Summary
Diabetes mellitus may be a risk factor of HCC development in chronic hepatitis B infected patients and affect the all‐cause mortality. This study aimed to examine whether DM was associated ...with the development of HCC with CHB and affected the all‐cause mortality. A total of 2966 CHB patients newly diagnosed with DM in 2000 were retrieved from the Longitudinal Cohort of Diabetes Patients database and used propensity scores matching based on age, sex‐gender, alcohol‐related liver disease and baseline liver cirrhosis to compare with the non‐DM patients from the Taiwanese National Health Insurance Research Database. The CHB patients with DM compared to the non‐DM had significantly increased (3.3%) risk for HCC development and significantly increased (2.8%) risk of HCC‐related mortality. Interestingly, the all‐cause mortality was significantly higher in the DM cohort (16.9%) compared to the non‐DM cohort (8.2%). In a multivariable transition‐specific Cox model to investigate the adjusted hazard ratio of CHB patients with DM or non‐DM during the transitions from start to HCC was 1.35; 95% CI (1.16‐1.57) and from HCC to death was 1.31; 95% CI (1.06‐1.62). All‐cause mortality between CHB patients with DM or non‐DM during the transitions from start to death was 2.32; 95% CI (1.84‐2.92). Taken together, DM is an independent risk factor associated with increasing disease development of HCC, HCC‐related mortality and all‐cause mortality in CHB patients. This study may provide a clinical strategy for strict DM control in order to reduce the risk of disease development in CHB patients.
This study aimed to analyze the association between elevated gamma‐glutamyl transpeptidase (GGT) and metabolic syndrome (MetS), hepatic steatosis, and fibrosis in patients with nonalcoholic fatty ...liver disease (NAFLD). From August 2013 to August 2018, a community‐based study was conducted in the northeastern part of Taiwan. Patients who underwent abdominal ultrasonography (US) and had no history of alcoholic liver disease were included. According to a US examination showing fatty liver degree, 1566 patients with NAFLD were divided into four groups: normal GGT, isolated GGT elevation, isolated alanine aminotransferase (ALT) elevation, and both GGT and ALT elevation groups. Further 1147 participants with normal serum ALT, GGT, and the abdominal US were included as the control group. GGT levels were associated with high sensitivity C‐reactive protein, lower adiponectin, diabetes mellitus, and chronic kidney disease. A stepwise increase in odds ratio (OR) for MetS was found in the normal GGT group (OR = 1.71), isolated GGT elevation group (OR = 3.06), isolated ALT elevation (OR = 4.00), and both GGT + ALT elevation group (OR = 4.17) than the control group. Linear regression analysis revealed a positive association between GGT/ALT value and hepatic steatosis degree, GGT value, and degree of hepatic fibrosis. Hence, GGT elevation is associated with MetS, hepatic steatosis, and fibrosis in patients with NAFLD.
A causal relationship exists among the aging process, organ decay and disfunction, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed
or
(K74R), ...carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/EKLF has been generated that possesses extended lifespan and healthy characteristics, including cancer resistance. We show that the healthy longevity characteristics of the
(K74R) mice, as exemplified by their higher anti-cancer capability, are likely gender-, age-, and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property of
(K74R) mice, could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at a young age of the latter. Furthermore, NK(K74R) cells carry higher in vitro cancer cell-killing ability than wild-type NK cells. Targeted/global gene expression profiling analysis has identified changes in the expression of specific proteins, including the immune checkpoint factors PDCD and CD274, and cellular pathways in the leukocytes of the
(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/blood system for long-term anti-cancer and, potentially, for anti-aging.
Objectives
Glymphatic system maintains brain fluid circulation via active transportation of astrocytic aquaporin-4 in perivascular space. The diffusion tensor imaging analysis along the perivascular ...space (DTI-ALPS) is an established method measuring perivascular glymphatic activity, but comprehensive investigations into its influential factors are lacking.
Methods
Community-dwelling older adults underwent brain MRI scans, neuropsychiatric, and multi-domain assessments. Blood biomarker tests included glial fibrillary acidic protein (GFAP) for astrocyte injury.
Results
In 71 enrolled participants, the DTI-ALPS index was associated with modifiable factors, including lipid profile (high-density lipoprotein,
r
= 0.396; very-low-density lipoprotein,
r
= − 0.342), glucose intolerance (diabetes mellitus, standardized mean difference (SMD) = 0.7662; glycated hemoglobin,
r
= − 0.324), obesity (body mass index,
r
= − 0.295; waist,
r
= − 0.455), metabolic syndrome (SMD = − 0.6068), cigarette-smoking (SMD = − 0.6292), and renal clearance (creatinine,
r
= − 0.387; blood urea nitrogen,
r
= − 0.303). Unmodifiable associative factors of DTI-ALPS were age (
r
= − 0.434) and sex (SMD = 1.0769) (all
p
< 0.05).
A correlation of DTI-ALPS and blood GFAP was noticed (
r
= − 0.201, one-tailed t-test for the assumption that astrocytic injury impaired glymphatic activity,
p
= 0.046). Their cognitive correlations diverged, domain-specific for DTI-ALPS (Facial Memory Test,
r
= 0.272,
p
= 0.022) but global cognition-related for blood GFAP (MoCA,
r
= − 0.264,
p
= 0.026; ADAS-cog,
r
= 0.304,
p
= 0.010).
Conclusion
This correlation analysis revealed multiple modifiable and unmodifiable association factors to the glymphatic image marker. The DTI-ALPS index correlated with various metabolic factors that are known to increase the risk of vascular diseases such as atherosclerosis. Furthermore, the DTI-ALPS index was associated with renal indices, and this connection might be a link of water regulation between the two systems. In addition, the astrocytic biomarker, plasma GFAP, might be a potential marker of the glymphatic system; however, more research is needed to confirm its effectiveness.
Background and Aim
The effect of diabetes mellitus (DM) on the development of hepatocellular carcinoma (HCC) and all‐cause mortality after HCC development in chronic hepatitis C virus (HCV)‐infected ...patients remains inconclusive. This cohort study aimed to investigate these issues using the Taiwanese National Health Insurance Research Database.
Methods
We retrieved and enrolled newly diagnosed DM patients with HCV from the Longitudinal Cohort of Diabetes Patients database. Propensity score matching—including age, sex, alcohol‐related liver disease, and baseline liver cirrhosis—was used to identify and enroll HCV patients without DM from the Longitudinal Health Insurance Database (n = 1686). A multi‐state model was used to investigate transitions from “start‐to‐HCC,” “start‐to‐death,” and “HCC‐to‐death.”
Results
The multi‐state model showed higher cumulative hazards for “start‐to‐HCC,” “start‐to‐death,” and “HCC‐to‐death” transitions in the DM (vs non‐DM) cohort. The cumulative probability of death with or without HCC after 10 years of follow‐up was higher in the DM cohort than in the non‐DM cohort. Multivariable transition‐specific Cox models demonstrated that DM significantly increased the risk for transition from “start‐to‐HCC” (adjusted hazard ratio aHR 1.36; 95% confidence interval CI 1.16–1.59; P < 0.001), “start‐to‐death” (aHR 2.61; 95% CI: 2.05–3.33; P < 0.001), and “HCC‐to‐death” (aHR 1.36; 95% CI 1.10–1.68; P = 0.005). The effect of liver cirrhosis on “start‐to‐HCC” and “start‐to‐death” transitions decreased over time, particularly within 2 years.
Conclusions
Diabetes mellitus increased the risk of HCC development in HCV‐infected patients and the risk of all‐cause mortality in patients with or without HCC.
It is currently unclear whether parenteral selenium supplementation should be recommended in the management of critically ill patients. Here we conducted a systematic review and meta-analysis to ...assess the efficacy of parenteral selenium supplementation on clinical outcomes.
Randomized trials investigating parenteral selenium supplementation administered in addition to standard of care to critically ill patients were included. CENTRAL, Medline, EMBASE, the Science Citation Index, and CINAHL were searched with complementary manual searches. The primary outcome was all-cause mortality. Trials published in any language were included. Two authors independently extracted data and assessed trial quality. A third author was consulted to resolve disagreements and for quality assurance. Twelve trials were included and meta-analysis was performed on nine trials that recruited critically ill septic patients. These comprised 965 participants in total. Of these, 148 patients (30.7%) in the treatment groups, and 180 patients (37.3%) in control groups died. Parenteral selenium treatment significantly reduced all-cause mortality in critically ill patients with sepsis (relative risk RR 0.83, 95% CI 0.70-0.99, p = 0.04, I(2) = 0%). Subgroup analyses demonstrated that the administration schedule employing longer duration (RR 0.77, 95% CI 0.63-0.94, p = 0.01, I(2) = 0%), loading boluses (RR 0.73, 95% CI 0.58-0.94, p = 0.01, I(2) = 0%) or high-dose selenium treatment (RR 0.77, 95% CI 0.61-0.99, p = 0.04, I(2) = 0%) might be associated with a lower mortality risk. There was no evidence of adverse events.
Parenteral selenium supplementation reduces risk of mortality among critically ill patients with sepsis. Owing to the varied methodological quality of the studies, future high-quality randomized trials that directly focus on the effect of adequate-duration of parenteral selenium supplementation for severe septic patients are needed to confirm our results. Clinicians should consider these findings when treating this high-risk population.
PROSPERO 2011; CRD42011001768.
Summary
Objective
The aim of this study was to examine the comorbid rates of thyroid dysfunction among patients with attention‐deficit/hyperactivity disorder (ADHD) and the general population. We ...further examined whether pharmacotherapy affects ADHD patients’ risk of developing thyroid dysfunction.
Design and Measurement
We recruited 75 247 newly diagnosed ADHD patient and 75 247 healthy controls between January 1999 and December 2011 from the National Health Insurance database in Taiwan. We compared hyperthyroidism, hypothyroidism and other common paediatric psychiatric diseases between ADHD patients and controls. We carried out logistic regression analysis to identify an independent factor for predicting thyroid dysfunction. Furthermore, we analysed the time sequence of the diagnosis and the risk of developing a thyroid disorder after receiving pharmacotherapy.
Results
Compared to the control group, the ADHD group had higher comorbidity rates of both hyperthyroidism (1.1% of ADHD vs 0.7% of controls, aOR: 1.72, P < 0.001) and hypothyroidism (0.6% of ADHD vs 0.2% of controls, aOR: 2.23, P < 0.001). Of the ADHD patients with comorbid thyroid dysfunction, about two‐thirds and half of patients were diagnosed with ADHD prior to their diagnosis of hyperthyroidism and hypothyroidism, respectively. Furthermore, pharmacotherapy had no significant influence on the risk of developing hyperthyroidism (aHR: 1.09, P = 0.363) or hypothyroidism (aHR: 0.95, P = 0.719) among ADHD patients.
Conclusion
Patients with ADHD had greater comorbid rates with thyroid dysfunction than the control subjects, but pharmacotherapy for treating ADHD did not affect thyroid dysfunction later in life. However, these findings should be further verified using a clinical cohort with comprehensive laboratory assessment in future.
Emerging evidence suggests that DNA methylation can be affected by physical activities and is associated with cardiac fibrosis. This translational research examined the implications of DNA ...methylation associated with the high-intensity interval training (HIIT) effects on cardiac fibrosis in patients with heart failure (HF).
Twelve HF patients were included and received cardiovascular magnetic resonance imaging with late gadolinium enhancement for cardiac fibrosis severity and a cardiopulmonary exercise test for peak oxygen consumption (Formula: see textO
). Afterwards, they underwent 36 sessions of HIIT at alternating 80% and 40% of Formula: see textO
for 30 min per session in 3-4 months. Human serum from 11 participants, as a means to link cell biology to clinical presentations, was used to investigate the exercise effects on cardiac fibrosis. Primary human cardiac fibroblasts (HCFs) were incubated in patient serum, and analyses of cell behaviour, proteomics (n = 6) and DNA methylation profiling (n = 3) were performed. All measurements were conducted after completing HIIT.
A significant increase (p = 0.009) in Formula: see textO
(pre- vs. post-HIIT = 19.0 ± 1.1 O
ml/kg/min vs. 21.8 ± 1.1 O
ml/kg/min) was observed after HIIT. The exercise strategy resulted in a significant decrease in left ventricle (LV) volume by 15% to 40% (p < 0.05) and a significant increase in LV ejection fraction by approximately 30% (p = 0.010). LV myocardial fibrosis significantly decreased from 30.9 ± 1.2% to 27.2 ± 0.8% (p = 0.013) and from 33.4 ± 1.6% to 30.1 ± 1.6% (p = 0.021) in the middle and apical LV myocardium after HIIT, respectively. The mean single-cell migration speed was significantly (p = 0.044) greater for HCFs treated with patient serum before (2.15 ± 0.17 μm/min) than after (1.11 ± 0.12 μm/min) HIIT. Forty-three of 1222 identified proteins were significantly involved in HIIT-induced altered HCF activities. There was significant (p = 0.044) hypermethylation of the acyl-CoA dehydrogenase very long chain (ACADVL) gene with a 4.474-fold increase after HIIT, which could activate downstream caspase-mediated actin disassembly and the cell death pathway.
Human investigation has shown that HIIT is associated with reduced cardiac fibrosis in HF patients. Hypermethylation of ACADVL after HIIT may contribute to impeding HCF activities. This exercise-associated epigenetic reprogramming may contribute to reduce cardiac fibrosis and promote cardiorespiratory fitness in HF patients.
NCT04038723. Registered 31 July 2019, https://clinicaltrials.gov/ct2/show/NCT04038723 .
•A 17-year population-based study examines the risk of corneal surface damage and epidemiology of aqueous-deficient dry eye disease in Taiwan.•Aqueous-deficient dry eye disease increases the risk of ...corneal surface damage, such as recurrent corneal erosion, corneal ulcers, or corneal scars.•The risk factors for corneal surface damage in aqueous-deficient dry eye disease include younger age (<18 years), female sex, diabetes mellitus, and autoimmune diseases.•The prevalence of aqueous-deficient dry eye disease increases during the study period, especially in patients older than 65 years.
To investigate the epidemiologic characteristics and risk of corneal surface damage in patients with aqueous-deficient dry eye disease (DED) in Taiwan.
Retrospective, population-based cohort study.
We used claims data in the Taiwan National Health Insurance Research Database from 1997 to 2013 of patients with DED, defined according to diagnoses, drug codes, and clinical follow-up. A comparison cohort without DED was selected through propensity score matching. The main outcome measures were corneal surface damage, including corneal erosion, corneal ulcers, or corneal scars.
Patients with DED had a significantly higher rate of corneal surface damage (hazard ratio HR: 2.70; 95% confidence interval CI 2.38-3.06, P < .001), especially higher in patients aged <18 years (HR 6.66; 95% CI 3.58-12.41) than in older patients and in women (HR 2.98; 95% CI 2.57-3.46) than in men (HR 2.22; 95% CI 1.78-2.77), compared to those in the non-DED cohort. DED with diabetes mellitus (P = .002), rheumatoid arthritis (P = .029), or systemic lupus erythematosus (P = .005) was positively associated with corneal surface damage. The overall prevalence of DED was 7.85%, higher among women (10.49%) than men (4.92%), and increased with age (0.53%, 3.94%, 10.08%, and 20.72% for ages <18, 18-39, 40-64, and >65 years, respectively). The prevalence increased gradually during the study period.
The younger age group (<18 years) had the highest risk of corneal surface damage in aqueous-deficient DED. Other predisposing factors included female sex, diabetes, and autoimmune diseases. To improve clinical care, special attention is required for patients with DED with these risk factors.
Gilbert’s syndrome is mainly diagnosed through genetic analysis and is primarily detected through a mutation in the promoter region of the UGT1A1 gene. However, most of the research has been ...conducted on Caucasian populations. In this study, we studied the Han population in Taiwan to investigate the possibility of other mutations that could cause Gilbert’s syndrome. This study comprised a test group of 45 Taiwanese individuals with Gilbert’s syndrome and 180 healthy Taiwanese individuals as a control group. We extracted DNA from the blood samples and then used Axiom Genome-Wide TWB 2.0 array plates for genotyping. Out of 302,771 single nucleotide polymorphisms (SNPs) from 225 subjects, we detected 57 SNPs with the most significant shift in allele frequency; 27 SNPs among them were located in the UGT1A region. Most of the detected SNPs highly correlated with each other and are located near the first exon of UGT1A1, UGT1A3, UGT1A6, and UGT1A7. We used these SNPs as an input for the machine learning algorithms and developed prediction models. Our study reveals a good association between the 27 SNPs detected and Gilbert’s syndrome. Hence, this study provides a reference for diagnosing Gilbert’s syndrome in the Taiwanese population in the future.
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