Exploring the Relationship between Gut Microbiome Composition and Blood Indole-3-acetic Acid in Hemodialysis Patients.

Indole-3-acetic acid (IAA), a protein-bound uremic toxin resulting from gut microbiota-driven tryptophan metabolism, increases in hemodialysis (HD) patients. IAA may induce endothelial dysfunction, inflammation, and oxidative stress, elevating cardiovascular and cognitive risk in HD patients. However, research on the microbiome-IAA association is limited. This study aimed to explore the gut microbiome's relationship with plasma IAA levels in 72 chronic HD patients aged over 18 (August 2016-January 2017). IAA levels were measured using tandem mass spectrometry, and gut microbiome analysis utilized 16s rRNA next-generation sequencing. Linear discriminative analysis effect size and random forest analysis distinguished microbial species linked to IAA levels. Patients with higher IAA levels had reduced microbial diversity. Six microbial species significantly associated with IAA levels were identified; Bacteroides clarus, Bacteroides coprocola, Bacteroides massiliensi, and Alisteps shahii were enriched in low-IAA individuals, while Bacteroides thetaiotaomicron and Fusobacterium varium were enriched in high-IAA individuals. This study sheds light on specific gut microbiota species influencing IAA levels, enhancing our understanding of the intricate interactions between the gut microbiota and IAA metabolism.

Decreased levels of perfluoroalkyl substances in patients receiving hemodialysis treatment.

Perfluoroalkyl substances (PFAS) have been reported to be harmful to multiple organs in the human body. Based on a previous study suggesting that hemodialysis (HD) may be a means of eliminating PFAS from the human body, we aimed to compare the serum PFAS concentrations of patients undergoing regular HD, patients with chronic kidney disease (CKD) and controls. Additionally, we also investigated the correlation between PFAS and biochemical data, as well as concurrent comorbidities. We recruited 301 participants who had been on maintenance dialysis for >90 days, 20 participants with stage 5 non-dialysis CKD, and 55 control participants who did not have a diagnosis of kidney disease, with a mean creatinine level of 0.77 mg/dl. Eight different PFAS, namely perfluorooctanoic acid (PFOA), total and linear perfluorooctanesulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Spearman correlation and multivariable linear regression with 5 % false discovery rate were used to evaluate the relationships between PFAS and clinical parameters in HD patients and controls. Circulating concentrations of seven PFAS, including total and linear PFOS (T-PFOS and L-PFOS) PFDA, PFNA, PFHxS, PFOA, and PFUnDA, were significantly lower in the HD group compared to the CKD and control group. For the interplay between biochemical data and PFAS, all of the studied PFAS were positively correlated with aspartate aminotransferase, alanine aminotransferase, glucose, blood urea nitrogen, ferritin, and vitamin D in the controls, while in HD patients, the PFAS were all positively correlated with albumin, uric acid, iron, and vitamin D. These findings may offer valuable insights for future studies seeking to eliminate PFAS.

Real-world evidence of hyperbaric oxygen therapy on cardiovascular outcomes in patients with chronic osteomyelitis.

BACKGROUND: The effectiveness of hyperbaric oxygen (HBO) therapy for chronic osteomyelitis remains inconclusive. In particular, recent studies have shown that chronic osteomyelitis is a crucial risk factor for cardiovascular diseases. However, the preventive effect of HBO on cardiovascular events has not been reported in patients with chronic osteomyelitis. METHODS: We conducted a population-based cohort study to evaluate the impact of HBO on patients with chronic osteomyelitis. Overall, 5312 patients with chronic osteomyelitis were selected from the Taiwan National Health Insurance Database to evaluate the impact of HBO in patients with chronic osteomyelitis. Propensity-score (PS) matching and inverse probability weighting (IPTW) were employed to balance covariates between the HBO and non-HBO groups. The primary outcome was all-cause mortality. The secondary outcomes were myocardial infarction (MI) and stroke hospitalisation. Furthermore, we evaluated the appropriate timing for HBO intervention by the restricted cubic spline (RCS) functions. RESULTS: After 1:4 PS-matching, the HBO group (n = 265) was associated with lower 1-year mortality (hazard ratio [HR], 0.49; 95 % confidence interval [CI], 0.25-0.95) than the non-HBO group (n = 994); this was consistent with the IPTW weighting results (HR, 0.25; 95 % CI, 0.20-0.33). The risk of stroke was lower in the HBO group (HR, 0.46; 95 % CI, 0.34-0.63) than that in the non-HBO group. However, HBO therapy failed to reduce the risk of MI. Using the RCS model, patients with intervals within 90 days (HR, 1.38; 95 % CI, 1.04-1.84) presented a significant risk of 1-year mortality. After 90 days, as the length of interval increased, the risk gradually decreased and became insignificant. CONCLUSION: The present study revealed that adjunctive HBO could benefit the 1-year mortality and stroke hospitalisation in patients with chronic osteomyelitis. HBO was recommended to be initiated within 90 days of chronic osteomyelitis hospitalisation.

A de novo partial trisomy 9p with Dandy-Walker malformation and ventriculomegaly.

OBJECTIVE: We present a female neonate with de novo trisomy 9p24.3-q21.2 presented with a neurological anomaly. CASE REPORT: Her birth length was 41 cm (<3rd percentile), birth body weight was 1600 g (<5th percentile), and head circumference was 29.5 cm (<5th percentile). She had low-set ears, deep and wide-set eyes with downslanting palpebral fissures, and a full nasal bridge with a globular nose. In addition, a rocker bottom foot was noted after further evaluation. Congenital heart anomalies, including patent ductus arteriosus (0.43 cm), large atrial septal defect, and malalignment ventricular septal defect (0.64 cm) were also confirmed. Brain magnetic resonance imaging showed partial agenesis of the cerebellum and corpus callosum. Furthermore, severe bilateral communicating hydrocephalus was found. CTG-banded chromosome analysis revealed 47, XX, +mar. CONCLUSION: DNA analysis may be mandatory for small gene segments. In trisomy 9p, we proposed further delineation of the critical region correlating to neurological malformations.

Discovery of 7, 4'-dimethoxy-3-hydroxyflavone as a protease-activated receptor 4 antagonist with antithrombotic activity and less bleeding tendency in mice.

There is growing evidence of the importance of protease-activated receptor 4 (PAR4), one of thrombin receptors, as a therapeutic target in thrombotic cardiovascular diseases. In the present study, we utilized ligand-based virtual screening, bioassay, and structure-activity relationship study to discover PAR4 antagonists with new chemical scaffolds from natural origin, and examined their application as antiplatelet agents. By using these approaches, we have identified a flavonoid, 7, 4'-dimethoxy-3-hydroxyflavone, that exhibits anti-PAR4 activity. 7, 4'-Dimethoxy-3-hydroxyflavone inhibited PAR4-mediated human platelet aggregation, GPIIb/IIIa activation, and P-selectin secretion. Also, it inhibited PAR4 downstream signaling pathways, including Ca2+/protein kinase C, Akt, and MAP kinases ERK and p38, in human platelets, and suppressed PAR4-mediated ß-arrestin recruitment in CHO-K1 cells exogenously expressed human PAR4. In a microfluidic system, 7, 4'-dimethoxy-3-hydroxyflavone reduced thrombus formation on collagen-coated chambers at an arterial shear rate in recalcified whole blood. Furthermore, mice treated with 7, 4'-dimethoxy-3-hydroxyflavone were significantly protected from FeCl3-induced carotid arterial occlusions, without significantly affecting tail bleeding time. In conclusion, 7, 4'-dimethoxy-3-hydroxyflavone represents a new class of nature-based PAR4 antagonist, it shows effective in vivo antithrombotic properties with less bleeding tendency, and could be a potential candidate for developing new antiplatelet agents.

The association between visual trajectories and cognitive impairment: insights from the Taiwan Longitudinal Study on Aging.

BACKGROUND: Visual impairment (VI) was associated with cognitive impairment. However, different visual trajectories might contribute to different risks of cognitive decline in the elderly. AIMS: This study aimed to evaluate the association between visual trajectories and cognitive impairment. METHODS: Four thousand two hundred eight community-dwelling elder adults were identified from Waves IV-VII (1999-2011) survey of the Taiwan Longitudinal Study on Aging (TLSA). Cognitive function was determined using the Short Portable Mental Status Questionnaire (SPMSQ) scores. Visual impairment was self-reported and visual trajectories were assessed in at least two waves of the survey. Ordinal logistic regression was performed to estimate adjusted odds ratios (adjORs) and 95% confidence intervals (CIs). RESULTS: Participants with visual trajectory from no VI to VI had significantly higher risk of cognitive impairment with an adjOR of 1.69 (95% CI 1.12-2.57) than participants without VI. Compared to participants without VI, participants with persistent VI (adjOR 1.32; 95% CI 0.89-1.96) and with visual trajectory from VI to no VI (adjOR 1.25; 95% CI 0.83-1.88) were not associated with cognitive impairment. A protective association between eyeglasses use and cognitive impairment (adjOR 0.69; 95% CI 0.55-0.87) was found in this study. Importantly, cataract was associated with higher risk of cognitive impairment (adjOR 1.34; 95% CI 1.10-1.62). However, nonsurgical cataract treatment did not show protective effect on cognitive impairment in patients with cataract. CONCLUSIONS AND DISCUSSION: Visual trajectory from no VI to VI is a significant risk factor for cognitive impairment that physicians should pay special attention during community screening.

The effectiveness of Fuzi in combination with routine heart failure treatment on chronic heart failure patients.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi, Aconiti Lateralis Radix Praeparata, is widely used in Traditional Chinese Medicine (TCM) for the treatment of acute heart failure (HF) for 2000 years. However, the clinical evidence of Fuzi in the treatment of chronic HF is limited, especially when used in combination with Western medications. MATERIALS AND METHODS: This population-based propensity score (PS)-matched cohort study aimed to evaluate the effectiveness of Fuzi on the chronic HF. From 4753 chronic HF patients who had used TCM herbal medicine, we performed 1:1 PS matching and selected target patients with (n = 921) and without (n = 921) Fuzi use for further analysis. The primary outcomes were all-cause mortality and composite cardiovascular (CV) outcomes. Hazard ratio (HR) was calculated by Cox proportional hazard regression and the competing risk analysis. The dose-response relationship and the association between the initiation of TCM herbal medicine and the primary outcomes were evaluated by restricted cubic spline (RCS) functions. RESULTS: There was no difference in all-cause mortality (HR, 0.99; 95% confidence interval [CI], 0.76-1.27) and composite CV outcomes (HR, 0.96; 95% CI, 0.84-1.11) between the Fuzi user and non-user groups. For CV safety issue, the result showed that Fuzi use was not associated with a higher risk of cardiac arrhythmias (HR, 1.03; 95% CI, 0.83-1.29). The dose-response relationship showed that Fuzi cumulative dose (≥150g) was associated with lower composite CV risk (HR, 0.76; 95% CI, 0.59-0.99). In addition, the RCS model showed that late initiation (≥2.5 years) of TCM herbal drugs in chronic HF patients had a higher risk of all-cause mortality (HR, 1.81; 95%CI, 1.07-3.08). CONCLUSIONS: This study is the first real-world evidence to demonstrate the effect of Fuzi combined with routine HF treatment. Importantly, the result indicated that long-term Fuzi use had a significant benefit in preventing cardiovascular events. The late initiation of TCM herbal drugs was associated with a higher risk of all-cause mortality. Further clinical trials are needed to support or undermine the assumption of using Fuzi and current Western medications to treat chronic HF.

The Impact of Urate-Lowering Therapy in Post-Myocardial Infarction Patients: Insights From a Population-Based, Propensity Score-Matched Analysis.

The role of urate-lowering therapy (ULT) for the primary prevention of cardiovascular (CV) events has been widely discussed, but its evidence for the secondary prevention of myocardial infarction (MI) is limited. Therefore, we conduct a population-based, propensity score-matched cohort study to investigate the CV outcomes among patients with post-MI with and without ULT. A total of 19,042 newly diagnosed in-hospital patients with MI were selected using the Taiwan National Health Insurance Database between January 1, 2005, and December 31, 2016. After 1:1 propensity score matching with covariates, patients with MI with (n = 963) and without (n = 963) ULT were selected for further analysis. The primary outcome was the all-cause mortality and the secondary outcomes were composite CV outcomes, including hospitalization for recurrent MI, stroke, heart failure, and cardiac arrhythmias. ULT users were associated with lower all-cause mortality (adjusted hazard ratio (adjHR), 0.67; 95% confidence interval (CI), 0.51-0.87) compared to the ULT nonusers. In addition, ULT users had a significantly lower risk of recurrent MI, which needed revascularization by percutaneous coronary intervention or coronary artery bypass grafting (adjHR, 0.67; 95% CI, 0.53-0.86) than the ULT nonusers. The primary and secondary outcomes were not different between patients with post-MI who received uricosuric agents and xanthine oxidase inhibitors. The anti-inflammatory effect of ULT plays an essential role in MI management. From a real-world setting, this study shows that ULT is associated with the lower risk of all-cause mortality in patients with post-MI. In addition, the result shows the possible lower incidence of repeat revascularization procedures in the ULT users.

Social Participation and Survival in Widowed Persons: Results of the Taiwan Longitudinal Study on Aging.

It has been considered that widowed persons have a higher risk of death. This study intended to explore whether social participation could improve this trend. A longitudinal study database was constructed to explore the trend of survival and its change with social participation in widowed persons. The Taiwan Longitudinal Study on Aging (TLSA), based on four consecutive waves of longitudinal follow-up data in 1999, 2003, 2007, and 2011 was linked with the National Death Registry from 1999 through 2012. In total, there were 1417 widowed persons and 4500 nonwidowed persons included in this study, excluding divorced and never-married people. The survival trend analysis was carried out with social participation as the main predictive factor stratified for comparative analysis. Our results showed that the widowed were older than the nonwidowed, were female-dominant, had a lower education level, were more economically stressed, and were less likely to engage in regular exercise, and thus showed generally poorer health; for example, being more vulnerable to having chronic diseases, disability with the Activities of Daily Living (ADL), cognitive impairment with the Short Portable Mental State Questionnaire (SPMSQ), and depression with The Center for Epidemiological Studies-Depression (CES-D). The death risk of the widowed was significantly higher than that of the nonwidowed, but the death trend for those with social participation was significantly lower than that of their counterparts in both the widowed and nonwidowed. After matching with gender and age for widowed persons, the widowed with social participation had a significantly lower risk of death (adjusted hazard ratio (HR), 0.83; 95% confidence interval (CI), 0.71-0.98) compared to the widowed without social participation. It was concluded that social participation can improve the death risk for the widowed, and it is worthily included in health promotion plans and social welfare services for widowed persons.

Uncovering Modern Clinical Applications of Fuzi and Fuzi-Based Formulas: A Nationwide Descriptive Study With Market Basket Analysis.

Background: As time evolved, traditional Chinese medicine (TCM) became integrated into the global medical system as complementary treatments. Some essential TCM herbs started to play a limited role in clinical practices because of Western medication development. For example, Fuzi (Aconiti Lateralis Radix Praeparata) is a toxic but indispensable TCM herb. Fuzi was mainly used in poor circulation and life-threatening conditions by history records. However, with various Western medication options for treating critical conditions currently, how is Fuzi used clinically and its indications in modern TCM are unclear. This study aimed to evaluate Fuzi and Fuzi-based formulas in modern clinical practices using artificial intelligence and data mining methods. Methods: This nationwide descriptive study with market basket analysis used a cohort selected from the Taiwan National Health Insurance database that contained one million national representatives between 2003 and 2010 used for our analysis. Descriptive statistics were performed to demonstrate the modern clinical indications of Fuzi. Market basket analysis was calculated by the Apriori algorithm to discover the association rules between Fuzi and other TCM herbs. Results: A total of 104,281 patients using 405,837 prescriptions of Fuzi and Fuzi-based formulas were identified. TCM doctors were found to use Fuzi in pulmonary (21.5%), gastrointestinal (17.3%), and rheumatologic (11.0%) diseases, but not commonly in cardiovascular diseases (7.4%). Long-term users of Fuzi and Fuzi-based formulas often had the following comorbidities diagnosed by Western doctors: osteoarthritis (31.0%), peptic ulcers (29.5%), hypertension (19.9%), and COPD (19.7%). Patients also used concurrent medications such as H2-receptor antagonists, nonsteroidal anti-inflammatory drugs, ß-blockers, calcium channel blockers, and aspirin. Through market basket analysis, for the first time, we noticed many practical Fuzi-related herbal pairs such as Fuzi-Hsihsin (Asari Radix et Rhizoma)-Dahuang (Rhei Radix et Rhizoma) for neurologic diseases and headache. Conclusion: For the first time, big data analysis was applied to uncover the modern clinical indications of Fuzi in addition to traditional use. We provided necessary evidence on the scientific use of Fuzi in current TCM practices, and the Fuzi-related herbal pairs discovered in this study are helpful to the development of new botanical drugs.

Association Between Digoxin Use and Cancer Incidence: A Propensity Score-Matched Cohort Study With Competing Risk Analysis.

Background: Previous studies neglected death as a critical competing risk while estimating the cancer risk for digoxin users. Therefore, the current study aims to assess the effectiveness of digoxin on cancer prevention by competing risk analysis. Methods: We performed a population-based retrospective cohort study using the Taiwan National Health Insurance Research database between 1998 and 2010. After one-to-one propensity score-matching from 36,160 patients with defined criteria, we enrolled 758 patients both in digoxin and ß-blocker group for further analysis. Results: The results showed that the digoxin group had higher all-cause mortality than the ß-blocker group in the 4- year (10.4 vs. 4.9%) and 8 years (13.6 vs. 7.0%) follow-up. The subdistribution HR of cancer incidence in the digoxin group compared to the ß-blocker group was 1.99 (95% confidence interval [CI]: 1.22-3.01) and 1.46 (95% CI: 1.01-2.15) in the 4 years and 8 years follow-up, respectively. Conclusions: The result of our study showed the usage of digoxin has no benefit in cancer prevention compared with ß-blocker. The possibility of ß-blocker as a new drug candidate for cancer prevention needs further clinical evaluation. The current study also emphasized the necessity of competing risk analysis applying to similar clinical researches.

Juglone prevents human platelet aggregation through inhibiting Akt and protein disulfide isomerase.

BACKGROUND/PURPOSE: Juglone, a natural compound widely found in Juglandaceae plants, has been suggested as a potential drug candidate for treating cancer, inflammation, and diabetic vascular complications. In the present study, the antiplatelet effect and underlying mechanisms of juglone were investigated for the first time. STUDY DESIGN/METHODS: Human platelet aggregation and activation were measured by turbidimetric aggregometry, flow cytometry, and Western blotting. In vitro antithrombotic activity of juglone was assessed using collagen-coated flow chambers under whole-blood flow conditions. The effect of juglone on protein disulfide isomerase (PDI) activity was determined by the dieosin glutathione disulfide assay. RESULTS: Juglone (1 - 5 µM) inhibited platelet aggregation and glycoprotein (GP) IIb/IIIa activation caused by various agonists. In a whole blood flow chamber system, juglone reduced thrombus formation on collagen-coated surfaces under arterial shear rates. Juglone abolished intracellular Ca2+ elevation and protein kinase C activation caused by collagen, but had no significant effect on that induced by G protein-coupled receptor agonists. In contrast, Akt activation caused by various agonists were inhibited in juglone-treated platelets. Additionally, juglone showed inhibitory effects on both recombinant human PDI and platelet surface PDI at concentrations similar to those needed to prevent platelet aggregation. CONCLUSION: Juglone exhibits potent in vitro antiplatelet and antithrombotic effects that are associated with inhibition of Akt activation and platelet surface PDI activity.

Effects of hearing impairment and hearing aid use on the incidence of cognitive impairment among community-dwelling older adults: evidence from the Taiwan Longitudinal Study on Aging (TLSA).

BACKGROUND: Previous studies have reported associations between hearing impairment (HI) and cognitive impairment, but the evidence is not conclusive while considering concurrent geriatric syndromes. Especially, evidence from previous studies rarely came from Asian studies. This study aimed to evaluate the independent effects of HI and hearing aid use on the incidence of cognitive impairment while considering most geriatric confounders. METHODS: This population-based, propensity-score matched cohort study used cohort from Waves IV-VII (1999-2011) survey of the Taiwan Longitudinal Study on Aging (TLSA). Cognitive impairment was identified based on Short Portable Mental Status Questionnaire (SPMSQ) scores. The hazard ratio (HR) was calculated using the Cox proportional hazard regression adjusting for age, sex, comorbidities, socioeconomic status, Center for Epidemiologic Studies Depression (CES-D) scores, the instrumental activities of daily living scale, mobility condition and quality of life. In addition, social support and participation were also considered as confounders in the analysis. To assess the robustness of our findings, we conducted a sensitivity analysis designed to access unmeasured confounding factors by calculating E-values. RESULTS: After 1:1 propensity-score matching, we included 709 participants in both the HI and non-HI groups with a mean age of 73.4 years and 39.4% of participants were female. The mean follow-up was 8.9 ± 3.9 years. The HI group had a higher incidence of cognitive impairment than the non-HI group (74.5% vs. 69.1%, respectively), with an adjusted HR of 1.16 (95% confidence interval [CI], 1.03-1.32) based on a 12-year follow up. The E-value was 1.45 for the estimate, which provided evidence for this study's robustness. Although, a subgroup analysis showed that hearing aid use was associated with lower incidences of cognitive impairment (66.3% vs. 75.6%) when compared to non-users in the HI group, the adjusted HR of 0.82 (95% CI, 0.61-1.09) revealed no significant differences. CONCLUSIONS: HI was an independent risk factor of incident cognitive impairment on top of concurrent geriatric syndromes. Early HI detection may thus be effective for preventing cognitive decline. Further studies are needed to evaluate the effect of hearing aid use on the prevention of cognitive decline.

Development of Taiwan Risk Score for Sarcopenia (TRSS) for Sarcopenia Screening among Community-Dwelling Older Adults.

The SARC-F questionnaire has been suggested by the European Working Group on Sarcopenia in Older People (EWGSOP) as a first-step screening tool for sarcopenia. However, the sensitivity to SARC-F is low among community-dwelling older adults. Therefore, this study aimed to develop a new prediction model for sarcopenia screening in the community setting. We conducted a cross-sectional analysis of data from the Taiwan Integration of Health and Welfare (TIHW) study. Covariates including comorbidities, socioeconomic status, social support, health behaviors, body composition, and serum biomarkers were collected for analysis. Sarcopenia was defined using handgrip strength and gait speed cut-off values suggested by the Asian Working Group for Sarcopenia. Risk scores for sarcopenia were estimated by stepwise logistic regression. Among 1025 participants (mean age, 71.95 ± 6.89 years), 179 (17.5%) had sarcopenia. Seven items, including age, female sex, receiving social assistance pension, absence of exercise, being underweight, abnormal fasting glucose levels, and abnormal creatinine levels were selected for the Taiwan Risk Scores for Sarcopenia (TRSS) with a cutoff value of 76 (sensitivity, 71.8%; specificity, 71.1%) and area under the curve (AUC) of 0.757. Our results suggested that the TRSS model could be applied cost-effectively in the community for early detection of sarcopenia.

Prediction of Frailty and Dementia Using Oral Health Impact Profile from a Population-Based Survey.

Oral health and dentition have been associated with cognitive ability and frailty, but an applicable screening tool has not yet been developed. This study aimed to establish risk prediction models for dementia and frailty. A sample of 2905 community-dwelling older adults aged ≥58 years using the Taiwan Longitudinal Study on Aging (TLSA) survey was adapted and analyzed for this study. Risk scores were estimated by stepwise logistic regression. In models adjusted for covariates, increased age, female sex, no dental prosthesis (adjusted Odds ratio [adjOR], 1.61; 95% confidence interval [CI], 1.11-2.35), diabetes mellitus, chronic kidney disease, and an increased Oral Health Impact Profile (OHIP)-7T Q3 score (adjOR, 1.33; 95% CI, 1.19-1.49) were all significantly associated with frailty. In addition to these factors, an inability to self-report height or weight (adjOR, 4.52; 95% CI, 3.52-5.81) and an increased OHIP-7T Q7 score (adjOR, 1.21; 95% CI, 1.06-1.37) were significantly associated with dementia. The cut-off points of the risk scores for frailty and dementia were 80 (sensitivity, 80.0%; specificity, 81.2%) and 77 (sensitivity, 83.4%; specificity, 71.5%), respectively. The findings highlighted a number of composite risk factors of frailty and dementia. Importantly, the developed prediction models were easily applicable to screen for frailty and dementia in communities or dental clinics.

Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical evidence for LMF use is relatively weak. This study aimed to evaluate the efficacy of LMF as a supplemental therapy to chemo-target agents in metastatic colorectal cancer (mCRC) patients. METHODS: We conducted a prospective, randomized, double-blind, controlled trial to evaluate the efficacy of LMF as a supplemental therapy to chemotarget agents in patients with metastatic colorectal cancer (mCRC). Sixty eligible patients with mCRC were included. Finally, 54 patients were enrolled, of whom 28 were included in the study group and 26 in the control group. The primary endpoint was the disease control rate (DCR), and secondary endpoints included the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and quality of life (QOL). RESULTS: The DCRs were 92.8% and 69.2% in the study and control groups, respectively (p = 0.026), in a median follow-up period of 11.5 months. The OS, PFS, ORR, AEs, and QOL did not significantly differ between the two groups. CONCLUSION: This is the first clinical trial evaluating the efficacy of LMF as a supplemental therapy in the management of patients with mCRC. The results indicate that LMF combined with chemotarget agents significantly improved the DCR.

Use, history, and liquid chromatography/mass spectrometry chemical analysis of Aconitum.

Aconitum and its products have been used in Asia for centuries to treat various ailments, including arthritis, gout, cancer, and inflammation. In general, their preparations and dispensing have been restricted to qualified folk medicine healers due to their low safety index and reported toxicity. In the past few decades, official guidelines have been introduced in Asian pharmacopeias to control Aconitum herbal products. However, these guidelines were based on primitive analytical techniques for the determination of the whole Aconitum alkaloids and were unable to distinguish between toxic and nontoxic components. Recent advances in analytical techniques, especially high performance liquid chromatography (HPLC) and electrophoresis coupled with highly sensitive detectors, allowed rapid and accurate determination of Aconitum secondary metabolites. Reports focusing on liquid chromatography/mass spectrometry analysis of Aconitum and its herbal products are discussed in the current review. This review can be used by the health regulatory authorities for updating pharmacopeial guidelines of Aconitum and its herbal products.

Clinical Aspects of Aconitum Preparations.

Aconite species have played an important role in human history. Aconitum species have been used worldwide as poisons as well as remedies. Their potential in targeting several ailments such as pain, rheumatism, and lethargy has been recognized by Western, Chinese, and Indian health care practitioners. Aconite use in herbal preparations has declined, especially in Europe and the United States, in the first half of the twentieth century due to several reported toxicity cases. The situation has changed with the application of new technologies for the accurate analysis of its toxic components and the development of efficient detoxification protocols. Some Asian countries started small clinical trials to evaluate the potency and safety of different marketed aconite preparations. The current review summarizes therapeutic uses of aconite preparations in China, Taiwan, India, and Japan. It also highlights clinical trial results with special emphasis on their limitations. Modern drugs and pharmacopoeial preparations derived from aconite are also discussed.