ABSTRACT
BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is the most common type of secondary osteoporosis. Recently, autophagy has been found to be related with the development of various diseases, including osteoporosis and osteoblast differentiation regulations. BTB and CNC homology 1 (BACH1) was a previously confirmed regulator for osteoblast differentiation, but whether it's could involve in glucocorticoid-induced human bone mesenchymal stem cells (hBMSCs) differentiation and autophagy regulation remain not been elucidated. METHODS: hBMSCs were identified by flow cytometry method, and its differentiation ability were measured by ARS staining, oil O red, and Alcian blue staining assays. Gene and proteins were quantified via qRT-PCR and western blot assays, respectively. Autophagy activity was determined using immunofluorescence. ChIP and dual luciferase assay validated the molecular interactions. RESULTS: The data revealed that isolated hBMSCs exhibited positive of CD29/CD44 and negative CD45/CD34. Moreover, BACH1 was abated gradually during osteoblast differentiation of hBMSCs, while dexamethasone (Dex) treatment led to BACH1 upregulation. Loss of BACH1 improved osteoblast differentiation and activated autophagy activity in Dex-challenged hBMSCs. Autophagy-related proteins (ATG3, ATG4, ATG5, ATG7, ATG12) were repressed after Dex treatment, while ATG3, ATG7 and BECN1 could be elevated by BACH1 knockdown, especially ATG7. Moreover, BACH1 could interact ATG7 promoter region to inhibit its transcription. Co-inhibition of ATG7 greatly overturned the protective roles of BACH1 loss on osteoblast differentiation and autophagy in Dex-induced hBMSCs. CONCLUSION: Taken together, our results demonstrated that silencing of BACH1 mitigated Dex-triggered osteogenic differentiation inhibition by transcriptionally activating ATG7-mediated autophagy, suggesting that BACH1 may be a therapeutic target for GIOP treatment.
Subject(s)
Autophagy , Basic-Leucine Zipper Transcription Factors , Cell Differentiation , Dexamethasone , Glucocorticoids , Mesenchymal Stem Cells , Osteoblasts , Osteogenesis , Humans , Autophagy/drug effects , Cell Differentiation/drug effects , Osteogenesis/drug effects , Basic-Leucine Zipper Transcription Factors/metabolism , Basic-Leucine Zipper Transcription Factors/genetics , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Glucocorticoids/pharmacology , Glucocorticoids/adverse effects , Osteoblasts/drug effects , Osteoblasts/metabolism , Dexamethasone/pharmacology , Cells, Cultured , Osteoporosis/chemically induced , Osteoporosis/genetics , Osteoporosis/pathologyABSTRACT
PURPOSE: To report a case of angiographically silent cystoid macular edema (CME) secondary to pentosan polysulfate sodium (PPS) maculopathy responsive to intravitreal steroids. METHODS: Observational case report. RESULTS: A 52-year-old female patient with a history of 4 years of PPS use for interstitial cystitis presented with PPS maculopathy that developed CME 2.5 years after drug cessation and had associated progression of pigmentary and atrophic changes. Her CME was nonresponsive to topical ketorolac and dorzolamide, but was responsive to intravitreal triamcinolone acetonide and subsequently intravitreal dexamethasone implant (Ozurdex) with reduction in central subfield thickness and improvement in visual acuity. CONCLUSION: Cystoid macular edema secondary to PPS maculopathy may be angiographically silent yet responsive to intravitreal steroids alone without the use of vascular endothelial growth factor agents. There is potential for both anatomic and functional improvements in such cases demonstrating the value of such treatment. Cystoid macular edema may be a delayed finding that can develop despite drug cessation. Steroid monotherapy should be further evaluated as possible first-line management for PPS maculopathy-associated CME.
Subject(s)
Dexamethasone , Glucocorticoids , Intravitreal Injections , Macular Edema , Pentosan Sulfuric Polyester , Humans , Macular Edema/drug therapy , Macular Edema/etiology , Macular Edema/diagnosis , Macular Edema/chemically induced , Female , Middle Aged , Pentosan Sulfuric Polyester/adverse effects , Glucocorticoids/adverse effects , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Triamcinolone Acetonide/adverse effects , Triamcinolone Acetonide/administration & dosage , Fluorescein Angiography , Cystitis, Interstitial/drug therapy , Visual Acuity , Tomography, Optical CoherenceABSTRACT
Osteoporosis is a common condition worldwide, affecting millions of people. Women are more commonly affected than men, and the risk increases with age. Inflammatory reaction plays a crucial role in the expansion of osteoporosis. Osteoporosis is characterized by a gradual decline in bone density and bone tissue quality, which increases fragility and raises the risk of fractures. We scrutinized the anti-osteoporosis effect of hydroxysafflor yellow A (HYA) against glucocorticoid-induced osteoporosis (GIOP) in rats. In-silico study was carried out on EGFR receptor (PDBID: 1m17), Estrogen Alpha (PDB id: 2IOG), MTOR (PDB id: 4FA6), RANKL (PDB id: 1S55), and VEGFR2 (PDB id: 1YWN) protein. For this investigation, Sprague-Dawley (SD) rats were used, and they received an oral dose of HYA (5, 10, and 20 mg/kg, b.w.) along with a subcutaneous injection of dexamethasone (0.1 mg/kg/day) to induce osteoporosis. The biomechanical, bone parameters, antioxidant, cytokines, inflammatory, nutrients, hormones, and urine parameters were estimated. HYA treatment significantly suppressed the body weight and altered the organ weight. HYA treatment remarkably suppressed the level of alkaline phosphatase, acid phosphatase, and improved the level of bone mineral density (total, proximal, mild, and dis). HYA treatment restored the level of calcium (Ca), phosphorus (P), estradiol (E2), and parathyroid hormone near to the normal level. HYA treatment remarkably altered the level of biomechanical parameters, antioxidant, cytokines, urine, and inflammatory parameters. HYA treatment altered the level of osteoprotegerin (OPG), receptor activator of nuclear factor kappa beta (RANKL) and RANKL/OPG ratio. The result clearly showed the anti-osteoporosis effect of HYA against GIOP-induced osteoporosis in rats via alteration of antioxidant, cytokines, inflammatory, and bone protective parameters.
Subject(s)
Chalcone , Glucocorticoids , Osteoporosis , Quinones , Rats, Sprague-Dawley , Animals , Osteoporosis/chemically induced , Osteoporosis/prevention & control , Osteoporosis/metabolism , Osteoporosis/drug therapy , Rats , Quinones/pharmacology , Chalcone/analogs & derivatives , Chalcone/pharmacology , Glucocorticoids/adverse effects , Anti-Inflammatory Agents/pharmacology , Bone Density/drug effects , Male , Female , Dexamethasone/pharmacologyABSTRACT
BACKGROUND: In nephrotic syndrome, protein leaks from the blood into the urine through the glomeruli, resulting in hypoproteinaemia and generalised oedema. While most children with nephrotic syndrome respond to corticosteroids, 80% experience a relapsing course. Corticosteroids have reduced the death rate to around 3%; however, corticosteroids have well-recognised potentially serious adverse events such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, cataracts, glaucoma and behavioural disturbances. This is an update of a review first published in 2000 and updated in 2002, 2005, 2007, 2015 and 2020. OBJECTIVES: The aim of this review was to assess the benefits and harms of different corticosteroid regimens in children with steroid-sensitive nephrotic syndrome (SSNS). The benefits and harms of therapy were studied in two groups of children: 1) children in their initial episode of SSNS and 2) children who experience a relapsing course of SSNS. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 9 July 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) performed in children (one to 18 years) during their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent. DATA COLLECTION AND ANALYSIS: Summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: In this 2024 update, we included five new studies, resulting in 54 studies randomising 4670 children. Risk of bias methodology was often poorly performed, with only 31 studies and 28 studies respectively assessed to be at low risk for random sequence generation and allocation concealment. Ten studies were at low risk of performance bias (blinding of participants and personnel), and 12 studies were at low risk of detection bias (blinding of outcome assessment); nine of these studies were placebo-controlled RCTs. Twenty-seven studies (fewer than 50%) were at low risk for attrition bias, and 26 studies were at low risk for reporting bias (selective outcome reporting). In studies at low risk of selection bias evaluating children in their initial episode of SSNS, there is little or no difference in the number of children with frequent relapses when comparing two months of prednisone with three months or more (RR 0.96, 95% CI 0.83 to 1.10; 755 children, 5 studies; I2 = 0%; high certainty evidence) or when comparing three months with five to seven months of therapy (RR 0.99, 95% CI 0.74 to 1.33; 376 children, 3 studies; I2 = 35%; high certainty evidence). In analyses of studies at low risk of selection bias, there is little or no difference in the number of children with any relapse by 12 to 24 months when comparing two months of prednisone with three months or more (RR 0.93, 95% CI 0.81 to 1.06; 808 children; 6 studies; I2 = 47%) or when comparing three months with five to seven months of therapy (RR 0.88, 95% CI 0.70 to 1.11; 377 children, 3 studies; I2 = 53%). Little or no difference was noted in adverse events between the different treatment durations. Amongst children with relapsing SSNS, four small studies (177 children) utilising lower doses of prednisone compared with standard regimens found little or no differences between groups in the numbers with relapse (RR 1.01, 95% CI 0.85 to 1.20; I2 = 0%). A fifth study (117 children) reported little or no difference between two weeks and four weeks of alternate-day prednisone after remission with daily prednisone. A recent large, well-designed study with 271 children found that administering daily prednisone compared with alternate-day prednisone or no prednisone during viral infection did not reduce the risk of relapse. In contrast, four previous small studies in children with frequently relapsing disease had reported that daily prednisone during viral infections compared with alternate-day prednisone or no treatment reduced the risk of relapse. AUTHORS' CONCLUSIONS: There are four well-designed studies randomising 823 children, which have demonstrated that there is no benefit of prolonging prednisone therapy beyond two to three months in the first episode of SSNS. Small studies in children with relapsing disease have identified no differences in efficacy using lower induction doses or shorter durations of prednisone therapy. Large, well-designed studies are required to confirm these findings. While previous small studies had suggested that changing from alternate-day to daily prednisone therapy at the onset of infection reduced the likelihood of relapse, a much larger and well-designed study found no reduction in the number relapsing when administering daily prednisone at the onset of infection.
Subject(s)
Nephrotic Syndrome , Randomized Controlled Trials as Topic , Recurrence , Nephrotic Syndrome/drug therapy , Humans , Child , Child, Preschool , Adolescent , Infant , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/adverse effects , Bias , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Dexamethasone/therapeutic useABSTRACT
OBJECTIVE: To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). MATERIALS AND METHODS: This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. RESULTS: In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). CONCLUSIONS: Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.
High-potency steroid plus CsA is more effective than CsA monotherapy in alleviating the signs and symptoms of DED.Dual therapy has acceptable safety particularly in terms of IOP and cataract risk.Dual therapy is a viable option for patients with severe DED without contraindications.
Subject(s)
Cyclosporine , Drug Therapy, Combination , Dry Eye Syndromes , Humans , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/diagnosis , Male , Female , Retrospective Studies , Middle Aged , Aged , Treatment Outcome , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Adult , Severity of Illness Index , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effectsSubject(s)
Collagen Diseases , Humans , Middle Aged , Administration, Cutaneous , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Collagen Diseases/chemically induced , Collagen Diseases/drug therapy , Collagen Diseases/pathology , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Treatment OutcomeABSTRACT
Background: Thyroid eye disease (TED) is an autoimmune orbital disease, with intravenous glucocorticoid (IVGC) therapy as the first-line treatment. Due to uncertain response rates and possible side effects, various prediction models have been developed to predict IVGC therapy outcomes. Methods: A thorough search was conducted in PubMed, Embase, and Web of Science databases. Data extraction included publication details, prediction model content, and performance. Statistical analysis was performed using R software, including heterogeneity evaluation, publication bias, subgroup analysis, and sensitivity analysis. Forest plots were utilized for result visualization. Results: Of the 12 eligible studies, 47 prediction models were extracted. All included studies exhibited a low-to-moderate risk of bias. The pooled area under the receiver operating characteristic curve (AUC) and the combined sensitivity and specificity for the models were 0.81, 0.75, and 0.79, respectively. In view of heterogeneity, multiple meta-regression and subgroup analysis were conducted, which showed that marker and modeling types may be the possible causes of heterogeneity (P < 0.001). Notably, imaging metrics alone (AUC = 0.81) or clinical characteristics combined with other markers (AUC = 0.87), incorporating with multivariate regression (AUC = 0.84) or radiomics analysis (AUC = 0.91), yielded robust and reliable prediction outcomes. Conclusion: This meta-analysis comprehensively reviews the predictive models for IVGC therapy response in TED. It underscores that integrating clinical characteristics with laboratory or imaging indicators and employing advanced techniques like multivariate regression or radiomics analysis significantly enhance the efficacy of prediction. Our research findings offer valuable insights that can guide future studies on prediction models for IVGC therapy in TED.
Subject(s)
Administration, Intravenous , Glucocorticoids , Graves Ophthalmopathy , Humans , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Graves Ophthalmopathy/drug therapy , Treatment OutcomeABSTRACT
In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.
What did we find out from the INBUILD trial about progressive lung fibrosis?Lung fibrosis is a rare disease in which the lung tissue becomes scarred and hardened. This makes it more difficult for the lungs to inflate and for the lungs to exchange oxygen with the blood. In some patients, lung fibrosis gets worse over time. This is known as progressive lung fibrosis. In the INBUILD trial, researchers looked at the effects of a drug called nintedanib in patients with progressive lung fibrosis. In this trial, 663 patients were randomly allocated to receive either nintedanib or a placebo and then followed for approximately 19 months. The patients and the researchers did not know which patients were taking the active drug (nintedanib) and which patients were taking placebo. The results showed that the criteria used to find patients with progressive lung fibrosis to take part in the trial successfully identified patients whose disease would continue to worsen. These criteria were based on a decline in the volume (size) of the lungs, worsening symptoms such as shortness of breath, and worsening of changes seen on a scan of the chest. The trial results also showed that nintedanib slowed down loss of lung function and had a similar benefit in patients with different severities of disease at the start of the trial. The most common side-effects of nintedanib were gastrointestinal problems, particularly diarrhea, but most patients given nintedanib were able to cope with these side-effects without needing to stop treatment. Large trials like the INBUILD trial are important for helping us understand how diseases progress and in which patients particular drugs should be used.
Subject(s)
Disease Progression , Indoles , Pulmonary Fibrosis , Tomography, X-Ray Computed , Humans , Indoles/adverse effects , Indoles/therapeutic use , Indoles/administration & dosage , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/physiopathology , Vital Capacity , Severity of Illness Index , Treatment Outcome , Randomized Controlled Trials as Topic , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Lung/drug effects , Lung/physiopathology , Lung/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/physiopathology , Lung Diseases, Interstitial/diagnosis , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/physiopathology , Idiopathic Pulmonary Fibrosis/diagnosis , Male , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/administration & dosageABSTRACT
BACKGROUND: Dysferlinopathies are a clinically heterogeneous group of muscular dystrophies caused by gene mutations resulting in deficiency of the membrane-associated protein dysferlin. They manifest post-growth and are characterised by muscle wasting (primarily in the limb and limb-gridle muscles), inflammation, and replacement of myofibres with adipose tissue. The precise pathomechanism for dysferlinopathy is currently unclear; as such there are no treatments currently available. Glucocorticoids (GCs) are widely used to reduce inflammation and treat muscular dystrophies, but when administered to patients with dysferlinopathy, they have unexpected adverse effects, with accelerated loss of muscle strength. METHODS: To investigate the mechanistic basis for the adverse effects of GCs in dysferlinopathy, the potent GC dexamethasone (Dex) was administered for 4-5 weeks (0.5-0.75 µg/mL in drinking water) to dysferlin-deficient BLA/J and normal wild-type (WT) male mice, sampled at 5 (Study 1) or 10 months (Study 2) of age. A wide range of analyses were conducted. Metabolism- and immune-related gene expression was assessed in psoas muscles at both ages and in quadriceps at 10 months of age. For the 10-month-old mice, quadriceps and psoas muscle histology was assessed. Additionally, we investigated the impact of Dex on the predominantly slow and fast-twitch soleus and extensor digitorum longus (EDL) muscles (respectively) in terms of contractile function, myofibre-type composition, and levels of proteins related to contractile function and metabolism, plus glycogen. RESULTS: At both ages, many complement-related genes were highly expressed in BLA/J muscles, and WT mice were generally more responsive to Dex than BLA/J. The effects of Dex on BLA/J mice included (i) increased expression of inflammasome-related genes in muscles (at 5 months) and (ii) exacerbated histopathology of quadriceps and psoas muscles at 10 months. A novel observation was pronounced staining for glycogen in many myofibres of the damaged quadriceps muscles, with large pale vacuolated myofibres, suggesting possible myofibre death by oncosis. CONCLUSION: These pilot studies provide a new focus for further investigation into the adverse effects of GCs on dysferlinopathic muscles.
Subject(s)
Dexamethasone , Dysferlin , Glucocorticoids , Muscle, Skeletal , Muscular Dystrophies, Limb-Girdle , Animals , Dysferlin/genetics , Dysferlin/metabolism , Dexamethasone/adverse effects , Dexamethasone/pharmacology , Male , Muscular Dystrophies, Limb-Girdle/genetics , Muscular Dystrophies, Limb-Girdle/metabolism , Muscular Dystrophies, Limb-Girdle/pathology , Glucocorticoids/adverse effects , Pilot Projects , Mice , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/drug effects , Membrane Proteins/genetics , Membrane Proteins/metabolism , Disease Models, Animal , Muscle Strength/drug effectsABSTRACT
Glucocorticoid-induced osteoporosis (GIOP) is the common reason for secondary osteoporosis. Dendrobine (DEN) is the major biologically active component of Dendrobium officinale with anti-inflammatory and antiaging properties. Whether DEN could alleviate osteogenic inhibition in GIOP rats is still unknown. The influence on osteogenic function caused by DEN on dexamethasone-treated bone marrow mesenchymal stem cells and rats was observed. The in vitro results showed that DEN reversed the inhibition of osteogenic differentiation by dexamethasone. Moreover, DEN supplementation attenuated dexamethasone-induced bone loss in vivo. DEN activated JNK and p38 MAPK pathways and restrained GR nuclear translocation, which could be prevented by the JNK (SP600125) or p38 (SB203580) pathway inhibitor. This study verified that DEN alleviated dexamethasone-induced nuclear translocation of GR, and inhibition of osteogenesis via JNK and p38 pathways, laying the foundation for DEN as a therapeutic agent for GIOP.
Subject(s)
Glucocorticoids , Mesenchymal Stem Cells , Osteogenesis , Osteoporosis , Rats, Sprague-Dawley , p38 Mitogen-Activated Protein Kinases , Animals , Humans , Male , Rats , Cell Differentiation/drug effects , Dexamethasone/adverse effects , Glucocorticoids/adverse effects , JNK Mitogen-Activated Protein Kinases/metabolism , JNK Mitogen-Activated Protein Kinases/genetics , MAP Kinase Signaling System/drug effects , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Osteogenesis/drug effects , Osteoporosis/drug therapy , Osteoporosis/metabolism , Osteoporosis/chemically induced , Osteoporosis/prevention & control , p38 Mitogen-Activated Protein Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/genetics , Plant Extracts/pharmacology , Receptors, Glucocorticoid/metabolism , Receptors, Glucocorticoid/geneticsABSTRACT
Glucocorticoid-induced neuropsychiatric side effects have been known since their initial usage and frequently manifest in clinical settings. Despite this, they remain unpredictable, variable and complex to manage, impacting patient outcomes and the healthcare system.We report a case of glucocorticoid-induced psychosis after the administration of dexamethasone post-neurosurgical intervention and its evolution with the initiation of chemotherapy. Although initially manic symptoms were prominent, with the beginning of chemotherapy psychotic symptoms dominated the clinical presentation, followed by depressive symptoms. Despite challenges in diagnosis and management, including adverse reactions to antipsychotic treatment, this case provides critical insights into the variable and dynamic nature of neuropsychiatric side effects induced by glucocorticoids.
Subject(s)
Dexamethasone , Glucocorticoids , Psychoses, Substance-Induced , Humans , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Psychoses, Substance-Induced/etiology , Psychoses, Substance-Induced/diagnosis , Antipsychotic Agents/adverse effects , Male , Female , Middle AgedABSTRACT
Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by hyperinflammation and organ failure, with a high mortality rate. Current first-line treatments for adult patients have limited efficacy and significant toxicity. The novel selective histone deacetylase inhibitor (HDACi), chidamide, has shown promise in preclinical studies for the potential treatment of HLH. Methods: An open-label, single-center study was conducted to evaluate the efficacy and safety of chidamide in combination with etoposide and glucocorticoids for the treatment of HLH in adult patients. Seventeen patients who fulfilled at least five of the eight HLH-2004 criteria were enrolled and treated with the combination therapy. The primary outcome was overall response rate (ORR), and secondary outcomes included survival, safety and tolerability, and changes in laboratory indicators. Results: A total of 17 HLH patients who met the inclusion criteria were enrolled in this study, with a male to female ratio of 1.8:1. The age range at enrollment was 31 to 71 years old, with a median age of 52 years old. The ORR was 76.5% (13/17 patients), with a complete response (CR) rate of 17.6% (3/17 patients) and a partial response (PR) rate of 58.8% (10/17 patients). The median overall survival (OS) was not achieved, with OS at 6 months and 12 months being 81% and 65%, respectively. The median progression free survival (PFS) was not achieved, with PFS at 6 months and 12 months being 68% and 55%, respectively. Hematologic toxicities is the most common. Safety profile was favorable, with very few cases of grade 3/4 toxicities observed. The results showed that the levels of sCD25, platelets, aspartate aminotransferase, lactate dehydrogenase, and albumin in these patients were significantly improved 3 weeks after treatment. Conclusion: The addition of chidamide to etoposide and glucocorticoids may be a promising new treatment option for patients with HLH, with a high ORR, manageable safety profile, and significant improvement in laboratory indicators. Further research is needed to confirm these findings and determine the optimal dosing and duration of therapy.
Subject(s)
Aminopyridines , Benzamides , Etoposide , Glucocorticoids , Lymphohistiocytosis, Hemophagocytic , Humans , Etoposide/administration & dosage , Etoposide/adverse effects , Etoposide/therapeutic use , Male , Female , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/mortality , Adult , Middle Aged , Benzamides/administration & dosage , Benzamides/adverse effects , Benzamides/therapeutic use , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Aminopyridines/administration & dosage , Aminopyridines/adverse effects , Aminopyridines/therapeutic use , Treatment Outcome , Aged , Drug Therapy, Combination , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylase Inhibitors/adverse effects , Histone Deacetylase Inhibitors/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
Drug-induced liver injury (DILI) is an adverse reaction to drugs and their metabolites. The activation of adaptive immune and inflammatory responses plays an important role in the pathogenesis of DILI. Glucocorticoids (GCs) have powerful anti-inflammatory and immunosuppressive effects and have been used to treat a variety of immune-mediated liver diseases. Due to the important role of the immune system in DILI, GCs are widely used in the clinical treatment of DILI; however, whether they are beneficial to patients remains controversial. There is no uniform standard for the timing, dosage, and population selection of GCs, which mainly depend on the clinician's experience. Therefore, elucidating whether GCs are beneficial for patients with DILI is an urgent clinical problem. Our review summarizes the recent literature and discusses the clinical efficacy, applicable population, application timing, and efficacy of GCs in special types of DILI, providing a reference for the clinical application of GCs.
Subject(s)
Chemical and Drug Induced Liver Injury , Glucocorticoids , Humans , Glucocorticoids/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Treatment Outcome , Anti-Inflammatory Agents/therapeutic useABSTRACT
Epimedium is thought to enhance the integrity of tendons and bones, ease joint discomfort and rigidity and enhance kidney function. Although glucocorticoids are commonly used in clinical practice, the mechanism by which the active compound Epimedin C (EC) alleviates glucocorticoid-induced osteoporosis (GIOP) is not well understood. The therapeutic potential of EC in treating GIOP was evaluated using alizarin red S staining, calcein immersion and fluorescence imaging, and bone mineralization, bone mass accumulation and bone density in zebrafish larvae were determined. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the key signalling pathways related to bone development were identified. A protein-protein interaction network (PPIN) was constructed to identify osteoclast characteristic genes and the findings were verified using real-time quantitative PCR (RT-qPCR). The bone tissue damage caused by prednisolone was reduced by EC. It also altered physiological processes, improved bone density, boosted mineralization and increased bone mass and activity. Subsequent empirical investigations showed that EC impacted the major signalling pathways involved in bone development, such as osteoclast differentiation, oestrogen, MAPK, insulin resistance, PPAR and AMPK signalling pathways. It also decreased the expression of genes typical of osteoclasts. The results of our study uncover a previously unknown function of EC in controlling bone formation and emphasize the potential of EC as a therapeutic target. The osteoprotective effect of EC indicates its potential as a cost-effective strategy for treating GIOP.
Subject(s)
Disease Models, Animal , Flavonoids , Glucocorticoids , Osteoclasts , Osteoporosis , Signal Transduction , Zebrafish , Animals , Osteoporosis/chemically induced , Osteoporosis/metabolism , Osteoporosis/genetics , Osteoporosis/pathology , Osteoporosis/drug therapy , Flavonoids/pharmacology , Glucocorticoids/adverse effects , Glucocorticoids/pharmacology , Osteoclasts/metabolism , Osteoclasts/drug effects , Signal Transduction/drug effects , Bone Density/drug effects , Protein Interaction Maps , Osteogenesis/drug effects , Osteogenesis/genetics , Calcification, Physiologic/drug effectsABSTRACT
OBJECTIVE: The objective of this meta-analysis was to compare the efficacy and safety between glucocorticoids combined with mycophenolate mofetil (MMF) versus glucocorticoids combined with cyclophosphamide (CTX) for henoch schonlein purpura nephritis (HSPN) in children. METHODS: Databases including PubMed, EMbase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched from the inception to April 5th, 2024. Eligible studies comparing glucocorticoids combined with MMF versus glucocorticoids combined with CTX for HSPN in children were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Ten studies were included in the meta-analysis. Six randomized controlled trials (RCTs) and 4 non-randomized studies involving 675 patients were identified. Compared with CTX therapeutic schedule, MMF therapeutic schedule had a higher complete remission (CR) within the 6 months (OR 1.61, 95%CI 1.16-2.22, Pâ =â .004) and CR within the 12 months (OR 1.73, 95%CI 1.00-2.97, Pâ =â .05). However, there was no significant difference between MMF and CTX therapeutic schedule concerning total remission (TR) within the 6 months (OR 1.54, 95%CI 0.82-2.92, Pâ =â .18) and TR within the 12 months (OR 2.08, 95%CI 0.86-5.01, Pâ =â .10). In addition, incidences of gastrointestinal discomfort (OR 0.33, 95%CI 0.19-0.56, Pâ <â .0001), liver function injury (OR 0.28, 95%CI 0.09-0.87, Pâ =â .03), myelosuppression (OR 0.15, 95%CI 0.06-0.41, Pâ =â .0001), alopecia (OR 0.25, 95%CI 0.07-0.91, Pâ =â .03) in MMF therapeutic schedule were all lower than CTX therapeutic schedule. There was no statistically significant difference between the 2 therapeutic schedules concerning infection (OR 0.90, 95%CI 0.50-1.61, Pâ =â .72), rash (OR 0.38, 95%CI 0.07-2.04, Pâ =â .26). CONCLUSION: Glucocorticoids combined with MMF had a higher CR and lower incidence of adverse effects compared with glucocorticoids combined with CTX in the treatment of HSPN in children.
Subject(s)
Cyclophosphamide , Drug Therapy, Combination , IgA Vasculitis , Immunosuppressive Agents , Mycophenolic Acid , Nephritis , Humans , IgA Vasculitis/drug therapy , IgA Vasculitis/complications , Cyclophosphamide/therapeutic use , Cyclophosphamide/adverse effects , Mycophenolic Acid/therapeutic use , Mycophenolic Acid/adverse effects , Child , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/administration & dosage , Nephritis/drug therapy , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Treatment Outcome , Randomized Controlled Trials as Topic , Child, PreschoolABSTRACT
Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant medications and remain the cornerstone of systemic lupus erythematosus (SLE) therapy. However, ongoing exposure to GCs has the potential to elicit multiple adverse effects. Considering the irreplaceability of GCs in SLE therapy, it is important to explore the optimal regimen of GCs. Here, we compared the long-term efficacy and safety of pulsed and oral GC therapy in a lupus-prone mouse model. Mice were grouped using a randomized block design. We monitored survival rates, proteinuria, serum autoantibodies, and complement 3 (C3) levels up to 28 weeks of age, and assessed renal damage, bone quality, lipid deposition in the liver and marrow, glucose metabolic parameters, and levels of hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, we explored the mechanisms underlying the superior efficacy of the pulse regimen over oral prednisone regimen. We found that both GC regimens alleviated the poor survival rate, proteinuria, and glomerulonephritis, while also reducing serum autoantibodies and increasing the level of C3. The pulsed GC regimen showed less resistance to insulin, less suppression of the HPA axis, less bone loss, and less bone marrow fat deposition than the oral GC regimen. Additionally, GC-induced leucine zipper (GILZ) was significantly overexpressed in the GC pulse group. These results suggest that the GC pulse regimen ameliorated symptoms in lupus-prone mice, with fewer side effects, which may be related to GILZ overexpression. Our findings offer a potentially promising GC treatment option for SLE.