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Neurologic Clinics May 2018With specialized care, patients with myasthenia gravis can have very good outcomes. The mainstays of treatment are acetylcholinesterase inhibitors, and immunosuppressive... (Review)
Review
With specialized care, patients with myasthenia gravis can have very good outcomes. The mainstays of treatment are acetylcholinesterase inhibitors, and immunosuppressive and immunomodulatory therapies. There is good evidence thymectomy is beneficial in thymomatous and nonthymomatous disease. Nearly all of the drugs used for MG are considered "off-label." The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis. This article reviews the evidence base and provides a framework for the treatment of myasthenia gravis, highlighting recent additions to the literature.
Topics: Humans; Immunosuppressive Agents; Myasthenia Gravis; Thymectomy
PubMed: 29655452
DOI: 10.1016/j.ncl.2018.01.011 -
The New England Journal of Medicine Aug 2023The function of the thymus in human adults is unclear, and routine removal of the thymus is performed in a variety of surgical procedures. We hypothesized that the adult...
BACKGROUND
The function of the thymus in human adults is unclear, and routine removal of the thymus is performed in a variety of surgical procedures. We hypothesized that the adult thymus is needed to sustain immune competence and overall health.
METHODS
We evaluated the risk of death, cancer, and autoimmune disease among adult patients who had undergone thymectomy as compared with demographically matched controls who had undergone similar cardiothoracic surgery without thymectomy. T-cell production and plasma cytokine levels were also compared in a subgroup of patients.
RESULTS
After exclusions, 1420 patients who had undergone thymectomy and 6021 controls were included in the study; 1146 of the patients who had undergone thymectomy had a matched control and were included in the primary cohort. At 5 years after surgery, all-cause mortality was higher in the thymectomy group than in the control group (8.1% vs. 2.8%; relative risk, 2.9; 95% confidence interval [CI], 1.7 to 4.8), as was the risk of cancer (7.4% vs. 3.7%; relative risk, 2.0; 95% CI, 1.3 to 3.2). Although the risk of autoimmune disease did not differ substantially between the groups in the overall primary cohort (relative risk, 1.1; 95% CI, 0.8 to 1.4), a difference was found when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis (12.3% vs. 7.9%; relative risk, 1.5; 95% CI, 1.02 to 2.2). In an analysis involving all patients with more than 5 years of follow-up (with or without a matched control), all-cause mortality was higher in the thymectomy group than in the general U.S. population (9.0% vs. 5.2%), as was mortality due to cancer (2.3% vs. 1.5%). In the subgroup of patients in whom T-cell production and plasma cytokine levels were measured (22 in the thymectomy group and 19 in the control group; mean follow-up, 14.2 postoperative years), those who had undergone thymectomy had less new production of CD4+ and CD8+ lymphocytes than controls (mean CD4+ signal joint T-cell receptor excision circle [sjTREC] count, 1451 vs. 526 per microgram of DNA [P = 0.009]; mean CD8+ sjTREC count, 1466 vs. 447 per microgram of DNA [P<0.001]) and higher levels of proinflammatory cytokines in the blood.
CONCLUSIONS
In this study, all-cause mortality and the risk of cancer were higher among patients who had undergone thymectomy than among controls. Thymectomy also appeared be associated with an increased risk of autoimmune disease when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis. (Funded by the Tracey and Craig A. Huff Harvard Stem Cell Institute Research Support Fund and others.).
Topics: Humans; Adult; Thymectomy; Thymus Gland; CD8-Positive T-Lymphocytes; Cytokines; Autoimmune Diseases
PubMed: 37530823
DOI: 10.1056/NEJMoa2302892 -
CMAJ : Canadian Medical Association... Sep 2018
Topics: Diagnostic Techniques, Ophthalmological; Electromyography; Humans; Myasthenia Gravis; Thymectomy
PubMed: 30249760
DOI: 10.1503/cmaj.180656 -
Interactive Cardiovascular and Thoracic... Jul 2022Robot-assisted thymectomy through a subxiphoid scopic approach can provide a good surgical view, similar to that of median sternotomy. We originally used the subxiphoid...
Robot-assisted thymectomy through a subxiphoid scopic approach can provide a good surgical view, similar to that of median sternotomy. We originally used the subxiphoid port only for the robotic scope to avoid instrument collision with the assistant device. This approach, robotic subxiphoid-optical thymectomy, is advantageous for the safe and accurate dissection of the bilateral phrenic nerves and the left brachiocephalic vein, which are especially needed in extended thymectomy for patients with myasthenia gravis.
Topics: Humans; Myasthenia Gravis; Robotic Surgical Procedures; Robotics; Sternotomy; Thymectomy
PubMed: 35416955
DOI: 10.1093/icvts/ivac104 -
PloS One 2023High-dose prednisone use, lasting several months or longer, is the primary initial therapy for myasthenia gravis (MG). Upwards of a third of patients do not respond to... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
High-dose prednisone use, lasting several months or longer, is the primary initial therapy for myasthenia gravis (MG). Upwards of a third of patients do not respond to treatment. Currently no biomarkers can predict clinical responsiveness to corticosteroid treatment. We conducted a discovery-based study to identify treatment responsive biomarkers in MG using sera obtained at study entry to the thymectomy clinical trial (MGTX), an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone.
METHODS
We applied ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry to obtain comparative serum metabolomic and lipidomic profiles at study entry to correlate with treatment response at 6 months. Treatment response was assessed using validated outcome measures of minimal manifestation status (MMS), MG-Activities of Daily Living (MG-ADL), Quantitative MG (QMG) score, or a strictly defined composite measure of response.
RESULTS
Increased serum levels of phospholipids were associated with treatment response as assessed by QMG, MMS, and the Responders classification, but all measures showed limited overlap in metabolomic profiles, in particular the MG-ADL. A panel including histidine, free fatty acid (13:0), γ-cholestenol and guanosine was highly predictive of the strictly defined treatment response measure. The AUC in Responders' prediction for these markers was 0.90 irrespective of gender, age, thymectomy or baseline prednisone use. Pathway analysis suggests that xenobiotic metabolism could play a major role in treatment resistance. There was no association with outcome and gender, age, thymectomy or baseline prednisone use.
INTERPRETATION
We have defined a metabolomic and lipidomic profile that can now undergo validation as a treatment predictive marker for MG patients undergoing corticosteroid therapy. Metabolomic profiles of outcome measures had limited overlap consistent with their assessing distinct aspects of treatment response and supporting unique biological underpinning for each outcome measure. Interindividual variation in prednisone metabolism may be a determinate of how well patients respond to treatment.
Topics: Humans; Prednisone; Activities of Daily Living; Glucocorticoids; Myasthenia Gravis; Combined Modality Therapy; Thymectomy; Treatment Outcome
PubMed: 37816000
DOI: 10.1371/journal.pone.0287654 -
Neurosciences (Riyadh, Saudi Arabia) Jan 2021To evaluate the prevalence and the factors associated with recurrence of myasthenia gravis following thymectomy.
OBJECTIVES
To evaluate the prevalence and the factors associated with recurrence of myasthenia gravis following thymectomy.
METHODS
Six electronic databases which reported on recurrence of myasthenia gravis following thymectomy and/or its risk factors from 1985 to 2018 were searched. Summary prevalence and risk values obtained based on the random effect models were reported.
RESULTS
Seventy (70) papers containing 7,287 individuals with myasthenia gravis who received thymectomy as part of their management were retrieved. The patients had a mean follow-up of 4.65 years post-thymectomy. The prevalence of myasthenia gravis recurrence post-thymectomy was 18.0% (95% CI 14.7-22.0%; 1865/7287). Evident heterogeneity was observed (I=93.6%; <0.001). Recurrence rate was insignificantly higher in male compared with female patients (31.3 vs. 23.8%; =0.104). Pooled recurrence rates for thymomatous (33.3%) was higher than the rate among non-thymomatous (20.8%) myasthenia gravis patients (Q=4.19, =0.041). Risk factors for recurrence include older age, male sex, disease severity, having thymomatous myasthenia gravis, longer duration of the myasthenia gravis before surgery, and having an ectopic thymic tissue.
CONCLUSION
A fifth of individuals with myasthenia gravis experience recurrence after thymectomy. Closer monitoring should be given to at-risk patients and further studies are needed to understand interventions to address these risks.
Topics: Databases, Factual; Humans; Myasthenia Gravis; Prevalence; Recurrence; Risk Factors; Thymectomy; Time Factors; Treatment Outcome
PubMed: 33530037
DOI: 10.17712/nsj.2021.1.20190041 -
The Journal of Thoracic and... Jul 2017
Topics: Biomedical Research; Humans; Myasthenia Gravis; Thymectomy; Treatment Outcome
PubMed: 28479053
DOI: 10.1016/j.jtcvs.2016.12.074 -
Proceedings of the National Academy of... Dec 2020
Topics: B-Lymphocytes; Clone Cells; Humans; Myasthenia Gravis; Thymectomy
PubMed: 33273117
DOI: 10.1073/pnas.2022901117 -
Thoracic Surgery Clinics May 2019Kido and colleagues in 1999 used for the first time the subxiphoid approach. Recently, video-assisted thoracoscopic surgery (VATS) thymectomy has been improved for the... (Review)
Review
Kido and colleagues in 1999 used for the first time the subxiphoid approach. Recently, video-assisted thoracoscopic surgery (VATS) thymectomy has been improved for the advancement of surgical materials and new instruments. The most important aspect regarding the subxiphoid approach is the possibility to avoid the intercostal nerve damage with the consequence of a decreased use of postoperative analgesics, quite short surgical duration, fast discharge from hospital and a guarantee of successful cosmetics results.
Topics: Humans; Myasthenia Gravis; Patient Positioning; Preoperative Care; Thoracic Surgery, Video-Assisted; Thymectomy
PubMed: 30928001
DOI: 10.1016/j.thorsurg.2018.12.010 -
PloS One 2022To study the updated prevalence and clinical features of myasthenia gravis (MG) in Japan during 2017.
OBJECTIVE
To study the updated prevalence and clinical features of myasthenia gravis (MG) in Japan during 2017.
METHODS
We sent survey sheets to the randomly selected medical departments (number = 7,545). First, we asked the number of MG patients who visited medical departments from January 1, 2017, to December 31, 2017. Then, we sent the second survey sheet to the medical departments that answered the first survey to obtain the clinical information of patients who received MG diagnosis between January 1, 2015, and December 31, 2017.
RESULTS
The received answer to the first survey were 2,708 (recovery rate: 35.9%). After all, the prevalence of the 100,000 population was estimated as 23.1 (95%CI: 20.5-25.6). As a result of the second survey, we obtained 1,464 case records. After checking the duplications and lacking data, we utilized 1,195 data for further analysis. The median [interquartile range (IQR)] from the onset age of total patients was 59 (43-70) years old. The male-female ratio was 1: 1.15. The onset age [median (IQR)] for female patients was 58 (40-72) years old, and that for male patients was 60 (49-69) years old (Wilcoxon-Mann-Whitney test, p = 0.0299). We divided patients into four categories: 1) anti-acetylcholine receptor antibody (AChRAb) (+) thymoma (Tm) (-), 2) AChRAb(+)Tm(+), 3) anti-muscle-specific kinase antibody (MuSKAb) (+), and AChRAb(-)MuSKAb(-) (double negative; DN). The onset age [median (IQR)] of AChRAb(+)Tm(-) was 64 (48-73) years old, and AChRb(+)Tm(+) was 55 (45-66), MuSKAb(+) was 49 (36-64), DN was 47 (35-60) year old. The multivariate logistic regression analysis using sex, initial symptoms, repetitive nerve stimulation test (RNST), and edrophonium test revealed that sex, ocular symptoms, bulbar symptoms, and RNST were factors to distinguish each category. The myasthenia gravis activities of daily living profile at the severest state were significantly higher in MuSKAb(+). MuSKAb(+) frequently received prednisolone, tacrolimus plasmapheresis, and intravenous immunoglobulin; however, they received less acetylcholine esterase inhibitor. 99.2% of AChRAb(+)Tm(+) and 15.4% of AChRAb(+)Tm(-) received thymectomy. MuSKAb(+) did not receive thymectomy, and only 5.7% of DN received thymectomy. The prognosis was favorable in all categories.
CONCLUSION
Our result revealed that the prevalence of Japanese MG doubled from the previous study using the same survey method in 2006. We also found that the onset age shifted to the elderly, and the male-female ratio reached almost even. Classification in four categories; AChRAb(+)Tm(-), AChRAb(+)Tm(+), MuSKAb(+), and DN, well describe the specific clinical features of each category and differences in therapeutic approaches.
Topics: Activities of Daily Living; Adult; Aged; Autoantibodies; Edrophonium; Esterases; Female; Humans; Immunoglobulins, Intravenous; Japan; Male; Middle Aged; Myasthenia Gravis; Prednisolone; Surveys and Questionnaires; Tacrolimus; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 36129914
DOI: 10.1371/journal.pone.0274161