Natural history and survival rate of familial amyloidosis with polyneuropathy: A nationwide databank.

OBJECTIVE: Hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy, a rare autosomal-dominant disease, has gained attention in recent years owing to treatment improvements. However, epidemiological real-world mega database of nationwide natural history and survival rates, especially with the specific mutation of Ala97Ser, are limited. METHODS: Taiwan National Health Insurance Research Database contains data from over 23 million individuals; Among them, 175 ATTRv amyloidosis patients validated by rare disease registry were enrolled. Multivariable Cox proportional hazard analyses were applied to investigate the association between baseline characteristics and all-cause mortality. FINDINGS: From 2008 to 2020, the annual incidence and prevalence rates of specific mutations (Ala97Ser) leading to ATTRv amyloidosis with polyneuropathy were 0.04-1.14 and 0.04-4.79 per million in Taiwan, respectively. In Taiwan, these patients exhibited male predominance with a mean age at validation of 62.75 years. At the 5th year after validation, patients exhibited a survival rate of approximately 50%, with higher mortality in male patients (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.15-4.31) and patients older at validation (HR: 1.10, 95% CI: 1.06-1.15). The two most common departments in outpatient were neurology and family medicine, and neurology and cardiology in inpatient. The three most common causes of death registered were unspecified amyloidosis (30.6%), organ-limited amyloidosis (20.9%), and neuropathic heredofamilial amyloidosis (9.7%). INTERPRETATION: The annual prevalence rate of specific mutation (Ala97Ser)-dominant ATTRv amyloidosis with polyneuropathy in Taiwan is comparable to the mid- to high-prevalence country level of the research by Schmidt et al. The extraordinarily high mortality, especially among patients older at validation, may reflect the inadequate awareness and the necessity of early intervention with novel disease-modifying regimens.

Inhibitory effect of PPARγ on NLRP3 inflammasome activation.

Rationale: Stimulation of the NLRP3 inflammasome by metabolic byproducts is known to result in inflammatory responses and metabolic diseases. However, how the host controls aberrant NLRP3 inflammasome activation remains unclear. PPARγ, a known regulator of energy metabolism, plays an anti-inflammatory role through the inhibition of NF-κB activation and additionally attenuates NLRP3-dependent IL-1ß and IL-18 production. Therefore, we hypothesized that PPARγ serves as an endogenous modulator that attenuates NLRP3 inflammasome activation in macrophages. Methods: Mouse peritoneal macrophages with exposure to a PPARγ agonist at different stages and the NLRP3 inflammasome-reconstituted system in HEK293T cells were used to investigate the additional anti-inflammatory effect of PPARγ on NLRP3 inflammasome regulation. Circulating mononuclear cells of obese patients with weight-loss surgery were used to identify the in vivo correlation between PPARγ and the NLRP3 inflammasome. Results: Exposure to the PPARγ agonist, rosiglitazone, during the second signal of NLRP3 inflammasome activation attenuated caspase-1 and IL-1ß maturation. Moreover, PPARγ interfered with NLRP3 inflammasome formation by decreasing NLRP3-ASC and NLRP3-NLRP3 interactions as well as NLRP3-dependent ASC oligomerization, which is mediated through interaction between the PPARγ DNA-binding domain and the nucleotide-binding and leucine-rich repeat domains of NLRP3. Furthermore, PPARγ was required to limit metabolic damage-associated molecular pattern-induced NLRP3 inflammasome activation in mouse macrophages. Finally, the mature caspase-1/PPARγ ratio was reduced in circulating mononuclear cells of obese patients after weight-loss surgery, which we define as an "NLRP3 accelerating index". Conclusions: These results revealed an additional anti-inflammatory role for PPARγ in suppressing NLRP3 inflammasome activation through interaction with NLRP3. Thus, our study highlights that PPARγ agonism may be a therapeutic option for targeting NLRP3-related metabolic diseases.

Interaction of central obesity and sarcopenia on nutritional status in the community-dwelling older people.

OBJECTIVES: To investigate the interrelationships between central obesity, sarcopenia and nutritional status in the elderly. METHODS: We enrolled 501 elderly (women: 47.5 %) with complete datasets. Biochemical and anthropometric data were measured after an overnight fast. Basic characteristics, psychosocial and behavioral factors, nutritional status, and history of chronic disease came from structured questionnaires. Central obesity was defined as waist circumference ≥ 90 cm for men, ≥ 80 cm for women. Sarcopenia was defined by the Asian consensus. Nutritional status was assessed using Mini Nutritional Assessment scores: abnormal nutritional status ≤ 23.5. Multiple logistic regression analysis was done to determine the independent factors of an abnormal nutritional status. RESULTS: Ninety (18.0 %) participants had an abnormal nutritional status, 300 (59.9 %) had central obesity, 52 (10.4 %) sarcopenia and 3 (0.6 %) sarcopenic obesity. Central obesity (OR = 0.455, 95 % CI: 0.244-0.847) and total lymphocyte count (OR = 0.526, 95 % CI: 0.315-0.880) were negatively and sarcopenia (OR = 3.170, 95 % CI: 1.485-6.767), current smoking (OR = 4.071, 95 % CI: 1.357-12.211), and total number of chronic diseases (OR = 1.484, 95 % CI: 1.234-1.785) were positively associated with abnormal nutritional status. An analysis of the combine effects of central obesity and sarcopenia on nutritional status showed that significantly fewer participants with central obesity but not sarcopenia had abnormal nutrition than participants with sarcopenia with or without central obesity (12.8 % vs 38.5 or 65.4 %, p < 0.001). CONCLUSIONS: Central obesity and sarcopenia were interactively associated with the nutritional status of older people living in a rural community.

Epidemiological survey of the feasibility of broadband ultrasound attenuation measured using calcaneal quantitative ultrasound to predict the incidence of falls in the middle aged and elderly.

OBJECTIVES: We investigated whether calcaneal quantitative ultrasound (QUS-C) is a feasible tool for predicting the incidence of falls. DESIGN: Prospective epidemiological cohort study. SETTING: Community-dwelling people sampled in central western Taiwan. PARTICIPANTS: A cohort of community-dwelling people who were ≥40 years old (men: 524; women: 676) in 2009-2010. Follow-up questionnaires were completed by 186 men and 257 women in 2012. METHODS: Structured questionnaires and broadband ultrasound attenuation (BUA) data were obtained in 2009-2010 using QUS-C, and follow-up surveys were done in a telephone interview in 2012. Using a binary logistic regression model, the risk factors associated with a new fall during follow-up were analysed with all significant variables from the bivariate comparisons and theoretically important variables. PRIMARY OUTCOME MEASURES: The incidence of falls was determined when the first new fall occurred during the follow-up period. The mean follow-up time was 2.83 years. RESULTS: The total incidence of falls was 28.0 per 1000 person-years for the ≥40 year old group (all participants), 23.3 per 1000 person-years for the 40-70 year old group, and 45.6 per 1000 person-years for the ≥70 year old group. Using multiple logistic regression models, the independent factors were current smoking, living alone, psychiatric drug usage and lower BUA (OR 0.93; 95% CI 0.88 to 0.99, p<0.05) in the ≥70 year old group. CONCLUSIONS: The incidence of falls was highest in the ≥70 year old group. Using QUS-C-derived BUA is feasible for predicting the incidence of falls in community-dwelling elderly people aged ≥70 years.

Cyclophilin A is associated with peripheral artery disease and chronic kidney disease in geriatrics: The Tianliao Old People (TOP) study.

Cyclophilin A (CyPA), secreted by vascular smooth muscle cells in response to oxidative stress, is important in the pathogenesis of progressive peripheral arterial occlusion disease (PAOD), which is common among chronic kidney disease. We explored the prevalence of PAOD in Taiwan's elderly (≥ 65 years old) population and its association with CyPA and renal function. Residents of Tianliao District, a rural community in southern Taiwan, were surveyed. An ankle-brachial index (ABI) < 0.91 was defined as PAOD. Chronic kidney disease (CKD) was defined based on eGFR levels < 60 mL/min/1.73 m(2). Serum CyPA was measured. Of the 473 participants, 68 (14.4%) had PAOD. Multiple logistic regression analysis showed PAOD was significantly associated with lower eGFR, lower BMI, higher glycated hemoglobin and higher pulse pressure. Serum CyPA levels in participants with PAOD were significantly higher than those with normal ABI values (47.3 ± 0.4 vs. 25.5 ± 0.2 ng/mL, p < 0.001). Moreover, eGFR inversely correlated with serum CyPA level (p < 0.05) in participants with CKD, but not in participants with normal renal function. In conclusion, with a prevalence of PAOD as high as 14.4% in an elderly community, CyPA might be the link between PAOD and advanced impaired renal function.

Moderate to severe, but not mild, nonalcoholic fatty liver disease associated with increased risk of gallstone disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GSD) share some of the same risk factors. The association between NAFLD and GSD was inconsistent. Moreover, there are no studies on the association between GSD and the severity of NAFLD in the literature. The aim of this study was to determine the relationship between the severity of NAFLD and GSD in a Taiwanese population. MATERIALS AND METHODS: A total of 12,033 subjects were enrolled. The diagnoses of GSD and NAFLD were based on the finding of abdominal ultrasonography. The severity of NAFLD was divided into mild, moderate, and severe. RESULTS: Compared with the non-GSD group, the GSD one was older and had a higher BMI, blood pressure, fasting plasma glucose, cholesterol, triglyceride, and higher prevalence of diabetes and hypertension, but they had a lower eGFR and HDL-C level and less prevalence of current smoking and alcohol drinking. There was a significant difference in the severity of NAFLD between subjects with and without GSD. Based on logistic regression, age ≥65 versus <40 years, 40-64.9 versus <40 years, female, current alcohol drinking, diabetes, hypertension, HDL-C level and moderate to severe NAFLD, but not mild NAFLD, were the independently associated risk factors of GSD. CONCLUSION: Moderate to severe, but not mild, NAFLD was associated with an increased risk of GSD, independent of the traditional cardio-metabolic risk factor. Age, female, diabetes, and hypertension were also related to a higher risk of GSD, but HDL-C level and moderate alcohol drinking showed a lower risk.

Epidemiological survey of quantitative ultrasound in risk assessment of falls in middle-aged and elderly people.

UNLABELLED: The risk assessment of falls is important, but still unsatisfactory and time-consuming. Our objective was to assess quantitative ultrasound (QUS) in the risk assessment of falls. Our study was designed as epidemiological cross-sectional study occurring from March 2009 to February 2010 by community survey at a medical center. The participants were collected from systemic sample of 1,200 community-dwelling people (Male/Female = 524/676) 40 years old and over in Yunlin County, Mid-Taiwan. Structural questionnaires including socioeconomic status, living status, smoking and drinking habits, exercise and medical history were completed. Quantitative ultrasound (QUS) at the non-dominant distal radial area (QUS-R) and the left calcaneal area (QUS-C) were measured. The overall prevalence of falls was 19.8%. In men, the independently associated factors for falls were age (OR: 1.04; 95%CI: 1.01~1.06), fracture history (OR: 1.89; 95%CI: 1.12~3.19), osteoarthritis history (OR: 3.66; 95%CI: 1.15~11.64) and speed of sound (OR: 0.99; 95%CI: 0.99~1.00; p<0.05) by QUS-R. In women, the independently associated factors for falls were current drinking (OR: 3.54; 95%CI: 1.35∼9.31) and broadband ultrasound attenuation (OR: 0.98; 95%CI: 0.97~0.99; p<0.01) by QUS-C. The cutoffs at -2.5< T-score<-1 derived using QUS-R (OR: 2.85; 95%CI: 1.64~4.96; p<0.01) in men or T-score ≦-2.5 derived using QUS-C (OR: 2.72; 95%CI: 1.42~5.21; p<0.01) in women showed an independent association with falls. The lowest T-score derived using either QUS-R or QUS-C was also revealed as an independent factor for falls in both men (OR: 2.13; 95%CI: 1.03~4.43; p<0.05) and women (OR: 2.36; 95%CI: 1.13~4.91; p<0.05). CONCLUSIONS: Quantitative ultrasounds, measured either at the radial or calcaneal area, are convenient tools by which to assess the risk of falls in middle-aged and elderly people.

Smoking, habitual tea drinking and metabolic syndrome in elderly men living in rural community: the Tianliao old people (TOP) study 02.

The literature shows an inconsistent relationship between lifestyle behaviors and metabolic syndrome (MetS), especially in the elderly. We designed this study to investigate the interrelationships among cigarette smoking, tea drinking and MetS, and to verify the factors associated with MetS in elderly males dwelling in rural community. In July 2010, with a whole community sampling method, 414 male subjects aged over 65 dwelling in Tianliao township were randomly sampled. The response rate was 60.8%. Each subject completed the structured questionnaires including sociodemographic characteristics, habitual behaviors (including cigarette smoking and tea drinking habits) and medical history. After an overnight fast, the laboratory and anthropometric data were obtained. MetS was confirmed according to the criteria defined by the modified NCEP ATP III for the male Chinese population. Subjects were split into either non-MetS or MetS groups for further analysis. Of the 361 subjects with complete data, 132 (36.6%) elderly men were classified as having MetS. Using binary logistic regression, body mass index, serum uric acid, high sensitivity C-reactive protein, HOMA index, current smokers (OR = 2.72, 95%CI: 1.03 ~ 7.19), total smoking amount > = 30 (OR = 2.78, 95%CI: 1.31 ~ 5.90) and more than 20 cigarettes daily (OR = 2.54, 95%CI: 1.24 ~ 5.18) were positively associated with MetS. Current un- or partial fermented tea drinker (OR = 0.42, 95%CI: 0.22 ~ 0.84), tea drinking habit for 1-9 years (OR = 0.36, 95%CI: 0.15 ~ 0.90) and more than 240 cc daily (OR = 0.35, 95%CI: 0.17 ~ 0.72) were negatively associated with MetS. In conclusion, this study suggests that smoking habit was positively associated with MetS, but tea drinking habit was negatively associated with MetS in elderly men dwelling in rural community.