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Background: To assess the food effects and pharmacokinetic profile of oral prednisone (test preparation,5 mg) and prednisolone tablets (reference preparation,5 mg) using a randomized, two-period, two crossover, single-dose, fast and fed trial in 48 (24 in fast, 24 in fed) healthy Chinese adult subjects., Materials and Methods: In the trial, the plasma concentrations were determined at different time points up to 24 h and the pharmacokinetic parameters were analyzed according to the concentration data by non-compartmental analysis using WinNonlin software. All laboratory parameters, vital signs and adverse events (AEs) were monitored and recorded under the supervision of the clinicians throughout the whole process of the study., Results: Prednisone and prednisolone undergo interconversion in liver. On average, the bioavailability of prednisolone after oral prednisone is approximately 80% of that after prednisolone. And about 20% of prednisolone is converted to prednisone after administration of equivalent oral of prednisolone tablet. Food taken with prednisone or prednisolone tablets delays the time reach the peak prednisone or prednisolone concentration (T max ) by approximately 0.5 h but does not affect systemic exposure. Prednisone and prednisolone tablets were well tolerated, and there were no serious adverse events reported in the study., Conclusions: For there was no information about the pharmacokinetic profile and food effects of oral prednisone and prednisolone tablets, the result of this research would be a clinical medication for doctors especially dealing patients with varying degrees of liver diseases., Clinical Trial Registration: CTR20200093; registered in http://www.chinadrugtrials.org.cn/ at 11 March 2020., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the Ethics Committee of the Hospital of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College (Nanjing, China).All subjects signed informed consent forms before their participation in the study after having received a thorough informed about the aim, course and possible risks of the clinical trial. Consent for publication: All authors read and approved the final manuscript for publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Blood eosinophilia remains a common finding in the general population, whereas hypereosinophilia (HE) is extremely rare. Different non-hematologic and hematologic disorders may be accompanied by blood eosinophilia. Clinical manifestations of eosinophilia-related disorders range from mild to life-threatening. Given the various symptoms, a comprehensive approach and close multidisciplinary cooperation are strongly recommended. Hypereosinophilic syndromes (HES) encompass a complex group of disorders defined as persistent peripheral blood HE ≥ 1500/mm 3 and end-organ damage. An initial step in a diagnostic algorithm of HE includes the evaluation of secondary, potentially easy-to-treat causes. This HES variant is called reactive and often remains beyond the interest of hematologists. The further evaluation for primary causes of HE relies on a combination of different specialized tests, which are mostly available in hematologic centers and include most of all morphologic assessments of peripheral blood and bone marrow, cytogenetics, and molecular studies. Using these sophisticated methods, one can diagnose the specific HES subtypes based on genetic findings and categorize them according to currently applicable classifications. The choice of therapy differs between HES variants, ranging from corticosteroids and anti-interleukin-5 monoclonal antibodies for not-molecularly defined variants to oral molecules directed against molecular targets. This review presents eosinophilia-related disorders from a hematologic perspective., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the long-term efficacy and safety of tacrolimus in patients with muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG)., Methods: We performed a retrospective, single-center, and cross-sectional study analyzing medical records of 18 MuSK-MG patients treated with tacrolimus for more than 1 year. The efficacy and safety of tacrolimus were evaluated by modified Osserman scale, Myasthenia Gravis Foundation of America post-intervention status, prednisone dosage, quantitative MG (QMG) scores, MG-activity of daily living (MG-ADL) scores, anti-MuSK antibody titers, blood routine, and serum biochemicals., Results: After 4 weeks of tacrolimus treatment, there was a significant improvement in prednisone dose, QMG, and MG-ADL scores, which continued to improve over 1 year. In addition, clinical grade of modified Osserman scale was improved in all patients, 16 (88.9%) of whom were asymptomatic at the last visit. More importantly, the mean titers of anti-MuSK antibody were significantly decreased from 0.777 ± 0.381 to 0.283 ± 0.178 nmol/L after a median of 1.4 years of tacrolimus treatment in 9 patients with MuSK-MG (P = 0.015). All patients achieved minimal manifestations status (MMS) after tacrolimus treatment (range, 4-32 weeks). Subsequently, seven patients (38.9%) underwent a taper of tacrolimus dosage. However, four patients (57.1%) experienced an exacerbation. Adverse events occurred in 2 patients (11.1%), all of which were mild and resolved after the tacrolimus dose was adjusted or discontinued., Conclusion: Our results suggest that tacrolimus may be an effective and safe steroid-sparing treatment for patients with MuSK-MG. However, tacrolimus should be carefully tapered to avoid disease exacerbation., Competing Interests: Declarations. Conflict of interest: The authors report no conflicts of interest in this work. Ethical statement: The study was approved by the Committee of Clinical Investigation at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan China (NO. TJ-IRB20220748). Informed consent: Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Liver injury manifesting as hepatic enzyme abnormalities, has been occasionally identified to be a feature of primary or secondary Addison's disease, an uncommon endocrine disease characterized by adrenal insufficiency. There have been no more than 30 reported cases of liver injury explicitly attributed to Addison's disease. Liver injury resulting from adrenal insufficiency due to glucocorticoid withdrawal is exceptionally rarer., Case Summary: A 42-year-old man presented with fatigue and mildly elevated transaminases. Laboratory investigations and imaging studies excluded common etiologies of liver injury. Based on the fact that the patient discontinued long-term therapy with prednisone approximately 2 weeks before he was found to have elevated transaminase levels and the observation that his cortisol was lower than the normal value, he was diagnosed as having hypertransaminasemia secondary to adrenal insufficiency caused by glucocorticoid withdrawal. The patient was infused intravenously with compound diisopropylamine dichloroacctate and compound glycyrrhizin, and his transaminase levels returned to normal after 1 week. Approximately 2 years later, the patient received hydroprednisone treatment for 2 days in an endoscopic sinus surgery. Eight days after he discontinued the hydroprednisone treatment, he developed symptoms reminiscent of glucocorticoid withdrawal syndrome. These symptoms resolved spontaneously after 1 week. Intriguingly, the patient did not develop hepatic dysfunction this time., Conclusion: The present case, showing some unusual clinical features, highlights the importance of education of clinicians and patients to avoid improper discontinuation of glucocorticoid therapy and complete history taking for prompt recognition., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Context: Vamorolone, a novel "dissociative" steroid, demonstrated similar efficacy in muscle function relative to prednisone 0.75 mg/kg/day but improved linear growth and bone turnover markers in a randomized trial of pediatric Duchenne muscular dystrophy (DMD)., Objectives: To determine the frequency of adrenal suppression (AS) induced by vamorolone and prednisone in pediatric DMD and to assess cortisol thresholds using a monoclonal antibody immunoassay., Methods: Post hoc analysis of cortisol levels was performed on data from a randomized, double-blind, placebo- and prednisone-controlled 24-week trial of vamorolone with a 24-week crossover extension. Morning and ACTH-stimulated cortisol levels were measured using the Elecsys II immunoassay, with AS defined as a stimulated cortisol of <500 nmol/L ("historical threshold") and <400 nmol/L ("revised threshold")., Results: Mean age at enrolment was 5.41 ± 0.86 years (n = 118). At week 24, the proportion of participants with AS using the historical and revised cortisol thresholds, respectively, were as follows: prednisone 0.75 mg/kg/day = 100% (25/25) and 92.0% (23/25); vamorolone 6 mg/kg/day = 95.2% (20/21) and 90.5% (19/21); vamorolone 2 mg/kg/day = 84.2% (16/19) and 47.5% (9/19); and placebo = 20.0% (4/20) and 0% (0/20). Morning and peak ACTH-stimulated cortisol were strongly correlated in steroid-treated boys (Spearman correlation week 48 = 0.83)., Conclusion: AS after vamorolone and prednisone was frequent and vamorolone-associated AS appeared dose-dependent. A lower stimulated cortisol threshold may be appropriate when using a monoclonal assay. We recommend hydrocortisone for glucocorticoid stress dosing in patients receiving vamorolone., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

The clinical manifestations of intravascular large B-cell lymphoma (IVLBCL) are highly variable and include constitutional B symptoms, neurological findings, and skin lesions. We report the case of a 64-year-old male patient who presented with myelopathy as a sole manifestation of IVLBCL. He had experienced progressive bilateral leg weakness along with bladder and rectal dysfunction for several months. He did not have non-neurological symptoms such as fever, night sweats, and weight loss at presentation. Blood tests, cerebrospinal fluid analysis, random skin biopsy, and bone marrow biopsy showed no evidence of lymphoproliferative disease. Subsequently, the patient developed a fever, and his LDH and soluble interleukin-2 receptor levels were elevated. PET/CT showed ground-glass opacity of the lung with associated FDG avidity. Transbronchial lung biopsy confirmed a diagnosis of IVLBCL. The patient received 6 cycles of R-CHOP combined with 2 cycles of high-dose methotrexate. His symptoms gradually improved with the chemotherapy, and PET/CT after completion of the treatment showed a complete metabolic response.

Peripheral T-cell Lymphoma (PTCL) represents a heterogenous group of aggressive non-Hodgkin Lymphomas with poor prognostic outcomes and limited treatment options. The development and refinement of therapeutic strategies for PTCL are impeded by a paucity of reliable preclinical models that accurately mimic the disease's pathophysiology. There is a dire need for more physiologically relevant models for PTCL. Here we describe a spontaneousCD8 + peripheral T-cell lymphoma cell line (LM-23) derived from a 12-week-old female Balb/cJ mouse. Both intravenous and subcutaneous administration of this cell line to syngeneic Balb/cJ mice resulted in rapid establishment of tumor growth. CHOP and anti-PD1 treatment both displayed no benefit to mice in regulating tumor growth. Such results along with its phenotypic characteristics, rapid growth, and metastatic behavior in syngeneic mice highlight its value in studying the elusive disease and discovery of novel therapeutics.

Recurrent pregnancy loss (RPL) represents a complication of pregnancy occurring in 1%-3% of all couples trying to conceive. About 50%-60% of RPL cases remain idiopathic, therefore therapeutic strategies seem empirical and based on unproven evidence. We investigated the efficacy of corticosteroids in women with RPL. We conducted a systematic review and meta-analysis, up to August 2024, in the PubMed, Scopus, and Web of Science databases, including studies on idiopathic RPL women and comparing corticosteroids versus control treatment. Primary outcome was the ongoing pregnancy rate beyond 12 weeks of gestation; secondary outcomes were live birth rate (LBR), stillbirth, birth weight, incidence of preeclampsia and/or gestational diabetes, gestational age at delivery, and fetal abnormalities. Four studies comprising 417 RPL women randomly assigned to steroid or control treatment were included. We found that oral corticosteroids significantly increase the ongoing pregnancy rate beyond 12 weeks of gestation compared to the control group (log OR [odds ratio] = 1.49 [0.32, 2.67], p = 0.01), with high heterogeneity (I 2 = 75%), and improve LBR (log OR = 0.9 [0.11, 1.69], p = 0.03), with low heterogeneity (I 2 = 0.05%). However, the limited number of studies significantly limits the strength of the findings. Also, the benefit/risk assessment of the use of corticosteroids in early pregnancy for RPL is still unclear., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Polymyalgia rheumatica (PMR) is a common and debilitating disease for which glucocorticoids remain the therapeutic mainstay. Guideline recommendations on tapering regimens have been largely based on expert consensus. This exploratory narrative review provides a discussion on the available evidence for the rates of steroid tapering in PMR, as well as relevant pharmacology of corticosteroids. Key studies related to rates of steroid tapering are reviewed. Results favor a slow tapering regimen from a low initial steroid dose (between 10 and 20 mg) to minimize risk of relapse. This should be balanced with the risk of steroid-induced adverse events. Individualization and close monitoring have also been identified as important factors during the steroid-tapering process. There is promising data on the role of steroid-sparing agents, including methotrexate, tocilizumab, and more recently sarilumab. There is individual variability of prednisone pharmacokinetics, and the tapering of prednisone remains an "art" that would benefit from further understanding of the variables involved. Overall, glucocorticoids remain the mainstay therapy for PMR, and there continues to be a lack of robust evidence to guide steroid taper. More research is needed to optimize steroid tapering and regimens, along with the expanding role of steroid-sparing agents such as tocilizumab and sarilumab. Key Points • Polymyalgia rheumatica is a common and debilitating disease for which glucocorticoids remain the mainstay of therapy, and there is a paucity of evidence to guide steroid taper. • Limited available research favors a slow tapering regimen from a low initial steroid dose to minimize risk of relapse and steroid exposure. • The process of steroid taper should be individualized and closely monitored, with growing evidence supporting the addition of steroid-sparing agents. • More research is needed to optimize steroid tapering and regimens, along with the expanding role of steroid-sparing agents such as methotrexate, tocilizumab, and sarilumab., Competing Interests: Compliance with ethical standards. Disclosures: None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background : The aim of this study was to evaluate the efficacy of 1-year treatment in children with IgAN and IgAVN using azathioprine, prednisone, and enalapril (AZA+PRED+E) combined with a control kidney biopsy. Methods : This study consists of 68 children diagnosed via kidney biopsy with Oxford classification. The study group included 36 children (15 IgAN, 21 IgAVN) treated with AZA+PRED+E (according to the protocol with a control kidney biopsy); and the control group included 32 children (21 IgAN, 11 IgAVN) who were treated with enalapril alone during one year after kidney biopsy. Results : After 1 year of combined therapy, a significant reduction in both proteinuria (proteinuria = 0 in 35 patients from the study group) and hematuria in the study group was found. It was confirmed that the Δ proteinuria between the start and end of treatment in IgAN and IgAVN patients from the study group was significantly higher than the Δ proteinuria between the start and end of treatment in the control IgAN and IgAVN group treated with enalapril (30.7 ± 43.6 vs. 8.7 ± 8.7; p = 0.015; 68.2 ± 58.3 vs. 19.3 ± 20.3; p = 0.008 respectively). In the Oxford classification a high frequency of improvement in E and T in the study group after treatment was observed. Conclusions : Patients with higher proteinuria and a higher MESTC score require consideration of the strategy of immunosuppressive treatment so that therapy with AZA+PRED+E may be used as a personal treatment plan for children with these diseases.

An 81-year-old woman was diagnosed with a tumor in the pancreas, detected on CT and MRI. The tumor was 12 mm in diameter and located close and in the distal side of the branch duct-type intraductal papillary mucinous neoplasm(IPMN)in the pancreas head observed for 4 years. Pancreatic ductal adenocarcinoma derived from IPMN was suspected and pylorus-preserving pancreatoduodenectomy was performed. The immunohistological diagnosis of the tumor using a resected specimen was diffuse large B cell lymphoma of the pancreas. After surgery, chemotherapy was not performed because of the patient's decision, but 2 years later, relapse of malignant lymphoma was suspected because of swelling of the bilateral adrenal glands on MRI. R-CHOP immunochemotherapy was started, but seven months later the patient died of lymphoma involving the central nervous system. Primary pancreatic lymphoma(PPL)is a rare disease representing 0.6% of extranodal lymphoma. Many cases of PPL are large, and small lesions under 2 cm in diameter are extremely rare. Furthermore, PPL associated with IPMN has never been reported. The pancreatic tumor close to the IPMN is difficult to diagnose differentially from adenocarcinoma on radiological findings. However, nonsurgical biopsy of the tumor in the pancreas is sometimes challenging if associated with IPMN.

Human T-lymphotropic virus 1 (HTLV-1) is the etiological agent of several pathologies, and some of them are not investigated, resulting in a lack of literature that impacts the correct diagnosis. Skin manifestations, such as HTLV-1-associated infectious dermatitis (IDH), are common in patients living with HTLV-1 but could not be the only one. Here, we report for the first time a patient infected with HTLV-1, without previous diagnosis of HTLV-1-related diseases, presenting erythema nodosum (EN). Given the patient's long-term asymptomatic carrier status, the emergence of EN underscores the importance of considering HTLV-1 in the differential diagnosis when encountering EN, especially in endemic regions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fernanda Khouri Barreto reports financial support was provided by Foundation for Research Support of Bahia State. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To explore the diagnosis and treatment of acquired hemophilia A (AHA) based on the analysis of clinical data., Methods: A retrospective analysis was conducted on the clinical manifestations, laboratory characteristics, treatment, and outcomes of 25 patients diagnosed with AHA who were admitted to the Second Hospital of Hebei Medical University., Results: Among all patients, 11 cases had secondary factors, including 5 cases of autoimmune diseases, 3 cases of pregnancy-related disease, 1 case of pemphigoid, 1 case of Graves' disease, and 1 case of monoclonal gammaglobulinemia of unknown significance (MGUS). The bleeding sites include the skin, mucous membrane, muscle, joint cavity and brain tissue. Twenty-three patients were treated with prednisone combined with cyclophosphamide (CP regimen), one patient with rituximab combined with cyclophosphamide because of femoral head necrosis, and one case with rituximab monotherapy because of gastrointestinal bleeding after prednisone treatment. Among them, 23 cases achieved complete remission (CR), 2 cases were partial remission (PR), and 8 cases relapsed after CR. All of 10 patients including 2 cases with PR and 8 relapsed cases after CR were treated with rituximab. At last, 8 patients achieved CR, and 2 patients (both were patients with recurrence after first CR) achieved PR. These two patients achieving PR were treated with low-dose rituximab combined with bortezomib (RB regimen). One patient reached CR after 4 cycles and the other reached CR after 6 cycles of RB regimen. After CR, 4 of the 10 patients treated with rituximab received maintenance therapy with rituximab monotherapy for 1.5 to 2 years, in which, none of them relapsed. Among the 6 patients who did not receive maintenance therapy, 4 patients relapsed after CR, and the median time to relapse was 15 months. Eight patients treated with CP regimen developed common infections, and two patients treated with rituximab developed severe pneumonia. All 25 patients survived until the end of follow-up., Conclusion: Skin ecchymosis, mucous hemorrhage and muscle hematoma are the most common hemorrhagic manifestations in AHA, and joint hemorrhage and cerebral hemorrhage can also occur. CP regimen is the preferred option of first-line therapy for AHA. Rituximab can be used for patients with steroid contraindication or who failed to respond to the above therapy or relapsed after effective treatment, and maintenance therapy is recommended to reduce the risk of recurrence. Meanwhile, close attention should be paid to the occurrence of infection events during rituximab treatment. Rituximab in combination with bortezomib can also be used in patients with refractory or relapsing AHA.

Prednisone, a synthetic glucocorticoid, is commonly used to treat autoimmune diseases in pregnant women. However, some studies suggest that the use of prednisone during pregnancy may lead to adverse pregnancy outcomes. In this study, we established PPE mouse models at different doses (0.25, 0.5, 1.0 mg/kg·d) and different stages (whole pregnancy, early pregnancy and middle-late pregnancy) and determined outcomes on the placenta and fetus. The results of our study indicated that at the highest dose of 1 mg/kg PPE using a GD 0-18 dosing regime, PPE caused placental morphological changes measured as a decrease in placental weight relative to controls and a decrease in the placenta junctional zone (JZ)/labyrinth zone (LZ) ratio. No changes were observed on the fetuses for number of live, stillborn, and absorbed fetuses between the experimental groups and the control group. In the placentas at some doses, there were decreases in cell proliferation markers measured at the RNA and protein level by Western blot and increased apoptosis. Measures of gene expression at the mRNA level showed altered nutrients (including glucose, amino acid, and cholesterol) transport gene expressions with the most significant change associated with the male placentas at high-dose and whole pregnancy PPE group. It was further found that PPE led to the inhibition of the insulin-like growth factor 2 (IGF2)/insulin-like growth factor 1 receptor (IGF1R) signaling pathway, which was well correlated with the indicators of cell proliferation, syncytialization and nutrient (glucose and amino acid) transport indices. In conclusion, PPE can alter placental morphology and nutrient transport function, with differences in effect related to dose, stage and gender. Differential gene expressions measured for genes of the IGF2/IGF1R signaling pathway suggested this pathway may be involved in the effects seen with PPE. This study provides a theoretical and experimental basis for enhancing the understanding of the effects of prednisone use on placenta during human pregnancy but does not currently raise concerns for human use as effects were not seen on the fetuses and while the effects on cell proliferation are informative they were inconsistent and the differential effects on female and male placentas unexplained suggesting that further work is required to elucidate if these findings have relevance for human use of PPE during pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Dr Ang received honoraria from Biogen and Bristol Myers Squibb. Drs Choy Heng Yoong, Tang-Lin, and Yew have no conflict of interests to declare.

Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and BMD, respectively). At study endpoint, there were trends towards increased lean mass, reduced fat mass, reduced creatine kinase and improved motor function. The investigation was motivated by studies in mouse muscular dystrophy models in which once weekly glucocorticoid exposure enhanced muscle strength and reduced fibrosis. WSiMD participants provided blood samples for aptamer serum profiling at baseline and after 6 months of weekly steroids. A subset completed magnetic resonance (MR) evaluation of muscle at study onset and endpoint. At baseline compared to age and sex-matched healthy controls, the aggregate serum protein profile in the WSiMD cohort was dominated by muscle proteins, reflecting leak of muscle proteins into serum. Disease status produced more proteins differentially present in serum compared to steroid-treatment effect. Nonetheless, a response to prednisone was discernable in the WSiMD cohort, even at this low dose. Glucocorticoids decreased muscle proteins and increased certain immune process- and matrix-associated proteins. Muscle MR fat fraction showed trends with functional status. The prednisone-responsive markers could be used in larger trial of prednisone efficacy., Competing Interests: Declarations. Competing interests: EMM has been a consultant to Amgen, AstraZeneca, Cytokinetics, Pfizer, Tenaya Therapeutics, and is a founder of Ikaika Therapeutics. ARD is CSO of Ikaika Therapeutics. The other authors have declared that no conflict of interest exists. There are no nonfinancial conflicts to report., (© 2024. The Author(s).)

This case report focuses on a rare presentation of Epstein-Barr virus as genital ulcers in a 14-year-old girl with no sexual activity history. Despite initial misdiagnosis and failed acyclovir treatment, investigations ruled out sexually transmitted causes but revealed elevated Epstein-Barr virus antibodies. Subsequent treatment with a 14-day prednisone course led to significant improvement. This case emphasizes the importance of considering nonsexual etiologies for genital ulcers to prevent delayed or inappropriate treatment and highlights the need for broader education on such atypical presentations., Competing Interests: CONFLICTS OF INTEREST None to report., (Copyright © 2024 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Background/Objectives: Polymyalgia Rheumatica (PMR) is an inflammatory condition that primarily affects individuals aged 50 and older, especially in Western countries. Although glucocorticoids are the cornerstone of PMR treatment, these drugs are associated with side effects, making it advisable to use them for the shortest duration possible. However, tapering or discontinuation of glucocorticoids often leads to disease relapses. In this review, we focus on the traditional management of PMR, as well as the potential for therapies that may reduce glucocorticoid use. Special attention is given to the efficacy of biologic agents in PMR management. Methods: A literature review, primarily based on articles published in PubMed, was conducted. In addition to discussing various glucocorticoids and conventional disease-modifying drugs used for the management of isolated PMR, this review specifically focused on the information reported regarding new therapies, with particular emphasis on biologic agents. Results: Prednisone or prednisolone at a dose ranging between 12.5 and 25 mg/day is the agreed-upon treatment for PMR. Due to the side effects associated with prolonged glucocorticoid use and the high frequency of relapses when glucocorticoids are tapered, glucocorticoid-sparing agents have emerged as tools in the management of PMR. Methotrexate has traditionally been the conventional disease-modifying antirheumatic drug (DMARD) unanimously recommended for use in PMR. Other conventional DMARDs, such as leflunomide, have shown promising results but require further study. The use of biologic agents has marked a significant step forward in the management of PMR. While anti-TNF agents failed to provide beneficial effects in isolated PMR, anti-IL-6 receptor agents, such as tocilizumab and sarilumab, have demonstrated efficacy in reducing relapse frequency, lowering the cumulative glucocorticoid burden, and achieving long-term remission of the disease. Other biologic agents, many of which have been used in giant cell arteritis, as well as Janus kinase (JAK) inhibitors, are currently under investigation. Conclusions: Glucocorticoids are the primary treatment for isolated PMR but are associated with comorbidities, especially in patients with pre-existing conditions or frequent relapses. Glucocorticoid-sparing agents, such as methotrexate and biologics, in particular tocilizumab and sarilumab, offer alternatives, improving symptoms and reducing glucocorticoid use. While biologic agents reduce long-term side effects and help achieve disease remission, their use must consider potential side effects and higher costs compared to traditional therapies.

This study outlines a scenario involving unilateral periocular inflammation exhibited resistance to conventional immunomodulatory therapy (IMT) and biologic response modifying agents, which was successfully managed with oral cyclophosphamide monotherapy. A 39-year-old male visited our clinic, expressing discomfort and swelling in his left upper eyelid for six months. All multidisciplinary consultations and imaging yielded normal results. He remained consistently on a dosage of 50 mg oral prednisone. Blood tests yielded results within the normal range or were negative, with the exception of the antinuclear antibody. He did not respond to conventional IMT and biological response modifier agents. Ultimately, the patient began oral cyclophosphamide. One month after commencing cyclophosphamide treatment, the oral prednisone dosage was gradually reduced without any flare-up. oral cyclophosphamide can serve as a valuable treatment for periocular inflammation that does not respond to standard conventional IMT and biologic response modifier agents., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Oman Ophthalmic Society.)

Thyroid eye disease (TED), also known as thyroid-associated ophthalmopathy, is an autoimmune disorder caused due to a complex interplay between autoantigens including the thyroid-stimulating hormone receptor and the insulin-like growth factor-I receptor. TED is characterized by progressive proptosis or diplopia. This systematic review aimed to compare the efficacy of the newer monoclonal antibody - teprotumumab and intravenous methylprednisolone (IVMP) in TED patients. We performed a systematic review of previously published studies from 2013 to June 2023. A total of 329 articles were screened; among them, 111 non-duplicate publications were identified. After the screening of titles and abstracts, 156 publications were excluded; then, another 47 published papers were excluded after the full-text screening. The remaining 15 eligible studies were included in this systematic review. The majority of studies used either teprotumumab alone or in combination with others. Among 15 studies, eight studies used teprotumumab in TED patients, whereas remaining 7 studies used a standard treatment regimen. This systematic review provides an overview of the existing treatment options using monoclonal antibody - teprotumumab and IVMP in TED patients. The overall assessment provides a finding that antibody - teprotumumab is is a good choice compared to conventional IVMP for providing better outcomes in patients with TED., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Oman Ophthalmic Society.)

Background and Purpose: The main features of the dynamics of the glucocorticoid receptor (GR) have been known for 50 years: 1) in the absence of glucocorticoid (G), the receptor is localized entirely in the cytoplasm; 2) upon G binding, GR is converted into a tightly bound G form and is rapidly imported into the nucleus where it can bind DNA and modulate transcription; 3) nuclear export of GR is very slow; and 4) the nuclear form of GR can recycle through an unbound form, back to the bound transcription modulating form without leaving the nucleus., Experimental Approach: A kinetic model that captures these features is presented, a set of model parameters for dexamethasone is derived, and the clinical implication for the commonly used glucocorticoids is discussed., Key Results: At the high concentrations normally used to describe G pharmacodynamics, the model reduces to the standard Michaelis-Menten equation with a K m that is a function of 4 model parameters. At very low concentrations, it reduces to another Michaelis-Menten equation with about a 1000-fold greater affinity, eg. at the nadir human endogenous cortisol concentration, the full model GR activity is 2.6 times greater than that predicted by extrapolation of the high concentration results., Conclusion: The model is used to relate normal human 24-hour endogenous plasma cortisol levels to transcriptional activity and is applied to the commonly prescribed glucocorticoids (dexamethasone, methylprednisolone, prednisone) in an attempt to provide a pharmacological rationale for the very large therapeutic dosage range that has been traditionally used., Competing Interests: Conflicts of Interest: The author certifies that he has no financial or other conflict of interest., (Copyright © 2024 by the authors.)

Objective: To assess the therapeutic efficacy of abiraterone combined with prednisone in patients with castration-resistant prostate cancer (CRPC) and investigate its effects on miR-221/222 expression., Methods: A retrospective cohort of 43 CRPC patients from Henan Provincial People's Hospital, People's Hospital of Zhengzhou University was divided into two groups: the treated group (n=22, treated with abiraterone and prednisone) and the control group (n=21, treated with prednisone acetate alone). Expression of miR-221/222 was quantified in CRPC cell lines using quantitative fluorescence polymerase chain reaction., Results: The treated group demonstrated significantly higher rates of bone pain relief and prostate-specific antigen (PSA) response compared to the control group (P=0.032, P=0.022, respectively). Post-treatment, the treated group also showed increased Karnofsky Performance Status scores and reduced plasma testosterone levels relative to controls (P=0.021, P=0.016). There was no significant difference in the incidence of adverse reactions between the treated group (31.82%) and the control group (28.57%) (P=0.125)., Conclusions: Abiraterone combined with prednisone effectively relieves bone pain and improves PSA response rates in CRPC patients, suggesting benefits in enhancing quality of life and reducing testosterone levels without increasing adverse reactions. This therapy appears to have a safety profile comparable to that of conventional treatments., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Inhalation of biomass smoke is associated with adverse respiratory effects in those with chronic pulmonary conditions. There are few published data regarding the effects of anti-inflammatory interventions on these outcomes., Objective: Our aim was to assess the effects of postexposure prednisone on woodsmoke (WS)-induced sputum neutrophilia., Methods: We carried out a randomized, placebo-controlled, crossover pilot study assessing the effect of a postexposure dose of 60 mg prednisone on induced sputum inflammation after controlled exposure to WS (500 μg/m 3 for 2 hours) in healthy adults who had been identified in a separate screening protocol as being "PMN responsive" to WS. Secondary end points were sputum cytokine level and mucociliary clearance as measured by γ-scintigraphy., Results: A total of 11 subjects yielded complete data for the primary analysis. At 24 hours after WS exposure, there was a significant increase in sputum percentage of PMNs (%PMN) versus at baseline after placebo (median = 42% [IQR = 31%-53%]) ( P  = .02) but not after prednisone (median = 32% [IQR = 18%-40%]) ( P  = .09). Prednisone reduced Δ%PMN at 24 hours, but this difference did not reach statistical significance. However, for the 8 of 11 subjects who were PMN responsive after placebo, prednisone reduced Δ%PMN significantly ( P  = .05). Prednisone had no significant effects on sputum levels of IL-1β, IL-6, IL-8, or TNF-α. WS exposure tended to reduce mucociliary clearance in the placebo arm but not in the prednisone arm., Conclusions: Prednisone taken immediately after exposure to WS mitigated short-term increase in sputum %PMN among healthy volunteers selected for their underlying inflammatory responsiveness to WS. Our data support future studies assessing anti-inflammatory interventions and the role of mucus clearance in WS-induced respiratory health effects., Competing Interests: Supported by the US 10.13039/100000005Department of Defense (grant W81XWH-18-1-0731), 10.13039/100000002National Institutes of Health (grants R01ES025124 and UM1TR004406), 10.13039/100000066National Institute of Environmental Health Sciences (grant T32ES007018), and US 10.13039/501100001589Environmental Protection Agency (grant 83578501-0). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, US Environmental Protection Agency, or US Department of Defense. Disclosure of potential conflict of interest. The authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

We report the case of a 48-year-old male who presented with right lower abdominal pain and a mass for 2 weeks and got constipation for 5 days. An abdominal CT scan conducted before admission at other hospitals revealed an obstruction in the blind ascending colon, which was suspected to be a malignant tumor. Proctoscopy revealed peritoneal implantation metastasis and multiple pelvic lymph nodes. Physical examination was unremarkable except for multiple lymph node enlargements in the inguinal area, without pain. A whole-body contrast-enhanced FDG-PET/CT revealed lymphoma involvement in the ascending colon, peritoneum, bone marrow, and lymph nodes in multiple regions of the body, with DLBCL as a suspected diagnosis. Pathological findings from the colonoscopy revealed atypical lymphocyte infiltration and Immunostaining indicated the presence of atypical lymphocytes with Ki-67 (90%) and tested positive for CD20, CD19, CD10, and BCL-6. Based on the above findings, stage IV DLBCL was diagnosed. Furthermore, EBV-DNA amplification was positive. The patient received R-CHOP treatment for 2 days before experiencing symptoms of fevers, chills, and abdominal pain. He underwent emergency surgery due to intestinal perforation, and preoperative blood tests revealed HIV-positive. The prognosis for the patient is poor due to sepsis.

Background: Abiraterone acetate (AA) is used in treatment of patients with metastatic prostate cancer. Despite the survival advantage, AA is associated with hypertension due to mineralocorticoid excess syndrome., Objective: We conducted a single-center retrospective analysis to evaluate the real-world incidence and severity of AA-induced hypertension., Methods: Electronic health records were used to collect baseline characteristics and prostate cancer history. Patient data, including blood pressure at each 4 (±2)-week interval, were collected for 24 weeks after the initiation of AA therapy. The primary endpoint was the incidence and severity of AA-induced hypertension. The secondary endpoints include effect of different prednisone dosing regimens and prostate cancer types on hypertensive incidence and the impact of clinical pharmacists' involvement in managing AA-induced hypertension., Results: A total of 142 patients who met our inclusion criteria received AA for metastatic prostate cancer, 73 (51.4%) with metastatic castration-resistant prostate cancer (mCRPC), and 69 (48.6%) with metastatic castration-sensitive prostate cancer (mCSPC). Of all, 43.7% experienced all-grade hypertension, and 28.2% experienced grade 3-4 hypertension. There was no difference in incidence of hypertension between patients receiving 5 mg of prednisone daily and those receiving 5 mg of prednisone twice daily. All-grade hypertension occurred in 39.7% of mCRPC and 47.8% of mCSPC patients ( P = 0.33). Thirty-two percent of patients were actively managed by a clinical pharmacist and had an overall trend of reduced hypertension severity after 12 weeks., Conclusion and Relevance: This single-center, retrospective cohort study found that real-world metastatic prostate cancer patients who received AA had substantially higher incidence and severity of hypertension compared with clinical trials regardless of prednisone dose. In patients with mCRPC and mCSPC, the role of prednisone dose in hypertension incidence and severity warrants further investigation. Overall, results indicate the need for closely monitoring hypertension and optimization of anti-hypertensive therapy by multidisciplinary teams in metastatic prostate cancer patients receiving AA., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration and weakness, caused by mutations in the dystrophin gene. DMD has effects in early age with significantly shortened lifespan and deteriorated quality of life in the second decade, creating an urgent need to develop better therapeutic options. Corticosteroid medication therapy is an integral tool for the management of DMD and several therapeutic options have been recently approved for use., Areas Covered: A comprehensive literature search was completed to examine efficacy and safety profiles of the three corticosteroid medications available for use in DMD patients. The review presents information about the three agents through clinical trials, significant preclinical trials, and comparative studies., Expert Opinion: Managing DMD takes a multidisciplinary approach, although long-term corticosteroid therapy remains a significant therapeutic tool. Based on the available published studies, unequivocal comparison between the benefits of the three medications cannot yet be made. When selecting a medication for a patient, the decision-making process will most likely rely on the minor differences in the adverse effect profiles. Whichever medication is utilized will surely be a part of a larger regimen that includes other novel therapeutic agents.

Background and Hypothesis: Patients with minimal change nephrotic syndrome (MCNS) usually experienced severe edema which can affect the absorption of oral corticosteroid during the first 2 weeks. We conducted a randomized controlled trial to compare the efficacy of intravenous isovalent methylprednisolone induction followed by oral prednisone therapy with conventional oral prednisone therapy in highly edematous MCNS patients, aiming to provide a better therapy for MCNS patients., Methods: A single-center, open-label, parallel-arm randomized controlled trial was performed in the Nephrology Department of the Affiliated Hospital of Guangdong Medical University. Patients who met the inclusion were enrolled in our study from May 2015 to October 2020, and were randomized to receive conventional oral steroid or 2 weeks intravenous methylprednisolone followed by oral prednisone., Results: 117 patients were enrolled and randomly assigned to either the sequential group (N = 57) or the oral group (N = 60). Total remission rate in the sequential group was higher than the oral group after treatment for 2 weeks and 4 weeks (P = 0.032, P = 0.027). Complete remission rate was higher in the sequential group than in the oral group (63.3% vs. 41.5%, P = 0.031) after treatment for 2 weeks. The time to achieve CR is shorter in the sequential group than the oral group, with a statistically significant difference (14.0 days, 95% CI [13.5 to 14.5] vs. 16.0 days, 95% CI [12.7 to 19.3], P = 0.024). There were no significant difference in relapse rate (24.5% vs 28.3%, P = 0.823) and time to relapse (155 ± 103 days vs 150.7 ± 103.7 days, P = 0.916) between two groups., Conclusion: This study suggested that highly edematous MCNS patients received intravenously isovalent methylprednisolone induction therapy follow by oral prednisone achieved earlier remission than the conventional oral prednisone regimen without differences in relapse rates or adverse effects. Short-term intravenous methylprednisolone followed by oral prednisone may be a better choice for MCNS patients with highly edema., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objective: To compare outcomes in patients with repeated implantation failure undergoing Intracytoplasmic Sperm Injection/In vitro fertilization (IVF/ICSI) plus immunosuppressants such as prednisolone, prednisone, or cyclosporine A versus the use of IVF/ICSI alone., Data Source: Databases were systematically searched in PubMed, Cochrane, and Embase databases in September 2023., Study Selection: Randomized clinical trials and observational studies with the outcomes of interest were included., Data Collect: We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed using I 2 statistics. Data were analyzed using Review Manager 5.4.The main outcomes were live birth, miscarriage, implantation rate, clinical pregnancy, and biochemical pregnancy., Data Synthesis: Seven studies with 2,829 patients were included. Immunosuppressive treatments were used in 1,312 (46.37%). Cyclosporine A improved implantation rate (OR 1.48; 95% CI 1.01-2.18) and clinical pregnancy (1.89, 95% CI 1.14-3.14). Compared to non-immunosuppressive treatment, prednisolone and prednisone did not improve live birth (OR 1.13, 95% CI 0.88-1.46) and miscarriage (OR 1.49, 95% CI 1.07-2.09). Prednisolone showed no significant effect in patients undergoing IVF/ICSI, clinical pregnancy (OR 1.34; 95% CI 0.76-2.36), or implantation rate (OR 1.36; 95% CI 0.76-2.42)., Conclusion: Cyclosporine A may promote implantation and clinical pregnancy rates. However, given the limited sample size, it is important to approach these findings with caution. Our results indicate that prednisolone and prednisone do not have any beneficial effects on clinical outcomes of IVF/ICSI patients with repeated implantation failure., Prospero: CRD42023449655., Competing Interests: Conflicts to interest: none to declare.

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., Competing Interests: Conflicts of interest – MQ is listed as co-inventor on a patent application related to intermittent glucocorticoid use filed by Northwestern University (PCT/US2019/068,618). All other authors declare they have no competing interests.

Introduction: Immune thrombocytopenia (ITP) affecting pregnancy is a diagnostic and often a therapeutic challenge., Areas Covered: We review the current diagnostic criteria for ITP in pregnancy and the potential utility of laboratory tests. We discuss the impact of ITP on pregnancy outcomes and the effects of pregnancy on patients living with chronic ITP.  We describe the criteria for intervention, the evidence supporting first-line treatment approaches and the therapeutic decisions and challenges in cases refractory to steroids and IVIG. We review the evidence supporting the potential use of thrombopoietin receptor agonists for refractory thrombocytopenia. Finally, we describe the diagnostic, prognostic, and treatment approaches to neonatal ITP and considerations regarding breastfeeding. We searched the terms 'immune thrombocytopenia' and 'pregnancy' on PubMed to identify the relevant literature published before 31 December 2023, including within cited references., Expert Opinion: Decreased platelet production may play a role in pregnancy-related ITP exacerbation. Putative mechanisms include placental hormones, such as inhibin. Although IVIG and prednisone usually suffice to achieve hemostasis for delivery, second-line agents are sometimes required to allow for neuraxial anesthesia. There is growing evidence supporting the use of romiplostim during pregnancy; however, its risk of venous thromboembolism warrants further evaluation.

Eosinophilic gastroenteritis poses a significant diagnostic challenge, particularly in developing countries, where the awareness of this condition may be limited. Here, the case of a patient in her early 30s, who presented with recurrent episodes of abdominal pain and diarrhea, is reported. Initial standard laboratory investigations revealed normal complete blood counts and elevated total serum immunoglobulin E levels. Upper and lower endoscopic evaluations with systemic biopsies did not reveal any significant abnormalities. However, computed tomography revealed a thickened small intestine wall, halo signs, and mild ascites. Analysis of the ascitic fluid confirmed eosinophilia. These findings prompted a diagnosis of eosinophilic gastroenteritis. The patient responded well to a targeted elimination diet, corticosteroids, and antileukotriene medication. The present case emphasizes the importance of considering eosinophilic gastroenteritis in the differential diagnosis of patients who present with abdominal pain and eosinophilic ascites., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Background and Objectives: Several recent clinical studies have indicated that vamorolone is comparable in effectiveness to glucocorticosteroids for treating Duchenne muscular dystrophy (DMD). However, there is a lack of extensive data regarding the efficacy and safety of various doses of vamorolone. We conducted a study to evaluate the efficacy of different doses of vamorolone in boys with DMD, and compare the safety of vamorolone vs. glucocorticosteroids, prednisone or deflazacort in boys with DMD., Methods: We performed systematic searches of the PubMed, Embase, and Cochrane Library databases for vamorolone, glucocorticosteroids, prednisone or deflazacort in boys with DMD. We assessed statistical heterogeneity across trials based on the Newcastle Ottawa scale (NOS) tool test and I 2 values, and mean differences were pooled using the random-effects model. We used traditional meta-analysis to evaluate efficacy and safety of vamorolone 6.0 mg/kg/d vs. vamorolone 2.0 mg/kg/d and vamorolone vs. prednisone. A network meta-analysis was applied to estimated the safety of vamorolone in comparison to glucocorticosteroids, prednisone and deflazacort. Our meta-analysis were performed using Revman 5.4 software, and our network meta-analysis were performed using Stata/MP 18.0., Results: In the meta-analysis, a total of 193 patients were analyzed across four clinical trials (97 patients receiving vamorolone 2 mg/kg per day; 96 patients receiving vamorolone 2 mg/kg per day). We observed that there were statistically significant differences in boys with DMD between vamorolone 6.0 mg/kg/d and vamorolone 2.0 mg/kg/d in TTSTANDV (MD = 0.03, 95%CI = 0.00-0.06, p  = 0.04), TTRWV (MD = 0.13, 95%CI = 0.08-0.19, p  < 0.01), 6MWT (MD = 24.54, 95%CI = 4.46-44.82, p  = 0.02), TTCLIMBV (MD = 0.04, 95%CI = 0.01-0.06, p  = 0.009), no significant difference in BMI z score (MD = 0.09, 95%CI = -0.03-0.20, p  = 0.13). Indirect comparisons derived from network meta-analysis did not show significant differences among vamorolone, glucocorticosteroids, prednisone and deflazacort in BMI z score., Conclusion: Our findings implied that boys with DMD who took vamorolone 6 mg/kg daily instead of 2 mg/kg daily may be safer and have superior motor function. However, more large sample randomized controlled trials are needed to confirm our results., Systematic Review Registration: This systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration number: CRD42024562916)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zeng, Jiao, He, Li, Guo and Song.)

Background: Immunoglobulin A (IgA) vasculitis is common in children and typically resolves spontaneously. However, when presenting in adults, it is more likely to be severe and recurrent., Case Presentation: We present the case of a 19-year-old female patient with recurrent steroid-dependent IgA vasculitis. She had a history of a prolonged episode of IgA vasculitis in childhood. She presented to our hospital with proteinuria and a painful, palpable purpuric rash on her bilateral lower extremities. She was treated with high-dose intravenous steroids. When steroids were tapered, the patient had a recurrence of her painful rash. Over several months, she developed steroid-induced hyperglycemia and worsening proteinuria., Conclusion: Recent studies have shown that corticosteroids have limited effect on long-term outcomes in IgA vasculitis, but steroid-sparing agents have potential for the treatment of recurrent steroid-dependent IgA vasculitis., Competing Interests: Conflicts of Interest: The authors declare they have no conflicts of interest., (© 2024 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Objective: To investigate the clinical features and prognostic factors of patients with primary extranodal diffuse large B-cell lymphoma (DLBCL) in the rituximab era., Methods: The continuous data of newly diagnosed DLBCL patients with complete case data and first-line treated with rituximab, cyclophosphamide, epirubicin, vincristine, prednisone (R-CHOP) or R-CHOP treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to November 2023 were retrospectively analyzed. The clinical and molecular immunological features and prognosis of extranodal DLBCL were analyzed, Logistics regression model was used to analyzed the influencing factors of patients prognosis., Results: A total of 237 patients were enrolled, of which 54.4% (129 cases) were primary extranodal sources of DLBCL, and the most common extranodal sites were as follows: stomach (19.4%), colon (14.7%), tonsils (12.4%), skin/muscle (9.3%), central (7.7%), nasal/nasopharynx (6.2%), bone marrow (5.4%), testes (4.7%). The 3-year PFS and OS of DLBCL patients with extranodal involvement of bone marrow, central, liver, gastrointestinal or pulmonary origin were significantly lower than those of other patients with extranodal DLBCL of non-special site origin, and the difference was statistically significant (PFS: 65.2% vs 76.7%, P =0.008; OS: 82.6% vs 88.3%, P =0.04). Multivariate analysis showed that the prognostic factors affecting OS included NCCN-IPI score >3 ( OR : 0.142, 95% CI : 0.041-0.495, P =0.002), non-germinal center source ( OR : 2.675，95% CI :1.069-6.694， P =0.036), and DEL patients ( OR : 0.327, 95% CI : 0.129-0.830, P =0.019). An NCCN-IPI score >3 was the only independent adverse prognostic factor for PFS ( OR : 0.235, 95% CI : 0.116-0.474, P < 0.001)., Conclusion: Patients with primary extranodal source DLBCL are more common in gastrointestinal involvement, and the overall prognosis is worse than that of patients with lymph node origin. NCCN-IPI score is an important independent adverse prognostic factor for predicting overall survival and progression-free survival in patients with primary extranodal diffuse large B-cell lymphoma.

Rheumatoid arthritis (RA) requires therapeutic approaches that alleviate symptoms and inhibit the progression of joint damage. Glucocorticoids (GCs) have been a cornerstone of RA treatment, yet their use is often limited by side effects. Recent advancements suggest that liposome-based delivery systems can improve GC biodistribution, minimizing toxicity. This study introduces an innovative tool for RA treatment using prednisone-encapsulated nonphospholipid liposomes (NPLs) in combination with a hyaluronic acid (HA) hydrogel. Our methodology involved incorporating prednisone (PR) with palmitic acid and cholesterol to formulate stable NPLs using a thin-film hydration technique. The synthesized PR-NPLs, characterized by a mean size of 150 nm, demonstrated uniform distribution and higher drug encapsulation in comparison with conventional phospholipid liposomes. In vitro assays revealed that PR-NPL markedly reduced inflammatory responses in macrophages. Additionally, we successfully incorporated PR-NPL into an HA hydrogel, employing a photoinitiated cross-linking process. This novel composite offered modulable PR release, governed by the degree of hydrogel cross-linking. The developed system presents a promising advancement in RA management, especially suited for intraarticular injections. It potentially enables targeted, controlled drug release with a reduced risk of side effects, signifying a significant improvement over existing RA therapies., (© 2024 Wiley Periodicals LLC.)

This study aimed to explore the effect of prednisone (PDN) combined with cyclophosphamide (CTX) on bleomycin-induced pulmonary fibrosis (PF) in rats via circular RNA mortality factor 4 like 1 (MORF4L1)/microRNA (miR)-29a-3p/Bromodomain protein 4 (BRD4) axis. A rat model of PF was induced by bleomycin and treated with PDN combined with CTX, and the lentiviral vectors that interfered with MORF4L1, miR-29a-3p, or BRD4 expression were injected into the tail vein at the same time. The mRNA expressions of MORF4L1, miR-29a-3p, BRD4, and fibrosis-associated proteins including fibronectin, connective tissue growth factor, and collagen I were detected by real-time quantitative polymerase chain reaction. The expression level of BRD4 protein in rat lungs was detected by Western blot analysis. Lung pathology of rats was observed by hematoxylin and eosin and Masson's trichrome staining. Apoptosis was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The targeting relationship between miR-29a-3p and MORF4L1 or BRD4 was verified by the bioinformatics website and dual luciferase reporter experiment. Bleomycin-induced PF enhanced MORF4L1 and BRD4 expression, inhibited miR-29a-3p expression, injured lung tissue, increased mRNA expression of fibrosis-related markers, and induced apoptosis in the lung tissue of rats. PDN combined with CTX had a therapeutic effect on PF in rats, which was further promoted by down-regulating MORF4L1 or up-regulating miR-29a-3p. After down-regulating miR-29a-3p or up-regulating BRD4, the effect of down-regulating MORF4L1 was reversed. MORF4L1 could bind to miR-29a-3p to target BRD4. In short, PDN combined with CTX can effectively improve PF through downregulating MORF4L1 to enhance miR-29a-3p-targeted regulation of BRD4.

Background Immunosuppressants are frequently administered to prevent transplant rejection in patients with renal transplants but cause various adverse events. The incidence of each adverse event may differ between pediatric and adult patients with renal transplants. Because the development of organs and bodies in pediatric patients varies greatly annually, the incidence of each adverse event following immunosuppressant administration may vary by age. Consequently, the age-specific incidence of each adverse event in pediatric patients represents invaluable information for clinical settings. To clarify trends in the occurrence of adverse events by age, a large sample size for each age is required. However, it is difficult to conduct clinical trials in pediatric patients with renal transplants with a large sample size for each age. One method to address this difficulty is to use a database.  Objectives This study aimed to investigate the trends in the occurrence of each adverse event following immunosuppressant administration in pediatric patients with renal transplants, categorized by two-year age increments. Methods We extracted data on pediatric patients aged 0-17 years who received immunosuppressants after renal transplant between January 2004 and March 2024 from the U.S. Food and Drug Administration Adverse Event Reporting System. Because adverse events were greatly affected by age, the patients were divided into groups by two-year age increments. We analyzed the relationship between the groups and the reporting proportion of each adverse event by using the reporting regression coefficient (RRC) from univariate regression analysis and the adjusted RRC (aRRC), which controlled for differences in patient background. Results Renal tubular necrosis, renal impairment, chronic allograft nephropathy, and headache were the adverse events that required more attention with increasing age because RRC and aRRC were significantly > 0. By contrast, Epstein-Barr virus infection was the adverse event that required attention, especially in younger pediatric patients, because RRC and aRRC were significantly < 0. Additionally, there were various trends among other adverse events, including those that required careful monitoring across all ages 0-17 years. Conclusions This study demonstrated that the types of adverse events requiring attention in pediatric patients with renal transplants differ by age. These findings can help enhance treatment and care in pediatric clinical settings., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ogura et al.)

Androgen deprivation therapy (ADT) is one of the effective treatment methods for prostate cancer, often used with radiation therapy. Among the key ADT agents is leuprolide, a synthetic gonadotropin-releasing hormone agonist, which effectively suppresses testosterone production which is a requisite for the growth and division of prostate cancer cells. However, leuprolide is associated with several well-known side effects and less common dermatological reactions. In this case, we present an 80-year-old male patient with stage IIB prostate cancer who developed diffuse maculopapular dermatitis following leuprolide acetate ADT. The patient first experienced mild dermatitis following the fifth monthly 7.5 mg leuprolide injection before it developed into a general body rash after six injections. The dermatitis manifested on the patient's arms, thighs, calves, dorsum, and back of hands but sparing the abdomen, face, and neck. The pruritic dermatitis was managed successfully with a three-week course of prednisone which led to complete resolution without long-term sequelae. This case highlights the importance of recognizing and managing dermatological side effects associated with ADT. Clinicians should maintain an index of suspicion and act promptly when these side effects manifest. Systematic reporting and further research are essential to enhance patient safety and understanding of drug-related dermatological manifestations., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Asare et al.)

Background: Prednisolone and prednisone are recommended treatment options for adults with congenital adrenal hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone., Design: Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study was the design of the study., Methods: The method of the study was hydrocortisone dose equivalent and 09:00-h 17-hydroxyprogesterone (17OHP) from 48 patients taking prednis(ol)one at baseline., Results: At baseline, the median hydrocortisone dose equivalent was 30 mg/day and 17OHP was < 36 nmol/L (3× upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to modified-release hydrocortisone capsule (MRHC) at the same hydrocortisone-equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP < 36 nmol/L. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg/day and 82% had 17OHP < 36 nmol/L. The per cent of patients with 17OHP < 36 nmol/L on a hydrocortisone dose equivalent ≤ 25 mg/day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P = 0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years)., Conclusion: MRHC reduces 17OHP at 09:00 h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.

Competing Interests: The authors made the following disclosures: A.B.K.’s institution received grants from Abbvie, Admirx, Anaptys Bio, Aristea, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, Moonlake, Novartis, Pfizer, Prometheus, UCB; Sonoma Bio; she received consulting fees from Abbvie, Alumis, Bayer, Boehringer Ingelheim, Eli Lilly, FIDE, Janssen, Moonlake, Novartis, Pfizer, Priovant, Sonoma Bio, Sanofi, UCB; Target RWE, Ventyx; and serves on the board of directors of Almirall. M.L.P. is a consultant and/or investigator for Abbvie, Bristol Meyers Squibb, Janssen, Eli Lilly, Moonlake, Novartis, Pfizer, Trifecta Clinical (on behalf of acelyrin), UCB, Aristea, Regeneron, Innovaderm, Bayer, and Incyte. R.S.G.’s fellowship was funded through the National Psoriasis Foundation. R.S.G. is an investigator for Abbvie, Janssen, Regeneron, Eli Lilly, Novartis, UCB, Aristea, Incyte, Innovaderm, Bayer, and Moonlake. C.L.S. has no conflicts of interest to disclose.

Since 1979 Austrian children and adolescents with acute lymphoblastic leukemia (ALL) have been treated according to protocols of the Berlin-Frankfurt-Münster (BFM) study group. The Associazione Italiana di Ematologia e Oncologia Pediatrica and BFM (AIEOP-BFM) ALL 2000 study was designed to prospectively study patient stratification into three risk groups using minimal residual disease (MRD) on two time points during the patient's early disease course. The MRD levels were monitored by detection of clone-specific rearrangements of the immunoglobulin and T‑cell receptor genes applying a quantitative polymerase chain reaction-based technique. The 7‑year event-free survival (EFS) and overall survival rates for all 608 Austrian patients treated between June 1999 and December 2009 within the AIEOP-BFM 2000 study were 84 ± 2% and 91 ± 1%, respectively, with a median observation time of 6.58 years. Event-free survival for patients with precursor B‑cell and T‑cell ALL were 84 ± 2% (n = 521) and 84 ± 4% (n = 87; p = 0.460), respectively. The MRD assessment was feasible in 94% of the patients and allowed the definition of precursor B‑cell ALL patients with a low, intermediate or high risk of relapse even on top of clinically relevant subgroups. A similar finding with respect to MRD relevance in T‑ALL patients was not possible due to the small number of patients and events. Since this pivotal international AIEOP-BFM ALL 2000 trial, molecular response to treatment has been continuously used with additional refinements to stratify patients into different risk groups in all successive trials of the AIEOP-BFM ALL study group., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Aim: The present study aims to investigate the prevalence, causes and outcomes of acute gastrointestinal (GI) bleeding in Rheumatoid arthritis (RA)., Methods: A systemic search was conducted from electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to 14 th November 2023. All statistical analyses were conducted in Review Manager 5.4.1. Studies meeting inclusion criteria were selected. A random-effect model was used when heterogeneity was seen to pool the studies, and the result was reported in prevalence and their corresponding 95% confidence interval (CI). Other outcomes were assessed using qualitative analysis., Results: A total of eight studies (six observational studies and 2 trials were used to conduct this systematic review and meta-analysis. A total population of 138,041 patients was used. Pooled analysis showed a statistically significant risk of GI bleeding in RA patients receiving NSAIDs (prevalence = 2% (1%, 3%); P < 0.00001; I2 = 98%). Qualitatively, causes and outcomes were discussed., Conclusion: Our study showed that 2% RA patients were subjected to GI bleeding, when they used NSAIDs. Other causes of GI bleeding were age-related factors, cardiovascular events, history of GI complications, and peptic ulcers. Outcome varied by the use of specific NSAIDs and the presence of comorbidities. Recent guidelines for the management of RA may mention GI bleeding as a potential complication, but the level of emphasis placed on this issue varies. Some guidelines provide comprehensive recommendations for its prevention and management, while others offer limited guidance., Competing Interests: The authors declare no conflict of interest., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Glucocorticoids (GCs) are one of the most effective first-line treatments for systemic lupus erythematosus (SLE). However, GC burden is associated with damage. The initial GC dose and tapering schedule should be tailored to the severity of the clinical scenario. As lupus therapy should prompt remission while minimising damage, recent guidelines recommend a more accurate approach to the use of GCs, setting lower starting doses and rapid tapering schemes, and encouraging maintenance prednisolone doses <5 mg/day. Methylprednisolone pulses (MP) help to reduce the dose of oral GCs and improve the clinical response in both severe and non-severe manifestations, without significant side effects. Fixed-tapering GC scheme provides a useful strategy to reduce GCs exposure. Long-term antimalarial treatment and early initiation of immunosuppressive drugs improve clinical efficacy while reducing GC toxicity. Besides, withdrawal of GCs is an achievable goal in patients in prolonged remission on stable treatment, and recent studies have attempted to identify the most suitable candidates. In this article, we review the pharmacological basis, clinical evidence of efficacy, dose-related harms, and potential withdrawal of GCs. We also review guidelines recommendations and finally give a personal and practical approach to dealing with the use of GCs in SLE patients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Previous studies showed tacrolimus monotherapy and dual therapy with tacrolimus and prednisone as effective treatment modalities in managing membranous nephropathy. However, few studies have compared these therapeutic regimens. The patients were divided into two groups based on the treatment regimen: (1) tacrolimus and prednisone dual therapy (T + P group, n = 67) treatment group; and (2) tacrolimus monotherapy (T group, n = 65) or the control group. Propensity matching method and subgroup analysis to eliminate the bias in the relationship between the treatment regimen and the outcomes. The mean remission times were 20.33 ± 2.75 weeks at T group and 9.50 ± 1.81 weeks at T + P group. The T group had a remission rates of 73.33, 76.66 and 66.66% at 12weeks, 24weeks and 48weeks, while the T + P group had a remission rate of 81.66, 86.66, 91.66%; At the follow-up of 48 weeks, the relapse rate for the T group was 21.66%, and that for the T + P group was 5%. The anti-PLA2R ab is positive and therapy may be the independent risk factors for predicting remission. Tacrolimus and low-dose prednisone dual therapy is efficacious in managing MN and lowers the recurrence rate in clinical practice., (© 2024. The Author(s).)

Background: Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and BMD, respectively). At study endpoint, there were trends towards increased lean mass, reduced fat mass, reduced creatine kinase and improved motor function. The investigation was motivated by studies in mouse muscular dystrophy models in which once weekly glucocorticoid exposure enhanced muscle strength and reduced fibrosis., Methods: WSiMD participants provided blood samples for aptamer serum profiling at baseline and after 6 months of weekly steroids. A subset completed magnetic resonance (MR) evaluation of muscle at study onset and endpoint., Results/conclusions: At baseline compared to age and sex-matched healthy controls, the aggregate serum protein profile in the WSiMD cohort was dominated by muscle proteins, reflecting leak of muscle proteins into serum. Disease status produced more proteins differentially present in serum compared to steroid-treatment effect. Nonetheless, a response to prednisone was discernable in the WSiMD cohort, even at this low dose. Glucocorticoids downregulated muscle proteins and upregulated certain immune process- and matrix-associated proteins. Muscle MR fat fraction showed trends with functional status. The prednisone-responsive markers could be used in larger trial of prednisone efficacy., Competing Interests: CONFLICTS Of INTEREST EMM has been a consultant to Amgen, AstraZeneca, Cytokinetics, Pfizer, Tenaya Therapeutics, and is a founder of Ikaika Therapeutics. ARD is CSO of Ikaika Therapeutics. The other authors have declared that no conflict of interest exists.

Atopic dermatitis is a chronic inflammatory skin disease that may progress to erythroderma in severe cases. Biologic agents such as dupilumab have recently become the mainstay of systemic treatment for moderate-to-severe cases, yet many patients remain refractory to therapy. Here, we present a case of erythrodermic atopic dermatitis, resistant to prednisone and dupilumab, with remarkably rapid achievement of remission following treatment with upadacitinib, an oral selective Janus kinase 1 inhibitor., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Recommendations for the treatment of myasthenia gravis (MG) have been difficult to develop because of limited evidence from large randomized controlled trials. New drugs and treatment approaches have recently been shown to be effective in phase 3 studies in seropositive generalized (g) MG. One such drug is efgartigimod, a human-Fc-fragment of IgG1, with a high affinity for the endosomal FcRn. We conducted a multicenter study to evaluate the real-world clinical and safety effects of efgartigimod in 22 gMG patients. We evaluated the strategies for the timing of re-treatment with it. The participants received a total of 59 efgartigimod -treatment cycles. The median number of cycles was 2 (range 1-6). Twenty patients (86.3%) improved by at least 2 MG-ADL points after the first treatment cycle. The median MG-ADL score at baseline was 6.5 (range: 3-17) and 2.5 (range: 0-9) post-treatment (p < 0.001). A consistent improvement of at least 2 points in the MG-ADL score after each cycle occurs in 18 patients. The effect duration of the treatment was usually between 4 and 12 weeks. Two major clinical patterns of treatment response were found. Treatment with efgartigimod was also associated with significant reductions of prednisone doses Overall, the treatment was safe and associated with only minor adverse events. The single fatality was apparently due tosevere respiratory failure. We found that efgartigimod is clinically effective, may be used as a steroid sparing agent and is generally safe for gMG patients. We recommend a personalized preventive treatment approach until clinical stabilization, followed by discontinuation and periodic evaluations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: Dihydroartemisinin (DHA) plays a very important role in various diseases. However, the precise involvement of DHA in systemic lupus erythematosus (SLE), relation to the equilibrium between M1 and M2 cells, remains uncertain. Therefore, we aimed to investigate the role of DHA in SLE and its effect on the M1/M2 cells balance., Methods: SLE mice model was established by pristane induction. Flow cytometry was employed to measure the abundance of M1 and M2 cells within the peripheral blood of individuals diagnosed with SLE. The concentrations of various cytokines, namely TNF-α, IL-1β, IL-4, IL-6, and IL-10, within the serum of SLE patients or SLE mice were assessed via ELISA. Immunofluorescence staining was utilized to detect the deposition of IgG and complement C3 in renal tissues of the mice. We conducted immunohistochemistry analysis to assess the expression levels of Collagen-I, a collagen protein, and α-SMA, a fibrosis marker protein, in the renal tissues of mice. Hematoxylin-eosin staining, Masson's trichrome staining, and Periodic acid Schiff staining were used to examine histological alterations. In this study, we employed qPCR and western blot techniques to assess the expression levels of key molecular markers, namely CD80 and CD86 for M1 cells, as well as CD206 and Arg-1 for M2 cells, within kidney tissue. Additionally, we investigated the involvement of the MAPK signaling pathway. The Venny 2.1 online software tool was employed to identify shared drug-disease targets, and subsequently, the Cytoscape 3.9.2 software was utilized to construct the "disease-target-ingredient" network diagram. Protein-protein interactions of the target proteins were analyzed using the String database, and the network proteins underwent enrichment analysis for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways., Results: The results showed that an increase in M1 cells and a decrease in M2 cells within the peripheral blood of individuals diagnosed with SLE. Further analysis revealed that prednisone (PDN) combined with DHA can alleviate kidney damage and regulate the balance of M1 and M2 cells in both glomerular mesangial cells (GMC) and kidney. The MAPK signaling pathway was found to be involved in SLE kidney damage and M1/M2 balance in the kidney. Furthermore, PDN and/or DHA were found to inhibit the MAPK signaling pathway in GMC and kidney., Conclusion: We demonstrated that PDN combined with DHA attenuates SLE by regulating M1/M2 balance through MAPK signaling pathway. These findings propose that the combination of PDN and DHA could serve as a promising therapeutic strategy for SLE, as it has the potential to mitigate kidney damage and reinstate the equilibrium of M1 and M2 cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Context: Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects., Objective: This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids., Methods: Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort studies, and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and nonusers were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model., Results: We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95% CI, 14%-33%), 11% for mania (2%-46%), 8% for anxiety (2%-25%), 16% for delirium (6%-36%), and 52% for behavioral changes (42%-61%). Questionnaire scores for depression (SMD of 0.80 [95% CI 0.35-1.26]), and mania (0.78 [0.14-1.42]) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use., Conclusion: The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)