treated with teriflunomide. We report clinical features, disease course and outcome, and we discuss similarities and differences among patients. RESULTS: Apart from the present report, since February 2020, five papers have been published describing 14 MS patients who developed SARS-CoV-2 infection during teriflunomide treatment. Patients were mostly female (53%), with an average age of 50.5 (±11.3) years. Median EDSS was 2.25 (range 0-6). The average time on treatment with teriflunomide was 3.7 (± 1.6) years. Relevant comorbidities were present in 4 patients (27%). Regarding SARS-CoV-2 infection, the most common symptom was fever (100%) followed by gastrointestinal disturbances (67%), fatigue (55%) and cough (55%). 5 patients were hospitalized and 2 required oxygen support. In patient hospitalized (n=5) compared to the others (n=10), age was significantly higher (59.6 vs 45.9 years, p=0.025) while gender, EDSS, duration of teriflunomide therapy and comorbidities were not significantly different. Outcome was good for all patients with a variable recovery time, ranging from few days to some weeks. Teriflunomide was continued during the entire course of SARS-CoV-2 infection in all patients except for two. Compared to the patients already described, our patient was 7 years older, average time on teriflunomide treatment was about 2.5 years shorter, and median EDSS was 1.5 point lower. Despite significant comorbidities, the outcome was good since our patient was hospitalized but he did not require oxygen supplementation nor intensive care and was able to return at home after only 10 days. Teriflunomide therapy was continued throughout the period. CONCLUSION: Available data suggest that teriflunomide therapy should not be discontinued in MS patients who develop SARS-CoV-2 infection, also in presence of significant comorbidities or clinical conditions requiring hospitalization. Additional studies are necessary to assess if the drug can also have a protective role against SARS-CoV-2.


Asunto(s)
/terapia , Crotonatos/administración & dosificación , Factores Inmunológicos/administración & dosificación , Esclerosis Múltiple/tratamiento farmacológico , Toluidinas/administración & dosificación , /epidemiología , Comorbilidad , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología
3.
BMC Infect Dis ; 21(1): 55, 2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33435866

RESUMEN

BACKGROUND: Small bowel obstruction is one of the leading reasons for accessing to the Emergency Department. Food poisoning from Clostridium botulinum has emerged as a very rare potential cause of small bowel obstruction. The relevance of this case report regards the subtle onset of pathognomonic neurological symptoms, which can delay diagnosis and subsequent life-saving treatment. CASE PRESENTATION: A 24-year-old man came to our Emergency Department complaining of abdominal pain, fever and sporadic self-limiting episodes of diplopia, starting 4 days earlier. Clinical presentation and radiological imaging suggested a case of small bowel obstruction. Non-operative management was adopted, which was followed by worsening of neurological signs. On specifically questioning the patient, we discovered that his parents had experienced similar, but milder symptoms. The patient also recalled eating home-made preserves some days earlier. A clinical diagnosis of foodborne botulism was established and antitoxin was promptly administered with rapid clinical resolution. CONCLUSIONS: Though very rare, botulism can mimic small bowel obstruction, and could be associated with a rapid clinical deterioration if misdiagnosed. An accurate family history, frequent clinical reassessments and involvement of different specialists can guide to identify this unexpected diagnosis.


Asunto(s)
Antitoxina Botulínica/administración & dosificación , Botulismo/diagnóstico , Botulismo/tratamiento farmacológico , Clostridium botulinum/genética , Íleon/fisiopatología , Factores Inmunológicos/administración & dosificación , Obstrucción Intestinal/diagnóstico por imagen , Botulismo/complicaciones , Botulismo/microbiología , Diagnóstico Diferencial , Diplopía/complicaciones , Servicio de Urgencia en Hospital , Heces/microbiología , Microbiología de Alimentos , Humanos , Íleon/diagnóstico por imagen , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto Joven
4.
Mult Scler Relat Disord ; 48: 102704, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33370649

RESUMEN

OBJECTIVE: To evaluate clinical and laboratory effects of delaying ocrelizumab infusions during the COVID-19 pandemics in people with multiple sclerosis (pwMS). METHODS: We have retrospectively searched our electronic database and identified 33 pwMS who had a delay in treatment due to COVID-19 pandemics. The following data were extracted: age, sex, multiple sclerosis (MS) phenotype: relapsing-remitting (RRMS) or primary progressive multiple sclerosis (PPMS), disease duration, Expanded Disability Status scale (EDSS), previous disease modifying therapy (DMT), number of ocrelizumab cycles prior to the lockdown, dates of first ocrelizumab infusion, last ocrelizumab infusion prior to the lockdown and delayed ocrelizumab infusion after the lockdown. Flow cytometry results, relapses and EDSS progression prior to the delayed ocrelizumab infusion after the lockdown were extracted. RESULTS: The mean time between two ocrelizumab infusion during the lockdown was 7.72±0.64 (range 6.07 to 8.92) months. The mean time between last ocrelizumab infusion and the lymphocyte sampling prior to post COVID infusion was 6.59±0.95 (range 5.18 to 8.49) months. In this period, none of the studied patients had a relapse. In a multivariable linear regression analysis, time from last ocrelizumab infusion to lymphocyte sampling prior to the next infusion was the only significant predictor for CD19+ B cells count, when corrected for the number of previous ocrelizumab cycles and MS phenotype (RRMS or PPMS) (B=7.981, 95% C.I. 3.277-12.686, p=0.002). CONCLUSIONS: We have not shown clinical consequences of delaying ocrelizumab due to COVID-19 pandemics. However, the delay in dosing of ocrelizumab was an independent predictor of repopulation of B cells.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Factores Inmunológicos/administración & dosificación , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/sangre , Esclerosis Múltiple Crónica Progresiva/inmunología , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/inmunología , Estudios Retrospectivos , Factores de Tiempo , Tiempo de Tratamiento
6.
Mult Scler Relat Disord ; 47: 102642, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33321356

RESUMEN

BACKGROUND: The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients. OBJECTIVE: To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic. METHODS: Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed. RESULTS: We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive. CONCLUSION: Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Factores Inmunológicos/administración & dosificación , Infusiones Intravenosas/métodos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/administración & dosificación , Adulto , Femenino , Humanos , Infusiones Intravenosas/efectos adversos , Masculino , Persona de Mediana Edad
7.
Phytomedicine ; 80: 153356, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33039729

RESUMEN

BACKGROUND: Using natural polysaccharides from Traditional Chinese Medicine as nanodrug delivery systems have considerable potential for tumor diagnostics and therapeutics. PURPOSE: On the basis of targeted therapy and combining the advantages of natural polysaccharides (angelica polysaccharide, APS) and natural Chinese medicine (curcumin, Cur) to design functionalized nanoparticles to improve the therapeutic through cell membrane encapsulation and immunotherapy. STUDY DESIGN AND METHODS: Cur-loaded, glycyrrhetic acid (GA)-APS-disulfide bond (DTA)-Cur nanomicelle (GACS-Cur), which were prepared by the dialysis method. GACS-Cur was encapsulated with the membranes from red blood cells (RBCm) termed GACS-Cur@RBCm, which were prepared by the principle of extrusion using a miniature extruder. The developed formulations were subjected to various in vitro and in vivo evaluation tests. RESULTS: The resulting APS nanocarriers supported a favorable drug-loading capacity, biocompatibility, and enhanced synergistic anti-hepatoma effects both in vitro and in vivo. After administration in mice, in vivo imaging results showed that the GACS-Cur and RBCm-coated groups had an obvious stronger tumor tissue targeting ability than the control treatment groups. Additionally, the immunomodulatory effect increased IL-12, TNF-α and IFN-γ expression and CD8+ T cell infiltration (1.9-fold) than that of the saline group. Notably, in comparison with hyaluronic acid (HA) nanocarriers, APS nanocarriers possess higher anti-hepatoma efficiency and targeting capabilities and, thus, should be further studied for a wide range of anti-cancer applications. CONCLUSION: Our data demonstrated that APS nanocarriers encapsulated with erythrocyte membrane mighty be a promising clinical method in the development of efficacy, safety and targeting of liver cancer therapy.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Curcumina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Polisacáridos/química , Angelica/química , Animales , Antineoplásicos Fitogénicos/inmunología , Antineoplásicos Fitogénicos/farmacología , Biomimética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Curcumina/farmacología , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Femenino , Células Hep G2 , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/farmacología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Ratones Desnudos , Micelas , Nanopartículas/administración & dosificación , Nanopartículas/química , Distribución Tisular , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Reumatol. clín. (Barc.) ; 16(6): 437-446, nov.-dic. 2020. tab, graf
Artículo en Español | IBECS | ID: ibc-194661

RESUMEN

OBJETIVO: Generar las recomendaciones para la atención de pacientes con enfermedades reumáticas que reciben terapias inmunomoduladoras e inmunosupresoras (fármacos convencionales, biológicos y moléculas pequeñas) durante la pandemia por COVID-19. MATERIALES Y MÉTODOS: Las recomendaciones se realizaron utilizando el método Delphi como herramienta de acuerdo. Se conformó un panel de expertos con trayectoria académica y experiencia en investigación en reumatología. Se realizó la búsqueda de la literatura y se generó el cuestionario del ejercicio Delphi conformado por 42 preguntas. El grado de acuerdo se logró con el 80% de aprobación de los participantes. RESULTADOS: Se conformó un grupo de 11 reumatólogos de 7 ciudades del país. La tasa de respuesta fue del 100% para las 3 rondas de consulta. En la primera ronda se logró acuerdo en 35 preguntas, en la segunda ronda 37 y en la tercera ronda se logró el acuerdo de las 42 preguntas. CONCLUSIÓN: La recomendación para la mayoría de los tratamientos inmunomoduladores utilizados en reumatología es continuar con las terapias en pacientes que no tengan la infección y suspenderlas en aquellos con diagnóstico de SARS-CoV-2/COVID-19


OBJECTIVE: To produce recommendations for patients with rheumatological diseases receiving immunomodulatory and immunosuppressive therapies (conventional drugs, biologicals, and small molecules) during the COVID-19 pandemic. MATERIALS AND METHODS: The recommendations were determined using the Delphi method as an agreement tool. A panel of experts was formed, with academic backgrounds and research experience in rheumatology. A literature search was conducted and 42 questions were generated. The level of agreement was made with 80% of approval by the participants. RESULTS: A group of eleven rheumatologists from 7 cities in the country participated. The response rate was 100% for the three consultation rounds. In the first round, agreement was reached on 35 questions, on 37 in the second round, and on 42 questions in the third round. CONCLUSION: The recommendation for the majority of the pharmacological treatments used in rheumatology is to continue with immunomodulatory or immunosuppressive therapies in patients who do not have the infection, and to suspend it in patients with a diagnosis of SARS-CoV-2/COVID-19


Asunto(s)
Humanos , Enfermedades Reumáticas/tratamiento farmacológico , Factores Inmunológicos/administración & dosificación , Antirreumáticos/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Enfermedades Reumáticas/complicaciones , Pautas de la Práctica en Medicina , Privación de Tratamiento/tendencias , Infecciones por Coronavirus/epidemiología , Pandemias/estadística & datos numéricos
9.
Trials ; 21(1): 905, 2020 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-33138867

RESUMEN

OBJECTIVES: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19. TRIAL DESIGN: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1). PARTICIPANTS: The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 <300, and lung infiltrates >50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study. INTERVENTION AND COMPARATOR: The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only MAIN OUTCOMES: The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation. RANDOMISATION: Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. BLINDING (MASKING): Single blinded study, with participants blinded to allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients. TRIAL STATUS: Current version of the protocol is "Version 2" dated 29th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).


Asunto(s)
Infecciones por Coronavirus/terapia , Inmunización Pasiva/métodos , Inmunoglobulinas Intravenosas , Neumonía Viral/terapia , Adulto , Betacoronavirus/aislamiento & purificación , Enfermedad Crítica/terapia , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunoglobulinas Intravenosas/efectos adversos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Masculino , Pandemias , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
10.
Urol Clin North Am ; 47(4): 413-417, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33008492

RESUMEN

In recent years, immunotherapy has been the focus of great interest to researchers, clinicians, and the general public. Traditionally cancer therapy has been thought to be limited to surgery, radiation therapy, or chemotherapy. Some clinicians have considered it the so-called fifth pillar of cancer therapy, following surgery, cytotoxic chemotherapy, radiation, and targeted therapy. However, the origins of immunotherapy in cancer treatment reach back at least into the nineteenth century. This article reviews the origins, development, and future of immunotherapy.


Asunto(s)
Factores Inmunológicos/administración & dosificación , Inmunoterapia/métodos , Neoplasias Urológicas/inmunología , Neoplasias Urológicas/terapia , Historia del Siglo XIX , Humanos , Inmunoterapia/historia , Estados Unidos , Neoplasias Urológicas/patología
11.
Artículo en Inglés | MEDLINE | ID: mdl-33031994

RESUMEN

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.


Asunto(s)
Ansiedad/prevención & control , Infecciones por Coronavirus/prevención & control , Depresión/prevención & control , Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Factores Inmunológicos/administración & dosificación , Pandemias/prevención & control , Neumonía Viral/prevención & control , Ansiedad/inmunología , Ansiedad/metabolismo , Ansiedad/virología , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Citocinas/biosíntesis , Citocinas/inmunología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/virología , Depresión/inmunología , Depresión/metabolismo , Depresión/virología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/virología , Ácidos Grasos Omega-3/inmunología , Ácidos Grasos Omega-3/metabolismo , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata/efectos de los fármacos , Factores Inmunológicos/inmunología , Factores Inmunológicos/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/virología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/virología , Neumonía Viral/inmunología , Neumonía Viral/metabolismo , Neumonía Viral/virología
12.
Rheumatol Int ; 40(12): 2015-2021, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32945944

RESUMEN

The objective of this study is to describe the characteristics and outcomes of rheumatic and musculoskeletal disease (RMD) patients who were treated with rituximab and had suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this descriptive study, RMD patients who were treated with rituximab in the last 12 months at the Rheumatology Department of our hospital were screened for SARS-CoV-2 infection via telephone interview and a comprehensive review of clinical health records (01/02/2020-26/05/2020). Those with probable or confirmed SARS-CoV-2 infection were included. In total, 76 patients were screened. Of these, 13 (17.1%) had suspected or confirmed SARS-CoV-2 infection. With regard to these 13 patients, the median age at coronavirus disease (COVID-19) diagnosis was 68 years (range 28-76 years) and 8 (61.5%) were female. Five patients had rheumatoid arthritis, three had systemic vasculitis, two had Sjögren syndrome, and two had systemic lupus erythematosus. Additionally, seven patients (53.8%) had pulmonary involvement secondary to RMD. Eight patients (61.5%) developed severe disease leading to hospitalization, and seven developed bilateral pneumonia and respiratory insufficiency. Of the eight hospitalized patients, five (62.5%) fulfilled the acute respiratory distress syndrome criteria and three developed a critical disease and died. Our cohort had a high rate of severe disease requiring hospitalization (61.5%), with bilateral pneumonia and hyperinflammation leading to a high mortality rate (23.1%). Treatment with rituximab should be considered a possible risk factor for unfavorable outcomes in COVID-19 patients with RMD. However, further study is required to confirm this association.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Infecciones por Coronavirus/mortalidad , Factores Inmunológicos/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Neumonía Viral/mortalidad , Rituximab/efectos adversos , Adulto , Anciano , Artritis Reumatoide/complicaciones , Betacoronavirus , Contraindicaciones de los Medicamentos , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , Estudios Retrospectivos , Rituximab/administración & dosificación , Índice de Severidad de la Enfermedad
13.
PLoS One ; 15(9): e0238844, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32913362

RESUMEN

BACKGROUND: Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of risk of bias or evaluate the certainty of the evidence. Our objective was to perform an updated review, by including new trials, any comparative observational studies, and assessing the certainty of the evidence using the GRADE framework. METHODS: We searched MEDLINE, Embase and the Cochrane Library from 2000 to November 26, 2019. Relevant websites and bibliographies of systematic reviews and guidelines were searched for studies published before 2000. Outcomes of interest were sensitization and adverse events. Risk of bias was evaluated with the Cochrane tool and ROBINS-I. The certainty of the evidence was performed using the GRADE framework. RESULTS: Thirteen randomized trials and eight comparative cohort studies were identified, evaluating 12 comparisons. Although there is some evidence of beneficial treatment effects (e.g., at 6-months postpartum, fewer women who received RhIg at delivery compared to no RhIg became sensitized [70 fewer sensitized women per 1,000 (95%CI: 67 to 71 fewer); I2 = 73%]), due to very low certainty of the evidence, the magnitude of the treatment effect may be overestimated. The certainty of the evidence was very low for most outcomes often due to high risk of bias (e.g., randomization method, allocation concealment, selective reporting) and imprecision (i.e., few events and small sample sizes). There is limited evidence on prophylaxis for invasive fetal procedures (e.g. amniocentesis) in the comparative literature, and few studies reported adverse events. CONCLUSION: Serious risk of bias and low to very low certainty of the evidence is found in existing RCTs and comparative observational studies addressing optimal effectiveness of Rh immunoprophylaxis. Guideline development committees should exercise caution when assessing the strength of the recommendations that inform and influence clinical practice in this area.


Asunto(s)
Factores Inmunológicos/administración & dosificación , Atención Posnatal/normas , Atención Prenatal/normas , Isoinmunización Rh/prevención & control , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Femenino , Enfoque GRADE , Humanos , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Isoinmunización Rh/inmunología
14.
J Interferon Cytokine Res ; 40(10): 469-471, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32881593

RESUMEN

Coronavirus disease 2019 (COVID-19), which is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently emerged as a global health threat. To address this health emergency, various therapeutic approaches are currently under investigation. There is limited evidence on the effectiveness of hydroxychloroquine (HCQ) and chloroquine (CQ) as COVID-19 therapies, and thus World Health Organization (WHO) mentioned that "Current data shows that this drug does not reduce deaths among hospitalized COVID-19 patients, nor help people with mild or moderate disease." CQ and HCQ are typically used for the treatment of malaria but have been recognized for certain beneficial effects in COVID-19 patients based on some clinical outcomes from the clinical treatment of COVID-19. A standard dose of HCQ has been proven effective and less toxic than CQ in COVID-19 patients; however, a comprehensive understanding of a patient's clinical condition is necessary. Based on several hospital findings, the Food and Drug Administration (FDA) has officially cancelled the emergency use authorization for HCQ and CQ for treating hospitalized COVID-19 patients on June 15, 2020. In this review, we highlight both pros and cons of the clinical use of CQ and HCQ in COVID-19 patients.


Asunto(s)
Antiinfecciosos/administración & dosificación , Betacoronavirus/efectos de los fármacos , Cloroquina/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/administración & dosificación , Factores Inmunológicos/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Antiinfecciosos/efectos adversos , Azitromicina/uso terapéutico , Betacoronavirus/crecimiento & desarrollo , Betacoronavirus/patogenicidad , Cloroquina/efectos adversos , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Sinergismo Farmacológico , Humanos , Hidroxicloroquina/efectos adversos , Factores Inmunológicos/efectos adversos , Pandemias , Neumonía Viral/patología , Neumonía Viral/virología , Resultado del Tratamiento
15.
Am J Trop Med Hyg ; 103(4): 1590-1592, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32830642

RESUMEN

The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.


Asunto(s)
Infecciones por Coronavirus/parasitología , Diabetes Mellitus/parasitología , Hipertensión/parasitología , Enfermedades del Sistema Nervioso Periférico/parasitología , Neumonía Viral/parasitología , Strongyloides stercoralis/patogenicidad , Estrongiloidiasis/parasitología , Corticoesteroides/administración & dosificación , Anciano , Animales , Antihelmínticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Betacoronavirus/patogenicidad , Coinfección , Connecticut , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/inmunología , Diabetes Mellitus/virología , Ecuador , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/inmunología , Hipertensión/virología , Factores Inmunológicos/administración & dosificación , Masculino , Pandemias , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inmunología , Enfermedades del Sistema Nervioso Periférico/virología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , Neumonía Viral/virología , Estrongiloidiasis/tratamiento farmacológico , Estrongiloidiasis/inmunología , Estrongiloidiasis/virología
16.
Front Immunol ; 11: 1660, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32760407

RESUMEN

The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. So far, the optimal treatment strategy for severe COVID-19 remains unknown. Intravenous immunoglobulin (IVIg) is a blood product pooled from healthy donors with high concentrations of immunoglobulin G (IgG) and has been used in patients with autoimmune and inflammatory diseases for more than 30 years. In this review, we aim to highlight the known mechanisms of immunomodulatory effects of high-dose IVIg therapy, the immunopathological hypothesis of viral pneumonia, and the clinical evidence of IVIg therapy in viral pneumonia. We then make cautious therapeutic inferences about high-dose IVIg therapy in treating severe COVID-19. These inferences may provide relevant and useful insights in order to aid treatment for COVID-19.


Asunto(s)
Anticuerpos Neutralizantes/uso terapéutico , Betacoronavirus/inmunología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Inmunoglobulina G/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , Adulto , Animales , Anticuerpos Neutralizantes/administración & dosificación , Acrecentamiento Dependiente de Anticuerpo , Niño , Infecciones por Coronavirus/virología , Citocinas/metabolismo , Humanos , Fragmentos Fab de Inmunoglobulinas/metabolismo , Fragmentos Fc de Inmunoglobulinas/metabolismo , Inmunoglobulina G/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Pandemias , Neumonía Viral/virología
17.
J Clin Pharmacol ; 60(10): 1275-1293, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32779201

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic caused by infection with SARS-CoV-2 has led to more than 600 000 deaths worldwide. Patients with severe disease often experience acute respiratory distress characterized by upregulation of multiple cytokines. Immunomodulatory biological therapies are being evaluated in clinical trials for the management of the systemic inflammatory response and pulmonary complications in patients with advanced stages of COVID-19. In this review, we summarize the clinical pharmacology considerations in the development of immunomodulatory therapeutic proteins for mitigating the heightened inflammatory response identified in COVID-19.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Factores Inmunológicos/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Proteínas/administración & dosificación , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Desarrollo de Medicamentos , Humanos , Factores Inmunológicos/farmacología , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Proteínas/inmunología , Proteínas/farmacología
18.
Nephrology (Carlton) ; 25(11): 845-849, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32776624

RESUMEN

COVID-19 remains a global pandemic with more than 10 million cases and half a million deaths worldwide. The disease manifestations in patients with chronic kidney disease and especially those on haemodialysis are still being understood, with only a few overseas case series, and small observational trials thus far. It appears that the disease is more severe in this patient cohort. Part of the pathophysiology of severe COVID-19 is related to accompanying cytokine release syndrome (CRS). Tocilizumab, an interleukin-6 inhibitor, has been trialled for treatment of CRS in COVID-19, but not yet approved. We present a case of an Australian patient on long-term haemodialysis with severe COVID-19 who was successfully treated with Tocilizumab. The peak of her illness was on day 7, with a C-reactive protein of 624 mg/L (reference < 5 mg/L), ferritin of 5293 ng/mL (reference 30-500 ng/mL), and interleukin-6 level 1959.7 pg/mL, consistent with CRS. She was severely hypoxic on a ventilator, with rising inotropic requirements. With the use of Tocilizumab, there was a significant and immediate response in her inflammatory markers, and she made a steady recovery. The patient was discharged home 6 weeks after presentation.


Asunto(s)
Anemia , Anticuerpos Monoclonales Humanizados/administración & dosificación , Infecciones por Coronavirus , Síndrome de Liberación de Citoquinas , Interleucina-6 , Fallo Renal Crónico , Pandemias , Neumonía Viral , Anciano , Anemia/etiología , Anemia/terapia , Transfusión Sanguínea/métodos , Proteína C-Reactiva/análisis , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/terapia , Síndrome de Liberación de Citoquinas/virología , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Interleucina-6/antagonistas & inhibidores , Interleucina-6/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Monitorización Inmunológica/métodos , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/inmunología , Neumonía Viral/terapia , Diálisis Renal/métodos , Respiración Artificial/métodos , Resultado del Tratamiento
19.
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1441-1448, July-Aug. 2020. tab
Artículo en Portugués | LILACS, VETINDEX | ID: biblio-1131488

RESUMEN

A mastite bovina, uma das principais doenças do rebanho leiteiro, caracteriza-se por um processo inflamatório no úbere. A inviabilidade econômica, o impacto ambiental negativo e os resíduos antimicrobianos têm estimulado a pesquisa de outros tratamentos alternativos para a prevenção e o tratamento de doenças na bovinocultura leiteira. O betaglucano é um agente imunomodulador com potencial ação preventiva para doenças infecciosas, inclusive a mastite. Este estudo teve como objetivo avaliar a eficácia do uso do betaglucano, por meio de administração oral, em animais em lactação. Foram utilizadas 20 vacas lactantes, distribuídas em dois grupos, um controle e um tratamento, com 10 animais em cada grupo. O grupo tratamento recebeu 5g/dia, durante 60 dias, de 1,3-1,6 betaglucano isolado da parede celular de Saccharomyces cerevisiae diluído em ração após a ordenha, enquanto o grupo controle recebia somente a ração. Foram realizados os testes de California Mastitis Test (CMT), contagem de células somáticas (CCS), produção de leite e percentual de gordura e proteína no leite. Não houve diferença estatisticamente significativa entre os grupos quanto à CCS, ao CMT, à composição do leite ou produção. Não se observou, portanto, eficácia do uso do betaglucano purificado, administrado por via oral, no controle e na prevenção da mastite em vacas leiteiras, quando comparadas com o grupo controle. Atribuem-se esses resultados, principalmente, à degradação ruminal do produto testado. Sugerem-se, portanto, mais pesquisas utilizando o 1,3-1,6 betaglucano purificado de parede de S. cerevisiae por outras vias de administração, tais como intramamária e subcutânea.(AU)


Bovine mastitis, one of the main diseases of dairy herds, is characterized by an inflammatory process in the udder. The economic and environmental impacts, as well as the residues of antimicrobial drugs have stimulated the research of novel alternative treatments for the prevention and treatment of diseases in dairy production cows. The beta-glucan is an immunomodulator agent, with potential preventive action for infectious diseases, including mastitis. This study aimed to assess the effectiveness of orally administered beta-glucan in lactating cows. 20 lactating cows were used, distributed into two groups, one control and one treatment, with 10 cows in each group. The treatment group received 5g of 1.3-1.6 betaglucan daily for 60 days, isolated from the cell-wall of Saccharomyces cerevisiae diluted into a grain meal, whereas the animals in the control group received only the ration. The California Mastitis Test (CMT), Somatic Cells Counting (SCC), daily production and assessments of fat and protein content in milk were done. There was no statistically significant difference between the groups concerning subclinical mastitis detected by CMT, SCC, milk production and composition regarding protein and fat content. It was not observed, therefore, the effectiveness of the use of purified beta-glucan orally administered on the control or prevention of mastitis in dairy cows. The results are attributed to the ruminal degradation of the product tested. It is, therefore, suggested that more research should be conducted using the 1.3-1.6 beta-glucan purified from the cell wall of S. cerevisiae by other administration means and ruminal protection technologies for the isolated beta-glucan.(AU)


Asunto(s)
Animales , Bovinos , Saccharomyces cerevisiae , beta-Glucanos/administración & dosificación , Mastitis Bovina/prevención & control , Suplementos Dietéticos/análisis , Prebióticos/administración & dosificación , Factores Inmunológicos/administración & dosificación
20.
Gene ; 759: 144987, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-32712065

RESUMEN

BACKGROUND: The immune response is influenced by the administration of omega-3 polyunsaturated fatty acids (PUFA). Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) are affected by PUFA. The combination of evening primrose/hemp seed oil (EPO/HSO) has essential fatty acids (EFAs) for human optimal health due to the favorable ratio of omega-6/omega-3 and antioxidantal properties. The study was conducted to evaluate the effects of EPO/HSO on improving the membrane fatty acids composition of spleen and blood cells and immunologic factors in compared to rapamycin (RAPA) in the EAE model. METHODS AND MATERIALS: Chronic-EAE was induced by induction of MOG in C57BL/6J mice (female, age: 6-8 weeks, weight 18-21). Mice were assigned to 5 groups (6/group) to evaluate the therapeutic effects of EPO/HSO supplement in comparison with rapamycin: A group; EPO/HSO + RAPA, B group; RAPA, C group; EPO/HSO. Results were compared to two control groups (EAE and naive). The fatty acid profile of the spleen and blood cell membrane was evaluated. Real-time-polymerase chain reaction was used for the evaluate the genes expression levels of interleukin (IL) -4, IL-5, and IL-13 in lymphocytes. Also, IL-4 of serum was evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our findings indicated that EPO/HSO therapy significantly increased the percentage of essential fatty acids in cell membrane of the spleen and blood. The relative expression of IL-4, IL-5, and IL-13 genes in lymphocytes and serum level of IL-4 was significantly increased in the HSO/EPO treated group versus other groups. CONCLUSION: These results point to potential therapeutic effects on the repair of the structure of cell membranes and suppression of inflammation by EPO/HSO in EAE.


Asunto(s)
Antioxidantes/uso terapéutico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Ácidos Grasos Esenciales/metabolismo , Factores Inmunológicos/uso terapéutico , Interleucinas/metabolismo , Aceites Vegetales/uso terapéutico , Sirolimus/uso terapéutico , Animales , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Cannabis/química , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Suplementos Dietéticos , Combinación de Medicamentos , Femenino , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/farmacología , Lípidos de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Aceites Vegetales/administración & dosificación , Primula/química , Sirolimus/administración & dosificación
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