Myasthenia gravis (MG) is an autoimmune disorder that disrupts neuromuscular junction function through autoantibodies. Platelets are emerging as key players in the pathogenesis of MG, bridging innate and adaptive immunity. We analyze platelet transcriptome signatures and their interactions with the immune system in AChR+ immunotherapy-naive MG (nMG) patients using bulk and single-cell RNA sequencing on peripheral blood mononuclear cells (PBMC). nMG patients exhibit upregulation of genes related to activation, inflammation, and cytoskeletal regulation. Increased platelet count, activation, altered morphology, enhanced CD62P expression, and elevated plasma CD40L levels are observed in PBMCs, which diminish with minimal clinical status (MMS). Functionally, platelets show heightened interactions with leukocytes, forming aggregates that correlate with disease severity. These features return to baseline after intravenous immunoglobulin or prolonged immunosuppressive therapy. This study underscores platelet activation's critical role in MG and supports platelet-targeted therapy. © 2025. The Author(s).

BACKGROUND AND PURPOSE: Efgartigimod has demonstrated efficacy in generalized myasthenia gravis (gMG) in both clinical trials and real-world studies. However, factors influencing early response have been less reported. This study aimed to evaluate the efficacy of efgartigimod in a multicenter gMG cohort and to identify the clinical factors associated with early therapeutic response.; METHODS: This multicenter, real-world, retrospective, observational study included 115 gMG patients administered efgartigimod across four myasthenia gravis (MG) centers. Responders were defined as patients with a≥2-point Myasthenia Gravis Activities of Daily Living (MG-ADL) or≥3-point Quantitative Myasthenia Gravis Score (QMG) score reduction, while early responders were those achieving score reductions after the first infusion. Subgroup analyses were conducted based on immunosuppressant (IST) use. Logistic regression analysis was performed to identify factors associated with response to first efgartigimod infusion according to MG-ADL or QMG scores reduction. Variables were compared between responders and non-responders to identify early response factors.; RESULTS: After the first infusion, 72.5% of patients achieved improvement in MG-ADL and 60.5% in QMG, with these rates increasing to 93.3% and 87.5% respectively by the fourth infusion. Efgartigimod demonstrated the most significant improvement in bulbar, limb, and ocular symptoms; however, there was no statistically significant improvement in respiratory symptoms occurred during the initial 4-week treatment period. Multivariate logistic analysis showed that short disease duration and high MG-ADL bulbar score at baseline indicated early response. High QMG bulbar score at baseline also indicated early response. Efficacy was independent of IST use. No patients discontinued treatment due to severe adverse events; minor side effects were not recorded.; CONCLUSIONS: Efgartigimod demonstrated robust efficacy in gMG patients. Early response was linked to shorter disease duration and severe bulbar symptoms, which promotes the identification of patients who are likely to benefit quickly from efgartigimod. © 2025. The Author(s).

Background: Myasthenia gravis (MG) is an autoimmune neuromuscular disease marked by dysregulation of several immune cell populations. Here we explored peripheral immune landscape, particularly the role of low- density granulocytes (LDGs). Methods: Single-cell and bulk RNA sequencing analyzed peripheral immune cells from MG patients pre- (n = 4) and after treatment (n = 2), as well as healthy controls (n = 3). Flow cytometry was employed for validating LDG subsets, and various functional assays were conducted to assess their impact on T cell proliferation and differentiation, NET formation, and ROS production. Results: Single-cell analysis highlighted a shift towards inflammatory Th1/Th17/Tfh subsets, an intense interferon-mediated immune response, and an expansion of immature myeloid subsets in MG. Flow cytometry showed increased LDGs correlated with disease severity. Unlike myeloid-derived suppressor cells, MG LDGs do not restrict T cell proliferation but induce a pro-inflammatory Th1/Th17 response. They also display enhanced spontaneous neutrophil extracellular traps (NETs) formation and basal reactive oxygen species (ROS) production. LDGs decreased after intravenous immunoglobulin and increased after prolonged immunotherapy in minimal manifestation status (MM), with reduced pro-inflammatory activity. Bulk RNA sequencing revealed significant transcriptional differences in LDGs, especially in cell cycle and granule protein genes. Conclusion: Peripheral immune profiling sheds light on the intricate role of LDGs in MG. These cells, as a distinct subtype of neutrophils with a proinflammatory phenotype, are notable increased in MG, exacerbating chronic inflammation. Furthermore, immunotherapy expanded LDGs but reduced their proinflammatory capacities. The complex interplay of LDGs in MG underscores their potential as biomarkers and therapeutic targets.

INTRODUCTION: Cognitive decline has become a growing public concern, yet large-scale exposure data identifying the contributing factors remain limited.; METHODS: We conducted an exposure-wide association study involving 1142 participants and 207 exposures, using machine learning to assess the relative contribution and joint effects of key factors. Cluster analysis and intervention simulation trials helped identify high-risk subpopulations and the potential benefits of targeted interventions.; RESULTS: In adjusted mixed models, the socioeconomic status domain emerged as the strongest predictor of longitudinal global cognitive score (beta=2.91, p<0.0001, q < 0.0001), while the dietary domain also played an important role in memory function. The cluster analysis found that the "unfavorable lifestyle" dominated phenotype was associated with the poorest cognitive outcomes. Simulation trials indicated that cognitive scores could improve by shifting individuals from unfavorable to favorable phenotypes.; DISCUSSION: Cognitive health requires multidomain interventions, particularly in the socioeconomic and dietary fields, and necessitates collaboration between government and individuals.; HIGHLIGHTS: The exposure-wide association study design, which assesses a broad range of exposures, is used to identify novel variables and understand their contributions to cognitive function. The findings from the multidomain analysis indicate that socioeconomic status is the most significant contributor to global cognitive function, while diet plays the largest role in memory function. Increasing the proportion of favorable phenotypes through multidomain interventions can significantly enhance public cognitive health. © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

BACKGROUND/OBJECTIVES: Sex differences in nutrition-related determinants of mild cognitive impairment (MCI) exist among the elderly. This study aimed to explore sex-specific influencing factors of MCI.; METHODS: A case-control study was conducted in 2020 involving 1086 elderly people aged 55 years and above from four sites in Zhejiang Province, China. Data on demographics, cognitive assessment, depression scale, daily food intake, and physical examinations were collected. The assessment of plant-based diet patterns depended on an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). Multivariate logistic regression models were employed to assess the determinants of MCI in females and males.; RESULTS: Among 571 females, 141 (24.7%) had MCI, and 126 (24.5%) had MCI among 514 male participants. In females, the multivariate analysis revealed that being unmarried/divorced/widowed (OR = 1.95, 95% CI: 1.10-3.45), having depression (OR = 6.06, 95% CI: 1.87-19.66), and having a uPDI score ≥ 55 (OR = 2.41, 95% CI: 1.50-3.89) were associated with a significantly elevated risk of MCI. Conversely, a cereal consumption of ≥300 g/d (OR = 0.32, 95% CI: 0.19-0.53) was linked to a significantly reduced risk. In males, vegetable consumption ≥ 150 g/d (OR = 0.39, 95% CI: 0.23-0.66), vegetable oil consumption ≥ 22 g/d (OR = 0.502, 95% CI: 0.307-0.820), and cereal consumption ≥ 300 g/d (OR = 0.44, 95% CI: 0.27-0.71) were associated with a lower MCI risk. Meanwhile, rural residence (OR = 1.90, 95% CI: 1.12-3.25) and advanced age, especially 75 years old and above (OR = 4.71, 95% CI: 2.44-9.12), were also risk factors in males. Notably, the Restricted Cubic Spline (RCS) model showed that females with a uPDI score < 55 had a lower prevalence of MCI, while those with a score ≥ 55 faced a higher risk.; CONCLUSIONS: This study indicates potential sex disparities in the risk factors for MCI. Future research should prospectively establish causal relationships. Additionally, precise intervention strategies are urgently needed.

Background/Objectives: Precise prevention strategies for mild cognitive impairment (MCI) are an urgent public health priority. This study aimed to investigate the association of the Composite Dietary Antioxidant Index and alcohol consumption, as well as their interaction, with the risk of MCI. Methods: A multicenter cross-sectional study was conducted in 2020, involving 1084 individuals aged ≥55 years, in Zhejiang Province, China. Data were collected on demographics, cognitive function, alcohol consumption, depression scale, dietary intake and physical examinations. The Composite Dietary Antioxidant Index (CDAI) was calculated based on the converted Food Frequency Questionnaire (FFQ) Food Composition Tables and the data of the FFQ. CDAI values were divided into four groups by interquartile ranges: Quartile-1 (Q1), Quartile-2 (Q2), Quartile-3 (Q3) and Quartile-4 (Q4). Multivariate logistic regression models were used to evaluate the association of CDAI and alcohol consumption with MCI risk and their interaction. Results: The prevalence of MCI was 24.6%. After adjusting for gender, age, educational level, job, marriage, Body Mass Index (BMI), central obesity, frequency of social activities, depression, sleep disturbances, smoking, diabetes, and energy intake, the Q2 (OR = 0.63, 95% CI: 0.42~0.95), Q3 (OR = 0.52, 95% CI: 0.34~0.81) and Q4 (OR = 0.25, 95% CI: 0.14~0.48) of CDAI were significantly associated a reduced risk of MCI. In contrast, alcohol consumption 1~2 times per week (OR = 2.38, 95% CI: 1.02~5.59) and at least 3 times a month (OR = 2.04, 95% CI: 1.19~3.50) was significantly associated with an increased risk of MCI. Interaction analysis indicated a negative additive interaction between alcohol consumption and CDAI on MCI risk, with the detrimental effects of alcohol predominating. Conclusions: A higher CDAI is associated with a reduced risk of MCI, while alcohol consumption is associated with an increased risk. There may be a negative additive interaction between CDAI and alcohol intake in relation to MCI. Targeted strategies that reduce alcohol consumption and improve dietary antioxidant intake are essential for MCI prevention.

Background/Objectives: The Jiangnan diet-a traditional dietary pattern prevalent in Eastern China-is a newly proposed dietary pattern. This study provides additional epidemiological evidence for the promotion of the Jiangnan diet through examining the association between the Jiangnan diet and mild cognitive impairment (MCI). Methods: A multicenter cross-sectional study was carried out during 2020 among 1084 community-dwelling adults aged 55 years and above across multiple sites in Zhejiang Province, China. Data collection encompassed basic information of the population, cognition (using the Montreal Cognitive Assessment), dietary intake information (using the Food Frequency Questionnaire, FFQ), life pattern, depressive symptoms (using the Mental Health Assessment Scale for the Elderly), and physical examinations (e.g., height, weight). The dietary patterns were assessed using a validated semi-quantitative FFQ. Factor analysis was used to analyze the 16 categories of food intake of the participants, and dietary patterns and the "Jiangnan diet" were extracted. The Jiangnan diet scores were categorized into quartiles: Q1 (lowest) to Q4 (highest). Multivariate logistic regression was employed to examine the association between adherence to the Jiangnan diet and the prevalence of MCI, with results expressed as odds ratios (OR) and 95% confidence intervals (CI). Results: The estimated prevalence of MCI in the study population was 24.6%. The dietary pattern characterized by whole grains, low salt, and low oil was identified as the "Jiangnan diet". Participants with the highest adherence to the "Jiangnan diet" pattern had 79.2% lower odds of MCI than those with the lowest adherence (odds ratio = 0.208, 95% CI = 0.120~0.362, p < 0.0001) after adjusting for age, frequency of social activities, depression, hypertension, alcohol consumption, and energy intake. Conclusions: High adherence to the Jiangnan diet was associated with lower odds of MCI. To further verify the relationship between the Jiangnan diet and MCI, future studies will focus on longitudinal research exploring different dietary patterns and disease outcomes across various regions.

OBJECTIVE: Limited evidence has led to ongoing debate about the benefits of thymectomy for late-onset myasthenia gravis (LOMG). This study aims to compare the outcomes of patients with LOMG who underwent thymectomy versus those who received medical treatment alone, and evaluate the incidence of surgical adverse events.; METHODS: Non-thymomatous acetylcholine-receptor antibody positive patients with LOMG were selected from a multi-center longitudinal clinical database. Rates of and time to response (remission and minimal manifestations status) were compared between 2 groups by propensity score matching (PSM), Kaplan-Meier analysis, and Cox regression models. Additionally, the incidence of adverse events about thymectomy was compared between LOMG and younger patients with myasthenia gravis (MG) aged 40 to 50years old.; RESULTS: A total of 55 and 210 patients with LOMG were enrolled in the thymectomy and medical treatment groups, respectively. The thymectomy group exhibited significantly younger onset age (56.31±6.15 vs. 62.04±7.83, p<0.001). After PSM adjustment, thymectomy demonstrated a greater cumulative probability (p<0.001), and the 2.356-fold (95% confidence interval [CI]=1.537-3.612, p<0.001) higher chance of better outcomes compared to medical treatment. In subgroup analysis, thymectomy showed significantly higher response rates compared to medical treatment alone at 24±2months (48.9%, 95% CI=33.7-64.1% vs 23.8%, 95% CI=14.2-33.3%, p=0.004), and 36±2months (59.5%, 95% CI=42.9-76.1% vs 28.9%, 95% CI=18.5-39.4%, p=0.002). The incidences of adverse events were comparable between patients with LOMG and younger patients with MG (32.0% vs 22.4%, p=0.286).; INTERPRETATION: Thymectomy may be an effective therapeutic option for LOMG. Our findings highlight the need for further development of a randomized trial targeting patients with LOMG. ANN NEUROL 2025. © 2025 American Neurological Association.

Background: Very-late-onset myasthenia gravis (VLOMG) refers to myasthenia gravis (MG) with onset at age 65 or older. Current research on VLOMG prognosis remains limited, especially regarding factors influencing outcomes. Objectives: To identify the clinical factors that affect the short- and long-term prognosis of MG patients with an onset age >= 65 years. Design: This was a single-center, retrospective cohort study of AChR-ab positive VLOMG patients, classified into two subgroups based on age of onset: sub-very-late-onset MG (S-VLOMG, onset age >= 65 and <75 years), and super-late-onset MG (SLOMG, onset age >= 75 years). Methods: A total of 93 patients were included, including 75 in the S-VLOMG group and 18 in the SLOMG group. Clinical, therapeutic, and prognosis data were reviewed, and the Cox regression model was used to identify factors influencing short- and long-term prognosis. Results: Patient characteristics were well balanced between the groups. Overall, 49.5% of patients achieved minimal symptom expression (MSE) within 6 months and 86% within 24 months. There was no significant difference between the groups in the proportion achieving MSE at 6 months (p = 0.635) or 24 months (p = 0.714). The median time to achieve MSE was also comparable between the S-VLOMG and SLOMG groups (199.0 days vs 280.5 days, p = 0.463). Low baseline MG-ADL score and steroid therapy were associated with better short-term prognosis (p = 0.007 and p = 0.002, respectively). For long-term prognosis, baseline bulbar and limb involvement, time to treatment initiation, and use of immunosuppressants were significant factors (p = 0.025, p = 0.004, p = 0.025, and p < 0.0001, respectively). There were no significant differences in side effects or drug withdrawal rates between two groups. Conclusion: This study demonstrated that AChR-ab positive VLOMG patients have a favorable prognosis and responded well to medication, with age and comorbidities showing no significant impact.

Platelets and neutrophils are among the most abundant cell types in peripheral blood. Beyond their traditional roles in thrombosis and haemostasis, they also play an active role in modulating immune responses. Current knowledge on the role of platelet-neutrophil interactions in the immune system has been rapidly expanding. Notably, circulating platelet-neutrophil complexes (PNCs) have been widely detected in various inflammatory diseases and infections, closely associated with inflammatory processes affecting multiple organs. These findings emphasise the critical role of platelet-neutrophil interactions in driving and sustaining inflammatory responses. In this review, we elucidate the mechanisms by which neutrophils and platelets physically interact, leading to mutual activation. Additionally, activated platelets release pro-inflammatory factors that further modulate neutrophil effector functions, enhancing their immune response capabilities. We highlight the role of platelets in promoting the formation of neutrophil extracellular traps (NETs), which, in turn, promote local platelet activation, thereby exacerbating the immune response and sustaining chronic inflammation. Furthermore, we review current evidence on the role of platelet-neutrophil interactions in common autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA). Finally, we identify gaps in understanding the mechanisms of these interactions in the context of other autoimmune diseases and underscore the potential of targeting platelets and neutrophils as a therapeutic strategy for these conditions. © 2025 John Wiley & Sons Ltd.