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Gene Therapy Mar 2024Adeno-associated virus (AAV) vector gene therapy is a promising approach to treat rare genetic diseases; however, an ongoing challenge is how to best modulate host...
Adeno-associated virus (AAV) vector gene therapy is a promising approach to treat rare genetic diseases; however, an ongoing challenge is how to best modulate host immunity to improve transduction efficiency and therapeutic outcomes. This report presents two studies characterizing multiple prophylactic immunosuppression regimens in male cynomolgus macaques receiving an AAVrh10 gene therapy vector expressing human coagulation factor VIII (hFVIII). In study 1, no immunosuppression was compared with prednisolone, rapamycin (or sirolimus), rapamycin and cyclosporin A in combination, and cyclosporin A and azathioprine in combination. Prednisolone alone demonstrated higher mean peripheral blood hFVIII expression; however, this was not sustained upon taper. Anti-capsid and anti-hFVIII antibody responses were robust, and vector genomes and transgene mRNA levels were similar to no immunosuppression at necropsy. Study 2 compared no immunosuppression with prednisolone alone or in combination with rapamycin or methotrexate. The prednisolone/rapamycin group demonstrated an increase in mean hFVIII expression and a mean delay in anti-capsid IgG development until after rapamycin taper. Additionally, a significant reduction in the plasma cell gene signature was observed with prednisolone/rapamycin, suggesting that rapamycin's tolerogenic effects may include plasma cell differentiation blockade. Immunosuppression with prednisolone and rapamycin in combination could improve therapeutic outcomes in AAV vector gene therapy.
Topics: Male; Humans; Animals; Sirolimus; Cyclosporine; Plasma Cells; Prednisolone; Genetic Therapy; Genetic Vectors; Macaca; Dependovirus
PubMed: 37833563
DOI: 10.1038/s41434-023-00423-z -
Journal of Medical Case Reports Feb 2024Kimura's disease is a rare chronic inflammatory disorder of unknown etiology that is seen in people of Asian descent. It is characterized by head and neck subcutaneous...
BACKGROUND
Kimura's disease is a rare chronic inflammatory disorder of unknown etiology that is seen in people of Asian descent. It is characterized by head and neck subcutaneous nodules along with lymphadenopathy, which is usually solitary but can be generalized. It is diagnosed histopathologically by the proliferation of blood vessels and germinal centers in lymphoid follicles, along with variable degrees of fibrosis and extensive eosinophil infiltration. Its localized form is treated with surgical excision, while generalized lesions and those that do not respond to surgical excision can be managed with steroids or radiotherapy.
CASE
In this report, we present the first case of Kimura's disease in the Ethiopian literature in a 40-year-old Ethiopian man that presented with generalized pruritic subcutaneous nodules and lymphadenopathy, which were effectively managed with a tapering course of prednisolone, and a relapse that showed good sustained response with slow steroid taper.
CONCLUSION
We have demonstrated that, even though it is very rare in the African continent, Kimura's disease is to be considered as a differential diagnosis for patients that present with subcutaneous nodules and lymphadenopathy. We also have demonstrated that relapses can be effectively managed with reinitiation of the same dose of steroids but with a very slow taper.
Topics: Male; Humans; Adult; Kimura Disease; Angiolymphoid Hyperplasia with Eosinophilia; Neoplasm Recurrence, Local; Lymphadenopathy; Prednisolone
PubMed: 38317181
DOI: 10.1186/s13256-024-04352-2 -
Trials Jan 2023Patients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology (CKDu), have been treated with oral prednisolone and doxycycline by physicians in Sri Lanka. This trial assessed the effectiveness of prednisolone and doxycycline based on eGFR changes at 6 months in patients with AIN of unknown aetiology.
METHOD
A randomized clinical trial with a 2 × 2 factorial design for patients presenting with AIN of unknown aetiology (n = 59) was enacted to compare treatments with; A-prednisolone, B-doxycycline, C-both treatments together, and D-neither. The primary outcome was a recovery of patients' presenting renal function to eGFR categories: 61-90 ml/min/1.73m (complete remission- CR) to 31-60 ml/min/1.73m (partial remission- PR) and 0-30 ml/min/1.73m no remission (NR) by 6 months. A secondary outcome was progression-free survival (not reaching < 30 ml/min/1.73m eGFR), by 6-36 months. Analysis was by intention to treat.
RESULTS
Seventy patients compatible with a clinical diagnosis of AIN were biopsied for eligibility; 59 AIN of unknown aetiology were enrolled, A = 15, B = 15, C = 14 and D = 15 randomly allocated to each group. Baseline characteristics were similar between groups. The number of patients with CR, PR and NR, respectively, by 6 months, in group A 3:8:2, group B 2:8:3 and group C 8:5:0 was compared with group D 8:6:1. There were no significant differences found between groups A vs. D (p = 0.2), B vs. D (p = 0.1) and C vs. D (p = 0.4). In an exploratory analysis, progression-free survival in prednisolone-treated (A + C) arms was 0/29 (100%) in comparison to 25/30 (83%) in those not so treated (B + D) arms, and the log-rank test was p = 0.02, whereas no such difference found (p = 0.60) between doxycycline-treated (B + C) arms 27/29 (93%) vs those not so treated (A + D) arms 27/30 (90%).
CONCLUSION
Prednisolone and doxycycline were not beneficial for the earliest presentation of CKDu at 6 months. However, there is a potential benefit of prednisolone on the long-term outcome of CKDu. An adequately powered steroid trial using patients reaching < 30 ml/min/1.73m eGFR by 3 years, as an outcome is warranted for AIN of unknown aetiology.
TRIAL REGISTRATION
Sri Lanka Clinical Trial Registry SLCTR/2014/007, Registered on the 31st of March 2014.
Topics: Humans; Doxycycline; Glucocorticoids; Nephritis, Interstitial; Prednisolone; Renal Insufficiency, Chronic; Sri Lanka
PubMed: 36600250
DOI: 10.1186/s13063-022-07056-4 -
Annals of Hematology Jul 2023Prednisolone, used as a standard initial treatment for immune thrombocytopenia (ITP), is an important risk factor for osteoporosis. Recently, we found that prescription... (Review)
Review
Prednisolone, used as a standard initial treatment for immune thrombocytopenia (ITP), is an important risk factor for osteoporosis. Recently, we found that prescription of bisphosphonate during initial loading of prednisolone may prevent reduction in bone mineral density and development of glucocorticoid-induced osteoporosis (GIO) in older patients with ITP receiving prolonged steroid therapy. In this review, I describe the treatment options for older patients with ITP, and present the best practices for screening, evaluating, and diagnosing ITP. I also summarize the literature from 2017 to 2022 on the treatment options for ITP, including discussions on the contraindications and side effects, with an emphasis on GIO, and the relative merits of bisphosphonates as a co-treatment for prevention of GIO. Finally, I present a perspective and an expert recommendation on how older patients with ITP would best be served in the future.
Topics: Humans; Aged; Diphosphonates; Glucocorticoids; Purpura, Thrombocytopenic, Idiopathic; Osteoporosis; Bone Density Conservation Agents; Bone Density; Prednisolone
PubMed: 37171596
DOI: 10.1007/s00277-023-05266-7 -
The Journal of Veterinary Medical... Jan 2021This study aimed to assess the structural and functional effects of long-term hyperglucocorticoidemia on canine myocardium and compare these parameters with...
This study aimed to assess the structural and functional effects of long-term hyperglucocorticoidemia on canine myocardium and compare these parameters with histopathological changes. Twelve healthy male beagle dogs were enrolled and assigned to the high-dose prednisolone (P; n=6) and control (C; n=6) groups. The P group was treated with 2 mg/kg of prednisolone BID for 84 days. Clinical parameters were measured using echocardiography and non-invasive systolic blood pressure (SBP) measured before the initiation of synthetic corticosteroids and at 7, 28, 56, and 84 days after the start of medication. For histological evaluation, cardiovascular tissue was harvested from dogs in groups P (at the end of the medication period) and C (scheduled to be euthanized for unrelated reasons). In the P group, clinical changes including thickening of the left ventricular free wall (LVFW) and interventricular septum (IVS), decreased left ventricular (LV) diastolic function, and increased SBP were observed after the start of medication. During histological evaluation, fibrosis was observed in the LVFW and IVS in the P group. Furthermore, decreased glucocorticoid receptor (GCR) levels were observed in the LVFW, right ventricular free wall (RVFW), and IVS and increased mineralocorticoid receptor (MCR) levels were observed in the LVFW and RVFW in the P group compared with those in the C group. In conclusion, fibrosis may cause LV structural and functional abnormalities in dogs with hyperadrenocorticism. Furthermore, GCR downregulation and upregulated MCR might influence the myocardial fibrosis.
Topics: Animals; Dogs; Echocardiography; Heart; Heart Ventricles; Male; Myocardium; Prednisolone
PubMed: 33268642
DOI: 10.1292/jvms.20-0401 -
Journal For Immunotherapy of Cancer Jul 2023There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).
BACKGROUND
There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).
METHODS
In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest.
RESULTS
Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician's decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death.
CONCLUSIONS
In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP.
TRIAL REGISTRATION NUMBER
jRCT: 1041190029.
Topics: Humans; Prospective Studies; Pneumonia; Prednisolone; Neoplasms; Recurrence
PubMed: 37500182
DOI: 10.1136/jitc-2023-007056 -
Journal of Cataract and Refractive... Nov 2022To compare the safety and efficacy of topical prednisolone and intracanalicular dexamethasone ophthalmic insert for the prevention of postoperative inflammation after...
PURPOSE
To compare the safety and efficacy of topical prednisolone and intracanalicular dexamethasone ophthalmic insert for the prevention of postoperative inflammation after cataract surgery.
SETTING
Penn State College of Medicine, Hershey, Pennsylvania.
DESIGN
Retrospective consecutive case series.
METHODS
Patients scheduled for elective phacoemulsification cataract surgery with a plan to receive inflammation prophylaxis with topical prednisolone (prednisolone acetate 1 mg/1 mL) between January 2018 and November 2019 or intracanalicular dexamethasone (Dextenza, 0.4 mg) between December 2019 and March 2021 were screened. Patients were seen 1 day, 1 week, and 4 to 16 weeks postoperatively. Medical records were also reviewed for any urgent messages between visits. Primary end points were proportion of eyes with (1) breakthrough inflammation requiring escalation of anti-inflammatory therapy and (2) intraocular pressure (IOP) increase ≥10 mm Hg at 4 to 16 weeks of follow-up. Secondary end points included incidence of intraoperative complications, cystoid macular edema, and infectious sequelae.
RESULTS
358 patient charts (358 eyes) were screened. Of these, 262 eyes of 262 patients met the criteria for inclusion in the study; 131 eyes received topical drops, and 131 eyes received the intracanalicular insert. Among eyes that completed follow-up, 9 eyes (6.9%) in the drops group and 12 eyes (9.2%) in the insert group experienced breakthrough inflammation necessitating treatment ( P = .50). 2 eyes in the drops group and 1 eye in the insert group had elevated IOP.
CONCLUSIONS
Postoperative inflammation prophylaxis with the intracanalicular insert may be associated with similar rates of breakthrough inflammation and IOP elevation as topical drops.
Topics: Humans; Retrospective Studies; Visual Acuity; Phacoemulsification; Prednisolone; Cataract; Adrenal Cortex Hormones; Inflammation; Dexamethasone; Postoperative Complications; Intraocular Pressure; Ophthalmic Solutions
PubMed: 35537939
DOI: 10.1097/j.jcrs.0000000000000963 -
BMJ Case Reports Sep 2019A 44-year-old asthmatic male patient presented to the health centre with a 3-week history of coryzal symptoms, persistent productive sputum and shortness of breath. The...
A 44-year-old asthmatic male patient presented to the health centre with a 3-week history of coryzal symptoms, persistent productive sputum and shortness of breath. The chest X-ray (CXR) revealed symmetrical, perihilar airspace shadowed with peribronchial cuffing and bilateral reticular markings. The patient did not improve despite treatment, and hence a high resolution CT (HRCT) scan of the thorax was recommended. The HRCT showed smooth interlobular septal thickening, central perihilar soft tissue thickening and patches of ground glass changes. Both the CXR and HRCT findings, along with the symptoms and eosinophilia counts, were suggestive of idiopathic acute eosinophilic pneumonia (IAEP) which was confirmed on bronchoalveolar lavage. The patient was successfully treated with steroids. This case highlights the symptoms, diagnosis, management and treatment of IAEP. A rapid diagnosis of this rare disease is essential since it can be completely cured with correct management but can be fatal if left untreated. Once properly treated, this disease does not recur.
Topics: Adult; Bronchoalveolar Lavage; Diagnosis, Differential; Dyspnea; Glucocorticoids; Humans; Male; Pneumonia; Prednisolone; Pulmonary Eosinophilia; Tomography Scanners, X-Ray Computed
PubMed: 31558489
DOI: 10.1136/bcr-2019-231095 -
BMJ Case Reports Feb 2021Rosai-Dorfman disease is a rare benign histiocytic proliferative disease of unknown cause that, in exceptional cases, presents with lesions confined to the skin....
Rosai-Dorfman disease is a rare benign histiocytic proliferative disease of unknown cause that, in exceptional cases, presents with lesions confined to the skin. Clinically variable types of lesions such as papules, nodules and plaques have been reported. We present a case of a 27-year-old woman with a 1-year history of erythematous papular and nodular lesions on the malar and right axillary regions, previously misdiagnosed as acne. She reported no fever, malaise or weight loss, while physical examination and laboratory workup were normal. Bacteriological and mycobacteriological cultures were negative. Histopathological findings showed dense infiltration of inflammatory cells involving the entire dermis, consisting of large macrophages with emperipolesis, S100 and CD68 positive, neutrophils, eosinophils, lymphocytes and plasma cells. The patient was treated with oral prednisolone without improvement. Dapsone was subsequently initiated with favourable clinical response. The present article aimed to emphasise the clinical and histological differential diagnosis and share the treatment experience.
Topics: Adult; Anti-Infective Agents; Dapsone; Diagnostic Errors; Emperipolesis; Eosinophils; Female; Glucocorticoids; Histiocytosis, Sinus; Humans; Prednisolone; Rare Diseases; S100 Proteins; Skin
PubMed: 33541998
DOI: 10.1136/bcr-2020-239244 -
Clinical and Experimental Allergy :... Jan 2021Although the efficacy of corticosteroid treatment in controlling asthma is widely accepted, its effectiveness is undermined by poor adherence. However, the optimal... (Review)
Review
BACKGROUND
Although the efficacy of corticosteroid treatment in controlling asthma is widely accepted, its effectiveness is undermined by poor adherence. However, the optimal method for measuring adherence to asthma therapy remains unclear.
OBJECTIVE
To perform a review of the literature reporting biological, objective methods for assessing adherence to inhaled or oral corticosteroids in asthma; we included studies reporting direct measurement of exogenous corticosteroids in blood, or the effect of adherence on exhaled nitric oxide.
DESIGN
We searched three databases MEDLINE (using both PubMed and Ovid), the Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Web of Science for articles published between January 1975 and July 2020. Quality of the studies was assessed using the National Institute of Health checklist.
RESULTS
From 2850 screened articles, 26 fulfilled the inclusion criteria. Measurement of blood prednisolone with or without cortisol was used in eight studies as a measure of oral corticosteroid adherence, and fractional exhaled nitric oxide (FeNO) in 17 studies for inhaled corticosteroid adherence. Inhaled corticosteroids were measured directly in the blood in one study. By direct measurement of drug levels in the blood, adherence rates to oral corticosteroids ranged from 47% to 92%, although the performance and timing of the test were often not known, making interpretation of findings and serum prednisolone concentrations difficult. FeNO is generally lower in adherent than non-adherent patients, but no absolute cut-off can be proposed based on the available data. However, a fall in FeNO following supervised inhaled corticosteroid dosing could indicate previous poor adherence.
CONCLUSIONS AND CLINICAL RELEVANCE
Despite prednisolone and cortisol levels commonly being used as adherence markers in clinical practice, further work is required to assess the influence of the dose and timing on blood levels. The promising findings of FeNO suppression testing should be explored in further prospective studies.
Topics: Administration, Inhalation; Administration, Oral; Asthma; Drug Monitoring; Fractional Exhaled Nitric Oxide Testing; Glucocorticoids; Humans; Hydrocortisone; Medication Adherence; Prednisolone
PubMed: 33190234
DOI: 10.1111/cea.13787