Search Results (36)

Background: Liver transplantation (LT) is a promising treatment option for patients with hepatocellular carcinoma (HCC) comorbid with cirrhosis. However, HCC with portal vein tumor thrombosis (PVTT) remains an absolute contraindication for LT. This study aimed to analyze the outcomes of LT in patients with HCC plus portal vein thrombosis and further evaluate the impact of PVTT on the long-term outcomes of patients. Methods: Among the 501 patients who underwent LT for HCC between January 2000 and March 2023, 29 (5.8%) patients with HCC who had portal vein thrombosis were further analyzed. Of these 29 patients with portal vein thrombosis, 12 (41.4%) were preoperatively diagnosed with PVTT and underwent LT after receiving downstaging therapy. The remaining 17 (58.6%) patients were PVTT-free prior to LT. Results: Overall, the recurrence-free survival rates at 1, 3, and 5 years were 96.3%, 74.2%, and 74.2%, respectively, while the 1-, 3-, and 5-year overall survival rates were 82.4%, 74.2%, and 70.1%, respectively. However, patients with viable PVTT had significantly worse outcomes than those without viable PVTT (p = 0.030). The 5-year recurrence-free and overall survival rates for patients with viable PVTT were 57.5% and 57.0%, respectively. Conclusions: LT may still be a promising option for patients with HCC and PVTT after appropriate downstaging. However, caution should be adopted, as remnant viable PVTT might lead to unsatisfactory outcomes after transplantation. Full article

Wearable smart devices have become ubiquitous in modern society, extensively researched for their health monitoring capabilities and convenience features. However, the “wearability” of these devices remains a relatively understudied area, particularly in terms of design informed by clinical trials. Wearable devices possess significant potential to enhance daily life, yet their success depends on understanding and validating the design factors that influence comfort, usability, and seamless integration into everyday routines. This review aimed to evaluate the “wearability” of smart devices through a mixed-methods scoping literature review. By analyzing studies on comfort, usability, and daily integration, it sought to identify design improvements and research gaps to enhance user experience and system design. From an initial pool of 130 publications (1998–2024), 19 studies met the inclusion criteria. The review identified three significant outcomes: (1) a lack of standardized assessment methods, (2) the predominance of qualitative over quantitative assessments, and (3) limited utility of findings for informing design. Although qualitative studies provide valuable insights, the absence of quantitative research hampers the development of validated, generalizable design criteria. This underscores the urgent need for future studies to adopt robust quantitative methodologies to better assess wearability and inform evidence-based design strategies. Full article

Background: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. Methods: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. Results: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (β ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. Conclusion: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults. Full article

A flexible pH sensor based on using iridium oxide (IrO_x) as the sensing film was developed by the roll-to-roll (R2R) process. The inert and biocompatible properties of IrO_x make it a desired metal oxide for pH-sensing applications. The flexible substrates being continuously processed by the R2R technique provides the advantages of scalability, reconfigurability, resiliency, on-demand manufacturing, and high throughput, without the need for vacuum systems. Potential sweeps by cyclic voltammetry across the IrO_x film against commercial and planar Ag/AgCl electrodes validated the reversible electrochemical mechanisms. Multiple IrO_x electrodes showed similar output potentials when continuously tested in the pH range of 2–13, indicating good fabrication uniformity. For practical applications, planar IrO_x/Ag-AgCl pairs developed on polyimide substrates were tested, with a good linear fit within pH 2–13, achieving Nernstian responses of around −60.6 mV/pH. The pH sensors showed good repeatability when analyzed with hysteresis, drift, fluctuation, and deviation as the stability factors. The selectivity of the interference ions and the effect of temperature were studied and compared with the reported values. The electrodes were further laminated in a process compatible with the R2R technique for packaging. The flexible sensors were tested under flat and curved surface conditions. Tests in artificial sweat and viscous solutions were analyzed in the Clarke error grid, showing reliable pH-sensing performance. The materials used during the manufacturing processes were sustainable, as the active materials were in small amounts and there was no waste during processing. No toxic chemicals were needed in the fabrication processes. The cost-effective and efficient materials and the fabrication process allow for rapid production that is necessary for disposable and point-of-care devices. Flexible electronics provide a platform for device and sensor integration and packaging, which enables Internet-of-things (IoT) network applications. Full article

A compact and planar imaging system was developed using a flexible polymer substrate that can distinguish subcutaneous tissue abnormalities, such as breast tumors, based on electromagnetic-wave interactions in materials where permittivity variations affect wave reflection. The sensing element is a tuned loop resonator operating in the industrial, scientific, and medical (ISM) band at 2.423 GHz, providing a localized high-intensity electric field that penetrates into tissues with sufficient spatial and spectral resolutions. The resonant frequency shifts and magnitudes of the reflection coefficients indicate the boundaries of abnormal tissues under the skin due to their high contrasts to normal tissues. The sensor was tuned to the desired resonant frequency with a reflection coefficient of −68.8 dB for a radius of 5.7 mm, with a tuning pad. Quality factors of 173.1 and 34.4 were achieved in simulations and measurements in phantoms. An image-processing method was introduced to fuse raster-scanned 9 × 9 images of resonant frequencies and reflection coefficients for image-contrast enhancement. The results showed a clear indication of the tumor’s location at a depth of 15 mm and the capability to identify two tumors both at the depth of 10 mm. The sensing element can be expanded to a four-element phased array for deeper field penetration. Field analysis showed the depths of −20 dB attenuation were improved from 19 to 42 mm, giving wider coverage in tissues at resonance. Results showed that a quality factor of 152.5 was achieved and a tumor could be identified at a depth of up to 50 mm. In this work, simulations and measurements were conducted to validate the concept, showing great potential for subcutaneous imaging in medical applications in a noninvasive, efficient, and lower-cost way. Full article

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients. Full article

Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver allograft recovery. How to define the damage of liver grafts is unclear. A total of 47 liver donors, 23 deceased and 24 living, were enrolled in this study. All deceased donors had suffered from severe brain damage, and six of them had experienced cardio-pulmonary-cerebral resuscitation (CPR). The exploration of liver graft metabolomics was conducted by liquid chromatography coupled with mass spectrometry. Compared with living donor grafts, the deceased liver grafts expressed higher levels of various diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, oleoylcarnitine and linoleylcarnitine; and lower levels of cardiolipin and phosphatidylcholine. The liver grafts from the donors with CPR had higher levels of cardiolipin, phosphatidic acid, phosphatidylcholine, phatidylethanolamine and amiodarone than the donors without CPR. When focusing on amino acids, the deceased livers had higher levels of histidine, taurine and tryptophan than the living donor livers. In conclusion, the deceased donors had suffered from cardio-circulation instability, and their lipid metabolites were increased. The elevation of lipid metabolites can be employed as an indicator of liver graft suffering. Full article

Background: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. Methods: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD—a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. Results: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Conclusions: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population. Full article

Background: Several biomarkers have been correlated with the prevalence and severity of chronic kidney disease (CKD); however, the association between biomarkers and rapid kidney function decline (RKFD) is unknown. This study aimed to evaluate the predictive performance of biomarkers to determine who is likely to develop RKFD in a healthy population. Methods: A community-based cohort of 2608 people residing in northern Taiwan were enrolled, and their renal function was followed annually from January 2014 to December 2019. The outcomes of interest were RKFD, defined as a 15% decrease in the estimated glomerular filtration rate (eGFR) within the first 4 years, and a decrease in eGFR without improvement in the fifth year. Clinical variables and potential predictors of RKFD, namely adiponectin, leptin, tumor necrosis factor-alpha, and cystatin C, were measured and analyzed. Results: The incidence of RKFD was 17.0% (105/619). After matching for age and sex at a 1:1 ratio, a total of 200 subjects were included for analysis. The levels of cystatin C and total vitamin D were significantly negatively correlated with eGFR. eGFR was negatively correlated with the levels of cystatin C and total vitamin D. Among the biomarkers, cystatin C showed the best predictive performance for RKFD (area under the receiver operating characteristic curve: 0.789). Lower serum cystatin C was associated with a higher rate of RKFD in healthy subjects. A generalized additive model showed that 0.82 mg/L was an adequate cut-off value of cystatin C to predict RKFD. Multivariable logistic regression analysis further indicated that low cystatin C and eGFR were independent predictors of the possibility of RKFD. Conclusions: Serum cystatin C level could predict the possibility of RKFD. We suggest that a low cystatin C level should be considered as a risk factor for RKFD in healthy subjects. Full article

A Cu micromembrane is successfully fabricated and validated as a porous flexible electrode. The Cu micromembrane is prepared by functionalizing individual polypropylene (PP) fibers in a polypropylene micromembrane (PPMM) using a mixture of polydopamine (PDA) and polyethyleneimine (PEI). The mixture of PDA and PEI provides adhesive, wetting, and reducing functionalities that facilitate subsequent Ag activation and Cu electroless plating. Scanning electron microscopy reveals conformal deposition of Cu on individual PP fibers. Porometer analysis indicates that the porous nature of PPMM is properly maintained. The Cu micromembrane demonstrates impressive electrical conductivities in both the X direction (1.04 ± 0.21 S/cm) and Z direction (2.99 ± 0.54 × 10⁻³ S/cm). In addition, its tensile strength and strain are better than those of pristine PPMM. The Cu micromembrane is flexible and mechanically robust enough to sustain 10,000 bending cycles with moderate deterioration. Thermogravimetric analysis shows a thermal stability of 400 °C and an effective Cu loading of 5.36 mg/cm². Cyclic voltammetric measurements reveal that the Cu micromembrane has an electrochemical surface area of 277.8 cm² in a 1 cm² geometric area (a roughness factor of 227.81), a value that is 45 times greater than that of planar Cu foil. Full article

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1–2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT₅₀ ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse. Full article

The equivalency of pH measurements between aqueous and non-aqueous or viscous solutions is of great interest in biomedical applications as well for processing food and pharmaceuticals. Commercial glass-type electrodes have practical limitations, such as bulky sizes and membrane clogging in viscous environments. In this study, planar and flexible electrochemical pH sensors with iridium oxide as the sensing film have been developed by sol-gel and oxidation processes. A reference electrode was prepared by screen printing Ag/AgCl ink on the same polyimide substrate. The small form factors of the planar flexible electrodes provide an advantage in small volume or conformal surface measurements. Cyclic voltammetry was performed in different pH solutions. The electrode originally produced a response of −70.1 mV/pH at room temperature in aqueous solutions. The sensitivities were reduced when salt was added into the buffer solutions, although output potentials were increased. Sensing performances in a wide range of viscous conditions with various concentrations of added salt have been analyzed to study their effects on pH-sensing responses. Suitable calibration techniques using aqueous buffer solutions were studied for output potentials and their respective pH readings in viscous salt-added solutions. The mechanisms affecting output potentials are explained and results matched well for two different thickening agents. Specificity to pH changes measured by the planar IrO_x-Ag/AgCl pH electrodes showed how the potential-pH calibration should consider the interference effect of salt. The viscosity effects on pH reading errors became more pronounced as solution viscosity increased. Comparisons of pH readings to those from a commercial glass-bodied pH meter indicated that the planar electrodes provided predictable pH deviations that were confined to a limited range. The planar IrO_x-Ag/AgCl electrodes on flexible polyimide substrates have mostly been demonstrated with aqueous solutions in various diagnostic and environmental monitoring applications. This work provides more insights into pH sensing performance when the fluid is viscous and contains salt, which often is the case in biomedical and food-processing applications. Full article

Background: Micronutrients are essential in maintaining normal human physiology. Data regarding the association between micronutrients and renal outcomes in chronic kidney disease (CKD) are lacking. Methods: This prospective observational cohort study enrolled 261 patients with CKD stages 1–5 and 30 subjects with normal renal function. Baseline serum zinc (Zn), selenium (Se), chromium, manganese, and copper, and laboratory tests were performed at enrolment. The primary endpoint was the presence of end-stage renal disease (ESRD) requiring long-term renal replacement therapy. Results: The median follow-up periods of renal and non-renal survivals were 67.78 and 29.03 months, respectively. Multiple linear regression showed that Zn and Se (β ± SE: 24.298 ± 8.616, p = 0.005; 60.316 ± 21.875, p = 0.006, respectively) levels were positively correlated with renal function. Time to ESRD was significantly longer for those with Zn levels ≥1287.24 ng/g and Se levels ≥189.28 ng/g (both p < 0.001). Cox regression analysis identified a higher Zn level as an independently negative predictor of ESRD after adjusting for renal function (hazard ratio, 0.450, p = 0.019). Conclusion: Serum Se and Zn concentrations are positively associated with renal function and better renal outcomes. A higher Zn concentration could independently predict better renal survival. Full article

Staged hepatectomy is a promising strategy for curative resection of advanced colorectal liver metastasis (CRLM) to prevent inadequate future remnant liver (FRL). However, the selection criteria for conventional two-stage hepatectomy (cTSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) remain unclear. This study aimed to propose a selection criterion for determining the optimal staged hepatectomy for patients with advanced CRLM. A selection criterion based on the degree of metastatic tumors within the FRL was established to determine staged hepatectomy approaches. Generally, ALPPS is recommended for patients with ≤3 metastatic nodules and whose nodules do not measure >3 cm in the FRL. cTSH is performed for patients whose tumor burden in FRL beyond the selection criteria. Data of 37 patients who underwent staged hepatectomy and curative intent of CRLM were analyzed. The clinical characteristics and outcomes of the two approaches were compared. Overall, cTSH and ALPPS were performed for 27 (73.0%) and 10 (27.0%) patients, respectively. Of those, 20 patients in the cTSH group and all patients in the ALPPS group had completed staged hepatectomy. The 1-, 3-, and 5-year survival rates were 91.6%, 62.4%, and 45.4% for all patients, respectively. The outcomes of patients who had successfully completed the staged hepatectomy were significantly better than those of other patients who failed to achieve staged hepatectomy. However, no significant difference was observed in the overall survival of patients who underwent staged hepatectomy between the two groups, but those in the ALPPS group had 100% survival at the end of this study. The individualized selection criteria based on tumor burden in the FRL that could balance the operative risk and oncologic outcome appear to be a promising strategy for achieving complete staged hepatectomy in patients with advanced CRLM. Full article

Hyperlipidemia and oxidative stress with elevated oxidized low-density lipoprotein (ox-LDL) exacerbate hepatic inflammation and fibrosis. The plasma level of low-density lipoprotein (LDL) is controlled by proprotein convertase subtilisin/kexin 9 (PCSK9). Alirocumab is a monoclonal antibody that decreases LDL via inhibiting PCSK9 function. Apart from lipid-lowering effects, alirocumab exerts anti-inflammation, anti-angiogenesis and anti-oxidant effects. This study aims to investigate the impact of alirocumab treatment on common bile duct ligation (BDL)-induced biliary cirrhotic rats. After a 4-week treatment of alirocumab, the hemodynamic data, blood biochemistry, ox-LDL level, oxidative stress markers, severity of hepatic encephalopathy and abnormal angiogenesis of BDL rats were measured and compared to the control group. BDL rats presented cirrhotic pictures and elevated ammonia, total cholesterol, LDL and ox-LDL levels compared to the control group. Alirocumab decreased plasma levels of total cholesterol, LDL, and oxidative stress markers; however, it did not affect the hemodynamics, liver and renal biochemistry, and the plasma levels of ammonia and ox-LDL. The motor activities, portal-systemic collaterals and mesenteric vascular density were not significantly different between alirocumab-treated and control groups. In addition, it did not affect hepatic inflammation, intrahepatic angiogenesis, liver fibrosis and free cholesterol accumulation in the liver of BDL rats. In conclusion, PCSK9 inhibition by alirocumab treatment ameliorates hyperlipidemia and systemic oxidative stress in biliary cirrhotic rats. However, it does not affect the plasma level of ox-LDL, intrahepatic inflammation and fibrosis. In addition, PCSK9 inhibition has a neutral effect on abnormal angiogenesis and hepatic encephalopathy in biliary cirrhotic rats. Full article