Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition characterized by significant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells within affected tissues, with or without elevated serum IgG4 levels. The prevalence of IgG4-RD remains largely undetermined due to diagnostic challenges, as the condition is frequently unrecognized or misdiagnosed. This report describes a case of a 63-year-old man who was ultimately diagnosed with this rare condition after an extensive two-year period of elusive symptoms. Initially presenting with intermittent body pains and fluctuating fever, his condition progressively evolved to include severe right orbital swelling with marked tenderness and ecchymosis, recurrent non-tender nodules on his arm, and diminished vision. A detailed review of his medical history prompted the consideration of IgG4-RD, leading to the measurement of serum human IgG4 levels, which were found to be significantly elevated at 1504 mg/L (normal range: 39.2-864 mg/L). Following his diagnosis, treatment with glucocorticoids (0.6 mg/kg for one month) was initiated, resulting in a positive clinical response. This case emphasizes the critical importance of considering less common conditions in the differential diagnosis of patients presenting with complex, multi-system symptoms.

Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16+ NK cells and proinflammatory M1 macrophages at the maternal-fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue-specific drug delivery systems, especially immune cell-specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC-Exo-CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC-Exo-CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16+ decidual natural killer (NK) cells and CD16+ macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion-prone mice. The developed GC-Exo-CD16Ab provides a feasible platform for precise and tissue-specific therapeutic strategies for miscarriage and pregnancy-related diseases.

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OBJECTIVE: Treatment with glucocorticoids following paediatric cataract surgery is crucial to prevent inflammation, but may lead to secondary glaucoma, and hypothalamic-pituitary-adrenal axis suppression. We wish to compare glaucoma outcomes following high-dose and low-dose glucocorticoid treatment after paediatric cataract surgery.
METHODS: This cohort study included Danish children undergoing cataract surgery before 10 years of age, receiving either a low-dose or high-dose postoperative glucocorticoid treatment. Case identification and collection of a standardized dataset were retrospective, from 1 January 2010 to 31 December 2016, and prospective thereafter, until 31 December 2021. High-dose treatment included 0.5-1.0 mg subconjunctival depot dexamethasone or methylprednisolone, followed by 6-8 drops of dexamethasone for 1 week, tapered by one drop weekly. Low-dose treatment included 6 drops for 3 days, followed by 3 drops for 18 days. Sustained (>3 months) ocular hypertension or glaucoma was compared between the two groups.
RESULTS: Overall, 267 children (388 eyes) were included in the study. Ninety-five children (133 eyes) had received high-dose treatment and had a median follow-up time of 89 months (IQR: 57.2-107.4), while 173 children (255 eyes) had received the low-dose treatment and had a median follow-up time of 40.5 months (IQR: 22.9-60.4). Survival curves showed a lower risk of glaucoma in the low-dose group for children with axial lengths ≥18 mm.
CONCLUSIONS: Low-dose glucocorticoid treatment was associated with a lower risk of glaucoma in children with axial lengths ≥18 mm. The same effect was not observed in children with shorter eyes. High-dose glucocorticoid should be limited in children undergoing cataract surgery.

UNASSIGNED: Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on reducing treatment toxicities, notably through reduction of exposure to glucocorticoids. Glucocorticoid-sparing therapies such as avacopan are not widely available in many countries, and patients are exposed to high glucocorticoid doses. There is little data concerning what clinicians should accept as the lowest glucocorticoid dosing that can be used in induction therapy for AAV.
UNASSIGNED: International, online survey.
UNASSIGNED: Clinicians in various countries with experience in managing vasculitis.
UNASSIGNED: Survey questions to gauge interest and preferences in studying an induction of remission regimen for severe AAV using only 2 or 4 weeks of glucocorticoids without avacopan. Data collected included general opinions about standard of care for induction agents, glucocorticoids, and avacopan. Respondents were presented with 3 candidate trial designs, 2 of which proposed a combination of cyclophosphamide and rituximab induction.
UNASSIGNED: Using a 10-point Likert scale, respondents ranked each candidate trial on its usefulness in demonstrating whether a minimal glucocorticoid regimen would be safe and effective and their willingness to randomize into the trial.
UNASSIGNED: There were 210 respondents to the survey. The candidate trials were rated moderate-to-high for usefulness to demonstrate safety and efficacy (scores 6-7/10), and moderate (scores 5-6/10) for willingness to randomize. Four-week glucocorticoid duration was preferred to 2 weeks, and combination cyclophosphamide-rituximab with 4-week glucocorticoids was the most preferred design. Forty-two percent of respondents felt avacopan had to be incorporated into a minimal GC trial design to want to recruit patients.
UNASSIGNED: Representativeness of survey sample and generalizability of findings.
UNASSIGNED: Combination cyclophosphamide-rituximab may be the ideal way of studying minimal glucocorticoid use in severe AAV. Given its increasing uptake, incorporating avacopan into a potential trial design is important.
Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on using less glucocorticoids to limit side effects. New drugs that drastically limit glucocorticoid use are not available in many countries. Studies are needed to find other ways of reducing glucocorticoid exposure to treat AAV, but it is unclear how best to achieve this. We administered a survey to doctors with experience in treating AAV and had them grade different combinations of widely available treatments with 2 or 4 weeks of glucocorticoids. We found that a combination of 2 doses cyclophosphamide with 2 doses rituximab and 4 weeks of glucocorticoids was the preferred treatment. The results will guide the development of a trial studying minimal use of glucocorticoids for the treatment of AAV.

Atypical femoral fracture (AFF) is generally a rare complication of long-term use of bisphosphonate (BP); glucocorticoid (GC) use and Asian race are also risk factors. Femoral localized periosteal thickening (LPT, also termed \"beaking\") of the lateral cortex often precedes AFF. This cohort study investigated the incidence of LPT and AFF and their clinical courses over 10 yr in patients with autoimmune inflammatory rheumatic diseases (AIRDs) treated with BP and GC. The study population consisted of 121 patients with AIRDs taking BP and GC. LPT was screened by X-ray, and the LPT shape was evaluated. Prednisolone (PSL) dose was 10 (8-12) mg/d at enrollment and 9 (6-10) mg/d at the last observation. LPT was evident in 10 patients at enrollment and increased linearly to 31 patients (26%) at the last observation. AFF occurred in 9 femurs of 5 patients with LPT. All patients with AFF had bilateral LPT, and the prevalence of pointed type and LPT height were higher in the AFF-positive group than in the AFF-negative group. AFF occurred before BP discontinuation in 2 patients, 1 yr after BP discontinuation in 1, after BP discontinuation followed by 7 yr of alfacalcidol use in 1, and after switching from alfacalcidol to denosumab in 1. The prevalence rates of AFF and LPT associated with long-term BP use with concomitant use of GC (mostly PSL ≥ 6 mg/d) in Japanese patients with AIRD increased over time. The selection of long-term osteoporosis treatment for LPT-positive patients is difficult in some cases.

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Phenotypic differences often stem from genetic/maternal differences and/or early-life adaptations to local environmental conditions. In colonial animals, little is known on how variation in the social environment is embedded into individual phenotypes, nor what the consequences are on individual fitness. We conducted an experimental cross-fostering study on king penguins (Aptenodytes patagonicus), exchanging eggs among 134 pairs breeding in high-density (67 pairs) or low-density (67 pairs) areas of the same breeding colony. We investigated differences in parent and chick phenotypes and survival in relation to the density of their origin and foster environment. Adults breeding in colony areas of high density exhibited decreased resting behaviour and increased aggression and vigilance, increased hypometabolism during incubation fasts, and more moderate corticosterone responses shaped by exposure to chronic stressors (e.g. constant aggression by neighbours). Chick phenotypes were more influenced by the environment in which they were raised than their genetic/maternal origin. Chicks raised in high-density colonial environments showed enhanced weight gain and survival rates regardless of the density of their genetic parents\' breeding areas. Our study experimentally shows advantages to breeding in colonial areas of higher breeder densities in king penguins, and highlights the importance of social settings in shaping phenotype expression in colonial seabirds.

Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations.

BACKGROUND: Secondary genetic alterations, which contribute to the dysregulation of cell cycle progression and lymphoid specialization, are frequently observed in B-cell precursor acute lymphoblastic leukemia (B-ALL). As IKZF1 and BTG1 deletions are associated with a worse outcome in B-ALL, this study aimed to address whether they synergistically promote glucocorticoid resistance.
METHODS: Small interfering RNA was used to downregulate either IKZF1, or BTG1, or both genes in the 207 B-ALL cell line. Cell viability was investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion assays. The expression levels of IKZF1, BTG1 and glucocorticoid-responsive genes (DUSP1, SGK1, FBXW7 and NR3C1) were evaluated by real time quantitative real time polymerase chain reaction (PCR).
RESULTS: Isolated silencing of BTG1, IKZF1, or both genes in combination under dexamethasone treatment increased cell viability by 24%, 40% and 84%, respectively. Although BTG1 silencing did not alter the expression of glucocorticoid-responsive genes, IKZF1 knockdown decreased the transcript levels of DUSP1 (2.6-fold), SGK1 (1.8-fold), FBXW7 (2.2-fold) and NR3C1 (1.7-fold). The expression of glucocorticoid-responsive genes reached even lower levels (reducing 2.4-4 fold) when IKZF1 and BTG1 silencing occurred in combination.
CONCLUSIONS: IKZF1 silencing impairs the transcription of glucocorticoid-responsive genes; this effect is enhanced by concomitant loss of BTG1. These results demonstrate the molecular mechanism by which the combination of both genetic deletions might contribute to higher relapse rates in B-ALL.