Cumulative Glucocorticoid Dose Research Articles

The Effects of Treatment on Body Mass Index in Giant Cell Arteritis: A Post Hoc Analysis of the GiACTA Trial.

IntroductionGiant cell arteritis (GCA) requires treatment with high-dose, long-term glucocorticoids (GCs), and tocilizumab is often used early in the treatment paradigm. Weight gain, which is associated with morbidity and mortality, is a major concern for patients, though the factors that contribute to changes in body mass index (BMI) throughout the treatment of GCA are poorly understood.MethodsWe analyzed GCA patients enrolled in the GiACTA (Tocilizumab in Giant Cell Arteritis) trial. We used univariable and multivariable mixed-effects modeling to examine the association between changes in BMI and cumulative GC dose, disease status at baseline (newly diagnosed versus relapsing), randomization to tocilizumab, and disease flares.ResultsA total of 250 patients were included (75% females, mean age 69 years). The mean ± SD BMI change over 52 weeks was 1.18 ± 1.98 kg/m2. On multivariable analysis, cumulative prednisone dose at 52 weeks was independently associated with BMI increase (β = 0.94 kg/m2 for 0–1 g exposure; β = 1.40 kg/m2 for ≥ 4 g exposure; p for trend < 0.001). Relapsing disease at baseline (β = − 0.42 kg/m2 compared to those with newly diagnosed disease; p = 0.002) and flares over 52 weeks in newly diagnosed patients (β = − 0.18 kg/m2 per flare; p = 0.03) were independently associated with lower BMI increase.ConclusionsCumulative prednisone exposure is associated with increased BMI in GCA patients. In those with newly diagnosed disease, effective disease control regardless of the treatment used also contributes to BMI increase. Modest weight gain may be an indicator of adequate treatment response.

Study of risk factors for the osteoporosis development in rheumatoid arthritis in real clinical practice

Introduction. Osteoporosis is a common complication of rheumatoid arthritis. Its development is associated with the mechanisms underlying in the progression of autoimmune inflammatory diseases and therapeutic approaches used for them. The study of risk factors for osteoporosis can contribute to the clarification of its pathogenesis components, as well as the development of new methods for prevention, diagnosis and treatment of this condition.Aim. To study the role of anamnestic, clinical and laboratory factors for secondary osteoporosis in women with rheumatoid arthritis.Materials and methods. 102 women with rheumatoid arthritis were enrolled in our study. Exclusion criterias were type 2 diabetes mellitus, hepatic cirrhosis, hepatocarcinoma and level of alanine aminotransferase ≥ than 3 upper limit ofnormal. The cumulative dose, duration and daily dose of glucocorticoids (GC) were determined by patient intake. All patients undergone standard clinical and immunological examination. Serum fetuin-A, 25-hydroxycalciferol, C-telopeptide of collagen I type, N-terminal propeptide of collagen I type levels were determined using ELISA. X-ray of afflicted joints and dual-energy x-ray absorptiometry were performed. Statistical analysis was performed using conventional methods. Forced data entry was used to perform multiple logistic regression. Hereinafter data is presented as odds ratio (OR) and 95% confirmation intervals (CI).Results. OR for osteoporosis were higher in women of age ≥ 58.5 years (OR 1,07 (1.02–1.12)), body mass index (BMI) ≤ 27 kg/m2 (OR 1.1 (1.01–1.2)), cumulative dose of GC ≥ 7.6 g (OR 1.09 (1.02–1.17), serum fetuin-A levels ≤ 660 μg/ml (OR 1,05 (1,01–1,09) and if the duration of GC intake is more than 3 months (hereinafter if dose of glucocorticoids is ≥ 5 mg for prednisolone daily) (OR 12.3 (4.12–36.5). Adjusted OR for osteoporosis were higher in women of age ≥ 58.5 years old (adjOR 1.08 (1.01–1.16), serum fetuin-A levels ≤ 660 μg/ml (adjOR 1.08 (1.01–1.15) andif the duration of GC intake is ≥ than 3 months (adjOR 12.1 (1.44–102.3).Conclusions. Women with RA of ≥ than 58.5 years old, duration of GCs intake more than 3 months and serum fetuin-A levels ≤ than 660 μg/ml had higher odds for osteoporosis.These are independent factors for osteoporosis in women with rheumatoid arthritis, whichshould be used in patient’s management.

As-Needed Versus Regular Use of Fluticasone Furoate Nasal Spray in Patients With Moderate to Severe, Persistent, Perennial Allergic Rhinitis: A Randomized Trial

To compare the effectiveness of as-needed fluticasone furoate (FF) nasal spray (27.5 μg; 2 sprays once daily for 1 week, followed by as-needed use for 5 more weeks) with that of regular use of FF once daily for 6 weeks in patients with moderate to severe, persistent allergic rhinitis.Patients were at least 18 years of age living in Thailand with year-round allergic rhinitis characterized by symptoms occurring >4 days per week for at least 4 consecutive weeks that impaired daily activities, school or work, sleep, or quality of life. Patients were excluded if they had rhinosinusitis, nasal polyps, significant deviated nasal septum, asthma or chronic lung disease, recent upper respiratory tract infection, or previous allergen immunotherapy. Patients had a mean age of 30 years (SD: 8.4 years) and an average duration of symptoms of 15 years, and 95% were allergic to dust mites.Outcome assessors were single-blinded in evaluating outcomes of this 2-arm, parallel group randomized controlled trial conducted from October 2017 to June 2019 at a large tertiary care university hospital. The primary outcome evaluated was the total nasal symptom score (TNSS), measured by summing the score of 4 primary symptoms (congestion, rhinorrhea, sneezing, and itching) recorded on a 4-point severity scale from 0 (no symptoms) to 3 (severe symptoms). Secondary outcomes included nasal peak inspiratory flow and rhinoconjunctivitis quality of life-36 questionnaire (RCQ-36). The study was adequately powered (80%) to detect a 0.16 point TNSS treatment difference between groups.Disease burden, as measured by primary and secondary outcomes, improved in both groups. The intention-to-treat analysis evaluated all of 108 patients randomly assigned, revealing a nonsignificant trend in TNSS improvement for patients with regular FF use (difference: 1.21; 95% CI: −.08 to 2.49; P = .066). Although RCQ-36, nasal itching scores, and rhinorrhea scores were not significantly different between groups, the nasal peak inspiratory flow (difference: −19.2; P = .009), nasal congestion scores (difference: 0.42; P = .049), and sneezing scores (difference: 0.51; P = .13) favored regular use of FF. Notably, the cumulative dose of FF was far lower in the as-needed group than in that of daily groups (difference: 1920 μg; P < .001), and as-needed FF use was associated with a lower rate of acne (2.0% vs 7.7%).Patients using as-needed FF reported a 49% reduction in cumulative nasal steroid dose over the study period but experienced similar reductions in TNSS and RSQ-36 score.Previous studies of seasonal allergic rhinitis have revealed improved symptom control with regular, compared with as-needed, use of nasal corticosteroids (NCSs). However, adherence to regular use of NCSs challenges this treatment paradigm in the real-world, where less than one-third of patients regularly use NCS as prescribed. The perfect is not the enemy of the good, and, with this study, the researchers add to a body of literature that as-needed NCS use for allergic rhinitis can be a good option, particularly when considered through a lens of patient-preference–sensitive care and shared decision-making. Although this is not a pediatric study, the issue of adherence and cumulative dose of topical glucocorticoid is highly relevant to children. Considering improvements that are possible with as-needed NCS, this option can be a consideration for children who do not have adequate control with a nonsedating oral or nasal 1H-antihistamine. Still, for patients with inadequate control with an as-needed NCS strategy, regular NCS (with or without a nasal antihistamine) may be even more effective, and additional treatment options, such as specific allergen immunotherapy, remain considerations.

Effects of different doses of glucocorticoids on minimally invasive procedures in pain patients with type 2 diabetes

Objective: To investigate the effects of different doses of glucocorticoids on minimally invasive procedures in patients with type 2 diabetes mellitus (T2DM), and optimize the clinical pathways of minimally invasive procedures. Methods: The clinical data of 284 patients with T2DM who received minially invasive procedures from the Department of Pain Medicine, West China Hospital, Sichuan University from May 2017 to May 2020 were retrospectively reviewed. The patients were divided into two groups according to the main diagnostic types: spine-related group (n=148) and herpes zoster group (n=136). According to the cumulative dose of glucocorticoids (GCs) per unit body surface area during the hospitalization, patients were further divided into three subgroups: low-dose group (GCs<3.5 mg/m2), medium-dose group (3.5 mg/m2 ≤GCs<7 mg/m2), and high-dose group (GCs≥7 mg/m2). The clinical characteristics of the patients in different subgroups of the two diseases groups were compared. The effects of the glucocorticoids on the pain intensity, blood glucose, length of hospital stay (LOS) and total hospitalization cost were compared among the 3 subgroups of the two diseases groups. Results: There were no significant differences in the age, gender, height, weight, visual analog scale (VAS) and fasting blood glucose before procedures between the two groups (all P>0.05). The VAS score of the low-dose group from the spine-related group was 4.5±1.6, which was higher than that of the medium-dose group (3.5±1.3) (P=0.004). VAS score was 4.3±1.3 in the medium-dose group and 4.4±1.6 in the high-dose group from the herpes zoster group, which were higher than that in the low-dose group (3.5±0.9) (P=0.006). In terms of blood glucose, the impact on the fasting blood glucose before and after the procedures in the low-dose group from the spine-related group was less than that in the medium dose group (P=0.013). In the herpes zoster group, the blood glucose of the low-dose group was (11±5) mmol/L, which had less influence on the blood glucose fluctuation during the hospitalization than that in the high-dose group [(15±5) mmol/L] (P<0.05). The LOS and hospitalization cost in the low-dose group from the spine-related group were (9±4) d and (10 583±4 851) yuan, respectively, which were less than those in the medium-dose group [(11±3) d and (15 202±7 418) yuan] and high-dose group [(13±6) d and (18 100±4 138) yuan] (all P<0.05); however, there was no significant difference among different subgroups in the herpes zoster group (all P>0.05). Conclusion: When used in the patients with T2DM undergoing minimally invasive procedures for spine-related diseases, low-dose glucocorticoids can obtain more clinical benefit than high dose, and high dose can lead to raised blood glucose, prolong the LOS, and increase the hospitalization cost.

Predictors of decreased bone mineral density in childhood systemic lupus erythematosus: possible role of osteoprotegerin gene polymorphisms.

This study aims to explore effects of osteoprotegerin (OPG) gene polymorphisms and other possible factors on bone mineral density (BMD) in children with systemic lupus erythematosus (SLE). Osteoprotegerin gene rs2073617 and rs3134069 were evaluated in 74 SLE patients and 100 controls then genotypes, alleles and haplotypes' frequencies were compared between cases and controls and between patients with BMD z-scores above and below -2 evaluated by dual energy X-ray absorptiometry (DEXA). Disease activity was evaluated by SLE disease activity index (SLEDAI). The patients aged 14.01±2.6 years and included 57 (77%) females and 27 (36%) patients with BMD z-score below -2. Genotypes, alleles, and haplotypes frequencies did not differ between patients and controls (p>0.05 for all). Rs3134069 GG genotype and G allele (p=0.001, 0.002) and rs2073617 TT genotype and T allele (p=0.01, 0.006) were significantly higher in patients with BMD below -2. Cumulative glucocorticoids dose, disease duration, and SLEDAI scores were higher in patients with BMD below -2 (p=0.01, 0.01, <0.001, respectively). Regression analysis showed T allele of rs2073617, duration of illness (above 36 months), and cumulative SLEDAI (above 10) as independent predictors of decreased BMD (p 0.02, 0.003, and 0.002, respectively). This is the first study to demonstrate OPG gene influence on BMD in children with SLE. The studied SNPs are not risk for developing SLE but, rs2073617T allele is a possible predictor for reduced BMD in SLE. Other predictors include long disease duration and high activity supporting that osteoporosis in SLE is multifactorial.

A Validated Risk Prediction Model for Bone Fragility in Children with Acute Lymphoblastic Leukemia

▪IntroductionDue to bone fragility, children with acute lymphoblastic leukemia (ALL) have a 6-fold greater fracture risk during therapy compared to peers. Osteoporotic fractures are a concern, as they lead to adverse health outcomes including pain, loss of height due to vertebral deformity, and (transient) disability. In previous studies, lower lumbar spine bone mineral density (LS BMD) at ALL diagnosis was found to be prognostic for the occurrence of future fractures. However, routinely performing dual-energy X-ray absorptiometry (DXA) in each newly diagnosed child is not universally feasible. The aim of this study is to develop and validate an easy to use clinical risk prediction model for low lumbar spine bone mineral density (LS BMD Z-score ≤-2.0) at diagnosis, as an important indicator for fracture risk and further treatment-related BMD aggravation.MethodsChildren treated for ALL according to the Dutch Childhood Oncology Group (DCOG-ALL9; model development) protocol (n=249; median age: 7.6 years [range: 4.0-16.6 years]) and children from the Canadian STeroid‐Associated Osteoporosis in the Pediatric Population (STOPP; model validation) cohort (n=99; median age: 7.3 years [range: 4.0-16.6 years]) were included in this study.Multivariable logistic regression analyses were used to develop the prediction model for low LS BMD at diagnosis, defined as a Z-score ≤-2.0 (evaluated with DXA). Candidate predictors included sex, age, height and weight Z-scores at diagnosis of ALL. The receiver operating characteristic area under the curve (AUC) was assessed for model performance.To confirm the association between low LS BMD at diagnosis and bone fragility during and shortly following ALL therapy, we performed multivariable logistic regression analyses. The dependent variables were: one or more symptomatic fractures from ALL diagnosis to 12 months following treatment cessation and low LS BMD at cessation of treatment.In addition, because of homogeneity in the intended glucocorticoid doses, we combined data from the DCOG-ALL9 and STOPP cohorts and performed multivariable pooled cohort analyses (meta-analysis). Potential associations between the six-month cumulative glucocorticoid dose and fractures that occurred in the first year of therapy, were explored. Furthermore, we assessed potential associations between the cumulative glucocorticoid dose at cessation of therapy, and the endpoints ‘low LS BMD at therapy cessation’ and ‘fractures that occurred during treatment and within 12 months following treatment cessation’.ResultsThe prediction model for low LS BMD at diagnosis included weight Z-scores (β = -0.70) and age (β = -0.10) at diagnosis. This model had an AUC of 0.71 (0.63 to 0.78) in the DCOG-ALL9 cohort, and resulted in correct identification of 71% of patients with low LS BMD at ALL diagnosis. Validation on the STOPP cohort showed an AUC of 0.74 (95% CI = 0.63 to 0.84). To calculate the probability of low LS BMD at ALL diagnosis for an individual patient, an online calculator is available at http://lsbmd-risk-calculator.azurewebsites.net/We confirmed that low LS BMD at diagnosis is associated with LS BMD at treatment cessation (OR = 5.9; 95% CI = 3.2 to 10.9) and with symptomatic fractures (OR = 1.7; 95% CI = 1.3 to 2.4) that occurred from diagnosis until 12 months following treatment cessation.In pooled meta-analysis, lower LS BMD at diagnosis (OR = 1.6, 95% CI = 1.1 to 2.4) and six-month cumulative glucocorticoid dose (OR = 1.9, 95% CI = 1.1 to 3.3, for every gram increase) were associated with symptomatic fractures that occurred in the first year of therapy. Higher cumulative glucocorticoid dose at cessation of therapy (OR = 1.5, 95% CI = 1.2 to 2.0, for every gram increase), lower LS BMD Z-scores at diagnosis (OR = 7.9, 95% CI = 4.8 to 13.1) and higher age at diagnosis (OR = 1.6, 95% CI = 1.4 to 1.8), were associated with low LS BMD at cessation of therapy.ConclusionWe developed and successfully validated a risk prediction model for low LSBMD at diagnosis in children aged 4-18 years with ALL. This is important because low LS BMD at diagnosis was strongly associated with bone fragility and fractures during and shortly following treatment for ALL. Our easy to use prediction model, can facilitate awareness and early identification of bone fragility in individual pediatric ALL patients, without performing DXA examination. DisclosuresNo relevant conflicts of interest to declare.

Risk factors for low bone mineral density in postmenopausal women with systemic sclerosis

Aim of the research – to determine the frequency of osteoporosis (OP) and to identify risk factors for a decrease in bone mineral density (BMD) in postmenopausal women with systemic sclerosis (SSс).Subjects and methods. The study included 113 postmenopausal women (median age – 60.0 [54.0; 63.0] years) with a reliable diagnosis of SSc according to the ACR/EULAR criteria (2013). The exclusion criterion was the presence of overlap syndromes. All women were interviewed according to a unified questionnaire, a laboratory and instrumental examination was conducted, including Dual-energy X-ray absorptiometry.Results. OP and osteopenia in at least one measurement area were diagnosed in 45.1% and 48.7% of women, respectively. Multivariate linear regression analysis revealed a negative effect of the total experience of taking glucocorticoids (GCs) on the value of BMD in the lumbar spine (b=–0.005; R2=0.136; p=0.017). Body mass index (BMI) (b=0.007; R2=0.208; p&lt;0.001), glomerular filtration rate (GFR) (b=0.313; R2=0.213; p&lt;0.001) is positive, and the cumulative dose of GCs (b=–0.269; R2=0.134; p&lt;0.001), the duration of taking proton pump inhibitors (PPI) (b=–0.277; R2=0.291; p&lt;0.001) and the duration of postmenopause (b=–0,223; R2=0.134; p&lt;0.001) negatively affected the BMD of the femoral neck. BMD in the total hip (TH) was generally positively associated with BMI (b=0.493; R2=0.244; p&lt;0.001), GFR (b=0.313; R2=0.150; p&lt;0.001), 25-hydroxy calciferol level (b=0.273; R2=0.284; p=0.001), and negatively – with the cumulative dose of GCs (b=–0.219; R2=0.289; p&lt;0.001).Conclusion. 93.8% of postmenopausal women with SSс had reduced BMD. Of the traditional risk factors, only BMI, the duration of postmenopause and the level of vitamin D had an impact on the state of BMD, and among the specific ones – the cumulative dose and duration of taking GCs, PPI and GFR.

New-onset versus relapsing giant cell arteritis treated with tocilizumab: 3-year results from a randomized controlled trial and extension.

ObjectiveTocilizumab plus prednisone induces sustained glucocorticoid-free remission in patients with GCA. However, its long-term benefits in new-onset vs relapsing disease are uncertain, and the value of weekly vs every-other-week dosing has not been evaluated.MethodsIn Giant-Cell Arteritis Actemra (GiACTA) part 1, patients with new-onset or relapsing GCA received blinded tocilizumab weekly (TCZ QW), tocilizumab every-other-week (TCZ Q2W) or placebo for 52 weeks, with a prednisone taper. In part 2 (open-label), patients were treated at investigator discretion for 104 weeks. In this analysis, patients were evaluated according to their original treatment assignments, and outcomes beyond 52 weeks were assessed. Outcomes of interest included time to first flare and cumulative glucocorticoid exposure over 3 years according to baseline disease status.ResultsPart 1 enrolled 250 patients; 215 entered part 2. At baseline, 48% had new-onset disease and 52% had relapsing disease. In patients with new-onset and relapsing disease, the median time to first flare in the TCZ QW group was 577 and 575 days, respectively, vs 479 and 428 days with TCZ Q2W and 179 and 224 days with placebo; the median cumulative glucocorticoid dose was 3068 mg and 2191 mg with TCZ QW, 4080 mg and 2353 mg with TCZ Q2W, and 4639 mg and 6178 mg with placebo.ConclusionTCZ QW delayed the time to flare and reduced the cumulative glucocorticoid dose in patients with relapsing GCA and new-onset GCA. These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA.Trial registrationClinicalTrials.gov, https://clinicaltrials.gov, NCT01791153.

The use of oral glucocorticoids and the risk of major osteoporotic fracture in patients with myasthenia gravis

SummaryOral glucocorticoids may increase major osteoporotic fracture risk (MOF) in myasthenia gravis patients. To assess this risk, we performed a case–control study including all Danish patients with a MOF between 1995 and 2011. We also pooled our data with data from another study. We found no increased risk. Osteoporosis prevention remains advisable.Purpose/introductionThe prolonged use of high doses of oral glucocorticoids (GCs), a common treatment in patients with myasthenia gravis (MG), may increase major osteoporotic fracture (MOF) risk. Previous epidemiological studies did not exclusively focus on patients with MG or had relatively few GC-exposed MG patients. Aims were to evaluate the risk of MOF in MG patients using oral GCs in a large study population and to perform a pooled analysis with data from previous work.MethodsA population-based case–control study (1995–2011) was conducted using the Danish National Health Service. Cases had sustained a MOF, and controls had not. All were aged ≥ 18 years. Multivariate conditional logistic regression estimated odds ratios (ORs) among MG patients using oral GCs versus non-users. Adjustments were made for comorbidities and comedications. In the pooled analysis, results were pooled by the use of generic inverse variance methods, assuming a random-effects model.ResultsWe identified 376,858 cases and 376,858 controls. MOF risk was not elevated in MG patients currently using oral GCs compared to MG patients not on oral GCs (ORadj.: 1.26 (95% CI 0.68–2.33)). The use of the highest cumulative dose of oral GCs (≥ 7 g) did not show an increased risk of MOF among MG patients (ORadj.: 2.00 (95% CI 0.90–4.44)). Our pooled analysis also showed no association between oral GC use and MOF risk.ConclusionThis study showed that oral GC use in patients with MG was not associated with increased risk of MOF in our case–control study and pooled analysis. Osteoporosis prevention in MG patients based on clinical guidelines remains advisable.

Lupus eritematoso sistémico diagnosticado durante una internación: mayor actividad basal de la enfermedad, daño y muerte a corto plazo

ObjectivesTo analyse initial and follow-up features of patients with systemic lupus erythematosus (SLE) diagnosed during hospitalization. MethodsRetrospective analysis of medical records: two groups were studied, a)SLE diagnosed during hospitalization (SLEin), b)SLE diagnosed on an outpatient basis (SLEout). Results123 patients were assessed, 87% female, mean age at diagnosis was 34years and 45 (37%) of them were SLEin. Patients in the SLEin group had a median of 144days from the onset of symptoms to diagnosis of SLE vs 287days in the SLEout group (P=.04). Initially, SLEin had an average SLEDAI of 10 vs 8 in SLEout (P=.004) and anti-dsDNA was positive in 71% vs 53% in SLEout (P=.07). Within the first 6months, the average cumulative glucocorticoid doses was 6493mg in SLEin patients vs 3563mg in SLEout (P<.001) and immunosuppressant usage was higher in SLEin: 62% vs 26% in SLEout (P<.001). Within the first year, SLEin's kidney biopsies showed lupus nephritisIII orIV in 31% vs 12% in SLEout. (P=.003, log-rank test). Within the first 2years, 6 SLEin patients died vs 1 SLEout patient (P=.02) and SLEin patients had more damage as measured by SLICC/ACR Damage Index (median 0, range 25%-75% 0-1 vs Median 0, range 25%-75% 0-0 in SLEout; P=.04). ConclusionsSLEin are initially more active, require higher doses of glucocorticoids and immunosuppressants, have more significant kidney involvement, and present more damage and greater mortality in the short term.

The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection.

BackgroundImmunosuppression may worsen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a nationwide cohort study of the effect of exposure to immunosuppressants on the prognosis of SARS-CoV-2 infection in Denmark.MethodsWe identified all SARS-CoV-2 test-positive patients from February 2020 to October 2020 and linked healthcare data from nationwide registers, including prescriptions for the exposure (immunosuppressant drugs). We estimated relative risks of hospital admission, intensive care unit (ICU) admission and death (each studied independently up to 30 days from testing) with a log-linear binomial regression adjusted for confounders using a propensity score-based matching weights model.ResultsA composite immunosuppressant exposure was associated with a significantly increased risk of death (adjusted relative risk 1.56 (95% CI 1.10–2.22)). The increased risk of death was mainly driven by exposure to systemic glucocorticoids (adjusted relative risk 2.38 (95% CI 1.72–3.30)), which were also associated with an increased risk of hospital admission (adjusted relative risk 1.34 (95% CI 1.10–1.62)), but not of ICU admission (adjusted relative risk 1.76 (95% CI 0.93–3.35)); these risks were greater for high cumulative doses of glucocorticoids than for moderate doses. Exposure to selective immunosuppressants, tumour necrosis factor inhibitors or interleukin inhibitors was not associated with an increased risk of hospitalisation, ICU admission or death, nor was exposure to calcineurin inhibitors, other immunosuppressants, hydroxychloroquine or chloroquine.ConclusionsExposure to glucocorticoids was associated with increased risks of hospital admission and death. Further investigation is needed to determine the optimal management of coronavirus disease 2019 (COVID-19) in patients with pre-morbid glucocorticoid usage, specifically whether these patients require altered doses of glucocorticoids.

Antineutrophil cytoplasmic antibody (ANCA) vasculitis: pathophysiology, diagnosis, and the evolving treatment landscape.

The antineutrophil cytoplasmic antibody (ANCA) vasculitides include several closely related, often severe, multisystem autoimmune diseases characterized by antibodies against serine proteinase 3 (PR3) or myeloperoxidase. Loss of tolerance to these antigens triggers a cascade of events, beginning with the priming of neutrophils by proinflammatory cytokines and complement activation, translocation of ANCA-specific antigens to the plasma membrane, neutrophil hyperactivation, and further activation of the alternative complement pathway, leading to tissue damage and the clinical manifestations of ANCA vasculitis. Due to the heterogeneity in presentation of these diseases, diagnosis is often substantially delayed, leading to poor outcomes. The current treatment pathway for most patients involves induction with cyclophosphamide or rituximab in combination with glucocorticoids, followed by a maintenance phase with rituximab, azathioprine, or methotrexate, during which time glucocorticoids are tapered. Current therapies are often effective in inducing and maintaining remission but are associated with a range of toxicities. Several new therapies are in development for ANCA vasculitis. Avacopan, an orally administered inhibitor of the complement fragment 5a (C5a) receptor, has been assessed in a phase 3 clinical trial and may play a role in reducing the cumulative glucocorticoid dose. Preliminary data suggest that cluster of differentiation (CD) 80 and CD86 blockade with abatacept may also have a role in the management of ANCA vasculitis. There is an unmet need for additional therapeutic options for patients with these diseases.

Bone Health Outcomes at 1 Year after Hematopoietic Stem Cell Transplantation in a Heterogeneous Pediatric Population

Impaired bone mineral density (BMD) is a known complication of hematopoietic stem cell transplantation (HSCT) in adults and may lead to increased fracture risk. Less is known in children about the risks for impaired BMD and fragility (low trauma) fractures after HSCT. In this study, we evaluated the incidence of fragility fractures in a large diverse pediatric HSCT recipient population and identified risk factors for both fracture and impaired BMD. We reviewed the records of 237 patients age ≤21 years at the time of transplantation who underwent HSCT at our institution between January 2015 and March 2018. The primary endpoint was the incidence of fragility fractures, and the secondary endpoint was assessment of BMD on dual-energy X-ray absorptiometry (DXA). DXA studies were available for analysis in 79 of 206 patients who were alive at 1 year after HSCT, and the median height-for-age adjusted z-score for spine BMD was 0.15. Among the 237 patients in this study, 25 (10.5%) had evidence of at least 1 fragility fracture on imaging. In the patients with at least 1 fragility fracture, 18 (72%) sustained spine fractures. The median time to fracture was 5.9 months after HSCT. Mortality at 1 year was proportionally higher, although not statistically significantly so (P=.11) in patients who had at least 1 fragility fracture (24%; 6 of 25) compared with patients without a fragility fracture (12%; 25 of 212). Vitamin D status at 1 year post-HSCT was sufficient (>20 ng/mL) in 94% of the patients assessed (160 of 171). There was no difference in the incidence of fracture between vitamin D-sufficient patients and vitamin D-insufficient patients (P=1.0). The incidence of fracture was significantly higher in patients with graft-versus-host disease (GVHD) compared with those without GVHD (15% vs 6%; P=.02). There was no significant difference in fracture occurrence between patients who received reduced-intensity conditioning and those who received myeloablative conditioning. The cumulative glucocorticoid dose was significantly associated with fracture in patients exposed to glucocorticoids for >3 months (P=.03). The incidence of fragility fractures, especially vertebral compression fractures, after pediatric HSCT is striking. Furthermore, there may have been additional, asymptomatic patients in our cohort with undetected, occult fractures. The high incidence of fragility fractures seen in this study advocates for establishing bone health screening protocols with attention to spinal imaging in pediatric patients undergoing HSCT.

Genetic factors contributing to late adverse musculoskeletal effects in childhood acute lymphoblastic leukemia survivors.

A substantial number of survivors of childhood acute lymphoblastic leukemia (ALL) suffer from treatment-related late adverse effects. While multiple studies have identified the effects of chemotherapeutics and radiation therapy on musculoskeletal outcomes, few have investigated their associations with genetic factors. Here we analyzed musculoskeletal complications in relation to common and rare genetic variants derived through whole-exome sequencing of the PETALE cohort. Top-ranking associations were further assessed through stratified and multivariate analyses. DUOX2 variant was associated with skeletal muscle function deficit, as defined by peak muscle power Z score ≤ -2 SD (P = 4.5 × 10-5 for genotyping model). Upon risk stratification analysis, common variants in the APOL3, COL12A1, and LY75 genes were associated with Z score ≤ -2 SD at the cross-sectional area (CSA) at 4% radial length and lumbar bone mineral density (BMD) in high-risk patients (P ≤ 0.01). The modulation of the effect by risk group was driven by the interaction of the genotype with cumulative glucocorticoid dose. Identified variants remained significant throughout multivariate analyses incorporating non-genetic factors of the studied cohort. This exploratory study identified novel genetic variants associated with long-term musculoskeletal impairments in childhood ALL survivors. Replication in an independent cohort is needed to confirm the association found in this study.

Postnatal glucocorticoid use impacts renal function in VLBW neonates.

BackgroundPreterm neonates often require glucocorticoids to manage refractory hypotension, prevent, and treat bronchopulmonary dysplasia. We have investigated the effect of cumulative dose and duration of glucocorticoids on blood pressure and renal function in VLBW infants.MethodsIn this retrospective cohort study, medical records of infants (GA ≤ 35 weeks) born January 2015 to December 2019 were reviewed to extract demographic and clinical characteristics, dose and duration of steroids, blood pressure (BP), and creatinine at the time of discharge from the neonatal intensive care unit.ResultsTwo hundred and eighty-three neonates with average GA (28 ± 3 weeks) and birthweight (1060±381 g). Twenty-eight percent (33/116) of infants who received postnatal steroids developed hypertension versus 16% (27/167) of controls (OR = 2.0, p = 0.011). There was a correlation between the cumulative dosage of postnatal steroids and systolic BP (R2 = 0.06, p < 0.001). With increasing steroid dose and total steroid days, there was a significant increase in creatinine clearance at the time of discharge (R2 = 0.13, p < 0.001; R2 = 0.13, p < 0.001, respectively).ConclusionsCumulative dose of postnatal steroids and duration of use is associated with increased systolic BP in premature infants. Postnatal steroids should be used prudently to prevent long-term cardiovascular and renal morbidity.Impact Preterm neonates are exposed to a high dose of glucocorticoids during their neonatal intensive care stay.The dose and duration of use of postnatal glucocorticoids was associated with significant increase in blood pressure at the time of discharge in preterm neonates.Postnatal glucocorticoid use is associated with improved creatinine clearance likely due to a state of hyperfiltration and may lead to chronic kidney disease later in life.Postnatal glucocorticoids should be used prudently in this highly vulnerable population

Moderate-to-Vigorous Physical Activity Is Associated With Higher Bone Mineral Density in Children With Inflammatory Bowel Disease.

Decreased mineral bone density (BMD) and reduced lean body mass (LBM) are common amongst children with inflammatory bowel disease (IBD). The aim of our cross-sectional, observational study was to evaluate the relationship between BMD, body composition and physical activity (PA) in children with IBD in remission. Total body less head (TLBH) dual energy X-ray absorptiometry (DXA) was used to measure BMD, fat mass (FM) and lean body mass (LBM). Triaxial accelerometer for five consecutive days was used to objectivize PA. Forty pediatric IBD patients in clinical remission (24 boys; age 15.3 ± 0.4 years; Crohn disease [CD], n = 20, ulcerative colitis [UC], n = 18, inflammatory bowel disease-unclassified [IBD-U], n = 2) were recruited. Mean BMD was 0.940 g/cm2 and mean BMD z score was -0.42 ± 0.14. Patients with CD had significantly lower BMD than UC counterparts (P < 0.001). Average time spent in PA was 247.24 ± 16.71 min/day with 45.73 ± 8.22 min/day spent in moderate-to-vigorous PA (MVPA). We observed a significant positive correlation between the time spent in MVPA and BMD z score (P = 0.003) and LBM z score (P = 0.026). Multivariate analysis confirmed that the positive correlation of MVPA and BMD z score. There was no significant correlation between daily protein intake and BMD. Cumulative glucocorticoid dose negatively correlated with LBM z score (P = 0.003), but not with BMD z score (P = 0.069). This study points to a strong positive relationship between MVPA, LBM and BMD. Longitudinal studies are required in order to elucidate the modifiable processes that determine body health and favorable body composition.

Perioperative Glucocorticoids in Patients With Rheumatoid Arthritis Having Total Joint Replacements: Help or Harm?

ObjectiveThe optimal strategy for perioperative glucocorticoid (GC) management in patients with rheumatoid arthritis (RA) on chronic GCs is unknown. Although there is a concern for hypotension if inadequate doses are used, higher GC exposure may increase perioperative complications. We aimed to investigate the relationships between perioperative GCs with hemodynamic instability and short‐term postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA) in patients with RA.MethodsThis retrospective study included patients with RA who underwent THA and TKA. GC exposure was assessed by the total cumulative dose (in prednisone equivalents) during hospitalization. Perioperative complications and hypotension were assessed.ResultsOf 432 patients, 387 (90%) received supraphysiologic perioperative GC. Thirty percent of patients were using chronic GCs (mean daily dose, 7 ± 4 mg). Half (54%) underwent TKA. The median age was 65 years, and 79% were women. The median cumulative GC dose during hospitalization was 37 mg (interquartile range, 27‐53.3). A lower cumulative dose of GC did not increase odds of hypotension during hospitalization (unadjusted odds ratio, 1.00 [95% confidence interval, 0.99‐1.01]; P = 0.66)]. However, postoperative complications were higher among patients who received higher cumulative doses after adjustment for age, body mass index, home GC use, smoking, and Charlson Comorbidity Index. Risk of short‐term complications increased by 8.4% (P = 0.017) for every 10‐mg increase in GC dose.ConclusionA lower GC dose was not associated with increased hypotension. However, patients with higher GC exposure were more likely to have hyperglycemia and other complications. These findings suggest that harms may be associated with high perioperative GC doses. Further research is needed to determine the optimal perioperative regimen for patients with RA.

Long-term results of hip arthroplasty and determination of unfavorable risk factors for early development of osteonecrosis in patients with systemic lupus erythematosus

Aim of the study – to determine the risk factors for the early development of osteonecrosis and to analyze the results of surgical treatment of patients with systemic lupus erythematosus in the long term after total hip arthroplasty.Materials and methods. The study group included 42 patients with systemic lupus erythematosus (SLE) complicated by osteonecrosis (ON) of the femoral head, who underwent 59 total hip arthroplasty (THA) operations. Before surgery and 6–21 years after THA, in order to assess the long-term results of surgical treatment of patients, the following was assessed: activity of the underlying disease – according to the SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index 2000); the severity of irreversible changes in internal organs – according to the SLICC/ACR index of damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology); the clinical and functional state of the hip joint – according to the HHS (Harris Hip Score); the intensity of pain syndrome – according to the visual analogue scale (VAS); quality of life (QOL) – using the SF-36 questionnaire. The concentration of antibodies to cardiolipin (aCL) of IgM and IgG isotypes was determined by enzyme-linked immunosorbent assay (normal range – 0.0–10.0 GPL for IgM, 0–7 MPL for IgG).Results. After 6–21 years of follow-up after THA, there was a statistically significant decrease in pain intensity according to VAS, improvement according to the HHS from 40.0±14.9 to 83.3±17.4 points, SLE activity according to the SLEDAI-2K from 0 to 20 points (median – 4 [4; 8] points) before surgery and from 0 to 41 points (median – 0 [0; 4] points) after a long period of observation. There was a pronounced statistically significant positive dynamics for all QOL indicators studied (p≤0.005 in all cases). The most significant changes were found on the scales RE (Role-Emotional), RP (Role-Physical Functioning) and BP (Bodily Pain). The early development of ON was associated with the degree of activity of the underlying disease, the cumulative dose of glucocorticoids, kidney damage and arthritis in the first year from the onset of SLE, as well as hematological disorders and the presence of aCL in the blood serum 3 years before the onset of ON. The total number of complications was 10.2%.Conclusion. Total hip arthroplasty in patients with systemic lupus erythematosus can achieve a statistically significant reduction in pain intensity, increase functional activity and improve their quality of life.

Low-dose oral glucocorticoid therapy and risk of osteoporotic fractures in patients with rheumatoid arthritis: a cohort study using the Clinical Practice Research Datalink.

ObjectivesClinical trials have shown that low-dose glucocorticoid therapy in patients with RA reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA.MethodsThis was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7–12 months) and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, adjusted for lifestyle parameters, comorbidities and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids.ResultsAmong 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent dose/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98, 1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11, 2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids.ConclusionClinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased.

Ultrasound halo sign as a potential monitoring tool for patients with giant cell arteritis: a prospective analysis

ObjectivesTo assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed giant cell arteritis (GCA).MethodsProspective study...