Nintedanib could potentially lead to improvements in anti-melanoma differentiation-associated 5 dermatomyositis-associated interstitial lung disease.

OBJECTIVES: To determine the efficacy and safety of nintedanib in patients with anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5+ DM-ILD). METHODS: The study was a retrospective cohort design that evaluated patients with anti-MDA5+ DM who either received or did not receive nintedanib. Clinical symptoms, laboratory tests, and survival were compared in the two groups using a propensity score-matched analysis. The primary endpoint was mortality, while adverse events were recorded descriptively. RESULTS: After propensity score matching, 14 patients who received nintedanib (nintedanib+ group) and matched 56 patients who did not receive nintedanib (nintedanib- group) were enrolled. Compared with the nintedanib- group, the nintedanib+ group had a lower incidence of heliotrope and arthritis, higher lymphocyte counts, lower serum ferritin levels, and greater 12-month survival (all p<0.005). Although lung function, HRCT score, and lung VAS were not statistically different between the two groups, the longitudinal study showed significant improvement in HRCT scores (p=0.028) and pulmonary VAS (p=0.019) in the nintedanib+ group. Adverse events occurred in 28.6% of patients, with the most common adverse event with nintedanib being diarrhoea. CONCLUSIONS: Nintedanib may be effective for improving clinical symptoms, laboratory parameters, lung lesions, and survival in anti-MDA5+ DM. Diarrhoea was the most common adverse event associated with nintedanib, although the drug was well tolerated by most patients.

Expansion of exhausted CD8+ T cells associates with increased pulmonary fungal infection risk in anti-melanoma differentiation associated gene 5 dermatomyositis.

OBJECTIVES: Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of this study is to investigate the abundance and clinical relevance of exhaustion markers on peripheral CD8 T cells from patients with idiopathic inflammatory myopathy (IIM). METHODS: Twenty-nine healthy controls (HCs) and 71 patients with IIM were enrolled, including 42 with anti-MDA5+ and 18 with anti-MDA5- dermatomyositis (DM) and 11 with anti-synthetase syndrome (ASS). Flow cytometry was applied to detect PD-1, TIM-3 and LAG-3 in CD8 T cells. The clinical associations of the CD8 T cell exhaustion phenotype in patients with anti-MDA5+ DM were analysed. RESULTS: CD8 T cells from patients with anti-MDA5+ DM showed significantly increased LAG-3, TIM-3 and PD-1 compared to those from patients with anti-MDA5- IIM (18 with anti-MDA5- DM and 11 with ASS) or HCs (adjusted p all < 0.05). CD8 T cells with distinct exhaustion levels were all significantly increased in anti-MDA5+ DM patients compared with HCs (p all < 0.05). Patients with high level of PD-1+ TIM-3+LAG-3+ CD8+ T cells had a significant higher incidence of pulmonary fungal infections but lower counts of CD4+ and CD8+ T cells. ROC analysis revealed that the frequency of PD-1+TIM-3+LAG-3+CD8+ T cell significantly predicted pulmonary fungal infections (area under the curve: 0.828). CONCLUSIONS: CD8 T cells from patients with anti-MDA5+ DM show significant exhausted phenotype, and increased exhausted CD8 T cells were associated with high risk of pulmonary fungal infection.

Peripheral lymphocyte count defines the clinical phenotypes and prognosis in patients with anti-MDA5-positive dermatomyositis.

OBJECTIVE: To explore the role of peripheral lymphocyte count in phenotyping and prognosis prediction in dermatomyositis (DM) patients with anti-MDA5 antibodies. METHODS: In total, 1669 patients with idiopathic inflammatory myopathy (IIM) were retrospectively enrolled. Clinical characteristics and prognosis of patients with anti-MDA5+ DM were analyzed in association with peripheral lymphocyte counts and clusters determined by unsupervised machine learning. RESULTS: The peripheral lymphocyte count was significantly lower in the anti-MDA5+ DM group (N = 421) than in the other IIM serotype groups. The anti-MDA5+ DM patients were divided into three groups; the severe lymphopenia group had skin ulcers and rapidly progressive interstitial lung disease (RP-ILD); patients with a normal lymphocyte count had a younger age of onset, more frequent arthritis, and normal serum ferritin levels, whereas mild lymphopenia group showed a moderate increase of serum ferritin and intermediate incidence of RP-ILD. Survival analysis revealed that the 3- and 6-month mortality rates were significantly higher in the severe lymphopenia group (29.0% and 42.1%, respectively) than in the mild lymphopenia group and normal lymphocyte count group (p value <0.001). Consistently, unsupervised machine learning identified three similar groups; the arthritis cluster shows the highest lymphocyte counts and best prognosis; the RP-ILD cluster presents the lowest peripheral lymphocyte, high incidence of RP-ILD, and poor prognosis; the typical DM rash cluster had a moderate peripheral lymphocyte count and an intermediate prognosis. CONCLUSIONS: Lymphopenia is a unique manifestation of anti-MDA5+ DM. Peripheral lymphocyte count can define clinical phenotypes and predict prognosis in anti-MDA5+ DM.

Clinical value of YKL-40 in patients with polymyositis/dermatomyositis: A cross-sectional study and a systematic review.

INTRODUCTION: We performed a cross-sectional study to investigate the clinical usefulness of YKL-40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL-40 in patients with polymyositis (PM)/DM. MATERIALS AND METHODS: A cross-sectional study and a systematic review were performed to study the clinical value of YKL-40 in patients with PM/DM. Serum YKL-40 level was detected using enzyme-linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL-40 in patients with PM/DM. RESULTS: In the cross-sectional study, serum YKL-40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72-176.4] ng/ml versus 27.37 [12.30-53.58] ng/ml, p < 0.0001). Serum levels of YKL-40 were associated with the course of DM (r = -0.469, p < 0.001), CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), and global disease activity (r = 0.628, p < 0.001). The area under the ROC curve was 0.835 (95% confidence interval 0.751-0.920). In the systematic review, a total of four studies were included with moderate to high quality. Serum level of YKL-40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death. CONCLUSION: Serum YKL-40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.

Gender differences in the relationship between walking activity and sleep disturbance among community-dwelling older adult with diabetes in Taiwan.

This study explored the gender differences in the relationship between walking activity and sleep disturbances. A cross-sectional study of 201 community-dwelling older adults with diabetes was conducted in southern Taiwan. Using the Taiwanese version of the International Physical Activity Questionnaire, self-administered short version (IPAQ-SS), information on physical activity and sleep disturbance conditions was collected. Among older female adults with diabetes, 54.2% reported sleep disturbance significantly higher than males (38.1%). Logistic regression analysis suggested that for women, in addition to the active group, older adults in the low-active, high-walking group exhibited a significantly lower rate of sleep disturbance than did those who walked less.

Transformation of nad7 into the nuclear genome rescues the slow growth3 mutant in Arabidopsis.

Plant pentatricopeptide repeat (PPR) proteins are mostly involved in chloroplast or mitochondrial RNA metabolism. However, direct evidence that correction of the molecular defects in the organelles can restore the plant phenotypes has yet to be demonstrated in a ppr mutant. Arabidopsis slow growth3 (slo3), a ppr mutant, is impaired in the splicing of mitochondrial nad7 intron 2. Here, we have used slo3 as an example to demonstrate that transformation of correctly spliced nad7 into the nuclear genome and targeting the Nad7 subunit into mitochondria can restore complex I activity and plant phenotypes in the mutant. These results provide direct evidence that the strong growth and developmental phenotypes of the slo3 mutant are caused by defects in mitochondrial nad7.

What works in falls prevention in Asia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is strong research evidence for falls prevention among older people in the community setting, although most is from Western countries. Differences between countries (eg sunlight exposure, diet, environment, exercise preferences) may influence the success of implementing falls prevention approaches in Asian countries that have been shown to be effective elsewhere in the world. The aim of this review is to evaluate the scope and effectiveness of falls prevention randomized controlled trials (RCTs) from the Asian region. METHOD: RCTs investigating falls prevention interventions conducted in Asian countries from (i) the most recent (2012) Cochrane community setting falls prevention review, and (ii) subsequent published RCTs meeting the same criteria were identified, classified and grouped according to the ProFANE intervention classification. Characteristics of included trials were extracted from both the Cochrane review and original publications. Where ≥2 studies investigated an intervention type in the Asian region, a meta-analysis was performed. RESULTS: Fifteen of 159 RCTs in the Cochrane review were conducted in the Asian region (9%), and a further 11 recent RCTs conducted in Asia were identified (total 26 Asian studies: median 160 participants, mean age:75.1, female:71.9%). Exercise (15 RCTs) and home assessment/modification (n = 2) were the only single interventions with ≥2 RCTs. Intervention types with ≥1 effective RCT in reducing fall outcomes were exercise (6 effective), home modification (1 effective), and medication (vitamin D) (1 effective). One multiple and one multifactorial intervention also had positive falls outcomes. Meta-analysis of exercise interventions identified significant benefit (number of fallers: Odds Ratio 0.43 [0.34,0.53]; number of falls: 0.35 [0.21,0.57]; and number of fallers injured: 0.50 [0.35,0.71]); but multifactorial interventions did not reach significance (number of fallers OR = 0.57 [0.23,1.44]). CONCLUSION: There is a small but growing research base of falls prevention RCTs from Asian countries, with exercise approaches being most researched and effective. For other interventions shown to be effective elsewhere, consideration of local issues is required to ensure that research and programs implemented in these countries are effective, and relevant to the local context, people, and health system. There is also a need for further high quality, appropriately powered falls prevention trials in Asian countries.

Functional mobility and its contributing factors for older adults in different cities in Taiwan.

BACKGROUND/PURPOSE: Impaired mobility is one of the primary causes of declined functional capacity in old age. The timed up-and-go test (TUG), a common mobility test, has been studied extensively in Western countries. The purposes of this study were to compare and identify factors associated with TUG performance in older adults with impaired mobility and living in different cities in Taiwan. METHODS: Older adults living in Taipei, Tainan, and Niaosong cities were screened for mobility impairments and then recruited. A series of questionnaires and physical and functional tests were used to obtain information and measurements for potential contributing factors and TUG. Regression analysis was conducted to determine factors contributing to TUG. RESULTS: A total of 413 older adults participated in the study. The mean TUG was 14.3 seconds for participants across the three cities, and was significantly shorter in Tainan. Age, number of medications, fear of falling, depression, high intensity activity time, reaction time, single leg stance time, and functional reach distance were found to have significant contribution. These factors accounted for approximately half of the variance in TUG. The regression equations were not equal for the different cities, with depression being the only common determinant. CONCLUSION: Taiwanese older adults with mobility problems living in different cities performed differently in TUG and the contributing factors were also different. These findings indicate a need of further studies examining older adults in different environments.

Measurement equivalence across gender and education in the WHOQOL-BREF for community-dwelling elderly Taiwanese.

BACKGROUND: The WHOQOL-BREF, a generic quality of life (QoL) instrument, has been widely used clinically and for research on older populations. However, its measurement equivalence/invariance (ME/I) has not been well examined for the elderly (≥ 65 years) across some different demographics. METHODS: The data were derived from a cross-sectional study with a convenience sampling design in Taiwan. We enrolled 244 elderly participants: men = 143 (58.6%); educational level ≤ primary school = 121 (49.6%). The ME/I was examined using multiple group confirmatory factor analysis (MGCFA) across gender and educational level. RESULTS: The fit indices were satisfactory for the configural models of gender and educational level (standardized root mean square residual [SRMR] = 0.0742 and 0.0770; root mean square error of approximation [RMSEA] = 0.0655 and 0.0686; comparative fit index [CFI] = 0.953). In addition, MGCFAs showed that ME/I was supported across gender (ΔSRMR = 0.001 to 0.019; ΔRMSEA = -0.003 to 0.001; ΔCFI = -0.003 to 0.000) and educational level (ΔSRMR = 0.002 to 0.006; ΔRMSEA = -0.002 to 0.004; ΔCFI = -0.007 to 0.000). CONCLUSION: The WHOQOL-BREF Taiwan version is appropriate for combined use and for comparisons in older people across gender and different educational levels.

Cognitive Function and Quality of Life in Community-Dwelling Seniors with Mild Cognitive Impairment in Taiwan.

The aims of this study were to examine the relationships between overall cognitive function and the quality of life (QOL) domains, and to compare the differences in these by age, gender, and educational level in community-dwelling seniors in Taiwan. A cross-sectional study was conducted, with the participants screened and recruited from Southern Tainan. The Saint Louis University Mental Status Examination was used to screen the cognitive status of the participants. A total of 144 seniors participated in this study were assessed using the Taiwanese version of WHOQOL-BREF. The results showed that the participants performed better in the cognitive domains of "figure identification" and "orientation" while they performed poor in "delayed recall" and "immediate paragraph recall". No significant relationship between cognitive function and overall QOL, but a positive relationship between cognitive function and the physical health domain of QOL was found. The findings of this study provide valuable information for community healthcare providers.

The relationships between activity and quality of life for older men and women at different ages in Taiwan.

This study investigated the relationships between types of activity and quality of life (QOL) for older men and women at different ages. Based on cross-sectional data that included 220 community-dwelling elderly persons aged 65 and older in southern Taiwan, the results showed that the participation rates in many activities declined with age for both genders. Social activity and solitary leisure activity were significantly associated with QOL for old-old men, but not for young-old men. Only social activity was significantly associated with QOL for young-old women, but there was no significant association between any activity and QOL for old-old women.

Ipsilateral lower limb motor performance and its association with gait after stroke.

BACKGROUND AND PURPOSE: Motor deficits of the ipsilateral lower limb could occur after stroke and may be associated with walking performance. This study aimed to determine whether the accuracy and movement path of targeted movement in the ipsilateral lower limb would be impaired in the chronic stage of stroke and whether this impairment would contribution to gait. METHODS: Twenty adults with chronic stroke and 20 age-matched controls went through Mini Mental Status Examination (MMSE), and a series of sensorimotor tests. The targeted movement tasks were to place the big toe ipsilateral to the lesion at an external visual target (EXT) or a proprioceptive target (PRO, contralateral big toe) with eyes open (EO) or closed (EC) in a seated position. A motion analysis system was used to obtain the data for the calculation of error distance, deviation from a straight path, and peak toe-height during the targeted movement tasks and gait velocity, step length, step width and step length symmetry of the lower limb ipsilateral to the brain lesion during walking. RESULTS: The stroke group had significantly lower MMSE and poorer visual acuity on the ipsilateral side, but did not differ in age or other sensorimotor functions when compared to the controls. For the targeted movement performance, only the deviation in PRO-EC showed significant between-group differences (p = 0.02). Toe-height in both EXT-EO and in PRO-EO was a significant predictor of step length (R2 = 0.294, p = 0.026) and step length symmetry (R2 = 0.359, p = 0.014), respectively. DISCUSSION AND CONCLUSIONS: The performance of ipsilateral lower limb targeted movement could be impaired after stroke and was associated with step length and its symmetry. The training of ipsilateral targeted movement with unseen proprioceptive target may be considered in stroke rehabilitation.

Prevalence, Risk Factors, and Mortality of Invasive Pulmonary Aspergillosis in Patients with Anti-MDA5+ Dermatomyositis: A Retrospective Study in China.

Objective: To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM). Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared. Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P>0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all<0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all<0.05). Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.

Spontaneous pneumomediastinum in anti-MDA5-positive dermatomyositis: Prevalence, risk factors, and prognosis.

OBJECTIVE: To depict the clinical panorama of spontaneous pneumomediastinum (SPM) in anti-MDA5 antibody-positive dermatomyositis (anti-MDA5+ DM). METHODS: A total of 1352 patients with idiopathic inflammatory myopathy (IIM), including 384 anti-MDA5+ DM patients were retrospectively enrolled. The clinical profiles of anti-MDA5+ DM-associated SPM were analyzed. RESULTS: We identified that 9.4 % (36/384) of anti-MDA5+ DM patients were complicated with SPM, which was significantly higher than that of non-anti-MDA5+ DM and other IIM subtypes (P all <0.001). SPM developed at a median of 5.5 (3.0, 12.0) months after anti-MDA5+ DM onset. Anti-MDA5+ DM patients complicated with SPM showed a significantly higher frequency of fever, dyspnea, and pulmonary infection including viral and fungal infections compared to those without SPM (P all < 0.05). Cytomegalovirus (CMV) and fungal infections were identified to be independent risk factors for SPM development in the anti-MDA5+ DM. SPM and non-SPM patients in our anti-MDA5+ DM cohort showed comparable short-term and long-term survival (P = 0.236). Furthermore, in the SPM group, we found that the non-survivors had a lower peripheral lymphocyte count, higher LDH level, and higher frequency of intensification of immunosuppressive treatment (IST) than survivors. The elevated LDH level and intensification of IST were independent risk factors for increased mortality in anti-MDA5+ DM-associated SPM patients. CONCLUSIONS: Nearly one-tenth of patients with anti-MDA5+ DM develop SPM. Both CMV and fungal infections are risk factors for SPM occurrence. The development of SPM does not worsen the prognosis of anti-MDA5+ DM patients, and the intensification of IST does harm to the SPM prognosis.

The cortical control of cycling exercise in stroke patients: an fNIRS study.

Stroke survivors suffering from deficits in motor control typically have limited functional abilities, which could result in poor quality of life. Cycling exercise is a common training paradigm for restoring locomotion rhythm in patients. The provision of speed feedback has been used to facilitate the learning of controlled cycling performance and the neuromuscular control of the affected leg. However, the central mechanism for motor relearning of active and passive pedaling motions in stroke patients has not been investigated as extensively. The aim of this study was to measure the cortical activation patterns during active cycling with and without speed feedback and during power-assisted (passive) cycling in stroke patients. A frequency-domain near-infrared spectroscopy (FD-NIRS) system was used to detect the hemodynamic changes resulting from neuronal activity during the pedaling exercise from the bilateral sensorimotor cortices (SMCs), supplementary motor areas (SMAs), and premotor cortices (PMCs). The variation in cycling speed and the level of symmetry of muscle activation of bilateral rectus femoris were used to evaluate cycling performance. The results showed that passive cycling had a similar cortical activation pattern to that observed during active cycling without feedback but with a smaller intensity of the SMC of the unaffected hemisphere. Enhanced PMC activation of the unaffected side with improved cycling performance was observed during active cycling with feedback, with respect to that observed without feedback. This suggests that the speed feedback enhanced the PMC activation and improved cycling performance in stroke patients.

Effects of a multifactorial fall prevention program on fall incidence and physical function in community-dwelling older adults with risk of falls.

OBJECTIVE: To evaluate effects of a multifactorial fall prevention program on fall incidence and physical function in community-dwelling older adults. DESIGN: Multicenter randomized controlled trial. SETTING: Three medical centers and adjacent community health centers. PARTICIPANTS: Community-dwelling older adults (N=616) who have fallen in the previous year or are at risk of falling. INTERVENTIONS: After baseline assessment, eligible subjects were randomly allocated into the intervention group (IG) or the control group (CG), stratified by the Physiological Profile Assessment (PPA) fall risk level. The IG received a 3-month multifactorial intervention program including 8 weeks of exercise training, health education, home hazards evaluation/modification, along with medication review and ophthalmology/other specialty consults. The CG received health education brochures, referrals, and recommendations without direct exercise intervention. MAIN OUTCOME MEASURES: Primary outcome was fall incidence within 1 year. Secondary outcomes were PPA battery (overall fall risk index, vision, muscular strength, reaction time, balance, and proprioception), Timed Up & Go (TUG) test, Taiwan version of the International Physical Activity Questionnaire, EuroQol-5D, Geriatric Depression Scale (GDS), and the Falls Efficacy Scale-International at 3 months after randomization. RESULTS: Participants were 76±7 years old and included low risk 25.6%, moderate risk 25.6%, and marked risk 48.7%. The cumulative 1-year fall incidence was 25.2% in the IG and 27.6% in the CG (hazard ratio=.90; 95% confidence interval, .66-1.23). The IG improved more favorably than the CG on overall PPA fall risk index, reaction time, postural sway with eyes open, TUG test, and GDS, especially for those with marked fall risk. CONCLUSIONS: The multifactorial fall prevention program with exercise intervention improved functional performance at 3 months for community-dwelling older adults with risk of falls, but did not reduce falls at 1-year follow-up. Fall incidence might have been decreased simultaneously in both groups by heightened awareness engendered during assessments, education, referrals, and recommendations.

Walking performance of persons with chronic stroke changed when looking down but not in dimly lit environment.

Background and purpose: It is common to walk under different conditions, such as looking straight head, looking down at the feet or in dimly lit environment. The purpose of this study was to determine the impact of these different conditions on walking performance in persons with and without stroke. Methods: This was a case-control study. Persons with chronic unilateral stroke and age-matched control (n = 29 each) underwent visual acuity test, Mini Mental Status Examination (MMSE) and joint position sense test of the knee and ankle. The participants walked at their preferred speed under three walking conditions, looking ahead (AHD), looking down (DWN), and in dimly lit environment (DIM). A motion analysis system was used for the recording of the limb matching test and walking tasks. Results: Stroke participants differed from the control group in MMSE, but not in age, visual acuity or joint position sense. For the control group, the differences between the three walking conditions were nonsignificant. For the stroke group, DWN had significantly slower walking speed, greater step width and shorter single leg support phase, but not different symmetry index or COM location, compared to AHD. The differences between AHD and DIM were nonsignificant. Conclusion: Healthy adults did not change their gait patterns under the different walking conditions. Persons with chronic stroke walked more cautiously but not more symmetrically when looking down at the feet, but not in dimly lit environment. Ambulatory persons with stroke may need to be advised that looking down at the feet while walking could be more challenging.