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Medical Science Monitor : International... Aug 2015The association between PTPN22 R620W polymorphism and risk of myasthenia gravis (MG) remains controversial. Therefore, we did this meta-analysis to investigate this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between PTPN22 R620W polymorphism and risk of myasthenia gravis (MG) remains controversial. Therefore, we did this meta-analysis to investigate this association.
MATERIAL AND METHODS
We did a comprehensive search in PubMed, Medline, Embase, CNKI (China National Knowledge Infrastructure), and Wanfang electronic databases to retrieve relevant articles. The overall effect was measured by odds ratios (ORs) with its 95% confidence intervals (CIs). Statistical analyses were conducted with STATA software.
RESULTS
Overall, a total of 7 case-control studies with 2802 cases and 3730 controls were finally included in this review. PTPN22 R620W polymorphism was significantly associated with an increased risk of MG (OR=1.57; 95% CI, 1.34-1.82; I(2)=31%). In the subgroup analysis, thymoma patients were significantly associated with risk of MG (OR=1.59; 95% CI, 1.28-1.98; I(2)=0%). However, non-thymoma patients with this polymorphism did not have increased MG risk (OR=1.36; 95% CI, 0.86-2.15; I(2)=77%). In addition, PTPN22 R620W polymorphism showed increased early-onset myasthenia gravis (EOMG) risk (OR=2.38; 95% CI, 1.52-3.71; I(2)=0%).
CONCLUSIONS
This meta-analysis shows a significant association between PTPN22 R620W polymorphism and MG risk.
Topics: Genetic Predisposition to Disease; Humans; Myasthenia Gravis; Polymorphism, Genetic; Protein Tyrosine Phosphatase, Non-Receptor Type 22
PubMed: 26318187
DOI: 10.12659/MSM.894307 -
Reviews in Endocrine & Metabolic... Dec 2021Knowledge of ectopic Cushing's syndrome (CS) due to thymic neuroendocrine tumours (NETs) comes from short series or single cases. Our aim is to perform a systematic... (Review)
Review
Knowledge of ectopic Cushing's syndrome (CS) due to thymic neuroendocrine tumours (NETs) comes from short series or single cases. Our aim is to perform a systematic review using PubMed, Embase, Scopus, Ovid Medline and Biosis Previews of all cases with ectopic CS due to thymic NETs reported in the last 40 years and describe one illustrative patient attended in our institution. Search of literature: From 162 patients, 58.6% were male and mean age was 34.6 ± 13.9 years-old. Median of symptoms until diagnosis was 6 [2-24] months and 62% had aggressive CS. Imaging was positive in 93.7% (chest X-ray), 97.8% (computed tomography), 80.7% (somatostatin receptor scintigraphy) and median tumour size was 47 [25-68.5] mm. At presentation, 18% had localized disease, 26.2% locally invasive and 55.7% advanced. Eighty-eight present underwent surgery and histological subtypes were atypical (46.7%), typical (30.4%) and carcinoma (21.7%). Tumour persisted or recurred in 70.1%, 63% received radiotherapy and 45.2% chemotherapy. Follow-up median was 26.6 [14.5-57.5] months and mortality was reported in 35.8% with median survival of 38 [19-60] months. MEN-1 mutation was referred in 3.1%. Comparatively, carcinomas had aggressive CS more frequently while atypical showed advanced disease more often. In conclusion, thymic NETs causing ectopic CS are presented as aggressive hypercortisolism in the middle aged population. The disease is commonly extended at diagnosis and persists or recurs after surgery in most patients with a short term high mortality.
Topics: ACTH Syndrome, Ectopic; Adult; Cushing Syndrome; Humans; Male; Middle Aged; Neuroendocrine Tumors; Thymoma; Thymus Neoplasms; Young Adult
PubMed: 33961211
DOI: 10.1007/s11154-021-09660-2 -
Cancer Treatment Reviews Jan 2021Primary enteric adenocarcinoma of the thymus (EAT) is a recently proposed rare subtype of thymic carcinoma. Unlike thymic carcinomas with squamous histology, for which...
BACKGROUND
Primary enteric adenocarcinoma of the thymus (EAT) is a recently proposed rare subtype of thymic carcinoma. Unlike thymic carcinomas with squamous histology, for which clinical guidelines are available, little knowledge is available regarding the clinical and pathological features of EAT, and there is no consensus on the best treatment algorithm for such tumors.
METHODS
We performed a systematic review of the literature, searching for all cases of EAT reported. We also retrospectively reviewed all cases of EAT treated at the European Institute of Oncology (IEO) between January 2000 and January 2020. Individual patient data were extracted and analyzed in order to delineate clinical and pathological features, as well as patients' prognosis and treatments outcome, evaluated in terms of Disease free Survival (DFS), Progression free survival (PFS) and overall survival (OS).
RESULTS
Thirty-three cases (29 reported in literature and 4 new cases treated at IEO) of thymic adenocarcinoma deploying enteric differentiation as defined by WHO-criteria were analyzed. All tumors showed positive immunoreactivity for cytokeratin (CK) 20 and/or caudal type homeobox 2 (CDX2). Data on molecular profiling by next-generation sequencing were available in only 3 cases, and did not show actionable findings. At diagnosis, 11 pts had an early-stage (Masaoka I-II) and 22 a locally advanced (10 pts) or metastatic (12 pts) disease. Median-DFS of patients with localized disease was 12 months (95% CI, 7-19). Patients who received systemic chemotherapy were mostly treated with regimens commonly used for thymic epithelial tumors, with a discouraging PFS of 3-5 months for patients with stage IV disease. Median OS of the whole population was 34 months (95% CI, 24-NA:. mOS was not reached for patients with stage I-II disease versus 34 months in stage III-IV (p < 0.05).
CONCLUSION
Available evidence suggests that EAT represents a distinct entity in the context of thymic epithelial tumors, characterized by aggressive clinical behavior, poor responsiveness to chemotherapy and dismal patients prognosis. More research is needed to better define optimal management strategies for patients with such rare disease.
Topics: Adenocarcinoma; Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Progression-Free Survival; Retrospective Studies; Thymoma; Treatment Outcome; Young Adult
PubMed: 33296826
DOI: 10.1016/j.ctrv.2020.102133 -
Lung Cancer (Amsterdam, Netherlands) Oct 2014To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in... (Meta-Analysis)
Meta-Analysis Review
AIM
To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in predicting the WHO grade of malignancy in thymic epithelial tumors (TETs).
METHODS
A comprehensive literature search of studies published up to March 2014 was performed. Data on maximum standardized uptake value (SUVmax) in patients with low-risk thymomas (A, AB, B1), high-risk thymomas (B2, B3) and thymic carcinomas (C) according to the WHO classification were collected when reported by the retrieved articles. The comparison of mean SUVmax between low-risk thymomas, high-risk thymomas and thymic carcinomas was expressed as weighted mean difference (WMD) and a pooled WMD was calculated including 95% confidence interval (95%CI).
RESULTS
Eleven studies were selected for the meta-analysis. The pooled WMD of SUVmax between high-risk and low-risk thymomas was 1.2 (95%CI: 0.4-2.0). The pooled WMD of SUVmax between thymic carcinomas and low-risk thymomas was 4.8 (95%CI: 3.4-6.1). Finally, the pooled WMD of SUVmax between thymic carcinomas and high-risk thymomas was 3.5 (95%CI: 2.7-4.3).
CONCLUSIONS
(18)F-FDG PET may predict the WHO grade of malignancy in TETs. In particular, we demonstrated a statistically significant difference of SUVmax between the different TETs (low-grade thymomas, high-grade thymomas and thymic carcinomas).
Topics: Fluorodeoxyglucose F18; Humans; Neoplasm Grading; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Positron-Emission Tomography; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed
PubMed: 25175317
DOI: 10.1016/j.lungcan.2014.08.008 -
Journal of Thoracic Disease Aug 2021Thymic epithelial tumors (TETs) are rare malignant neoplasms originating from thymic epithelial cells. The current treatment for localized TETs is surgical removal.... (Review)
Review
BACKGROUND
Thymic epithelial tumors (TETs) are rare malignant neoplasms originating from thymic epithelial cells. The current treatment for localized TETs is surgical removal. However, 20-30% of thymomas and 70-80% of thymic carcinomas are unresectable, recurrent, or metastatic at the time of detection. The standard therapy for these patients is chemotherapy, but the effect is limited. With a deeper understanding of tumor immunity, immunotherapy for various cancers has rapidly developed. Antibodies against cytotoxic T-lymphocyte antigen-4, programmed death-1, and programmed death-ligand 1 have been approved for the treatment of many solid tumors. Compared with traditional treatments, these immune checkpoint inhibitors (ICIs) have better efficacy and lower toxicity. Recently, ICIs have been used more enthusiastically in the treatment of TETs. However, due to the unique biological characteristics of the thymus, immunotherapy usually causes severe immune-related adverse events (irAEs). Most previous studies on immunotherapy in TETs had small sample sizes and reported diverse conclusions.
METHODS
We collected relevant studies in PubMed during the last five years and analyzed the available data to discuss the efficacy and safety of ICIs in TETs.
RESULTS
According to 14 previous studies in the past five years, all TETs showed expression of programmed death-ligand 1, while thymic carcinomas showed 100% expression. The best median progression-free survival (mPFS) among the five studies was 6.5 months, and the best median overall survival (mOS) was 24.9 months. In addition, the most common irAEs were myasthenic symptoms, liver enzyme elevation, and elevated creatine phosphokinase levels.
CONCLUSIONS
ICIs can be used in TET treatment, especially for thymic carcinomas, in the absence of standard second-line treatment. However, more attention should be paid to irAEs.
PubMed: 34527346
DOI: 10.21037/jtd-21-290 -
Clinical Immunology (Orlando, Fla.) Jun 2010Good syndrome (GS) is a rare association of thymoma and immunodeficiency first described more than 50 years ago. However, this syndrome still remains a mystery to... (Review)
Review
Good syndrome (GS) is a rare association of thymoma and immunodeficiency first described more than 50 years ago. However, this syndrome still remains a mystery to clinicians. We systematically reviewed all the clinical, laboratory and immunologic findings from 152 patients with Good syndrome. The syndrome has a worldwide distribution and approximately half of the cases (47%) have been described in Europe. The diagnosis of thymoma preceded the diagnosis of hypogammaglobulinemia, infection, or diarrhea in 42% of patients whereas in 38% of patients the diagnoses were made almost simultaneously within 2 months of each other. We found significant mortality in patients with this syndrome (44.5%). Astute clinical acumen and increased awareness about the clinical and immunological profile of this syndrome may increase early recognition of this syndrome and prevent mortality. Further studies are needed to elucidate this clinical entity.
Topics: Humans; Immunologic Deficiency Syndromes; Thymoma; Thymus Neoplasms
PubMed: 20149753
DOI: 10.1016/j.clim.2010.01.006 -
Current Opinion in Neurology Jun 2020To systematically review the clinical features, diagnosis, and management of anti-gamma-aminobutyric acid receptor Type A (GABAA) autoimmune encephalitis with a focus on...
PURPOSE OF REVIEW
To systematically review the clinical features, diagnosis, and management of anti-gamma-aminobutyric acid receptor Type A (GABAA) autoimmune encephalitis with a focus on recent data.
RECENT FINDINGS
In a review of published reports, we identified 50 cases of anti-GABAA receptor encephalitis with clinical features reported. The median age at presentation was 47 years old (range, 2.5 months-88 years old), 64% were adults, 36% were children and it occurred in both males and females. Eight-two percent (41/50) presented with seizures, 72% (36/50) with encephalopathy, and 58% (29/50) with both. Of those presenting with seizures, 42% developed status epilepticus during their disease course. Ninety-six percent (48/50) had MRI results reported, with 83% of these cases having abnormal findings, most commonly multifocal/diffuse cortical and subcortical T2/FLAIR hyperintense lesions without associated gadolinium enhancement. Almost one-third, 28% (14/50), had an associated malignancy detected by the time of diagnosis, 64% (9/14) of which was thymoma. Of 44 patients with outcomes reported, 80% had partial or complete recovery, whereas 20% had poor outcomes including 11% (5/44) who died. Of the 42 patients with type of treatment(s) and outcomes reported, 54% (23/42) received only first-line immunotherapy and 31% (13/42) received first-line and second-line immunotherapy. Receiving a combination of first-line and second-line immunotherapy may be associated with higher likelihood of complete recovery. When follow-up MRIs were reported, all showed improvement, and sometimes complete resolution, of T2/FLAIR hyperintensities.
SUMMARY
Anti-GABAA receptor encephalitis can present across the age spectrum and should be considered in patients who present with rapidly progressive encephalopathy and/or seizures. Brain MRI often shows a distinctive pattern of multifocal cortical and subcortical T2/FLAIR hyperintense lesions, generally not typical of other known central nervous system autoantibody associated encephalitis syndromes. High clinical suspicion and early diagnosis are important given the potential for clinical improvement with immunotherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Child; Child, Preschool; Encephalitis; Female; Hashimoto Disease; Humans; Immunotherapy; Infant; Magnetic Resonance Imaging; Male; Middle Aged; Receptors, GABA-A; Seizures; Young Adult
PubMed: 32374573
DOI: 10.1097/WCO.0000000000000814 -
Journal of Neurology Dec 2021Corticosteroids (CS) are among the most widely- used immunosuppressive agents for immune-mediated conditions, including myasthenia gravis (MG). While their effectiveness... (Review)
Review
Corticosteroids (CS) are among the most widely- used immunosuppressive agents for immune-mediated conditions, including myasthenia gravis (MG). While their effectiveness in MG is documented and supported in the clinical practice over several decades, one of the main drawbacks of treatment results from the notion that MG patients may experience symptom worsening following CS treatment initiation. This may lead to the administration of lower than necessary doses of CS for the disorder, or even avoiding them altogether. As a consequence, some patients may not receive the optimal treatment to control their disease. In the present review, we analyzed 27 relevant publications and determined the prevalence of clinical exacerbation following CS treatment, its' severity and relation to the type and dose of CS. The rate of MG exacerbation is highest with the administration of cortisone, intermediate with prednisone, and lowest with methylprednisolone. High dose daily or alternate-day prednisone is associated with exacerbation more frequently than low-dose treatment, but most exacerbations are of mild to moderate severity. Other factors related to increased risk of an initial exacerbation include older age, generalized MG, bulbar symptoms, disease severity, presence of thymoma, and thymectomy. However, the current information is based mostly on heterogeneous studies of low quality, and prospective clinical trials designed to compare between the various agents and doses and assess the rate and severity of the exacerbation by a unified scale are warranted.
Topics: Adrenal Cortex Hormones; Aged; Humans; Myasthenia Gravis; Prospective Studies; Thymectomy; Thymus Neoplasms
PubMed: 33064188
DOI: 10.1007/s00415-020-10264-0 -
International Immunopharmacology Nov 2022Studies have described the role of microRNAs (miRNAs) in thymic function, along with directly observing the altered expression of miRNAs in thymuses of myasthenia gravis...
BACKGROUND
Studies have described the role of microRNAs (miRNAs) in thymic function, along with directly observing the altered expression of miRNAs in thymuses of myasthenia gravis (MG) patients; so, miRNAs became a core component in the pathophysiology of MG. However, because the miRNA analysis results are contradictory, the identification of MG-related miRNAs is daunting.
OBJECTIVE
We did a systematic review of studies analyzing the miRNA expression profile of peripheral blood and mononuclear cells for patients with MG.
METHODS
We ran a database search in PubMed, Scopus, and Web of Science on August 17, 2021. Original articles that analyzed miRNA profiles in peripheral blood (serum, plasma, and whole blood) and peripheral blood mononuclear cells (PBMCs) for patients with MG in comparison with a non-MG or healthy control (HC) group were eligible. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).
RESULTS
26 studies were included. The quality of studies was fair (median score, 5). Among 226 different miRNAs that were deregulated in at least one study (range, 1-87), ten miRNAs were significantly deregulated in three or more studies. Five miRNAs (50%) showed the same deregulation: miR-106b-3p and miR-21-5p were consistently upregulated, and miR-20b, miR-15b, and miR-16 were consistently downregulated. Also, there were five miRNAs that were mostly upregulated, miR-150-5p, miR-146a, miR-30e-5p, and miR-338-3p, or downregulated, miR-324-3p, across studies.
CONCLUSION
These miRNAs contribute to different pathways, importantly neural apoptosis and autophagy, inflammation, T regulatory cell development, and T helper cell balance. Prior to being used for diagnostic and therapeutic purposes, it is required to pursue molecular mechanisms these consistently and mostly dysregulated miRNAs specifically use in the context of MG.
Topics: Humans; Gene Expression Profiling; Leukocytes, Mononuclear; MicroRNAs; Myasthenia Gravis; Leukocyte Count
PubMed: 36087508
DOI: 10.1016/j.intimp.2022.109205 -
Acta Neurologica Belgica Oct 2023To ascertain the clinical characteristics of pediatric patients with contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis (AEs). (Review)
Review
OBJECTIVES
To ascertain the clinical characteristics of pediatric patients with contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis (AEs).
METHODS
Two cases of CASPR2 antibody-associated AEs have been reported. In addition, a systematic search of literature published between January 2010 and March 2022 through six online databases was conducted to identify the pediatric patients with CASPR2 antibody-associated AEs. Data on demographics, clinical symptoms, laboratory examinations, imaging, treatment, and outcome were collected.
RESULTS
Our updated literature search yielded 1,837 publications, of which 21 were selected, and 40 patients in this study met the diagnostic criteria for AE. There were 25 males and 15 females with a mean age of 9.2 years. The most common presenting symptoms are psychiatric symptoms (72.5%), sleep changes (62.5%), and movement disorders (60%). The psychiatric symptoms included mood changes (39.1%), behavior changes (25%), and hallucination (7.5%). In total, 23 cases (57.5%) combined with autonomic dysfunction, such as gastrointestinal dysmotility, cardiovascular-related symptoms, and sweating. No tumors were observed in children. Thirty-eight patients received first-line immunotherapy, and eight received first-line and second-line immunotherapy. All patients had a good clinical response to immune therapy. Mean mRS at onset was 3.4; It was 0.88 at the last follow-up. There was no recurrence during follow-up.
CONCLUSION
Psychiatric symptoms, sleep disorders, movement disorders, and cardiovascular-related symptoms are the most common presentation in pediatric patients with CASPR2 antibody-associated AEs. Tumor, particularly with thymoma, is uncommon in children diagnosed with CASPR2 antibody-associated AEs. In addition, prompt diagnosis and immunotherapy can relieve symptoms and improve the prognosis.
Topics: Male; Female; Humans; Child; Autoantibodies; Thymus Neoplasms; Movement Disorders; Autoimmune Diseases of the Nervous System; Contactins
PubMed: 36662402
DOI: 10.1007/s13760-023-02174-5