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Abstract Corticosteroid is essential in the treatment regimen for connective tissue disease (CTD); however, its long-term use poses significant risks, including pulmonary infections. The relationship between cumulative corticosteroid doses and adverse pneumonia outcomes requires further investigation. This study aimed to explore the association between cumulative methylprednisolone dosages (CMD) and pneumonia mortality risks among CTD patients. We conducted a retrospective analysis of data from CTD patients treated with intravenous or oral corticosteroids across six academic hospitals over approximately five years in China. We evaluated follow-up outcomes at 30 and 90 days after the onset of pneumonia. Piecewise linear regression, Cox regression analysis, and survival analysis were employed to investigate the relationship between CMD and 30-day and 90-day mortality risks. Among 335 CTD patients with pneumonia, the mean CMD was 12 g. The 30-day and 90-day mortality rates were 25.07% and 29.55%, respectively. After adjusting for potential confounders, smooth curve fitting analysis revealed a specific nonlinear relationship between CMD and 30-day and 90-day mortality risks. Cox regression analysis indicated that the lowest pneumonia mortality risk occurred when CMD ranged from 11 to 24 g (30-day adjusted hazard ratio (aHR) 0.33, 95% CI 0.14–0.77; 90-day aHR 0.37, 95% CI 0.17–0.81). Patients in the 11–24 g CMD group demonstrated significantly lower cumulative hazard and death rates compared to both the low CMD ( 24 g) groups (P

Background: Glucocorticoids are the first-line pharmacotherapy for amiodarone-induced destructive thyroiditis. Despite the availability of clinical guidelines, there is no unified approach to patient management (indications for prescription, starting dose, duration of therapy and withdrawal algorithm). The issues of dose-dependent effect of glucocorticoids, verification of factor of delayed treatment response, prediction of severity and duration of thyrotoxicosis remain unresolved. Aim: To evaluate the efficacy of various regimens of tablet glucocorticoids in patients with type 2 amiodarone-induced thyrotoxicosis. Methods: This was a prospective randomized open-label comparative controlled trial of the efficacy of two starting doses of prednisolone 30 mg (n = 22) and 60 (n = 22) mg daily. The study groups were comparable for gender (men to women ratio 2:1), age, anthropometric and main clinical and laboratory characteristics. After euthyroidism has been achieved, thyroid function was assessed twice at 1 and 2 months during the dose reduction and at 1, 3, 6, 9, and 12 months after prednisolone withdrawal. The follow up was 15 to 24 months. The efficacy of therapy was evaluated by the time to euthyroidism, thyrotoxicosis duration, rate of recurrent waves of destruction and relapses. We looked for predictors of delayed treatment response and severe and prolonged thyrotoxicosis. Results: There were no significant differences in the time to euthyroidism (Mantel-Cox log rank test 0.859), duration of thyrotoxicosis (Mantel-Cox log rank test 0.813), rate of recurrent waves of destruction (0.721) and relapses (0.464). Within 30 days of therapy, remission was obtained in 11/22 (50.0%) patients in active control group (prednisolone 30 mg) and in 12/22 (54.5%) patients in the 60 mg group. Delayed response ( 60 days) was defined by recurrent waves of destruction (RR = 34.7, 95% CI: 3.7–321.8; R² = 0.430; p = 0.002). High risk of severe thyrotoxicosis was predicted by the age ≤ 54 years (AUC 0.749 ± 0.095, 95% CI: 0.562–0.936; p = 0.038; sensitivity 71.4%, specificity 62.2%). The duration of thyrotoxicosis was associated with body mass index (B = -7.4, R = 0.481, R² = 0.0231; p = 0.024) and cumulative amiodarone dose (B = 0.4, R = 0.472, R² = 0.223; p = 0.026). A combination of adverse events (hyperglycemia, infection, proximal myopathy, change in appearance, hematomas) and their severity were more frequent in the patients who had received the 60 mg prednisolone starting dose (p = 0.014). Conclusion: Compared to lower doses, the use of high doses of glucocorticoids is associated with a greater severity of side effects and does not ensure any significant acceleration of thyrotoxicosis remission. The potential factors of unfavorable clinical course of type 2 amiodarone-induced thyrotoxicosis are age, body mass index, and cumulative dose of amiodarone.

Graves' disease (GD) is an autoimmune disease that affects the thyroid and the eyes. Graves' ophthalmopathy (GO), an autoimmune disease, usually appears 18 months after GD diagnosis. Clinical activity and disease severity determine the strategy, with steroid treatment recommended during active disease progression.

Patients with immune-mediated inflammatory rheumatic diseases (IIRD) are more likely to develop herpes zoster (HZ) than individuals in the general population. Live attenuated vaccines and inactivated recombinant vaccines with adjuvant are available to prevent the disease and its complications. Live attenuated vaccine can be used in patients with IIRD if certain conditions are met, although these cannot always be fulfilled. The advantage of the inactivated recombinant adjuvant vaccine is that it can be used against a background of anti-rheumatic therapy. The review analyzes foreign studies on the safety, immunogenicity and efficacy of recombinant adjuvant vaccine against HZ in patients with IIRD.

The treatment of juvenile-onset systemic lupus erythematosus (jSLE) is a complex task in view of the diversity of clinical manifestations and the course of the disease as well as the high risk of organ damage. The need to create separate therapeutic principles for jSLE is justified by the greater intensification of therapy due to both the doses used and the combination of a larger number of different drugs in a patient. However, the basis for the treatment of jSLE today is mainly the extrapolation of data obtained in studies with adult patients. The review reflects modern ideas about the spectrum of drugs used in jSLE, with particular emphasis on efficacy, safety and timing of therapy as well as possible optimization options.

Abstract Background The hypothalamic–pituitary–adrenal (HPA) and -gonadal (HPG) axes are two major pathways that connect the neural and endocrine systems in vertebrates. Factors such as prenatal stress and maternal exposure to exogenous steroids have been shown to affect these pathways during fetal development. Another less studied factor is the transfer of hormones across fetuses in multifetal pregnancies. This form of transfer has been shown to influence the morphology, anatomy, physiology, and behavior of the offspring in litter-bearing mammals, an influence termed the intrauterine position (IUP) effect. In this study, we sought to delineate how the IUP effects HPA and HPG brain receptors, peptides, and enzymes (hereafter components) in utero and how these influences may differ between males and females. Methods We utilized the unconventional model of culled free-ranging nutria (Myocastor coypus), with its large natural variation. We collected brain tissues from nutria fetuses and quantified the expression of key HPA and HPG components in three brain regions: prefrontal cortex, hypothalamus, and striatum. Results We found an interaction between sex and IUP in the mineralocorticoid receptor (MR), gonadotropin-releasing hormone receptor (GNRHR), androgen receptor (AR), and estrogen receptor alpha (ESR1). IUP was significant in both gonadotropin-releasing hormone (GnRH) and its receptor GNRHR, but in different ways. In the hypothalamus, fetuses adjacent to same-sex neighbors had higher expression of GnRH than fetuses neighboring the opposite sex. Conversely, in the cortex, GNRHR exhibited the inverse pattern, and fetuses that were neighboring the opposite sex had higher expression levels than those neighboring the same sex. Regardless of IUP, in most components that showed significant sex differences, female fetuses had higher mRNA expression levels than male fetuses. We also found that HPA and HPG components were highly related in the early stages of gestation, and that there was an interaction between sex and developmental stage. In the early stages of pregnancy, female component expression levels were more correlated than males’, but in the last trimester of pregnancy, male components were more related to each other than female’s. Conclusions This study suggests that there are sexually different mechanisms to regulate the HPA and HPG axes during fetal development. Higher mRNA expression levels of endocrine axes components may be a mechanism to help females cope with prolonged androgen exposure over a long gestational period. Additionally, these findings suggest different coordination requirements of male and female endocrine axes during stages of fetal development.

Objective To investigate the application of mycophenolate mofetil (MMF) in oral mucosal pemphigoid and provide a clinical reference. Methods One case of glucocorticoids combined with MMF in the treatment of oral mucosal pemphigoid was reported, and the clinical application of MMF in oral mucosa-related bullous diseases was discussed. Results One patient with a clinical diagnosis of “oral mucosal pemphigoid” was treated with methylprednisolone (36 mg, qd, morning dose) or combined hydroxychloroquine sulfate (0.1 g/time, bid) and thalidomide capsules (50 mg, qd, bedtime) and other drugs. The patient’s disease was slowly controlled but prone to recurrence. The treatment regimen was immediately adjusted, i.e., methylprednisolone (36 mg, qd, morning dose) was combined with MMF (0.5 g/time, bid) for 2 weeks, which resulted in ideal lesion healing control. After 8 weeks of methylprednisolone combined with MMF, the dose of methylprednisolone was gradually reduced to 12 mg, qd, and MMF was reduced to 0.5 g, qd, the patient’s symptoms improved significantly, and no obvious lesions were found in the mouth. The dose was then reduced and maintained according to the principle of pemphigoid treatment. Methylprednisolone (8 mg, qd, morning dose) and MMF (0.5 g, qd) have been used for 6 months of maintenance treatment, and they are still being followed up. As yet, the patient’s condition is stable without obvious lesions and new blisters, and no obvious side effects have been observed. A review of the literature shows that MMF is widely used in the field of dermatology to treat a variety of immune diseases, such as connective tissue diseases and autoimmune blistering diseases. According to the reports of adverse reactions to MMF, digestive system reactions are the most common adverse reactions; therefore, patients with active gastrointestinal diseases should be treated with caution, followed by bone marrow suppression, and it is recommended to monitor liver function and blood routine in patients using MMF. The safety and efficacy of MMF for treating pemphigoid involving the skin have been reported in the literature, but oral mucosal doctors still lack experience for treating mucous membrane pemphigoid. Conclusions As a new immunosuppressant, MMF has high safety and no obvious side effects and can be considered as a combination adjuvant drug for patients with severe clinical disease and refractory oral mucosal pemphigoid.

Abstract Intensive care unit-acquired infections are complicating events in critically ill patients. In this study we analyzed the incidence, microbiological patterns, and outcome in patients with COVID-19 versus influenza in the intensive care unit (ICU). We included all adult patients treated with invasive mechanical ventilation due to (1) COVID-19 between January 2020 and March 2022, and (2) influenza between January 2015 and May 2023 at Sahlgrenska University Hospital, Sweden. Of the 480 participants included in the final analysis, 436 had COVID-19. The incidence rates of ICU-acquired infections were 31.6/1000 and 9.9/1000 ICU-days in the COVID-19 and influenza cohorts, respectively. Ventilator-associated lower respiratory tract infections were most common in both groups. In patients with COVID-19, corticosteroid treatment was associated with an increased risk of ICU-acquired infections and with higher 90-day mortality in case of infection. Furthermore, ICU-acquired infection was associated with a prolonged time in the ICU, with more difficult-to-treat gram-negative infections in late versus early ventilator-associated lower respiratory tract infections. Further research is needed to understand how the association between corticosteroid treatment and incidence and outcome of ICU-acquired infections varies across different patient categories.

Background. Clinical guidelines for the treatment of rheumatoid arthritis (RA) recommend reducing the use of glucocorticoids (GCs) due to the high risk of associated complications. Aim. To determine the frequency of GC cancellations and dose reductions in real clinical practice, while taking into account active RA therapy. Materials and methods. The study group consisted of 303 patients with RA reliable according to ACR/EULAR criteria (women 79.9%, age 52.8±13.3, disease duration 9 [4; 16] years, DAS-28-CRP 4.9±1.0, RF seropositivity 77.4%, ACPA seropositivity 70.3%), who were prescribed or changed therapy with disease-modifying antirheumatic drugs (DMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (iJAK) due to disease exacerbation and ineffectiveness of previous treatment. All patients initially received GC (7.7±3.8 mg/day equivalent of prednisolone). After adjustment of therapy, 42.9% of patients received methotrexate, 27.6% leflunomide, 2.5% sulfasalazine, hydroxychloroquine, or a combination with an Non-steroidal anti-inflammatory drugs, 63.7% bDMARDs, and 7.2% iJAK. The need for GC intake was assessed by a telephone survey conducted 6 months after the start of follow-up. Results. Telephone survey was possible in 274 (90.4%) persons. There was a significant decrease in pain intensity (numerical rating scale, NRS 0–10) from 6.3±1.4 to 4.3±2.4 (p0.001), fatigue (NRS) from 6.7±2.3 to 5.2±2.1 (p0.001), and functional impairment (NRS) from 5.4±2.1 to 3.9±2.0 (p0.001). A positive PASS index (symptom status acceptable to patients) was noted in 139 (50.7%) patients. GC cancellation was noted in 19.7%, dose reduction in 25.9%, maintaining the same dose in 42.7%, and dose increase in 11.7%. Conclusion. Against the background of intensive RA therapy, including combination of DMARDs with bDMARDs or iJAK, complete withdrawal or reduction of GC dose was achieved in less than half (45.6%) of patients after 6 months.

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

Iodine-induced thyrotoxicosis (IIT) is an abnormal function of the thyroid gland towards increasing caused by excessive iodine intakes of the body. The main reasons for the development of IIT are effects of increased amounts of iodine in people with long-standing iodine deficiency, medical procedures with exposure to radiographic iodinated contrast media as well as long-term treatment with iodine-containing drugs, primarily amiodarone. Aim: to describe an original practical case of the type 2 amiodarone-induced thyrotoxicosis development, to analyze the peculiarities of its clinical manifestations, to evaluate the possibilities for pharmacological correction of thyropathy, and to show the importance of the thyroid gland function systematic monitoring to prevent amiodarone-associated thyroid complications on the example of a particular patient taking antiarrhythmic therapy for a long time. A 71-year-old patient S. was on inpatient treatment in the Endocrinology Department of MNE “Zaporizhzhia Regional Clinical Hospital” ZRC with diagnosed thyrotoxicosis based on complaints, laboratory and instrumental examinations, which was probably caused by long-term amiodarone treatment. A vitally important situation for the patient was the compression of mediastinal organs of unspecified genesis, which significantly complicated swallowing in the first place and impaired food passage into the stomach. Additional examinations using imaging methods were contraindicated due to thyrotoxicosis, since iodine-containing contrast agents could not be used. Surgical decompression of mediastinal organs was also not considered due to the presence of concomitant pathology which greatly increased the operative risk. Treatment of thyrotoxicosis with the use of thyrostatic drugs in dynamics did not result in a significant decrease in serum levels of thyroid hormones. It was decided to prescribe glucocorticoids. The patient started prednisolone therapy at a dose of 30 mg per day. A week later, positive dynamics were obtained as a reduction in compression phenomena. The patient began to swallow normally and take food independently. According to the treatment regimen, the dose of prednisolone and methimazole was gradually reduced to maintenance. On the 17th day of hospital stay, the patient was discharged for further treatment in an outpatient setting. After 4 months, the patient was examined by an endocrinologist. A palpable decrease in the thyroid gland size was noted. There were no objective signs of thyrotoxicosis. Based on laboratory tests, TSH was 1.28 μIU/ml (0.38–4.31 μIU/ml), free T4 was 15.52 ng/dL (0.82–1.63 ng/dL). The patient was capable of eating independently and did not complain of swallowing disorders or other clinical manifestations of mediastinal compression. He continued to take prednisolone at a dose of 5 mg per day, tyrosol 5 mg per day. Conclusions. Thus, the paper has described and analyzed the clinical case of the patient with type 2 amiodarone-induced thyrotoxicosis. Findings have indicated that cessation of amiodarone and management with glucocorticoids in view of ineffective thyrostatic treatment resulted in positive response to therapy of thyropathy in the patient. The importance of routine thyroid function monitoring to prevent amiodarone-induced thyroid complications of long-term antiarrhythmic therapy has also been shown.

Polycystic ovary syndrome (PCOS) is a popular illness in women after puberty age. It’s described via overdone androgen production, and ovulation unrest while elevating metabolic syndrome. PCOS was usually diagnosed by Ultrasound or blood test to check the androgens and other hormone levels. There are many causes of having pathogenesis of POCS which was related to abnormalities in hormone levels, insulin resistance, obesity, and others. the symptoms of PCOS could include irregular periods, excess body hair, weight gain, oily skin, and infertility. Due to the variety of symptoms, the POCS has many different types of treatment options, for instant use of medications or lifestyle changes such as weight loss. Many medications are used to treat PCOS like organic compounds and have proven effective in treating PCOS as well as many metallic elements will aid medicinal chemists in planning, organizing, and implementing new approaches toward the discovery of novel drugs. One of the most important medications which were used to treat PCOS is clomiphene citrate and that is commonly used for the treatment of infertility. This review highlights to the causes and treatments of PCOS and gives many examples of recent research that uses drugs and metallic elements as a medication.

Andrew N Menzies-Gow,1,2 Trung N Tran,3 Brooklyn Stanley,4 Victoria Ann Carter,4 Josef S Smolen,5 Arnaud Bourdin,6 J Mark Fitzgerald7 ,† Tim Raine,8 Jatin Chapaneri,2 Benjamin Emmanuel,3 David J Jackson,9,10 David B Price4,11 1Royal Brompton and Harefield Hospitals, Guys & St Thomas’ NHS Foundation Trust, London, UK; 2AstraZeneca, Cambridge, UK; 3AstraZeneca, Gaithersburg, MD, USA; 4Observational and Pragmatic Research Institute, Singapore; 5Medical University of Vienna, Vienna, Austria; 6Université de Montpellier, CHU Montpellier, PhyMedExp, INSERM, CNRS, Montpellier, France; 7The University of British Columbia, Vancouver, British Columbia, Canada; 8Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK; 9Guy’s Severe Asthma Centre, Guy’s & St Thomas’ NHS Trust, London, UK; 10School of Immunology & Microbial Sciences, King’s College London, London, UK; 11Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK†J. Mark Fitzgerald passed away on January 18, 2022Correspondence: David B Price, Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building-Foresterhill, Aberdeen, AB25 2ZD, UK, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Associations between systemic glucocorticoid (SGC) exposure and risk for adverse outcomes have spurred a move toward steroid-sparing treatment strategies. Real-world changes in SGC exposure over time, after the introduction of steroid-sparing treatment strategies, reveal areas of successful risk mitigation as well as unmet needs.Patients and Methods: A population-based ecological study was performed from the Optimum Patient Care Research Database to describe SGC prescribing trends of steroid-sparing treatment strategies in primary care practices before and after licensure of biologics in the United Kingdom from 1990 to 2019. Each analysis year included patients aged ≥ 5 years who were registered for ≥ 1 year with a participating primary care practice. The primary analysis was SGC exposure, defined as total cumulative SGC dose per patient per year, for asthma, severe asthma, chronic obstructive pulmonary disease (COPD), nasal polyps, Crohn’s disease, rheumatoid arthritis, ulcerative colitis, and systemic lupus erythematosus. Secondary outcomes were percentages of patients prescribed SGCs and number of SGC prescriptions per patient per year.Results: The number of patients who met study inclusion criteria ranged from 219,862 (1990) to 1,261,550 (2019). At the population level, patients with asthma or COPD accounted for 67.7% to 73.2% of patients per year with an SGC prescription. Over three decades, decreases in SGC total yearly dose ≥ 1000 mg have been achieved in multiple conditions. Patients with COPD prescribed SGCs increased from 5.8% (1990) to 34.8% (2017). SGC prescribing trends for severe asthma, Crohn’s disease, and ulcerative colitis show decreased prescribing trends after the introduction of biologics.Conclusion: Decreases in total yearly SGC doses have been shown in multiple conditions; however, for conditions such as severe asthma and COPD, an unmet need remains for increased awareness of SGC burden and the adoption or development of SGC-sparing alternatives to reduce overuse.Keywords: glucocorticoids, practice patterns, drug prescriptions, biological products, drug utilization

The association between sleep and the immune-endocrine system is well recognized, but the nature of that relationship is not well understood. Sleep fragmentation induces a pro-inflammatory response in peripheral tissues and brain, but it also activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing glucocorticoids (GCs) (cortisol in humans and corticosterone in mice). It is unclear whether this rapid release of glucocorticoids acts to potentiate or dampen the inflammatory response in the short term. The purpose of this study was to determine whether blocking or suppressing glucocorticoid activity will affect the inflammatory response from acute sleep fragmentation (ASF). Male C57BL/6J mice were injected i.p. with either 0.9% NaCl (vehicle 1), metyrapone (a glucocorticoid synthesis inhibitor, dissolved in vehicle 1), 2% ethanol in polyethylene glycol (vehicle 2), or mifepristone (a glucocorticoid receptor antagonist, dissolved in vehicle 2) 10 min before the start of ASF or no sleep fragmentation (NSF). After 24 h, samples were collected from brain (prefrontal cortex, hypothalamus, hippocampus) and periphery (liver, spleen, heart, and epididymal white adipose tissue (EWAT)). Proinflammatory gene expression (TNF-α and IL-1β) was measured, followed by gene expression analysis. Metyrapone treatment affected pro-inflammatory cytokine gene expression during ASF in some peripheral tissues, but not in the brain. More specifically, metyrapone treatment suppressed IL-1β expression in EWAT during ASF, which implies a pro-inflammatory effect of GCs. However, in cardiac tissue, metyrapone treatment increased TNF-α expression in ASF mice, suggesting an anti-inflammatory effect of GCs. Mifepristone treatment yielded more significant results than metyrapone, reducing TNF-α expression in liver (only NSF mice) and cardiac tissue during ASF, indicating a pro-inflammatory role. Conversely, in the spleen of ASF-mice, mifepristone increased pro-inflammatory cytokines (TNF-α and IL-1β), demonstrating an anti-inflammatory role. Furthermore, irrespective of sleep fragmentation, mifepristone increased pro-inflammatory cytokine gene expression in heart (IL-1β), pre-frontal cortex (IL-1β), and hypothalamus (IL-1β). The results provide mixed evidence for pro- and anti-inflammatory functions of corticosterone to regulate inflammatory responses to acute sleep loss.

Objective: a comparative study of the peculiarities of pharmacotherapy of rheumatoid arthritis (RA) in presence and in absence of interstitial lung disease (ILD).Material and methods. The study included 1034 patients with active RA who met the 2010 ACR/EULAR criteria. Patients were divided into two groups: with ILD according to high-resolution computed tomography of the lungs (n=82) and without ILD or other types of chronic obstructive pulmonary diseases, including bronchial asthma (52 patients excluded; n=900). Based on medical documentation, archived medical records and medical history, a “drug card” was created for all stages of pharmacotherapy of patients with active RA. The Cumulative Illness Index Score (CIRS) was used to assess the profile and severity of comorbidities.Results and discussion. The main indicators of RA activity in the patients of the two groups were comparable, but a greater number of comorbidities (p˂0.0001) and a higher value of the CIRS multimorbidity index (p˂0.0001) were found in the group with ILD. The presence of ILD had no influence on the frequency of prescription, the total duration of use and the maximum dose of glucocorticoids (GC) (p˂0.05). The average dose of GC was statistically significantly higher in the group with ILD (p=0.008). These patients were taking disease-modifying antirheumatic drugs (DMARDs): methotrexate (p=0.04), leflunomide (p=0.02) and sulfasalazine (p=0.03), less frequently, but they took hydroxychloroquine significantly more frequently (p=0.02) with a comparable total duration of use of each medication. RA patients with ILD and without ILD received biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in 62.2 and 59.6% of cases, respectively (p˂0.05). At the same time, patients without ILD had experience of taking a greater number of different bDMARDs/tsDMARDs (p=0.03). In the group with ILD, patients more frequently received anti-B-cell therapy (p˂0.0001) and significantly less frequently drugs of other classes: tumour necrosis factor α inhibitors (p˂0.0001) and interleukin 6 inhibitors (p=0.01), T-cell costimulation blocker (p=0.04) and Janus kinase inhibitors (p=0.001). Patients with ILD were statistically significantly older at the start of bDMARD/tsDMARD therapy (p˂0.0001), and the period from the onset of RA to the start of bDMARD/tsDMARD therapy was comparable in both groups (p˂0.05).Conclusion. The observed peculiarities of pharmacotherapy in the group with ILD (frequency of use, choice and dose of GC, DMARDs, biologics and tsDMARDs) are probably related to the presence of ILD on the one hand and to the characteristics of concomitant pathology and older age on the other, as the activity of RA was comparable in our patients with and without ILD.

Objective: to investigate the contribution of glucocorticoids (GC) to the development of irreversible organ damage in patients with systemic lupus erythematosus (SLE) using the GC toxicity index (GTI).Material and methods. The study included 65 patients with SLE who met the 2012 SLICC classification criteria. GTI, disease activity according to the SLEDAI-2K index and the SLICC damage index (DI) were determined in all patients, and standard laboratory and immunological tests were performed.Results and discussion. Patients were predominantly female (n=56, 86%), median disease duration was 76 [2; 288] months, SLEDAI-2K – 8.8 [0; 26], DI SLICC – 1.0 [0; 5], DI SLICC >0 was found in 28 (43%) patients. The median duration of GC therapy during the disease period was 66.0 [0; 288] months, maximum dose of GC – 32.7 [0; 80] mg, median of total GC dose during intravenous administration was 2942 [0; 17 812.5] mg, GTI at the time of enrolment in the study – 19 [0; 37] points. GTI >0 was present in 47 (72%) of 65 patients. GTI correlated with disease duration (r=0.33; p˂0.008); maximum dose of oral GCs (r=0.31; p˂0.012); duration of GC use (r=0.35; p˂0.005); DI SLICC (r=-0.43; p˂0.0001). In patients with an average disease duration of more than 3 years, GTI was significantly higher than in patients with a disease duration of 1–3 years (p=0.023).Conclusion. An GTI>0 was found in 72% of SLE patients, which increased significantly with disease duration. The GTI value was influenced by the duration of SLE, the duration of GC treatment and the maximum GC dose during the disease period. A statistically significant correlation was found between the GTI and the SLICC DI, allowing the GTI value to be used as an additional component in the assessment of the contribution of GCs to the development of irreversible organ damage in patients with SLE. It is recommended that GTI is assessed in all patients with SLE receiving long-term GC treatment for the purpose of dose adjustment.

Background IgA nephropathy (IgAN) is a common primary glomerulonephritis worldwide, and the improvement of glucocorticoid on the renal prognosis of IgAN patients with high risk of CKD progression remains unclear. Objective To explore the effect of glucocorticoid therapy on the therapeutic response and renal prognosis of IgAN patients with high risk of CKD progression. Methods IgAN patients with high risk of CKD progression were recruited in the First Affiliated Hospital of Zhengzhou University from January 2017 to October 2021 as study subjects and divided into the glucocorticoid treatment group and supportive treatment group according to whether glucocorticoid therapy was performed. Propensity matching method (PSM) was used to screen patients for cases by 1∶1 matching according to gender, age, 24 h urine protein and eGFR, the clinicopathological data of patients, disease remission, adverse reactions within 1 year were recorded. The patients were followed up from the date of initiation of supportive therapy until October 31, 2022. The primary endpoint event was defined as progression to end-stage renal disease (ESRD) or receiving dialysis. The composite endpoint event was defined as sustained decline in eGFR of more than 30% from baseline, or progression to ESRD, or receiving dialysis or death. Kaplan-Meier method was used to plot survival curves and log-rank test was used to compare differences in the cumulative incidence of the primary/composite endpoint events between the two groups of patients. Cox proportional hazards regression analysis was used to analyze the possible influencing factors of renal prognosis in IgAN patients with high risk of CKD progression. Results A total of 236 patients with primary IgAN met the inclusion criteria. After 1∶1 matching, 97 cases in the glucocorticoid treatment group were successfully matched with 97 cases in the supportive therapy group with balanced baseline data. The complete remission rate and partial remission rate of patients in the glucocorticoid treatment group were higher than those in supportive treatment group (χ2=6.171, P=0.013; χ2=3.973, P=0.046) . The median follow-up time was 18.00 (9.75, 28.00) months. Kaplan-Meier survival curve analysis showed that the cumulative incidence of primary endpoint event in the glucocorticoid treatment group was lower than the supportive treatment group (χ2=4.495, P=0.034) and the cumulative survival rate of composite endpoint event in the glucocorticoid therapy group was lower than the supportive therapy group (χ2=4.419, P=0.036) . Among the 236 patients who met the inclusion criteria, there were 177 patients with moderate proteinuria. After 1∶1 matching of the 177 patients on glucocorticoid treatment and supportive treatment by sex, age, 24 h urine protein and eGFR using PSM, 76 cases in each group were successfully matched. Kaplan-Meier survival curve analysis showed that the cumulative incidence of primary endpoint event in the patients on glucocorticoid treatment with moderate proteinuria was lower than those on supportive treatment with moderate proteinuria (χ2=4.127, P=0.042) ; and the cumulative survival rate of composite endpoint event in the patients on glucocorticoid treatment with moderate proteinuria was lower than those on supportive treatment with moderate proteinuria (χ2=4.934, P=0.026) . Multivariate Cox proportional hazard regression analysis showed that hemoglobin (HR=0.982) , serum creatinine (HR=1.019) , eGFR (HR=1.020) and 24-hour urine protein (HR=1.205) were influencing factors of primary endpoints event in IgAN patients with high risk of CKD progression. The incidence of infection in the glucocorticoid treatment group was higher than the supportive treatment group (P

Background/Aims Despite short-acting β2-agonist (SABA) overuse being associated with poor asthma outcomes, data on SABA use in South Korea is scarce. Herein, we describe prescription patterns of SABA and other asthma medications in patients from the South Korean cohort of the SABA use IN Asthma (SABINA) III study. Methods This study included patients with asthma aged ≥ 12 years, who had ≥ 3 consultations with the same healthcare provider, and medical records containing data for ≥ 12 months prior to the study visit. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma recommendations) and practice type (primary or specialist care). Data on disease characteristics, asthma treatments, and clinical outcomes in the 12 months before the study visit were collected using electronic case report forms. Results Data from 476 patients (mean age, 55.4 years; female, 63.0%) were analyzed. Most patients were treated by specialists (83.7%) and had moderate-to-severe asthma (91.0%). Overall, 7.6% of patients were prescribed ≥ 3 SABA canisters (defined as over-prescription). In patients prescribed SABA in addition to maintenance therapy, 47.4% were over-prescribed SABA. Most patients (95.4%) were prescribed a fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist as maintenance therapy. Although asthma was well-controlled/partly-controlled in 91.6% of patients, 29.6% experienced ≥ 1 severe asthma exacerbation. Conclusions SABA over-prescription was reported in nearly 50% of patients prescribed SABA in addition to maintenance therapy, underscoring the need to align clinical practices with the latest evidence-based recommendations and educate physicians and patients on appropriate SABA use.

The global prevalence of chronic cough in adults is 9.6%.In 2008, the cough special issue of Lancet published a diagnosis and treatment plan to distinguish the causes of chronic cough based on eosinophilic airway inflammation or sensitivity to glucocorticoids therapy. In 2014, Professor Lai Kefang of China first proposed the Chinese name “corticosteroid-responsive cough” (CRC). CRC refers to chronic cough that is effectively treated with glucocorticoids, accounting for 63% of the causes of chronic cough in China, including cough variant asthma, eosinophilic bronchitis, and atopic cough. Cough variant asthma is the most common cause of chronic cough in China, accounting for 30% to 50% Chronic cough has a complex etiology and involves numerous examinations, especially bronchial provocation tests, induced sputum cell analysis, multi-channel esophageal impedance pH monitoring, etc., which have not been carried out in many tertiary hospitals, and not all chronic patients can undergo relevant examinations to confirm diagnosis and receive treatment. The concept of corticosteroid-responsive cough has important guiding significance for the empirical treatment of chronic cough, and is suitable for promotion in grassroots hospitals. In clinical practice, it is only necessary to determine whether it is a CRC based on the clinical characteristics of the patient without the need for further tests, such as induced sputum cell analysis and bronchial provocation tests to distinguish cough variant asthma, eosinophilic bronchitis, and allergic cough, and then empirical treatment can be given. However, there is currently insufficient understanding of the standardized diagnosis and treatment of CRC. For example, there is still a lack of consensus on determining whether it is CRC, how to select hormone treatment and the duration of hormone treatment. It is necessary to further emphasize and promote the relevant concepts and diagnosis and treatment plans of corticosteroid-responsive cough.

Active moderate-to-severe TAO is a disease, the treatment of which requires a multidisciplinary team, an individualized approach and strict follow-up, yet it is often suboptimal. Recent knowledge about the pathogenesis of the disease and the randomized controlled trials conducted in recent years made it possible to use new therapeutic combinations and biological agents. The currently recommended first-line therapy for active moderate-to-severe TAO is the combination of intravenous glucocorticoids (GCs) in moderate doses and mycophenolate or, in more severe cases, a high-dose GC treatment alone. There are several options for second-choice therapy, if needed: a new course with GCs, combination of orbital radiotherapy and GCs (preferably intravenous), cyclosporine and oral GCs, azathioprine and oral GCs, rituximab, tocilizumab or teprotumumab. The clinical manifestations of TAO should also be considered when choosing second-line treatment. Thus, for example, teprotumumab best affects diplopia, orbital radiotherapy – visual disturbances and diplopia, while intravenous GCs, mycophenolate, cyclosporine, rituximab and tocilizumab – the inflammatory manifestations of TAO. However, the question of the availability of the new drugs in routine clinical practice remains unsolved.

Abstract Background Damage in the ischemic core and penumbra after stroke affects patient prognosis. Microglia immediately respond to ischemic insult and initiate immune inflammation, playing an important role in the cellular injury after stroke. However, the microglial heterogeneity and the mechanisms involved remain unclear. Methods We first performed single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST) on middle cerebral artery occlusion (MCAO) mice from three time points to determine stroke-associated microglial subclusters and their spatial distributions. Furthermore, the expression of microglial subcluster-specific marker genes and the localization of different microglial subclusters were verified on MCAO mice through RNAscope and immunofluorescence. Gene set variation analysis (GSVA) was performed to reveal functional characteristics of microglia sub-clusters. Additionally, ingenuity pathway analysis (IPA) was used to explore upstream regulators of microglial subclusters, which was confirmed by immunofluorescence, RT-qPCR, shRNA-mediated knockdown, and targeted metabolomics. Finally, the infarct size, neurological deficits, and neuronal apoptosis were evaluated in MCAO mice after manipulation of specific microglial subcluster. Results We discovered stroke-associated microglial subclusters in the brains of MCAO mice. We also identified novel marker genes of these microglial subclusters and defined these cells as ischemic core-associated (ICAM) and ischemic penumbra-associated (IPAM) microglia, according to their spatial distribution. ICAM, induced by damage-associated molecular patterns, are probably fueled by glycolysis, and exhibit increased pro-inflammatory cytokines and chemokines production. BACH1 is a key transcription factor driving ICAM generation. In contrast, glucocorticoids, which are enriched in the penumbra, likely trigger IPAM formation, which are presumably powered by the citrate cycle and oxidative phosphorylation and are characterized by moderate pro-inflammatory responses, inflammation-alleviating metabolic features, and myelinotrophic properties. Conclusions ICAM could induce excessive neuroinflammation, aggravating brain injury, whereas IPAM probably exhibit neuroprotective features, which could be essential for the homeostasis and survival of cells in the penumbra. Our findings provide a biological basis for targeting specific microglial subclusters as a potential therapeutic strategy for ischemic stroke.

Local injection therapy (LIT) is an important component of the complex treatment of musculoskeletal disorders (MSD), which is widely used in real clinical practice. Glucocorticoids, hyaluronic acid drugs (HA), autologous cell drugs, botulinum toxin type A, radioactive isotopes, etc. are used for LIT. LIT makes it possible to achieve a pronounced symptomatic effect, while in some cases, for example, repeated HA treatments in patients with osteoarthritis, the possibility of slowing the progression of the disease and reducing the need for surgical treatment is discussed.The performance of LIT requires special skills and abilities of the physician, careful compliance with the rules of asepsis and antisepsis, and instrumental visualization. LIT can be associated with serious complications and therefore must be performed according to strict indications.The Expert Council was devoted to defining the basic principles of LIT. The indications for the use of certain types of this therapies, the evidence base for its efficacy and safety, the order of application of different drugs, and the need to combine LIT with other drug and non-drug treatments of MSD were reviewed.

As a new type of anti-cancer therapy, immune checkpoint inhibitors (ICIs) have transformed the treatment of various cancers. However, ICIs are associated with many potential complications, namely immune-related adverse events (irAEs) , possibly involving the nervous, cardiac, pulmonary, cutaneous, renal, gastrointestinal, hepatic, and hematologic systems. Although a series of guidelines for the management of irAEs have been issued, early identification, diagnosis and treatment of irAEs in clinical practice are still not standardized enough due to different levels of awareness and attention regarding the disease across clinicians. We analyzed the clinical data of a patient with severe multisystem irAEs developed after treatment with cindilimab, and reviewed relevant literature, then summarized the benefits and limitations of treatments for irAEs, providing ideas for better managing multisystem irAEs clinically.

Glucocorticoids (GCs) are one of the most commonly used drugs for the treatment of rheumatoid arthritis (RA), the effectiveness of which is beyond doubt. The review considers current literature data on the safety of GCs use, as well as the most common adverse events associated with such therapy. Most authors point to an increased risk of complications with an increase in the daily dose and/or duration of GCs treatment. At the same time, a safe dose of GCs has not been determined. Probably, the optimal tactic is the selection of an individual dose of GCs in each individual case, taking into account the activity of RA and the spectrum of comorbid conditions. In this case, the minimum effective doses and short courses of GCs should be used, regular monitoring of clinical and laboratory parameters should be carried out in order to detect adverse events early.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disease encompassing enzyme deficiencies in the process of adrenal steroidogenesis, which leads to adrenal cortex dysfunction. Hypersecretion of corticotrophin-releasing hormone and insufficient cortisol production often lead to enlarged adrenal glands. Existing studies have reported that most of space-occupying adrenal masses in CAH are benign, only very few are malignant. It is difficult for clinicians to distinguish the nature of space-occupying adrenal masses, and physicians have insufficient experiences in treating the disease. We reported a phenotypically male case of CAH with huge space-occupying adrenal masses and reviewed relevant literature, aiming to provide evidence on the diagnosis and treatment of this disease for clinicians. The space-occupying adrenal masses in CAH often show tumor-like hyperplasia before diagnosis and treatment or effective hormone replacement therapy, but most of them will be significantly reduced or disappear after glucocorticoid replacement therapy. But a follow-up of several years showed that space-occupying adrenal masses in the CAH patient encountered by us had no significant changes and no significant impact on the patient's body, even without effective drug intervention.

The aim of the work is to study the possibility of glucocorticoid (GC) discontinuation or their target dose achievement in patients (pts) with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Materials and methods. 270 pts with RA (women – 86.6 %) aged 51.2 ± 0.71 years, with a disease duration of 50.20 ± 3.82 months were examined. Rheumatoid factor was found in 64.8 % of individuals, anti-cyclic citrullinated peptide (ACCP) antibodies – in 66.6 %. DMARD therapy included methotrexate (n = 91), leflunomide (n = 95), sulfasalazine (n = 51), hydroxychloroquine (n = 3) or its combination (n = 126). The SPSS (version 22.0) software was used for the statistical analysis. Results. During the 3-year study, GC was withdrawn in 33 % of pts in the period from 3 to 30 months (mostly in the first 6 moths). Among those who continued to take GC, the target dose (

Background. In Russia, as well as throughout the world, the use of glucocorticoids (GC) in the treatment of rheumatoid arthritis (RA) is widespread, often going beyond the recommendations for both duration and dose regimen, which makes it relevant to study the long-term consequences of such a wrong (EULAR, 2022) use of GC in RA therapy. Materials and methods. Of 1143 patients with active RA (ACR/EULAR 2010), two groups were formed: A (n=782) RA patients with more than 6 months of experience with systemic GC; group B (n=245) no experience of taking GC. The cumulative disease index (CIRS) was used to assess the comorbidity profile. Results. Patients in group A were older (p0.0001), with a longer duration of RA (p=0.0004) and more often with IV radiological stage (p=0.02). With comparable (DAS28) RA activity, the D2T variant of RA was more often detected in them (p=0.036). RA therapy in group A was characterized by a large number of used disease-modifying anti-rheumatic drugs (p=0.0003), more frequent development of methotrexate-induced hepatitis (p=0.03). In group A, the time interval between the onset of RA and the initiation of biological therapy was longer (p=0.0001) and directly correlated with the duration of GC therapy (Rs=0.38) with a comparable qualitative structure of the used b/tsDMARDs. In the same group, tuberculosis, hypertension, chronic kidney disease, cataract and osteoporosis (p0.05) and its complications were diagnosed significantly more often with a comparable frequency of cardiovascular disease, diabetes, and gastrointestinal lesions. In group A, a higher CIRS multimorbidity index was detected, and the CIRS severity index was lower than in group B (p0.05). Conclusion. Long-term use of GC did not lead to a decrease in disease activity, inhibition of radiographic progression, delayed the timely administration of b/tsDMARDS and was accompanied by an increase in the multimorbid load.

Objective To summarize the clinical characteristics of posterior reversible encephalopathy syndrome (PRES) in children with renal disease in order to provide reference for early prevention, diagnosis and treatment and improving prognosis. Methods A retrospective analysis was conducted on the clinical characteristics, auxiliary examinations, medication use and prognosis of children with renal disease complicated with PRES confirmed in the First Affiliated Hospital of Henan University of Chinese Medicine from 2015 to 2022, and the relevant literatures were reviewed. Results Thirteen children aged 3 to 14 (8.38±3.36) years old were enrolled, including 9 males and 4 females. There were 10 cases (76.92%) of infection before the onset of the disease, 10 cases (76.92%) of lower serum albumin levels than normal, 4 cases (30.77%) accompanied by varying degrees of hypertension, 10 cases (76.92%) treated with glucocorticoids (GC) combined with immunosuppressive agents, 2 cases (15.38%) treated with GC and 1 case (7.69%) treated with immunosuppressive agents. The main clinical manifestations were seizures, disturbance of consciousness, nausea and vomiting, dizziness, headache and ocular discomfort. The lesions were mostly distributed in bilateral frontal lobe, parietal lobe, temporal lobe, occipital cortex and subcortex. After treatment, the clinical manifestations and imaging findings returned to normal in a short period of time. Conclusion The incidence of PRES in children with renal disease is related to GC and immunosuppressive therapy, and cyclic lipopeptide antibiotics, hypoproteinemia and hypertension may increase the risk of disease. PRES usually is reversible and has a good prognosis, but delayed treatment can worsen progressively and even cause irreversible craniocerebral nerve damage.

Pemphigus is a rare autoimmune bullous disease with chronic and high rates of relapse. The diagnosis of pemphigus in China has following problems: first, the difficulty of early diagnosis commonly causes missed diagnosis or misdiagnosis with eczema, seborrheic dermatitis, behcet disease, ect. Patients are diagnosed clearly only after several months or years. Second, patients’ cognitive dificiency of pemphigus. Shortage of education on pemphigus patients, low acceptance and obedience and self-reduction or-withdrawal of drug causing common relapse and low sensitivity and increasing adverse reactions in retreatment. Thrid, lack of management of doctors in adverse reaction treatment. Some primary hospitals still have the overdosage of hormone to disease control and nonstandard drug combination as the primary treatment of pemphigus. In January 2020, the Dermatology Branch of China Association for the Promotion of International Exchanges in Healthcare has released Expert Recommendations on the Diagnosis and Treatment of Pemphigus Vlgaris (2020) and update the diagnosis standard of pemphigus in China. In April 2021, the China Autoimmune Bullous Disease Collaboration Network was officially established to promote the further update of pemphigus diagnosis and treatment with multi-center and multidisciplinary collaborative research. “Early diagnosis, timely treatment, careful nursing, long-term follow-up” is the principle of pemphigus diagnosis and treatment. This article concludes the situation of pemphigus in China, compares differences between home and abroad in diagnosis and treatment of pemphigus and triggers thoughts of future development.

Glucocorticoid therapies are used widely in arrange of medical conditions including respiratory, allergic, inflammatory and autoimmune diseases. All forms of glucocorticoid delivery, even at therapeutic doses, have the potential to cause Cushing’s syndrome. Here, we present a case of exogenous Cushing’s syndrome resulting from recurrent use of intermittent high dose oral prednisone to treat asthma exacerbation.

The treatment goal in alopecia areata is induction of hair regrowth and halting the progression of the disease. Treatment decisions depend on the severity of the alopecia areata as assessed by the Severity of Alopecia Tool (SALT) or the Alopecia Areata Scale (AAS). In mild alopecia areata, very ultra-high potency topical glucocorticoids and intralesional triamcinolone acetonide are the mainstay of treatment. In moderate to severe alopecia areata, systemic treatment is usually required. Currently, the only drug dedicated for alopecia areata, approved in Europe and the United States is baricitinib. Ritlecitinib, a JAK3/TEC inhibitor is approved in the United States for individuals 12 years of age and older with severe alopecia areata and is expected to be approved in Europe soon. Other systemic medications used in alopecia areata include glucocorticoids, cyclosporine, and methotrexate. Contact immunotherapy may be considered. In alopecia areata, long-maintenance treatment is of substantial significance.

The historical essay presents the main stages in the development of scientific views on rheumatoid arthritis, starting from the middle of the 19th century and until the middle of the 20th century, history of research of its characteristic clinical and instrumental signs, diagnostic criteria, methods of drug therapy.

Objectives: Hallux rigidus is one of the main etiologies of disability in the elderly. It is a degenerative disease of the first metatarsophalangeal joint causing restriction of movement as well as pain and swelling. This study was conducted to evaluate the effectiveness of methylprednisolone and dextrose prolotherapy in pain reduction and functional improvement of patients with hallux rigidus. Methods: A randomized double-blind control trial was designed with the inclusion of 32 patients assigned to the two groups. Group one received a mixture of 1 cc methylprednisolone 40 mg with 1 cc lidocaine 2% while the second group received a combination of 1 cc dextrose 50% with 1 cc lidocaine 2%. Standard questionnaires, including visual analog scale (VAS) and Manchester-Oxford foot questionnaire (MOXFQ) were completed by all patients at baseline and 1, 4, and 8 weeks after injections. Results: Both groups revealed significant improvement in VAS and MOXFQ scores 1, 4, and 8 weeks post-injection with no difference between the two groups in the follow-up. Discussion: Both corticosteroid injections and prolotherapy are effective in pain reduction and functional improvement in patients with hallux rigidus but neither is superior to the other.

Background/Aims Corticosteroids (CSs) are frequently used in coronavirus disease 2019 (COVID-19); however, their utility remains controversial in mild to moderate cases. The timing of CSs initiation during the disease course remains unaddressed. The study aims to evaluate the impact of early CSs in non-severe COVID-19. Methods A randomized controlled, open-label study was conducted on 754 COVID-19 patients randomized into a study group (n = 377) in which patients received CSs with COVID-19 protocol and a control group (n = 377) in which patients received COVID-19 protocol only. Results Both groups were comparable regarding baseline characteristics, presenting symptoms, and inflammatory markers. The composite endpoint (need for O2, need for hospitalization or 28-day mortality) was significantly (p = 0.004) lower in the CS group 42 (11.14%) versus the control group 70 (18.67%) with odds ratio 0.55 (95% confidence interval [CI], 0.36 to 0.83), absolute risk reduction 7.53% (95% CI, 2.46% to 12.59%) and number needed to treat of 13.29 (95% CI, 7.94 to 40.61). Regarding severity at day 10, only (11.1%) of the study group patients were severe versus (18.7%) of the control group patients (p < 0.001). The median time-to-return to daily activity in the CS group was 8.0 days, while in the control group, it was 22.0 days (p < 0.001). Conclusions In non-severe COVID-19, CS may decrease hospitalization, severity, and mortality.

Summary: Background: Glucocorticoids (GCs) are widely applied anti-inflammatory drugs that are associated with adverse metabolic effects including insulin resistance and weight gain. Previous research indicates that GCs may negatively impact brown adipose tissue (BAT) activity in rodents and humans. Methods: We performed a randomised, double-blinded cross-over trial in 16 healthy men (clinicaltrials.gov NCT03269747). Participants received 40 mg of prednisone per day for one week or placebo. After a washout period of four weeks, participants crossed-over to the other treatment arm. Primary endpoint was the increase in resting energy expenditure (EE) in response to a mild-cold stimulus (cold-induced thermogenesis, CIT). Secondary outcomes comprised mean 18F-FDG uptake into supraclavicular BAT (SUVmean) as determined by FDG-PET/CT, volume of the BAT depot as well as fat content determined by MRI. The plasma metabolome and the transcriptome of supraclavicular BAT and of skeletal muscle biopsies after each treatment period were analysed. Findings: Sixteen participants were recruited to the trial and completed it successfully per protocol. After prednisone treatment resting EE was higher both during warm and cold conditions. However, CIT was similar, 153 kcal/24 h (95% CI 40–266 kcal/24 h) after placebo and 186 kcal/24 h (95% CI 94–277 kcal/24 h, p = 0.38) after prednisone. SUVmean of BAT after cold exposure was not significantly affected by prednisone (3.36 g/ml, 95% CI 2.69–4.02 g/ml, vs 3.07 g/ml, 95% CI 2.52–3.62 g/ml, p = 0.28). Results of plasma metabolomics and BAT transcriptomics corroborated these findings. RNA sequencing of muscle biopsies revealed higher expression of genes involved in calcium cycling. No serious adverse events were reported and adverse events were evenly distributed between the two treatments. Interpretation: Prednisone increased EE in healthy men possibly by altering skeletal muscle calcium cycling. Cold-induced BAT activity was not affected by GC treatment, which indicates that the unfavourable metabolic effects of GCs are independent from thermogenic adipocytes. Funding: Grants from Swiss National Science Foundation (PZ00P3_167823), Bangerter-Rhyner Foundation and from Nora van der Meeuwen-Häfliger Foundation to MJB. A fellowship-grant from the Swiss National Science Foundation (SNF211053) to WS. Grants from German Research Foundation (project number: 314061271-TRR 205) and Else Kröner-Fresenius (grant support 2012_A103 and 2015_A228) to MR.

Background Limited data are available in COVID-19 patients on the prediction of treatment response to systemic corticosteroid therapy based on systemic inflammatory markers. There is a concern whether the response to systemic corticosteroid is different according to white blood cell (WBC) counts in COVID-19 patients. We aimed to assess whether WBC count is related with the clinical outcomes after treatment with systemic corticosteroids in severe COVID-19.Methods We conducted a retrospective cohort study and analysed the patients hospitalised for severe COVID-19 and received systemic corticosteroids between July 2020 and June 2021. The primary endpoint was to compare the composite poor outcome of mechanical ventilation, extracorporeal membrane oxygenation, and mortality among the patients with different WBC counts.Results Of the 585 COVID-19 patients who required oxygen supplementation and systemic corticosteroids, 145 (24.8%) belonged to the leukopoenia group, 375 (64.1%) belonged to the normal WBC group, and 65 (11.1%) belonged to the leukocytosis group. In Kaplan-Meier curve, the composite poor outcome was significantly reduced in leukopoenia group compared to leukocytosis group (log-rank p-value < 0.001). In the multivariable Cox regression analysis, leukopoenia group was significantly associated with a lower risk of the composite poor outcome compared to normal WBC group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.14–0.76, p-value = 0.009) and leukocytosis group (aHR = 0.30, 95% CI = 0.12–0.78, p-value = 0.013). There was no significant difference in aHR for composite poor outcome between leukocytosis and normal WBC group.Conclusion Leukopoenia may be related with a better response to systemic corticosteroid therapy in COVID-19 patients requiring oxygen supplementation.KEY MESSAGESIn severe COVID-19 treated with systemic corticosteroids, patients with leukopoenia showed a lower hazard for composite poor outcome compared to patients with normal white blood cell counts or leukocytosis.Leukopoenia may be a potential biomarker for better response to systemic corticosteroid therapy in COVID-19 pneumonia.

Background: Glucocorticoids are used in different conditions such as autoimmune disorders and organ transplantation and their administration is the most common cause of secondary osteoporosis. Rutin is a flavonoid found in many plants. Flavonoids are natural products with various therapeutic and biological effects. Objective: Is to investigate the effect of Rutin Hydrate as a form of Rutin on glucocorticoid induced osteoporosis in mandibular alveolar bone radiologically, histologically and histochemically. Methods: Twenty-one adult male Albino rats were randomly divided into three groups. Group I (control), group II (osteoporotic) and group III (Rutin Hydrate treated). In both group II and III rats received 21 mg/kg of methylprednisolone daily for four weeks. Then group III received 50 mg/kg of rutin hydrate in distilled water daily for another four weeks. At the end of the experiment, mandibles were dissected for radiographic assessment, then processed for histological and histochemical examination and statistical analysis. Results: Radiologically, administration of Rutin Hydrate was able to enhance bone density than osteoporotic group. Histological examination revealed preserved cortical bone thickness that had been statistically proved. Apparently normal sized marrow cavities, some plump osteoblasts and normal osteocytes were seen in group III. Histochemical examination showed statistical increase in the area percentage of newly formed collagen in group III than group II. Conclusions: Rutin Hydrate was able to modify the radiological and histological picture of osteoporotic alveolar bone. This was achieved by the ability of Rutin Hydrate to increase bone density, preserve cortical plates thickness and enhance new collagen formation that was proved histochemically.

The hypothalamus-pituitary-adrenal (HPA) axis is activated in response to inflammation leading to increased production of anti-inflammatory glucocorticoids by the adrenal cortex, thereby representing an endogenous feedback loop. However, severe inflammation reduces the responsiveness of the adrenal gland to adrenocorticotropic hormone (ACTH), although the underlying mechanisms are poorly understood. Here, we show by transcriptomic, proteomic, and metabolomic analyses that LPS-induced systemic inflammation triggers profound metabolic changes in steroidogenic adrenocortical cells, including downregulation of the TCA cycle and oxidative phosphorylation, in mice. Inflammation disrupts the TCA cycle at the level of succinate dehydrogenase (SDH), leading to succinate accumulation and disturbed steroidogenesis. Mechanistically, IL-1β reduces SDHB expression through upregulation of DNA methyltransferase 1 (DNMT1) and methylation of the SDHB promoter. Consequently, increased succinate levels impair oxidative phosphorylation and ATP synthesis and enhance ROS production, leading to reduced steroidogenesis. Together, we demonstrate that the IL-1β-DNMT1-SDHB-succinate axis disrupts steroidogenesis. Our findings not only provide a mechanistic explanation for adrenal dysfunction in severe inflammation, but also offer a potential target for therapeutic intervention.

Background There are rare studies assessing the efficacy of inhaled glucocorticoids (ICS) , the common therapy for chronic obstructive pulmonary disease (COPD) . MicroRNAs (miRNAs) have been confirmed to be involved in the development of COPD, among which miR-210 and miR-181a are closely related to COPD. Moreover, there is lack of clinical research on changes of miR-210 and miR-181a in COPD patients treated with ICS. Objective To examine the changes and response predictive values of serum miR-210 and miR-181a levels in stable COPD patients treated with ICS. Methods Eighty-six COPD outpatients were recruited from 363 Hospital from January 2017 to June 2020. All of them received four-week budesonide and formoterol inhalation. Treatment efficacy was assessed by the results of spirometry test or COPD Assessment Test (CAT) 〔responsive to treatment was defined as the COPD stage was reduced at least one stage or CAT score was reduced at least 2 points after treatment〕. Pre- and post-treatment lung function parameters〔including forced expiratory volume in one second (FEV1) , forced vital capacity (FVC) , and peak expiratory flow (PEF) 〕 and serum miR-210 and miR-181a levels were collected. Pearson correlation analysis was used to assess the associations of serum miR-210 and miR-181a levels with FEV1, FVC, and PEF as well as CAT score before and after the treatment. ROC analysis was used to assess the predictive values of serum miR-210 and miR-181a levels for treatment response in stable COPD. Results Compared with pre-treatment, stable COPD patients demonstrated significantly increased values of FEV1, FVC, and PEF, and significantly decreased CAT score, serum miR-210 and miR-181a levels after treatment (P

Synthetic glucocorticoids are widely used in pregnancies at risk of preterm delivery and in pregnant women at risk of having a child with severe 21-hydroxylase deficiency. The positive effects of reducing mortality in preterm and virilisation in girls with congenital adrenal hyperplasia are now unquestionable. The adrenogenital syndrome responding to 21-hydroxylase deficiency is a common, potential fatal disease. Its incidence calculated on the basis of neonatal screening data makes 1 case for 14000 live newborns among the worldwide population, 1 for 9638 – In Russia. DEX passes through the placenta and decreases fetal ACTH production thereby suppressing the fetal production of androgens. The prenatal treatment does not preclude from a life-long treatment in future and it is not prevention of a salt-losing syndrome at the postnatal period, and dexamethasone safety in relation to cognitive development of children prenatally treated with dexamethasone is still up for debate. Adding to the concern is the fact that the doses of DEX that the fetus is exposed to are estimated to be 60 times the normal fetal cortisol level. The glucocorticoid and the mineralocorticoid receptors are highly expressed in the hippocampus, amygdala, and prefrontal cortex. These areas, important for executive functioning, emotional regulation, and memory, are vulnerable to high doses of GCs. Most experimental data from animal have shown that prenatal exposure to synthetic glucocorticoids programs the foetal HPA and may lead to altered susceptibility to metabolic and cardiovascular disease i.e. metabolic syndrome, high blood pressure. Prenatal glucocorticoid exposure also leads to modification of HPAassociated behaviours and cognition.

Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide. A polymorphism in FAAH (FAAH C385A) reduces FAAH expression, increases anandamide levels, and increases the risk of obesity. Nevertheless, some studies have found no association between FAAH C385A and obesity. We investigated whether the environmental context governs the impact of FAAH C385A on metabolic outcomes. Using a C385A knock-in mouse model, we found that FAAH A/A mice are more susceptible to glucocorticoid-induced hyperphagia, weight gain, and activation of hypothalamic AMP-activated protein kinase (AMPK). AMPK inhibition occluded the amplified hyperphagic response to glucocorticoids in FAAH A/A mice. FAAH knockdown exclusively in agouti-related protein (AgRP) neurons mimicked the exaggerated feeding response of FAAH A/A mice to glucocorticoids. FAAH A/A mice likewise presented exaggerated orexigenic responses to ghrelin, while FAAH knockdown in AgRP neurons blunted leptin anorectic responses. Together, the FAAH A/A genotype amplifies orexigenic responses and decreases anorexigenic responses, providing a putative mechanism explaining the diverging human findings.

Abstract A 48‐year‐old woman with a history of primary hypothyroidism, presented with compressive symptoms secondary to a rapid enlargement of a preexisting goiter. She had no clinical signs of hypocalcemia. Biological tests revealed hypoparathyroidism. Cervicothoracic computed tomography scan showed a heterogeneous compressive goiter. The patient was treated with levothyroxine, calcium, and alfacalcidol. A total thyroidectomy was not performed because of the hard adhesion to neighboring structures. Histopathological examination of the thyroid biopsy was consistent with the diagnosis of Riedel's thyroiditis (RT). The patient was treated with glucocorticoids. The outcome was marked by the resolution of compressive symptoms and the decrease of the thyroid gland volume. Serum calcium and parathyroid hormone levels reached normal ranges after the discontinuation of vitaminocalcic supplementation. Hypoparathyroidism may be clinically asymptomatic in a patient with RT as in our case. Early administration of glucocorticoids may be effective in reducing the fibrosclerotic process and lead to the recovery of parathyroid dysfunction.

Drug-induced lung injury has received more and more attention. The most common pattern is interstitial lung disease. The diagnosis, treatment and prognosis of drug-induced interstitial lung disease (DIILD) have been explored in many researches. However, there are still many subtypes of DIILD, including usual interstitial pneumonia, non-specific interstitial pneumonia, organizing pneumonia, hypersensitivity pneumonia and diffuse alveolar damage depending on the pathology. Each subtype may be different in treatment and management and further clarification is needed. This paper focused on the common subcategory of organizing pneumonia, naming it as drug-induced organizing pneumonia (DIOP) , explored the most common anticancer drugs, understood the potential mechanism of anticancer drugs to cause OP, and explored the diagnosis, differential diagnosis, treatment and prognosis of DIOP, so as to make a better guide on the diagnosis and treatment of organizing pneumonia induced by anticancer drugs.

Background Acute exacerbation is an important cause for the significant decline of lung function in patients with chronic airway disease, which seriously affects the health and quality of life of patients, and significantly increases the medical and economic burden of the disease. Early identification of different inflammatory phenotypes in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma-COPD overlap (ACO) and timely and precise treatment are important in reducing the occurrence of exacerbations, controlling disease progression, and improving quality of life. Objective To compare the clinical characteristics of AECOPD with different inflammatory phenotypes and ACO patients and their response to glucocorticoid therapy, and to provide a reference for further guiding the application of glucocorticoids. Methods The basic clinical data of AECOPD and ACO patients hospitalized in respiratory and critical care Medicine Department of the Second Hospital of Hebei Medical University from January 2018 to December 2020 were collected. The basic clinical data were collected, and the peripheral blood eosinophils (EOS) percentage (2%) was used as the critical value, EOS%≥2% was defined as EOS group, EOS%

Objective: to compare the course of the disease and therapy in rheumatoid arthritis (RA) patients who meet and do not meet the criteria for difficult- to-treat RA (D2T).Patients and methods. The study included RA patients who met the 2010 ACR/EULAR criteria and who were hospitalized in the V.A. Nasonova Research Institute of Rheumatology from March to October 2021. All patients underwent a conventional clinical and laboratory examination, radiography of the hands and distal feet, and the radiological stage of RA according to Steinbroker was assessed. To determine the inflammatory activity, the DAS28-ESR and DAS28-CRP indices were calculated.Results and discussion. The study included 303 patients with RA, 25 (8.4%) of them had D2T RA. The duration of RA in the D2T group was significantly longer than in other patients (15.9±11.8 and 11.9±9 years, respectively; p=0.04). X-ray changes in the joints in D2T were more pronounced. Patients with D2T had higher inflammatory activity at the time of hospitalization than patients who had continued prior therapy with biologic/targeted synthetic DMARDs. The dose of glucocorticoids (GC) in patients with D2T RA was higher compared to patients of other groups: on average 8.3±5.1 and 6.4±2.9 mg/day, respectively (p=0.02).Conclusion. The results of this study suggest that in Russia, as well as abroad, the treat-to-target principle has not yet become widespread, and the selection of adequate therapy takes too much time. At the same time, Russian rheumatologists primarily use GC to suppress inflammatory activity. The introduction of modern recommendations for the management of patients with RA into routine clinical practice, could possibly restrain the formation of D2T RA.

ABSTRACT Adrenal steroid biosynthesis and its related pathology are constant evolving disciplines. In this paper, we review classic and current concepts of adrenal steroidogenesis, plus control mechanisms of steroid pathways, distribution of unique enzymes and cofactors, and major steroid families. We highlight the presence of a “mineralocorticoid (MC) pathway of zona fasciculata (ZF)”, where most circulating corticosterone and deoxycorticosterone (DOC) originate together with 18OHDOC, under ACTH control, a claim based on functional studies in normal subjects and in patients with 11β-, and 17α-hydroxylase deficiencies. We emphasize key differences between CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) and the onset of a hybrid enzyme – CYP11B1/CYP11B2 –, responsible for aldosterone formation in ZF under ACTH control, in “type I familial hyperaldosteronism” (dexamethasone suppressible). In “apparent MC excess syndrome”, peripheral conversion of cortisol to cortisone is impaired by lack of 11β-hydroxysteroid dehydrogenase type 2, permitting free cortisol access to MC receptors resulting in severe hypertension. We discuss two novel conditions involving the synthesis of adrenal androgens: the “backdoor pathway”, through which dihydrotestosterone is formed directly from androsterone, being relevant for the fetoplacental setting and sexual differentiation of male fetuses, and the rediscovery of C19 11-oxygenated steroids (11-hydroxyandrostenedione and 11-ketotestosterone), active androgens and important markers of virilization in 21-hydroxylase deficiency and polycystic ovaries syndrome. Finally, we underline two enzyme cofactor deficiencies: cytochrome P450 oxidoreductase which partially affects 21- and 17α-hydroxylation, producing a combined clinical/hormonal picture and causing typical skeletal malformations (Antley-Bixler syndrome), and PAPSS2, coupled to SULT2A1, that promotes sulfation of DHEA to DHEAS, preventing active androgens to accumulate. Its deficiency results in reduced DHEAS and elevated DHEA and androgens with virilization. Future and necessary studies will shed light on remaining issues and questions on adrenal steroidogenesis.

Local methods are widely used in the treatment of osteoarthritis (OA) and play a significant role in the complex therapy of this disease. A special place among them belongs to intra-articular (i/a) administration of drugs. The most widely used for this purpose are glucocorticoids (GC) and hyaluronic acid (HA) drugs. When comparing the effectiveness of these drugs, it was shown that during the 1st month, HA had more favorable results, after 3 months the results did not differ significantly, and after 6 months, the effectiveness of HA was higher. Some authors believe that the optimal result can be obtained with the combined use of HA and GC.The efficacy and tolerability of HA drugs in patients with OA have been studied in numerous randomized controlled trials (RCTs), and the data obtained in these studies have been summarized in a number of meta-analyses. At the same time, both in RCTs and in meta-analyses, the results of such treatment were assessed differently. However, when summarizing the materials of various meta-analyses within the framework of a systematic review, it was shown that i/a injections of HA are an effective and safe method of local treatment of OA. However, there are no generally accepted recommendations for the use of HA in the treatment of OA, and the question of their administration in each case is decided individually, taking into account the history, clinical picture, OA phenotype, and tolerability of therapy. The Russian Association of Rheumatologists recommends the use of i/a HA injections in knee OA with synovitis and the use of HA injections to reduce pain and improve joint function.

Background The use of long-term oral glucocorticoid therapy, specifically in the treatment of systemic lupus erythematosus (SLE), has increased in the past two decades. Chronic glucocorticoid use may lead to a linear growth disturbances. Objective To determine the association between linear growth and systemic glucocorticoid therapy in pediatric SLE patients. Methods This retrospective cohort study used medical record data of pediatric SLE patients. All subjects received systemic glucocorticoids. The linear growth parameters recorded in this study were height-for-age z-score (HAZ) and height velocity at 0, 6, and 12 months of treatment. We recorded potential risk factors of linear growth disturbance, such as pubertal status, sex, SLE severity, pulse methylprednisolone use, daily glucocorticoid dose, and nutritional status. Results Of 42 patients with SLE, 83.3% were female, with a mean age of 13 years at diagnosis. Eighteen subjects (42.9%) experienced abnormal height velocity. There was a significant reduction in HAZ between 0, 6, and 12 months of treatment (P=0.016). Between 0 and 6 months of treatment, there was a mean HAZ decrease of 0.11 (P=0.015). There was a trend towards a risk for decreased HAZ at 6 and 12 months of treatment with pulse methylprednisolone (RR 1.25 and 1.27, respectively), as well as for abnormal height velocity (RR 1.73), but they did not reach statistical significance. Conclusion There is a reduction in linear growth in the first 12 months of systemic glucocorticoid therapy in children with SLE. Administration of systemic glucocorticoid significantly reduced HAZ in the first six months of therapy.

This study aimed to determine whether patients with active rheumatoid arthritis (RA) regularly take non-steroidal anti-inflammatory drugs (NSAIDs) and to clarify whether their decision to take NSAIDs depends on disease activity, intensity of pain, or functional status. The study also aimed to identify the risk factors for gastrointestinal side effects. Over 6 months, we conducted a cross-sectional single-center study of consecutively hospitalized patients with confirmed RA. Activities of daily living, pain intensity, and disease activity were evaluated by the Health Assessment Questionnaire, visual analog scale, and disease activity score, respectively, in 28 joints. Of 73 patients diagnosed with RA, 48 (66%) regularly took NSAIDs. Compared to non-users, NSAID users used glucocorticoids less frequently. The decision to use NSAIDs was independent of disease activity, pain intensity, degree of functional impairment, or presence of gastrointestinal risk factors. However, a higher degree of functional impairment was associated with a longer duration of continuous NSAID and glucocorticoid use. NSAIDs are still relevant for RA treatment. The decision to use them is not necessarily affected by disease activity or pain intensity, but their prolonged use is required in patients with a higher degree of functional disability. NSAIDs enable exclusion of glucocorticoid use, sparing patients of glucocorticoid-related side effects.