Patients Receiving Glucocorticoid Therapy Research Articles

Glucocorticoid-Induced Myopathy: Typology, Pathogenesis, Diagnosis, and Treatment.

Glucocorticoid-induced myopathy is a non-inflammatory toxic myopathy typified by proximal muscle weakness, muscle atrophy, fatigue, and easy fatigability. These vague symptoms coupled with underlying disorders may mask the signs of glucocorticoid-induced myopathy, leading to an underestimation of the disease's impact. This review briefly summarizes the classification, pathogenesis, and treatment options for glucocorticoid-induced muscle wasting. Additionally, we discuss current diagnostic measures in clinical research and routine care used for diagnosing and monitoring glucocorticoid-induced myopathy, which includes gait speed tests, muscle strength tests, hematologic tests, bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI), electromyography, quantitative muscle ultrasound, histological examination, and genetic analysis. Continuous monitoring of patients receiving glucocorticoid therapy plays an important role in enabling early detection of glucocorticoid-induced myopathy, allowing physicians to modify treatment plans before significant clinical weakness arises.

Navigating the waves in Colombia: a cohort study of inpatient care during four COVID-19 waves

IntroductionUnderstanding the intricate dynamics between different waves of the COVID-19 pandemic and the corresponding variations in clinical outcomes is essential for informed public health decision-making. Comprehensive insights into these fluctuations can guide resource allocation, healthcare policies, and the development of effective interventions. This study aimed to compare the characteristics and clinical outcomes of COVID-19 at peak transmission points by including all patients attended during the first four pandemic waves in a referral center in Colombia. Material and methodsIn a prospective observational study of 2733 patients, clinical and demographic data were extracted from the Fundacion Valle de Lili's COVID-19 Registry, focusing on ICU admission, Invasive Mechanical Ventilation (IMV), length of hospital stay, and mortality. ResultsOur analysis unveiled substantial shifts in patient care patterns. Notably, the proportion of patients receiving glucocorticoid therapy and experiencing secondary infections exhibited a pronounced decrease across waves (p < 0.001). Remarkably, there was a significant reduction in ICU admissions (62.83% vs. 51.23% vs. 58.23% vs. 46.70 %, p < 0.001), Invasive Mechanical Ventilation (IMV) usage (39.25% vs. 32.22% vs. 31.22% vs. 21.55 %, p < 0.001), and Length of Hospital Stay (LOS) (9 vs. 8 vs. 8 vs. 8 days, p < 0.001) over the successive waves. Surprisingly, hospital mortality remained stable at approximately 18‒20 % (p > 0.05). Notably, vaccination coverage with one or more doses surged from 0 % during the initial waves to 66.71 % in the fourth wave. ConclusionsOur findings emphasize the critical importance of adapting healthcare strategies to the evolving dynamics of the pandemic. The reduction in ICU admissions, IMV utilization, and LOS, coupled with the rise in vaccination rates, underscores the adaptability of healthcare systems. Hospital mortality's persistence may warrant further exploration of treatment strategies. These insights can inform public health responses, helping policymakers allocate resources effectively and tailor interventions to specific phases of the pandemic.

Donor Pericardial Interleukin and Apolipoprotein Levels May Predict the Outcome after Human Orthotopic Heart Transplantation

The proinflammatory cascade that is activated at the time of brain death plays a crucial role in organ procurement. Our aim of this study was to explore the relationship between the clinical outcome of orthotopic heart transplantation, as well as cytokine and apolipoprotein profiles of the pericardial fluid obtained at donation. Interleukin, adipokine and lipoprotein levels in the pericardial fluid, as well as clinical data of twenty donors after brain death, were investigated. Outcome variables included primary graft dysfunction, the need for posttransplantation mechanical cardiac support and International Society for Heart and Lung Transplantation grade ≥ 2R rejection. Hormone management and donor risk scores were also investigated. Lower levels of IL-6 were observed in primary graft dysfunction (median: 36.72 [IQR: 19.47-62.90] versus 183.67 [41.21-452.56]; p = 0.029) and in the need for mechanical cardiac support (44.12 [20.12-85.70] versus 247.13 [38.51-510.38]; p = 0.043). Rejection was associated with lower ApoAII (p = 0.021), ApoB100 (p = 0.032) and ApoM levels (p = 0.025). Lower adipsin levels were detected in those patients receiving desmopressin (p = 0.037); moreover, lower leptin levels were found in those patients receiving glucocorticoid therapy (p = 0.045), and higher T3 levels were found in those patients treated with L-thyroxine (p = 0.047) compared to those patients not receiving these hormone replacement therapies. IL-5 levels were significantly associated with UNOS-D score (p = 0.004), Heart Donor Score (HDS) and Adapted HDS (p < 0.001). The monitoring of immunological and metabolic changes in donors after brain death may help in the prediction of potential complications after heart transplantation, thus potentially optimizing donor heart allocation.

Association between hospital-acquired pneumonia and proton pump inhibitor prophylaxis in patients treated with glucocorticoids: a retrospective cohort study based on 307,622 admissions in China.

BackgroundProphylaxis with proton pump inhibitor (PPI) in patients treated with glucocorticoid therapy is a common phenomenon in the general wards of Chinese hospitals. Many of these prescriptions are inappropriate and lead to overuse. Hospital-acquired pneumonia (HAP) is a possible adverse effect for this combination but remains controversial.MethodsWe designed a retrospective cohort study using electronic medical record databases from multiple hospitals to investigate whether PPI prophylaxis increases the risk of HAP in hospitalized patients receiving glucocorticoid therapy. The study population was adult patients who were not critical and treated with at least 1 dose of glucocorticoid during hospitalization and the exposure factor was PPIs prophylaxis. The odds ratio of HAP between the exposed and unexposed groups was calculated based on the cohort which was established by propensity score matching. The dose-effect relationship between PPI prophylaxis and HAP was also evaluated.ResultsAmong the 307,622 admissions eligible for the study, a total of 217,460 (70.7%) admissions had a record of PPI prophylaxis. After reconstructed the cohort by propensity score matching, the exposed and unexposed groups both included 83,786 admissions. The incidence of HAP in the exposed group was higher than that in the unexposed group (2.1% vs. 1.5%, OR: 1.4, 95% CI: 1.3 to 1.5). The risk of HAP increased when the cumulative dose of PPI during hospital was more than 2 defined drug doses. Compared to the unexposed group, the adjusted odds ratio was 1.3 (95% CI: 1.2 to 1.4) in the medium-dose group (2–7 defined drug doses) and 1.9 (95% CI: 1.8 to 2.1) in the high-dose group (>7 defined drug doses).ConclusionsPPI prophylaxis increased the risk of HAP in hospitalized patients treated with glucocorticoid therapy and the risk of HAP increased as the dose of PPIs accumulated.

Corticosteroid use in chronic dermatologic disorders and osteoporosis.

Glucocorticoid-induced osteoporosis (GIOP) is a frequently encountered and serious side effect of glucocorticoid use. Bone loss leading to an increased risk for fracture occurs early in the use of glucocorticoids, yet patients at risk for this complication are often undertreated. All physicians prescribing glucocorticoids should therefore be familiar with a basic approach to anticipating and preventing GIOP when starting patients on glucocorticoid therapy. This manuscript and its case vignettes are designed to help dermatologists assess and manage bone health to prevent GIOP in patients receiving glucocorticoid therapy.

Polymeric micelle mediated follicular delivery of spironolactone: Targeting the mineralocorticoid receptor to prevent glucocorticoid-induced activation and delayed cutaneous wound healing

Impaired wound healing in patients receiving glucocorticoid therapy is a serious clinical concern: mineralocorticoid receptor (MR) antagonists can counter glucocorticoid-induced off-target activation of MR receptors. The aim of this study was to investigate the cutaneous delivery of the potent MR antagonist, spironolactone (SPL), from polymeric micelle nanocarriers, prepared using a biodegradable copolymer, methoxy-poly(ethylene glycol)-di-hexyl-substituted-poly(lactic acid). Immunofluorescent labelling of the MR showed that it was principally located in the pilosebaceous unit (PSU), justifying the study rationale since polymeric micelles accumulate preferentially in appendageal structures. Cutaneous biodistribution studies under infinite and finite dose conditions, demonstrated delivery of pharmacologically relevant amounts of SPL to the epidermis and upper dermis. Preferential PSU targeting was confirmed by comparing amounts of SPL in PSU-containing and PSU-free skin biopsies: SPL nanomicelles showed 5-fold higher delivery of SPL in the PSU-containing biopsies, 0.54 ± 0.18 ng/mm2vs. 0.10 ± 0.03 ng/mm2, after application of a hydrogel in finite conditions. Canrenone, an active metabolite of SPL, was also quantified in skin samples. In addition to being used for the treatment of delayed cutaneous wound healing by site-specific antagonism of the MR, the formulation might also be used to treat pilosebaceous androgen-related skin diseases, e.g. acne vulgaris, since SPL is a potent androgen receptor antagonist.

Chinese expert consensus on the diagnosis and treatment of severely and critically ill patients with coronavirus disease 2019.

Chinese expert consensus on the diagnosis and treatment of severely and critically ill patients with coronavirus disease 2019.

Нарушения углеводного обмена у ревматологических пациентов, получающих терапию глюкокортикоидами (обзор литературы)

Нарушения углеводного обмена у ревматологических пациентов, получающих терапию глюкокортикоидами (обзор литературы)

Factors impacting on the action of glucocorticoids in patients receiving glucocorticoid therapy.

Glucocorticoids (GCs) are steroid hormones, which are essential for life. They are secreted by the adrenal cortex under the control of the hypothalamic-pituitary-adrenal (HPA) axis. Glucocorticoids are essential for the normal function of most organ systems and, in both, excess and deficiency can lead to significant adverse consequences. Adrenal insufficiency (AI) is a rare, life-threatening disorder characterized by insufficient production of corticosteroid hormones. Primary AI is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids despite normal or increased adrenocorticotropin hormone (ACTH). Secondary AI is adrenal hypofunction due to insufficient amount of ACTH produced by the pituitary gland. Conventional treatment of both primary and secondary adrenal insufficiencies involves lifelong glucocorticoid replacement therapy. The role of cortisol deficiency and the impact of hydrocortisone replacement on morbidity and mortality in this patient group are under increasing scrutiny. Established glucocorticoid replacement regimens do not completely mirror endogenous hormonal production, and their monitoring to ensure optimum therapy is hampered by the lack of reliable biomarkers of hormone sufficiency. A further confounding issue is the tissue-specific regulation of glucocorticoid through the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) with research focusing on the role of this prereceptor regulation in the development of adverse metabolic features in patients. This review defines the factors influencing glucocorticoid action in patients with adrenal insufficiency receiving glucocorticoid therapy.

Assessment of drug–drug interactions between voriconazole and glucocorticoids

Voriconazole is used to treat fungal infections in patients receiving glucocorticoid therapy in clinic. The objective of this study was to characterize the potential drug–drug interactions (DDIs) between voriconazole and glucocorticoids using physiologically based pharmacokinetic (PBPK) models. Voriconazole and glucocorticoids PBPK models were constructed by using physicochemical data and pharmacokinetic parameters in healthy subjects, and verified by comparing the predicted pharmacokinetic parameters with corresponding data acquired from published literatures. The refined PBPK models were employed to predict the potential DDIs between voriconazole and glucocorticoids. The results showed that the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from 0 h to infinity (AUC0→inf) of dexamethasone were increased by 2.44-fold and 2.60-fold when combined with voriconazole, respectively. For methylprednisolone, the Cmax and AUC0→inf were increased by 1.56-fold and 2.23-fold, respectively. Our results indicate that the dose of dexamethasone or methylprednisolone can be reduced to maintain approximately similar exposures when used concomitantly with voriconazole.

Trabecular Bone Score Reflects Trabecular Microarchitecture Deterioration and Fragility Fracture in Female Adult Patients Receiving Glucocorticoid Therapy: A Pre-Post Controlled Study

A recently developed diagnostic tool, trabecular bone score (TBS), can provide quality of trabecular microarchitecture based on images obtained from dual-energy X-ray absorptiometry (DXA). Since patients receiving glucocorticoid are at a higher risk of developing secondary osteoporosis, assessment of bone microarchitecture may be used to evaluate risk of fragility fractures of osteoporosis. In this pre-post study of female patients, TBS and fracture risk assessment tool (FRAX) adjusted with TBS (T-FRAX) were evaluated along with bone mineral density (BMD) and FRAX. Medical records of patients with (n = 30) and without (n = 16) glucocorticoid treatment were retrospectively reviewed. All patients had undergone DXA twice within a 12- to 24-month interval. Analysis of covariance was conducted to compare the outcomes between the two groups of patients, adjusting for age and baseline values. Results showed that a significant lower adjusted mean of TBS (p = 0.035) and a significant higher adjusted mean of T-FRAX for major osteoporotic fracture (p = 0.006) were observed in the glucocorticoid group. Conversely, no significant differences were observed in the adjusted means for BMD and FRAX. These findings suggested that TBS and T-FRAX could be used as an adjunct in the evaluation of risk of fragility fractures in patients receiving glucocorticoid therapy.

Contribution of the Polymyalgia Rheumatica Activity Score to Glucocorticoid Dosage Adjustment in Everyday Practice

To evaluate the usefulness of the polymyalgia rheumatica (PMR) activity score (PMR-AS) in guiding adjustment of glucocorticoid (GC) dosage. Rheumatologists prospectively included patients receiving GC therapy for PMR. At each visit, they assessed disease activity using a visual analog scale for physician's global assessment (VASph) and recorded whether a flare was diagnosed and/or the GC dosage was changed. In each patient, the PMR-AS was calculated using the formula of Leeb and Bird: C-reactive protein (mg/dl) + VAS pain score (0 to 10) + VASph (0 to 10) + (morning stiffness in min × 0.1) + elevation of upper limbs (0-3). We evaluated the correlation between PMR-AS and GC dosage changes in the group already treated with GC. We included 89 patients (mean age 74.6 ± 6.2 yrs; disease duration 1.6 ± 2.2 yrs), who had a total of 149 visits. PMR-AS was available for 137 visits. Of those, 124 involved patients already treated with GC, and 13 patients who started GC treatment. The Spearman correlation coefficient between PMR-AS values and GC dosage change was 0.58 (p < 0.001). In the group already treated with GC, when the PMR-AS was higher than 20, GC dosages were never decreased. When the PMR-AS was between 10 and 20, GC dosages were decreased in 4 patients, unchanged in 4, and increased by < 5 mg in 4 patients. When PMR-AS was < 10, GC dosages were generally decreased. The PMR-AS is helpful for diagnosing flares of PMR and may also assist in everyday practice to decide how to change the GC dosage.

Glucocorticoid-induced autophagy in osteocytes

Glucocorticoid (GC) therapy is the most frequent cause of secondary osteoporosis. In this study we have demonstrated that GC treatment induced the development of autophagy, preserving osteocyte viability. GC treatment resulted in an increase in autophagy markers and the accumulation of autophagosome vacuoles in vitro and in vivo promoted the onset of the osteocyte autophagy, as determined by expression of autophagy markers in an animal model of GC-induced osteoporosis. An autophagy inhibitor reversed the protective effects of GCs. The effects of GCs on osteocytes were in contrast to tumor necrosis factor α (TNF-α), which induced apoptosis but not autophagy. Together this study reveals a novel mechanism for the effect of GC on osteocytes, shedding new insight into mechanisms responsible for bone loss in patients receiving GC therapy. © 2010 American Society for Bone and Mineral Research.

Effect of Single Annual Infusion of Zoledronic Acid (5 Mg) on Lumbar Spine Bone Mineral Density versus Daily Oral Risedronate (5 Mg) in Subgroups of Patients Receiving Glucocorticoid Therapy

No data exist in the current literature on the glycemic index (GI) and glycemic load (GL) of the diet of phenylketonuric (PKU) children. The aims of this study were to examine the dietary GI and GL in PKU children on a low-phenylalanine (Phe)-diet and to evaluate whether an association may exist between the carbohydrate quality and the metabolic profile.Twenty-one PKU children (age 5–11 years) and 21 healthy children, gender and age matched, were enrolled. Dietary (including GI and GL) and blood biochemical assessments were performed.No difference was observed for daily energy intake between PKU and healthy children. Compared to healthy controls, PKU children consumed less protein (p = 0.001) and fat (p = 0.028), and more carbohydrate (% of total energy, p = 0.004) and fiber (p = 0.009). PKU children had higher daily GI than healthy children (mean difference (95% confidence interval), 13.7 (9.3–18.3)) and higher GL (31.7 (10.1–53.2)). PKU children exhibited lower blood total and low density lipoprotein cholesterol (LDL) levels (p < 0.01) and higher triglyceride level (p = 0.014) than healthy children, while glucose and insulin concentrations did not differ. In PKU children the dietary GL was associated with triglyceride glucose index (Spearman's correlation coefficient = 0.515, p = 0.034).In PKU children a relationship of the dietary treatment with GI and GL, blood triglycerides and triglyceride glucose index may exist. Improvement towards an optimal diet for PKU children could include additional attention to the management of dietary carbohydrate quality.

Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

We evaluated the efficacy and safety of tacrolimus in patients receiving glucocorticoid therapy for lupus nephritis. Patients with persistent nephritis were randomized to receive 28 weeks of double-blind treatment with tacrolimus (3 mg/day) or placebo. The primary endpoint was the change in the lupus nephritis disease activity index (LNDAI) calculated from scores for daily urinary protein excretion, urinary red cells, serum creatinine, anti-double-stranded DNA antibody, and serum complement. Statistical analysis was performed using the full analysis set. The LNDAI was decreased by 32.9 ± 31.0% (mean ± SD) in the tacrolimus group (n = 28) and was increased by 2.3 ± 38.2% in the placebo group (n = 35) at final evaluation. There was significant improvement in the tacrolimus group. Daily urinary protein excretion showed a significant decrease in the tacrolimus group (p < 0.001). The complement (C3) level showed a significant increase in the tacrolimus group (p = 0.001). Treatment-related adverse events occurred in 92.9% of the tacrolimus group and 80.0% of the placebo group, but the difference was not significant. In patients on glucocorticoid therapy for lupus nephritis, addition of tacrolimus to basal therapy achieved significant improvement compared with placebo. Tacrolimus may therefore be a useful alternative treatment for lupus nephritis.

Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis

The total serum IgE level is a marker of immunological activity in allergic bronchopulmonary aspergillosis (ABPA), and a 35% decline beyond six weeks is traditionally taken as criteria for remission. The aim of this study was to evaluate the magnitude and clinical significance of decline in serum IgE levels at six weeks in patients with ABPA. All consecutive patients with ABPA presenting to the Chest Clinic were followed up with clinical evaluation, total IgE levels and chest x-ray every six weeks for three months. We analyzed the percentage decline in IgE levels and correlated it with clinical outcomes of relapse and complete remission. Of the 242 asthmatics, 54 were diagnosed with ABPA (29 males, 25 females; mean age-34 years). There was clinical and radiological improvement at six weeks in all patients receiving glucocorticoid therapy. The IgE levels fell by a mean of 38.8%, and the decline was significantly higher in patients with baseline IgE levels >2500IU/mL than with levels <or=2500IU/mL (44% vs. 26%). Twenty-two patients did not attain a 35% decline in IgE levels, and this number was significantly higher in patients with IgE levels <2500IU/mL. On multivariate analysis, the decline in IgE levels at six weeks did not predict clinical outcomes. A 35% decline in serum IgE levels at six weeks is not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE levels <2500IU/mL. The quantum decline in serum IgE levels does not predict clinical outcomes.

Poster 43: Effect of Intravenous Zoledronic Acid on Lumbar Spine Bone Mineral Density Compared to Oral Risedronate in Subgroups of Patients Receiving Glucocorticoid Therapy

Poster 43: Effect of Intravenous Zoledronic Acid on Lumbar Spine Bone Mineral Density Compared to Oral Risedronate in Subgroups of Patients Receiving Glucocorticoid Therapy

Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

We evaluated the efficacy and safety of tacrolimus in patients receiving glucocorticoid therapy for lupus nephritis. Patients with persistent nephritis were randomized to receive 28 weeks of double-blind treatment with tacrolimus (3 mg/day) or placebo. The primary endpoint was the change in the lupus nephritis disease activity index (LNDAI) calculated from scores for daily urinary protein excretion, urinary red cells, serum creatinine, anti-double-stranded DNA antibody, and serum complement. Statistical analysis was performed using the full analysis set. The LNDAI was decreased by 32.9 +/- 31.0% (mean +/- SD) in the tacrolimus group (n = 28) and was increased by 2.3 +/- 38.2% in the placebo group (n = 35) at final evaluation. There was significant improvement in the tacrolimus group. Daily urinary protein excretion showed a significant decrease in the tacrolimus group (p < 0.001). The complement (C3) level showed a significant increase in the tacrolimus group (p = 0.001). Treatment-related adverse events occurred in 92.9% of the tacrolimus group and 80.0% of the placebo group, but the difference was not significant. In patients on glucocorticoid therapy for lupus nephritis, addition of tacrolimus to basal therapy achieved significant improvement compared with placebo. Tacrolimus may therefore be a useful alternative treatment for lupus nephritis.

Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD.

Patients on systemic glucocorticoids for graft-versus-host disease (GVHD) after hematopoietic cell transplant are susceptible to invasive fungal infections (IFI), which greatly contribute to morbidity and mortality. We evaluated the efficacy of prophylactic treatment options (voriconazole versus fluconazole or itraconazole) for IFI by performing a retrospective review of patients on glucocorticoids for GVHD given voriconazole (n = 97), fluconazole (n = 36), or itraconazole (n = 36). IFI developed in 7/72 (10%) patients on fluconazole/itraconazole versus 2/97 (2%) on voriconazole (P = 0.03) within the first 100 days of glucocorticoids. Five patients developed Aspergillus IFI on fluconazole/itraconazole (7%), compared to none on voriconazole (0%) (P = 0.008); Aspergillus IFI resulted in death in all 5 patients. We found that IFI occurred in patients who received an initial dose of at least 2 mg/kg/day of prednisone or equivalent; when the analysis was restricted to these patients, the hazard ratio (0.39; 95% confidence interval: 0.08–1.86) was consistent with a protective effect of voriconazole compared with fluconazole/itraconazole, although this subset analysis did not reach significance. Overall survival at 100 days after start of glucocorticoids was 77% in patients given fluconazole/itraconazole and 85% in those given voriconazole (P = 0.22). Our results suggest that voriconazole is more effective than fluconazole/itraconazole in preventing IFI, especially aspergillosis, in patients receiving glucocorticoids posttransplant.

Preventive Effect of Sulfamethoxasole-trimethoprim on Pneumocystis jiroveci Pneumonia in Patients with Interstitial Pneumonia

Pneumocystis jiroveci pneumonia (PCP) is a potentially fatal complication in interstitial pneumonia patients receiving glucocorticoid therapy. Prophylaxis of PCP during glucocorticoid therapy is an important issue in the treatment of interstitial pneumonia. We evaluated the prophylactic effect of sulfamethoxasole-trimethoprim (TMP-SMX) in interstitial pneumonia patients receiving glucocorticoids. We retrospectively analyzed 74 interstitial pneumonia patients who received glucocorticoid therapy. Seven of the 74 patients developed PCP. At the time of diagnosis of PCP, the mean duration of glucocorticoid therapy was 71 days and the mean daily dose of prednisolone was 37 mg. Among the 7 patients, the circulating CD4+ lymphocyte count was 370 /microl on average and it was over 200 /microl in 3 cases. The PCP patients showed a significant reduction of the lymphocyte count at 4 weeks after initiation of steroid therapy. None of the patients who received prophylactic TMP-SMX therapy developed PCP even if the CD4+ lymphocyte count was less than 200 /microl. Interstitial pneumonia patients receiving glucocorticoid therapy can benefit from TMP-SMX prophylaxis against PCP. Development of PCP cannot be ruled out in patients with a CD4+ lymphocyte count of greater than 200 /microl.