Glucocorticoid Therapy Research Articles

Case report: Rapid clinical improvement of anti-HMGCR immune-mediated necrotizing myopathy treated with efgartigimod

Immune-mediated necrotizing myopathy (IMNM) with anti-HMGCR antibody positivity is characterized by proximal extremity weakness, increased creatine kinase, and extensive muscle edema. There is an urgent need to find more appropriate treatment options for anti-HMGCR IMNM patients who do not respond well to conventional therapy in the acute phase. With the advent of targeted biologics, new treatment options are available. We report on a 66-year-old anti-HMGCR IMNM patient who initially presented with a 1-month history of progressive proximal extremity weakness and dysphagia with markedly elevated creatine kinase. The patient did not respond to conventional high-dose glucocorticoid and intravenous immunoglobulin therapy, and his symptoms rapidly deteriorated over the 2 weeks after this treatment, with worsening limb weakness that prevented walking, marked proximal muscle atrophy, and weight loss. After one cycle (four infusions) of efgartigimod, the patient’s symptoms improved markedly and he has since (for several months) remained in a good clinical state.

Diagnosis and approach to glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome

Introduction and purpose: Primary adrenal insufficiency can result from diseases affecting the adrenal glands, while secondary adrenal insufficiency is caused by suppression of the hypothalamic-pituitary-adrenal axis. The most common cause of adrenal suppression is exogenous steroids, a condition recently termed glucocorticoid-induced adrenal insufficiency (GIAI). Glucocorticoid-induced adrenal suppression is a common adverse effect of glucocorticoid therapy, which can have severe consequences. This review provides a comprehensive overview of the diagnosis and management of glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome. Material and methods: An extensive examination of articles published in scientific journals was carried out through online research platforms PubMed and Google Scholar. We searched articles by entering keywords in appropriate configuration: “glucocorticoid-induced adrenal insufficiency”, “glucocorticoids”, “steroids”, “adrenal crisis”, “substitution therapy”, “glucocorticoid withdrawal”. Description of the state of knowledge: Glucocorticoids are widely used in the treatment of various inflammatory and autoimmune disorders due to their potent anti-inflammatory and immunosuppressive effects. However, chronic glucocorticoid therapy can lead to a number of adverse effects, including adrenal suppression, which can result in adrenal insufficiency. Summary: Primary care clinicians should recognize the high prevalence of glucocorticoid-induced adrenal insufficiency in patients receiving non-oral glucocorticoid formulations. The glucocorticoid withdrawal syndrome exhibits symptoms analogous to glucocorticoid-induced adrenal insufficiency. Additional data on the morbidity and mortality linked to glucocorticoid-induced adrenal insufficiency is needed to comprehend the associated health risks, which will ultimately guide the approach to care for patients tapering long-term glucocorticoid therapy.

Effectiveness of pulse methylprednisolone in patients with non-human immunodeficiency virus pneumocystis pneumonia: a multicentre, retrospective registry-based cohort study

BackgroundA recent database study and meta-analysis reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-human immunodeficiency virus-associated (non-HIV) Pneumocystis jirovecii pneumonia (PCP), having hypoxemia. However, the optimal glucocorticoid dose remains unclear. Our study aimed to evaluate the effectiveness of pulse methylprednisolone compared with mild-to-moderate steroid doses in patients with non-HIV PCP.MethodsThis multicentre retrospective cohort study included adults with non-HIV PCP receiving adjunctive steroids at three Japanese tertiary care hospitals from June 2006 to March 2021. Patients were categorised into pulse methylprednisolone and mild-to-moderate dose groups. Pulse methylprednisolone involved an initial intravenous infusion of 500–1000 mg methylprednisolone daily, while the mild-to-moderate dose was lower. Primary and secondary outcomes were 30-day and 180-day mortality from treatment initiation. Patient characteristics were adjusted using propensity score analysis with overlap weighting. Subgroup analysis focused on patients with respiratory failure.ResultsThe study included 139 patients with non-HIV PCP: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. After adjusting for patient background, 30-day mortality (14.2% vs. 15.5%, P = 0.850) and 180-day mortality (33.5% vs. 27.3%, P = 0.516) did not differ significantly between groups. Subgroup analysis revealed no significant associations among patients with respiratory failure.ConclusionsAfter adjusting for patient characteristics, no difference in prognosis was observed between pulse methylprednisolone and mild-to-moderate dose groups in patients with non-HIV PCP. A mild-to-moderate dose of adjunctive corticosteroid may suffice for treating non-HIV PCP.

Use of immunosuppressants and biologics in giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA)

PurposeAn updated revision of the 2016 recommendations from the French Study Group for Large Vessel Vasculitis (GEFA) was needed to better delineate the place and management of immunosuppressants or biologics in giant cell arteritis (GCA). MethodsA panel of 18 physicians, including internists and rheumatologists, constituted the task force of this project and drafted the recommendations. Twelve additional readers were asked to analyse and comment on the recommendations. Two face-to-face virtual meetings were held to discuss and validate the recommendations. Each member voted individually, and a>85% consensus was required to validate each recommendation. ResultsFrom the initial 6 questions, 26 recommendations were validated. The following main recommendations were validated. (1) Subcutaneous 162mg tocilizumab (TCZ) for at least 12months should be used first when glucocorticoid (GC)-sparing treatment is needed with the objective of discontinuing GCs within the subsequent 6months. (2) GCA patients who have experienced any of the following conditions must receive TCZ at GCA diagnosis with 6months of GC therapy: major cardiovascular event, osteoporosis with fracture, psychiatric event with GC use, complicated diabetes mellitus, or any previous>6months of GC treatment. (3) In patients in whom GC discontinuation is not possible after 12months of treatment because of persistent disease activity or in patients in whom GC-related adverse events are unacceptable, TCZ (or alternatively methotrexate) may be proposed. ConclusionsThese recommendations were constructed based on the results of the published literature and the experts’ experiences to standardise therapeutic practices in France. Further updates will likely be necessary following new publications.

Management of Glucocorticoid-Induced Hyperglycemia in Cancer Patients: A Feasibility Study.

Glucocorticoids are commonly used in the management of patients with hematological and solid malignancies. However, their use may be associated with impaired glycemic metabolism and increased treatment-related morbidity and mortality. This study aimed to examine the feasibility and acceptability of a nurse-led model of care (MOC) for screening and managing glucocorticoid-induced hyperglycemia (GIH) in non-diabetic patients requiring high-dose glucocorticoid (HDG) therapies, as well as patients' and health professionals' experiences with the MOC. This study was a single-site feasibility study. Patients with hematological or oncological malignancies who were >18 years of age, receiving a chemotherapy regimen including HDGs, had no prior diagnosis of diabetes or prediabetes, and were not at the end of life were considered eligible for this study. Participants were recruited from a district hospital's Cancer Centre in Australia. All consenting participants were screened for diabetes and were provided with a blood glucose meter to monitor their blood glucose levels (BGLs) four times a day on the days of glucocorticoid therapy (GT) plus one extra day following GT, for the first four cycles of their treatment, to screen for the presence of GIH. Feasibility and acceptability were assessed using rates of consent, study completion, and staff and patient surveys. Forty-eight percent (35/74) of patients approached consented to participate in the study and had screening tests for preexisting diabetes. None were diagnosed with diabetes. Six out of 35 patients withdrew, and 10/29 patients did not complete the recommended BGL monitoring. Thirteen percent (4/29) of patients developed GIH. The most common reasons for non-participation and study withdrawal were related to the self-monitoring of BGLs. While clinical stakeholders found the MOC feasible and acceptable, the results of this study suggest that alternative methods for encouraging self-monitoring of BGL and monitoring the presence of GIH during high-dose chemotherapy need to be explored to address issues associated with adherence and sustainability.

HbA1c and leukocyte mtDNA levels as major factors associated with post-COVID-19 syndrome in type 2 diabetes patients

Post-COVID-19 syndrome (PCS) is an emerging health problem in people recovering from COVID-19 infection within the past 3–6 months. The current study aimed to define the predictive factors of PCS development by assessing the mitochondrial DNA (mtDNA) levels in blood leukocytes, inflammatory markers and HbA1c in type 2 diabetes patients (T2D) with regard to clinical phenotype, gender, and biological age. In this case-control study, 65 T2D patients were selected. Patients were divided into 2 groups depending on PCS presence: the PCS group (n = 44) and patients who did not develop PCS (n = 21) for up to 6 months after COVID-19 infection. HbA1c and mtDNA levels were the primary factors linked to PCS in different models. We observed significantly lower mtDNA content in T2D patients with PCS compared to those without PCS (1.26 ± 0.25 vs. 1.44 ± 0.24; p = 0.011). In gender-specific and age-related analyses, the mt-DNA amount did not differ significantly between the subgroups. According to the stepwise multivariate logistic regression analysis, low mtDNA content and HbA1c were independent variables associated with PCS development, regardless of oxygen, glucocorticoid therapy and COVID-19 severity. The top-performing model for PCS prediction was the gradient boosting machine (GBM). HbA1c and mtDNA had a notably greater influence than the other variables, indicating their potential as prognostic biomarkers.

Клинико-эпидемиологические особенности системной красной волчанки у детей: данные наблюдений ГБУЗ “Морозовская ДГКБ ДЗМ”

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown etiology characterized by hyperproduction of autoantibodies. The problems of timely diagnosis and identification of predictors of an unfavorable outcome of SLE are relevant due to the variable clinical picture and a high risk of 5-year mortality in the absence of treatment. The purposes of this research were to assess the frequency of various variants of SLE onset, to identify trigger factors contributing to the development of the disease and to analyze the degree of disease activity in children. Materials and methods used: a single-center cohort retrospective study was conducted involving patients aged 9 to 17 y/o who had undergone inpatient treatment at the rheumatological department of the Morozov Children’s City Clinical Hospital (Moscow, Russia) in 2020-2023, specifying age, gender, assessing the frequency of observed symptoms of SLE onset, disease activity according to the SLEDAI scale, laboratory parameters and drug treatment. Results: total of 45 records were analyzed: 75.5% (34) girls/24.5% (11) boys; median age 15 [13; 15] y/o; most frequent clinical syndrome was cutaneous (75.5%); kidney damage was noted in 40% of cases. 86.6% had hematological disorders as follows: thrombocytopenia and leukopenia (48.9%), anemia (46.6%): Coombs-positive anemia (71.4%), lymphopenia (37.7%) and increased ESR (66.6%). Antinuclear factor (ANF Hep2) was detected in all cases. According to the SLEDAI-2K scale, the median disease activity was 11 [7; 16] points. Low disease activity (less than 6 points) was observed in 4.4% (2), average (6 to 10 points) in 44.4% (20), high (11 to 19 points) in 37.7% (17), above average (over 20 points) in 13.3% (6). Moreover, disease activity was higher in girls (p=0.940) and a relationship was found between the time required for diagnosis and disease activity according to the SLEDAI-2K scale (p=0.206). Drug therapy: glucocorticoids (GCS) orally in all cases, intravenous pulse GCS therapy in 71.0%. Hydroxychloroquine therapy was prescribed in 100.0%, mycophenolate mofetil in 57.7%, intravenous immunoglobulin in 37.7%, cyclophosphamide in 13.3%, methotrexate in 6.6%, biological therapy in 31.0%, the drug of choice was rituximab. Conclusion: updating the data on the frequency of various variants of SLE debut as well as identifying the new trigger factors contributing to the development of the disease are necessary steps aiming to increasing the awareness of the SLE course with its debut in childhood, optimizing the diagnosis process and reducing the risk for complications.

Genetic factors associated with changes in muscle strength and mass during glucocorticoid therapy

Genetic factors associated with changes in muscle strength and mass during glucocorticoid therapy

Development and validation of a predictive scoring system for hypoglycaemic agents for optimal control of blood glucose during glucocorticoid therapy.

Glucocorticoid (GC) treatments are often used. There is limited information on the prediction of hyperglycaemia after GC administration. This study aimed to identify the risk factors for hyperglycaemia after glucocorticoid (GC) administration and the need for hypoglycaemic agents to correct it and to develop and validate a novel scoring system for predicting GC-induced hyperglycaemia. In a development set, 508 adults receiving prednisolone (PSL) for the first time were divided into two groups based on treatment with or without hypoglycaemic agents. Clinical and laboratory parameters were compared, and risk factors were identified using logistic regression analysis after performing univariate analyses between the two groups. A point-addition scoring system with several categories and coefficients for each risk factor was constructed to predict the need for hypoglycaemic agents. The scoring system was then applied and validated on two validation sets: A and B. Older age, higher glycated haemoglobin percentage, body mass index and initial PSL dosage were identified as risk factors. The sensitivity, specificity and accuracy of the scoring system were 70.6%, 81.9% and 77.1% in the development set; 75.8%, 78.4% and 77.4% in validation set A; and 79.4%, 73.9% and 75.3% in validation set B respectively. By fitting the total score in the development set and the probability of hyperglycaemia to a logistic curve, a figure was created to show the probability of GC-induced hyperglycaemia in patients scheduled to receive GC. This scoring system is a novel, valid and reliable tool for predicting GC-induced hyperglycaemia and the need for hypoglycaemic agents to correct it.

Beneficial effect of sequential treatment with high-dose steroids and short-course oral glucocorticoids in patients with severe influenza virus-associated pneumonia

Accumulating evidence supports that glucocorticoid treatment for viral pneumonia (VPA) can shorten the disease course and improve survival. However, currently, the use of glucocorticoids in treating VPA remains controversial. Moreover, a unified standard for the dosage and duration of glucocorticoid therapy has not been presented in published articles. A retrospective analysis was conducted in patients who were hospitalized for severe influenza virus-associated pneumonia, and they received sequential treatment with high-dose glucocorticoids and short-course oral glucocorticoids. Patients were followed up for 3 months. A total of 11 patients were included in the study (average age 56 years). There was no gender difference, but age and underlying diseases could be risk factors for severe influenza virus-associated pneumonia. The types of viruses causing pneumonia included influenza A/B. The main clinical symptoms of patients were fever, cough, sputum production, and dyspnea. Chest computed tomography showed multiple ground-glass shadows in the lobes, and the presence of bacterial and fungal infections was accompanied by consolidation shadows. After glucocorticoid therapy, the symptoms improved. None of the patients underwent tracheal intubation, and all survived. After a 3-month follow-up, lung CT absorption in all patients had reached more than 80%, and lung imaging absorption in 20% patients was complete. No serious complications occurred in any of the patients. Sequential treatment with high-dose steroids and short-course oral glucocorticoids may be helpful for reducing the tracheal intubation rate and mortality rate in patients with severe influenza virus-associated pneumonia. Additionally, short-course oral glucocorticoids may reduce pulmonary fibrosis in patients with severe influenza virus-associated pneumonia without any serious complications.

Efficacy and safety of rituximab in the treatment of pediatric myasthenia gravis

Objective: To evaluate the efficacy and safety of rituximab in pediatric myasthenia gravis (MG). Methods: Case series study. The clinical manifestations, laboratory tests, treatment plans and prognosis of 27 pediatric MG patients treated with rituximab from June 2013 to June 2023 at Children's Medical Center of Peking University First Hospital were retrospectively collected. Results: There were 5 males and 22 females in 27 MG children. The onset age was 2.1 (1.6, 4.8) years, ranging from 8 months to 11 years. The clinical classification included 20 children (74%) of ocular MG and 7 children (26%) of generalized MG. Seventeen children (63%) had positive MG-related pathogenic antibodies, including 17 children of anti-AchR antibody and 1 of them also had anti-MuSK antibody. Rituximab was used as first-line immunosuppressant in 13 children, second-line immunosuppressant in 13 children and third-line immunosuppressant in 1 child. Immunosuppressants used before rituximab including 8 children of cyclosporine, 3 children of tacrolimus, 1 child of azathioprine, 1 child of mycophenolate mofetil and 1 child of cyclosporine combined with azathioprine. Rituximab was used for at least half a year with a follow-up period of more than 12 months. At the last follow-up after rituximab treatment, all children achieved improved or above, 14 children (52%) achieved complete stable remission, 7 children (26%) achieved pharmacologic remission, 1 child (4%) achieved minimal manifestations, and 5 children (18%) improved. After rituximab treatment, 27 children all could reduce the immunomodulation therapy and shorten the course of glucocorticoid therapy, and 22 children (81%) had stopped the glucocorticoid therapy. Among the 14 children with poor efficacy of other immunosuppressants, rituximab had complete stable remission of 7 children. The most common adverse reaction was respiratory infection (4 children (15%)). Only 2 children had allergic reaction to rituximab and got better after symptomatic treatment. Conclusions: Rituximab has good efficacy and tolerance in pediatric MG. Early application of rituximab can improve the prognosis and shorten the course of glucocorticoid treatment.

Rapid reduction in fracture risk after the discontinuation of long-term oral glucocorticoid therapy: a retrospective cohort study using a nationwide health insurance claims database in Japan.

We investigated changes in fracture risk following discontinuation of long-term oral glucocorticoids (GCs) using Japan's nationwide health insurance claims database (NDBJ). We identified patients aged ≥ 50 years who initiated GC therapy in 2012-2019. Those receiving ≥ 5mg (prednisolone or equivalent, PSL)/day for ≥ 72days in the initial 90days of GC therapy were classified as the GC-exposure group, and those receiving < 5mg PSL/day for < 30days were classified as the reference group. Patients discontinuing GC after 90days of GC therapy were classified as the GC-discontinuation group; all others were classified as the GC-continuation group. We tracked the incidence rates of hip and clinical vertebral fractures for up to 990days, and assessed fracture risk after GC discontinuation by hazard ratios (HR) adjusted by inverse probability weighting using propensity scores for GC discontinuation. There was a total of 52,179 GC-discontinuation, 91,969 GC-continuation, and 43,138 reference group women, and 57,560, 93,736, and 33,696 men in the corresponding groups, respectively. According to adjusted HRs, incidence rates of fractures were significantly lower in the GC-discontinuation group than in the GC-continuation group in the initial 90days after GC discontinuation and remained significant for 360days, except for hip fracture in men. HRs for hip fractures remained significantly higher in the GC-discontinuation group compared to the reference group for 720days post-discontinuation. Fracture risk declines rapidly in the first year after GC discontinuation, but vigilance is necessary as the increased risk persists for two years post-discontinuation.

A case series: Three cases of Morvan's syndrome as a rare autoimmune disorder with anti-Caspr2 antibody.

Morvan syndrome (MoS) is an uncommon male-dominant autoimmune disorder marked by peripherally innervated hyperexcitability, autonomic disturbances, and encephalopathic encephalopathy, frequently with mass complaints manifesting as neuromyotonia (involuntary jerking, twitching, and stiffening of muscles), myotonia, neuropathic pain, hyperhidrosis, severe constipation, and severe sleep disturbances accompanied by dream reenactments, agrypnia agitation, and delusions, associated with autoantibodies to voltage-gated and potassium channel complexes such as anti-contactin-associated protein-like 2 (Caspr2) antibody. All this misery can be very disabling and even life-threatening. Reported cases show an unforeseeable outcome, with fatalities occurring even in those who initially responded. It has been reported that patients have reacted to immunologic therapies-corticosteroids, intravenous immunoglobulins, plasma exchanges, azathioprine, cyclophosphamide, rituximab, or carbamazepine, gabapentin, and clonazepam. However, no long-term effective cure has yet been found for this condition. Clinicians and researchers increasingly emphasize alternative and complementary medicine, with a growing trend toward traditional Chinese medicine (TCM). Following glucocorticoid therapy, all 3 patients experienced a recurrence of the disease. Patients 1 and 2 observed symptomatic relief after intravenous immunoglobulin administration; however, upon discontinuation of the treatment, their conditions relapsed and worsened compared with the previous state. The 3 patients were definitively diagnosed with serum Caspr2-positive MoS, accompanied by a constellation of neurological manifestations. The 3 patients were treated under the guidance of TCM theory. According to the principles of TCM, the patients were characterized by the deficiency of Yin, so the prescriptions were as follows: Shaoyao-Gancao decoction combined with Sanjia-Fumai decoction. After the application of TCM, there was a reversal of neuropsychiatric manifestations such as unintentional rippling, jerking, muscle stiffness, myokymia, hyperhidrosis, and extreme constipation. Patients' quality of life improved significantly; to date, they have achieved Karnofsky Performance Status scores of 100, and the anti-Caspr2 antibody result in case 2 dropped from 1:32 to normal. We first report the effective treatment of the MoS case series with TCM as complementary and alternative medicine.

Oral Lichenoid lesions induced by programmed cell death protein 1 and cytotoxic T-lymphocyte-associated protein 4 bispecific antibody: a case report

BackgroundCadonilimab is the first approved dual immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), currently utilized for the treatment of various solid tumors. Oral mucosal adverse reactions, such as oral lichenoid lesions, represent one of the most prevalent immune-related adverse events associated with immune checkpoint antibodies. However, reports detailing oral side effects specifically linked to Cadonilimab are lacking. Documenting these side effects is essential to alert oncologists and stomatologists, facilitating timely intervention for affected patients.Case PresentationWe present a case involving a 35-year-old male patient diagnosed with hepatocellular carcinoma who received Cadonilimab following hepatectomy and subsequently developed extensive oral lichenoid lesions along with mucosal erosion at 13–14 weeks post-treatment initiation. A biopsy was conducted revealing immunohistochemical findings of CD3+, CD4+, CD8+, CD20 + lymphocytes, CD68 + macrophages, and α-SMA + myofibroblasts infiltrating the tissue of the oral lichenoid lesions. The patient’s oral lesions improved after administration of systemic and local glucocorticoid therapy alongside cessation of Cadonilimab treatment.ConclusionThis report marks the first documented instance of an oral adverse effect associated with Cadonilimab use. It underscores that administration of this agent may lead to significant lichenoid lesions and erosions within the oral cavity—an issue warranting increased vigilance from both oncologists and stomatologists.

Relationship between Serum Vitamin D Levels and Asthma Control in Adult Patients

Asthma is a heterogeneous disease characterized by respiratory symptoms that vary both over time and in intensity, along with limited expiratory airflow. This heterogeneity is related to the patient's genetic and environmental phenotype. Vitamin D levels can affect the severity of asthma and the success of asthma treatment. Vitamin D can also influence the effectiveness of glucocorticoid therapy as an anti-inflammatory. This study aimed to determine the relationship between serum vitamin D levels and asthma control, severity, obstruction, and exacerbation levels. This research was a descriptive cross-sectional study on asthma patients at Wahidin Sudirohusodo Hospital and its network for the period October–December 2023. Each research subject had a venous blood sample taken and then checked vitamin D levels at the Hasanuddin University Teaching Hospital Research Laboratory. This research involved 72 research subjects. Most of the research subjects were female (61.1%), aged &lt;45 years (52.8%), worked as housewives (29.2%), had overweight BMI (33.3%), and had a history of atopy (59.7%). The degree of airway obstruction in the study subjects was mostly mild (66.7%) and the degree of severity was intermittent, persistent, and the degree of exacerbation in the same sample (33.3%). The results of the study showed a relationship between vitamin D levels and nutritional status, history of atopy, degree of asthma control using the ACT questionnaire, degree of stable asthma, and exacerbations where p&lt;0.05. Also, it is found that a weakly positive connection (R: 0.2–0.4) between vitamin D levels and ACT, FEV1, FEV/FVC. There is a relationship between vitamin D levels and nutritional status, history of atopy, degree of asthma control using the ACT questionnaire, degree of stable asthma, and exacerbations. There was a relationship between vitamin D levels and the degree of obstruction assessed by spirometry in this study.

The efficacy and safety of intravenous tocilizumab to treat Graves' ophthalmopathy: A systematic review and single-arm meta-analysis.

This study aims to evaluate the efficacy and safety of intravenous tocilizumab (TCZ) in the treatment of Graves' ophthalmopathy (GO). A comprehensive search was conducted across the Web of Science, PubMed, Embase, Cochrane Library, World Health Organization International Clinical Trials Registry Platform, and https://ClinicalTrials.gov databases from inception to April 2024. Randomized controlled trials (RCTs) and cohort studies that utilized intravenous TCZ for treating GO were included. Twelve studies encompassing 219 patients with active, steroid-resistant GO were analyzed. The meta-analysis demonstrated significant improvements in Clinical Activity Score (CAS) response (effect size [ES] = 0.98, 95% confidence interval [CI]: 0.93-1.00), proptosis response (ES = 0.50, 95% CI: 0.27-0.73), and diplopia response (ES = 0.48, 95% CI: 0.24-0.74). The ES for adverse events was 0.27 (95% CI: 0.22-0.33), with only three severe cases necessitating treatment discontinuation, and a low reactivation rate (ES = 0.01, 95% CI: 0.00-0.04). TCZ treatment led to a mean CAS reduction of 4.60 points (95% CI: 3.88-5.32) across 10 studies, a mean proptosis reduction of 2.04 mm (95% CI: 1.42-2.65) across 7 studies, and a mean decrease in thyroid-stimulating hormone receptor antibodies (TRAb) levels of 10.62 IU (95% CI: 4.67-10.62) across 5 studies. This meta-analysis provides robust evidence supporting the efficacy and safety of intravenous TCZ in patients with GO who are resistant to glucocorticoid therapy. The results highlight TCZ's comparable efficacy to glucocorticoids and suggest that TCZ could significantly expand clinical management options for GO. In the future, more high-quality, large-scale RCTs are still needed to confirm these findings.

A case of de novo glomerulonephritis following COVID-19 in a patient with preexistent IgA vasculitis.

During the unprecedented COVID-19 outbreak, new-onset or relapsing glomerulonephritis, such as ANCA-associated glomerulonephritis and Immunoglobulin A (IgA) nephropathy, following COVID-19 has been reported. However, to date, the association of COVID-19 with preexistent IgA vasculitis (IgAV) remains unclear. Here, we present the case of a 20-something old Japanese woman with preexistent IgAV who newly developed glomerulonephritis following COVID-19. At the diagnosis of IgAV, she had cutaneous purpura, joint pains, and gastrointestinal symptoms, but no signs of kidney involvement. Three months ago, she was tested positive for COVID-19 and subsequently developed hematuria and proteinuria. She was then admitted to our hospital and renal biopsy showed glomerular mesangial expansion and hypercellularity and cellular and fibrocellular crescents, accompanied by diffuse IgA and C3 deposits. With the diagnosis of de novo IgAV nephritis, the patient was treated with intravenous methylprednisolone followed by oral prednisolone. She had favorable responses to this treatment and has achieved and maintained the remission of hematuria and proteinuria after initiation of glucocorticoid therapy. Our case highlights that immune response to SARS-CoV-2 infection could trigger the onset of glomerulonephritis in the IgAV patients who have no renal involvement.

No Effect of Low-Dose Glucocorticoid Maintenance Therapy on Damage in SLE Patients in Prolonged Remission: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort

Background/Objectives: Prolonged remission on low-dose glucocorticoids (GC) is a main goal in patients with systemic lupus erythematosus (SLE). The aim of this study is to assess whether GC ≤ 5 mg/d increases the risk of damage accrual in patients with SLE in prolonged remission. Methods: Observational study of routine clinical care data of the inception Lupus Cruces-Bordeaux cohort. Only patients in DORIS remission during five consecutive yearly visits were included. The endpoint was damage accrual during the 5-year follow-up, either global or specific damage: GC-induced, cardiovascular (CV), lupus and other. Patients no longer on GC therapy by year 5 (GC5-Off) were compared with those who continued GC therapy (GC5-On). Comparisons were made by Cox and Poisson regressions, which were adjusted with propensity score (PE) in order to control for confounding by indication. Results: 132 patients were included, 56 in the GC5-On and 76 in the GC5-Off groups. All patients were on GC ≤ 5 mg/d for the whole follow-up, the mean prednisone dose in the GC5-On group being 2.96 mg/d during the whole study period and 2.6 mg/d during the 5th year. Fourteen patients (10.6%) accrued damage. More patients in the GC5-On group accrued global damage, 16% vs. 7% in the GC5-Off group, p = 0.08, mainly at CV domains (7% vs. 1%, respectively, p = 0.16). In the PS-adjusted Cox and Poisson regressions, the GC5-On group was not significantly associated with global (p = 0.39) or CV damage accrual (p = 0.62), nor with the absolute (p = 0.40) or CV-restricted final SDI scores (p = 0.63). The C-index of the propensity score model was 0.79. Conclusions: Maintaining doses of prednisone &lt; 5 mg/d in lupus patients in prolonged remission is not associated with an increased risk of damage accrual.

Clinical features of Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuritis associated with SLE

ObjectiveWe report on the clinical characteristics, treatments and outcomes of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuritis (CIDP) associated with SLE.MethodsPatients treated at Peking Union Medical College Hospital between...

Glucocorticoid chrono-pharmacology promotes glucose metabolism in heart through a cardiomyocyte-autonomous transactivation program.

Circadian time-of-intake gates the cardioprotective effects of glucocorticoid administration in both healthy and infarcted hearts. The cardiomyocyte-specific glucocorticoid receptor (GR) and its co-factor, Krüppel-like factor (Klf15), play critical roles in maintaining normal heart function in the long-term and serve as pleiotropic regulators of cardiac metabolism. Despite this understanding, the cardiomyocyte-autonomous metabolic targets influenced by the concerted epigenetic action of GR-Klf15 axis remain undefined. Here, we demonstrate the critical roles of the cardiomyocyte-specific GR and Klf15 in orchestrating a circadian-dependent glucose oxidation program within the heart. Combining integrated transcriptomics and epigenomics with cardiomyocyte-specific inducible ablation of GR or Klf15, we identified their synergistic role in the activation of adiponectin receptor expression (Adipor1) and the mitochondrial pyruvate complex (Mpc1/2), thereby enhancing insulin-stimulated glucose uptake and pyruvate oxidation. Furthermore, in obese diabetic (db/db) mice exhibiting insulin resistance and impaired glucose oxidation, light-phase prednisone administration, as opposed to dark-phase prednisone dosing, effectively restored cardiomyocyte glucose oxidation and improved diastolic function towards control-like levels in a sex-independent manner. Collectively, our findings uncover novel cardiomyocyte-autonomous metabolic targets of the GR-Klf15 axis. This study highlights the circadian-dependent cardioprotective effects of glucocorticoids on cardiomyocyte glucose metabolism, providing critical insights into chrono-pharmacological strategies for glucocorticoid therapy in cardiovascular disease.