Single Dose Of Corticosteroids Research Articles

Rapid Osteoarthritis and Femoral Head Collapse: A Case Series.

Rapidly progressive hip osteoarthritis (OA) leading to femoral head collapse (FHC) following intra-articular (IA) corticosteroid injections is a perplexing variant of OA. We explored eight cases of chronic joint pain treated with IA corticosteroid injections. Subsequently, they experienced swift deterioration of the femoral head integrity within as little as 10 weeks. These cases underscore the need for a comprehensive assessment of risk factors versus benefits in this patient population. The study reveals a complex interplay between comorbidities, treatments, and outcomes. Patients exhibited various health factors, including obesity, smoking history, cancer treatment, and deficiencies in Vitamin D levels, which have been found to increase the risk of FHC. Furthermore, the study explores the chondrotoxicity of corticosteroids and local anesthetics used in IA injections. In vitro studies show complete loss of chondrocyte viability after a single dose of corticosteroids, potentially leading to cartilage degradation. In addition, local anesthetics may induce cellular demise and structural alterations in the articular cartilage. These factors highlight various influences affecting treatment outcomes in patients with OA. In conclusion, this case series highlights the rare adverse outcome of rapidly progressive hip OA and FHC following IA corticosteroid injections and possible risk factors. While a definitive etiology remains unclear, the study provides valuable conclusions to aid in future treatment decision-making.

A Phase 1 First-in-Human Study of AMG 330, an Anti-CD33 Bispecific T-Cell Engager (BiTE®) Antibody Construct, in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

A Phase 1 First-in-Human Study of AMG 330, an Anti-CD33 Bispecific T-Cell Engager (BiTE®) Antibody Construct, in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, the most common periodic disorder of childhood, presents with the cardinal symptoms of periodic fever, aphthous stomatitis, pharyngitis, and adenitis typically before age 5. This review presents the recent literature on PFAPA and summarizes key findings in the pathogenesis, evaluation, and treatment of the disease. Theories surrounding the pathogenesis of PFAPA include a faulty innate immunologic response in conjunction with dysregulated T-cell activation. A potential genetic link is also under consideration. Mediterranean fever (MEFV) gene variants have been implicated and appear to modify disease severity. In individuals with the heterozygous variant, PFAPA episodes are milder and shorter in duration. Diagnostic criteria include the traditional clinical signs, in addition to the following biomarkers: elevated C-reactive protein in the absence of elevated procalcitonin, vitamin D, CD64, mean corpuscular volume, and other nonspecific inflammatory mediators in the absence of an infectious explanation for fever. Treatment of PFAPA includes tonsillectomy, a single dose of corticosteroids, and, most recently, interleukin 1 blockers such as anakinra, rilonacept, and canakinumab. Tonsillectomy remains the only permanent treatment modality.

Tandem analysis of transcriptome and proteome changes after a single dose of corticosteroid: a systems approach to liver function in pharmacogenomics.

Corticosteroids (CS) such as methylprednisolone (MPL) affect almost all liver functions through multiple mechanisms of action, and long-term use results in dysregulation causing diverse side effects. The complexity of involved molecular mechanisms necessitates a systems approach. Integration of information from the transcriptomic and proteomic responses has potential to provide deeper insights into CS actions. The present report describes the tandem analysis of rich time-series transcriptomic and proteomic data in rat liver after a single dose of MPL. Hierarchical clustering of the common genes represented in both mRNA and protein datasets displayed two dominant patterns. One of these patterns exhibited complementary mRNA and protein expression profiles indicating that MPL affected the regulation of these genes at the transcriptional level. Some of the classic pharmacodynamic markers for CS actions, including tyrosine aminotransferase (TAT), were among this group, together with genes encoding urea cycle enzymes and ribosomal proteins. The other pattern was rather unexpected. For this group of genes, MPL had distinctly observable effects at the protein expression level, although a change in the reverse direction occurred at the transcriptional level. These genes were functionally associated with metabolic processes that might be essential to elucidate side effects of MPL on liver, most importantly including modulation of oxidative stress, fatty acid oxidation, and bile acid biosynthesis. Furthermore, profiling of gene and protein expression data was also done independently of one another by a two-way sequential approach. Prominent temporal shifts in expression and relevant cellular functions were described together with the assessment of changes in the complementary side.

Spontaneous Rupture of Multiple Extensor Tendons Following Repeated Steroid Injections: a Case Report

Spontaneous rupture of the extensor carpi and extensor pollicis longus tendons is very uncommon and is caused by inflammatory conditions such as rheumatoid arthritis, osteoarthritis of the radio‐ulnar joint, chronic tenosynovitis caused by repetitive activity and long‐term administration of fluoroquinolone antibiotics and corticosteroids. Spontaneous rupture of multiple extensor tendons has rarely been reported. We report a case of spontaneous rupture of multiple extensor tendons following repeated steroid injection in an older woman with De Quervain's disease.

Superior vena cava obstruction: Dangers of a missed diagnosis

We report the case of a 7 year old girl who presented to the Children's Emergency Department with a 6 week history of bilateral facial and neck swelling. She had felt generally unwell, tired, with a recent onset of dry cough, and had presented multiple times to her general practitioner (GP) who after initially unsuccessfully trying an antihistamine, had given her five courses of soluble Betamethasone (corticosteroid) over six weeks, for presumed allergy; this temporarily relieved her symptoms for a couple of days each time. On subsequent referral to Accident and Emergency she was found to have a superior mediastinal mass, with a left pleural effusion and mediastinal deviation to the right. Further investigation confirmed the diagnosis of a T-cell lymphoma causing superior vena cava obstruction of blood flow through the SVC to the right atrium and is a classical oncological emergency. This case report highlights the importance of recognizing superior vena cava obstruction and the need for awareness of malignancy as a differential diagnosis when initially presented with a child with non-specific respiratory findings. We highlight that acute tumour lysis syndrome, a life threatening metabolic emergency that results from massive cytolysis of malignant cells, may occur after a single dose of corticosteroids and one should be aware of this potentially life-threatening complication.

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

BackgroundEarly and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.MethodsA multicenter stratified randomized single-blind controlled trial is currently being performed in patients 18 years or older with recent-onset arthritis. Eight hundred ten patients are being stratified according to the likelihood of their developing persistent arthritis. In patients with a high probability of persistent arthritis, we will study combination Disease Modifying Antirheumatic Drug therapy compared to monotherapy methotrexate. In patients with an intermediate probability of persistent arthritis, we will study Disease Modifying Antirheumatic Drug of various intensities. In patients with a low probability, we will study non-steroidal anti-inflammatory drugs, hydroxychloroquine and a single dose of corticosteroids. If disease activity is not sufficiently reduced, treatment will be adjusted according to a step-up protocol. If remission is achieved for at least six months, medication will be tapered off. Patients will be followed up every three months over two years.DiscussionThis is the first rheumatological study to base treatment in early arthritis on a prediction rule. Treatment will be stratified according to the probability of persistent arthritis, and different combinations of treatment per stratum will be evaluated. Treatment will be started early, and patients will not need to meet the ACR-criteria for rheumatoid arthritis.Trial registrationThis trial has been registered in Current Controlled Trials with the ISRCTN26791028.

Life-Threatening Tumor Lysis Syndrome Within 12 Hours of a Single Dose of Corticosteroid in a Patient with Lymphoma

Tumor lysis syndrome is an oncologic emergency characterized by electrolyte derangements and the frequent development of acute renal failure. We describe a patient with acute lymphoblastic lymphoma in whom rapid and severe tumor lysis syndrome developed within 10 h of the administration of a single dose of corticosteroid. Our case and a review of the literature indicate that patients with lymphoproliferative malignancies given a single dose of corticosteroid may be at significant risk for rapid and life-threatening tumor lysis syndrome. We recommend that such patients receive aggressive and frequent laboratory monitoring even in the setting of appropriate prophylaxis.

Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens

The transcriptional response of skeletal muscle to chronic corticosteroid exposure was examined over 168 h and compared with the response profiles observed following a single dose of corticosteroid. Male adrenalectomized Wistar rats were given a constant-rate infusion of 0.3 mg x kg(-1) x h(-1) methylprednisolone for up to 7 days via subcutaneously implanted minipumps. Four control and forty drug-treated animals were killed at ten different time points during infusion. Liver total RNAs were hybridized to 44 individual Affymetrix REA230A gene chips. Previously, we described a filtration approach for identifying genes of interest in microarray data sets developed from tissues of rats treated with methylprednisolone (MPL) following acute dosing. Here, a similar approach involving a series of three filters was applied sequentially to identify genes of interest. These filters were designed to eliminate probe sets that were not expressed in the tissue, not regulated by the drug, or did not meet defined quality control standards. Filtering eliminated 86% of probe sets, leaving a remainder of 2,316 for further consideration. In a previous study, 653 probe sets were identified as MPL regulated following administration of a single (acute) dose of the drug. Comparison of the two data sets yielded 196 genes identified as regulated by MPL in both dosing regimens. Because of receptor downregulation, it was predicted that genes regulated by receptor-glucocorticoid response element interactions would exhibit tolerance in chronic profiles. However, many genes did not exhibit steroid tolerance, indicating that present perspectives on the mechanism of glucocorticoid action cannot entirely explain all temporal profiles.

THE EFFECT OF CORTICOSTEROID ON COLLAGEN EXPRESSION IN INJURED ROTATOR CUFF TENDON

Background: Subacromial corticosteroid injections are commonly used in the nonoperative management of rotator cuff disease. The effects of corticosteroid injection on injured rotator cuff tendons have not been studied. Our aims were to characterize the acute response of rotator cuff tendons to injury through the analysis of the type-III to type-I collagen expression ratio, a tendon injury marker, and to examine the effects of corticosteroid on this response. Methods: Sixty Sprague-Dawley rats were randomly assigned to four groups: control, tendon injury, steroid treatment, and tendon injury and steroid treatment. Six rats served as sham controls. Unilateral tendon injuries were created with full-thickness defects across 50% of the total width of the infraspinatus tendon, 5 mm from its humeral insertion. Steroid treatment with a single dose of methylprednisolone (0.6 mg/kg), equivalent to that given to humans, was injected into the subacromial space under direct visualization. Steroid treatment followed the creation of an injury in the rats in the injury and steroid treatment group. At one, three, and five weeks after the injury, the total RNA isolated from tendons was quantified with real-time polymerase chain reaction with use of primers for type-I and type-III collagen and ribosomal 18s RNA. Results: The type-III to type-I collagen expression ratio remained at baseline at all time-points in the control and sham groups. At one week, the type-III to type-I collagen expression ratio increased more than fourfold above the control level in the tendon injury group (p = 0.017) and the tendon injury and steroid treatment group (p = 0.003). The ratio remained greater than twofold above the control at three weeks in both groups (p = 0.003 and p = 0.037) and returned to baseline at five weeks. Interestingly, the group that had steroid treatment only showed an increase of >4.5-fold (p = 0.001) in the type-III to type-I collagen expression ratio, without structural injury to the tendon. This ratio returned to baseline levels by three weeks. Conclusions: A single dose of corticosteroid does not alter the acute phase response of an injured rotator cuff tendon in the rat. However, the same steroid dose in uninjured tendons initiates a short-term response equivalent to that of structural injury. Clinical Relevance: These findings suggest that while a single corticosteroid dose may have no long-term effects on tendon collagen gene expression, collagen composition may be acutely altered by the injection. Therapy and activity recommendations following subacromial corticosteroid exposure should be made with the awareness of possible compromised rotator cuff tendon properties.

The Effect of Corticosteroid on Collagen Expression in Injured Rotator Cuff Tendon

Subacromial corticosteroid injections are commonly used in the nonoperative management of rotator cuff disease. The effects of corticosteroid injection on injured rotator cuff tendons have not been studied. Our aims were to characterize the acute response of rotator cuff tendons to injury through the analysis of the type-III to type-I collagen expression ratio, a tendon injury marker, and to examine the effects of corticosteroid on this response. Sixty Sprague-Dawley rats were randomly assigned to four groups: control, tendon injury, steroid treatment, and tendon injury and steroid treatment. Six rats served as sham controls. Unilateral tendon injuries were created with full-thickness defects across 50% of the total width of the infraspinatus tendon, 5 mm from its humeral insertion. Steroid treatment with a single dose of methylprednisolone (0.6 mg/kg), equivalent to that given to humans, was injected into the subacromial space under direct visualization. Steroid treatment followed the creation of an injury in the rats in the injury and steroid treatment group. At one, three, and five weeks after the injury, the total RNA isolated from tendons was quantified with real-time polymerase chain reaction with use of primers for type-I and type-III collagen and ribosomal 18s RNA. The type-III to type-I collagen expression ratio remained at baseline at all time-points in the control and sham groups. At one week, the type-III to type-I collagen expression ratio increased more than fourfold above the control level in the tendon injury group (p = 0.017) and the tendon injury and steroid treatment group (p = 0.003). The ratio remained greater than twofold above the control at three weeks in both groups (p = 0.003 and p = 0.037) and returned to baseline at five weeks. Interestingly, the group that had steroid treatment only showed an increase of >4.5-fold (p = 0.001) in the type-III to type-I collagen expression ratio, without structural injury to the tendon. This ratio returned to baseline levels by three weeks. A single dose of corticosteroid does not alter the acute phase response of an injured rotator cuff tendon in the rat. However, the same steroid dose in uninjured tendons initiates a short-term response equivalent to that of structural injury.

A cluster randomized controlled trial comparing three methods of disseminating practice guidelines for children with croup [ISRCTN73394937

BackgroundThe optimal management of croup – a common respiratory illness in young children – is well established. In particular, treatment with corticosteroids has been shown to significantly reduce the rate and duration of intubation, hospitalization, and return to care for on-going croup symptoms. Furthermore treatment with a single dose of corticosteroids does not appear to result in any significant adverse outcomes, and yields overall cost-savings for both families and the health care system.However, as has been shown with many other diseases, there is a significant gap between what we know and what we do. The overall aim of this study is to identify, from a societal perspective, the costs and associated benefits of three strategies for implementing a practice guideline that addresses the management of croup.Methods/designsWe propose to use a matched pair cluster trial in 24 Alberta hospitals randomized into three intervention groups. We will use mixed methods to assess outcomes including linkage and analysis of administrative databases obtained from Alberta Health and Wellness, retrospective medical chart audit, and prospective telephone surveys of the parents of children diagnosed to have croup. The intervention strategies to be compared will be mailing of printed educational materials (low intensity intervention), mailing plus a combination of interactive educational meetings, educational outreach visits, and reminders (intermediate intensity intervention), and a combination of mailing, interactive sessions, outreach visits, reminders plus identification of local opinion leaders and establishment of local consensus processes (high intensity intervention). The primary objective is to determine which of the three intervention strategies are most effective at lowering the rate of hospital days per 1,000 disease episodes. Secondary objectives are to determine which of the three dissemination strategies are most effective at increasing the use of therapies of known benefit. An economic analysis will be conducted to determine which of the three intervention strategies will most effectively reduce total societal costs including all health care costs, costs borne by the family, and costs stemming from the strategies for disseminating guidelines.

Undesired effects of steroids during pregnancy

Antenatal corticosteroid administration for enhancing fetal lung maturity can be expected to induce negative maternal and fetal side-effects. Maternal short-term effects after multiple courses of corticosteroids are an increase of infections and a higher incidence of endometritis and chorionamnionitis in patients with premature rupture of membranes. A single dose of corticosteroid induces an increase in the count of maternal white blood cells and metabolic effects such as the augmentation of amino acid concentration and of fasting glucose levels in maternal plasma. Negative fetal effects of antenatal corticosteroids are a reduction of fetal body and breathing movements and a reduction of fetal heart rate variation, without any changes in Doppler waveform patterns of fetoplacental vessels. It has been suggested that a multiple course of corticosteroids antenatally might induce negative effects on fetal intrauterine growth and on neonatal birth weight. In addition, multiple courses are associated with an increased risk of early-onset neonatal sepsis.

Acute tumour lysis syndrome following a single‐dose corticosteroid in children with acute lymphoblastic leukaemia

Acute tumour lysis syndrome (ATLS) is a well recognised complication of treatment of a variety of malignant disorders. It commonly occurs in patients with non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukaemia (ALL) with the administration of combined cytotoxic chemotherapy. It is rarely reported after single-agent corticosteroid therapy. We present two children with acute lymphoblastic leukaemia of T-cell lineage who developed acute tumour lysis syndrome after a single dose of prednisolone, and methylprednisolone at the beginning of the induction chemotherapy. In the first case (an 11-yr-old) ATLS had occurred after an oral dose of prednisolone as small as 12 mg and within 18 h. The second case was a 14-yr-old boy with ALL who developed ATLS following a single dose of methylprednisolone. A few similar cases in the English literature are summarised in the report. These cases indicate that acute tumour lysis syndrome may occur after a single dose of corticosteroids. One should be aware of this potentially life-threatening complication especially while prescribing corticosteroids to patients with NHL and leukaemia.

Persistence of mild, early inflammatory arthritis: the importance of disease duration, rheumatoid factor, and the shared epitope.

To determine the factors that predict clinical outcome at 6 months for patients with mild, early inflammatory arthritis. Sixty-three patients with mild, untreated, early arthritis were given a single dose of corticosteroids at presentation. Administration was intramuscular if disease was polyarticular (n = 53) or intraarticular if patients had <5 synovitic joints (n = 10). The primary outcome measure was clinical disease remission or persistence of arthritis at 6 months following injection. At 6 months following injection, 49 of the 63 patients (78%) had persistent inflammatory joint disease. The other 14 (22%) had clinical disease remission. Regression analysis showed that only disease duration was significantly associated with persistent arthritis (P < 0.05). The other significant factor (by chi-square test) was the presence of the shared epitope (SE). Of the patients fulfilling the American College of Rheumatology (ACR) criteria at presentation (51% of the total), 53% with disease duration of < or = 12 weeks at presentation had persistent disease 6 months later, compared with 94% of those who presented with disease duration of >12 weeks. The strongest predictor of persistent disease was a disease duration of >12 weeks. Rheumatoid factor and SE were also predictors to a lesser extent. Patients who both fulfilled the ACR classification criteria for rheumatoid arthritis (RA) and had a short disease duration included some with an excellent prognosis. Therefore, 12 weeks may be a more appropriate disease duration to use for the RA classification criteria. Administering a bolus of corticosteroids may be a useful diagnostic/therapeutic approach.

Higher lung antioxidant enzyme activity persists after single dose of corticosteroids in preterm lambs.

Although administration of exogenous corticosteroids accelerates the late gestational rise in fetal rat and lamb lung antioxidant enzyme activity, the effect of dosing intervals on these responses remains uncertain. We studied the persistence and efficacy of the antioxidant response in fetal lamb lung to a single fetal dose of corticosteroids injected between 121 and 127 days gestational age. Fetal lambs received 0.5 mg/kg of betamethasone (n = 35) or saline (n = 26) by fetal intramuscular injection 24 h, 48 h, 4 days, or 7 days before preterm delivery at 128 days gestation (term = 150 days). After delivery, the lambs were ventilated for 40 min and killed. Total superoxide dismutase, catalase, glutathione peroxidase activities, and lipid hydroperoxide levels were measured, using homogenized lung. The saline-injected controls were similar at all time points. Lung antioxidant enzyme activity was consistently higher and lipid hydroperoxide presence was lower in the betamethasone-treated groups. We conclude that the positive effect of a single fetal dose of betamethasone on lung antioxidant enzyme activity occurs within 24 h after exposure, persists over a period of 7 days without a major change in the magnitude of the response, and leads to a reduction in lipid hydroperoxide formation during immediate postdelivery oxygen exposure.

Effects of corticosteroids on distribution of histamine in the blood of asthmatic children.

Blood and plasma histamine levels, together with circulating basophil and eosinophil counts, were estimated in a group of asthmatic children. Short-term studies were carried out on 7 patients, each of whom was given a single dose of corticosteroid, and the effects of the hormone were monitored for periods of up to two hours. Usually a fall occurred in the whole blood histamine level, basophil count, and eosinophil count, but no change occurred in the plasma histamine level, which remained very low throughout. In 3 cases, follow-up studies showed that in 2 cases out of 3, whole blood histamine levels were lower during treatment with corticosteroids, than when steroids were not being given.