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Objective and Design: Glucocorticoids (GCs) have been widely used in symptomatic patients for the treatment of COVID-19. The risk for adrenal insufficiency must be considered after GC withdrawal given that it is a life-threatening condition if left unrecognized and untreated. Our study aimed to diagnose adrenal insufficiency early on through a GC reduction schedule in patients with COVID-19 infection., Patients and Measurements: From November 2021 to May 2022, 233 patients were admitted to the Geriatric Division of the University Hospital of Padova with COVID-19 infection. A total of 122 patients were treated with dexamethasone, after which the GC tapering was performed according to a structured schedule. It consists of step-by-step GC tapering with prednisone, from 25 mg to 2.5 mg over 2 weeks. Morning serum sodium, potassium, and cortisol levels were assessed 3 days after the last dose of prednisone., Results: At the end of GC withdrawal, no adrenal crisis or signs/symptoms of acute adrenal insufficiency were reported. Median serum cortisol, sodium, and potassium levels after GC discontinuation were, respectively, 427 nmol/L, 140 nmol/L, and 4 nmol/L (interquartile range 395-479, 138-142, and 3.7-4.3). A morning serum cortisol level below the selected threshold of 270 nmol/L was observed in two asymptomatic cases (respectively, 173 and 239 nmol/L, reference range 138-690 nmol/L). Mild hyponatremia (serum sodium 132 to 134 nmol/L, reference range 135-145 nmol/L) was detected in five patients, without being related to cortisol levels., Conclusions: A structured schedule for the tapering of GC treatment used in patients with severe COVID-19 can reduce the risk of adrenal crisis and acute adrenal insufficiency., (© 2024. The Author(s).)

During the unprecedented COVID-19 outbreak, new-onset or relapsing glomerulonephritis, such as ANCA-associated glomerulonephritis and Immunoglobulin A (IgA) nephropathy, following COVID-19 has been reported. However, to date, the association of COVID-19 with preexistent IgA vasculitis (IgAV) remains unclear. Here, we present the case of a 20-something old Japanese woman with preexistent IgAV who newly developed glomerulonephritis following COVID-19. At the diagnosis of IgAV, she had cutaneous purpura, joint pains, and gastrointestinal symptoms, but no signs of kidney involvement. Three months ago, she was tested positive for COVID-19 and subsequently developed hematuria and proteinuria. She was then admitted to our hospital and renal biopsy showed glomerular mesangial expansion and hypercellularity and cellular and fibrocellular crescents, accompanied by diffuse IgA and C3 deposits. With the diagnosis of de novo IgAV nephritis, the patient was treated with intravenous methylprednisolone followed by oral prednisolone. She had favorable responses to this treatment and has achieved and maintained the remission of hematuria and proteinuria after initiation of glucocorticoid therapy. Our case highlights that immune response to SARS-CoV-2 infection could trigger the onset of glomerulonephritis in the IgAV patients who have no renal involvement., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Dermoid cysts, or mature cystic teratomas, are germ cell neoplasms that can arise on the ovaries. Being of germ cell origin, such cysts can have extensive variance in presentation, including a rare paraneoplastic effect where they produce N-methyl-D-aspartate receptor (NMDAR) antibodies, resulting in anti-NMDAR encephalitis. This can cause various neuropsychiatric symptoms, including confusion, hallucinations, psychosis, disorientation, and a change in cognition. This case study presents the unusual occurrence of a 39-year-old female patient who presented to the emergency department with encephalitis, headaches, and auditory hallucinations after recent glucocorticoid use. Through an extensive workup, imaging, and various physician consults, the patient was diagnosed with anti-NMDAR encephalitis secondary to a paraneoplastic effect originating from an ovarian dermoid cyst., 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, Casarcia et al.)

Background: Autoimmune pancreatitis (AIP) is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct. Some studies have reported that AIP can cause hemorrhage of gastric varices (GV) related to portal hypertension (PH). However, such cases are rare. In addition, the association of PH with AIP is unclear. At the same time, the efficacy and duration of glucocorticoid therapy is also controversial., Case Summary: In this case, we reported a case of GV in pancreatic PH associated with AIP. Enhanced abdominal computed tomography (CT) suggested splenic vein (SV) and superior mesenteric vein (SMV) thromboses. The patient received a long-term glucocorticoid therapy, that the initial dose of 40 mg is reduced weekly by 5 mg, and then reduced to 5 mg for long-term maintenance. CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized, pancreatic stiffness and swelling were ameliorated, and the GV almost completely disappeared., Conclusion: Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Isolated adrenocorticotropic hormone deficiency (IAD) is a rare pituitary disorder that can cause adrenal insufficiency. However, due to its nonspecific symptoms, its diagnosis is often difficult and may be delayed. Patients with IAD require lifelong glucocorticoid (GC) replacement therapy. Contrastingly, GC-induced secondary adrenal insufficiency is a reversible condition that arises when patients receiving GC therapy reduce their GC dosage or discontinue therapy. Differentiating between IAD and GC-induced secondary adrenal insufficiency is clinically crucial. We report a unique case that required differentiation between these two conditions. A 71-year-old Japanese woman presented with symptoms of adrenal insufficiency after discontinuation of GC therapy for eosinophilic esophagitis. We conducted detailed interviews and repeated the endocrinological examinations. We concluded that her symptoms were owing to IAD rather than GC-induced secondary adrenal insufficiency. She began a lifelong hydrocortisone replacement therapy. This case suggests that when caring for patients undergoing GC therapy, it is important to consider the possibility of coexisting IAD and arrange endocrinological examinations if signs of adrenal insufficiency arise during the gradual reduction of GC treatment., 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, Iwamura et al.)

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., 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, Khan et al.)

Objective: This retrospective study aimed to investigate the clinical features of optic neuritis associated with COVID-19 (COVID-19 ON), comparing them with neuromyelitis optica-associated optic neuritis (NMO-ON), myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON), and antibody-negative optic neuritis (antibody-negative ON)., Methods: Data from 117 patients (145 eyes) with optic neuritis at the Shantou International Eye Center (March 2020-June 2023) were categorized into four groups based on etiology: Group 1 (neuromyelitis optica-related optic neuritis, NMO-ON), Group 2 (myelin oligodendrocyte glycoprotein optic neuritis, MOG-ON), Group 3 (antibody-negative optic neuritis, antibody-negative ON), and Group 4 (optic neuritis associated with COVID-19, COVID-19 ON). Characteristics of T2 and enhancement in orbital magnetic resonance imaging (MRI) were assessed. Best-corrected visual acuity (BCVA) was compared before treatment, at a short-term follow-up (14 days), and at the last follow-up after treatment., Results: The COVID-19-associated optic neuritis (COVID-19 ON) group exhibited 100% bilateral involvement, significantly surpassing other groups ( P < 0.001). Optic disk edema was observed in 100% of COVID-19 ON cases, markedly differing from neuromyelitis optica-related optic neuritis (NMO-ON) ( P = 0.023). Orbital magnetic resonance imaging (MRI) revealed distinctive long-segment lesions without intracranial involvement in T1-enhanced sequences for the COVID-19 ON group compared to the other three groups ( P < 0.001). Discrepancies in optic nerve sheath involvement were noted between the COVID-19 ON group and both NMO-ON and antibody-negative optic neuritis (antibody-negative ON) groups ( P = 0.028). Before treatment, no significant difference in best-corrected visual acuity (BCVA) existed between the COVID-19 ON group and other groups. At the 14-day follow-up, BCVA in the COVID-19 ON group outperformed the NMO-ON ( P < 0.001) and antibody-negative ON ( P = 0.028) groups, with no significant difference observed compared to the myelin oligodendrocyte glycoprotein optic neuritis (MOG-ON) group. At the last follow-up after treatment, BCVA in the COVID-19 ON group significantly differed from the NMO-ON group ( P < 0.001)., Conclusion: Optic neuritis associated with COVID-19 (COVID-19 ON) predominantly presents with bilateral onset and optic disk edema. Orbital magnetic resonance imaging (MRI) demonstrates that COVID-19 ON presents as long-segment enhancement without the involvement of the intracranial segment of the optic nerve in T1-enhanced images. Glucocorticoid therapy showed positive outcomes., 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 Zhao, Wang, Li, Hu, Yu, Li, Cen, Huang, Lin, Yang, Chen and Cen.)

Sepsis, a life-threatening medical condition, manifests as new or worsening organ failures due to a dysregulated host response to infection. Many patients with sepsis have manifested a hyperinflammatory phenotype leading to the identification of inflammatory modulation by corticosteroids as a key treatment modality. However, the optimal use of corticosteroids in sepsis treatment remains a contentious subject, necessitating a deeper understanding of their physiological and pharmacological effects. Our study conducts a comprehensive review of randomized controlled trials (RCTs) focusing on traditional corticosteroid treatment in sepsis, alongside an analysis of evolving clinical guidelines. Additionally, we explore the emerging role of artificial intelligence (AI) in medicine, particularly in diagnosing, prognosticating, and treating sepsis. AI's advanced data processing capabilities reveal new avenues for enhancing corticosteroid therapeutic strategies in sepsis. The integration of AI in sepsis treatment has the potential to address existing gaps in knowledge, especially in the application of corticosteroids. Our findings suggest that combining corticosteroid therapy with AI-driven insights could lead to more personalized and effective sepsis treatments. This approach holds promise for improving clinical outcomes and presents a significant advancement in the management of this complex and often fatal condition., 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., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Glucocorticoid (GC) therapy had been strongly recommended for pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. About 32.8% of patients with pediatric septic develop relative adrenal insufficiency (RAI). But whether GC therapy should be determined by RAI status is controversial. This study utilized 21-day-old SF1CreSRBIfl/fl mice as the first pediatric RAI mouse model to assess the pathogenesis of RAI and evaluate GC therapy. RAI mice exhibited a substantially higher mortality rate in cecal ligation and puncture and cecal slurry-induced sepsis. These mice featured persistent inflammatory responses and were effectively rescued by GC therapy. RNA sequencing analysis revealed persistent inflammatory responses in RAI mice, caused by transcriptional dysregulation of AP-1 and NF-κB, and cytokine-induced secondary inflammatory response. Our findings support a precision medicine approach to guide GC therapy for pediatric patients based on the status of RAI., Competing Interests: Potential conflicts of interest. The authors declare no conflict of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and objective High-dose intravenous pulsed glucocorticosteroids (GCS) are not part of the standard treatment in acute respiratory distress syndrome (ARDS), and the evidence supporting their use is conflicting. In clinical practice, however, they are used in specialist settings when clinico-patho-radiological features suggest a potentially steroid-responsive pattern, or as a last resort in cases where patients are unable to be weaned off mechanical ventilation. This study aimed to investigate if an early objective response to high-dose GCS treatment in selected critically ill patients is predictive of survival in ARDS. Methods This study involved a case series of 63 patients treated at a tertiary specialist respiratory ICU between 2009 and 2017 who received high-dose GCS for ARDS following a multidisciplinary board agreement. Patients were stratified according to the change in their modified lung injury score (mLIS) between days 0 and 10 following GCS initiation. Changes in mLIS (range: 0-4) were grouped as follows - full responders: ≥2, partial responders: ≥1 and <2, and non-responders: <1. Mortality on discharge and at 6, 12, 18, and 24 months post-ICU discharge was assessed for each group. Data were analysed using logistic regression and a receiver operating curve (ROC) to determine a statistically significant association between the change in mLIS and survival. Results Of the 63 patients, there were seven full responders, 12 partial responders, and 44 non-responders to high-dose GCS. Overall mortality at ICU discharge and 6, 12, 18 and 24 months post-discharge was 29/63 (46.0%), 33/63 (52.4%), 34/63 (54.0%), 34/63 (54.0%), and 35/63 (55.6%) respectively. Mortality was significantly lower in the partial and full-response groups than in the non-response group at all time frames. Logistic regression showed a significant association between the change in mLIS and survival (p<0.001), and a ROC demonstrated that categorising the change in mLIS was a good predictive model for survival (c-statistic 0.86). Conclusions Measuring the change in mLIS by day 10 following high-dose GCS administration for ARDS may be clinically useful in prognosticating such patients. Further research using mLIS as a measure of response to GCS, and larger datasets to enable the evaluation of prognostic factors, may assist clinicians in predicting which patients with persistent ARDS are likely to respond to GCS therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Leahy et al.)

Background and Purpose: The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION)., Materials and Methods: This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7-14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement., Results: No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up (p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7-14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups (p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 (p = 0.045)., Conclusion: Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact., (© 2024. The Author(s).)

Context: Moon-like facies (MLF) are a typical side effect of glucocorticoid (GC) therapy; however, its predisposing factors, relationship with GC-induced complications, and effects on body image are not well understood., Objective: This study aimed to determine the predisposing factors for MLF during GC therapy; its association with GC-induced diabetes, hypertension, and dyslipidemia; and its effects on body image., Methods: This prospective observational study spanned 24 weeks and targeted patients who received GC therapy at the University of Yamanashi Hospital from June 2020 to August 2022. The MLF was defined based on the following 3 factors: (1) an increase in facial measurement lengths, (2) subjective facial changes by patients' self-assessment using a visual analog scale; (3) objective and qualitative facial changes assessed by physicians. We examined the predisposing factors for MLF and the association of MLF with GC-induced diabetes, hypertension, dyslipidemia, and body image., Results: The cumulative incidence rate of MLF at 24 weeks was 37.6%. Predisposing factors for MLF were an initial oral prednisolone dosage of ≥ 30 mg/day [odds ratio (OR) 63.91, 95% confidence interval (CI) 5.82-701.81] and female (OR 6.66, 95% CI 1.35-32.79). MLF showed a significant association with the onset of GC-induced diabetes (OR 6.58, 95% CI 1.25-34.74). MLF was also an independent factor contributing to body image disturbance (β = -18.94, P = .01)., Conclusion: MLF contributes to body image disturbance and is associated with the development of GC-induced diabetes; therefore, it is clinically important as a physical manifestation of GC therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To investigate the brain structural and functional alterations in patients with thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid therapy, using voxel-based morphometry (VBM) as well as resting-state functional magnetic resonance imaging (MRI) with amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo)., Methods: Between 2019 and 2022, 32 patients with TAO and 23 healthy controls underwent pre-therapy MRI in Nanjing, China. Intravenous glucocorticoid therapy was administered to all patients. At 3 months after end of therapy, 26 patients were available for rescanned MRI. VBM, ALFF, and ReHo were used to evaluate the brain structural and functional differences., Results: Before therapy, TAO patients showed significantly decreased gray matter volume (GMV) in the left orbital part of superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed) than healthy controls. Patients had higher ALFF values in bilateral gyrus rectus and olfactory cortex and lower values in bilateral cuneus. Patients also showed decreased ReHo values in bilateral lingual gyrus. After therapy, increased GMV in the left anterior cingulate gyrus and SFGmed, increased ALFF values in bilateral cuneus and superior occipital gyrus, and increased ReHo values in bilateral SFGmed were found in TAO patients compared to the pre-therapy cohort. Compared to controls, decreased GMV in left ORBsup was observed in post-therapy TAO patients., Conclusion: Our results indicated that TAO might cause functional and structural deficits in the visual and emotional regions of the brain, with recovery in the former and partial restoration in the latter after effective glucocorticoid therapy. These findings may lead to deeper understanding of the pathophysiological mechanism behind TAO., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The aim was to determine the combined value of serological lipid metabolism and an orbital MRI quantitative parameter in predicting the effectiveness of glucocorticoid (GC) therapy in patients with thyroid eye disease (TED)., Methods: This study retrospectively enrolled 46 patients with active and moderate-to-severe TED (GC-effective group, n = 29; GC-ineffective group, n = 17). Serological lipid metabolism, the orbital MRI-based minimum signal intensity ratio of extraocular muscles (EOM-SIRmin), as well as other clinical parameters before GC therapy were collected and compared between the two groups. Multivariate logistic regression and receiver operating characteristic curve analysis were adopted to identify independent predictable variables and assess their predictive performances., Results: Compared to the GC-ineffective group, the GC-effective group showed lower serum total cholesterol levels (P = 0.006), lower serum low-density lipoprotein cholesterol levels (P = 0.019), higher EOM-SIRmin values (P = 0.005), and shorter disease durations (P = 0.017). Serum total cholesterol and EOM-SIRmin were found to be independent predictors of GC-effective TED through multivariate analysis (odds ratios = 0.253 and 2.036 per 0.1 units, respectively) (both P < 0.05). The integration of serum total cholesterol ≤4.8 mmol/L and EOM-SIRmin ≥ 1.12 had a better predictive efficacy (area under the curve, 0.834) than EOM-SIRmin alone, with a sensitivity of 75.9% and a specificity of 82.4% (P = 0.031)., Conclusion: Serological lipid metabolism, combined with an orbital MRI-derived parameter, was a useful marker for predicting the effectiveness of GCs in patients with active and moderate-to-severe TED.

Objective: We aim to establish the utility of a trial of low-dose systemic glucocorticoid therapy in the assessment of new clinically suspected inflammatory arthritis patients., Methods: We retrospectively identified patients from a private rheumatology practice in Melbourne, Australia between January 1st, 2019, and December 31st, 2021, who presented with clinically suspected inflammatory arthritis and subsequently underwent a trial of low-dose prednisolone (15 mg daily weaned over three weeks in 5 mg increments). We excluded patients with known autoimmune/ inflammatory disorders or concurrent immunosuppression at presentation. We collected basic participant demographic details and clinical details of their presentation, glucocorticoid response, investigations, and treatment., Results: We recruited 177 participants with a median age of 52, and 69.5% were female gender. The median symptom time to presentation was 12 months. Hands were the most affected joint in 63.3% and 85% had bilateral disease. Among the participants, 29.4% had synovitis on clinical review and 75.7% had imaging performed as part of the initial assessment. At presentation, the median CRP was 11 and the median ESR was 16. 79.7% of the cohort experienced significant improvement in their arthritis symptoms from low-dose glucocorticoids and 83.6% of the cohort required long-term immunosuppression for an underlying inflammatory condition. Of those who responded to glucocorticoids, 92.1% were diagnosed with an inflammatory condition. Rheumatoid arthritis was the most common overall diagnosis in 28%., Conclusion: An initial trial of low-dose glucocorticoids in undifferentiated arthritis patients is useful in predicting the diagnosis of inflammatory arthritis. It is also a predictor of further long-term steroid-sparing therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: COVID-19 is a potentially serious new infection first reported in North East Italy in Spring, 2020. Patients with adrenal insufficiency (AI) have a known increased risk of infections that could precipitate to adrenal crisis. Even COVID-19-related psycho-social impact could affect their health, requiring a dynamic adaptation of daily glucocorticoid (GC) therapy. The aim of this study was to evaluate the incidence of COVID-19 infection and self-reported outcomes in AI patients after the first pandemic waves., Methods: It was an open-label, cross-sectional monocentric study on 84 (65 primary, 19 secondary) AI patients resident in Veneto and followed-up in our clinical Endocrine Unit. All patients underwent serological investigation of anti-SARS-CoV2 IgG, answered the purpose-built "ADDICOVID" questionnaire in August, 2020, and were re-contacted to reevaluate COVID-19 infection occurrence in March-April, 2021., Results: All patients resulted negative to the serological test for anti-SARS-CoV2 IgG at the end of the first pandemic wave. After the third wave, COVID-19 infection occurred in 8 patients without the need for hospitalization. Half patients felt an increased risk of COVID-19 infection, significantly associated with increased stress and GC stress dose. Only one patient reported stress-correlated adrenal crisis. The majority of AI workers changed working habits, significantly reducing COVID- 19-related stress., Conclusion: AI patients did not show an increased incidence of COVID-19, but the perception of increased COVID-19 infection risk significantly impacted their psychological well-being, working habits, and GC daily doses. Therapeutic patient education is crucial, especially for AI workers, to prevent and treat situations that could lead to an adrenal crisis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We conducted the current systematic review and meta-analysis to evaluate the efficacy and safety of the combination of glucocorticoid and immunosuppressive agents (IM) compared to glucocorticoid (GC) monotherapy for the treatment of immunoglobulin G4-related disease (IgG4-RD). PubMed, Web of Science, Scopus, OVID, and the Cochrane Library were searched for related articles. Meta-analysis was conducted with outcomes including relapse rate, remission, and adverse events. We calculated the odds ratio (ORs) and 95% confidence interval (CI) with the meta-analysis model. Ten studies involving 906 patients were included in the systematic review; of them, seven studies were included in the meta-analysis. The effect size showed that the GC group was associated with a higher relapse rate (OR = 2.97, 95% CI [1.91, 4.62], p < 0.0001) and a less complete remission rate (OR = 0.27, 95% CI [0.16, 0.47], p < 0.0001) than the combination of GC and IM group. While there was no significant difference between the two compared groups in terms of adverse events (OR = 0.73, 95% CI [0.44, 1.21], p = 0.22). No significant heterogeneity was detected regarding all outcomes (p > 0.1, I2 < 50%). Treatment of IgG4-RD patients with a combination of GC and IM was associated with higher remission rates, lower relapse rates, and comparable safety profiles. Larger RCTs should be conducted and focused on exploring the genetic and geographic differences between different cohorts., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alsalamah et al.)

Introduction: Hypereosinophilic syndrome is a rare clinical condition, and cardiac involvement confers a poor prognosis. Hypereosinophilic myocarditis is a medical emergency and targeted treatment should be started promptly even before a definitive diagnosis could be made., Case Presentation: A 27-year-old female patient is hospitalized for exertional dyspnea, chest pain, and fatigue for the past 2 weeks. She also describes left leg paresthesias. Clinical examination was in normal limits. ECG showed sinus tachycardia, QS pattern in V1-V4, and diffuse flattened T waves. Laboratory tests revealed increased inflammatory markers, hypereosinophilia, elevated cardiac enzymes, high NT-proBNP. Echocardiography revealed LV dysfunction (EF 31%), while cardiac MRI showed diffuse delayed enhancement with predominant subendocardial disposition. The electromyogram was suggestive of left tibial nerve neuropathy. We interpreted the case as eosinophilic myocarditis with an urgent requirement of therapy and initiated high-dose glucocorticoid therapy and the GDMT 4-pillar heart failure treatment. We excluded common infectious, myeloproliferative syndromes, and frequent associated autoimmune diseases. With prednisone, the eosinophil count rapidly normalized and we gradually tapered the dose by 5 mg per week, however continuing with heart failure therapy. At monthly follow-up visits, there was a significant clinical improvement, with normalization of the eosinophilic count, and a near-normalization of myocardial function. The only symptom that persisted was paresthesias linked to left tibial neuropathy., Conclusion: The surprisingly rapid and favorable course of the disease offers a high index of suspicion for a toxic or a reactive transitory etiology, however still unidentified. In our case, the cause of eosinophilia remained unknown, although we managed to narrow down the possible etiologies. A surprisingly good clinical response was obtained with non-specific treatment targeting mainly hyperosinophilic myocarditis., (© 2023 Andreea-Cristina Ivănescu et al., published by Sciendo.)

Introduction: Congenital hemophilia B (HB) is an X-linked bleeding disorder resulting in Factor IX (FIX) deficiency and bleeding of variable severity. There is no cure for HB. Typical management consists of prophylactic intravenous (IV) recombinant or plasma-derived FIX infusions. Etranacogene dezaparvovec-drlb (Hemgenix, AMT-061) is an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant of the human F9 gene with a liver-specific promoter. Etranacogene dezaparvovec-drlb received FDA approval on 22 November 2022 for the treatment of HB in adult patients who use FIX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have experienced repeated, serious spontaneous bleeding episodes., Areas Covered: This drug profile discusses the safety and efficacy of etranacogene dezaparvovec-drlb in patients with HB., Expert Opinion: Etranacogene dezaparvovec-drlb therapy results in stable and sustained expression of near-normal to normal FIX levels in patients with HB regardless of neutralizing antibodies to AAV5 up to a titer of 678. Its use has led to significant reduction in bleeding and FIX prophylaxis. Etranacogene dezaparvovec-drlb was well tolerated; however, 17% of patients required corticosteroid therapy for alanine aminotransferase (ALT) elevation. Etranacogene dezaparvovec-drlb therapy marks the beginning of an exciting era in HB treatment and opens questions regarding treatment longevity and long-term safety.

Objective: To evaluate the impact of prior glucocorticoid (GC) treatment on the diagnostic accuracy of 18 F-FDG PET-CT in giant cell arteritis (GCA)., Methods: Retrospective study of a consecutive cohort of 85 patients with proven GCA who received high-dose GC before PET-CT., Results: Thirty-nine patients previously treated with methylprednisolone (MP) boluses, of whom 37% were PET-CT (uptakes grade 3 or 2) positive. The positivity rate was 80% with MP doses of 125 mg, 33% with 250 or 500 mg, and 0% with doses of 1 g.  If we also classify as positive those cases with a grade 1 uptake (with a circumferencial uptake and smooth linear or long segmental pattern, possibly indicative of "apparently inactive" vasculitis), the positivity rate increases to 62% (100%, 50-60%, and 33% for the different MP doses, respectively). In patients with new-onset GCA treated with high-dose oral GC, PET-CT positivity was 54.5% in patients treated for less than two weeks, 38.5% in those treated for 2 to 4 weeks, and 25% in those treated for 4 to 6 weeks (increasing to 91%, 77%, and 50%, respectively, if we include cases with grade 1 uptake and these characteristics). In patients with relapsing/refractory GCA, or who developed GCA having a prior history of PMR, PET-CT positivity reached 54% despite long-term treatment with low-to-moderate doses of GC (68% including cases with a grade 1 uptake)., Conclusion: A late 18 F-FDG PET-CT (beyond the first 10 days of treatment) can also be informative in a considerable percentage of cases., Competing Interests: Declaration of Competing Interests The authors declare that there are no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: A comparison of topical glucocorticoids with CO 2 fractional laser treatment was conducted to investigate the differences in the efficacy of non-neoplastic vulvar epithelial lesion treatments in different pathological types and to provide a scientific basis for the management of these disorders. This paper was to study the difference of curative effect of different pathological types of non-tumor vulvar epithelial lesions and provide scientific basis for the treatment of these diseases., Methods: From November 2016 to July 2018, 178 cases of vulvar lichen simplex chronicus (LSC) or lichen sclerosus were confirmed with vulvar biopsy at our institute. Finally, 160 patients were enrolled in this trial. The patients were divided into 2 groups: a group treated with topical hormone and a group treated with CO 2 lattice laser therapies. There were 80 cases in each group, including 40 with LSC and 40 with lichen sclerosus. Patients applied 1 gram of progesterone cream and betamethasone cream to the affected area in the morning and evening, respectively, once a day for 3 months. The efficacy was evaluated with the Patient Global Impression of Change (PGI-C) subjective symptom improvement scale and clinical efficacy evaluation scale. The formula was applied to calculate the curative effect index., Results: The PGI-C scores at 1, 3, and 6 months of treatment showed that the laser treatment group had remarkably superior outcomes to the glucocorticoid treatment group. The clinical efficacy score scale at 3- and 6-month treatments indicated a significantly greater curative effect in the laser than in the glucocorticoid treatment (P=0.006 and P=0.002 respectively). In the glucocorticoid group, the clinical effects of different pathological subtypes were significantly different following the 1- and 3-month treatments. The efficacy of treatment for LSC was better than that for lichen sclerosus. Following the 3- and 6-month treatments, the clinical effect for LSC was better than that of lichen sclerosus (3 months: 95% vs . 75%; 6 months: and 95% vs . 70%)., Conclusions: Ultrapulse CO 2 lattice laser was more effective than was glucocorticoid therapy in the treatment of vulvar epithelial non-tumor-like lesions., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-677/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: Lichen-like lesions with degeneration and pigmentation alterations can be divided into the following 2 types: (I) chronic simple lichen; and (II) sclerosing lichen. The etiology of the disease is unknown. This study sought to examine the therapeutic effects of electrophysiological smooth-muscle electrical stimulation in the treatment of lichen-like lesions of the vulva., Methods: A total of 80 outpatients, who had been confirmed to have vulvar lichen-like lesions by vulvar biopsy at our hospital from November 2016 to March 2018, were prospectively included in this study. The patients received electrophysiology or glucocorticoid therapy. After completing a treatment cycle according to the clinical treatment routine, the outpatients were monitored at 1-, 3- and 6-month intervals. Patients used an improvement scale (i.e., the patient global impression of change scale) to score their subjective perceptions and subjective symptoms. The clinical curative effect scale was used to calculate the curative effect index and grade the curative effect., Results: After 1 month of treatment, the active enhancement of simple lichen in the electrophysiological treatment group and glucocorticoid treatment group improved, while the active enhancement of simple lichen in the electrophysiological treatment group improved after 3 months of treatment. After 6 months of treatment, the subjective improvement score of the electrophysiological treatment group was better than that of lichen sclerosus. After 3 months of treatment, the effective rate of the electrophysiological therapy group was better than that of the glucocorticoid therapy group. After 6 months of treatment in the electrophysiological treatment group, the efficacy of simple lichen is also better than that of sclerotic lichen., Conclusions: Conventional hormone therapy is easier for patients to accept because of its convenience and low costs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-224/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background Although the incidence of post-COVID-19 organizing pneumonia (OP) is low, the mortality and morbidity in select patients appear to be high. Anticipating specific populations who may be at higher risk and initiating treatment earlier could reduce mortality. Research question Does treatment with high dose, standard dose, or no glucocorticoids for COVID-19 infection impact the incidence and clinical outcome in COVID-19-induced OP? Study design and methods This was a single-center, retrospective, observational cohort study conducted from 03/01/2020 to 06/30/2021 in hospitalized patients over the age of 18 with confirmed COVID-19 infection and computed tomography (CT) scan evidence of OP. Institutional review board (IRB) approval was obtained from the institution (STUDY00002241). Patients' demographics and oxygen requirements at the time of diagnosis, at the time of discharge, and at one, three, six, 10, and 12 months post-discharge were obtained. The dose, duration, and choice of glucocorticoid therapy were recorded for each subject, as well as oxygen requirements during hospitalization. Despite radiological evidence of OP, patients on minimal supplemental oxygen requirements did not receive high-dose or long-duration glucocorticoid therapy. Results A total of 881 patients were admitted with COVID-19, of which 42 met the study criteria. Three patients underwent a lung biopsy to confirm the diagnosis of organizing pneumonia. All other patients were diagnosed based on CT imaging and clinical presentation. Of the patients, 17% did not receive any steroid treatment, while 36% received dexamethasone and 43% received prednisone. The most common oxygen requirement at the time of discharge for steroid-treated patients was nasal cannula (55%) and room air (29%). The incidence of OP in this patient population was 0.05 with a mortality rate of 14%. Interpretation and relevance The incidence of post-COVID-19 OP appears to be lower than anticipated. Steroids for patients on lower supplemental oxygen requirements were discontinued although they had radiological evidence of OP. Patients who were on higher supplemental oxygen requirements at 10 days were continued on steroids regardless of imaging. The decision to continue steroids should be based on individual patient characteristics such as oxygen requirements. In the future, larger multicenter cohort studies would help understand further treatment of post-COVID-19-associated OP. Anticipating specific populations who may be at higher risk and starting treatment earlier could help reduce mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Yazdi et al.)

Background: We aimed to determine whether the methylation status of thymosin β4 (Tβ4) promoter reflects the severity of acute-on-chronic hepatitis B liver failure (ACHBLF) and whether glucocorticoids affect this status., Methods: Fifty-six patients with ACHBLF, 45 with chronic hepatitis B (CHB) and 32 healthy controls (HCs), were retrospectively enrolled. Methylation-specific PCR and real-time PCR were used to detect Tβ4 methylation frequency and mRNA level. The expression of Tβ4 was measured before and after glucocorticoid treatment in patients with ACHBLF. Clinical and laboratory parameters were obtained., Results: Tβ4 mRNA expression of patients with ACHBLF was lower than in patients with CHB or HCs, but the methylation frequency was higher. Tβ4 promoter methylation frequency was correlated with serum total bilirubin, prothrombin activity and model for end-stage liver disease score. Moreover, Tβ4 promoter methylation frequency decreased and demethylation occurred during glucocorticoid therapy. After glucocorticoid therapy, Tβ4 mRNA expression and liver function were better in patients with low levels of methylation than in those with higher levels. After 90 d, the survival of patients with low levels of methylation was significantly higher than those with high levels., Conclusions: Patients with ACHBLF who have low levels of Tβ4 methylation may show a more favorable response to glucocorticoid treatment., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Patients with multiple sclerosis (MS) have many potential factors (spasticity, immobilization, glucocorticoids use) for the deterioration of body composition. Aim: To assess the nutritional status (by classical anthropometry and by bioelectrical impedance analysis (BIA)) in MS patients and to correlate it with clinical state, MS duration time and the presence of glucocorticoid therapy in anamnesis (ever used). Methods: Anthropometrical (BMI and waist and hip circumferences, waist-to-height ratio (W/HtR), and waist-to-hip ratio (WHR)) and body composition (BIA) data were evaluated in 176 patients with MS. Fat mass (FM), and fat-free mass (FFM) were expressed as kilograms (kg), percentage (%) and indexes (FMI: fat mass index, FFMI: fat-free mass index) expressed in kg/m2. The median Expanded Disability Status Scale score was 4.5. Patients were then divided according to EDSS score as mild (EDSS 1.0−4.0) or moderate (EDSS 4.5−6.5) disability subgroup. Results: Waist c., WHtR, WHR, and FM% were significantly higher in the moderate MS group (p < 0.01; p < 0.001; p < 0.001; and p < 0.05, respectively). Whilst, FFM% was significantly lower (p < 0.05). BMI did not correlate significantly with any disability status score and MS time. Significant correlations were observed between EDSS, ΔEDSS and MS time and Waist c., WHtR, WHR, FM% and FFM%. WHtR had the strongest significance (p < 0.0001 vs. EDSS; p < 0.0001 vs. ΔEDSS; and p < 0.01 vs. MS time, respectively). After the adjustment to the MS time, only FM% was no longer significantly related to both EDSS and ΔEDSS. MS duration time, EDSS, ΔEDSS, WHtR, FM(kg), FM%, and FMI were significantly higher in the patients with a positive history of glucocorticoid therapy (all p < 0.05). Whilst, FFM% was significantly lower in MS patients treated with glucocorticoids (p < 0.01). Conclusions: Greater disability in MS patients is strongly related to lower fat-free mass and higher fat mass, especially with the abdominal distribution, irrespective of the duration time of the disease. Oral glucocorticoid therapy seems to have a negative impact on the body composition of MS patients. However, further prospective multifactorial studies in this field have to be done. For the proper assessment of nutritional status in MS patients, Waist c., WHtR, WHR, or body composition parameters seem to be of greater use than BMI.

Purpose: Ocular hypertension (OHT) is an important clinical feature of thyroid-associated orbitopathy (TAO).While the prevalence and outcome of OHT in TAO remains unclear. This study investigates this in moderate-severe active TAO., Methods: Sixty-eight patients with active moderate-severe TAO were recruited, 49 of whom were treated with 12-week GC therapy.The clinical and biochemical parameters were collected.Treatment outcomes were evaluated after GC therapy., Results: The prevalence of OHT was 44.85% in moderate-severe active TAO patients,including 81.97% of mild hypertension, 13.11% of moderate hypertension and 4.92% of severe hypertension. Clinical and biochemical parameters had no significant difference between OHT patients and non-OHT patients,such as age, sex distributions, smoking status, the kind and the duration of thyroid disease,the duration of eye symptoms and the level of FT3,FT4,TSH, TR-Ab, and Tpo-Ab, Tg-Ab(all P > 0.05). After GC therapy,the intraocular pressure(IOP) in OHT eyes decreased significantly (P < 0.05), while IOP in non-OHT eyes remained unchanged (P > 0.05).There was no significant difference in CAS and the effective rate of GC therapy between OHT eyes and non-OHT eyes (P > 0.05)., Conclusion: In moderate-severe active TAO, the prevalence of OHT was 44.85%, most of which were mild hypertension.OHT was relieved by GC therapy,which had no effect on the efficacy of GC therapy.Our results will enhance physicians' confidence in GC therapy., (© 2022. The Author(s).)

Since the introduction of glucocorticoid (GC) replacement therapy, congenital adrenal hyperplasia (CAH) is no longer a fatal disease. The development of neonatal screening programs and the amelioration of GC treatment strategies have improved significantly life expectancy in CAH patients. Thanks to these achievements, CAH patients are now in their adulthood, but an increased incidence of cardiovascular risk factors has been reported compared to general population in this stage of life. The aim of CAH treatment is to both prevent adrenal insufficiency and suppress androgen excess; in this delicate balance, under- as well as overtreatment might be equally harmful to long-term cardiovascular health. This work examines the prevalence of metabolic features and cardiovascular events, their correlation with hormone levels and GC replacement regimen in CAH patients and focuses on precocious markers to early detect patients at higher risk and new potential treatment approaches., 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 © 2022 Barbot, Mazzeo, Lazzara, Ceccato and Scaroni.)

We describe a retrospective cohort, 156 patients with chronic lymphocytic leukemia (CLL) diagnosed with COVID-19, analyze factors associated with a severe disease course and the effects of various treatment regimens. Anti-SARS-CoV-2 IgG and IgM levels are significantly lower. Patients with CLL are more likely to have a severe course of COVID-19, with IL-6 levels acting as a consistent biomarker of disease severity. Ten patients had recurrent episodes, fatality rate of 20%. Overall survival did not differ between patients receiving ibrutinib monotherapy and anti-CD20 antibodies ± chemotherapy. It seems that the immunodeficiency inherent to CLL influences outcomes to a larger degree than does the treatment. Glucocorticoids are not associated with significant OS improvement whereas anti-cytokine compounds usage seemed to be beneficial in patients with mild pulmonary involvement. Our data attest to the necessity of reorganizing health care for patients with CLL. Early administration of effective antiviral compounds and tailored vaccination protocols are warranted.

Methylprednisolone acetate (MPA) is often prescribed to cats despite being recognized eventually as diabetogenic. To assess MPA-related insulin resistance and evaluate the efficacy of metformin or an obesity and diabetes mellitus (O&D) adjuvant diet as protective factors, a randomized clinical trial was conducted with 28 owned cats undergoing glucocorticoid therapy. A single MPA dose of 20 mg intramuscularly was administered to each cat. Controls (n = 10) received only MPA. In the diet group (n = 9), replacement of their habitual diet by ad-libitum feeding of a feline commercial O&D diet (Equilíbrio O&D, Total Alimentos ADM) was made. In the metformin group (n = 9), metformin chlorhydrate 25mg/cat PO/q24h was administered for 30 days. All patients were clinically evaluated at baseline (T0), day 15 (T15), and day 30 (T30) and blood draw for complete blood count, serum biochemistry, and determination of insulin concentrations. Fasting Insulin Sensitivity Index (SI), Amended Insulin to Glucose Ratio (AIGR), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and Homeostatic Model Assessment of beta-cell function (HOMA-B) were calculated based on fasting glycemia and insulinemia. All groups showed significantly higher levels (P < .05) of neutrophils, albumin, glucose, cholesterol, triglycerides, and serum insulin at T15. Patients in the metformin group showed also higher SI, AIGR, and HOMA-IR results at T15. Also, at T15, reduced levels (P < .05) of eosinophils, lymphocytes, and creatinine were documented in all groups. An MPA single dose induced changes in insulin sensitivity in cats; however, neither metformin nor O&D feeding used in this study was effective as protective factors against MPA-related insulin resistance., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Context: Current evidence on determinants of quality of life (QoL) in patients with adrenal insufficiency (AI) is limited., Objective: This work aimed to identify the determinants of QoL in different subtypes of AI., Methods: This multicenter cross-sectional survey study was conducted using a patient-centered questionnaire, the Short Form-36., Results: Of 529 participants, 223 (42.2%) had primary AI, 190 (35.9%) had secondary AI, and 116 (21.9%) had glucocorticoid-induced AI. Median age was 58 years (interquartile range: 43-68 years) and 342 (64.8%) were women. In multivariable analyses, patients were more likely to report worse physical scores if they were women (odds ratio [OR]: 3.3; 95% CI, 1.8-6.0), had secondary AI or glucocorticoid-induced AI (OR: 2.5; 95% CI, 1.4-4.3), had shorter duration of AI (OR: 2.0; 95% CI, 1.1-3.6), were treated with more than 25 mg hydrocortisone equivalent daily (OR: 2.3; 95% CI, 1.2-4.6), had more comorbidities related to glucocorticoid excess (OR: 2.3; 95% CI, 1.3-4.0), reported a higher financial burden from AI (OR: 2.1; 95% CI, 1.3-3.6), and reported difficulties with AI management (OR: 2.5; 95% CI, 1.2-5.2). Women (OR: 2.1; 95% CI, 1.08-4.0), shorter duration of AI (OR: 2.4; 95% CI, 1.4-4.3), higher financial burden (OR: 2.3; 95% CI, 1.3-4.0), difficulties with AI management (OR: 2.6; 95% CI, 1.4-4.9), and lack of family support (OR: 9.1; 95% CI, 2.3-33.3) were associated with worse mental component scores., Conclusion: In patients with AI, QoL could be improved by addressing certain determinants, such as avoiding GC overreplacement, providing in-depth education on self-management, offering more comprehensive insurance coverage, and ensuring better family support., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic syndrome (NS) in paediatric patients. We hypothesized that lipoprotein particle distributions moved toward less atherogenic profile and that cholesterol homeostasis was achieved., Materials and Methods: Thirty-three children, 2 to 9 years old with NS were recruited. Blood sampling took place both in the acute phase and during remission. Serum low-density lipoprotein particles (LDL) and high-density lipoprotein particles (HDL) were separated using non-denaturing polyacrylamide gradient gel (3-31%) electrophoresis. Serum non-cholesterols sterols (NCSs), desmosterol, lathosterol, 7-dehydrocholesterol (7-DHC), campesterol and β-sitosterol were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)., Results: All patients had desirable serum HDL cholesterol concentrations during remission. The dominant lipoprotein diameters and LDL subclass distribution did not change significantly during follow-up. In contrast, HDL lipoprotein particle distribution shifted towards larger particles. The absolute concentration of desmosterol was significantly lower during remission (P = 0.023). β-sitosterol concentration markedly increased during remission (P = 0.005). Desmosterol/β-sitosterol (P < 0.001) and 7-DHC/β-sitosterol (P = 0.005) ratios significantly declined during disease remission., Conclusions: Favourable changes in the serum lipid profiles, HDL particle subclass distribution and cholesterol metabolism in paediatric patients with NS during remission took place. For the first time, we found that cholesterol homeostasis changed in favour of increased cholesterol absorption during disease remission. Nevertheless, complete cholesterol homeostasis was not achieved during disease remission., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Introduction: Serum cortisol levels within the first days after pituitary surgery have been shown to be a predictor of post-surgical adrenal insufficiency. However, the indication of empirical glucocorticoids to avoid this complication remains controversial. The objective is to assess the role of cortisol in the early postoperative period as a predictor of long-term corticotropic function according to the pituitary perisurgical protocol with corticosteroid replacement followed in our center., Methods: One hundred eighteen patients who underwent surgery in a single center between December 2012 and January 2020 for a pituitary adenoma were included. Of these, 54 patients with previous adrenal insufficiency (AI), Cushing's disease, or tumors that required treatment with high-dose glucocorticoids (GC) were excluded. A treatment protocol with glucocorticoids was established, consisting of its empirical administration at rapidly decreasing doses, and serum cortisol was determined on the third day after surgery. Subsequent adrenal status was assessed through follow-up biochemical and clinical evaluations., Results: Out of the 64 patients treated, there were 56 macroadenomas and 8 microadenomas. The incidence of adrenal insufficiency after pituitary surgery was 4.7%. The optimal cut-off value that predicted an adequate corticotropic reserve, taking into account the best relationship of specificity and sensitivity, was ≥4.1 μg/dl for serum cortisol on the third day (sensitivity 95.1%, specificity 100%)., Conclusion: Serum cortisol on the third day predicts the development of adrenal insufficiency. We suggest a cortisol cut-off point of ≥4.1 μg/dl on postoperative on the third day after surgery as a predictor of the adrenal reserve in the long-term., (Copyright © 2022. Published by Elsevier España, S.L.U.)

The results achieved by the medical service of the Armed Forces of the Russian Federation to overcome the new coronavirus infection are presented. The high efficiency of the established unified system of biological safety and strict ranking of the priorities of anti-epidemic measures is shown. The experience of organizing traveling medical and nursing teams, as well as temporary military medical units on the territory of Russia, as well as in foreign countries, is demonstrated. Among the priority scientific results of military doctors, especially noteworthy is the study of the world's first COVID-19 vaccine Sputnik V, its immunogenicity, the effectiveness of its use in previously ill patients and revaccination, as well as the use of immune plasma from those who have been ill and vaccinated. By the examples of organized military groups and the general population, the features of the formation of herd immunity have been studied. Military doctors were the first in the country to show the effectiveness of hormone therapy in the treatment of coronavirus infection and to study its effects. They carried out ultrastructural studies of the life cycle of the virus. It is shown that the system of comprehensive measures implemented by military medicine determined a lower incidence of new coronavirus infection among the personnel of the Ministry of Defense of Russia and a lower mortality among the military., Competing Interests: The authors declare that they have no conflicts of interest., (© Pleiades Publishing, Ltd. 2022, ISSN 1019-3316, Herald of the Russian Academy of Sciences, 2022, Vol. 92, No. 4, pp. 437–444. © Pleiades Publishing, Ltd., 2022.Russian Text © The Author(s), 2022, published in Vestnik Rossiiskoi Akademii Nauk, 2022, Vol. 92, No. 7, pp. 699–706.)

Objective: Previous study suggested IgG4 levels were associated with the development of Graves' ophthalmopathy (GO). The aims of the present study were to investigate the role of IgG4 levels in glucocorticoid (GC) treatment in GO patients., Design: 69 GO patients were enrolled. Serum thyroid hormones, thyroid antibodies, IgG, IgG4, ophthalmological examinations and orbital MRI were performed. Furthermore, the clinical outcomes (a composite response endpoint including the clinical activity score (CAS), proptosis, vision, intraocular pressure, diplopia and lid width) after high-dose intravenous GC treatment in 32 active moderate-to-severe GO patients were compared., Patients: 69 consecutive patients with GO were asked to participate in the study. 32 of 69 GO patients were treated with high-dose intravenous GCs., Measurements: Measurement of serum IgG and IgG4, serum thyroid hormones and thyroid autoantibodies. An overall ophthalmic assessment was performed pretherapy (week 0) and post-therapy (week 12)., Results: 33.3% of GO patients (23/69) had elevated IgG4 levels. IgG4 levels were positively correlated with the severity and activity of GO. After GC therapy, IgG4, IgG4/IgG, vision and CAS were significantly improved in GO patients. Patients with high IgG4 levels had a significantly reduced extraocular muscle area (EOMs) and better clinical outcomes than patients with normal IgG4 levels., Conclusions: Our results suggest a possible subgroup of elevated IgG4 GO patients, with more severe ophthalmopathy and better response to GCs treatment compare with normal IgG4 GO patients., (© 2021 John Wiley & Sons Ltd.)

Kawasaki disease (KD) is a common systemic vasculitis in childhood that can result in damage to multiple body systems. However, prominent gallbladder (GB) enlargement in the acute stage is especially rare. A 5-year-old boy was admitted to the hospital with an 8-day history of a cervical mass, 7-day history of fever, and 5-day history of abdominal pain and rash. The child was diagnosed with KD. After treatment with high-dose intravenous immunoglobulin therapy (2 g/kg), all clinical manifestations were relieved except the abdominal pain. Enhanced computed tomography showed distinct enlargement of the GB, and a congenital choledochal cyst was strongly suspected. After high-dose glucocorticoid treatment, his obviously enlarged GB returned to normal size in the subacute phase. No abnormality was found during 2 years of follow-up. Prominent GB enlargement may emerge in the acute stage of KD. The enlarged GB can return to normal size within the subacute stage by standard treatment for KD. Proper diagnosis, thorough differential diagnosis, and active anti-inflammatory treatment of KD are crucial to avoid surgery.

Purpose: Presentation of the role of the dopaminergic system and microRNAs in the development of depression after glucocorticoids (GCs) therapy., Views: GCs are steroid hormones secreted by the adrenal glands, and their synthesis is regulated by the hypothalamic-pituitary- adrenal (HPA) axis. The secretion of GCs (cortisol in humans and corticosterone in rodents) is dependent directly on corticotropin, secreted from the pituitary gland and indirectly on the corticotropin-releasing factor, a hormone released from the paraventricular nuclei of the hypothalamus. Prolonged treatment with GCs disrupts the functions of the HPA axis, impairs the dopaminergic system, suppresses hippocampal neurogenesis and sensitizes the amygdala, leading to an increased susceptibility to depression. This is an important problem because GCs are commonly prescribed for a broad range of medical conditions, including inflammatory and autoimmune disorders. The action of GCs may be at least partially regulated by epigenetic mechanisms (microRNAs), in addition to which microRNAs modulate GCs production and cellular response to GCs., Conclusions: The administration of GCs may lead to changes in dopaminergic system activity (e.g. D2 receptors activity), which significantly contribute to the predisposition to depression. Additionally, GCs therapy may cause changes in the activity of micro-RNAs (e.g. miR-124), which exacerbates symptoms of depression. Searching for specific changes in microRNA expression will provide clinically practical and easily applicable biomarkers of depression risk and new forms of pharmacotherapy in GC-induced depression., Competing Interests: Absent./Nie występuje., (Copyright © 2021 Institute of Psychiatry and Neurology.)

Context: The COVID-19 pandemic has impacted healthcare environment., Objective: To determine the impact of the pandemic on self-reported outcomes in patients with adrenal insufficiency (AI)., Design and Setting: Prospective longitudinal survey study at 2 tertiary centers., Participants: Patients with AI., Intervention: Patient-centered questionnaire., Main Outcome Measures: Depression Anxiety Stress Scales-21, Short Form-36, and AI self-management., Results: Of 342 patients, 157 (46%) had primary AI, 109 (32%) had secondary AI, and 76 (22%) had glucocorticoid-induced AI. When compared to prepandemic, daily glucocorticoid dose and number of adrenal crises did not change. However, patients reported a higher financial impact from AI (34% vs 23%, P = 0.006) and difficulty accessing medical care (31% vs 7%, P < 0.0001) during the pandemic. A third of patients reported difficulty managing AI during the pandemic. After adjusting for duration and subtypes of AI, younger patients [odds ratio (OR) 2.3, CI 95% 1.3-4.1], women (OR 3.7, CI 95% 1.9-7.1), poor healthcare access(OR 4.2, CI 95% 2.3-7.7), lack of good insurance support (OR 2.8, CI 95% 1.3-5.9), and those with a higher financial impact (OR 2.3, CI 95% 1.3-4.3) reported greater difficulties managing AI. Patients were more likely to report a higher anxiety score (≥8) if they found managing AI challenging during the pandemic (OR 3.0, CI 95% 1.3-6.9), and had lower Physical Component Summary (OR 4.9, CI 95% 2.2-11.0) and Mental Component Summary (OR 4.1, CI 95% 1.8-9.5) scores prior to the pandemic., Conclusions: A third of patients with AI reported difficulties with management of AI during the pandemic, particularly in younger patients, women, and those with poor healthcare access., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The indications for maintenance glucocorticoid therapy (MGT) and its duration after initial remission of type 1 autoimmune pancreatitis (AIP) remain controversial. In contrast to the Japanese treatment protocol, the Mayo protocol does not recommend MGT after initial remission. This study aimed to evaluate the relapse rate in patients with type 1 AIP according to the duration of glucocorticoid therapy., Methods: We conducted a systematic literature review up until November 30, 2020, and identified 40 studies reporting AIP relapse rates. The pooled relapse rates were compared between groups according to the protocol and duration of glucocorticoids (routine vs. no MGT; glucocorticoids ≤6 months vs. 6-12 months vs. 12-36 months vs. ≥ 36 months). The pooled rates of adverse events related to glucocorticoids were also evaluated., Results: Meta-analysis indicated calculated pooled relapse rates of 46.6% (95% confidence interval (CI), 38.9-54.3%) with glucocorticoids for ≤ 6 months, 44.3% (95% CI, 38.8-49.8%) for 6-12 months, 34.1% (95% CI, 28.6-39.7%) for 12-36 months, and 27.0% (95% CI, 23.4-30.6%) for ≥ 36 months. The rate of relapse was also significantly lower in patients with routine-use protocol of MGT (31.2%; 95% CI, 27.5-34.8%) than in patients with no MGT protocol (44.1%; 95% CI, 35.8-52.4%). Adverse events were comparable between groups., Conclusions: The rate of relapse tended to decrease with extended durations of glucocorticoid therapy up to 36 months. Clinicians may decide the duration of glucocorticoids according to patient condition, including comorbidities and risk of relapse., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Context: Current evidence on determinants of adverse health outcomes in patients with adrenal insufficiency (AI) is scarce, especially in regards to AI subtypes., Objective: To determine predictors of adverse outcomes in different subtypes of AI., Design and Setting: Cross-sectional survey study at 2 tertiary centers., Participants: A total of 696 patients with AI: primary AI (PAI, 42%), secondary AI (SAI, 32%), and glucocorticoid-induced AI (GIAI, 26%)., Intervention: Patient-centered questionnaire., Main Outcome Measures: Patients' knowledge, self-management of AI, self-perceived health, and adverse outcomes., Results: The incidence rate of adrenal crisis was 24/100 patient-years with 44% experiencing at least 1 adrenal crisis since diagnosis (59% in PAI vs 31% in SAI vs 37% in GIAI, P < .0001). All patients described high degrees of discomfort with self-management and receiving prompt treatment. Patients with PAI were most likely to develop adrenal crises (adjusted OR 2.8, 95% CI 1.9-4.0) despite reporting better self-perceived health (adjusted OR 3.3, 95% CI 2.1-5.3), understanding of their diagnosis (89% vs 74-81% in other subtypes, P = .002), higher comfort with self-management (62% vs 52-61% in other sub types, P = .005), and higher likelihood to receive prompt treatment for adrenal crises in the emergency department (42% vs 19-30% in other subtypes, P < .0001)., Conclusions: Patients with AI reported high degrees of discomfort with self-management and treatment delays when presenting with adrenal crises. Despite better self-perceived health and understanding of diagnosis, patients with PAI experienced the highest frequency of adrenal crises. A multidimensional educational effort is needed for patients and providers to improve the outcomes of all subtypes of AI., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12 th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs . 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs . 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects., (Copyright © 2020, Spandidos Publications.)