Glucocorticosteroid Treatment Research Articles

Prognostic role of the updated Kiel classification in canine high-grade T-cell lymphomas.

The aim of this study was to determine and describe the prognostic role of the morphological subtype determined according to the updated Kiel classification in dogs with high-grade T-cell lymphomas (HGTCLs) depending on the treatment applied. The HGTCLs were classified into three subtypes according to the updated Kiel classification: pleomorphic mixed (PM), lymphoblastic lymphoma/acute lymphoblastic leukaemia and plasmacytoid (P). The treatment was divided into a palliative therapy (PlT) group and a chemotherapy (ChT) group. The study was conducted between 2009 and 2017, and it enrolled 58 dogs in which cytomorphological and immunocytochemistry diagnoses were HGTCL. Overall survival (OS) was significantly longer in the ChT group (median OS-4 months, interquartile range [IQR] from 2 to 8 months) than in the PlT group (median OS-6 weeks, IQR from 1 week to 3 months). In the PlT group, PM subtype and glucocorticosteroids (GCSs) treatment proved significantly and independently linked to longer OS and approximately three-fold lower risk of death during the study period (adjusted hazard ratio [HRadj] = 0.26, confidence interval [CI] 95%: 0.08-0.81; p = 0.020 and HRadj = 0.30, CI 95%: 0.11-0.77; p = 0.013, respectively), although due to small group size, precision of estimations was poor (wide CI 95%). In the ChT group, >7 days elapsing between diagnosis and the beginning of chemotherapy and GCS treatment prior to chemotherapy were significantly associated with lower chance of complete remission (CR; p = 0.034 for both); GCS treatment prior to chemotherapy was significantly associated with shorter OS (p = 0.016); chemotherapy based on the modified CHOP protocol was significantly associated with higher chance of CR (p = 0.034) and longer OS (p = 0.039); and CR was significantly linked to longer OS (p = 0.001). The morphological subtype of HGTCL has some prognostic value in dogs treated palliatively (with PM subtype associated with longer OS than P subtype); however, this effect is no longer visible when a dog is treated with chemotherapy.

The Impact of Steroid Responder Status on Long-Term Outcomes in Critically Ill Patients With Acute Respiratory Distress Syndrome Receiving High-Dose Glucocorticoids.

Background and objective High-dose intravenous pulsed glucocorticosteroids (GCS) are not part of the standard treatment in acute respiratory distress syndrome (ARDS), and the evidencesupporting their use is conflicting. In clinical practice, however, they are used in specialist settings when clinico-patho-radiological features suggest a potentially steroid-responsive pattern, or as a last resort in cases where patients are unable to be weaned off mechanical ventilation. This study aimed to investigate if an early objective response to high-dose GCS treatment in selected critically ill patients is predictive of survival in ARDS. Methods This study involved a case series of 63 patients treated at a tertiary specialist respiratory ICUbetween 2009 and 2017 who received high-dose GCS for ARDS following a multidisciplinary board agreement. Patients were stratified according to the change in their modified lung injury score (mLIS) between days 0 and 10 following GCS initiation. Changes in mLIS (range: 0-4)were grouped as follows - full responders: ≥2, partial responders: ≥1 and <2, and non-responders: <1. Mortality on discharge and at 6, 12, 18, and 24 months post-ICU discharge was assessed for each group. Data were analysed using logistic regression and a receiver operating curve (ROC) to determine a statistically significant association between the change in mLIS and survival. Results Of the 63 patients, there were seven full responders, 12 partial responders, and 44 non-responders to high-dose GCS. Overall mortality at ICU discharge and 6, 12, 18 and 24 months post-discharge was 29/63 (46.0%), 33/63 (52.4%), 34/63 (54.0%), 34/63 (54.0%), and 35/63 (55.6%) respectively. Mortality was significantly lower in the partial and full-response groups than in the non-response group at all time frames. Logistic regression showed a significant association between the change in mLIS and survival (p<0.001), and a ROC demonstrated that categorising the change in mLIS was a good predictive model for survival (c-statistic 0.86). Conclusions Measuring the change in mLIS by day 10 following high-dose GCS administration for ARDS may beclinically useful in prognosticating such patients. Further research using mLIS as a measure of response to GCS, and larger datasets to enable the evaluation of prognostic factors, may assist clinicians in predicting which patients with persistent ARDS are likely to respond to GCS therapy.

Steroid myopathy and rehabilitation in patients with cancer.

Steroids are broadly used in oncology, despite known adverse events such as glucocorticosteroid-induced myopathy (SM). To date there are no accepted guidelines on the diagnosis and treatment of SM. The purpose of this review is to provide up-to-date information regarding SM with emphasis on neuro-oncology and hematopoietic stem cell transplant patients, given they are at high risk of experiencing SM following routine treatment with steroids. Our work is a combination of a comprehensive narrative review regarding etiology, pathogenesis, incidence, clinical presentation and treatment options for SM and a scoping review on the exercise therapy for SM. We have identified 24 in vivo studies of different exercise modalities in the settings of glucocorticosteroid treatment. Twenty of 24 studies demonstrated decreased muscle catabolism with exercise training. Both endurance and resistance exercises at mild to moderate intensity were beneficial. The value of high-intensity activities remains questionable as it may worsen muscle atrophy. Rehabilitation interventions, along with pharmacologic and dietary considerations, may be beneficial in preventing or reversing SM. Potential adverse events of some of these interventions and expected caveats in translating findings in preclinical models to human settings warrant caution and demand controlled clinical studies.

Search for predictors of methotrexate toxicity in rheumatoid arthritis

Aim. To determine prognostic markers of methotrexate (MT) toxicity in rheumatoid arthritis (RA).Materials and methods. The study included 294 patients with RA who were prescribed MT at a dose of 10 to 25 mg per week for the first time as basic anti-inflammatory therapy (BPVT). The following adverse events (AEs) were recorded: hepatotoxicity, toxicity from the gastrointestinal tract, blood system. Qualitative parameters were considered as possible predictors of MT intolerance: gender, obesity, smoking, systemic manifestations, as well as rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (ACCP), intake of glucocorticosteroids (GCS), form of administration of MT; and quantitative: age of RA onset, baseline disease activity according to DAS28 (Disease Activity Score 28) and HAQ (Health Assessment Questionnaire), MT dose. Statistical processing was performed by one-factor methods using Pearson’s χ2 test with Yates correction, Fisher’s exact two-tailed test, Mann–Whitney U-test, and Student’s t-test. Multivariate analysis was carried out by binary logistic regression.Results. In a univariate analysis, significant results were obtained for hepatotoxicity: a direct correlation with the use of corticosteroids at the onset (odds ratio (OR) 2.0; 95 % confidence interval (CI) 1.1–3.8, p = 0.03), inversely correlated with MT tablet intake (OR 0.5, 95 % CI 0.2–0.95, p = 0.03). According to the results of multivariate analysis, hepatotoxicity was recorded more often when taking GCS in the debut 2.01 times (95 % CI 1.02–3.96, p = 0.043), and in the presence of ACCP – 3.16 times (95 % CI 1.06–9.45, p = 0.039); and less frequently when taking tableted MT by 2.62 times (95 % CI 0.17–0.84, p = 0.017). Gastrointestinal toxicity tends to be associated with a younger age of RA onset (p = 0.06) and greater RA HAQ activity at onset (p = 0.07).Conclusions. Hepatotoxicity is more expected in patients seropositive for ACCP and GCS treatment in the onset of RA, but is less common when taking MT tablets. AEs from the gastrointestinal tract are associated with a younger age of onset of the disease and a greater degree of activity according to the HAQ index.

NMR-based metabolomics in giant cell arteritis and polymyalgia rheumatica sequential sera differentiates active and inactive disease.

Giant Cell Arteritis-(GCA) is an inflammatory disease following a chronic, relapsing course. The metabolic alterations related to the intense inflammatory process during the active phase and to the rapid impact of steroid treatment, remain unknown. The study aims to investigate the serum metabolome in active and inactive disease state. 110 serum samples from 50 patients [33-GCA and 17-Polymyalgia rheumatica-(PMR)] at 3 time points, 0-(V1: active disease), 1 and 6 months-(V2 and V3: remission) of treatment with glucocorticosteroids (GCs), were subjected to Nuclear Magnetic Resonance (NMR)-based metabolomic analysis. Multi- and univariate statistical analyses were utilized to unveil metabolome alterations following treatment. Distinct metabolic profiles were identified between activity and remission, independently to disease type. N-acetylglycoproteins and cholines of bound phospholipids, emerged as predictive markers of disease activity. Altered levels of 4 out of the 21 small molecules were also observed, including increased levels of phenylalanine, and decreased of glutamine, alanine, and creatinine in active disease. Metabolic fingerprinting discriminated GCA from PMR in remission. GCA and PMR patients exhibited characteristic lipid alterations as a response and/or adverse effect of GCs treatment. Correlation analysis showed that several identified biomarkers were further associated with acute phase reactants, C-Reactive Protein and Erythrocyte Sedimentation Rate. The NMR profile of serum metabolome could identify and propose sensitive biomarkers of inflammation. Metabolome alterations, following GCs treatment, could provide predictors for future steroid-induced side effects.

The dichotomy of glucocorticosteroid treatment in immune-inflammatory rheumatic diseases: an evidence-based perspective and insights from clinical practice.

Glucocorticosteroids (GCs) are the most used anti-inflammatory and immunosuppressive drugs due to their effectiveness in managing pain and disease modification in many immune-inflammatory rheumatic diseases (IRDs). However, their use is limited because of adverse effects (AEs). The authors analyzed recent studies, including randomized controlled trials (RCTs), observational, translational studies and systematic reviews, providing an in-depth viewpoint on the benefits and drawbacks of GC use in rheumatology. Glucocorticosteroids are essential in managing life-threatening autoimmune diseases and a cornerstone in many IRDs given their swift onset of action, necessary in flares. Several RCTs and meta-analyses have demonstrated that when administered over a long time and on a low-dose basis, GC can slow the radiographic progression in early rheumatoid arthritis (RA) patients by at least 50%, satisfying the conventional definition of a disease-modifying anti-rheumatic drug (DMARD). In the context of RA treatment, the use of modified-release prednisone formulations at night may offer the option of respecting circadian rhythms of both inflammatory response and HPA activation, thereby enabling low-dose GC administration to mitigate nocturnal inflammation and prolonged morning fatigue and joint stiffness. Long-term GC use should be individualized based on patient characteristics and minimized due to their potential AEs. Their chronic use, especially at medium/high dosages, might cause irreversible organ damage due to the burden of metabolic systemic effects and increased risk of infections. Many international guidelines recommend tapering/withdrawal of GCs in sustained remission. Treat-to-target (T2T) strategies are critical in setting targets for disease activity and reducing/discontinuing GCs once control is achieved. Glucocorticosteroids' use in treating IRDs should be judicious, focused on minimizing use, tapering and discontinuing treatment, when possible, to improve long-term safety. Glucocorticosteroids remain part of many therapeutic regimens, particularly at low doses, and elderly RA patients, especially with associated chronic comorbidities, may benefit from long-term low-dose GC treatment. A personalized GC therapy is essential for optimal long-term outcomes.

Chronic Spontaneous Urticaria in Belgium: Deciphering the Clinical Profile and Treatment of Patients Visiting an Urban City Immunology Department

Background: Chronic urticaria (CSU) is a chronic inflammatory mast cell-driven disorder of which reliable clinical data in Belgium are lacking. This study focusses on clinical characteristics of CSU patients presenting at an urban Immunology-Allergology department. Methods: Outpatients with CSU were included from 2018 to 2021. Clinical characteristics, Dermatology Life Quality Index (DLQI) and Urticaria activity score (UAS7) were collected by thorough anamnesis and questionnaires. Furthermore, patients underwent provocational testing, an autologous serum skin test (ASST) and a blood analysis. Results: The study included 49 CSU patients and 20 non-CSU subjects. CSU was distributed differently with age and sex, showing higher numbers in female patients below the age of 46 years. 67% of CSU patients had accompanying angioedema of which 9% were reported genital. CSU patients scored a mean 8/30 on their DLQI questionnaire. There was no significant difference in immunoglobulin E (IgE), C-reactive protein, and tryptase levels between CSU patients and controls. Oral glucocorticosteroids were prescribed in 23% of CSU patients during their disease course though only half of these patients had a severity grade 4 CSU. In 82% of the included CSU patients, Urticaria Control Test (UCT) scores were below 12. When we hypothetically considered low IgE levels and high IgG anti-thyroid peroxidase levels as differentiation marker for autoimmune (ai)CSU and non-aiCSU, we found that 4% of all included CSU patients could be considered aiCSU. Conclusion: Generally, the inner-city population displayed the same clinical characteristics, as previous cohorts from Northern Europe. The relatively high rate of CSU patients receiving oral glucocorticosteroid treatment for their disease though not always classified as severe, underlines the need to train doctors of various specialties in the treatment algorithms of CSU. Furthermore, by looking at potential autoimmune characteristics, our findings open perspectives on the identification of new routinely used clinical parameters for the detection of aiCSU, a relatively small immunological subtype of CSU.

СИНДРОМ МУЛЬТИКІСТОЗНОЇ ЛЕГЕНІ: РІДКІСНІ ВИПАДКИ РЕГРЕСІЇ

Multicystic lung syndrome (MLS) is defined by a presence on chest computed tomography of multiple, round parenchymal attenuations, having distinct borders with normal parenchyma and &lt; 2 mm thick wall. Pneumothorax, usually relapsing, and respiratory failry are the major clinical manifestations of MLS. CT findings can make certain contribution into recognition of the disease but diagnosis is largely based on appropriate symptoms, extrapulmonary signs of systemic disease and/or congenital disease. There has been described three major causes of MLS — lymphangioleiomyomatosis — LAM (sporadic or associated with tuberal sclerosis complex), pulmonary Lanherhans cell histiocytosis (LCH) and in recent time — Birt-Hogg-Dube) syndrome, associated with gene FLCN mutations. Other causes of MLS include lymphoid disorders of lung, especially in Sjögren's syndrome, non-amyloid immunoglobulin deposition disease; infections; malignancy, mainly sarcoma metastasis; desquamative interstitial pneumonia, hypersensitivity pneumonitis, cryptogenic organizing pneumonia with atypical cavity forming regression etc. The cases of regression of MLS in other diseases are rare. In most cases according to literature data regression is documented based on functional improvement which is not confirmed by CT data. The article presents the brief description of two clinical cases of MLS with demonstration of positive CT changes. Presented cases of MLS regression confirm the effectiveness of glucocorticosteroid treatment, which help to restore bronchial passability by means of reduction of compression caused by pulmonary infiltration in patient with organizing pneumonia and involution of granulamatous process in patient with hypersensitivity pneumonitis. In both cases the valvular mechanism of cyst genesis has been interrupted. Key words: multicystic lung syndrome caused by organizing pneumonia and hypersensitivity pneumonitis, glucocorticosteroid therapy, regression.

Centrifugal lipodystrophy on a spectrum with lupus erythematosus panniculitis in children and efficacy and safety of hydroxychloroquine: A clinicopathological study.

This study aimed to investigate the relationship between centrifugal lipodystrophy (CLD) and lupus erythematosus panniculitis (LEP), and the efficacy and safety of hydroxychloroquine (HCQ) for treating CLD in children. A total of 29 cases clinically diagnosed as CLD (n=24) and CLD/LEP overlap (n=5) were enrolled and all were confirmed by skin biopsies of CLD and LEP. The clinicopathological findings, clinical outcomes, and prognosis with the treatment of HCQ between CLD and LEP were compared. All 29 cases (male: female=1:1.6; median age at onset: 3 years) had cutaneous lesions of centrifugally expanding lipoatrophy, of which five cases overlapped with LEP lesions presented as erythematous indurated plaque (n=2), subcutaneous nodules (n=2) and alopecia along Blaschko's lines (n=1). Antinuclear antibodies were found in six (25.0%) CLD and two (40.0%) overlapped patients (p=0.597). Histopathologically, of the 24 cases of CLD, 14 (58.5%) exhibited subcutis loss or mild lobular inflammation. Ten (41.7%) cases displayed lobular panniculitis with moderate to dense lymphohistiocytic infiltrate and plasma cells, similar to the five cases of overlap. Small clusters of CD123 positive plasmacytoid dendritic cells were found in 62.5% (5/8) of CLD and 66.7% (2/3) of overlap cases (p > 0.99). HCQ (5mg/kg/d) treatment showed improvement in 91.3% (21/23) of CLD and all overlap cases, including four cases unresponsive to previous oral glucocorticosteroid treatment. Our findings suggested that CLD and LEP represent a spectrum within the same disease. HCQ (5mg/kg/d) was effective and safe for treating CLD (age >1.5 years), and early treatment and a regular long-term follow-up are essential.

Antenatal glucocorticosteroids treatment: mechanisms of child healths programming

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

Combination therapy of tacrolimus, high doses of glucocorticosteroids, and cyclophosphamide against existing historical treatment for patients in severe conditions of interstitial lung diseases complicated with dermatomyositis: A retrospective analysis.

The high-dose glucocorticosteroid (GC) treatment is the first choice for dermatomyositis complicated with interstitial lung disease (DM-ILD) but patients are resistant to the high-dose GC monotherapy. Besides, the high dose of GC, the secondary immunosuppressive agent(s) is necessary but there is controversy for the selection of immunosuppressive agent(s). The objectives of the study were to analyze the efficacy of different therapeutic options for DM-ILD to identify the optimal therapy. A total of 60 patients had received intravenous 1.0–2.0 mg/ kg/day prednisolone for DM-ILD. In severe conditions, patients had received oral 1 to 3 mg/day tacrolimus (TAC), 500 mg/ m2/month cyclophosphamide (CY), and/or 1 g/ day methylprednisolone pulse (TI cohort, n = 24). In severe conditions, patients had received 1 g/day methylprednisolone pulse and 2–3 mg/ kg/day cyclosporine A (CsA) and/or 500 mg/ m2/month CY (existing historical treatment; CT cohort, n = 36). Patients of the TI cohort did not receive CsA. Patients in the CT cohort were received CY in significantly fewer numbers than those of the TI cohort during treatment (P = .0112). A total of 11 (46%) patients from the TI cohort and 14 (39%) patients from the CT cohort were developed relapsed. At the end of the 30-months, higher numbers of patients of the TI cohort had an event(s) free survival than those of the CT cohort (7 (29%) vs 2 (6%), P = .0229). Also, higher numbers of patients of the TI cohort had survived irrespective of an event(s) than those of the CT cohort (21 (87%) vs 22 (61%), P = .0399). Patients of the TI cohort had developed herpes zoster (2 (8%)) and cytomegalovirus (4 (17%)) infections. Patients of the CT cohort developed renal dysfunction (10 (28%)). Hyperglycemia, hyperlipidemia, and fracture (GC-related toxicities) were also reported in both cohorts and these toxicities were fever in the TI cohort. The addition of TAC to high doses GC with CY is an ideal treatment for severe conditions of DM-ILD (Level of Evidence: III; Technical Efficacy Stage: 4).

MO220: Comparison of the Effects of Hydroxychloroquine and Glucocorticosteroids on Immunological Parametrs in Patients with IGA Nephropathy

Abstract BACKGROUND AND AIMS Current treatment strategies of IgA nephropathy (IgAN) primarily involve blood pressure control, renin–angiotensin–aldosterone system inhibitors (RAASIs), and glucocorticosteroids (GCs), which are recommended when the supporting therapies fail to reduce proteinuria (PU) levels below 1 g/day. Hydroxychloroquine (HCQ) is considered to have an immunomodulatory rather than an immunosuppressant effect. The immune pathways targeted by HCQ are not fully investigated during treatment of IgAN. The aim of this study was to compare effects of HCQ and GCs on immunological parameters in patients with IgAN. METHOD 32 IgAN patients aged 32.0 (26.7 ÷ 36.0) y.o., male/female ratio as 24/8 with PU &amp;gt; 1 g/day and estimated glomerular filtration rate (eGFR) 78 (61; 103) mL/min were divided into three treatment groups: RAASIs (n = 12); HCQ (n = 10); GCs Pozzi protocol (n = 10). The changes in clinical and immunological parameters were analyzed 6 months after treatment. Phenotypic and functional markers of peripheral blood lymphoid cells were identified by flow cytometry method (Cytoflex, «Beckman Coulter», USA). The concentrations of total immunoglobulins (Ig) class M, G, A and E were determined by ELISA method («VectorBest», Russia). Statistical analysis was done using Statistica 8.0. RESULTS After 6 months of treatment HCQ has shown effectiveness in decreasing of PU (P &amp;lt; .001), haematuria level (P &amp;lt;.01) as well as the same effect was noted in the other treatment groups after 6 months course. The renal function was stable in all investigated groups during follow up. There were no any adverse effects of the treatment. The decrease of potential cytotoxic γδTCR+Т-cells (P &amp;lt;.01) and CD3 + 56 + TNK-cells (P &amp;lt; .01) numbers in peripheral blood (Fig. 1) as well as the reduction of IgM (P &amp;lt; 0.05) and IgG (P &amp;lt; .05) serum levels (Table 1) were established in patients receiving HCQ. While GCs treatment resulted in CD3 + T-cells (P &amp;lt; .05) suppression (Fig. 1) mainly due to CD3 + CD4 + T-helpers down-regulation (P &amp;lt; .05) but stimulation of cytotoxic CD3 + CD8 + T-cells (P &amp;lt; .05) (data not shown) and increasing of IgE level (P &amp;lt; .05) (Table 1). It was not revealed any influence of RAASIs treatment either on the number of lymphoid cells populations (Fig. 1) or Ig levels. CONCLUSION This study demonstrates different ways of pathogenic treatment in IgAN. HCQ has exhibited an immunomodulatory action on the effector mechanisms of cellular cytotoxicity via minor lymphoid T-cells populations reduction as well as on productive phase of humoral immunity via IgM and IgG levels decreasing. While GCs have suppressed CD3 + T-cell and supported IgE-mediated autoinflammation.

Dysglycemia in COVID-19 and Type 2 Diabetes Mellitus: Peculiarities of the Glycemic Profile in Hospitalized Patients and the Role of Steroid-Induced Disorders

There is a lack of data on the features of dysglycemia in hospitalized patients with COVID-19 and concomitant diabetes mellitus (DM) confirmed by continuous glucose monitoring (CGM). to study the glycemic profile in hospitalized patients with COVID-19 and type 2 diabetes mellitus by continuous glucose monitoring and the role of steroid therapy in dysglycemiadevelopment. We examined 21 patients with COVID-19 and DM 2 and 21 patients with DM 2 withoutCOVID-19(control group) using a professional 4-7-day CGM. We also compared two subgroups of patients with COVID-19 and DM 2: 1) patients received systemic glucocorticosteroids (GCS) during CGM and 2) patients in whomCGMwas performed after discontinuation of GCS. Compared with controls, patients with COVID-19 and DM2 had lesser values of glycemic «time in range» (32.7 ± 20.40vs 48.0 ± 15.60%, p = 0.026) andhigher parameters of mean glycemia (p &lt;0.05) but similar proportion of patients with episodes of hypoglycemia (33.3% vs 38.1%, p = 0.75). Patients who received dexamethasone during CGM were characterized by higher hyperglycemia and the absence of episodes of hypoglycemia. In patients who hadCGM after dexamethasone discontinuation, hyperglycemia was less pronounced, but 60% of them had episodes of hypoglycemia, often nocturnal, clinically significant and not detected by routine methods. Patients with COVID-19 and DM 2had severe and persistent hyperglycemia but a third of them hadalso episodes of hypoglycemia. During therapy with dexamethasone, they had the most pronounced hyperglycemia without episodes of hypoglycemia. In patients who underwent CGM after discontinuation of dexamethasone, hyperglycemia was less pronounced but 60% of them have episodes of hypoglycemia, often nocturnal, clinically significant and not diagnosed by routine methods. It would be advisable to recommend at least a 5-6-fold study of the blood glucose level (with its obligatory assessment at night) even for stable patients with COVID-19 and DM 2after the end of GCS treatment.

Retrospective Analysis of Factors Associated with Fracture in 714 Patients with Polymyalgia Rheumatica.

Introduction Polymyalgia rheumatica (PMR) is a disease of the elderly, associated with increased fracture risk due to glucocorticosteroid (GC) treatment with the additional possible influence of chronic inflammation. Risk factors for fracture in PMR have not been extensively studied. Hip structure analysis (HSA) is a way to measure bone morphology in the hip using dual X-ray absorptiometry (DEXA). It has been used as a predictor of fracture in epidemiological settings. HSA has not been studied in PMR before. Objectives The object of this retrospective study was to determine if fracture risk in PMR was associated with densitometry data and to determine the influence, if any, of HSA on that association. Methods 714 patients with PMR referred for a bone density estimate at a district general hospital from June 2004 to October 2010 were studied. Demographic data, GC use, alcohol consumption, smoking status, secondary osteoporosis, and fracture history were recorded. Bone mineral density (BMD), Z score, T score, body composition data, and HSA measurements were collected. These were geometric measurements taken from 2-dimensional DEXA images of the hip. Fracture was modelled as an outcome variable using logistic regression models, adjusted for age and sex. And the fit of the model was assessed by comparing the area under the curve (AUC). Results 714 patients were studied, 532 (75%) were female, and mean age was 70.5 with SD of 8.8. 703 (98%) had been treated with GCs. Lumbar and femoral BMD models were significantly associated with fracture. Right femur OR 0.062 (0.014-0.285), left femur OR 0.098 (0.023-0.412), right femoral neck 0.078 (0.014-0.43), left femoral neck 0.104 (0.022-0.492), L1 0.192 (0.066-0.56), L2 OR 0.138 (0.053-0.358), L3 0.192 (0.079-0.463), and L4 0.243 (0.108-0.544). Cross-sectional area was the only HSA parameter that was associated with fracture OR 0.988 (0.980–0.997). Conclusion L2 association models were strongest. Prospective studies are needed to elucidate whether these factors predict future fracture. GC data were binary, not reflecting dose and duration.

Biomarkers Predicting Treatment-Response in Nephrotic Syndrome of Children: A Systematic Review

Purpose: Nephrotic syndrome (NS) is the most common form of glomerulopathy in children. Most pediatric patients respond to glucocorticosteroid treatment (steroid-sensitive NS, SSNS), while approximately 10–15% will remain unresponsive or later become steroid-resistant. There has been a long-standing effort to find biomarkers that may predict steroid responsiveness.Methods: We systematically reviewed current studies which investigated clinically relevant biomarkers for predicting steroid responsiveness in pediatric NS. We performed a PubMed and EMBASE search to identify eligible articles. We collected data on urinary markers, blood/serum markers (including cellular phenotypes and mRNA expression), genotypes and HLA allele frequency.Results: A total of 659 articles were identified following electronic and manual searches. After reviewing the titles, abstracts, and full texts, 72 eligible articles were finally included. Vitamin D-binding protein (VDBP) seemed to be significantly elevated in SRNS than in SSNS, in both serum and urine specimen, although further validation is required.Conclusions: The present paper narratively illustrates current understandings of potential biomarkers that may help predict steroid responsiveness. Further investigation and collaboration involving a larger number of patients are necessary.

Immunogenicity trends 1 and 3 months after second BNT162B2 vaccination among healthcare workers in Israel

ObjectivesWe evaluated the antibody response to the BNT162B2 vaccine among healthcare workers (HCWs) to identify factors associated with decreased immunogenicity. MethodsThis prospective cohort study included consenting HCWs who completed a questionnaire regarding background illnesses, medications, and post-vaccination allergic reactions or rash. All HCWs were tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) 1 and 3 months after the second vaccine dose. A multivariate mixed linear model was adjusted to participants' data and fit to predict antibody levels after the second BNT162B2 vaccine dose, based on antibody levels at 1 month and the slope between 3 months and 1 month. Multivariate analyses identified factors associated with lower antibody levels. ResultsIn total 1506 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Older age was associated with lower mean antibody levels (–1.22 AU/mL, p < 0.001, 95%CI –1.43 to –1.01). In addition, male sex (–22.16 AU/mL, p < 0.001, 95%CI –27.93 to –16.39), underlying condition (–10.86 AU/mL, p 0.007, 95%CI –18.81 to –2.91) and immunosuppressive treatment (–28.57 AU/mL, p 0.002, 95%CI –46.85 to –10.29) were associated with significantly lower mean antibody levels. Allergic reactions after vaccine administration or peri-vaccination glucocorticosteroid treatment were not correlated with antibody levels. ConclusionsMost HCWs had measurable antibodies at 3 months. Risk factors for lower antibody levels were older age, male sex, underlying condition, and immunosuppressive treatment. These factors may be considered when planning booster doses during vaccine shortages.

Корекція порушень ремоделювання кісткової тканини при довготривалій кортикостероїдній терапії

Актуальність. При тяжких дерматозах зазвичай призначаються препарати кортикостероїдних гормонів досить тривалими курсами і навіть довічно, у зв’язку з чим діагностика виникнення побічних ефектів від тривалого використання системних глюкокортикостероїдів (ГКС), зокрема порушень кісткового обміну, а також їх профілактика є важливою складовою комплексної терапії тяжких дерматозів. Тому розробка методів ранньої діагностики, лікування і профілактики появи порушень ремоделювання кісткової тканини під впливом тривалої глюкокортикостероїдної терапії у хворих на тяжкі дерматози вкрай актуальна для сучасної дерматології. Мета дослідження — підвищення ефективності та безпечності лікування хворих на тяжкі дерматози шляхом запобігання або мінімізації розвитку побічних ефектів лікування глюкокортикостероїдними гормонами. Матеріали та методи. У дослідження було залучено 134 хворих на тяжкі дерматози (акантолітична пухирчатка, бульозний пемфігоїд, дерматоз Дюрінга, еритродермія тощо). Використовувалися клініко-анамнестичні, біохімічні, цитологічні, імуноферментні, інструментальні та статистичні методи дослідження. Результати. У хворих у результаті тривалої системної глюкокортикостероїдної терапії виявлялося вірогідне зниження кісткової фракції лужної фосфатази у 2,1 раза, рівня остеокальцину — у 6,6 раза і підвищення рівня С-кінцевого телопептиду у 2,2 раза. За даними ультразвукової денситометрії, остеопенію було виявлено у 35,5 %, остеопороз — у 64,5 % пацієнтів. Для корекції ремоделювання кісткової тканини призначалися препарати кальцію з вітаміном D3 та антирезорбтивний засіб. У результаті відзначалося підвищення зазначених показників, що свідчило про відновлення процесів остеосинтезу та нормалізацію процесів резорбції кісткової тканини, що підтверджувалося підвищенням мінеральної щільності кісткової тканини в 1,8 раза. Для запобігання розвитку порушень процесів ремоделювання кісткової тканини в комплексному лікуванні призначалися препарати антирезорбтивної дії, кальцію і вітаміну D3 в поєднанні із системними ГКС протягом усього курсу терапії. Висновки. Проведене дослідження дозволило підвищити ефективність та безпеку терапії хворих на тяжкі дерматози шляхом запобігання або мінімізації розвитку побічних ефектів лікування глюкокортикостероїдами.

Hip osteoarthritis in juvenile idiopathic arthritis is complication of the disease course or side effect of systemic glucocorticosteroid treatment?

Hip osteoarthritis in juvenile idiopathic arthritis is complication of the disease course or side effect of systemic glucocorticosteroid treatment?

D-dimer concentrations in acute urticaria in children.

Urticaria is a clinical entity presenting as wheals, angioedema, or both simultaneously. Elevated D-dimer levels were reported in the course of chronic spontaneous urticaria. Data regarding D-dimer levels in acute urticaria in children are limited. To assess potential associations between duration of glucocorticosteroid (GCS) therapy and D-dimer concentrations in children with acute urticaria. Hospital records of 106 children (59 females), aged 5.57 ± 4.91 years, hospitalized in 2014-2018 were analyzed retrospectively. The study group consisted of pediatric patients admitted to the hospital due to severe acute urticaria resistant to antihistaminic treatment that was ordered in the ambulatory care (out-patient clinic). Patients were divided into subgroups: no GCS treatment, short-duration treatment (up to 5 days) and long-duration treatment (6 and more days) GCS treatment. Simultaneously, patients received antihistaminic drugs. D-dimer level and other inflammatory factors such as white blood cell (WBC) count, platelet (PLT) count, and C-reactive protein (CRP) in each group were analyzed. The D-dimer level was elevated in 51% of cases. In the subgroup with longer GCS treatment, D-dimer concentration was significantly higher in comparison to patients with a shorter GCS course. There were no differences in the distribution of CRP, PLT, and WBC concentrations between these subgroups. In the studied group of children, there was a tendency for higher D-dimer levels in patients, who required a longer GCS treatment. This finding is hypothesis-generating and requires further investigation to confirm if D-dimers can be used as a prognostic factor in acute urticaria in children.

Clinical characteristics and management of immune checkpoint inhibitor-related pneumonitis: A single-institution retrospective study.

IntroductionThe increasing application of immune checkpoint inhibitors (ICIs) will cause more checkpoint inhibitor‐related pneumonitis (CIP), which is a common cause of ICI‐related death. The clinical management of CIP needs further optimization.MethodsPatients who were managed at Peking Union Medical College Hospital (PUMCH) between February 2017 and December 2019 with a diagnosis of CIP were retrospectively analyzed. Clinical data including clinical manifestations, radiologic data, laboratory and bronchoscopy results, treatments, and outcomes were collected and analyzed. The Mann–Whitney test was used to compare patients with and without co‐infections.ResultsIn total, 48 CIP cases in 42 patients were analyzed. The median time from the first dose of ICI to the onset of CIP was 1.9 months (range: 0.1–13.7). Grade 3–4 (G3–4) accounted for 30 cases (71.4%). The most common symptoms were cough (88.1%) and dyspnea (78.6%). The median starting dose of equivalent prednisone (EP) was 55 mg (range: 30–200) for all patients. The median total duration of glucocorticosteroids (GCS) treatment was 42.5 days (range: 15−89). Three patients (7.14%) died because of infection. A higher starting dose and longer duration of GCS (≥30 mg/day; p = 0.001) were associated with opportunistic infection. Chest computed tomography (CT) showed diverse and asymmetrical lesions. Twelve patients were re‐challenged, and six patients developed recurrent CIP.ConclusionsThe clinical and imaging manifestations of CIP are various, and differential diagnosis of exclusion is essential. GCS at 1–2 mg/kg is feasible to treat CIP, but the duration of GCS ≥30 mg/day should be used with caution, given the high risk of acquired infections. Re‐challenges of ICI are feasible, but the recurrence of CIP needs to be closely monitored.