ABSTRACT
PURPOSE: The purpose of this study was to evaluate the effectiveness and safety of an intravitreal dexamethasone (DEX) implant for the treatment of macular edema (ME) following pars plana vitrectomy (PPV) and removal of the primary epiretinal membrane (ERM) and to assess the impact of the integrity of the ellipsoid zone (EZ) and disorganization of the retinal inner layer (DRIL) grade on visual and anatomical outcomes. METHODS: Forty-two pseudophakic patients who developed ME following PPV and removal of the primary stage 2-3 ERM were included. Patients were divided into two groups when ME was diagnosed via spectral domain optic coherence tomography (SD-OCT). In the DEX group (n = 22), DEX was implanted for the treatment of ME. In the control group (n = 20), only observation was conducted, without any treatment. The best-corrected visual acuity (BCVA) and macular thickness (MT) of the two groups were compared at baseline and 1, 6, and 12 months after DEX implantation. The effects of OCT parameters such as EZ integrity and DRIL grade were also evaluated in terms of decreases in MT and increases in VA in the treatment of ME with DEX implantation. Intraocular pressure (IOP), number of DEX implantations and adverse effects were also recorded. RESULTS: While a statistically significant increase in the mean BCVA was observed in the DEX group (p < 0.001 at months 1, 6, and 12, respectively), no such increase was detected in the control group (p = 0.169, p = 0.065, and p = 0.058 at months 1, 6 and 12, respectively) compared with the baseline. A statistically significant decrease in the mean MT was observed in the DEX group (p < 0.001 at months 1, 6, and 12); however, no significant difference was observed in the control group (p = 0.081, p = 0.065, and p = 0.054 at months 1, 6 and 12, respectively) compared with the baseline. Significant differences were found between the two groups in terms of the increase in BCVA (p < 0.01) and decrease in MT (p < 0.01) at all visits, with the outcomes being more favorable in the DEX group. A statistically significant relationship was found between the increase in VA and EZ integrity and DRIL grade in both groups. Ten patients (45.4%) received two injections of DEX during the follow-up. An increase in IOP was observed in five patients (22.7%) who were treated with topical antiglaucomatous drops. No significant side effects were observed. CONCLUSION: DEX implantation was found to be effective and safe for the treatment of ME following PPV and primary ERM removal, although some eyes may require repeated injections to achieve visual and anatomical success. Additionally, a relationship was found between EZ integrity, DRIL grade and visual-anatomical outcomes.
Subject(s)
Dexamethasone , Drug Implants , Epiretinal Membrane , Glucocorticoids , Intravitreal Injections , Macular Edema , Tomography, Optical Coherence , Visual Acuity , Vitrectomy , Humans , Dexamethasone/administration & dosage , Macular Edema/etiology , Macular Edema/drug therapy , Macular Edema/diagnosis , Macular Edema/therapy , Male , Female , Epiretinal Membrane/surgery , Epiretinal Membrane/diagnosis , Vitrectomy/methods , Glucocorticoids/administration & dosage , Tomography, Optical Coherence/methods , Aged , Middle Aged , Follow-Up Studies , Retrospective Studies , Treatment Outcome , Macula Lutea/pathology , Postoperative Complications/drug therapyABSTRACT
BACKGROUND: The first line treatment for moderate to severe active thyroid associated ophthalmopathy is glucocorticoid pulse therapy, but for patients with contraindications to hormone therapy or hormone resistance, it is urgent to find a suitable treatment plan. AIMS: To find a reliable alternative to hormone pulse therapy for thyroid associated ophthalmopathy by comparing the efficacy with first-line treatment regimens. METHODS: Search PubMed, Ovid, Web of science, Cochrane library, and Clinical Trials.gov for randomized controlled trials on the treatment of thyroid associated ophthalmopathy published as of July 7, 2024. Quality evaluation and Bayesian network analysis were conducted using RevMan 5.3 software, STATA15.0 software, and ADDIS 1.16.8 software. RESULTS: A total of 666 patients were included in 11 studies and 8 interventions. Network analysis showed that the three interventions of mycophenolate mofetil combined with glucocorticoids, Teprotumumab and 99Tc-MDP were superior to glucocorticoid pulse therapy in improving clinical activity scores and proptosis. The regimen of glucocorticoids combined with statins can improve the quality of life score and diplopia score of patients. Neither methotrexate combined with glucocorticoids nor rituximab alone showed additional advantages when compared with glucocorticoid pulse therapy. CONCLUSION: Mycophenolate mofetil combined with glucocorticoid therapy is very beneficial for moderate to severe active thyroid associated ophthalmopathy. Mycophenolate mofetil may be a good choice when patients have contraindications to hormone use or hormone resistance. Teprotumumab is very promising and may be able to avoid patients undergoing orbital decompression surgery. The durability and safety of its long-term efficacy need to be further observed.
Subject(s)
Bayes Theorem , Glucocorticoids , Graves Ophthalmopathy , Humans , Graves Ophthalmopathy/drug therapy , Graves Ophthalmopathy/diagnosis , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Network Meta-Analysis , Quality of Life , Antibodies, Monoclonal, HumanizedABSTRACT
Glucocorticoids (GC) and parathyroid hormone (PTH) are widely used therapeutic endocrine hormones where their effects on bone and joint arise from actions on multiple skeletal cell types. In osteocytes, GC and PTH exert opposing effects on perilacunar canalicular remodeling (PLR). Suppressed PLR can impair bone quality and joint homeostasis, including in GC-induced osteonecrosis. However, combined effects of GC and PTH on PLR are unknown. Given the untapped potential to target osteocytes to improve skeletal health, this study sought to test the feasibility of therapeutically mitigating PLR suppression. Focusing on subchondral bone and joint homeostasis, we hypothesize that PTH(1-34), a PLR agonist, could rescue GC-suppressed PLR. The skeletal effects of GC and PTH(1-34), alone or combined, were examined in male and female mice by micro-computed tomography, mechanical testing, histology, and gene expression analysis. For each outcome, females were more responsive to GC and PTH(1-34) than males. GC and PTH(1-34) exerted regional differences, with GC increasing trabecular bone volume but reducing cortical bone thickness, stiffness, and ultimate force. Despite PTH(1-34)'s anabolic effects on trabecular bone, it did not rescue GC's catabolic effects on cortical bone. Likewise, cartilage integrity and subchondral bone apoptosis, tartrate-resistant acid phosphatase (TRAP) activity, and osteocyte lacunocanalicular networks showed no evidence that PTH(1-34) could offset GC-dependent effects. Rather, GC and PTH(1-34) each increased cortical bone gene expression implicated in bone resorption by osteoclasts and osteocytes, including Acp5, Mmp13, Atp6v0d2, Ctsk, differences maintained when GC and PTH(1-34) were combined. Since PTH(1-34) is insufficient to rescue GC's effects on young female mouse bone, future studies are needed to determine if osteocyte PLR suppression, due to GC, aging, or other factors, can be offset by a PLR agonist.
Subject(s)
Bone Density , Bone Remodeling , Glucocorticoids , Osteocytes , Parathyroid Hormone , Animals , Osteocytes/drug effects , Osteocytes/metabolism , Parathyroid Hormone/pharmacology , Female , Male , Mice , Glucocorticoids/pharmacology , Bone Remodeling/drug effects , Bone Density/drug effects , Mice, Inbred C57BL , Bone and Bones/drug effects , Bone and Bones/metabolism , X-Ray MicrotomographyABSTRACT
Submitted as: (mark with X) X_Case Report _Case Presentation _Photo Vignette _Letter Authors declare that the contents of this article are their own original unpublished findings. Title: The use of systemic corticosteroids in debilitating sycosis barbae, sycosis barbae fulminans Authors: Kathleen R Krivda MD, Uzoamaka J Okoro MD, Nicholas F Logemann DO Affiliations: Department of Dermatology, Walter Reed National Military Medical Center, Bethesda, Bethesda, Maryland, USA Corresponding Author: Kathleen Krivda MD, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda MD 20889, Tel: 240-751-3823, Email: kathleenkrivda@gmail.com Abstract (no more than 200 words).
Subject(s)
Glucocorticoids , Humans , Male , Glucocorticoids/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Middle Aged , AdultABSTRACT
PURPOSE: To evaluate the responses of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) to intravitreal injection therapy. METHODS: In this retrospective, comparative, and multicenter study, patients who had previously untreated DME, who received intravitreal ranibizumab (IVR) or aflibercept (IVA) and/or steroid treatment with the pro re nata (PRN) treatment regimen after a 3-month loading dose, and had a 12-month follow-up in the MARMASIA Study Group were included. Morphological patterns of DME were divided into four groups based on OCT features diffuse/spongious edema (Group 1), cystoid edema (Group 2), diffuse/spongious edema+subretinal fluid (SRF) (Group 3), and cystoid edema+SRF (Group 4). Changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) at months 3, 6, and 12, and the number of injections at month 12 were compared between the DME groups. RESULTS: 455 eyes of 299 patients were included in the study. The mean baseline BCVAs [Logarithm of the Minimum Angle of Resolution (logMAR)] in groups 1, 2, 3, and 4 were 0.54 ± 0.24, 0.52 ± 0.25, 0.55 ± 0.23, and 0.57 ± 0.27, respectively. There was no significant difference between the baseline mean BCVAs between the groups (p = .35). The mean BCVAs were significantly improved to 0,47 ± 0,33 in group 1, 0,42 ± 0,33 in group 2, 0,47 ± 0,31 in group 3, and 0,45 ± 0,43 at month 12. There was no significant difference between the groups in terms of BCVA change at month 12 (p = .71). The mean baseline CMTs in groups 1, 2, 3, and 4 were 387,19 ± 128,19, 447,02 ± 132,39, 449,12 ± 109,24, and 544,19 ± 178,61, respectively. At baseline, the mean CMT was significantly higher in Group 4 than in the other groups (p = .000). The mean CMTs were significantly decreased to 325,16 ± 97,55, 334,94 ± 115,99, 324,33 ± 79,20, and 332,08 ± 150,40 in four groups at month 12 respectively (p > .05). The groups had no significant difference in mean CMT at month 12 (p = .835). The change in CMT was significantly higher in Group 4 than in the other groups at month 12 (p = .000). The mean number of intravitreal anti-VEGF injections at month 12 was 4.51 ± 1.57 in Group 1, 4.63 ± 1.54 in Group 2, 4.88 ± 1.38 in Group 3, and 5.07 ± 1.49 in Group 4. The mean number of anti-VEGF injections in Group 1 and Group 2 was significantly lower than in Group 4 (p = 0,014 and p = 0,017). CONCLUSIONS: In real life, there was no significant difference between the DME groups in terms of visual improvement at month 12. However, better anatomical improvement was achieved in Group 4 than in the other DME groups.
Subject(s)
Angiogenesis Inhibitors , Diabetic Retinopathy , Intravitreal Injections , Macular Edema , Ranibizumab , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Tomography, Optical Coherence , Visual Acuity , Humans , Macular Edema/drug therapy , Macular Edema/diagnosis , Macular Edema/physiopathology , Macular Edema/etiology , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/physiopathology , Retrospective Studies , Tomography, Optical Coherence/methods , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Visual Acuity/physiology , Recombinant Fusion Proteins/administration & dosage , Male , Female , Ranibizumab/administration & dosage , Middle Aged , Follow-Up Studies , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Prognosis , Macula Lutea/pathology , Macula Lutea/diagnostic imaging , Glucocorticoids/administration & dosageABSTRACT
In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.
What did we find out from the INBUILD trial about progressive lung fibrosis?Lung fibrosis is a rare disease in which the lung tissue becomes scarred and hardened. This makes it more difficult for the lungs to inflate and for the lungs to exchange oxygen with the blood. In some patients, lung fibrosis gets worse over time. This is known as progressive lung fibrosis. In the INBUILD trial, researchers looked at the effects of a drug called nintedanib in patients with progressive lung fibrosis. In this trial, 663 patients were randomly allocated to receive either nintedanib or a placebo and then followed for approximately 19 months. The patients and the researchers did not know which patients were taking the active drug (nintedanib) and which patients were taking placebo. The results showed that the criteria used to find patients with progressive lung fibrosis to take part in the trial successfully identified patients whose disease would continue to worsen. These criteria were based on a decline in the volume (size) of the lungs, worsening symptoms such as shortness of breath, and worsening of changes seen on a scan of the chest. The trial results also showed that nintedanib slowed down loss of lung function and had a similar benefit in patients with different severities of disease at the start of the trial. The most common side-effects of nintedanib were gastrointestinal problems, particularly diarrhea, but most patients given nintedanib were able to cope with these side-effects without needing to stop treatment. Large trials like the INBUILD trial are important for helping us understand how diseases progress and in which patients particular drugs should be used.
Subject(s)
Disease Progression , Indoles , Pulmonary Fibrosis , Tomography, X-Ray Computed , Humans , Indoles/adverse effects , Indoles/therapeutic use , Indoles/administration & dosage , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/physiopathology , Vital Capacity , Severity of Illness Index , Treatment Outcome , Randomized Controlled Trials as Topic , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Lung/drug effects , Lung/physiopathology , Lung/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/physiopathology , Lung Diseases, Interstitial/diagnosis , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/physiopathology , Idiopathic Pulmonary Fibrosis/diagnosis , Male , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/administration & dosageABSTRACT
This study aimed to investigate the association between glucocorticoid administration and outcomes in critically ill patients with ARDS using the Medical Information Mart for Intensive Care (MIMIC)-III database. Data were collected from the MIMIC-III database, which consists of critically ill participants between 2001 and 2012 in the USA. A total of 1831 adult critically ill patients with ARDS were enrolled from the MIMIC-III database. The 60-day and in-hospital mortality, were the primary endpoints. Secondary outcomes included length of stay (LOS) in the hospital and intensive care unit (ICU), 28-day ventilator-free days, ICU mortality, and 28-day mortality. A total of 1831 patients were included in the data analysis. After propensity score (PS) matching, 464 patients diagnosed with ARDS were matched between the glucocorticoid treatment and control groups. Glucocorticoids were associated with increased in-hospital mortality [hazard ratio (HR) 1.32; 95% CI 1.01-1.71; Pâ =â .039], longer ICU stay [HR 2.25; 95% CI 0.84-3.65; Pâ =â .002], and shorter ventilation-free days at 28 days in all ARDS patients [HR -2.70; 95% CI -4.28--1.13; Pâ =â .001]. The 60-day mortality was higher in the glucocorticoid group (44.83% vs 35.34%; Pâ =â .154; HR 1.24; 95% CI 0.93-1.66). Excluding the impact of the glucocorticoid initiation time, from day 15 to day 60, mortality was significantly higher in the glucocorticoid group compared to the non-glucocorticoid group (27.16% vs 12.70%; Pâ <â .001; HR 1.75; 95% CI 1.32-2.32). Glucocorticoid administration was associated with worse 60-day and in-hospital survival, longer ICU stay, and shorter ventilator-free days on day 28 in patients with ARDS. Our findings suggest careful consideration of glucocorticoids for ARDS.
Subject(s)
Glucocorticoids , Hospital Mortality , Intensive Care Units , Length of Stay , Propensity Score , Respiratory Distress Syndrome , Humans , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Male , Female , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/drug therapy , Middle Aged , Length of Stay/statistics & numerical data , Intensive Care Units/statistics & numerical data , Aged , Databases, Factual , Critical Illness/mortality , Adult , Respiration, Artificial/statistics & numerical data , United States/epidemiologyABSTRACT
Pemphigus foliaceus (PF) is a superficial form of pemphigus. Treatment options for PF resemble pemphigus vulgaris, including glucocorticosteroids, immunosuppressive agents and rituximab et al. These treatment approaches can effectively improve the condition but may also be accompanied by high risks of side effects. Therefore, it is crucial to find a safe and effective treatment options for patients with PF. It will not only benefit/be necessary for patients who refuse glucocorticosteroids or immunosuppressive agents treatments, but also for patients who cannot be treated with glucocorticosteroids or immunosuppressive agents. Herein, we reported a case of PF that was treated with apremilast without systemic glucocorticosteroids or immunosuppressive agents. A 54-year-old woman presented with itchy erythema and erosions on the trunk for more than 1 month. The patient applied mometasonefuroate cream without improvement for a duration of two weeks. The past history of diabetes mellitus and atrophic gastritis was reported. Physical examination revealed scattered erythematous macules and erosions on the trunk. No mucosal involvement was observed. The condition was assessed by the pemphigus disease area index and numerical rating scale, with baseline scores of 7 and 8, respectively. Histopathological examination showed acantholysis and intraepithelial blister. Direct immunofluorescence revealed the presence of IgG and Complement 3 deposition between the acanthocytes with the reticular distribution. Based on enzyme-linked immunosorbent assay results, the levels of Dsg1 and Dsg3 antibodies were 28.18 and 0.26 kU/L respectively. The diagnosis of PF was made. This patient was successfully treated with apremilast without systemic glucocorticosteroids or immunosuppressive agents. The patient has continued with apremilast 30mg once daily for maintenance and no adverse events related to apremilast such as gastrointestinal side effects were observed during the 9-month follow-up period. In conclusion, apremilast therapy without systemic glucocorticosteroids nor immunosuppressive agents might provide an effective alternative to management of mild PF without obvious side effect.
Subject(s)
Pemphigus , Thalidomide , Humans , Pemphigus/drug therapy , Female , Middle Aged , Thalidomide/analogs & derivatives , Thalidomide/therapeutic use , Immunosuppressive Agents/therapeutic use , Treatment Outcome , Glucocorticoids/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic useABSTRACT
OBJECTIVES: To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. METHODS: This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. RESULTS: A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. CONCLUSION: HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.
Subject(s)
Agammaglobulinemia , Autoimmune Diseases , Infections , Rituximab , Humans , Rituximab/therapeutic use , Rituximab/adverse effects , Female , Male , Agammaglobulinemia/epidemiology , Middle Aged , Autoimmune Diseases/drug therapy , Autoimmune Diseases/complications , Retrospective Studies , Adult , Infections/etiology , Infections/epidemiology , Aged , Glucocorticoids/therapeutic use , Risk Factors , China/epidemiology , Immunoglobulin G/bloodABSTRACT
OBJECTIVES: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt. METHODS: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups. RESULTS: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%). CONCLUSION: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104. TRIAL REGISTRATION NUMBER: NCT03649061. CTR PILOT APPROVAL BELGIUM: S59474, EudraCT number: 2017-004054-41.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Drug Therapy, Combination , Etanercept , Glucocorticoids , Methotrexate , Humans , Etanercept/therapeutic use , Etanercept/administration & dosage , Methotrexate/therapeutic use , Methotrexate/administration & dosage , Arthritis, Rheumatoid/drug therapy , Male , Female , Middle Aged , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/administration & dosage , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Treatment Outcome , Aged , Adult , Remission Induction , Severity of Illness IndexABSTRACT
Purpose: To study the impact of early and late treatment on chorioretinal microvasculature in Vogt-Koyanagi-Harada (VKH) disease using optical coherence tomography angiography (OCTA). Methods: A total of 103 patients with VKH disease were divided into early (group 1, starting treatment within 2 months after disease onset) and late (group 2, starting treatment 2 months after disease onset) treatment groups. Flow area (FA) and vessel density (VD) of the retinal superficial vascular complex (SVC) and deep vascular complex (DVC), FA of the choriocapillaris, three-dimensional choroidal vascular volume (CVV), and choroidal vascularity index (CVI) were analyzed and compared to 103 healthy individuals. The relationship between the final best-corrected visual acuity (BCVA) and the aforementioned parameters was also analyzed. Results: FA of the SVC (all P < 0.05, except 0-1 mm P = 0.087), DVC (all P < 0.05), choriocapillaris (1-2.5 mm P = 0.033), and CVV (all P < 0.05) were lower in group 2 as compared to group 1. Compared to healthy controls, FA of the SVC (all P < 0.001, except 0-1 mm P = 0.104) and DVC (all P < 0.05), VD of the SVC (1-2.5 mm P = 0.001) and DVC (1-5 mm P = 0.003, 2.5-5 mm P < 0.001), FA of the choriocapillaris (all P < 0.05), and CVV (total area P = 0.049, 1-5 mm P = 0.045, 2.5-5 mm P = 0.041) were lower in group 2, while FA (all P < 0.05, except 0-1 mm P = 0.925) and VD (1-5 mm P = 0.003, 2.5-5 mm P = 0.004) of the DVC and FA of the choriocapillaris (total area P = 0.007, 0-1 mm P < 0.001, 1-2.5 mm P = 0.007) were lower in group 1. There was no significant difference concerning CVI among groups (all P > 0.05). FA of the SVC, DVC, and choriocapillaris and VD of DVC and CVI were negatively associated with the final logarithm of the minimum angle of resolution BCVA. Conclusions: Patients with VKH disease who are treated within 2 months of disease onset showed a better chorioretinal microvascular outcome as defined by OCTA compared to those treated late. Translational Relevance: Our study employs OCTA to design three-dimensional metrics for the retina and choroid, bridging the gap between traditional two-dimensional OCTA findings and enhanced clinical outcomes for patients with VKH disease.
Subject(s)
Choroid , Fluorescein Angiography , Microvessels , Retinal Vessels , Tomography, Optical Coherence , Uveomeningoencephalitic Syndrome , Visual Acuity , Humans , Tomography, Optical Coherence/methods , Uveomeningoencephalitic Syndrome/diagnostic imaging , Uveomeningoencephalitic Syndrome/drug therapy , Male , Female , Adult , Choroid/blood supply , Choroid/diagnostic imaging , Visual Acuity/physiology , Middle Aged , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Fluorescein Angiography/methods , Microvessels/diagnostic imaging , Young Adult , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Retrospective StudiesABSTRACT
Social bonds increase fitness in a range of mammals. One pathway by which social bonds may increase fitness is by reducing the exposure to physiological stress, i.e. glucocorticoid (GC) hormones, that can be detrimental to health and survival. This is achieved through downregulating hypothalamic-pituitary-adrenal (HPA)-axis activity. Indeed, long-term measures of social (grooming) bonds are often negatively correlated with HPA-axis activity. However, the proximate role of physical touch through allogrooming remains an open question in the sociality-health-fitness debate. Demonstrating the potential anxiolytic benefits of grooming in the wild is hindered by methodological limitations. Here, we match accelerometer-identified grooming in wild female chacma baboons (Papio ursinus) to non-invasive faecal GC metabolite concentrations (fGCs). Consistent with previous work, we found a negative (but statistically non-significant) overall relationship between individual averaged fGCs and grooming rates. However, when time-matching grooming to fGCs, we found that both more giving and receiving grooming were followed by higher fGCs. This upregulation of HPA-axis activity suggests that maintaining social bonds (and its ultimate fitness benefits) may come at a shorter-term physiological cost. This finding sheds new light on a ubiquitous social behaviour typically considered 'relaxing' and suggests that sociopositive contact can trigger physiological stress.
Subject(s)
Grooming , Stress, Physiological , Animals , Female , Feces/chemistry , Glucocorticoids/metabolism , Social Behavior , Papio ursinus/physiology , Hypothalamo-Hypophyseal System/physiology , Pituitary-Adrenal System/physiologyABSTRACT
Glucocorticoid use may cause elevated intraocular pressure, leading to the development of glucocorticoid-induced glaucoma (GIG). However, the mechanism of GIG development remains incompletely understood. In this study, we subjected primary human trabecular meshwork cells (TMCs) and mice to dexamethasone treatment to mimic glucocorticoid exposure. The myofibroblast transdifferentiation of TMCs was observed in cellular and mouse models, as well as in human trabecular mesh specimens. This was demonstrated by the cytoskeletal reorganization, alterations in cell morphology, heightened transdifferentiation markers, increased extracellular matrix deposition, and cellular dysfunction. Knockdown of Rho guanine nucleotide exchange factor 26 (ARHGEF26) expression ameliorated dexamethasone-induced changes in cell morphology and upregulation of myofibroblast markers, reversed dysfunction and extracellular matrix deposition in TMCs, and prevented the development of dexamethasone-induced intraocular hypertension. And, this process may be related to the TGF-ß pathway. In conclusion, glucocorticoids induced the myofibroblast transdifferentiation in TMCs, which played a crucial role in the pathogenesis of GIG. Inhibition of ARHGEF26 expression protected TMCs by reversing myofibroblast transdifferentiation. This study demonstrated the potential of reversing the myofibroblast transdifferentiation of TMCs as a new target for treating GIG.
Subject(s)
Cell Transdifferentiation , Dexamethasone , Glaucoma , Myofibroblasts , Rho Guanine Nucleotide Exchange Factors , Trabecular Meshwork , Dexamethasone/pharmacology , Trabecular Meshwork/drug effects , Trabecular Meshwork/metabolism , Trabecular Meshwork/cytology , Cell Transdifferentiation/drug effects , Animals , Humans , Myofibroblasts/drug effects , Myofibroblasts/metabolism , Myofibroblasts/cytology , Mice , Rho Guanine Nucleotide Exchange Factors/metabolism , Rho Guanine Nucleotide Exchange Factors/genetics , Glaucoma/pathology , Glaucoma/metabolism , Cells, Cultured , Glucocorticoids/pharmacology , Mice, Inbred C57BL , MaleABSTRACT
The KDIGO Update 2024 was supplemented by new "Clinical Practice Points", which were derived from the current evidence but are not necessarily comprehensively proven by prospective controlled studies. The most significant change in the Update 2024 for Lupus nephritis concerns the recommendations for induction therapy for lupus nephritis classes III and IV. The basis is still high-dose glucocorticoid treatment and the use of hydroxychloroquine. The 2 new developments in the 2024 Update concerning ANCA-associated nephritis are based on the studies on the use of the C5a receptor inhibitor Avacopan and the increasing data on induction protocols with reduced glucocorticoid dosage. Due to the inconsistency and variability of the conditions under which blood pressure measurements are carried out in practice, an international consensus statement was issued which defines 4 steps to achieve sufficient validity of the measurement results. CKD-MBD Controversies Conference 2023: The update for CKD-MBD, which was discussed in the Controversies Conference 2023, is in progress and has not been released yet. However, there were no serious contradictions between the 2023 data and the 2017 guidelines - the risk assessment regarding calcium-containing phosphate binders may have been put into perspective.
Subject(s)
Practice Guidelines as Topic , Humans , Lupus Nephritis/drug therapy , Glucocorticoids/therapeutic use , Kidney Diseases/therapy , Hydroxychloroquine/therapeutic useABSTRACT
Currently, only 25% of all polymyalgia rheumatica (PMR) patients are referred to specialists. An expert committee has recently recommended confirmation of diagnosis by specialist care. This can help to avoid misdiagnoses and hospital stays and can result in lower glucocorticoid doses.Using ultrasound, magnetic resonance imagining (MRI), or positron emission tomography-computed tomography (PET-CT), typical periarticular inflammatory changes are observed, especially in the shoulder and pelvic girdle area. However, for clinical use, ultrasound is usually sufficient.In 20-25% of newly diagnosed PMR patients without symptoms of giant cell arteritis (GCA), GCA can be detected through vascular ultrasound. These patients require higher glucocorticoid doses in analogy to GCA therapy. There is growing awareness of a joint GCA-PMR spectrum disease.Glucocorticoids remain the primary treatment. The interleukin-6 inhibitor Sarilumab has recently been approved in the USA for patients with recurrent PMR. Studies have also demonstrated the effectiveness of Tocilizumab in PMR.
Subject(s)
Polymyalgia Rheumatica , Polymyalgia Rheumatica/diagnosis , Polymyalgia Rheumatica/drug therapy , Humans , Glucocorticoids/therapeutic use , Giant Cell Arteritis/drug therapy , Giant Cell Arteritis/diagnosis , Antibodies, Monoclonal, Humanized/therapeutic useABSTRACT
BACKGROUND: Toxic anterior segment syndrome (TASS) is a rare, noninfectious inflammation that occurs after anterior segment surgery. We report a case herein that developed presumed atypical late-onset TASS after V4c implantable collamer lens (ICL) implantation surgery. CASE PRESENTATION: A 26-year-old man underwent ICL implantation surgeries of both eyes on two separate days. The 1-day and 7-day postoperative routine follow-up visits revealed no abnormalities. However, one month after surgery, dense white spots attached to the posterior surface and scattered ones to the anterior surface of ICL in the left eye were noted on anterior segment examination. His uncorrected distance visual acuity (UDVA) was 20/16 in both eyes and the fundus examination was normal. Despite the absence of typical clinical manifestations, late-onset TASS was suspect and intense topical steroid was administered. After 6 weeks of tapering topical steroid therapy, the white spots disappeared and the patient had no subjective complains throughout the treatment period. CONCLUSIONS: This case suggested that the traditionally considered acute and serious TASS could also present as delayed and insidious onset after ICL implantation surgery. Due to its variabilities, the awareness of TASS should be raised to ophthalmologists and regular follow-up visits should be emphasized to patients. Once TASS was suspected, intensive steroid therapy should be implemented in time.
Subject(s)
Anterior Eye Segment , Lens Implantation, Intraocular , Phakic Intraocular Lenses , Humans , Male , Adult , Anterior Eye Segment/diagnostic imaging , Anterior Eye Segment/pathology , Phakic Intraocular Lenses/adverse effects , Lens Implantation, Intraocular/adverse effects , Visual Acuity , Postoperative Complications/diagnosis , Syndrome , Glucocorticoids/therapeutic useABSTRACT
BACKGROUND: Dysferlinopathies are a clinically heterogeneous group of muscular dystrophies caused by gene mutations resulting in deficiency of the membrane-associated protein dysferlin. They manifest post-growth and are characterised by muscle wasting (primarily in the limb and limb-gridle muscles), inflammation, and replacement of myofibres with adipose tissue. The precise pathomechanism for dysferlinopathy is currently unclear; as such there are no treatments currently available. Glucocorticoids (GCs) are widely used to reduce inflammation and treat muscular dystrophies, but when administered to patients with dysferlinopathy, they have unexpected adverse effects, with accelerated loss of muscle strength. METHODS: To investigate the mechanistic basis for the adverse effects of GCs in dysferlinopathy, the potent GC dexamethasone (Dex) was administered for 4-5 weeks (0.5-0.75 µg/mL in drinking water) to dysferlin-deficient BLA/J and normal wild-type (WT) male mice, sampled at 5 (Study 1) or 10 months (Study 2) of age. A wide range of analyses were conducted. Metabolism- and immune-related gene expression was assessed in psoas muscles at both ages and in quadriceps at 10 months of age. For the 10-month-old mice, quadriceps and psoas muscle histology was assessed. Additionally, we investigated the impact of Dex on the predominantly slow and fast-twitch soleus and extensor digitorum longus (EDL) muscles (respectively) in terms of contractile function, myofibre-type composition, and levels of proteins related to contractile function and metabolism, plus glycogen. RESULTS: At both ages, many complement-related genes were highly expressed in BLA/J muscles, and WT mice were generally more responsive to Dex than BLA/J. The effects of Dex on BLA/J mice included (i) increased expression of inflammasome-related genes in muscles (at 5 months) and (ii) exacerbated histopathology of quadriceps and psoas muscles at 10 months. A novel observation was pronounced staining for glycogen in many myofibres of the damaged quadriceps muscles, with large pale vacuolated myofibres, suggesting possible myofibre death by oncosis. CONCLUSION: These pilot studies provide a new focus for further investigation into the adverse effects of GCs on dysferlinopathic muscles.