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Journal of Gastroenterology and... Aug 2023The socioeconomic burden of alcohol-related liver disease has been increasing worldwide. Its prevalence is underestimated, and patients with alcohol-related liver... (Review)
Review
The socioeconomic burden of alcohol-related liver disease has been increasing worldwide. Its prevalence is underestimated, and patients with alcohol-related liver disease are rarely diagnosed in the earlier phase of the disease spectrum. Alcoholic hepatitis is a distinct syndrome with life-threatening signs of systemic inflammation. In severe alcoholic hepatitis, prednisolone is indicated as the first-line treatment even with the possibility of various complications. Early liver transplantation can be another option for highly selected patients with a null response to prednisolone. Most importantly, abstinence is the mainstay of long-term care, but relapse is frequent among patients. Recent findings on the pathogenesis of alcoholic hepatitis have enabled us to discover new therapeutic targets. Preventing hepatic inflammation, reducing oxidative stress, improving gut dysbiosis, and enhancing liver regeneration are the main targets of emerging therapies. Herein, we review the pathogenesis, current treatment, and barriers to successful clinical trials of alcoholic hepatitis. Additionally, clinical trials for alcoholic hepatitis, either ongoing or recently completed, will be briefly introduced.
Topics: Humans; Hepatitis, Alcoholic; Liver Diseases, Alcoholic; Prednisolone; Liver Transplantation; Inflammation
PubMed: 37300449
DOI: 10.1111/jgh.16257 -
Annals of the Rheumatic Diseases Jan 2024The LoVAS trial reported non-inferiority in remission induction rates between the reduced-dose and conventional high-dose glucocorticoid regimens plus rituximab for... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The LoVAS trial reported non-inferiority in remission induction rates between the reduced-dose and conventional high-dose glucocorticoid regimens plus rituximab for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 6 months; however, maintenance glucocorticoid requirements and long-term outcomes are unknown.
METHODS
A total of 140 patients with new-onset ANCA-associated vasculitis without severe glomerulonephritis or alveolar haemorrhage were randomised to receive reduced-dose prednisolone (0.5 mg/kg/day) plus rituximab (375 mg/m/week×4) or high-dose prednisolone (1 mg/kg/day) plus rituximab. After achieving remission, patients received the rituximab maintenance therapy (1 g/6 months).
RESULTS
A total of 134 patients were analysed. Among patients who achieved remission with the protocolised treatments, the majority of patients in the reduced-dose group (89.7%) and 15.5% in the high-dose group discontinued prednisolone (median time to withdrawal, 150 and 375 days, respectively). During 24-month trial period, two patients in the reduced-dose group (2.8%) died, while five patients in the high-dose group (7.6%) died (p=0.225). Relapse occurred in nine patients in the reduced-dose group (13.0%) (two major and seven minor) and five in the high-dose group (7.6%) (two major and three minor) (p=0.311). Serious adverse events (SAEs) were less frequent in the reduced-dose group (36 events in 19 patients, 27.5%) than in the high-dose group (54 events in 30 patients, 46.2%) (p=0.025).
CONCLUSION
At 24 months, frequencies of relapse did not differ between the groups, and SAEs were less frequent in the reduced-dose group due to the lower event rate in the 6-month induction phase. The bias to myeloperoxidase-ANCA positivity (85.8%) in the trial population should be noted.
TRIAL REGISTRATION NUMBER
NCT02198248.
Topics: Humans; Rituximab; Glucocorticoids; Follow-Up Studies; Immunosuppressive Agents; Antibodies, Antineutrophil Cytoplasmic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Prednisolone; Remission Induction; Recurrence; Cyclophosphamide
PubMed: 37734880
DOI: 10.1136/ard-2023-224343 -
Annals of Medicine Dec 2023Liver transplant recipients have an increased risk of osteoporosis and fractures. The aim of this study was to identify risk factors for fractures after liver transplant...
BACKGROUND
Liver transplant recipients have an increased risk of osteoporosis and fractures. The aim of this study was to identify risk factors for fractures after liver transplant in a Taiwanese population.
METHODS
We identified newly diagnosed liver transplant recipients from the National Health Insurance Research Database in Taiwan between 2003 and 2015. Risk factors of post-transplant fractures were analyzed using a Cox proportional hazards model.
RESULTS
A total of 4821 patients underwent liver transplantation, of whom 419 (8.7%) had post-transplant fractures. Independent predictors of post-transplant fractures were age ≥65 years at transplantation (hazard ratio (HR): 1.566; 95% confidence interval (CI) 1.122-2.186), female sex (HR: 1.648; 95% CI 1.319-2.057), fractures within 1 year prior to transplant (HR: 3.664; 95% CI 2.503-5.364), hepatitis C carriers (HR: 1.594; 95% CI 1.289-1.970), alcoholism (HR: 1.557; 95% CI 1.087-2.230) and daily prednisolone dose >1.61-3.78 mg/day (HR: 1.354; 95% CI 1.005-1.824), >3.78-9.18 mg (HR: 4.182; 95% CI 3.155-5.544) and >9.18 mg (HR: 13.334; 95% CI 9.506-18.703). Post-transplant fractures were inversely correlated with tacrolimus (HR: 0.617; 95% CI 0.417-0.913) and sirolimus/everolimus (HR: 0.504; 95% CI 0.391-0.650) treatment.
CONCLUSIONS
The liver transplant recipients, and especially those who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were associated with an increased risk of post-transplant fractures. Conversely, the use of tacrolimus and sirolimus/everolimus was associated with a decreased risk of fractures.
Topics: Humans; Female; Liver Transplantation; Tacrolimus; Everolimus; Cohort Studies; Alcoholism; Risk Factors; Sirolimus; Proportional Hazards Models; Fractures, Bone; Hepatitis C; Prednisolone; Immunosuppressive Agents
PubMed: 37455447
DOI: 10.1080/07853890.2023.2230871 -
The Journal of the American Academy of... Sep 2023Spinal cord injury (SCI) is a leading cause of disability worldwide, and effective management is necessary to improve clinical outcomes. Many long-standing therapies... (Review)
Review
Spinal cord injury (SCI) is a leading cause of disability worldwide, and effective management is necessary to improve clinical outcomes. Many long-standing therapies including early reduction and spinal cord decompression, methylprednisolone administration, and optimization of spinal cord perfusion have been around for decades; however, their efficacy has remained controversial because of limited high-quality data. This review article highlights studies surrounding the role of early surgical decompression and its role in relieving mechanical pressure on the microvascular circulation thereby reducing intraspinal pressure. Furthermore, the article touches on the current role of methylprednisolone and identifies promising studies evaluating neuroprotective and neuroregenerative agents. Finally, this article outlines the expanding body of literature evaluating mean arterial pressure goals, cerebrospinal fluid drainage, and expansive duroplasty to further optimize vascularization to the spinal cord. Overall, this review aims to highlight evidence for SCI treatments and ongoing trials that may markedly affect SCI care in the near future.
Topics: Humans; Spinal Cord Injuries; Decompression, Surgical; Methylprednisolone; Pressure; Spinal Cord
PubMed: 37432977
DOI: 10.5435/JAAOS-D-23-00281 -
Nephrology (Carlton, Vic.) Sep 2023A male aged in his mid-60s was diagnosed with xanthogranulomatous pyelonephritis after a left nephrectomy for a renal mass that was detected during the investigation of...
A male aged in his mid-60s was diagnosed with xanthogranulomatous pyelonephritis after a left nephrectomy for a renal mass that was detected during the investigation of weight loss and drenching night sweats. Past medical history includes type 2 diabetes mellitus, transient ischaemic attack, hypertension, non-alcoholic fatty liver disease, dyslipidaemia, osteoarthritis and active smoking. Three years after the initial diagnosis, the patient represented with abdominal pain. CT imaging demonstrated new pulmonary and pancreatic lesions, which were histologically confirmed to be xanthogranulomatous disease. The patient was too unstable for surgical intervention so was commenced on glucocorticoids with marked improvement in his clinical condition with resolution of inflammatory markers and radiographic improvement. Weaning of prednisolone led to a relapse of disease, which was managed with re-introduction of high-dose prednisolone and the initiation of azathioprine. The patient is now 2 years post initiation of immunosuppressive therapy with stable renal function and no active inflammation.
Topics: Humans; Male; Pyelonephritis, Xanthogranulomatous; Diabetes Mellitus, Type 2; Nephrectomy; Immunosuppression Therapy; Prednisolone
PubMed: 37222079
DOI: 10.1111/nep.14188 -
Human Molecular Genetics Jan 2024Duchenne muscular dystrophy (DMD) is a progressive disabling X-linked recessive disorder that causes gradual and irreversible loss of muscle, resulting in early death....
Duchenne muscular dystrophy (DMD) is a progressive disabling X-linked recessive disorder that causes gradual and irreversible loss of muscle, resulting in early death. The corticosteroids prednisone/prednisolone and deflazacort are used to treat DMD as the standard of care; however, only deflazacort is FDA approved for DMD. The novel atypical corticosteroid vamorolone is being investigated for treatment of DMD. We compared the pharmaceutical properties as well as the efficacy and safety of the three corticosteroids across multiple doses in the B10-mdx DMD mouse model. Pharmacokinetic studies in the mouse and evaluation of p-glycoprotein (P-gP) efflux in a cellular system demonstrated that vamorolone is not a strong P-gp substrate resulting in measurable central nervous system (CNS) exposure in the mouse. In contrast, deflazacort and prednisolone are strong P-gp substrates. All three corticosteroids showed efficacy, but also side effects at efficacious doses. After dosing mdx mice for two weeks, all three corticosteroids induced changes in gene expression in the liver and the muscle, but prednisolone and vamorolone induced more changes in the brain than did deflazacort. Both prednisolone and vamorolone induced depression-like behavior. All three corticosteroids reduced endogenous corticosterone levels, increased glucose levels, and reduced osteocalcin levels. Using micro-computed tomography, femur bone density was decreased, reaching significance with prednisolone. The results of these studies indicate that efficacious doses of vamorolone, are associated with similar side effects as seen with other corticosteroids. Further, because vamorolone is not a strong P-gp substrate, vamorolone distributes into the CNS increasing the potential CNS side-effects.
Topics: Animals; Mice; Prednisolone; X-Ray Microtomography; Mice, Inbred mdx; Muscular Dystrophy, Duchenne; Corticosterone; Pharmaceutical Preparations; Pregnadienediols; Pregnenediones
PubMed: 37819629
DOI: 10.1093/hmg/ddad173 -
Danish Medical Journal Oct 2023The diagnosis and management of subacute thyroiditis (SAT) may be challenging, and more evidence on patient and disease characteristics is warranted.
INTRODUCTION
The diagnosis and management of subacute thyroiditis (SAT) may be challenging, and more evidence on patient and disease characteristics is warranted.
METHODS
This was a retrospective cohort study of all patients in the North Denmark Region with a SAT diagnosis in the Danish National Patient Registry, 2016-2018. The medical records and biochemical results prior to the diagnosis and during a two-year follow-up period were reviewed.
RESULTS
A total of 71 patients with a SAT diagnosis were identified, and the diagnosis was verified in 44 (62.0%) cases with an incidence rate of 2.4/100,000/year. Patients with verified SAT were predominantly females (72.7%) with a median age of 50.7 years. Biochemical results showed thyrotoxicosis at the initial examination in 69.8% and elevated C-reactive protein in 86.5% of patients. Longitudinal biochemical assessment showed a biphasic response (median thyroid-stimulating hormone, initially: 0.02 mIU/l, at three months: 4.7 mIU/l and 2.4 mIU/l after two years). Treatment with non-steroidal anti-inflammatory drugs, beta-blockers and/or prednisolone was initiated in 23 of the 38 patients (60.5%) evaluated, and ten of 33 patients (30.3%) with follow-up data received thyroid hormone replacement therapy.
CONCLUSION
In the North Denmark Region, a hospital diagnosis of SAT was verified in less than two thirds of cases. Further large studies are warranted to extend the findings concerning the treatment and outcome of SAT.
FUNDING
None.
TRIAL REGISTRATION
Not relevant.
Topics: Female; Humans; Middle Aged; Male; Thyroiditis, Subacute; Retrospective Studies; Prednisolone; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37897374
DOI: No ID Found -
The Journal of Allergy and Clinical... Nov 2023Systemic corticosteroids (SCSs) are associated with short- and long-term adverse effects. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Systemic corticosteroids (SCSs) are associated with short- and long-term adverse effects.
OBJECTIVE
To assess mepolizumab efficacy according to prior SCS use and characterize mepolizumab's SCS-sparing capabilities, in patients with severe chronic rhinosinusitis with nasal polyps.
METHODS
In the randomized, double-blind, phase III SYNAPSE trial (NCT03085797), adults with severe chronic rhinosinusitis with nasal polyps eligible for repeat sinus surgery despite standard of care treatment received mepolizumab (100 mg subcutaneously) or placebo every 4 weeks for 52 weeks. The impact of prior SCS courses (0/1/>1) on mepolizumab versus placebo treatment responses (changes from baseline in total endoscopic nasal polyp [week 52], nasal obstruction visual analog scale [weeks 49-52], and 22-item Sino-Nasal Outcome Test total [week 52] scores) was analyzed post hoc. To characterize mepolizumab's SCS-sparing capabilities, time-to-first SCS course for nasal polyps (prespecified) and total prednisolone-equivalent oral corticosteroid dose by patient baseline characteristics (post hoc, in patients with ≥1 SCS course during SYNAPSE) were assessed up to week 52.
RESULTS
Mepolizumab versus placebo improved treatment responses, irrespective of prior SCS use. By week 52, the probability of requiring SCSs for nasal polyps (Kaplan-Meier estimate [95% CI]) was lower with mepolizumab (25.4% [20.0-32.1]) versus placebo (37.5% [31.1-44.6]). In patients requiring 1 or more dose of SCSs, total (mean ± SD mg/y) prednisolone-equivalent oral corticosteroid dose was lower with mepolizumab (438.9 ± 350.40) versus placebo (505.2 ± 455.091), overall and irrespective of prior sinus surgeries, blood eosinophil count, or comorbidities.
CONCLUSIONS
Mepolizumab is associated with clinical benefits in patients with severe chronic rhinosinusitis with nasal polyps regardless of prior SCS use and has an SCS-sparing effect.
Topics: Adult; Humans; Adrenal Cortex Hormones; Chronic Disease; Nasal Polyps; Prednisolone; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 37586475
DOI: 10.1016/j.jaip.2023.08.015 -
Kidney360 Sep 2023The contribution of IV methylprednisolone to glucocorticoid toxicity is often overlooked with limited evidence supporting its use. Markedly reduced cumulative...
KEY POINTS
The contribution of IV methylprednisolone to glucocorticoid toxicity is often overlooked with limited evidence supporting its use. Markedly reduced cumulative glucocorticoid dosing for remission induction therapy in AAV is safe and effective. Reduced IV methylprednisolone and radical steroid avoidance strategies have not been shown to have any significant adverse effect on outcomes.
BACKGROUND
Glucocorticoids (GCs) remain integral to the management of ANCA-associated vasculitis (AAV), but are associated with significant adverse effects. Recent studies have shown reduced oral GC dosing to be safe and effective; however, data guiding the use of intravenous (IV) methylprednisolone (MTP) are limited.
METHOD
A single-center retrospective cohort of patients with AAV were divided into two groups: low-dose GC (patients receiving 250 mg of IV MTP, followed by a tapering course of 30 mg of prednisolone daily) versus high-dose GC (1.5 g of IV MTP, followed by a tapering course of 40–60 mg of prednisolone daily). Primary outcomes included ESKD and mortality, and secondary outcomes included GC-related toxicity, remission, and relapse rates. This study was applied to patients with newly diagnosed AAV, including those with severe or life-threatening disease.
RESULTS
Sixty-five patients were included in the final analysis—34 in the high-dose treatment group and 31 in the low-dose treatment group. At diagnosis, more advanced renal impairment and histological disease were present in the low-dose cohort. The rate of ESKD was similar between the groups at 6 and 12 months ( = 0.22, = 0.60, respectively). More deaths occurred in the high-dose group (26.5% versus 6.5%, = 0.05), although this was not significant on multivariable analysis ( = 0.06). Remission rates were comparable, and there was no significant difference in relapses. Adverse events were seen in both groups, but patients in the high-dose group experienced a higher incidence of severe infections, weight gain, and steroid-induced diabetes.
CONCLUSION
We demonstrate that a markedly reduced dose of IV MTP with a lower overall cumulative dose of GCs is safe and effective in the management of severe AAV disease, with no significant difference in primary outcomes.
Topics: Humans; Methylprednisolone; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Immunosuppressive Agents; Remission Induction
PubMed: 37668468
DOI: 10.34067/KID.0000000000000222 -
Frontiers in Immunology 2023Imiquimod (IMQ) is a topical agent that induces local inflammation the Toll-like receptor 7 pathway. Recently, an IMQ-driven skin inflammation model was developed in... (Randomized Controlled Trial)
Randomized Controlled Trial
Imiquimod (IMQ) is a topical agent that induces local inflammation the Toll-like receptor 7 pathway. Recently, an IMQ-driven skin inflammation model was developed in healthy volunteers for proof-of-pharmacology trials. The aim of this study was to profile the cellular, biochemical, and clinical effects of the marketed anti-inflammatory compound prednisolone in an IMQ model. This randomized, double-blind, placebo-controlled study was conducted in 24 healthy volunteers. Oral prednisolone (0.25 mg/kg/dose) or placebo (1:1) was administered twice daily for 6 consecutive days. Two days after treatment initiation with prednisolone or placebo, 5 mg imiquimod (IMQ) once daily for two following days was applied under occlusion on the tape-stripped skin of the back for 48 h in healthy volunteers. Non-invasive (imaging and biophysical) and invasive (skin punch biopsies and blister induction) assessments were performed, as well as IMQ stimulation of whole blood. Prednisolone reduced blood perfusion and skin erythema following 48 h of IMQ application (95% CI [-26.4%, -4.3%], p = 0.0111 and 95% CI [-7.96, -2.13], p = 0.0016). Oral prednisolone suppressed the IMQ-elevated total cell count (95% CI [-79.7%, -16.3%], p = 0.0165), NK and dendritic cells (95% CI [-68.7%, -5.2%], p = 0.0333, 95% CI [-76.9%, -13.9%], p = 0.0184), and classical monocytes (95% CI [-76.7%, -26.6%], p = 0.0043) in blister fluid. Notably, TNF, IL-6, IL-8, and Mx-A responses in blister exudate were also reduced by prednisolone compared to placebo. Oral prednisolone suppresses IMQ-induced skin inflammation, which underlines the value of this cutaneous challenge model in clinical pharmacology studies of novel anti-inflammatory compounds. In these studies, prednisolone can be used as a benchmark.
Topics: Humans; Imiquimod; Blister; Healthy Volunteers; Dermatitis; Prednisolone; Inflammation; Anti-Inflammatory Agents
PubMed: 37545524
DOI: 10.3389/fimmu.2023.1197650