Efficacy and safety of tocilizumab in patients with refractory generalized myasthenia gravis.

BACKGROUND: We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). METHODS: This single-center prospective cohort study was based on patients from an MG registry study in China and conducted from February 10, 2021 to March 31, 2022. Adult refractory patients with AChR-Ab+ gMG were assigned to tocilizumab or conventional immunotherapy groups. The primary efficacy outcome was the mean difference of MG activities of daily living (MG-ADL) change at weeks 4, 8, 12, 16, 20, 24 corresponding to that at the baseline between the two groups. A generalized estimating equation model was used for the primary outcome analysis. Safety was assessed based on adverse events. RESULTS: Of 34 eligible patients, 20 (mean [standard deviation] age, 53.8 [21.9] years; 12 [60.0%] female) received tocilizumab and 14 received conventional immunotherapy (45.8 [18.0] years; 8 [57.1%] female). The tocilizumab group had greater reduction in MG-ADL score at week 4 (adjusted mean difference, -3.4; 95% CI, -4.7 to -2.0; p < 0.001) than the conventional immunotherapy group, with significant differences sustained through week 24 (adjusted mean difference, -4.5; 95% CI, -6.4 to -2.6; p < 0.001). At week 24, the proportion of patients achieving higher levels of MG-ADL (up to 7-point reduction) and QMG (up to 11-point reduction) scores improvement was significantly greater with tocilizumab. Tocilizumab had acceptable safety profiles without severe or unexpected safety issues. CONCLUSION: Tocilizumab is safe and effective in improving the MG-ADL score and reducing prednisone dose in refractory AChR-Ab+ gMG, suggesting tocilizumab has the potential to be a valuable therapeutic option for such patients.

A predictive nomogram for short-term outcomes of myasthenia gravis patients treated with low-dose rituximab.

BACKGROUND: This study aims to establish and validate a predictive nomogram for the short-term clinical outcomes of myasthenia gravis (MG) patients treated with low-dose rituximab. METHODS: We retrospectively reviewed 108 patients who received rituximab of 600 mg every 6 months in Huashan Hospital and Tangdu Hospital. Of them, 76 patients from Huashan Hospital were included in the derivation cohort to develop the predictive nomogram, which was externally validated using 32 patients from Tangdu Hospital. The clinical response is defined as a ≥ 3 points decrease in QMG score within 6 months. Both clinical and genetic characteristics were included to screen predictors via multivariate logistic regression. Discrimination and calibration were measured by the area under the receiver operating characteristic curve (AUC-ROC) and Hosmer-Lemeshow test, respectively. RESULTS: Disease duration (OR = 0.987, p = 0.032), positive anti-muscle-specific tyrosine kinase antibodies (OR = 19.8, p = 0.007), and genotypes in FCGR2A rs1801274 (AG: OR = 0.131, p = 0.024;GG:OR = 0.037, p = 0.010) were independently associated with clinical response of post-rituximab patients. The nomogram identified MG patients with clinical response with an AUC-ROC (95% CI) of 0.875 (0.798-0.952) in the derivation cohort and 0.741(0.501-0.982) in the validation cohort. Hosmer-Lemeshow test showed a good calibration (derivation: Chi-square = 3.181, p = 0.923; validation: Chi-square = 8.098, p = 0.424). CONCLUSIONS: The nomogram achieved an optimal prediction of short-term outcomes in patients treated with low-dose rituximab.

Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study.

BACKGROUND: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM: To investigate the association between specific environmental factors and the generalization of OMG. DESIGN: The cohort study was conducted in China based on a nationwide multicenter database. METHODS: Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS: A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS: Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.

Engineering an injectable gellan gum-based hydrogel with osteogenesis and angiogenesis for bone regeneration.

Injectable hydrogels are currently a topic of great interest in bone tissue engineering, which could fill irregular bone defects in a short time and avoid traditional major surgery. Herein, we developed an injectable gellan gum (GG)-based hydrogel for bone defect repair by blending nano-hydroxyapatite (nHA) and magnesium sulfate (MgSO4). In order to acquire an injectable GG-based hydrogel with superior osteogenesis, nHA were blended into GG solution with an optimized proportion. For the aim of endowing this hydrogel capable of angiogenesis, MgSO4 was also incorporated. Physicochemical evaluation revealed that GG-based hydrogel containing 5% nHA (w/v) and 2.5 mM MgSO4 (GG/5%nHA/MgSO4) had appropriate sol-gel transition time, showed a porosity-like structure, and could release magnesium ions for at least 14 days. Rheological studies showed that the GG/5%nHA/MgSO4 hydrogel had a stable structure and repeatable self-healing properties. In-vitro results determined that GG/5%nHA/MgSO4 hydrogel presented superior ability on stimulating bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteogenic linage and human umbilical vein endothelial cells (HUVECs) to generate vascularization. In-vivo, GG/5%nHA/MgSO4 hydrogel was evaluated via a rat cranial defect model, as shown by better new bone formation and more neovascularization invasion. Therefore, the study demonstrated that the new injectable hydrogel, is a favorable bioactive GG-based hydrogel, and provides potential strategies for robust therapeutic interventions to improve the repair of bone defect.

Factors associated with the disease family burden of caregivers of myasthenia gravis patients in northwestern China: A cross-sectional study.

BACKGROUND: Patients with myasthenia gravis (MG) lose part of their working or living ability due to illness, and bring burden to caregivers. The purpose of this study was to explore the factors related to caregivers' disease family burden for MG patients in Northwest China. METHODS: The study utilized our Myasthenia Gravis database and distributed online questionnaires to both MG patients and their caregivers. The questionnaires included a general data collection form, the Patient Health Questionnaire-9 (PHQ-9) scale, and the Caregivers' Family Burden Scale of Disease (FBSD). Univariate analysis and multivariate linear regression analysis were run, with FBSD as the outcome variable for separate analyses. RESULTS: 178 MG patients were eligible for inclusion in the analysis, of whom 80 patients' caregivers had a positive family burden of MG. The daily activity burden of the family and the economic burden of the family were the heaviest among the six dimensions of the caregivers' family disease burdens. The factors independently associated with FBSD were depression symptom level, MG severity classification and family's monthly per capita income (p < 0.05). CONCLUSIONS: Depression symptom level, MG severity classification and family's monthly per capita income are independent factors related to the caregivers' disease family burden for MG patients.

Clinical outcome and peripheral immune profile of myasthenic crisis with omicron infections: A prospective cohort study.

The impact of Omicron infections on the clinical outcome and immune responses of myasthenia gravis (MG) remained largely unknown. From a prospective multicenter MG cohort (n = 189) with 197 myasthenic crisis (MC), we finally included 41 independent MG patients to classify into two groups: the Omicron Group (n = 13) and the Control Group (n = 28). In this matched cohort study, all-cause mortality was 7.69% (1/13) in Omicron Group and 14.29% (4/28) in Control Group. A higher proportion of elevated serum IL-6 was identified in the Omicron Group (88.89% vs 52.38%, P = 0.049). In addition, the proportions of CD3+CD8+T in lymphocytes and Tregs in CD3+CD4+ T cells were significantly elevated in the Omicron Group (both P = 0.0101). After treatment, the Omicron Group exhibited a marked improvement in MG-ADL score (P = 0.026) and MG-QoL-15 (P = 0.0357). MCs with Omicron infections were associated with elevated serum IL-6 and CD3+CD8+T response. These patients tended to present a better therapeutic response after fast-acting therapies and anti-IL-6 treatment.

Myasthenic crisis in thymoma-associated myasthenia gravis: a multicenter retrospective cohort study.

Thymoma-associated myasthenia gravis (TMG) had more severe symptoms and worse prognoses in comparison to non-thymoma-associated MG. Thymoma recurrence was frequently associated with transient worsening of MG and even acute respiratory failure, namely myasthenic crisis (MC). However, little is known about the clinical features and outcomes of MC in thymoma-associated MG patients. We performed a retrospective cohort study in MG patients recruited from 9 independent tertiary neuromuscular centers in China from Jan 2015, through Oct 2022. Overall, 156 MC from 149 MG patients with positive anti-acetylcholine receptor (AChR) antibodies were finally analyzed. Next, these patients were divided into two subgroups: the TMG group (n = 60 MCs, 58 patients) and the non-thymoma-associated MG group (n = 96 MCs, 91 patients). Compared with non-thymoma-associated MG, TMG patients had a significantly shorter disease duration from symptom onset to the crisis (17.95±40.9 vs 51.31±60.61 months, P<0.0001), a larger proportion of MGFA IVa as the initial onset clinical classification (6.67% vs 0, P = 0.0205), and a longer hospital stay (39.24±22.09 [6-111] vs. 33.2 ± 23.42 days [7-120]; P = 0.0317) during the crisis. Within the TMG group, the hospital stay was significantly longer in patients with unresected thymoma compared to that in postoperative myasthenic crisis (POMC) (47.68±24.9 [6-111] vs. 34.21±18.87 days [12-82]; P = 0.0257). Early identification of the MG categories may provide some hints in tailoring therapeutic strategies to improve the prognosis.

Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.

Background: The safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients. Methods: The data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression. Results: Inactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination. Conclusion: COVID-19 vaccination has no long-term impact on MG relapse.

Nomogram for predicting the risk of postoperative myasthenic crisis in patients with thymectomy.

OBJECTIVE: This study aimed to develop and validate internally a clinical predictive model, for predicting myasthenic crisis within 30 days after thymectomy in patients with myasthenia gravis. METHODS: Eligible patients were enrolled between January 2015 and May 2019. The primary outcome measure was postoperative myasthenic crisis (POMC). A predictive model was constructed using logistic regression and presented in a nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to examine the performance. The study population was divided into high- and low-risk groups according to Youden index. Calibration curves with 1000 replications bootstrap resampling were plotted to visualize the calibration of the nomogram. Decision curve analyses (DCA) with 1000 replications bootstrap resampling were performed to evaluate the clinical usefulness of the model. RESULTS: A total of 445 patients were enrolled. Five variables were screened including thymus imaging, onset age, MGFA classification, preoperative treatment regimen, and surgical approach. The model exhibited moderate discriminative ability with AUC value 0.771. The threshold probability was 0.113, which was used to differentiate between high- and low-risk groups. The sensitivity and specificity were 72.1% and 77.1%, respectively. The high-risk group had an 8.70-fold higher risk of POMC. The calibration plot showed that when the probability was between 0 and 0.5, the deviation calibration curve of the model was consistent with the ideal curve. INTERPRETATION: This nomogram could assist in identifying patients at higher risk of POMC and determining the optimal surgical time for these patients.

Landscape analysis of m6A modification regulators related biological functions and immune characteristics in myasthenia gravis.

BACKGROUND: N6-methyladenosine (m6A) modification has been recognized to play fundamental roles in the development of autoimmune diseases. However, the implication of m6A modification in myasthenia gravis (MG) remains largely unknown. Thus, we aimed to systematically explore the potential functions and related immune characteristics of m6A regulators in MG. METHODS: The GSE85452 dataset with MG and healthy samples was downloaded from Gene Expression Omnibus (GEO) database. m6A modification regulators were manually curated. The targets of m6A regulators were obtained from m6A2Target database. The differential expressed m6A regulators in GSE85452 dataset were identified by "limma" package and were validated by RT-PCR. Function enrichment analysis of dysregulated m6A regulators was performed using "clusterProfiler" package. Correlation analysis was applied for analyzing the relationships between m6A regulators and immune characteristics. Unsupervised clustering analysis was used to identify distinct m6A modification subtypes. The differences between subtypes were analyzed, including the expression level of all genes and the enrichment degree of immune characteristics. Weighted gene co-expression network analysis (WGCNA) was conducted to obtain modules associated with m6A modification subtypes. RESULTS: We found that CBLL1, RBM15 and YTHDF1 were upregulated in MG samples of GSE85452 dataset, and the results were verified by RT-PCR in blood samples from19 MG patients and 19 controls. The targeted genes common modified by CBLL1, RBM15, and YTHDF1 were mainly enriched in histone modification and Wnt signaling pathway. Correlation analysis showed that three dysregulated m6A regulators were closely associated with immune characteristics. Among them, RBM15 possessed the strongest correlation with immune characteristics, including CD56dim natural killer cell (r = 0.77, P = 0.0023), T follicular helper cell (r = - 0.86, P = 0.0002), Interferon Receptor (r = 0.78, P = 0.0017), and HLA-DOA (r = 0.64, P = 0.0200). Further two distinct m6A modification patterns mediated by three dysregulated m6A regulators was identified. Bioinformatics analysis found that there were 3029 differentially expressed genes and different immune characteristics between two m6A modification patterns. Finally, WGCNA analysis obtained a total of 12 modules and yellow module was the most positively correlated to subtype-2. CONCLUSION: Our findings suggested that m6A RNA modification had an important effect on immunity molecular mechanism of MG and provided a new perspective into understanding the pathogenesis of MG.

Clinical characteristics and prognosis of very late-onset myasthenia gravis in China.

Alteration in onset-age distribution in myasthenia gravis (MG) and its increasing prevalence among the elderly underscores the need for a better understanding of the clinical course of MG and the establishment of personalized treatment. In this study we reviewed the demographics, clinical profile, and treatment of MG. Based on onset age, eligible patients were classified as early-onset MG (onset age ≥18 and <50 years), late-onset MG (onset age ≥50 and <65 years), and very late-onset MG (onset age ≥65 years). Overall, 1160 eligible patients were enrolled. Patients with late- and very late-onset MG showed a male predominance (P=0.02), ocular MG subtype (P=0.001), and seropositivity for acetylcholine receptors and titin antibodies (P<0.001). In very late-onset MG, a lower proportion of patients retained minimal manifestations status or better, a higher proportion of patients had MG-related deaths (P<0.001), and a shorter maintenance time of minimal manifestation status or better was seen at the last follow-up (P=0.007) than that in patients with early- and late-onset MG. Non-immunotherapy may associated with a poor prognosis in patients in the very late-onset group. Further studies on very late-onset MG patients should be performed to evaluate the relationship between immunotherapy and prognosis.

Development and Validation of a Nomogram for Predicting Generalization in Patients With Ocular Myasthenia Gravis.

Background: This study aims to develop and validate a nomogram for predicting 1- and 2-year generalization probabilities in patients with ocular myasthenia gravis (OMG). Methods: In total, 501 eligible patients with OMG treated at seven tertiary hospitals in China between January 2015 and May 2019 were included. The primary outcome measure was disease generalization. A nomogram for predicting 1- and 2-year generalization probabilities was constructed using a stepwise Cox regression model. Nomogram performance was quantified using C-indexes and calibration curves. Two-year cumulative generalization rates were analyzed using the Kaplan-Meier method for distinct nomogram-stratified risk groups. The clinical usefulness of the nomogram was evaluated using decision curve analysis (DCA). Result: The eligible patients were randomly divided into a development cohort (n=351, 70%) and a validation cohort (n=150, 30%). The final model included five variables: sex, onset age, repetitive nerve stimulation findings, acetylcholine receptor antibody test results, and thymic status. The model demonstrated good discrimination (C-indexes of 0.733 and 0.788 in the development and validation cohorts, respectively) and calibration, with good agreement between actual and nomogram-estimated generalization probabilities. Kaplan-Meier curves revealed higher 2-year cumulative generalization rates in the high-risk group than that in the low-risk group. DCA demonstrated a higher net benefit of nomogram-assisted decisions compared to treatment of all patients or none. Conclusion: The nomogram model can predict 1- and 2-year generalization probabilities in patients with OMG and stratified these patients into distinct generalization risk groups. The nomogram has potential to aid neurologists in selecting suitable patients for initiating immunotherapy and for enrolment in clinical trials of risk-modifying treatments.

Bone marrow hematopoiesis drives multiple sclerosis progression.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive T cells in MS is unknown. Here, we report that bone marrow HSPCs are skewed toward myeloid lineage concomitant with the clonal expansion of T cells in MS patients. Lineage tracing in experimental autoimmune encephalomyelitis, a mouse model of MS, reveals remarkable bone marrow myelopoiesis with an augmented output of neutrophils and Ly6Chigh monocytes that invade the CNS. We found that myelin-reactive T cells preferentially migrate into the bone marrow compartment in a CXCR4-dependent manner. This aberrant bone marrow myelopoiesis involves the CCL5-CCR5 axis and augments CNS inflammation and demyelination. Our study suggests that targeting the bone marrow niche presents an avenue to treat MS and other autoimmune disorders.

Association of immunosuppression treatment with generalization among patients with ocular myasthenia gravis: A propensity score analysis.

BACKGROUND: To analyze disease generalization in patients with ocular myasthenia gravis (OMG) treated with immunosuppression compared with patients without immunosuppression treatment. METHODS: In this retrospective cohort study, we analyzed data from patients with OMG at seven medical centers in China from January 1, 2015 to May 1, 2019 and compared disease generalization in patients (treated with immunosuppression vs. not treated) within 2 years of disease onset using raw and inverse probability of treatment weighting (IPTW) analyses. RESULTS: In the study population of 813 patients with OMG, 425 (52.3%) with immunosuppression had a mean (SD) onset age of 50.0 (15.1) years, and 188 (44.2%) were women. The remaining 388 (47.7%) patients were not immunosuppressed (mean age, 48.4 [15.0] years; 185 [47.7%] women). Disease generalization developed in 122 (31.4%) and 37 (8.7%) patients in the non-immunosuppression and immunosuppression groups, respectively. Relative to non-immunosuppression, immunosuppression was associated with a lower risk of generalization in a multivariable-adjusted Cox model (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.18-0.40; p < 0.001) and IPTW-weighted Cox model (HR 0.28; 95% CI 0.19-0.42; p < 0.001). In sensitivity analyses, longer duration of immunosuppression was associated with a lower risk of generalization (HR 0.90 for every 1-month increase; 95% CI 0.87-0.92; p < 0.001; IPTW-adjusted). Combination therapy with steroids and non-steroidal immunosuppressants showed superior efficacy in reducing the risk of generalization (HR 0.14; 95% CI 0.07-0.26; p < 0.001). CONCLUSION: Immunosuppression significantly reduced the 2-year risk of generalization in patients with OMG.

Mg2+ -mediated autophagy-dependent polarization of macrophages mediates the osteogenesis of bone marrow stromal stem cells by interfering with macrophage-derived exosomes containing miR-381.

Magnesium ion (Mg2+ ) has received increased attention due to the roles it plays in promoting osteogenesis and preventing inflammation. This study was designed to investigate the mechanism by which Mg2+ influences the osteoblastic differentiation of bone marrow stromal stem cells (BMSCs). The polarization of Mø (macrophages) was measured after treatment with Mg2+ . Meanwhile, autophagy in Mø was measured by detecting LC3B expression. Mø-derived exosomes were isolated and cocultured with BMSCs; after which, osteogenic differentiation was evaluated by Alizarin Red staining and detection of alkaline phosphatase (ALP). Our results showed that Mg2+ could induce autophagy in macrophages and modulate the M1/M2 polarization of macrophages. Mg2+ -mediated macrophages could facilitate the osteogenic differentiation of BMSCs by regulating autophagy, and this facilitation by Mg2+ -mediated macrophages was closely related to macrophage-derived exosomes, and especially exosomes containing miR-381. However, miR-381 in macrophages did not influence autophagy or the polarization of Mg2+ -mediated macrophages. Furthermore, macrophage-derived exosomes containing miR-381 mainly determined the osteogenic differentiation of BMSCs. Mg2+ -mediated macrophages were shown to promote the osteogenic differentiation of BMSCs via autophagy through reducing miR-381 in macrophage-derived exosomes. In conclusion, our results suggest Mg2+ -mediated macrophage-derived exosomes containing miR-381 as novel vehicles for promoting the osteogenic differentiation of BMSCs.

Risk Factors for Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Many patients with ocular myasthenia gravis (OMG) progress to generalized disease within the first 2 years of the onset of ocular symptoms. Several retrospective studies have identified risk factors associated with generalization, however these studies included patients on immunosuppression therapy or those undergoing thymectomy, which may reduce the generalization risk. In this study we explored the risk factors for generalization in non-immunosuppressed and non-thymectomized patients with OMG. METHODS: Data from patients with OMG treated at seven tertiary hospitals in China were retrospectively reviewed. Clinical characteristics, including sex, age at onset, symptoms at onset, comorbid autoimmune diseases, neostigmine test response, repetitive nerve stimulation (RNS) findings, presence of serum anti-acetylcholine receptor antibody (AChR-Ab), and thymic status based on radiological and pathological studies, were collected. The main outcome measure was disease generalization. The follow-up period was defined as the date of ocular symptom onset to the date of confirmation of generalization or immunotherapy initiation, or last follow-up (defined as 60 months). The Cox proportional hazards model was used to assess the risk factors for generalization. RESULTS: Overall, 572 patients (269 women) were eligible for inclusion in the analysis, of whom 144 developed generalization. The mean (standard deviation) onset age was 45.5 (19.8) years, and the median (interquartile range) follow-up period was 14.5 (7.0-47.3) months. Multivariable Cox regression analysis demonstrated that both early-onset (adjusted hazard ratio [aHR] 5.34; 95% confidence interval [CI] 1.64-17.36; p = 0.005) and late-onset (aHR 7.18; 95% CI 2.22-23.27; p = 0.001) in adulthood, abnormal RNS findings (aHR 3.01; 95% CI 1.97-4.61; p < 0.001), seropositivity for AChR-Ab (aHR 2.58; 95% CI 1.26-5.26; p = 0.01), and thymoma (aHR 1.62; 95% CI 1.05-2.49; p = 0.03) were independently associated with increased risk of generalization. CONCLUSION: The risk of generalization increased significantly in patients with adult-onset OMG, abnormal RNS findings, seropositivity for AChR-Ab, and thymoma, suggesting that these risk factors may predict OMG generalization.

Thymectomy and Risk of Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study.

This study aims to investigate the association between thymectomy and the risk of generalization in patients with ocular myasthenia gravis (MG). Data on patients with ocular MG from seven neurological centers in China were retrospectively reviewed. Ocular MG naïve to immunotherapy was categorized according to whether thymectomy was performed (thymectomized group vs. nonsurgical group). Patients in the thymectomized group all underwent surgery within 2 years since ocular symptom onset. The main outcome measure was the generalization. The follow-up period was defined from the date of ocular symptom onset to the date of generalization confirmation, immunotherapy initiation, or last follow-up (defined as 60 months). Of 519 eligible patients (mean [SD] age, 48.7 [15.2] years, 46.6% women), 31 (23.7%) of 131 generalized in the thymectomized group and 122 (31.4%) of 388 did in the nonsurgical group during a median follow-up of 19 months (IQR 8.0-50.0). Thymectomy was independently associated with reduced generalization risk (adjusted HR 0.41, 95% CI 0.25-0.66, P < 0.001). Multivariable stratified analysis also verified this association across the subgroups. Kaplan-Meier curves showed that the 5-year cumulative rate was significantly lower in the thymectomized group than in the nonsurgical group. To conclude, thymectomy may be considered effective in modifying the progression from ocular to generalized MG irrespective of thymoma.

COVID-19 Vaccination in Patients with Myasthenia Gravis: A Single-Center Case Series.

In this study, we report the safety of coronavirus disease 2019 (COVID-19) vaccine in patients with myasthenia gravis (MG). Patients who were vaccinated against COVID-19 were included. Demographics, clinical characteristics, medications, and vaccination information were collected. The main observation outcome is the worsening of MG symptoms within 4 weeks following COVID-19 vaccination. A total of 22 patients with MG vaccinated for COVID-19 were included. Ten (45.5%) patients had ocular MG (OMG), and 12 (55.5%) patients had generalized MG (GMG). Six (27.3%) patients were female, and the mean (SD) onset age was 45.4 (11.8) years. Nineteen (86.4%) patients were seropositive for acetylcholine receptors (AChR) antibody. Seven (31.8%) patients underwent thymectomy, and four of them confirmed thymoma pathologically. Twenty-one patients were administrated with inactivated vaccines, and the remaining one was administrated with recombinant subunit vaccine. Twenty (90.9%) patients did not present MG symptom worsening within 4 weeks of COVID-19 vaccination, and two (9.1%) patients reported slight symptom worsening but resolved quickly within a few days. Our findings suggest inactivated COVID-19 vaccines might be safe in MG patients with Myasthenia Gravis Foundation of America (MGFA) classification I to II, supporting the recommendation to promote vaccination for MG patients during the still expanding COVID-19 pandemic.

Association between long non-coding RNA (lncRNA) GAS5 polymorphism rs145204276 and cancer risk.

OBJECTIVE: The long non-coding RNA (lncRNA) growth arrest­specific transcript 5 (GAS5) plays an important role in various tumors, and an increasing number of studies have explored the association of the GAS5 rs145204276 polymorphism with cancer risk with inconclusive results. METHODS: PubMed, Medline, EMBASE, Cochrane databases, and Web of Science were searched, and nine studies involving 6107 cases and 7909 controls were deemed eligible. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the relationship between rs145204276 and cancer risk in six genetic models. RESULTS: The pooled results suggest that the variant allele del was not associated with overall cancer risk. However, the subgroup analysis showed that allele del was significantly associated with a 22% decreased risk of gastrointestinal cancer (OR = 0.78, 95% CI: 0.72-0.85). Both sensitivity analyses and trial sequential analyses (TSA) demonstrated that the subgroup results were reliable and robust. Moreover, False-Positive Report Probability (FPRP) analysis indicated that the results had true significant correlations. CONCLUSION: These findings provide evidence that the GAS5 rs145204276 polymorphism is associated with the susceptibility to gastrointestinal cancer. Further studies with different ethnicities and larger sample sizes are warranted to confirm these results.

Nomogram for short-term outcome assessment in AChR subtype generalized myasthenia gravis.

BACKGROUND: An accurate prediction for prognosis can help in guiding the therapeutic options and optimizing the trial design for generalized myasthenia gravis (gMG). We aimed to develop and validate a predictive nomogram to assess the short-term outcome in patients with the anti-acetylcholine receptor (AChR) subtype gMG. METHODS: We retrospectively reviewed 165 patients with AChR subtype gMG who were immunotherapy naïve at the first visit from five tertiary centers in China. The short-term clinical outcome is defined as the achievement of minimal symptom expression (MSE) at 12 months. Of them, 120 gMG patients from Huashan Hospital were enrolled to form a derivation cohort (n = 96) and a temporal validation cohort (n = 24) for the nomogram. Then, this nomogram was externally validated using 45 immunotherapy naïve AChR subtype gMG from the other four hospitals. Multivariate logistic regression was used to screen independent factors and construct the nomogram. RESULTS: MSE was achieved in 70 (72.9%), 20 (83.3%), and 33 (73.3%) patients in the training, temporal validation, and external validation cohort, respectively. The duration ≤ 12 months (p = 0.021), ocular score ≤ 2 (p = 0.006), QMG score > 13 (p = 0.008), and gross motor score ≤ 9 (p = 0.006) were statistically associated with MSE in AChR subtype gMG. The nomogram has good performance in predicting MSE as the concordance indexes are 0.81 (95% CI, 0.72-0.90) in the development cohort, 0.944 (95% CI, 0.83-1.00) in the temporal validation cohort, and 0.773 (95% CI, 0.63-0.92) in the external validation cohort. CONCLUSION: The nomogram achieved an optimal prediction of MSE in AChR subtype gMG patients using the baseline clinical characters.