Intravenous Glucocorticoid Therapy Research Articles

Fat-suppression T2 relaxation time and water fraction predict response to intravenous glucocorticoid therapy for thyroid-associated ophthalmopathy.

To investigate the value of fat-suppression (FS) T2 relaxation time (T2RT) derived from FS T2 mapping and water fraction (WF) derived from T2 IDEAL to predict the treatment response to intravenous glucocorticoids (IVGC) in patients with thyroid-associated ophthalmopathy (TAO) based on texture analysis. In this study, 89 patients clinically diagnosed with active and moderate-to-severe TAO were enroled (responsive group, 48 patients; unresponsive group, 41 patients). The baseline clinical characteristics and texture features were compared between the two groups. Multivariate analysis was performed to identify the independent predictors of treatment response to IVGC. ROC analysis and the DeLong test were used to assess and compare the predictive performance of different models. The responsive group exhibited significantly shorter disease duration and higher 90th percentile of FS T2RT and kurtosis of WF in the extraocular muscle (EOM) and 95th percentile of WF in the orbital fat (OF) than the unresponsive group. Model 2 (disease duration + WF; AUC, 0.816) and model 3 (disease duration + FS T2RT + WF; AUC, 0.823) demonstrated superior predictive efficacy compared to model 1 (disease duration + FS T2RT; AUC, 0.756), while there was no significant difference between models 2 and 3. The orbital tissues of responders exhibited more oedema and heterogeneity. Furthermore, OF is as valuable as EOM for assessing the therapeutic efficacy of IVGC. Finally, WF derived from T2 IDEAL processed by texture analysis can provide valuable information for predicting the treatment response to IVGC in patients with active and moderate-to-severe TAO. The texture features of FS T2RT and WF are different between responders and non-responders, which can be the predictive tool for treatment response to IVGC. Texture analysis can be used for predicting response to IVGC in TAO patients. TAO patients responsive to IVGC show more oedema and heterogeneity in the orbital tissues. WF from T2 IDEAL is a tool to predict the therapeutic response of TAO.

Prediction models of intravenous glucocorticoids therapy response in thyroid eye disease.

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. 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. 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. 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.

A novel nomogram to predict glucocorticoid response in thyroid-associated ophthalmopathy: findings from a pilot study.

Aimed to create a nomogram using clinical and eye-specific metrics to predict the efficacy of intravenous glucocorticoid (IVGC) therapy in patients with active and moderate-to-severe Thyroid-Associated Ophthalmopathy (TAO). This study was conducted on 84 eyes from 42 moderate-to-severe TAO patients who received systemic IVGC therapy, and 42 eyes from 21 controls. Data were collected retrospectively from June 2020 to December 2021. The least absolute shrinkage and selection operator (LASSO) method was used to identify predictive factors for "unresponsiveness" to IVGC therapy. These factors were then analyzed using logistic regression to create a nomogram. The model's discriminative ability was robustly assessed using a Bootstrap resampling method with 1000 iterations for receiver operating characteristic (ROC) curve analysis. The LASSO analysis identified six factors with non-zero coefficients as significant, including Schirmer I test values, Meibomian gland (MG) diameter, MG length, disease duration, whole capillary vessel density (VD) in the radial peripapillary capillary (RPC), and whole macular VD for the superficial retinal capillary plexus (SRCP). The subsequent logistic regression model highlighted MG length, whole macular VD for SRCP, and disease duration as independent predictors of IVGC therapy response. The constructed nomogram demonstrated an area under the curve (AUC) of 0.82 (95% CI: 0.73-0.91), affirming the model's consistent and reliable ability to distinguish between responsive and non-responsive TAO patients. Our nomogram, combining MG length (<4.875 mm), SRCP VD (<50.25%), and disease duration (>5.5 months), reliably predicts lower IVGC therapy effectiveness in active, moderate-to-severe TAO patients.

Whole-orbit radiomics: machine learning-based multi- and fused- region radiomics signatures for intravenous glucocorticoid response prediction in thyroid eye disease

BackgroundRadiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model.MethodsIn this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms.ResultsThe support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions.ConclusionsThe WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.

Determinants of clinical outcome in patients with moderate/severe Graves' orbitopathy undergoing treatment with parenteral glucocorticoids: a retrospective study.

Graves' orbitopathy (GO) occurs in approximately 25-40% of patients with Graves' disease (GD). High levels of anti-thyrotropin receptor antibodies (TRAbs), smoking habit, sex, older age, longer duration and amount of hyperthyroidism or hypothyroidism are well-recognized risk factors for the occurrence, severity and clinical course of GO. Oxidative stress (OX) has recently been shown to play a role in the pathogenesis of GO, and several clinical conditions related to OX have been investigated regarding the presentation and severity of GO. We aimed to evaluate the impact of clinical conditions related to oxidative stress on the outcome of intravenous glucocorticoid (ivGCs) therapy in a cohort of patients with active moderate to severe GO (AMS-GOs) treated at a single institution. We retrospectively studied a series of patients with AMS-GOs who were treated with ivGCs from January 2013 to May 2022. GO clinical evaluation was performed at baseline and at 6 (W6), 12 (W12) and 24 (W24) weeks after starting ivGCs by the seven-point clinical activity score (CAS) alone and by overall clinical criteria (CI) according to the European Group of Graves' Ophthalmopathy (EUGOGO). Total cholesterol and calculated LDL cholesterol (LDLc), triglyceride, body mass index (BMI), diabetes status, history of hypertension (HoH), smoking status, age and sex were used as covariates for the clinical outcome of GO to ivGCs. LDLc and HoH negatively and independently modulated the response of AMS-GOs to ivGCs. Notably, slightly elevated LDLc levels (> 130 mg/dl) reduced the response of orbital soft tissue to ivGCs, whereas more elevated LDLc levels (from 175 mg/dl to 190 mg/dl) and HoH were associated with poorer clinical response of eye motility and proptosis.

Factors predictive of poor visual outcome in indirect traumatic optic neuropathy: A retrospective cohort study

IntroductionThe gold standard treatment for indirect traumatic optic neuropathy (ITON) has not yet been conclusively established, and it is essential to gain an understanding of visual prognosis and to counsel patients regarding the predictive risk factors of poor visual outcomes. Currently, there is limited information regarding ITON in Thai populations; therefore, this study aimed to determine the risk factors of poor visual outcome in patients with this condition. MethodsA retrospective review was conducted of all ITON cases diagnosed at Rajavithi Hospital and Sawanpracharak Hospital between January 2016 and December 2022 in order to determine clinical characteristics and evaluate associated risk factors of poor visual prognosis using binary logistic regression analysis. ResultsThe mean age of this cohort of 101 patients was 36.17 years, with a male predominance of 73.3 %. Motor vehicle accidents were the most common cause of ITON, with a statistically significant 79.2 % of cases. The patients were categorized into an “improved group” of 29 patients and an “unimproved group” of 72. The unimproved group had a significantly older mean age and poorer initial visual acuity of 20/200 (p-values 0.001 and p < 0.001 respectively). There was no significant difference between Computed Tomography (CT) findings in the two groups. The improved group had significantly better visual acuity (VA) at 1-month and final follow-up visit than the unimproved group (both p < 0.001). Differences between gender, Glasgow coma score, associated underlying diseases, and duration from trauma to intravenous glucocorticoids therapy in the two groups were not statistically significant. Multivariable logistic regression analysis identified patient age of 40 years or more (Odds ratio (OR) 3.447, 95 % CI, 1.085–10.955, p = 0.036) and poor baseline VA (OR 6.628, 95 % Confidence Interval (CI), 2.308–19.036, p < 0.001) as significant risk factors for poor visual outcome in ITON patients. ConclusionsNo clear benefit was found of intravenous glucocorticoids in treatment of ITON. Patients aged 40 years or more and/or with poor baseline visual status should be advised that they are at increased risk of poor final visual outcomes.

Cardiovascular effects of COVID-19 in children

Introduction: Although severe acute respiratory failure is the primary cause of morbidity and mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, this viral infection leads to cardiovascular disease in some individuals. Cardiac effects of the virus include myocarditis, pericarditis, arrhythmias, coronary aneurysms and cardiomyopathy, and can result in cardiogenic shock and multisystem organ failure. Method: This review summarises cardiac manifestations of SARS-CoV-2 in the paediatric population. We performed a scoping review of cardiovascular disease associated with acute coronavirus disease 2019 (COVID-19) infection, multisystem inflammatory syndrome in children (MIS-C), and mRNA COVID-19 vaccines. Also examined are special considerations for paediatric athletes and return to play following COVID-19 infection. Results: Children presenting with acute COVID-19 should be screened for cardiac dysfunction and a thorough history should be obtained. Further cardiovascular evaluation should be considered following any signs/symptoms of arrhythmias, low cardiac output, and/or myopericarditis. Patients admitted with severe acute COVID-19 should be monitored with continuous cardiac monitoring. Laboratory testing, as clinically indicated, includes tests for troponin and B-type natriuretic peptide or N-terminal pro-brain natriuretic peptide. Echocardiography with strain evaluation and/or cardiac magnetic resonance imaging should be considered to evaluate diastolic and systolic dysfunction, coronary anatomy, the pericardium and the myocardium. For patients with MIS-C, combination therapy with intravenous immunoglobulin and glucocorticoid therapy is safe and potentially disease altering. Treatment of MIS-C targets the hyperimmune response. Supportive care, including mechanical support, is needed in some cases. Conclusion: Cardiovascular disease is a striking feature of SARS-CoV-2 infection. Most infants, children and adolescents with COVID-19 cardiac disease fully recover with no lasting cardiac dysfunction. However, long-term studies and further research are needed to assess cardiovascular risk with variants of SARS-CoV-2 and to understand the pathophysiology of cardiac dysfunction with COVID-19.

Cardiovascular effects of COVID-19 in children.

Although severe acute respiratory failure is the primary cause of morbidity and mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, this viral infection leads to cardiovascular disease in some individuals. Cardiac effects of the virus include myocarditis, pericarditis, arrhythmias, coronary aneurysms and cardiomyopathy, and can result in cardiogenic shock and multisystem organ failure. This review summarises cardiac manifesta-tions of SARS-CoV-2 in the paediatric population. We performed a scoping review of cardiovascular disease associated with acute coronavirus disease 2019 (COVID-19) infection, multisystem inflammatory syndrome in children (MIS-C), and mRNA COVID-19 vaccines. Also examined are special considerations for paediatric athletes and return to play following COVID-19 infection. Children presenting with acute COVID-19 should be screened for cardiac dysfunction and a thorough history should be obtained. Further cardiovascular evaluation should be considered following any signs/symptoms of arrhythmias, low cardiac output, and/or myopericarditis. Patients admitted with severe acute COVID-19 should be monitored with continuous cardiac monitoring. Laboratory testing, as clinically indicated, includes tests for troponin and B-type natriuretic peptide or N-terminal pro-brain natriuretic peptide. Echocardiography with strain evaluation and/or cardiac magnetic resonance imaging should be considered to evaluate diastolic and systolic dysfunction, coronary anatomy, the pericardium and the myocardium. For patients with MIS-C, combination therapy with intravenous immunoglobulin and glucocorticoid therapy is safe and potentially disease altering. Treatment of MIS-C targets the hyperimmune response. Supportive care, including mechanical support, is needed in some cases. Cardiovascular disease is a striking feature of SARS-CoV-2 infection. Most infants, children and adolescents with COVID-19 cardiac disease fully recover with no lasting cardiac dysfunction. However, long-term studies and further research are needed to assess cardiovascular risk with variants of SARS-CoV-2 and to understand the pathophysiology of cardiac dysfunction with COVID-19.

Structural and Functional Brain Changes After Glucocorticoid Therapy in Thyroid-Associated Ophthalmopathy.

To investigate the brain structural and functional alterations in patients with thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid therapy, using voxel-based morphometry (VBM) as well as resting-state functional magnetic resonance imaging (MRI) with amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo). Between 2019 and 2022, 32 patients with TAO and 23 healthy controls underwent pre-therapy MRI in Nanjing, China. Intravenous glucocorticoid therapy was administered to all patients. At 3 months after end of therapy, 26 patients were available for rescanned MRI. VBM, ALFF, and ReHo were used to evaluate the brain structural and functional differences. Before therapy, TAO patients showed significantly decreased gray matter volume (GMV) in the left orbital part of superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed) than healthy controls. Patients had higher ALFF values in bilateral gyrus rectus and olfactory cortex and lower values in bilateral cuneus. Patients also showed decreased ReHo values in bilateral lingual gyrus. After therapy, increased GMV in the left anterior cingulate gyrus and SFGmed, increased ALFF values in bilateral cuneus and superior occipital gyrus, and increased ReHo values in bilateral SFGmed were found in TAO patients compared to the pre-therapy cohort. Compared to controls, decreased GMV in left ORBsup was observed in post-therapy TAO patients. Our results indicated that TAO might cause functional and structural deficits in the visual and emotional regions of the brain, with recovery in the former and partial restoration in the latter after effective glucocorticoid therapy. These findings may lead to deeper understanding of the pathophysiological mechanism behind TAO.

T Cell Subsets are Associated with Clinical Activity and Efficacy of 4.5g Intravenous Glucocorticoid for Moderate-To-Severe Thyroid-Associated Ophthalmopathy

ABSTRACT Background Intravenous glucocorticoid (IVGC) remains the main treatment for moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, a substantial number (20–30%) of active moderate-to-severe TAO patients may not respond to IVGC. Some patients may have disease progression despite IVGC treatment or relapse after steroid withdrawal. Objectives To analyze risk factors for clinical activity and predictive factors for clinical outcomes of 4.5 g IVGC therapy in patients with moderate-to-severe TAO. Design and methods Our study was performed in two steps: step 1 involved 110 moderate-to-severe TAO patients and analyzed risk factors for TAO activity; step 2 involved 53 active moderate-to-severe TAO patients from step 1 who were treated with 4.5 g IVGC therapy and analyzed predictive factors for clinical outcomes of IVGC therapy. Multivariate logistic regression analysis was used to identify the independent predictors and establish the predictive model. Results Abnormal TRAb (OR = 4.717; P = 0.019) and the percentage of CD3+CD4+ T cell (OR = 1.092; P = 0.028) were independently associated with the activity of moderate-to-severe TAO patients. The pretreatment CAS-max in both eyes (OR = 7.221; P = 0.013) and the percentage of pretreatment CD3+T cell (OR = 0.718; P = 0.037) were independently associated with therapeutic efficacy. The pretreatment CAS-max in both eyes (OR = 156.53; P = 0.028) and the percentage of post-treatment CD3+T cell (OR = 0.554; P = 0.043) were independently associated with therapeutic efficacy. Besides, multivariable prediction models were established, which were better in the forecasting aspect than single-variable prediction models. Conclusions Based on the findings of this study, we should monitor the peripheral blood T cell subsets for TAO, which could be helpful to timely judge the condition of clinical manifestation and effect of treatment for TAO patients. Multivariable prediction models have been established, which have great significance for clinical work.

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Efficacy and safety of intravenous glucocorticoid therapy for IgG4-related ophthalmic disease.

To evaluate and compare the efficacy and safety of intravenous (IV) glucocorticoid therapy with those of oral glucocorticoids as a first-line treatment for IgG4-related ophthalmic disease (IgG4-ROD). We retrospectively reviewed the medical records of patients who underwent systemic glucocorticoid therapy for biopsy-proven IgG4-ROD from June 2012 to June 2022. Glucocorticoids were given either oral prednisolone at an initial dose of 0.6 mg/kg/day for four weeks with subsequent tapering or once weekly IV methylprednisolone (500 mg for six weeks, then 250 mg for six weeks), according to the date of treatment. Clinicoserological features, initial response, relapse during follow-ups, cumulative doses of glucocorticoids, and adverse effects of glucocorticoids were compared for the IV and oral steroid groups. Sixty one eyes of 35 patients were evaluated over a median follow-up period of 32.9 months. The complete response rate was significantly higher in the IV steroid group (n = 30 eyes) than in the oral steroid group (n = 31 eyes) (66.7% vs. 38.7%, p = 0.041). Kaplan-Meier analysis showed that the 2-year relapse-free survival was 71.5% (95% confidence interval: 51.6-91.4) and 21.5% (95% confidence interval: 4.5-38.5) in the IV steroid and oral steroid group, respectively (p < 0.001). Although the cumulative dose of glucocorticoids was significantly higher in the IV steroid group than in the oral steroid group (7.8 g vs. 4.9 g, p = 0.012), systemic and ophthalmic adverse effects were not significantly different between the two groups throughout follow-ups (all p > 0.05). As a first-line treatment for IgG4-ROD, IV glucocorticoid therapy was well-tolerated, led to better clinical remission and more effectively prevented inflammatory relapse than oral steroids. Further research is needed to establish guidelines on dosage regimens.

Changes in Clinical Activity, Serum Autoantibody Levels, and Chorioretinal Vessels After Systemic Glucocorticoid Therapy in Thyroid Eye Disease.

The aim of this study was to investigate changes in the Clinical Activity Score, serum thyroid-stimulating hormone receptor antibody and thyroid-stimulating immunoglobulin levels, chorioretinal blood vessels, and extraocular muscle thickness in patients with thyroid eye disease following systemic steroid treatment. This prospective observational study enrolled 57 patients with active thyroid eye disease who received systemic intravenous glucocorticoids for 12weeks. Demographics, clinical activity scores, optical coherence tomography images, and serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were assessed at baseline, at 6 and 12weeks after intravenous (IV) GC therapy initiation, and 2months after IV GC therapy termination. The extraocular muscle thickness, choroidal thickness, and choroidal vascularity index were measured. The clinical activity scores showed a significant decrease. Serum thyroid-stimulating immunoglobulin levels dropped continuously for 2months. The thyroid-stimulating hormone receptor antibody level decreased until 12weeks after treatment but returned to within the normal range in 75% of patients after 77 and 126days, respectively. The choroidal thickness decreased at all time points. The thickness of the medial and inferior rectus muscles decreased at 2months after treatment. The clinical activity score decreased to < 3 points in 50% of patients after 78days. Intravenous glucocorticoid therapy improved the clinical activity score, chorioretinal blood flow, and extraocular muscle thickness. The serum autoantibody levels were normalized in patients with active thyroid eye disease 2 months after IV GC termination. The serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels correlated with restoration of chorioretinal capillary perfusion and improved clinical symptoms and muscle thickness. Non-invasive optical coherence tomography findings and serologic factors predict the response to intravenous glucocorticoid therapy.

Clinical observation of glucocorticoid therapy for critically ill patients with COVID-19 pneumonia

We aimed to investigate the clinical effects of intravenous glucocorticoid (GC) therapy for severe COVID-19 pneumonia. Seventy-two patients hospitalized with severe COVID-19 pneumonia who were discharged or died between 5 January 2020 and 3 March 2020 at Huangshi Infectious Disease Hospital were included. Patients were divided into a treatment group (GC group) and non-treatment group (non-GC group) according to whether they had received GCs within 7 days of hospital admission. There was no significant difference between groups for Acute Physiology and Chronic Health Evaluation (APACHE) II score and 28-day survival rate. The rate of invasive mechanical ventilation was higher in the GC group than in the non-GC group. On day 7 after admission, the GC group had shorter fever duration and higher white blood cell count than the non-GC group. In subgroup analysis by age and severity, there was no significant difference in 28-day survival rate and other indicators. Compared with those in the non-GC group, patients in the GC group more frequently required admission to the intensive care unit. In the present study, we found no significant improvement in patients with severe COVID-19 pneumonia treated with GCs within 7 days of admission.

Postdischarge Glucocorticoid Use and Clinical Outcomes of Multisystem Inflammatory Syndrome in Children

Minimal data are available regarding the postdischarge treatment of multisystem inflammatory syndrome in children (MIS-C). To evaluate clinical characteristics associated with duration of postdischarge glucocorticoid use and assess postdischarge clinical course, laboratory test result trajectories, and adverse events in a multicenter cohort with MIS-C. This retrospective cohort study included patients with MIS-C hospitalized with severe illness and followed up for 3 months in an ambulatory setting. Patients younger than 21 years who were admitted between May 15, 2020, and May 31, 2021, at 13 US hospitals were included. Inclusion criteria were inpatient treatment comprising intravenous immunoglobulin, diagnosis of cardiovascular dysfunction (vasopressor requirement or left ventricular ejection fraction ≤55%), and availability of complete outpatient data for 3 months. Glucocorticoid treatment. Main outcomes were patient characteristics associated with postdischarge glucocorticoid treatment, laboratory test result trajectories, and adverse events. Multivariable regression was used to evaluate factors associated with postdischarge weight gain (≥2 kg in 3 months) and hyperglycemia during illness. Among 186 patients, the median age was 10.4 years (IQR, 6.7-14.2 years); most were male (107 [57.5%]), Black non-Hispanic (60 [32.3%]), and Hispanic or Latino (59 [31.7%]). Most children were critically ill (intensive care unit admission, 163 [87.6%]; vasopressor receipt, 134 [72.0%]) and received inpatient glucocorticoid treatment (178 [95.7%]). Most were discharged with continued glucocorticoid treatment (173 [93.0%]); median discharge dose was 42 mg/d (IQR, 30-60 mg/d) or 1.1 mg/kg/d (IQR, 0.7-1.7 mg/kg/d). Inpatient severity of illness was not associated with duration of postdischarge glucocorticoid treatment. Outpatient treatment duration varied (median, 23 days; IQR, 15-32 days). Time to normalization of C-reactive protein and ferritin levels was similar for glucocorticoid duration of less than 3 weeks vs 3 or more weeks. Readmission occurred in 7 patients (3.8%); none was for cardiovascular dysfunction. Hyperglycemia developed in 14 patients (8.1%). Seventy-five patients (43%) gained 2 kg or more after discharge (median 4.1 kg; IQR, 3.0-6.0 kg). Inpatient high-dose intravenous and oral glucocorticoid therapy was associated with postdischarge weight gain (adjusted odds ratio, 6.91; 95% CI, 1.92-24.91). In this multicenter cohort of patients with MIS-C and cardiovascular dysfunction, postdischarge glucocorticoid treatment was often prolonged, but clinical outcomes were similar in patients prescribed shorter courses. Outpatient weight gain was common. Readmission was infrequent, with none for cardiovascular dysfunction. These findings suggest that strategies are needed to optimize postdischarge glucocorticoid courses for patients with MIS-C.

Plasma Exosomes Transfer miR-885-3p Targeting the AKT/NFκB Signaling Pathway to Improve the Sensitivity of Intravenous Glucocorticoid Therapy Against Graves Ophthalmopathy.

Graves ophthalmopathy (GO), a manifestation of Graves’ disease, is an organ-specific autoimmune disease. Intravenous glucocorticoid therapy (ivGCs) is the first-line treatment for moderate-to-severe and active GO. However, ivGCs is only effective in 70%–80% of GO patients. Insensitive patients who choose 12-week ivGCs not only were delayed in treatment but also took the risk of adverse reactions of glucocorticoids. At present, there is still a lack of effective indicators to predict the therapeutic effect of ivGCs. Therefore, the purpose of this study is to find biomarkers that can determine the sensitivity of ivGCs before the formulation of treatment, and to clarify the mechanism of its regulation of ivGCs sensitivity. This study first characterized the miRNA profiles of plasma exosomes by miRNA sequencing to identify miRNAs differentially expressed between GO patients with significant improvement (SI) and non-significant improvement (NSI) after ivGCs treatment. Subsequently, we analyzed the function of the predicted target genes of differential miRNAs. According to the function of the target genes, we screened 10 differentially expressed miRNAs. An expanded cohort verification showed that compared with NSI patients, mir-885-3p was upregulated and mir-4474-3p and mir-615-3p were downregulated in the exosomes of SI patients. Based on statistical difference and miRNA function, mir-885-3p was selected for follow-up study. The in vitro functional analysis of exosomes mir-885-3p showed that exosomes from SI patients (SI-exo) could transfer mir-885-3p to orbital fibroblasts (OFs), upregulate the GRE luciferase reporter gene plasmid activity and the level of glucocorticoid receptor (GR), downregulate the level of inflammatory factors, and improve the glucocorticoid sensitivity of OFs. Moreover, these effects can be inhibited by the corresponding miR inhibitor. In addition, we found that high levels of mir-885-3p could inhibit the AKT/NFκB signaling pathway, upregulate the GRE plasmid activity and GR level, and downregulate the level of inflammatory factors of OFs. Moreover, the improvement of glucocorticoid sensitivity by mir-885-3p transmitted by SI-exo can also be inhibited by the AKT/NFκB agonist. Finally, through the in vivo experiment of the GO mouse model, we further determined the relationship between exosomes’ mir-885-3p sequence, AKT/NFκB signaling pathway, and glucocorticoid sensitivity. As a conclusion, plasma exosomes deliver mir-885-3p and inhibit the AKT/NFκB signaling pathway to improve the glucocorticoid sensitivity of OFs. Exosome mir-885-3p can be used as a biomarker to determine the sensitivity of ivGCs in GO patients.

T2 Mapping with and without Fat-Suppression to Predict Treatment Response to Intravenous Glucocorticoid Therapy for Thyroid-Associated Ophthalmopathy.

ObjectiveTo evaluate the performance of baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping of the extraocular muscles (EOMs) in the prediction of treatment response to intravenous glucocorticoid (IVGC) therapy for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO) and to investigate the effect of fat-suppression (FS) in T2 mapping in this prediction.Materials and MethodsA total of 79 patients clinically diagnosed with active, moderate-to-severe TAO (47 female, 32 male; mean age ± standard deviation, 46.1 ± 10 years), including 43 patients with a total of 86 orbits in the responsive group and 36 patients with a total of 72 orbits in the unresponsive group, were enrolled. Baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping with FS (i.e., FS T2 mapping) or without FS (i.e., conventional T2 mapping) of EOMs were compared between the two groups. Independent predictors of treatment response to IVGC were identified using multivariable analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the prediction models. Differences between the models were examined using the DeLong test.ResultsCompared to the unresponsive group, the responsive group had a shorter disease duration, lower kurtosis (FS-kurtosis), lower standard deviation, larger 75th, 90th, and 95th (FS-95th) T2 relaxation times in FS mapping and lower kurtosis in conventional T2 mapping. Multivariable analysis revealed that disease duration, FS-95th percentile, and FS-kurtosis were independent predictors of treatment response. The combined model, integrating all identified predictors, had an optimized area under the ROC curve of 0.797, 88.4% sensitivity, and 62.5% specificity, which were significantly superior to those of the imaging model (p = 0.013).ConclusionAn integrated combination of disease duration, FS-95th percentile, and FS-kurtosis was a potential predictor of treatment response to IVGC in patients with active and moderate-to-severe TAO. FS T2 mapping was superior to conventional T2 mapping in terms of prediction.

Influence of 4-week or 12-week glucocorticoid treatment on metabolic changes in patients with active moderate-to-severe thyroid-associated ophthalmopathy.

Thyroid‐associated ophthalmopathy (TAO) is a serious, progressive, vision‐threatening and difficult‐to‐treat organ‐specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High‐dose intravenous glucocorticoid (IVGC) therapy is considered a first‐line treatment for active moderate‐to‐severe TAO, but there is still insufficient evidence regarding the treatment duration. Long‐term IVGC therapy can influence the metabolism of glucose, lipids, and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 and 12 weeks of IVGC therapy. Forty‐eight patients with active moderate‐to‐severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12‐week group had increased fasting plasma glucose (p = 0.004), glycated hemoglobin (p = 0.028), total cholesterol (p < 0.001), and low‐density lipoprotein (p < 0.001) after therapy. The patients in both groups had reduced bone metabolism markers after therapy. Thyroid peroxidase antibody and thyrotropin receptor antibody levels decreased after treatment in both groups (p < 0.001). A significant decrease in thyroglobulin antibody levels was found in the 4‐week group (p = 0.006). The change in the ADC was higher in the 4‐week group than in the 12‐week group (p = 0.014). However, there were no significant differences in CAS values between the two groups. Therefore, 4‐week IVGC therapy was recommended for patients with TAO with glucose and lipid disorders.

Evidence That Baseline Levels of Low-Density Lipoproteins Cholesterol Affect the Clinical Response of Graves' Ophthalmopathy to Parenteral Corticosteroids.

BackgroundHigh dose intravenous glucocorticoid (ivGC) therapy is the first line treatment in moderate to severe Graves’ ophthalmopathy (GO) and is associated with a clinical response rate ranging from 50% to 80%. Recently, a positive correlation between total cholesterol and low-density lipoproteins cholesterol (LDLc) with GO presentation and activity has been described.ObjectiveWe aimed at evaluating whether, in patients with moderate to severe active GO treated with ivGC therapy, cholesterol, and LDLc could represent valuable predictive factors of medium-term GO outcome.MethodsThis single center retrospective study was conducted in a consecutive series of 87 patients undergone ivGC therapy because affected by moderate to severe active GO. Clinical outcome of GO was evaluated at week 6 (W6) and 12 (W12) in respect to baseline conditions (week 0) by the seven points CAS according to EUGOGO recommendations. Univariate analysis and binary logistic regression were performed for the outcome variable W12CAS.ResultsIn patients with active GO, an early positive clinical response to ivGC therapy (as evaluated by CAS at 6W) was a strong determinant (OR=13) of the clinical outcome at week 12. Moreover, high levels of LDLc at baseline were positively associated with a reduction in the likelihood of being classified as improved at 12W. Patients with LDLc >193.6 mg/dl were very likely to respond negatively to ivGC therapy independently from the response at 6W. Based on these results, we propose a predictive decision-making model to be tested in future prospective studies.DiscussionWe found that, in patients with active GO, both an early clinical response to ivGC therapy and baseline LDLc levels are significant determinants of GO outcome (W12CAS). These data support the need of a cholesterol-lowering treatment before addressing these patients to ivGC therapy.

A CASE OF ACUTE SILICOSIS WITH SEVERE PULMONARY HYPERTENSION

SESSION TITLE: Medical Student/Resident Occupational and Environmental Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Silicosis occurs from inhalation of silica dust particles. Acute and accelerated silicosis share nodular formations as seen in chronic silicosis but have granular lipo-proteinaceous collections in the alveolar spaces [1]. These collections impair gas exchange resulting in cyanosis, and ultimately respiratory failure usually exacerbated by respiratory infections. We report a case of a young patient developing acute silicosis from working in a gold mine. CASE PRESENTATION: A 30-year-old African man presented with a 2-week history of worsening shortness of breath associated with productive cough and pleuritic chest pain. The patient was previously diagnosed with progressive massive fibrosis (PMF) and silicosis via lung biopsy at an outside hospital, attributed to a 3-year long silica exposure from gold mining in West Africa. Our patient was initiated on intravenous glucocorticoids, broad spectrum antibiotics, and noninvasive positive pressure ventilation for acute hypoxic and hypercarbic respiratory failure. Chest radiograph revealed extensive bilateral airspace opacities (figure 1). CT-chest showed extensive bilateral perihilar parenchymal opacities with traction bronchiectasis, consistent with PMF (figure 2)(figure 3). Transthoracic echocardiogram showed septal wall abnormalities and a right ventricular systolic pressure of 173 mmHg measured via tricuspid regurgitant jet. The patient’s condition stabilized during hospitalization and the patient was discharged home on prednisone and oxygen supplementation via nasal cannula. Three weeks after discharge, the patient presented again with recurrent acute respiratory failure with a positive viral PCR for RSV requiring intubation and mechanical ventilation. Shortly after intubation, the patient went into cardiac arrest and expired. DISCUSSION: Generally, silicosis presents as a chronic condition but rarely, acute silicosis, most often related to massive exposure, can present within a few years . Lung transplantation is the only definitive treatment of advanced silicosis with studies showing successful lung transplantation with the 6-month, 1-year and 3-year survival rates of 86, 86, and 76 percent respectively [2]. One case report examined initiation of intravenous glucocorticoid therapy followed by oral prednisone which showed transient improvement in chest radiography and pulmonary function tests [3]. Unfortunately, treatment with glucocorticoid therapy was unable to alter the outcome of our patient. Lung transplantation was in the process for the patient but was unable to be obtained. CONCLUSIONS: This case presents a rare case of acute silicosis/PMF with severe pulmonary hypertension, who developed respiratory failure after RSV infection leading to death. Reference #1: Ozkan M, Ayan A, Arik D, Balkan A, Ongürü O, Gümüş S. FDG PET findings in a case with acute pulmonary silicosis. Ann Nucl Med 2009;23:883–886. Reference #2: Singer, J. P., et al. “Survival Following Lung Transplantation for Silicosis and Other Occupational Lung Diseases.” Occup Med (Lond) 62.2 (2012): 134-7. Print. Reference #3: Goodman, George B., et al. “Acute Silicosis Responding to Corticosteroid Therapy.” Chest 101.2 (1992): 366-70. Print. DISCLOSURES: No relevant relationships by Khaled Abu-Ihweij, source=Web Response No relevant relationships by Sung Choi, source=Web Response no disclosure on file for Keith Guevarra; No relevant relationships by John Wisener, source=Web Response