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Clinical and Experimental Rheumatology Sep 2023Rheumatoid arthritis (RA) is an autoimmune disease. Methotrexate (MTX) and prednisolone (PSL) are used in combination for severe RA therapy. However, it can increase the...
OBJECTIVES
Rheumatoid arthritis (RA) is an autoimmune disease. Methotrexate (MTX) and prednisolone (PSL) are used in combination for severe RA therapy. However, it can increase the risk of osteoporosis and osteonecrosis. Saireito (114) can be used to reduce PSL dose owing to its immunosuppressive effects. However, the effect of combination therapy of PSL+114 on the immune system of RA patients remains unknown. This study compared the effect of PSL alone and PSL+114 on peripheral blood mononuclear cell (PBMC) proliferation, T-cell subsets, and cytokine production in adult RA patients receiving MTX monotherapy.
METHODS
We isolated PBMCs from 14 consenting RA patients, and cultured them with PSL (0.0001-1.0 μM) in combination with or without 114 (300 μg/mL) for 96 h in the presence of concanavalin A. We measured the proliferation rates of PBMC, proportions of CD4+, CD8+, and CD4+CD25+Foxp3+T-cells (induced T-regulatory cells), and concentrations of interferon-γ, interleukin (IL)-6, IL-10, IL-17A, and tumour necrosis factor in the culture supernatant.
RESULTS
Compared to the blank, the PBMC proliferation rate significantly decreased at a reduced PSL concentration after 114 administration. The 50% inhibition concentration was 0.43 μM PSL for the PSL-only group as compared to 0.29 μM PSL for the PSL+114 co-administration group. The PSL+114 co-administration group had a significantly higher concentration of IL-6 compared to the PSL-only group.
CONCLUSIONS
The use of 114 in combination with low-concentration PSL intensified its immunosuppressive effect. However, the concentration of IL-6 was elevated in the co-administration group, suggesting exacerbation of RA activity.
Topics: Adult; Humans; Prednisolone; Antirheumatic Agents; Leukocytes, Mononuclear; Interleukin-6; Arthritis, Rheumatoid; Methotrexate
PubMed: 36826781
DOI: 10.55563/clinexprheumatol/ohcf0k -
BMJ Case Reports Jun 2024Steroid-induced acute pancreatitis is a rare form of pancreatitis that requires intensive care and has a high morbidity and mortality rate as there is no specific...
Steroid-induced acute pancreatitis is a rare form of pancreatitis that requires intensive care and has a high morbidity and mortality rate as there is no specific treatment. Management of steroid-induced pancreatitis is generally non-specific and supportive. Here, we are presenting a man in his 40s presented with epigastric pain, fever and vomiting. The patient was diagnosed case of rheumatoid arthritis, for which he was receiving regular 5 mg oral prednisolone therapy. Based on history, and clinical, biochemical and radiological imaging a diagnosis of steroid-induced pancreatitis was made, which was successfully managed with the help of ulinastatin and other supportive treatments. A serine protease inhibitor like ulinastatin may be used early in the clinical management of steroid-induced pancreatitis.
Topics: Humans; Male; Prednisolone; Glycoproteins; Pancreatitis; Adult; Trypsin Inhibitors; Arthritis, Rheumatoid; Glucocorticoids
PubMed: 38839406
DOI: 10.1136/bcr-2024-260019 -
Clinical Journal of the American... Oct 2023Early morning single-dose prednisolone has a hypothetical advantage of less hypothalamic-pituitary-adrenal (HPA) axis suppression, but lack of robust evidence has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Early morning single-dose prednisolone has a hypothetical advantage of less hypothalamic-pituitary-adrenal (HPA) axis suppression, but lack of robust evidence has resulted in variation in practice, with divided-dose prednisolone still commonly used. We conducted this open-label randomized control trial to compare HPA axis suppression between single-dose or divided-dose prednisolone among children with first episode of nephrotic syndrome.
METHODS
Sixty children with first episode of nephrotic syndrome were randomized (1:1) to receive prednisolone (2 mg/kg per day), either as single or two divided doses for 6 weeks, followed by single alternative daily dose of 1.5 mg/kg for 6 weeks. The Short Synacthen Test was conducted at 6 weeks, with HPA suppression defined as postadrenocorticotropic hormone cortisol <18 µ mg/dl.
RESULTS
Four children (single=1 and divided dose=3) did not attend the Short Synacthen Test and were hence excluded from analysis. Remission was induced in all, and no relapse postremission was noted during the 6+6 weeks of steroid therapy. After 6 weeks of daily steroids, HPA suppression was greater in divided (100%) versus single dose (83%) ( P = 0.02). Time to remission and final relapse rates were similar, but for those children who relapsed within 6 months of follow-up period, time to first relapse was shorter for divided dose (median 28 versus 131 days) P = 0.002.
CONCLUSIONS
Among children with first episode of nephrotic syndrome, single-dose and/or divided-dose prednisolone were equally effective in inducing remission with similar relapse rates, but single dose had less HPA suppression and longer time to first relapse.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
CTRI/2021/11/037940.
PODCAST
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_10_09_CJN0000000000000216.mp3.
Topics: Child; Humans; Prednisolone; Nephrotic Syndrome; Glucocorticoids; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Recurrence
PubMed: 37335578
DOI: 10.2215/CJN.0000000000000216 -
American Journal of Hematology Oct 2023Acute graft versus host disease (aGvHD) is a severe complication that arises in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Acute graft versus host disease (aGvHD) is a severe complication that arises in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and remains the primary cause of nonrelapse mortality (NRM). The MAGIC algorithm probability (MAP) has been proposed to identify patients at intermediate and high risk of developing aGvHD. The levels of suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3α (Reg3α) were assessed, and MAP was calculated on days 7, 14, 21, and 28 after allo-HSCT. Based on the MAP results, patients were classified into low-, intermediate-, or high-risk groups for the development of aGvHD. Random assignment was performed to allocate intermediate- or high-risk patients to receive preemptive therapy with methylprednisolone or not. The 100-day cumulative incidences of grade 2 or higher (35.5% ± 8.6%) and grade 3 or higher (12.9% ± 6.0%) aGvHD in the methylprednisolone group were significantly lower than those in the control group (66.7% ± 7.9%, p = .01; 42.9% ± 8.4%, p = .01), and similar to those observed in the low-risk group (31.7% ± 7.3%, p = .75; 2.4% ± 2.4%, p = .08). The 6-month cumulative incidences of NRM were 14.1% ± 6.6%, 22.7% ± 7.1%, and 2.4% ± 2.4% in the methylprednisolone, control, and low-risk groups, respectively, with no significant difference between the methylprednisolone and control groups (p = .29). Methylprednisolone did not increase infections (p = .34). The 100-day cumulative incidences of cytomegalovirus (CMV) reactivation were 67.7% ± 8.4%, 65.6% ± 8.4%, and 46.3% ± 7.8% (p = .08), and those of grade 2 or higher hemorrhagic cystitis were 29.0% ± 8.2%, 45.2% ± 8.9% and 22.0% ± 6.5% (p = .11) in the methylprednisolone, control, and low-risk groups, respectively. MAP-guided preemptive therapy for aGvHD is promising. The long-term efficacy and safety remain to be investigated.
Topics: Humans; Methylprednisolone; Transplantation, Homologous; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Risk Factors; Algorithms; Retrospective Studies; Acute Disease
PubMed: 37497879
DOI: 10.1002/ajh.27020 -
European Journal of Nuclear Medicine... Apr 20242-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia...
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.
PURPOSE
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.
METHODS
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 8 weeks 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 1 year.
RESULTS
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 8 weeks 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%.
CONCLUSION
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.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.
PubMed: 38563881
DOI: 10.1007/s00259-024-06697-8 -
Clinical and Investigative Medicine.... Dec 2023Glucocorticoids are often used to treat acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19). However, the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glucocorticoids are often used to treat acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19). However, the efficacy and safety of glucocorticoids in the treatment of ARDS caused by COVID-19 are still controversial; therefore, we conducted this meta-analysis of the literature on this topic.
METHODS
Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from the establishment of the databases to August 16, 2023. Randomized controlled trials (RCTs) and cohort studies that compared glucocorticoid versus standard treatment for ARDS caused by COVID-19 were included. The Newcastle-Ottawa Scale (NOS) checklist and the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias. Review Manager 5.4 software and STATA 17.0 were used for meta-analy-sis, and the relative risk (RR), mean difference, and 95% confidence intervals (CIs) were then determined. Results: A total of 17 studies involving 8592 patients were evaluated, including 14 retrospective studies and 3 RCTs. Sixteen studies reported data on all-cause mortality. The results of the meta-analysis showed that glucocorticoids did not reduce all-cause (RR, 0.96; 95% CI 0.82-1.13, P = .62) or 28-day (RR, 1.01; 95% CI 0.78-1.32, P = .93) mortality. Subgroup analysis showed that only methylprednisolone reduced all-cause mortality. No matter whether glucocorticoid use was early or delayed, high-dose or low-dose, long-term or short-term, no regimen reduced all-cause mortality. Furthermore, there were no significant differences in length of intensive care unit (ICU) stay, length of hospital stay, hyperglycemia, and ventilator-associated pneumonia (VAP); how-ever, glucocorticoids increased the number of ventilator-free days.
CONCLUSIONS
Although methylprednisolone may reduce all-cause mortality from ARDS caused by COVID-19, this effect was not found with other types of glucocorticoids. At the same time, glucocorticoid use was associ-ated with more ventilator-free days, without increasing the incidence of hyperglycemic events or VAP. Con-sidering that almost all of the included studies were retrospective cohort studies, more RCTs are needed to confirm these findings.
Topics: Humans; COVID-19; Glucocorticoids; Respiratory Distress Syndrome; Methylprednisolone
PubMed: 38330183
DOI: 10.3138/cim.v46i4e03 -
ACS Nano Jul 2023Spinal cord injury (SCI), which is characterized by excessive inflammatory cell infiltration and accumulation of oxidative substance, would severely impede neurological...
Spinal cord injury (SCI), which is characterized by excessive inflammatory cell infiltration and accumulation of oxidative substance, would severely impede neurological functional recovery and lead to permanent and profound neurologic deficits and even disability. Methylprednisolone (MP) is the most commonly used clinical anti-inflammatory drug for SCI treatment, but high doses are typically required that can cause severe side effects. Here, we developed a carrier-free thioketal linked MP dimer@rutin nanoparticles (MP-TK@RU NPs) which can achieve combined SCI treatment by coassembling reactive oxygen species (ROS) cleavable MP dimers and rutin. This proposed nanodrug possesses the following favorable advantages: (1) the carrier-free system is easily accessible and has a high drug-loading capacity, which is preferred by the pharmaceutical industry; (2) The ROS-cleavable linker increases the efficiency of targeted drug delivery to the injury site; (3) Rutin, a type of plant-derived natural flavonoid with good biocompatibility, anti-inflammatory, and antioxidant properties, is codelivered to enhance the therapy outcomes. The obtained MP-TK@RU NPs exhibited potent anti-inflammatory and antioxidative properties both and , demonstrating superior locomotor function recovery and neuroprotective efficacy in rats with SCI. This carrier-free nanodrug is anticipated to provide a promising therapeutic strategy for clinical SCI treatment.
Topics: Rats; Animals; Methylprednisolone; Reactive Oxygen Species; Rutin; Spinal Cord Injuries; Anti-Inflammatory Agents; Antioxidants; Polymers; Nanoparticles; Spinal Cord; Neuroprotective Agents
PubMed: 37387550
DOI: 10.1021/acsnano.3c00360 -
Journal of Neurology, Neurosurgery, and... Dec 2023Greater occipital nerve (GON) blockade is a short-term preventive therapy for cluster headache (CH). We conducted a systematic review to evaluate the effectiveness and...
BACKGROUND
Greater occipital nerve (GON) blockade is a short-term preventive therapy for cluster headache (CH). We conducted a systematic review to evaluate the effectiveness and safety of GON blockade in patients with CH.
METHODS
On 23 October 2020, we searched MEDLINE, Embase, Embase Classic, PsycINFO, CINAHL, CENTRAL and Web of Science databases from their inception date. Studies included participants with a CH diagnosis who received corticosteroid and local anaesthetic suboccipital region injections. Outcomes were change in the frequency/severity/duration of attacks; proportion of participants responding to treatment, time to attack freedom from an attack, change in attack bout length and/or the presence of adverse effects after GON blockade. Risk of bias was assessed with the Cochrane Risk of Bias V.2.0 (RoB2)/Risk of Bias in Non-randomized Studies - of Interventions (ROBINS- I) tools and a specific tool for case reports/series.
RESULTS
Two RCTs, eight prospective and eight retrospective studies, and four case reports were included in the narrative synthesis. Every effectiveness study found a significant response in one or more of frequency/severity/duration of individual attacks or proportion of patients responding to treatment (47.8%-100.0%). There were five instances of potentially irreversible adverse effects. A higher injectate volume and use of concurrent prophylaxis may be associated with an increased likelihood of response. Methylprednisolone may have the best safety profile of available corticosteroids.
DISCUSSION
GON blockade is safe and effective for CH prevention. Higher injectate volumes may improve likelihood of response, and the likelihood of serious adverse events may be reduced by using methylprednisolone.
PROSPERO REGISTRATION NUMBER
CRD42020208435.
Topics: Humans; Cluster Headache; Retrospective Studies; Prospective Studies; Adrenal Cortex Hormones; Methylprednisolone; Nerve Block
PubMed: 36948579
DOI: 10.1136/jnnp-2023-331066 -
The Journal of Craniofacial Surgery Oct 2023The authors show a case with immunoglobulin G4 (IgG4)-related bilateral palpebral conjunctival mass and reviewed 7 similar previously reported cases. Our case was a...
The authors show a case with immunoglobulin G4 (IgG4)-related bilateral palpebral conjunctival mass and reviewed 7 similar previously reported cases. Our case was a 42-year-old woman who presented with a 2-year history of a left palpebral conjunctival mass. Pathologic examination of the specimens harvested from the mass revealed marked IgG4-positive plasma cell infiltration. The serum IgG4 level was within the normal limit. Although the mass was completely excised, the lesion recurred 1 month after the surgery, and another new lesion developed in the right upper palpebral conjunctiva. The patient was given 30 mg of oral prednisolone daily, which was tapered gradually. At a 10-month follow-up, the patient continued to take 15 mg of oral prednisolone. The lesions subsided on both sides. On the basis of the literature review, normal serum IgG4 level and upper eyelid lesions may be features of IgG4-related bilateral palpebral conjunctival lesions, and systemic steroids may be effective for this entity.
Topics: Female; Humans; Adult; Prednisolone; Conjunctiva; Eyelids; Glucocorticoids; Immunoglobulin G
PubMed: 37246303
DOI: 10.1097/SCS.0000000000009426 -
Journal of the American Animal Hospital... Jan 2024A 5 yr old castrated male bichon frise presented with chronic bilateral uveitis that had previously been controlled with systemic steroid administration for 6 mo,...
A 5 yr old castrated male bichon frise presented with chronic bilateral uveitis that had previously been controlled with systemic steroid administration for 6 mo, resulting in weight gain, polyuria, and polydipsia. To control the uveitis without systemic side effects, oral cyclosporine was started after discontinuing oral steroid, but discontinued one month later because of severe vomiting. Leflunomide (2 mg/kg q 12 hr) was initiated, and the uveitis symptoms resolved after 2 mo. The dose was tapered according to the remission of clinical signs, with no relapse during the following 13 mo. Leflunomide therapy was then discontinued due to vomiting caused by severe gastroenteritis and pancreatitis, and topical prednisolone monotherapy was continued . At 8 mo after discontinuation of leflunomide, bilateral uveitis recurred, and leflunomide therapy was resumed. However, the patient lost vision due to the progression of clinical signs at 33 mo after commencing leflunomide, and evisceration of the glaucomatous right eye was performed at 43 mo. Histopathologic examination revealed lymphocyte and plasma cell infiltration and melanin-laden macrophages in the uveal tissue, and the patient was diagnosed with immune-mediated uveitis. This case indicated that oral leflunomide may be a viable treatment option for canine idiopathic immune-mediated uveitis.
Topics: Dogs; Male; Animals; Leflunomide; Dog Diseases; Uveitis; Prednisolone; Vomiting
PubMed: 38175978
DOI: 10.5326/JAAHA-MS-7383