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.

Serum Homer1 is a Novel Biomarker for Predicting the Clinical Outcomes of Acute Ischemic Stroke Patients.

Purpose: We aim to explore the relationship between Homer1 and the outcomes of AIS patients at 3 months. Patients and Methods: This prospective cohort study was conducted from May 2022 to March 2023. In this study, we investigated the association between serum Homer1 levels by enzyme-linked immunosorbent assay at admission and functional outcomes of patients at 3 months after AIS. Results: Overall, 89 AIS patients (48 good outcomes and 41 poor outcomes) and 83 healthy controls were included. The median serum Homer1 level of patients at admission with poor outcomes was significantly higher than that of patients with good outcomes (39.33 vs 33.15, P<0.001). Serum Homer1 levels at admission were positively correlated with the severity of AIS (r = 0.488, P<0.001). The optimal cutoff of serum Homer1 level as an indicator for an auxiliary diagnosis of 3 months functional outcomes was 35.07 pg/mL, with a sensitivity of 75.0% and a specificity of 92.7% (AUC 0.837; 95% CI [0.744-0.907]; P<0 0.001). The odds ratio of MRS > 2 predicted by the level of serum Homer1 after 3 months was 1.665 (1.306-2.122; P<0.001). Conclusion: Serum concentrations of Homer1 have a high predictive value for neurobehavioral outcomes after acute ischemic stroke. Higher serum Homer1 levels (>35.07 pg/mL) were positively associated with poor functional outcomes of patients 3 months post-stroke.

Safety of SARS-CoV-2 vaccine in patients with autoimmune neurological conditions: A systematic review and meta-analysis.

Introduction: Risk of adverse effects and exacerbation in autoimmune neurological conditions (ANC)are frequently cited reasons for COVID-19 vaccine hesitancy. This study evaluates the ANC safety of COVID-19 vaccines in the real world. Methods: Electronic databases were searched to identify studies reporting the use of the COVID-19 vaccine in ANC. We selected studies that provided data on adverse effects and worsening conditions related to ANC after vaccination. The pooled incidence rates for various adverse effects, stratified for the disease category, dosage, and type of vaccine, were estimated. Results: Twenty-eight studies (31 vaccination cohorts) were included. The pooled incidence rate of general adverse events was 0.35 (95%CI, 0.27-0.43, I2 = 100 %). The pooled incidence rates of local injection reaction, fatigue, weakness, myalgia, fever, headache, and chills were 0.27 (0.18-0.36, I2 = 98 %), 0.16(0.11-0.21, I2 = 93 %), 0.15(0.00-0.31, I2 = 97 %), 0.13(0.08-0.19, I2 = 97 %), 0.11(0.07-0.15, I2 = 95 %), 0.11(0.07-0.16, I2 = 97 %), and 0.09 (0.03-0.16, I2 = 96 %), respectively. The pooled incidence rate of exacerbation adverse events was 0.05 (95%CI, 0.04-0.07, I2 = 84 %). Conclusion: According to available evidence, the administration of COVID-19 vaccines in individuals with autoimmune neurological disorders seems well-tolerated, with few reports of adverse events. Furthermore, exacerbation of autoimmune neurological conditions following vaccination appears to be infrequent.

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.

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.

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.

Causal relationships between CD25 on immune cells and hip osteoarthritis.

Objectives: Previous research has indicated a potential association between immune factors and osteoarthritis (OA), but the causal relationship between CD25 expression on immune cells and hip OA remains enigmatic. To shed light on this relationship, this study utilized the two-sample Mendelian Randomization (MR) method. Methods: Leveraging genome-wide association studies (GWAS) data from the UK Biobank and arcOGEN, the investigation encompasses a substantial European cohort comprising 15,704 hip OA cases and 378,169 controls. Genetic insights into CD25 stem from a subgroup of 3,757 individuals with European ancestry, encompassing 77 CD25-related traits. Several MR methods were applied, and robustness was assessed through heterogeneity and sensitivity analysis. Results: Among the 77 traits examined, 66 shared the same single nucleotide polymorphisms (SNPs) with hip OA. Of these, 7 CD25-related traits were found to be causally associated with hip OA (adjusted P><0.05), with F-statistics ranging from 33 to 122. These traits are specifically related to CD4+CD25+ T cells, exhibiting odds ratios (OR) and 95% confidence intervals (CI) less than 1. Notably, no causal link was discerned with the CD8+CD25+ T cell subset. Within absolute count (AC) and relative count (RC) trait types, a significant causal relationship was observed solely between CD4+CD25+ T cells and hip OA, without subtype localization. A more intricate examination of CD25 expression levels within the CD4+CD25+ T cell subset revealed a correlation with the CD39+ regulatory T (Treg) subset and hip OA, particularly within the CD39+ activated Treg subset. Furthermore, a notable causal relationship emerged between CD25 expression levels in the CD45RA- not Treg subset and hip OA. However, no significant causal link was established with any subsets of B cells. Conclusion: The genetic prediction suggests that CD25, particularly within the realm of CD4+CD25+ T cells, may exert a protective influence against the development of hip OA. These findings provide a novel therapeutic approach for the prevention and treatment of hip OA.

Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression.

Due to increasing morbidity worldwide, fractures are becoming an emerging public health concern. This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures. Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis. Here, we show that metformin accelerated fracture healing in both osteoporotic and normal mice. Moreover, metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing. Mechanistically, metformin increased the expression of HIF-1α, an important positive regulator of type H vessel formation, by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells (HMECs). The results of HIF-1α or YAP1/TAZ interference in hypoxia-cultured HMECs using siRNA further suggested that the enhancement of HIF-1α and its target genes by metformin is primarily through YAP1/TAZ inhibition. Finally, overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair. In summary, our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.

Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study.

In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS) summary statistics of 1 325 brain imaging-derived phenotypes (BIDPs) of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations, including the total body, femoral neck, lumbar spine, forearm, and heel from the GEFOS Consortium, linkage disequilibrium score regression (LDSC) was conducted to determine the genetic correlations, and Mendelian randomization (MR) was then performed to explore the causal relationship between the BIDPs and BMD. Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes. To increase confidence in our findings, we also performed confirmatory MR between BIDPs and osteoporosis. LDSC revealed that 1.93% of BIDPs, with a false discovery rate (FDR) < 0.01, were genetically correlated with BMD. Additionally, we observed that 1.31% of BIDPs exhibited a significant causal relationship with BMD (FDR < 0.01) through MR. Both the LDSC and MR results demonstrated that the BIDPs "Volume of normalized brain," "Volume of gray matter in Left Inferior Frontal Gyrus, pars opercularis," "Volume of Estimated Total Intra Cranial" and "Volume-ratio of brain segmentation/estimated total intracranial" had strong associations with BMD. Interestingly, our results showed that more left BIDPs were causally associated with BMD, especially within and around the left frontal region. In conclusion, a part of the brain structure causally influences BMD, which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.

Emerging trends and research foci of neuromyelitis optica spectrum disorder: a 20-year bibliometric analysis.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating syndrome of the central nervous system. A tremendous amount of literature on NMOSD has been published. This study aimed to perform a bibliometric analysis of the publications on NMOSD and show its hotspots and development trends. Methods: We used the Web of Science Core Collection as a database and searched the literature published between 2002 and 2022. CiteSpace, VOSviewer, online bibliometric platform, and R-bibliometrix were used to conduct bibliometric analysis and network visualization, including the number of publications, citations, countries/regions, institutions, journals, authors, references, and keywords. Results: A total of 3,057 publications on NMOSD were published in 198 journals by 200 authors at 200 institutions from 93 countries/regions. The United States published the most literature and made great contributions to this field. The Mayo Clinic was the institution with the largest number of publications. The journal with the most publications was Multiple Sclerosis and Related Disorders, and the most co-cited journal was Neurology. The author with the most publications was Fujihara, K., while the most frequently co-cited author was Wingerchuk, DM. The current research hotspots may be focused on "efficacy," "multicenter," "interleukin-6 receptor blockade," "safety," "azathioprine," "tolerance," and "adult". Conclusion: This study was the first bibliometric analysis of publications on the NMOSD field, visualizing its bibliometric characteristics and gaining insight into the direction, hotspots, and development of global NMOSD research, which may provide helpful information for researchers. Future research hotspots might be conducting randomized controlled trials on targeted immunotherapy in the NMOSD field.

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.

Short-term outcome prediction for myasthenia gravis: an explainable machine learning model.

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigability. The fluctuating nature of the disease course impedes the clinical management. Objective: The purpose of the study was to establish and validate a machine learning (ML)-based model for predicting the short-term clinical outcome in MG patients with different antibody types. Methods: We studied 890 MG patients who had regular follow-ups at 11 tertiary centers in China from 1 January 2015 to 31 July 2021 (653 patients for derivation and 237 for validation). The short-term outcome was the modified post-intervention status (PIS) at a 6-month visit. A two-step variable screening was used to determine the factors for model construction and 14 ML algorithms were used for model optimisation. Results: The derivation cohort included 653 patients from Huashan hospital [age 44.24 (17.22) years, female 57.6%, generalized MG 73.5%], and the validation cohort included 237 patients from 10 independent centers [age 44.24 (17.22) years, female 55.0%, generalized MG 81.2%]. The ML model identified patients who were improved with an area under the receiver operating characteristic curve (AUC) of 0.91 [0.89-0.93], 'Unchanged' 0.89 [0.87-0.91], and 'Worse' 0.89 [0.85-0.92] in the derivation cohort, whereas identified patients who were improved with an AUC of 0.84 [0.79-0.89], 'Unchanged' 0.74 [0.67-0.82], and 'Worse' 0.79 [0.70-0.88] in the validation cohort. Both datasets presented a good calibration ability by fitting the expectation slopes. The model is finally explained by 25 simple predictors and transferred to a feasible web tool for an initial assessment. Conclusion: The explainable, ML-based predictive model can aid in forecasting the short-term outcome for MG with good accuracy in clinical practice.

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.

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.

Causal association of the brain structure with the susceptibility, hospitalization, and severity of COVID-19: A large-scale genetic correlation study.

Brain structure is related to its ability to resist external pathogens. Furthermore, there are several abnormal anatomical brain events and central system symptoms associated with COVID-19. This study, which was conducted based on genetic variables, aimed to identify the causal association between brain structure and COVID-19 phenotypes. We performed a two-sample bidirectional Mendelian randomization analysis using genetic variables obtained from large genome-wide association studies as instruments to identify the potential causal effects of various brain imaging-derived phenotypes (BIDPs) traits on susceptibility, hospitalisation, and severity of COVID-19. We explored the genetic correlations of 1325 BIDPs with the susceptibility, hospitalisation, and severity of COVID-19 using Linkage Disequilibrium Score Regression. We observed a causal relationship between increased cortical thickness of the left inferior temporal area and an increased risk of increased COVID-19 infection (p = 4.29 × 10-4) and hospitalisation (p = 3.67 × 10-3). Moreover, the larger total surface area of the whole brain was negatively correlated with the risk of hospitalisation for COVID-19. Furthermore, there was a significant causal association between increased cerebrospinal fluid volume and decreased severity of COVID-19 (p = 3.74 × 10-3). In a conclusion, we provide new insights into the causal association between BIDPs and COVID-19 phenotypes, which may help elucidate the aetiology of COVID-19.

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.

High indirect bilirubin levels as an independent predictor of postoperative myasthenic crisis: a single-center, retrospective study.

Background: Thymectomy is an efficient and standard treatment strategy for patients with myasthenia gravis (MG), postoperative myasthenic crisis (POMC) is the major complication related to thymectomy and has a strongly life-threatening effect. As a biomarker, whether the bilirubin level is a risk factor for MG progression remains unclear. This study aimed to investigate the association between the preoperative bilirubin level and postoperative myasthenic crisis (POMC). Methods: We analyzed 375 patients with MG who underwent thymectomy at Tangdu Hospital between January 2012 and September 2021. The primary outcome measurement was POMC. The association between POMC and bilirubin level was analyzed by restricted cubic spline (RCS). Indirect bilirubin (IBIL) was divided into two subgroups based on the normal upper limit of IBIL, 14 µmol/L. Results: Compared with non-POMC group, IBIL levels were significantly higher in patients with POMC. Elevated IBIL levels were closely associated with an increased risk of POMC (p for trend = 0.002). There was a dose-response curve relationship between IBIL levels and POMC incidence (p for non-linearity = 0.93). However, DBIL levels showed a U-shaped association with POMC incidence. High IBIL level (≥14 µmol/L) was an independent predictive factor for POMC [odds ratio = 3.47, 95% confidence interval (CI): 1.56-7.8, p = 0.002]. The addition of high IBIL levels improved the prediction model performance (net reclassification index = 0.186, 95% CI: 0.039-0.334; integrated discrimination improvement = 0.0345, 95% CI: 0.005-0.065). Conclusion: High preoperative IBIL levels, especially those exceeding the normal upper limit, could independently predict the incidence of POMC.

Knowledge mapping of targeted immunotherapy for myasthenia gravis from 1998 to 2022: A bibliometric analysis.

Background: The treatment of myasthenia gravis (MG) has advanced from steroids and traditional immunosuppressants to targeted immunotherapy. Targeted immunotherapy has been successfully employed in clinical practice in recent years. This study aimed to explore the emerging trend of targeted immunotherapy in MG and summarize the knowledge structure through bibliometric methods. Methods: The Web of Science Core Collection database (WoSCC) was chosen to retrieve the literature on targeted immunotherapy for MG. Two bibliometric analysis software, VOSviewer and CiteSpace, and bibliometric online platform were mainly used to evaluate the contributions from countries/regions, institutions, journals, and authors through the construction and visualization of bibliometric networks. By systematically reviewing a knowledge domain, future research developments were determined. The R version 4.1.2 and Microsoft Excel 365 were used for statistical analysis. Results: A total of 562 original articles and 262 reviews relevant to MG targeted immunotherapy were included. The number of publications on targeted immunotherapy for MG exhibited a two-phase advancement. The first stage showed a steady growth trend from 1998 to 2016, with an annual number of no more than 35 publications. The second stage revealed an explosive growth trend from 2017, reaching a peak number of publications in 2020. The United States ranked first in the number of publications, citations, and h-index. The author with the highest citation and h-index was Vincent A. And 28.03% of the articles were published in the top 10 journals. In addition to "myasthenia gravis", the keyword with the highest consideration was "rituximab", followed by "double-blind", which indicate research hotspots gradually from basic research to clinical research over time, especially in the field of targeted immunotherapy. The MG treatment has entered a personalized precision treatment phase. Exploration into new target molecules and conducting high-quality randomized controlled trials on existing biological agents are the further research direction. Conclusion: The current study summarized the global research trends concerning targeted immunotherapy for MG. Research interests gradually advanced from basic research to clinical research. MG treatment has entered a personalized precision treatment phase. Further investigations into new target molecules and high-quality randomized controlled trials on existing biological agents are required urgently to direct future immunotherapy research.