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1.
BMJ Open Respir Res ; 8(1)2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33811098

RESUMEN

BACKGROUND: Corticosteroids are a potential therapeutic agent for patients with COVID-19 pneumonia. The RECOVERY (Randomised Trials in COVID-19 Therapy) trial provided data on the mortality benefits of corticosteroids. The study aimed to determine the association between corticosteroid use on mortality and infection rates and to define subgroups who may benefit from corticosteroids in a real-world setting. METHODS: Clinical data were extracted that included demographic, laboratory data and details of the therapy, including the administration of corticosteroids, azithromycin, hydroxychloroquine, tocilizumab and anticoagulation. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission and invasive mechanical ventilation. Outcomes were compared in patients who did and did not receive corticosteroids using the multivariate Cox regression model. RESULTS: 4313 patients were hospitalised with COVID-19 during the study period, of whom 1270 died (29.4%). When administered within the first 7 days after admission, corticosteroids were associated with reduced mortality (OR 0.73, 95% CI 0.55 to 0.97, p=0.03) and decreased transfers to the ICU (OR 0.72, 95% CI 0.47 to 1.11, p=0.02). This mortality benefit was particularly impressive in younger patients (<65 years of age), females and those with elevated inflammatory markers, defined as C reactive protein ≥150 mg/L (p≤0.05), interleukin-6 ≥20 pg/mL (p≤0.05) or D-dimer ≥2.0 µg/L (p≤0.05). Therapy was safe with similar rates of bacteraemia and fungaemia in corticosteroid-treated and non-corticosteroid-treated patients. CONCLUSION: In patients hospitalised with COVID-19 pneumonia, corticosteroid use within the first 7 days of admission decreased mortality and ICU admissions with no associated increase in bacteraemia or fungaemia.


Asunto(s)
Corticoesteroides/uso terapéutico , Hospitalización , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/uso terapéutico , /mortalidad , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Ciudad de Nueva York , Tasa de Supervivencia
2.
Front Public Health ; 9: 652842, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33816427

RESUMEN

Background: The viral shedding time (VST) of SARS-CoV-2 mainly determines its transmission and duration of infectiousness. However, it was heterogeneous in the existing studies. Here, we performed a meta-analysis to comprehensively summarize the VST of SARS-CoV-2. Methods: We searched PubMed, Web of Science, MedRxiv, BioRxiv, CNKI, CSTJ, and Wanfang up to October 25, 2020, for studies that reported VSTs of SARS-CoV-2. Pooled estimates and 95% CIs for the VSTs were calculated using log-transformed data. The VSTs in SARS-CoV-2 infections based on different demographic and clinical characteristics, treatments and specimens were stratified by subgroup analysis. Results: A total of 35 studies involving 3,385 participants met the inclusion criteria. The pooled mean VST was 16.8 days (95% CI: 14.8-19.4, I 2 = 99.56%) in SARS-CoV-2 infections. The VST was significantly longer in symptomatic infections (19.7 days, 95% CI: 17.2-22.7, I 2 = 99.34%) than in asymptomatic infections (10.9 days, 95% CI: 8.3-14.3, I 2 = 98.89%) (P < 0.05). The VST was 23.2 days (95% CI: 19.0-28.4, I 2 = 99.24%) in adults, which was significantly longer than that in children (9.9 days, 95% CI: 8.1-12.2, I 2 = 85.74%) (P < 0.05). The VST was significantly longer in persons with chronic diseases (24.2 days, 95% CI: 19.2-30.2, I 2 = 84.07%) than in those without chronic diseases (11.5 days, 95% CI: 5.3-25.0, I 2 = 82.11%) (P < 0.05). Persons receiving corticosteroid treatment (28.3 days, 95% CI: 25.6-31.2, I 2 = 0.00%) had a longer VST than those without corticosteroid treatment (16.2 days, 95% CI: 11.5-22.5, I 2 = 92.27%) (P = 0.06). The VST was significantly longer in stool specimens (30.3 days, 95% CI: 23.1-39.2, I 2 = 92.09%) than in respiratory tract specimens (17.5 days, 95% CI: 14.9-20.6, I 2 = 99.67%) (P < 0.05). Conclusions: A longer VST was found in symptomatic infections, infected adults, persons with chronic diseases, and stool specimens.


Asunto(s)
/virología , Esparcimiento de Virus , Corticoesteroides/uso terapéutico , Adulto , Infecciones Asintomáticas , Niño , Comorbilidad , Heces/virología , Humanos
3.
BMJ Case Rep ; 14(4)2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33827880

RESUMEN

A 77-year-old man was admitted with severe acute kidney injury and nephrotic syndrome. He was started on eltrombopag for chronic idiopathic thrombocytopenic purpura 6 weeks earlier. An ultrasound of the kidneys was normal and an auto-antibody screen was negative. The use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of acute renal failure and eltrombopag therapy. Literature review identified only one other case of nephrotic syndrome and acute kidney injury associated with eltrombopag therapy in which a kidney biopsy revealed focal segmental glomerulosclerosis. Due to the challenges faced during the prevailing SARS-CoV-2 pandemic and persistent low platelet counts a renal biopsy was not undertaken. On stopping eltrombopag, the patients renal function stabilised and he successfully went into remission following treatment with high dose corticosteroids and diuretics. This report of a serious case of reversible renal failure and nephrotic syndrome after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before its commencement for future use.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Benzoatos/efectos adversos , Hidrazinas/efectos adversos , Síndrome Nefrótico/inducido químicamente , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/efectos adversos , Corticoesteroides/uso terapéutico , Anciano , Humanos , Riñón/efectos de los fármacos , Masculino
4.
BMC Infect Dis ; 21(1): 337, 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33838657

RESUMEN

BACKGROUND: Although almost a year has passed since the Coronavirus disease 2019 (COVID-19) outbreak and promising reports of vaccines have been presented, we still have a long way until these measures are available for all. Furthermore, the most appropriate corticosteroid and dose in the treatment of COVID-19 have remained uncertain. We conducted a study to assess the effectiveness of methylprednisolone treatment versus dexamethasone for hospitalized COVID-19 patients. METHODS: In this prospective triple-blinded randomized controlled trial, we enrolled 86 hospitalized COVID-19 patients from August to November 2020, in Shiraz, Iran. The patients were randomly allocated into two groups to receive either methylprednisolone (2 mg/kg/day; intervention group) or dexamethasone (6 mg/kg/day; control group). Data were assessed based on a 9-point WHO ordinal scale extending from uninfected (point 0) to death (point 8). RESULTS: There were no significant differences between the groups on admission. However, the intervention group demonstrated significantly better clinical status compared to the control group at day 5 (4.02 vs. 5.21, p = 0.002) and day 10 (2.90 vs. 4.71, p = 0.001) of admission. There was also a significant difference in the overall mean score between the intervention group and the control group, (3.909 vs. 4.873 respectively, p = 0.004). The mean length of hospital stay was 7.43 ± 3.64 and 10.52 ± 5.47 days in the intervention and control groups, respectively (p = 0.015). The need for a ventilator was significantly lower in the intervention group than in the control group (18.2% vs 38.1% p = 0.040). CONCLUSION: In hospitalized hypoxic COVID-19 patients, methylprednisolone demonstrated better results compared to dexamethasone. TRIAL REGISTRATION: The trial was registered with IRCT.IR (08/04/2020-No. IRCT20200204046369N1 ).


Asunto(s)
/tratamiento farmacológico , Dexametasona/uso terapéutico , Metilprednisolona/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Anciano , Femenino , Hospitalización , Humanos , Irán , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Respiración Artificial , Resultado del Tratamiento
6.
Recenti Prog Med ; 112(3): 195-206, 2021 03.
Artículo en Italiano | MEDLINE | ID: mdl-33687358

RESUMEN

BACKGROUND: SARS-CoV-2 is a coronavirus that causes a disease which can leads to a severe form of fatal pneumonia. At december 2020 in Italy, more than 2 million people have contracted the virus and 78,755 people have died. The scientific community is studying and testing numerous compounds that can be effective and safe for treating people with covid-19. AIM: To synthesize and evaluate the quality of evidence of efficacy and safety for the treatment. The available evidence is summarized in a living systematic review, a review that is constantly updated on the basis of the results of the new clinical studies. METHODS: A bibliographic search is launched weekly on the electronic databases and on the main clinical trial registers. Two researchers independently select the articles and assess the quality of the studies using the criteria developed by the Cochrane Collaboration, the certainty of the overall quality of the evidence is assessed using the GRADE criteria. RESULTS: At 31/12/2020, 101 randomized controlled studies were included that consider 72 different comparisons and include a total of 55,281 patients. 37 drugs are tested with respect to the standard treatment, 6 are evaluated against placebo and finally 29 compare different drugs with each other. By selecting studies that evaluate the efficacy and safety of a drug compared to standard treatment, which include at least 2 studies and which have low to high certainty of evidence, results show that corticosteroids, remdesivir, favipiravir, immunoglobulins, colchicine, and umbilical cord mesenchymal stem cell infusion could reduce overall mortality. No differences for the risk of any adverse events are observed between convalescent plasma and remdesivir compared to standard treatment. Remdesivir probably reduces the risk of serious adverse events; a similar effect, although less strong, is also noted for tocilizumab and the lopinavir-ritonavir combination. In contrast, hydroxychloroquine, corticosteroids and convalescent plasma transfusion are associated with safety concerns with respect to the risk of serious adverse events. CONCLUSIONS: The 101 studies included consider 72 comparisons and numerous outcomes, the results often coming from single studies and of small dimensions, and for 61% with a very low certainty of evidence, are difficult to summarize and the final result is to increase the uncertainty rather than providing useful information to the clinic and research. From all the work carried out it seems to us that the pandemic has highlighted the many shadows of scientific literature as tool to improve knowledge.


Asunto(s)
Antivirales/uso terapéutico , /tratamiento farmacológico , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Alanina/efectos adversos , Alanina/análogos & derivados , Alanina/uso terapéutico , Amidas/efectos adversos , Amidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/efectos adversos , Antivirales/farmacología , /terapia , Terapia Combinada , Combinación de Medicamentos , Reposicionamiento de Medicamentos , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Inmunoglobulinas Intravenosas/uso terapéutico , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Trasplante de Células Madre Mesenquimatosas , Pandemias , Pirazinas/efectos adversos , Pirazinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Resultado del Tratamiento , Incertidumbre
7.
Future Microbiol ; 16: 317-322, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33709775

RESUMEN

The host inflammatory response is critical in the progression of lung injuries in patients with SARS-CoV-2. Corticosteroids (CS) have been widely used as immunomodulating agents, but the right timing, dosage and type of molecule are unknown. In fact, the early use of CS could facilitate the viral replication but late administration may not prevent the alveolar damage. Nevertheless, a short administration of high doses of CS in the early stage of the inflammatory phase resulted in favorable outcomes. Noteworthy, some inhaled CS inhibited in vitro the viral replication of SARS-CoV-2. We aimed to define the place in therapy for CS in COVID-19 infection describing the features of patients who may benefit from their administration.


Asunto(s)
Corticoesteroides/uso terapéutico , Inflamación/tratamiento farmacológico , Administración por Inhalación , Corticoesteroides/administración & dosificación , Guías como Asunto , Humanos , Inflamación/virología , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo
8.
Artículo en Inglés | MEDLINE | ID: mdl-33753426

RESUMEN

BACKGROUND: The impact of COVID-19 on pregnant inflammatory bowel disease (IBD) patients is currently unknown. Reconfiguration of services during the pandemic may negatively affect medical and obstetric care. We aimed to examine the impacts on IBD antenatal care and pregnancy outcomes. METHODS: Retrospective data were recorded in consecutive patients attending for IBD antenatal care including outpatient appointments, infusion unit visits and advice line encounters. RESULTS: We included 244 pregnant women with IBD, of which 75 (30.7%) were on biologics in whom the treatment was stopped in 29.3% at a median 28 weeks gestation. In addition, 9% of patients were on corticosteroids and 21.5% continued on thiopurines. The care provided during 460 patient encounters was not affected by the pandemic in 94.1% but 68.2% were performed via telephone (compared with 3% prepandemic practice; p<0.0001). One-hundred-ten women delivered 111 alive babies (mean 38.2 weeks gestation, mean birth weight 3324 g) with 12 (11.0%) giving birth before week 37. Birth occurred by vaginal delivery in 72 (56.4%) and by caesarean section in 48 (43.6%) cases. Thirty-three were elective (12 for IBD indications) and 15 emergency caesarean sections. Breast feeding rates were low (38.6%). Among 244 pregnant women with IBD, 1 suspected COVID-19 infection was recorded. CONCLUSION: IBD antenatal care adjustments during the COVID-19 pandemic have not negatively affected patient care. Despite high levels of immunosuppression, only a single COVID-19 infection occurred. Adverse pregnancy outcomes were infrequent.


Asunto(s)
/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Atención Prenatal/estadística & datos numéricos , Corticoesteroides/uso terapéutico , Adulto , Alopurinol/análogos & derivados , Alopurinol/uso terapéutico , Productos Biológicos/uso terapéutico , Lactancia Materna/estadística & datos numéricos , /epidemiología , Cesárea/estadística & datos numéricos , Parto Obstétrico/estadística & datos numéricos , Femenino , Edad Gestacional , Humanos , Enfermedades Inflamatorias del Intestino/virología , Embarazo , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Reino Unido/epidemiología , Privación de Tratamiento
9.
Medicine (Baltimore) ; 100(12): e25171, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761695

RESUMEN

RATIONALE: Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection. It has an aggressive clinical course; however, it usually does not recur after recovery in cases of spontaneous ANE. Nevertheless, there are several studies reporting recurrences in familial ANE with RAN-binding protein 2 (RANBP2) mutation. There are few cases of familial ANE with RANBP2 mutation in Asian populations. PATIENTS CONCERNS: A 21-month-old Korean boy who was previously healthy, presented with seizure following parainfluenza - a virus and bocavirus infection, followed by 2 recurrent seizure episodes and encephalitis after febrile respiratory illnesses. Meanwhile, his 3-year-old sister had focal brain lesions on neuroimaging studies when evaluated for head trauma. The siblings also had an older brother who presented status epilepticus after febrile respiratory illness at the age of 10 months old. DIAGNOSIS: Brain magnetic resonance imaging was performed to evaluate the seizure and neurologic symptoms. Imaging findings showed variable spectrum - from non-specific diffuse white matter injury pattern to typical "tricolor pattern" of the ANE on diffusion-weighted images. The other 2 siblings showed focal lesions in both external capsules and severe diffuse brain edema. Genetic tests identified a heterozygous missense mutation in the RANBP2 [c.1754C>T (p.Thr585Met)] in 2 siblings and their mother. INTERVENTIONS: Patients were treated conservatively with anticonvulsive agents, intravascular immunoglobulin, and steroids. OUTCOMES: Among the 3 siblings, 2 male siblings died from familial ANE, whereas the female sibling was asymptomatic. LESSONS: These cases highlight the radiological aspects of familial ANE with incomplete penetrance of the RANBP2 gene in 3 family members, showing variable involvements of the brain and natural history on magnetic resonance images. Radiologists should be aware of the typical and atypical imaging findings of familial ANE for prompt management of affected patients.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Leucoencefalitis Hemorrágica Aguda/diagnóstico por imagen , Leucoencefalitis Hemorrágica Aguda/genética , Chaperonas Moleculares/genética , Mutación Missense , Proteínas de Complejo Poro Nuclear/genética , Corticoesteroides/uso terapéutico , Anticonvulsivantes/uso terapéutico , Preescolar , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Leucoencefalitis Hemorrágica Aguda/complicaciones , Leucoencefalitis Hemorrágica Aguda/tratamiento farmacológico , Masculino , Penetrancia , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Sustancia Blanca/diagnóstico por imagen , Adulto Joven
10.
Medicine (Baltimore) ; 100(8): e24541, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663060

RESUMEN

BACKGROUND: IgA nephropathy (IgAN) is one of the significant contributing factors of end-stage renal disease (ESRD). It is reported that over half of patients with IgAN accompany multiple high-risk factors, which increase the risk of ESRD progression. Studies have shown that immunosuppressive agents were beneficial in high-risk IgAN, but the efficacy and safety have not been fully demonstrated yet. The present study aims to elucidate the efficacy of commonly used immunosuppressants in high-risk IgAN and their relative safety profiles via a network meta-analysis strategy. METHODS: Randomized controlled trials (RCTs) eligible for this network meta-analysis were included to evaluate the efficacy and safety of different immunosuppressants for high-risk IgAN. Main outcomes and measures include incidence of renal composite end point, the rate of total remission, adverse events, and proteinuria. Besides, subgroup analysis and cluster analysis were carried out. RESULTS: This network meta-analysis of 37 RCTs involving 3012 participants found that Mycophenolate mofetil (MMF) combined with corticosteroids (CS) was superior to other interventions in end point events and proteinuria. Cyclosporine A (CsA) plus CS was the best option for clinical remission rate, and supportive care (SC) was the safest treatment. Cluster analysis showed that MMF+CS and Leflunomide (LEF)+CS were best protocols in efficacy and safety. Subgroup analysis indicated the best benefits of MMF were presented among the Asian population, and the benefits increased with the increase of follow-up duration. The effect of Cyclophosphamide (CTX) +CS on crescent IgAN was better than that of other risk factors. Moreover, the increasing follow-up duration was negatively associated with the effect. CONCLUSIONS: MMF+CS and LEF+CS appear to serve as the best choice for treating high-risk IgAN than other immunosuppressive therapies.


Asunto(s)
Glomerulonefritis por IGA/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Corticoesteroides/uso terapéutico , Ciclofosfamida/uso terapéutico , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Tasa de Filtración Glomerular , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Ácido Micofenólico/uso terapéutico , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto
11.
Infez Med ; 29(1): 20-36, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33664170

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative pathogen for the COVID-19, first emerged in Wuhan, China, in December 2019 and by March 2020, it was declared a pandemic. COVID-19 pandemic has overburdened healthcare systems in most countries and has led to massive economic losses. SARS-CoV-2 transmission typically occurs by respiratory droplets. The average incubation period is 6.4 days and presenting symptoms typically include fever, cough, dyspnea, myalgia or fatigue. While the majority of patients tend to have a mild illness, a minority of patients develop severe hypoxia requiring hospitalization and mechanical ventilation. Management is mostly supportive. However, several direct anti-viral agents, and immunomodulatory therapy with steroids and various cytokine blockers seem promising in early results. However, an effective vaccine has been established, which will help curb the pandemic.


Asunto(s)
Salud Global/estadística & datos numéricos , Pandemias , /patogenicidad , Corticoesteroides/uso terapéutico , Microbiología del Aire , Antivirales/uso terapéutico , /diagnóstico , /terapia , /uso terapéutico , Transmisión de Enfermedad Infecciosa , Hospitalización , Humanos , Hipoxia/etiología , Hipoxia/terapia , Inmunización Pasiva , Factores Inmunológicos/uso terapéutico , Periodo de Incubación de Enfermedades Infecciosas , Prevención Primaria/métodos , Respiración Artificial , /genética , Esteroides/uso terapéutico , Evaluación de Síntomas/métodos
12.
BMC Pharmacol Toxicol ; 22(1): 14, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33706794

RESUMEN

BACKGROUND: The impact of prior exposure to systemic corticosteroids on COVID-19 severity in patients hospitalized for a SARS-CoV-2 pneumonia is not known. The present study was designed to answer to this question. METHODS: The population study was the Covid-Clinic-Toul cohort which records data about all hospitalized patients with a positive reverse transcriptase polymerase chain reaction for a SARS-CoV-2 infection at Toulouse University hospital, France. Exposure to systemic corticosteroids was assessed at hospital admission. A propensity score (PS) according to corticosteroid exposure was calculated including comorbidities, clinical, radiological and biological variables that impact COVID-19 severity. The primary outcome was composite, including admission to intensive care unit, need of mechanical ventilation and death occurring during the 14 days after hospital admission. Logistic regression models adjusted for the PS (overlap weighting) provided odds ratios (ORs) and their 95% confidence intervals (95% CIs). RESULTS: Overall, 253 patients were included in the study. Median age was 64 years, 140 patients (59.6%) were men and 218 (86.2%) had at least one comorbidity. Seventeen patients (6.7%) were exposed to corticosteroids before hospital admission. Chronic inflammatory disease (n = 8) was the most frequent indication. One hundred and twenty patients (47.4%) met the composite outcome. In the crude model, the OR of previous exposure to systemic corticosteroids was 1.64; 95% CI: 0.60-4.44. In the adjusted model, it was 1.09 (95% CI: 0.65-1.83). CONCLUSION: Overall, this study provide some evidences for an absence of an increased risk of unfavorable outcome with previous exposure to corticosteroids in the general setting of patients hospitalized for COVID-19.


Asunto(s)
Corticoesteroides/uso terapéutico , /tratamiento farmacológico , Anciano , Estudios de Cohortes , Comorbilidad , Cuidados Críticos/estadística & datos numéricos , Femenino , Hospitalización , Humanos , Inflamación/tratamiento farmacológico , Inflamación/etiología , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Respiración Artificial/estadística & datos numéricos , Resultado del Tratamiento
14.
Adv Exp Med Biol ; 1303: 1-12, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33788184

RESUMEN

The mechanisms driving corticosteroid insensitivity in asthma are still unclear although evidence points toward a potential role of lung mast cells. Indeed, a number of in vitro studies using various cell types showed that different mediators produced by activated mast cells, including cytokines, have the capacity to interfere with the therapeutic action of corticosteroids. In patients with severe allergic refractory asthma, the anti-IgE monoclonal antibody (mAb), Omalizumab, has been shown to be associated with a marked reduction in inhaled and systemic use of corticosteroids, further suggesting a key role of mast cells in the poor response of patients to these drugs. The present chapter will discuss the possible underlying mechanisms by which mast cells could contribute to reducing corticosteroid sensitivity seen in patients with severe asthma.


Asunto(s)
Asma , Mastocitos , Corticoesteroides/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Asma/tratamiento farmacológico , Humanos
15.
Front Immunol ; 12: 632890, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732254

RESUMEN

Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. MIS-C linked to COVID-19 teaches us infection-associated autoimmune vasculitis and vice versa. Studies on genetic susceptibility have identified certain human leukocyte antigen (HLA) locus and toll-like receptor (TLR) associated with KD and/or COVID-19. Certain HLA subtypes, such as HLA-DRB1 and HLA-MICA A4 are associated with KD. HLA-B*46:01 is proposed to be the risk allele of severe COVID-19 infection, and blood group O type is a protective factor of COVID-19. The autoimmune vasculitis of KD, KD shock syndrome (KDSS), or MIS-C is mediated by a genetic variant of HLA, FcγR, and/or antibody-dependent enhancement (ADE) resulting in hyperinflammation with T helper 17 (Th17)/Treg imbalance with augmented Th17/Th1 mediators: interleukin-6 (IL-6), IL-10, inducible protein-10 (IP-10), Interferon (IFNγ), and IL-17A, and lower expression of Treg-signaling molecules, FoxP3, and transforming growth factor (TGF-ß). There are certain similarities and differences in phenotypes, susceptibility, and pathogenesis of KD, KDSS, and MIS-C, by which a physician can make early protection, prevention, and precision treatment of the diseases. The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called "Know thyself, enemy (pathogen), and ever-victorious" strategy for the prevention and immunotherapy of KD and/or MIS-C.


Asunto(s)
Autoinmunidad , /terapia , Predisposición Genética a la Enfermedad/genética , Inmunoterapia/métodos , Síndrome Mucocutáneo Linfonodular/inmunología , Síndrome Mucocutáneo Linfonodular/terapia , Fenotipo , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Adolescente , Corticoesteroides/uso terapéutico , /virología , Niño , Preescolar , Citocinas/sangre , Femenino , Antígenos HLA/genética , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/genética , Síndrome de Respuesta Inflamatoria Sistémica/genética , Síndrome de Respuesta Inflamatoria Sistémica/virología
16.
Medicine (Baltimore) ; 100(11): e25130, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725992

RESUMEN

BACKGROUND: Postoperative atrial fibrillation (POAF) occurs commonly after cardiac surgery. Studies suggest that corticosteroid can reduce the incident of POAF. However, the results remain controversial. This meta-analysis aimed to evaluate the efficacy and safety corticosteroid on the prevention of POAF following cardiac surgery. METHODS: Randomized controlled trials were identified through a systematic literature search. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Primary outcome was the incidence of POAF as well as length of hospital stay and intensive care unit stay, wound and other infection, mortality, duration of ventilation, myocardial infarction, gastrointestinal complications, high blood sugar, stroke, and postoperative bleeding. RESULTS: Fourteen studies with 13,803 patients were finally involved in the present study. Overall, corticosteroid significantly decreased the risk of POAF (relative risk [RR], 0.7; 95% confidence interval [CI], 0.55-0.89; P = .003). There were no significant differences in the incidence of length of intensive care unit stay (RR, -2.32; 95% CI, -5.44 to 0.80; P = .14) and hospital stay (RR, -0.43; 95% CI, -0.84 to -0.02; P = .04), infections (RR, 1.01; 95% CI, 0.83-1.23; P = .9), mortality (RR, 0.87; 95% CI, 0.71-1.06; P = .16), duration of ventilation (RR, -0.29; 95% CI, -0.65 to 0.07; P = .12), gastrointestinal complications (RR, 1.26; 95% CI, 0.91-1.76; P = .16), high blood sugar (RR, 1.98; 95% CI, 0.91-4.31; P = .09), stroke (RR, 0.9; 95% CI, 0.69-1.18; P = .45), postoperative bleeding (RR -44.54; 95% CI, -115.28 to 26.20; P = .22) and myocardial infarction (RR, 1.71; 95% CI, 0.96-1.43; P = .12). CONCLUSION: Our review suggests that the efficacy of corticosteroid might be beneficial to POAF development in patients undergoing cardiac surgery. The strength of this association remains uncertain because of statistical and clinical heterogeneity among the included studies.


Asunto(s)
Corticoesteroides/uso terapéutico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/prevención & control , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Posoperatorias , Anciano , Femenino , Humanos , Incidencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Riesgo , Factores de Tiempo , Resultado del Tratamiento
17.
Cir Cir ; 89(2): 269-274, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33784290

RESUMEN

ANTECEDENTES: En diciembre de 2019 se identificó en la ciudad de Wuhan, China, un nuevo beta coronavirus, el SARS-CoV-2, como agente causal de neumonía grave, conocida como COVID-19, lo cual ha provocado medidas estrictas de aislamiento, cierre de programas de trasplante hepático y la necesidad de modificar los protocolos de tratamiento. OBJETIVO: Documentar la información publicada sobre el impacto de la COVID-19 en la población con antecedente de trasplante hepático y establecer un protocolo de tratamiento. MÉTODO: Se buscaron en PubMed los términos MeSH "SARS-CoV-2", "COVID-19", "trasplante hepático" y "tratamiento". RESULTADOS: Hasta el momento se ha demostrado en la población con trasplante hepático una mayor facilidad para adquirir el virus, sin una diferencia en la mortalidad al compararla con la población general. La inmunosupresión debe continuar, sin suspender los inhibidores de la calcineurina. Del tratamiento específico, los esteroides son los que han demostrado el mayor beneficio clínico y una disminución de la mortalidad. CONCLUSIÓN: El trasplante hepático no se asocia de manera independiente a una mayor mortalidad. Otros factores, además del trasplante, deben tomarse en cuenta al momento de establecer la gravedad. BACKGROUND: In December 2019, a new beta coronavirus, SARS-CoV-2, was identified in the city of Wuhan, China, as a causative agent of severe pneumonia, known as COVID-19, which has led to strict isolation measures, closure of liver transplantation programs and the need to modify treatment protocols. OBJECTIVE: Document the information published so far on the impact of COVID-19 in the population with a history of liver transplantation and establish a treatment protocol. METHOD: MeSH terms were searched for "SARS-CoV-2", "COVID-19", "liver transplantation" and "treatment". RESULTS: Up to now, a greater ease in acquiring the virus has been shown in the liver transplant population, without a difference in mortality when compared to the general population. Immunosuppression should continue at the minimum tolerated levels, without suspending calcineurin inhibitors. Of the specific treatment, steroids are those that have shown the greatest clinical benefit and decreased mortality. CONCLUSION: Liver transplantation is not independently associated with higher mortality. Factors other than transplantation must be taken into account when considering the risk of severity.


Asunto(s)
/epidemiología , Huésped Inmunocomprometido , Trasplante de Hígado , Pandemias , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Corticoesteroides/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Transfusión de Componentes Sanguíneos , /transmisión , Rechazo de Injerto/prevención & control , Humanos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Inmunosupresores/administración & dosificación , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Listas de Espera , Privación de Tratamiento
18.
Mediators Inflamm ; 2021: 6637227, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33776574

RESUMEN

Objectives: To assess the influence of corticosteroid pulses on 60-day mortality in hospitalized patients with severe COVID-19. Methods: We designed a multicenter retrospective cohort study in three teaching hospitals of Castilla y León, Spain (865,096 people). We selected patients with confirmed COVID-19 and lung involvement with a pO2/FiO2<300, excluding those exposed to immunosuppressors before or during hospitalization, patients terminally ill at admission, or those who died in the first 24 hours. We performed a propensity score matching (PSM) adjusting covariates that modify the probability of being treated. Then, we used a Cox regression model in the PSM group to consider factors affecting mortality. Results: From 2933 patients, 257 fulfilled the inclusion and exclusion criteria. 124 patients were on corticosteroid pulses (250 mg of methylprednisolone for three days), and 133 were not. 30.3% (37/122) of patients died in the corticosteroid pulse group and 42.9% (57/133) in the nonexposed cohort. These differences (12.6%, 95% CI [8·54-16.65]) were statically significant (log-rank 4.72, p = 0, 03). We performed PSM using the exact method. Mortality differences remained in the PSM group (log-rank 5.31, p = 0.021) and were still significant after a Cox regression model (HR for corticosteroid pulses 0.561; p = 0.039). Conclusions: This study provides evidence about treatment with corticosteroid pulses in severe COVID-19 that might significantly reduce mortality. Strict inclusion and exclusion criteria with that selection process set a reliable frame to compare mortality in both the exposed and nonexposed groups.


Asunto(s)
Corticoesteroides/uso terapéutico , /mortalidad , Hospitalización , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunosupresores/uso terapéutico , Pacientes Internos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , España/epidemiología , Resultado del Tratamiento
19.
PLoS One ; 16(3): e0248132, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33705495

RESUMEN

BACKGROUND: COVID-19 is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. This is the second edition of a living systematic review of randomized clinical trials assessing the effects of all treatment interventions for participants in all age groups with COVID-19. METHODS AND FINDINGS: We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review was based on PRISMA and Cochrane guidelines, and our eight-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. According to the number of outcome comparisons, we adjusted our threshold for significance to p = 0.033. We used GRADE to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until November 2, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 82 randomized clinical trials enrolling a total of 40,249 participants. 81 out of 82 trials were at overall high risk of bias. Meta-analyses showed no evidence of a difference between corticosteroids versus control on all-cause mortality (risk ratio [RR] 0.89; 95% confidence interval [CI] 0.79 to 1.00; p = 0.05; I2 = 23.1%; eight trials; very low certainty), on serious adverse events (RR 0.89; 95% CI 0.80 to 0.99; p = 0.04; I2 = 39.1%; eight trials; very low certainty), and on mechanical ventilation (RR 0.86; 95% CI 0.55 to 1.33; p = 0.49; I2 = 55.3%; two trials; very low certainty). The fixed-effect meta-analyses showed indications of beneficial effects. Trial sequential analyses showed that the required information size for all three analyses was not reached. Meta-analysis (RR 0.93; 95% CI 0.82 to 1.07; p = 0.31; I2 = 0%; four trials; moderate certainty) and trial sequential analysis (boundary for futility crossed) showed that we could reject that remdesivir versus control reduced the risk of death by 20%. Meta-analysis (RR 0.82; 95% CI 0.68 to 1.00; p = 0.05; I2 = 38.9%; four trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of difference between remdesivir versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of remdesivir on serious adverse events. Meta-analysis (RR 0.40; 95% CI 0.19 to 0.87; p = 0.02; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of intravenous immunoglobulin versus control on all-cause mortality, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analysis (RR 0.63; 95% CI 0.35 to 1.14; p = 0.12; I2 = 77.4%; five trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of a difference between tocilizumab versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of tocilizumab on serious adverse events. Meta-analysis (RR 0.70; 95% CI 0.51 to 0.96; p = 0.02; I2 = 0%; three trials; very low certainty) showed evidence of a beneficial effect of tocilizumab versus control on mechanical ventilation, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm of reject realistic intervention effects. Meta-analysis (RR 0.32; 95% CI 0.15 to 0.69; p < 0.00; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of bromhexine versus standard care on non-serious adverse events, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that hydroxychloroquine versus control reduced the risk of death and serious adverse events by 20%. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that lopinavir-ritonavir versus control reduced the risk of death, serious adverse events, and mechanical ventilation by 20%. All remaining outcome comparisons showed that we did not have enough information to confirm or reject realistic intervention effects. Nine single trials showed statistically significant results on our outcomes, but were underpowered to confirm or reject realistic intervention effects. Due to lack of data, it was not relevant to perform network meta-analysis or possible to perform individual patient data meta-analyses. CONCLUSIONS: No evidence-based treatment for COVID-19 currently exists. Very low certainty evidence indicates that corticosteroids might reduce the risk of death, serious adverse events, and mechanical ventilation; that remdesivir might reduce the risk of serious adverse events; that intravenous immunoglobin might reduce the risk of death and serious adverse events; that tocilizumab might reduce the risk of serious adverse events and mechanical ventilation; and that bromhexine might reduce the risk of non-serious adverse events. More trials with low risks of bias and random errors are urgently needed. This review will continuously inform best practice in treatment and clinical research of COVID-19. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178787.


Asunto(s)
/terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Corticoesteroides/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Bromhexina/uso terapéutico , /mortalidad , Ensayos Clínicos como Asunto , Expectorantes/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Respiración Artificial , /aislamiento & purificación , Resultado del Tratamiento
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