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Frontiers in Immunology 2023Graves' disease (GD) and Graves' orbitopathy (GO) development were suspected to be HLA-related in both Asian and Caucasian populations. However, most studies were...
INTRODUCTION
Graves' disease (GD) and Graves' orbitopathy (GO) development were suspected to be HLA-related in both Asian and Caucasian populations. However, most studies were performed with application of serological methods or low resolution genetic typing, which led to inconsistent results even among the same population. The present review is intended to summarize the state-of-art knowledge on the HLA significance in GD and GO in Asians and Caucasians, as well as to find the most significant alleles for each of the populations.
METHODS
PubMed was searched for relevant articles using the following search terms: HLA plus thyroid-associated ophthalmopathy or Graves' disease or Graves' orbitopathy or thyroid eye disease or thyroid-associated orbitopathy.
RESULTS
In Asian population GD was found to be associated mostly with , , , , , and , while , , are potentially protective. can be considered associated with increased risk of GO in Asians, while may play protective role. In Caucasians, , , are associated with GD risk while , may be protective. Significance of HLA in the course of GD and novel aspects of HLA amino acid variants and potential HLA-based treatment modalities were also discussed.
Topics: Humans; Graves Ophthalmopathy; HLA-DQ Antigens; HLA-DRB1 Chains; Haplotypes; Graves Disease; HLA-B Antigens
PubMed: 37841270
DOI: 10.3389/fimmu.2023.1256922 -
Journal of Clinical Medicine Sep 2023Spheno-orbital meningiomas (SOMs) are rare tumors arising from the meninges surrounding the sphenoid bone and orbital structures. Surgical resection is the primary... (Review)
Review
BACKGROUND
Spheno-orbital meningiomas (SOMs) are rare tumors arising from the meninges surrounding the sphenoid bone and orbital structures. Surgical resection is the primary treatment approach for SOMs. Several surgical approaches have been described during the decades, including microsurgical transcranial (MTAs), endoscopic endonasal (EEAs), endoscopic transorbital (ETOAs), and combined approaches, and the choice of surgical approach remains a topic of debate.
PURPOSE
This systematic review and meta-analysis aim to compare the clinical and surgical outcomes of different surgical approaches used for the treatment of SOMs, discussing surgical techniques, outcomes, and factors influencing surgical decision making.
METHODS
A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on the role of surgery for the treatment of SOMs until 2023. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications.
RESULTS
A total of 59 studies comprising 1903 patients were included in the systematic review and meta-analysis. Gross total resection (GTR) rates ranged from 23.5% for ETOAs to 59.8% for MTAs. Overall recurrence rate after surgery was 20.7%. Progression-free survival (PFS) rates at 5 and 10 years were 75.5% and 49.1%, respectively. Visual acuity and proptosis improvement rates were 57.5% and 79.3%, respectively. Postoperative cranial nerve (CN) focal deficits were observed in 20.6% of cases. The overall cerebro-spinal fluid (CSF) leak rate was 3.9%, and other complications occurred in 13.9% of cases. MTAs showed the highest GTR rates (59.8%, 95%CI = 49.5-70.2%; = 0.001) but were associated with increased CN deficits (21.0%, 95%CI = 14.5-27.6%). ETOAs had the lowest GTR rates (23.5%, 95%CI = 0.0-52.5%; = 0.001), while combined ETOA and EEA had the highest CSF leak rates (20.3%, 95%CI = 0.0-46.7%; = 0.551). ETOAs were associated with better proptosis improvement (79.4%, 95%CI = 57.3-100%; = 0.002), while anatomical class I lesions were associated with better visual acuity (71.5%, 95%CI = 63.7-79.4; = 0.003) and proptosis (60.1%, 95%CI = 38.0-82.2; = 0.001) recovery. No significant differences were found in PFS rates between surgical approaches.
CONCLUSION
Surgical treatment of SOMs aims to preserve visual function and improve proptosis. Different surgical approaches offer varying rates of GTR, complications, and functional outcomes. A multidisciplinary approach involving a skull base team is crucial for optimizing patient outcomes.
PubMed: 37762781
DOI: 10.3390/jcm12185840 -
BMC Endocrine Disorders Sep 2023The effect of stress on Graves' disease (GD) is controversial. Our purpose was to quantify the impacts of stress on patients with Graves' disease. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of stress on Graves' disease (GD) is controversial. Our purpose was to quantify the impacts of stress on patients with Graves' disease.
METHODS
Systematic searches of PubMed, MEDLINE, Embase, Web of Science, Scopus, Cochrane Library and PsycInfo were conducted from inception to 1 January 2023. Studies comparing the incidence of stressful life events (SLEs) that occurred before diagnosis and during drug therapy in cases diagnosed with GD and controls were included in the final analysis.
RESULTS
Nine case-control studies and four cohort studies enrolling 2892 participants (1685 [58%] patients) were included. Meta-analysis revealed a high and significant effect-size index in a random effect model (d = 1.81, P = 0.01), indicating that stress is an important factor in the onset of GD. The relationship between SLEs and GD was stronger in studies with higher proportions of female patients (β = 0.22, P < 0.01) and weaker in studies with older patients with GD (β =-0.62, P < 0.01). However, stress did not significantly affect the outcome of antithyroid drug therapy for GD (d = 0.32, P = 0.09).
CONCLUSIONS
The results of this meta-analysis suggest that stress is one of the environmental triggers for the onset of GD. Therefore, we recommend stress management assistance for individuals genetically susceptible to GD, especially for young females.
Topics: Humans; Female; Graves Disease; Antithyroid Agents; Case-Control Studies; Genetic Predisposition to Disease
PubMed: 37700292
DOI: 10.1186/s12902-023-01450-y -
BMC Ophthalmology Aug 2023Thyroid eye disease is an extrathyroidal manifestation of Graves' disease and is associated with dry eye disease. This is the first systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thyroid eye disease is an extrathyroidal manifestation of Graves' disease and is associated with dry eye disease. This is the first systematic review and meta-analysis to evaluate the role of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease diagnosis, activity grading, and therapeutic responses prediction.
METHODS
Up to 23 August, 2022, 504 studies from PubMed and Cochrane Library were analyzed. After removing duplicates and imposing selection criteria, nine eligible studies were included. Risk of bias assessment was done. Meta-analyses were performed using random-effect model if heterogeneity was significant. Otherwise, fixed-effect model was used. Main outcome measures include seven structural magnetic resonance imaging parameters (lacrimal gland herniation, maximum axial area, maximum coronal area, maximum axial length, maximum coronal length, maximum axial width, maximum coronal width), and three functional magnetic resonance imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-apparent diffusion coefficient or mean diffusivity, diffusion-weighted imaging-apparent diffusion coefficient).
RESULTS
Thyroid eye disease showed larger maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width, diffusion tensor imaging-apparent diffusion coefficient/ mean diffusivity, and lower diffusion tensor imaging-fractional anisotropy than controls. Active thyroid eye disease showed larger lacrimal gland herniation, maximum coronal area, diffusion-weighted imaging-apparent diffusion coefficient than inactive. Lacrimal gland dimensional (maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width) and functional parameters (diffusion tensor imaging-apparent diffusion coefficient, diffusion tensor imaging-apparent diffusion coefficient) could be used for diagnosing thyroid eye disease; lacrimal gland herniation, maximum coronal area, and diffusion-weighted imaging-apparent diffusion coefficient for differentiating active from inactive thyroid eye disease; diffusion tensor imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-mean diffusivity) and lacrimal gland herniation for helping grading and therapeutic responses prediction respectively.
CONCLUSIONS
Magnetic resonance imaging lacrimal gland parameters can detect active thyroid eye disease and differentiate thyroid eye disease from controls. Maximum coronal area is the most effective indicator for thyroid eye disease diagnosis and activity grading. There are inconclusive results showing whether structural or functional lacrimal gland parameters have diagnostic superiority. Future studies are warranted to determine the use of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease.
Topics: Humans; Graves Ophthalmopathy; Lacrimal Apparatus; Diffusion Tensor Imaging; Magnetic Resonance Imaging; Outcome Assessment, Health Care
PubMed: 37550660
DOI: 10.1186/s12886-023-03008-x -
Saudi Journal of Ophthalmology :... 2023The traditional standard of care for Graves' ophthalmopathy (GO) is glucocorticoid therapy, which is associated with many long-term side effects. The aim of this...
PURPOSE
The traditional standard of care for Graves' ophthalmopathy (GO) is glucocorticoid therapy, which is associated with many long-term side effects. The aim of this systematic review and meta-analysis was to compare the traditional therapy to novel monoclonal antibodies (e.g. rituximab [RTX], teprotumumab, and tocilizumab [TCZ]).
METHODS
We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials (RCTs) that compared different monoclonal antibodies (e.g. RTX, teprotumumab, and TCZ) with glucocorticoids or placebo in patients with GO. We evaluated the clinical activity score (CAS), proptosis, subjective diplopia using the Gorman score, quality of life (QoT), adverse events, change in lid fissure, NOSPECS score, and TSH receptor antibody (TRAb) levels. The odds ratio (OR) was used to represent dichotomous outcomes. The continuous outcomes were represented as standardized mean difference (SMD). Data were pooled using the inverse variance weighting method. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials.
RESULTS
Six ( = 571) RCTs were deemed eligible. The different monoclonal antibodies were significantly more efficacious than glucocorticoid/placebo in terms of reduction in CAS (SMD = -1.44, 95% confidence interval (CI): -1.91--0.97, < 0.00001, = 74%), change in proptosis (SMD = -4.96, 95% CI: -8.02--1.89, = 0.002, = 99%), QoL (SMD = 2.64, 95% CI: 0.50-4.79, = 0.02, = 97%), and Gorman score for diplopia (OR = 3.42, 95% CI: 1.62-7.22, = 0.001, = 8%). However, monoclonal antibodies have shown higher rates of adverse events (OR = 2.91, 95% CI: 1.12-7.56, = 0.03, = 62%). No significant difference was found with respect to lid fissure, NOSPECS, and TRAb levels.
CONCLUSION
This meta-analysis demonstrated that monoclonal antibodies were associated with more favorable clinical outcomes than standard steroid therapy or placebo, especially with regard to CAS, change in proptosis, diplopia, and QoL, with teprotumumab being superior. In addition, only minor safety concerns were identified with monoclonal antibodies though less worrisome than using traditional steroids.
PubMed: 37492211
DOI: 10.4103/sjopt.sjopt_176_22 -
World Neurosurgery Jun 2023Transorbital neuroendoscopic surgery (TONES) comprises a group of approaches with indications expanding from orbital tumors to more complex skull base lesions. We...
BACKGROUND
Transorbital neuroendoscopic surgery (TONES) comprises a group of approaches with indications expanding from orbital tumors to more complex skull base lesions. We analyzed the role of the endoscopic transorbital approach (eTOA) for spheno-orbital tumors, reporting the results of our clinical series and of a systematic review of the literature.
MATERIALS AND METHODS
All patients operated on from 2016 to 2022 at our institution for a spheno-orbital tumor through an eTOA were included in a clinical series, and a systematic review of the literature was performed.
RESULTS
Our series consisted of 22 patients (16 females, mean age 57 ± 13 years). Gross tumor removal was achieved in 8 patients (36.4%) after the eTOA and in 11 (50.0%) after a multistaged strategy combining the eTOA with the endoscopic endonasal approach. Complications included 1 chronic subdural hematoma and 1 permanent extrinsic ocular muscle deficit. Patients were discharged after 2.4 ± 1.3 days. The most common histotype was meningioma (86.4%). Proptosis improved in all cases, visual deficit in 66.6%, and diplopia in 76.9%. These results were confirmed by the review of the 127 cases reported in the literature.
CONCLUSIONS
Despite its recent introduction, a significant number of spheno-orbital lesions treated with an eTOA are being reported. Its main advantages are favorable patient outcome and optimal cosmetic results, with minimal morbidity and quick recovery. This approach can be combined with other surgical routes or adjuvant therapies for complex tumors. However, it is a technically demanding procedure, requiring specific skills in endoscopic surgery, that should be reserved to dedicated centers.
PubMed: 37331478
DOI: 10.1016/j.wneu.2023.06.026 -
Frontiers in Endocrinology 2023The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking.We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs.
METHODS
To identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase,Cochrane Library, CBM, CNKI,Wan-Fang and ICTRP databases.The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies.The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS),the improvement of proptosis and diplopia improvement,and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses.
RESULTS
A total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab).TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX.TCZ was the highest probability of safety, followed by RTX and TMB.
CONCLUSIONS
Based on the best available evidence,TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials,indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition,the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established,and it is encouraging that the treatment paradigm for GO may change in the future.This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA)(27).
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/prospero, identifier CRD42023398170.
Topics: Humans; Antibodies, Monoclonal; Immunoglobulins, Intravenous; Diplopia; Rituximab; Graves Ophthalmopathy; Exophthalmos
PubMed: 37288301
DOI: 10.3389/fendo.2023.1160936 -
World Neurosurgery: X Jul 2023Carotid-cavernous fistulas (CCFs) represent a group of rare, abnormal arteriovenous communications between the carotid arterial system and the cavernous sinuses (CS).... (Review)
Review
BACKGROUND AND OBJECTIVES
Carotid-cavernous fistulas (CCFs) represent a group of rare, abnormal arteriovenous communications between the carotid arterial system and the cavernous sinuses (CS). CCFs often produce ophthalmologic symptoms related to increased CS pressures and retrograde venous drainage of the eye. Although endovascular occlusion remains the preferred treatment for symptomatic or high-risk CCFs, most of the data for these lesions is limited to small, single-center series. As such, we performed a systematic review and meta-analysis evaluating endovascular occlusions of CCFs to determine any differences in clinical outcomes based on presentation, fistula type, and treatment paradigm.
METHOD
A retrospective review of all studies discussing the endovascular treatment of CCFs published through March 2023 was conducted using PubMed, Scopus, Web of Science, and Embase databases. A total of 36 studies were included in the meta-analysis. Data from the selected articles were extracted and analyzed using Stata software version 14.
RESULTS
1494 patients were included. 55.08% were female and the mean age of the cohort was 48.10 years. A total number of 1516 fistulas underwent endovascular treatment, 48.05% of which were direct and 51.95% of which were indirect. 87.17% of CCFs were secondary to a known trauma while 10.18% were spontaneous. The most common presenting symptoms were 89% exophthalmos (95% CI: 78.0-100.0; I = 75.7%), 84% chemosis (95% CI: 79.0-88.0; I = 91.6%), 79% proptosis (95% CI: 72.0-86.0; I = 91.8%), 75.0% bruits (95% CI: 67.0-82.0; I = 90.7%), 56% diplopia (95% CI: 42.0-71.0; I = 92.3%), 49% cranial nerve palsy (95% CI: 32.0-66.0; I = 95.1%), 39% visual decline (95% CI: 32.0-45.0; I = 71.4%), 32% tinnitus (95% CI: 6.0-58.0; I = 96.7%), 29% elevated intraocular pain (95% CI: 22.0-36.0; I = 0.0%), 31% orbital or pre-orbital pain (95% CI: 14.0-48.0; I = 89.9%) and 24% headache (95% CI: 13.0-34.0; I = 74.98%). Coils, balloons, and stents were the three most used embolization methods respectively. Immediate complete occlusion of the fistula was seen in 68% of cases and complete remission was seen in 82%. Recurrence of CCF occurred in only 35% of the patients. Cranial nerve paralysis after treatment was observed in 7% of the cases.
CONCLUSIONS
Exophthalmos, Chemosis, proptosis, bruits, cranial nerve palsy, diplopia, orbital and periorbital pain, tinnitus, elevated intraocular pressure, visual decline and headache are the most common clinical manifestations of CCFs. The majority of endovascular treatments involved coiling, balloons and onyx and a high percentage of CCF patients experienced complete remission with the improvement of their clinical symptoms.
PubMed: 37223772
DOI: 10.1016/j.wnsx.2023.100189 -
International Journal of Environmental... Mar 2023Autoimmune thyroid disease (AITD) is a dysregulation of the immune system that causes an attack on the thyroid gland. Two major clinical manifestations are Hashimoto's... (Review)
Review
Autoimmune thyroid disease (AITD) is a dysregulation of the immune system that causes an attack on the thyroid gland. Two major clinical manifestations are Hashimoto's thyroiditis and Graves' disease. Saliva performs many functions and, importantly, has the potential for easy, non-invasive diagnostics of several systemic disorders. This systematic review was designed to answer the question whether salivary alterations are reliable for the diagnosis of autoimmune thyroid diseases. Following the inclusion and exclusion criteria, fifteen studies were included. Due to their heterogeneity, saliva analysis was divided into two subgroups: quantitative assessment analysing salivation and qualitative assessment concerning potential salivary biomarkers for AITD. In addition to detecting altered levels of thyroid hormones and antibodies, salivary changes were also observed in the concentrations of total protein, cytokines and chemokines, as well as markers of oxidative status. According to the saliva flow rate values, significantly reduced saliva secretion was observed in patients with HT. In conclusion, it is not possible to unequivocally state if salivary biomarkers can potentially be used in autoimmune thyroid disease diagnosis. Therefore, further investigations, including salivation disorders, are necessary to validate these findings.
Topics: Humans; Thyroiditis, Autoimmune; Hashimoto Disease; Graves Disease; Thyroid Hormones; Autoimmune Diseases; Thyroid Diseases
PubMed: 36981758
DOI: 10.3390/ijerph20064849 -
Sao Paulo Medical Journal = Revista... 2023The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial.
OBJECTIVE
To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves' disease.
DESIGN AND SETTING
A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria.
METHODS
A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021.
RESULTS
Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62-1.66; P = 0.95, I2 = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28-2.58).
CONCLUSIONS
The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves' disease.
PROSPERO REGISTRATION
CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.
Topics: Humans; Methimazole; Antithyroid Agents; Iodine Radioisotopes; Nigeria; Thyroid Neoplasms; Graves Disease; Hyperthyroidism
PubMed: 36629663
DOI: 10.1590/1516-3180.2022.0225.R1.19102022