Glucocorticoid Usage Research Articles

Factors affecting discrepancies in disease activity evaluation between patients and physicians in systemic lupus erythematosus-The importance of symptoms such as fatigue.

There are often discrepancies in the evaluation of disease activity between patients and physicians in systemic lupus erythematosus (SLE). In this study, we examined the factors that affect those evaluations. Physician visual analogue scale (Ph-VAS), patient VAS (Pt-VAS), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k), glucocorticoid (GC) usage and dose, age, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and three patient-reported outcomes (SLE symptom checklist [SSC], short-form 36 questionnaire [SF-36], and LupusPRO) were obtained from a study performed in 2019 using 225 SLE outpatients of the Kyoto Lupus Cohort at Kyoto University Hospital. Correlations among Ph-VAS, Pt-VAS, or dif (Pt-VAS-Ph-VAS) (Pt-VAS minus Ph-VAS) and other factors were examined. We found a significant discrepancy between Pt-VAS (median 38.0mm) and Ph-VAS (median 18.7mm) scores (p < 0.001). SSC score showed a significant correlation with Pt-VAS and dif (Pt-VAS-Ph-VAS) (p < 0.001). Among SSC items, fatigue showed the most significant correlation with dif (Pt-VAS-Ph-VAS). We also showed that higher dif (Pt-VAS-Ph-VAS) was associated with lower quality of life (QOL) evaluated by SF-36 and LupusPRO. Pt-VAS scores tended to be higher than Ph-VAS scores, and the discrepancy was influenced mainly by fatigue. Higher dif (Pt-VAS-Ph-VAS) was associated with lower patient QOL.

ED-71 promotes osseointegration of titanium implants in a rat model of GIOP by alleviating the effects of dexamethasone on bone remodeling in a SIRT1-dependent manner

ObjectiveGlucocorticoid-induced osteoporosis (GIOP), a common complication of glucocorticoid usage, plays a critical role in the success of dental implant restoration by affecting osseointegration. Eldecalcitol (ED-71) prevents GIOP; however, its role in the osseointegration of implants under GIOP conditions remains elusive. MethodsDexamethasone was used to establish a rat model of GIOP. Subsequently, mini-implant surgery was performed on the femur. GIOP rats were administered ED-71 via gavage to assess its role in the osseointegration of titanium implants under GIOP conditions. MC3T3-E1 and RAW264.7 cells were utilized to explore the molecular mechanism of ED-71 in ameliorating disorder of bone remodeling caused by dexamethasone. ResultsThe administration of ED-71 promoted the formation of newly formed woven bone and the resolution of inflammation around titanium implants. In vitro experiments indicated that ED-71 ameliorated dexamethasone-induced dysfunction of osteoblasts and osteoclasts by increasing the expression level of sirtuin 1 (SIRT1). Inhibition of SIRT1 by selisistat counteracts the regulatory effects of ED-71 on dexamethasone-induced disorder of bone remodeling. Molecular docking and Western blotting revealed that the neurogenic locus notch homolog protein and nuclear factor kappa B signaling pathways are essential for the effects of ED-71 on dexamethasone-induced disorder of bone remodeling. ConclusionED-71 promoted implant osseointegration in a rat model of GIOP by alleviating the effects of dexamethasone on bone remodeling in a SIRT1-dependent manner.

Clinical outcomes of tocilizumab therapy in polyarticular and systemic juvenile idiopathic arthritis: a single-center analysis (2018-2022)

AbstractThis single-center retrospective study aimed to evaluate the safety and efficacy of Tocilizumab (TOC) in children with polyarticular (pJIA) and systemic juvenile idiopathic arthritis (sJIA) who exhibited inadequate responses to disease-modifying antirheumatic drugs (DMARDs) and biological modifiers (bDMARDs). Conducted at the Department of Pediatric Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation in Warsaw, Poland, between 2018 and 2022, the study enrolled 29 patients diagnosed with JIA based on International League of Associations for Rheumatology (ILAR) criteria. The cohort comprised 13 sJIA and 16 pJIA patients, aged 2-18 years, receiving TOC treatment for 24 months. Safety and efficacy assessments included analysis of medical documentation, laboratory tests (CRP, ESR, WBC), and Juvenile Disease Activity Score (JADAS) 71 at baseline, 3, 6, 12, and 24 months post-treatment initiation. Significant reductions in CRP and ESR levels were observed within three months, with sustained improvement in JADAS71 scores over the 24-month treatment period. A substantial majority, 73.07% of patients, achieved inactive disease status or low disease activity, highlighting T0C’s effectiveness. Adverse effects were manageable, predominantly involving mild to moderate infections, with no serious adverse events or instances of macrophage activation syndrome (MAS). The study also noted a steroid-sparing effect of TOC, with a reduction in glucocorticoid usage among the cohort. Tocilizumab demonstrates substantial efficacy in reducing disease activity and improving clinical outcomes in patients with pJIA and sJIA, coupled with a favorable safety profile. These findings reinforce the role of TOC as a critical component of the therapeutic arsenal for JIA, offering hope for improved quality of life and disease management in this patient population.

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

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

An article reviews of anti-cataract activity of hydroalcoholic extract of Annona squamosa leaves

Other medicines and natural remedies have been used for the treatment and health of people since ancient times. Medicinal plants are considered useful and of the most important purpose. It can be applied to botanical medicines, nutraceuticals, medicines, food products, cosmetics, etc. There is an increasing demand for. Custard apples. It is a versatile tree whose fruit is edible and a source of medicine and products. It is used as antioxidant, antidiabetic, hepatoprotective, cytotoxic activity, genotoxicity, antitumor activity, anti-inflammatory drug. Cataract is nothing but visual impairment caused by a defect in the lens. It is one of the causes of blindness worldwide; It accounts for approximately 42% of all blindness. One significant risk factor for the development of posterior subcapsular cataracts is long-term glucocorticoid usage. The preventive and therapeutic effects of many herbs such as onion, Chinese cinnamon and ginkgo, which have protective properties against cataracts, have been reported. This review demonstrates the therapeutic potential of custard apple leaf extract as an anti-cataract effec

Clinical efficacy of various regimens of systemic glucocorticoids therapy in COVID-19 patients

Introduction. Systemic glucocorticoids have been successfully used in the treatment of patients with moderate to severe COVID-19. However, the best clinical efficacy dosage regimen and duration of glucocorticoid usage is remained unclear.Aim. To evaluate the results of using different regimens of systemic glucocorticoid therapy in the treatment of patients with moderate and severe COVID-19.Materials and methods. The results of a retrospective study of medical papers of 200 patients who had moderate to severe COVID-19 in the period from May 2020 to December 2021 are presented. The inclusion criterion was the use different regimens of doses and durations systemic glucocorticoid therapy in these patients without the use blockers of Janus kinases. and genetically engineered biological drugs. Clinical effectiveness was assessed by the severity and sufficiency of the anti-inflammatory effect, the frequency and nature of side effects of this therapy.Results. The regimen of glucocorticoids at a dose equivalent to 6 mg/day of dexamethasone for 7 days demonstrated the greatest clinical effectiveness: it significantly reduced C-reactive protein, hematological inflammatory indices,% lung tissue damage, minimally affecting carbohydrate metabolism and hemostasis. Glucocorticoid therapy equivalent to 20 mg/day of dexamethasone for more than 7 days and pulse-therapy for 3 days demonstrated significantly lower clinical effectiveness.Conclusions. In patients with moderate to severe COVID-19, it is reasonable to use a dose of glucocorticoid equivalent to 6 mg/day of dexamethasone for 7 to 10 days, or equivalent to 20 mg/day for no more than 7 days. The use of pulse therapy and the use of glucocorticoids at a dose equivalent to ≥ 20 mg/day of dexamethasone for a duration of 7 days are not recommended. To assess the dynamics of inflammation and monitor the effectiveness of glucorticoid therapy, in addition to routine markers of inflammation, it is recommended to use hematological inflammatory indices.

Risk factors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: A multicenter retrospective study.

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.

The efficacy and safety of perioperative glucocorticoid for total knee arthroplasty: a systematic review and meta-analysis

BackgroundAn increasing number of individuals undergo total knee arthroplasty (TKA), which can result in pain, limited motor function and adverse complications such as infection, nausea and vomiting. Glucocorticoids have been shown anti-inflammatory and antiemetic effects, but can also elevate blood glucose levels and increase the risk of wound infection. Thus, it is essential to investigate the efficacy and safety of glucocorticoid usage in TKA.MethodA comprehensive systematic search of PubMed, Medline, EMBASE, Cochrane databases, to identify relevant randomized controlled trials (RCTs) of glucocorticoid application in TKA. The primary outcomes assessed were the postoperative pain assessment. Secondary outcomes included the range of motion in knee joint, levels of inflammatory cytokines, adverse complications, and the length of hospital stay.ResultsThirty-six randomized controlled trials were included in the final analysis. The glucocorticoid group exhibited significant reduction in the resting VAS scores on postoperative days 1, 2 (POD1, 2)and postoperative 3 months (POM3), as well as decreased morphine consumption on POD1 and increased range of motion (ROM) in knee joint on POD1, 3. Additionally, the glucocorticoid group exhibited decreased levels of postoperative inflammatory cytokines and the incidence of PONV along with a shorter length of hospital stay. The blood glucose concentration was significantly increased in the glucocorticoid group on POD1 compared with the control group. While the blood glucose on POD2 and occurrence of postoperative adverse complications were similar between two groups including wound infection and venous thrombosis. The periarticular injection analgesia (PIA) group demonstrated lower VAS scores on POD2 comparing to the systemic administration (SA) group according to two studies. However, there was no significant difference of the resting VAS on POD1 and POD2 between PIA and SA group across all studies.ConclusionPerioperative glucocorticoids treatment in TKA significantly reduced short-term pain score and opioid-use which was probably not patient relevant. The application of glucocorticoids in TKA implied a beneficial trend in analgesic, anti-inflammatory, and antiemetic effects, as well as improved range of motion and shortened hospital stay. While it will not increase the risk of continued high glucose, postoperative wound infection and venous thrombosis.

Unraveling the Role of Endothelial Dysfunction in Osteonecrosis of the Femoral Head: A Pathway to New Therapies.

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis.

Glucocorticoid use in psoriatic arthritis and treatment outcomes: does the gender have a role?

BackgroundSystemic glucocorticoids are commonly used in practice in the treatment of psoriatic arthritis. However, authorities advise against prescribing it, primarily because of the risk of psoriasis flare-ups. The authors aimed to assess the glucocorticoid use in psoriatic arthritis (PsA), factors associated with the use of glucocorticoids and to uncover whether gender has an impact on glucocorticoid use and treatment responses. Disease-modifying antirheumatic drug (DMARD)-naive PsA patients were included in this cross-sectional study. Baseline clinical and demographic characteristics were recorded. After starting DMARD treatment, patients were followed for 2 years. The number of patients who started glucocorticoids, the clinical demographics of these patients, the duration of glucocorticoid administration, and the dose for administration were recorded. Patient outcomes and gender differences were analyzed. Disease activity was measured using the Disease Activity Scale 28 (DAS28-CRP) and the Disease Activity Index for Psoriatic Arthritis (DAPSA).ResultsFifty-five of the 141 patients (39%) received glucocorticoids at the 2-year follow-up. There was no difference between the sexes who are in remission-low disease activity (LDA) on cDMARD monotherapy (p = 0.300). Glucocorticoid usage (p = 0.660), dose (p = 0.054), and duration (p = 0.159) did not differ between male and female patients. Higher glucocorticoid doses were associated with dactylitis, higher CRP levels, higher DAS-28 and DAPSA scores, and longer (> 3 months) glucocorticoid administration. Glucocorticoid duration was longer in patients with higher TJS, SJS, serum CRP, higher DAS-28 and DAPSA scores, and higher glucocorticoid doses. Sustained remission-LDA was achieved in 16 of 55 patients after cessation of glucocorticoids and no sex difference was observed.ConclusionSystemic glucocorticoids are commonly prescribed in PsA, and when added to treatment even for short periods and in low doses, they help achieve significant disease control. Except for axial involvement, there is no difference in treatment responses between male and female patients, making it unnecessary to make a gender distinction in the treatment algorithm. Given these findings, prospective studies are needed to evaluate glucocorticoids as a bridging treatment in PsA, such as rheumatoid arthritis.

Smoking, alcohol consumption, drug abuse, and osteoporosis among older adults: a cross-sectional study on PERSIAN cohort study in Fasa

BackgroundWith increasing life expectancy and a growing population of older adults, the prevalence of osteoporosis has risen, resulting in a higher incidence of bone fractures, which necessitate extended treatment and specialized medical care. This study investigates the relationship between smoking, alcohol consumption, drug abuse, and osteoporosis among older adults in southern Iran, utilizing cohort data.MethodsThis cross–sectional study is derived from the Fasa Adult Cohort Study (FACS), which included 10,133 individuals. From this cohort, we selected 1,631 older adults using census sampling methods. Our study aimed to explore the correlation between smoking, alcohol consumption, and drug abuse among older adults and the incidence of osteoporosis. We collected demographic information, nutritional indexes, medical history, glucocorticoid usage, and self-reported data on smoking, alcohol consumption, drug abuse, and osteoporosis through questionnaires. To investigate the relationship between smoking, alcohol, and drug use with osteoporosis while accounting for confounding factors, we employed logistic regression analysis.ResultsThe average age of the study participants was 64.09 ± 3.8 years, with a majority (898 (55.1%)) being female. Osteoporosis prevalence among the subjects was 25.20%. The results did not reveal a significant correlation between smoking, alcohol consumption, drug abuse, and osteoporosis (p > 0.05). Regression analysis identified gender, recent history of fractures within the past five years, history of using glucocorticoids, and physical activity as significant predictive risk factors for osteoporosis within the study population (p < 0.05).ConclusionThe study underscores the significance of addressing osteoporosis risk factors in older adults. Healthcare policymakers and administrators can use these findings to identify and mitigate influential factors contributing to osteoporosis in this demographic.

P-78 Life-threatening fungal infection due to long term glucocorticoid usage in amiadarone thyrotoxicosis

Abstract Introduction Amiadorone-associated thyroiditis (AIT) has 2 subtypes. In type 1, there is usually underlying thyroid disease and thyrotoxicosis occurs due to increased hormone synthesis. In type 2, thyrotoxicosis occurs as a result of T4-T3 release due to destruction(1). Steroid use is recommended in the treatment of AIT. Steroids may cause infections by affecting both innate and acquired immunity. If the patient has other comorbidities, long-term hospitalization, type 2 diabetes mellitus or lymphopenia, these factors may also predispose to infection(2). Clinical Case V.E., age 63, male. The patient was diagnosed atrial fibrillation 4 years ago and was started on amiadorone. After 3 years of amiadorone use, amiadorone was discontinued in January 2023. In April, thyrotoxicosis was detected in an external center where he went with complaint of weight loss. The patient was considered to have amiadorone-associated thyroiditis and methyl prednisolone treatment was started. He used approximately 2 grams of steroid and methimazole 2×15 mg regularly for 2 months. During the period of steroid use, TSH value was always suppressed and T4 value was always 3-4 times the reference value. With the use of methyl prednisolone, severe myopathy developed especially in the proximal muscles and steroid induced diabetes was diagnosed. The patient was admitted to our hospital on 06.07.2023.TSH value was found to be suppressed and T4&amp;gt;100 pmol/liter (reference:11-22). On admission examination, there were diffuse candida plaques in the mouth. On pulmonary examination, rales were heard in the right lung and voriconazole was started because of fungal infection in the right hilar region on tomography. Steroid was discontinued and methimazole was increased to 2×30 mg in the patient who was thought to have fungal infection and had severe myopathy. Cholestyramine was added to his treatment. Voriconazole was discontinued in the patient who had visual hallucinations after 5 days of voriconazole use. During follow-up, the patient developed hypoxia 6 days later and a newly developed cavity in the lower lobe of the right lung was observed in the tomography. The findings were evaluated in favor of fungal pneumonia in the foreground and amphotericin B was started with the recommendation of infectious diseases. Galactomannan, aspergillus and Quantiferon tests were negative. The patient was consulted to pulmonology department because of the newly developed cavity and fiberoptic bronchoscopy was planned. Bronchoscopy showed no appearance suggestive of malignancy. Tuberculosis PCR was negative. T4 values and acute phase reactants completely regressed under treatment and the patient was discharged. Conclusion Steroid treatment is used in AIT type 2 and in cases of indistinguishable AIT, but it should not be ignored that this treatment has its own side effects. Especially, not giving steroids for a long time and trying to reduce the dose as soon as possible will be important in reducing steroid-related side effects.

Effect of methylprednisolone in reducing severe COVID-19 and mortality in high-risk patients: A retrospective study.

The treatment of COVID-19 patients, especially high-risk patients, remains a large challenge. Glucocorticoids have been accepted as effective medicines for severe COVID-19. However, the glucocorticoid usage guidelines do not cover all the indications for high-risk patients. To identify more effective treatments for high-risk patients with COVID-19, this retrospective study analyzed routine epidemiological, clinical, and laboratory data from 33 high-risk patients with COVID-19 in Beijing Gobroad Boren Hospital, Beijing, China, most of whom responded well to treatment. Severe acute respiratory syndrome coronavirus-2 infection was confirmed via real-time reverse transcriptase polymerase chain reaction assays. Outcome measures such as duration of mechanical ventilation, intensive care unit length of stay, and 28-day mortality were analyzed. Patients were divided into two groups: mild to moderate COVID-19 (n = 26) and severe COVID-19 (n = 7). Chest computed tomography images were used to guide methylprednisolone administration or withdrawal. Upon intensive care unit admission, 12.1% of patients were mechanically ventilated with an average partial pressure of oxygen/fraction of inspired oxygen(PaO2/FiO2) ratio of 279 ± 146. No coinfections with other endemic viruses were observed. The duration of mechanical ventilation was 16 days (interquartile range: 8-28); the intensive care unit length of stay was 11 (interquartile range: 2-33) days; and the 28-day total mortality was 3.0%. Multivariate regression analysis revealed that low-dose, timely methylprednisolone administration was associated with a lower severe COVID-19 rate and mortality in high-risk patients. For high-risk patients, once there are ground-glass opacities (GGO) in the computed tomography image, continuous and low-dose methylprednisolone administration promotes inflammation remission and protects them from severe COVID-19 or mortality.

Agomelatine alleviates steroid-induced osteoporosis by targeting SIRT1/RANKL/FOXO1/OPG signalling in rats.

One of the major contributors to secondary osteoporosis is long-term glucocorticoid usage. Clinically used antidepressant agomelatine also has anti-inflammatory properties. Our research aimed to inspect the probable defensive effect of agomelatine against steroid-promoted osteoporosis. There were four groups of rats; group I had saline as a negative control; rats of group II had dexamethasone (0.6 mg/kg, s.c.), twice weekly for 12 weeks; rats of group III had agomelatine (40 mg/kg/day, orally), as a positive control, daily for 12 weeks; and rats of group IV had dexamethasone + agomelatine in the same previous doses combined for 12 weeks. Finally, biochemical as well as histopathological changes were evaluated and dexamethasone treatment caused osteoporosis, as evidenced by discontinuous thin cancellous bone trabeculae, minor fissures and fractures, irregular eroded endosteal surface with elevated alkaline phosphate, tartarate resistant acid phosphate (TRACP) and osteocalcin levels. Osteoprotegerin (OPG), calcium, and phosphorus levels decreased with disturbed receptor activator of nuclear factor κ B ligand (RANKL), forkhead box O1 (FOXO1), and silent information regulator 1 (SIRT1)protein expression. However, treatment with agomelatine restored the normal levels of biochemical parameters to a great extent, supported by SIRT activation with an improvement in histopathological changes. Here, we concluded that agomelatine ameliorates steroid-induced osteoporosis through a SIRT1/RANKL/FOXO1/OPG-dependent pathway.

Coronary artery calcification in Takayasu's arteritis: clinical characteristics and risk factors.

Coronary artery calcification (CAC) is frequently observed in Takayasu's arteritis (TAK). Our objective is to calculate the prevalence and severity of CAC in TAK, while evaluating the influence of traditional cardiovascular risk factors, glucocorticoid exposure, and disease activity on CAC. This retrospective study involved 155 TAK patients. We measured the Agatston score by coronary computed tomography angiography (CCTA) and categorised all patients into groups with or without CAC (41 vs. 114) to compare clinical characteristics and ancillary findings between the two groups. Among the TAK patients, a total of 41 TAK patients (26.45%) exhibited CAC. Age of onset, disease duration, history of hypertension, history of hyperlipidaemia, Numano V and glucocorticoid use emerged as the independent risk factors for developing CAC in TAK (OR [95% CI] 1.084[1.028-1.142], p=0.003; 1.005 [1.001-1.010], p=0.020; 4.792 [1.713-13.411], p=0.003; 4.199 [1.087-16.219], p=0.037; 3.287 [1.070-10.100], p=0.038; 3.558[1.269-9.977], p=0.016). Nonetheless, CAC was not associated with disease activity. Moreover, the extent of calcification score in TAK showed a positive correlation with the number of traditional cardiovascular risk factors. We recommend CCTA screening for Numano V classified TAK patients. Glucocorticoid usage significantly escalates the risk of CAC. Therefore, in cases of effectively controlled disease, the inclusion of immunosuppressants aimed at reducing glucocorticoid dosage is advisable.

P037 The NIHR IMID Bioresource: a descriptive analysis of the first 5000 participants

Abstract Background/Aims The NIHR Immune-mediated inflammatory diseases (IMID)-Bioresource is a recallable resource of patients with an IMID, pre-disease states and unaffected first-degree relatives. Here, we report on the recruited cohort to date, focusing on co-existent comorbidities. Methods Patients are categorised into one of three primary IMID groups: rheumatoid arthritis (RA), axial-spondyloarthropathy-psoriasis spectrum (AxSpA-PsO: AxSpA, PsO, psoriatic arthritis [PsA], reactive arthritis) and systemic autoimmune rheumatic diseases (SARDs: systemic lupus erythematosus [SLE], mixed and undifferentiated connective tissue disease). Data were collected on clinical phenotype, secondary IMIDs, medications and key co-morbidities. Results 5028 participants (4965 IMIDs, 46 pre-disease, 17 relatives) have been enrolled to the IMID-Bioresource Sept-2020-Aug-2022 from 63 UK-centres. Of those with a diagnosed IMID, RA (N = 2472) was the largest group, then AxSpA-PsO (N = 2012) and SARDs (n = 479). Two-thirds (N = 3210, 64.7%) female, median (IQR) age 57.9 (47.3-67.6) years. 1544 (62.5%) patients with primary IMID RA were seropositive. The commonest AxSpA-PsO diseases included PsO (N = 1232, 24.8%), PsA (N = 1116, 22.5%) and AxSpA (N = 467, 9.4%). SLE was the commonest SARD (N = 376, 7.6%), a third (N = 133, 35.4%) reported previous lupus nephritis. 1241 (25.0%) patients reported &amp;gt;1 IMID diagnoses. The commonest overlaps were PsO and RA (N = 108, 2.2%), PsO and AxSpA (N = 72, 1.5%) and RA and Sjögren’s syndrome (N = 65, 1.3%). 2880 (58.0%) reported minimum one (range 1-11) co-morbidity, the commonest, hypertension (N = 1201, 24.2%), depression (N = 820, 16.5%) and asthma (N = 580, 11.7%). 274 (5.5%) patients reported ischaemic heart disease, commonest in RA (N = 152, 6.2%). Interstitial lung disease was reported by 75 (1.5%) patients, again most frequent in RA (N = 48, 1.9%). Overall, 696 (14.0%) IMID patients had ≥3 co-morbidities. Oral steroid use was highest in SARD (N = 166, 34.7%). The commonest DMARD in all groups was methotrexate, followed by sulfasalazine in RA (N = 379, 15.3%) and AxSpA-PsO (N = 189, 9.4%) and mycophenolate mofetil in SARDs (N = 69, 14.4%). Overall, 2079 (41.9%) IMID patients were receiving a biological DMARD. Conclusion A high proportion of IMID patients have more than one IMID diagnoses. Significant multi-morbidity with cardiovascular, respiratory and mood disorders was observed and considerable ongoing glucocorticoid usage. The IMID-Bioresource aims to refine patient subsets based on shared immune mechanisms to ultimately, improve precision medicine and patient outcomes. Disclosure S. Dyball: Grants/research support; MRC. Other; GSK, UCB. E. Vital: None. S. Plein: None. D. McGonagle: None. A.G. Pratt: None. J. Isaacs: None. B. Griffiths: None. W. Ng: None. J. McBeth: None. C.E.M. Griffiths: None. B. Parker: Honoraria; Fresenius-Kabi, AbbVie. Grants/research support; GSK, Genzyme/Sanofi. Other; Eli Lilly, Roche. M.H. Buch: None. I. Bruce: Consultancies; ILTOO, AstraZeneca, Eli Lilly, GSK, Merck Serono, UCB. Grants/research support; Genzyme/Sanofi, GSK, UCB, Roche. Other; AstraZeneca, GSK, UCB.

Glucocorticoids Accelerate Erythropoiesis in Healthy Humans-Should the Use in Sports Be Reevaluated?

The World Anti-Doping Agency prohibits glucocorticoid administration in competition but not in periods out of competition. Glucocorticoid usage is controversial as it may improve performance, albeit debated. A hitherto undescribed but performance-relevant effect of glucocorticoids in healthy humans is accelerated erythropoiesis. We investigated whether a glucocorticoid injection accelerates erythropoiesis, increases total hemoglobin mass, and improves exercise performance. In a counterbalanced, randomized, double-blinded, placebo-controlled crossover design (3 months washout), 10 well-trained males (peak oxygen uptake, 60 ± 3 mL O 2 ·min -1 ·kg -1 ) were injected with 40 mg triamcinolone acetonide (glucocorticoid group) or saline (placebo group) in the gluteal muscles. Venous blood samples collected before and 7-10 h, 1, 3, 7, 14, and 21 d after treatment were analyzed for hemoglobin concentration and reticulocyte percentage. Hemoglobin mass and mean power output in a 450-kcal time trial were measured before as well as 1 and 3 wk after treatment. A higher reticulocyte percentage was evident 3 d (19% ± 30%, P < 0.05) and 7 d (48% ± 38%, P < 0.001) after glucocorticoid administration, compared with placebo, whereas hemoglobin concentration was similar between groups. Additionally, hemoglobin mass was higher ( P < 0.05) 7 d (glucocorticoid, 886 ± 104 g; placebo, 872 ± 103 g) and 21 d (glucocorticoid, 879 ± 111 g; placebo, 866 ± 103 g) after glucocorticoid administration compared with placebo. Mean power output was similar between groups 7 d (glucocorticoid, 278 ± 64 W; placebo, 275 ± 62 W) and 21 d (glucocorticoid, 274 ± 62 W; placebo, 275 ± 60 W) after treatment. Intramuscular injection of 40 mg triamcinolone acetonide accelerates erythropoiesis and increases hemoglobin mass but does not improve aerobic exercise performance in the present study. The results are important for sport physicians administering glucocorticoids and prompt a reconsideration of glucocorticoid usage in sport.

474. Differences In Clinical Manifestation, Prognostic Factors, and Outcomes Between Patients With Community-onset And Nosocomial Candidemia

Abstract Background Candidemia is an invasive and deadly infectious disease. The associated risk factors of candidemia include immunosuppression, broad-spectrum antibiotics, catheters, glucocorticoids, critical illness, surgery, neonates, previous candida colonization, and illicit drug use. In previous studies, the characteristic of community-onset candidemia was distinct from nosocomial candidemia. Methods We selected patients who were admitted for equal or more than two days in Taichung Veterans General Hospital of Taiwan from 2015 to 2018 with electronic medical charts. The diagnosis of candidemia was defined as Candida species identified in blood cultures by commercial identification systems. We applied Kaplan-Meier survival curves with a log-rank test and built multivariate Cox proportional-hazards models for risk factors associated with in-hospital mortality. The purpose of this study is to investigate the difference in the characteristics, outcomes, and associated risks of death between community-onset and nosocomial candidemia. Results A total of 339 patients were included for analysis. The incidence was 1.50 per 1000 admission person-years. 64.60% of patients were male, and the mean age was 64.24-year-old. The characteristics of patients were similar in both groups except for the status of port-A, glucocorticoid usage, and diabetes mellitus. In the community-onset group, a higher proportion of C. glabrata and C. parapsilosis, but fewer C. albicans and C. tropicalis were identified than in the nosocomial group. The all-cause mortality rate was 55.75%. Multivariate Cox proportional-hazards model showed that nosocomial (hazard ratio; HR, 1.96; 95CI, 1.291 - 2.97 ; p =0.002), glucocorticoids within seven days before candidemia (HR, 1.68; 95CI, 1.21 -2.32, p = 0.002), and septic shock (HR, 1.85; 95CI, 1.292 - 2.641, p &amp;lt; 0.001) were associated with poor outcome whereas treatment with an echinocandin within two days after candidemia was a protective factor (HR, 0.65; 95CI, 0.466 - 0.911, p = 0.012). Survival curves analysis between community-onset candidemia and nosocomial candidemia A log-rank test was applied to assess the statistical significance, and a p-value less than 0.05 was considered statistically significant. Conclusion In conclusion, candidemia is a lethal disease with a better outcome noted in those with community-onset candidemia. Species diversity existed in both groups, and Early initiation of echinocandin therapy within two days could reduce 35% mortality. Disclosures All Authors: No reported disclosures.

The effects of synthetic glucocorticoid treatment for inflammatory disease on brain structure, function, and dementia outcomes: A systematic review

Many regions of the brain have a high density of glucocorticoid receptors, and the prolonged elevation of endogenous glucocorticoids may cause neurotoxicity and increase risk for cognitive decline and dementia. However, despite synthetic glucocorticoids being the first line of treatment for many inflammatory diseases, few studies have addressed whether therapeutic glucocorticoids may have similar undesirable effects on the brain. Thus, our systematic review investigated the impact of long-term glucocorticoid usage on adult brain structure, cognitive function, and dementia risk. We identified 13 studies that met our eligibility criteria and found conflicting results dependent on the outcome studied. In particular, all but one study on hippocampal and amygdalar volumes found significant atrophy of both structures occurred in those who took glucocorticoids. Additionally, executive function, particularly working memory, and global cognitive function were significantly poorer in those taking long-term glucocorticoids. Notably, declines in episodic memory were not associated with long-term usage. Furthermore, most studies of dementia (all-cause) and Alzheimer’s disease, excluding vascular dementia, showed null to negative associations with glucocorticoids, suggesting a potential protective effect. Therefore, glucocorticoid therapy in those with inflammatory disease may impair certain brain structures and specific cognitive functions, but could lead to a significantly reduced risk of dementia.

Glucocorticoid use as a cause of non-cellular immune response to SARS-Cov2 Spike in patients with immune system diseases

Disease modifying therapies compromise immune response to SARS-Cov2 or its vaccine in patients with immune system diseases (ISD). Therefore, analysis of the humoral and cellular responses against Spike is of utmost importance to manage ISD patients. A single-center retrospective study was conducted to evaluate the impact of COVID-19 immunization in 87 ISD patients and 81 healthy controls. We performed a whole blood interferon gamma release assay using SARS-Cov2 Spike and Nucleocapsid recombinant proteins in order to evaluate T-cell memory response, and an IgG anti-Spike ELISA to evaluate humoral response. Cellular (26.4%) and humoral (44.8%) responses were negative against Spike in ISD patients following COVID-19 immunization. In univariate analysis, an anti-Spike T cell defective response was associated with the use of glucocorticoids (Odds ratio [OR] = 10.0; p < 10−4), serum albumin level ≤40 g/L (OR = 18.9; p < 10−4), age over 55 years old (OR = 3.9, p = 0.009) and ≤2 vaccine injections (OR = 4.9; p = 0.001). The impact of glucocorticoids persisted after adjustment for age and number of vaccine injections (OR = 8.38, p < 0.001). In contrast, the humoral response was impacted by the use of anti-CD20 mAb (OR = 24.8, p < 10−4), and an extended time since immunization (≥75 days; OR = 4.3, p = 0.002). Double defective cellular/humoral responses (6.9%) were typically encountered in glucocorticoids and/or anti-CD20 mAb treated ISD with a serum albumin level ≤40 g/L (OR = 17.5; p = 0.002). Glucocorticoid usage, B cell depleting therapies, and a low serum albumin level were the main factors associated with a non-response to COVID-19 immunization in ISD patients. These results need further confirmation in larger studies.