Do patients with nephrotic syndrome have an increased risk of osteoporosis? A nationwide population-based retrospective cohort study in Taiwan.

OBJECTIVES: To evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000-December 2010. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All healthcare facilities in Taiwan. PARTICIPANTS: A total of 28 772 individuals were enrolled. INTERVENTIONS: 26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted. PRIMARY OUTCOME MEASURE: To identify risk differences in developing osteoporosis among patients with a medical history of NS. RESULTS: After adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis. CONCLUSION: NS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.

[Corticosteroids in intensive care medicine]. / Kortikosteroide in der Intensivmedizin.

In the case of septic shock, recent studies show benefits from a combination of hydrocortisone and fludrocortisone, but clear guideline recommendations are still lacking. For severe community-acquired pneumonia, early corticosteroid therapy is recommended. Corticosteroid therapy should not be used in influenza-associated community-acquired pneumonia. In contrast, a significantly lower 28-day mortality rate was observed for COVID-19 by the use of dexamethasone. Current guidelines also recommend the use of corticosteroids in Acute Respiratory Distress Syndrome. These recommendations are based primarily on studies that started steroid therapy early. However, many questions such as the type of corticosteroid, the timing and duration of therapy, and the dosage still remain unanswered.

Oral Prescription Management.

The treatment of atopic dermatitis (AD) with oral treatments has been limited in the past due to the increased risk of adverse effects associated with oral agents. However, in recent years, a shift toward the minimization of adverse effects has been explored. Although existing treatment options like oral corticosteroids and Immunosuppressive therapies have been utilized for acute flare-ups of AD, their long-term use is limited by adverse effects and the need for lab monitoring. New systemic treatment options such as Janus kinase (JAK) inhibitors are emerging as a promising therapy, due to their quick onset and antipruritic features. However, the black box warning associated with this medication class requires careful selection of appropriate candidates and patient education despite early favorable safety profiles seen in AD trials. Discussion of other oral agents, like antibiotics and antihistamines, and their role in AD management are also clarified.

Treatment with systemic corticosteroid versus placebo for exacerbations of COPD: A systematic review and meta-analysis.

BACKGROUND: For the treatment of COPD exacerbations, systemic corticosteroids are recommended in addition to short-acting bronchodilators. Although there have been several systemic reviews, many of the included studies were conducted before 2007 and a re-evaluation has not been performed since 2014. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety profile of systemic corticosteroids in patients with COPD during exacerbations. METHODS: We searched relevant randomized control trials (RCTs) and analyzed the treatment failure, relapse, lung function, improvement in PaO2 and PaCO2, dyspnea, quality of life (QOL), length of stay in hospital and adverse events including hyperglycemia and mortality as the outcomes of interest. RESULTS: We identified a total of 12 RCTs (N = 1336). Systemic corticosteroids significantly reduced the treatment failure (odds ratios; OR 0.41, 95% confidence intervals; CI 0.25 to 0.67) and hospital length of stay (mean difference; MD -1.57 days, 95% CI -2.36 to -0.78) and improved FEV1 (MD 0.18 L, 95% CI 0.08 to 0.28) and dyspnea (transitional dyspnea index; MD 1.90, 95% CI 0.26 to 3.54) in COPD exacerbations compared to placebo. However, systemic corticosteroids were associated with a significantly higher incidence of adverse events (OR 1.83, 95% CI 1.25 to 2.69) and hyperglycemia (OR 2.94, 95% CI 1.68 to 5.14). CONCLUSIONS: In patients with moderate and severe COPD and severe obstructive impairment during exacerbations, systemic corticosteroids cause more adverse events, including hyperglycemia, than placebo but significantly reduce the treatment failure and hospital length of stay and improve FEV1 and dyspnea.

Perioperative steroid injection in elbow arthroscopy.

The goal of the present study was to evaluate the incidence of infection after perioperative intra-articular steroid injection during elbow arthroscopy. Starting from May 2019, we prospectively included all patients that underwent an elbow arthroscopy for various indications. All patients received preoperative antibiotics intravenously and a corticosteroid injection immediately after portal closure. Patients who needed ligamentous repair and aged below 18 years old were excluded. Final follow up of all patients was 3 months. In total, 108 elbow arthroscopies were performed in 100 patients. No major complications and 1 minor complication were seen. One patient developed a seroma that resolved spontaneously after 14 days without intervention or antibiotics. In this patient group, a perioperative corticosteroid injection following elbow arthroscopy did not increase the chance of infection.

The World Health Organization Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns (ACTION-III) Trial: study protocol for a multi-country, multi-centre, double-blind, three-arm, placebo-controlled, individually randomized trial of antenatal corticosteroids for women at high probability of late preterm birth in hospitals in low- resource countries.

BACKGROUND: Preterm birth complications are the leading cause of newborn and under-5 mortality. Over 85% of all preterm births occur in the late preterm period, i.e. between 34 and < 37 weeks of gestation. Antenatal corticosteroids (ACS) prevent mortality and respiratory morbidity when administered to women at high risk of an early preterm birth, i.e. < 34 weeks' gestation. However, the benefits and risks of ACS in the late preterm period are less clear; both guidelines and practices vary between settings. Emerging evidence suggests that the benefits of ACS may be achievable at lower doses than presently used. This trial aims to determine the efficacy and safety of two ACS regimens compared to placebo, when given to women with a high probability of late preterm birth, in hospitals in low-resource countries. METHODS: WHO ACTION III trial is a parallel-group, three-arm, individually randomized, double-blind, placebo-controlled trial of two ACS regimens: dexamethasone phosphate 4 × 6 mg q12h or betamethasone phosphate 4 × 2 mg q 12 h. The trial is being conducted across seven sites in five countries-Bangladesh, India, Kenya, Nigeria, and Pakistan. Eligible women are those with a gestational age between 34 weeks 0 days and 36 weeks 5 days, who have a high probability of preterm birth between 12 h and 7 days (up to 36 weeks 6 days gestation). The primary outcome is a composite of stillbirth or neonatal death within 72 h of birth or use of newborn respiratory support within 72 h of birth or prior to discharge from hospital, whichever is earlier. Secondary outcomes include safety and health utilization measures for both women and newborns. The sample size is 13,500 women. DISCUSSION: This trial will evaluate the benefits and possible harms of ACS when used in women likely to have a late preterm birth. It will also evaluate a lower-dose ACS regimen based on literature from pharmacokinetic studies. The results of this trial will provide robust critical evidence on the safe and appropriate use of ACS in the late preterm period internationally. TRIAL REGISTRATION: ISRCTN11434567 . Registered on 7 June 2021.

Management of Scleritis in Older Adults.

Scleritis, an inflammatory disease of the eye affecting scleral tissue, presents unique challenges in the older adult population. Unlike their younger counterparts, older individuals manifest a distinct spectrum of the disease with different underlying etiologies, co-morbidities, altered immune function, and an increased risk of systemic side effects from medication choices. Addressing these complexities necessitates a comprehensive and multidisciplinary approach. Treatment of choice will depend on any underlying cause but generally involves non-steroidal anti-inflammatory drugs, systemic or local corticosteroids, and potentially disease-modifying anti-rheumatic drugs. Utilization of these therapeutic agents in older adults warrants careful consideration because of their potential side-effect profiles. This article critically examines the specific concerns for the use of these drugs in older patients and reviews the existing literature on their use in this specific cohort.

Dexamethasone protects against asthma via regulating Hif-1α-glycolysis-lactate axis and protein lactylation.

PURPOSE: Asthma can not be eradicated till now and its control primarily relies on the application of corticosteroids. Recently, glycolytic reprogramming has been reportedly contributed to asthma, this study aimed to reveal whether the effect of corticosteroids on asthma control is related to their regulation of glycolysis and glycolysis-dependent protein lactylation. METHODS: Ovalbumin (OVA) aeroallergen was used to challenge mice and stimulate human macrophage cell line THP-1 following dexamethasone (DEX) treatment. Airway hyperresponsiveness, airway inflammation, the expressions of key glycolytic enzymes and pyroptosis markers, the level of lactic acid, real-time glycolysis and oxidative phosphorylation (OXPHOS), and protein lactylation were analyzed. RESULTS: DEX significantly attenuated OVA-induced eosinophilic airway inflammation, including airway hyperresponsiveness, leukocyte infiltration, goblet cell hyperplasia, Th2 cytokines production and pyroptosis markers expression. Meanwhile, OVA-induced Hif-1α-glycolysis axis was substantially downregulated by DEX, which resulted in low level of lactic acid. Besides, key glycolytic enzymes in the lungs of asthmatic mice were notably co-localized with F4/80-positive macrophages, indicating metabolic shift to glycolysis in lung macrophages during asthma. This was confirmed in OVA-stimulated THP-1 cells that DEX treatment resulted in reductions in pyroptosis, glycolysis and lactic acid level. Finally, protein lactylation was found significantly increased in the lungs of asthmatic mice and OVA-stimulated THP-1 cells, which were both inhibited by DEX. CONCLUSION: Our present study revealed that the effect of DEX on asthma control was associated with its suppressing of Hif-1α-glycolysis-lactateaxis and subsequent protein lactylation, which may open new avenues for the therapy of eosinophilic asthma.

Corticosteroid in non-COVID-19 induced community-acquired pneumonia, a meta-analysis.

BACKGROUND: Corticosteroid treatment in non-COVID-19 induced Community-acquired pneumonia (CAP) remains inconclusive. OBJECTIVES: We aimed to assess the role of corticosteroid treatment in CAP. METHODS: We conducted a comprehensive search of online databases, including PubMed, Embase, and Cochrane, to identify articles published from January 1, 2000, to May 5, 2023. Double-blind RCTs were selected. Two authors screened studies and extracted data. The evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: We analyzed data from 12 RCTs, involving 2446 patients. Corticosteroids therapy may reduce short-term mortality in patients with severe CAP (sCAP) and shorten the hospital length of stay in patients with CAP. Furthermore, corticosteroids treatment can decrease the risk of requiring mechanical ventilation, developing septic shock and multiple organ dysfunction syndrome (MODS). There were no significant differences between the corticosteroid and control groups concerning gastrointestinal bleeding and nosocomial infection. The use of corticosteroids could increase the risk of hyperglycemia. CONCLUSION: Corticosteroid treatment for sCAP has the potential to provide benefits in reducing short-term mortality, but this conclusion necessitates more evidence. Besides, we found no evidence that strongly prevents us from using corticosteroids in patients with sCAP or those at risk of progressing to sCAP.

The efficacy and safety of deucravacitinib compared to methotrexate, in patients with vulvar lichen planus who have failed topical therapy with potent corticosteroids: a study protocol for a single-centre double-blinded randomised controlled trial.

BACKGROUND: Vulvar lichen planus (VLP) is a chronic vulvar dermatosis that is difficult to treat and can severely impair quality of life in the absence of adequate treatment. There is a lack of high-quality evidence to direct therapy for VLP. This randomised controlled trial will be the first double-blinded study comparing systemic treatments in VLP and aims to investigate the safety and efficacy of deucravacitinib compared to methotrexate, in patients with VLP who have failed treatment with potent topical corticosteroids. METHODS: A total of 116 women aged ≥ 18 years with moderate to severe VLP (Genital Erosive Lichen Planus (GELP) score ≥ 5) will be recruited. All participants will initially be treated with Diprosone® OV daily, and their outcome will be assessed using the GELP score. At 8 weeks' follow-up, responders (GELP < 5) will be continued on Diprosone® OV. Non-responders (GELP ≥ 5) will be randomised 1:1 in a blinded fashion to receive (i) methotrexate 10 mg weekly + placebo tablet twice daily + folic acid 5 mg weekly or (ii) deucravacitinib 6 mg twice daily + placebo tablet weekly + folic acid 5 mg weekly. The primary endpoint is the difference in the mean change of GELP scores from baseline to week 32 between deucravacitinib and methotrexate groups. DISCUSSION: High-quality evidence guiding the management of women with VLP is lacking. Once completed, this will be the first double-blinded RCT to compare systemic treatments in VLP. The results of this study will provide valuable, high-quality data to guide second-line therapy options for VLP that is recalcitrant to potent topical corticosteroids. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000682640. Registered on 26 June 2023.

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery.

BACKGROUND: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. OBJECTIVES: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. SECONDARY OBJECTIVE: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. SEARCH METHODS: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. SELECTION CRITERIA: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. AUTHORS' CONCLUSIONS: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts.

Performance of a fast-track pathway for giant cell arteritis in Waikato, Aotearoa New Zealand.

AIMS: Giant cell arteritis (GCA) is the most common primary vasculitis in adults over 50 years of age. To facilitate early diagnosis and reduce harms from corticosteroids and temporal artery biopsies, fast-track pathways have been established. We review the benefits of the fast-track pathway set up in Waikato, Aotearoa New Zealand. METHODS: Patients were collected prospectively as part of the fast-track pathway from 2014 to 2022. Their records were then reviewed retrospectively to collect data on clinical features, investigations and treatment. RESULTS: There were 648 individual patients over the study period who had a colour Doppler ultrasound (CDUS) of the temporal arteries. There were 17 true positive CDUS, giving a sensitivity of 10.3% (95% confidence interval [CI] 6.3-15.5%) and specificity of 99.8% (95% CI 99.1-100%). Patients with GCA and a positive scan had significantly fewer steroids than those with GCA and a negative scan (p=0.0037). There were 376 patients discharged after a CDUS who did not have a diagnosis of GCA, resulting in reduced corticosteroid and temporal artery biopsy exposure. CONCLUSIONS: This is a real-life study that reflects the benefits of fast-track pathways in Aotearoa New Zealand to patients and healthcare systems. It also shows the effect of corticosteroids on positive CDUS, an important consideration when setting up an fast-track pathway.

Reduced Corticosteroid Exposure Is Safe and Does Not Reduce Disease Control among Hodgkin Lymphoma Patients Treated with Escalated BEACOPP (eBEACOPP).

Background and Objectives: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with significant toxicities. The 14-day/cycle prednisone course contributes to side effects, including osteoarticular events like avascular bone necrosis (AVN). Our center has been using eBEACOPP since 2009 for AS and 2014 for EU patients. In 2016, we reduced prednisone treatment to 7-10 days to lessen AVN risk. We analyzed the effects of this approach. Materials and Methods: We retrospectively collected data on patients who received at least two cycles of eBEACOPP for first-line HL treatment. Results: A total of 162 patients (33 EU, 129 AS) were included. Their median age was 31 (range 19-59 years), and 88 were males. A total of 94 patients received full corticosteroid courses, and 68 received reduced corticosteroid courses. The overall response rate (ORR) was 98%. Different corticosteroid dosings had no significant effect on ORR, febrile neutropenia episodes, or hospital admissions. After a median follow-up (mFU) of 58 months, the 5yPFS for the entire cohort was 98% vs. 95% for the standard course vs. the short corticosteroids course, respectively (p = 0.37), while the 5yOS was 98% vs. 99% for the standard course vs. short corticosteroids course, respectively (p = 0.87). In AS patients intended to be treated with six eBEACOPP cycles, 5yPFS and 5yOS were 100% vs. 97% and 100% vs. 99% for standard vs. short corticosteroid courses, respectively (p = 0.56 and p = 0.17). In EU patients, 5yPFS was 97% (standard) vs. 95% (short) (p = 0.98) and 5yOS 100% vs. 93.3% (p = 0.87). Osteoarticular events were numerically lower in patients receiving the shorter prednisone course, both in the whole cohort and in the subgroup of patients treated with six cycles of eBEACOPP, but this difference failed to reach statistical significance. Conclusions: eBEACOPP provides excellent and durable first-line disease control. Shortening the corticosteroid course does not compromise efficacy, potentially reducing toxicity. However, longer follow-ups and larger studies are needed for confirmation.

Toxicity due to steroid treatment in ITP remains a concern.

Corticosteroids are the preferred first-line treatment in ITP in guidelines. The analyses by Wang et al. shows that hospital-registered steroid-related toxicity occurs frequently and emphasizes that exposure should be for a limited duration of time. Commentary on: Wang et al. Longitudinal evaluation of adverse events due to steroid use in primary immune thrombocytopenia: a population-based study. Br J Haematol 2024;204:1986-1993.

Inhaled versus systemic corticosteroids for acute exacerbations of COPD: a systematic review and meta-analysis.

This meta-analysis compares the efficacy and safety of inhaled versus systemic corticosteroids for COPD exacerbations.Following a pre-registered protocol, we appraised eligible randomised controlled trials (RCTs) according to Cochrane methodology, performed random-effects meta-analyses for all outcomes prioritised in the European Respiratory Society COPD core outcome set and rated the certainty of evidence as per Grading of Recommendations Assessment, Development and Evaluation methodology.We included 20 RCTs totalling 2140 participants with moderate or severe exacerbations. All trials were at high risk of methodological bias. Low-certainty evidence did not reveal significant differences between inhaled and systemic corticosteroids for treatment failure rate (relative risk 1.75, 95% CI 0.76-4.02, n=569 participants); breathlessness (mean change: standardised mean difference (SMD) -0.11, 95% CI -0.36-0.15, n=239; post-treatment scores: SMD -0.18, 95% CI -0.41-0.05, n=293); serious adverse events (relative risk 1.47, 95% CI 0.56-3.88, n=246); or any other efficacy outcomes. Moderate-certainty evidence implied a tendency for fewer adverse events with inhaled compared to systemic corticosteroids (relative risk 0.80, 95% CI 0.64-1.0, n=480). Hyperglycaemia and oral fungal infections were observed more frequently with systemic and inhaled corticosteroids, respectively.Limited available evidence suggests potential noninferiority of inhaled to systemic corticosteroids in COPD exacerbations. Appropriately designed and powered RCTs are warranted to confirm these findings.