Glucocorticoid Administration Research Articles

Corticotropin-releasing hormone deficiency results in impaired analgesic response during CFA-induced inflammation.

Corticotropin-releasing hormone (CRH) plays an important role in relief of pain by releasing analgesia-associated molecules in several inflammatory states. During inflammation, peripheral CRH acts on cells of the immune system to stimulate the local expression of proopiomelanocortin (POMC) and the production of β-endorphin, which in turn binds to opioid receptors on sensory neurons to produce antinociception. In the present study, we further investigated the role of endogenous CRH in inflammatory pain by determining the effects of Crh-deficiency on this process. For this purpose, we used Crh-deficient (Crh-/-) mice and their wildtype (Crh + / +) littermates in the CFA (Complete Freund's Adjuvant)-induced inflammatory pain model. Pain thresholds were evaluated with the Hargreaves apparatus. Our experiments showed that Crh deficiency led to increased pain response, which was associated with decreased POMC mRNA levels in locally inflamed paws of these mice. Furthermore, Crh-/- mice had higher paw edema than Crh + / + mice. Histological evaluation of inflamed paw tissues revealed increased inflammatory response in Crh-/- mice. Protein levels of proinflammatory cytokines, such as IL-6, TNF-α, and IL-1β, were higher in inflamed tissue of Crh-/- mice compared to wildtype mice. Corticosterone replacement increased the pain threshold of Crh-/- mice, restored their paw volume to the levels of wildtype mice, and significantly reduced their proinflammatory cytokine levels. Furthermore, glucocorticoid administration significantly increased POMC mRNA expression in the inflamed paw. Our data suggest that genetic deficiency of CRH is associated with increased pain. This effect is likely attributable to the accompanying glucocorticoid insufficiency and is in part mediated by opioids expressed locally.

Depletion of hepatic glutathione and adenosine by glucocorticoid exposure in Wistar rats is pregnancy-independent

Liver diseases have gained increasing attention due to their substantial impact on health, independently as well as in association with cardio-metabolic disorders. Studies have suggested that glutathione and adenosine assist in providing protection against oxidative stress and inflammation while glucocorticoid (GC) therapy has been associated with chronic inflammatory disorders, even in pregnancy. The implications of Glucocorticoid exposure on maternal health and fetal growth is a concern, however, the possible role of glutathione and adenosine has not been thoroughly investigated. The study therefore hypothesize that exposure to glucocorticoids leads to depletion of hepatic glutathione and adenosine levels, contributing to oxidative stress and tissue injury. Additionally, we aim to investigate whether the effects of glucocorticoids on hepatic health are pregnancy dependent in female rats. Twelve Pregnant and twelve age-matched non-pregnant rats were used for this study; an exogenous administration of glucocorticoid (Dex: 0.2 mg/kg) or vehicle (po) was administered to six pregnant and six non-pregnant rats from gestational day 14 to 19 or for a period of 6 days respectively. Data obtained showed that GC exposure led to a decrease in hepatic glucose-6-phosphate dehydrogenase, glutathione peroxidase, GSH/GSSG ratio and adenosine content in both pregnant and non-pregnant rats. In addition, increased activities of adenosine deaminase and xanthine oxidase, along with increased production of uric acid and increased levels of lactate dehydrogenase, aspartate aminotransferase, alanine transferase, alkaline phosphatase and gamma-glutamyl transferase were observed. In summary, the study indicates that GC-induced liver damage is underlined by depleted hepatic adenosine and glutathione levels as well as elevated markers of tissue inflammation and/or injury. Furthermore, the findings suggest that the effects of GC exposure on hepatic health are pregnancy independent.

Interventional diagnosis and treatment methods of discogenic and musculoskeletal low back pain

Low back pain (lumbar pain) is one of the most common causes of disability in the population. In cases where conservative treatment of discogenic or musculoskeletal low back pain does not have a positive effect, interventional methods of diagnosis and treatment are used, which are developing actively on the background of rapid technological progress. Being on the border of interdisciplinary interaction, interventional methods can significantly shorten the duration of conservative therapy and, in many cases, avoid surgical decompressive interventions, which are associated with a considerable risk of complications. The methods, efficacy and safety of epidural administration of glucocorticoids for discogenic radiculopathy and lumbar stenosis as well as the methods of radiofrequency denervation for musculoskeletal pain due to the facet joints and the sacroiliac joint involvement are discussed. The possibilities of drug therapy for musculoskeletal pain of the lumbar spine, and combination of non-steroidal anti-inflammatory drugs and a vitamin B complex, are discussed.

The Effect of Preoperative Administration of Glucocorticoids on the Postoperative Complication Rate in Liver Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Glucocorticoids may grant a protective effect against postoperative complications. The evidence on their efficacy, however, has been inconclusive thus far. We investigated the effects of preoperatively administered glucocorticoids on the overall postoperative complication rate, and on liver function recovery in patients undergoing major liver surgery. Methods: We performed a systematic literature search on PubMed, Embase, and CENTRAL in October 2021, and repeated the search in April 2023. Pre-study protocol was registered on PROSPERO (ID: CRD42021284559). Studies investigating patients undergoing liver resections or transplantation who were administered glucocorticoids preoperatively and reported postoperative complications were eligible. Meta-analyses were performed using META and DMETAR packages in R with a random effects model. Risk of bias was assessed using RoB2. Results: The selection yielded 11 eligible randomized controlled trials (RCTs) with 964 patients. Data from nine RCTs (n = 837) revealed a tendency toward a lower overall complication rate with glucocorticoid administration (odds ratio: 0.71; 95% confidence interval: 0.38-1.31, p = 0.23), but it was not statistically significant. Data pooled from seven RCTs showed a significant reduction in wound infections with glucocorticoid administration [odds ratio: 0.64; 95% confidence interval: 0.45-0.92 p = 0.02]. Due to limited data availability, meta-analysis of liver function recovery parameters was not possible. Conclusions: The preoperative administration of glucocorticoids did not significantly reduce the overall postoperative complication rate. Future clinical trials should investigate homogenous patient populations with a specific focus on postoperative liver recovery.

The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica-a prospective study of 101 patients.

2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1year. A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

Experimental interventions attenuate a conjunctival epidermal metaplasia model

The conjunctiva is a non-keratinized, stratified columnar epithelium with characteristics different from the cornea and eyelid epidermis. From development to adulthood, a distinguishing feature of ocular versus epidermal epithelia is the expression of the master regulator PAX6. A conditionally immortalized conjunctival epithelial cell line (iHCjEC) devoid of stromal or immune cells established in our laboratory spontaneously manifested epidermal metaplasia and upregulated expression of the keratinization-related genes SPRR1A/B and the epidermal cytokeratins KRT1 and KRT10 at the expense of the conjunctival trait. In addition, iHCjEC indicated a significant decrease in PAX6 expression. Dry eye syndrome (DES) and severe ocular surface diseases, such as Sjögren’s syndrome and Stevens-Johnson syndrome, cause the keratinization of the entire ocular surface epithelia. We used iHCjECs as a conjunctiva epidermal metaplasia model to test PAX6, serum, and glucocorticoid interventions. Reintroducing PAX6 to iHCjECs resulted in upregulating genes related to cell adhesion and tight junctions, including MIR200CHG and CLDN1. The administration of glucocorticoids or serum resulted in the downregulation of epidermal genes (DSG1, SPRR1A/B, and KRT1) and partially corrected epidermal metaplasia. Our results using an isolated conjunctival epidermal metaplasia model point toward the possibility of rationally “repurposing” clinical interventions, such as glucocorticoid, serum, or PAX6 administration, for treating epidermal metaplasia of the conjunctiva.

Pro-opiomelanocortin and ACTH-cortisol dissociation during pediatric cardiac surgery.

In critically ill adults, high plasma cortisol in face of low ACTH coincides with high pro-opiomelanocortin (POMC) levels. Glucocorticoids further lower ACTH without affecting POMC. We hypothesized that in pediatric cardiac surgery-induced critical illness, plasma POMC is elevated, plasma ACTH transiently rises intraoperatively but becomes suppressed post-operatively, and glucocorticoid administration amplifies this phenotype. From 53 patients (0-36 months), plasma was obtained pre-operatively, intraoperatively and on post-operative day 1 and 2. Plasma was also collected from 24 healthy children. In patients, POMC was supra-normal pre-operatively (p<0.0001) but no longer thereafter (p<0.05). ACTH was never high in patients. While in glucocorticoid-naive patients ACTH became suppressed by post-operative day 1 (p<0.0001), glucocorticoid-treated patients had suppressed ACTH already intraoperatively (p≤0.0001). Pre-operatively high POMC, not accompanied by increased plasma ACTH, suggests a centrally-activated HPA-axis with reduced pituitary processing of POMC into ACTH. Increasing systemic glucocorticoid availability with glucocorticoid treatment accelerated the suppression of plasma ACTH.

Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96weeks of belimumab. This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96weeks. Forty-seven patients were enrolled, with a median daily prednisolone of 5mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), p = .047). Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.

HIF-1α in cartilage homeostasis, apoptosis, and glycolysis in mice with steroid-induced osteonecrosis of the femoral head.

With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high-dose GCs leads to a variety of problems, of which steroid-induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia-inducible factor 1α (HIF-1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF-1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS-treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co-treated with MPS and HIF-1α inhibitor. And the effects observed in HIF-1α activator-treated chondrocytes were similar to those induced by MPS. And HIF-1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF-1α. Furthermore, HIF-1α affected glucose metabolism in cartilage by increasing the expression of glycolysis-related genes. In conclusion, HIF-1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis.

Risk of Systemic Inflammatory Response Syndrome Following Preoperative Glucocorticoids Administration in Patients After Percutaneous Nephrolithotomy: A Retrospective Cohort Study.

Systemic inflammatory response syndrome (SIRS) is one of the most serious complications in patients undergoing percutaneous nephrolithotomy (PCNL). Although glucocorticoids are increasingly used during PCNL, few studies have been concerned about the association between glucocorticoids and postoperative SIRS. The study aims to explore whether preoperative use of glucocorticoids is associated with SIRS after PCNL. A total of 1259 patients who underwent PCNL between January 2015 and April 2021 were enrolled in the retrospective cohort study. Risk factors for post-PCNL SIRS were identified by univariate and multivariate regression analysis. To further explore the association between preoperative administration of glucocorticoids and SIRS, 113 pairs of patients were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95 % confidence intervals (CI) for the above variables were analyzed. The incidence of SIRS after PCNL was 9.6 % (121/1259) and the patients who suffered from postoperative SIRS had longer hospital stays and higher hospital costs (all p < 0.05). Multivariate logistic regression analysis indicated that female, preoperative leukocyte count, insertion of central vein catheter, serum albumin, preoperative high-sensitive C-reactive protein/albumin ratio, preoperative transfusion, preoperative administration of glucocorticoids were independent risk factors for SIRS (all p < 0.05). After minimization, the effects of confounding factors by PSM, preoperative administration of glucocorticoids was significantly correlated with SIRS in patients after PCNL (OR=2.44, 95 %CI: 1.31-4.55, p = 0.005). Preoperative administration of glucocorticoids is an independent risk factor for SIRS in patients undergoing PCNL.

Osteoarthritis of “atypical” localization: Epidemiology, clinical manifestations, principles of therapy

The problem of osteoarthritis (OA), the most common chronic rheumatic disease, is usually considered in relation to three groups of joints – knee, hip and hands. However, OA can affect any joints of the human body, causing pathological changes characteristic of this nosological form: destruction of joint tissue associated with mechanical stress, chronic inflammation and degenerative processes (neoangiogenesis, fibrosis, heterotopic ossification). This review examines 5 “atypical” OA localizations – shoulder, acromioclavicular, elbow, ankle and foot. The defeat of these joints is observed quite often: shoulder – about 15%, ankle – 3–5%, foot joints – 17% of the inhabitants of the modern population. The main risk factors for this disease are injuries, repeated significant stress, instability and deformities of the joints. The clinic is typical for OA and is manifested by “mechanical” and “starting” pains, stiffness, increasing dysfunction, crunching and deformation. In some cases, persistent synovitis is noted, accompanied by pain at rest and at night. Generally recognized criteria for OA of “atypical” localization have not yet been developed, therefore, its diagnosis is based on the presence of characteristic complaints, typical radiological changes (narrowing of the articular gap, subchondral sclerosis, osteophytes) and the exclusion of other pathology that can cause joint damage. Treatment of this pathology should be complex and include the combined use of non-drug methods (orthosis, physical therapy, physiotherapy) and pharmacological agents, such as nonsteroidal anti-inflammatory drugs, slow-acting symptomatic agents and local injection therapy (intra-articular administration of glucocorticoids, hyaluronic acid, platelet-enriched plasma). When conservative therapy is ineffective, a wide range of surgical interventions is used, from arthroscopic chondroplasty to total endoprosthetics.

Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids(OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Glucocorticoid use in psoriatic arthritis and treatment outcomes: does the gender have a role?

BackgroundSystemic glucocorticoids are commonly used in practice in the treatment of psoriatic arthritis. However, authorities advise against prescribing it, primarily because of the risk of psoriasis flare-ups. The authors aimed to assess the glucocorticoid use in psoriatic arthritis (PsA), factors associated with the use of glucocorticoids and to uncover whether gender has an impact on glucocorticoid use and treatment responses. Disease-modifying antirheumatic drug (DMARD)-naive PsA patients were included in this cross-sectional study. Baseline clinical and demographic characteristics were recorded. After starting DMARD treatment, patients were followed for 2 years. The number of patients who started glucocorticoids, the clinical demographics of these patients, the duration of glucocorticoid administration, and the dose for administration were recorded. Patient outcomes and gender differences were analyzed. Disease activity was measured using the Disease Activity Scale 28 (DAS28-CRP) and the Disease Activity Index for Psoriatic Arthritis (DAPSA).ResultsFifty-five of the 141 patients (39%) received glucocorticoids at the 2-year follow-up. There was no difference between the sexes who are in remission-low disease activity (LDA) on cDMARD monotherapy (p = 0.300). Glucocorticoid usage (p = 0.660), dose (p = 0.054), and duration (p = 0.159) did not differ between male and female patients. Higher glucocorticoid doses were associated with dactylitis, higher CRP levels, higher DAS-28 and DAPSA scores, and longer (> 3 months) glucocorticoid administration. Glucocorticoid duration was longer in patients with higher TJS, SJS, serum CRP, higher DAS-28 and DAPSA scores, and higher glucocorticoid doses. Sustained remission-LDA was achieved in 16 of 55 patients after cessation of glucocorticoids and no sex difference was observed.ConclusionSystemic glucocorticoids are commonly prescribed in PsA, and when added to treatment even for short periods and in low doses, they help achieve significant disease control. Except for axial involvement, there is no difference in treatment responses between male and female patients, making it unnecessary to make a gender distinction in the treatment algorithm. Given these findings, prospective studies are needed to evaluate glucocorticoids as a bridging treatment in PsA, such as rheumatoid arthritis.

Achilles' Heel of currently approved immune checkpoint inhibitors: immune related adverse events.

Immunotherapy has revolutionized the cancer treatment landscape by opening up novel avenues for intervention. As the use of immune checkpoint inhibitors (ICIs) has exponentially increased, so have immune-related adverse events (irAEs). The mechanism of irAEs may involve the direct damage caused by monoclonal antibodies and a sequence of immune responses triggered by T cell activation. Common side effects include dermatologic toxicity, endocrine toxicity, gastrointestinal toxicity, and hepatic toxicity. While relatively rare, neurotoxicity, cardiotoxicity, and pulmonary toxicity can be fatal. These toxicities pose a clinical dilemma regarding treatment discontinuation since they can result in severe complications and necessitate frequent hospitalization. Vigilant monitoring of irAEs is vital in clinical practice, and the principal therapeutic strategy entails the administration of oral or intravenous glucocorticoids (GSCs). It may be necessary to temporarily or permanently discontinue the use of ICIs in severe cases. Given that irAEs can impact multiple organs and require diverse treatment approaches, the involvement of a multidisciplinary team of experts is imperative. This review aims to comprehensively examine the pathogenesis, clinical manifestations, incidence, and treatment options for various irAEs.

The Effect of HPA-Axis Dysregulation and Glucocorticoid Administration on Strength and Generalization of Extinction Memory

The Effect of HPA-Axis Dysregulation and Glucocorticoid Administration on Strength and Generalization of Extinction Memory

Acute Diabetes-Related Complications in Patients Receiving Chemoradiotherapy for Head and Neck Cancer.

Consecutive patients with head and neck squamous cell or nasopharyngeal cancer who underwent definitive or adjuvant CCRT between 2010 and 2019 at two large cancer centers in Australia were included. Clinicopathological characteristics, treatment complications and outcomes were collected from medical records. Of 282 patients who received CCRT, 29 (10.3%) had pre-existing type 2 diabetes. None had type 1 diabetes. The majority (74.5%) required enteral feeding. A higher proportion of patients with diabetes required admission to a high-dependency or intensive care unit (17.2 versus 4.0%, p = 0.003). This difference was driven by the group who required insulin at baseline (n = 5), of which four (80.0%) were admitted to a high-dependency unit with diabetes-related complications, and three (60.0%) required omission of at least one cycle of chemotherapy. Patients with diabetes requiring insulin have a high risk of acute life-threatening diabetes-related complications while receiving CCRT. We recommend multidisciplinary management involving a diabetes specialist, educator, dietitian, and pharmacist, in collaboration with the cancer care team, to better avoid these complications.

Belimumab in a Patient with Systemic Lupus Erythematosus with Juvenile Onset and Steroid-induced Diabetes: Clinical Case

Background. The management of children with systemic lupus erythematosus (SLE) is usually associated with lifelong systemic glucocorticoids administration and, thereby, high risk of serious side effects, including steroid-induced diabetes. The belimumab (B-lymphocyte stimulator inhibitor) administration significantly reduces the glucocorticoids dose, the risk and severity of steroid therapy complications. Clinical case description. The patient was diagnosed with SLE at the age of 16 years. Therapy with hydroxychloroquine and oral glucocorticoid at a high dose (methylprednisolone 56 mg per day) was initiated. Steroid-induced diabetes was diagnosed 1 month after the therapy start; avascular necrosis sites were revealed in 2 months. Mycophenolate mofetil made it possible to achieve the disease activity control. However, the belimumab was prescribed 5 months after diagnosis verification due to continuous insulin requirement and avascular necrosis progression. Conclusion. Belimumab is the only genetically engineered biologic drug approved for the treatment of children with SLE. As a result of its use, it was possible to stabilize the patient's condition quickly (within 3 months), to reduce significantly the dose of oral glucocorticoid, methylprednisolone (from 24 to 8 mg/day), to achieve remission of steroidinduced diabetes with further insulin withdrawal, and also to relieve avascular necrosis clinical symptoms.

Determining the Associations Between Glucocorticoid Use During Hematologic Chemotherapy Treatment and New-onset Diabetes and Hyperglycemia and Mortality: A Population-based Cohort Study

ObjectivesThe aim of this study was to determine the associations between glucocorticoid administration during chemotherapy for hematologic malignancy and hyperglycemia, new-onset diabetes, and mortality in Ontario, Canada. Hospitalization and emergency room utilization during the chemotherapy treatment period were also described. MethodsWe conducted a retrospective cohort study using health administrative data from ICES, Ontario, to assess risk of new-onset diabetes, new-onset hyperglycemia, and hyperglycemia for individuals with leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) receiving glucocorticoids during chemotherapy between 2006 and 2016. Using multivariable regression models, we determined the associations between glucocorticoid exposure and our outcomes of interest, controlling for age, sex, marginalization, and comorbidities. ResultsOur cohort included 19,530 individuals; 71.1% (n=13,893) received a glucocorticoid. The highest proportion of hyperglycemia occurred with leukemia (25.4%, n=1,301). Of the 15,580 individuals with no history of diabetes, those with leukemia had the highest rate of new-onset diabetes (7.1%, n=279) and new-onset hyperglycemia (18.1%, n=641), and glucocorticoid exposure increased the risk of new-onset diabetes (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p=0.04) and new-onset hyperglycemia (HR 1.28, 95% CI 1.09 to 1.5, p=0.003). Hyperglycemia during chemotherapy increased the risk of all-cause mortality for the combined (HR 1.18, 95% CI 1.09 to 1.27, p<0.0001) and NHL (HR 1.16, 95% CI 1.04 to 1.28, p=0.007) cohorts. ConclusionsHyperglycemia is common during hematologic chemotherapy treatment and is associated with a modest increased risk of all-cause mortality. Routine screening, monitoring, and management of hyperglycemia should be an integral part of treatment plans for leukemia, NHL, or HL, with or without glucocorticoid administration.

Risk of Death and Cardiovascular Events Following an Exacerbation of COPD: The EXACOS-CV US Study.

This study estimated the magnitude and duration of risk of cardiovascular events and mortality following acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and whether risks varied by number and severity of exacerbation in a commercially insured population in the United States. This was a retrospective cohort study of newly diagnosed COPD patients ≥40 years old in the Healthcare Integrated Research Database from 2012 to 2019. Patients experiencing exacerbations comprised the "exacerbation cohort". Moderate exacerbations were outpatient visits with contemporaneous antibiotic or glucocorticoid administration; severe exacerbations were emergency department visits or hospitalizations for AECOPD. Follow-up started on the exacerbation date. Distribution of time between diagnosis and first exacerbation was used to assign index dates to the "unexposed" cohort. Cox proportional hazards models estimated risks of a cardiovascular event or death following an exacerbation adjusted for medical and prescription history and stratified by follow-up time, type of cardiovascular event, exacerbation severity, and rank of exacerbation (first, second, or third). Among 435,925 patients, 170,236 experienced ≥1 exacerbation. Risk of death was increased for 2 years following an exacerbation and was highest during the first 30 days (any exacerbation hazard ratio (HR)=1.79, 95% CI=1.58-2.04; moderate HR=1.22, 95% CI=1.04-1.43; severe HR=5.09, 95% CI=4.30-6.03). Risks of cardiovascular events were increased for 1 year following an AECOPD and highest in the first 30-days (any exacerbation HR=1.34, 95% CI=1.23-1.46; moderate HR=1.23 (95% CI 1.12-1.35); severe HR=1.93 (95% CI=1.67-2.22)). Each subsequent AECOPD was associated with incrementally higher rates of both death and cardiovascular events. Risk of death and cardiovascular events was greatest in the first 30 days and rose with subsequent exacerbations. Risks were elevated for 1-2 years following moderate and severe exacerbations, highlighting a sustained increased cardiopulmonary risk associated with exacerbations.

Варианты адаптационных реакций у детей с острыми респираторными инфекциями

The endocrine and immune systems play an important role in the child’s adaptation to acute respiratory infection (ARI). The course and outcome of the disease depend on the effectiveness of their work; hence the relevance of this topic. The purpose is to establish variants of adaptive reactions in children with ARI based on the study of clinical and laboratory parameters. Material and methods. 210 children from 1 to 16 years of age were examined in the acute period of ARI. In addition to the standard clinical laboratory and instrumental examination, patients were assessed for the level of thyroid hormones (T4 free, T3 free), TSH, cortisol, IFN-ɑ and IFN-ɣ in blood serum. Results. 4 adaptive reactions have been established in children with ARI. The training reaction, the markers of which are increased cortisol and IFN-ɣ, develops in children with a mild form of ARI. The reaction of quiet activation, the markers of which are elevated cortisol, IFN-ɣ and TSH, proceeds with the development of moderate -severe forms of ARI. The low activation reaction, the markers of which are low cortisol and IFN-ɑ, is characterized by a severe form with the development of obstructive syndrome. The reactivation reaction, the markers of which are represented by very high levels of cortisol, IFN-ɑ, TSH and low IFN-ɣ, develops in children with severe ARI complicated with pneumonia. Conclusion. During adaptive reactions of training, quiet activation and reactivation in children with ARI, the administration of interferons and glucocorticoids is not indicated. Therapy with recombinant interferons-α and glucocorticoids is recommended for children with a low activation reaction.