Single institution experience with efgartigimod in patients with myasthenia gravis: Patient selection, dosing schedules, treatment response, and adverse events.

INTRODUCTION/AIMS: Efgartigimod is a neonatal Fc receptor blocker and was the first approved medication in its class for the treatment of generalized myasthenia gravis (gMG). As a novel therapy, little is known about the use of efgartigimod in clinical practice. This study aims to describe how efgartigimod is being incorporated into the current therapeutic landscape of MG. METHODS: We reviewed the charts of 17 patients with gMG treated with efgartigimod at the University of Pennsylvania between January 2022 and June 2023. RESULTS: Efgartigimod was selected mainly for patients who were treatment refractory, had side effects to other treatments, and/or required quick improvement in their symptoms. All patients had been previously treated with at least one medication for MG and had an average baseline Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 9.1. The patients treated with efgartigimod improved their MG-ADL score by an average of 5.5 points at 3 months (p < .001) and 7.1 points by 6 months (p < .001). Forty percent of patients achieved minimal symptom expression. Adverse events (AEs) were reported in 43.7% of patients on efgartigimod, the most common being mild infection (urinary tract infection and thrush). There were no serious AEs. DISCUSSION: This study found efgartigimod to be efficacious, well tolerated, and safe in patients with MG. Efgartigimod should be considered as an add-on therapy, a bridge therapy, or as a monotherapy if patients have difficulty tolerating other treatments.

Short-term changes in serum miRNA levels and patient-reported clinical outcomes in myasthenia gravis.

INTRODUCTION/AIMS: The circulating microRNAs (miRNAs) miR-150-5p, miR-30e-5p, and miR-21-5p have been suggested as potential biomarkers for myasthenia gravis (MG); however, the relationships between short-term natural changes of the miRNAs and patient-reported MG outcome scores have not been well-studied. We assessed the short-term fluctuations in miRNA levels and patient-reported outcome measures in MG. METHODS: This prospective cohort study included 39 MG patients with regular follow-ups and unchanged medications at the Neurology outpatient clinic at Uppsala University Hospital. Patients had weekly follow-up visits for 1 month, at which blood samples were drawn, and scores from MG activities of daily living (MG-ADL), MG quality-of-life-15 (MG-QoL15), and Fatigue Severity Scale (FSS) were assessed. Serum levels of miRNA miR-150-5p, miR-30e-5p, and miR-21-5p were analyzed using quantitative real-time PCR. RESULTS: Intra-individual levels of miR-30e-5p and miR-150-5p were stable, whereas a significant reduction in miR-21-5p was observed from week 1 to week 2 (p = .0024) and from week 2 to week 3 (p < .0001). There were intra-individual differences over a short time in MG-ADL, with higher scores in female patients (p = .0281) and a significant reduction from the first to the second weeks (p = .0281), whereas MG-QoL15 and FSS scores were stable. DISCUSSION: The suggested MG biomarkers miR-30e-5p and miR-150-5p were more stable than miR-21-5p over a short time, indicating their short-term stability as biomarkers. Prospective multi-center studies with longer periods of follow-up and matched controls are needed to validate these miRNAs as biomarkers in MG.

Associations of body mass index, waist circumference and the weight-adjusted waist index with daily living ability impairment in older Chinese people: A cross-sectional study of the Chinese Longitudinal Healthy Longevity Survey.

AIM: To investigate the associations of body mass index (BMI), waist circumference (WC) and the weight-adjusted waist index (WWI) with the impairment of activities of daily living (ADL) in older Chinese people. METHODS: A total of 13 260 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey were included in this cross-sectional study. BMI, WC and the WWI were calculated from measurements of height, weight and WC. Binary logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Non-linear correlations were investigated using restricted cubic spline curves. RESULTS: In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between WC and WWI and ADL impairment, with adjusted ORs (95% CI) of 1.01 (1.00, 1.01) and 1.08 (1.03, 1.12), respectively. Meanwhile, participants with a high WWI had a higher risk of ADL impairment compared with those with a low WWI, with an adjusted OR (95% CI) of 1.12 (1.02, 1.23). Subgroup analyses showed that only the association between WWI and ADL impairment did not differ in any of the different populations. In addition, we found that BMI, WC and WWI were non-linearly associated with ADL impairment. CONCLUSIONS: There are significant associations between WC and WWI and ADL impairment in older Chinese people. The findings show the ability of the WWI to serve as a comprehensive and effective indicator of obesity in older Chinese people and emphasize the importance of assessing WWI in screening and preventing ADL impairment in older people.

Expert consensus recommendations for improving and standardising the assessment of patients with generalised myasthenia gravis.

BACKGROUND: Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) and improve patient care; however, the use of assessment tools in practice lacks standardisation. This modified Delphi approach was taken to review current evidence on assessment tool use in gMG and develop expert-derived consensus recommendations for good practice. METHODS: A European expert panel of 15 experienced gMG neurologists contributed to development of this consensus, four of whom formed a lead Sub-committee. The PICO (Population, Intervention, Control, Outcomes) framework was used to define six clinical questions on gMG assessment tools, a systematic literature review was conducted, and evidence-based statements were developed. According to a modified Delphi voting process, consensus was reached when ≥70% of the experts rated agreement with a statement as ≥8 on a scale of 1-10. RESULTS: Eighteen expert- and evidence-based consensus statements based on six themes were developed. Key recommendations include: consistent use of the Myasthenia Gravis Activities of Daily Living score (MG-ADL) across clinical settings, followed by a simple question (e.g., Patient Acceptable Symptom State [PASS]) or scale to determine patient satisfaction in clinical practice; use of a Quantitative Myasthenia Gravis [QMG] or quality of life [QoL] assessment when the MG-ADL indicates disease worsening; and consideration of symptom state to determine the timing and frequency of recommended assessments. Expert panel consensus was reached on all 18 statements after two voting rounds. CONCLUSIONS: This process provided evidence- and expert consensus-based recommendations for the use of objective and subjective assessment tools across gMG research and care to improve management and outcomes for patients.

Housework participation and mortality in Japanese male patients undergoing cancer surgery: A propensity score-matched study.

BACKGROUND: Participation in housework and meal preparation are instrumental activity of daily living (IADL) evaluation items that is known to predict prognosis and complications in cancer care. However, these items are often assessed only for females, not for males, in IADL. METHODS: We examined the impact of habit of housework and meal preparation on overall survival (OS) in 1025 Japanese male patients who underwent elective urologic cancer surgery at our institution. The study also used a cohort that was matched by propensity score. RESULTS: We found that patients who did not prepare meals or do housework had significantly shorter OS (hazard ratio [HR] = 3.34, P = 0.005; HR = 5.01, P < 0.001, respectively). Even in the cohort of 448 patients matched by propensity score and adjusted for age, body mass index, comorbidities, performance status, living status, cancer type, stage groups of cancer, and surgical approach, lack of participation in housework was associated with shorter OS (HR = 2.92, P = 0.04) and was an independent predictor of worse OS in multivariable analysis (HR = 5.13, P = 0.008). CONCLUSIONS: Males who did not regularly do household chores before elective cancer surgery had worse life outcomes. Doing more daily physical activities, such as household chores like making the bed and cleaning the room, might have a positive impact on survival when fighting cancer.

Dynamic changes and lifetime effect of functional disability profiles for stroke patients: real-world evidence from South Korea.

PURPOSE: This work aimed to investigate the long-term dynamic changes of functional disabilities and estimate lifetime outcomes of different functional disabilities after a stroke, using real-world data from a nationally representative South Korean cohort. METHODS: Patients aged 18 and above with ischemic and hemorrhagic strokes were identified from the Korea Health Panel (KHP) data (2008-2018). Functional disabilities were repeatedly measured for patients aged 55 and over for the prevalence of disabilities associated with activities of daily living (ADL), and kernel smoothing means were estimated for each item. The lifetime survival function of stroke patients in Korea was adopted from another study utilizing the National Health Insurance Service of Korea's national sample cohort. By multiplying the disability-free proportion with the survival function throughout life, disability-free life expectancy (DFLE) for each ADL item was estimated. The loss-of-DFLE was calculated by subtracting the DFLE from age-, sex-, and calendar year-matched referents simulated from Korean life tables. RESULTS: The KHP dataset included 466 stroke patients. The overall functional disability needs increased over time after stroke diagnosis. DFLE was lowest for bathing (10.1 years for ischemic stroke and 12.8 years for hemorrhagic stroke), followed by those for dressing and washing. Loss-of-DFLE was highest for bathing for ischemic and hemorrhagic strokes (7.2 and 10.7 years, respectively), indicating that this task required the most assistance for stroke patients compared with the other tasks. DFLEs were slightly lower than the quality-adjusted life expectancy of stroke patients. CONCLUSION: Our findings provide valuable insights for resource allocation and policy decisions in long-term stroke care, potentially enhancing the quality of life for stroke survivors and caregivers.

Association between depressive symptoms and sarcopenia among middle-aged and elderly individuals in China: the mediation effect of activities of daily living (ADL) disability.

BACKGROUND: Depressive symptoms and sarcopenia, often observed among middle-aged and elderly individuals, are significant health concerns in China, particularly given the country's rapidly aging population. Depressive symptoms, characterized by persistent feelings of sadness and loss of interest, can significantly impact quality of life. Little is known about the underlying pathway connecting these two conditions. METHODS: The data for this study were derived from the China Health and Retirement Longitudinal Study (CHARLS). Depressive symptoms were evaluated using the Centre for Epidemiological Studies Depression (CSED) scale. Logistic regression analyses were employed to investigate the association between depressive symptoms, activities of daily living (ADL) disability, and sarcopenia, while adjusting for potential confounding factors. The selection of predictor variables, including social activity, chronic diseases, demographic factors, and lifestyle habits, was based on their known associations with mental health, physical functioning and sarcopenia. These variables were included to ensure a comprehensive adjustment for potential confounding factors and to provide a more accurate estimation of the relationship between depressive symptoms and sarcopenia. Additionally, mediation analysis was conducted to assess the mediating role of ADL disability in the relationship between depressive symptoms and sarcopenia. RESULTS: A comprehensive study was conducted on a total of 8,238 participants aged 45 years and older, comprising 3,358 men and 4,880 women. Logistic regression analyses were conducted to identify significant associations between depressive symptoms (OR = 1.30, P = 0.0269,95%CI = 1.03-1.63), ADL disability (OR = 1.94, P < 0.001,95%CI = 1.37-2.75) and sarcopenia. The results revealed significant relationships among these variables. Furthermore, mediation effect analyses demonstrated that ADL disability partially mediated the association between depressive symptoms and sarcopenia (estimated indirect effect: 0.006, 95% CI: 0.003, 0.008, proportion of mediation effect: 20.00%). CONCLUSIONS: The study underscores a significant association between depressive symptoms and sarcopenia among middle-aged and elderly individuals in China, with ADL disability acting as a mediator. These findings offer novel insights for targeted health interventions. Future interventions should effectively combat sarcopenia by integrating psychological support with muscle-strengthening exercise programs. By addressing both depressive symptoms and ADL disability, clinicians and public health professionals can enhance outcomes for this demographic. Collaborative efforts across disciplines are essential for providing comprehensive health management tailored to the needs of middle-aged and elderly individuals. Future research should longitudinally assess the impact of such integrated interventions on sarcopenia prevention and depressive symptom alleviation. Additionally, investigating the role of social and environmental factors in mediating this relationship is crucial for developing more effective health strategies for this vulnerable population.

Responses of Wheat (Triticum aestivum) Constitutively Expressing Four Different Monolignol Biosynthetic Genes to Fusarium Head Blight Caused by Fusarium graminearum.

The Fusarium head blight (FHB) pathogen Fusarium graminearum produces the trichothecene mycotoxin deoxynivalenol and reduces wheat yield and grain quality. Spring wheat (Triticum aestivum) genotype CB037 was transformed with constitutive expression (CE) constructs containing sorghum (Sorghum bicolor) genes encoding monolignol biosynthetic enzymes caffeoyl coenzyme A (CoA) 3-O-methyltransferase (SbCCoAOMT), 4-coumarate-CoA ligase (Sb4CL), or coumaroyl shikimate 3-hydroxylase (SbC3'H) or monolignol pathway transcriptional activator SbMyb60. Spring wheats were screened for type I (resistance to initial infection, using spray inoculations) and type II (resistance to spread within the spike, using single-floret inoculations) resistances in the field (spray) and greenhouse (spray and single floret). Following field inoculations, disease index, percentage of Fusarium-damaged kernels (FDK), and deoxynivalenol measurements of CE plants were similar to or greater than those of CB037. For greenhouse inoculations, the area under the disease progress curve (AUDPC) and FDK were determined. Following screens, focus was placed on two each of SbC3'H and SbCCoAOMT CE lines because of trends toward a decreased AUDPC and FDK observed following single-floret inoculations. These four lines were as susceptible as CB037 following spray inoculations. However, single-floret inoculations showed that these CE lines had a significantly reduced AUDPC (P < 0.01) and FDK (P ≤ 0.02) compared with CB037, indicating improved type II resistance. None of these CE lines had increased acid detergent lignin compared with CB037, indicating that lignin concentration may not be a major factor in FHB resistance. The SbC3'H and SbCCoAOMT CE lines are valuable for investigating phenylpropanoid-based resistance to FHB.

Screening for frailty and its association with activities of daily living, cognitive impairment, and falls among community-dwelling older adults in China.

OBJECTIVES: Frailty is a prevalent geriatric condition that significantly impacts the health of older adults. This study aimed to examine the prevalence of frailty among older Chinese adults aged ≥ 65 years and to assess its association with adverse geriatric outcomes. METHOD: This study included 20,724 older adults aged ≥ 65 years in Jiangsu Province, China, utilizing a random, stratified, multistage cluster sampling approach. Frailty was assessed using the 5-item FRAIL scale. Geriatric outcomes, such as independence in activities of daily living (ADL), cognitive impairment, and frequent fall events (occurring four or more times in the preceding year), were evaluated. Logistic regression models were employed to evaluate the association between frailty and geriatric outcomes, with results presented as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The mean age of the participants was 73.4 ± 6.4 years. The standardized prevalence of prefrailty and frailty was 35.2% and 10.3%, respectively. Individuals identified as prefrail or frail tended to live in rural areas, have lower educational levels, be widowed, have lower incomes, and engage in less physical activity. Prefrailty and frailty were associated with an increased risk of limitations in BADL (OR: 9.62, 95% CI: 7.43-12.46; and OR: 29.25, 95% CI: 22.42-38.17, respectively) and IADL (OR: 2.54, 95% CI 2.35-2.74; and OR: 5.19, 95% CI 4.66-5.78, respectively), positive cognitive impairment screening (OR: 1.23, 95% CI: 1.16-1.31; and OR: 1.72, 95% CI: 1.56-1.91, respectively), and frequent falls (occurring four or more times in the preceding year) (OR: 3.38, 95% CI: 2.50-4.56; and OR: 8.37, 95% CI: 6.01-11.65). The association between frailty and both limitations in BADL and falls was notably more pronounced among the younger age groups (p for interaction < 0.001). CONCLUSIONS: According to the 5-item FRAIL scale, frailty was associated with limitations in BADLs and IADLs, positive cognitive impairment screening, and recent falls among older adults living in the community. Screening for frailty in younger age groups has the potential to prevent declines in physical function and falls.

What factors preventing the older adults in China from living longer: a machine learning study.

BACKGROUND: The fact that most older people do not live long means that they do not have more time to pursue self-actualization and contribute value to society. Although there are many studies on the longevity of the elderly, the limitations of traditional statistics lack the good ability to study together the important influencing factors and build a simple and effective prediction model. METHODS: Based on the the data of Chinese Longitudinal Healthy Longevity Survey (CLHLS), 2008-2018 cohort and 2014-2018 cohort were selected and 16 features were filtered and integrated. Five machine learning algorithms, Elastic-Net Regression (ENR), Decision Tree (DT), Random Forest (RF), K-Nearest Neighbor (KNN), and eXtreme Gradient Boosting (XGBoost), were used to develop models and assessed by internal validation with CLHLS 2008-2018 cohort and temporal validation with CLHLS 2014-2018 cohort. Besides, the best performing model was explained and according to the variable importance results, simpler models would be developed. RESULTS: The results showed that the model developed by XGBoost algorithm had the best performance with AUC of 0.788 in internal validation and 0.806 in temporal validation. Instrumental activity of daily living (IADL), leisure activity, marital status, sex, activity of daily living (ADL), cognitive function, overall plant-based diet index (PDI) and psychological resilience, 8 features were more important in the model. Finally, with these 8 features simpler models were developed, it was found that the model performance did not decrease in both internal and temporal validation. CONCLUSIONS: The study indicated that the importance of these 8 factors for predicting the death of elderly people in China and built a simple machine learning model with good predictive performance. It can inspire future key research directions to promote longevity of the elderly, as well as in practical life to make the elderly healthy longevity, or timely end-of-life care for the elderly, and can use predictive model to aid decision-making.