Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy.

OBJECTIVE: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. METHODS: Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician's Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. RESULTS: Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (ß = 3.830; p < 0.0001), muscle VAS (ß = 2.893; p < 0.0001), MMT8 (ß=-19.368; p < 0.0001), and creatine kinase (CK) levels (ß = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (ß = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). CONCLUSION: In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis.

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.

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.

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.

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.

Carrier-Free Nanovaccine: An Innovative Strategy for Ultrahigh Melanoma Neoantigen Loading.

In personalized cancer immunotherapy, developing an effective neoantigen nanovaccine with high immunogenicity is a significant challenge. Traditional nanovaccine delivery systems often require nanocarriers, which can hinder the delivery of the neoantigen and cause significant toxicity. In this study, we present an innovative strategy of carrier-free nanovaccine achieved through direct self-assembly of 2'-fluorinated CpG (2'F-CpG) with melanoma neoantigen peptide (Obsl1). Molecular dynamics simulations demonstrated that the introduction of a fluorine atom into CpG increases the noncovalent interaction between 2'F-CpG and Obsl1, which enhanced the loading of Obsl1 on 2'F-CpG, resulting in the spontaneous formation of a hybrid 2'F-CpG/Obsl1 nanovaccine. This nanovaccine without extra nanocarriers showed ultrahigh Obsl1 loading up to 83.19 wt %, increasing the neoantigen peptide uptake by antigen-presenting cells (APCs). In C57BL/6 mice models, we demonstrated the long-term preventive and therapeutic effects of the prepared 2'F-CpG/Obsl1 nanovaccine against B16F10 melanoma. Immunocellular analysis revealed that the nanovaccine activated innate and adaptive immune responses to cancer cells. Hence, this study established a simple, safe, and effective preparation strategy for a carrier-free neoantigen nanovaccine, which could be adapted for the future design of personalized cancer vaccines in clinical settings.

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.

Clinical, radiological and pathological features of anti-MDA5 antibody-associated interstitial lung disease.

INTRODUCTION: To investigate the clinical, radiographic and pathological features of interstitial lung disease (ILD) in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5+DM). METHODS: We retrospectively analysed the medical records of patients with anti-MDA5+DM who had undergone radiological examination, and lung histopathology was performed on 17 of them. RESULTS: This study examined 329 patients with anti-MDA5+DM, of whom 308 (93.6%) were diagnosed with ILD and 177 (53.8%) exhibited rapidly progressive ILD (RPILD). The most common radiographic patterns were organising pneumonia (OP) (43.2%), non-specific interstitial pneumonia (NSIP) (26.4%) and NSIP+OP (18.5%). Histological analysis showed NSIP (41.2%) and NSIP+OP (47.1%) to be the predominant patterns. However, in the 17 patients who underwent lung histopathology, the coincidence rate between radiological and histopathological diagnoses was only 11.8%. Compared with patients without RPILD, those with RPILD showed a higher prevalence of NSIP+OP (26.6% vs 10.7%, p=0.001) and a lower prevalence of NSIP pattern (21.5% vs 37.4%, p=0.002) on high-resolution CT. Furthermore, patients with radiographic patterns of NSIP+OP or diffuse alveolar damage (DAD) had more risk factors for poor prognosis, with 12-month mortality rates of 45.9% and 100%, respectively. CONCLUSIONS: RPILD was commonly observed in patients with anti-MDA5+DM. OP was identified as the predominant radiographic pattern, which corresponded to a histopathological pattern of NSIP or NSIP+OP. Notably, patients exhibiting radiographic patterns of NSIP+OP or DAD were shown to have a poor prognosis.

Decrease in cell counts and alteration of phenotype characterize peripheral NK cells of patients with anti-MDA5-positive dermatomyositis.

OBJECTIVE: To investigate the levels and phenotypes of peripheral natural killer (NK) cells in anti-MDA5+ dermatomyositis (DM) patients, and their association with clinical features. METHODS: Peripheral NK cell counts (NKCCs) were retrospectively collected from 497 patients with idiopathic inflammatory myopathies and 60 healthy controls. Multi-color flow cytometry was used to determine the NK cell phenotypes in additional 48 DM patients and 26 healthy controls. The association of NKCC and NK cell phenotypes with the clinical features and prognosis were analyzed in anti-MDA5+ DM patients. RESULTS: NKCC was significantly lower in anti-MDA5+ DM patients than in those with other IIM subtypes and healthy controls. A significant decrease in NKCC was associated with disease activity. Furthermore, NKCC < 27 cells/µL was an independent risk factor for 6-month mortality in anti-MDA5+ DM patients. In addition, identification of the functional phenotype of NK cells revealed significantly increased expression of the inhibitory marker CD39 in CD56brightCD16dimNK cells of anti-MDA5+ DM patients. CD39+NK cells of anti-MDA5+ DM patients showed increased expression of NKG2A, NKG2D, Ki-67, decreased expression of Tim-3, LAG-3, CD25, CD107a, and reduced TNF-α production. CONCLUSION: Decreased cell counts and inhibitory phenotype are significant characteristics of peripheral NK cells in anti-MDA5+ DM patients.

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.

Associations between blood-based biomarkers of Alzheimer's disease with cognition in motoric cognitive risk syndrome: A pilot study using plasma Aß42 and total tau.

Background: Motoric cognitive risk (MCR) syndrome is a conceptual construct that combines slow gait speed with subjective cognitive complaints and has been shown to be associated with an increased risk of developing dementia. However, the relationships between the pathology of Alzheimer's disease (AD) and MCR syndrome remain uncertain. Therefore, the purpose of this study was to determine the levels of plasma AD biomarkers (Aß42 and total tau) and their relationships with cognition in individuals with MCR. Materials and methods: This was a cross-sectional pilot study that enrolled 25 individuals with normal cognition (NC), 27 with MCR, and 16 with AD. Plasma Aß42 and total tau (t-tau) levels were measured using immunomagnetic reduction (IMR) assays. A comprehensive neuropsychological assessment was also performed. Results: The levels of plasma t-tau proteins did not differ significantly between the MCR and AD groups, but that of plasma t-tau was significantly increased in the MCR and AD groups, compared to the NC group. Visuospatial performance was significantly lower in the MCR group than in the NC group. The levels of plasma t-tau correlated significantly with the Montreal Cognitive Assessment (MoCA) and Boston naming test scores in the MCR group. Conclusion: In this pilot study, we found significantly increased plasma t-tau proteins in the MCR and AD groups, compared with the NC group. The plasma t-tau levels were also significantly correlated with the cognitive function of older adults with MCR. These results implied that MCR and AD may share similar pathology. However, these findings need further confirmation in longitudinal studies.

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.

The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis.

Aims: This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled via traditional pairwise meta-analysis and Bayesian network meta-analysis. Results: The pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective non-users. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%. Conclusion: Metformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably had the most significant protective effect against death, followed by SGLT2i and metformin. Systematic Review Registration: PROSPERO (CRD42021288200).

Executive function predict the quality of life and negative emotion in older adults with diabetes: A longitudinal study.

AIMS: To investigate the influence of executive function (EF) on current and future quality of life (QoL) and negative emotion (NE) in older adults with diabetes. METHODS: A total of 128 older adults with diabetes were recruited. Independent variables (demographic information, health and medical conditions, cognitive function, life function) were collected in the first year. Dependent variables (QoL and NE) were collected for 3 years. Pearson's correlation coefficient analysis and stepwise multiple linear regression analysis were performed to identify the predictors of QoL and NE. RESULTS: EF was the strongest predictor for overall QoL and NE in all 3 years, and accounted for 23.0-36.2% and 11.1-17.1% of the variance, respectively. The second strongest predictor for overall QoL in all 3 years was pain interference, which accounted for 3.2-5.8% of the variance. Pain interference was also the second strongest predictor for NE in the second year, accounting for 5.5% of the variance. CONCLUSIONS: The present study revealed that EF is more predictive than pain for current and future QoL and NE in older adults with diabetes. We recommend that EF be included as an indicator for diabetes surveillance, and that prevention of EF decline be a part of diabetes management plans.

Resistin Expression Is Associated With Interstitial Lung Disease in Dermatomyositis.

Objective: In the current study, we aimed to assess resistin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of dermatomyositis patients with interstitial lung disease (DM-ILD) and their correlation with disease activity. Methods: We detected resistin mRNA levels in the PBMCs of 37 DM-ILD, 8 DM patients without ILD, and 19 healthy control (HC) subjects by performing quantitative reverse transcription real-time polymerase chain reaction analysis. Associations between resistin expression levels and major clinical manifestations, laboratory examinations, and disease activity were also analyzed. In addition, resistin expression in lung specimens from patients with DM-ILD was examined via immunohistochemistry and immunofluorescence. Results: Resistin mRNA levels in PBMCs were significantly higher in DM-ILD than that in DM patients without ILD and HCs (p = 0.043, 0.014, respectively). Among these DM-ILD patients, the resistin levels were significantly elevated in those with rapidly progressive ILD than in those with chronic ILD (p = 0.012). The resistin mRNA levels in DM-ILD positively correlated with serum alanine aminotransferase (r = 0.476, p = 0.003), aspartate aminotransferase (r = 0.488, p = 0.002), lactate dehydrogenase (r = 0.397, p = 0.014), C-reactive protein (r = 0.423, p = 0.008), ferritin (r = 0.468, p = 0.003), carcinoembryonic antigen (r = 0.416, p = 0.011), carbohydrate antigen 125 (r = 0.332, p = 0.047), interleukin-18 (r = 0.600, p < 0.001), and lung visual analog scale values (r = 0.326, p = 0.048), but negatively correlated with the diffusing capacity of carbon monoxide (DLco)% (r = -0.447, p = 0.041). Immunohistochemical analysis of resistin showed its elevated expression in the macrophages, alveolar epithelial cells, and weak fibrotic lesions from patients with DM-ILD. Immunofluorescence staining confirmed CD68+ macrophages co-express resistin. Conclusions: Resistin levels were increased in patients with DM-ILD and associated with disease activity and ILD severity. Therefore, resistin may participate in the pathogenesis of DM-ILD and may act as a useful biomarker.

Elevated Serum IGFBP-2 and CTGF Levels Are Associated with Disease Activity in Patients with Dermatomyositis.

Background: Insulin-like growth factor-binding proteins (IGFBPs) and connective tissue growth factor (CTGF) participate in angiogenesis. Dermatomyositis (DM) is characterized by microvasculopathy-derived skin lesions. Here, we investigated the clinical significance of serum IGFBP and CTGF levels in DM patients. Methods: In this study, 65 DM patients and 30 healthy controls were enrolled. Serum IGFBP and CTGF levels were examined by ELISA, and their correlation with clinical and laboratory findings was analyzed by Spearman's correlation. Results: Serum IGFBP-2, IGFBP-4, and CTGF levels were higher in DM patients than in healthy controls (median (quartile): 258.9 (176.4-326.1) ng/mL vs. 167.7 (116.1-209.4) ng/mL, p < 0.0001; 450.4 (327.3-631.8) ng/mL vs. 392.2 (339.0-480.2) ng/mL, p = 0.04; and 45.71 (38.54-57.45) ng/mL vs. 35.52 (30.23-41.52) ng/mL, p = 0.001, respectively). IGFBP-2 and CTGF levels were positively correlated with cutaneous (r = 0.257, p = 0.040 and r = 0.427, p = 0.015, respectively) and global (r = 0.380, p = 0.002 and r = 0.292, p = 0.019, respectively) disease activity in DM patients. Conclusion: Serum IGFBP-2 and CTGF levels were increased in patients with DM and correlated with cutaneous and global disease activity.

Comparison of NH3 and N2O Plasma Treatments on Bi2O3 Sensing Membranes Applied in an Electrolyte-Insulator-Semiconductor Structure.

In this study, bismuth trioxide (Bi2O3) membranes in an electrolyte-insulator-semiconductor (EIS) structure were fabricated with pH sensing capability. To optimize the sensing performance, the membranes were treated with two types of plasma-NH3 and N2O. To investigate the material property improvements, multiple material characterizations were conducted. Material analysis results indicate that plasma treatments with appropriate time could enhance the crystallization, remove the silicate and facilitate crystallizations. Owing to the material optimizations, the pH sensing capability could be greatly boosted. NH3 or N2O plasma treated-Bi2O3 membranes could reach the pH sensitivity around 60 mV/pH and show promise for future biomedical applications.