Cumulative Glucocorticoid Dose Research Articles

Retroperitoneal fibrosis - diagnosis and treatment.

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. Common symptoms at onset include lower back, abdominal or flank pain. Pain is frequently referred to the hip, to the groin and to the lateral regions of the leg, often with nocturnal exacerbations and not responding to position changes. The disease is commonly associated with signs of systemic inflammatory response (malaise, fever, and anorexia and weight loss). Glucocorticoids are considered the cornerstone of the therapy. The use of other immunosuppressive agents, including cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil and biological agents such as rituximab, tocilizumab and infliximab have been reported as a valuable option mostly in case reports, cases series and small studies. These agents allowed to reduce cumulative dose of glucocorticoids and their adverse effects. Combined therapy is preferable for all patients who suffer from significant glucocorticoid- related toxicity or in cases where glucocorticoids alone are insufficient to treat the condition.

Patients' Baseline Characteristics, but Not Tocilizumab Exposure, Affect Severe Outcomes Onset in Giant Cell Arteritis: A Real-World Study.

Objectives: Giant cell arteritis (GCA) is associated with severe outcomes such as infections and cardiovascular diseases. We describe here the impact of GCA patients’ characteristics and treatment exposure on the occurrence of severe outcomes. Methods: Data were collected retrospectively from real-world GCA patients with a minimum of six-months follow-up. We recorded severe outcomes and treatment exposure. In the survival analysis, we studied the predictive factors of severe outcomes occurrence, including treatment exposure (major glucocorticoids (GCs) exposure (>10 g of the cumulative dose) and tocilizumab (TCZ) exposure), as time-dependent covariates. Results: Among the 77 included patients, 26% were overweight (BMI ≥ 25 kg/m2). The mean cumulative dose of GCs was 7977 ± 4585 mg, 18 patients (23%) had a major GCs exposure, and 40 (52%) received TCZ. Over the 48-month mean follow-up period, 114 severe outcomes occurred in 77% of the patients: infections—29%, cardiovascular diseases—18%, hypertension—15%, fractural osteoporosis—8%, and deaths—6%. Baseline diabetes and overweight were predictive factors of severe outcomes onset (HR, 2.41 [1.05–5.55], p = 0.039; HR, 2.08 [1.14–3.81], p = 0.018, respectively) independently of age, sex, hypertension, and treatment exposure. Conclusion: Diabetic and overweight GCA patients constitute an at-risk group requiring tailored treatment, including vaccination. The effect of TCZ exposure on the reduction of severe outcomes was not proved here.

Medium Versus High Initial Prednisone Dose for Remission Induction in Lupus Nephritis: A Propensity Score-Matched Analysis.

The existing guidelines for lupus nephritis (LN) recommend initial prednisone doses of 0.3-1.0 mg/kg/day. However, recent studies reported noninferior outcomes with lower doses. The aim of this study was to compare the complete renal response rates in LN patients treated with prednisone ≤30 mg/day or ≥40 mg/day. Patients with new-onset LN and standard immunosuppressive treatment were followed for at least 12 months, divided into medium (≤30 mg/day) and high prednisone groups (≥40 mg/day) and matched (propensity score) based on the baseline differences. Complete renal response was defined as proteinuria <0.5 gm/day and no worsening in renal function. Glucocorticoid-related damage was also assessed. High-dose prednisone patients (n = 103; mean ± SD dose 48.6 ± 12.3 mg/day) achieved better rates of complete response compared to the medium group (n = 103; mean ± SD dose 24.2 ± 4.6 mg/day) (61.8% versus 38.2%; P = 0.024) at 12 months. The difference in response rates was reproduced for several subgroups (concomitant immunosuppressive treatment, proliferative/nonproliferative LN). Complete remission rates were higher at 2 years (67.8% versus 39%; P = 0.002) and 3 years (64.9% versus 49.1%; P = 0.025) after LN diagnosis. Cumulative glucocorticoid dose was comparable at 2 and 3 years. Glucocorticoid-related damage was accelerated in both groups for the same period. Higher initial prednisone doses (median 45 mg/day) achieved significantly better rates of complete renal response at 12 months in new-onset LN. Cumulative glucocorticoid dose and damage accrual were not different at 2 and 3 years after LN. Damage was more prominent in the late phases of LN in both groups, underlining the importance of rapid tapering and the need to implement alternative strategies.

Long-term use of glucocorticoids for polymyalgia rheumatica: follow-up of the PMR Cohort Study.

ObjectivesPMR is a common inflammatory condition in older adults, characterized by bilateral hip and shoulder pain and stiffness. Reducing oral glucocorticoids, classically used for ≤2 years, are the mainstay of treatment. This study considers the factors early in the disease course that might be associated with prolonged treatment.MethodsSix hundred and fifty-two people with incident PMR were recruited from English general practices (2012–2014). Participants completed seven questionnaires over 2 years (used to allocate people to pain–stiffness trajectories) and a further long-term follow-up (LTFU) questionnaire a median of 5.16 years after diagnosis. Characteristics of those still taking and having ceased glucocorticoids were described and compared using Kruskal–Wallis and χ2 and Student’s 2-sample t-tests as appropriate.ResultsOf the 197 people completing the LTFUQ questionnaire, 179 people reported ever having taken glucocorticoids. Of these, 40.1% were still on treatment, with a median (quartile 1, quartile 3) daily dose of 5 (1.5, 9) mg. People still taking glucocorticoids were more likely to be older (72.5 vs 70.2 years, P = 0.035), live alone (31.8 vs 15.0%, P = 0.01) and have self-managed their glucocorticoid dose (39.1 vs 11.0%, P < 0.0001). They were also more likely to belong to a pain–stiffness trajectory class with sustained symptoms.ConclusionsPMR is not always a time-limited condition. Few patient characteristics are associated with prolonged treatment early in the disease course, but those who are older and who have sustained symptoms might be at greater risk. Although accurate prediction is not yet possible, clinicians should monitor people with PMR carefully to manage symptoms and reduce the cumulative glucocorticoid dose.

Pentraxin-3 – a potential biomarker in ANCA-associated vasculitis

Objective The aim of this study was to investigate pentraxin-3 (PTX3) as a potential biomarker of inflammatory activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at baseline and 6 month follow-up in a longitudinal cohort. Method Plasma PTX3 levels were measured in 79 newly diagnosed or relapsing AAV patients at baseline and 6 month follow-up, and in 23 healthy controls. Urinary PTX3 levels were measured in 34 of the patients. C-reactive protein (CRP), creatinine, and albuminuria were measured and the cumulative glucocorticoid dose at inclusion was calculated. The Birmingham Vasculitis Activity Score (BVAS) was assessed at baseline and follow-up. Results Plasma PTX3 levels were significantly higher at baseline than at 6 months (2.85 vs 1.23 ng/mL, p < 0.001). Plasma and urinary PTX3 levels correlated with BVAS at baseline (ρ = 0.45, p < 0.001, and ρ = 0.49, p = 0.008, respectively). A significant correlation between both plasma and urinary PTX3 levels and estimated glomerular filtration rate and albuminuria was found. However, there was no correlation between plasma and urinary PTX3 levels. At baseline, plasma and urinary PTX3 levels were significantly higher in patients with kidney involvement. PTX3 levels did not correlate with CRP, nor was there a correlation between CRP levels and BVAS at baseline. Conclusion Plasma and urinary PTX3 seem to reflect disease activity in AAV better than the commonly used CRP. PTX3 may have a potential role as a biomarker in monitoring disease activity in AAV patients, particularly in patients with kidney involvement.

Systemic lupus erythematosus diagnosed during hospitalization: Greater baseline disease activity, short-term damage, and death

ObjectivesTo analyze 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 34 years and 45 (37%) of them were SLEin. Patients in the SLEin group had a median of 144 days from the onset of symptoms to diagnosis of SLE vs. 287 days in the SLEout group (p = 0.04). Initially, SLEin had an average SLEDAI of 10 vs. 8 in SLEout (p = 0.004) and anti-dsDNA was positive in 71% vs. 53% in SLEout (p = 0.07). Within the first 6 months, the average cumulative glucocorticoid dose was 6493 mg in SLEin patients vs. 3563 mg in SLEout (p < 0.001) and immunosuppressant usage was higher in SLEin: 62% vs. 26% in SLEout (p < 0.001). Within the first year, SLEin’s kidney biopsies showed lupus nephritis III or IV in 31% vs. 12% in SLEout (p = 0.003, log-rank test). Within the first 2 years, 6 SLEin patients died vs. 1 SLEout patient (p = 0.02) 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 = 0.04). 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.

Advances in the Treatment of Giant Cell Arteritis.

Giant cell arteritis (GCA) is the most common vasculitis among elderly people. The clinical spectrum of the disease is heterogeneous, with a classic/cranial phenotype, and another extracranial or large vessel phenotype as the two more characteristic patterns. Permanent visual loss is the main short-term complication. Glucocorticoids (GC) remain the cornerstone of treatment. However, the percentage of relapses with GC alone is high, and the rate of adverse events affects more than 80% of patients, so it is necessary to have alternative therapeutic options, especially in patients with worse prognostic factors or high comorbidity. MTX is the only DMARD that has shown to reduce the cumulative dose of GC, while tocilizumab is the first biologic agent approved due to its ability to decrease the relapse rate and lower the cumulative GC doses. However, apart from the IL-6 pathway, there are other pro-inflammatory cytokines and growth factors involved in the typical intima hyperplasia and vascular remodeling of GCA. Among them, the more promising targets in GCA treatment are the IL12/IL23 axis antagonists, IL17 inhibitors, modulators of T lymphocytes, and inhibitors of either the JAK/STAT pathway, the granulocyte-macrophage colony-stimulating factor, or the endothelin, all of which are updated in this review.

Association of androgen excess and bone mineral density in women with classical congenital adrenal hyperplasia with 21-hydroxylase deficiency.

This study aims to assess BMD and its association with androgen excess in women with CAH. We enrolled 92 women with CAH with 21-OH deficiency and retrospectively reviewed their clinical features, hormone concentrations, body composition, glucocorticoid (GC) dose, and BMD. BMD was not different according to the subtypes of CAH. BMD at the lumbar spine was lower in women with CAH with regular menstruation than those with irregular menstruation (1.081 vs. 1.165g/cm2, P < 0.05). BMD was lower in women with CAH with 17-hydroxyprogesterone (17-OHP) < 10ng/mL than in those with ≥ 10ng/mL (lumbar spine, 1.019 vs. 1.150g/cm2; femur neck, 0.806 vs. 0.899g/cm2; total hip, 0.795 vs. 0.943g/cm2; all P < 0.05). After adjusting for age and BMI in correlation analyses, testosterone concentrations were positively correlated with lumbar spine, femur neck, and total hip BMD (r = 0.46, r = 0.38, and r = 0.35, respectively; all P < 0.05), while 17-OHP was positively correlated with lumbar spine BMD (r = 0.38, P < 0.01). In subgroup analysis, 17-OHP was positively correlated with BMD (lumbar spine, r = 0.22; femur neck, r = 0.22; total hip, r = 0.24; all P < 0.05) only in the group with a total cumulative dose of GC ≥ 156.0g/m2. Androgen excess may have a protective effect on BMD in women with classic CAH and high cumulative doses of GC.

Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial

BackgroundPolymyalgia rheumatica is the second most common inflammatory rheumatic disease of people >50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing...

Impact of Glucocorticoid Cumulative Doses in a Real-Life Cohort of Patients Affected by Giant Cell Arteritis.

Objectives: To describe the impact of cumulative glucocorticoid (GC) doses on related adverse events (AEs) in giant cell arteritis (GCA) in a real-life setting. Methods: The medical charts of the last 139 consecutive GCA patients followed in a tertiary centre were retrospectively analysed. The cumulative GC doses were calculated, and the main GC-related AEs were collected during the follow-up. Results: After a median follow-up duration of 35.6 (2–111) months, the median cumulative GC dose in the 139 patients was 9184 (1770–24,640) mg, and 131 patients (94%) presented at least one GC-related AE. Infections (63%) were the most frequently reported GC-related AE, followed by metabolic events (63%), including weight gain in 51% of them. Cardiovascular and neuropsychiatric events occurred in 51% and 47% of patients, respectively. Osteoporotic fractures, muscular involvement, digestive events, geriatric deterioration, skin fragility, ophthalmologic complications and hypokalaemia were reported in <35% of patients. Cardiovascular events (p = 0.01), osteoporotic fractures (p = 0.004), cataract occurrence (p = 0.03), weight gain (p = 0.04) and infections (p = 0.01) were significantly associated with GC cumulative doses > 9 g. Longer GC durations were associated with cataract occurrence (p = 0.01), weight gain (p = 0.03) and all-grade infections (p = 0.048), especially herpes zoster occurrence (p = 0.003). Neuropsychiatric and metabolic events appeared within the first months after GC introduction, whereas herpes zoster recurred, and most cardiovascular AEs emerged after 1 year. Geriatric events, especially osteoporotic fractures, occurred 2 years after GC introduction. Conclusion: This study highlights how frequent GC-related AEs are and the impact of prolonged GC and cumulative doses.

The Impact of High Dose Glucocorticoids on Bone Health and Fracture Risk in Systemic Vasculitides.

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.

Menopause and rheumatoid arthritis as factors associated with osteoporosis development

The aim of the research. To study the role of menopause, glucocorticoids (GCs) intake and characteristics of rheumatoid arthritis (RA) in development of osteoporosis (OP) and osteoporotic fractures. Material and methods. A total of 73 female RA patients in menopause were examined. The control group included 29 female RA patients in premenopause. In addition to standard clinical and laboratory examinations, P1NP, 25(OH)D, CTX-1 were measured, dual-energy x-ray absorptiometry and x-ray of the thoracic and lumbar spine were performed. Statistical analysis was performed using the “Statistica 12.0” software package. Results. Premenopausal patients had lower BMI. Patients in postmenopause had higher rate of OP (42 patients) than the controls (8 patients) (57.5% vs 27.6%, respectively). Among patients in postmenopause, OP was associated with lower BMI (27.6 vs 30.5 kg/m2), higher cumulative dose of GCs (6.9 vs 1.65 g), higher duration of GCs intake (32 vs 18 months), lower RA activity (3.37 vs 3.9 according to DAS28-CRP) and lower CTX-1 level (0.52 vs 0.7 ng/ml). In the same group, osteoporotic fractures were only associated with longer GCs intake (32 vs 24 months). In premenopause patients, OP was associated with longer RA duration (21 vs 6 months), cumulative dose of GCs (13.9 vs 0.45 g), duration of GCs intake (48 vs 3 months), higher level of hs-CRP (46 vs 8 mg/l) and lower P1NP level (51.8 vs 43.8 ng/ml). Osteoporotic fractures in premenopause were associated with RA duration (28 vs 6 months), cumulative dose of GCs (12.5 vs 1.2 g) and lower BMD in all examined areas. Conclusion. The OP rate was higher in postmenopause patients. In both groups, the duration of GCs intake and accumulated dose of GCs were associated with OP. In postmenopause, OP was also associated with lower BMI. In premenopause, OP and osteoporotic fractures were associated with longer RA duration, cumulative dose of GCs and lower BMD in all studied areas.

Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases

BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were...

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.