Low-dose Glucocorticoid Therapy Research Articles

Does high hepatic bioavailability enhance the effect of oral compared to subcutaneous glucocorticoids?

Glucocorticoids (GC) are important in the treatment of autoinflammatory disorders. Oral prednisolone ≤5 mg/day can be effective, but such doses are at or even below physiological daily endogenous GC production. We hypothesised that their immunosuppressive effect might be explained by high hepatic bioavailability of oral GC, exposing the liver to supraphysiological GC via the portal circulation. We tested this by comparing the effect of oral versus subcutaneous low-dose prednisolone, on erythrocyte sedimentation rate (ESR). Patients with rheumatoid arthritis or psoriatic arthritis, elevated ESR (≥30 mm/h) and no current or recent GC therapy were eligible. In a pilot study (n=5), 5 mg/day oral prednisolone decreased ESR significantly, suggesting a sample size of 10 patients for a randomised, non-blinded crossover trial. Patients received 5 mg/day prednisolone for 2 periods of 4 days: one treatment period orally and one subcutaneously with a 10-day washout period between treatments. ESR was measured before (day 1 and 15) and after (day 5 and 19) each treatment course. 10 patients were included. ESR decreased after both oral and subcutaneous prednisolone, by -5.6 (20.9) and -5.8 (3.0) mm/h, respectively (p=0.98). The treatment order had no effect on the outcome. . Short-term oral low-dose GC therapy is not more effective than parental GC in decreasing ESR, arguing against therapeutic high hepatic bioavailability effects. More likely, systemic concentration peaks following administration explain why oral physiological steroid doses are clinically effective.

Low-dose glucocorticoid increase the risk of fracture in postmenopausal women with low bone mass: a retrospective cohort study.

The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated. 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up. The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]). Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.

Diagnostic Value of Short Course Low-dose Prednisolone in Patients with Clinically Suspected Seronegative Inflammatory Arthritis - A Retrospective Study.

We aim to establish the utility of a trial of low-dose systemic glucocorticoid therapy in the assessment of new clinically suspected inflammatory arthritis patients. We retrospectively identified patients from a private rheumatology practice in Melbourne, Australia between January 1st, 2019, and December 31st, 2021, who presented with clinically suspected inflammatory arthritis and subsequently underwent a trial of low-dose prednisolone (15 mg daily weaned over three weeks in 5 mg increments). We excluded patients with known autoimmune/ inflammatory disorders or concurrent immunosuppression at presentation. We collected basic participant demographic details and clinical details of their presentation, glucocorticoid response, investigations, and treatment. We recruited 177 participants with a median age of 52, and 69.5% were female gender. The median symptom time to presentation was 12 months. Hands were the most affected joint in 63.3% and 85% had bilateral disease. Among the participants, 29.4% had synovitis on clinical review and 75.7% had imaging performed as part of the initial assessment. At presentation, the median CRP was 11 and the median ESR was 16. 79.7% of the cohort experienced significant improvement in their arthritis symptoms from low-dose glucocorticoids and 83.6% of the cohort required long-term immunosuppression for an underlying inflammatory condition. Of those who responded to glucocorticoids, 92.1% were diagnosed with an inflammatory condition. Rheumatoid arthritis was the most common overall diagnosis in 28%. An initial trial of low-dose glucocorticoids in undifferentiated arthritis patients is useful in predicting the diagnosis of inflammatory arthritis. It is also a predictor of further long-term steroid-sparing therapy.

Case report: Regression after low-dose glucocorticoid therapy in a case of acute immune myocarditis induced by anti-PD-1 therapy for NSCLC

BackgroundPD-1 inhibitors exhibit efficacy in managing unresectable/metastatic driver gene-negative NSCLC, albeit with potential immune-related adverse events (irAEs). Among these, immune checkpoint inhibitor-associated myocarditis (ICI-M) is rare yet lethal. This study presents the initial successful instance of ICI-M in a lung cancer patient, rescued by low-dose glucocorticoids post-deterioration during treatment.Case summaryA 78-year-old male with a medical history of stage IV pT3N2M1 NSCLC underwent four cycles of palliative chemotherapy, resulting in stable disease (SD). Subsequent to declining further chemotherapy, the patient was transitioned to a targeted therapy regimen comprising Anlotinib in conjunction with PD-1 inhibitor immunotherapy. On the 26th day post-administration of the PD-1 inhibitor, the patient manifested Grade 2 immune-mediated myocarditis. Treatment encompassing 1mg/kg methylprednisolone combined with immunoglobulin shock therapy was initiated for 3 days, achieving symptomatic control. Nonetheless, upon tapering methylprednisolone dosage to 4–8mg/3–4d, the condition deteriorated, necessitating transfer to the intensive care unit. Methylprednisolone dosage was escalated to 80mg/day for 3 days, followed by gradual reduction by one-third to two-thirds weekly, culminating in the patient’s safe discharge from the hospital.ConclusionImmune-related myocarditis linked to checkpoint inhibitors is often managed effectively with high-dose glucocorticoid therapy. However, in Asian populations, low-dose glucocorticoids are increasingly utilized for salvage therapy, yielding favorable outcomes and improving prognosis compared to European populations.

The analysis of low-dose glucocorticoid maintenance therapy in patients with primary nephrotic syndrome suffering from COVID-19.

Objectives: This study aimed to describe the effects of low-dose (prednisolone acetate 2.5-7.5mg/day) glucocorticoids (GCs) maintenance therapy in patients with primary nephrotic syndrome (NS) suffering from coronavirus disease 2019 (COVID-19). Methods: A single-center retrospective study of NS patients with COVID-19 infection in Zhongda Hospital Affiliated to Southeast University from 1 February 2022 to 31 March 2023 was conducted. All enrolled patients underwent renal biopsy for the pathological diagnosis and reached complete remission (CR) or near-CR before COVID-19 infection. According to the maintained therapy regimen, patients were divided into low-dose GCs group and non-GCs group. Results: A total of 125 patients were enrolled in the study. Their median age was 46.0 ± 15.6years, and the median value of 24-h urine protein was 0.77g. The majority of these patients received treatment for more than 6months, with a significant portion achieving CR (29.6%) or near-CR (43.2%). The leading cause of NS was membranous nephropathy (52%). There were no significant differences in the baseline characteristics between low-dose GCs and non-GCs group. As compared to those in the non-GCs group, patients receiving low-dose GCs treatment showed less fatigue or muscle weakness, smell disorder, palpitations, decreased appetite, taste disorder, dizziness, sore throat or difficult to swallow and fever (p < 0.05). Moreover, patients in the low-dose GCs group were with higher median quality of life scores (85.0) than in the non-GCs group (p = 0.001). Further serum inflammatory factor analysis indicated that interleukin-6 (IL-6) levels in the non-GCs group were significantly higher than that in the low-dose GCs group (p < 0.05). Conclusion: Patients with NS in low-dose GCs maintenance therapy stage showed milder symptom, higher quality of life and decreased serum IL-6 levels compared to those, who were not on GCs maintenance therapy. These results suggest the beneficial effect of low-dose GCs therapy in NS patients with CR/near-CR suffering from COVID-19 infection.

Clinical efficacy of low-dose glucocorticoid therapy for critically ill patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study

ObjectivesTo determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may benefit from the treatment. MethodsA retrospective study was performed to include patients with confirmed SFTS from designated hospitals. The effect of glucocorticoids in reducing case fatality rate (CFR) and improving clinical recovery was evaluated by multivariate logistic regression models. ResultsA total of 2478 eligible patients were analyzed, of whom 331 received glucocorticoids. An integrated parameter (L-index) based on Log10(lactate dehydrogenase*blood urea nitrogen/lymphocyte count) was constructed to discriminate disease severity. In patients with L-index >3.823 indicating severe SFTS, significantly reduced CFR was observed in patients receiving low-moderate glucocorticoid doses with ≤60 mg daily methylprednisolone or equivalent (odds ratio [OR] 0.46, 95% confidence interval [CI], 0.23-0.88), but not in patients receiving high doses. In patients with L-index ≤3.823 indicating mild SFTS, glucocorticoid treatment was significantly associated with increased CFR (OR 3.34, 95% CI, 1.35-9.51), and mainly attributable to high-dose glucocorticoids (OR 2.83, 95% CI, 1.72-4.96). Disaggregated data analysis revealed a significant effect only in patients ≤65 years old, male, and early admission within 7 days after onset, but not in their counterparts. ConclusionGlucocorticoids are not recommended for mild patients defined by L-index <3.823; however, patients with severe SFTS may benefit from low-moderate doses of glucocorticoids.

Development of prediction models to select older RA patients with comorbidities for treatment with chronic low-dose glucocorticoids.

To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients ≥65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12-15%, area under the curve 0.67-0.69). Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm. https://clinicaltrials.gov; NCT02585258.

Safety and efficacy of low-dose glucocorticoid regimen in the induction phase treatment of class 4, 5 lupus nephritis: a retrospective study

Background Renal involvement in systemic lupus erythematosus is known as lupus nephritis (LN). LN presents with varied renal features. Class 4 and 5 LN are traditionally treated with prolonged standard high doses of prednisolone with various immunosuppressants such as cyclophosphamide and mycophenolate. These high doses of prednisolone are associated with numerous side effects. There is deficient data on the dose, duration of glucocorticoid therapy, and also paucity of data on comparison between the standard dose versus low-dose glucocorticoid therapy. Hence, this study can help in evaluating the use of low-dose glucocorticoids, its impact on renal outcome, and looking at side effects. Materials and methods It was a retrospective observational study conducted to look at the safety and efficacy of low-dose glucocorticoid regimen in induction phase treatment of class 4, 5 LN. Results On treatment, it was found that the resolution of microscopic hematuria, and improvement of low C4, and hypoalbuminemia were statistically significant in the low-dose steroid group. The resolution of proteinuria was seen in both groups and the resolution of renal failure was noted in both groups but was statistically significant in the standard dose group. Increased incidence of steroid-related complications was seen in the standard dose steroid group. Conclusions These findings possibly indicate that low-dose steroid therapy is good enough to treat LN with proteinuria, but a standard dose steroid is required in the presence of renal failure in LN, though increased incidence of steroid-related complications was seen in the standard dose steroid group.

Efficacy and safety of belimumab during maintenance therapy in patients with systemic lupus erythematosus.

ObjectivesThe efficacy of belimumab (BEL) during maintenance therapy in patients with SLE remains unclear in the real-life clinical setting. This study investigated the efficacy and safety of BEL in patients with SLE during maintenance therapy.MethodsIn this retrospective observational study, maintenance therapy was defined as low-dose glucocorticoid (GC) therapy (prednisolone equivalent dose of ≤0.2 mg/kg/day) in patients with a Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score <10. Participants comprised patients with SLE on HCQ or MMF [standard-of-care (SoC) group: n = 103] and those on BEL plus SoC (BEL+SoC group: n = 100). Selection bias was minimized using propensity score-based inverse probability of treatment weighting (IPTW). GC dose trajectories were modelled using growth mixture modelling (GMM). The primary end point was GC dose at 52 weeks.ResultsNo significant difference was observed in patient characteristics between the two groups after IPTW adjustment. The BEL+SoC group exhibited a significant decrease in GC dose. GC dose at 52 weeks and relapse rate were significantly lower in the BEL+SoC group than in the SoC group. The proportion of patients in one of four groups defined by GMM for which GC dose was tapered to 0 mg within 52 weeks (GC tapering-discontinuation group) was significantly higher in the BEL+SoC group than in the SoC group. In the BEL+SoC group, low SELENA-SLEDAI score and low GC dose at baseline were associated with being GC dose-tapering discontinuation.ConclusionThe present study suggests that BEL is suitable for patients with SLE during maintenance therapy.

Low-dose oral glucocorticoid therapy and risk of osteoporotic fractures in patients with rheumatoid arthritis: a cohort study using the Clinical Practice Research Datalink.

ObjectivesClinical trials have shown that low-dose glucocorticoid therapy in patients with RA reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA.MethodsThis was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7–12 months) and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, adjusted for lifestyle parameters, comorbidities and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids.ResultsAmong 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent dose/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98, 1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11, 2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids.ConclusionClinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased.

Effectiveness of Glucocorticoids in Acute Respiratory Distress Syndrome: An Umbrella Review

Objectives. Acute respiratory distress syndrome is a very challenging condition that is associated with high morbidity and mortality. This review was intended to evaluate evidence on the effectiveness of glucocorticoid treatment for acute respiratory distress syndrome. Method. A comprehensive search strategy was conducted on PubMed/Medline, Cochrane Library, Science Direct, and LILACS. Data extraction was carried out by two independent reviewers using a customized checklist. The quality of each systematic review was assessed by two independent reviewers using an AMSTAR tool, and the overall quality of evidence was generated with online GRADEpro GDT software for primary and secondary outcomes. Results. The umbrella review included nine systematic reviews and meta-analysis and one narrative review with 8491 participants. The methodological quality of the included studies was moderate-to-high quality. The overall quality of evidence and recommendations varied form high to very low. Conclusion. There is high-to-moderate quality evidence that early low-dose prolonged glucocorticoid therapy reduces mortality in ARDS. However, randomized controlled trials with large sample sizes to address ventilator-free days, the incidence of infection, and other glucocorticoid-associated adverse events are required as the quality of evidence for these secondary outcomes which were low to very low. Registration. This umbrella review was registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42019130539).

Some aspects of application glucocorticoid drugs in the complex treatment of new coronaviral infection

The aim of the study was to evaluate the clinical and lab- oratory parameters of the effectiveness of low-dose glu- cocorticoid therapy in the complex treatment of patients with lung disease caused by a new coronavirus infection (COVID-19). Methods. The study included 40 hospitalized patients aged 37 to 68 years (mean age 52.2 years) with a confirmed diagnosis of medium severe to severe COVID- 19 pneumonia and CT-2 or CT-3 lung tissue involvement. All patients received standard therapy. Patients were randomized into two groups: the main group (n=20) and the control group (n=20). The main group additionally received MPS, according to the protocol: 4 mg tablets, 7 tablets per day, divided into 2 doses (4 tablets in the morning and 3 at lunchtime) in the course of 10 days. On admission to hospital, all patients demonstrated clinical symptoms of the disease, fever and decline in oxygen saturation. Based on the dynamics of clinical, radiological, and la boratory parameters, the additional effectiveness of oral glucocorticoids in the pathogenetic therapy of COVID-19 in comparison with control group was assessed. Results. According to laboratory test re- sults, the screened patients on hospital admission had an increased level of acute phase indicators and proin- flammatory cytokines. Correlation analysis revealed the credible link between the vo lume of lung involvement (based on CT-scans), oxygen sa turation, body mass index (BMI), and interleukin-10 levels (anti-inflammatory cy- tokine activation marker). Credible correlation between concentration of acute-phase parameters and proinflam- matory cytokines (IL-1, IL-6) in blood was detected. The use of methylprednisolone in the comprehensive treat- ment of patients with severe pneumonia associated with COVID-19 has been accompanied by reliable increase in ferritin, C-reactive protein, and interleukin-1, interleu- kin-6, interleukin-10. Less time was needed for symptom resolution and recovery of oxygen saturation in patients who took methylprednisolone. Meanwhile, a timeframe for reaching positive CT dynamics and the total duration of treatment hadn’t changed significantly. Conclusion. Prescribing cycles of oral glucocorticoid therapy helps to reduce proinflammatory cytokines in blood and accel- erate oxygen saturation recovery, however, it does not influence the duration of hospitalization and the time frame of resolution of inflammatory changes in lungs du ring the period of hospitalization.

Thalidomide combined with short-term low-dose glucocorticoid therapy for the treatment of severe COVID-19: A case-series study

ObjectivesThe aim was to evaluate the safety and effectiveness of thalidomide, an immunomodulatory agent, in combination with glucocorticoid, for the treatment of COVID-19 patients with life-threatening symptoms. MethodsA nonrandomized comparative case series study was performed. Six patients received thalidomide 100 mg per day (with therapy lasting for ≥7 days) plus low-dose short-term dexamethasone, and 6 control patients matched with patients in the thalidomide group, received low-dose short-term treatment with dexamethasone alone. The main outcomes were: the duration of SARS-CoV-2 negative conversion from admission; length of hospital stay; and changes in inflammatory cytokine concentrations and lymphocyte subsets. ResultsThe median thalidomide treatment time was 12.0 days. The median duration of SARS-CoV-2 negative conversion from admission and hospital stay length were briefer in the thalidomide group compared to the control group (respectively, 11.0 vs 23.0 days, P = 0.043; 18.5 vs 30.0 days, P = 0.043). The mean reduction rates at 7–10 days after treatment for serum interleukin-6 and interferon-γ concentrations were greater in the thalidomide group compared to the control group. Alterations in lymphocyte numbers in the subsets between the 2 groups were similar. ConclusionsThalidomide plus short-term glucocorticoid therapy is an effective and safe regimen for the treatment of severely ill COVID-19 patients. The mechanism of action is most likely inhibition of inflammatory cytokine production.

High prevalence of steroid-induced glucose intolerance with normal fasting glycaemia during low-dose glucocorticoid therapy: an oral glucose tolerance test screening study.

To evaluate the prevalence and risk factors of new-onset glucose metabolism impairment using an oral glucose tolerance test (OGTT) in patients with normal fasting glycaemia on long-term glucocorticoid (GC) treatment. An OGTT was performed in 150 patients without a previous history of pre-diabetes or diabetes who were diagnosed with inflammatory rheumatic diseases and treated with GCs >3 months. All participants underwent clinical and biochemical evaluation for risk factors of diabetes: age, sex, current and cumulative dose of steroids, treatment duration, waist circumference, BMI, Homeostatic Model Assessment for Insulin Resistance, fasting insulin concentration, family history of diabetes, CRP, 28-joint DAS with CRP, type of connective tissue disease and trunk fat percentage measured by DXA. Logistic regression analysis was conducted to evaluate the association between the presence of impaired glucose tolerance (IGT) in the OGTT and analysed risk factors. A total of 102 patients (68%) had fully normal glucose tolerance. Diabetes, isolated impaired fasting glucose, isolated IGT and combined impaired fasting glucose + IGT was diagnosed in 3.3, 4.67, 19.33 and 4.67% of patients, respectively; 20% of participants had IGT or diabetes despite normal fasting glucose concentration. The median cumulative dose and current dose (5 mg) of GCs and treatment duration were similar compared with the normal glucose tolerance group. In a multivariate logistic regression model, only older age (particularly ≥50 years of age) and trunk fat percentage remained significant factors predicting IGT or diabetes in the OGTT. New-onset GC-induced glucose intolerance, even in patients on long-term low-dose treatment, is prevalent despite normal fasting glucose concentration and patients should be screened with an OGTT despite the absence of classic risk factors of diabetes.

Neutrophil to lymphocyte ratio predicts glucocorticoid resistance in polymyalgia rheumatica.

Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) correlate with disease activity in several rheumatic diseases; however, their utility in polymyalgia rheumatica (PMR) remains unclear. This study evaluated their relationship with disease activity and glucocorticoid resistance in PMR. Data for disease activity (PMR-AS) and full blood examination was obtained from a prospective observational cohort comprising newly diagnosed, steroid-naïve PMR patients treated with low-dose glucocorticoid therapy. Glucocorticoid resistance was defined as non-response to prednisolone 15mg/d or initial response followed by flare (PMR-AS≥9.35 or ∆ ≥6.6) upon weaning to 5mg/d. Univariable Bayesian linear regression analysis of the relationship between PMR-AS (baseline and mean) and NLR and PLR was performed. Predictors of glucocorticoid resistance were identified using a multivariable outcome model, with variables derived from Bayesian model selection. Of the 32 included patients, 16 (50%) fulfilled the primary outcome measure of glucocorticoid resistance. These participants were older, typically female, and had higher baseline C-reactive protein than their glucocorticoid-responsive counterparts. A statistically significant relationship was identified between PMR-AS and both NLR (odds ratio [OR] 28.1; 95% CI 1.6-54.7) and PLR (OR 40.6; 95% CI 10.1-71.4) at baseline, with PLR also found to correlate with disease activity during follow-up (OR 15.6; 95% CI 2.7-28.2). Baseline NLR proved a statistically significant predictor of glucocorticoid-resistant PMR (OR 14.01; 95% CI 1.49-278.06). Baseline NLR can predict glucocorticoid resistance in newly diagnosed PMR patients. Both NLR and PLR may be reliable biomarkers of disease activity in PMR.

Early, short-term, low-dose glucocorticoid therapy effectively blocks progression of severe acute exacerbation of chronic hepatitis B to liver failure

ObjectiveTo determine whether early, short-term, low-dose glucocorticoid treatment prevents the progression of severe acute exacerbation of chronic hepatitis B to liver failure. MethodsWe prospectively enrolled 125 patients with severe acute exacerbation of chronic hepatitis B from the Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University between September 2013 and March 2016. The patients were randomized to a hormone group (3-day, low-dose glucocorticoid treatment plus conventional treatment; 63 patients) and a control group (conventional treatment only; 62 patients). We analyzed markers of liver function, complications, mortality rates, and duration and cost of hospitalization. ResultsSerum alanine transaminase levels were significantly lower in the hormone group than in the control group at 3 days (P = 0.009) and 1 week (P = 0.018) after treatment. The decrease in this level from the baseline value on day 3 was greater in the hormone group than in the control group (P = 0.023). The trend of the changes in this level significantly differed between the two groups (P = 0.008). The incidence of liver failure (8.06% vs. 30.16%; P = 0.002) and the duration of hospitalization (23.79 vs. 31.79 days; P = 0.031) were significantly lower in the hormone group than in the control group. ConclusionLow-dose, short-term glucocorticoid treatment early in the course of severe acute exacerbation of chronic hepatitis B along with conventional treatment significantly reduced the risk of progression to liver failure and shortened the duration of hospitalization, without increasing the complication rate.

Nationwide survey on clinical treatment of coronavirus disease 2019 in 9 provinces and municipalities

To investigate the clinical treatment and assess the knowledge and use of the coronavirus disease 2019 (COVID-19) treatment plan issued by the nation. A nationwide questionnaire survey on line was administered to medical staffs involved in COVID-19 treatment on February 28th, 2020. The questionnaire included drug treatment, respiratory support therapy, sedation and analgesia, continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO), etc. There were 1 103 respondents, of whom 699 (504 doctors and 195 nurses) participated in the treatment of COVID-19. Finally, 432 doctors and 170 nurses from 9 provinces submitted valid questionnaires. The results of the questionnaire surveys of doctors and nurses were basically the same. Considering that doctors dominated in the diagnosis and treatment of COVID-19, the results of the questionnaires of doctors were mainly analyzed. The doctors participating in the survey were mainly from Hubei (29.2%), followed by Henan (24.5%), Guizhou (22.7%), and Guangxi (14.6%), etc. 55.4% of the doctors came from tertiary three hospitals, and most of them have senior titles (56.4%). 232 doctors (53.7%) participated in the treatment of mild COVID-19, and 200 doctors (46.3%) participated in the treatment of severe and critically ill patients. More than 95% of the doctors expressed that they would carry out antiviral treatment for patients with COVID-19 regardless of disease severity. The main antiviral drugs included α-interferon (69.5%), lopinavir/ritonavir (65.0%), abidol (60.0%), and ribavirin (55.7%). The choice of antiviral drugs was highly consistent with the national treatment programs of COVID-19. At the same time, 95.5% of doctors would routinely prescribe antibiotics to severe and critically ill patients. 94.0% of doctors agreed to prescribe low-dose glucocorticoid therapy to severe and critically ill patients. About 2/3 of doctors would perform lung recruitment or prone position treatment for critical patients with invasive ventilation. 79.0% of doctors preferred to use deep sedation for patients with invasive ventilation. About 1/3 of doctors believed that CRRT should be initiated early, and nearly 1/3 of doctors suggested that ECMO should be used more aggressively in critically ill patients. Medical staffs are familiar with the national treatment plan of COVID-19 and willing to follow it. However, as a new disease, we have limited knowledge about COVID-19 and there are still many controversies. Further practical training is needed to make clinicians more aware of the disease, and more evidence-based evidence is needed to guide clinical treatment.

A case of type B insulin resistance syndrome treated with low-dose glucocorticoids.

SummaryType B insulin resistance syndrome is characterized by the presence of autoantibodies to the insulin receptor. We present a 57-year-old male admitted to a hospital due to body weight loss of 16 kg and hyperglycemia of 13.6 mmol/L. He was diagnosed with type B insulin resistance syndrome because the anti-insulin receptor antibodies were positive. We informed him that some hyperglycemic cases of this syndrome had been reported to be spontaneously remitted in 5 years, and he did not agree to be treated with high-dose glucocorticoids and/or immunosuppressive agents due to his concern for their adverse effects such as hyperglycemia and immunosuppression. He chose to be treated with insulin and voglibose, but fair glucose control could not be obtained. Six years later, he agreed to be treated with low-dose glucocorticoids practicable in outpatient settings. One milligram per day of betamethasone was tried orally and reduced gradually according to the values of glycated hemoglobin. After 30 months of glucocorticoid treatment, the anti-insulin receptor antibodies became undetectable and his fasting plasma glucose and glycated hemoglobin were normalized. This case suggests that low-dose glucocorticoids could be a choice to treat type B insulin resistance syndrome in outpatient settings.Learning points:Type B insulin resistance syndrome is an acquired autoimmune disease for insulin receptors.This case suggested the possibility of long-lasting, low-dose glucocorticoid therapy for the syndrome as an alternative for high-dose glucocorticoids or immunosuppressive agents.Since the prevalence of autoimmune nephritis is high in the syndrome, a delay of immunosuppressive therapy initiation might result in an exacerbation of nephropathy.

Effect of glucocorticoids on mortality in patients with acute respiratory distress syndrome: A meta-analysis.

To date, the efficacy of glucocorticoid therapy to reduce mortality in patients with acute respiratory distress syndrome (ARDS) has remained controversial among the studies available. The present meta-analysis study aimed to further clarify the impact of glucocorticoid therapy on mortality in patients with ARDS by performing a pooled analysis of the previous data. The PubMed, Chinese Knowledge Infrastructure, Wanfang and Cochrane trials databases were searched for relevant studies published between 1966 and 2016. Randomized controlled trials (RCTs) that included the use of glucocorticoids in patients with ARDS and had reported on mortality were included. Odds ratios (OR) and 95% confidence intervals (CI) for mortality were calculated. A total of 10 RCTs were included in the meta-analysis. Of these, 4 studies used high-dose glucocorticoid therapy, while 6 used low-dose glucocorticoid therapy. In the pooled analysis, glucocorticoids were indicated to significantly reduce ARDS-associated mortality (OR=0.64, 95% CI: 0.48-0.85, P=0.002). Further subgroup analysis indicated the following: i) Long-term low-dose glucocorticoid therapy reduced ARDS-associated mortality compared with that in the control group (OR=0.60, 95% CI: 0.44-0.82, P=0.001), whereas high-dose short-term glucocorticoid therapy did not reduce mortality (OR=0.82, 95% CI: 0.43-1.57, P=0.55). ii) Early initiation of glucocorticoid therapy was associated with reduced mortality compared with that in the control group (OR=0.60, 95% CI: 0.44-0.83, P=0.002); however, late initiation did not reduce mortality (OR=0.36, 95% CI: 0.03-3.76, P=0.39). iii) Therapeutic rather than preventive use of glucocorticoids reduced mortality (OR=0.65, 95% CI: 0.49-0.86, P=0.003). Overall, the present meta-analysis suggests that early initiation of long-term low-dose glucocorticoid therapy reduces mortality of patients with ARDS.

Oral glucose tolerance test is recommended for screening for new-onset glucose metabolism impairment during chronic low-dose glucocorticoid therapy

Oral glucose tolerance test is recommended for screening for new-onset glucose metabolism impairment during chronic low-dose glucocorticoid therapy