Glucocorticoid Treatment In Patients Research Articles

A schedule for tapering glucocorticoid treatment in patients with severe SARS-CoV 2 infection can prevent acute adrenal insufficiency in the geriatric population.

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. 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 25mg to 2.5mg over 2 weeks. Morning serum sodium, potassium, and cortisol levels were assessed 3 days after the last dose of prednisone. 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. 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.

Serum cytokine profiles predict response to systemic glucocorticoid in active vitiligo.

Vitiligo is an immune-related skin disease. Cytokines regulate immune response and inflammation and are involved in the pathogenesis of vitiligo. To assess the serum levels of pro-inflammatory cytokines pre- and post- systemic glucocorticoid treatment in patients with active vitiligo. We measured serum cytokine levels using the enzyme-linked immunosorbent assay in 31 patients with active vitiligo before and after treatment. All patients received systemic glucocorticoid (compound betamethasone injection) in combination with topical halometasone cream and tacrolimus ointment for 3 months. Twenty healthy controls were also examined. The cytokines measured included TNF-α, IL-1β, IL-6, IFN-γ, IL-2, IL-17, IL-10, IL-8, and CXCL10. The serum levels of TNF-α, IL-1β, IL-6, IFN-γ, IL-2, IL-17, IL-8, and CXCL10 were significantly higher, and levels of IL-10 were lower in vitiligo patients compared to controls. Additionally, serum IFN-γ (r = 0.378; p = 0.036), IL-17 (r = 0.426; p = 0.017), and CXCL10 (r = 0.514; p = 0.003) showed a positive correlation with affected body surface area in vitiligo patients. After 3 months of systemic glucocorticoid treatment, the levels of IL-1β, IFN-γ, IL-2, IL-17, and CXCL10 in responders were significantly decreased and nearly restored to normal levels. The IL-10 level was also increased in response to treatment. In contrast, the non-responder group had persistently high IL-6, IL-17, IL-8, and CXCL10 levels, and negligible changes in TNF-α, IL-1β, IFN-γ, IL-2, and IL-10. Our study indicated that the levels of inflammatory cytokines were significantly ameliorated in the glucocorticoid responder group. Altered cell-mediated immunity may contribute to the resistance in vitiligo. The cytokines such as TNF-α, IL-1β, IFN-γ and IL-2 could serve as therapeutic targets for managing glucocorticoid-resistant vitiligo.

HLA-DRB1 Is Associated with Therapeutic Responsiveness in IgG4-related Disease.

Objective Glucocorticoids are key drugs used in remission induction therapy for IgG4-related disease (IgG4-RD). However, the therapeutic outcomes vary widely, with some patients requiring long-term maintenance therapy and others relapsing repeatedly, whereas still others can tolerate withdrawal. These variations underscore the need for personalized treatment strategies for IgG4-RD. We examined the relationship between human leukocyte antigen (HLA) genotypes and the response to glucocorticoid treatment in patients with IgG4-RD. Methods Eighteen IgG4-RD patients visiting our hospital were included in the study. Peripheral blood samples were collected, HLA genotypes were determined, and the response to glucocorticoid treatment (maintenance dose at the time of last observation, glucocorticoid dose when the serum IgG4 level was the lowest after remission induction therapy, and occurrence of relapse) was examined retrospectively. Results The DQB1*12:01 genotypes were associated with a prednisolone maintenance dose of <7 mg/day. A prednisolone dose ≥10 mg with a minimum serum IgG4 level was significantly more common in B*40:01 and DRB1-GB-7-Val (DRB1*04:01, *04:03, *04:05, *04:06, and *04:10) patients than other alleles. Relapse also tended to be more common in DRB1-GB-7-Val carriers than other alleles. Conclusion These data suggest that HLA-DRB1 is associated with glucocorticoid treatment responsiveness and is important for follow-up monitoring of serum IgG4 levels during glucocorticoid tapering. We believe that these data will contribute to the future development of personalized medicine for IgG4-RD.

Safety of corticosteroid therapy in sarcoidosis treatment

Introduction: Sarcoidosis is a multisystemic granulomatous disease of unknown origin and unpredictable cause, characterized by a dysregulated immune response. If histopathological hallmark is represented by the presence of non-caseating granulomas, clinical manifestations are variable and symptoms are not specific, and they depend on organs affected. Although thoracic involvement (lung and mediastinum) is the most common clinical manifestation, any organ can be virtually affected.Methods: This paper is structured as a narrative review. A literature search was performed in four electronic databases (Pubmed, Cochrane, Scopus, and Ovid Medline) and Google from inception until February 2023 for relevant studies, meta-analyses, and reviews on corticosteroids’ adverse events in sarcoidosis. English language only papers were included.Discussion: Although antimetabolites (such as Methotrexate) and immunosuppressant agents can be used as alternative therapy in refractory cases, traditionally systemic glucocorticoids represent the first choice for sarcoidosis treatment. However, their use is still debated, due to potential adverse effects, leading to a wide spectrum of complications particularly in patients who required long-term therapy. Hence, this article aims to provide a comprehensive updated review on the safety profile of glucocorticoid treatment in patients with sarcoidosis and their systemic effects.Conclusion: corticosteroids remain the first choice in Sarcoidosis, however, due to numerous side effects, dose and duration of treatment should be carefully adjusted and monitored by clinicians.

Changes in Arterial Stiffness Monitored Using the Cardio-Ankle Vascular Index in Patients with Rheumatic Disease Receiving Initial Glucocorticoid Therapy: A Clinical Pilot Study.

Systemic inflammatory rheumatic diseases predispose to premature birth, accelerated atherosclerosis, and increased cardiovascular disease (CVD). While glucocorticoids (GCs) are used in various rheumatic diseases, and the associations between GC excess and increased prevalence of CVD complications are well established, the mechanisms underlying GCs' role in atheroma development are unclear. We conducted an observational study to address GC therapy's effect on arterial stiffness using the cardio-ankle vascular index (CAVI) in patients with rheumatic diseases. Twenty-eight patients with rheumatic disease received initial GC therapy with prednisolone at doses ranging from 20 to 60 mg/d. CAVI was examined at baseline and 3 and 6 months after GC therapy. Changes in CAVI and inflammatory parameters were evaluated. GC therapy increased the mean CAVI after 3 months but decreased it to pretreatment levels after 6 months. The mean CAVI substantially decreased with GC treatment in patients <65 years but increased in patients ≥65 years. Alterations in CAVI during the 6-month GC treatment negatively correlated with the lymphocyte-to-monocyte ratio (LMR) at baseline. Conversely, no correlation was observed between alterations in CAVI values and conventional inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Multivariate analysis of factors related to changes in CAVI highlighted young age, high prednisolone dosage, and LMR at baseline. GC temporarily exacerbates but eventually improves arterial stiffness in rheumatic diseases. Particularly in young patients, GC may improve arterial stiffness by reducing inflammation. Therefore, the LMR before GC therapy in rheumatic diseases may be a potential predictor of arterial stiffness.

Inadequate therapeutic responses to glucocorticoid treatment in bronchial asthma.

Bronchial asthma (BA) is a heterogeneous disease. Some patients benefit greatly from glucocorticoid (GC) treatment, whereas others are non-responders. This could be attributable to differences in pathobiology. Thus, predicting the responses to GC treatment in patients with BA is necessary to increase the success rates of GC therapy and avoid adverse effects. The sustained inflammation in BA decreases glucocorticoid receptor (GR, NR3C1) function. Meanwhile, GRβ overexpression might contribute to GC resistance. Important factors in decreased GR function include p38 mitogen-activated protein kinase-dependent GR phosphorylated at Ser226, reduced expression of histone deacetylase 2 following activation of the phosphatidylinositol 3-kinase-δ signaling pathway, and increased nuclear factor-kappa B activity. MicroRNAs, which are involved in GC sensitivity, are considered biomarkers of the response to inhaled GCs. Some studies revealed that inflammatory phenotypes and disease-related modifiable factors, including infections, the airway microbiome, mental stress, smoking, and obesity, regulate individual sensitivity to GCs. Therefore, future investigations are warranted to improve treatment outcomes.

Short-Term Vs. Long-Term Glucocorticoids in COPD Exacerbation: A Comparative Efficacy Study

The current study aims to evaluate the comparative efficacy of short-term and long-term glucocorticoid treatment in patients with COPD exacerbation. A randomized clinical trial will compare the effectiveness of short-term and long-term glucocorticoid treatments in COPD exacerbation. One hundred ninety patients will be recruited and randomized into two groups: a short-term glucocorticoid group and a long-term glucocorticoid group. The primary outcomes will be assessed at the end of the treatment period to determine the efficacy of the treatments. Secondary effects will include quality of life, length of hospitalization, and adverse events. The results of this study will provide insight into the comparative efficacy of short-term and long-term glucocorticoid treatments in COPD exacerbation. Objective: Comparative efficacy of short-term (5-days) versus long-term (10-days) glucocorticoids at equivalent doses in managing COPD patients with acute exacerbations. Materials and Methods: Pakistan Institute of Medical Sciences (PIMS), Islamabad, conducted this randomized clinical trial in the inpatient pulmonology department. This research took six months following ethical clearance. The experiment included 190 patients in two groups of 95. Patients in the two groups were randomly administered Tab—prednisolone 5mg (40mg/24 Hours) for five days or ten days. Using a carefully constructed pro-forma, postgraduate residents gathered data on five parameters (FEV1, FEV1/FVC, Arterial Blood Gases, mMRC Dyspnoea Scale, Sputum color and amount, presentation with identical symptoms within 30 days following discharge). Results: Patients averaged 58.13 ± 11.12. Long-term patients were 58.34 ± 11.53 years old, whereas short-term patients were 57.93 ± 10.752. The short-term group included 86 (90.53%) male and 9 (9.47%) female cases, whereas the long-term group had 89 (93.68%) male and 6 (6.32%) female cases. Sputum color was normal in all groups after therapy. Short-term and long-term therapy groups had mean FEV1 changes of 8.12±4.85 and 7.14± 1.75, respectively. Following treatment, short-term mMRC was significantly lower (2.14±0.32) than long-term (2.73±0.44), with p-value &lt; 0.001. The short-term group mMRC mean change was 1.67±0.53 compared to the long-term group 1.07±0.26, p-value &lt; 0.001. Sputum amounts changed by 2.63 ± 1.67 in the short-term and 2.49 ± 0.72 in the long-term groups. Both groups had similar mean sputum quantities before, after, and after treatment, with a p-value &gt; 0.05. Both groups had the same ABG parameter mean change following therapy. One month after discharge, neither group relapsed. Conclusion: The efficacy of short-term (5-days) glucocorticoids is better than long-term (10-days) glucocorticoids at equivalent doses in terms of mMRC reduction. At the same time, the therapeutic effect was statistically the same in both groups regarding improvement in FEV1, sputum color, sputum quantity, all parameters of ABGs, and relapse rates. Keywords: COPD, exacerbation, glucocorticoids, efficacy

Glucocorticoid treatment in patients with complex regional pain syndrome: A systematic review.

The pathophysiology of complex regional pain syndrome (CRPS) is multifactorial, with an exaggerated inflammatory response being the most prominent. Treatment for CRPS is carried out according to the presenting pathophysiological mechanism. Anti-inflammatory treatment with glucocorticoids is therefore an option. The aim of this study was to systematically review the efficacy of glucocorticoids in CRPS. Embase, Medline, Web of Science and Google Scholar were systematically searched for articles focusing on glucocorticoid treatment and CRPS. Screening based on title and abstract was followed by full-text reading (including reference lists) to determine the final set of relevant articles. Bias was assessed using the revised Cochrane risk-of-bias-tool for randomized trials (Rob2). Forty-one studies were included, which reported on 1208 CRPS patients. A wide variety of glucocorticoid administration strategies were applied, with oral being the most frequently chosen. Additionally, researchers found great heterogeneity in outcome parameters, including clinical symptoms, pain relief and range of motion. The use of glucocorticoids caused an improvement of parameters in all but two studies. In particular, improvement in pain relief and range of motion were reported. Using glucocorticoids in CRPS of longer duration (i.e. more than 3 months) appears to be less effective. Based on the present review, there is evidence to support glucocorticoid treatment in CRPS. However, the ideal administration route and dose remain unclear. We therefore recommend future research via an intervention study, as well as studies on the aetiological mechanisms and corresponding optimal treatment because CRPS pathogenesis is only partially understood. Several studies point towards CRPS being an inflammatory response after tissue or nerve damage, with higher levels of pro-inflammatory cytokines in serum, plasma, cerebrospinal fluid and artificial skin blisters. Inflammation provides a possible role for glucocorticoids in treating CRPS. This systematic review provides a structured overview of glucocorticoid treatment in patients with CRPS. Improvement in pain and range of motion is shown. Systematic review registration number: PROSPERO-CRD42020144671.

NCD64 index as a novel inflammatory indicator for the early prediction of prognosis in infectious and non-infectious inflammatory diseases: An observational study of febrile patients

BackgroundGenerally, febrile patients admitted to the Department of Infectious Diseases, Fudan University Affiliated Huashan Hospital, China may eventually be diagnosed as infectious (ID) or non-infectious inflammatory diseases (NIID). Furthermore, mortality from sepsis remains incredibly high. Thus, early diagnosis and prognosis evaluation of sepsis is necessary. Here, we investigated neutrophil (n)CD64 index profile in a cohort of febrile patients and explored its diagnostic and prognostic value in ID and NIID.MethodsThis observational cohort study enrolled 348 febrile patients from the Emergency Department and Department of Infectious Diseases. nCD64 index were detected using flow cytometry, and dynamically measured at different timepoints during follow-up. Procalcitonin (PCT), C-reactive protein (CRP), and ferritin levels were measured routinely. Finally, the diagnostic and prognostic value of nCD64 index were evaluated by receiver operating characteristic (ROC) analysis and Kaplan-Meier curve analysis.ResultsOf included 348 febrile patients, 238, 81, and 29 were categorized into ID, NIID, and lymphoma groups, respectively. In ID patients, both SOFA score and infection site had impact on nCD64 index expression. In NIID patients, adult-onset Still’s disease patients had the highest nCD64 index value, however, nCD64 index couldn’t distinguish between ID and NIID. Regardless of the site of infection, nCD64 index was significantly higher in bacterial and viral infections than in fungal infections, but it could not discriminate between bacterial and viral infections. In bloodstream infections, gram-negative (G-) bacterial infections showed an obvious increase in nCD64 index compared to that of gram-positive (G+) bacterial infections. nCD64 index has the potential to be a biomarker for distinguishing between DNA and RNA virus infections. The routine measurement of nCD64 index can facilitate septic shock diagnosis and predict 28-day hospital mortality in patients with sepsis. Serial monitoring of nCD64 index in patients with sepsis is helpful for evaluating prognosis and treatment efficacy. Notably, nCD64 index is more sensitive to predict disease progression and monitor glucocorticoid treatment in patients with NIID.ConclusionsnCD64 index can be used to predict 28-day hospital mortality in patients with sepsis and to evaluate the prognosis. Serial determinations of nCD64 index can be used to predict and monitor disease progression in patients with NIID.

Meta-Analysis of the Effectiveness and Safety of Glucocorticoid for the Treatment of IgA Kidney Disease

Purpose To explore the effect of glucocorticoid on immune globulin A (IgA) nephropathy by meta-analysis. Method Search the data and literature libraries of ScienceDirect, EBSCO, Wiley, PubMed, CBMdisc, and CNKI and collect the literature on the treatment of IgA nephropathy with glucocorticoids as randomized controlled trials published at home and abroad from 1995 to 2021. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by fixed-effects model. RevMan 5.0 software was used for meta-analysis of the subgroups of overall curative effect, different degree of proteinuria, different course of treatment, different creatinine level, and combined ACEI. Result ① The overall efficacy of glucocorticoid in the treatment of IgA nephropathy was better than that in the control group (P = 0.00001). ② The efficacy of glucocorticoid treatment in patients with IgA nephropathy with proteinuria greater than 1.50 g/d and less than 1.50 g/d was better than that in the control group (P < 0.01). ③ For IgA nephropathy patients with serum creatinine less than 1.50 mg/dl, the curative effect of glucocorticoid treatment was better than that of the control group (P < 0.01). ④ The effects of short-term treatment (<1 year) and long-term treatment (≥1 year) with glucocorticoid were better than those in the control group (P < 0.01). ⑤ The effect of hormone combined with ACEI drugs on IgA nephropathy was more significant (P < 0.01). Conclusion The overall efficacy of glucocorticoid in the treatment of IgA nephropathy is accurate. Hormone treatment is effective for different degrees of IgA nephropathy. Considering that there is no significant effect on the efficacy of different courses of treatment, it is suggested that the course of hormone treatment can be appropriately shortened. Hormone combined with angiotensin-converting enzyme inhibitors (ACEI) can reduce proteinuria more effectively than ACEI drugs alone.

Hypomethylation of thymosin β4 promoter is associated with glucocorticoid therapy in patients with acute-on-chronic hepatitis B-induced liver failure.

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. 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. 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. Patients with ACHBLF who have low levels of Tβ4 methylation may show a more favorable response to glucocorticoid treatment.

Tocilizumab monotherapy after ultra-short glucocorticoid administration in giant cell arteritis: a single-arm, open-label, proof-of-concept study.

Two randomised controlled trials showed a glucocorticoid-sparing effect of tocilizumab in patients with giant cell arteritis. In the GUSTO trial we aimed to evaluate the efficacy and safety of tocilizumab monotherapy after ultra-short-term glucocorticoid treatment in patients with new-onset giant cell arteritis. This investigator-initiated, single-arm, single-centre, open-label, proof-of-concept trial with a Simon's two stage design was done at University Hospital Bern, Bern, Switzerland. We enrolled patients aged older than 50 years newly diagnosed with giant cell arteritis (within 4 weeks before the screening visit) satisfying the American College of Rheumatology criteria or with large vessel vasculitis-associated polymyalgia rheumatica. The participants received 500 mg methylprednisolone intravenously for 3 consecutive days. Thereafter, glucocorticoid treatment was discontinued and a single infusion of tocilizumab (8 mg/kg bodyweight) was administered intravenously, followed by weekly subcutaneous tocilizumab injections (162 mg) until week 52. The primary endpoint was the proportion of patients who had remission within 31 days and showed no relapse at week 24. The secondary endpoints were the proportion of patients with complete relapse-free remission of disease at weeks 24 and 52, and time to first remission, first relapse (after induction of remission), and first partial remission. This study is registered with ClinicalTrials.gov, NCT03745586. From Nov 23, 2018, to Sept 22, 2019, 18 patients were enrolled (12 of 18 were female, 18 of 18 were White) with a median age of 72 (IQR 67-75) years. Overall, 15 of 18 patients had cranial symptoms, ten of 18 had polymyalgia rheumatica symptoms, and 13 of 18 showed a positive histopathology. At the interim analysis, three (25%) of 12 patients were in remission. The null hypothesis could not be rejected, and the study was futile with respect to the primary endpoint. However, 14 (78%) of 18 patients had remission within 24 weeks (mean time to first remission 11·1 weeks, 95% CI 8·3-13·9) and 13 of 18 showed no relapses up to 52 weeks (72%, 47-90). Mean time to first partial remission was 6·2 [3·7-8·7] weeks. Time to first relapse (after induction of remission) could not be estimated as there was no relapse after induction of remission. Overall, three of 18 patients did not respond to treatment and two of 18 discontinued the study due to an adverse event (hepatopathy [one] and diverticulitis [one]). Anterior ischaemic optic neuropathy occurred in one patient. The data show a slow remission-inducing and a lasting remission-maintaining effect of tocilizumab after an ultra-short pulse of glucocorticoids in patients with newly diagnosed giant cell arteritis. As a proof-of-concept study, our data do not allow us to propose clinical recommendations. Bern University Hospital, University of Bern, and F Hoffmann-La Roche.

Association of altered lipid profile with disease activity, duration, and glucocorticoid treatment in patients with idiopathic inflammatory myopathies

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): AZV CR, Czech health research council MHCR, Ministry of Health Dzech republic Background Systemic inflammation, limited mobility, and glucocorticoid treatment in Idiopathic inflammatory myopathies (IIM) can have a negative impact on intermediate metabolic pathways, especially on lipid metabolism. Purpose The aim of this study was to assess the differences in the lipid profile of IIM patients and healthy controls (HC) and the association with disease-specific features. Methods 133 patients with IIM (106 females; mean age 60.3; disease duration 2.2 years; dermatomyositis, DM 47 / polymyositis, PM 41 / immune-mediated necrotizing myopathy, IMNM 45) and 133 age-/sex-matched HC (106 females, mean age 60.2) were included. Data are presented as median (IQR). Results Several differences in disease activity, the dose of glucocorticoids, prevalence of comorbidities, and serum lipid levels were observed among the three subtypes of IIM. Lipid profile parameters, especially levels of negative cardiovascular predictive markers such as TC, TG, LDL-C, Apo-B, and the atherogenic index were significantly higher compared to HC. The most significant changes were observed in IMNM compared to age-/sex-matched HC. Levels of TC, TG, LDL-C, apo-B, and non-HDL negatively correlated with disease duration but positively with laboratory markers of disease activity and the current prednisone equivalent dose. Higher levels of HDL-C were associated with decreased levels of CRP, which is in line with the negative correlation of apo-A levels with CRP, CK, and myoglobin. Conclusions: We have observed significant alterations in serum lipid parameters in our IIM patients compared to healthy age-/sex-matched individuals. Differences were also found among the three IIM subtypes. These alterations were associated with laboratory parameters of disease activity and the current dose of corticosteroids. Abstract Figure. Results - lipidogram in IIM and HC

Prognostic impacts of glucocorticoid treatment in patients with polymyalgia rheumatica and giant cell arteritis

Identifying comorbidities in polymyalgia rheumatica/giant cell arteritis (PMR/GCA) is crucial for patients’ outcomes. The present study aimed to evaluate the impact of the inflammatory process and glucocorticoid treatment on aortic arterial stiffness and body composition in PMR/GCA. 77 patients with newly diagnosed PMR/GCA were treated with oral glucocorticoids and followed for 40 weeks. Aortic pulse wave velocity (PWV) was measured at baseline and during the follow-up period and compared to the results of temporal artery biopsy (TAB) and 18F-FDG PET/CT. Body composition was assessed by total body DXA at baseline and the end of the study. Of 77 patients (49 (63.6%) female, mean of age: (71.8 ± 8.0)), 64 (83.1%) had pure PMR, 10 (13.0%) concomitant PMR and GCA, and 3 (3.9%) pure GCA. Compared to baseline values, aortic PWV was initially decreased at week 16 (p = 0.010) and remained lower than baseline at week 28 (p = 0.002) and week 40 (p < 0.001), with no association with results of TAB and 18F-FDG PET/CT. Aortic PWV was significantly associated with age, male gender, left systolic and diastolic blood pressure, right diastolic blood pressure, and CRP. Total bone mineral content (BMC) was decreased in both genders (p < 0.001), while fat mass (FM) was significantly increased (p < 0.001). However, lean body mass did not significantly change during the study. Changes in FM were correlated with cumulative prednisolone dose (rho: 0.26, p = 0.031). Glucocorticoid treatment of patients with PMR/GCA had several prognostic impacts. Arterial stiffness was decreased due either to the treatment or a reduction in the inflammatory load. Additionally, treatment led to changes in body composition, including a decrease in BMC and FM excess.

Glucocorticoid treatment in patients with newly diagnosed immune thrombocytopenia switches CD14++ CD16+ intermediate monocytes from a pro-inflammatory to an anti-inflammatory phenotype.

Immune thrombocytopenia (ITP) is thought to result from an aberrant adaptive autoimmune response, involving autoantibodies, B and T lymphocytes, directed at platelets and megakaryocytes. Previous reports have demonstrated skewed CD4+ T-helper subset distribution and enhanced production of pro-inflammatory cytokines such as interleukin 17A and interferon gamma. The role of monocytes (MCs) in ITP is less widely described, but innate immune cells have a role in shaping CD4+ T-cell phenotypes. Glucocorticoids (GCs) are commonly used for first-line ITP treatment and modulate a broad range of immune cells including T cells and MCs. Using multiparameter flow cytometry analysis, we demonstrate the expansion of intermediate MCs (CD14++ CD16+ ) in untreated patients with newly diagnosed ITP, with these cells displaying a pro-inflammatory phenotype, characterised by enhanced expression of CD64 and CD80. After 2weeks of prednisolone treatment (1mg/kg daily), the proportion of intermediate MCs reduced, with enhanced expression of the anti-inflammatory markers CD206 and CD163. Healthy control MCs were distinctly different than MCs from patients with ITP before and after GC treatment. Furthermore, the GC-induced phenotype was not observed in patients with chronic ITP receiving thrombopoietin receptor agonists. These data suggest a role of MCs in ITP pathogenesis and clinical response to GC therapy.

Differential Levels of Endoplasmic Reticulum Stress in Peripheral Blood Mononuclear Cells from Patients with Sudden Sensorineural Hearing Loss.

BackgroundSudden sensorineural hearing loss (SSNHL) is currently treated with a combination of drugs, predominantly with glucocorticoids (GCs). However, the mechanisms of action of GCs in SSNHL are unknown. This study aimed to analyze the role of endoplasmic reticulum stress (ERS) in SSNHL pathogenesis and prognosis.Material/MethodsIn this study, we evaluated the expression and activation status of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-C/EBP homologous protein (CHOP) pathway in peripheral blood mononuclear cells (PBMCs) from patients with SSNHL and compared them with those in healthy controls. We also compared differences in expression of activating transcription factor 4 (ATF4) and CHOP before and after glucocorticoid treatment in patients with improved and unimproved SSNHL.ResultsTreatment with GCs significantly improved hearing in 55% of patients with SSNHL. Levels of phosphorylated PERK (p-PERK) and phosphorylated eukaryotic initiation factor 2α were increased in PBMCs from patients with SSNHL compared with healthy controls. ATF4 and CHOP expression were also significantly elevated. After treatment, the amount of ATF4 and CHOP proteins in PBMCs in the patients whose SSNHL improved was significantly reduced compared with the levels measured before treatment in all patients with SSNHL. The expression of the ATF4 and CHOP proteins in PBMCs in the unimproved group, however, was not significantly changed relative to pretreatment levels.ConclusionsERS may play a significant role in the pathogenesis of SSNHL, and the responsiveness of the condition to GC-mediated mitigation of ERS may be one of the key factors that affect patient prognosis.

Glucocorticoids Increase Risk for Infection in Patients with Rheumatoid Arthritis

The goal of glucocorticoid treatment in patients with rheumatoid arthritis (RA) is to use the lowest possible steroid dose that alleviates symptoms.

Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19.

The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.

Early variation of ultrasound halo sign with treatment and relation with clinical features in patients with giant cell arteritis

To compare the ultrasound characteristics with clinical features, final diagnosis and outcome; and to evaluate the halo size following glucocorticoid treatment in patients with newly diagnosed GCA. Patients with suspected GCA, recruited from an international cohort, had an ultrasound of temporal (TA) and axillary (AX) arteries performed within 7 days of commencing glucocorticoids. We compared differences in clinical features at disease presentation, after 2 weeks and after 6 months, according to the presence or absence of halo sign. We undertook a cross-sectional analysis of the differences in halo thickness using Pearson's correlation coefficient (r) and Analysis of Variance (ANOVA). A total of 345 patients with 6 months follow-up data were included; 226 (65.5%) had a diagnosis of GCA. Jaw claudication and visual symptoms were more frequent in patients with halo sign (P=0.018 and P=0.003, respectively). Physical examination abnormalities were significantly associated with the presence of ipsilateral halo (P<0.05). Stenosis or occlusion on ultrasound failed to contribute to the diagnosis of GCA. During 7 days of glucocorticoid treatment, there was a consistent reduction in halo size in the TA (maximum halo size per patient: r=-0.30, P=0.001; and all halos r=-0.23, P<0.001), but not in the AX (P>0.05). However, the presence of halo at baseline failed to predict future ischaemic events occurring during follow-up. In newly diagnosed GCA, TA halo is associated with the presence of ischaemic features and its size decreases following glucocorticoid treatment, supporting its early use as a marker of disease activity, in addition to its diagnostic role.

Shoulder ultrasound and serum lactate dehydrogenase predict inadequate response to glucocorticoid treatment in patients with polymyalgia rheumatica.

We aimed to identify predictors of inadequate response to glucocorticoid (GC) treatment in patients with polymyalgia rheumatica (PMR). We retrospectively studied 32 patients as a derivation cohort and 24 patients as a validation cohort. The patients were divided into two groups according to the response to GC treatment: GC-responders and GC-inadequate responders (GC-IRs). We compared laboratory data and bilateral shoulder ultrasound findings between the groups. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff value of candidate predictors of treatment response; the predictors were examined using multivariate logistic analysis. Gray-scale ultrasound findings of long head of the biceps (LHB) tenosynovitis and subacromial/subdeltoid (SAD) bursitis were scored semiquantitatively (0-3). A total gray-scale score (TGSS) was calculated as the sum of the gray-scale scores. In the derivation cohort, serum lactate dehydrogenase (LDH) levels and TGSS were significantly higher in GC-IRs than in GC-responders. On ROC analysis, the cutoff values of serum LDH levels ≥ 175IU/ml and TGSS ≥ 5 were found to be the candidate predictors. Multivariate logistic analysis revealed an independent association of both the predictors with inadequate response to GC treatment. In the validation cohort, patients with one or both predictors exhibited a higher incidence of inadequate response to GC treatment. These findings indicate that the severities of LHB tenosynovitis and SAD bursitis evaluated using ultrasound and serum LDH levels are independent predictors of inadequate response to GC treatment in patients with PMR. Treatment adjustment based on prediction model may allow precise treatment of patients with PMR.