Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue.

After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.

Exploring the nexus between fatigue, body composition, and muscle strength in hemodialysis patients.

BACKGROUND: Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. METHODS: This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. RESULTS: The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p < 0.001). Age (r = - 0.411, p < 0.001), IMAT % (r = - 0.424, p < 0.001), negatively associated with FACIT-F score. Multivariate logistic regression analysis shows that older age, lower serum phosphorus, higher IMAT% are associated with a high risk of fatigue. CONCLUSION: The significantly increased incidence and degree of fatigue in hemodialysis patients is associated with more intermuscular adipose tissue in paraspinal muscle.

Impact of specialized fatigue and backhand smash on the ankle biomechanics of female badminton players.

During fatigued conditions, badminton players may experience adverse effects on their ankle joints during smash landings. In addition, the risk of ankle injury may vary with different landing strategies. This study aimed to investigate the influence of sport-specific fatigue factors and two backhand smash actions on ankle biomechanical indices. Thirteen female badminton players (age: 21.2 ± 1.9 years; height: 167.1 ± 4.1 cm; weight: 57.3 ± 5.1 kg; BMI: 20.54 ± 1.57 kg/m2) participated in this study. An 8-camera Vicon motion capture system and three Kistler force platforms were used to collect kinematic and kinetic data before and after fatigue for backhand rear-court jump smash (BRJS) and backhand lateral jump smash (BLJS). A 2 × 2 repeated measures analysis of variance was employed to analyze the effects of these smash landing actions and fatigue factors on ankle biomechanical parameters. Fatigue significantly affected the ankle-joint plantarflexion and inversion angles at the initial contact (IC) phase (p < 0.05), with both angles increasing substantially post-fatigue. From a kinetic perspective, fatigue considerably influenced the peak plantarflexion and peak inversion moments at the ankle joint, which resulted in a decrease the former and an increase in the latter after fatigue. The two smash landing actions demonstrated different landing strategies, and significant main effects were observed on the ankle plantarflexion angle, inversion angle, peak dorsiflexion/plantarflexion moment, peak inversion/eversion moment, and peak internal rotation moment (p < 0.05). The BLJS landing had a much greater landing inversion angle, peak inversion moment, and peak internal rotation moment compared with BRJS landing. The interaction effects of fatigue and smash actions significantly affected the muscle force of the peroneus longus (PL), with a more pronounced decrease in the force of the PL muscle post-fatigue in the BLJS action(post-hoc < 0.05). This study demonstrated that fatigue and smash actions, specifically BRJS and BLJS, significantly affect ankle biomechanical parameters. After fatigue, both actions showed a notable increase in IC plantarflexion and inversion angles and peak inversion moments, which may elevate the risk of lateral ankle sprains. Compared with BRJS, BLJS poses a higher risk of lateral ankle sprains after fatigue.

Effects of Ninjin'yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial.

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.

A Multimodal Feature Fusion Brain Fatigue Recognition System Based on Bayes-gcForest.

Modern society increasingly recognizes brain fatigue as a critical factor affecting human health and productivity. This study introduces a novel, portable, cost-effective, and user-friendly system for real-time collection, monitoring, and analysis of physiological signals aimed at enhancing the precision and efficiency of brain fatigue recognition and broadening its application scope. Utilizing raw physiological data, this study constructed a compact dataset that incorporated EEG and ECG data from 20 subjects to index fatigue characteristics. By employing a Bayesian-optimized multi-granularity cascade forest (Bayes-gcForest) for fatigue state recognition, this study achieved recognition rates of 95.71% and 96.13% on the DROZY public dataset and constructed dataset, respectively. These results highlight the effectiveness of the multi-modal feature fusion model in brain fatigue recognition, providing a viable solution for cost-effective and efficient fatigue monitoring. Furthermore, this approach offers theoretical support for designing rest systems for researchers.

Thrombolysis treatment protected impairment of functional ability, quality of life and fatigue seven years after stroke.

OBJECTIVES: We studied quality of life, functional outcome, depression, and fatigue of ischemic stroke patients treated with or without thrombolysis seven years post-stroke. MATERIALS AND METHODS: A total of 204 ischemic stroke patients treated with or without thrombolysis during 2013-2015. After seven years the 136 survivors were assessed with telephone interview, which included questions about subjective quality of life (European Quality of Life-5 Dimensions), depression, fatigue with Fatigue Severity Scale, functional ability assessed with Barthel Index and Modified Rankin Scale, living conditions, need of care, and medical aids. RESULTS: At admission patients with thrombolysis had higher National Institutes of Health Stroke Scale scores compared with those not treated with thrombolysis. At seven years post-stroke, 99% of alive patients answered the questionnaires. There were no group differences concerning functional outcome, quality of life, depression, fatigue, or insomnia. The Barthel Index was normal in both groups. The quality of life was good in both groups without group differences in any domains. Of all patients, 68% reported no problems in usual activities, and 61% were without pain. Anxiety or depression were experienced by 19% of all stroke patients, while fatigue was present in 32% of cases. CONCLUSIONS: Seven years post-stroke the quality of life was good and functional outcome remained in good level in both study groups. One third experienced fatigue, while every fifth experienced depression. The thrombolysis treatment seems to protect from decreased quality of life, fatigue, and decreased mobility, self-care, and usual activities despite more severe stroke.

Clinical and neuroanatomical predictors of post-stroke fatigue.

INTRODUCTION: Post-stroke fatigue (PSF) has been described as early exhaustion with tiredness that develops during physical or mental activity and generally does not improve with rest. There are inconsistent findings on the relationship between the characteristics of the ischemic brain lesion and PSF. However, some studies suggest that specific neuroanatomical and neuroplastic changes could explain post-stroke fatigue. The aim was to evaluate the severity of PSF in relation to the location and the size of the ischemic lesion in acute stroke patients to establish possible predictors of PSF. PATIENTS AND METHODS: We performed a prospective observational study to establish potential early predictors of long-term PSF, which was assessed using the Fatigue Assessment Scale six months after ischemic stroke. After segmenting brain infarcts on Diffusion-Weighted Imaging (DWI) images, we studied the association with PSF using Voxel-Based Lesion-Symptom Mapping (VLSM). RESULTS: Out of 104 patients, 61 (59 %) reported PSF. Female sex and history of diabetes mellitus were associated with a greater risk of developing PSF. The association of PSF with female sex was confirmed in a replication cohort of 50 patients. The ischemic lesion volume was not associated with PSF, and VBLSM analysis did not identify any specific brain area significantly associated with PSF. CONCLUSIONS: PSF is frequent in stroke patients, especially women, even after six months. The absence of neuroanatomical correlates of PSF suggests that it is a multifactorial process with biological, psychological, and social risk factors that require further study.

Scented Solutions: Examining the Efficacy of Scent Interventions in Mitigating Driving Fatigue.

Fatigued driving threatens the safety of people's lives and property. Scent countermeasures offer minimal disruption and high efficacy, making them a promising approach. The aim of this study was to explore the application of scent countermeasures in alleviating fatigued driving. This study explored changes in EEG frequency bands (alpha, beta, theta, and gamma) and the activity of EEG metrics (R(α/ß), Rθ/(α+ß) and R(α+θ)/(α+ß)) in the temporal lobe during driving tasks, selected fatigued driving identifiers, and aided validation by investigating subjective fatigue with the Karolinska Sleepiness Scale (KSS). The EEG indicators all increased, with a significant increase in R(α/ß). R(α/ß) was combined with the KSS to explore the effects of three scents, peppermint, grapefruit, and lavender, on driving fatigue. The subjective questionnaire results indicated that all three scents significantly improved driving fatigue, with significantly lower levels of driving fatigue compared to the control group. The analysis of EEG signals revealed a significant decrease in R(α/ß) after the implementation of scent countermeasures. Moreover, R(α/ß) was found to be lower in all three odor intervention groups compared to the control group. All three scents were found to significantly alleviate driving fatigue. The grapefruit scent had a better timely effect in relieving driving fatigue and the lavender scent had a longer effectiveness. This study provides further exploration for the application of odor interventions to alleviate driving fatigue. This study provides a practical reference for drivers to use odors to avoid fatigue in order to improve road safety.

Fatigue in children using motor imagery and P300 brain-computer interfaces.

BACKGROUND: Brain-computer interface (BCI) technology offers children with quadriplegic cerebral palsy unique opportunities for communication, environmental exploration, learning, and game play. Research in adults demonstrates a negative impact of fatigue on BCI enjoyment, while effects on BCI performance are variable. To date, there have been no pediatric studies of BCI fatigue. The purpose of this study was to assess the effects of two different BCI paradigms, motor imagery and visual P300, on the development of self-reported fatigue and an electroencephalography (EEG) biomarker of fatigue in typically developing children. METHODS: Thirty-seven typically-developing school-aged children were recruited to a prospective, crossover study. Participants attended three sessions: (A) motor imagery-BCI, (B) visual P300-BCI, and (C) video viewing (control). The motor imagery task involved an imagined left- or right-hand squeeze. The P300 task involved attending to one square on a 3 × 3 grid during a random single flash sequence. Each paradigm had respective calibration periods and a similar visual counting game. Primary outcomes were self-reported fatigue and the power of the EEG alpha band both collected during resting-state periods pre- and post-task. Self-reported fatigue was measured using a 10-point visual analog scale. EEG alpha band power was calculated as the integrated power spectral density from 8 to 12 Hz of the EEG spectrum. RESULTS: Thirty-two children completed the protocol (age range 7-16, 63% female). Self-reported fatigue and EEG alpha band power increased across all sessions (F(1,155) = 33.9, p < 0.001; F = 5.0(1,149), p = 0.027 respectively). No differences in fatigue development were observed between session types. There was no correlation between self-reported fatigue and EEG alpha band power change. BCI performance varied between participants and paradigms as expected but was not associated with self-reported fatigue or EEG alpha band power. CONCLUSION: Short periods (30-mintues) of BCI use can increase self-reported fatigue and EEG alpha band power to a similar degree in children performing motor imagery and P300 BCI paradigms. Performance was not associated with our measures of fatigue; the impact of fatigue on useability and enjoyment is unclear. Our results reflect the variability of fatigue and the BCI experience more broadly in children and warrant further investigation.

Association between sleep-disordered breathing and post-stroke fatigue in patients with ischemic stroke.

OBJECTIVES: Post-stroke fatigue (PSF) is common and often disabling. Sleep-disordered breathing (SDB) is highly prevalent among stroke survivors and can cause fatigue. We explored the relationship between SDB and PSF over time. MATERIALS AND METHODS: Ischemic stroke (IS) patients within the BASIC project were offered SDB screening with a well-validated cardiopulmonary sleep apnea test at 0, 3-, 6-, and 12-months post-stroke. The primary exposure was the respiratory event index (REI; sum of apneas plus hypopneas per hour). The primary outcome was PSF, measured by the SF-36 vitality scale. Associations between REI and PSF were evaluated using linear regression including time-by-REI interactions, allowing the effect of REI to vary over time. RESULTS: Of the 411 IS patients who completed at least one outcome interview, 44 % were female, 61 % Mexican American (MA), 26 % non-Hispanic white, with a mean age of 64 (SD 10). Averaged across timepoints, REI was not associated with PSF. In a time-varying model, higher REI was associated with greater PSF at 3-months (ß = 1.75, CI = 0.08, 3.43), but not at 6- or 12-months. Across timepoints, female sex, depressive symptoms, and comorbidity burden were associated with greater PSF, whereas MA ethnicity was associated with less PSF. CONCLUSIONS: Higher REI was associated with modestly greater PSF in the early post-stroke period, but no association was observed at 6 months and beyond. SDB may be a modest modifiable risk factor for early PSF, but its treatment is unlikely to have a substantial impact on long-term PSF. MA ethnicity seems to be protective against PSF.

Recovery following exercise-induced fatigue: Influence of a single heart rate clamped cycling session under systemic hypoxia.

We investigated whether a single heart rate clamped cycling session under systemic hypoxia affects the recovery of physical and psycho-physiological responses from residual fatigue compared to normoxia. On separate occasions, twelve trained males performed a 3-d acute training camp scenario. On days 1 and 3, participants cycled for 60 min at a constant heart rate (80% of ventilatory threshold). On day 2, fatigue was induced through a simulated team game circuit (STGC), followed by a 60-min intervention of either: (1) heart rate clamped cycling in normoxia; (2) heart rate clamped cycling in hypoxia (simulated altitude ~ 3500 m); or (3) no cycling. Countermovement jump height and leg stiffness were assessed before and after every session. Perceptual fatigue was evaluated daily. Compared to baseline, jump height decreased at all timepoints following the STGC (all p < 0.05). Leg stiffness and cycling power output only decreased immediately following the STGC, with a 48% further decrease in cycling power output in hypoxia compared to normoxia (p < 0.05). Perceived fatigue, decreased sleep quality, and increased muscle soreness responses occurred on day 3 (p < 0.05). A single heart rate-clamped cycling session in hypoxia reduced mechanical output without affecting recovery of physical performance and perceptual measures from residual fatigue induced through team sport activity.

Resting-state EEG rhythms are abnormal in post COVID-19 patients with brain fog without cognitive and affective disorders.

OBJECTIVES: Several persons experiencing post-covid-19 (post-COVID) with "brain fog" (e.g., fatigue, cognitive and psychiatric disorders, etc.) show abnormal resting-state electroencephalographic (rsEEG) rhythms reflecting a vigilance dysfunction. Here, we tested the hypothesis that in those post-COVID persons, abnormal rsEEG rhythms may occur even when cognitive and psychiatric disorders are absent. METHODS: The experiments were performed on post-COVID participants about one year after hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inclusion criteria included a "brain fog" claim, no pre-infection, and actual organic chronic disease. Matched controls (no COVID) were also enrolled. All participants underwent clinical/neuropsychological assessment (including fatigue assessment) and rsEEG recordings. The eLORETA freeware estimated regional rsEEG cortical sources at individual delta (<4 Hz), theta (4-7 Hz), and alpha (8-13 Hz) bands. Beta (14-30 Hz) and gamma (30-40 Hz) bands were pre-fixed. RESULTS: More than 90% of all post-COVID participants showed no cognitive or psychiatric disorders, and 75% showed ≥ 2 fatigue symptoms. The post-COVID group globally presented lower posterior rsEEG alpha source activities than the Control group. This effect was more significant in the long COVID-19 patients with ≥ 2 fatigue symptoms. CONCLUSIONS: In post-COVID patients with no chronic diseases and cognitive/psychiatric disorders, "brain fog" can be associated with abnormal posterior rsEEG alpha rhythms and subjective fatigue. SIGNIFICANCE: These abnormalities may be related to vigilance and allostatic dysfunctions.

Prevalence and Associated Clinical Characteristics of Walking-Related Motor, Cognitive, and Fatigability in Progressive Multiple Sclerosis: Baseline Results From the CogEx Study.

BACKGROUND: People with progressive multiple sclerosis (PMS) present motor (eg, walking) and cognitive impairments, and report fatigue. Fatigue encompasses fatigability which is objectively measured by the capacity to sustain a motor or cognitive task. OBJECTIVE: To investigate the prevalence of walking and cognitive fatigability (CF) and the associated clinical characteristics in a large sample of PMS patients. METHODS: PMS patients (25-65 years old) were included from 11 sites (Europe and North America), having cognitive impairment (1.28 standard deviation below normative data for the symbol digit modality test [SDMT]). Walking fatigability (WF) was assessed using the distance walk index (DWI) and CF using the SDMT (scores from the last 30 seconds compared to the first 30 seconds). Additional measures were: cognitive assessment-Brief International Cognitive Assessment for multiple sclerosis (MS), cardiorespiratory fitness, 6-minute walk, physical activity, depressive symptoms, perceived fatigue-Modified Fatigue Impact Scale (MFIS), MS impact-MSIS-29, and walking ability. RESULTS: Of 298 participants, 153 (51%) presented WF (DWI = -28.9 ± 22.1%) and 196 (66%) presented CF (-29.7 ± 15%). Clinical characteristics (EDSS, disease duration, and use of assistive device) were worse in patients with versus without WF. They also presented worse scores on MSIS-29 physical, MFIS total and physical and reduced physical capacity. CF patients scored better in the MSIS-29 physical and MFIS psychosocial, compared to non-CF group. Magnitude of CF and WF were not related. CONCLUSIONS: Half of the cognitively-impaired PMS population presented WF which was associated with higher disability, physical functions, and fatigue. There was a high prevalence of CF but without strong associations with clinical, cognitive, and physical functions. TRIAL REGISTRATION NUMBER: The "CogEx-study," www.clinicaltrial.gov identifier number: NCT03679468.

The measurement of fatigability severity in individuals with multiple sclerosis and healthy controls.

BACKGROUND: Multiple Sclerosis (MS) is a chronic disease that substantially diminishes one's ability to undertake daily living activities. Fatigue has been reported by at least 80 % of persons with MS (PwMS). Yet, little is known concerning the quantification of fatigability using prolonged walking tests. OBJECTIVES: To compare fatigability severity measures using the 10-minute walk test for PwMS against age- and gender-matched healthy controls (HCs). METHODS: Participants included 53 ambulatory PwMS and 49 HCs. Perceived fatigability was measured by dividing a participant's change in self-reported tiredness by the number of meters walked. Performance fatigability was calculated by dividing the change in walking speed (at 2.5 and 10 min) by the total distance walked in meters. RESULTS: There was a significant difference in perceived fatigability between PwMS and HCs (mean difference: 2.73 ± 0.83; p = 0.001) and in performance fatigability (mean difference: 0.24 ± 0.11; p = 0.01). Moreover, there were significant differences in speed and distance at all time points (p ≤ 0.05) between PwMS and HCs. CONCLUSIONS: PwMS have significant walking deficits as reflected by greater fatigability in both perceived and performance measures. These methods can enhance therapeutic strategies that improve the walking performances of PwMS.

Comparing the effects of cerebellar and prefrontal anodal transcranial direct current stimulation concurrent with postural training on balance and fatigue in patients with multiple sclerosis: a double-blind, randomized, sham-controlled trial.

Fatigue and balance disorders are common challenges experienced by Multiple Sclerosis (MS) individuals. The purpose of this study was to compare the concurrent effects of cerebellar and prefrontal anodal trans-cranial direct current stimulation (a-tDCS) with postural training on balance and fatigue in MS patients. 51 patients were evaluated to randomly allocation to a-tDCS over cerebellum, a-tDCS over dorsolateral prefrontal cortex (DLPFC) and sham group. 46 individuals (n = 16 in experimental groups and n = 14 in control group) followed treatment. All the groups received 10 sessions of postural training. The experimental groups underwent a-tDCS with a current of 1.5 mA for a period of 20 min. While, in the sham group, tDCS was only activated for 30 s and then turned off. The treatment included 10 sessions for four weeks. Before and after intervention, fatigue and balance were assessed using Fatigue Severity Scale (FSS), Timed Up and Go (TUG) test and Berg Balance Score (BBS), respectively. There was found a significant reduction in fatigue in the group receiving a-tDCS over the prefrontal cortex with postural training compared to the other two groups (P < 0.001). Additionally, a significant improvement was found in balance in the group receiving a-tDCS over the cerebellum concurrent with postural training in comparison to the other two groups (P < 0.001). Besides, in the sham group, the significant results were not reported in the variables. (P > 0.001). The results demonstrated that a-tDCS enhances the effects of postural training on balance and fatigue in MS patients.

The Quantification of Physical Performance and Internal Training Load in Youth Male Soccer Players During Preseason.

PURPOSE: The monitoring of training loads and quantification of physical performance are common practices in youth soccer academies to support coaches in prescribing and programming training for individuals. The interaction between training load and physical performance is unknown during a preseason period in youth soccer players. The current study assessed changes in training load and physical assessments across a 4-week preseason period. The relationship between physical performance and match playing time in youth male soccer players was also investigated. METHODS: The training loads of 25 professional youth academy male soccer players were monitored throughout a 4-week preseason period. Assessments of power, agility, speed, and aerobic capacity were undertaken in the first training session. Session ratings of perceived exertion (sRPE) and well-being questionnaires were collected during all training sessions and preseason matches. Playing time during subsequent competitive matches was recorded. RESULTS: T test and 30-m-sprint assessments, conducted on the first day of preseason, were predictors of sRPE throughout preseason (t test χ2/df = 2.895, poor adjustment; 30-m sprint χ2/df = 1.608, good adjustment). YoYo Test performance was related with changes in perceived fatigue (χ2/df = 0.534, very good adjustment). Faster players reported higher values of sRPE, and players with higher aerobic capacity reported higher levels of fatigue across preseason. Well-being, perceived fatigue and soreness, and sRPE decreased across preseason. Greater match durations were related to higher levels of fatigue during preseason (P < .05). CONCLUSION: The current study highlights the relationship between training load, physical assessments, and playing time. Coaches and practitioners can use physical test data at the start of preseason as an indication of players that report higher sRPE, perceived fatigue, and reduced well-being across preseason, supporting decisions around individualized training prescriptions.

Physical fitness in children with Marfan and Loeys-Dietz syndrome: associations between cardiovascular parameters, systemic manifestations, fatigue, and pain.

Children with Marfan (MFS) and Loeys-Dietz syndrome (LDS) report limitations in physical activities, sports, school, leisure, and work participation in daily life. This observational, cross-sectional, multicenter study explores associations between physical fitness and cardiovascular parameters, systemic manifestations, fatigue, and pain in children with MFS and LDS. Forty-two participants, aged 6-18 years (mean (SD) 11.5(3.7)), diagnosed with MFS (n = 36) or LDS (n = 6), were enrolled. Physical fitness was evaluated using the Fitkids Treadmill Test's time to exhaustion (TTE) outcome measure. Cardiovascular parameters (e.g., echocardiographic parameters, aortic surgery, cardiovascular medication) and systemic manifestations (systemic score of the revised Ghent criteria) were collected. Pain was obtained by visual analog scale. Fatigue was evaluated by PROMIS® Fatigue-10a-Pediatric-v2.0-short-form and PROMIS® Fatigue-10a-Parent-Proxy-v2.0-short-form. Multivariate linear regression analyses explored associations between physical fitness (dependent variable) and independent variables that emerged from the univariate linear regression analyses (criterion p < .05). The total group (MFS and LDS) and the MFS subgroup scored below norms on physical fitness TTE Z-score (mean (SD) -3.1 (2.9); -3.0 (3.0), respectively). Univariate analyses showed associations between TTE Z-score aortic surgery, fatigue, and pain (criterion p < .05). Multivariate analyses showed an association between physical fitness and pediatric self-reported fatigue that explained 48%; 49%, respectively, of TTE Z-score variance (F (1,18) = 18.6, p ≤ .001, r2 = .48; F (1,15) = 16,3, p = .01, r2 = .49, respectively).    Conclusions: Physical fitness is low in children with MFS or LDS and associated with self-reported fatigue. Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with MFS and LDS. What is Known: • Marfan and Loeys-Dietz syndrome are heritable connective tissue disorders and share cardiovascular and systemic manifestations. • Children with Marfan and Loeys-Dietz syndrome report increased levels of disability, fatigue and pain, as well as reduced levels of physical activity, overall health and health-related quality of life. What is New: • Physical fitness is low in children with Marfan and Loeys-Dietz syndrome and associated with self-reported fatigue. • Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with Marfan and Loeys-Dietz syndrome.

Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

Biologics initiation in moderate versus severe rheumatoid arthritis: real-world experience from a Canadian registry.

OBJECTIVES: To evaluate the treat-to-target experience, and quality of life measures of moderate and severe rheumatoid arthritis (RA) patients initiating a biologic in a real-world setting of a publicly funded payer system. METHODS: Biologic naive RA patients who had initiated their first biologic while enrolled in the Ontario Best Practices Research Initiative registry from 2008 to 2020 were selected if they had moderate (DAS28 >3.2 to ≤5.1) or severe (DAS28 >5.1) RA. Remission, LDA, DAS28, HAQ-DI, fatigue, sleep, drug persistence and characteristics associated with remission were assessed at 12 months post biologic initiation. RESULTS: Overall, 838 patients initiated their first biologic, 264 had moderate RA and 219 had severe RA. After 12 months, 44% moderate RA vs. 21% severe RA achieved remission (p<0.0001), and 59% moderate RA vs. 35% severe RA reached LDA (p<0.0001). Mean change (SD) from baseline in DAS28 was 2.2 (1.5) in severe RA vs. 1.4 (1.3) in moderate RA (p<0.0001), in fatigue score was 1.11 (3.2) in severe RA vs. 0.98 (3.2) in moderate RA (p<0.0001). Moderate disease at a biologic initiation was positively associated with remission (p=0.0016). Female gender (p=0.0170), and a higher HAQ-DI score at baseline (p=0.0042) were negatively associated with remission. Biologic persistence was 77% for moderate, and 73% for severe (p=0.2444). CONCLUSIONS: Severe RA patients had higher mean score improvements in DAS28, sleep and fatigue. Moderate RA was more likely to reach remission or LDA. Both groups had similar biologic persistence at 12 months. These findings highlight the importance of the treat-to-target approach and its potential underutilisation in the real-world setting.

Improvement of fatigue in generalised myasthenia gravis with zilucoplan.

BACKGROUND: Fatigue is a debilitating symptom of myasthenia gravis (MG). The impact of fatigue on MG can be assessed by Quality of Life in Neurological Disorders (Neuro-QoL) Short Form Fatigue scale. Transformation of raw Neuro-QoL fatigue scores to T-scores is a known approach for facilitating clinical interpretation of clinically meaningful and fatigue severity thresholds. METHODS: In the Phase 3, double-blind, placebo-controlled RAISE study (NCT04115293), adults with acetylcholine receptor autoantibody-positive generalised MG (MG Foundation of America Disease Class II-IV) were randomised 1:1 to daily subcutaneous zilucoplan 0.3 mg/kg or placebo for 12 weeks. Patients completing RAISE could opt to receive zilucoplan 0.3 mg/kg in an ongoing, open-label extension study, RAISE-XT (NCT04225871). In this post-hoc analysis, we evaluated the long-term effect of zilucoplan on fatigue in RAISE patients who entered RAISE-XT. We report change in Neuro-QoL Short Form Fatigue T-scores and fatigue severity levels from RAISE baseline to Week 60. RESULTS: Mean Neuro-QoL Short Form Fatigue T-scores improved from baseline to Week 12 in the zilucoplan group (n = 86) with a clinically meaningful difference versus placebo (n = 88; least squares mean difference: - 3.61 (nominal p-value = 0.0060]), and these improvements continued further to Week 60. At Week 12, more patients on zilucoplan (n = 34, 47.2%) experienced improvements in ≥ 1 fatigue severity level from baseline versus placebo (n = 23, 28.4%; p = 0.017). At Week 60, most (n = 55, 65.5%) patients had mild fatigue or none. CONCLUSION: Treatment with zilucoplan demonstrated statistical and clinically meaningful improvements in fatigue scores and severity versus placebo during RAISE, which were sustained to Week 60 in RAISE-XT.