Search Results (90)

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Background/Objectives: Glucocorticoids (GCs) are frequently prescribed to control disease in Rheumatoid Arthritis (RA). However, long-term GC therapy with high daily doses is associated with bone involvement, which is considered the main extra-articular complication of RA. The trabecular bone score (TBS) has proven useful in assessing vertebral trabecular bone quality and fracture risk. To identify whether the long-term treatment of low doses of GCs are associated with low vertebral TBS in RA patients. Methods: A cross-sectional study, including 203 women with RA (ACR, 1987). Clinical, epidemiologic, and therapeutic variables were assessed. We identified the current daily dose, duration, and cumulative dose of GCs. Vertebral bone quality was assessed by TBS. Low vertebral trabecular bone quality was defined as TBS ≤ 1.300. Multivariate logistic regression analyses were used to identify risk factors of low TBS. Results: Prevalence of low TBS in RA women was 52%. RA + low TBS were older (61.9 vs. 55.5, p < 0.001) and had higher prevalence of menopause (90% vs. 75%, p = 0.004), hypertension (50% vs. 34%, p ≤ 0.02), and diabetes mellitus (13% vs. 4%, p = 0.02). There were no associations between GC use, neither doses or cumulative doses, and TBS. Multivariate analyses showed the following: age (OR: 1.05, 95% CI: 1.02–1.08) and the presence of diabetes mellitus (OR: 3.30, 95% CI: 1.03–10.60) were associated with a high risk of low vertebral trabecular bone quality in RA. Conclusions: Half of the RA patients had low trabecular bone quality. Older age and diabetes mellitus are important risk factors for low trabecular bone quality in RA. These findings should give alert to early detection of low TBS, establishing strategies aimed at avoiding the consequences of this complication, including vertebral fractures. Full article

Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Endocrine disorders such as hypercortisolism, hypothyroidism, and polycystic ovary syndrome (PCOS) are closely linked to MASLD through shared metabolic pathways. Mechanisms include glucocorticoid-induced gluconeogenesis and lipolysis, impaired lipid clearance in hypothyroidism, and the hyperandrogenism-induced downregulation of hepatic low-density lipoprotein (LDL) receptors. PCOS-related factors—such as central obesity, adipocyte hypertrophy, low adiponectin levels, and genetic predisposition—further promote hepatic steatosis. Thyroid dysfunction may also impair the hepatic deiodination of T4, contributing to lipid accumulation and inflammation. Given the overlapping pathophysiology among endocrine, hepatic, and reproductive disorders, multidisciplinary collaboration is essential to optimize diagnosis, treatment, and long-term cardiometabolic outcomes. Full article

Glehnia littoralis Fr. Schmidt ex Miq. has been cultivated in China for a long time and used as a medicinal plant called “Beishashen” in traditional Chinese medicine and has been traditionally known to have antibacterial and anti-inflammatory effects, but its direct role in periodontitis has not been known. Currently used periodontal treatments require long-term administration, which causes many side effects. Therefore, in this study, we evaluated the effects of G. littoralis extract (GLE) on periodontitis in an experimental periodontitis-induced in vitro and vivo model and understood its potential molecular mechanism. The effect of GLE on periodontitis in vitro was investigated using human periodontal ligament (HPDL) cells mediated by PG-LPS. Additionally, a ligature-induced periodontitis model and a PG-LPS-induced periodontal inflammation model were used to investigate the effect of GLE in vivo. In vitro study results showed that GLE down-regulated the increased inflammatory cytokines and mediators in HPDL cells stimulated with PG-LPS, and simultaneously down-regulated the levels of 11β-HSD1 and glucocorticoid receptor (GR), thereby alleviating periodontal inflammation. At the same time, it restored the lost osteoblast differentiation potential of HPDL cells. In addition, in an in vivo model representatively used for periodontitis research, the periodontal inflammation-alleviating effect and the effect of restoring or protecting damaged periodontal tissue were confirmed. GLE can be considered as a new periodontitis treatment agent through regulating 11β-HSD1. Full article

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being. Full article

Summary: COVID-19, caused by SARS-CoV-2, has been associated with a range of cardiovascular complications, including myocarditis. This review aims to systematically present the clinical manifestations, underlying pathophysiological mechanisms, diagnostic approaches, and management strategies for both COVID-19-associated myocarditis and myocarditis related to SARS-CoV-2 vaccination. We conducted a literature search using the PubMed database, covering studies published up to early 2024. Search terms included combinations of “COVID-19”, “Coronavirus”, “SARS-CoV-2”, and/or “vaccination” with “cardiac injury”, “cardiac inflammation”, “myocarditis”. The reported prevalence of COVID-19-associated myocarditis varies between 2.3% and 5.0%, though myocardial injury is more frequently observed than confirmed myocarditis. Pathophysiological mechanisms include direct viral damage, immune-mediated injury, and molecular mimicry. Clinically, patients may present with chest pain, dyspnea, and fever. Diagnostic workup includes electrocardiography (ECG), troponin measurement, echocardiography, cardiac magnetic resonance imaging (cMRI), and in selected cases, endomyocardial biopsy (EMB). The management and disposition of COVID-19-associated myocarditis varies according to severity, especially to allow targeted treatment of complications. Glucocorticoids are a mainstay of treatment in severe cases. Myocarditis following SARS-CoV-2 vaccination is rare, more frequently reported in males under 30 years, and is generally associated with a favorable prognosis. Despite this, the benefits of vaccination continue to outweigh the risks. COVID-19 is associated with an increased risk of heart failure and other cardiovascular complications, underlining the importance of long-term follow-up and preventive strategies. Further research is needed to better understand the pathogenesis and optimal management of myocarditis in the context of COVID-19, with the goal of developing evidence-based therapeutic algorithms. Full article

Stress reactions play an important role in animals’ ability to cope with various situations. Glucocorticoids are measured as a stress parameter, and analysis of their faecal metabolites has proven to be a good method for evaluating long term stress. We hypothesised that dogs suffering from cancer would have a higher stress level during cancer therapy, which would be reflected in higher levels of faecal cortisol metabolites (FCMs). Faeces were collected from 40 dogs receiving radiation or chemotherapy before and during the treatment, and from 53 healthy dogs, who served as a control group. FCMs were extracted and quantified by a cortisol enzyme immunoassay. The results showed that the stress levels were not significantly higher in the cancer patients before therapy compared to those in the control group. Additionally, there were no significant differences in the FCM concentrations of dogs at specific time points during chemotherapy or radiotherapy. Therefore, suspected stress should not be a criterion to exclude animals from cancer treatment. Such a treatment seems ethically justifiable if it is expected to provide benefits and improvement in the quality of life for patients. Full article

Background/Objectives: Children with congenital adrenal hyperplasia (CAH) face significant risks of impaired growth and metabolic disturbances despite standard glucocorticoid therapy. This cross-sectional study aimed to evaluate growth outcomes, nutritional status, and associated factors among children with CAH treated in a Vietnamese tertiary pediatric center. Methods: We assessed 201 children aged 1.1–16.5 years in a tertiary pediatric center in Vietnam for anthropometric parameters, biochemical markers (calcium, phosphate, 25-hydroxyvitamin D), and clinical features. Growth status was evaluated using WHO standards, and bone age was assessed radiographically. Statistical analyses explored associations between growth outcomes and clinical, biochemical, and treatment-related factors. Results: Stunting was present in 16.4% of children, while 53.3% were overweight or obese. Bone age advancement occurred in 51.7% of cases. Vitamin D insufficiency or deficiency was detected in 85.6% of patients, and hypocalcemia was present in 85.1%. Overweight/obesity, vitamin D deficiency, and bone age advancement were associated with older age, prolonged corticosteroid therapy, higher androgen levels, and clinical features of treatment imbalance (e.g., Cushingoid appearance, hyperpigmentation). Female sex was significantly associated with higher rates of stunting. Conclusions: Growth impairment, nutritional deficiencies, and skeletal maturation disturbances are prevalent among children with CAH in Vietnam. Early identification of risk factors and the implementation of tailored management strategies that address both endocrine and nutritional health are crucial for optimizing long-term outcomes. Full article

Background and clinical significance: Osteonecrosis of the femoral head (ONFH) is a disease of the epiphysis caused by the death of osteocytes and osteoblasts, resulting in debilitating pain. ONFH can be traumatic or nontraumatic, with prolonged glucocorticoid use being the leading cause of nontraumatic ONFH. Atopic dermatitis (AD) is a chronic inflammatory skin condition typically treated with topical corticosteroids. ONFH following topical corticosteroid treatment is exceedingly rare, with limited documentation in the literature. We present a case of an under-recognized complication of prolonged topical corticosteroid treatment. Case presentation: We report a case of a 29-year-old Caucasian male patient with sharp right hip pain. Plain radiographs, a CT scan, and an MRI indicated Ficat and Arlet stage 3 ONFH. The patient reported the prolonged uncontrolled use of topical mometasone furoate for five years due to AD. Following the diagnosis, topical corticosteroids were discontinued, and the treatment was shifted to tacrolimus and, subsequently, to oral methotrexate with folic acid. The patient underwent a total hip arthroplasty in June 2022. Given his young age and poor response to previous treatments, he was transitioned to upadacitinib, which led to significant improvement without skin flare-ups or postoperative hip pain. Conclusions: This case highlights the rare, but serious, risk of ONFH associated with long-term topical corticosteroid use. It underscores the importance of monitoring systemic side effects in dermatological therapies and educating patients on proper corticosteroid use. Alternative treatments, such as upadacitinib, should be considered in young male patients to prevent severe complications. Full article

Background: The association between Coronavirus Disease-2019 (COVID-19) and new-onset cardiomyopathy (NOC) is unclear. Objectives: We aim to assess the incidence of NOC in hospitalized COVID-19 patients and its impact on short- and long-term survival. Methods: We retrospectively studied 2219 COVID-19 patients hospitalized between March 2020 and February 2022 who underwent an in-hospital echocardiogram. NOC was defined as a left-ventricular ejection fraction (LVEF) reduction of >10%, resulting in an LVEF of <54% for females and <52% for males. The 30-day and 1-year survival outcomes in patients without and with NOC were studied. Results: Among 25,943 hospitalized COVID-19 patients, 2219 met our inclusion criteria, with 209 (9.4%) having NOC. NOC patients were more likely to be male (56.1% vs. 68.4%, p = 0.001) and have chronic kidney disease (51.4% vs. 60.3%, p = 0.018). They had a higher 30-day mortality rate (29.1% vs. 32%, p = 0.033), but the 1-year survival rate was similar between the patients without and with NOC (36.9% vs. 41.6%, p = 0.12). Multivariable regression revealed that advanced age, admission to intensive care unit, mechanical ventilation, treatment with glucocorticoids, and treatment with vasopressors were associated with higher odds of 30-day mortality in NOC patients. Only 74 (35.4%) NOC patients had follow-up echocardiograms after discharge, of which 47 showed persistent cardiomyopathy. Conclusions: NOC can affect around 1 out of 10 hospitalized COVID-19 patients undergoing echocardiography. While NOC was associated with worse short-term survival, it did not impact the long-term mortality of these patients. Persistent LVEF deficits in some patients emphasize the need for improved outpatient follow-up to identify at-risk individuals and optimize treatment. Full article

Background/Objectives: Autoimmune thrombocytopenia is a common manifestation of systemic lupus erythematosus (SLE). Its main treatments are glucocorticoids, intravenous immunoglobulin, and immunosuppressants, but thrombopoietin mimetics may be considered with refractory to conventional treatment. Romiplostim, a thrombopoietin receptor agonist, has been approved for increasing platelet counts in corticosteroid-refractory chronic immune thrombocytopenia. However, data on its long-term safety and efficacy in patients with SLE are still lacking. Case Presentation: We present the case of a 55-year-old woman with SLE and refractory immune thrombocytopenia who developed bilateral adrenal hemorrhage and progressed to fatal catastrophic anti-phospholipid syndrome while using romiplostim. Full article

Background/Objectives: Chronic macular edema (CME) is a common complication of diabetic retinopathy or non-infectious uveitis affecting the posterior segment (NIU-PS). Alongside anti-VEGF therapy, glucocorticoids are frequently used to manage CME. Given the heterogeneous nature of patients’ medical history, their social conditions, and disease manifestations, individualized treatment is essential for optimal outcomes. This study assesses the effectiveness of intravitreal fluocinolone acetonide (FA) (Iluvien^®) in treating persistent and recurrent macular edema in clinical practice at the University Hospital of Erlangen–Nuremberg, Germany. Methods: A total of 46 eyes with diabetic macular edema (DME) (21 eyes) and NIU-PS (25 eyes) were retrospectively analyzed over a follow-up period of up to 36 months. Since persistent retinal thickness fluctuations are linked to long-term retinal damage and functional decline, this study analyzed central retinal thickness (CRT)—including its fluctuations measured as CRT amplitude—alongside BCVA as the primary outcomes. Results: After an initial decrease in CRT in the first year after FA treatment, the maximum CRT amplitude significantly decreased in the following years. For patients with DME, CRT amplitude reduced from 271.4 µm to 91.57 µm in the first year (p = 0.0056) and 106.0 µm in the second year (p = 0.0109). For patients with NIU-PS, CRT amplitude decreased from 185.2 µm to 87.7 µm in the first year (p = 0.0131) and 97.3 µm in the second year (p = 0.0375). Mean BCVA remained stable in both cohorts. Conclusions: Intravitreal FA proved to be effective in reducing and stabilizing CRT in patients with chronic DME and NIU-PS without losing visual acuity, reducing treatment burden. Full article

Background/Objectives: A limited number of previous studies have reported high rates of end-stage renal disease (ESRD) in adults with IgA vasculitis nephritis (IgAVN). Despite the high prevalence of the disease and the high rates of ESRD reported in the literature, no specific guidelines for adult patients have been established and there is no consensus on the management of the disease. This study aimed to prospectively investigate adults with IgAVN from a broad perspective. Methods: This investigation was designed as a prospective observational study and was conducted between 01.02.2022 and 01.10.2024. A total of 49 newly diagnosed adult (>18 years) patients with IgAVN were regularly followed up. At the end of the study, the renal remission rates, factors influencing remission, treatment data, treatment-related adverse events, and disease outcomes were determined. Results: The median follow-up time was 22 (IQR: 11–24) months. A total of 42 patients (87%) received immunosuppressive treatment in addition to the initial glucocorticoid treatment. Azathioprine (AZA) was the preferred (41%) first steroid-sparing agent. ESRD occurred in only one patient (2%), while a total of ten patients (20%) had an unfavorable outcome. The rate of nephrotic-range proteinuria (NRP) was significantly higher in the patients who did not achieve renal remission at the end of the 12-month follow-up period (9,7% vs. 60%; p = 0.02) and NRP was an independent risk factor for unfavorable outcomes [OR: 17.18; 95% CI: 1.31–224.95; p = 0.03]. A total of 16% of the patients developed an infection that required hospitalization during follow-up; these patients had a higher rate of IgAVN-associated acute kidney injury (62.5% vs. 22%; p = 0.02) and were significantly older (mean: 46 ± 15.3 vs. 65 ± 13.3; p = 0.002). One patient died of sepsis at 4 months and another died of a myocardial infarction at 32 months. Conclusions: These results suggest that adults with IgVAN do not have a high rate of ESRD if they receive effective immunosuppressive therapy. However, immunosuppressive therapy is associated with an increased risk of infection, particularly in the elderly. The presence of NRP is associated with lower long-term remission rates and has a predictive value for unfavorable outcomes. Full article

Background: Depression is a common psychiatric disorder that may be caused by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. The glucocorticoid receptor (GR) plays a significant role in regulating this axis. One negative regulator of GR action, previously associated with depressive behavior, is the overexpression of FK506-binding protein 5 (FKBP5), which may be regulated by microRNAs, including miR-511-5p. Objectives: In a rat model of depression, we aimed to investigate the expression of Fkbp5 and its regulator, miRNA-511-5p, during short- and long-term lithium treatment in four brain regions: the hypothalamus, hippocampus, pituitary, and frontal cortex. Methods: We used a rat model of depression induced by chronic mild stress (CMS) to assess if short- and long-term lithium treatment (7 and 42 days) influences Fkbp5 expression in the brain. We also assessed the effects of lithium treatment on the blood levels of corticosterone in CMS-exposed rats as compared to control groups. The changes in the expression of Fkbp5 were assessed by qPCR and Western blot. The expression of rno-miR-511-5p was assessed using qPCR. Statistical analysis was conducted in GraphPad Prism 9. Results: We found that long-term lithium treatment increased the expression of the FKBP5 protein in the pituitary gland in the lithium-treated rats compared to the control group. We also observed significant changes in Fkbp5 mRNA levels between CMS-exposed rats compared to the control animals, without significant changes in mRNA levels observed during short- and long-term lithium treatment in any brain region. We found no expression of rno-miR-511-5p in the analyzed brain regions. The corticosterone levels were significantly higher in CMS-exposed rats compared to the control, with no significant changes found between lithium-treated and control rats. Conclusions: FKBP5 protein expression in the brain may be regulated by long-term lithium treatment, thus affecting GR signaling in the rat depression model. Full article

Background/Objectives: Muscle atrophy, defined by diminished muscle mass and function, is a notable concern associated with aging, disease, and glucocorticoid treatment. Pueraria montana var. lobata extract (PMLE) demonstrates multiple bioactive properties, such as antioxidant, anti-inflammatory, and metabolic regulatory activities; however, its role in muscle atrophy has not been extensively investigated to date. This study examined how PMLE influences both muscle cell differentiation and dexamethasone (DEX)-induced muscle degeneration by focusing on the underlying molecular mechanisms. Methods: This study examined the effects of PMLE on myogenic differentiation and DEX-induced muscle atrophy. C2C12 myoblasts were treated with PMLE (10–100 ng/mL) and assessed for changes in the expression of myogenesis-related genes and activation of Akt/mTOR and AMPK/SIRT1/PGC-1α signaling cascades. In vivo, a DEX-induced muscle atrophy model was used to assess muscle mass, fiber morphology, and molecular changes. Results: PMLE PMLE promoted muscle cell development by increasing the expression of MyHC, MyoD, and myogenin while activating protein synthesis and mitochondrial biogenesis pathways. PMLE counteracted DEX-induced myotube atrophy, restoring myotube diameter and promoting cellular fusion in vitro. In vivo, PMLE mitigated muscle degradation in fast-twitch muscle groups and reversed DEX-induced suppression of key anabolic and mitochondrial pathways. Conclusions: These findings suggest that PMLE promotes myogenic differentiation and protects against muscle atrophy by regulating critical molecular pathways, indicating its promise as a treatment candidate for conditions involving muscle wasting. Further studies are required to assess its clinical application and long-term safety efficacy. Full article