Therapeutic Effect Of Corticosteroids Research Articles

Role of corticosteroids in the treatment of critically ill sepsis patients: a meta-analysis review.

It was to systematically evaluate the effect of corticosteroids on 28d all-cause mortality (ACM), in-hospital death rate, and ICU death rate in critically ill sepsis patients. PubMed, Embase, and Medline databases were used to screen the published literatures on the therapeutic effect of corticosteroids in the treatment of critically ill sepsis patients. After evaluating the quality of the included literatures, RevMan 5.3 software was used for meta-analysis. 4524 literatures regarding the application of corticosteroids to treat critically ill sepsis patients were preliminarily searched. After screening was carried out, 9 literatures were finally included. 2,850 patients were treated with corticosteroids and 2867 patients were treated with placebo. The meta-analysis of the effect of corticosteroids versus placebo on 28dACM showed [OR = 0.87, 95% CI 0.78-0.98, Z = 2.22, P = 0.03], P < 0.05; the meta-analysis of the outcome of corticosteroids versus placebo on ICU death rate showed [OR = 0.77, 95% CI 0.63-0.94, Z = 2.60, P = 0.009], P < 0.05; and the meta-analysis of the effect of corticosteroids versus placebo on in-hospital death rate showed [OR = 0.80, 95% CI 0.66-0.96, Z = 2.34, P = 0.002], P < 0.05. In summary, corticosteroids can reduce the death rate of critically ill sepsis patients to a certain extent and have good clinical application value.

Steroid-sensitive nephrotic syndrome candidate gene CLVS1 regulates podocyte oxidative stress and endocytosis.

We performed next-generation sequencing in patients with familial steroid-sensitive nephrotic syndrome (SSNS) and identified a homozygous segregating variant (p.H310Y) in the gene encoding clavesin-1 (CLVS1) in a consanguineous family with 3 affected individuals. Knockdown of the clavesin gene in zebrafish (clvs2) produced edema phenotypes due to disruption of podocyte structure and loss of glomerular filtration barrier integrity that could be rescued by WT CLVS1 but not the p.H310Y variant. Analysis of cultured human podocytes with CRISPR/Cas9-mediated CLVS1 knockout or homozygous H310Y knockin revealed deficits in clathrin-mediated endocytosis and increased susceptibility to apoptosis that could be rescued with corticosteroid treatment, mimicking the steroid responsiveness observed in patients with SSNS. The p.H310Y variant also disrupted binding of clavesin-1 to α-tocopherol transfer protein, resulting in increased reactive oxygen species (ROS) accumulation in CLVS1-deficient podocytes. Treatment of CLVS1-knockout or homozygous H310Y-knockin podocytes with pharmacological ROS inhibitors restored viability to control levels. Taken together, these data identify CLVS1 as a candidate gene for SSNS, provide insight into therapeutic effects of corticosteroids on podocyte cellular dynamics, and add to the growing evidence of the importance of endocytosis and oxidative stress regulation to podocyte function.

Extensively disturbance of regulatory T cells - Th17 cells balance in stage II pulmonary sarcoidosis.

Background: Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Not enough evidences correlate the derangement of CD4+ T subsets, which have an impact on the therapeutic effects of corticosteroids, with the radiographical staging of sarcoidosis. Here we show the disturbance of CD4+ T subsets in newly diagnosed stage II pulmonary sarcoidosis, which is the most common stage in which corticosteroids treatment is used.Materials and methods: 39 newly diagnosed and treatment-naïve patients and 9 subjects after corticosteroids treatment were included. CD4+ CD45RA+/ CD45RO+ cells, CCR4+ CCR6+ cells, and T regulatory cells (Tregs) were tested by Flow Cytometry Analysis. Th1/Th2, Tregs/Th17 related cytokines and mRNAs, SAA and CCL20 were also measured. The activation of PI3K/PTEN/Akt signaling pathway was detected.Results: Percentages of CD4+CD45RO+ memory T cells and Tregs, serum levels of IL-17A, TGF-β1, IL-6, IFN-γ, IL-10, SAA and CCL20, copies of T-bet, FoxP3, IL-17 and RORc in the periphery were elevated in newly diagnosed stage II pulmonary sarcoidosis patients. Additionally, PI3K/Akt signaling pathway was activated in bronchoalveolar lavage fluid cells.Conclusions: Disturbance of T memory cells, Th1/Th2, and Tregs/Th17 cells, and activation of PI3K/Akt signaling were seen in newly diagnosed stage II pulmonary sarcoidosis, which can be partly ameliorated by corticosteroids treatment.

Corticosteroid treatment of childhood Bell’s palsy

The therapeutic effect of corticosteroids in acute idiopathic peripheral nerve paralysis (Bell’s palsy) in children is controversial. The authors evaluated the effect of steroids on the early and late outcome of children with Bell’s palsy in a prospective randomized controlled setting. Forty-two patients (21 females, 21 males) with complete paralysis were enrolled in the study. Group 1 (n = 21) received methylprednisolone (1 mg/kg daily for 10 days orally); Group 2 (n = 21) did not. All patients were observed in the first 3 days of the disease and at 4, 6, and 12 months of follow-up. The mean age of Group 1 was 52.4 ± 4.3 months, not significantly different from that of Group 2. In Group 1, 86% and 100% exhibited normal nerve function at 4 and 6 months of follow-up, respectively; in Group 2, 72% and 86% demonstrated complete recovery at 4 and 6 months, respectively, with improvement in all patients by 12 months. The improvement rates between the treated and untreated groups did not differ significantly. No side effects necessitated steroid withdrawal. The results of this study indicate that steroid therapy initiated at an early stage of childhood Bell’s palsy does not significantly improve the outcome.

Drug-induced thrombocytopenia: clinical data on 309 cases and the effect of corticosteroid therapy.

To analyse the clinical picture and the course of thrombocytopenia induced by non-cytotoxic drugs, and to evaluate a possible therapeutic effect of corticosteroids. A retrospective analysis of 309 well-documented cases of drug-induced thrombocytopenia was performed. Data sources were reports from the files of the Danish Committee on Adverse Drug Reactions and discharge summaries. The median length of exposure to the offending drug, before development of thrombocytopenia, was 21 days. The median nadir platelet count was 11 x 10(9).l-1, and 74% of the patients had clinical haemorrhage. Bone marrow examination generally showed hyperplastic reactive changes and a variable number of megakaryocytes. Slight leucopenia was present in 6% of the patients and 16% were anaemic. Complete recovery was seen in 87% of cases, with a median recovery rate of 8 days. The standard treatment was corticosteroids, which were administered in 53% of the cases. No difference in recovery between corticosteroid-treated and untreated patients was observed. No other clinical parameter affected the recovery rate. The mortality rate due to haemorrhage was 3.6%. Thrombocytopenia induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due to the difficult initial differentiation between the two conditions.

Nervous System Lupus: Pathogenesis and Rationale for Therapy

Several different pathogenic mechanisms appear to be involved in CNS lupus. These include: B-cell/autoantibody-mediated nervous system compromise; immune complex deposition and vasculitis; microthrombosis and vasculopathy; aberrant MHC Class II antigen expression with T-cell mediated disease (multiple-sclerosis model); and, cytokine-induced brain inflammation. These processes are not mutually exclusive: there exist in vitro and in vivo models for each of these. A number of autoantibodies, especially those with specificities for shared neuronal/lymphocyte antigens, are associated with certain forms of cognitive dysfunction or overt nervous system manifestations. In MRL/lpr mice, lymphoid infiltrates in the brain parenchyma are related to a neurobehavioural dysfunction which develops very early in the course of autoimmune disease. Recent results, both in animal models and in human studies on the therapeutic effects of corticosteroids, immunosuppressive drugs or anticoagulants on clinical and subclinical manifestations of CNS lupus are highlighted in an attempt to develop a rationale for intervention based upon presumed pathogenesis.