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Abstract We present a method for modification of silicon nitride (Si3N4) waveguide resonators using femtosecond laser annealing. The quality (Q) factor of the waveguide resonators can be improved by approximately 1.3 times after annealing. Notably, waveguides that originally had a high Q value maintained their quality after the annealing process. However, those with a lower initial Q value experienced a noticeable improvement post-annealing. To characterize the annealing effect, the surface morphologies of Si3N4 films, both pre- and post-annealing, were analyzed using atomic force microscopy. The findings suggest a potential enhancement in surface refinement. Furthermore, Raman spectroscopy confirmed that the Si3N4 film's composition remains largely consistent with its original state within the annealing power range of 0.6–1.6 W. This research underscores the potential of femtosecond laser annealing as an efficient, cost-effective, and localized technique for fabricating low-loss integrated photonics.

Background: /Purpose: To achieve the World Health Organization goal of eliminating viral hepatitis by 2030, a key strategy in resource-limited areas is to identify the areas with high prevalence and to prioritize screening and treatment intervention. We hypothesized that a hospital-based laboratory database could be used to estimate the township- and village-specific anti-hepatitis C virus (HCV) prevalence. Methods: Yunlin County Public Health Bureau has been collecting anti-HCV test data from eight major hospitals. Township- and village-specific screening testing rates and anti-HCV prevalence were calculated for residents 40 years or older. A township with a wide range of anti-HCV prevalence rates was selected for outreach universal screening and for validating the village-specific prevalence of anti-HCV in the analysis of the data from the hospitals. Results: The overall anti-HCV screening testing rate in Yunlin County was 30.4 %, whereas the anti-HCV prevalence rate for persons 40 years or older was 15.4 %. The village-specific anti-HCV prevalence rates ranged from 3.8 % to 85.8 %. Community-based screening was conducted in Kouhu Township. The village-specific anti-HCV prevalence rates ranged from 0 % to 18.8 %. Three of the four villages had the highest village-specific anti-HCV prevalence in the community-based study and the hospital-based study. Additionally, 95.8 % of the new HCV cases detected by universal screening received anti-HCV therapy. Conclusion: The hospital-based database provided a framework for identifying the villages with high anti-HCV prevalence. Additionally, community-based universal screening should be prioritized for villages with high prevalence in hospital-based databases.

Abstract Background No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF). Methods A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled. Results The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (

In this study, we demonstrate the fabrication of waveguide resonators using nanoimprint technology. Without relying on traditionally costly lithography methods, such as electron-beam lithography or stepper lithography, silicon nitride (Si3N4) resonators with high-quality factors up to the order of 105 can be realized at C-band by nanoimprint lithography. In addition, by properly designing the waveguide geometry, a low-dispersive waveguide can be achieved with waveguide dispersion at around −35 ps/nm/km in the normal dispersion regime, and the waveguide dispersion can be further tuned to be 29 ps/nm/km in the anomalous dispersion regime with the polymer cladding. The tunability of nanoimprinted devices is demonstrated by the aid of microheaters, realizing on-chip optical functionalities. This work offers the potential to fabricate low-dispersive waveguide resonators for integrated modulators and filters in a significantly cost-effective and process-friendly scheme.

This paper introduces a dual-polarized spline-loop antenna element and array. The antenna element consists of two pairs of cross spline-ring dipoles, each with four thin metal strips connected to the adjacent dipole arms, serving as antenna radiators. These radiators resonate within the frequency band n78 (3300-3800 MHz). To achieve one wavelength resonance, the radiators are designed as spline-loop to increase the resonant path. Each spline-loop is fed by an integrated balun connected to a $50~\Omega $ SMA. The thin strips connect the ends of the spline-ring dipoles to form a full-wave spline-loop. An integrated balun circuit is utilized to improve impedance matching and enhance the antenna’s operating bandwidth (approximately 36%). Moreover, to fulfill the electrical down-tilt range of 0 to 10 degrees for the 4-element dual-polarized antenna array used in base stations, a series-connected 4-way power divider is incorporated into the feed network. Each output Port of the power divider has a phase difference of 45 degrees, thereby inducing beam steering effects for the antenna array. Based on actual measurement results, the operating bandwidth of this antenna array covers the range of 2740 to 3910 MHz (approximately 34%), with isolation of 15 dB or greater, an electrical down-tilt of 10 degrees, and an antenna gain of approximately 11 dBi.

Abstract Lenvatinib has been approved as one of the first‐line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non‐inferior to sorafenib. Previous studies have shown well‐controlled viremia contributes to the prognosis of HCC patients receiving first‐line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first‐line lenvatinib treatment in our institute were assessed. High‐effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct‐acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well‐controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV‐related HCC (HBV‐HCC) and 44 patients with HCV‐related HCC (HCV‐HCC), respectively. Progression‐free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV‐HCC patients and 88.4% of the HCV‐HCC patients had well‐controlled viremia, and their PFS (8.8 vs. 3.1 months, p

Introduction The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized. Methods Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.1 for more than 8 months after initiation of immunotherapy. Oligoprogression and polyprogression were defined as progression at ≤ 3 and > 3 lesions, respectively. Results A total of 91 durable responders (63 PR and 28 SD) were identified. The majority had chronic viral hepatitis (n=69, 75.8%). Forty-seven (51.6%) and 44 (48.4%) patients received the index immunotherapy as first-line and second or beyond-line therapy, respectively. Fifty-four (59.3%) patients subsequently developed progression, with a predominant pattern of oligoprogression (66.7%). The median overall survival (OS) was 46.2 months (95% CI: 34.1–58.3). For patients with subsequent progression, employment of locoregional therapy (LRT) for progression was associated with prolonged OS (univariate analysis: hazard ratio [HR] 0.397, p=0.009; multivariate analysis: HR 0.363, p=0.050). Patients with oligoprogression who received LRT showed longer median OS than those who did not (48.4 vs. 20.5 months, p

RNA editing of the hepatitis delta virus (HDV) is essential for generating the large delta antigen, which is crucial for virion assembly. In HDV genotype 1 (HDV-1), editing occurs within the context of the unbranched rod-like structure characteristic of HDV RNA, while RNA editing in HDV-3 requires a branched double-hairpin structure. The regulation of RNA editing in HDV-2 and HDV-4 remains uncertain. Based on predictions of the unbranched rod-like RNA structures of HDV-2 and HDV-4, the editing site occurs as an A.C mismatch pair, surrounded by four base pairs upstream and two base pairs downstream of the editing site, respectively. To investigate HDV-2 and HDV-4 RNA editing, cultured cells were transfected with non-replicating editing reporters carrying wild-type sequences or specific mutations. The results revealed that the editing rates observed for wild-type HDV-2 and HDV-4 were fairly similar, albeit lower than that of HDV-1. Like HDV-1, both HDV-2 and HDV-4 showed a reduction in editing rate when the A.C mismatch pair and the immediately upstream base-paired region were disturbed. Notably, extending the downstream base-paired region from two to three or four (forming a structure identical to that of HDV-1) base pairs increased editing rate. Furthermore, we presented novel evidence that indicates the importance of the first bulge's size, located upstream of the editing site, and the base-pairing length within 7–13 and 28–39 nucleotides downstream of the editing site in influencing the HDV-4 editing rate. To summarize, our analyses suggest that the unbranched rod-like structures surrounding the editing site of HDV-2 and HDV-4 play a crucial role in regulating their RNA editing rates.

Abstract Background and Aim Ropeginterferon alfa‐2b is a novel mono‐pegylated, extra‐long‐acting interferon. It is administered infrequently and showed good tolerability and clinical activity for the chronic hepatitis B or C treatment in our previous Phase 2 clinical trials. This study aims to validate the potency and safety of this novel agent in a Phase 3 chronic viral hepatitis setting. Methods Patients with chronic hepatitis C genotype 2 were randomized to receive subcutaneous injections of ropeginterferon alfa‐2b biweekly or the conventional pegylated interferon alfa‐2b weekly for 24 weeks, combined with ribavirin. The primary endpoint was to assess the safety and antiviral potency of ropeginterferon alfa‐2b by the non‐inferiority in sustained virologic response at 12 weeks after treatment. Results A total of 222 patients were enrolled. Ropeginterferon alfa‐2b group showed a favorable safety profile. Side effects that were generally associated with prior interferon therapies, including neutropenia, asthenia, fatigue, alopecia, dizziness, decreased appetite, nausea, flu‐like symptoms including myalgia, pyrexia, and headache, and administration site reactions, were notably less in the ropeginterferon alfa‐2b group. The cumulative incidence of adverse events of special interest was also notably higher in the control group. The primary endpoint was met and ropeginterferon alfa‐2b showed a better SVR12 rate of 79.8% than 71.9% of the control group. Conclusion Ropeginterferon alfa‐2b is efficacious and has a favorable safety profile as compared with the conventional pegylated interferon alfa‐2b. This study together with previous Phase 2 data validated ropeginterferon alfa‐2b to be a new treatment option for chronic hepatitis C genotype 2.

Background: To evaluate the protective efficacy of a hepatitis B (HB) vaccination program in Taiwan among high-risk children. Methods: Children born to HBeAg-positive mothers from 2001 to 2010 were invited back. Blood samples for hepatitis B virus (HBV) seromarkers were taken and the children underwent hepatobiliary ultrasonography. Perinatal factors including delivery mode and vaccination history were collected from their medical records. According to the results of HBV serological markers, the children were initially classified into five groups: HBV naïve, HB vaccine responder, HBsAg carrier, recovered from HBV infection, and anti-HBc-positive alone. Children in the HBV naïve and anti-HBc-positive alone groups who presented with an anamnestic response after a booster HB vaccine were re-assigned to the vaccine responder and recovered from infection groups, respectively. Results: All of the 196 enrolled children received postnatal hepatitis B immunoglobulin (HBIG) and HB vaccinations, of whom one was HBV naïve (0.5%), 109 were vaccine responders (55.6%), 21 were carriers (10.7%), and 65 recovered from infection (33.2%). Among the 21 carriers, 14 (66.7%) presented in the immunotolerant phase. Cesarean section was the only significant perinatal factor between the carriers (5.3%) and those who recovered from infection (37.7%) (p = 0.007). Conclusion: In this study, there was a 43.9% HBV infection rate and 10.7% HBsAg carrier rate in high-risk Taiwanese children even after receiving HBIG and HB vaccinations. C-section may protect newborns from becoming HBsAg carriers, while HBV genotype and time of HBIG injection did not contribute to the HBV carrier rate.

Background/Purpose: Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. Methods: This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. Results: The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. Conclusion: This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.

Background & Aims: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. Methods: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA >2,000 IU/ml + alanine aminotransferase >2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal. Results: We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels 20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p

Background/purpose: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. Methods: Patients enrolled in TACR from 2017–2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). Results: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P

Background/Purpose: This study is to use albumin-bilirubin (ALBI) grade and up-to-7 (UT7) criteria to assess outcomes of patients with intermediate stage hepatocellular carcinoma (HCC) after transarterial (chemo)embolization (TA(C)E). Methods: Between January 2012 and January 2019, newly diagnosed intermediate HCC patients underwent TA(C)E were enrolled and analyzed. The demographics, clinical characteristics and survival were obtained from medical chart reviews. Results: A total of 359 patients were enrolled and 30.4% of them were within UT7 criteria (UT7 (−)). There were 36.5%, 59.3%, and 4.2% of the patients with ALBI grade I, II, and III, respectively. Beyond UT7 (UT7 (+)) and ALBI grade II/III were associated with overall mortality in multivariate analysis. Based on ALBI grade I/II/III and UT7 −/+, patients were classified into six groups as ALBI grade I plus UT7 (−), II plus UT7 (−), III plus UT7 (−), I plus UT7 (+), II plus UT7 (+), and III plus UT7(+). Distributions of median survival were 47.5, 32.9, 15, 34.3, 16.7 and 14.3 months, respectively. Patients with statistically insignificant survivals were further combined. Patients with ALBI grade I plus UT7 (−) were reclassified as ALBI-U class I, whereas ALBI grade II plus UT7 (−) and I plus UT7 (+) were ALBI-U class II, and the others were ALBI-U class III. There were 8.4%, 48.7%, and 42.9% of patients in ALBI-U class I, II, and III, respectively. The 5-year survival rate was 48.8%, 22.5%, and 13.7% in ALBI-U class I, II, and III, respectively (p

Abstract To determine whether liver stiffness (LS) and fibrosis‐4 (Fib‐4) index were useful in assessing the occurrence of liver‐related complications (LRC) in chronic hepatitis C (CHC) patients after direct‐acting antivirals (DAAs) had been administered. This retrospective study enrolled CHC patients achieving sustained virological response (SVR) after DAA. A total of 697 (male/female: 294/403, mean age: 63.8 year) patients with measured LS and complete lab data at SVR were enrolled, followed, and analyzed. In a median follow‐up of 21.4 months after SVR, 39 patients developed LRC including 28 with hepatocellular carcinoma (HCC), with the 30‐month cumulative incidence of LRC and HCC being 7.7% and 5.1%, respectively. Predictions of occurrence of LRC and HCC were 0.820 and 0.774 for LS, and 0.775 and 0.737 for Fib‐4, with optimal cutoffs of LS and Fib‐4 being 14.5 kPa and 2.9 for LRC prediction. In multivariate analysis, LS was associated with the occurrence of LRC (hazard ratio: 3.97, 95% confidence interval [1.866, 8.446], p

Abstract Background Soluble programmed death-1 (sPD-1) is a novel immune markers and possibly predictive of chronic hepatitis B (CHB) outcome. However, results were inconsistent by different ELISA kits. This study aims to compare the characteristics and correlations with other markers for sPD-1 measured by MyBioSource (MB) and R&D (RD) kits. Methods A total of 254 untreated CHB patients from three sites were assayed with sPD-1 by MB and RD kits at the same time. Spearman’s correlations between the kits, and those with viral markers and ALT levels were calculated. Multivariate linear regression analysis was applied for independent factors associated with the sPD-1 levels. Results There’s no correlation between sPD-1 level using MB and RD assays. sPD-1 by MB correlated profoundly with HBsAg (r = 0.8311, P

Introduction: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide. While there has been rapid evolution in the treatment paradigm of HCC across the past decade, the extent to which these newly approved therapies are utilised in clinical practice in the real world is however, unknown. The INSIGHT study was an investigator-initiated, multi-site longitudinal cohort study conducted to reflect real-world epidemiology and clinical practice in Asia-Pacific in the immediate 7-year period after the conclusion of the BRIDGE study. Methods: Data was collected both retrospectively (planned 30% of total cohort size) and prospectively (planned 70%) from January 2013 to December 2019 from eligible patients newly diagnosed with HCC from 33 participating sites across 9 Asia-Pacific countries. Results: A total of 2,533 newly diagnosed HCC patients (1052 in retrospective cohort and 1481 in prospective cohort) were enrolled. The most common risk factor was hepatitis B in all countries except Japan, Australia and New Zealand, where the prevalence of Hepatitis C and diabetes were more common. The top three comorbidities reported in the INSIGHT study include cirrhosis, hypertension and diabetes. We observe high heterogeneity in the first-line treatment recorded across countries and across disease stage, which significantly affects survival outcomes. Stratification by factors such as etiologies, tumor characteristics, presence of extrahepatic metastases or macrovascular invasion and the use of subsequent lines of treatment were performed. Conclusion: The INSIGHT study describes a wide spectrum of clinical management practices in HCC, where patient demographics, differential costs and patient access to therapies may lead to wide geographical variations through the patient’s treatment cycle, from diagnosis to clinical outcome. The high heterogeneity in patient outcomes demonstrates the need for more robust and clinical management strategies to be designed and adopted to bring about better patient outcomes.

Abstract Sorafenib is the recommended first‐line treatment option for patients with advanced hepatocellular carcinoma (HCC). Hepatitis C virus (HCV)‐related advanced HCC (HCV–HCC) seemed to have a better response than hepatitis B virus (HBV)‐related HCC (HBV–HCC) in sorafenib use, but it was undetermined. Hence, we aimed to investigate the effect of sorafenib between HBV–HCC and HCV–HCC patients in Taiwan. From August 2012 to December 2016, 575 consecutive advanced HCC patients received sorafenib under the reimbursement of Taiwan national health insurance in our hospital. Radiologic assessment was performed at a 2‐month interval. Those patients with tumor progression or liver function deterioration were disallowed for further sorafenib use. Patients with HBV or HCV infection were, retrospectively, enrolled and followed till December 2018. There were 277 (62.4%) HBV–HCC patients and 167 (37.6%) HCV–HCC patients. Before sorafenib, 192 (69.3%) HBV–HCC patients who had used nucleoside analogs (NAs) for HBV management, whereas only 5 (3%) HCV–HCC patients received interferon‐based antiviral therapy. Overall survival (OS) of HCV–HCC patients was significantly superior to HBV–HCC patients without NAs (8.8 months vs. 4.9 months, p = 0.006), but was noninferior to HBV–HCC patients with NAs (8.8 months vs. 10.7 months, p = 0.54). Using propensity score matching, progression‐free survival (2.0 months vs. 2.1 months, p = 0.374) and OS (10.5 months vs. 9.6 months, p = 0.746) between HBV–HCC and HCV–HCC groups were not different. Antiviral therapy might increase survival benefits of advanced HBV–HCC patients underwent sorafenib use, leading to a comparable OS to HCV–HCC patients in Taiwan.

Background: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. Aims: The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. Methods: From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. Result: After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027–2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763–12.558, p = 0.002), but not in early recurrence. Conclusions: TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.

Washing and blanching are two important steps for the processing of fresh good grade small shiitake into casual snacks and prepared foods. This study explored their effects on the dimensions, weights, proximate compositions, taste and bioactive compounds of the shiitake caps and stipes. Results showed that the dimensions and weights of the caps and stipes increased after washing but decreased after blanching. On a dry basis, washing did not affect the nutrients and bioactive compounds contents of shiitake except sugars and polyols compared to fresh samples. However, blanching greatly reduced all the quality contents of the shiitake. The major minerals in the caps and stipes were potassium, magnesium and calcium. The main polyol, sugar, free amino acid, and 5'-nucleotide of shiitake were mannitol, trehalose, glutamine and 5'-adenosine monophosphate, respectively. Equivalent umami concentration (EUC) in the caps was three-fold higher than that in the stipes. Ergosterol, ergothioneine, γ-aminobutyric acid (GABA), and total phenols contents in the caps were significantly higher than those of the stipes, but the polysaccharides showed the reversed. Overall, both caps and stipes contain the necessary nutrients and bioactive compounds, and the blanching significantly affected the above-mentioned components of all tested samples.

Liver abscess formation is one of the major complications following radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC). Clostridium perfringens is a rare but fatal (mortality rate: 70–100%) organism that could lead to severe sepsis. We presented a case where a 63-year-old woman with diabetes mellitus, hypertension, chronic hepatitis B-related cirrhosis in Child-Pugh class A and HCC with initial TNM stage II who had undergone 2 sessions of transarterial chemoembolization. RFA was performed for 4 small HCC due to poor effect of previous transarterial chemoembolization. However, all 4 treated tumors developed liver abscesses presenting with septic shock within 1 day. Aspirated abscesses and blood culture both yielded C. perfringens infection. After intensive care, optimal intravenous antibiotic, and abscesses aspiration, the patient recovered successfully. All tumors achieved complete response during the follow-up period without local recurrence. The clinical presentations and risk factors of C. perfringens-related liver abscess after RFA will be discussed in this manuscript.

Abstract Background Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and interpretation of pathway alteration patterns of individual patients. Methods We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets. Results Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target. Conclusions Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan had established a management consensus guideline in 2016. The current recommendations focus on updating critical issues regarding the management of HCC, including surveillance, diagnosis, and systemic treatment. For surveillance, the updated guideline suggests the role of dynamic computed tomography or magnetic resonance imaging and contrast-enhanced ultrasound (CEUS) in selected patients. For diagnosis, this update incorporates CEUS and recognizes the role of gadoxetic acid–enhanced magnetic resonance imaging. For systemic therapy, the updated guideline summarizes the multiple choices of targeted therapy, immune checkpoint inhibitors, and the combination of both. Through this update of the management consensus guideline, patients with HCC can benefit from receiving optimal diagnostic and therapeutic modalities.

Abstract Since the photolysis rate plays an important role in any photoreaction leading to compound sink and radical formation/destruction and eventually O3 formation, its impact on the simulated O3 concentration was evaluated in the present study. Both RADM2 and RACM were adopted with and without updated photolysis rate constants. The newly developed photolysis rates were determined based on two major absorption cross-section and quantum yield data sources. CMAQ in conjunction with meteorological MM5 and emission data retrieved from Taiwan and East Asia were employed to provide spatial and temporal O3 predictions over a one-week period in a three-level nested domain [from 81 km × 81 km in Domain 1 (East Asia) to 9 km × 9 km in Domain 3 (Taiwan)]. Four cases were analyzed, namely, RADM2, with the original photolysis rates applied in Case 1 as a reference case, RADM2, with the updated photolysis rates applied in Case 2, and RACM, with and without the updated photolysis rates applied in Cases 3 and 4, respectively. A comparison of the simulation and observed results indicates that both the application of updated photolysis rate constants and RACM instead of RADM2 enhanced all three error analysis indicators (unpaired peak prediction accuracy, mean normalized bias error and mean absolute normalized gross error). Specifically, RADM2 with the updated photolysis rates resulted in an increase of 12 ppb (10%) in the daily maximum O3 concentration in southwestern Taiwan, while RACM without the updated photolysis rates resulted in an increase of 20 ppb (17%) in the daily maximum O3 concentration in the same area. When RACM with the updated photolysis rate constants was applied in the air quality model, the difference in the daily maximum O3 concentration reached up to 30 ppb (25%). The implication of Case 4 (RACM with the updated photolysis rates) for the formation and degradation of α-pinene and d-limonene was examined.

Background/Purpose: Effective antiviral-therapy can reduce the risk of liver cirrhosis related hepatocellular carcinoma in patients with chronic hepatitis B and hepatitis C. Yet, the difference of hepatocellular carcinoma development in chronic hepatitis B and hepatitis C patients with cirrhosis after effective antiviral therapy treatment is unknown. In this study, We comprehensive explored the difference among them. Methods: 1363 patients with cirrhosis and hepatitis B virus treated with nucleos(t)ide analogues (NUCs) with completely suppressed virus, and patients with cirrhosis and hepatitis C virus treated with pegylated interferon (peg-IFN)/ribavirin (RBV) combination therapy who achieved sustained virologic response were enrolled. Results: Total 261 developed hepatocellular carcinoma within a median follow-up of 4.25 years. Univariate analysis, patients developed hepatocellular carcinoma tended to be of older age, and had lower platelet counts, were chronic hepatitis B carriers, and had higher serum alfa-fetoprotein (AFP) (≥20 ng/mL), FIB-4 index and APRI scores. Subsequent multivariate analysis revealed older age, lower platelet counts, high AFP levels and chronic hepatitis B carriers were independent risk factors of hepatocellular carcinoma. Conclusion: Our findings identify that chronic hepatitis B patients were with a higher risk of hepatocellular carcinoma compared to chronic hepatitis C patients after achieving virological response. Special attention should be paid to those patients.

This study developed a miniature tag antenna attached to a backing metal for ultrahigh-frequency radio frequency identification (RFID) applications. The impedance of this antenna can be easily controlled at the desired fixed frequency by using different mechanisms and was not considerably affected by backing metal size. This antenna comprises a radiating patch with double I-shaped slots and a ground layer shorted to a narrow inductive plate. Loading a closed slot in the center of the patch and the open slits enabled flexible frequency tuning to match the complex impedance of the microchip used. This tag antenna has a low profile of $28.02\times 25.02\times2.61$ mm3 ( $0.086\times 0.076\times 0.0079\,\,\lambda _{0}^{3}$ ), and it provides a high power transmission coefficient of 99.74%, realized gain of −2.3 dB, and a reading distance of 8.1 m when it is located at the center of a metallic plate of size $250\times250$ mm2. The operational frequency of the proposed antenna was designed to reside the frequency bands for North and South America (860–960 and 902–928 MHz, respectively). Measurements of the antenna prototype proved that the experimental results agreed with the simulated data.

Shiitake (Lentinula edodes) is well-known for its distinct flavor and texture as well as its medicinal and nutritional properties. Small good grade fresh shiitake mushrooms are highly perishable and have a low commodity value in the Taiwan market. As a result, these are frequently used as raw materials for vacuum-fried crisps. However, manufacturers continue to use traditional maltose (MO) syrup with no functional properties as a sweetener, and shiitake stipes are frequently discarded, increasing production costs. Isomalto-oligosaccharide (IMO) is a functional oligosaccharide sweetener with health benefits. The purpose of this research is to study the use of functional IMO in the processing of shiitake crisps to replace MO, and the reusability of stipes. In the manufacture of vacuum-fried shiitake cap and stipe crisps, the 30–40°Brix IMO syrup replaces the 35°Brix MO syrup. Vacuum-fried crisps’ quality characteristics were determined using physicochemical and sensory evaluation. The results showed that centrifuged caps and stipes reach equilibrium after 3 h of being soaked in various concentrations of 90–95°C syrup. The L*, a*, b*, h*, and c* values for the cap crisps decreased with the increase in the level of IMO syrup. The breaking force for the stipe crisps was less than that for cap crisps. The crude protein and crude fat content of vacuum-fried cap and stipe crisps decreased as the level of IMO syrup increased, but the carbohydrate content increased. For a nine-point hedonic test, the sensory scores for cap and stipe crisps without seasoning powder were 6.9–7.4 and 6.1–6.5, respectively. Addition of seasoning powder increased the flavor and overall scores to 8.1–8.2 and 7.2–7.4, respectively. Overall, the addition of IMO syrup reduced the calories and increased the health benefits of vacuum-fried shiitake crisps. Furthermore, the result showed that stipes can also be used to make vacuum-fried crisps and increase profitability for manufacturers.

Background/Aims Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. Methods We prospectively recruited patients with Child’s A cirrhosis and eGFR

Abstract Background Hepatitis D virus (HDV) infection is a major global health issue around the world. There are approximately 15–20 million individuals infected with HDV worldwide. HDV infection usually causes increased mortality compared with infection with hepatitis B virus (HBV) alone. However, testing for the detection of HDV is not widely available in Taiwan. Therefore, the General Biologicals Corporation (GB) HDV Ab kit was developed for detecting anti-HDV antibodies. Methods A total of 913 serum and 462 EDTA-treated plasma samples were obtained from HBsAg-positive individuals in three hospitals in Taiwan from June 2014 to November 2017. We used three commercially available ELISA kits, DiaPro HDV Ab, DiaSorin ETI-AB-DELTAK-2 and GB HDV Ab, which were utilized strictly according to the instructions of the manufacturers. Results A comparative study of the results from the GB HDV Ab kit and the other commercial ELISA kits (DiaPro and DiaSorin) was performed to determine their efficacy for anti-HDV detection. The results indicated that the sensitivity of the GB HDV Ab kit for serum and EDTA samples was 100% compared to that of the DiaPro and DiaSorin kits, whereas the specificity for serum and EDTA samples was 99.3 and 98.1%, respectively. In addition, the overall agreement of the results of the GB HDV Ab kit for the serum and EDTA samples was 99.3 and 98.3%, respectively. It is worth noting that the performance of the GB HDV Ab kit was not affected by interference from triglyceride, bilirubin, hemoglobin, or human anti-mouse antibody. The limit of detection of the GB HDV Ab kit is approximately 100-fold lower than that of the other two commercial kits. Conclusions The GB HDV Ab kit, which presented equivalent sensitivity and specificity compared to both certified anti-HDV kits, would be a suitable kit for HDV diagnosis in Taiwan.

Background and purpose: Hepatitis C virus (HCV) core antigen is highly sensitive and specific in viremic HCV diagnosis. This study evaluated the cost-effectiveness of HCV core antigen (HCVcAg) in community-based screening for active HCV infection. Methods: Between 2017/07 and 2018/07, community-based screenings for active HCV infection with two-step (anti-HCV for screening and HCVRNA for diagnosis) and one-step processes (HCVcAg for screening and diagnosis) were conducted in two districts in Kaohsiung City. While HCVcAg test was positive at ≥3 fmol/L, the lowest level of HCV-RNA detection was 12 IU/mL. We analyzed the cost-effectiveness of two algorithms in identifying active HCV infection. Results: There were two large-scale screenings using the two-step process with a total of 2452 residents enrolled; while six hundred and forty-four residents participated in continuous small-scale screening with the one-step process. The prevalence of anti-HCV and positive HCVcAg was 3.4% and 2.8%. The viremic rate was 1.4% and 2.8% for two- and one-step processes (p

Background: The role of des-γ-carboxy prothrombin (DCP) in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) needs to be clarified. Materials and methods: 174 HCC patients that underwent RFA were enrolled. We calculated the HLs of DCP from the available values before and on first day after ablation and assessed the correlation between HLs of DCP and RFA efficacy. Results: Of 174 patients, 63 with pre-ablation DCP concentrations of ≥80 mAU/mL were analyzed. The ROC analysis showed the optimal cut-off value of HLs of DCP for predicting RFA response was 47.5 h. Therefore, we defined short HLs of DCP < 48 h as a predictor of favorable treatment response. Of 43 patients with a complete radiological response, 34 (79.1%) had short HLs of DCP. In 36 patients with short HLs of DCP, 34 (94.4%) had a complete radiologic response. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.1%, 90.0%, 82.5%, 94.4%, and 66.7%. During the 12-month follow-up, patients who had short HLs of DCP had a better disease-free survival rate than patients with long HLs of DCP (p < 0.001). Conclusions: Short HLs of DCP < 48 h calculated on the first day post-RFA are a useful predictor for treatment response and recurrence-free survival after RFA.

Introduction: Sarcopenia is an adverse prognostic factor in patients with liver cirrhosis and hepatocellular carcinoma (HCC). Image-based sarcopenia assessment allows a standardized method to assess abdominal skeletal muscle. However, which is an index muscle for sarcopenia remains unclear. Therefore, we investigated whether sarcopenia defined according to different muscle groups with computed tomography (CT) scans can predict the prognosis of HCC after radioembolization. Methods: In this retrospective study, we analyzed patients who underwent radioembolization for unresectable HCC between January 2010 and December 2019. Before treatment, the total abdominal muscle (TAM), psoas muscle (PM), and paraspinal muscle (PS) areas were evaluated using a single CT slice at the third lumbar vertebra. In previous studies, sarcopenia was determined using the TAM, PM, and PS after stratifying by sex. Finally, we investigated each muscle-defined sarcopenia to decide whether or not it can serve as a prognostic factor for overall survival (OS). Results: We included 92 patients (74 men and 18 women). TAM, PM, and PS areas were significantly higher in the men than in the women (all p < 0.05). The patients with sarcopenia defined using PM, but not TAM and PS, exhibited significantly poorer OS than those without sarcopenia (median 15.3 vs. 23.8 months, p = 0.034, 0.821, and 0.341, respectively). After adjustment for clinical variables, such as body mass index, liver function, alpha-fetoprotein level, clinical staging, treatment response, and posttreatment curative therapy, PM-defined sarcopenia (hazard ratio: 1.899, 95% confidence interval: 1.087–3.315) remained an independent predictor for the poor OS. Conclusion: CT-assessed sarcopenia defined using PM was an independent prognostic factor for the poorer prognosis of unresectable HCC after radioembolization.

Extractions of the underground parts of valerian were prepared with water and ethanol (25–95%) at 25–75 °C. Extraction yields, bioactive compounds, and the 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability of lyophilized extracts were determined. The inhibitory effects of the extracts, valerenic acid derivatives and phenolic acids, on metabolic syndrome (MS)-related enzymes activities were further examined. Both roots and rhizomes extracted with 95% ethanol at 75 °C had the highest levels of bioactive compounds. The antioxidant capacity and inhibition of MS-related enzymes of the roots extract were better than those of the rhizomes. The roots extract more strongly inhibited pancreatic lipase (inhibition of 50% of enzyme activity (IC50), 17.59 mg/mL), angiotensin-converting enzyme (ACE, IC50, 3.75 mg/mL), α-amylase (IC50, 12.53 mg/mL), and α-glucosidase (IC50, 15.40 mg/mL). These four phenolic acids inhibited the activity of MS-related enzymes. Valerenic acid demonstrated more of an inhibitory ability for ACE (IC50, 0.225 mg/mL, except for caffeic acid) and α-glucosidase (IC50, 0.617 mg/mL) than phenolic acids. Valerian extract inhibited key enzyme activities that were associated with obesity (lipase), hypertension (ACE), and type 2 diabetes (α-amylase and α-glucosidase), suggesting that it is a potential candidate for the development of functional supplements.

Abstract Background Urokinase plasminogen activator (uPA) is an extracellular matrix-degrading protease that is involved in the invasiveness and progression of cancer. There is good evidence that uPA expression is a clinically relevant biomarker in some solid tumors, but its role in hepatocellulcar carcinoma (HCC) is uncertain. We evaluated the prognostic value of serum uPA before surgery in HCC patients receiving curative resection. Methods Serum uPA levels were determined by enzyme-linked immunosorbent assay in 282 HCC patients who received complete liver resections at Kaohsiung Chang Gung Memorial Hospital. Overall survival (OS) curves were constructed using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional -hazards regression model was used to identify independent prognostic factors. The median follow-up time was 52 months. Results Patients with higher pretreatment serum uPA (≥1 ng/ml) had significantly shorter OS (p = 0.002). Patients with liver cirrhosis, hypoalbuminemia, and thrombocytopenia were significantly more likely to present with elevated uPA levels. Multivariate Cox regression analyses indicated that high pretreatment serum uPA [hazard ratio (HR), 1.848, p = 0.006], vascular invasion (HR, 2.940, p

Nanoprobes provide advantages for real-time monitoring of tumor markers and tumorigenesis during cancer progression and development. Epidermal growth factor receptor (EGFR) is a key protein that plays crucial roles for tumorigenesis and cancer therapy of lung cancers. Here, we show a carbon-based nanoprobe, nanodiamond (ND), which can be applied for targeting EGFR and monitoring tumorigenesis of human lung cancer cells in vitro and in vivo. The optimal fluorescent intensities of ND particles were observed in the human lung cancer cells and nude mice under in vivo imaging system. The fluorescence signal of ND particles can be real-time detected in the xenografted human lung tumor formation of nude mice. Moreover, the ND-conjugated specific EGFR antibody cetuximab (Cet) can track the location and distribution of EGFR proteins of lung cancer cells in vitro and in vivo. ND-Cet treatment increased cellular uptake ability of nanocomposites in the EGFR-expressed cells but not in the EGFR-negative lung cancer cells. Interestingly, single ND-Cet complex can be directly observed on the protein G bead by immunoprecipitation and confocal microscopy. Besides, the EGFR proteins were transported to lysosomes for degradation. Together, this study demonstrates that ND-conjugated Cet can apply for targeting EGFR and monitoring tumorigenesis during lung cancer progression and therapy.

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Taiwan, and in the past 30–40 years, Taiwan has been committed to its prevention and treatment. We aimed to investigate the secular trends of characteristics and the survival of HCC in recent decades after making increased efforts. Between 2011 and 2019, a total of 73,817 cases were enrolled from the TCR database. The overall male-to-female ratio was 7/3. The overall, male and female mean ages increased from 63.8 to 66.1 years, 62.0 to 64.3 years and 68.3 to 70.4 years, respectively. After dividing by viral etiologies and gender, the mean age showed increasing trends in all subgroups. The proportions of HBV-HCC, HCV-HCC, HBV+HCV-HCC and Non-HBV+non-HCV-HCC were 48.3%, 25.2%, 5.3% and 21.3% in males, compared with 25.5%, 48.6%, 5.3% and 20.5% in females, respectively. The 5-year survival rates of BCLC stages 0, A, B, C and D were 70%, 58%, 34%, 11% and 4%, respectively. The proportion of BCLC stage 0 increased from 6.2% to 11.3%. Multivariate analysis showed that being female, older age, diagnostic year, BCLC stages, hospital level, body mass index, smoking, alcohol consumption, AFP, Child–Pugh classification and HBV/HCV status were independent predictors for survival. In recent decades, the overall survival of HCC in Taiwan has been improving and might be partly associated with increased BCLC 0 and Child–Pugh A patients, while with the consequent age of patients increasing over time. The proportion of viral-related HCC is decreasing, while nonviral-related HCC is increasing.

BackgroundLenvatinib is approved for patients with advanced hepatocellular carcinoma (HCC) due to its non-inferiority to sorafenib of overall survival (OR) in clinical trials. This study was to compare the effectiveness and safety of lenvatinib and sorafenib in the real world.MethodsWe retrospectively evaluated 338 patients with unresectable HCC who had undergone lenvatinib or sorafenib treatment between January 2018 and August 2020. Propensity-score matching analysis was performed with a 1:2 ratio to reduce the real-life baseline difference between the two groups.ResultsA total of 210 patients (Male/Female: 150/60, mean age: 65.8 years) were recruited including 70 patients in the Lenvatinib group and 140 patients in the Sorafenib group. Compared with sorafenib, lenvatinib had significantly longer progression-free survival (PFS) (5.2 vs 3.3 months, p=0.019) but similar OR (13.3 vs 11.8 months, p=0.714). Additionally, lenvatinib had better disease control rates (62.3 vs 48.6%, p=0.029) and equivalent incidences of treatment-related adverse events over sorafenib. In multivariate analysis, lenvatinib was associated with better PFS over sorafenib (hazard ratio: 0.49, 95% confidence interval: 0.3–0.79, p=0.004) after adjustments of albumin-bilirubin grade and alpha-fetoprotein level; however, different agents using lenvatinib or sorafenib did not contribute to OS, whether in univariate or multivariate analysis. Patients who failed lenvatinib had a lower proportion of having sequential systemic therapies compared with the Sorafenib group (36.2 vs 47.8%, p=0.02). The most frequently used sequential therapy following lenvatinib and sorafenib was chemotherapy (n=9, 42.8%) and regorafenib (n=33, 50.8%), respectively.ConclusionsIn clinical real-life practice, lenvatinib illustrated promising survival benefits and acceptable safety for patients with unresectable HCC, while reducing the risk of progression disease compared with sorafenib. Additionally, lack of approved post-lenvatinib systemic therapies is a serious issue in the real world.

Hepatitis B core-related antigen (HBcrAg) is a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Studies on anti-viral therapy have shown that the use of NUC therapy in HBV patients could reduce the incidence of HCC. However, the incidence of HCC continues to increase after long-term anti-viral therapy. The relationship between HBcrAg and HCC development in CHB-related liver cirrhosis (LC) patients undergoing long-term anti-viral therapy is still unclear. This study enrolled 1108 treatment-naïve CHB patients diagnosed with HBV-related LC receiving NUC therapy from April 1999 to February 2015. The baseline biomarkers, disease history, and following results were collected by the hospital. Among the 1108 patients, 219 developed HCC within a median follow-up period of 6.85 years. A multivariable Cox regression model was used, with adjustment for age, gender, FIB-4, DM, and HBsAg-HQ. The adjusted hazard ratios for the HBcrAg tertile levels were 1.70 (95%CI: 1.21, 2.39) and 2.14 (95%CI: 1.50, 3.05) for levels 3.4–4.9 and >4.9 logU/mL, respectively, compared with levels ≤3.4. The effect of the HBcrAg level on HCC incidence was found to be significantly modified by HBsAg-HQ, where lower HBsAg-HQ (≤ 3) values were associated with a significantly higher risk, but HBsAg-HQ levels >3 were not. Our results highlight that, after adjustment for potential confounding factors, patients with CHB-related LC and higher HBcrAg levels are at significant risk for HCC development, even while undergoing long-term effective anti-viral therapy. The HBcrAg level is therefore an independent risk factor for HCC development, especially for patients with HBsAg-HQ levels

Objective: Cancer patients undergo therapies that might lead to severe adverse events. The enhanced daycare of Traditional Chinese medicine (TCM) we describe was intended to help cancer patients suffering from severe adverse events to obtain relief. We used the Taiwan brief version of the Common Terminology Criteria for Adverse Events Version 4.0 (Taiwan brief version questionnaire of CTCAE) as a primary measurement to evaluate the efficacy of the enhanced day care of TCM. The secondary measurements were the Taiwanese version of the Brief Fatigue Inventory (BFI-T) questionnaire and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire, which were used to quantify fatigue and quality of life (QOL), respectively. Methods/Design: This is a retrospective study of medical records. There were 401 patients treated with enhanced daycare of TCM from June 2017 to November 2019. Results: Among 22 common adverse symptoms in the Taiwan brief version questionnaire of CTCAE4.0, 14 symptoms achieved a significant improvement, and the change of the total scores was also statistically significant ( P

Abstract Hepatocellular carcinoma (HCC) development is ameliorated with nucleos(t)ide agent (NA) therapy for hepatitis B virus (HBV)‐related cirrhosis patients. This study investigates whether liver stiffness (LS) measurement at complete virological response (CVR) was useful in predicting HCC development. Between July 2006 and August 2016, HBV‐related cirrhosis patients with potent NA (entecavir/tenofovir) with the first LS measurement during CVR and with serial LS were enrolled. Patients developing HCC 6 months after potent NA or before the first LS measurement were excluded. Three hundred and seventy‐one patients were enrolled. The median follow‐up was 5.6 and 3.8 years from potent NA treatment and the first LS measurement respectively. Twenty‐seven patients developed HCC. The 1‐, 3‐, 5‐ and 7‐year cumulated incidences of HCC occurrence were 0%, 2.8%, 5.8% and 9%, respectively. In addition to age > 57 years, LS > =21.5 kPa (HR: 3.86, 95%CI: 1.67‐8.94) was an independent factor associated with HCC occurrence in multivariate analysis. However, the magnitude of change in LS was not associated with HCC development. For the first LS in HCC prediction, the performance was 0.636. There were two to thirteen LS measurements during CVR. The change in LS was classified into four patterns stratified by the first and serial LS. Compared with those with serial LS =21.5 kPa tend to have higher HCC occurrence (P = .062). In summary, LS at CVR was an independent factor associated with HCC development for HBV‐related cirrhosis patients with potent NA. However, LS was not satisfactory in the prediction performance of HCC development.

Abstract Background The early stages of lung cancer with ground‐glass opacity (GGO) pattern are detectable. However, it remains a challenge for physicians how best to treat GGO nodules as invasive tumors are occasionally found, even in pure GGO nodules. This study identified the invasiveness by the clinical features of the GGO nodules. Methods A retrospective review of patients with resected GGO nodules from August 2015 to February 2019 was performed. A total of 92 patients were enrolled and gender, age, tumor location, operation times, tumor size, histopathologic and radiological findings were analyzed. Results In this study, the sequential of GGO nodules invasiveness was significantly related to the tumor size and solid component. After regrouping the population into preinvasive and invasive groups, the invasiveness was significantly related to tumor size, solid component, tumor volume and maximal computed tomography (CT) value. Conclusions The invasiveness is difficult to evaluate according to the CT features only when the GGO nodules are less than 2 cm and consolidation/tumor ratio (C/T ratio) are less than 0.25. Tumor size and solid component are significant factors for predicting invasiveness. Part‐solid GGO nodules with a diameter greater than 1 cm require surgical consideration due to their high risk of invasiveness.

Background: Glecaprevir/pibrentasvir (GLE/PIB) is a pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. Real-world data of GLE/PIB in Asian patients other than Japanese are limited. We thus investigated the effectiveness and safety profile of GLE/PIB in Taiwanese patients with chronic hepatitis C (CHC). Methods: CHC patients who received 8, 12, or 16 weeks of GLE/PIB between August and October of 2018 were consecutively enrolled. The treatment duration was determined according to drug label. The hepatic fibrosis was staged according to liver histology, transient elastography, fibrosis index based on 4 factors (FIB-4), or findings of ultrasonography/endoscopy. The primary endpoint was sustained virological response at week 12 off therapy (SVR12). The safety profiles were also assessed. Results: A total of 110 CHC patients with 51% of males were enrolled. The median age was 70 years. A majority (82%) of patients were infected with HCV genotype 2. Forty-six (42%) and 64 (58%) patients had advanced hepatic fibrosis and compensated cirrhosis, respectively. Forty-five (41%) non-cirrhotic patients were treated for 8 weeks. The overall SVR12 rates were 100%, regardless of baseline clinical characteristics. The common adverse events (AEs) were pruritus (12%), anorexia (6%), and fatigue (5%). Nine (8%) serious AEs unrelated to GLE/PIB occurred. Three (2%) patients had Grade 3 elevation of total bilirubin level. None had premature treatment termination, hepatic decompensation, or death. Conclusion: Interferon-free GLE/PIB regimen is highly effective and safe for Asian chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis. Keywords: Chronic hepatitis C, Direct-acting antiviral, Glecaprevir, Pibrentasvir, Taiwan

Background: Hepatitis C virus (HCV)-infected patients who achieved sustained virologic response (SVR) may still develop hepatocellular carcinoma (HCC). The characteristic of HCC and the prognosis between SVR and non-SVR patients were not well known. Methods: Among 1884 HCV-infected patients who were treated with pegylated IFN plus ribavirin therapies, 122 patients developed HCC during follow-up were enrolled in this study. Laboratory data were collected before and at least 1 year after IFN-based therapy, as well as the latest follow-up. Results: Both SVR and non-SVR patients had similar risk factors to develop HCC, but with a little difference. Liver cirrhosis plays a key role in HCC occurrence in both groups. Among the patients who developed HCC, non-SVR patients had significantly higher total bilirubin, higher FIB-4, lower pre-treatment platelet count, higher pre-treatment AFP levels and higher proportion of cirrhosis than SVR patients before occurrence of HCC. After curative treatment, SVR patients had lower recurrence and longer overall survival than non-SVR patients by Kaplan–Meier analysis. Multivariate analysis revealed that APRI ≥0.7 was the independent risk factor for HCC recurrence; and AFP ≥20 ng/ml post IFN therapy, as well as HCC recurrence were the independent risk factors of mortality. Conclusion: Liver cirrhosis plays a key role in HCC occurrence after antiviral therapies. SVR patients may have lower HCC recurrence and longer survival rates than non-SVR patients. Only APRI was associated with HCC recurrence; and post-IFN AFP and HCC recurrence were predictive of subsequent mortality independently. Keywords: Hepatitis C virus, Hepatocellular carcinoma, Mortality, Recurrence, Antiviral therapy

The experts of Taiwan Association for the Study of Liver (TASL) have actively participated and led the guidelines on hepatitis B virus (HBV) management by Asian Pacific Association for the Study of Liver (APASL) which is the first international association for the study of liver to publish the statement on HBV management before. However, there are more and more new data on the natural history and treatment of HBV infection in the past decade. These include new application of an old biomarker (quantitative HBsAg), clinical significance of HBV genotype and naturally occurring mutations, the role of non-invasive examination in evaluating severity of hepatic fibrosis, clinical significance of outcome calculators, new drug or new combination strategies towards more effective therapy and organ transplantation including liver and non-liver transplantation. It is time to publish the guidelines on HBV management of Taiwan. Hence, TASL have conducted an expert meeting to review, to discuss and to debate the relevant literatures, followed by draft the manuscript of HBV management guidelines and recommendations. The guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patient receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included. Keywords: Chronic hepatitis B, Pegylated interferon alfa, Entecavir, Tenofovir disoproxil fumarate, Tenofovir alafenamide

BackgroundNivolumab and regorafenib are approved second-line therapies for patients with hepatocellular carcinoma (HCC) after sorafenib failure. This study compared the effectiveness of nivolumab and regorafenib following sorafenib.MethodsWe retrospectively enrolled HCC patients who had undergone nivolumab or regorafenib after sorafenib failure. Treatment response, treatment-related adverse events (TRAE) and clinical outcomes of study patients were recorded and analyzed.ResultsA total of 90 patients (male/female: 67/23, mean age: 63 years) were enrolled, including 32 patients in the Nivolumab group and 58 patients in the Regorafenib group. The Nivolumab group had better objective response rates (16% vs 6.4%) and disease control rates (44% vs 31.9%) than the Regorafenib group, but there was no statistical difference. The comparison of time to progression (3.0 months vs 2.6 months, p=0.786) and overall survival (OS) (14 months vs 11 months, p = 0.763) between Nivolumab and Regorafenib groups were also insignificant. Regarding number of TRAE incidences, the Nivolumab group was significantly lower than the Regorafenib group (37.5% vs 68%). After cession of nivolumab/regorafenib, 34 patients (37.8%) (Nivolumab group/Regorafenib group: 11/23) could afford the following therapies. Concerning sequential systemic therapies, 17 patients (18.9%) received third-line therapy, whereas six patients (6.7%) could move to fourth-line therapy. In multivariable analysis, patients who achieved disease control were associated with improved OS (hazard ratio, 0.18; 95% confidence interval, 0.07–0.46; p

Background and aimsThe Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely applied staging system for hepatocellular carcinoma (HCC) and is recommended for treatment allocation and prognostic prediction. The BCLC guidelines were modified in 2018 to indicate that Child-Pugh A without any ascites is essential for all stages except stage D. This study sought to provide a description of patients with HCC treated at a high-volume liver surgery center in Taiwan where referral is not needed and all treatment modalities are available and reimbursed by the National Health Insurance program. As such, certain variables that could modulate treatment decisions in clinical practice, including financial constraints, the availability of treatment procedures, and the expertise of the hospital, could be excluded. The study further sought to evaluate the adherence to the modified BCLC guidelines.MethodsThis was a retrospective study with prospectively collected data. 1801 consecutive patients with de novo HCC were enrolled through our institution from 2011-2017.ResultsThere were 302 patients with stage 0, 783 with stage A, 242 with stage B, 358 with stage C, and 116 with stage D HCC. Treatment adhering to the modified BCLC guidelines recommendations was provided to 259 (85.8%) stage 0 patients, 606 (77.4%) stage A patients, 120 (49.6%) stage B patients, 93 (26.0%) stage C patients, and 83 (71.6%) stage D patients.ConclusionsWe reported treatment adhering to the modified BCLC guidelines at a high-volume liver surgery center in Taiwan. We found that non-adherence to the modified BCLC staging system was common in treating stage B and C patients.

This study investigated the kinetics in HBsAg and the HBsAg loss rate after entecavir or tenofovir disoproxil fumarate (TDF) cessation in patients with chronic hepatitis B (CHB) who achieved virological suppression after virological relapse without clinical relapse. A total 504 HBeAg-negative, non-cirrhotic patients who previously received entecavir or TDF with post-treatment and who were followed up for at least 30 months were included. Of the 504 patients, 128 achieved sustained virological suppression (Group I), and 81 experienced virological relapse without clinical relapse. Of the 81 patients, 52 had intermittent or persistent HBV DNA > 2000 IU/mL (Group II), and 29 achieved persistent virological suppression (HBV DNA < 2000 IU/mL) for at least 1.5 years (Group III) after virological relapse. A generalized estimating equations analysis showed that Groups I and III experienced larger off-treatment HBsAg declines than Group II (both, p < 0.001). The post-treatment HBsAg declines of Group I and Group III were similar (p = 0.414). A multivariate analysis showed that there were no differences in the HBsAg change and HBsAg decline (p = 0.920 and 0.886, respectively) or HBsAg loss rate (p = 0.192) between Group I and Group III. The patients who achieved persistent viral suppression after HBV relapse without clinical relapse have a similar decline in HBsAg and the HBsAg loss rate as the sustained responders.

Colorectal cancer is the second leading cause of cancer death globally. The gold standard for locally advanced rectal cancer (LARC) nowadays is preoperative concurrent chemoradiation (CCRT). Approximately three quarters of LARC patients do not achieve pathological complete response and hence suffer from relapse, metastases and inevitable death. The exploration of trustworthy and timely biomarkers for CCRT response is urgently called for. This review focused upon a broad spectrum of biomarkers, including circulating tumor cells, DNA, RNA, oncogenes, tumor suppressor genes, epigenetics, impaired DNA mismatch repair, patient-derived xenografts, in vitro tumor organoids, immunity and microbiomes. Utilizing proper biomarkers can assist in categorizing appropriate patients by the most efficient treatment modality with the best outcome and accompanied by minimal side effects. The purpose of this review is to inspect and analyze accessible data in order to fully realize the promise of precision oncology for rectal cancer patients.

Accelerometer-based devices have been employed in seismocardiography fiducial point detection with the aid of quasi-synchronous alignment between echocardiography images and seismocardiogram signals. However, signal misalignments have been observed, due to the heartbeat cycle length variation. This paper not only analyzes the misalignments and detection errors but also proposes to mitigate the issues by introducing reference signals and adynamic time warping (DTW) algorithm. Two diagnostic parameters, the ratio of pre-ejection period to left ventricular ejection time (PEP/LVET) and the Tei index, were examined with two statistical verification approaches: (1) the coefficient of determination (R2) of the parameters versus the left ventricular ejection fraction (LVEF) assessments, and (2) the receiver operating characteristic (ROC) classification to distinguish the heart failure patients with reduced ejection fraction (HFrEF). Favorable R2 values were obtained, R2 = 0.768 for PEP/LVET versus LVEF and R2 = 0.86 for Tei index versus LVEF. The areas under the ROC curve indicate the parameters that are good predictors to identify HFrEF patients, with an accuracy of more than 92%. The proof-of-concept experiments exhibited the effectiveness of the DTW-based quasi-synchronous alignment in seismocardiography fiducial point detection. The proposed approach may enable the standardization of the fiducial point detection and the signal template generation. Meanwhile, the program-generated annotation data may serve as the labeled training set for the supervised machine learning.