Increased serum adipokines are associated with sarcopenia in non-obese women with rheumatoid arthritis.

Large cohort studies have disclosed the association between obesity and rheumatoid arthritis (RA) risk. The sarcopenia prevalence in RA patients can be up to 31%. However, there is little information linking adipokines to sarcopenia in RA, so this study aimed to investigate whether adipokines were indeed involved in secondary sarcopenia in RA with a focus on non-obese females. Sixty-four female patients and 36 controls were included in this study. The serum adipokine levels (leptin and adiponectin) were determined by ELISA kits. The impacts of adipokines on muscle atrophy and potential autophagy were examined in mouse myoblasts, C2C12, upon treatment with recombinant leptin and adiponectin agonist (AdipoRan). Interestingly, serum adiponectin was significantly increased but the ratio of leptin/adiponectin was dramatically decreased in the RA patients with sarcopenia. After normalization by body mass, serum leptin was positively associated but adiponectin was negatively associated with muscle mass respectively, even after adjustment for fat mass. Treating C2C12 cells with leptin and AdipoRan inhibited proliferation of mature myotube respectively, as did treatment with the serum from RA patients. A combination of low leptin and high AdipoRan greatly decreased myogenin, but instead increased MAFbx and MuRF-1 as well as increased Beclin 1, Atg5, and LC3ß. Taken together, our study reveals that secondary sarcopenia of RA females may be an imbalance of RA-related, but not obesity-related, increase in adipokine production; additionally, the reduced leptin/adiponectin ratio could be a better indicator in monitoring sarcopenia in non-obese RA females. Moreover, adipokine imbalance may promote muscle atrophy through inducing autophagy.

Testing a Conceptual Model of Physiologic Reserve, Intrinsic Capacity, and Physical Resilience in Hospitalized Older Patients: A Structural Equation Modelling.

INTRODUCTION: The relationship among physiologic reserve, intrinsic capacity, and physical resilience has not been examined, and a conceptual model that includes these key determinants of healthy ageing is needed. This study aimed to test a conceptual model using real-world data to determine the relationships among physiologic reserve, intrinsic capacity, physical resilience, and clinical outcomes. METHODS: This longitudinal study was conducted at a 1,343-bed tertiary-care medical centre. Patients were eligible for inclusion if they were 65 years of age or older and able to communicate independently. Demographic factors, cumulative illness rating scale for geriatrics [CIRS-G] (assessing physiologic reserve), intrinsic capacity, physical resilience instrument for older adults [PRIFOR] (assessing physical resilience), and clinical frailty scale [CFS] were collected at admission. The CFS and EuroQoL 5-dimension 3-level questionnaire [EQ5D] were administered at discharge. RESULTS: The mean age of the 413 patients was 76.34 ± 6.72 (52.5% female). Two conceptual models were identified and supported. Specifically, the path coefficients in the two models showed that the CIRS-G had diverse associations with each intrinsic capacity domain, and that all intrinsic capacity domains (except vitality) were significantly associated with PRIFOR. Moreover, PRIFOR was significantly associated with follow-up CFS, baseline control, and EQ5D scores. CONCLUSION: Physiologic reserve positively correlated with the cognitive and locomotive domains of intrinsic capacity. Moreover, older patients with better intrinsic capacity may have improved physical resilience, which may lead to better clinical outcomes. Efforts to improve the intrinsic capacity and physical resilience of older patients are necessary to promote healthy ageing.

NLRP3 Gene Polymorphisms in Rheumatoid Arthritis and Primary Sjogren's Syndrome Patients.

Aim: The activation of NLRP3 inflammasome leads to the stimulation of cytokines and is significantly involved in the pathogenesis and progression of autoimmune diseases. The purpose of this study is to examine the associations of NLRP3 gene polymorphisms with rheumatoid arthritis (RA) and primary Sjogren's syndrome (SS) patients. Methods: A total of 239 patients with RA, 285 patients with primary SS, and 170 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells, and gene polymorphisms were genotyped through the TaqMan assay. Antinuclear antibody (ANA), anti-Ro, and anti-CCP antibodies were detected using immunofluorescence immunoassay. Results: The T allele of rs4612666 CT elevated the susceptibility to RA disease. The RF titer during diagnosis of RA was significantly high in RA patients with the A allele of rs12079994 G/A polymorphism. The titer of anti-CCP during diagnosis of RA was high in the absence of the C allele of rs10754558 C/G polymorphisms in RA patients. Antinuclear antibody and anti-CCP were positively associated with the A allele of rs12079994 G/A polymorphism in primary SS. The C allele of rs4612666 C/T was negatively associated with ANA in primary SS. Conclusions: The results have shown that NLRP3 gene polymorphisms may play a role in the pathogenesis of RA and primary SS.

A multi-strain probiotic blend reshaped obesity-related gut dysbiosis and improved lipid metabolism in obese children.

Background and aims: Obese children are more prone to becoming obese adults, and excess adiposity consequently increases the risk of many complications, such as metabolic syndromes, non-alcoholic fatty liver disease, cardiovascular disease, etc. This study aimed to evaluate the effects of multi-strain probiotics on the gut microbiota and weight control in obese children. Methods: A double-blind, randomized, placebo-controlled trial was carried out on overweight and obese children. Subjects received 12 weeks of treatment with supplementary probiotics that contained three strains: Lactobacillus salivarius AP-32, L. rhamnosus bv-77, and Bifidobacterium animalis CP-9, plus diet and exercise guidance. A total of 82 children were enrolled, and 53 children completed the study. Results: The supplementation of multi-strain probiotics resulted in a significant effect demonstrating high-density lipoprotein (HDL) and adiponectin elevation. At the same time, body mass index (BMI) and serum total cholesterol, low-density lipoprotein (LDL), leptin, and tumor necrosis factor-alpha (TNF-α) levels were reduced. Lactobacillus spp. and B. animalis were particularly increased in subjects who received probiotic supplements. The abundance of Lactobacillus spp. was inversely correlated with the ether lipid metabolism pathway, while that of B. animalis was positively correlated with serum adiponectin levels. Conclusion: Our results show that obesity-related gut dysbiosis can be reshaped by the supplementation of a multi-strain probiotic to improve lipid metabolism. The regular administration of a multi-strain probiotic supplement may be helpful for weight control and health management in overweight and obese children.

The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.

Liver fibrosis is a key pathophysiology process in chronic liver disease. It is still unclear whether the impact of liver fibrosis is not fully realized in type 2 diabetes mellitus (T2D) patients with nonalcoholic fatty liver disease (NAFLD), and the factors affecting nonalcoholic steatohepatitis (NASH) or liver stiffness also remain unclear. The aim of this study was to evaluate the determinants of liver fibrosis and in T2D patients with NAFLD. Liver fibrosis and steatosis were measured using transient elastography (FibroScan). Of 226 T2D patients with NAFLD, 50 with liver fibrosis had higher body mass index, serum uric acid, triglyceride and glycated hemoglobin levels and lower high density lipoprotein levels than 176 without liver fibrosis. Multivariate analysis revealed that aging, obesity, sulfonylurea usage and high levels of AST increased the risk of liver fibrosis in T2D patients with NAFLD. Our findings provide useful information to clinical physicians for earlier detection of liver fibrosis in T2D patients with NAFLD and to prevent liver fibrosis through controlling these risk factors.

Lower HDAC6 mRNA expression and promoter hypomethylation are associated with RA susceptibility.

BACKGROUND/PURPOSE: Recent studies showed that Histone deacetylases 6 (HDAC6) inhibitors could improve arthritis in rheumatoid arthritis (RA) rodent models, whereas lower HDAC6 expression was observed in RA patients' synovial fibroblasts, raising the concerns to use HDAC6 inhibitors to treat RA patients. In the present study, we investigated the involvement of HDAC6 mRNA expression and promoter methylation in RA. METHODS: The DNA and RNAs were extracted from the peripheral blood mononuclear cells (PBMCs) from 138 RA patients and 102 healthy controls. The pyrosequencing technique was used for promoter methylation analysis. The quantitative real-time polymerase chain reaction was used to determine the HDAC6 mRNA expression. The patients' clinical characteristics and disease biomarkers were recorded when blood sampling. RESULTS: The HDAC6 mRNA expression was lower in the RA patients than controls (p = 0.001). The RA patients had significant hypomethylation of the HDAC6 promoter (p < 0.001). The HDAC6 promoter was hypo-methylated in the -229, -225, -144, and -142 CpG sites in RA patients (p < 0.05). Unexpectedly, promoter methylation and mRNA expression of the HDAC6 gene were positively associated (p < 0.001). The HDAC6 mRNA expression and promoter methylation status were associated with the risk of RA (p = 0.006 and 0.002, respectively). The inflammatory cytokines, TNF-α and IL-6, were significantly increased after HDAC6 knockdown in PMA-stimulated THP1 cells and SW982 cells (p < 0.05). CONCLUSION: The HDAC6 mRNA expression and promoter methylation were lower in RA patients. Both HDAC6 mRNA expression level and promoter hypomethylation were associated the susceptibility of RA. HDAC6 inhibitors seem not proper for RA patients' treatment.

Exploring the Mediating Effects of Cognitive Function, Social Support, Activities of Daily Living and Depression in the Relationship between Age and Frailty among Community-Dwelling Elderly.

With 16.15% of its total population aged 65 or above, Taiwan is already an aging society. Frailty is a natural consequence of aging, which may decrease physical strength and deteriorate physiological functioning. We examined the mediating effects of cognitive function, social support, activities of daily living (ADL), and depression in the relationship between age and frailty in older people living in the community. This cross-sectional study used a structured questionnaire to collect data from a convenience sample of 200 pre-frail to mildly frail older adults in southern Taiwan. Structural equation modeling was used for data analysis, with data collected from July to November 2020. ADL mediated the relationship between age and frailty, while cognitive function also mediated the relationship between age and frailty, indicating that ADL and cognitive function were significant determinants of frailty. The path from age to frailty was significant, indicating that age was a significant determinant of frailty. The standardized total effect of age affected frailty through the mediating roles of ADL and cognitive function. Age, depression, ADL, and cognitive function explained 59% of the variance in frailty among older adults. ADL and cognitive function are significant mediators of frailty among older adults.

Factors associated with do-not-resuscitate document completion among patients hospitalized in geriatric ward.

BACKGROUND: With a rapidly aging population, there is an increasing need for do-not-resuscitate (DNR) and advance care planning (ACP) discussions. This study investigated the factors associated with signing DNR documents of older patients in the geriatric ward. METHODS: We conducted a retrospective cohort study at a geriatric ward in a tertiary hospital in Southern Taiwan. Three hundred and thirty-seven hospitalized older patients aged ≥65 years in the geriatric ward from 2018 to 2019. The Hospital Information System and electronic medical records were accessed to obtain details regarding patients' demographics, daily living activities, serum albumin level, nutrition screening score, intensive care unit transferal, resuscitation procedure, days of hospital stay, and survival status on discharge, and DNR status was recorded retrospectively. Patients were classified into DNR and non-DNR groups, with t-tests and Chi-square tests applied to compare the differences between groups. Logistic regression was performed to predict factors related to the DNR documents. RESULTS: A total of 337 patients were included, 66 of whom had signed a DNR during hospitalization. After multivariate logistic regression, age 85 or more compared to age 65-74 (adjusted odds ratio, aOR 5.94), poor nutrition with screening score two or more (aOR 2.71), albumin level less than 3 (aOR 3.24), Charlson Comorbidity Index higher than 2 (aOR 2.46) and once transferred to ICU (aOR 5.11) were independently associated with DNR documentation during hospitalization. CONCLUSIONS: Several factors related to DNR documents for geriatric patients were identified which could provide clinical information for physicians, patients, and their families to discuss DNR and ACP.

Association of F11R polymorphisms and gene expression with primary Sjögren's syndrome patients.

AIMS: F11R gene encodes junctional adhesion molecule-A protein (JAM-A), which is expressed in various types of cells and is involved in leukocyte extravasation during inflammation. Sjögren's syndrome (SS) is a chronic systemic inflammatory disease that involves lymphocytes invasion of exocrine glands. F11R has been studied in autoimmune diseases, but any association between F11R and SS has not yet been investigated. Therefore, experiments were undertaken to examine the relationships among F11R gene polymorphism, messenger RNA (mRNA) expression and SS patients. METHODS: Three hundred and twenty-nine patients with SS, and 223 healthy controls were enrolled in their recruitment from the Kaohsiung Medical University Hospital. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphisms were genotyped by TaqMan real-time polymerase chain reaction (PCR). F11R mRNA expression was quantitated by quantitative real-time PCR with TaqMan Gene Expression Assay. RESULTS: Our study showed the genotype -688A/C (rs6695707) was not found in relation to SS patients. The odds ratio of -436A/G (rs12567886) genotype was notably associated with less susceptibility of SS in human leukocyte antigen (HLA)-DR2 negative and HLA-DR3 negative individuals. F11R mRNA expression was lower in SS patients than in the cells of healthy controls. CONCLUSION: The result indicated that G allele of -436A/G genotype has the potential protective effect against SS disease condition. F11R mRNA was expressed significantly lower in SS patients.

The influence of integrated geriatric outpatient clinics on the health care utilization of older people.

BACKGROUND: The number of people aged greater than 65 years is growing in many countries. Taiwan will be a superaged society in 2026, and health care utilization will increase considerably. Our study aimed to evaluate the efficacy of the geriatric integrated outpatient clinic model for reducing health care utilization by older people. METHODS: This was a retrospective case-control study. Patients aged greater than 65 years seen at the geriatric outpatient clinic (Geri-OPD) and non-geriatric outpatient clinic (non-Geri-OPD) at a single medical centre were age and sex matched. Data on the number of outpatient clinic visits, emergency department visits, hospitalizations and medical expenditures were collected during the first and second years. A subgroup analysis by Charlson comorbidity index (CCI) and older age (age≧80 years) was performed, and the results were compared between the Geri-OPD and non-Geri-OPD groups. RESULTS: A total of 6723 patients were included (3796 women and 2927 men). The mean age was 80.42 ± 6.39 years. There were 1291 (19.2%) patients in the Geri-OPD group and 5432 (80.8%) patients in the non-Geri-OPD group. After one year of regular follow-up, the Geri-OPD patients showed a significant reduction in the types of drugs included in each prescription (5.62 ± 10.85) and the number of clinic visits per year (18.18 ± 48.85) (P < 0.01). After a two-year follow-up, the number of clinic visits, emergency department visits, and hospitalizations and the annual medical costs were still decreased in the Geri-OPD patients. The Geri-OPD patients had more comorbidities and a higher rate of health care utilization than the non-Geri-OPD patients. In the subgroup analysis, patients with more comorbidities (CCI≧2) and an older age (≧80 years) in the Geri-OPD group showed a significant reduction in health care utilization. The Geri-OPD patients also showed a significant decrease in medical utilization in the second year compared with the non-Geri-POD patients. CONCLUSION: The Geri-OPD reduced medical costs, the number of drugs prescribed, and the frequency of outpatient clinic visits, emergency department visits and hospitalizations in older patients with complicated conditions. The effect was even better in the second year.

Impact of orthogeriatric care, comorbidity, and complication on 1-year mortality in surgical hip fracture patients: An observational study.

After acute hip surgery, the 1-year mortality rate is high. Therefore, this study evaluated the risk factors for 1-year mortality. The purposes of this study was first to examine the effect of integrated care on 1-year mortality in surgical patients and secondly to explore magnitude of comorbidity and complication on mortality.This retrospective cohort study included 313 patients received surgery for hip fragility fracture. Patients with multiple fractures or combined trauma were excluded. The patients were grouping into integrated (n = 106) and non-integrated care group (n = 207) models. Univariate and multiple Cox regression were used to examine effect of care model, comorbidity, and complication event.One-year mortality in integrated and non-integrated patients was 4.7% and 14.0% respectively. After adjustments, patients in non-integrated care, have 2.89 times (95% confidence interval [CI] 1.07-7.81) likely to die 1-year after discharged.Patients had elevated comorbidity or postoperative complications contributed to the mortality. Our study found the effect of patients treated by integrated care models, compared with usual model, significantly reduced 1-year mortality rate. Appropriated treatment of comorbidities during hospitalization and after discharge is critical to post-surgical survival. The findings imply that the co-care for hip fracture of hip surgical patients with orthogeriatricians is strongly recommended, particularly for those with >3 comorbidities.

Methylation and gene expression of histone deacetylases 6 in systemic lupus erythematosus.

AIM: The purpose of this study is to investigate the role of methylation in the histone deacetylases 6 (HDAC6) promoter and HDAC6 messenger RNA (mRNA) expression in the pathogenesis of systemic lupus erythematosus (SLE). METHOD: Direct bisulfite-polymerase chain reaction (PCR) sequencing was performed to detect the HDAC6 promoter methylation in 33 patients with SLE and 35 healthy controls. The HDAC6 mRNA expression was measured in 93 SLE patients and 84 healthy controls by using the method of quantitative real-time PCR. RESULTS: This study demonstrated that the methylation rates at HDAC6-680, -660 and -658 were significantly increased in the SLE patients compared with healthy controls (P = 0.041, 0.034 and 0.029, respectively). The SLE patients also had lower HDAC6 mRNA expression than the controls (P = 0.031). However, there was no significant difference in HDAC6 mRNA expression between patients with active and inactive SLE. CONCLUSION: The SLE patients had higher methylation in the HDAC6 promoter and lower HDAC6 mRNA expression than the controls. These changes may be related to the susceptibility of SLE. However, they are not associated with the disease activity of SLE.

F11R mRNA expression and promoter polymorphisms in patients with rheumatoid arthritis.

AIM: Although F11 receptor (F11R), also named junctional adhesion molecular A (JAM-A), participates in leukocyte migration, its role in autoimmune diseases has not been specifically disclosed. In this study, we examined the association of F11R expression with the development and clinical manifestations of rheumatoid arthritis (RA). METHOD: RNA from peripheral blood mononuclear cells (PBMCs) and DNA from the peripheral blood in RA patients and a healthy control group were extracted. F11R messenger RNA (mRNA) expression was determined by quantitative real-time polymerase chain reaction. The F11R polymorphisms were determined by the TaqMan genotyping assay. RESULTS: There was more F11R mRNA expression in the PBMCs of RA patients than those of the control group (P = 0.018). In F11R promoter -688 A > C, C carriers have lower titers of the anticyclic citrullinated peptide (anti-CCP) antibodies (P = 0.002) and fewer positive rates of Schirmer's tests (P = 0.009). The effect is independent of the existence of HLA-DR4. Different genotypes in F11R promoter -688 A > C and -436 A > G do not lead to changes of the gene expression in RA patients. CONCLUSION: RA patients have higher mRNA expression of F11R. In RA patients, F11R -688 C may be a protective factor for the development of anti-CCP antibodies and positive rates of Schirmer's tests.

Global DNA methylation, DNMT1, and MBD2 in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the associations of DNA methylation levels and mRNA expressions of DNA cytosine-5-methyltransferase 1 (DNMT1) and methyl CpG-binding domain 2 (MBD2) with rheumatoid arthritis (RA). METHODS: The global methylation status of DNA was measured in 65 patients with RA and 64 healthy controls by the ELISA method. DNMT1 and MBD2 mRNA were also detected in 177 RA patients and 95 controls using the quantitative real-time polymerase chain reaction method. RESULTS: The global methylation of DNA was significantly decreased in the RA patients compared to the controls (p=0.005, 95% CI=0.0835-0.4503). The patients with RA had higher expressions of DNMT1 and MBD2 mRNA than the controls (p<0.001, 95% CI=-0.0024 to -0.0053 and p<0.001, 95% CI=-0.0079 to -0.0167, respectively). We also found that the MBD2 mRNA level was not related to the disease activity of RA. However, the expression of DNMT1 mRNA tended to be associated with the disease activity of RA (p=0.08). The levels of DNA methylation and DNMT1 mRNA were significantly decreased in the patients with anti-CCP antibody compared with those without (p=0.005, 95% CI=-0.7333 to -0.1373 and p=0.003, 95% CI=-0.0071 to -0.0022, respectively). The differences in the methylation level and expressions of DNMT1 and MBD2 were not significant between the patients treated with and without anti-TNFα biological agents (Enbrel or Humira). CONCLUSION: This study demonstrated that the RA patients have a significantly lower level of DNA methylation than the controls. Moreover, RA patients have higher expressions of DNMT1 and MBD2 mRNA. The anti-TNFα biological agents do not seem to affect DNA methylation and mRNA expressions of DNMT1 and MBD2 in RA patients.

Previous hepatitis a virus infection is related to slower psychomotor speed in elderly adults.

BACKGROUND: Patients with chronic viral hepatitis are at a higher risk for cognitive dysfunction. Little is known about the association between hepatitis A virus (HAV) infection and cognitive function. METHODS: From the National Health and Nutrition Examination Survey, 1999-2002, we selected study participants (> or =60 years, n = 1,529) without hepatitis B, C, or D virus infection; without previous hepatitis A vaccination; and without abnormal liver function. HAV-seropositive participants represented people with previous HAV infection. Psychomotor speed and executive functioning domain of cognitive function were measured by the Digit Symbol Substitution Test (DSST). RESULTS: HAV-seropositive participants had lower DSST scores than HAV-seronegative participants (weighted mean, 44.4 vs 53.9, p < .001). We designated HAV-seronegative participants as the reference group. Univariate analysis demonstrated that the weighted beta coefficient of DSST score was -9.55 (95% confidence interval [CI] -9.57 to -9.54, p < .001) for the HAV-seropositive participants. In a multivariable model, the weighted adjusted beta coefficient of DSST score was -2.48 (95% CI -2.49 to -2.46, p < .001) for the HAV-seropositive participants. CONCLUSION: HAV seropositivity is associated with slower psychomotor speed among the U.S. community-dwelling elders.

Spontaneous retroperitoneal hemorrhage in a mediastinal tumor in a patient with polymyositis: a case report.

Spontaneous retroperitoneal hemorrhage is a lethal cause of acute abdomen that is most frequently related to drugs, coagulopathy and intra-abdominal tumors. In patients with polymyositis and dermatomyositis, acute abdomen is attributed to intestinal vasculitis causing ischemia, ulceration or perforation. Spontaneous retroperitoneal hemorrhage, however, has rarely been reported in patients with polymyositis. We report the case of a 65-year-old woman with newly diagnosed polymyositis and suspected thymoma who suffered from spontaneous retroperitoneal hemorrhage. She experienced two massive retroperitoneal hemorrhage episodes within 24 hours, which resulted in shock and required emergent angiographic embolization. There was no evidence of tumor, vasculitis or aneurysm from abdominal angiography and computed tomography.