1.Feline mammary carcinoma‑derived extracellular vesicle promotes liver metastasis via sphingosine kinase‑1‑mediated premetastatic niche formation
Yi‑Chih CHANG ; Hao‑Ping LIU ; Hsiao‑Li CHUANG ; Jiunn‑Wang LIAO ; Pei‑Ling KAO ; Hsun‑Lung CHAN ; Ter‑Hsin CHEN ; Yu‑Chih WANG
Laboratory Animal Research 2023;39(4):329-343
Background:
Feline mammary carcinoma (FMC) is one of the most prevalent malignancies of female cats. FMC is highly metastatic and thus leads to poor disease outcomes. Among all metastases, liver metastasis occurs in about 25% of FMC patients. However, the mechanism underlying hepatic metastasis of FMC remains largely uncharacterized.
Results:
Herein, we demonstrate that FMC-derived extracellular vesicles (FMC-EVs) promotes the liver metastasis of FMC by activating hepatic stellate cells (HSCs) to prime a hepatic premetastatic niche (PMN). Moreover, we provide evidence that sphingosine kinase 1 (SK1) delivered by FMC-EV was pivotal for the activation of HSC and the formation of hepatic PMN. Depletion of SK1 impaired cargo sorting in FMC-EV and the EV-potentiated HSC activation, and abol‑ ished hepatic colonization of FMC cells.
Conclusions
Taken together, our findings uncover a previously uncharacterized mechanism underlying liver-metas‑ tasis of FMC and provide new insights into prognosis and treatment of this feline malignancy.
2.Health Care Utilization and Expenditures of Patients with Diabetes Comorbid with Depression Disorder: A National Population-Based Cohort Study.
Chun Jen HUANG ; Hui Min HSIEH ; Herng Chia CHIU ; Peng Wei WANG ; Mei Hsuan LEE ; Chih Yi LI ; Ching Hua LIN
Psychiatry Investigation 2017;14(6):770-778
OBJECTIVE: The study investigated to compare health care utilization and expenditures between diabetic patients with and without depression in Taiwan. METHODS: Health care utilization and expenditure among diabetic patients with and without depression disorder during 2000 and 2004 were examined using Taiwan's population-based National Health Insurance claims database. Health care utilization included outpatient visits and the use of inpatient services, and health expenditures were outpatient, inpatient, and total medical expenditures. Moreover, general estimation equation models were used for analyzing the factors associated with outpatient visits and expenditures. Multiple logistic regression analysis was applied for identifying the factors associated with hospitalization. RESULTS: The average annual outpatient visits and annual total medical expenditures in the study period were 44.23–52.20; NT$87,496–133,077 and 30.75–32.92; NT$64,411–80,955 for diabetic patients with and without depression. After adjustment for covariates, our results revealed that gender and complication were associated with out-patient visits. Moreover, the time factor was associated with the total medical expenditure, and residential urbanization and complication factors were associated with hospitalization. CONCLUSION: Health care utilization and expenditures for diabetic patients with depression were significantly higher than those without depression. Sex, complications, time, and urbanization are the factors associated with health care utilization and expenditures.
Cohort Studies*
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Delivery of Health Care*
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Depression*
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Health Expenditures*
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Hospitalization
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Humans
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Inpatients
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Logistic Models
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National Health Programs
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Outpatients
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Patient Acceptance of Health Care*
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Taiwan
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Time Factors
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Urbanization
3.Treatment Retention Rates of 3-monthly Paliperidone Palmitate and Risk Factors Associated with Discontinuation: A Population-based Cohort Study
Chien-Heng LIN ; Huang-Li LIN ; Chih-Lin CHIANG ; Yi-Wen CHEN ; Yan-Fang LIU ; Yen-Kuang YANG ; Chao-Hsiun TANG
Clinical Psychopharmacology and Neuroscience 2023;21(3):544-558
Objective:
Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors.
Methods:
We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation.
Results:
The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration > 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180−360 days (adjusted relative risk [aRR], 1.76) or < 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year.
Conclusion
Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.
4.Rapidly increasing liver progenitor cell numbers in human regenerating liver after portal vein ligation and liver partition
Kuo-Hua LIN ; Hui-Ting HSU ; Tsung-Han TENG ; Ping-Yi LIN ; Chih-Jan KO ; Chia-En HSIEH ; Yao-Li CHEN
The Malaysian Journal of Pathology 2017;39(3):289-291
Background: Liver regeneration is dependent on the proliferation of hepatocytes. Hepatic progenitorcells are intra-hepatic precursor cells capable of differentiating into hepatocytes or biliary cells.Although liver progenitor cell proliferation during the regenerative process has been observed in animalmodels of severe liver injury, it has never been observed in vivo in humans because it is unethicalto take multiple biopsy specimens for the purpose of studying the proliferation of liver progenitorcells and the roles they play in liver regeneration. Associating liver partition and portal vein ligationfor staged hepatectomy (ALPPS) is a staged procedure for inducing remnant liver hypertrophy sothat major hepatectomy can be performed safely. This staged procedure allows for liver biopsyspecimens to be taken before and after the liver begins to regenerate. Case presentation: The liverprogenitor cell proliferation is observed in a patient undergoing ALPPS for a metastatic hepatictumour. Liver biopsy is acquired before and after ALPPS for the calculation of average number ofliver progenitor cell under high magnification examination by stain of immunomarkers. This is thefirst in vivo evidence of growing liver progenitor cells demonstrated in a regenerating human liver.
5.Unveiling the enigma of acute kidney disease: predicting prognosis, exploring interventions, and embracing amultidisciplinary approach
Szu-Yu PAN ; Thomas Tao-Min HUANG ; Zheng-Hong JIANG ; Li-Chun LIN ; I-Jung TSAI ; Tsung-Lin WU ; Chih-Yi HSU ; Ting WANG ; Hui-Chuen CHEN ; Yu-Feng LIN ; Vin-Cent WU
Kidney Research and Clinical Practice 2024;43(4):406-416
Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury is approximately 33.6%, and it can occur without identifiable preceding acute kidney injury. The development of AKD is associated with increased risks of chronic kidney disease, dialysis, and mortality. Biomarkers and subphenotypes are promising tools to predict prognosis in AKD. The complex clinical situations in patients with AKD necessitate a comprehensive and structured approach, termed “KAMPS” (kidney function check, advocacy, medications, pressure, sick day protocols). We introduce “MAND-MASS,” an acronym devised to summarize the reconciliation of medications during episodes of acute illness, as a critical component of the sick day protocols at AKD. A multidisciplinary team care, consisting of nephrologists, pharmacists, dietitians, health educators, and nurses, is an optimal model to achieve the care bundle in KAMPS. Although the evidence for patients with AKD is still lacking, several potential pharmacological agents may improve outcomes, including but not limited to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists. In conclusion, accurate prognosis prediction and effective treatment for AKD are critical yet unmet clinical needs. Future studies are urgently needed to improve patient care in this complex and rapidly evolving field.
6.Non-linear association between long-term air pollution exposure and risk of metabolic dysfunction-associated steatotic liver disease.
Wei-Chun CHENG ; Pei-Yi WONG ; Chih-Da WU ; Pin-Nan CHENG ; Pei-Chen LEE ; Chung-Yi LI
Environmental Health and Preventive Medicine 2024;29():7-7
BACKGROUND:
Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) has become a global epidemic, and air pollution has been identified as a potential risk factor. This study aims to investigate the non-linear relationship between ambient air pollution and MASLD prevalence.
METHOD:
In this cross-sectional study, participants undergoing health checkups were assessed for three-year average air pollution exposure. MASLD diagnosis required hepatic steatosis with at least 1 out of 5 cardiometabolic criteria. A stepwise approach combining data visualization and regression modeling was used to determine the most appropriate link function between each of the six air pollutants and MASLD. A covariate-adjusted six-pollutant model was constructed accordingly.
RESULTS:
A total of 131,592 participants were included, with 40.6% met the criteria of MASLD. "Threshold link function," "interaction link function," and "restricted cubic spline (RCS) link functions" best-fitted associations between MASLD and PM2.5, PM10/CO, and O3 /SO2/NO2, respectively. In the six-pollutant model, significant positive associations were observed when pollutant concentrations were over: 34.64 µg/m3 for PM2.5, 57.93 µg/m3 for PM10, 56 µg/m3 for O3, below 643.6 µg/m3 for CO, and within 33 and 48 µg/m3 for NO2. The six-pollutant model using these best-fitted link functions demonstrated superior model fitting compared to exposure-categorized model or linear link function model assuming proportionality of odds.
CONCLUSION
Non-linear associations were found between air pollutants and MASLD prevalence. PM2.5, PM10, O3, CO, and NO2 exhibited positive associations with MASLD in specific concentration ranges, highlighting the need to consider non-linear relationships in assessing the impact of air pollution on MASLD.
Humans
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Nitrogen Dioxide
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Cross-Sectional Studies
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Air Pollution/analysis*
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Air Pollutants/analysis*
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Particulate Matter/analysis*
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Liver Diseases
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Environmental Exposure/analysis*
7.Taiwan Association for the Study of the Liver-Taiwan Society of Cardiology Taiwan position statement for the management of metabolic dysfunction- associated fatty liver disease and cardiovascular diseases
Pin-Nan CHENG ; Wen-Jone CHEN ; Charles Jia-Yin HOU ; Chih-Lin LIN ; Ming-Ling CHANG ; Chia-Chi WANG ; Wei-Ting CHANG ; Chao-Yung WANG ; Chun-Yen LIN ; Chung-Lieh HUNG ; Cheng-Yuan PENG ; Ming-Lung YU ; Ting-Hsing CHAO ; Jee-Fu HUANG ; Yi-Hsiang HUANG ; Chi-Yi CHEN ; Chern-En CHIANG ; Han-Chieh LIN ; Yi-Heng LI ; Tsung-Hsien LIN ; Jia-Horng KAO ; Tzung-Dau WANG ; Ping-Yen LIU ; Yen-Wen WU ; Chun-Jen LIU
Clinical and Molecular Hepatology 2024;30(1):16-36
Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.